Sample records for completely autologous human

  1. Neutralizing antibody responses against autologous and heterologous viruses in acute versus chronic human immunodeficiency virus (HIV) infection: evidence for a constraint on the ability of HIV to completely evade neutralizing antibody responses. (United States)

    Deeks, Steven G; Schweighardt, Becky; Wrin, Terri; Galovich, Justin; Hoh, Rebecca; Sinclair, Elizabeth; Hunt, Peter; McCune, Joseph M; Martin, Jeffrey N; Petropoulos, Christos J; Hecht, Frederick M


    Acute human immunodeficiency virus (HIV) infection is associated with the rapid development of neutralization escape mutations. The degree to which viral evolution persists in chronic infection has not been well characterized, nor is it clear if all patients develop high-level neutralization antibody escape. We therefore measured neutralizing antibody responses against autologous and heterologous viruses in a cohort of acutely and chronically infected subjects (n = 65). Neutralizing antibody responses against both autologous virus and heterologous viruses were lower among individuals with acute infection than among those with chronic infection. Among chronically infected individuals, there was a negative correlation between the level of neutralizing antibodies against autologous virus and the level of viremia. In contrast, there was a positive correlation between the level of neutralizing antibodies against a panel of heterologous viruses and the level of viremia. Viral evolution, as defined by the presence of higher neutralizing titers directed against earlier viruses than against contemporaneous viruses, was evident for subjects with recent infection but absent for those with chronic infection. In summary, neutralizing antibody responses against contemporaneous autologous viruses are absent in early HIV infection but can be detected at low levels in chronic infection, particularly among those controlling HIV in the absence of therapy. HIV replication either directly or indirectly drives the production of increasing levels of antibodies that cross-neutralize heterologous primary isolates. Collectively, these observations indicate that although HIV continuously drives the production of neutralizing antibodies, there may be limits to the capacity of the virus to evolve continuously in response to these antibodies. These observations also suggest that the neutralizing antibody response may contribute to the long-term control of HIV in some patients while protecting

  2. Use of autologous platelet-rich plasma in complete cleft palate repair. (United States)

    El-Anwar, Mohammad Waheed; Nofal, Ahmed Abdel Fattah; Khalifa, Mohamed; Quriba, Amal Saeed


    Evaluate the effect of topical application of autologous platelet-rich plasma (PRP) in primary repair of complete cleft palate and then compare the result with another group of patients using the same surgical technique, without application of PRP with regard to the incidence of oronasal fistula, velopharyngeal closure, and grade of nasality. Case control study. This study was carried on 44 children with complete cleft palate with age range from 12 to 23 months. The children were divided into two age- and gender-matched groups: All children were subjected to the same technique of V-Y pushback repair of the complete cleft palate. In group A (22 children), the PRP prepared from the patient was topically applied between the nasal and oral mucosa layer during palatoplasty, whereas in group B (22 children) the PRP was not applied. All cases were recovered smoothly without problems. In group A, no oronasal fistula was reported, whereas in group B three patients (13.6%) had postoperative fistulae and two patients (9.1%) needed revision palatoplasty. At 6 months postoperative assessment, group A (with PRP application) showed significantly better grade of nasality (P = 0.024) and better endoscopic velopharyngeal closure (P = 0.016) than group B. Usage of autologous PRP in complete cleft palate repair is simple; effective; can decrease the incidence of oronasal fistula; and also significantly improves the grade of nasality and velopharyngeal closure, which decreases the need of further surgical intervention in cleft palate patients. 3b. Laryngoscope, 126:1524-1528, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  3. In vitro engineering of complete autologous oral mucosa equivalents: characterization of a novel scaffold. (United States)

    Peña, I; Junquera, L M; Meana, A; García, E; García, V; De Vicente, J C


    Restoration of oral mucosa defects by means of in vitro-cultured equivalents has become a valid alternative in the field of oral and periodontics surgery. Although different techniques have been described, none has been able to provide an equivalent with an autologous scaffold for the epithelium. The purpose of this study was to obtain complete autologous oral mucosa equivalents (CAOME) using the patient's own fibroblasts and plasma and to characterize these equivalents both morphologically and immunohistochemically. We acquired cell types (keratinocytes and fibroblasts) from the same mucosal samples, which were taken from healthy patients who underwent oral surgery. To construct the CAOME, a small sample of blood was obtained from the patient and subsequently processed to obtain a fibrin glue scaffold. All CAOME thus obtained were stained using the standard hematoxylin and eosin method to study their morphological characteristics. To establish the type of cells in the epithelial layer, CAOME were stained with pancytokeratin AE1/AE3, cytokeratins 5/6 and 13, p-63 and Ki-67. Finally, laminin 5 and collagen IV were used to reveal the presence of a basal membrane. The CAOME featured a monolayer of cube-shaped epithelial cells similar to that found on the basal layer of the oral mucosa. Close to the epithelial layer lay the fibrin and fibroblasts-embedded scaffold. The CAOME was positive to pancytokeratin AE1/AE3, cytokeratin 5/6 and p-63. No reaction was found to cytokeratin 13 and Ki-67. There was staining to laminin 5 but not to collagen IV. It is possible to engineer a CAOME with an epithelium of basal-like and immature keratinocytes, which could potentially reconstruct in vivo loss of tissue.

  4. Autologous biological pacing function with adrenergic-responsiveness in porcine of complete heart block. (United States)

    Zhang, Hao; Li, Shuchun; Qu, Dan; Li, Bailing; He, Bin; Wang, Chong; Xu, Zhiyun


    To assess the efficacy of autologous biological pacing function by autograft of gene-transferred mesenchymal stem cells in a porcine model of complete heart block. Fourteen healthy young male pigs were randomized into active group (n=8) and control group (n=6). Porcine MSCs were transfected with Ad.HCN4 or Ad.Null. The pacemaker function of transfected MSCs was studied by whole-cell patch clamp. The CHB model of porcine was created with transthoracic ablation technique and the transfected MSCs were autografted into the free wall of right ventricle. The pacing function was studied by ECG and ambulatory Holter recording weekly. The adrenergic responsiveness was evaluated by the variation of heart rate after isoprenaline infusion or food provision following an overnight fasting. HCN4-MSCs expressed a robust time-dependent inward current (If) and the current density of If was 4.3±0.6 pA/pF at -105 mV. In week 2 after autograft, the heart rate of active group became significantly higher than control (53±5 bpm vs. 38±4 bpm, Pheart rate was increased significantly in both groups. However, there was a significant increase of heart rate when presenting food for active group (Pheart rate by providing an adrenergic-responsive biological pacing function, indicating a promising approach without immunological or ethical issues for the treatment of complete heart block. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Latissimus Dorsi and Immediate Fat Transfer (LIFT for Complete Autologous Breast Reconstruction

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    James M. Economides, MD


    Conclusion:. Autologous augmentation of the LD flap with lipotransfer has been used to avoid placement of an implant. We improve the technique by performing lipotransfer during index reconstruction. Furthermore, we perform lipotransfer prior to disorigination of the LD muscle to minimize trauma to the flap and increase the efficiency of fat grafting. Our experience demonstrates that this technique is a viable autologous alternative to microsurgical breast reconstruction.

  6. Regeneration of Cartilage in Human Knee Osteoarthritis with Autologous Adipose Tissue-Derived Stem Cells and Autologous Extracellular Matrix

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    Jaewoo Pak


    Full Text Available This clinical case series demonstrates that percutaneous injections of autologous adipose tissue-derived stem cells (ADSCs and homogenized extracellular matrix (ECM in the form of adipose stromal vascular fraction (SVF, along with hyaluronic acid (HA and platelet-rich plasma (PRP activated by calcium chloride, could regenerate cartilage-like tissue in human knee osteoarthritis (OA patients. Autologous lipoaspirates were obtained from adipose tissue of the abdominal origin. Afterward, the lipoaspirates were minced to homogenize the ECM. These homogenized lipoaspirates were then mixed with collagenase and incubated. The resulting mixture of ADSCs and ECM in the form of SVF was injected, along with HA and PRP activated by calcium chloride, into knees of three Korean patients with OA. The same affected knees were reinjected weekly with additional PRP activated by calcium chloride for 3 weeks. Pretreatment and post-treatment magnetic resonance imaging (MRI data, functional rating index, range of motion (ROM, and pain score data were then analyzed. All patients' MRI data showed cartilage-like tissue regeneration. Along with MRI evidence, the measured physical therapy outcomes in terms of ROM, subjective pain, and functional status were all improved. This study demonstrates that percutaneous injection of ADSCs with ECM contained in autologous adipose SVF, in conjunction with HA and PRP activated by calcium chloride, is a safe and potentially effective minimally invasive therapy for OA of human knees.

  7. Ex Vivo Expanded Human NK Cells Survive and Proliferate in Humanized Mice with Autologous Human Immune Cells. (United States)

    Vahedi, Fatemeh; Nham, Tina; Poznanski, Sophie M; Chew, Marianne V; Shenouda, Mira M; Lee, Dean; Ashkar, Ali A


    Adoptive immune cell therapy is emerging as a promising immunotherapy for cancer. Particularly, the adoptive transfer of NK cells has garnered attention due to their natural cytotoxicity against tumor cells and safety upon adoptive transfer to patients. Although strategies exist to efficiently generate large quantities of expanded NK cells ex vivo, it remains unknown whether these expanded NK cells can persist and/or proliferate in vivo in the absence of exogenous human cytokines. Here, we have examined the adoptive transfer of ex vivo expanded human cord blood-derived NK cells into humanized mice reconstituted with autologous human cord blood immune cells. We report that ex vivo expanded NK cells are able to survive and possibly proliferate in vivo in humanized mice without exogenous cytokine administration, but not in control mice that lack human immune cells. These findings demonstrate that the presence of autologous human immune cells supports the in vivo survival of ex vivo expanded human NK cells. These results support the application of ex vivo expanded NK cells in cancer immunotherapy and provide a translational humanized mouse model to test the lifespan, safety, and functionality of adoptively transferred cells in the presence of autologous human immune cells prior to clinical use.

  8. Human autologous serum as a substitute for fetal bovine serum in human Schwann cell culture.

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    Parisa Goodarzi


    Full Text Available Nowadays, cell -based and tissue engineered products have opened new horizons in treatment of incurable nervous system disorders. The number of studies on the role of Schwann cells (SC in treating nervous disorders is higher than other cell types. Different protocols have been suggested for isolation and expansion of SC which most of them have used multiple growth factors, mitogens and fetal bovine sera (FBS in culture medium. Because of potential hazards of animal-derived reagents, this study was designed to evaluate the effect of replacing FBS with human autologous serum (HAS on SC's yield and culture parameters. Samples from 10 peripheral nerve biopsies were retrieved and processed under aseptic condition. The isolated cells cultured in FBS (1st group or autologous serum (2nd group. After primary culture the cells were seeded at 10000 cell/cm2 in a 12 wells cell culture plate for each group. At 100% confluency, the cell culture parameters (count, viability, purity and culture duration of 2 groups were compared using paired t-test. The average donors' age was 35.80 (SD=13.35 and except for 1 sample the others cultured successfully. In first group, the averages of cell purity, viability and culture duration were 97% (SD=1.32, 97/33% (SD=1.22 and 11.77 (SD=2.58 days respectively. This parameters were 97.33% (SD=1.00, 97.55% (SD=1.33 and 10.33 days (SD=1.65 in second group. The difference of cell count, purity and viability were not significant between 2 groups (P>0.05. The cells of second group reached to 100% confluency in shorter period of time (P=0.03. The results of this study showed that autologous serum can be a good substitute for FBS in human SC culture. This can reduce the costs and improve the safety of cell product for clinical application.

  9. Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury. (United States)

    Dai, Guanghui; Liu, Xuebin; Zhang, Zan; Yang, Zhijun; Dai, Yiwu; Xu, Ruxiang


    Neuronal injuries have been a challenging problem for treatment, especially in the case of complete and chronic cervical spinal cord injury (SCI). Recently, particular attention is paid to the potential of stem cell in treating SCI, but there are only few clinical studies and insufficient data. This study explored the efficacy of autologous bone marrow mesenchymal stem cells (BMMSCs) transplantation in the treatment of SCI. Forty patients with complete and chronic cervical SCI were selected and randomly assigned to one of the two experimental groups, treatment group and control group. The treatment group received BMMSCs transplantation to the area surrounding injury, while the control group was not treated with any cell transplantation. Both the transplant recipients and the control group were followed up to 6 months, postoperatively. Preoperative and postoperative neurological functions were evaluated with AIS grading, ASIA score, residual urine volume and neurophysiological examination. Results showed that in the treatment group 10 patients had a significant clinical improvement in terms of motor, light touch, pin prick sensory and residual urine volume, while nine patients showed changes in AIS grade. Neurophysiological examination was consistent with clinical observations. No sign of tumor was evident until 6 months postoperatively. In the control group, no improvement was observed in any of the neurological functions specified above. BMMSCs transplantation improves neurological function in patients with complete and chronic cervical SCI, providing valuable information on applications of BMMSCs for the treatment of SCI. © 2013 Published by Elsevier B.V.

  10. Selective purging of human multiple myeloma cells from autologous stem cell transplant grafts using oncolytic myxoma virus


    Bartee, Eric; Chan, Winnie S.; Moreb, Jan S.; Cogle, Christopher R.; McFadden, Grant


    Autologous stem cell transplantation (ASCT) and novel therapies have improved overall survival of patients with multiple myeloma; however, most patients relapse and eventually succumb to their disease. Evidence indicates that residual cancer cells contaminate autologous grafts and may contribute to early relapses after ASCT. Here, we demonstrate that ex vivo treatment with an oncolytic poxvirus called myxoma virus results in specific elimination of human myeloma cells by inducing rapid cellul...

  11. Cryopreservation of human dental follicle tissue for use as a resource of autologous mesenchymal stem cells. (United States)

    Park, Bong-Wook; Jang, Si-Jung; Byun, June-Ho; Kang, Young-Hoon; Choi, Mun-Jeong; Park, Won-Uk; Lee, Won-Jae; Rho, Gyu-Jin


    The main purpose of this study was to develop a cryopreservation method for human dental follicle tissue to maintain autologous stem cells as a resource. A modified cryoprotectant, consisting of 0.05 m glucose, 0.05 m sucrose and 1.5 m ethylene glycol in phosphate-buffered saline (PBS) was employed, with a slow-ramp freezing rate. We observed > 70% of cell survival rate after 3 months of tissue storage. Isolated and cultured human dental stem cells (hDSCs) from cryopreserved dental follicles expressed mesenchymal stem cell markers at a level similar to that of hDSCs from fresh tissue. They also successfully differentiated in vitro into the mesenchymal lineage, osteocytes, adipocytes and chondrocytes under specific inductions. Using immunohistochemistry, the early transcription factors OCT4, NANOG and SOX2 were moderately or weakly detected in the nucleus of both fresh and cryopreserved dental follicles. In addition, p63, CCND1, BCL2 and BAX protein expression levels were the same in both fresh and cryopreserved tissues. However, the positive-cell ratio and intensity of p53 protein was higher in cryopreserved tissues than in fresh tissues, indicating direct damage of the freeze-thawing process. Real-time PCR analysis of hDSCs at passage 2 from both fresh and cryopreserved dental follicles showed similar levels of mRNA for apoptosis- and transcription-related genes. Based on these results, a newly developed cryoprotectant, along with a slow ramp rate freezing procedure allows for long-term dental tissue preservation for later use as an autologous stem cell resource in regenerative cell therapy. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  12. The complete sequence of human chromosome 5

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    Schmutz, Jeremy; Martin, Joel; Terry, Astrid; Couronne, Olivier; Grimwood, Jane; Lowry, State; Gordon, Laurie A.; Scott, Duncan; Xie, Gary; Huang, Wayne; Hellsten, Uffe; Tran-Gyamfi, Mary; She, Xinwei; Prabhakar, Shyam; Aerts, Andrea; Altherr, Michael; Bajorek, Eva; Black, Stacey; Branscomb, Elbert; Caoile, Chenier; Challacombe, Jean F.; Chan, Yee Man; Denys, Mirian; Detter, Chris; Escobar, Julio; Flowers, Dave; Fotopulos, Dea; Glavina, Tijana; Gomez, Maria; Gonzales, Eidelyn; Goodstenin, David; Grigoriev, Igor; Groza, Matthew; Hammon, Nancy; Hawkins, Trevor; Haydu, Lauren; Israni, Sanjay; Jett, Jamie; Kadner, Kristen; Kimbal, Heather; Kobayashi, Arthur; Lopez, Frederick; Lou, Yunian; Martinez, Diego; Medina, Catherine; Morgan, Jenna; Nandkeshwar, Richard; Noonan, James P.; Pitluck, Sam; Pollard, Martin; Predki, Paul; Priest, James; Ramirez, Lucia; Rash, Sam; Retterer, James; Rodriguez, Alex; Rogers, Stephanie; Salamov, Asaf; Salazar, Angelica; Thayer, Nina; Tice, Hope; Tsai, Ming; Ustaszewska, Anna; Vo, Nu; Wheeler, Jeremy; Wu, Kevin; Yang, Joan; Dickson, Mark; Cheng, Jan-Fang; Eichler, Evan E.; Olsen, Anne; Pennacchio, Len A.; Rokhsar, Daniel S.; Richardson, Paul; Lucas, Susan M.; Myers, Richard M.; Rubin, Edward M.


    Chromosome 5 is one of the largest human chromosomes yet has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding and syntenic conservation with non-mammalian vertebrates, suggesting they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-encoding genes including the protocadherin and interleukin gene families and the first complete versions of each of the large chromosome 5 specific internal duplications. These duplications are very recent evolutionary events and play a likely mechanistic role, since deletions of these regions are the cause of debilitating disorders including spinal muscular atrophy (SMA).

  13. Selective purging of human multiple myeloma cells from autologous stem cell transplantation grafts using oncolytic myxoma virus. (United States)

    Bartee, Eric; Chan, Winnie M; Moreb, Jan S; Cogle, Christopher R; McFadden, Grant


    Autologous stem cell transplantation and novel therapies have improved overall survival of patients with multiple myeloma; however, most patients relapse and eventually succumb to their disease. Evidence indicates that residual cancer cells contaminate autologous grafts and may contribute to early relapses after autologous stem cell transplantation. Here, we demonstrate that ex vivo treatment with an oncolytic poxvirus called myxoma virus results in specific elimination of human myeloma cells by inducing rapid cellular apoptosis while fully sparing normal hematopoietic stem and progenitor cells. The specificity of this elimination is based on strong binding of the virus to myeloma cells coupled with an inability of the virus to bind or infect CD34(+) hematopoietic stem and progenitor cells. These 2 features allow myxoma to readily identify and distinguish even low levels of myeloma cells in complex mixtures. This ex vivo rabbit-specific oncolytic poxvirus called myxoma virus treatment also effectively inhibits systemic in vivo engraftment of human myeloma cells into immunodeficient mice and results in efficient elimination of primary CD138(+) myeloma cells contaminating patient hematopoietic cell products. We conclude that ex vivo myxoma treatment represents a safe and effective method to selectively eliminate myeloma cells from hematopoietic autografts before reinfusion. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  14. Clinical grade cultivation of human Schwann cell, by the using of human autologous serum instead of fetal bovine serum and without growth factors. (United States)

    Aghayan, Hamid-Reza; Arjmand, Babak; Norouzi-Javidan, Abbas; Saberi, Hooshang; Soleimani, Masoud; Tavakoli, Seyed Amir-Hossein; Khodadadi, Abbas; Tirgar, Niloufar; Mohammadi-Jahani, Fereshteh


    Clinical grade cultivation of human schwann cell by the utilization of human autologous serum instead of fetal bovine serum, and also avoiding any growth factors, can increase safety level of this procedure in cases of clinical cell transplantation. The aim of this study was demonstration of the feasibility of clinical grade schwann cell cultivation. In this experimental study after obtaining consent from close relatives we harvested 10 sural nerves from brain death donors and then cultured in 10 seperated culture media plus autologous serum. We also prepared autologous serum from donor's whole blood. Then cultured cells were evaluated by S100 antibody staining for both morphology and purity. Cell purity range was from 97% to 99% (mean=98.11 ± 0.782%). Mean of the cell count was 14,055.56 ± 2,480.479 per micro liter. There was not significant correlation between cell purity and either the culture period or the age of donors (P>0.05). The spearman correlation coefficient for the cell purity with the period or the age of donors was 0.21 and 0.09, respectively. We demonstrated the feasibility of clinical grade schwann cell cultivation by the using of human autologous serum instead of fetal bovine serum and also without the using of growth factors. We also recommended all cell preparation facilities to adhere to the GMP and other similar quality disciplines especially in the preparation of clinically-used cell products.

  15. Characterization of Human Vaginal Mucosa Cells for Autologous In Vitro Cultured Vaginal Tissue Transplantation in Patients with MRKH Syndrome

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    Cristina Nodale


    Full Text Available Mayer-Rokitansky-Küster-Hauser (MRKH is a rare syndrome characterized by congenital aplasia of the uterus and vagina. The most common procedure used for surgical reconstruction of the neovagina is the McIndoe vaginoplasty, which consists in creation of a vaginal canal covered with a full-thickness skin graft. Here we characterized the autologous in vitro cultured vaginal tissue proposed as alternative material in our developed modified McIndoe vaginoplasty in order to underlie its importance in autologous total vaginal replacement. To this aim human vaginal mucosa cells (HVMs were isolated from vaginal mucosa of patients affected by MRKH syndrome and characterized with respect to growth kinetics, morphology, PAS staining, and expression of specific epithelial markers by immunofluorescence, Western blot, and qRT-PCR analyses. The presence of specific epithelial markers along with the morphology and the presence of mucified cells demonstrated the epithelial nature of HMVs, important for an efficient epithelialization of the neovagina walls and for creating a functional vaginal cavity. Moreover, these cells presented characteristics of effective proliferation as demonstrated by growth kinetics assay. Therefore, the autologous in vitro cultured vaginal tissue might represent a highly promising and valid material for McIndoe vaginoplasty.

  16. A phase 2 autologous cellular therapy trial in patients with acute, complete spinal cord injury: pragmatics, recruitment, and demographics. (United States)

    Jones, L A T; Lammertse, D P; Charlifue, S B; Kirshblum, S C; Apple, D F; Ragnarsson, K T; Poonian, D; Betz, R R; Knoller, N; Heary, R F; Choudhri, T F; Jenkins, A L; Falci, S P; Snyder, D A


    Post hoc analysis from a randomized controlled cellular therapy trial in acute, complete spinal cord injury (SCI). Description and quantitative review of study logistics, referral patterns, current practice patterns and subject demographics. Subjects were recruited to one of six international study centers. Data are presented from 1816 patients pre-screened, 75 participants screened and 50 randomized. Of the 1816 patients pre-screened, 53.7% did not meet initial study criteria, primarily due to an injury outside the time window (14 days) or failure to meet neurological criteria (complete SCI between C5 motor/C4 sensory and T11). MRIs were obtained on 339 patients; 51.0% were ineligible based on imaging criteria. Of the 75 participants enrolled, 25 failed screening (SF), leaving 50 randomized. The primary reason for SF was based on the neurological exam (51.9%), followed by failure to meet MRI criteria (22.2%). Of the 50 randomized subjects, there were no significant differences in demographics in the active versus control arms. In those participants for whom data was available, 93.8% (45 of 48) of randomized participants received steroids before study entry, whereas 94.0% (47 of 50) had spine surgery before study enrollment. The 'funnel effect' (large numbers of potentially eligible participants with a small number enrolled) impacts all trials, but was particularly challenging in this trial due to eligibility criteria and logistics. Data collected may provide information on current practice patterns and the issues encountered and addressed may facilitate design of future trials.

  17. Human autologous in vitro models of glioma immunogene therapy using B7-2, GM-CSF, and IL12

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    Parney, I.F.; Farr-Jones, M.A. [Univ. of Alberta, Div. of Neurosurgery, Edmonton, Alberta (Canada); Kane, K.; Chang, L.-J. [Univ. of Alberta, Dept. of Surgery and Dept. of Medical Microbiology and Immunology, Edmonton, Alberta (Canada); Petruk, K.C. [Univ. of Alberta, Div. of Neurosurgery, Edmonton, Alberta (Canada)


    Cancer immunogene therapy is based on vaccination with radiated, autologous tumor cells transduced with immunostimulatory genes. To help determine an optimal glioma immunogene therapy strategy, we stimulated lymphocytes with autologous human glioma cells transduced with B7-2 (CD86), granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or interleukin-12 (IL12). A human glioma-derived cell culture (Ed147.BT) was transduced with B7-2, GM-CSF, and/or IL12 using retroviral vectors. Autologous peripheral blood mononuclear cells (PBMC) were co-cultured with irradiated gene-transduced tumor alone or a combination of radiated wild type and gene-transduced cells. Peripheral blood mononuclear cells proliferation was determined by serial cell counts. Peripheral blood mononuclear cells phenotype was assessed by flow cytometry for CD4, CD8, and CD16. Anti-tumor cytotoxicity was determined by chromium-51 ({sup 51}Cr) release assay. Peripheral blood mononuclear cells cell numbers all decreased during primary stimulation but tumor cells expressing B7-2 or GM-CSF consistently caused secondary proliferation. Tumors expressing B7-2 and GM-CSF or B7-2,GM-CSF,and IL12 consistently increased PBMC CD8+ (cytotoxic T) and CD16+ (natural killer) percentages. Interestingly, anti-tumor cytotoxicity only exceeded that of PBMC stimulated with wild type tumor alone when peripheral blood mononuclear cells were stimulated with both wild type tumor and B7-2/GM-CSF- (but not IL12) transduced cells. PBMC proliferation and phenotype is altered as expected by exposure to immunostimulatory gene-transduced tumor. However, transduced tumor cells alone do not stimulate greater anti-tumor cytotoxicity than wild type tumor. Only B7-2/GM-CSF-transduced cells combined with wild type produced increased cytotoxicity. This may reflect selection of turnor subclones with limited antigenic spectra during retrovirus-mediated gene transfer. (author)

  18. Cytolytic T-cell clones against an autologous human melanoma: specificity study and definition of three antigens by immunoselection.


    Knuth, A; Wölfel, T; Klehmann, E; Boon, T.; Meyer zum Büschenfelde, K H


    Cytolytic T-lymphocyte (CTL) clones against an autologous melanoma (SK-MEL-29) were generated by mixed lymphocyte tumor culture and subsequent cloning of responder lymphocytes at limiting dilutions. These CTL clones lysed autologous melanoma but not autologous Epstein-Barr virus-transformed B cells and none of the allogeneic tumor targets included in the specificity analysis. The lysis of autologous melanoma targets could be inhibited by monoclonal antibodies against monomorphic HLA class I d...

  19. Effect of human autologous serum and fetal bovine serum on human corneal epithelial cell viability, migration and proliferation in vitro

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    Ming-Feng Wu


    Full Text Available AIM: To analyze the concentration-dependent effects of autologous serum (AS and fetal bovine serum (FBS on human corneal epithelial cell (HCEC viability, migration and proliferation. METHODS: AS was prepared from 13 patients with non-healing epithelial defects Dulbecco's modified eagle medium/Ham’s F12 (DMEM/F12 with 5% FBS, 0.5% dimethyl sulphoxide (DMSO, 10 ng/mL human epidermal growth factor, 1% insulin-transferrin-selenium, then were incubated in serum media: DMEM/F12 supplemented by 5%, 10%, 15% or 30% AS or FBS. HCEC viability was analyzed using cell proliferation kit XTT, migration using a wound healing assay, proliferation by the cell proliferation enzyme-linked immunosorbent assay (ELISA BrdU kit. Statistical analysis was performed using the generalized linear model, the values at 30% AS or 30% FBS were used as the baselines. RESULTS: HCEC viability was the highest at 30% AS or 15% FBS and the lowest at 10% AS or 30% FBS application. HCEC migration was the quickest through 30% AS or 30% FBS and the slowest through 5% AS or 5% FBS concentrations. Proliferation was the most increased through 15% AS or 5% FBS and the least increased through 30% AS or 30% FBS concentrations. HCEC viability at 10% and 15% AS was significantly worse (P=0.001, P=0.023 compared to baseline and significantly better at 15% FBS (P=0.003 concentrations. HCEC migration was significantly worse (P≤0.007 and HCEC proliferation significantly better (P<0.001 in all concentration groups compared to baseline. CONCLUSION: For the best viability of HCEC 30% AS or 15% FBS, for HCEC migration 30% AS or 30% FBS, for proliferation 15% AS or 5% FBS should be used. Therefore, we suggest the use of 30% AS in clinical practice.

  20. Effect of human autologous serum and fetal bovine serum on human corneal epithelial cell viability, migration and proliferation in vitro. (United States)

    Wu, Ming-Feng; Stachon, Tanja; Seitz, Berthold; Langenbucher, Achim; Szentmáry, Nóra


    To analyze the concentration-dependent effects of autologous serum (AS) and fetal bovine serum (FBS) on human corneal epithelial cell (HCEC) viability, migration and proliferation. AS was prepared from 13 patients with non-healing epithelial defects Dulbecco's modified eagle medium/Ham's F12 (DMEM/F12) with 5% FBS, 0.5% dimethyl sulphoxide (DMSO), 10 ng/mL human epidermal growth factor, 1% insulin-transferrin-selenium, then were incubated in serum media: DMEM/F12 supplemented by 5%, 10%, 15% or 30% AS or FBS. HCEC viability was analyzed using cell proliferation kit XTT, migration using a wound healing assay, proliferation by the cell proliferation enzyme-linked immunosorbent assay (ELISA) BrdU kit. Statistical analysis was performed using the generalized linear model, the values at 30% AS or 30% FBS were used as the baselines. HCEC viability was the highest at 30% AS or 15% FBS and the lowest at 10% AS or 30% FBS application. HCEC migration was the quickest through 30% AS or 30% FBS and the slowest through 5% AS or 5% FBS concentrations. Proliferation was the most increased through 15% AS or 5% FBS and the least increased through 30% AS or 30% FBS concentrations. HCEC viability at 10% and 15% AS was significantly worse (P=0.001, P=0.023) compared to baseline and significantly better at 15% FBS (P=0.003) concentrations. HCEC migration was significantly worse (P≤0.007) and HCEC proliferation significantly better (Pmigration 30% AS or 30% FBS, for proliferation 15% AS or 5% FBS should be used. Therefore, we suggest the use of 30% AS in clinical practice.

  1. Selective purging of human multiple myeloma cells from autologous stem cell transplant grafts using oncolytic myxoma virus (United States)

    Bartee, Eric; Chan, Winnie S.; Moreb, Jan S.; Cogle, Christopher R.; McFadden, Grant


    Autologous stem cell transplantation (ASCT) and novel therapies have improved overall survival of patients with multiple myeloma; however, most patients relapse and eventually succumb to their disease. Evidence indicates that residual cancer cells contaminate autologous grafts and may contribute to early relapses after ASCT. Here, we demonstrate that ex vivo treatment with an oncolytic poxvirus called myxoma virus results in specific elimination of human myeloma cells by inducing rapid cellular apoptosis while fully sparing normal hematopoietic stem and progenitor cells (HSPCs). The specificity of this elimination is based on strong binding of the virus to myeloma cells coupled with an inability of the virus to bind or infect CD34+ HSPCs. These two features allow myxoma to readily identify and distinguish even low levels of myeloma cells in complex mixtures. This ex vivo MYXV treatment also effectively inhibits systemic in vivo engraftment of human myeloma cells into immunodeficient mice and results in efficient elimination of primary CD138+ myeloma cells contaminating patient hematopoietic cell products. We conclude that ex vivo myxoma treatment represents a safe and effective method to selectively eliminate myeloma cells from hematopoietic autografts prior to reinfusion. PMID:22516053

  2. Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model

    DEFF Research Database (Denmark)

    Jespersen, Henrik; Lindberg, Mattias F; Donia, Marco


    Immune checkpoint inhibitors and adoptive cell transfer (ACT) of autologous tumor-infiltrating T cells have shown durable responses in patients with melanoma. To study ACT and immunotherapies in a humanized model, we have developed PDXv2.0 - a melanoma PDX model where tumor cells and tumor......-infiltrating T cells from the same patient are transplanted sequentially in non-obese diabetic/severe combined immune-deficient/common gamma chain (NOG/NSG) knockout mouse. Key to T-cell survival/effect in this model is the continuous presence of interleukin-2 (IL-2). Tumors that grow in PDXv2.0 are eradicated...... if the autologous tumor cells and T cells come from a patient that exhibited an objective response to ACT in the clinic. However, T cells from patients that are non-responders to ACT cannot kill tumor cells in PDXv2.0. Taken together, PDXv2.0 provides the potential framework to further model genetically diverse...

  3. Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson's disease

    DEFF Research Database (Denmark)

    Hallett, Penelope J; Deleidi, Michela; Astradsson, Arnar


    Autologous transplantation of patient-specific induced pluripotent stem cell (iPSC)-derived neurons is a potential clinical approach for treatment of neurological disease. Preclinical demonstration of long-term efficacy, feasibility, and safety of iPSC-derived dopamine neurons in non-human primat...

  4. Autologous neutralizing humoral immunity and evolution of the viral envelope in the course of subtype B human immunodeficiency virus type 1 infection

    NARCIS (Netherlands)

    Bunnik, Evelien M.; Pisas, Linaida; van Nuenen, Ad C.; Schuitemaker, Hanneke


    Most human immunodeficiency virus type 1 (HIV-1)-infected individuals develop an HIV-specific neutralizing antibody (NAb) response that selects for escape variants of the virus. Here, we studied autologous NAb responses in five typical CCR5-using progressors in relation to viral NAb escape and

  5. Tissue engineering human small-caliber autologous vessels using a xenogenous decellularized connective tissue matrix approach: preclinical comparative biomechanical studies. (United States)

    Heine, Jörg; Schmiedl, Andreas; Cebotari, Serghei; Karck, Matthias; Mertsching, Heike; Haverich, Axel; Kallenbach, Klaus


    Suggesting that bioartificial vascular scaffolds cannot but tissue-engineered vessels can withstand biomechanical stress, we developed in vitro methods for preclinical biological material testings. The aim of the study was to evaluate the influence of revitalization of xenogenous scaffolds on biomechanical stability of tissue-engineered vessels. For measurement of radial distensibility, a salt-solution inflation method was used. The longitudinal tensile strength test (DIN 50145) was applied on bone-shaped specimen: tensile/tear strength (SigmaB/R), elongation at maximum yield stress/rupture (DeltaB/R), and modulus of elasticity were determined of native (NAs; n = 6), decellularized (DAs; n = 6), and decellularized carotid arteries reseeded with human vascular smooth muscle cells and human vascular endothelial cells (RAs; n = 7). Radial distensibility of DAs was significantly lower (113%) than for NAs (135%) (P caliber vascular graft testing, this study proved that revitalization of decellularized connective tissue scaffolds led to vascular graft stability able to withstand biomechanical stress mimicking the human circulation. This tissue engineering approach provides a sufficiently stable autologized graft. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  6. V(H)H (nanobody) directed against human glycophorin A: a tool for autologous red cell agglutination assays. (United States)

    Habib, Ibrahim; Smolarek, Dorota; Hattab, Claude; Grodecka, Magdalena; Hassanzadeh-Ghassabeh, Gholamreza; Muyldermans, Serge; Sagan, Sandrine; Gutiérrez, Carlos; Laperche, Syria; Le-Van-Kim, Caroline; Aronovicz, Yves Colin; Wasniowska, Kazimiera; Gangnard, Stephane; Bertrand, Olivier


    The preparation of a V(H)H (nanobody) named IH4 that recognizes human glycophorin A (GPA) is described. IH4 was isolated by screening a library prepared from the lymphocytes of a dromedary immunized by human blood transfusion. Phage display and panning against GPA as the immobilized antigen allowed isolating this V(H)H. IH4, representing 67% of the retrieved V(H)H sequences, was expressed as a soluble correctly folded protein in SHuffle Escherichia coli cells, routinely yielding approximately 100 mg/L fermentation medium. Because IH4 recognizes GPA independently of the blood group antigens, it recognizes red cells of all humans with the possible exception of those with some extremely rare genetic background. The targeted linear epitope comprises the GPA Y52PPE55 sequence. Based on surface plasmon resonance results, the dissociation constant of the IH4-GPA equilibrium is 33 nM. IH4 is a stable protein with a transition melting temperature of 75.8 °C (measured by differential scanning calorimetry). As proof of concept, we fused HIV p24 to IH4 and used the purified construct expressed in E. coli to show that IH4 was amenable to the preparation of autologous erythrocyte agglutination reagents: reconstituted blood prepared with serum from an HIV-positive patient was readily agglutinated by the addition of the bifunctional reagent. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Complete human serum maintains viability and chondrogenic potential of human synovial stem cells: suitable conditions for transplantation. (United States)

    Mizuno, Mitsuru; Katano, Hisako; Otabe, Koji; Komori, Keiichiro; Kohno, Yuji; Fujii, Shizuka; Ozeki, Nobutake; Horie, Masafumi; Tsuji, Kunikazu; Koga, Hideyuki; Muneta, Takeshi; Sekiya, Ichiro


    In our clinical practice, we perform transplantations of autologous synovial mesenchymal stem cells (MSCs) for cartilage and meniscus regenerative medicine. One of the most important issues to ensuring clinical efficacy involves the transport of synovial MSCs from the processing facility to the clinic. Complete human serum (100% human serum) is an attractive candidate material in which to suspend synovial MSCs for their preservation during transport. The purpose of this study was to investigate whether complete human serum maintained MSC viability and chondrogenic potential and to examine the optimal temperature conditions for the preservation of human synovial MSCs. Human synovium was harvested from the knees of 14 donors with osteoarthritis during total knee arthroplasty. Passage 2 synovial MSCs were suspended at 2 million cells/100 μL in Ringer's solution or complete human serum at 4, 13, and 37 °C for 48 h. These cells were analyzed for live cell rates, cell surface marker expression, metabolic activity, proliferation, and adipogenic, calcification, and chondrogenic differentiation potentials before and after preservation. After preservation, synovial MSCs maintained higher live cell rates in human serum than in Ringer's solution at 4 and 13 °C. Synovial MSCs preserved in human serum at 4 and 13 °C also maintained high ratios of propidium iodide(-) and annexin V(-) cells. MSC surface marker expression was not altered in cells preserved at 4 and 13 °C. The metabolic activities of cells preserved in human serum at 4 and 13 °C was maintained, while significantly reduced in other conditions. Replated MSCs retained their proliferation ability when preserved in human serum at 4 and 13 °C. Adipogenesis and calcification potential could be observed in cells preserved in each condition, whereas chondrogenic potential was retained only in cells preserved in human serum at 4 and 13 °C. The viability and chondrogenic potential of synovial MSCs were

  8. Complete Genome Sequence of the Human Gut Symbiont Roseburia hominis

    DEFF Research Database (Denmark)

    Travis, Anthony J.; Kelly, Denise; Flint, Harry J


    We report here the complete genome sequence of the human gut symbiont Roseburia hominis A2-183(T) (= DSM 16839(T) = NCIMB 14029(T)), isolated from human feces. The genome is represented by a 3,592,125-bp chromosome with 3,405 coding sequences. A number of potential functions contributing to host-...

  9. Autologous neutralizing humoral immunity and evolution of the viral envelope in the course of subtype B human immunodeficiency virus type 1 infection. (United States)

    Bunnik, Evelien M; Pisas, Linaida; van Nuenen, Ad C; Schuitemaker, Hanneke


    Most human immunodeficiency virus type 1 (HIV-1)-infected individuals develop an HIV-specific neutralizing antibody (NAb) response that selects for escape variants of the virus. Here, we studied autologous NAb responses in five typical CCR5-using progressors in relation to viral NAb escape and molecular changes in the viral envelope (Env) in the period from seroconversion until after AIDS diagnosis. In sera from three patients, high-titer neutralizing activity was observed against the earliest autologous virus variants, followed by declining humoral immune responses against subsequent viral escape variants. Autologous neutralizing activity was undetectable in sera from two patients. Patients with high-titer neutralizing activity in serum showed the strongest positive selection pressure on Env early in infection. In the initial phase of infection, gp160 length and the number of potential N-linked glycosylation sites (PNGS) increased in viruses from all patients. Over the course of infection, positive selection pressure declined as the NAb response subsided, coinciding with reversions of changes in gp160 length and the number of PNGS. A number of identical amino acid changes were observed over the course of infection in the viral quasispecies of different patients. Our results indicate that although neutralizing autologous humoral immunity may have a limited effect on the disease course, it is an important selection pressure in virus evolution early in infection, while declining HIV-specific humoral immunity in later stages may coincide with reversion of NAb-driven changes in Env.

  10. Immunotherapy for human renal cell carcinoma by adoptive transfer of autologous transforming growth factor beta-insensitive CD8+ T cells. (United States)

    Wang, Longxin; Wen, Weihong; Yuan, Jianlin; Helfand, Brian; Li, Yu; Shi, Changhong; Tian, Feng; Zheng, Jia; Wang, Fuli; Chen, Lin; Liang, Lili; Zhou, Liqun; Lee, Chung; Chen, Zhinan; Guo, Yinglu; Wang, He; Zhang, Qiang; Qin, Weijun


    Transforming growth factor-beta (TGF-beta) is a potent immunosuppressor that has been associated with tumor evasion from the host immune surveillance and, thus, tumor progression. We tested a novel immunotherapy for human renal cell cancer (RCC) using a technique that involves the adoptive transfer of autologous tumor-reactive, TGF-beta-insensitive CD8(+) T cells into human RCC-challenged immunodeficient mice to identify its potent antitumor responses. The present study was conducted using a one-to-one adoptive transfer strategy to treat tumor-bearing severe combined immunodeficient (SCID/beige) mouse. The SCID/beige mice were humanized with peripheral blood mononuclear cells from patients with RCC (Hu-PBMC-SCID) before adoptive transfer. Autologous CD8(+) T cells were expanded ex vivo using autologous patient's dendritic cells pulsed with the tumor lysate and rendered TGF-beta insensitive by dominant-negative TGF-beta type II receptor. In addition, human RCC cell lines were generated using patients' tumor cells injected into SCID/beige mice. Using flow cytometry analysis, we confirmed the expression of the tumor-reactive, TGF-beta-insensitive CD8(+) T cells were the effector CD8(+) cells (CD27(-)CDRA(+)). Adoptive transfer of autologous TGF-beta-insensitive CD8(+) T cells into tumor-bearing Hu-PBMC-SCID mice induced robust tumor-specific CTL responses in vitro, were associated with tumor apoptosis, suppressed lung metastasis, and prolonged survival times in vivo. The one-to-one adoptive transfer strategy is an ideal in vivo murine model for studying the relationship between TGF-beta and immunosurveillance in RCC in vivo. Furthermore, this technique may offer the promise of a novel therapeutic option for the treatment of human patients with RCC.

  11. Cytolytic T-Cell Clones against an Autologous Human Melanoma: Specificity Study and Definition of Three Antigens by Immunoselection

    National Research Council Canada - National Science Library

    Alexander Knuth; Thomas Wolfel; Eva Klehmann; Thierry Boon; Karl-Hermann Meyer Zum Buschenfelde


    Cytolytic T-lymphocyte (CTL) clones against an autologous melanoma (SK-MEL-29) were generated by mixed lymphocyte tumor culture and subsequent cloning of responder lymphocytes at limiting dilutions...

  12. Safety reporting on implantation of autologous adipose tissue-derived stem cells with platelet-rich plasma into human articular joints


    Pak, Jaewoo; Chang, Jae-Jin; Lee, Jung Hun; Lee, Sang Hee


    Background Adipose tissue-derived stem cells (ADSCs), a type of mesenchymal stem cells (MSCs), have great potential as therapeutic agents in regenerative medicine. Numerous animal studies have documented the multipotency of ADSCs, showing their capabilities to differentiate into tissues such as muscle, bone, cartilage, and tendon. However, the safety of autologous ADSC injections into human joints is only beginning to be understood and the data are lacking. Methods Between 2009 and 2010, 91 p...

  13. Restoring the quantity and quality of elderly human mesenchymal stem cells for autologous cell-based therapies. (United States)

    Block, Travis J; Marinkovic, Milos; Tran, Olivia N; Gonzalez, Aaron O; Marshall, Amanda; Dean, David D; Chen, Xiao-Dong


    Degenerative diseases are a major public health concern for the aging population and mesenchymal stem cells (MSCs) have great potential for treating many of these diseases. However, the quantity and quality of MSCs declines with aging, limiting the potential efficacy of autologous MSCs for treating the elderly population. Human bone marrow (BM)-derived MSCs from young and elderly donors were obtained and characterized using standard cell surface marker criteria (CD73, CD90, CD105) as recommended by the International Society for Cellular Therapy (ISCT). The elderly MSC population was isolated into four subpopulations based on size and stage-specific embryonic antigen-4 (SSEA-4) expression using fluorescence-activated cell sorting (FACS), and subpopulations were compared to the unfractionated young and elderly MSCs using assays that evaluate MSC proliferation, quality, morphology, intracellular reactive oxygen species, β-galactosidase expression, and adenosine triphosphate (ATP) content. The ISCT-recommended cell surface markers failed to detect any differences between young and elderly MSCs. Here, we report that elderly MSCs were larger in size and displayed substantially higher concentrations of intracellular reactive oxygen species and β-galactosidase expression and lower amounts of ATP and SSEA-4 expression. Based on these findings, cell size and SSEA-4 expression were used to separate the elderly MSCs into four subpopulations by FACS. The original populations (young and elderly MSCs), as well as the four subpopulations, were then characterized before and after culture on tissue culture plastic and BM-derived extracellular matrix (BM-ECM). The small SSEA-4-positive subpopulation representing ~ 8% of the original elderly MSC population exhibited a "youthful" phenotype that was similar to that of young MSCs. The biological activity of this elderly subpopulation was inhibited by senescence-associated factors produced by the unfractionated parent population

  14. The complete amino acid sequence of human serum transferrin.


    MacGillivray, R. T.; Mendez, E. (Elena); Sinha, S. K.; Sutton, M.R.; Lineback-Zins, J; Brew, K


    The complete amino acid sequence of human serum transferrin has been determined by aligning the structures of the 10 CNBr fragments. The order of these fragments in the polypeptide chain is deduced from the structures of peptides overlapping methionine residues and other evidence. Human transferrin contains 678 amino acid residues and--including the two asparagine-linked glycans--has an overall molecular weight of 79,550. The polypeptide chain contains two homologous domains consisting of res...

  15. Expansion of Human Tregs from Cryopreserved Umbilical Cord Blood for GMP-Compliant Autologous Adoptive Cell Transfer Therapy

    Directory of Open Access Journals (Sweden)

    Howard R. Seay


    Full Text Available Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory T cells (Tregs are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1.26 × 109 Tregs from single-donor cryopreserved units. The resulting Tregs passed prior clinical trial release criteria for Treg purity and sterility, including additional rigorous assessments of FOXP3 and Helios expression and epigenetic analysis of the FOXP3 Treg-specific demethylated region (TSDR. Compared with expanded adult peripheral blood Tregs, expanded cord blood Tregs remained more naive, as assessed by continued expression of CD45RA, produced reduced IFN-γ following activation, and effectively inhibited responder T cell proliferation. Immunosequencing of the T cell receptor revealed a remarkably diverse receptor repertoire within cord blood Tregs that was maintained following in vitro expansion. These data support the feasibility of generating GMP-compliant Tregs from cord blood for adoptive cell transfer therapies and highlight potential advantages in terms of safety, phenotypic stability, autoantigen specificity, and tissue distribution.

  16. Isolation, expansion and neural differentiation of stem cells from human plucked hair: a further step towards autologous nerve recovery. (United States)

    Gho, Coen G; Schomann, Timo; de Groot, Simon C; Frijns, Johan H M; Rivolta, Marcelo N; Neumann, Martino H A; Huisman, Margriet A


    Stem cells from the adult hair follicle bulge can differentiate into neurons and glia, which is advantageous for the development of an autologous cell-based therapy for neurological diseases. Consequently, bulge stem cells from plucked hair may increase opportunities for personalized neuroregenerative therapy. Hairs were plucked from the scalps of healthy donors, and the bulges were cultured without prior tissue treatment. Shortly after outgrowth from the bulge, cellular protein expression was established immunohistochemically. The doubling time was calculated upon expansion, and the viability of expanded, cryopreserved cells was assessed after shear stress. The neuroglial differentiation potential was assessed from cryopreserved cells. Shortly after outgrowth, the cells were immunopositive for nestin, SLUG, AP-2α and SOX9, and negative for SOX10. Each bulge yielded approximately 1 × 10(4) cells after three passages. Doubling time was 3.3 (±1.5) days. Cellular viability did not differ significantly from control cells after shear stress. The cells expressed class III β-tubulin (TUBB3) and synapsin-1 after 3 weeks of neuronal differentiation. Glial differentiation yielded KROX20- and MPZ-immunopositive cells after 2 weeks. We demonstrated that human hair follicle bulge-derived stem cells can be cultivated easily, expanded efficiently and kept frozen until needed. After cryopreservation, the cells were viable and displayed both neuronal and glial differentiation potential.

  17. Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series

    Directory of Open Access Journals (Sweden)

    Pak Jaewoo


    Full Text Available Abstract Introduction This is a series of clinical case reports demonstrating that a combination of percutaneously injected autologous adipose-tissue-derived stem cells, hyaluronic acid, platelet rich plasma and calcium chloride may be able to regenerate bones in human osteonecrosis, and with addition of a very low dose of dexamethasone, cartilage in human knee osteoarthritis. Case reports Stem cells were obtained from adipose tissue of abdominal origin by digesting lipoaspirate tissue with collagenase. These stem cells, along with hyaluronic acid, platelet rich plasma and calcium chloride, were injected into the right hip of a 29-year-old Korean woman and a 47-year-old Korean man. They both had a history of right hip osteonecrosis of the femoral head. For cartilage regeneration, a 70-year-old Korean woman and a 79-year-old Korean woman, both with a long history of knee pain due to osteoarthritis, were injected with stem cells along with hyaluronic acid, platelet rich plasma, calcium chloride and a nanogram dose of dexamethasone. Pre-treatment and post-treatment MRI scans, physical therapy, and pain score data were then analyzed. Conclusions The MRI data for all the patients in this series showed significant positive changes. Probable bone formation was clear in the patients with osteonecrosis, and cartilage regeneration in the patients with osteoarthritis. Along with MRI evidence, the measured physical therapy outcomes, subjective pain, and functional status all improved. Autologous mesenchymal stem cell injection, in conjunction with hyaluronic acid, platelet rich plasma and calcium chloride, is a promising minimally invasive therapy for osteonecrosis of femoral head and, with low-dose dexamethasone, for osteoarthritis of human knees.

  18. A complete human pelvis from the Middle Pleistocene of Spain. (United States)

    Arsuaga, J L; Lorenzo, C; Carretero, J M; Gracia, A; Martínez, I; García, N; Bermúdez de Castro, J M; Carbonell, E


    The Middle Pleistocene site of Sima de los Huesos in Sierra de Atapuerca, Spain, has yielded around 2,500 fossils from at least 33 different hominid individuals. These have been dated at more than 200,000 years ago and have been classified as ancestors of Neanderthals. An almost complete human male pelvis (labelled Pelvis 1) has been found, which we associate with two fragmentary femora. Pelvis 1 is robust and very broad with a very long superior pubic ramus, marked iliac flare, and a long femoral neck. This pattern is probably the primitive condition from which modern humans departed. A modern human newborn would pass through the birth canal of Pelvis 1 and this would be even larger in a female individual. We estimate the body mass of this individual at 95 kg or more. Using the cranial capacities of three specimens from Sima de los Huesos, the encephalization quotients are substantially smaller than in Neanderthals and modern humans.

  19. Sinus grafting using recombinant human tissue factor, platelet-rich plasma gel, autologous bone, and anorganic bovine bone mineral xenograft: histologic analysis and case reports. (United States)

    Philippart, Pierre; Daubie, Valéry; Pochet, Roland


    The purpose of this study was to analyze healthy bone formation by means of histology and immunohistochemistry after grafting with a mixture of autologous ground calvarial bone, inorganic xenograft, platelet-rich plasma (PRP), and recombinant human tissue factor (rhTF). Maxillary sinus floor augmentation was performed on 3 patients by grafting with 5 to 10 mL of a paste consisting of autologous powder from calvarial bone (diameter plasma), and about 1 microg rhTF. Six and 10 months after grafting, bone cores were extracted for implant fixation and analyzed. Histology demonstrated a high degree of inorganic xenograft integration and natural bone regeneration. Both the xenograft and newly synthesized bone were colonized with osteocytes and surrounded by osteoblasts. Six-month-old bone cores demonstrated a ratio of synthesized bone to xenograft particles ratio of 0.5, whereas 10-month-old cores demonstrated a ratio of 2. A low degree of inflammation could also be observed using S100A8 immunohistochemistry. Autologous grafting in edentulous patients is a complex procedure; the successful substitution of synthetic analogs for ground bone is a major challenge. In this investigation, it was shown that inorganic xenograft in the harvested bone paste could be safe for patients and had high bone regeneration capacity over time. The sinus graft showed intense bone formation 6 months after grafting and a further increase in bone growth 10 months after grafting.

  20. Safety and feasibility of cell-based therapy of autologous bone marrow-derived mononuclear cells in plate-stabilized proximal humeral fractures in humans. (United States)

    Seebach, Caroline; Henrich, Dirk; Meier, Simon; Nau, Christoph; Bonig, Halvard; Marzi, Ingo


    Local implantation of ex vivo concentrated, washed and filtrated human bone marrow-derived mononuclear cells (BMC) seeded onto β-tricalciumphosphate (TCP) significantly enhanced bone healing in a preclinical segmental defect model. Based on these results, we evaluated in a first clinical phase-I trial safety and feasibility of augmentation with preoperatively isolated autologous BMC seeded onto β-TCP in combination with angle stable plate fixation for the therapy of proximal humeral fractures as a potential alternative to autologous bone graft from the iliac crest. 10 patients were enrolled to assess whether cell therapy with 1.3 × 106 autologous BMC/ml/ml β-TCP, collected on the day preceding the definitive surgery, is safe and feasible when seeded onto β-TCP in patients with a proximal humeral fracture. 5 follow-up visits for clinical and radiological controls up to 12 weeks were performed. β-tricalciumphosphate fortification with BMC was feasible and safe; specifically, neither morbidity at the harvest site nor at the surgical wound site were observed. Neither local nor systemic inflammation was noted. All fractures healed within the observation time without secondary dislocation. Three adverse events were reported: one case each of abdominal wall shingles, tendon loosening and initial screw perforation, none of which presumed related to the IND. Cell therapy with autologous BMC for bone regeneration appeared to be safe and feasible with no drug-related adverse reactions being described to date. The impression of efficacy was given, although the study was not powered nor controlled to detect such. A clinical trial phase-II will be forthcoming in order to formally test the clinical benefit of BMC-laden β-TCP for PHF patients. Trial registration The study was registered in the European Clinical Trial Register as EudraCT No. 2012-004037-17. Date of registration 30th of August 2012. Informed consent was signed from all patients enrolled.

  1. Reduction in deposition of indium 111-labeled platelets after autologous endothelial cell seeding of Dacron aortic bifurcation grafts in humans: a preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Ortenwall, P.; Wadenvik, H.; Kutti, J.; Risberg, B.


    Autologous endothelial seeding (AES) of vascular prostheses in dogs increases thrombus-free surface and improves prosthetic prostacyclin production, patency, and the ability to withstand hematogenous challenge with bacteria. No such information is available in human subjects. In the present study one limb of an aortic Dacron bifurcation prosthesis was seeded with autologous endothelial cells (ECs) harvested from the distal portion of the saphenous vein by enzymatic treatment. The deposition of indium 111-labeled platelets on the vascular prostheses was studied 1 and 4 months after operation. In seven of nine patients seeding resulted in decreased accumulation of radiolabeled platelets compared with sham-seeded control limbs (p less than 0.04), when studied 1 month after surgery. A decrease in platelet accumulation occurred over the whole prosthesis between 1 and 4 months, and no significant difference was noted at 4 months between seeded and nonseeded graft limbs. Although the seeding density was very low (440 ECs/cm2), the observed difference in platelet accumulation for AES-treated graft limbs in the early postoperative course merits further investigation of this technique in human beings.

  2. Safety and feasibility of cell-based therapy of autologous bone marrow-derived mononuclear cells in plate-stabilized proximal humeral fractures in humans

    Directory of Open Access Journals (Sweden)

    Caroline Seebach


    Full Text Available Abstract Background Local implantation of ex vivo concentrated, washed and filtrated human bone marrow-derived mononuclear cells (BMC seeded onto β-tricalciumphosphate (TCP significantly enhanced bone healing in a preclinical segmental defect model. Based on these results, we evaluated in a first clinical phase-I trial safety and feasibility of augmentation with preoperatively isolated autologous BMC seeded onto β-TCP in combination with angle stable plate fixation for the therapy of proximal humeral fractures as a potential alternative to autologous bone graft from the iliac crest. Methods 10 patients were enrolled to assess whether cell therapy with 1.3 × 106 autologous BMC/ml/ml β-TCP, collected on the day preceding the definitive surgery, is safe and feasible when seeded onto β-TCP in patients with a proximal humeral fracture. 5 follow-up visits for clinical and radiological controls up to 12 weeks were performed. Results β-tricalciumphosphate fortification with BMC was feasible and safe; specifically, neither morbidity at the harvest site nor at the surgical wound site were observed. Neither local nor systemic inflammation was noted. All fractures healed within the observation time without secondary dislocation. Three adverse events were reported: one case each of abdominal wall shingles, tendon loosening and initial screw perforation, none of which presumed related to the IND. Conclusions Cell therapy with autologous BMC for bone regeneration appeared to be safe and feasible with no drug-related adverse reactions being described to date. The impression of efficacy was given, although the study was not powered nor controlled to detect such. A clinical trial phase-II will be forthcoming in order to formally test the clinical benefit of BMC-laden β-TCP for PHF patients. Trial registration The study was registered in the European Clinical Trial Register as EudraCT No. 2012-004037-17. Date of registration 30th of August 2012. Informed

  3. Bio-artificial pleura using an autologous dermal fibroblast sheet (United States)

    Kanzaki, Masato; Takagi, Ryo; Washio, Kaoru; Kokubo, Mami; Yamato, Masayuki


    Air leaks (ALs) are observed after pulmonary resections, and without proper treatment, can produce severe complications. AL prevention is a critical objective for managing patients after pulmonary resection. This study applied autologous dermal fibroblast sheets (DFS) to close ALs. For sealing ALs in a 44-year-old male human patient with multiple bullae, a 5 × 15-mm section of skin was surgically excised. From this skin specimen, primary dermal fibroblasts were isolated and cultured for 4 weeks to produce DFSs that were harvested after a 10-day culture. ALs were completely sealed using surgical placement of these autologous DFSs. DFS were found to be a durable long-term AL sealant, exhibiting requisite flexibility, elasticity, durability, biocompatibility, and usability, resulting reliable AL closure. DFS should prove to be an extremely useful tissue-engineered pleura substitute.

  4. Improvement of the Survival of Human Autologous Fat Transplantation by Adipose-Derived Stem-Cells-Assisted Lipotransfer Combined with bFGF

    Directory of Open Access Journals (Sweden)

    Aimei Jiang


    Full Text Available Adipose-derived stem cells (ASCs transplanted along with autologous adipose tissue may improve fat graft survival; however, the efficacy of ASCs has been diluted by low vascularization. This study was designed to test the hypothesis that basic fibroblast growth factor (bFGF may improve the effects of ASCs because it owns the property to boost angiogenesis. In the present study, human fat tissues were mixed with ASCs, ASCs plus 100 U bFGF, or medium as the control and then injected subcutaneously into immunologically compromised nude mice for 12 weeks. Our findings demonstrated that mixture with the ASCs significantly increased the weight and volume of the fat grafts compared to control grafts, and histological analysis revealed that both ASCs and ASCs plus bFGF grafts consisted predominantly of adipose tissue and had significantly less fibrosis but greater microvascular density compared with control and also grafts mixed with ASCs had a high expression of angiogenic factors. More importantly, the bFGF treated fat grafts shown elevate in survival, vascularization, and angiogenic factors expression when compared with the grafts that received ASCs alone. These results indicated that bFGF together with ASCs can enhance the efficacy of autologous fat transplantation and increase blood vessel generation involved in the benefits from bFGF.

  5. Adoptively transferred human lung tumor specific cytotoxic T cells can control autologous tumor growth and shape tumor phenotype in a SCID mouse xenograft model

    Directory of Open Access Journals (Sweden)

    Ferrone Soldano


    Full Text Available Abstract Background The anti-tumor efficacy of human immune effector cells, such as cytolytic T lymphocytes (CTLs, has been difficult to study in lung cancer patients in the clinical setting. Improved experimental models for the study of lung tumor-immune cell interaction as well as for evaluating the efficacy of adoptive transfer of immune effector cells are needed. Methods To address questions related to the in vivo interaction of human lung tumor cells and immune effector cells, we obtained an HLA class I + lung tumor cell line from a fresh surgical specimen, and using the infiltrating immune cells, isolated and characterized tumor antigen-specific, CD8+ CTLs. We then established a SCID mouse-human tumor xenograft model with the tumor cell line and used it to study the function of the autologous CTLs provided via adoptive transfer. Results The tumor antigen specific CTLs isolated from the tumor were found to have an activated memory phenotype and able to kill tumor cells in an antigen specific manner in vitro. Additionally, the tumor antigen-specific CTLs were fully capable of homing to and killing autologous tumors in vivo, and expressing IFN-γ, each in an antigen-dependent manner. A single injection of these CTLs was able to provide significant but temporary control of the growth of autologous tumors in vivo without the need for IL-2. The timing of injection of CTLs played an essential role in the outcome of tumor growth control. Moreover, immunohistochemical analysis of surviving tumor cells following CTL treatment indicated that the surviving tumor cells expressed reduced MHC class I antigens on their surface. Conclusion These studies confirm and extend previous studies and provide additional information regarding the characteristics of CTLs which can be found within a patient's tumor. Moreover, the in vivo model described here provides a unique window for observing events that may also occur in patients undergoing adoptive cellular

  6. 40 CFR 26.1602 - EPA review of completed human research. (United States)


    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false EPA review of completed human research... OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1602 EPA review of completed... shall submit its review of data from human research covered by subpart Q, together with the available...

  7. 76 FR 14058 - Notice of Inventory Completion: University of Wyoming, Anthropology Department, Human Remains... (United States)


    ... National Park Service Notice of Inventory Completion: University of Wyoming, Anthropology Department, Human... University of Wyoming Anthropology Department, Human Remains Repository, Laramie, WY. The human remains were..., Anthropology Department, Human Remains Repository, professional staff in consultation with representatives of...

  8. Safety reporting on implantation of autologous adipose tissue-derived stem cells with platelet-rich plasma into human articular joints. (United States)

    Pak, Jaewoo; Chang, Jae-Jin; Lee, Jung Hun; Lee, Sang Hee


    Adipose tissue-derived stem cells (ADSCs), a type of mesenchymal stem cells (MSCs), have great potential as therapeutic agents in regenerative medicine. Numerous animal studies have documented the multipotency of ADSCs, showing their capabilities to differentiate into tissues such as muscle, bone, cartilage, and tendon. However, the safety of autologous ADSC injections into human joints is only beginning to be understood and the data are lacking. Between 2009 and 2010, 91 patients were treated with autologous ADSCs with platelet-rich plasma (PRP) for various orthopedic conditions. Stem cells in the form of stromal vascular fraction (SVF) were injected with PRP into various joints (n = 100). All patients were followed for symptom improvement with visual analog score (VAS) at one month and three months. Approximately one third of the patients were followed up with third month magnetic resonance imaging (MRI) of the injected sites. All patients were followed up by telephone questionnaires every six months for up to 30 months. The mean follow-up time for all patients was 26.62 ± 0.32 months. The follow-up time for patients who were treated in 2009 and early 2010 was close to three years. The relative mean VAS of patients at the end of one month follow-up was 6.55 ± 0.32, and at the end of three months follow-up was 4.43 ± 0.41. Post-procedure MRIs performed on one third of the patients at three months failed to demonstrate any tumor formation at the implant sites. Further, no tumor formation was reported in telephone long-term follow-ups. However, swelling of injected joints was common and was thought to be associated with death of stem cells. Also, tenosinovitis and tendonitis in elderly patients, all of which were either self-limited or were remedied with simple therapeutic measures, were common as well. Using both MRI tracking and telephone follow ups in 100 joints in 91 patients treated, no neoplastic complications were detected at any ADSC implantation sites

  9. Comparative anatomical dimensions of the complete human and porcine spine

    NARCIS (Netherlands)

    Busscher, Iris; Ploegmakers, Joris J. W.; Verkerke, Gijsbertus J.; Veldhuizen, Albert G.

    New spinal implants and surgical procedures are often tested pre-clinically on human cadaver spines. However, the availability of fresh frozen human cadaver material is very limited and alternative animal spines are more easily available in all desired age groups, and have more uniform geometrical

  10. The use of gamma-irradiation and ultraviolet-irradiation in the preparation of human melanoma cells for use in autologous whole-cell vaccines

    Directory of Open Access Journals (Sweden)

    Denlinger Chadrick E


    Full Text Available Abstract Background Human cancer vaccines incorporating autologous tumor cells carry a risk of implantation and subsequent metastasis of viable tumor cells into the patient who is being treated. Despite the fact that the melanoma cell preparations used in a recent vaccine trial (Mel37 were gamma-irradiated (200 Gy, approximately 25% of the preparations failed quality control release criteria which required that the irradiated cells incorporate 3H-thymidine at no more than 5% the level seen in the non-irradiated cells. We have, therefore, investigated ultraviolet (UV-irradiation as a possible adjunct to, or replacement for gamma-irradiation. Methods Melanoma cells were gamma- and/or UV-irradiated. 3H-thymidine uptake was used to assess proliferation of the treated and untreated cells. Caspase-3 activity and DNA fragmentation were measured as indicators of apoptosis. Immunohistochemistry and Western blot analysis was used to assess antigen expression. Results UV-irradiation, either alone or in combination with gamma-irradiation, proved to be extremely effective in controlling the proliferation of melanoma cells. In contrast to gamma-irradiation, UV-irradiation was also capable of inducing significant levels of apoptosis. UV-irradiation, but not gamma-irradiation, was associated with the loss of tyrosinase expression. Neither form of radiation affected the expression of gp100, MART-1/MelanA, or S100. Conclusion These results indicate that UV-irradiation may increase the safety of autologous melanoma vaccines, although it may do so at the expense of altering the antigenic profile of the irradiated tumor cells.

  11. 76 FR 14057 - Notice of Inventory Completion: University of Wyoming, Anthropology Department, Human Remains... (United States)


    ... National Park Service Notice of Inventory Completion: University of Wyoming, Anthropology Department, Human... possession and control of the University of Wyoming Anthropology Department, Human Remains Repository... of Wyoming, Anthropology Department, Human Remains Repository, professional staff in consultation...

  12. Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission: a retrospective, propensity score-weighted analysis from the ALWP of the EBMT

    Directory of Open Access Journals (Sweden)

    Francesco Saraceni


    Full Text Available Abstract Background Optimal post-remission strategy for patients with acute myeloid leukemia (AML is matter of intense debate. Recent reports have shown stronger anti-leukemic activity but similar survival for allogeneic stem cell transplantation (allo-HSCT from matched sibling donor compared to autologous transplantation (auto-HSCT; however, there is scarcity of literature confronting auto-HSCT with allo-HSCT from unrelated donor (UD-HSCT, especially mismatched UD-HSCT. Methods We retrospectively compared outcome of allogeneic transplantation from matched (10/10 UD-HSCT or mismatched at a single HLA-locus unrelated donor (9/10 UD-HSCT to autologous transplantation in patients with AML in first complete remission (CR1. A total of 2879 patients were included; 1202 patients received auto-HSCT, 1302 10/10 UD-HSCT, and 375 9/10 UD-HSCT. A propensity score-weighted analysis was conducted to control for disease risk imbalances between the groups. Results Matched 10/10 UD-HSCT was associated with the best leukemia-free survival (10/10 UD-HSCT vs auto-HSCT: HR 0.7, p = 0.0016. Leukemia-free survival was not statistically different between auto-HSCT and 9/10 UD-HSCT (9/10 UD-HSCT vs auto-HSCT: HR 0.8, p = 0.2. Overall survival was similar across the groups (10/10 UD-HSCT vs auto-HSCT: HR 0.98, p = 0.84; 9/10 UD-HSCT vs auto-HSCT: HR 1.1, p = 0.49. Notably, in intermediate-risk patients, OS was significantly worse for 9/10 UD-HSCT (9/10 UD-HSCT vs auto-HSCT: HR 1.6, p = 0.049, while it did not differ between auto-HSCT and 10/10 UD-HSCT (HR 0.95, p = 0.88. In favorable risk patients, auto-HSCT resulted in 3-year LFS and OS rates of 59 and 78 %, respectively. Conclusions Our findings suggest that in AML patients in CR1 lacking an HLA-matched sibling donor, 10/10 UD-HSCT significantly improves LFS, but this advantage does not translate in better OS compared to auto-HSCT. In intermediate-risk patients lacking a fully HLA-matched donor

  13. Can Technology Completely Replace Human Interaction in Class?

    Directory of Open Access Journals (Sweden)

    Fernando Alonso Gómez Carrillo


    Full Text Available Nowadays there are so many different and surprising possibilities of applications for ICT ́s in the educational field, that there is a belief that one day ICT will be able to replace the teacher, and in general terms, the man, in any field or human activity. Is it possible that technology will replace the teacher in the pedagogical work? Can technology replace the man himself?

  14. Correlation of synovial cytokine expression with quality of cells used for autologous chondrocyte implantation in human knees. (United States)

    Schmal, Hagen; Mehlhorn, Alexander T; Dovi-Akue, David; Pestka, Jan M; Südkamp, Norbert P; Niemeyer, Philipp


    The cell quality plays a decisive role in autologous chondrocyte implantation (ACI). Aim of the study was the analysis of in vivo interactions between synovial concentrations of cytokines and cell quality used for ACI. Knee lavage fluids of patients undergoing an ACI were examined for total protein content (TPC) and by ELISA for levels of basic fibroblast growth factor (bFGF), insulin-like growth factor 1, bone morphogenetic proteins 2 and 7 (BMP-2 and BMP-7). Cell quality following amplification for ACI was determined by surface expression of CD44, aggrecan, collagen type II and evaluation of cell characteristics. Data of 17 patients were supplemented by epidemiological parameters and clinical scores (IKDC, Lysholm, pain strength, subjective knee function). CD44 expression was positively associated with TPC and bFGF, and negatively linked to BMP-2 levels (p < 0.01). In contrast, expression of collagen type II did not show any statistically significant correlations with synovial protein concentrations. TPC was positively associated with intraarticular bFGF levels and pain strength (p < 0.01), both indicators for osteoarthritis (OA). Correlating with the negative relation of TPC and BMP-2, subjective knee function after 1 year was positively linked to intraarticular BMP-2 concentrations (p < 0.001). Similarly, expression of collagen type II indicated a favorable clinical result reaching statistical significance in case of pain strength (p < 0.01). Initially increased bFGF levels and CD44 expression indicated a worse clinical outcome after 1 year (IKDC, Lysholm Scores, pain strength). Surface expression of CD44 on chondrocytes used for ACI was negatively associated with synovial BMP-2 and positively to TPC and bFGF indicating catabolic synovial conditions. These correlations were also reflected by clinical outcome parameters.

  15. Transplantation of autologous ex vivo expanded human conjunctival epithelial cells for treatment of pterygia: A prospective open-label single arm multicentric clinical trial

    Directory of Open Access Journals (Sweden)

    Viraf Sam Vasania


    Conclusion: We have, for the 1 st time, standardized a protocol for preparing autologous hCjEC grafts that can be safely transported to multiple centers across the country for transplantation. The clinical outcome was satisfactory for treating pterygia.

  16. Human treated dentin matrix as a natural scaffold for complete human dentin tissue regeneration. (United States)

    Li, Rui; Guo, Weihua; Yang, Bo; Guo, Lijuan; Sheng, Lei; Chen, Gang; Li, Ye; Zou, Qing; Xie, Dan; An, Xiaoxue; Chen, Yali; Tian, Weidong


    An essential aspect of tooth tissue engineering is the identification of suitable scaffolding materials to support cell growth and tissue regeneration. Treated dentin matrix (TDM) from a rat has recently been shown to be a suitable scaffold for rat dentin regeneration. However, due to species-specific differences, it remains unclear whether a similar fabrication method can be extended to human TDM and human dentin regeneration. Therefore, this present study explored the biological response to a human TDM (hTDM) created using a modified dentin treatment method. Various biological characteristics, including cell proliferation, cell migration, cell viability, and cytotoxity were investigated. To assess the inductive capacity of hTDM, dental follicle cells (DFCs) were combined with hTDM and were implanted in vivo for 8 weeks in a mouse model. The resulting grafts were studied histologically. The results showed hTDM released dentinogenic factors, indicating that hTDM could play a sustained role in odontogenesis. DFC attachment, growth, viability, and cytotoxicity on the surface of hTDM showed a notable improvement over those on calcium phosphate controls. Most importantly, in vivo hTDM induced and supported regeneration of complete dentin tissues, which expressed dentin markers DSP and DMP-1. As cells in and around the regenerated dentin were positive for human mitochondria, implanted DFCs and hTDM were responsible for the regenerated dentin tissues. In conclusion, hTDM is indicated as an ideal biomaterial for human dentin regeneration. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. TOOTH (The Open study Of dental pulp stem cell Therapy in Humans): Study protocol for evaluating safety and feasibility of autologous human adult dental pulp stem cell therapy in patients with chronic disability after stroke. (United States)

    Nagpal, Anjali; Kremer, Karlea L; Hamilton-Bruce, Monica A; Kaidonis, Xenia; Milton, Austin G; Levi, Christopher; Shi, Songtao; Carey, Leeanne; Hillier, Susan; Rose, Miranda; Zacest, Andrew; Takhar, Parabjit; Koblar, Simon A


    Stroke represents a significant global disease burden. As of 2015, there is no chemical or biological therapy proven to actively enhance neurological recovery during the chronic phase post-stroke. Globally, cell-based therapy in stroke is at the stage of clinical translation and may improve neurological function through various mechanisms such as neural replacement, neuroprotection, angiogenesis, immuno-modulation, and neuroplasticity. Preclinical evidence in a rodent model of middle cerebral artery ischemic stroke as reported in four independent studies indicates improvement in neurobehavioral function with adult human dental pulp stem cell therapy. Human adult dental pulp stem cells present an exciting potential therapeutic option for improving post-stroke disability. TOOTH (The Open study Of dental pulp stem cell Therapy in Humans) will investigate the use of autologous stem cell therapy for stroke survivors with chronic disability, with the following objectives: (a) determine the maximum tolerable dose of autologous dental pulp stem cell therapy; (b) define that dental pulp stem cell therapy at the maximum tolerable dose is safe and feasible in chronic stroke; and (c) estimate the parameters of efficacy required to design a future Phase 2/3 clinical trial. TOOTH is a Phase 1, open-label, single-blinded clinical trial with a pragmatic design that comprises three stages: Stage 1 will involve the selection of 27 participants with middle cerebral artery ischemic stroke and the commencement of autologous dental pulp stem cell isolation, growth, and testing in sequential cohorts (n = 3). Stage 2 will involve the transplantation of dental pulp stem cell in each cohort of participants with an ascending dose and subsequent observation for a 6-month period for any dental pulp stem cell-related adverse events. Stage 3 will investigate the neurosurgical intervention of the maximum tolerable dose of autologous dental pulp stem cell followed by 9 weeks of intensive task

  18. Human Amygdala Represents the Complete Spectrum of Subjective Valence (United States)

    Jin, Jingwen; Zelano, Christina; Gottfried, Jay A.


    Although the amygdala is a major locus for hedonic processing, how it encodes valence information is poorly understood. Given the hedonic potency of odor stimuli and the amygdala's anatomical proximity to the peripheral olfactory system, we combined high-resolution fMRI with pattern-based multivariate techniques to examine how valence information is encoded in the amygdala. Ten human subjects underwent fMRI scanning while smelling 9 odorants that systematically varied in perceived valence. Representational similarity analyses showed that amygdala codes the entire dimension of valence, ranging from pleasantness to unpleasantness. This unidimensional representation significantly correlated with self-reported valence ratings but not with intensity ratings. Furthermore, within-trial valence representations evolved over time, prioritizing earlier differentiation of unpleasant stimuli. Together, these findings underscore the idea that both spatial and temporal features uniquely encode pleasant and unpleasant odor valence in the amygdala. The availability of a unidimensional valence code in the amygdala, distributed in both space and time, would create greater flexibility in determining the pleasantness or unpleasantness of stimuli, providing a mechanism by which expectation, context, attention, and learning could influence affective boundaries for guiding behavior. SIGNIFICANCE STATEMENT Our findings elucidate the mechanisms of affective processing in the amygdala by demonstrating that this brain region represents the entire valence dimension from pleasant to unpleasant. An important implication of this unidimensional valence code is that pleasant and unpleasant valence cannot coexist in the amygdale because overlap of fMRI ensemble patterns for these two valence extremes obscures their unique content. This functional architecture, whereby subjective valence maps onto a pattern continuum between pleasant and unpleasant poles, offers a robust mechanism by which context

  19. Detection of Antibody-Dependent Complement-Mediated Inactivation of both Autologous and Heterologous Virus in Primary Human Immunodeficiency Virus Type 1 Infection† (United States)

    Aasa-Chapman, Marlén M. I.; Holuigue, Sophie; Aubin, Keith; Wong, MaiLee; Jones, Nicola A.; Cornforth, David; Pellegrino, Pierre; Newton, Philippa; Williams, Ian; Borrow, Persephone; McKnight, Áine


    Specific CD8 T-cell responses to human immunodeficiency virus type 1 (HIV-1) are induced in primary infection and make an important contribution to the control of early viral replication. The importance of neutralizing antibodies in containing primary viremia is questioned because they usually arise much later. Nevertheless antienvelope antibodies develop simultaneously with, or even before, peak viremia. We determined whether such antibodies might control viremia by complement-mediated inactivation (CMI). In each of seven patients studied, antibodies capable of CMI appeared at or shortly after the peak in viremia, concomitantly with detection of virus-specific T-cell responses. The CMI was effective on both autologous and heterologous HIV-1 isolates. Activation of the classical pathway and direct viral lysis were at least partly responsible. Since immunoglobulin G (IgG)-antibodies triggered the CMI, specific memory B cells could also be induced by vaccination. Thus, consideration should be given to vaccination strategies that induce IgG antibodies capable of CMI. PMID:15709001

  20. Technological progress and challenges towards cGMP manufacturing of human pluripotent stem cells based therapeutic products for allogeneic and autologous cell therapies. (United States)

    Abbasalizadeh, Saeed; Baharvand, Hossein


    Recent technological advances in the generation, characterization, and bioprocessing of human pluripotent stem cells (hPSCs) have created new hope for their use as a source for production of cell-based therapeutic products. To date, a few clinical trials that have used therapeutic cells derived from hESCs have been approved by the Food and Drug Administration (FDA), but numerous new hPSC-based cell therapy products are under various stages of development in cell therapy-specialized companies and their future market is estimated to be very promising. However, the multitude of critical challenges regarding different aspects of hPSC-based therapeutic product manufacturing and their therapies have made progress for the introduction of new products and clinical applications very slow. These challenges include scientific, technological, clinical, policy, and financial aspects. The technological aspects of manufacturing hPSC-based therapeutic products for allogeneic and autologous cell therapies according to good manufacturing practice (cGMP) quality requirements is one of the most important challenging and emerging topics in the development of new hPSCs for clinical use. In this review, we describe main critical challenges and highlight a series of technological advances in all aspects of hPSC-based therapeutic product manufacturing including clinical grade cell line development, large-scale banking, upstream processing, downstream processing, and quality assessment of final cell therapeutic products that have brought hPSCs closer to clinical application and commercial cGMP manufacturing. © 2013.

  1. Unchanging attitudes to autologous transfusion in the UK. (United States)

    Torella, F; Haynes, S L; Lardi, A; O'Dwyer, S T; McCollum, C N


    Our aim was to assess changes in attitudes to autologous transfusion amongst surgeons over a 10-year period in response to scientific evidence, public awareness, published guidelines, management and the increasing cost of blood products. Surgeons across the north-west of England completed questionnaires on knowledge, experience and attitude towards autologous transfusion in 1990, 1994 and 1999. Main outcome measures were changes in knowledge, experience and utilization of autologous transfusion; perceived advantages of autologous transfusion, obstacles to its implementation in surgical practice and preferences for specific techniques (preoperative autologous donation, acute normovolaemic haemodilution, intraoperative and postoperative cell salvage). There has been little change in practice over 10 years. Many more surgeons were keen to employ autologous transfusion than were using it. Autologous transfusion was only used in general, orthopaedic and cardiothoracic surgery. Safety and patient preference were the main arguments for implementation and logistics the main obstacles. Autologous transfusion was used sporadically in surgical practice. Clinical trials are needed to guide clinicians in the choice of transfusion techniques.

  2. Complete genome sequence of Bifidobacterium catenulatum JCM 1194(T) isolated from human feces. (United States)

    Morita, Hidetoshi; Toh, Hidehiro; Oshima, Kenshiro; Nakano, Akiyo; Yamashita, Naoko; Iioka, Erica; Arakawa, Kensuke; Suda, Wataru; Honda, Kenya; Hattori, Masahira


    Bifidobacterium catenulatum JCM 1194(T) was isolated from human feces. This paper is the first report demonstrating the fully sequenced and completely annotated genome of a B. catenulatum strain. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Specificity of the autologous neutralizing antibody response. (United States)

    Moore, Penny L; Gray, Elin S; Morris, Lynn


    It has long been known that autologous neutralizing antibodies (AnAbs) exert pressure on the envelope of HIV, resulting in neutralization escape. However, recently, progress has been made in uncovering the precise targets of these potent early antibodies. AnAbs primarily target variable regions of the HIV-1 envelope, explaining the strain-specificity of these antibodies. Despite high neutralizing potential and cross-reactivity, anti-V3 antibodies do not contribute to autologous neutralization. The V1V2 is commonly immunogenic in early HIV-1 and simian human immunodeficiency virus infections, though the nature of these epitopes remains to be determined. In subtype C viruses, the C3 region is a neutralization target, possibly as a result of its more exposed and amphipathic structure. Autologous neutralization appears to be mediated by very few AnAb specificities that develop sequentially suggesting the possibility of immunological hierarchies for both binding and neutralizing antibodies. The role of AnAbs in preventing superinfection and in restricting virus replication is reexamined in the context of recent data. New studies have greatly contributed toward our understanding of the specificities mediating autologous neutralization and highlighted potential vulnerabilities on transmitted viruses. However, the contribution of AnAbs to the development of neutralization breadth remains to be characterized.

  4. Complete genome sequence of Bifidobacterium angulatum JCM 7096(T) isolated from human feces. (United States)

    Morita, Hidetoshi; Toh, Hidehiro; Oshima, Kenshiro; Nakano, Akiyo; Kiuchi, Misa; Kuroyanagi, Hiromi; Arakawa, Kensuke; Suda, Wataru; Honda, Kenya; Hattori, Masahira


    Bifidobacterium angulatum JCM 7096(T) was isolated from human feces. Here we report the complete genome sequence of this organism. This paper is the first report demonstrating the fully sequenced and completely annotated genome of a B. angulatum strain. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Use of autologous human mesenchymal stromal cell/fibrin clot constructs in upper limb non-unions: long-term assessment.

    Directory of Open Access Journals (Sweden)

    Stefano Giannotti

    Full Text Available BACKGROUND: Tissue engineering appears to be an attractive alternative to the traditional approach in the treatment of fracture non-unions. Mesenchymal stromal cells (MSCs are considered an appealing cell source for clinical intervention. However, ex vivo cell expansion and differentiation towards the osteogenic lineage, together with the design of a suitable scaffold have yet to be optimized. Major concerns exist about the safety of MSC-based therapies, including possible abnormal overgrowth and potential cancer evolution. AIMS: We examined the long-term efficacy and safety of ex vivo expanded bone marrow MSCs, embedded in autologous fibrin clots, for the healing of atrophic pseudarthrosis of the upper limb. Our research work relied on three main issues: use of an entirely autologous context (cells, serum for ex vivo cell culture, scaffold components, reduced ex vivo cell expansion, and short-term MSC osteoinduction before implantation. METHODS AND FINDINGS: Bone marrow MSCs isolated from 8 patients were expanded ex vivo until passage 1 and short-term osteo-differentiated in autologous-based culture conditions. Tissue-engineered constructs designed to embed MSCs in autologous fibrin clots were locally implanted with bone grafts, calibrating their number on the extension of bone damage. Radiographic healing was evaluated with short- and long-term follow-ups (range averages: 6.7 and 76.0 months, respectively. All patients recovered limb function, with no evidence of tissue overgrowth or tumor formation. CONCLUSIONS: Our study indicates that highly autologous treatment can be effective and safe in the long-term healing of bone non-unions. This tissue engineering approach resulted in successful clinical and functional outcomes for all patients.

  6. The Complete Correctional Officer: Human Service and the Human Environment of Prison. (United States)

    Johnson, Robert; Price, Shelley


    Examines the correctional officer role in relation to possibilities for the delivery of human services to inmates with problems and adjustment crises. Describes aspects of this approach to the correctional officer's role including building resilient prison environments, and a more human community. Discusses implications for officer support and…

  7. Complete Genome Sequence of a Human Cytomegalovirus Strain AD169 Bacterial Artificial Chromosome Clone


    Ostermann, Eleonore; Spohn, Michael; Indenbirken, Daniela; Brune, Wolfram


    The complete sequence of the human cytomegalovirus strain AD169 (variant ATCC) cloned as a bacterial artificial chromosome (AD169-BAC, also known as HB15 or pHB15) was determined. The viral genome has a length of 230,290?bp and shows 52 nucleotide differences compared to a previously sequenced AD169varATCC clone.

  8. Complete genome sequence of Bifidobacterium breve CECT 7263, a strain isolated from human milk. (United States)

    Jiménez, Esther; Villar-Tajadura, M Antonia; Marín, María; Fontecha, Javier; Requena, Teresa; Arroyo, Rebeca; Fernández, Leónides; Rodríguez, Juan M


    Bifidobacterium breve is an actinobacterium frequently isolated from colonic microbiota of breastfeeding babies. Here, we report the complete and annotated genome sequence of a B. breve strain isolated from human milk, B. breve CECT 7263. The genome sequence will provide new insights into the biology of this potential probiotic organism and will allow the characterization of genes related to beneficial properties.

  9. Earlier diagnosis and serum human chorionic gonadotropin regression in complete hydatidiform moles.

    NARCIS (Netherlands)

    Kerkmeijer, L.G.W.; Massuger, L.F.A.G.; Kate-Booij, M.J. ten; Sweep, F.C.; Thomas, C.M.G.


    OBJECTIVE: To estimate serum human chorionic gonadotropin (hCG) regression in uneventful complete hydatidiform moles before and after the introduction of routine first-trimester ultrasonography. METHODS: Gestational age, maternal age, preevacuation hCG concentrations, serum hCG regression, and hCG

  10. Complete amino acid sequence of human intestinal aminopeptidase N as deduced from cloned cDNA

    DEFF Research Database (Denmark)

    Cowell, G M; Kønigshøfer, E; Danielsen, E M


    The complete primary structure (967 amino acids) of an intestinal human aminopeptidase N (EC was deduced from the sequence of a cDNA clone. Aminopeptidase N is anchored to the microvillar membrane via an uncleaved signal for membrane insertion. A domain constituting amino acid 250...

  11. The complete genome sequence and analysis of the human pathogen Campylobacter lari

    DEFF Research Database (Denmark)

    Miller, WG; Wang, G; Binnewies, Tim Terence


    Campylobacter lari is a member of the epsilon subdivision of the Proteobacteria and is part of the thermotolerant Campylobacter group, a clade that includes the human pathogen C. jejuni. Here we present the complete genome sequence of the human clinical isolate, C. lari RM2100. The genome of strain...... biosynthetic pathways in this organism could be potentially compensated by the large number of encoded peptidases. Nevertheless, the apparent absence of certain key enzymatic functions in strain RM2100 would be expected to have an impact on C. lari biology. It is also possible that the reduction in the C. lari...

  12. Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders (United States)

    Lim, Elaine T.; Raychaudhuri, Soumya; Sanders, Stephan J.; Stevens, Christine; Sabo, Aniko; MacArthur, Daniel G.; Neale, Benjamin M.; Kirby, Andrew; Ruderfer, Douglas M.; Fromer, Menachem; Lek, Monkol; Liu, Li; Flannick, Jason; Ripke, Stephan; Nagaswamy, Uma; Muzny, Donna; Reid, Jeffrey G.; Hawes, Alicia; Newsham, Irene; Wu, Yuanqing; Lewis, Lora; Dinh, Huyen; Gross, Shannon; Wang, Li-San; Lin, Chiao-Feng; Valladares, Otto; Gabriel, Stacey B.; dePristo, Mark; Altshuler, David M.; Purcell, Shaun M.; State, Matthew W.; Boerwinkle, Eric; Buxbaum, Joseph D.; Cook, Edwin H.; Gibbs, Richard A.; Schellenberg, Gerard D.; Sutcliffe, James S.; Devlin, Bernie; Roeder, Kathryn; Daly, Mark J.


    SUMMARY To characterize the role of rare complete human knockouts in autism spectrum disorders (ASD), we identify genes with homozygous or compound heterozygous loss-of-function (LoF) variants (defined as nonsense and essential splice sites) from exome sequencing of 933 cases and 869 controls. We identify a two-fold increase in complete knockouts of autosomal genes with low rates of LoF variation (≤5% frequency) in cases and estimate a 3% contribution to ASD risk by these events, confirming this observation in an independent set of 563 probands and 4,605 controls. Outside the pseudo-autosomal regions on the X-chromosome, we similarly observe a significant 1.5-fold increase in rare hemizygous knockouts in males, contributing to another 2% of ASDs in males. Taken together these results provide compelling evidence that rare autosomal and X-chromosome complete gene knockouts are important inherited risk factors for ASD. PMID:23352160

  13. Complete Genome Sequence of a Human Cytomegalovirus Strain AD169 Bacterial Artificial Chromosome Clone. (United States)

    Ostermann, Eleonore; Spohn, Michael; Indenbirken, Daniela; Brune, Wolfram


    The complete sequence of the human cytomegalovirus strain AD169 (variant ATCC) cloned as a bacterial artificial chromosome (AD169-BAC, also known as HB15 or pHB15) was determined. The viral genome has a length of 230,290 bp and shows 52 nucleotide differences compared to a previously sequenced AD169varATCC clone. Copyright © 2016 Ostermann et al.

  14. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia

    NARCIS (Netherlands)

    Vellenga, Edo; van Putten, Wim; Ossenkoppele, Gert J.; Verdonck, Leo F.; Theobald, Matthias; Cornelissen, Jan J.; Huijgens, Peter C.; Maertens, Johan; Gratwohl, Alois; Schaafsma, Ron; Schanz, Urs; Graux, Carlos; Schouten, Harry C.; Ferrant, Augustin; Bargetzi, Mario; Fey, Martin F.; Löwenberg, Bob; Ferrant, A.; Delannoy, A.; Maertens, J.; Verhoef, G.; Bosly, A.; Graux, C.; Breems, D. A.; Zachee, P.; Mineur, P.; Jaeger, E.; Theobald, M.; Beck, J.; Fischer, Th; Bargetzi, M.; Wernli, M.; Gratwohl, A.; Fey, M. F.; Pabst, T.; Chapuis, B.; Chalandon, Y.; Herr, A.; Wuillemin, W. A.; Gregor, M.; Jacky, E.; Schanz, U.; Leoncini-Francini, L.; Marini, G.; Piquet, D.; Zimmerli-Schwab, B.; Hess, U.; Binder, D.; Kroner, Th; Wittebol, S.; van der Lelie, J.; Biemond, B. J.; Leeksma, O. C.; Ossenkoppele, G. J.; Huijgens, P. C.; Soesan, M.; Wijermans, P. W.; Schaafsma, M. R.; Legdeur, M.; Vellenga, E.; Daenen, S. M. G. J.; Voogt, P. J.; Schouten, H. C.; Biesma, D. H.; de Weerdt, O.; Löwenberg, B.; Cornelissen, J. J.; Sonneveld, P.; Zijlmans, J.; Jongen-Lavrencic, M.; de Greef, G. E.; Verdonck, L. F.; Kuball, J.; van Marwijk Kooy, M.


    We report the results of a prospective, randomized phase 3 trial evaluating autologous peripheral blood stem cell transplantation (ASCT) versus intensive consolidation chemotherapy in newly diagnosed AML patients in complete remission (CR1). Patients with AML (16-60 years) in CR1 after 2 cycles of

  15. Breast Imaging after Breast Augmentation with Autologous Tissues

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Kyu Won; Seo, Bo Kyung; Shim, Eddeum; Song, Sung Eun; Cho, Kyu Ran [Dept. of Radiology, Korea University Anam Hospital, Seoul (Korea, Republic of); Yoon, Eul Sik [Korea University Ansan Hospital, Ansan (Korea, Republic of); Woo, Ok Hee [Dept. of Radiology, Korea University Guro Hospital, Seoul (Korea, Republic of)


    The use of autologous tissue transfer for breast augmentation is an alternative to using foreign implant materials. The benefits of this method are the removal of unwanted fat from other body parts, no risk of implant rupture, and the same feel as real breast tissue. However, sometimes there is a dilemma about whether or not to biopsy for calcifications or masses detected after the procedure is completed. The purpose of this study is to illustrate the procedures of breast augmentation with autologous tissues, the imaging features of various complications, and the role of imaging in the diagnosis and management of complications and hidden breast diseases.

  16. Complement activated granulocytes can cause autologous tissue destruction in man

    Directory of Open Access Journals (Sweden)

    E. Löhde


    Full Text Available Activation of polymorphonuclear granulocytes (PMNs by C5a is thought to be important in the pathogenesis of multiple organ failure during sepsis and after trauma. In our experiment exposure of human PMNs to autologous zymosan activated plasma (ZAP leads to a rapid increase in chemiluminescence. Heating the ZAP at 56°C for 30 min did not alter the changes, while untreated plasma induced only baseline activity. The respiratory burst could be completely abolished by decomplementation and preincubation with rabbit antihuman C5a antibodies. Observation of human omentum using electron microscopy showed intravascular aggregation of PMNs, with capillary thrombosis and diapedesis of the cells through endothelial junctions 90 s after exposure to ZAP. PMNs caused disruption of connections between the mesothelial cells. After 4 min the mesothelium was completely destroyed, and connective tissue and fat cells exposed. Native plasma and minimum essential medium did not induce any morphological changes. These data support the concept that C5a activated PMNs can cause endothelial and mesothelial damage in man. Even though a causal relationship between anaphylatoxins and organ failure cannot be proved by these experiments C5a seems to be an important mediator in the pathogenesis of changes induced by severe sepsis and trauma in man.

  17. [Complete human Klüver-Bucy syndrome after encephalitis caused by herpes simplex type 2]. (United States)

    Bakchine, S; Chain, F; Lhermitte, F


    A case of complete Klüver-Bucy syndrome is reported. A 42 year-old man developed Herpes Simplex type II (H.S.V.II) encephalitis. Good sparing of language functions allowed thorough neuropsychological testing. The troubles usually described in Klüver-Bucy syndrome as psychic blindness, colour agnosia, prosopagnosia, auditive and tactile agnosia were present. The authors theorize that these symptoms are mainly correlated with the amnestic syndrome, which is constantly reported in human Klüver-Bucy syndrome. Unfortunately, after 8 weeks, the encephalitis recurred and the patient was left demented and untestable.

  18. Large-scale population study of human cell lines indicates that dosage compensation is virtually complete.

    Directory of Open Access Journals (Sweden)

    Colette M Johnston


    Full Text Available X chromosome inactivation in female mammals results in dosage compensation of X-linked gene products between the sexes. In humans there is evidence that a substantial proportion of genes escape from silencing. We have carried out a large-scale analysis of gene expression in lymphoblastoid cell lines from four human populations to determine the extent to which escape from X chromosome inactivation disrupts dosage compensation. We conclude that dosage compensation is virtually complete. Overall expression from the X chromosome is only slightly higher in females and can largely be accounted for by elevated female expression of approximately 5% of X-linked genes. We suggest that the potential contribution of escape from X chromosome inactivation to phenotypic differences between the sexes is more limited than previously believed.

  19. The human fungal pathogen Cryptococcus can complete its sexual cycle during a pathogenic association with plants. (United States)

    Xue, Chaoyang; Tada, Yasuomi; Dong, Xinnian; Heitman, Joseph


    Cryptococcus is a globally distributed human fungal pathogen that primarily afflicts immunocompromised individuals. How and why this human fungal pathogen associates with plants and how this environmental niche influences its life cycle remains a mystery. We established Cryptococcus-Arabidopsis and Cryptococcus-Eucalyptus systems and discovered that Cryptococcus proliferates and mates on plant surfaces. Mating efficiency of C. gattii was markedly enhanced on plants and myo-inositol and indole acetic acid were specific plant products that stimulated mating. On Arabidopsis, dwarfing and chlorosis were observed following infection with a fungal mixture of two opposite mating-type strains, but not with either mating-type alone. This infection process is countered by the plant jasmonate-mediated defense mechanism. These findings reveal that Cryptococcus can parasitically interact with plants to complete its sexual cycle, which may impact an understanding of the origin and evolution of both plant and animal fungal pathogens in nature.

  20. Effects of Lumbosacral Spinal Cord Epidural Stimulation for Standing after Chronic Complete Paralysis in Humans (United States)

    Rejc, Enrico; Angeli, Claudia; Harkema, Susan


    Sensory and motor complete spinal cord injury (SCI) has been considered functionally complete resulting in permanent paralysis with no recovery of voluntary movement, standing or walking. Previous findings demonstrated that lumbosacral spinal cord epidural stimulation can activate the spinal neural networks in one individual with motor complete, but sensory incomplete SCI, who achieved full body weight-bearing standing with independent knee extension, minimal self-assistance for balance and minimal external assistance for facilitating hip extension. In this study, we showed that two clinically sensory and motor complete participants were able to stand over-ground bearing full body-weight without any external assistance, using their hands to assist balance. The two clinically motor complete, but sensory incomplete participants also used minimal external assistance for hip extension. Standing with the least amount of assistance was achieved with individual-specific stimulation parameters, which promoted overall continuous EMG patterns in the lower limbs’ muscles. Stimulation parameters optimized for one individual resulted in poor standing and additional need of external assistance for hip and knee extension in the other participants. During sitting, little or negligible EMG activity of lower limb muscles was induced by epidural stimulation, showing that the weight-bearing related sensory information was needed to generate sufficient EMG patterns to effectively support full weight-bearing standing. In general, electrode configurations with cathodes selected in the caudal region of the array at relatively higher frequencies (25–60 Hz) resulted in the more effective EMG patterns for standing. These results show that human spinal circuitry can generate motor patterns effective for standing in the absence of functional supraspinal connections; however the appropriate selection of stimulation parameters is critical. PMID:26207623

  1. Computational study of depth completion consistent with human bi-stable perception for ambiguous figures. (United States)

    Mitsukura, Eiichi; Satoh, Shunji


    We propose a computational model that is consistent with human perception of depth in "ambiguous regions," in which no binocular disparity exists. Results obtained from our model reveal a new characteristic of depth perception. Random dot stereograms (RDS) are often used as examples because RDS provides sufficient disparity for depth calculation. A simple question confronts us: "How can we estimate the depth of a no-texture image region, such as one on white paper?" In such ambiguous regions, mathematical solutions related to binocular disparities are not unique or indefinite. We examine a mathematical description of depth completion that is consistent with human perception of depth for ambiguous regions. Using computer simulation, we demonstrate that resultant depth-maps qualitatively reproduce human depth perception of two kinds. The resultant depth maps produced using our model depend on the initial depth in the ambiguous region. Considering this dependence from psychological viewpoints, we conjecture that humans perceive completed surfaces that are affected by prior-stimuli corresponding to the initial condition of depth. We conducted psychological experiments to verify the model prediction. An ambiguous stimulus was presented after a prior stimulus removed ambiguity. The inter-stimulus interval (ISI) was inserted between the prior stimulus and post-stimulus. Results show that correlation of perception between the prior stimulus and post-stimulus depends on the ISI duration. Correlation is positive, negative, and nearly zero in the respective cases of short (0-200 ms), medium (200-400 ms), and long ISI (>400 ms). Furthermore, based on our model, we propose a computational model that can explain the dependence. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Autologous growth factor injections in chronic tendinopathy. (United States)

    Sandrey, Michelle A


    de Vos RJ, van Veldhoven PLJ, Moen MH, Weir A, Tol JL. Autologous growth factor injections in chronic tendinopathy: a systematic review. Br Med Bull. 2010;95:63-77. The authors of this systematic review evaluated the literature to critically consider the effects of growth factors delivered through autologous whole-blood and platelet-rich-plasma (PRP) injections in managing wrist-flexor and -extensor tendinopathies, plantar fasciopathy, and patellar tendinopathy. The primary question was, according to the published literature, is there sufficient evidence to support the use of growth factors delivered through autologous whole-blood and PRP injections for chronic tendinopathy? The authors performed a comprehensive, systematic literature search in October 2009 using PubMed, MEDLINE, EMBASE, CINAHL, and the Cochrane library without time limits. The following key words were used in different combinations: tendinopathy, tendinosis, tendinitis, tendons, tennis elbow, plantar fasciitis, platelet rich plasma, platelet transfusion, and autologous blood or injection. The search was limited to human studies in English. All bibliographies from the initial literature search were also viewed to identify additional relevant studies. Studies were eligible based on the following criteria: (1) Articles were suitable (inclusion criteria) if the participants had been clinically diagnosed as having chronic tendinopathy; (2) the design had to be a prospective clinical study, randomized controlled trial, nonrandomized clinical trial, or prospective case series; (3) a well-described intervention in the form of a growth factor injection with either PRP or autologous whole blood was used; and (4) the outcome was reported in terms of pain or function (or both). All titles and abstracts were assessed by 2 researchers, and all relevant articles were obtained. Two researchers independently read the full text of each article to determine if it met the inclusion criteria. If opinions differed on

  3. Syllabic discrimination in premature human infants prior to complete formation of cortical layers. (United States)

    Mahmoudzadeh, Mahdi; Dehaene-Lambertz, Ghislaine; Fournier, Marc; Kongolo, Guy; Goudjil, Sabrina; Dubois, Jessica; Grebe, Reinhard; Wallois, Fabrice


    The ontogeny of linguistic functions in the human brain remains elusive. Although some auditory capacities are described before term, whether and how such immature cortical circuits might process speech are unknown. Here we used functional optical imaging to evaluate the cerebral responses to syllables at the earliest age at which cortical responses to external stimuli can be recorded in humans (28- to 32-wk gestational age). At this age, the cortical organization in layers is not completed. Many neurons are still located in the subplate and in the process of migrating to their final location. Nevertheless, we observed several points of similarity with the adult linguistic network. First, whereas syllables elicited larger right than left responses, the posterior temporal region escaped this general pattern, showing faster and more sustained responses over the left than over the right hemisphere. Second, discrimination responses to a change of phoneme (ba vs. ga) and a change of human voice (male vs. female) were already present and involved inferior frontal areas, even in the youngest infants (29-wk gestational age). Third, whereas both types of changes elicited responses in the right frontal region, the left frontal region only reacted to a change of phoneme. These results demonstrate a sophisticated organization of perisylvian areas at the very onset of cortical circuitry, 3 mo before term. They emphasize the influence of innate factors on regions involved in linguistic processing and social communication in humans.

  4. Block randomization versus complete randomization of human perception stimuli: is there a difference? (United States)

    Moyer, Steve; Uhl, Elizabeth R.


    For more than 50 years, the U.S. Army RDECOM CERDEC Night Vision and Electronic Sensors Directorate (NVESD) has been studying and modeling the human visual discrimination process as it pertains to military imaging systems. In order to develop sensor performance models, human observers are trained to expert levels in the identification of military vehicles. From 1998 until 2006, the experimental stimuli were block randomized, meaning that stimuli with similar difficulty levels (for example, in terms of distance from target, blur, noise, etc.) were presented together in blocks of approximately 24 images but the order of images within the block was random. Starting in 2006, complete randomization came into vogue, meaning that difficulty could change image to image. It was thought that this would provide a more statistically robust result. In this study we investigated the impact of the two types of randomization on performance in two groups of observers matched for skill to create equivalent groups. It is hypothesized that Soldiers in the Complete Randomized condition will have to shift their decision criterion more frequently than Soldiers in the Block Randomization group and this shifting is expected to impede performance so that Soldiers in the Block Randomized group perform better.

  5. A naturally occurring variant of the human prion protein completely prevents prion disease. (United States)

    Asante, Emmanuel A; Smidak, Michelle; Grimshaw, Andrew; Houghton, Richard; Tomlinson, Andrew; Jeelani, Asif; Jakubcova, Tatiana; Hamdan, Shyma; Richard-Londt, Angela; Linehan, Jacqueline M; Brandner, Sebastian; Alpers, Michael; Whitfield, Jerome; Mead, Simon; Wadsworth, Jonathan D F; Collinge, John


    Mammalian prions, transmissible agents causing lethal neurodegenerative diseases, are composed of assemblies of misfolded cellular prion protein (PrP). A novel PrP variant, G127V, was under positive evolutionary selection during the epidemic of kuru--an acquired prion disease epidemic of the Fore population in Papua New Guinea--and appeared to provide strong protection against disease in the heterozygous state. Here we have investigated the protective role of this variant and its interaction with the common, worldwide M129V PrP polymorphism. V127 was seen exclusively on a M129 PRNP allele. We demonstrate that transgenic mice expressing both variant and wild-type human PrP are completely resistant to both kuru and classical Creutzfeldt-Jakob disease (CJD) prions (which are closely similar) but can be infected with variant CJD prions, a human prion strain resulting from exposure to bovine spongiform encephalopathy prions to which the Fore were not exposed. Notably, mice expressing only PrP V127 were completely resistant to all prion strains, demonstrating a different molecular mechanism to M129V, which provides its relative protection against classical CJD and kuru in the heterozygous state. Indeed, this single amino acid substitution (G→V) at a residue invariant in vertebrate evolution is as protective as deletion of the protein. Further study in transgenic mice expressing different ratios of variant and wild-type PrP indicates that not only is PrP V127 completely refractory to prion conversion but acts as a potent dose-dependent inhibitor of wild-type prion propagation.

  6. Complete Genome Analysis of a Rabbit Rotavirus Causing Gastroenteritis in a Human Infant

    Directory of Open Access Journals (Sweden)

    Melisa Berenice Bonica


    Full Text Available Group A rotaviruses (RVA are responsible for causing infantile diarrhea both in humans and animals. The molecular characteristics of lapine RVA strains are only studied to a limited extent and so far G3P[14] and G3P[22] were found to be the most common G/P-genotypes. During the 2012-2013 rotavirus season in Belgium, a G3P[14] RVA strain was isolated from stool collected from a two-year-old boy. We investigated whether RVA/Human-wt/BEL/BE5028/2012/G3P[14] is completely of lapine origin or the result of reassortment event(s. Phylogenetic analyses of all gene segments revealed the following genotype constellation: G3-P[14]-I2-R2-C2-M3-A9-N2-T6-E5-H3 and indicated that BE5028 probably represents a rabbit to human interspecies transmission able to cause disease in a human child. Interestingly, BE5028 showed a close evolutionary relationship to RVA/Human-wt/BEL/B4106/2000/G3P[14], another lapine-like strain isolated in a Belgian child in 2000. The phylogenetic analysis of the NSP3 segment suggests the introduction of a bovine(-like NSP3 into the lapine RVA population in the past 12 years. Sequence analysis of NSP5 revealed a head-to-tail partial duplication, combined with two short insertions and a deletion, indicative of the continuous circulation of this RVA lineage within the rabbit population.

  7. Coursera’s Introductory Human Physiology Course: Factors that Characterize Successful Completion of a MOOC

    Directory of Open Access Journals (Sweden)

    Deborah Engle


    Full Text Available Since Massive Open Online Courses (MOOCs are accessible by anyone in the world at no cost, they have large enrollments that are conducive to educational research. This study examines students in the Coursera MOOC, Introductory Human Physiology. Of the 33,378 students who accessed the course, around 15,000 students responded to items on the pre-course survey about their age, educational background, proficiency in English, and plans for participating in the course. We categorized students who completed the pre-course survey into groups based on the number of exams completed and corresponding course achievement level. We used Chi-square goodness of fit tests to analyze the distribution of students’ responses on the pre-course survey and associated achievement level. Of the students who responded to the pre-course survey and passed with distinction, a larger percentage self-identified as fluent in English while a smaller percentage self-identified as beginners. Students with graduate degrees were more likely to pass the course or pass with distinction than students with only some college experience or a bachelor’s degree. Students who completed either some or all exams were more likely to self-report intention to complete all course activities than students who did not take any exams. A greater proportion of students who passed the course or passed with distinction posted two or more times on the course discussion forum. Understanding MOOC students and the characteristics that lead to their success will enable modification to courses for increased student achievement and may also inform teaching in the traditional classroom.

  8. Age-Based Comparison of Human Dendritic Spine Structure Using Complete Three-Dimensional Reconstructions (United States)

    Benavides-Piccione, Ruth; Fernaud-Espinosa, Isabel; Robles, Victor; Yuste, Rafael; DeFelipe, Javier


    Dendritic spines of pyramidal neurons are targets of most excitatory synapses in the cerebral cortex. Recent evidence suggests that the morphology of the dendritic spine could determine its synaptic strength and learning rules. However, unfortunately, there are scant data available regarding the detailed morphology of these structures for the human cerebral cortex. In the present study, we analyzed over 8900 individual dendritic spines that were completely 3D reconstructed along the length of apical and basal dendrites of layer III pyramidal neurons in the cingulate cortex of 2 male humans (aged 40 and 85 years old), using intracellular injections of Lucifer Yellow in fixed tissue. We assembled a large, quantitative database, which revealed a major reduction in spine densities in the aged case. Specifically, small and short spines of basal dendrites and long spines of apical dendrites were lost, regardless of the distance from the soma. Given the age difference between the cases, our results suggest selective alterations in spines with aging in humans and indicate that the spine volume and length are regulated by different biological mechanisms. PMID:22710613

  9. Improved targeting and enhanced retention of the human, autologous, fibroblast-derived, induced, pluripotent stem cells to the sarcomeres of the infarcted myocardium with the aid of the bioengineered, heterospecific, tetravalent antibodies. (United States)

    Malecki, Marek


    Clinical trials, to regenerate the human heart injured by myocardial infarction, involve the delivery of stem cells to the site of the injury. However, only a small fraction of the introduced stem cells are detected at the site of the injury, merely two weeks after this therapeutic intervention. This significantly hampers the effectiveness of the stem cell therapy. To resolve the aforementioned problem, we genetically and molecularly bioengineered heterospecific, tetravalent antibodies (htAbs), which have both exquisite specificity and high affinity towards human, pluripotent, stem cells through the htAbs' domains binding SSEA-4, SSEA-3, TRA-1-60, and TRA-1-81, as well as towards the injured cardiac muscle through the htAbs' domains binding human cardiac myosin, α-actinin, actin, and titin. The cardiac tissue was acquired from the patients, who were receiving heart transplants. The autologous, human, induced, pluripotent stem cells (hiPSCs) were generated from the patients' fibroblasts by non-viral delivery and transient expression of the DNA constructs for: Oct4, Nanog, Sox2, Lin28, Klf4, c-Myc. In the trials involving the htAbs, the human, induced, pluripotent stem cells anchored to the myocardial sarcomeres with the efficiency, statistically, significantly higher, than in the trials with non-specific or without antibodies (p < 0.0003). Moreover, application of the htAbs resulted in cross-linking of the sarcomeric proteins to create the stable scaffolds for anchoring of the stem cells. Thereafter, these human, induced pluripotent stem cells differentiated into cardiomyocytes at their anchorage sites. By bioengineering of these novel heterospecific, tetravalent antibodies and using them to guide and to anchor the stem cells specifically to the stabilized sarcomeric scaffolds, we demonstrated the proof of concept in vitro for improving effectiveness of regenerative therapy of myocardial infarction and created the foundations for the trials in vivo.

  10. A qualitative and quantitative analysis of autologous human multipotent adult stem cells derived from three anatomic areas by marrow aspiration: tibia, anterior ilium, and posterior ilium. (United States)

    Marx, Robert E; Tursun, Ramzey


    The purpose of this article was to compare the yields of stromal multipotent stem cells (CD34+ and CD105+) and hematopoetic multipotent stem cells (CD44+) obtained from different areas via bone marrow aspiration (BMA). Sixty 60-mL bone marrow aspirates were taken from the tibial plateau, the anterior ilium, and the posterior ilium using a single point-of-care BMA technique and a single BMA concentration (BMAC) device. A 1-mL portion of each sample was used to determine CD stem cell concentrations and the nucleated cell count. The remaining BMA was centrifuged to separate the more mature red blood cell precursors from the stem cells and then concentrate the latter into a BMAC. The BMAC yield of 10 mL was analyzed with flow cytometry and nucleated cell counts to derive a concentration factor for the BMAC. The yield of total nucleated cells was equal between the anterior and posterior ilium and more than twice that obtained from the tibial plateau. The CD44+ and CD105+ cell yields were also nearly equal between the anterior and posterior ilium but more than twice that of the tibial plateau; however, the ratios between the three different stem cell types in BMAC obtained from the different areas suggest varying potentials for tissue development. The ilium is the preferred donor site for obtaining autologous stem cells at the point of care. The tibial plateau yielded only half as much bone marrow multipotent/progenitor stem cells as did the anterior and posterior ilium. The composition of the BMAC from each site suggests that the potential for differentiation into various cell types changes depending on the source of bone marrow, but that BMAC represents 6.5 ± 1.0 concentration factor from BMA.

  11. Potential of human dental stem cells in repairing the complete transection of rat spinal cord (United States)

    Yang, Chao; Li, Xinghan; Sun, Liang; Guo, Weihua; Tian, Weidong


    Objective. The adult spinal cord of mammals contains a certain amount of neural precursor cells, but these endogenous cells have a limited capacity for replacement of lost cells after spinal cord injury. The exogenous stem cells transplantation has become a therapeutic strategy for spinal cord repairing because of their immunomodulatory and differentiation capacity. In addition, dental stem cells originating from the cranial neural crest might be candidate cell sources for neural engineering. Approach. Human dental follicle stem cells (DFSCs), stem cells from apical papilla (SCAPs) and dental pulp stem cells (DPSCs) were isolated and identified in vitro, then green GFP-labeled stem cells with pellets were transplanted into completely transected spinal cord. The functional recovery of rats and multiple neuro-regenerative mechanisms were explored. Main results. The dental stem cells, especially DFSCs, demonstrated the potential in repairing the completely transected spinal cord and promote functional recovery after injury. The major involved mechanisms were speculated below: First, dental stem cells inhibited the expression of interleukin-1β to reduce the inflammatory response; second, they inhibited the expression of ras homolog gene family member A (RhoA) to promote neurite regeneration; third, they inhibited the sulfonylurea receptor1 (SUR-1) expression to reduce progressive hemorrhagic necrosis; lastly, parts of the transplanted cells survived and differentiated into mature neurons and oligodendrocytes but not astrocyte, which is beneficial for promoting axons growth. Significance. Dental stem cells presented remarkable tissue regenerative capability after spinal cord injury through immunomodulatory, differentiation and protection capacity.

  12. Complete genome sequence of Yersinia pestis strain 91001, an isolate avirulent to humans

    DEFF Research Database (Denmark)

    Song, Yajun; Tong, Zongzhong; Wang, Jin


    Genomics provides an unprecedented opportunity to probe in minute detail into the genomes of the world's most deadly pathogenic bacteria- Yersinia pestis. Here we report the complete genome sequence of Y. pestis strain 91001, a human-avirulent strain isolated from the rodent Brandt's vole......-Microtus brandti. The genome of strain 91001 consists of one chromosome and four plasmids (pPCP1, pCD1, pMT1 and pCRY). The 9609-bp pPCP1 plasmid of strain 91001 is almost identical to the counterparts from reference strains (CO92 and KIM). There are 98 genes in the 70,159-bp range of plasmid pCD1. The 106,642-bp...... comparison, we conclude that strain 91001 and other strains isolated from M. brandti might have evolved from ancestral Y. pestis in a different lineage. The large genome fragment deletions in the 91001 chromosome and some pseudogenes may contribute to its unique nonpathogenicity to humans and host...

  13. The evolution of human influenza A viruses from 1999 to 2006: A complete genome study

    Directory of Open Access Journals (Sweden)

    Fomsgaard Anders


    Full Text Available Abstract Background Knowledge about the complete genome constellation of seasonal influenza A viruses from different countries is valuable for monitoring and understanding of the evolution and migration of strains. Few complete genome sequences of influenza A viruses from Europe are publicly available at the present time and there have been few longitudinal genome studies of human influenza A viruses. We have studied the evolution of circulating human H3N2, H1N1 and H1N2 influenza A viruses from 1999 to 2006, we analysed 234 Danish human influenza A viruses and characterised 24 complete genomes. Results H3N2 was the prevalent strain in Denmark during the study period, but H1N1 dominated the 2000–2001 season. H1N2 viruses were first observed in Denmark in 2002–2003. After years of little genetic change in the H1N1 viruses the 2005–2006 season presented H1N1 of greater variability than before. This indicates that H1N1 viruses are evolving and that H1N1 soon is likely to be the prevalent strain again. Generally, the influenza A haemagglutinin (HA of H3N2 viruses formed seasonal phylogenetic clusters. Different lineages co-circulating within the same season were also observed. The evolution has been stochastic, influenced by small "jumps" in genetic distance rather than constant drift, especially with the introduction of the Fujian-like viruses in 2002–2003. Also evolutionary stasis-periods were observed which might indicate well fit viruses. The evolution of H3N2 viruses have also been influenced by gene reassortments between lineages from different seasons. None of the influenza genes were influenced by strong positive selection pressure. The antigenic site B in H3N2 HA was the preferred site for genetic change during the study period probably because the site A has been masked by glycosylations. Substitutions at CTL-epitopes in the genes coding for the neuraminidase (NA, polymerase acidic protein (PA, matrix protein 1 (M1, non

  14. The complete mitochondrial genomes for three Toxocara species of human and animal health significance

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    Wu Xiang-Yun


    Full Text Available Abstract Background Studying mitochondrial (mt genomics has important implications for various fundamental areas, including mt biochemistry, physiology and molecular biology. In addition, mt genome sequences have provided useful markers for investigating population genetic structures, systematics and phylogenetics of organisms. Toxocara canis, Toxocara cati and Toxocara malaysiensis cause significant health problems in animals and humans. Although they are of importance in human and animal health, no information on the mt genomes for any of Toxocara species is available. Results The sizes of the entire mt genome are 14,322 bp for T. canis, 14029 bp for T. cati and 14266 bp for T. malaysiensis, respectively. These circular genomes are amongst the largest reported to date for all secernentean nematodes. Their relatively large sizes relate mainly to an increased length in the AT-rich region. The mt genomes of the three Toxocara species all encode 12 proteins, two ribosomal RNAs and 22 transfer RNA genes, but lack the ATP synthetase subunit 8 gene, which is consistent with all other species of Nematode studied to date, with the exception of Trichinella spiralis. All genes are transcribed in the same direction and have a nucleotide composition high in A and T, but low in G and C. The contents of A+T of the complete genomes are 68.57% for T. canis, 69.95% for T. cati and 68.86% for T. malaysiensis, among which the A+T for T. canis is the lowest among all nematodes studied to date. The AT bias had a significant effect on both the codon usage pattern and amino acid composition of proteins. The mt genome structures for three Toxocara species, including genes and non-coding regions, are in the same order as for Ascaris suum and Anisakis simplex, but differ from Ancylostoma duodenale, Necator americanus and Caenorhabditis elegans only in the location of the AT-rich region, whereas there are substantial differences when compared with Onchocerca volvulus

  15. How effective is autologous serum therapy in chronic autoimmune urticaria

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    Imran Majid


    Full Text Available Background: Chronic autoimmune urticaria (CAU is one of the most challenging therapeutic problems faced by a dermatologist. Recently, weekly autologous serum injections have been shown to induce a prolonged remission in this disease. Aim: To evaluate the efficacy of repeated autologous serum injections in patients with CAU. Materials and Methods: Seventy patients of CAU were prospectively analyzed for the efficacy of nine consecutive weekly autologous serum injections with a post-intervention follow-up of 12 weeks. Total urticaria severity score (TSS was monitored at the baseline, at the end of treatment and lastly at the end of 12 weeks of follow up. Response to treatment was judged by the percentage reduction in baseline TSS at the end of treatment and again at the end of 12 weeks-follow-up. Results: Out of the 70 patients enrolled, 11 dropped out of the injection treatment after one or the first few doses only. Among the rest of 59 patients, only 7 patients (12% went into a partial or complete remission and remained so over the follow-up period of 12 weeks. Forty patients (68% did not demonstrate any significant reduction in TSS at the end of the treatment period. Rest of the 12 patients showed either a good or excellent response while on weekly injection treatment, but all of them relapsed over the follow-up period of 12 weeks. Conclusion: Autologous serum therapy does not seem to lead to any prolonged remission in patients of CAU.

  16. Autologous Blood Versus Fibrin Glue in Pterygium Excision With Conjunctival Autograft Surgery. (United States)

    Nadarajah, Gaayathri; Ratnalingam, Vanitha Hema; Mohd Isa, Hazlita


    To evaluate graft stability and recurrence rate between fibrin glue and autologous blood in pterygium conjunctival autograft surgery. A prospective, randomized, single-blinded clinical trial to assess the efficacy of autologous blood in place of fibrin glue in pterygium surgery. A total of 120 eyes of 111 patients were randomized according to pterygium morphology, to undergo pterygium surgery with autografting using either autologous blood or fibrin glue. All patients were operated by a single surgeon; 58 eyes were operated using fibrin glue and 62 eyes had a conjunctival autograft with autologous blood. Patients were seen on postoperative day 1, 1 week, 1 month, 6 months, and 1 year after surgery. Graft stability and pterygium recurrence were graded by an independent observer who was masked to the method of treatment. All 120 eyes completed the 1-year follow-up. Graft loss was seen only in the autologous blood group. Of the 62 eyes in this group, a total of 15 (24.2%) grafts dislodged. Recurrence was calculated after excluding grafts that were dislodged. Of the 105 patients, there were a total of 7 recurrences, 2 (3.4%) from the fibrin adhesive method and 5 (10.6%) from the autologous blood method. This was not statistically significant (P = 0.238). Autologous blood does not exhibit similar graft stability seen with fibrin glue. Although the recurrence rate may not be significant, careful patient selection and a standard method needs to be laid out before the use of this method is widely accepted.

  17. Complete genotype constellation of human rotavirus group A circulating in Thailand, 2008-2011. (United States)

    Theamboonlers, A; Maiklang, O; Thongmee, T; Chieochansin, T; Vuthitanachot, V; Poovorawan, Y


    This study has identified diverse and re-assorted group A rotavirus (RVA) strains by sequence and phylogenetic analysis of the 11 genomic segments. The 22 cases investigated in this study were collected from children with diarrhea between 2008 and 2011. The RVA genomic constellations identified in this study were identified as G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 22.7% (5/22); G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 27.3% (6/22); G3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 18.2% (4/22); G3-P[9]-I3-R3-C3-M3-A3-N3-T3-E3-H6 4.6% (1/22); G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 9.1% (2/22); G12-P[6]-I1-R1-C1-M1-A1-N1-T1-E1-H1 4.6% (1/22) and G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 13.6% (3/22). Two RVA strains, possessing a complete AU-1-like genomic backbone, showed re-assortment for genes 3 and 11, revealing possible zoonotic re-assortment events between human and canine strains. In addition, one of the analyzed strains revealed a G12 specificity for VP7 in combination with a porcine-like P[6] VP4 and a complete Wa-like constellation. Continuous surveillance of rotavirus strains and their evolution may be useful for understanding the emergence of novel strains through interspecies genome re-assortment between human and animal viruses. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Identification and complete sequencing of novel human transcripts through the use of mouse orthologs and testis cDNA sequences

    DEFF Research Database (Denmark)

    Ferreira, Elisa N; Pires, Lilian C; Parmigiani, Raphael B


    the human genome sequence. We generated 47 complete human transcript sequences, comprising 27 unannotated and 20 annotated sequences. Eight of these transcripts are variants of previously known genes. These transcripts were characterized according to size, number of exons, and chromosomal localization...

  19. Replication-defective recombinant Semliki Forest virus encoding GM-CSF as a vector system for rapid and facile generation of autologous human tumor cell vaccines

    NARCIS (Netherlands)

    Withoff, S; Glazenburg, KL; van Veen, ML; Kraak, MMJ; Hospers, GAP; Storkel, S; de Vries, EGE; Wischut, J; Daemen, T


    This paper describes the production of recombinant Semliki Forest virus encoding murine or human granulocyte-macrophage colony-stimulating factor (GM-CSF) and the capacity of these vectors to transduce murine and human tumor cells ex vivo. High-titer stocks (up to 3 x 10(9) particles/ml) of


    Directory of Open Access Journals (Sweden)

    Don F Du Toit


    en la escala ASIA aumentaron de 29/112 a 64/112 a los 6 meses después del tratamiento y se ganó al menos un nivel de la escala ASIA. Conclusión: En comparación con los hallazgos iniciales, se documentó mejoría neurológica cuantificada en la cintura escapular y las extremidades superiores, entre 6 y 12 meses después del trasplante celular autólogo intralesional con SCNT en un caso de cuadriplejia crónica. The scientific literature reports that about 180,000 cases of spinal-cord injuries (SCI occur yearly in the world. Recent publications show neurological benefit in selected quadriplegics undergoing intra-lesion transplantation of autologous cultured bone-marrow mesenchymal stem cells. Objectives: This case-study reports level–III objective evidence and partial neurological clinical recovery in a 32-year old-male with chronic complete quadriplegia that underwent somatic nuclear cell transfer (SCNT and embryonic cell therapy for traumatic spinal-cord injury (SCI sustained 6-years previously. The research question was: “Can autologous SCNT cell-therapy improve extremity motor and sensory impairment in chronic quadriplegia?” The hypothesis tested: “SCNT cell-therapy is unable to improve severe motor and sensory impairment in selected persons with chronic complete quadriplegia and unable to improve functional outcome or independence”. Material and methods: Cell-transplantation was by neuro-surgical implantation into the damaged cervical cord 6-years after SCI that rendered the patient a complete quadriplegic confirmed on neurological examination and magnetic resonance imaging (MRI. Neurologic assessment, restoration of dermatomes and myotomes were evaluated post-procedurally for 12-months together with MRI, and American Spinal Injury Association grading (ASIA. Results: Neurological improvement was asymmetrically improved in the shoulder girdle, upper extremity bilaterally and trunk without dramatic change in leg-function at 12-months. ASIA

  1. Assessing quality and completeness of human transcriptional regulatory pathways on a genome-wide scale

    Directory of Open Access Journals (Sweden)

    Aifantis Iannis


    Full Text Available Abstract Background Pathway databases are becoming increasingly important and almost omnipresent in most types of biological and translational research. However, little is known about the quality and completeness of pathways stored in these databases. The present study conducts a comprehensive assessment of transcriptional regulatory pathways in humans for seven well-studied transcription factors: MYC, NOTCH1, BCL6, TP53, AR, STAT1, and RELA. The employed benchmarking methodology first involves integrating genome-wide binding with functional gene expression data to derive direct targets of transcription factors. Then the lists of experimentally obtained direct targets are compared with relevant lists of transcriptional targets from 10 commonly used pathway databases. Results The results of this study show that for the majority of pathway databases, the overlap between experimentally obtained target genes and targets reported in transcriptional regulatory pathway databases is surprisingly small and often is not statistically significant. The only exception is MetaCore pathway database which yields statistically significant intersection with experimental results in 84% cases. Additionally, we suggest that the lists of experimentally derived direct targets obtained in this study can be used to reveal new biological insight in transcriptional regulation and suggest novel putative therapeutic targets in cancer. Conclusions Our study opens a debate on validity of using many popular pathway databases to obtain transcriptional regulatory targets. We conclude that the choice of pathway databases should be informed by solid scientific evidence and rigorous empirical evaluation. Reviewers This article was reviewed by Prof. Wing Hung Wong, Dr. Thiago Motta Venancio (nominated by Dr. L Aravind, and Prof. Geoff J McLachlan.

  2. Hydroxymethylbilane synthase: Complete genomic sequence and amplifiable polymorphisms in the human gene

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Hanwook; Warner, C.A.; Chen, Chiahsiang; Desnick, R.J. (Mount Sinai School of Medicine, New York, NY (United States))


    Acute intermittent porphyria (AIP), an autosomal dominant inborn error of heme biosynthesis, results from the half-normal activity of the heme biosynthetic enzyme hydroxymethylbilane synthase (HMB-synthase). Heterozygous individuals are prone to life-threatening acute neurologic attacks, which are precipitated by certain drugs and other metabolic, hormonal, and nutritional factors. Since the biochemical diagnosis of heterozygous individuals has been problematic, recent efforts have focused on the identification of mutations and diagnostically useful restriction fragment length polymorphisms (RFLPS) in the HMB-synthase gene. To facilitate these endeavors, the human HMB-synthase gene, including 1.1 kb of the 5[prime] flanking region, was isolated and completely sequenced in both orientations. The 10,024-bp gene contained 15 exons ranging in size from 39 to 438 bp and 14 introns ranging from 87 to 2913 bp. All intron/exon boundaries conformed to the GT/AG consensus rule. There were six Alu repetitive elements, one of the J and five of the Sa subfamilies. Analysis of the 1. I -kb 5[prime]flanking region revealed putative regulatory elements for the housekeeping promoter including AP1, AP4, SP1, TRE, ENH, and CAC. This region contained 10 HpaII sites and had an overall GC content of 54%. Three new polymorphic sites were identified by the single-strand conformation polymorphism (SSCP) technique, a common BsmAI site in intron 3 (3581 A/G), a common HinfI RFLP in intron 10 (7064 C/A), and a rare MnlI site in intron 14 (7998G/A). The allele frequencies of five previously known and the new polymorphic sites in a normal Caucasian population indicated that the intron 1 and intron 3 RFLPs were in linkage disequilibrium; however, the Hint I site segregated independently. 54 refs., 6 figs., 3 tabs.

  3. Identification and complete sequencing of novel human transcripts through the use of mouse orthologs and testis cDNA sequences

    DEFF Research Database (Denmark)

    Ferreira, Elisa N; Pires, Lilian C; Parmigiani, Raphael B


    The correct identification of all human genes, and their derived transcripts, has not yet been achieved, and it remains one of the major aims of the worldwide genomics community. Computational programs suggest the existence of 30,000 to 40,000 human genes. However, definitive gene identification...... the human genome sequence. We generated 47 complete human transcript sequences, comprising 27 unannotated and 20 annotated sequences. Eight of these transcripts are variants of previously known genes. These transcripts were characterized according to size, number of exons, and chromosomal localization...

  4. Virtual Human Analogs to Rodent Spatial Pattern Separation and Completion Memory Tasks (United States)

    Paleja, Meera; Girard, Todd A.; Christensen, Bruce K.


    Spatial pattern separation (SPS) and spatial pattern completion (SPC) have played an increasingly important role in computational and rodent literatures as processes underlying associative memory. SPS and SPC are complementary processes, allowing the formation of unique representations and the reconstruction of complete spatial environments based…

  5. Human anti-idiotypic T lymphocyte clones are activated by autologous anti- rabies virus antibodies presented in association with HLA-DQ molecules.

    NARCIS (Netherlands)

    F. UytdeHaag; I.J.Th.M. Claassen (Ivo); H. Bunschoten; H. Loggen; T. Ottenhoff; V. Teeuwsen; A.D.M.E. Osterhaus (Albert)


    textabstractThe regulatory function of antigen-specific T cells in human antibody responses to protein and carbohydrate determinants of many viral and bacterial antigens has extensively been studied in systems involving in vitro triggering of B cells by antigens or polyclonal activators. Although

  6. Therapeutic Efficacy of Fresh, Autologous Mesenchymal Stem Cells for Severe Refractory Gingivostomatitis in Cats (United States)

    Mills-Ko, Emily; Verstraete, Frank J.M.; Kol, Amir; Walker, Naomi J.; Badgley, Megan R.; Fazel, Nasim; Murphy, William J.; Vapniarsky, Natalia; Borjesson, Dori L.


    Mesenchymal stem cells (MSCs) are a promising therapy for immune-mediated and inflammatory disorders, because of their potent immunomodulatory properties. In this study, we investigated the use of fresh, autologous, adipose-derived MSCs (ASCs) for feline chronic gingivostomatitis (FCGS), a chronic, debilitating, idiopathic, oral mucosal inflammatory disease. Nine cats with refractory FCGS were enrolled in this pilot study. Each cat received 2 intravenous injections of 20 million autologous ASCs, 1 month apart. Oral biopsies were taken before and at 6 months after the first ASC injection. Blood immune cell subsets, serum protein, and cytokine levels were measured at 0, 1, 3, and 6 months after treatment to assess immunomodulatory effects. Seven of the 9 cats completed the study. Five cats responded to treatment by either complete clinical remission (n = 3) or substantial clinical improvement (n = 2). Two cats were nonresponders. Cats that responded to treatment also exhibited systemic immunomodulation demonstrated by decreased numbers of circulating CD8+ T cells, a normalization of the CD4/CD8 ratio, decreased neutrophil counts, and interferon-γ and interleukin (IL)-1β concentration, and a temporary increase in serum IL-6 and tumor necrosis factor-α concentration. No clinical recurrence has occurred following complete clinical remission (follow-up of 6–24 months). In this study, cats with cats with >15% CD8lo cells were nonresponders. The relative absence of CD8lo cells may be a biomarker to predict response to ASC therapy, and may shed light on pathogenesis of FCGS and mechanisms by which ASCs decrease oral inflammation and affect T-cell phenotype. Significance This study is the first to demonstrate the safety and efficacy of fresh, autologous, adipose-derived stem cell systemic therapy for a naturally occurring, chronic inflammatory disease in cats. The findings demonstrate that this therapy resulted in complete clinical and histological resolution or

  7. Characterisation of complete high- and low-risk human papillomavirus genomes isolated from cervical specimens in southern Brazil (United States)

    de Oliveira, Gisele R; Siqueira, Juliana D; Finger-Jardim, Fabiana; Vieira, Valdimara C; Silva, Ronald L; Gonçalves, Carla V; Soares, Esmeralda A; de Martinez, Ana Maria Barral; Soares, Marcelo A


    The classification of human papillomavirus (HPV) intratypic lineages by complete genome sequencing is a determinant in understanding biological differences in association with this disease. In this work, we have characterised complete HPV genomes from southern Brazil. Fifteen cervicovaginal Pap smear negative samples previously categorised as HPV-positive were sequenced using ultradeep sequencing, and 18 complete genomes from 13 different HPV types were assembled. Phylogenetic and genetic distance analyses were performed to classify the HPV genomes into lineages and sublineages. This is the first report describing the distribution of HPV intratype lineages of high and low oncogenic risk in asymptomatic women from southern Brazil. PMID:28954002

  8. Screening for autologous blood transfusions

    DEFF Research Database (Denmark)

    Mørkeberg, J; Belhage, B; Ashenden, M


    The ratio between the amount of hemoglobin in the mature erythrocyte population and the reticulocytes (RBCHb:RetHb ratio) has previously been suggested as a marker to screen for EPO-abuse. We speculated that the reinfusion of blood would lead to a marked increase in this ratio, making it a valuable...... parameter in the screening for autologous blood doping. Three bags of blood (approximately 201+/-11 g of Hb) were withdrawn from 16 males and stored at either -80 degrees C (-80 T, n=8) or +4 degrees C (+4 T, n=8) and reinfused 10 weeks or 4 weeks later, respectively. Seven subjects served as controls...... week wash-out period were identified as 'suspicious', and 18.8% (-80 T) and 4.3% (+4 T) as 'positive'. In total, 7 out of 16 (43.8%) subjects had at least one sample exceeding 182.9. Compared to the currently used indirect parameters, the RBCHb:RetHb ratio is the best indicator of autologous blood...

  9. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. (United States)

    Angeli, Claudia A; Edgerton, V Reggie; Gerasimenko, Yury P; Harkema, Susan J


    Previously, we reported that one individual who had a motor complete, but sensory incomplete spinal cord injury regained voluntary movement after 7 months of epidural stimulation and stand training. We presumed that the residual sensory pathways were critical in this recovery. However, we now report in three more individuals voluntary movement occurred with epidural stimulation immediately after implant even in two who were diagnosed with a motor and sensory complete lesion. We demonstrate that neuromodulating the spinal circuitry with epidural stimulation, enables completely paralysed individuals to process conceptual, auditory and visual input to regain relatively fine voluntary control of paralysed muscles. We show that neuromodulation of the sub-threshold motor state of excitability of the lumbosacral spinal networks was the key to recovery of intentional movement in four of four individuals diagnosed as having complete paralysis of the legs. We have uncovered a fundamentally new intervention strategy that can dramatically affect recovery of voluntary movement in individuals with complete paralysis even years after injury.

  10. Bussulfano e melfalano como regime de condicionamento para o transplante autogênico de células-tronco hematopoéticas na leucemia mielóide aguda em primeira remissão completa Busulfan and melphalan as conditioning regimen for autologous hematopoietic stem cell transplantation in acute myeloid leukemia in first complete remission

    Directory of Open Access Journals (Sweden)

    Nadjanara D. Bueno


    Full Text Available Vinte e dois pacientes consecutivos portadores de leucemia mielóide aguda (LMA em primeira remissão completa (1ªRC submetidos a transplante de células-tronco hematopoéticas autogênico (TCTH Auto condicionados com bussulfano e melfalano (Bu/Mel foram selecionados entre 1993 e 2006. A probabilidade de sobrevida global (SG pelo método de Kaplan-Meier foi de 57,5% após 36 meses, com "plateau" aos 20 meses após o transplante. Fatores como sexo, classificação Franco-Americana-Britânica (FAB da LMA, tratamento de indução, consolidação intensiva, remissão após o primeiro ciclo de indução e fonte de células não tiveram impacto na sobrevida. Pela análise citogenética, um paciente de mau prognóstico submetido ao procedimento, foi a óbito um ano após o transplante. Nove pacientes foram a óbito, oito por recidiva e um por hemorragia. Morte antes dos 100 dias ocorreu em dois pacientes, um por recidiva e outro por hemorragia decorrente da plaquetopenia refratária, relacionada ao procedimento. Concluímos que o regime de condicionamento Bu/Mel é opção válida ao uso de outros regimes de condicionamento, apresentando excelente taxa da sobrevida.Twenty-two consecutive patients with acute myeloid leukemia in first complete remission submitted to autologous hematopoietic stem cells transplantation conditioned with busulfan and melphalan were evaluated between 1993 and 2006. The overall survival, according to the Kaplan-Meier curve, was 57.5% at 36 months, with a "plateau" at 20 months after transplant. Factors such as gender, French-American-British (FAB classification of acute myeloid leukemia, induction therapy, intensive consolidation, remission after the first cycle of induction and source of cells had no impact on survival. One patient with poor prognosis before the procedure died a year after transplantation. Nine patients died, eight by relapse and one because of bleeding. Death before 100 days occurred for two patients, one

  11. Human Capital Investment and the Completion of Risky R&D Projects

    DEFF Research Database (Denmark)

    Siyahhan, Baran; Engelbert, Dockner


    of the firm is driven by fixed labor costs that occur until the breakthrough is made, the call option to invest in human capital and market the product, and the put option to abandon the project. These options together with labor costs’ based operating leverage determine the risk dynamics. Risk varies non...... and risk consequences, and derive optimal investment in the stock of human capital. While optimal investment in human capital is very sensitive to its productivity do increase the probability of a breakthrough it is insensitive to changes in the volatility of the present value of the patent. The value...

  12. The Power and the Promise of Cell Reprogramming: Personalized Autologous Body Organ and Cell Transplantation. (United States)

    Palomo, Ana Belen Alvarez; Lucas, Michaela; Dilley, Rodney J; McLenachan, Samuel; Chen, Fred Kuanfu; Requena, Jordi; Sal, Marti Farrera; Lucas, Andrew; Alvarez, Inaki; Jaraquemada, Dolores; Edel, Michael J


    Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) or direct reprogramming to desired cell types are powerful and new in vitro methods for the study of human disease, cell replacement therapy, and drug development. Both methods to reprogram cells are unconstrained by the ethical and social questions raised by embryonic stem cells. iPSC technology promises to enable personalized autologous cell therapy and has the potential to revolutionize cell replacement therapy and regenerative medicine. Potential applications of iPSC technology are rapidly increasing in ambition from discrete cell replacement applications to the iPSC assisted bioengineering of body organs for personalized autologous body organ transplant. Recent work has demonstrated that the generation of organs from iPSCs is a future possibility. The development of embryonic-like organ structures bioengineered from iPSCs has been achieved, such as an early brain structure (cerebral organoids), bone, optic vesicle-like structures (eye), cardiac muscle tissue (heart), primitive pancreas islet cells, a tooth-like structure (teeth), and functional liver buds (liver). Thus, iPSC technology offers, in the future, the powerful and unique possibility to make body organs for transplantation removing the need for organ donation and immune suppressing drugs. Whilst it is clear that iPSCs are rapidly becoming the lead cell type for research into cell replacement therapy and body organ transplantation strategies in humans, it is not known whether (1) such transplants will stimulate host immune responses; and (2) whether this technology will be capable of the bioengineering of a complete and fully functional human organ. This review will not focus on reprogramming to iPSCs, of which a plethora of reviews can be found, but instead focus on the latest developments in direct reprogramming of cells, the bioengineering of body organs from iPSCs, and an analysis of the immune response induced by i

  13. The Power and the Promise of Cell Reprogramming: Personalized Autologous Body Organ and Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Ana Belen Alvarez Palomo


    Full Text Available Reprogramming somatic cells to induced pluripotent stem cells (iPSCs or direct reprogramming to desired cell types are powerful and new in vitro methods for the study of human disease, cell replacement therapy, and drug development. Both methods to reprogram cells are unconstrained by the ethical and social questions raised by embryonic stem cells. iPSC technology promises to enable personalized autologous cell therapy and has the potential to revolutionize cell replacement therapy and regenerative medicine. Potential applications of iPSC technology are rapidly increasing in ambition from discrete cell replacement applications to the iPSC assisted bioengineering of body organs for personalized autologous body organ transplant. Recent work has demonstrated that the generation of organs from iPSCs is a future possibility. The development of embryonic-like organ structures bioengineered from iPSCs has been achieved, such as an early brain structure (cerebral organoids, bone, optic vesicle-like structures (eye, cardiac muscle tissue (heart, primitive pancreas islet cells, a tooth-like structure (teeth, and functional liver buds (liver. Thus, iPSC technology offers, in the future, the powerful and unique possibility to make body organs for transplantation removing the need for organ donation and immune suppressing drugs. Whilst it is clear that iPSCs are rapidly becoming the lead cell type for research into cell replacement therapy and body organ transplantation strategies in humans, it is not known whether (1 such transplants will stimulate host immune responses; and (2 whether this technology will be capable of the bioengineering of a complete and fully functional human organ. This review will not focus on reprogramming to iPSCs, of which a plethora of reviews can be found, but instead focus on the latest developments in direct reprogramming of cells, the bioengineering of body organs from iPSCs, and an analysis of the immune response induced by i

  14. Impact of electronic health record (EHR) reminder on human papillomavirus (HPV) vaccine initiation and timely completion (United States)

    Ruffin, Mack T.; Plegue, Melissa A.; Rockwell, Pamela G.; Young, Alisa P.; Patel, Divya A.; Yeazel, Mark W.


    Background Initiation and timely completion of the HPV vaccine in young women is critical. We compared initiation and completion of HPV vaccine among women in two community-based networks with electronic health records: one with a prompt and reminder system (prompted cohort) and one without (unprompted cohort). Methods Female patients aged 9–26 years seen between March 1, 2007 and January 25, 2010 were used as retrospective cohorts. Patient demographics and vaccination dates were extracted from the electronic health record. Results Patients eligible for the vaccine included 6019 from the prompted cohort and 9096 from the unprompted cohort. Mean age at initiation was 17.3 years in prompted cohort and 18.1 years at unprompted cohort with significantly more (p<0.001) patients initiating in the prompted cohort (34.9%) compared to the unprompted cohort (21.5%). African Americans age 9–18 years with three or more visits during the observation period were significantly more likely to initiate in the prompted cohort (p<0.001). Prompted cohort was significantly more (p<0.001) likely to complete the vaccine series timely compared to unprompted cohort. Conclusion More patients age 9–26 years initiated and timely completed the HPV vaccine series in clinics using an electronic health record system with prompts compared to clinics without prompts. PMID:25957365

  15. Optimization of Human NK Cell Manufacturing: Fully Automated Separation, Improved Ex Vivo Expansion Using IL-21 with Autologous Feeder Cells, and Generation of Anti-CD123-CAR-Expressing Effector Cells. (United States)

    Klöß, Stephan; Oberschmidt, Olaf; Morgan, Michael; Dahlke, Julia; Arseniev, Lubomir; Huppert, Volker; Granzin, Markus; Gardlowski, Tanja; Matthies, Nadine; Soltenborn, Stephanie; Schambach, Axel; Koehl, Ulrike


    The administration of ex vivo expanded natural killer (NK) cells as potential antitumor effector cells appears to be suitable for effector cell-based immunotherapies in high-risk cancer patients. However, good manufacturing practice (GMP)-compliant manufacturing of clinical-grade NK cells at sufficiently high numbers represents a great challenge. Therefore, previous expansion protocols for those effector cells were improved and optimized by using newly developed culture medium, interleukin (IL)-21, and autologous feeder cells (FCs). Separation of primary human NK cells (CD56 + CD3 - ) was carried out with the CliniMACS Prodigy ® in a single process, starting with approximately 1.2 × 10 9 leukocytes collected by small-scale lymphapheresis or from buffy coats. Enriched NK cells were adjusted to starting cell concentrations within approximately 1 × 10 6 effector cells/mL and cultured in comparative expansion experiments for 14 days with IL-2 (1,000 IU/mL) in different GMP-compliant media (X-VIVO ™ 10, CellGro ® , TexMACS ™ , and NK MACS ® ). After medium optimization, beneficial effects for functionality and phenotype were investigated at the beginning of cell expansion with irradiated (25 Gy) autologous FCs at a ratio of 20:1 (feeder: NK) in the presence or absence of IL-21 (100 ng/mL). Additionally, expanded NK cells were gene modified to express chimeric antigen receptors (CARs) against CD123, a common marker for acute myeloid leukemia (AML). Cytotoxicity, degranulation, and cytokine release of transduced NK cells were determined against KG1a cells in flow cytometric analysis and fluorescent imaging. The Prodigy manufacturing process revealed high target cell viabilities (median 95.4%), adequate NK cell recovery (median 60.4%), and purity of 95.4% in regard to CD56 + CD3 - target cells. The process in its early phase of development led to a median T-cell depletion of log 3.5 after CD3 depletion and log 3.6 after the whole process, including CD3

  16. Recombinant human platelet-derived growth factor-BB versus autologous bone graft in foot and ankle fusion: A systematic review and meta-analysis. (United States)

    Sun, Han; Lu, Pei-Pei; Zhou, Ping-Hui; Sun, Si-Wei; Zhang, Hong-Tao; Liu, Yi-Jie; Yang, Xu; Shen, Xiao-Feng; Yang, Hui-Lin


    Today, autogenous bone graft (ABG) is still considered as the gold standard for joint fusion. Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) which is of chemotactic and mitogenic to mesenchymal stem cells and possesses outstanding osteogenetic potentials has been used for ankle and foot fusion in recent years. The goal of this article is to evaluate the safety and efficacy of rhPDGF-BB versus ABG in foot and ankle fusion. The PubMed MEDLINE, EMBASE, Web of Science, and Cochrane Library were systematic searched. Finally, three randomized controlled trials (RCTs) with 634 patients were enrolled in this study. Results of radiologic effectiveness which included CT and radiographic union rates revealed that there was no significant difference between rhPDGF-BB approach and ABG approach. Analysis of clinical results held the same outcomes expect that ABG group was superior in long-term Short Form-12 physical component scores. The pooled results also demonstrated that rhPDGF-BB was as safe as ABG in foot and ankle surgery. However, autograft harvesting procedure has some drawbacks such as donor-site pain and morbidity, additional operation time, blood loss, and scarring, which can be overcome by rhPDGF-BB. Thus, rhPDGF-BB is a viable alternative to autograft in foot and ankle fusion surgery. Yet, more high-quality RCTs with long-term follow-up are still required to make the final conclusion. Copyright © 2016 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  17. On random field Completely Automated Public Turing Test to Tell Computers and Humans Apart generation. (United States)

    Kouritzin, Michael A; Newton, Fraser; Wu, Biao


    Herein, we propose generating CAPTCHAs through random field simulation and give a novel, effective and efficient algorithm to do so. Indeed, we demonstrate that sufficient information about word tests for easy human recognition is contained in the site marginal probabilities and the site-to-nearby-site covariances and that these quantities can be embedded directly into certain conditional probabilities, designed for effective simulation. The CAPTCHAs are then partial random realizations of the random CAPTCHA word. We start with an initial random field (e.g., randomly scattered letter pieces) and use Gibbs resampling to re-simulate portions of the field repeatedly using these conditional probabilities until the word becomes human-readable. The residual randomness from the initial random field together with the random implementation of the CAPTCHA word provide significant resistance to attack. This results in a CAPTCHA, which is unrecognizable to modern optical character recognition but is recognized about 95% of the time in a human readability study.

  18. Coursera's Introductory Human Physiology Course: Factors That Characterize Successful Completion of a MOOC (United States)

    Engle, Deborah; Mankoff, Chris; Carbrey, Jennifer


    Since Massive Open Online Courses (MOOCs) are accessible by anyone in the world at no cost, they have large enrollments that are conducive to educational research. This study examines students in the Coursera MOOC, Introductory Human Physiology. Of the 33,378 students who accessed the course, around 15,000 students responded to items on the…

  19. 77 FR 68825 - Notice of Inventory Completion for Native American Human Remains and Associated Funerary Objects... (United States)


    ... Casa Grande Ruins National Monument, National Park Service, Coolidge, AZ; Correction AGENCY: National... Interior, National Park Service, Casa Grande Ruins National Monument, Coolidge, AZ. The human remains and... notice are the sole responsibility of the Superintendent, Casa Grande Ruins National Monument. This...

  20. Clinical Allogeneic and Autologous Islet Cell Transplantation: Update

    Directory of Open Access Journals (Sweden)

    Shinichi Matsumoto


    Full Text Available Islet cell transplantation is categorized as a β-cell replacement therapy for diabetic patients who lack the ability to secrete insulin. Allogeneic islet cell transplantation is for the treatment of type 1 diabetes, and autologous islet cell transplantation is for the prevention of surgical diabetes after a total pancreatectomy. The issues of allogeneic islet cell transplantation include poor efficacy of islet isolation, the need for multiple donor pancreata, difficulty maintaining insulin independence and undesirable side effects of immunosuppressive drugs. Those issues have been solved step by step and allogeneic islet cell transplantation is almost ready to be the standard therapy. The donor shortage will be the next issue and marginal and/or living donor islet cell transplantation might alleviate the issue. Xeno-islet cell transplantation, β-cell regeneration from human stem cells and gene induction of the naïve pancreas represent the next generation of β-cell replacement therapy. Autologous islet cell transplantation after total pancreatectomy for the treatment of chronic pancreatitis with severe abdominal pain is the standard therapy, even though only limited centers are able to perform this treatment. Remote center autologous islet cell transplantation is an attractive option for hospitals performing total pancreatectomies without the proper islet isolation facilities.


    Directory of Open Access Journals (Sweden)

    Giuseppe Visani


    Full Text Available The role of high-dose therapy (HDT followed by autologous stem cell transplantation (ASCT in the treatment armamentarium of aggressive B- and T-cell non-Hodgkin lymphoma (NHL is still a matter of debate. In the pre-Rituximab era, the PARMA study demonstrated the superiority of HDT/ASCT over conventional salvage chemotherapy in chemosensitive, relapsed patients. Subsequently, HDT/ASCT has become a standard approach for relapsed NHL. With the advent of Rituximab in the landscape of NHL, transplantation as part of first-line therapy has been challenged. However, no benefit in terms of disease-free or overall survival of HDT/ASCT over standard therapy was shown when Rituximab was added to both arms. Moreover, the superiority of HDT/ASCT over conventional salvage therapy in patients relapsing from first-line therapy including Rituximab was not confirmed. From these disappointing results, novel strategies, which can enhance the anti-lymphoma effect, at the same time reducing toxicity have been developed, with the aim of improving the outcome of HDT/ASCT in aggressive NHL. In T-cell lymphoma, few publications demonstrated that consolidation of complete remission with HDT/ASCT is safe and feasible. However, up to one-third of patients may never receive transplant, mostly due to progressive disease, and relapse still remains a major concern even after transplant.

  2. Clinical outcomes of repeat autologous cultivated limbal epithelial transplantation for ocular surface burns. (United States)

    Basu, Sayan; Ali, Hasnat; Sangwan, Virender S


    To report the clinical outcomes of repeat autologous cultivated limbal epithelial transplantation in patients with recurrence of limbal stem cell deficiency after a failed primary procedure. Retrospective case series. This study included 50 patients, above 8 years of age, with clinically diagnosed unilateral limbal stem cell deficiency following ocular surface burns, treated between 2001 and 2010. Following failure of primary surgery all patients underwent a repeat limbal biopsy from the unaffected eye. The limbal cells were expanded ex vivo on a human amniotic membrane substrate for 10 to 14 days using a completely xeno-free explant culture technique. The resulting cultured epithelial monolayer and amniotic membrane were transplanted onto the patient's affected eye. All patients underwent a comprehensive ophthalmic examination of both eyes at every follow-up visit. Postoperative corneal surface stability, change in visual acuity, and complications were objectively analyzed. At a mean follow-up of 2.3±1.4 (median: 1.96, range: 1 to 7.5) years, 33 of the 50 recipient eyes (66%) maintained a completely epithelialized, avascular, and clinically stable corneal surface. A 2-line improvement in visual acuity was seen in 38 of the 50 recipient eyes (76%). None of the donor eyes developed any clinical features of ocular surface disease, conjunctival overgrowth of the donor site, or decrease in vision throughout the follow-up period. Repeat autologous cultivated limbal epithelial transplantation successfully restores corneal epithelial stability and improves vision in eyes with recurrence of limbal stem cell deficiency, following failed primary surgery for ocular burns, without adversely affecting donor eyes. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Autologous serum therapy in chronic urticaria

    Directory of Open Access Journals (Sweden)

    Sharmila Patil


    Full Text Available Autologous serum therapy is a promising therapy for treatment resistant urticaria. This is useful in developing countries as this is economical option. Minimum instruments like centrifuge, syringe and needles are required for the procedure.

  4. Intraurethral Injection of Autologous Minced Skeletal Muscle

    DEFF Research Database (Denmark)

    Gräs, Søren; Klarskov, Niels; Lose, Gunnar


    PURPOSE: Intraurethral injection of in vitro expanded autologous skeletal muscle derived cells is a new regenerative therapy for stress urinary incontinence. We examined the efficacy and safety of a simpler alternative strategy using freshly harvested, minced autologous skeletal muscle tissue...... with its inherent content of regenerative cells. MATERIALS AND METHODS: A total of 20 and 15 women with uncomplicated and complicated stress urinary incontinence, respectively, received intraurethral injections of minced autologous skeletal muscle tissue and were followed for 1 year. Efficacy was assessed...... noted. CONCLUSIONS: Intraurethral injection of minced autologous muscle tissue is a simple surgical procedure that appears safe and moderately effective in women with uncomplicated stress urinary incontinence. It compares well to a more complicated regenerative strategy using in vitro expanded muscle...

  5. Human papillomavirus type 70 genome cloned from overlapping PCR products: complete nucleotide sequence and genomic organization.


    Forslund, O; Hansson, B G


    The genome of human papillomavirus (HPV) type 70 (HPV 70), isolated from a cervical condyloma, was obtained by cloning overlapping PCR products. By automated DNA sequence analysis, the genome was found to consist of 7,905 bp with a G + C content of 40%. The genomic organization showed the characteristic features shared by other sequenced HPVs. Nucleotide sequence comparison with previously known HPV types demonstrated the closest homology with HPV 68 (82%), HPV 39 (82%), HPV 18 (70%), HPV 45 ...

  6. Angiomyeloproliferative Lesions Following Autologous Stem Cell Therapy


    Thirabanjasak, Duangpen; Tantiwongse, Kavirach; Thorner, Paul Scott


    Some reports suggest that autologous hematopoietic stem cell transplantation holds potential for treatment of renal diseases such as lupus nephritis, but the safety of delivering various stem cell types (hematopoietic, mesenchymal, and endothelial precursors) is not well established. Here, we report a case of lupus nephritis treated by direct renal injection of autologous stem cells recovered from peripheral blood. The patient developed masses at the sites of injection and hematuria. We suspe...

  7. The product of the imprinted gene IPL marks human villous cytotrophoblast and is lost in complete hydatidiform mole. (United States)

    Saxena, A; Frank, D; Panichkul, P; Van den Veyver, I B; Tycko, B; Thaker, H


    The IPL/TSSC3 gene is expressed nearly exclusively from the maternal allele, and its protein product acts to limit placental growth in mice. This protein specifically marks Type II trophoblast in the labyrinthine layer of the mouse placenta. To investigate mouse-human homologies, we carried out immunohistochemistry with antibodies against human IPL. There was strong expression of IPL in villous cytotrophoblast of the human placenta, contrasting with complete lack of expression in syncytiotrophoblast. Staining for IPL was weak in cells of the villous mesenchyme and extravillous trophoblast, including the cytotrophoblast columns in the basal plate and the intervillous trophoblast islands. The IPL and p57(KIP2)/CDKN1C genes are closely linked and coordinately imprinted, and immunostaining showed that their protein products are co-expressed in villous cytotrophoblast. However, other cell types, including extravillous cytotrophoblast and cells in various non-placental tissues, expressed p57(KIP2), but not IPL. IPL protein was absent in both of two cases of androgenetic complete hydatidiform mole examined by immunostaining, and IPL mRNA was absent in an additional three cases of this neoplasm examined by northern blotting. In the mouse, Ipl-expressing cells disappear at mid- to late-gestation when placental growth ceases, but persistent IPL mRNA and protein expression was observed throughout human gestation, correlating with the continuous growth of the human placenta. These findings highlight dosage regulation of human IPL by imprinting and, more generally, suggest homology between Type II labyrinthine trophoblast in the mouse and villous cytotrophoblast in humans, both of which are proliferative stem cell-like compartments.

  8. Complete fold annotation of the human proteome using a novel structural feature space. (United States)

    Middleton, Sarah A; Illuminati, Joseph; Kim, Junhyong


    Recognition of protein structural fold is the starting point for many structure prediction tools and protein function inference. Fold prediction is computationally demanding and recognizing novel folds is difficult such that the majority of proteins have not been annotated for fold classification. Here we describe a new machine learning approach using a novel feature space that can be used for accurate recognition of all 1,221 currently known folds and inference of unknown novel folds. We show that our method achieves better than 94% accuracy even when many folds have only one training example. We demonstrate the utility of this method by predicting the folds of 34,330 human protein domains and showing that these predictions can yield useful insights into potential biological function, such as prediction of RNA-binding ability. Our method can be applied to de novo fold prediction of entire proteomes and identify candidate novel fold families.

  9. Complete fold annotation of the human proteome using a novel structural feature space (United States)

    Middleton, Sarah A.; Illuminati, Joseph; Kim, Junhyong


    Recognition of protein structural fold is the starting point for many structure prediction tools and protein function inference. Fold prediction is computationally demanding and recognizing novel folds is difficult such that the majority of proteins have not been annotated for fold classification. Here we describe a new machine learning approach using a novel feature space that can be used for accurate recognition of all 1,221 currently known folds and inference of unknown novel folds. We show that our method achieves better than 94% accuracy even when many folds have only one training example. We demonstrate the utility of this method by predicting the folds of 34,330 human protein domains and showing that these predictions can yield useful insights into potential biological function, such as prediction of RNA-binding ability. Our method can be applied to de novo fold prediction of entire proteomes and identify candidate novel fold families.

  10. Complete and unidirectional conversion of human embryonic stem cells to trophoblast by BMP4. (United States)

    Amita, Mitsuyoshi; Adachi, Katsuyuki; Alexenko, Andrei P; Sinha, Sunilima; Schust, Danny J; Schulz, Laura C; Roberts, R Michael; Ezashi, Toshihiko


    Human ES cells (hESC) exposed to bone morphogenic protein 4 (BMP4) in the absence of FGF2 have become widely used for studying trophoblast development, but the soundness of this model has been challenged by others, who concluded that differentiation was primarily toward mesoderm rather than trophoblast. Here we confirm that hESC grown under the standard conditions on a medium conditioned by mouse embryonic fibroblasts in the presence of BMP4 and absence of FGF2 on a Matrigel substratum rapidly convert to an epithelium that is largely KRT7(+) within 48 h, with minimal expression of mesoderm markers, including T (Brachyury). Instead, they begin to express a series of trophoblast markers, including HLA-G, demonstrate invasive properties that are independent of the continued presence of BMP4 in the medium, and, over time, produce extensive amounts of human chorionic gonadotropin, progesterone, placental growth factor, and placental lactogen. This process of differentiation is not dependent on conditioning of the medium by mouse embryonic fibroblasts and is accelerated in the presence of inhibitors of Activin and FGF2 signaling, which at day 2 provide colonies that are entirely KRT7(+) and in which the majority of cells are transiently CDX2(+). Colonies grown on two chemically defined media, including the one in which BMP4 was reported to drive mesoderm formation, also differentiate at least partially to trophoblast in response to BMP4. The experiments demonstrate that the in vitro BMP4/hESC model is valid for studying the emergence and differentiation of trophoblasts.

  11. Induction of complete and incomplete chromosome aberrations by bleomycin in human lymphocytes

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    Benkhaled, L.; Xuncla, M.; Caballin, M.R. [Universitat Autonoma de Barcelona, Unitat d' Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, E-08193 Bellaterra (Spain); Barrios, L. [Universitat Autonoma de Barcelona, Unitat de Biologia Cel.lular, Departament de Biologia Cel.lular, Fisiologia i Immunologia (Spain); Barquinero, J.F. [Universitat Autonoma de Barcelona, Unitat d' Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, E-08193 Bellaterra (Spain)], E-mail:


    Bleomycin (BLM) is a clastogenic compound, which due to the overdispersion in the cell distribution of induced dicentrics has been compared to the effect of high-LET radiation. Recently, it has been described that in fibroblast derived cell lines BLM induces incomplete chromosome elements more efficiently than any type of ionizing radiation. The objective of the present study was to evaluate in human lymphocytes the induction of dicentrics and incomplete chromosome elements by BLM. Peripheral blood samples have been treated with different concentrations of BLM. Two cytogenetic techniques were applied, fluorescence plus Giemsa (FPG) and FISH using pan-centromeric and pan-telomeric probes. The observed frequency of dicentric equivalents increases linearly with the BLM concentration, and for all BLM concentrations the distribution of dicentric equivalents was overdispersed. In the FISH study the ratio between total incomplete elements and multicentrics was 0.27. The overdispersion in the dicentric cell distribution, and the linear BLM-concentration dependence of dicentrics can be compared to the effect of high-LET radiation, on the contrary the ratio of incomplete elements and multicentrics is similar to the one induced by low-LET radiation ({approx}0.40). The elevated proportion of interstitial deletions in relation to total acentric fragments, higher than any type of ionizing radiation could be a characteristic signature of the clastogenic effect of BLM.


    NARCIS (Netherlands)


    A method was developed to obtain rapid endothelialization of a fabric vascular prosthesis by seeding autologous venous tissue fragments into its wall. In an animal study, complete endothelialization was observed in the entire inner surface of the prosthesis within 2 weeks after implantation. A piece

  13. Postoperative Autologous Reinfusion in Total Knee Replacement

    Directory of Open Access Journals (Sweden)

    A. Crescibene


    Full Text Available Surgeries for total knee replacement (TKR are increasing and in this context there is a need to develop new protocols for management and use of blood transfusion therapy. Autologous blood reduces the need for allogeneic blood transfusion and the aim of the present study was to verify the safety and the clinical efficacy. An observational retrospective study has been conducted on 124 patients, undergoing cemented total knee prosthesis replacement. Observed population was stratified into two groups: the first group received reinfusion of autologous blood collected in the postoperative surgery and the second group did not receive autologous blood reinfusion. Analysis of data shows that patients undergoing autologous blood reinfusion received less homologous blood bags (10.6% versus 30%; p=0.08 and reduced days of hospitalization (7.88 ± 0.7 days versus 8.96 ± 2.47 days for the control group; p=0.03. Microbiological tests were negative in all postoperatively salvaged and reinfused units. Our results emphasize the effectiveness of this procedure and have the characteristics of simplicity, low cost (€97.53 versus €103.79; p<0.01, and easy reproducibility. Use of autologous drainage system postoperatively is a procedure that allows reducing transfusion of homologous blood bags in patients undergoing TKR.

  14. Transabdominal sacrocolpopexy with autologous rectus fascia graft. (United States)

    Abraham, Nitya; Quirouet, Adrienne; Goldman, Howard B


    Extrusion and infection are potential postoperative complications when using synthetic mesh for abdominal sacrocolpopexy. Long-term follow-up in the Colpopexy and Urinary Reduction Efforts (CARE) trial revealed an estimated 9.9 % risk of mesh extrusion. There are 26 reports of spondylodiscitis after sacrocolpopexy with synthetic mesh. These surgical risks may be decreased by using autologous fascia. To date, there have been no reports of extrusion or spondylodiscitis after using autologous fascia for sacrocolpopexy. This video demonstrates transabdominal sacrocolpopexy with an autologous rectus fascia graft. A 76-year-old woman with symptomatic stage 3 prolapse also had a history of diverticulitis and sigmoid abscess requiring sigmoid colectomy with end colostomy and incidental left ureteral transection with subsequent left nephrostomy tube placement. She presented for colostomy reversal, ureteral reimplantation, and prolapse repair. Given the need for concomitant colon and ureteral reconstruction, the risk of infection was potentially higher if synthetic mesh were used. The patient therefore underwent transabdominal sacrocolpopexy with autologous rectus fascia graft. At 4 months' follow-up the patient reported resolution of her symptoms and on examination she had no pelvic organ prolapse. Transabdominal sacrocolpopexy using autologous rectus fascia graft is a feasible option, especially in cases in which infection and synthetic mesh extrusion risks are potentially higher.

  15. Autologous serum therapy in chronic urticaria: Old wine in a new bottle

    Directory of Open Access Journals (Sweden)

    Bajaj A


    Full Text Available Background: Chronic urticaria (CU is one of the most challenging and frustrating therapeutic problems faced by a dermatologist. A recent demonstration of abnormal type 1 reactions to intradermal autologous serum injections in some CU patients has led to the characterization of a new subgroup of "autoimmune chronic urticaria". This has rekindled interest in the age-old practice of autologous blood injections as a theoretically sound treatment option in these patients. Aims: To evaluate the efficacy of repeated autologous serum injections (ASIs in patients with recalcitrant chronic urticaria. Methods: A cohort of 62 (32 females CU patients with a positive autologous serum skin test (ASST (group 1 was prospectively analyzed for the efficacy of nine consecutive weekly autologous serum injections with a postintervention follow-up of 12 weeks. Another group of 13 (seven females CU patients with negative ASST (group 2 was also treated similarly. In both groups, six separate parameters of disease severity and activity were recorded. Results: Demographic and disease variables were comparable in both groups. The mean duration of disease was 1.9 ± 0.3 years (range = 3 months to 32 years in group 1 and 1.5 ± 0.2 years (range = 3 months to 10 years in group 2. In the ASST (+ group, 35.5% patients were completely asymptomatic at the end of the follow-up while an additional 24.2% were markedly improved. In the ASST (− group, these figures were 23 and 23% respectively. The intergroup difference for complete subsidence was statistically significant (P < 0.05. In both groups, the most marked reduction was seen in pruritus and antihistamine use scores followed by the size and frequency of the wheals. Conclusion: Autologous serum therapy is effective in a significant proportion of ASST (+ patients with CU. A smaller but still substantial number of ASST (− patients also benefited from this treatment.

  16. Endothelial cell loss after autologous rotational keratoplasty. (United States)

    Birnbaum, Florian; Reinhard, Thomas; Böhringer, Daniel; Sundmacher, Rainer


    To investigate whether it may be possible to ascertain the influence of immunological factors on chronic endothelial cell loss by comparing chronic endothelial cell loss after autologous rotational penetrating keratoplasty and after homologous penetrating keratoplasty. For six patients who had undergone autologous rotational penetrating keratoplasty the relative annual loss of endothelial cells was calculated by means of an exponential regression analysis. The findings were compared with those in a homogeneous historical control group (53 patients undergoing homologous penetrating keratoplasty for keratoconus). After autologous rotational keratoplasty relative annual loss of endothelial cells was 1.1%+/-2.6% (mean +/- standard deviation). Relative annual loss of endothelial cells in the control-group was 16.7%+/-20.8%. The results of the study lead to the assumption that immunological influences might be the main cause for chronic endothelial cell loss after homologous penetrating keratoplasty.

  17. Autologous conjunctival resurfacing of leaking filtering blebs. (United States)

    Harris, L D; Yang, G; Feldman, R M; Fellman, R L; Starita, R J; Lynn, J; Chuang, A Z


    To present a case series of a new technique to repair late bleb leaks. Retrospective, noncomparative, consecutive case series. Forty-seven autologous conjunctival resurfacings of late bleb leaks were performed by four surgeons at two institutions. Autologous conjunctival grafts were placed over existing de-epithelialized leaking blebs. Leak-free, Seidel-negative blebs and controlled glaucoma. After a mean follow-up of 14 +/- 12 months, one patient continued to have bleb leak at the last follow-up, and one frank leak resolved with aqueous suppression. Intraocular pressure increased from 6.6 +/- 4.4 mmHg (0.13 glaucoma medications) to 11.9 +/- 4.1 mmHg (0.41 glaucoma medications). Conjunctival resurfacing with autologous tissue is an effective technique to repair late bleb leaks.

  18. The utilization of animal product-free media and autologous serum in an autologous dermal substitute culture. (United States)

    Morimoto, Naoki; Takemoto, Satoru; Kanda, Norikazu; Ayvazyan, Artem; Taira, M Tsuguyoshi; Suzuki, Shigehiko


    Cultured dermal substitutes are used for the treatment of skin ulcers. However, the biological risks of fetal bovine serum (FBS) in the culture process have been reported. The use of the patient's autologous serum (AS) is another possibility, but the amount available is limited. In this study, we examined whether animal product-free media (HFDM-1) supplemented with 2% AS could support the growth of autologous fibroblasts in primary culture and their dissemination to dermal substitutes. We cultured autologous fibroblasts using HFDM-1 with 2% AS, Dulbecco's modified eagle medium (DMEM) with 10% FBS, and DMEM with 10% human serum (HS). Then, we disseminated and cultured the cells for 10 d. The fibroblast proliferation and concentrations of vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGF-β1) in each medium, as well as the deposition of human type I collagen into dermal substitutes were examined. The number of fibroblasts cultured in HFDM-1 with AS was highest. After seeding, the number of fibroblasts cultured in DMEM with HS was higher than those in DMEM with FBS and HFDM-1 with AS, but no significant difference was found between these two media. The VEGF concentration in DMEM with HS was also larger, but no significant difference was found between two other media. No significant difference was observed in TGF-β1 concentration or the deposition of collagen. This study shows that HFDM-1 with 2% AS can be used to produce cultured dermal substitutes instead of DMEM with 10% FBS. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Autologous limbus conjunctival flap transplantation for pterygium accompaniedwith conjunctival cyst

    Directory of Open Access Journals (Sweden)

    Jin-Hua Wang


    Full Text Available AIM: To observe the efficacy of surgical excision combined with autologous limbus conjunctival flap transplantation in the treatment of pterygium accompanied with conjunctival cyst. METHODS: Totally 126 patients 188 eyes with pterygium were hospitalized in Department of Ophthalmology of Tongji Hospital of Huazhong University of Science and Technology during August 2013 and August 2015. The patients were divided into two groups: observation group(11 eyes of 11 patientswith pterygium accompanied with conjunctival cyst and control group(177 eyes of 115 patientswith primary pterygium. All patients underwent slit lamp microscope examination, anterior segment photography, and anterior segment optical coherence tomography(OCT. The size of pterygium was calculated by multiplying neck width and length of the covered corneal. All patients underwent excision combined with autologous conjunctival flap transplantation, and the resections were performed pathological section with hematoxylin and eosin staining. All patients were followed up postoperatively for 4-28mo. RESULTS: All cases in the observation group were confirmed by postoperative pathological examination. All cyst walls were complete, and containing single layer of epithelial cells. The mean size of pterygium of the observation group was 6.9±1.7mm2, and 6.3±1.8mm2 for the control group. There was no significant difference between the two groups(P>0.05. The mean postoperative healing time of observation group was 2.1±0.9d, and 1.9±0.8d for the control group. There was no significant difference between the two groups(P>0.05. Recurrence was seen in two eyes within the follow-up period in the control group, and no recurrence in the observation group. CONCLUSION: Surgical excision combined with autologous limbus conjunctival flap transplantation is a safe and effective treatment for pterygium accompanied with conjunctival cyst.

  20. Autologous fibrin adhesive in experimental tubal anastomosis. (United States)

    Rajaram, S; Rusia, U; Agarwal, S; Agarwal, N


    To evaluate autologous fibrin in rabbit oviduct anastomosis versus 7-0 vikryl, a conventional suture material used in tubal anastomosis. Thrombin was added to the autologous fibrinogen at the site of anastomosis to obtain a tissue adhesive. The anastomotic time, pregnancy rate, and litter size were evaluated. Three months later, a relaparotomy was done to evaluate patency and degree of adhesions, and a tubal biopsy was taken from the site of anastomosis. Analysis of results showed a statistically significant (P < .001) shortened anastomotic time and superior histopathological union in the tissue adhesive group. Patency rate, pregnancy rate, and degree of adhesions were comparable in both groups.

  1. Autologous blood transfusion - a review | Charles | South African ...

    African Journals Online (AJOL)

    The discovery of HIV and other transfusion-transmissible infections has increased the demand for alternatives to allogeneic blood transfusion. One such alternative is autologous transfusion. This review presents an analysis of autologous transfusion. We conclude that autologous transfusion should form part of a strategy to ...

  2. Autologous Bone Marrow-Derived Cells Regenerate Urethral Sphincters. (United States)

    Imamura, Tetsuya; Ishizuka, Osamu; Nishizawa, Osamu


    Regenerative medicine based on tissue engineering and/or stem cell therapy techniques has the potential to improve irreversibly damaged tissues. Surgical injury to the lower urinary tract can occur as a result of radical prostatectomy or bladder neck surgery. Regeneration of urethral sphincters could be an effective treatment for post-surgical intrinsic sphincter deficiency (ISD)-related urinary incontinence. The replacement, enhancement, and/or recovery the urethral sphincter striated and smooth muscles could increase urethral closure pressure to help patients regain continence. Stem cells from muscle-derived satellite or adipose-derived mesenchymal cells provide temporary improvement in urethral closure pressure but do not reconstruct the muscle layer structures. Our strategy to accomplish regeneration of urethral sphincters is the utilization of autologous bone marrow-derived cells. We have developed a freeze injury model of ISD in rabbits. Freezing of the urinary sphincter causes loss of the majority of striated and smooth muscle cells, and causes a significant decrease in leak point pressure. In this review, we show that the autologous bone marrow-derived cells implanted within the freeze-injured sphincters differentiate into striated or smooth muscle cells. These cells then develop to reconstitute muscle layer structures within the sphincter. Furthermore, the leak point pressure of cell-implanted rabbits is significantly higher than that of cell-free injected controls. We conclude that implantation of autologous bone marrow-derived cells could be an effective treatment for human post-surgical ISD-related urinary incontinence. © 2012 Blackwell Publishing Asia Pty Ltd.

  3. Autologous serum eye drops diluted with sodium hyaluronate: clinical and experimental comparative study. (United States)

    López-García, José S; García-Lozano, Isabel; Rivas, Luis; Ramírez, Nuria; Raposo, Rafaela; Méndez, Maria T


    To assess the efficacy of sodium hyaluronate as vehicle for diluting autologous serum. The concentration and temporal stability of EGF, TGF-β, PDGF-AB and albumin in fresh and frozen samples of autologous serum diluted with sodium hyaluronate and saline solution, as well as the pH, osmolarity and density was studied. In parallel, the clinic effects of autologous serum diluted to 20% with sodium hyaluronate were compared with another solution of autologous serum diluted to 20% with saline in a prospective, comparative, randomized and double-blind study in 26 patients (52 eyes) with Sjögren syndrome. Patients underwent a complete ophthalmic assessment including tear film evaluation and corneal and conjunctival impression cytology at the beginning of the study and 2 months later. The growth factor (GF) concentration remained stable during 1 month at 4°C both in fresh and defrosted samples without any differences being found between both preparations. No differences were found related to osmolarity, pH and density between these preparations before and after frosting. Autologous serum diluted with sodium hyaluronate caused a significant improvement of the tear film stability, fluorescein and rose Bengal stain, break-up time, corneal and conjunctival squamous metaplasia as well as in the patient subjective perception. Sodium hyaluronate is an excellent vehicle for diluting autologous serum due to the gradual release of GF and increasing their duration and effect on the ocular surface. Preparations diluted with sodium hyaluronate are better tolerated by patients and require a lower number of drops administrations. © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  4. Cord Blood Banking Standards: Autologous Versus Altruistic. (United States)

    Armitage, Sue


    Cord blood (CB) is either donated to public CB banks for use by any patient worldwide for whom it is a match or stored in a private bank for potential autologous or family use. It is a unique cell product that has potential for treating life-threatening diseases. The majority of CB products used today are for hematopoietic stem cell transplantation and are accessed from public banks. CB is still evolving as a hematopoietic stem cell source, developing as a source for cellular immunotherapy products, such as natural killer, dendritic, and T-cells, and fast emerging as a non-hematopoietic stem cell source in the field of regenerative medicine. This review explores the regulations, standards, and accreditation schemes that are currently available nationally and internationally for public and private CB banking. Currently, most of private banking is under regulated as compared to public banking. Regulations and standards were initially developed to address the public arena. Early responses from the medical field regarding private CB banking was that at the present time, because of insufficient scientific data to support autologous banking and given the difficulty of making an accurate estimate of the need for autologous transplantation, private storage of CB as "biological insurance" should be discouraged (1, 2, 3). To ensure success and the true realization of the full potential of CB, whether for autologous or allogeneic use, it is essential that each and every product provided for current and future treatments meets high-quality, international standards.

  5. Cord Blood Banking Standards: Autologous Versus Altruistic (United States)

    Armitage, Sue


    Cord blood (CB) is either donated to public CB banks for use by any patient worldwide for whom it is a match or stored in a private bank for potential autologous or family use. It is a unique cell product that has potential for treating life-threatening diseases. The majority of CB products used today are for hematopoietic stem cell transplantation and are accessed from public banks. CB is still evolving as a hematopoietic stem cell source, developing as a source for cellular immunotherapy products, such as natural killer, dendritic, and T-cells, and fast emerging as a non-hematopoietic stem cell source in the field of regenerative medicine. This review explores the regulations, standards, and accreditation schemes that are currently available nationally and internationally for public and private CB banking. Currently, most of private banking is under regulated as compared to public banking. Regulations and standards were initially developed to address the public arena. Early responses from the medical field regarding private CB banking was that at the present time, because of insufficient scientific data to support autologous banking and given the difficulty of making an accurate estimate of the need for autologous transplantation, private storage of CB as “biological insurance” should be discouraged (1, 2, 3). To ensure success and the true realization of the full potential of CB, whether for autologous or allogeneic use, it is essential that each and every product provided for current and future treatments meets high-quality, international standards. PMID:26779485

  6. Sweet Syndrome After Autologous Stem Cell Transplant. (United States)

    Alkan, Ali; İdemen, Celal; Okçu Heper, Aylin; Utkan, Güngör


    Sweet syndrome (acute febrile neutrophilic dermatosis) is a rare clinical entity characterized by skin lesions, neutrophilia, fever, and neutrophilic infiltration of the dermis. It may be a consequence of malignant disease, comorbidities, or drugs. We present a case of acute febrile neutrophilic dermatosis in a patient after autologous stem cell transplant.

  7. Knowledge and Acceptance of Autologous Blood Transfusion.

    African Journals Online (AJOL)

    Background: Homologous blood transfusion carries a well-documented array of risks especially in an HIV endemic environment like Nigeria. It is therefore imperative to consider other forms of restoring blood volume in surgical patients. Autologous blood transfusion (ABT) is one of the ways the problem of HIV transmission ...

  8. Predonated autologous blood transfusion in elective orthopaedic ...

    African Journals Online (AJOL)

    Background: The use of homologous blood carries significant risk of viral infections and immune-mediated reactions. Preoperative autologous blood donation is an attractive alternative to homologous transfusion and has become common in elective orthopaedic surgery. Objective: To present our experience with the use of ...

  9. Specific Modifications to Contract Policy for Staff Members and Project Associates related to the Human Resources Plan and LHC Completion

    CERN Document Server


    As agreed at the Committee meetings last December, the Management hereby submits two specific proposals to adjust staff contract policy and a third concerning appointments of Project Associates, following indications given in the Human Resources Plan presented last December. These proposals are limited to changes which are urgently required for the implementation of the HR Plan and the completion of the LHC. Other aspects concerning contract policy, raised by Internal Task Force 4 last year, and in particular the policy and procedures governing the award of indefinite contracts, require more in-depth study on which the Management will report progress on the clarification of these wider policy issues later in the year to TREF. After discussion at TREF in February 2003, the Management hereby submits these proposals for approval by the Finance Committee (paragraph 2.1 below) and by the Council (paragraphs 2.2 and 3.1 below), for entry into force on 1 April 2003.

  10. Autologous Blood Injection and Wrist Immobilisation for Chronic Lateral Epicondylitis

    Directory of Open Access Journals (Sweden)

    Nicola Massy-Westropp


    Full Text Available Purpose. This study explored the effect of autologous blood injection (with ultrasound guidance to the elbows of patients who had radiologically assessed degeneration of the origin of extensor carpi radialis brevis and failed cortisone injection/s to the lateral epicondylitis. Methods. This prospective longitudinal series involved preinjection assessment of pain, grip strength, and function, using the patient-rated tennis elbow evaluation. Patients were injected with blood from the contralateral limb and then wore a customised wrist support for five days, after which they commenced a stretching, strengthening, and massage programme with an occupational therapist. These patients were assessed after six months and then finally between 18 months and five years after injection, using the patient-rated tennis elbow evaluation. Results. Thirty-eight of 40 patients completed the study, showing significant improvement in pain; the worst pain decreased by two to five points out of a 10-point visual analogue for pain. Self-perceived function improved by 11–25 points out of 100. Women showed significant increase in grip, but men did not. Conclusions. Autologous blood injection improved pain and function in a worker’s compensation cohort of patients with chronic lateral epicondylitis, who had not had relief with cortisone injection.

  11. Autologous Fat Grafting for Whole Breast Reconstruction

    Directory of Open Access Journals (Sweden)

    Benjamin H. L. Howes, MBBS


    Full Text Available Summary: This is the first reported case of a patient who had a single-stage large-volume breast reconstruction with autologous fat grafting, following rotation flap approach (RoFA mastectomy. The purpose of this case study was to evaluate the viability of reconstruction of the breast by autologous fat grafting alone, in the context of RoFA mastectomy. The hypothesis was that there would be minimal interval loss of autologous fat on the whole breast reconstruction side. Right RoFA mastectomy was used for resection of an invasive primary breast cancer and resulted in the right breast skin envelope. Eleven months later, the patient underwent grafting of 400 ml of autologous fat into the skin envelope and underlying pectoralis major muscle. Outcome was assessed by using a validated 3D laser scan technique for quantitative breast volume measurement. Other outcome measures included the BREAST-Q questionnaire and 2D clinical photography. At 12-month follow-up, the patient was observed to have maintenance of volume of the reconstructed breast. Her BREAST-Q scores were markedly improved compared with before fat grafting, and there was observable improvement in shape, contour, and symmetry on 2D clinical photography. The 2 new techniques, RoFA mastectomy and large-volume single-stage autologous fat grafting, were used in combination to achieve a satisfactory postmastectomy breast reconstruction. Novel tools for measurement of outcome were the 3D whole-body laser scanner and BREAST-Q questionnaire. This case demonstrates the potential for the use of fat grafting for reconstruction. Outcomes in a larger patient populations are needed to confirm these findings.

  12. Phenotype and polarization of autologous T cells by biomaterial-treated dendritic cells. (United States)

    Park, Jaehyung; Gerber, Michael H; Babensee, Julia E


    Given the central role of dendritic cells (DCs) in directing T-cell phenotypes, the ability of biomaterial-treated DCs to dictate autologous T-cell phenotype was investigated. In this study, we demonstrate that differentially biomaterial-treated DCs differentially directed autologous T-cell phenotype and polarization, depending on the biomaterial used to pretreat the DCs. Immature DCs (iDCs) were derived from human peripheral blood monocytes and treated with biomaterial films of alginate, agarose, chitosan, hyaluronic acid, or 75:25 poly(lactic-co-glycolic acid) (PLGA), followed by co-culture of these biomaterial-treated DCs and autologous T cells. When autologous T cells were co-cultured with DCs treated with biomaterial film/antigen (ovalbumin, OVA) combinations, different biomaterial films induced differential levels of T-cell marker (CD4, CD8, CD25, CD69) expression, as well as differential cytokine profiles [interferon (IFN)-γ, interleukin (IL)-12p70, IL-10, IL-4] in the polarization of T helper (Th) types. Dendritic cells treated with agarose films/OVA induced CD4+CD25+FoxP3+ (T regulatory cells) expression, comparable to untreated iDCs, on autologous T cells in the DC-T co-culture system. Furthermore, in this co-culture, agarose treatment induced release of IL-12p70 and IL-10 at higher levels as compared with DC treatment with other biomaterial films/OVA, suggesting Th1 and Th2 polarization, respectively. Dendritic cells treated with PLGA film/OVA treatment induced release of IFN-γ at higher levels compared with that observed for co-cultures with iDCs or DCs treated with all other biomaterial films. These results indicate that DC treatment with different biomaterial films has potential as a tool for immunomodulation by directing autologous T-cell responses. © 2014 Wiley Periodicals, Inc.

  13. Chronic Spinal Injury Repair by Olfactory Bulb Ensheathing Glia and Feasibility for Autologous Therapy (United States)

    Muñoz-Quiles, Cintia; Santos-Benito, Fernando F.; Llamusí, M. Beatriz; Ramón-Cueto, Almudena


    Olfactory bulb ensheathing glia (OB-OEG) promote repair of spinal cord injury (SCI) in rats after transplantation at acute or subacute (up to 45 days) stages. The most relevant clinical scenario in humans, however, is chronic SCI, in which no more major cellular or molecular changes occur at the injury site; this occurs after the third month in rodents. Whether adult OB-OEG grafts promote repair of severe chronic SCI has not been previously addressed. Rats with complete SCI that were transplanted with OB-OEG 4 months after injury exhibited progressive improvement in motor function and axonal regeneration from different brainstem nuclei across and beyond the SCI site. A positive correlation between motor outcome and axonal regeneration suggested a role for brainstem neurons in the recovery. Functional and histological outcomes did not differ at subacute or chronic stages. Thus, autologous transplantation is a feasible approach as there is time for patient stabilization and OEG preparation in human chronic SCI; the healing effects of OB-OEG on established injuries may offer new therapeutic opportunities for chronic SCI patients. PMID:19915486

  14. Clinician knowledge, clinician barriers, and perceived parental barriers regarding human papillomavirus vaccination: Association with initiation and completion rates. (United States)

    Rutten, Lila J Finney; St Sauver, Jennifer L; Beebe, Timothy J; Wilson, Patrick M; Jacobson, Debra J; Fan, Chun; Breitkopf, Carmen Radecki; Vadaparampil, Susan T; Jacobson, Robert M


    We tested the hypothesis that clinician knowledge, clinician barriers, and perceived parental barriers relevant to the human papillomavirus (HPV) vaccination account for the variation in vaccine delivery at the practice-site level. We conducted a survey from October 2015 through January 2016 among primary care clinicians (n=280) in a 27-county geographic region to assess clinician knowledge, clinician barriers, and perceived parental barriers regarding HPV vaccination. Primary care clinicians included family medicine physicians, general pediatricians, and family and pediatric nurse-practitioners. We also used the Rochester Epidemiology Project to measure HPV vaccination delivery. Specifically we used administrative data to measure receipt of at least one valid HPV vaccine dose (initiation) and receipt of three valid HPV vaccine doses (completion) among 9-18year old patients residing in the same 27-county geographic region. We assessed associations of clinician survey data with variation in vaccine delivery at the clinical site using administrative data on patients aged 9-18years (n=68,272). Consistent with our hypothesis, we found that greater knowledge of HPV and the HPV vaccination was associated with higher rates of HPV vaccination initiation (Incidence rate ratio [IRR]=1.05) and completion of three doses (IRR=1.28). We also found support for the hypothesis that greater perceived parental barriers to the HPV vaccination were associated with lower rates of initiation (IRR=0.94) and completion (IRR=0.90). These IRRs were statistically significant even after adjustment for site-level characteristics including percent white, percent female, percent ages 9-13, and percent with government insurance or self-pay at each site. Clinician knowledge and their report of the frequency of experiencing parental barriers are associated with HPV vaccine delivery rates-initiation and completion. Higher measures of knowledge correlated with higher rates. Fewer perceived occurrences


    Directory of Open Access Journals (Sweden)

    Syam Sunder B


    corticosteroid injection. MATERIALS AND METHODS A total of 120 patients who attended Orthopaedic OPD at Government General Hospital, Kakinada, during the time spanning January 2015 to December 2015, who were suffering from plantar fasciitis were randomly allocated either autologous blood injection or corticosteroid injection as treatment. Both groups were analysed with VAS and Nirschl pain staging at presentation, 1 st week, 4 th week, 12 th week and at six-month intervals. Results were tabulated and analysed statistically. All patients were treated on OPD basis. No inpatient care was needed in any patient. RESULTS In this study, slight male preponderance was seen in both the groups (53.33%. The mean in group A was 41.80±10.96 years and in group B the mean age was 40.68±10.47 years. Most of the patients in group A and B presented with right foot involvement (51.67% and 65.00%. The mean duration in group A was 10.88 weeks compared to 8.62 weeks in group B. The mean VAS scores at the beginning were comparable in both the groups (7.55±1.40 vs. 7.70±1.14. At fourth week, the mean VAS score in group A significantly reduced to 3.18±2.38 and at 12 weeks and six months to 0.3±1.37 suggesting significantly less pain in group A compared to group B. Similar trend of reduction among patients is group A was observed with Nirschl staging scores. No patient in group A reported complications and recurrence was not observed in patients with group A. CONCLUSION Based on the results of our present study, it maybe concluded that autologous blood injection significantly reduced the pain based on VAS and Nirschl staging without complications there by lowering the recurrence rate up to six months in patients with plantar fasciitis. It also provided complete relief of pain for the period of six months without any complication. Autologous blood is simple to acquire and prepare, easy to carry out. Hence, autologous blood provides intermediate and long-term results in term of pain relief when

  16. Comparative analyses of the complete mitochondrial genomes of Ascaris lumbricoides and Ascaris suum from humans and pigs. (United States)

    Liu, Guo-Hua; Wu, Chang-Yi; Song, Hui-Qun; Wei, Shu-Jun; Xu, Min-Jun; Lin, Rui-Qing; Zhao, Guang-Hui; Huang, Si-Yang; Zhu, Xing-Quan


    Ascaris lumbricoides and Ascaris suum are parasitic nematodes living in the small intestine of humans and pigs, and can cause the disease ascariasis. For long, there has been controversy as to whether the two ascaridoid taxa represent the same species due to their significant resemblances in morphology. However, the complete mitochondrial (mt) genome data have been lacking for A. lumbricoides in spite of human and animal health significance and socio-economic impact globally of these parasites. In the present study, we sequenced the complete mt genomes of A. lumbricoides and A. suum (China isolate), which was 14,303 bp and 14,311 bp in size, respectively. The identity of the mt genomes was 98.1% between A. lumbricoides and A. suum (China isolate), and 98.5% between A. suum (China isolate) and A. suum (USA isolate). Both genomes are circular, and consist of 36 genes, including 12 genes for proteins, 2 genes for rRNA and 22 genes for tRNA, which are consistent with that of all other species of ascaridoid studied to date. All genes are transcribed in the same direction and have a nucleotide composition high in A and T (71.7% for A. lumbricoides and 71.8% for A. suum). The AT bias had a significant effect on both the codon usage pattern and amino acid composition of proteins. Phylogenetic analyses of A. lumbricoides and A. suum using concatenated amino acid sequences of 12 protein-coding genes, with three different computational algorithms (Bayesian analysis, maximum likelihood and maximum parsimony) all clustered in a clade with high statistical support, indicating that A. lumbricoides and A. suum was very closely related. These mt genome data and the results provide some additional genetic evidence that A. lumbricoides and A. suum may represent the same species. The mt genome data presented in this study are also useful novel markers for studying the molecular epidemiology and population genetics of Ascaris. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Treatment of Recurrent Corneal Epithelial Defect by Autologous Serum Eye Drop

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    Hossein Mohammad Rabei


    Full Text Available Background: The aim of the present study was to evaluate the efficacy of autologous serum eye drop in treatment of recurrent corneal epithelial defect.Materials and Methods: Fourteen patients with recurrent corneal epithelial defect were studied. Autologous serum was prepared from the patients and diluted in 20% normal saline. The patients were instructed to use the autologous serum every six hours. Patients were followed for a mean period of 18 months.Results: Four males (28.6% and 10 females (71.4% entered the study. Four patients stopped the treatment after three months with complete satisfaction from treatment. Patients reported a reduction in frequency and severity of attacks 4.6±2 weeks after the start of treatment. The mean number of attacks before the procedure was 7.6±0.9 per year which was reduced to 2.2±0.9 per year after treatment (p<0.001. The main side effects in patients were eye pruritus and redness which were well tolerated by patients.Conclusion: Autologous serum application seems to be a safe and effective method to treat recurrent corneal epithelial defect.

  18. PD-1 pathway and its clinical application: A 20year journey after discovery of the complete human PD-1 gene. (United States)

    Berger, Kristin Nicole; Pu, Jeffrey Jiayu


    Anti-PD-1 therapy is a novel immune-checkpoint inhibition therapy with tremendous potential in treating refractory/relapsed cancers. The 20year journey of human PD-1 research went through 3 phases: 1) discovering PD-1 gene structure and genomic organization, 2) understanding the mechanism of PD-1 mediated immune-checkpoint regulatory effects in coordination with its ligands (PD-L1 and L2), 3) and translating our knowledge of PD-1 gene into a robust clinical anticancer approach by targeting the PD-1 immune-checkpoint pathway. The success of human PD-1 gene study reflects the advancement and trends of modern biomedical research from the laboratory to the bedside. However, our journey of understanding the PD-1 gene is not yet complete. Clinical investigation data show a high variety of response rates among different types of cancers to PD-1 immune-checkpoint inhibition therapy, with a range of 18% to 87%. There is no reliable biomarker to predict an individual patient's response to PD-1 inhibitory immunotherapy. Patients can present with primary, adaptive, or even acquired resistance to PD-1 immune-checkpoint inhibition therapy. Furthermore, the emerging data demonstrates that certain patients experience hyperprogressive disease status after receiving PD-1 immune-checkpoint inhibition therapy. In conclusion, PD-1 immune-checkpoint inhibition therapy has opened up a new venue of advanced cancer immunotherapy. Meanwhile, further efforts are still warranted in both basic scientific mechanism studies and clinical investigation using the principles of personalized and precision medicine. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Autologous Fat Grafting Improves Facial Nerve Function

    Directory of Open Access Journals (Sweden)

    Marco Klinger


    Full Text Available We describe the case of a 45-year-old male patient who presented a retractile and painful scar in the nasolabial fold due to trauma which determined partial motor impairment of the mouth movements. We subsequently treated him with autologous fat grafting according to Coleman’s technique. Clinical assessments were performed at 5 and 14 days and 1, 3, and 6 months after surgical procedure and we observed a progressive release of scar retraction together with an important improvement of pain symptoms. A second procedure was performed 6 months after the previous one. We observed total restoration of mimic movements within one-year follow-up. The case described confirms autologous fat grafting regenerative effect on scar tissue enlightening a possible therapeutic effect on peripheral nerve activity, hypothesizing that its entrapment into scar tissue can determine a partial loss of function.

  20. Complete genome of Phenylobacterium zucineum – a novel facultative intracellular bacterium isolated from human erythroleukemia cell line K562

    Directory of Open Access Journals (Sweden)

    Sun Jie


    Full Text Available Abstract Background Phenylobacterium zucineum is a recently identified facultative intracellular species isolated from the human leukemia cell line K562. Unlike the known intracellular pathogens, P. zucineum maintains a stable association with its host cell without affecting the growth and morphology of the latter. Results Here, we report the whole genome sequence of the type strain HLK1T. The genome consists of a circular chromosome (3,996,255 bp and a circular plasmid (382,976 bp. It encodes 3,861 putative proteins, 42 tRNAs, and a 16S-23S-5S rRNA operon. Comparative genomic analysis revealed that it is phylogenetically closest to Caulobacter crescentus, a model species for cell cycle research. Notably, P. zucineum has a gene that is strikingly similar, both structurally and functionally, to the cell cycle master regulator CtrA of C. crescentus, and most of the genes directly regulated by CtrA in the latter have orthologs in the former. Conclusion This work presents the first complete bacterial genome in the genus Phenylobacterium. Comparative genomic analysis indicated that the CtrA regulon is well conserved between C. crescentus and P. zucineum.

  1. Complete identification of proteins responsible for human blood plasma fouling on poly(ethylene glycol)-based surfaces. (United States)

    Riedel, Tomáš; Riedelová-Reicheltová, Zuzana; Májek, Pavel; Rodriguez-Emmenegger, César; Houska, Milan; Dyr, Jan E; Brynda, Eduard


    The resistance of poly(ethylene glycol) (PEG) against protein adsorption is crucial and has been widely utilized in various biomedical applications. In this work, the complete protein composition of biofilms deposited on PEG-based surfaces from human blood plasma (BP) was identified for the first time using nanoLC-MS/MS, a powerful tool in protein analysis. The mass of deposited BP and the number of different proteins contained in the deposits on individual surfaces decreased in the order of self-assembling monolayers of oligo(ethylene glycol) alkanethiolates (SAM) > poly(ethylene glycol) end-grafted onto a SAM > poly(oligo(ethylene glycol) methacrylate) brushes prepared by surface initiated polymerization (poly(OEGMA)). The BP deposit on the poly(OEGMA) surface was composed only of apolipoprotein A-I, apolipoprotein B-100, complement C3, complement C4-A, complement C4-B, histidine-rich glycoprotein, Ig mu chain C region, fibrinogen (Fbg), and serum albumin (HSA). The total resistance of the surface to the Fbg and HSA adsorption from single protein solutions suggested that their deposition from BP was mediated by some of the other proteins. Current theories of protein resistance are not sufficient to explain the observed plasma fouling. The research focused on the identified proteins, and the experimental approach used in this work can provide the basis for the understanding and rational design of plasma-resistant surfaces.

  2. Complete genome sequence analysis of Nocardia brasiliensis HUJEG-1 reveals a saprobic lifestyle and the genes needed for human pathogenesis.

    Directory of Open Access Journals (Sweden)

    Lucio Vera-Cabrera

    Full Text Available Nocardia brasiliensis is an important etiologic agent of mycetoma. These bacteria live as a saprobe in soil or organic material and enter the tissue via minor trauma. Mycetoma is characterized by tumefaction and the production of fistula and abscesses, with no spontaneous cure. By using mass sequencing, we determined the complete genomic nucleotide sequence of the bacteria. According to our data, the genome is a circular chromosome 9,436,348-bp long with 68% G+C content that encodes 8,414 proteins. We observed orthologs for virulence factors, a higher number of genes involved in lipid biosynthesis and catabolism, and gene clusters for the synthesis of bioactive compounds, such as antibiotics, terpenes, and polyketides. An in silico analysis of the sequence supports the conclusion that the bacteria acquired diverse genes by horizontal transfer from other soil bacteria, even from eukaryotic organisms. The genome composition reflects the evolution of bacteria via the acquisition of a large amount of DNA, which allows it to survive in new ecological niches, including humans.

  3. Complete genome sequence analysis of Nocardia brasiliensis HUJEG-1 reveals a saprobic lifestyle and the genes needed for human pathogenesis. (United States)

    Vera-Cabrera, Lucio; Ortiz-Lopez, Rocio; Elizondo-Gonzalez, Ramiro; Ocampo-Candiani, Jorge


    Nocardia brasiliensis is an important etiologic agent of mycetoma. These bacteria live as a saprobe in soil or organic material and enter the tissue via minor trauma. Mycetoma is characterized by tumefaction and the production of fistula and abscesses, with no spontaneous cure. By using mass sequencing, we determined the complete genomic nucleotide sequence of the bacteria. According to our data, the genome is a circular chromosome 9,436,348-bp long with 68% G+C content that encodes 8,414 proteins. We observed orthologs for virulence factors, a higher number of genes involved in lipid biosynthesis and catabolism, and gene clusters for the synthesis of bioactive compounds, such as antibiotics, terpenes, and polyketides. An in silico analysis of the sequence supports the conclusion that the bacteria acquired diverse genes by horizontal transfer from other soil bacteria, even from eukaryotic organisms. The genome composition reflects the evolution of bacteria via the acquisition of a large amount of DNA, which allows it to survive in new ecological niches, including humans.

  4. Complete Genome Sequence Analysis of Nocardia brasiliensis HUJEG-1 Reveals a Saprobic Lifestyle and the Genes Needed for Human Pathogenesis (United States)

    Vera-Cabrera, Lucio; Ortiz-Lopez, Rocio; Elizondo-Gonzalez, Ramiro; Ocampo-Candiani, Jorge


    Nocardia brasiliensis is an important etiologic agent of mycetoma. These bacteria live as a saprobe in soil or organic material and enter the tissue via minor trauma. Mycetoma is characterized by tumefaction and the production of fistula and abscesses, with no spontaneous cure. By using mass sequencing, we determined the complete genomic nucleotide sequence of the bacteria. According to our data, the genome is a circular chromosome 9,436,348-bp long with 68% G+C content that encodes 8,414 proteins. We observed orthologs for virulence factors, a higher number of genes involved in lipid biosynthesis and catabolism, and gene clusters for the synthesis of bioactive compounds, such as antibiotics, terpenes, and polyketides. An in silico analysis of the sequence supports the conclusion that the bacteria acquired diverse genes by horizontal transfer from other soil bacteria, even from eukaryotic organisms. The genome composition reflects the evolution of bacteria via the acquisition of a large amount of DNA, which allows it to survive in new ecological niches, including humans. PMID:23755230

  5. Effects of complement inactivation and IgG depletion on skin reactivity to autologous serum in chronic idiopathic urticaria. (United States)

    Fagiolo, U; Kricek, F; Ruf, C; Peserico, A; Amadori, A; Cancian, M


    Intradermal injection of autologous serum elicits a wheal-and-flare response in about 60% of patients with chronic idiopathic urticaria (CIU). This reactivity has been attributed to the presence of IgG autoantibodies directed against IgE or the alpha-chain of the high-affinity IgE receptor (FcepsilonRIalpha) expressed on basophils and mast cells, leading to the hypothesis that at least some forms of CIU could be sustained by an autoimmune process. The aim of this study was to investigate the relationship between the presence of anti-IgE or anti-FcepsilonRI antibodies and the ability to induce wheal-and-flare responses in CIU sera selected for the capacity to give a positive skin test response. Fifteen patients with CIU and a positive skin test response to autologous serum were injected intradermally with native serum and with serum heated at 56 degrees C for 30 minutes and then adsorbed on Sepharose-protein G to obtain IgG depletion. Serum levels of anti-IgE and anti-FcepsilonRIalpha antibodies were measured by ELISA by using purified IgE and recombinant RIalpha-soluble double-fusion protein RIalpha-human serum albumin-RIalpha, respectively. The histamine-releasing activity of sera was tested by using ELISA with whole human blood from a healthy donor. All patients had positive cutaneous responses to native serum injection. Anti-FcepsilonRIalpha antibodies were present in 14 of 15 native sera, only two of which were able to induce in vitro basophil degranulation. On the contrary, detectable amounts of anti-IgE antibodies were not found in any serum. IgG depletion by protein G resulted in complete (10/14 samples) or considerable (4/14 samples) removal of anti-FcepsilonRIalpha antibodies. The two sera endowed with functional activity lost their capacity to trigger histamine release from basophils after heating and protein G adsorption. Nonetheless, heat-decomplemented/IgG-depleted sera elicited wheal-and-flare reactions comparable with those observed with untreated

  6. Autologous serum skin test in children

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    Godse Kiran


    Full Text Available Chronic urticaria in children occurs less often than adults. Out of 17 children (age group 6-16 years, [Table 2], six children (2 boys and 4 girls, 35% showed a positive result in form of wheal and flare more than 1.5 mm than saline control.Autologous serum skin test is cheap, is easy to perform, and, if performed as appropriate, it has good sensitivity and even better specificity at detecting autoantibodies in children.

  7. Autologous miniature punch grafting in stable vitiligo


    Rajagopal R; Murthy P; Kar P; Vijendran P


    Autologous miniature punch grafting with certain modifications was taken up in 54 sites in 30 patients with stable vitiligo for 6 months or more. The modifications were: (a) use of same sized disposable punches for both donor and recipient areas except over convex body surfaces, (b) use of Castraviejo′s scissors for harvesting donor grafts, (c) use of medial side of thigh as donor site and (d) not removing the primary dressing of the recipient site till 8 postoperaive day. The patients...

  8. Autopoiesis: Autology, Autotranscendence and Autonomy

    DEFF Research Database (Denmark)

    and 1990s – particularly in a French context. While his work has remained (to date) at distance from the rising number of suggestions, especi- ally regarding social and cultural theory, that have come out of these debates on self-organization, Castoriadis made a speci¿c and original contribution to them....... His work touches importantly on two aspects of self-organization. First, it takes issue with the problem of how self-organization – and its relations to various aspects of systems theory – may be thought at all within the options and constraints of a ‘human strata of the real’. Second, it probes...... ‘reality-modeling’ (John Casti) – whether via cognitive frameworks or models of society and culture. Secondly, attempts to adapt debates within the humanities, e.g. in philosophy, social theory and cultural studies, have tended to end in anti-humanism, ranging from Deleuze and Guattari’s ‘abstract machine...

  9. Comparison of Outcomes with Tissue Expander, Immediate Implant, and Autologous Breast Reconstruction in Greater Than 1000 Nipple-Sparing Mastectomies. (United States)

    Frey, Jordan D; Choi, Mihye; Salibian, Ara A; Karp, Nolan S


    Nipple-sparing mastectomy permits complete preservation of the nipple-areola complex with excellent aesthetic results and with oncologic safety similar to that associated with traditional mastectomy techniques. However, outcomes have not been directly compared for tissue expander-, immediate implant-, and autologous tissue-based breast reconstruction after nipple-sparing mastectomy. All patients undergoing nipple-sparing mastectomy from 2006 to June of 2016 were identified at a single institution. Demographics and outcomes were analyzed and compared among different types of breast reconstruction. A total of 1028 nipple-sparing mastectomies were performed. Of these, 533 (51.8 percent) were tissue expander-based, 263 (25.6 percent) were autologous tissue-based, and 232 (22.6 percent) were immediate implant-based reconstructions. Tissue expander-based reconstructions had significantly more minor cellulitis (p = 0.0002) but less complete nipple necrosis (p = 0.0126) and major mastectomy flap necrosis (p < 0.0001) compared with autologous tissue-based reconstructions. Compared to immediate implant-based reconstruction, tissue expander-based reconstructions had significantly more minor cellulitis (p = 0.0006) but less complete nipple necrosis (p = 0.0005) and major (p < 0.0001) and minor (p = 0.0028) mastectomy flap necrosis (p = 0.0059). Immediate implant-based reconstructions had significantly more minor cellulitis (p = 0.0051), minor mastectomy flap necrosis (p = 0.0425), and partial nipple necrosis (p = 0.0437) compared with autologous tissue-based reconstructions. Outcomes were otherwise equivalent among the three groups. Tissue expander, immediate implant, and autologous tissue breast reconstruction techniques may all be safely offered with nipple-sparing mastectomy. However, reconstructive complications appear to be greater with immediate implant- and autologous tissue-based techniques compared with tissue expander-based reconstruction. Therapeutic, III.

  10. Safety and Efficacy of Autologous CD34+ Hematopoietic Progenitor Cells Transduced with an Anti-Tat Ribozyme in a Multi-Center, Randomized, Placebo-Controlled, Phase II Gene Therapy Trial for the Human Immunodeficiency Virus (United States)

    Mitsuyasu, Ronald T; Merigan, Thomas C; Carr, Andrew; Zack, Jerome A; Winters, Mark A; Workman, Cassy; Bloch, Mark; Lalezari, Jacob; Becker, Stephen; Thornton, Lorna; Akil, Bisher; Khanlou, Homayoon; Finlayson, Robert; McFarlane, Robert; Smith, Don E; Garsia, Roger; Ma, David; Law, Matthew; Murray, John M.; von Kalle, Christof; Ely, Julie A; Patino, Sharon M; Knop, Alison E; Wong, Philip; Todd, Alison V; Haughton, Margaret; Fuery, Caroline; Macpherson, Janet L; Symonds, Geoff P; Evans, Louise A; Pond, Susan M; Cooper, David A


    SUMMARY Gene transfer has potential as a once-only treatment that reduces viral load, preserves the immune system, and avoids lifetime highly active antiretroviral therapy. This study, the first randomized, double-blind, placebo-controlled, phase II cell-delivered gene transfer clinical trial, was conducted in 74 HIV-1 infected adults who received a tat/vpr specific anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34+ hematopoietic progenitor cells. There were no OZ1-related adverse events. There was no statistical difference in viral load between the OZ1 and placebo group at the primary end-point (average at weeks 47 and 48) but time weighted areas under the curve from weeks 40-48 and 40-100 were significantly lower in the OZ1 group. Throughout the 100 weeks, CD4+ lymphocyte counts were higher in the OZ1 group. This study provides the first indication that cell-delivered gene transfer is safe and biologically active in HIV patients and can be developed as a conventional therapeutic product. PMID:19219022

  11. Injectable living marrow stromal cell-based autologous tissue engineered heart valves: first experiences with a one-step intervention in primates


    Weber, B.; Scherman, J.; Emmert, M. Y.; Gruenenfelder, J.; Verbeek, R.; Bracher, M.; Black, M.; Kortsmit, J.; Franz, T.; Schoenauer, R.; Baumgartner, L.; Brokopp, C.; Agarkova, I.; Wolint, P.; Zund, G.


    Aims A living heart valve with regeneration capacity based on autologous cells and minimally invasive implantation technology would represent a substantial improvement upon contemporary heart valve prostheses. This study investigates the feasibility of injectable, marrow stromal cell-based, autologous, living tissue engineered heart valves (TEHV) generated and implanted in a one-step intervention in non-human primates. Methods and results Trileaflet heart valves were fabricated from non-woven...

  12. Lysosomal-cationic test and NBT reduction test just partially reflect the completeness of phagocytic process in human granulocytes. (United States)

    Belokrylov, G A; Popova, O Ya


    The results of NBT test correlated with the index of phagocytosis completeness in only 43% of 21 clinically healthy volunteers. The level of the lysosomal-cationic test was significantly reduced only if the phagocytosis completeness index was markedly decreased. The latter is an integral value reflecting the bactericidal activity of granulocytes.

  13. Human papillomavirus knowledge, vaccine acceptance, and vaccine series completion among female entertainment and sex workers in Phnom Penh, Cambodia: the Young Women's Health Study. (United States)

    Wadhera, Priya; Evans, Jennifer L; Stein, Ellen; Gandhi, Monica; Couture, Marie-Claude; Sansothy, Neth; Sichan, Keo; Maher, Lisa; Kaldor, John; Page, Kimberly; Kien


    Human papillomavirus is a common sexually transmitted infection and the causative agent for cervical cancer, a frequently occurring malignant disease among women in developing countries. We assessed human papillomavirus awareness prior to the delivery of a brief information and education intervention, and human papillomavirus vaccine provision to female entertainment and sex workers (N = 220). At baseline, only 23.6% of women had heard of human papillomavirus. Following the educational intervention, 90% answered all the human papillomavirus knowledge questions correctly. Of 192 participants attending the first quarterly cohort visit where vaccine was offered, 149 (78%) were eligible for vaccination; HIV-positive (n = 32) and pregnant (n = 11) women were excluded. Acceptance of vaccine among eligible women was universal, and 79.2% completed the three-dose vaccination series. Women who reported use of amphetamine-type stimulants had significantly and independently lower odds of vaccine completion (adjusted odds ratio [AOR] 0.24; 95% confidence interval [CI] 0.08, 0.69). New pregnancies also had an impact on vaccine completion: 5.4% (8/149 5.4%) who started the series had to stop due to new pregnancy. Results demonstrate the effectiveness of a simple education intervention designed to increase human papillomavirus knowledge and the feasibility of successful human papillomavirus vaccine in a population that is often difficult to engage in preventive health care. © The Author(s) 2015.

  14. hWJECM-Derived Oriented Scaffolds with Autologous Chondrocytes for Rabbit Cartilage Defect Repairing. (United States)

    Zhao, Peng; Liu, Shuyun; Bai, Yuhe; Lu, Shibi; Peng, Jiang; Zhang, Li; Huang, Jingxiang; Zhao, Bin; Xu, Wenjing; Guo, Quanyi


    Previously, we synthesized an articular cartilage extracellular matrix (ECM)-derived oriented scaffold for cartilage tissue engineering, which was biomimetic in terms of structure and biochemical composition. However, the limit resource of the cartilage-derived ECM is a hindrance for its application. In this study, we developed a new material for cartilage tissue engineering-human umbilical cord Wharton's jelly-derived ECM (hWJECM). The hWJECM has an abundant resource and similar biochemistry with cartilage ECM, and the use of it is not associated with ethical controversy. We adopted the method previously used in cartilage ECM-derived oriented scaffold preparation to generate the oriented hWJECM-derived scaffold, and the scaffold properties were tested in vitro and in vivo. The three-dimensional scaffold has a porous and well-oriented structure, with a mean pore diameter of ∼104 μm. Scanning electron microscopy and cell viability staining results demonstrated that the oriented scaffold has good biocompatibility and cell alignment. In addition, we used functional autologous chondrocytes to seed the hWJECM-derived oriented scaffold and tested the efficacy of the cell-scaffold constructs to repair the full-thickness articular cartilage defect in a rabbit model. Defects of 4 mm diameter were generated in the patellar grooves of the femurs of both knees and were implanted with chondrocyte-scaffold constructs (group A) or scaffolds alone (group B); rabbits with untreated defects were used as a control (group C). Six months after surgery, all defects in group A were filled completely with repaired tissue, and most of which were hyaline cartilage. In contrast, the defects in group B were filled partially with repaired tissue, and approximately half of these repaired tissues were hyaline cartilage. The defects in group C were only filled with fibrotic tissue. Histological grading score of group A was lower than those of groups B and C. Quantification of

  15. Autologous Immune Enhancement Therapy for Cancer - Our experience since 2004

    Directory of Open Access Journals (Sweden)

    Hiroshi Terunuma


    Full Text Available Cancer, the major killer disease of the century requires a multi-pronged approach and among the latest modalities of treatments, Immunotherapy occupies a promising role. Immunotherapy for cancer was first started to be practised in the NIH and cell based immunotherapy for cancer is in practice for the past three decades. [1, 2] There are several literatures from various countries on the successful application of cell based Immunotherapies for various solid tumours and haematological malignancies. [3-8] Our team’s association with immune cells started when I was working on RNA transcriptome analysis to understand the immune system in HIV carriers which in turn required in vitro expansion of human Natural Killer (NK cells. [9] This led to the customization of protocols which has resulted in successful in vitro expansion, activation of NK cells and T cells for Immunotherapy. The purpose of Biotherapy institute of Japan (BIJ is to support research and clinical application of immune cells like NK cells, γδT cells, αβT cells, Cytotoxic T lymphocytes (CTL and Dendritic cells (DC for application as Autologous Immune Enhancement Therapy (AIET to fight against cancer. AIET using NK cells, CTLs, DCs etc have been administered for more than 5000 patients since 2004 till date by BIJ. Principle of AIET: For AIET using NK cells, the process involves separation of lymphocytes from the peripheral blood of the patient followed by selective NK cell expansion using the expansion kit (BINKIT, BIJ, JAPAN without feeder layers and then infusion of the expanded-activated NK cells. [10,11] As reports suggest that the activity of peripheral blood NK cells are lower in cancer patients compared to normal individuals [12] and as in vitro expansion of NK cells increases the cytotoxic ability 5 to 10 fold, [13] the NK cells are expanded in vivo and then infused to the patient in AIET. We are also working on combination immunotherapy using NK cells and CTLs and also NK

  16. Autologous HIV-1 neutralizing antibodies: emergence of neutralization-resistant escape virus and subsequent development of escape virus neutralizing antibodies

    DEFF Research Database (Denmark)

    Arendrup, M; Nielsen, C; Hansen, J E


    The capacity of consecutive human sera to neutralize sequentially obtained autologous virus isolates was studied. HIV-1 was isolated three times over a 48-164-week period from three individuals immediately after seroconversion and from two individuals in later stages of infection. Development...... escape virus may be part of the explanation of the apparent failure of the immune system to control HIV infection....... of neutralizing antibodies to the primary virus isolates was detected 13-45 weeks after seroconversion. Emergence of escape virus with reduced sensitivity to neutralization by autologous sera was demonstrated. The patients subsequently developed neutralizing antibodies against the escape virus but after a delay...

  17. Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone implantation. (United States)

    Sebecić, B; Nikolić, V; Sikirić, P; Seiwerth, S; Sosa, T; Patrlj, L; Grabarević, Z; Rucman, R; Petek, M; Konjevoda, P; Jadrijević, S; Perović, D; Slaj, M


    Gastrectomy often results in increased likelihood of osteoporosis, metabolic aberration, and risk of fracture, and there is a need for a gastric peptide with osteogenic activity. A novel stomach pentadecapeptide, BPC-157, improves wound and fracture healing in rats in addition to having an angiogenic effect. Therefore, in the present study, using a segmental osteoperiosteal bone defect (0.8 cm, in the middle of the left radius) that remained incompletely healed in all control rabbits for 6 weeks (assessed in 2 week intervals), pentadecapeptide BPC-157 was further studied (either percutaneously given locally [10 microg/kg body weight] into the bone defect, or applied intramuscularly [intermittently, at postoperative days 7, 9, 14, and 16 at 10 microg/kg body weight] or continuously [once per day, postoperative days 7-21 at 10 microg or 10 ng/kg body weight]). For comparison, rabbits percutaneously received locally autologous bone marrow (2 mL, postoperative day 7). As standard treatment, immediately after its formation, the bone defect was filled with an autologous cortical graft. Saline-treated (2 mL intramuscularly [i.m.] and 2 mL locally into the bone defect), injured animals were used as controls. Pentadecapeptide BPC-157 significantly improved the healing of segmental bone defects. For instance, upon radiographic assessment, the callus surface, microphotodensitometry, quantitative histomorphometry (10 microg/kg body weight i.m. for 14 days), or quantitative histomorphometry (10 ng/kg body weight i.m. for 14 days) the effect of pentadecapeptide BPC-157 was shown to correspond to improvement after local application of bone marrow or autologous cortical graft. Moreover, a comparison of the number of animals with unhealed defects (all controls) or healed defects (complete bony continuity across the defect site) showed that besides pentadecapeptide intramuscular application for 14 days (i.e., local application of bone marrow or autologous cortical graft), also

  18. Disseminated Fusarium infection in autologous stem cell transplant recipient

    Directory of Open Access Journals (Sweden)

    Vivian Iida Avelino-Silva


    Full Text Available Disseminated infection by Fusarium is a rare, frequently lethal condition in severely immunocompromised patients, including bone marrow transplant recipients. However, autologous bone marrow transplant recipients are not expected to be at high risk to develop fusariosis. We report a rare case of lethal disseminated Fusarium infection in an autologous bone marrow transplant recipient during pre-engraftment phase.

  19. Sites of Autologous Bone Grafts in Orthopaedic Traumatology ...

    African Journals Online (AJOL)

    Results: Outcome was satisfactory in 72 patients. 6 patients reported pain in the iliac crest. In 11 patients, the scar to the iliac crest was unsightly. Conclusion: The authors conclude that the commonly used donor sites for autologous bone grafts are safe. Keywords:autologous bone graft, pseudoarthrosis, bone reconstruction

  20. Cost effectiveness of autologous blood transfusion – A developing ...

    African Journals Online (AJOL)

    An autologous blood donation program was set up at National Orthopaedic Hospital, Igbobi Lagos in 1992 in response to the rising sero prevalence of HIV observed in our “relative replacement” donors. A retrospective batch analysis of patients who received autologous transfusion and those who received homologous ...

  1. Review of autologous blood transfusion at the Kenyatta National ...

    African Journals Online (AJOL)

    Autologous blood transfusion refers to transfusion of blood and/or blood components that are donated by the intended recipient (1). It is considered as one of the safest methods of blood transfusion (1,2). Different types of autologous blood include: preoperative blood deposit, preoperative haemodilution,intraope.


    Directory of Open Access Journals (Sweden)

    Patrizia Tosi


    Full Text Available Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achivng a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate.

  3. Identity and ownership issues in the regulation of autologous cells. (United States)

    Sipp, Douglas


    Clinical application of autologous cells by businesses promoting unproven stem cell treatments represents the largest growth sector in this problematic industry, but also presents special challenges to regulators. Patients frequently identify autologous cells as personal property, using the language of 'ownership'. Through an analysis of comments submitted to the US FDA in 2016 in response to recent draft guidance documents, I show that a sense of ownership and identity in autologous cells is consistently expressed by stakeholders. In the USA and other countries, regulation of cell and tissue biologics as 'drugs' relies substantially on whether a given product has been modified in ways that alter its biological properties, which has direct implications for property and ownership rights. Competing views on property rights in 'natural' and modified autologous cells have profound implications for the future of regulation of marketed autologous cells.

  4. Complete Genome Sequence of a Cytomegalovirus Towne-BAC (Bacterial Artificial Chromosome) Isolate Maintained in Escherichia?coli for 10?Years and Then Serially Passaged in Human Fibroblasts


    Brechtel, Teal; Tyner, Molly; Tandon, Ritesh


    Here, we present the complete genome sequence of a cytomegalovirus, the Towne-BAC (bacterial artificial chromosome) isolate, which was maintained in bacterial cells for 10?years and then serially passaged in human fibroblasts for 10 passages. A total of 132 nucleotide differences were discovered in the Towne sequence compared to the reference sequence (GenBank accession no. AC146851).

  5. Complete Genome Sequence of a Cytomegalovirus Towne-BAC (Bacterial Artificial Chromosome) Isolate Maintained in Escherichia coli for 10 Years and Then Serially Passaged in Human Fibroblasts. (United States)

    Brechtel, Teal; Tyner, Molly; Tandon, Ritesh


    Here, we present the complete genome sequence of a cytomegalovirus, the Towne-BAC (bacterial artificial chromosome) isolate, which was maintained in bacterial cells for 10 years and then serially passaged in human fibroblasts for 10 passages. A total of 132 nucleotide differences were discovered in the Towne sequence compared to the reference sequence (GenBank accession no. AC146851).

  6. Pacman in the sky with shadows: the effect of cast shadows on the perceptual completion of occluded figures by chimpanzees and humans

    Directory of Open Access Journals (Sweden)

    Imura Tomoko


    Full Text Available Abstract Background Humans readily perceive whole shapes as intact when some portions of these shapes are occluded by another object. This type of amodal completion has also been widely reported among nonhuman animals and is related to pictorial depth perception. However, the effect of a cast shadow, a critical pictorial-depth cue for amodal completion has been investigated only rarely from the comparative-cognitive perspective. In the present study, we examined this effect in chimpanzees and humans. Results Chimpanzees were slower in responding to a Pacman target with an occluding square than to the control condition, suggesting that participants perceptually completed the whole circle. When a cast shadow was added to the square, amodal completion occurred in both species. On the other hand, however, critical differences between the species emerged when the cast shadow was added to the Pacman figure, implying that Pacman was in the sky casting a shadow on the square. The cast shadow prevented, to a significant extent, compulsory amodal completion in humans, but had no effect on chimpanzees. Conclusion These results suggest that cast shadows played a critical role in enabling humans to infer the spatial relationship between Pacman and the square. For chimpanzees, however, a cast shadow may be perceived as another "object". A limited role for cast shadows in the perception of pictorial depth has also been reported with respect to human cognitive development. Further studies on nonhuman primates using a comparative-developmental perspective will clarify the evolutionary origin of the role of cast shadows in visual perception.

  7. Concentrated autologous plasma protein: a biochemically neutral solder for tissue welding. (United States)

    Stewart, R B; Bleustein, C B; Petratos, P B; Chin, K C; Poppas, D P; Kung, R T


    Xenographic or allographic serum protein solders used for laser welding may have immunologic and/or pathogenic complications. The objective of these studies was to develop a safe, autologous solder. Five methods of preparing concentrated autologous plasma protein solder (CAPPS) were evaluated. Next, the CAPPS was evaluated via (1) thermal denaturation studies using differential scanning calorimetry, (2) tissue welding studies to characterize both acute and healing properties. The optimal concentration method to produce CAPPS rapidly was a dialysis method using chemical (osmotic) forces. The CAPPS showed similar denaturation profiles to serum albumin (SA) solders. Acutely, CAPPS provided comparable breaking strengths to SA solders. At 7 days, there was no significant difference in breaking strength or histology between 50% human SA solder and CAPPS (using a porcine skin model). These studies demonstrate that the CAPPS system provides acceptable acute and chronic properties for laser welding. Copyright 2001 Wiley-Liss, Inc.

  8. Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model (United States)

    Ono, Mitsuaki; Oshima, Masamitsu; Ogawa, Miho; Sonoyama, Wataru; Hara, Emilio Satoshi; Oida, Yasutaka; Shinkawa, Shigehiko; Nakajima, Ryu; Mine, Atsushi; Hayano, Satoru; Fukumoto, Satoshi; Kasugai, Shohei; Yamaguchi, Akira; Tsuji, Takashi; Kuboki, Takuo


    Whole-organ regeneration has great potential for the replacement of dysfunctional organs through the reconstruction of a fully functional bioengineered organ using three-dimensional cell manipulation in vitro. Recently, many basic studies of whole-tooth replacement using three-dimensional cell manipulation have been conducted in a mouse model. Further evidence of the practical application to human medicine is required to demonstrate tooth restoration by reconstructing bioengineered tooth germ using a postnatal large-animal model. Herein, we demonstrate functional tooth restoration through the autologous transplantation of bioengineered tooth germ in a postnatal canine model. The bioengineered tooth, which was reconstructed using permanent tooth germ cells, erupted into the jawbone after autologous transplantation and achieved physiological function equivalent to that of a natural tooth. This study represents a substantial advancement in whole-organ replacement therapy through the transplantation of bioengineered organ germ as a practical model for future clinical regenerative medicine. PMID:28300208

  9. Predeposit autologous blood transfusion: Do we require to promote it?

    Directory of Open Access Journals (Sweden)

    Gurjit Singh


    Full Text Available Introduction: Safest blood a patient can receive is his own. Quest for safe blood transfusion has remained of prime concern. To meet this aspiration, various forms of autologous blood transfusions can be practiced. It is especially suitable for patients with rare blood groups and religious sects such as Jehovah′s witness autologous transfusion is extremely safe. Cross matching is not required; iso-immunization to a foreign body is excluded. Fear of transfusion transmissible disease can be ignored. Therefore, autologous blood transfusion is required to be revisited. Materials and Methods: This is a prospective study carried out at Padmashree Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune between July 2010 and May 2012. Study comprised of 100 patients divided into two groups, autologous and homologous. Benefits of autologous transfusion were studied. Results: There was no significant change in hematocrit and blood parameters after blood donation. That is mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration (P < 0.001 after blood donation. Only one complication of vasovagal syncope was observed at the time of blood donation. Conclusion: Autologous blood transfusion is safe. Easy alternative to be practiced in elective surgeries, especially in patients with rare blood group or believers of Jehovah′s witness faith. It helps to reduce the shortfall in national blood inventory. Autologous blood donation should be practiced whenever possible.

  10. Activated autologous T cells exert an anti-B-cell chronic lymphatic leukemia effect in vitro and in vivo. (United States)

    Di Ianni, Mauro; Moretti, Lorenzo; Terenzi, Adelmo; Bazzucchi, Federico; Del Papa, Beatrice; Bazzucchi, Moira; Ciurnelli, Raffaella; Lucchesi, Alessandro; Sportoletti, Paolo; Rosati, Emanuela; Marconi, Pier Francesco; Falzetti, Franca; Tabilio, Antonio


    The impact of chronic lymphatic leukemia (CLL) tumor burden on the autologous immune system has already been demonstrated. This study attempted to elucidate the molecular mechanisms underlying T-cell immunologic deficiencies in CLL. Freshly isolated CD3(+) T cells from patients with a diagnosis of CLL and healthy donors were analyzed by gene expression profiling. Activated T cells from 20 patients with CLL were tested in vitro for cytotoxicity against mutated and unmutated autologous B cells and DAUDI, K562 and P815 cell lines. To investigate T-cell mediated cytotoxicity in vivo, we co-transplanted OKT3-activated T lymphocytes and autologous B-cell CLL (B-CLL) cells into NOD/SCID mice. Gene expression profiles of peripheral blood T cells from B-CLL patients showed 25 down-regulated, and 31 up-regulated, genes that were mainly involved in cell differentiation, proliferation, survival, apoptosis, cytoskeleton formation, vesicle trafficking and T-cell activation. After culture, the T-cell count remained unchanged, CD8 cells expanded more than CD4 and a cytotoxicity index >30% was present in 5/20 patients. Cytotoxicity against B autologous leukemic cells did not correlate with B-cell mutational status. Only activated T cells exerting cytotoxicity against autologous leukemic B cells prevented CLL in a human-mouse chimera. This study indicates that patients with CLL are affected by a partial immunologic defect that might be somewhat susceptible to repair. This study identifies the molecular pathways underlying T-cell deficiencies in CLL and shows that cytotoxic T-cell functions against autologous B-CLL can be rebuilt at least in part in vitro and in vivo.

  11. Oral mucosa: an alternative epidermic cell source to develop autologous dermal-epidermal substitutes from diabetic subjects

    Directory of Open Access Journals (Sweden)

    Daniela GUZMÁN-URIBE

    Full Text Available Abstract Oral mucosa has been highlighted as a suitable source of epidermal cells due to its intrinsic characteristics such as its higher proliferation rate and its obtainability. Diabetic ulcers have a worldwide prevalence that is variable (1%-11%, meanwhile treatment of this has been proven ineffective. Tissue-engineered skin plays an important role in wound care focusing on strategies such autologous dermal-epidermal substitutes. Objective The aim of this study was to obtain autologous dermal-epidermal skin substitutes from oral mucosa from diabetic subjects as a first step towards a possible clinical application for cases of diabetic foot. Material and Methods Oral mucosa was obtained from diabetic and healthy subjects (n=20 per group. Epidermal cells were isolated and cultured using autologous fibrin to develop dermal-epidermal in vitro substitutes by the air-liquid technique with autologous human serum as a supplement media. Substitutes were immunocharacterized with collagen IV and cytokeratin 5-14 as specific markers. A Student´s t- test was performed to assess the differences between both groups. Results It was possible to isolate epidermal cells from the oral mucosa of diabetic and healthy subjects and develop autologous dermal-epidermal skin substitutes using autologous serum as a supplement. Differences in the expression of specific markers were observed and the cytokeratin 5-14 expression was lower in the diabetic substitutes, and the collagen IV expression was higher in the diabetic substitutes when compared with the healthy group, showing a significant difference. Conclusion Cells from oral mucosa could be an alternative and less invasive source for skin substitutes and wound healing. A difference in collagen production of diabetic cells suggests diabetic substitutes could improve diabetic wound healing. More research is needed to determine the crosstalk between components of these skin substitutes and damaged tissues.

  12. Myeloablative Chemotherapy with Autologous Stem Cell Transplant for Desmoplastic Small Round Cell Tumor

    Directory of Open Access Journals (Sweden)

    Christopher J. Forlenza


    Full Text Available Desmoplastic small round cell tumor (DSRCT, a rare, aggressive neoplasm, has a poor prognosis. In this prospective study, we evaluated the role of myeloablative chemotherapy, followed by autologous stem cell transplant in improving survival in DSRCT. After high-dose induction chemotherapy and surgery, 19 patients with chemoresponsive DSRCT underwent autologous stem cell transplant. Myeloablative chemotherapy consisted of carboplatin (400–700 mg/m2/day for 3 days + thiotepa (300 mg/m2/day for 3 days ± topotecan (2 mg/m2/day for 5 days. All patients were engrafted and there was no treatment-related mortality. Seventeen patients received radiotherapy to sites of prior or residual disease at a median of 12 weeks after transplant. Five-year event-free and overall survival were 11 ± 7% and 16 ± 8%, respectively. Two patients survive disease-free 16 and 19 years after transplant (both in complete remission before transplant. 14 patients had progression and died of disease at a median of 18 months following autologous transplant. These data do not justify the use of myeloablative chemotherapy with carboplatin plus thiotepa in patients with DSRCT. Alternative therapies should be considered for this aggressive neoplasm.

  13. Immunotherapy with subcutaneous immunogenic autologous tumor lysate increases murine glioblastoma survival. (United States)

    Belmans, Jochen; Van Woensel, Matthias; Creyns, Brecht; Dejaegher, Joost; Bullens, Dominique M; Van Gool, Stefaan W


    Immunotherapeutic strategies for glioblastoma, the most frequent malignant primary brain tumor, aim to improve its disastrous consequences. On top of the standard treatment, one strategy uses T cell activation by autologous dendritic cells (DC) ex vivo loaded with tumor lysate to attack remaining cancer cells. Wondering whether 'targeting' in vivo DCs could replace these ex vivo ones, immunogenic autologous tumor lysate was used to treat glioma-inoculated mice in the absence of ex vivo loaded DCs. Potential immune mechanisms were studied in two orthotopic, immunocompetent murine glioma models. Pre-tumoral subcutaneous lysate treatment resulted in a survival benefit comparable to subcutaneous DC therapy. Focussing on the immune response, glioma T cell infiltration was observed in parallel with decreased amounts of regulatory T cells. Moreover, these results were accompanied by the presence of strong tumor-specific immunological memory, shown by complete survival of a second glioblastoma tumor, inoculated 100 days after the first one. Finally, in combination with temozolomide, survival of established glioma in mice could be increased. Our results show the potential of immunogenic autologous tumor lysate used to treat murine glioblastoma, which will be worthwhile to study in clinical trials as it has potential as a cost-efficient adjuvant treatment strategy for gliomas.

  14. Disparities in Human Papillomavirus Vaccine Literacy and Vaccine Completion among Asian American Pacific Islander Undergraduates: Implications for Cancer Health Equity (United States)

    Lee, Hee Yun; Kwon, Melissa; Vang, Suzanne; DeWolfe, Jessica; Kim, Nam Keol; Lee, Do Kyung; Yeung, Miriam


    Purpose: Low rates of human papillomavirus (HPV) vaccination among young Asian American and Pacific Islander (AAPI) women need to be addressed, particularly given the high incidence of cervical cancer in this population. The current study aims to investigate predictors of HPV vaccination in young AAPI and non-Latina white (NLW) women. Methods: A…

  15. Lawrence Livermore National Laboratory- Completing the Human Genome Project and Triggering Nearly $1 Trillion in U.S. Economic Activity

    Energy Technology Data Exchange (ETDEWEB)

    Stewart, Jeffrey S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)


    The success of the Human Genome project is already nearing $1 Trillion dollars of U.S. economic activity. Lawrence Livermore National Laboratory (LLNL) was a co-leader in one of the biggest biological research effort in history, sequencing the Human Genome Project. This ambitious research effort set out to sequence the approximately 3 billion nucleotides in the human genome, an effort many thought was nearly impossible. Deoxyribonucleic acid (DNA) was discovered in 1869, and by 1943 came the discovery that DNA was a molecule that encodes the genetic instructions used in the development and functioning of living organisms and many viruses. To make full use of the information, scientists needed to first sequence the billions of nucleotides to begin linking them to genetic traits and illnesses, and eventually more effective treatments. New medical discoveries and improved agriculture productivity were some of the expected benefits. While the potential benefits were vast, the timeline (over a decade) and cost ($3.8 Billion) exceeded what the private sector would normally attempt, especially when this would only be the first phase toward the path to new discoveries and market opportunities. The Department of Energy believed its best research laboratories could meet this Grand Challenge and soon convinced the National Institute of Health to formally propose the Human Genome project to the federal government. The U.S. government accepted the risk and challenge to potentially create new healthcare and food discoveries that could benefit the world and the U.S. Industry.

  16. Autologous miniature punch grafting in stable vitiligo

    Directory of Open Access Journals (Sweden)

    Rajagopal R


    Full Text Available Autologous miniature punch grafting with certain modifications was taken up in 54 sites in 30 patients with stable vitiligo for 6 months or more. The modifications were: (a use of same sized disposable punches for both donor and recipient areas except over convex body surfaces, (b use of Castraviejo′s scissors for harvesting donor grafts, (c use of medial side of thigh as donor site and (d not removing the primary dressing of the recipient site till 8 postoperaive day. The patients were given systemic PUVASOL after the procedure for a period of three months and mean pigment spread was noted at each site. Results showed that the extent of repigmentation varied among the recipient sites, the maximum being over upper eyelids, axillae and umbilicus. The modifications in the standard procedure were found to produce less complications, like cobblestoning, graft rejection.

  17. Autologous Stem Cell Transplant for AL Amyloidosis

    Directory of Open Access Journals (Sweden)

    Vivek Roy


    Full Text Available AL amyloidosis is caused by clonal plasma cells that produce immunoglobulin light chains which misfold and get deposited as amyloid fibrils. Therapy directed against the plasma cell clone leads to clinical benefit. Melphalan and corticosteroids have been the mainstay of treatment for a number of years and the recent availability of other effective agents (IMiDs and proteasome inhibitors has increased treatment options. Autologous stem cell transplant (ASCT has been used in the treatment of AL amyloidosis for many years. It is associated with high rates of hematologic response and improvement in organ function. However, transplant carries considerable risks. Careful patient selection is important to minimize transplant related morbidity and mortality and ensure optimal patient outcomes. As newer more affective therapies become available the role and timing of ASCT in the overall treatment strategy of AL amyloidosis will need to be continually reassessed.

  18. Promotion of oral surgical wound healing using autologous mucosal cell sheets. (United States)

    Roh, Jong-Lyel; Jang, Hyejin; Lee, Jaewang; Kim, Eun Hye; Shin, Daiha


    Severe oral mucosal and tissue defects can lead to pain, infection, and later undesirable healing of scarring and adhesion, resulting in a poor quality of life. In vitro-engineered oral mucosal equivalents for covering such defects are an alternative to avoiding the donor site morbidity of conventional skin or tissue grafts. We examined the efficacy of our newly developed three-dimensional mucosal cell sheets in an in vivo tongue wound model mimicking the surgical extirpation of tongue cancer. Small oral mucosal and autologous fibrin samples were obtained from surgical patients and Sprague-Dawley rats. The fibrin was mixed with fibroblasts and seeded with keratinocytes that had been primarily cultured for in vitro cell expansion. The three-dimensional autologous cell sheets, cultured in air-lift interface inserts, were transplanted into deep wounds of the rat ventral tongue. Gross and microscopic findings of the postsurgical wounds were compared between wound control and cell sheet groups. The cell sheets were flexible, expandable, and easy to transfer, and had histological characteristics similar to that of the normal oral mucosa, with high p63 positivity. They promoted oral wound healing with earlier re-epithelialization and less fibrosis than that in the wound control. The cell sheet-healed tongue had similar histology to that of a normal tongue. Our engineered cell sheets have potential applicability for the rapid healing of oral mucosal and soft tissue defects, without scarring, adhesion, and functional deficits. The efficacy of in vitro-engineered mucosal equivalents, using completely autologous mucosa and plasma, was examined. Transplantation of the autologous cell sheets into deep wounds of the rat ventral tongue promoted oral wound healing with earlier re-epithelialization and less fibrosis than that in controls. Healed and normal tongues showed similar histology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Complete Genome Sequence of the Human Herpesvirus 6A Strain AJ from Africa Resembles Strain GS from North America. (United States)

    Tweedy, J; Spyrou, M A; Donaldson, C D; Depledge, D; Breuer, J; Gompels, U A


    The genome sequence of human herpesvirus 6A (HHV-6A) strain AJ was determined in a comparison of target enrichment and long-range PCR using next-generation sequencing methodologies. The analyses show 85 predicted open reading frames (ORFs), conservation with sequenced HHV-6A reference strain U1102, and closest identity to the recently determined GS strain, despite different geographic origins (United States and Gambia). Copyright © 2015 Tweedy et al.

  20. Generation of cleidocranial dysplasia-specific human induced pluripotent stem cells in completely serum-, feeder-, and integration-free culture. (United States)

    Yamasaki, Sachiko; Hamada, Atsuko; Akagi, Eri; Nakatao, Hirotaka; Ohtaka, Manami; Nishimura, Ken; Nakanishi, Mahito; Toratani, Shigeaki; Okamoto, Tetsuji


    Human pluripotent stem cells hold great promise for their practical and scientific potentials. To improve understanding of self-renewal and differentiation, we previously reported a defined serum-free medium hESF9 could generate and maintain human induced pluripotent stem cells (iPSCs) in serum- and feeder-free culture conditions using retroviral vectors. To avoid the unpredictable side effects associated with retrovirus integration, we report here the successful generation of hiPSCs from dental pulp cells with a non-integrating replication-defective and persistent Sendai virus (SeVdp) vector expressing four key reprogramming genes. We found that hESF9 medium in combination with fibronectin are effective for generating and maintaining hiPSCs with SeVdp (KOSM). Using this system, pluripotent and self-renewing hiPSCs could be easily and stably generated and propagated. With this system, we successfully generated hiPSCs from cleidocranial dysplasia (CCD) caused by a heterozygous germ-line mutation of runt-related protein2 (RUNX2), which has an important role in the differentiation of osteoblasts and maturation of chondrocytes. This is the first report of the establishment of CCD-specific iPSCs. The cartilage in the teratomas of CCD-iPSCs showed abnormalities. These CCD-iPSCs would be beneficial to clarify the molecular mechanism and for development of medical applications. Moreover, it brings new pathophysiological role of RUNX2 in the differentiation of the human chondrocytes and osteocytes.

  1. Tumour-infiltrating lymphocytes mediate lysis of autologous squamous cell carcinomas of the head and neck

    DEFF Research Database (Denmark)

    Hald, Jeppe; Rasmussen, N; Claesson, Mogens Helweg


    , the cancer cells either overexpressed the tumour-suppressor gene product p53 or harboured human papilloma virus 16/18 (HPV). The TIL were expanded in vitro in the presence of interleukin-2, immobilised anti-CD3 mAb and soluble anti-CD28 mAb. Expanded TIL cultures contained both CD4+ and CD8+ T cells......, but generally contained few CD56+CD3- cells of the natural killer (NK) phenotype. CD8+ T cells dominated the individual TIL cultures from five of the six patients and showed significant autologous tumour cell lysis. In TIL cultures derived from four of these tumour-reactive TIL cultures, killing could...... be partially blocked by an anti-MHC class I mAb. TIL cultures reacting with autologous tumour cells also showed strong TCR/CD3-redirected cytotoxicity when assayed against hybridoma cells expressing anti-TCR/CD3 mAb as well as natural-killer(NK)-like activity. A number of TIL cultures devoid of autologous...

  2. Improving oocyte quality by transfer of autologous mitochondria from fully grown oocytes. (United States)

    Kristensen, Stine Gry; Pors, Susanne Elisabeth; Andersen, Claus Yding


    Older women are often the most challenging group of patients in fertility clinics due to a decline in both number and overall quality of oocytes. The quality of oocytes has been linked to mitochondrial dysfunction. In this mini-review, we discuss this hypothesis and suggest alternative treatment options using autologous mitochondria to potentially augment pregnancy potential in ART. Autologous transfer of mitochondria from the patient's own germline cells has attracted much attention as a possible new treatment to revitalize deficient oocytes. IVF births have been reported after transfer of oogonial precursor cell-derived mitochondria; however, the source and quality of the mitochondria are still unclear. In contrast, fully grown oocytes are loaded with mitochondria which have passed the genetic bottleneck and are likely to be of high quality. An increased supply of such oocytes could potentially be obtained by in vitro follicle activation of ovarian cortical biopsies or from surplus immature oocytes collected from women undergoing ART or fertility preservation of ovarian tissue. Taken together, autologous oocytes are not necessarily a limiting resource in ART as fully grown oocytes with high quality mitochondria can be obtained from natural or stimulated ovaries and potentially be used to improve both quality and quantity of oocytes available for fertility treatment. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail:

  3. Development of Autologous C5 Vaccine Nanoparticles to Reduce Intravascular Hemolysis in Vivo. (United States)

    Zhang, Lingjun; Qiu, Wen; Crooke, Stephen; Li, Yan; Abid, Areeba; Xu, Bin; Finn, M G; Lin, Feng


    The complement system is emerging as a new target for treating many diseases. For example, Eculizumab, a humanized monoclonal antibody against complement component 5 (C5), has been approved for paroxysmal nocturnal hemoglobinuria (PNH) in which patient erythrocytes are lysed by complement. In this study, we developed vaccines to elicit autologous anti-C5 antibody production in mice for complement inhibition. Immunization of mice with a conservative C5 xenoprotein raised high titers of IgG's against the xenogenous C5, but these antibodies did not reduce C5 activity in the blood. In contrast, an autologous mouse C5 vaccine containing multiple predicted epitopes together with a tolerance-breaking peptide was found to induce anti-C5 autoantibody production in vivo, resulting in decreased hemolytic activity in the blood. We further validated a peptide epitope within this C5 vaccine and created recombinant virus-like particles (VLPs) displaying this epitope fused with the tolerance breaking peptide. Immunizing mice with these novel nanoparticles elicited strong humoral responses against recombinant mouse C5, reduced hemolytic activity, and protected the mice from complement-mediated intravascular hemolysis in a model of PNH. This proof-of-concept study demonstrated that autologous C5-based vaccines could be an effective alternative or supplement for treating complement-mediated diseases such as PNH.

  4. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Puente, Pilar de la, E-mail: [Tissue Bank, San Francisco Clinic Foundation, Av./Facultad 51, 5°, 24004 León (Spain); Ludeña, Dolores [Pathology Service, University Hospital of Salamanca, P/San Vicente 58-182, 37007 Salamanca (Spain); López, Marta; Ramos, Jennifer; Iglesias, Javier [Tissue Bank, San Francisco Clinic Foundation, Av./Facultad 51, 5°, 24004 León (Spain)


    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.

  5. Transplantation of autologous Schwann cells for the repair of segmental peripheral nerve defects. (United States)

    Hood, Brian; Levene, Howard B; Levi, Allan D


    Peripheral nerve injuries are a source of chronic disability. Incomplete recovery from such injuries results in motor and sensory dysfunction and the potential for the development of chronic pain. The repair of human peripheral nerve injuries with traditional surgical techniques has limited success, particularly when a damaged nerve segment needs to be replaced. An injury to a long segment of peripheral nerve is often repaired using autologous grafting of "noncritical" sensory nerve. Although extensive axonal regeneration can be observed extending into these grafts, recovery of function may be absent or incomplete if the axons fail to reach their intended target. The goal of this review was to summarize the progress that has occurred in developing an artificial neural prosthesis consisting of autologous Schwann cells (SCs), and to detail future directions required in translating this promising therapy to the clinic. In the authors' laboratory, methods are being explored to combine autologous SCs isolated using cell culture techniques with axon guidance channel (AGC) technology to develop the potential to repair critical gap length lesions within the peripheral nervous system. To test the clinical efficacy of such constructs, it is critically important to characterize the fate of the transplanted SCs with regard to cell survival, migration, differentiation, and myelin production. The authors sought to determine whether the use of SC-filled channels is superior or equivalent to strategies that are currently used clinically (for example, autologous nerve grafts). Finally, although many nerve repair paradigms demonstrate evidence of regeneration within the AGC, the authors further sought to determine if the regeneration observed was physiologically relevant by including electrophysiological, behavioral, and pain assessments. If successful, the development of this reparative approach will bring together techniques that are readily available for clinical use and should

  6. Autologous Transplantation of Amniotic Fluid-Derived Mesenchymal Stem Cells into Sheep Fetuses. (United States)

    Shaw, S W Steven; Bollini, Sveva; Nader, Khalil Abi; Gastaldello, Annalisa; Mehta, Vedanta; Filppi, Elisa; Cananzi, Mara; Gaspar, H Bobby; Qasim, Waseem; De Coppi, Paolo; David, Anna L


    Long-term engraftment and phenotype correction has been difficult to achieve in humans after in utero stem cell transplantation mainly because of allogeneic rejection. Autologous cells could be obtained during gestation from the amniotic fluid with minimal risk for the fetus and the mother. Using a sheep model, we explored the possibility of using amniotic fluid mesenchymal stem cells (AFMSCs) for autologous in utero stem cell/gene therapy. We collected amniotic fluid (AF) under ultrasound-guided amniocentesis in early gestation pregnant sheep ( n = 9, 58 days of gestation, term = 145 days). AFMSCs were isolated and expanded in all sampled fetal sheep. Those cells were transduced using an HIV vector encoding enhanced green fluorescent protein (GFP) with 63.2% (range 38.3-96.2%) transduction efficiency rate. After expansion, transduced AFMSCs were injected into the peritoneal cavity of each donor fetal sheep at 76 days under ultrasound guidance. One ewe miscarried twin fetuses after amniocentesis. Intraperitoneal injection was successful in the remaining 7 fetal sheep giving a 78% survival for the full procedure. Tissues were sampled at postmortem examination 2 weeks later. PCR analysis detected GFP-positive cells in fetal tissues including liver, heart, placenta, membrane, umbilical cord, adrenal gland, and muscle. GFP protein was detected in these tissues by Western blotting and further confirmed by cytofluorimetric and immunofluorescence analyses. This is the first demonstration of autologous stem cell transplantation in the fetus using AFMSCs. Autologous cells derived from AF showed widespread organ migration and could offer an alternative way to ameliorate prenatal congenital disease.

  7. Human immunodeficiency virus-associated giant conjunctival Kaposi's sarcoma: complete remission with antiretroviral therapy and systemic chemotherapy. (United States)

    Eduardo-Sánchez, Y W; Fernández-Agrafojo, D


    A 35-year-old male patient with a large unilateral haemorrhagic conjunctival tumour lesion and another contralateral haemorrhagic conjunctival flat lesion associated with violaceous cutaneous macules on the extremities and angiomatous lesions in the upper gastrointestinal tract as initial clinical manifestation of HIV-related immunodeficiency. Cutaneous, gastric mucosal and conjunctival biopsy was consistent with Kaposi's sarcoma with complete remission after highly active antiretroviral therapy and systemic chemotherapy. HIV-related conjunctival Kaposi's sarcoma, even a large one, can have a good response to antiretroviral therapy and systemic chemotherapy without any additional topical eye treatment. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Two novel circo-like viruses detected in human feces: complete genome sequencing and electron microscopy analysis. (United States)

    Castrignano, Silvana Beres; Nagasse-Sugahara, Teresa Keico; Kisielius, Jonas José; Ueda-Ito, Marli; Brandão, Paulo Eduardo; Curti, Suely Pires


    The application of viral metagenomic techniques and a series of PCRs in a human fecal sample enabled the detection of two novel circular unisense DNA viral genomes with 92% nucleotide similarity. The viruses were tentatively named circo-like virus-Brazil (CLV-BR) strains hs1 and hs2 and have genome lengths of 2526 and 2533 nucleotides, respectively. Four major open reading frames (ORFs) were identified in each of the genomes, and differences between the two genomes were primarily observed in ORF 2. Only ORF 3 showed significant amino acid similarities to a putative rolling circle replication initiator protein (Rep), although with low identity (36%). Our phylogenetic analysis, based on the Rep protein, demonstrated that the CLV-BRs do not cluster with members of the Circoviridae, Nanoviridae or Geminiviridae families and are more closely related to circo-like genomes previously identified in reclaimed water and feces of a wild rodent and of a bat. The CLV-BRs are members of a putative new family of circular Rep-encoding ssDNA viruses. Electron microscopy revealed icosahedral (~23 nm) structures, likely reflecting the novel viruses, and rod-shaped viral particles (~65-460 × 21 × 10 nm in length, diameter, and axial canal, respectively). Circo-like viruses have been detected in stool samples from humans and other mammals (bats, rodents, chimpanzees and bovines), cerebrospinal fluid and sera from humans, as well as samples from many other sources, e.g., insects, meat and the environment. Further studies are needed to classify all novel circular DNA viruses and elucidate their hosts, pathogenicity and evolutionary history. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Acute mental change and hemiplegia after autologous fat injection. (United States)

    Kang, Jun Ho; Park, Kyung Hye; Park, Jung Soo


    Autologous fat injection is a common procedure used for skin augmentation. It is known to be safe and simple, but severe complications have been reported at times. The authors observed a patient with acute large cerebral infarction including the territories of the anterior and middle cerebral arteries and optic nerve infarction developing after autologous fat transplantation. A 32-year-old woman was referred to the emergency room of our hospital due to sudden stupor. Thirty minutes earlier, she was undergoing cosmetic autologous fat injection into the glabella area by a plastic surgeon at a private clinic. The cause was confirmed to be anterior and middle cerebral arteries infarction on brain imaging studies. When a patient presents abrupt mental change, hemiplegia, ocular pain, or blindness after autologous fat particle injection, physicians must consider cerebral infarction and combined retinal artery occlusion.

  10. Autologous anti-metatype immune response in rabbits. (United States)

    Voss, E W; Moore, J K; Weidner-McGufficke, K M; Denzin, L K; Bedzyk, W D; Voss, V H


    Rabbits hyperimmunized with fluorescyl-conjugated KLH exhibited bound ligand associated with a high affinity circulating IgG anti-fluorescein population. After cessation of immunogen administration the liganded complexes were eventually spontaneously cleared from the circulation. Individual rabbits synthesized autologous anti-metatype antibodies specific for ligand-antibody complexes. Autologous anti-metatype antibodies reacted optimally with autologous liganded anti-fluorescein antibodies. However, cross reactivity was noted with allogenic rabbit liganded antibodies from three affinity-purified pools. An autologous anti-metatype response, reminiscent of autoanti-idiotype responses, has important implications concerning in vivo clearance of antigen-antibody complexes and may serve as a model to study immune complex diseases.

  11. Complete Genome Sequence of Treponema paraluiscuniculi, Strain Cuniculi A: The Loss of Infectivity to Humans Is Associated with Genome Decay (United States)

    Šmajs, David; Zobaníková, Marie; Strouhal, Michal; Čejková, Darina; Dugan-Rocha, Shannon; Pospíšilová, Petra; Norris, Steven J.; Albert, Tom; Qin, Xiang; Hallsworth-Pepin, Kym; Buhay, Christian; Muzny, Donna M.; Chen, Lei; Gibbs, Richard A.; Weinstock, George M.


    Treponema paraluiscuniculi is the causative agent of rabbit venereal spirochetosis. It is not infectious to humans, although its genome structure is very closely related to other pathogenic Treponema species including Treponema pallidum subspecies pallidum, the etiological agent of syphilis. In this study, the genome sequence of Treponema paraluiscuniculi, strain Cuniculi A, was determined by a combination of several high-throughput sequencing strategies. Whereas the overall size (1,133,390 bp), arrangement, and gene content of the Cuniculi A genome closely resembled those of the T. pallidum genome, the T. paraluiscuniculi genome contained a markedly higher number of pseudogenes and gene fragments (51). In addition to pseudogenes, 33 divergent genes were also found in the T. paraluiscuniculi genome. A set of 32 (out of 84) affected genes encoded proteins of known or predicted function in the Nichols genome. These proteins included virulence factors, gene regulators and components of DNA repair and recombination. The majority (52 or 61.9%) of the Cuniculi A pseudogenes and divergent genes were of unknown function. Our results indicate that T. paraluiscuniculi has evolved from a T. pallidum-like ancestor and adapted to a specialized host-associated niche (rabbits) during loss of infectivity to humans. The genes that are inactivated or altered in T. paraluiscuniculi are candidates for virulence factors important in the infectivity and pathogenesis of T. pallidum subspecies. PMID:21655244

  12. Complete genome sequence of Treponema paraluiscuniculi, strain Cuniculi A: the loss of infectivity to humans is associated with genome decay.

    Directory of Open Access Journals (Sweden)

    David Šmajs

    Full Text Available Treponema paraluiscuniculi is the causative agent of rabbit venereal spirochetosis. It is not infectious to humans, although its genome structure is very closely related to other pathogenic Treponema species including Treponema pallidum subspecies pallidum, the etiological agent of syphilis. In this study, the genome sequence of Treponema paraluiscuniculi, strain Cuniculi A, was determined by a combination of several high-throughput sequencing strategies. Whereas the overall size (1,133,390 bp, arrangement, and gene content of the Cuniculi A genome closely resembled those of the T. pallidum genome, the T. paraluiscuniculi genome contained a markedly higher number of pseudogenes and gene fragments (51. In addition to pseudogenes, 33 divergent genes were also found in the T. paraluiscuniculi genome. A set of 32 (out of 84 affected genes encoded proteins of known or predicted function in the Nichols genome. These proteins included virulence factors, gene regulators and components of DNA repair and recombination. The majority (52 or 61.9% of the Cuniculi A pseudogenes and divergent genes were of unknown function. Our results indicate that T. paraluiscuniculi has evolved from a T. pallidum-like ancestor and adapted to a specialized host-associated niche (rabbits during loss of infectivity to humans. The genes that are inactivated or altered in T. paraluiscuniculi are candidates for virulence factors important in the infectivity and pathogenesis of T. pallidum subspecies.

  13. Corneal blood staining following autologous blood injection for hypotony maculopathy. (United States)

    Ayyala, R S; Urban, R C; Krishnamurthy, M S; Mendelblatt, D J


    Hypotony is a common complication following trabeculectomy in which antimetabolites are used. Autologous blood injection is an accepted form of treatment for hypotony that occurs secondary to overfiltration; however, injection into the filtering bleb has been associated with a rise in intraocular pressure for some patients with chronic postoperative hypotony. The authors describe a patient in whom corneal blood staining with raised intraocular pressure and loss of vision occurred as a result of autologous blood injection.

  14. Estimating how and why Dr Okuda made a complete wooden human skeleton in the Edo era, Japan. (United States)

    Baba, Hisao


    Probably in 1820 (late Edo era), a human skeleton for medical education was precisely carved from cypress wood, based on a criminal's skeleton, by a craftsman under the supervision of the medical doctor Banri Okuda in Osaka City. By and large, the wooden skeleton shows morphological characteristics usually seen in early middle-aged females of the Edo era. However, the claviculae, distal ends of the femora and the patellae are exceptionally larger than those of a female, implying that the bones of the original model skeleton had already been lost or were deformed before the wooden skeleton was made. Furthermore, the skeleton may not have been used for medical education, but rather for the promotion of European medicine, which was gradually developing in the Edo era.

  15. [Role of viscosity and permeability of erythrocyte plasmatic membrane in controlling the oxygen transport effectiveness by human hemoglobin on completion of space flight]. (United States)

    Ivanova, S M; Maksimov, G V; Morukov, B V; Iarlykova, Iu V; Labetskaia, O I; Luneva, O G; Maksimova, N V; Brazhe, N A; Bryzgalova, N Iu; Parshina, E Iu


    Plasmatic membrane viscosity and permeability and hemoporphyrine conformation in human hemoglobin were studied on completion of long-duration space flight (LSF). Reversible increases in viscosity and selective permeability (Na+/H+ -turnover) of erythrocyte plasmatic membrane were observed immediately after and in the period of recovery from LSF. Viscosity of lipids in both external and internal locations of plasmatic membrane in human erythrocytes was changed after LSF. The reversible rise of the Na+/H+ -turnover is likely to alter intracellular pH and oxygen binding with hemoglobin. The former is confirmed by the concurrent reversible decline in the deoxyhemoglobin ability to bind oxygen and the oxyhemoglobin ability to retain oxygen. In LSF and during readaptation to the normal gravity blood levels of hemoglobin and free iron are known to be reduced and may be answerable for the hypoxic state of human organism.

  16. Stature estimation from complete long bones in the Middle Pleistocene humans from the Sima de los Huesos, Sierra de Atapuerca (Spain). (United States)

    Carretero, José-Miguel; Rodríguez, Laura; García-González, Rebeca; Arsuaga, Juan-Luis; Gómez-Olivencia, Asier; Lorenzo, Carlos; Bonmatí, Alejandro; Gracia, Ana; Martínez, Ignacio; Quam, Rolf


    Systematic excavations at the site of the Sima de los Huesos (SH) in the Sierra de Atapuerca (Burgos, Spain) have allowed us to reconstruct 27 complete long bones of the human species Homo heidelbergensis. The SH sample is used here, together with a sample of 39 complete Homo neanderthalensis long bones and 17 complete early Homo sapiens (Skhul/Qafzeh) long bones, to compare the stature of these three different human species. Stature is estimated for each bone using race- and sex-independent regression formulae, yielding an average stature for each bone within each taxon. The mean length of each long bone from SH is significantly greater (p stature has been calculated for male and female specimens separately, averaging both means to calculate a general mean. This general mean stature for the entire sample of long bones is 163.6 cm for the SH hominins, 160.6 cm for Neandertals and 177.4 cm for early modern humans. Despite some overlap in the ranges of variation, all mean values in the SH sample (whether considering isolated bones, the upper or lower limb, males or females or more complete individuals) are larger than those of Neandertals. Given the strong relationship between long bone length and stature, we conclude that SH hominins represent a slightly taller population or species than the Neandertals. However, compared with living European Mediterranean populations, neither the Sima de los Huesos hominins nor the Neandertals should be considered 'short' people. In fact, the average stature within the genus Homo seems to have changed little over the course of the last two million years, since the appearance of Homo ergaster in East Africa. It is only with the emergence of H. sapiens, whose earliest representatives were 'very tall', that a significant increase in stature can be documented. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Human lipoproteins have divergent neutralizing effects on E. coli LPS, N. meningitidis LPS, and complete Gram-negative bacteria. (United States)

    Sprong, Tom; Netea, Mihai G; van der Ley, Peter; Verver-Jansen, Trees J G; Jacobs, Liesbeth E H; Stalenhoef, Anton; van der Meer, Jos W M; van Deuren, Marcel


    The use of lipoproteins has been suggested as a treatment for Gram-negative sepsis because they inhibit lipopolysaccharide (LPS)-mediated cytokine production. However, little is known about the neutralizing effects of lipoproteins on cytokine production by meningococcal LPS or whole Gram-negative bacteria. We assessed the neutralizing effect of LDLs, HDLs, and VLDLs on LPS- or whole bacteria-induced cytokines in human mononuclear cells. A strong inhibition of Escherichia coli LPS-induced interleukin-1beta (IL-1beta), tumor necrosis factor-alpha, and IL-10 by LDL and HDL was seen, whereas VLDL had a less pronounced effect. In contrast, Neisseria meningitidis LPS, in similar concentrations, was neutralized much less effectively than E. coli LPS. Effective neutralization of meningococcal LPS required a longer interaction time, a lower concentration of LPS, or higher concentrations of lipoproteins. The difference in neutralization was independent of the saccharide tail, suggesting that the lipid A moiety accounted for the difference. Minimal neutralizing effects of the lipoproteins were observed on whole E. coli or N. meningitidis bacteria under all conditions tested. These results indicate that efficient neutralization of LPS depends on the type of LPS, but a sufficiently long interaction time, a low LPS concentration, or high lipoprotein concentration also inhibited cytokines by the less efficiently neutralized N. meningitidis LPS. Irrespective of these differences, whole bacteria showed no neutralization by lipoproteins.

  18. Lysosome vacuolation disrupts the completion of autophagy during norephedrine exposure in SH-SY5Y human neuroblastoma cells. (United States)

    Funakoshi, Takeshi; Aki, Toshihiko; Unuma, Kana; Uemura, Koichi


    In our current study, we examined the mechanism underlying neuronal cell injuries caused by norephedrine in SH-SY5Y human neuroblastoma cells. Norephedrine was found to induce cytoplasmic vacuolation and a resultant loss of cell viability. In the cells treated with norephedrine also, an autophagic marker LC3 was converted to its LC3-II activated form, suggesting the induction of autophagy. In cells transfected with RFP-LC3 and GFP-LAMP1, a punctate patterning of LC3 expression and colocalization of LAMP1 with the formed vacuoles were observed, highlighting the lysosomal nature of the vacuoles and their association with autophagosomes. An autophagic flux assay using tfLC3 (mRFP-GFP-LC3) indicated the formation of autophagosomes and autolysosomes by norephedrine stimulation at an early timepoint (∼3 h). However, at a later timepoint (∼6 h), both the dilation of autolysosomes/lysosomes and the neutralization of the vacuolar pH were also observed. These results thus indicate that norephedrine induces autophagy at an early timepoint and cell death with lysosomal dysfunction and autophagy disruption at a later timepoint. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Localization of the human fibromodulin gene (FMOD) to chromosome 1q32 and completion of the cDNA sequence

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    Sztrolovics, R.; Grover, J.; Roughley, P.J. [McGill Univ., Montreal (Canada)] [and others


    This report describes the cloning of the 3{prime}-untranslated region of the human fibromodulin cDNA and its use to map the gene. For somatic cell hybrids, the generation of the PCR product was concordant with the presence of chromosome 1 and discordant with the presence of all other chromosomes, confirming that the fibromodulin gene is located within region q32 of chromosome 1. The physical mapping of genes is a critical step in the process of identifying which genes may be responsible for various inherited disorders. Specifically, the mapping of the fibromodulin gene now provides the information necessary to evaluate its potential role in genetic disorders of connective tissues. The analysis of previously reported diseases mapped to chromosome 1 reveals two genes located in the proximity of the fibromodulin locus. These are Usher syndrome type II, a recessive disorder characterized by hearing loss and retinitis pigmentosa, and Van der Woude syndrome, a dominant condition associated with abnormalities such as cleft lip and palate and hyperdontia. The genes for both of these disorders have been projected to be localized to 1q32 of a physical map that integrates available genetic linkage and physical data. However, it seems improbable that either of these disorders, exhibiting restricted tissue involvement, could be linked to the fibromodulin gene, given the wide tissue distribution of the encoded proteoglycan, although it remains possible that the relative importance of the quantity and function of the proteoglycan may avry between tissues. 11 refs., 1 fig.

  20. Autologous fat grafting: use of closed syringe microcannula system for enhanced autologous structural grafting

    Directory of Open Access Journals (Sweden)

    Alexander RW


    Full Text Available Robert W Alexander,1 David Harrell2 1Department of Surgery, School of Medicine and Dentistry, University of Washington, Seattle, WA, USA; 2Harvest-Terumo Inc, Plymouth, MA, USA Objectives: Provide background for use of acquiring autologous adipose tissue as a tissue graft and source of adult progenitor cells for use in cosmetic plastic surgery. Discuss the background and mechanisms of action of closed syringe vacuum lipoaspiration, with emphasis on accessing adipose-derived mesenchymal/stromal cells and the stromal vascular fraction (SVF for use in aesthetic, structural reconstruction and regenerative applications. Explain a proven protocol for acquiring high-quality autologous fat grafts (AFG with use of disposable, microcannula systems. Design: Explain the components and advantage of use of the patented super luer-lock and microcannulas system for use with the closed-syringe system. A sequential explanation of equipment selection for minimally traumatic lipoaspiration in small volumes is presented, including use of blunt injection cannulas to reduce risk of embolism. Results: Thousands of AFG have proven safe and efficacious for lipoaspiration techniques for large and small structural fat grafting procedures. The importance and advantages of gentle harvesting of the adipose tissue complex has become very clear in the past 5 years. The closed-syringe system offers a minimally invasive, gentle system with which to mobilize subdermal fat tissues in a suspension form. Resulting total nuclear counting of undifferentiated cells of the adipose-derived -SVF suggests that the yield achieved is better than use of always-on, constant mechanical pump applied vacuum systems. Conclusion: Use of a closed-syringe lipoaspiration system featuring disposable microcannulas offers a safe and effective means of harvesting small volumes of nonmanipulated adipose tissues and its accompanying progenitor cells within the SVF. Closed syringes and microcannulas are

  1. Inflammatory effects of autologous, genetically modified autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses. (United States)

    Pigott, J H; Ishihara, A; Wellman, M L; Russell, D S; Bertone, A L


    To compare the clinical and inflammatory joint responses to intra-articular injection of bone marrow-derived mesenchymal stem cells (MSC) including autologous, genetically modified autologous, allogeneic, or xenogeneic cells in horses. Six five-year-old Thoroughbred mares had one fetlock joint injected with Gey's balanced salt solution as the vehicle control. Each fetlock joint of each horse was subsequently injected with 15 million MSC from the described MSC groups, and were assessed for 28 days for clinical and inflammatory parameters representing synovitis, joint swelling, and pain. There were not any significant differences between autologous and genetically modified autologous MSC for synovial fluid total nucleated cell count, total protein, interleukin (IL)-6, IL-10, fetlock circumference, oedema score, pain-free range-of-motion, and soluble gene products that were detected for at least two days. Allogeneic and xenogeneic MSC produced a greater increase in peak of inflammation at 24 hours than either autologous MSC group. Genetically engineered MSC can act as vehicles to deliver gene products to the joint; further investigation into the therapeutic potential of this cell therapy is warranted. Intra-articular MSC injection resulted in a moderate acute inflammatory joint response that was greater for allogeneic and xenogeneic MSC than autologous MSC. Clinical management of this response may minimize this effect.

  2. Twente spine model: A complete and coherent dataset for musculo-skeletal modeling of the thoracic and cervical regions of the human spine. (United States)

    Bayoglu, Riza; Geeraedts, Leo; Groenen, Karlijn H J; Verdonschot, Nico; Koopman, Bart; Homminga, Jasper


    Musculo-skeletal modeling could play a key role in advancing our understanding of the healthy and pathological spine, but the credibility of such models are strictly dependent on the accuracy of the anatomical data incorporated. In this study, we present a complete and coherent musculo-skeletal dataset for the thoracic and cervical regions of the human spine, obtained through detailed dissection of an embalmed male cadaver. We divided the muscles into a number of muscle-tendon elements, digitized their attachments at the bones, and measured morphological muscle parameters. In total, 225 muscle elements were measured over 39 muscles. For every muscle element, we provide the coordinates of its attachments, fiber length, tendon length, sarcomere length, optimal fiber length, pennation angle, mass, and physiological cross-sectional area together with the skeletal geometry of the cadaver. Results were consistent with similar anatomical studies. Furthermore, we report new data for several muscles such as rotatores, multifidus, levatores costarum, spinalis, semispinalis, subcostales, transversus thoracis, and intercostales muscles. This dataset complements our previous study where we presented a consistent dataset for the lumbar region of the spine (Bayoglu et al., 2017). Therefore, when used together, these datasets enable a complete and coherent dataset for the entire spine. The complete dataset will be used to develop a musculo-skeletal model for the entire human spine to study clinical and ergonomic applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model (United States)

    Kobari, Ladan; Yates, Frank; Oudrhiri, Noufissa; Francina, Alain; Kiger, Laurent; Mazurier, Christelle; Rouzbeh, Shaghayegh; El-Nemer, Wassim; Hebert, Nicolas; Giarratana, Marie-Catherine; François, Sabine; Chapel, Alain; Lapillonne, Hélène; Luton, Dominique; Bennaceur-Griscelli, Annelise; Douay, Luc


    Background Human induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors. Design and Methods We addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin. Sickle cell disease induced pluripotent stem cells were differentiated in vitro into red blood cells and characterized for their terminal maturation in terms of hemoglobin content, oxygen transport capacity, deformability, sickling and adherence. Nucleated erythroblast populations generated from normal and pathological induced pluripotent stem cells were then injected into non-obese diabetic severe combined immunodeficiency mice to follow the in vivo hemoglobin maturation. Results We observed that in vitro erythroid differentiation results in predominance of fetal hemoglobin which rescues the functionality of red blood cells in the pathological model of sickle cell disease. We observed, in vivo, the switch from fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from either normal or pathological induced pluripotent stem cells into mice. Conclusions These results demonstrate that human induced pluripotent stem cells: i) can achieve complete terminal erythroid maturation, in vitro in terms of nucleus expulsion and in vivo in terms of hemoglobin maturation; and ii) open the way to generation of functionally corrected red blood cells from sickle cell disease induced pluripotent stem cells, without any genetic modification or drug treatment. PMID:22733021

  4. Genetic variability among complete human respiratory syncytial virus subgroup A genomes: bridging molecular evolutionary dynamics and epidemiology.

    Directory of Open Access Journals (Sweden)

    Lydia Tan

    Full Text Available Human respiratory syncytial virus (RSV is an important cause of severe lower respiratory tract infections in infants and the elderly. In the vast majority of cases, however, RSV infections run mild and symptoms resemble those of a common cold. The immunological, clinical, and epidemiological profile of severe RSV infections suggests a disease caused by a virus with typical seasonal transmission behavior, lacking clear-cut virulence factors, but instead causing disease by modifying the host's immune response in a way that stimulates pathogenesis. Yet, the interplay between RSV-evoked immune responses and epidemic behavior, and how this affects the genomic evolutionary dynamics of the virus, remains poorly understood. Here, we present a comprehensive collection of 33 novel RSV subgroup A genomes from strains sampled over the last decade, and provide the first measurement of RSV-A genomic diversity through time in a phylodynamic framework. In addition, we map amino acid substitutions per protein to determine mutational hotspots in specific domains. Using Bayesian genealogical inference, we estimated the genomic evolutionary rate to be 6.47 × 10(-4 (credible interval: 5.56 × 10(-4, 7.38 × 10(-4 substitutions/site/year, considerably slower than previous estimates based on G gene sequences only. The G gene is however marked by elevated substitution rates compared to other RSV genes, which can be attributed to relaxed selective constraints. In line with this, site-specific selection analyses identify the G gene as the major target of diversifying selection. Importantly, statistical analysis demonstrates that the immune driven positive selection does not leave a measurable imprint on the genome phylogeny, implying that RSV lineage replacement mainly follows nonselective epidemiological processes. The roughly 50 years of RSV-A genomic evolution are characterized by a constant population size through time and general co-circulation of lineages over

  5. PolyI:C and mouse survivin artificially embedding human 2B peptide induce a CD4+ T cell response to autologous survivin in HLA-A*2402 transgenic mice. (United States)

    Kasamatsu, Jun; Takahashi, Shojiro; Azuma, Masahiro; Matsumoto, Misako; Morii-Sakai, Akiko; Imamura, Masahiro; Teshima, Takanori; Takahashi, Akari; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Sato, Noriyuki; Seya, Tsukasa


    CD4(+) T cell effectors are crucial for establishing antitumor immunity. Dendritic cell maturation by immune adjuvants appears to facilitate subset-specific CD4(+) T cell proliferation, but the adjuvant effect for CD4 T on induction of cytotoxic T lymphocytes (CTLs) is largely unknown. Self-antigenic determinants with low avidity are usually CD4 epitopes in mutated proteins with tumor-associated class I-antigens (TAAs). In this study, we made a chimeric version of survivin, a target of human CTLs. The chimeric survivin, where human survivin-2B containing a TAA was embedded in the mouse survivin frame (MmSVN2B), was used to immunize HLA-A-2402/K(b)-transgenic (HLA24(b)-Tg) mice. Subcutaneous administration of MmSVN2B or xenogeneic human survivin (control HsSNV2B) to HLA24(b)-Tg mice failed to induce an immune response without co-administration of an RNA adjuvant polyI:C, which was required for effector induction in vivo. Although HLA-A-2402/K(b) presented the survivin-2B peptide in C57BL/6 mice, 2B-specific tetramer assays showed that no CD8(+) T CTLs specific to survivin-2B proliferated above the detection limit in immunized mice, even with polyI:C treatment. However, the CD4(+) T cell response, as monitored by IFN-γ, was significantly increased in mice given polyI:C+MmSVN2B. The Th1 response and antibody production were enhanced in the mice with polyI:C. The CD4 epitope responsible for effector function was not Hs/MmSNV13-27, a nonconserved region between human and mouse survivin, but region 53-67, which was identical between human and mouse survivin. These results suggest that activated, self-reactive CD4(+) helper T cells proliferate in MmSVN2B+polyI:C immunization and contribute to Th1 polarization followed by antibody production, but hardly participate in CTL induction. Copyright © 2014 Elsevier GmbH. All rights reserved.

  6. Completion of hepatitis C virus replication cycle in heterokaryons excludes dominant restrictions in human non-liver and mouse liver cell lines.

    Directory of Open Access Journals (Sweden)

    Anne Frentzen


    Full Text Available Hepatitis C virus (HCV is hepatotropic and only infects humans and chimpanzees. Consequently, an immunocompetent small animal model is lacking. The restricted tropism of HCV likely reflects specific host factor requirements. We investigated if dominant restriction factors expressed in non-liver or non-human cell lines inhibit HCV propagation thus rendering these cells non-permissive. To this end we explored if HCV completes its replication cycle in heterokaryons between human liver cell lines and non-permissive cell lines from human non-liver or mouse liver origin. Despite functional viral pattern recognition pathways and responsiveness to interferon, virus production was observed in all fused cells and was only ablated when cells were treated with exogenous interferon. These results exclude that constitutive or virus-induced expression of dominant restriction factors prevents propagation of HCV in these cell types, which has important implications for HCV tissue and species tropism. In turn, these data strongly advocate transgenic approaches of crucial human HCV cofactors to establish an immunocompetent small animal model.

  7. Autologous blood transfusion for kidney transplant recipients. (United States)

    Sasaki, H; Chikaraishi, T; Furuhata, S; Tsutsumi, H; Miyano, S; Nakazawa, R; Nakano, T; Kudo, H; Kitajima, K; Takahashi, T; Satoh, Y; Kimura, K


    Autologous blood transfusion (ABT) is rarely employed in patients with end-stage renal disease (ESRD); these patients are usually anemic. Since 1998, we have attempted ABT for ESRD patients undergoing living-related kidney transplantation. Among 20 patients enrolled in this study the preoperative hemoglobin and hematocrit levels were 10.0 +/- 1.2 mg/dL (range, 8.1-11.7) and 30.0 +/- 3.7% (range, 24.7-34.3), respectively. Blood volume collected on each occasion was 235.7 +/- 57.7 mL (range, 200-400), and the number of blood collections was 2.45 +/- 0.9 (range, 1-4). Total collected volume was 567.5 +/- 157.5 mL (range, 400-800). Symptomatic hypotension was seen in two patients, but vital signs recovered spontaneously. No other problems related to blood collection were observed. Allogeneic transfusion was need in only one patient (5%). ABT was safe and efficacious in ESRD patients scheduled for living-related kidney transplantation.

  8. Autologous chondrocyte implantation in children and adolescents. (United States)

    Schmal, H; Pestka, J M; Salzmann, G; Strohm, P C; Südkamp, N P; Niemeyer, P


    Autologous chondrocyte implantation (ACI) is a well-established treatment method for cartilage defects in knees. Age-related grouping was based on expression data of cartilage-specific markers. Specificities of ACI in the different populations were analysed. Two hundred and sixty-seven patients undergoing ACI in the knee between 2006 and 2010 were included in this analysis. Cell characteristics and expression data of cartilage-specific surface markers as CD44, aggrecan and collagen type II were statistically analysed for age association. Epidemiological data of the defined groups were compared. Course of treatment was evaluated using MRI. A correlation analysis showed statistically significant associations between age and aggrecan or collagen type II expression in all patients patella was significantly more affected. Cartilage lesions were mainly caused by osteochondritis dissecans (OCD) and trauma. The Knee Osteoarthritis Scoring System in MRI reached 4.8 ± 2.3 points before, declining to 3.3 ± 2.3 points 6 and 12 months after the operation. Age-related expression of cartilage-specific markers allows definition of adolescents in cartilage regenerating surgery. Chondromalacia in these patients is mainly caused by OCD or trauma. Case series, Level IV.

  9. Immediate effects of isolated transmyocardial laser revascularization procedures combined with intramyocardial injection of autologous bone marrow stem cells in patients with terminal stage of coronary artery disease

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    Leo A. Bockeria


    Conclusions ― TMLR with intramyocardial autologous stem cells injections in patients with end-stage CAD is safe. This procedure can be done in the most severe group of patients who cannot be completely revascularized with either PCI or CABG surgery. Futher investigation is needed to assess the effectiveness of the procedure.

  10. Autologous Serum Skin Test versus Autologous Plasma Skin Test in Patients with Chronic Spontaneous Urticaria

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    Aysegul Alpay


    Full Text Available Previous studies indicate that 25–45% of chronic urticaria patients have an autoimmune etiology. Autologous serum skin test (ASST and autologous plasma skin test (APST are simple tests for diagnosing chronic autoimmune urticaria (CAU. However, there are still some questions about the specificity of these tests. This study consisted of 50 patients with chronic spontaneous urticaria (CSU and 50 sex- and age-matched healthy individuals aged 18 years, and older. A total of 31 (62% patients and 5 (10% control patients had positive ASST; 21 (42% patients and 3 (6% control patients had positive APST. Statistically significant differences were noted in ASST and APST positivity between the patient and control groups (ASST P<0.001; APST P<0.001. Thirteen (26% patients and 5 (10% control patients had antithyroglobulin antibodies or antithyroid peroxidase antibody positivity. No statistically significant differences were noted in thyroid autoantibodies between the patient and control groups (anti-TG P=0.317; anti-TPO P=0.269. We consider that the ASST and APST can both be used as in vivo tests for the assessment of autoimmunity in the etiology of CSU and that thyroid autoantibodies should be checked even when thyroid function tests reveal normal results in patients with CSU.

  11. Integrating the Advanced Human Eye Model (AHEM) and optical instrument models to model complete visual optical systems inclusive of the typical or atypical eye (United States)

    Donnelly, William J., III


    PURPOSE: To present a commercially available optical modeling software tool to assist the development of optical instrumentation and systems that utilize and/or integrate with the human eye. METHODS: A commercially available flexible eye modeling system is presented, the Advanced Human Eye Model (AHEM). AHEM is a module that the engineer can use to perform rapid development and test scenarios on systems that integrate with the eye. Methods include merging modeled systems initially developed outside of AHEM and performing a series of wizard-type operations that relieve the user from requiring an optometric or ophthalmic background to produce a complete eye inclusive system. Scenarios consist of retinal imaging of targets and sources through integrated systems. Uses include, but are not limited to, optimization, telescopes, microscopes, spectacles, contact and intraocular lenses, ocular aberrations, cataract simulation and scattering, and twin eye model (binocular) systems. RESULTS: Metrics, graphical data, and exportable CAD geometry are generated from the various modeling scenarios.

  12. Clinical results of an autologous engineered skin. (United States)

    Llames, Sara; García, Eva; García, Verónica; del Río, Marcela; Larcher, Fernando; Jorcano, Jose Luis; López, Eva; Holguín, Purificación; Miralles, Francisca; Otero, Jesús; Meana, Alvaro


    An artificial complete skin (dermis and epidermis) model has been developed in the Tissue engineering unit of the Centro Comunitario de Sangre y Tejidos del Principado de Asturias (CCST) and CIEMAT. This engineered skin has been employed for the treatment of severe epithelial injuries. In this paper, the clinical results obtained with this engineered skin during the last 18 months were evaluated. (a) Culture: Cells (fibroblasts and keratinocytes) were obtained from biopsies by a double enzymatic digestion. After an expansion period, fibroblasts were seeded in an artificial dermis based on human plasma. Keratinocytes were seeded over this dermal surface. (b) 20 skin biopsies were processed (13 burned patients, 5 giant nevus, 1 GVHD, 1 neurofibromatosis), which came from different hospitals across the country. About 97,525 cm(2) of engineered skin were cultured. The engineered skin took in all patients. The take percentage depended on previous pathology (burned patients 10-90%; non-critical patients 70-90%). The epithelization obtained was permanent in all cases. During the follow-up period, epithelial loss, blistering injuries or skin retractions were not observed. The aesthetic and functional results were acceptable. This artificial skin has demonstrated to be useful for the definitive treatment of patients with severe skin injuries. This work shows that it is possible to produce this prototype in an hospitalarian laboratory and distribute it to different hospitals across the country.

  13. Cryopreservation of Autologous Blood (Red Blood Cells, Platelets and Plasma) (United States)

    Ebine, Kunio

    Prevention of post-transfusion hepatitis is still a problem in cardiovascular surgery. We initiated the cryopreservation of autologous blood for the transfusion in elective cardiovascular surgery since 1981. This study includes 152 surgical cases in which autologous frozen, allogeneic frozen, and/or allogeneic non-frozen blood were used. In the 152 surgical cases, there were 69 cases in which autologous blood only (Group I) was used; 12 cases with autologous and allogeneic frozen blood (Group II); 46 cases with autologous and allgeneic frozen plus allogeneic non-frozen blood (Group III); and 25 cases with allogeneic frozen plus allogeneic non-frozen blood (Group IV). No hepatitis developed in Groups I (0%) and II (0%), but there was positive hepatitis in Groups III (4.3%) and IV (8.0%) . In 357 cases of those who underwent surgery with allogeneic non-frozen whole blood during the same period, the incidence rate of hepatitis was 13.7% (49/357). Patients awaiting elective surgery can store their own blood in the frozen state. Patients who undergo surgery with the cryoautotransfusion will not produce any infections or immunologic reactions as opposed to those who undergo surgery with the allogeneic non-frozen blood.

  14. Spanish Experience in Autologous Chondrocyte Implantation (United States)

    Pérez-Cachafeiro, Santiago; Ruano-Raviña, Alberto; Couceiro-Follente, José; Benedí-Alcaine, Jose Antonio; Nebot-Sanchis, Ignacio; Casquete-Román, Ciriaco; Bello-Prats, Santiago; Couceiro-Sánchez, Gonzalo; Blanco, Francisco J.


    Introduction: The Spanish Ministry of Health commissioned the Galician Agency for Health Technology Assessment to monitor and follow-up Autologous Chondrocyte Implantation (ACI) used to treat chondral lesions of the knee in Spain. The objective of this monitoring was to assess efficacy and safety of the technique. Design: One-hundred and eleven consecutive patients with knee chondral lesions were included in a multi-center study between January 2001 and January 2005. ACI was used in these patients as a second-line treatment option (or a first-line treatment option if the cause was Osteocondritis dissecans). The Cincinnati score and the Short Form 36 (SF-36) questionnaire were used to assess the patients’ self-reported satisfaction with the outcomes of ACI. A descriptive analysis was performed and non-parametric tests were used to establish correlations and compare results among subgroups. A multivariate analysis was also performed to measure the effect of different variables on changes in the condition of the knee. Results: Eighty men (72%) and 31 women (21%) with an age range from 16 to 49 years, underwent ACI surgery. Among these subjects, the most common previous first-line treatment was debridement (64 individuals, 74.4%). The mean size of the lesion treated with ACI was 3.82 cm2, and the most frequent location of the lesion was the inner femoral condyle (53.6%). The patient satisfaction was high or very high in 36 subjects (66.7%). Overall knee joint assessment improved from 4.32 points to 6.78. All SF-36 questionnaire categories improved, notably those related to physical condition. Conclusions: The results of this study indicate that ACI is safe; however, further studies are mandated to assess the efficacy of ACI compared to alternative treatment options. PMID:20148094

  15. Using Behavioral Risk Factor Data as a surveillance tool to monitor the prevalence of initiation, continuation and completion of Human Papilloma Virus vaccination in children

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    Gia Elise Barboza


    Full Text Available The Human Papilloma Virus (“HPV” is a common sexually transmitted disease that has infected approximately 79 million men and women in the United States alone. A vaccination is available but in order to be effective it must be received prior to becoming sexually active and recipients must complete a three-dose sequence. In this article we explore the predisposing, enabling and need-based factors associated with parents’ or guardians’ decision to have their child initiate, continue and complete the Human Papilloma Virus (HPV vaccine. The data file includes 5531 parents and guardians with presumptive knowledge regarding the number of HPV vaccination their child received. Data includes information on the child (e.g. child׳s age as well as the adult respondent (e.g. health insurance status. A smaller subset of the dataset along with the code to run the model are supplied with this article. The interpretation of these data can be found in the research article published by the authors in the Journal of Preventive Medicine in 2015 [1].

  16. Outcomes in relapsed Hodgkin's lymphoma treated with autologous and allogeneic hematopoietic cell transplantation at the Pontificia Universidad Católica de Chile. (United States)

    Ramirez, Pablo; Ocqueteau, Mauricio; Rodriguez, Alejandra; Garcia, Maria Jose; Sarmiento, Mauricio; Ernst, Daniel; Jara, Veronica; Bertin, Pablo


    Hodgkin's lymphoma is a highly curable disease. Autologous and reduced intensity allogeneic hematopoietic cell transplantations are alternatives to treat relapsed patients. Here, we report on the results of one service using these procedures. All patients who underwent transplantations in our institution between 1996 and 2014 were retrospectively studied and demographics, toxicities and survival rate were analyzed. This study evaluated 24 autologous and five reduced intensity allogeneic transplantations: the median ages of the patients were 29 and 32 years, respectively. At the time of autologous transplantation, ten patients were in complete remission, nine had chemosensitive disease but were not in complete remission, three had refractory disease and the status of two is unknown. In the allogeneic group, two were in complete remission and three had chemosensitive disease. The 5-year overall survival after autologous transplantation was 42% (66% patients were in complete remission, 37% had chemosensitive disease with incomplete remission and 0% had refractory disease) and 1-year overall survival after allogeneic transplantation was 80%. Transplant-related mortality was 0% in patients conditioned with the ifosfamide/carboplatin/etoposide (ICE), carmustine/etoposide/cyclophosphamide (BEC) and carmustine/etoposide/cytarabine/melphalan (BEAM) regimens, 37% in patients conditioned with busulfan-based regimens and 20% in allogeneic transplantations. Hematopoietic cell transplantation for relapsed Hodgkin's lymphoma is a potentially curative procedure especially in patients in complete remission at the time of autologous transplantations, and possibly after allogeneic transplantations. Further studies are necessary to clarify the role of allogeneic transplantations in the treatment of relapsed Hodgkin's lymphoma. Copyright © 2015 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

  17. Outcomes in relapsed Hodgkin's lymphoma treated with autologous and allogeneic hematopoietic cell transplantation at the Pontificia Universidad Católica de Chile

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    Pablo Ramirez


    Full Text Available Introduction: Hodgkin's lymphoma is a highly curable disease. Autologous and reduced intensity allogeneic hematopoietic cell transplantations are alternatives to treat relapsed patients. Here, we report on the results of one service using these procedures. Methods: All patients who underwent transplantations in our institution between 1996 and 2014 were retrospectively studied and demographics, toxicities and survival rate were analyzed. Results: This study evaluated 24 autologous and five reduced intensity allogeneic transplantations: the median ages of the patients were 29 and 32 years, respectively. At the time of autologous transplantation, ten patients were in complete remission, nine had chemosensitive disease but were not in complete remission, three had refractory disease and the status of two is unknown. In the allogeneic group, two were in complete remission and three had chemosensitive disease. The 5-year overall survival after autologous transplantation was 42% (66% patients were in complete remission, 37% had chemosensitive disease with incom- plete remission and 0% had refractory disease and 1-year overall survival after allogeneic transplantation was 80%. Transplant-related mortality was 0% in patients conditioned with the ifosfamide/carboplatin/etoposide (ICE, carmustine/etoposide/cyclophosphamide (BEC and carmustine/etoposide/cytarabine/melphalan (BEAM regimens, 37% in patients condi- tioned with busulfan-based regimens and 20% in allogeneic transplantations. Conclusions: Hematopoietic cell transplantation for relapsed Hodgkin's lymphoma is a potentially curative procedure especially in patients in complete remission at the time of autologous transplantations, and possibly after allogeneic transplantations. Further studies are necessary to clarify the role of allogeneic transplantations in the treatment of relapsed Hodgkin's lymphoma.

  18. Enteric Neural Cells From Hirschsprung Disease Patients Form Ganglia in Autologous Aneuronal ColonSummary

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    Benjamin N. Rollo


    Full Text Available Background & Aims: Hirschsprung disease (HSCR is caused by failure of cells derived from the neural crest (NC to colonize the distal bowel in early embryogenesis, resulting in absence of the enteric nervous system (ENS and failure of intestinal transit postnatally. Treatment is by distal bowel resection, but neural cell replacement may be an alternative. We tested whether aneuronal (aganglionic colon tissue from patients may be colonized by autologous ENS-derived cells. Methods: Cells were obtained and cryopreserved from 31 HSCR patients from the proximal resection margin of colon, and ENS cells were isolated using flow cytometry for the NC marker p75 (nine patients. Aneuronal colon tissue was obtained from the distal resection margin (23 patients. ENS cells were assessed for NC markers immunohistologically and by quantitative reverse-transcription polymerase chain reaction, and mitosis was detected by ethynyl-2′-deoxyuridine labeling. The ability of human HSCR postnatal ENS-derived cells to colonize the embryonic intestine was demonstrated by organ coculture with avian embryo gut, and the ability of human postnatal HSCR aneuronal colon muscle to support ENS formation was tested by organ coculture with embryonic mouse ENS cells. Finally, the ability of HSCR patient ENS cells to colonize autologous aneuronal colon muscle tissue was assessed. Results: ENS-derived p75-sorted cells from patients expressed multiple NC progenitor and differentiation markers and proliferated in culture under conditions simulating Wnt signaling. In organ culture, patient ENS cells migrated appropriately in aneural quail embryo gut, and mouse embryo ENS cells rapidly spread, differentiated, and extended axons in patient aneuronal colon muscle tissue. Postnatal ENS cells derived from HSCR patients colonized autologous aneuronal colon tissue in cocultures, proliferating and differentiating as neurons and glia. Conclusions: NC-lineage cells can be obtained from HSCR

  19. Autologous reconstruction of the inguinal ligament using pedicled fascia lata flap: A new technique. (United States)

    Bott, Alasdair R; Chummun, Shaheel; Rickard, Rory F; Kingsnorth, Andrew N


    A technique of reconstructing the inguinal ligament using a pedicled fascia lata flap is described. A 62-year-old man was referred with massive bilateral abdominal wall hernias, following numerous attempts at repair and subsequent recurrences. There was complete absence of the right inguinal ligament. The inguinal ligament was reconstructed using a strip of fascia lata, pedicled on the anterior superior iliac spine. This was transposed to cover the external iliac vessels, and sutured to the pubic tubercle. The musculoaponeurotic abdominal wall was reconstructed with two 20cm×20cm sheets of porcine acellular dermal matrix and an overlying sheet of polypropylene mesh, sutured to the remaining abdominal wall muscles laterally, and to both inguinal ligaments. The cutaneous abdominal wall was closed with an abdominoplasty technique. The reconstruction has remained intact nine months following surgery. Complete destruction of the inguinal ligament is rare but can occur following multiple operative procedures or trauma. To date, the only published reports of inguinal ligament reconstruction have been performed using synthetic mesh. The use of autologous tissue should reduce the risk of erosion into the neurovascular bundle, seroma formation, and enhance integration into surrounding tissues. This new technique for autologous reconstruction of the inguinal ligament provides a safe alternative to the use of synthetic mesh in the operative armamentarium of plastic and hernia surgeons. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  20. Effectiveness of autologous transfusion system in primary total hip and knee arthroplasty.

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    Schneider, Marco M


    Autologous transfusion has become a cost-efficient and useful option in the treatment of patients with high blood loss following major orthopaedic surgery. However, the effectiveness of autologous transfusion in total joint replacement remains controversial.

  1. Lumbar herniation following extended autologous latissimus dorsi breast reconstruction. (United States)

    Fraser, Sheila Margaret; Fatayer, Hiba; Achuthan, Rajgopal


    Reconstructive breast surgery is now recognized to be an important part of the treatment for breast cancer. Surgical reconstruction options consist of implants, autologous tissue transfer or a combination of the two. The latissimus dorsi flap is a pedicled musculocutaneous flap and is an established method of autologous breast reconstruction.Lumbar hernias are an unusual type of hernia, the majority occurring after surgery or trauma in this area. The reported incidence of a lumbar hernia subsequent to a latissimus dorsi reconstruction is very low. We present the unusual case of lumbar herniation after an extended autologous latissimus dorsi flap for breast reconstruction following a mastectomy. The lumbar hernia was confirmed on CT scanning and the patient underwent an open mesh repair of the hernia through the previous latissimus dorsi scar. Lumbar hernias are a rare complication that can occur following latissimus dorsi breast reconstruction. It should be considered in all patients presenting with persistent pain or swelling in the lumbar region.

  2. Improving diagnosis of appendicitis. Early autologous leukocyte scanning. (United States)

    DeLaney, A R; Raviola, C A; Weber, P N; McDonald, P T; Navarro, D A; Jasko, I


    A prospective nonrandomized study investigating the accuracy and utility of autologous leukocyte scanning in the diagnosis of apendicitis was performed. One hundred patients in whom the clinical diagnosis of appendicitis was uncertain underwent indium 111 oxyquinoline labelling of autologous leukocytes and underwent scanning 2 hours following reinjection. Of 32 patients with proved appendicitis, three scans revealed normal results (false-negative rate, 0.09). Of 68 patients without appendicitis, three scans had positive results (false-positive rate, 0.03; sensitivity, 0.91; specificity, 0.97; predictive value of positive scan, 0.94; predictive value of negative scan, 0.96; and overall accuracy, 0.95). Scan results altered clinical decisions in 19 patients. In 13 cases, the scan produced images consistent with diagnoses other than appendicitis, expediting appropriate management. Early-imaging111 In oxyquinoline autologous leukocyte scanning is a practical and highly accurate adjunct for diagnosing appendicitis.

  3. Autologous serum skin test in chronic idiopathic urticaria

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    Godse Kiran


    Full Text Available BACKGROUND AND AIMS: Chronic urticaria has a spectrum of clinical presentations and causes. About 25%-45% of patients have histamine releasing autoantibodies in their blood. The term autoimmune urticaria is increasingly being accepted for this subgroup of patients. The term autoimmune urticaria is used to reflect advances in knowledge about functional autoantibodies that activate mast cells and basophils through cross linking high affinity IgE receptors to secrete histamine. This study was started to find out incidence of autoimmune urticaria in Indian patients. METHODS: The autologous serum skin test was done in 45 patients with chronic urticaria of more than six weeks duration. Physical urticaria patients were not included in the study. RESULTS: Twelve patients had positive autologous serum skin test suggestive of autoimmune urticaria. CONCLUSIONS: Positive autologous serum skin test was seen in 26.67% of patients which is less than reports from Western literature. This is a useful screening test for autoimmune urticaria.

  4. Therapeutic Potential of Autologous Stem Cell Transplantation for Cerebral Palsy

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    Chaitanya Purandare


    Full Text Available Background. Cerebral palsy (CP is a severe disabling disease with worldwide incidence being 2 to 3 per 1000 live births. CP was considered as a noncurable, nonreparative disorder, but stem cell therapy offers a potential treatment for CP. Objective. The present study evaluates the safety and efficacy of autologous bone-marrow-derived mononuclear cell (BMMNCs transplantation in CP patient. Material and Methods. In the present study, five infusions of autologous stem cells were injected intrathecally. Changes in neurological deficits and improvements in function were assessed using Gross Motor Function Classification System (GMFCS-E&R scale. Results. Significant motor, sensory, cognitive, and speech improvements were observed. Bowel and bladder control has been achieved. On the GMFCS-E&R level, the patient was promoted from grade III to I. Conclusion. In this study, we report that intrathecal infusion of autologous BMMNCs seems to be feasible, effective, and safe with encouraging functional outcome improvements in CP patient.

  5. Autologous fat grafting does not improve burn scar appearance: A prospective, randomized, double-blinded, placebo-controlled, pilot study. (United States)

    Gal, Shaili; Ramirez, Jesus Ignacio; Maguina, Pirko


    It has been proposed that fat grafts can improve the appearance of mature burn scars. The pluripotent progenitor cells contained within autologous adipose tissue grafts are believed to induce skin repair and improve scar appearance. We conducted a prospective, randomized, double-blinded, placebo-controlled study to evaluate the effects of fat grafts on the appearance of mature burn scars. Pediatric burn survivors with mature scars were recruited for this study. A homogeneous scar measuring 10×5cm was randomized into two halves: one was injected with autologous fat graft and the other with normal saline. Scar injection was performed using standard Coleman technique. Appearance of the two scar halves was assessed, six to twelve months later by the operating surgeon, by blinded observers and by the blinded patients. Eight patients completed the study pilot with 6-12 month follow-up. Assessment by the patients did not clearly favor fat grafts or saline injections; the operating surgeon did not identify any differences on any of the patients; the blinded observers measured all scars using Vancouver Scar Scale and noticed no differences in pigmentation, vascularity and height; differences in pliability showed similar changes in both the fat grafted and control arms. After the pilot was completed, decision was made to stop enrolling patients for this study since no benefit to fat grafting was observed. Single treatment with autologous fat grafts did not improve mature pediatric burn scars when compared to normal saline injections. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  6. Randomized clinical trial of autologous skin cell suspension for accelerating re-epithelialization of split-thickness donor sites. (United States)

    Hu, Z; Guo, D; Liu, P; Cao, X; Li, S; Zhu, J; Tang, B


    Split-thickness skin graft (STSG) is used frequently, but may result in complications at the donor site. Rapid healing of donor-site wounds is critical to relieving morbidity. This study investigated whether autologous skin cell suspension could improve healing of STSG donor-site wounds. Between September 2014 and February 2016, patients requiring STSGs were randomized to receive autologous skin cell suspension plus hydrocolloid dressings (experimental group) or hydrocolloid dressings alone (control group) for the donor site. The primary outcome was time to complete re-epithelialization. Secondary outcomes included pain and itching scores measured on a visual analogue scale, and adverse events. Patients were followed for 12 weeks to evaluate quality of healing. Analysis was by intention to treat. Some 106 patients were included, 53 in each group. Median time to complete re-epithelialization was 9·0 (95 per cent c.i. 8·3 to 9·7) days in the experimental group, compared with 13·0 (12·4 to 13·6) days in the control group (P suspension had been used. The use of autologous skin cell suspension with hydrocolloid dressings accelerated epithelialization and improved healing quality of the donor site compared with hydrocolloid dressings alone. Registration number: UMIN000015000 ( © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

  7. Tissue engineering approaches for the construction of a completely autologous tendon substitute

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    Bassetto Franco


    Full Text Available Tissue engineering is a multidisciplinary field that involves the application of the principles and methods of engineering and life sciences towards i the fundamental understanding of structure-function relationships in normal and pathological mammalian tissues and ii the development of biological substitutes that restore, maintain or improve tissue function. The goal of tissue engineering is to surpass the limitations of conventional treatments based on organ transplantation and biomaterial implantation. The field of tendon tissue engineering is relatively unexplored due to the difficulty in in vitro preservation of tenocyte phenotype. Only recently has mechanobiology allowed us to gain a better understanding of the fundamental role of in vitro mechanical stimuli in maintaining the phenotype of tendinous tissue. This review analyzes the techniques used so far for in vitro regeneration of tendinous tissue.

  8. Successful autologous simple limbal epithelial transplantation (SLET) in previously failed paediatric limbal transplantation for ocular surface burns. (United States)

    Bhalekar, Swapnil; Basu, Sayan; Lal, Ikeda; Sangwan, Virender S


    A 3-year-old child sustained severe ocular surface burns in her left eye after accidental lime injury. Despite appropriate management in the acute stage, she developed limbal stem cell deficiency (LSCD) in that eye. This was initially treated with autologous ex vivo cultivated limbal epithelial transplantation (CLET), which unfortunately failed after 6 months resulting in recurrence of LSCD. One year following CLET, she underwent simple limbal epithelial transplantation (SLET) using autologous donor tissue from the healthy fellow eye. Successful restoration of the ocular surface following SLET combined with amblyopia therapy led to significant cosmetic and functional improvement. One year following SLET her vision in the left eye was 20/80 and she continues to maintain a stable, avascular and completely epithelised corneal surface. This case illustrates that SLET is effective in treating LSCD even in cases that are conventionally considered to be at high risk for failure of limbal stem cell transplantation.

  9. Bortezomib/dexamethasone followed by autologous stem cell transplantation as front line treatment for light-chain deposition disease. (United States)

    Tovar, Natalia; Cibeira, Ma Teresa; Rosiñol, Laura; Solé, Manel; de Larrea, Carlos Fernández; Escoda, Lourdes; Rovira, Montserrat; Bladé, Joan


    Limited data has been published on the treatment results in patients with light-chain deposition disease (LCDD). Whenever possible, high-dose melphalan followed by autologous stem cell transplantation (ASCT) has been the first treatment option, achieving somehow better results than conventional therapy. However, and based on the promising results obtained by treating patients with light-chain amyloidosis with bortezomib/dexamethasone, new treatment options appear in LCDD. Herein, we describe three patients with LCDD treated with bortezomib/dexamethasone followed by high-dose melphalan and autologous transplantation. We believe that this new approach should be the treatment of choice in this disease. In addition, those patients achieving hematologic complete response after ASCT could benefit from a kidney transplant if the renal impairment requiring dialysis persists. © 2012 John Wiley & Sons A/S.

  10. Evaluation of dermal substitute in a novel co-transplantation model with autologous epidermal sheet.

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    Guofeng Huang

    Full Text Available The development of more and more new dermal substitutes requires a reliable and effective animal model to evaluate their safety and efficacy. In this study we constructed a novel animal model using co-transplantation of autologous epidermal sheets with dermal substitutes to repair full-thickness skin defects. Autologous epidermal sheets were obtained by digesting the basement membrane (BM and dermal components from rat split-thickness skins in Dispase II solution (1.2 u/ml at 4 °C for 8, 10 and 12 h. H&E, immunohistochemical and live/dead staining showed that the epidermal sheet preserved an intact epidermis without any BM or dermal components, and a high percentage of viable cells (92.10 ± 4.19% and P63 positive cells (67.43 ± 4.21% under an optimized condition. Porcine acellular dermal matrixes were co-transplanted with the autologous epidermal sheets to repair full-thickness skin defects in Sprague-Dawley rats. The epidermal sheets survived and completely re-covered the wounds within 3 weeks. Histological staining showed that the newly formed stratified epidermis attached directly onto the dermal matrix. Inflammatory cell infiltration and vascularization of the dermal matrix were not significantly different from those in the subcutaneous implantation model. Collagen IV and laminin distributed continuously at the epidermis and dermal matrix junction 4 weeks after transplantation. Transmission electron microscopy further confirmed the presence of continuous lamina densa and hemidesmosome structures. This novel animal model can be used not only to observe the biocompatibility of dermal substitutes, but also to evaluate their effects on new epidermis and BM formation. Therefore, it is a simple and reliable model for evaluating the safety and efficacy of dermal substitutes.


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    Littera Aperta


    Full Text Available LITTERA APERTA (Vol. 2 - 2014. Abstract: In its open and interdisciplinary scope, volume 2 of Littera Aperta. Journal of Literary and Cultural Studies continues the path opened in volume 1. It includes papers which belong to a wide range of periods, genres, nationalities and methodological approaches. Two complementary papers look into the figure of ghosts in the Classical writers Aristophanes and Lucretius: “The ghosts in Aristophanes’ Frogs” by Soraya Planchas Gallarte (Universidad Complutense de Madrid; and “Templa Serena against Acherusia Templa: A Materialistic Explanation of Ghosts in Lucretius” by Ángel J. Traver Vera (Junta de Extremadura. Juan de Dios Torralbo Caballero (Universidad de Córdoba analyzes the narrative techniques of the novel History of the Nun (1688 by the English writer Aphra Behn. In the field of contemporary world literature in English, Miryam Librán Moreno (Universidad de Extremadura traces the far-reaching influence of Sophocles’ Oedipus Tyrannus on the story of Túrin Turambar by J.R.R. Tolkien; and the researcher Damlègue Lare, from the University of Lomé (Togo, surveys Efo Kodjo Mawugbe’s procedures to debunk African patriarchal patterns of thought in his feminist play In the Chest of a Woman (2008. As a cultural complement to these research pieces, Gabriel Laguna Mariscal (Universidad de Córdoba interviews the Spanish philosopher Javier Gomá Lanzón about the philosophy of the interviewee himself, the role of the philosopher in the modern society and the relevance of Humanities in the education of citizenry. Gabriel Laguna also publishes a review about a book that Javier Gomá coauthors together with Carlos García Gual and Fernando Savater: Muchas felicidades. Tres visiones y más de la idea de felicidad. // LITTERA APERTA (Vol. 2 - 2014. Resumen: El volumen 2 de Littera Aperta. Journal of Literary and Cultural Studies continúa la línea interdisciplinar y abierta del volumen 1, al incluir

  12. Scaffold-based delivery of autologous mesenchymal stem cells for mandibular distraction osteogenesis: preliminary studies in a porcine model.

    Directory of Open Access Journals (Sweden)

    Zongyang Sun

    Full Text Available Bone regeneration through distraction osteogenesis (DO is promising but remarkably slow. To accelerate it, autologous mesenchymal stem cells have been directly injected to the distraction site in a few recent studies. Compared to direct injection, a scaffold-based method can provide earlier cell delivery with potentially better controlled cell distribution and retention. This pilot project investigated a scaffold-based cell-delivery approach in a porcine mandibular DO model.Eleven adolescent domestic pigs were used for two major sets of studies. The in-vitro set established methodologies to: aspirate bone marrow from the tibia; isolate, characterize and expand bone marrow-derived mesenchymal stem cells (BM-MSCs; enhance BM-MSC osteogenic differentiation using FGF-2; and confirm cell integration with a gelatin-based Gelfoam scaffold. The in-vivo set transplanted autologous stem cells into the mandibular distraction sites using Gelfoam scaffolds; completed a standard DO-course and assessed bone regeneration by macroscopic, radiographic and histological methods. Repeated-measure ANOVAs and t-tests were used for statistical analyses.From aspirated bone marrow, multi-potent, heterogeneous BM-MSCs purified from hematopoietic stem cell contamination were obtained. FGF-2 significantly enhanced pig BM-MSC osteogenic differentiation and proliferation, with 5 ng/ml determined as the optimal dosage. Pig BM-MSCs integrated readily with Gelfoam and maintained viability and proliferative ability. After integration with Gelfoam scaffolds, 2.4-5.8×10(7 autologous BM-MSCs (undifferentiated or differentiated were transplanted to each experimental DO site. Among 8 evaluable DO sites included in the final analyses, the experimental DO sites demonstrated less interfragmentary mobility, more advanced gap obliteration, higher mineral content and faster mineral apposition than the control sites, and all transplanted scaffolds were completely degraded.It is technically

  13. Complete Response to Trastuzumab-Based Chemotherapy in a Patient with Human Epidermal Growth Factor Receptor-2-Positive Metastatic Salivary Duct Carcinoma ex Pleomorphic Adenoma

    Directory of Open Access Journals (Sweden)

    Shigenori Kadowaki


    Full Text Available Introduction: Carcinoma ex pleomorphic adenoma (CXPA of the salivary glands has often a salivary duct carcinoma (SDC component, which resembles ductal carcinoma of the breast and frequently overexpresses human epidermal growth factor receptor-2 (HER2. We report a case of metastatic CXPA with SDC component who was treated with trastuzumab-based chemotherapy and has had a durable complete response. Case Report: A 74-year-old man was diagnosed with CXPA of the right parotid gland. The resected tumor was histologically diagnosed as CXPA with a predominant SDC component that showed strong positivity for HER2 protein and HER2 gene amplification. Multiple pulmonary metastatic lesions were detected after surgery, and combination chemotherapy with paclitaxel and trastuzumab was initiated. A complete response was confirmed after 7 treatment cycles, and no evidence of disease progression has been observed after 13 months of initiation of therapy. Conclusions: This report suggests a potential utility of trastuzumab-based chemotherapy for HER2-positive CXPA.

  14. Perilesional intrathecal administration of autologous bone marrow stromal cells achieves functional improvement in pigs with chronic paraplegia. (United States)

    Zurita, Mercedes; Aguayo, Concepcion; Bonilla, Celia; Rodriguez, Alicia; Vaquero, Jesus


    At present, on the basis of the great number of preclinical studies and preliminary clinical trials in humans, bone marrow stromal cell (BMSC) transplantation offers promise in the treatment of paraplegia. Nevertheless, there is not enough experience in humans about the best candidates for this type of cell therapy or details about the best parameters or best route of administration. Two adult paraplegic pigs with chronic paraplegia were treated only with perilesional intrathecal administration of 40 × 10(6) autologous BMSC suspended in autologous plasma and followed for 1 year after cell transplantation. Our study showed clinical improvement, starting at 2 mo after BMSC administration and reaching stabilization at 10 mo. This was associated with recovery of previously abolished somatosensory-evoked potentials. At the end of the study, histological images suggested spinal cord regeneration. Our present findings suggest the possible utility of perilesional intrathecal administration of autologous BMSC in patients with chronic paraplegia. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  15. The Influence of Barrier Membranes on Autologous Bone Grafts

    NARCIS (Netherlands)

    Gielkens, P. F. M.; Schortinghuis, J.; de Jong, J. R.; Paans, A. M. J.; Ruben, J. L.; Raghoebar, G. M.; Stegenga, B.; Bos, R. R. M.


    In implant dentistry, there is continuing debate regarding whether a barrier membrane should be applied to cover autologous bone grafts in jaw augmentation. A membrane would prevent graft remodeling with resorption and enhance graft incorporation. We hypothesized that membrane coverage does not

  16. Resorbable screws for fixation of autologous bone grafts

    NARCIS (Netherlands)

    Raghoebar, GM; Liem, RSB; Bos, RRM; van der Wal, JE; Vissink, A

    The aim of this study was to evaluate the suitability of resorbable screws made of poly (D,L-lactide) acid (PDLLA) for fixation of autologous bone grafts related to graft regeneration and osseointegration of dental implants. In eight edentulous patients suffering from insufficient retention of their

  17. Vaccination with apoptosis colorectal cancer cell pulsed autologous ...

    African Journals Online (AJOL)



    Feb 18, 2011 ... To investigate vaccination with apoptosis colorectal cancer (CRC) cell pulsed autologous dendritic cells. (DCs) in advanced CRC, 14 patients with advanced colorectal cancer (CRC) were enrolled and treated with DCs vaccine to assess toxicity, tolerability, immune and clinical responses to the vaccine. No.

  18. Experimental autologous substitute vascular graft for transplantation surgery

    NARCIS (Netherlands)

    Kobori, L; Dallos, G; Gouw, ASH; Nemeth, T; Nemes, B; Fehervari, I; Tegzess, Adam; Slooff, MJH; Perner, F; De Jong, KP


    Vascular complications in fiver transplantation are a major cause of graft failure and mortality. The aim of the study was to create autologous vascular graft without risk of rejection. Posterior rectus fascia sheath lined with peritoneum was used for iliac artery replacement in seven mongrel dogs.

  19. Autologous bone marrow mononuclear cell delivery to dilated ...

    African Journals Online (AJOL)



    Feb 5, 2008 ... therapeutic procedures, such as the intracoronary or intramyocardial implant of stem cells (mononuclear and mesenchymal) derived from bone-marrow aspirate from the individual's own bone marrow (autologous), consti- tutes a promising therapeutic option for these advanced cases (Helena et al., 2006).

  20. HIV Facial lipoatrophy correction with autologous whole blood as filler

    African Journals Online (AJOL)

    Serial treatment sessions produced a noticeable improvement in the facial volume and contour, eve n up to 5 months post treatment. Bruising was minimal and subtle and no other complications were encountered. Subcision with autologous whole blood injection is a potentially low-cost and effective treatment option to ...

  1. Autologous free fat transfer in patients with velopharyngeal insufficiency. (United States)

    Foroglou, Pericles; Goula, Olga Christina; Tsimponis, Antonis; Georgiadou, Elena; Demiri, Efterpi


    To report our initial experience and preliminary results of autologous free fat transfer to improve speech and hypernasality in patients with velopharyngeal insufficiency (VPI) as a sequela of cleft lip and palate repair. To date 2 patients with a mean age of 25 years were treated with this method. Both had initially received multiple procedures elsewhere for cleft lip and palate repair. We recorded the number of free fat transfer sessions, anatomical places of placement and volumes injected in-patient stay, occurrence or absence of complications and effectiveness of this operation in terms of clinical speech evaluation, functional velopharyngeal closure measurements and speech improvement percentage by an Ear, Nose and Throat (ENT) specialist. Two autologous free fat transfer sessions per patient were performed. Mean hospitalization time was 1 day per operation. Following liposuction, autologous free fat was transferred to the following anatomical areas: a) Passavant's ridge, b) uvula, c) palatopharyngeal and palatoglossal folds. The volume of fat injected varied from 6.5 cc to 8 cc per session. Postoperative periods were uneventful for both cases in each session. On clinical examination, improvement in speech was noted as well as a reduction in hypernasality with an improvement in articulation and audibility of consonant words, which were also reported by the patients' relatives. This was confirmed by objective nasendoscopy velopharyngeal closure measurements, both during speech and deglutition. Augmentation pharyngoveloplasty with autologous free fat transfer in patients with velopharyngeal insufficiency is a safe and innovative alternative, particularly for small to medium degrees of structural velophayngeal dysfunction.

  2. Osteoarthritis treatment using autologous conditioned serum after placebo

    NARCIS (Netherlands)

    Rutgers, Marijn; Creemers, Laura B; Yang, Kiem Gie Auw; Raijmakers, Natasja J H; Dhert, Wouter J A; Saris, Daniel B F


    Background and purpose - Autologous conditioned serum (ACS) is a disease-modifying drug for treatment of knee osteoarthritis, and modest superiority over placebo was reported in an earlier randomized controlled trial (RCT). We hypothesized that when given the opportunity, placebo-treated patients

  3. Osteoarthritis treatment using autologous conditioned serum after placebo

    NARCIS (Netherlands)

    Rutgers, Marijn; Creemers, Laura B; Auw Yang, Kiem Gie; Raijmakers, Natasja J H; Dhert, Wouter J A; Saris, Daniel B F

    BACKGROUND AND PURPOSE: Autologous conditioned serum (ACS) is a disease-modifying drug for treatment of knee osteoarthritis, and modest superiority over placebo was reported in an earlier randomized controlled trial (RCT). We hypothesized that when given the opportunity, placebo-treated patients

  4. Cost effectiveness of autologous blood transfusion -— A developing ...

    African Journals Online (AJOL)

    cipients (P=0.009). The rate of infection was 85.7% for ho- mologous blood recipients and 14.3% for autologous blood recipients. There was no significant difference in the means hospital charges, length of hospital stay and rate of infection in the entire population of patients who received blood transfusion when analysed ...

  5. Autologous bone marrow mononuclear cell delivery to dilated ...

    African Journals Online (AJOL)



    Feb 5, 2008 ... Autologous bone marrow mononuclear cell delivery to dilated cardiomyopathy patients: A clinical trial. P. L. N Kaparthi1*, Gupta Namita2, Lakshmi K. Chelluri2, .... Severe Co-morbid medical condition. 2. Severe LV systolic dysfunction with EF ≤ 30%. 2. LVEF ≥ 31%. 3. Stroke with significant sequel. 4.

  6. Vaccination with apoptosis colorectal cancer cell pulsed autologous ...

    African Journals Online (AJOL)

    To investigate vaccination with apoptosis colorectal cancer (CRC) cell pulsed autologous dendritic cells (DCs) in advanced CRC, 14 patients with advanced colorectal cancer (CRC) were enrolled and treated with DCs vaccine to assess toxicity, tolerability, immune and clinical responses to the vaccine. No severe toxicity ...

  7. Autologous epidermal cell suspension: A promising treatment for chronic wounds. (United States)

    Zhao, Hongliang; Chen, Yan; Zhang, Cuiping; Fu, Xiaobing


    Chronic wounds have become an increasing medical and economic problem of aging societies because they are difficult to manage. Skin grafting is an important treatment method for chronic wounds, which are refractory to conservative therapy. The technique involving epidermal cell suspensions was invented to enable the possibility of treating larger wounds with only a small piece of donor skin. Both uncultured and cultured autologous epidermal cell suspensions can be prepared and survive permanently on the wound bed. A systematic search was conducted of EMBASE, Cochrane Library, PubMed and web of science by using Boolean search terms, from the establishment of the database until May 31, 2014. The bibliographies of all retrieved articles in English were searched. The search terms were: (epithelial cell suspension OR keratinocyte suspension) and chronic and wound. From the included, 6 studies are descriptive interventions and discussed the use of autologous keratinocyte suspension to treat 61 patients' chronic wound. The various methods of preparation of epidermal cell suspension are described. The advantages and shortcomings of different carriers for epidermal cell suspensions are also summarised. Both uncultured and cultured autologous epidermal cell suspensions have been used to treat chronic wounds. Although the limitations of these studies include the small number of patient populations with chronic wounds and many important problems that remain to be solved, autologous epidermal cell suspension is a promising treatment for chronic wounds. Copyright © 2015 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

  8. Do autologous blood and PRP injections effectively treat tennis elbow? (United States)

    Widstrom, Luke; Slattengren, Andrew


    Both approaches reduce pain, but the improvement with platelet-rich plasma (PRP) is not clinically meaningful. Autologous blood injections (ABIs) are more effective than corticosteroid injections for reducing pain and disability in patients with tennis elbow in both the short and long term.

  9. Review of autologous blood transfusion at the Kenyatta National ...

    African Journals Online (AJOL)

    Objective: This study was performed over a three- month period to establish the pattern of autologous blood transfusion with specific focus on age, sex, type of surgery, duration of hospital stay and religious beliefs. Design: Hospital based prospective study. Setting: The study was conducted at the Kenyatta National Hospital ...

  10. Experience with predonated autologous blood transfusion in open ...

    African Journals Online (AJOL)

    Objectives: To find out the practicability, the acceptability, the effectiveness and the safety level of pre-donated, autologous blood transfusion (ABT) in patients who underwent open prostatectomy. Study design: Prospective. Patients and methods: It was a prospective study carried out in Nigeria over a 5-year period.

  11. Autologous buccal mucosa graft augmentation for foreshortened vagina. (United States)

    Grimsby, Gwen M; Bradshaw, Karen; Baker, Linda A


    Vaginal foreshortening after pelvic surgery or radiotherapy may lead to dyspareunia and decreased quality of life. Unfortunately, little literature exists regarding treatment options for this debilitating problem. Autologous buccal mucosal grafting has been previously reported for creation of a total neovagina and the repair of postvaginoplasty vaginal stenosis. Autologous buccal mucosa offers several advantages as a replacement material for vaginal reconstruction. Vaginal and oral buccal mucosa are both hairless, moist, nonkeratinized stratified squamous epithelia. Buccal mucosa has a dense layer of elastic fibers, imparting both elasticity and strength, and acquires a robust neovascularity with excellent graft take. The graft material is readily available and donor site scars are hidden in the mouth. A 60-year-old woman had vaginal foreshortening to 4.5 cm 15 years after radical hysterectomy and brachytherapy for endometrial cancer. She was unable to have intercourse despite attempted vaginal dilation. Her foreshortened vagina was successfully augmented with autologous buccal mucosa grafting at the apex, increasing her vaginal length to 8 cm and permitting pain-free intercourse. Even in the face of an altered surgical field after radical hysterectomy and radiation, autologous buccal mucosa is an option for vaginal reconstruction for vaginal foreshortening.

  12. Treatment of alveolar cleft performing a pyramidal pocket and an autologous bone grafting. (United States)

    Morselli, Paolo Giovanni; Giuliani, Renzo; Pinto, Valentina; Oranges, Carlo Maria; Negosanti, Luca; Tavaniello, Beatrice; Morellini, Andrea


    Alveolar cleft repair is a debate topic in cleft lip and palate treatment.The aim of this article is to analyze the outcomes and the advantages of the autologous bone grafting performed during the period between 1981 and 2006. In our plastic surgery unit, 468 patients with alveolar clefts have been treated. According to our protocol, the timing for the closure of the alveolar cleft ranged from 7 to 11 years (mean, 9.4 years). Autologous bone was taken from the skull in the 45% of patients, from the iliac crest in 35% of cases, and from the chin in 20% of cases. The surgical technique of creating a pyramidal pocket to secure the bone graft was central to achieving a good result. The postoperative evaluation of the results, using clinical criteria and endoral radiography, orthopantomography, and teleradiography at 3, 6, 12 months after surgery, and more recently, in the last 82 cases by a three-dimensional computed tomography, allows us to assert that we obtained optimal results in 50% of treated cases, good results in 40%, sufficient in 4%, partial failure in 5.4%, and complete failure in 0.6%.


    Directory of Open Access Journals (Sweden)

    Patrizia Tosi


    Full Text Available

    Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achivng a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate.

  14. A Simple, Reliable, and Inexpensive Intraoperative External Expansion System for Enhanced Autologous Structural Fat Grafting

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    Carlo M. Oranges


    Full Text Available External volume expansion of the recipient site by suction has been proposed as a way of improving fat graft survival. The objective of this study was to present an innovative and simple intraoperative external expansion system to enhance small-volume autologous fat grafting (40–80 mL and to discuss its background and its mechanism of action. In this system, expansion is performed using a complete vacuum delivery system known as the Kiwi VAC-6000M with a PalmPump (Clinical Innovations. The recipient site is rapidly expanded intraoperatively 10 times for 30 seconds each with a negative pressure of up to 550 mm Hg before autologous fat injection. During this repetitive stimulation, the tissues become grossly expanded, developing macroscopic swelling that regresses slowly over the course of hours following the cessation of the stimulus. The system sets various mechanisms in motion, including scar release, mechanical stimulation, edema, ischemia, and inflammation, which provide an environment conducive for cell proliferation and angiogenesis. In order to maintain the graft construct in its expansive state, all patients are encouraged postoperatively to use the Kiwi three times daily for one minute per session over the course of three days. The handling of this system is simple for both the patients and the surgeon. Satisfactory clinical outcomes have been achieved without significant complications.

  15. Comparative study of autologous fat vs hyaluronic acid in correction of the nasolabial folds. (United States)

    Hu, Xiaogen; Xue, Zhiqiang; Qi, Huijie; Chen, Bo


    In the article, comparison of the hyaluronic acid (HA) and autologous fat is conducted to evaluate the effectiveness and safety in correction of the nasolabial folds (NLFs). From November 2012 to December 2015, a single-blinded, randomized study was conducted. Sixty-two patients were included in the study, and 57 of them completed the whole procedure. The patients were randomly allocated to receive the treatments of HA or fat in both NLFs. The Wrinkle Severity Rating Scale (WSRS) and Global Aesthetic Improvement Scale (GAIS) were used for assessment. Efficacy was assessed using two parameters: evaluation of final improvement by blinded evaluator and patient-self using photographs. The effectiveness endpoint was improvement of scores at 1, 3, 6, 9, and 12 months from baseline. The adverse events (AEs) were recorded. In the blinded evaluator scores for NLF in accordance with WSRS, there were no significant differences between the two methods within 9 months. A statistically significant difference between the lipoinjection and HA groups was found at 12-month follow-up period. Subjects' self-assessment was similar to the results seen for the evaluator scores. The difference of AEs between the HA and fat group was obvious in the early stage of recovery. In the later stage, the AEs of the HA and fat group were similar. Both HA gel and autologous fat provide augmentation of NLFs. The magnitude and duration of NLF correction appear to be similarly effective and safe within a period. © 2017 Wiley Periodicals, Inc.

  16. Autologous mini punch grafting: An experience of using motorized power punch in 10 patients

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    B S Chandrashekar


    Full Text Available Background: Autologous mini punch grafting (MPG is a safe, effective and easy technique that can be performed on any site with minimal side effects and good cosmetic results. Large areas of stable generalised vitiligo require more grafts and are time consuming. Hence multiple sessions of surgery need to be scheduled. We share our experience of using motorised power punches to increase the speed of surgery in large areas of stable vitiligo in 10 patients. Materials and Methods: Ten patients in the age group of 12-55 years were treated with miniature punch grafting using power punches in single session on various sites. The power punches of 1-1.5 mm diameter were used to score donor and recipient sites, either of same or less than 0.2-0.3 mm size punches. The harvested grafts from donor site were then secured in the recipient beds and dressed. Results: The average number of grafts harvested per session was 125-185, the duration of surgery ranged from 45 to 90 minutes. Perigraft pigment spread was seen at 3 weeks. Complete repigmentation was observed in 3-4 months in eight patients. Cobble stoning was observed in one patient, and all donor sites healed well with superficial scarring. Conclusion: We conclude that autologous MPG with motorised power punches for stable vitiligo, especially on large areas including difficult sites can be performed with ease in comparatively lesser time in a single session, greatly benefiting the patients.

  17. Identification of a Novel Human Papillomavirus, Type HPV199, Isolated from a Nasopharynx and Anal Canal, and Complete Genomic Characterization of Papillomavirus Species Gamma-12.

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    Anja Oštrbenk

    Full Text Available The novel human papillomavirus type 199 (HPV199 was initially identified in a nasopharyngeal swab sample obtained from a 25 year-old immunocompetent male. The complete genome of HPV199 is 7,184 bp in length with a GC content of 36.5%. Comparative genomic characterization of HPV199 and its closest relatives showed the classical genomic organization of Gammapapillomaviruses (Gamma-PVs. HPV199 has seven major open reading frames (ORFs, encoding five early (E1, E2, E4, E6, and E7 and two late (L1 and L2 proteins, while lacking the E5 ORF. The long control region (LCR of 513 bp is located between the L1 and E6 ORFs. Phylogenetic analysis additionally confirmed that HPV-199 clusters into the Gamma-PV genus, species Gamma-12, additionally containing HPV127, HV132, HPV148, HPV165, and three putative HPV types: KC5, CG2 and CG3. HPV199 is most closely related to HPV127 (nucleotide identity 77%. The complete viral genome sequence of additional HPV199 isolate was determined from anal canal swab sample. Two HPV199 complete viral sequences exhibit 99.4% nucleotide identity. To the best of our knowledge, this is the first member of Gamma-PV with complete nucleotide sequences determined from two independent clinical samples. To evaluate the tissue tropism of the novel HPV type, 916 clinical samples were tested using HPV199 type-specific real-time PCR: HPV199 was detected in 2/76 tissue samples of histologically confirmed common warts, 2/108 samples of eyebrow hair follicles, 2/137 anal canal swabs obtained from individuals with clinically evident anal pathology, 4/184 nasopharyngeal swabs and 3/411 cervical swabs obtained from women with normal cervical cytology. Although HPV199 was found in 1.4% of cutaneous and mucosal samples only, it exhibits dual tissue tropism. According to the results of our study and literature data, dual tropism of all Gamma-12 members is highly possible.

  18. Complete mitochondrial genomes of Taenia multiceps, T. hydatigena and T. pisiformis: additional molecular markers for a tapeworm genus of human and animal health significance (United States)


    Background Mitochondrial genomes provide a rich source of molecular variation of proven and widespread utility in molecular ecology, population genetics and evolutionary biology. The tapeworm genus Taenia includes a diversity of tapeworm parasites of significant human and veterinary importance. Here we add complete sequences of the mt genomes of T. multiceps, T. hydatigena and T. pisiformis, to a data set of 4 published mtDNAs in the same genus. Seven complete mt genomes of Taenia species are used to compare and contrast variation within and between genomes in the genus, to estimate a phylogeny for the genus, and to develop novel molecular markers as part of an extended mitochondrial toolkit. Results The complete circular mtDNAs of T. multiceps, T. hydatigena and T. pisiformis were 13,693, 13,492 and 13,387 bp in size respectively, comprising the usual complement of flatworm genes. Start and stop codons of protein coding genes included those found commonly amongst other platyhelminth mt genomes, but the much rarer initiation codon GTT was inferred for the gene atp6 in T. pisiformis. Phylogenetic analysis of mtDNAs offered novel estimates of the interrelationships of Taenia. Sliding window analyses showed nad6, nad5, atp6, nad3 and nad2 are amongst the most variable of genes per unit length, with the highest peaks in nucleotide diversity found in nad5. New primer pairs capable of amplifying fragments of variable DNA in nad1, rrnS and nad5 genes were designed in silico and tested as possible alternatives to existing mitochondrial markers for Taenia. Conclusions With the availability of complete mtDNAs of 7 Taenia species, we have shown that analysis of amino acids provides a robust estimate of phylogeny for the genus that differs markedly from morphological estimates or those using partial genes; with implications for understanding the evolutionary radiation of important Taenia. Full alignment of the nucleotides of Taenia mtDNAs and sliding window analysis suggests

  19. Factors associated with initiation and completion of the quadrivalent human papillomavirus vaccine series in an ontario cohort of grade 8 girls

    Directory of Open Access Journals (Sweden)

    Kwong Jeffrey C


    Full Text Available Abstract Background Although over a hundred million dollars have been invested in offering free quadrivalent human papillomavirus (HPV vaccination to young girls in Ontario, there continues to be very little information about its usage. In order to successfully guide future HPV vaccine programming, it is important to monitor HPV vaccine use and determine factors associated with use in this population. Methods Linking administrative health and immunization databases, we conducted a population-based, retrospective cohort study of girls eligible for Ontario's Grade 8 HPV vaccination program in Kingston, Frontenac, Lennox, and Addington. We determined the proportion of girls who initiated (at least one dose and completed (all three doses the vaccination series overall and according to socio-demographics, vaccination history, health services utilization, medical history, and program year. Multivariable logistic regression was used to estimate the strength of association between individual factors and initiation and completion, adjusted for all other factors. Results We identified a cohort of 2519 girls, 56.6% of whom received at least one dose of the HPV vaccine. Among vaccinated girls, 85.3% received all three doses. Vaccination history was the strongest predictor of initiation in that girls who received the measles-mumps-rubella, meningococcal C, and hepatitis B vaccines were considerably more likely to also receive the HPV vaccine (odds ratio 4.89; 95% confidence interval 4.04-5.92. Nevertheless, HPV vaccine uptake was more than 20% lower than that of these other vaccines. In addition, while series initiation was not influenced by income, series completion was. In particular, girls of low income were the least likely to receive all three indicated doses of the HPV vaccine (odds ratio 0.45; 95% confidence interval 0.28-0.72. Conclusions The current low level of HPV vaccine acceptance in Kingston, Frontenac, Lennox, and Addington will likely have

  20. Regeneration of Tissues and Organs Using Autologous Cells

    Energy Technology Data Exchange (ETDEWEB)

    Anthony Atala


    The Joint Commission for Health Care Organizations recently declared the shortage of transplantable organs and tissues a public health crisis. As such, there is about one death every 30 seconds due to organ failure. Complications and rejection are still significant albeit underappreciated problems. It is often overlooked that organ transplantation results in the patient being placed on an immune suppression regimen that will ultimate shorten their life span. Patients facing reconstruction often find that surgery is difficult or impossible due to the shortage of healthy autologous tissue. In many cases, autografting is a compromise between the condition and the cure that can result in substantial diminution of quality of life. The national cost of caring for persons who might benefit from engineered tissues or organs has reached $600 billion annually. Autologous tissue technologies have been developed as an alternative to transplantation or reconstructive surgery. Autologous tissues derived from the patient's own cells are capable of correcting numerous pathologies and injuries. The use of autologous cells eliminates the risks of rejection and immunological reactions, drastically reduces the time that patients must wait for lifesaving surgery, and negates the need for autologous tissue harvest, thereby eliminating the associated morbidities. In fact, the use of autologous tissues to create functional organs is one of the most important and groundbreaking steps ever taken in medicine. Although the basic premise of creating tissues in the laboratory has progressed dramatically, only a limited number of tissue developments have reached the patients to date. This is due, in part, to the several major technological challenges that require solutions. To that end, we have been in pursuit of more efficient ways to expand cells in vitro, methods to improve vascular support so that relevant volumes of engineered tissues can be grown, and constructs that can mimic the

  1. Company profile: Complete Genomics Inc. (United States)

    Reid, Clifford


    Complete Genomics Inc. is a life sciences company that focuses on complete human genome sequencing. It is taking a completely different approach to DNA sequencing than other companies in the industry. Rather than building a general-purpose platform for sequencing all organisms and all applications, it has focused on a single application - complete human genome sequencing. The company's Complete Genomics Analysis Platform (CGA™ Platform) comprises an integrated package of biochemistry, instrumentation and software that sequences human genomes at the highest quality, lowest cost and largest scale available. Complete Genomics offers a turnkey service that enables customers to outsource their human genome sequencing to the company's genome sequencing center in Mountain View, CA, USA. Customers send in their DNA samples, the company does all the library preparation, DNA sequencing, assembly and variant analysis, and customers receive research-ready data that they can use for biological discovery.

  2. Treatment of chronic non-healing ulcers using autologous platelet rich plasma: a case series. (United States)

    Suthar, Manish; Gupta, Saniya; Bukhari, Suhail; Ponemone, Venkatesh


    Non-healing ulcers are a major health problem worldwide and have great impact at personal, professional and social levels, with high cost in terms of human and material resources. Recalcitrant non-healing ulcers are inevitable and detrimental to the lower limb and are a major cause of non-traumatic lower limb amputations. Application of autologous Platelet Rich Plasma (PRP) has been a major breakthrough for the treatment of non-healing and diabetic foot ulcers, as it is an easy and cost-effective method, and provides the necessary growth factors that enhance tissue healing. PRP is a conglomeration of thrombocytes, cytokines and various growth factors which are secreted by α-granules of platelets that augment the rate of natural healing process with decrease in time. The purpose of this case series was to evaluate the safety and efficacy of autologous platelet rich plasma for the treatment of chronic non-healing ulcers on the lower extremity. Autologous PRP was prepared from whole blood utilizing a rapid, intraoperative point-of-care system that works on the principle of density gradient centrifugation. Twenty Four (24) patients with non-healing ulcers of different etiologies, who met the inclusion criteria, were treated with single dose of subcutaneous PRP injections along with topical application of PRP gel under compassionate use. The mean age of the treated patients was 62.5 ± 13.53 years and they were followed-up for a period of 24 weeks. All the patients showed signs of wound healing with reduction in wound size, and the mean time duration to ulcer healing was 8.2 weeks. Also, an average five fold increase in the platelet concentrate was observed in the final PRP product obtained using the rapid point-of-care device, and the average platelet dose administered to the patients was 70.10 × 10(8). This case series has demonstrated the potential safety and efficacy of autologous platelet rich plasma for the treatment of chronic non-healing ulcers. NCT

  3. Use of containers with sterilizing filter in autologous serum eyedrops. (United States)

    López-García, José S; García-Lozano, Isabel


    To assess the effect of the use of containers with an adapted sterilizing filter on the contamination of autologous serum eyedrops. Prospective, consecutive, comparative, and randomized study. Thirty patients with Sjögren syndrome. One hundred seventy-six autologous serum containers used in home therapy were studied; 48 of them included an adapted filter (Hyabak; Thea, Clermont-Ferrand, France), and the other 128 were conventional containers. Containers equipped with a filter were tested at 7, 14, 21, and 28 days of use, whereas conventional containers were studied after 7 days of use. In addition, testing for contamination was carried out in 14 conventional containers used during in-patient therapy every week for 4 weeks. In all cases, the preparation of the autologous serum was similar. Blood agar and chocolate agar were used as regular culture media for the microbiologic studies, whereas Sabouraud agar with chloramphenicol was the medium for fungal studies. Microbiologic contamination of containers with autologous serum eyedrops. Only one of the containers with an adapted sterilizing filter (2.1%) became contaminated with Staphylococcus epidermidis after 1 month of treatment, whereas the contamination rate among conventional containers reached 28.9% after 7 days of treatment. The most frequent germs found in the samples were coagulase-negative Staphylococcus (48.6%). With regard the containers used in the in-patient setting, 2 (14.3%) became contaminated after 2 weeks, 5 (35.7%) became contaminated after 3 weeks, and 5 (50%) became contaminated after 4 weeks, leaving 7 (50%) that did not become contaminated after 1 month of treatment. Using containers with an adapted filter significantly reduces the contamination rates in autologous serum eyedrops, thus extending the use of such container by the patients for up to 4 weeks with virtually no contamination risks. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  4. Survival of Mexican Children with Acute Myeloid Leukaemia Who Received Early Intensification Chemotherapy and an Autologous Transplant

    Directory of Open Access Journals (Sweden)

    Elva Jiménez-Hernández


    Full Text Available Background. In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. Procedure. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients, diagnosed in the period 2005–2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients, diagnosed in the period 1999–2004, was treated as Group A, but without the early intensified chemotherapy. Results. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P=0.041. Overall survival for Group A (18, 90% was higher than that for Group B (60%. Complete remission continued for two years of follow-up. Conclusions. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy.

  5. Arthrocentesis followed by intra-articular autologous blood injection for the treatment of recurrent temporomandibular joint dislocation. (United States)

    Bayoumi, A M; Al-Sebaei, M O; Mohamed, K M; Al-Yamani, A O; Makrami, A M


    Temporomandibular joint (TMJ) dislocation is an excessive forward movement of the condyle beyond the articular eminence with complete separation of the articular surfaces and fixation in that position. This study was conducted to assess autologous blood injection to the TMJ for the treatment of chronic recurrent TMJ dislocation. Fifteen patients with bilateral chronic recurrent condylar dislocation were included in the study. Bilateral TMJ arthrocentesis was performed on each patient, followed by the injection of 2ml of autologous blood into the superior joint compartment and 1ml onto the outer surface of the joint capsule. Preoperative and postoperative assessment included a thorough history and physical examination to determine the maximal mouth opening, presence of pain and sounds, frequency of luxation, recurrence rate, and presence of facial nerve paralysis. Eighty percent of the subjects (12 patients) had a successful outcome with no further episodes of dislocation and required no further treatment at their 1-year follow-up, whereas three patients had recurrent dislocation as early as 2 weeks after treatment. Autologous blood injection is a safe, simple, and cost-effective treatment for chronic recurrent TMJ dislocation. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  6. Autologous adult cortical cell transplantation enhances functional recovery following unilateral lesion of motor cortex in primates: a pilot study. (United States)

    Kaeser, Mélanie; Brunet, Jean-François; Wyss, Alexander; Belhaj-Saif, Abderraouf; Liu, Yu; Hamadjida, Adjia; Rouiller, Eric M; Bloch, Jocelyne


    Although cell therapy is a promising approach after cerebral cortex lesion, few studies assess quantitatively its behavioral gain in nonhuman primates. Furthermore, implantations of fetal grafts of exogenous stem cells are limited by safety and ethical issues. To test in nonhuman primates the transplantation of autologous adult neural progenitor cortical cells with assessment of functional outcome. Seven adult macaque monkeys were trained to perform a manual dexterity task, before the hand representation in motor cortex was chemically lesioned unilaterally. Five monkeys were used as control, compared with 2 monkeys subjected to different autologous cells transplantation protocols performed at different time intervals. After lesion, there was a complete loss of manual dexterity in the contralesional hand. The 5 "control" monkeys recovered progressively and spontaneously part of their manual dexterity, reaching a unique and definitive plateau of recovery, ranging from 38% to 98% of prelesion score after 10 to 120 days. The 2 "treated" monkeys reached a first spontaneous recovery plateau at about 25 and 40 days postlesion, representing 35% and 61% of the prelesion performance, respectively. In contrast to the controls, a second recovery plateau took place 2 to 3 months after cell transplantation, corresponding to an additional enhancement of functional recovery, representing 24% and 37% improvement, respectively. These pilot data, derived from 2 monkeys treated differently, suggest that, in the present experimental conditions, autologous adult brain progenitor cell transplantation in a nonhuman primate is safe and promotes enhancement of functional recovery.

  7. Treatment of severe osteochondral defects of the knee by combined autologous bone grafting and autologous chondrocyte implantation using fibrin gel

    NARCIS (Netherlands)

    Konst, Y.E.; Benink, R.J.; Veldstra, R.; van der Krieke, T.J.; Helder, M.N.; van Royen, B.J.


    Purpose: Severe symptomatic and unstable osteochondral defects of the knee are difficult to treat. A variety of surgical techniques have been developed. However, the optimal surgical technique is still controversial. We present a novel technique in which autologous bone grafting is combined with

  8. Genomic organization and complete cDNA sequence of the human phosphoinositide-specific phospholipase C {beta}3 gene (PLCB3)

    Energy Technology Data Exchange (ETDEWEB)

    Lagercrantz, J.; Carson, E.; Phelan, C. [Karolinska Hospital, Stockholm (Sweden)] [and others


    We have characterized the complete cDNA sequence, genomic structure, and expression of the human phosphoinositide-specific phospholipase C {beta}3 (PLC {beta}3) gene (gene symbol PLCB3). PLC {beta}3 plays an important role in initiating receptor-mediated signal transduction. Activation of PLC takes place in many cells as a response to stimulation by hormones, growth factors, neurotransmitters, and other ligands. The partial cDNA sequence of PLC {beta}3, previously published, was extended with 876 bp in the 5{prime} direction, giving a transcript of 4400 bp and a total open reading frame of 1234 amino acids. This was in accordance with expression analysis by Northern blotting that revealed a single 4.4-kb transcript in all tissues tested. Genomic data were obtained by sequencing plasmid subclones of a cosmid that contained the whole gene. The size of the complete transcription unit was estimated to be on the order of 15 kb. The gene contains 31 exons, with all splice donor and acceptor sites conforming to the GT/AG rule. No exon exceeds 571 bp in length, and the shortest exon spans only 36 bp. More than half of the introns are smaller than 200 bp, with the smallest being only 79 bp long. The transcription initiation site was determined to be within an 8-bp cluster 328-321 bp upstream of the translation initiation site. The 5{prime} flanking region is highly GC rich, with multiple CpG doublets, and contains multiple binding sites for Sp1. Lacking typical transcriptional regulatory sequences such as TATA and CAAT boxes, the putative promoter region conforms to the group of housekeeping promoters. 28 refs., 4 figs., 1 tab.

  9. Complete genome sequence, lifestyle, and multi-drug resistance of the human pathogen Corynebacterium resistens DSM 45100 isolated from blood samples of a leukemia patient

    Directory of Open Access Journals (Sweden)

    Schröder Jasmin


    Full Text Available Abstract Background Corynebacterium resistens was initially recovered from human infections and recognized as a new coryneform species that is highly resistant to antimicrobial agents. Bacteremia associated with this organism in immunocompromised patients was rapidly fatal as standard minocycline therapies failed. C. resistens DSM 45100 was isolated from a blood culture of samples taken from a patient with acute myelocytic leukemia. The complete genome sequence of C. resistens DSM 45100 was determined by pyrosequencing to identify genes contributing to multi-drug resistance, virulence, and the lipophilic lifestyle of this newly described human pathogen. Results The genome of C. resistens DSM 45100 consists of a circular chromosome of 2,601,311 bp in size and the 28,312-bp plasmid pJA144188. Metabolic analysis showed that the genome of C. resistens DSM 45100 lacks genes for typical sugar uptake systems, anaplerotic functions, and a fatty acid synthase, explaining the strict lipophilic lifestyle of this species. The genome encodes a broad spectrum of enzymes ensuring the availability of exogenous fatty acids for growth, including predicted virulence factors that probably contribute to fatty acid metabolism by damaging host tissue. C. resistens DSM 45100 is able to use external L-histidine as a combined carbon and nitrogen source, presumably as a result of adaptation to the hitherto unknown habitat on the human skin. Plasmid pJA144188 harbors several genes contributing to antibiotic resistance of C. resistens DSM 45100, including a tetracycline resistance region of the Tet W type known from Lactobacillus reuteri and Streptococcus suis. The tet(W gene of pJA144188 was cloned in Corynebacterium glutamicum and was shown to confer high levels of resistance to tetracycline, doxycycline, and minocycline in vitro. Conclusions The detected gene repertoire of C. resistens DSM 45100 provides insights into the lipophilic lifestyle and virulence functions of

  10. Completely continuous and weakly completely continuous abstract ...

    Indian Academy of Sciences (India)

    if the operator ρa of right multiplication by a is compact (weakly compact, respectively). An algebra A is called right completely continuous (right weakly completely continuous) if any element a ∈ A is right completely continuous (right weakly completely con- tinuous, respectively). Left completely continuous (left weakly ...

  11. Beneficial effects of autologous bone marrow-derived mesenchymal stem cells in naturally occurring tendinopathy.

    Directory of Open Access Journals (Sweden)

    Roger Kenneth Whealands Smith

    Full Text Available Tendon injuries are a common age-related degenerative condition where current treatment strategies fail to restore functionality and normal quality of life. This disease also occurs naturally in horses, with many similarities to human tendinopathy making it an ideal large animal model for human disease. Regenerative approaches are increasingly used to improve outcome involving mesenchymal stem cells (MSCs, supported by clinical data where injection of autologous bone marrow derived MSCs (BM-MSCs suspended in marrow supernatant into injured tendons has halved the re-injury rate in racehorses. We hypothesized that stem cell therapy induces a matrix more closely resembling normal tendon than the fibrous scar tissue formed by natural repair. Twelve horses with career-ending naturally-occurring superficial digital flexor tendon injury were allocated randomly to treatment and control groups. 1X10(7 autologous BM-MSCs suspended in 2 ml of marrow supernatant were implanted into the damaged tendon of the treated group. The control group received the same volume of saline. Following a 6 month exercise programme horses were euthanized and tendons assessed for structural stiffness by non-destructive mechanical testing and for morphological and molecular composition. BM-MSC treated tendons exhibited statistically significant improvements in key parameters compared to saline-injected control tendons towards that of normal tendons and those in the contralateral limbs. Specifically, treated tendons had lower structural stiffness (p<0.05 although no significant difference in calculated modulus of elasticity, lower (improved histological scoring of organisation (p<0.003 and crimp pattern (p<0.05, lower cellularity (p<0.007, DNA content (p<0.05, vascularity (p<0.03, water content (p<0.05, GAG content (p<0.05, and MMP-13 activity (p<0.02. Treatment with autologous MSCs in marrow supernatant therefore provides significant benefits compared to untreated tendon repair

  12. Safety and neurological assessments after autologous transplantation of bone marrow mesenchymal stem cells in subjects with chronic spinal cord injury. (United States)

    Mendonça, Marcus Vinícius Pinheiro; Larocca, Ticiana Ferreira; de Freitas Souza, Bruno Solano; Villarreal, Cristiane Flora; Silva, Luiz Flávio Maia; Matos, André Costa; Novaes, Marco Antonio; Bahia, Cláudia Maria Pinheiro; de Oliveira Melo Martinez, Ana Carine; Kaneto, Carla Martins; Furtado, Sissi Brandão Carneiro; Sampaio, Geraldo Pedral; Soares, Milena Botelho Pereira; dos Santos, Ricardo Ribeiro


    The administration of stem cells holds promise as a potential therapy for spinal cord injury (SCI). Mesenchymal stem cells have advantages for clinical applications, since they can be easily obtained, are suitable for autologous transplantation and have been previously shown to induce regeneration of the spinal cord in experimental settings. Here we evaluated the feasibility, safety and potential efficacy of autologous transplantation of mesenchymal stem cells in subjects with chronic complete SCI. We conducted a phase I, non-controlled study in 14 subjects of both genders aging between 18 to 65 years, with chronic traumatic SCI (>6 months), at thoracic or lumbar levels, classified as American Spinal Injury Association (ASIA) A - complete injury. Baseline somatosensory evoked potentials (SSEP), spinal magnetic resonance imaging (MRI) and urodynamics were assessed before and after treatment. Pain rating was performed using the McGill Pain Questionnaire and a visual analogue score scale. Bone marrow-derived mesenchymal stem cells were cultured and characterized by flow cytometry, cell differentiation assays and G-band karyotyping. Mesenchymal stem cells were injected directly into the lesion following laminectomy and durotomy. Cell transplantation was an overall safe and well-tolerated procedure. All subjects displayed variable improvements in tactile sensitivity and eight subjects developed lower limbs motor functional gains, principally in the hip flexors. Seven subjects presented sacral sparing and improved American Spinal Injury Association impairment scale (AIS) grades to B or C - incomplete injury. Nine subjects had improvements in urologic function. One subject presented changes in SSEP 3 and 6 months after mesenchymal stem cells transplantation. Statistically significant correlations between the improvements in neurological function and both injury size and level were found. Intralesional transplantation of autologous mesenchymal stem cells in subjects with

  13. Autologous stem cell transplantation in myelodysplastic syndromes.

    NARCIS (Netherlands)

    Witte, T.J.M. de; Suciu, S.; Brand, R.; Muus, P.; Kroger, N.


    Allogeneic stem cell transplantation (SCT) is the treatment of choice for the majority of young patients with myelodysplasia (MDS) who have a histocompatible donor (sibling or unrelated donor). For some patients lacking a human leukocyte antigen (HLA)-compatible donor, chemotherapy followed by

  14. Autologous bone marrow stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the jaw

    Directory of Open Access Journals (Sweden)

    Cella Luigi


    Full Text Available Abstract Purpose Bisphosphonate - related osteonecrosis of the JAW (BRONJ is a well known side effect of bisphosphonate therapies in oncologic and non oncologic patients. Since to date no definitive consensus has been reached on the treatment of BRONJ, novel strategies for the prevention, risk reduction and treatment need to be developed. We report a 75 year old woman with stage 3 BRONJ secondary to alendronate and pamidronate treatment of osteoporosis. The patient was unresponsive to recommended treatment of the disease, and her BRONJ was worsening. Since bone marrow stem cells are know as being multipotent and exhibit the potential for differentiation into different cells/tissue lineages, including cartilage, bone and other tissue, we performed autologous bone marrow stem cell transplantation into the BRONJ lesion of the patient. Methods Under local anesthesia a volume of 75 ml of bone marrow were harvested from the posterior superior iliac crest by aspiration into heparinized siringes. The cell suspension was concentrated, using Ficoll - Hypaque® centrifugation procedures, in a final volume of 6 ml. Before the injection of stem cells into the osteonecrosis, the patient underwent surgical toilet, local anesthesia was done and spongostan was applied as a carrier of stem cells suspension in the bone cavity, then 4 ml of stem cells suspension and 1 ml of patient's activated platelet-rich plasma were injected in the lesion of BRONJ. Results A week later the residual spongostan was removed and two weeks later resolution of symptoms was obtained. Then the lesion improved with progressive superficialization of the mucosal layer and CT scan, performed 15 months later, shows improvement also of bone via concentric ossification: so complete healing of BRONJ (stage 0 was obtained in our patient, and 30 months later the patient is well and without signs of BRONJ. Conclusion To our knowledge this is the first case of BRONJ successfully treated with

  15. Facial Fat Necrosis Following Autologous Fat Transfer and its Management


    Sweta Rai; Alexander M Marsland; Vishal Madan


    Autologous fat transfer (AFT) is an increasingly popular cosmetic procedure practiced by dermatologic surgeons worldwide. As this is an office based procedure performed under local or tumescent anaesthesia with fat transferred within the same individual and limited associated down time its is considered relatively safe and risk free in the cosmetic surgery arena. We describe a case of AFT related fat necrosis causing significant facial dysmorphia and psychosocial distress. We also discuss the...

  16. Autologous platelet-poor plasma gel for injection laryngoplasty. (United States)

    Woo, Seung Hoon; Kim, Jin Pyeong; Park, Jung Je; Chung, Phil-Sang; Lee, Sang-Hyuk; Jeong, Han-Sin


    To overcome the potential disadvantages of the use of foreign materials and autologous fat or collagen, we introduce here an autologous plasma gel for injection laryngoplasty. The purpose of this study was to present a new injection material, a plasma gel, and to discuss its clinical effectiveness. From 2 mL of blood, the platelet poor serum layer was collected and heated at 100°C for 12 min to form a plasma gel. The plasma gel was then injected into a targeted site; the safety and efficacy thereof were evaluated in 30 rats. We also conducted a phase I/II clinical study of plasma gel injection laryngoplasty in 11 unilateral vocal fold paralysis patients. The plasma gel was semi-solid and an easily injectable material. Of note, plasma gel maintains the same consistency for up to 1 year in a sealed bottle. However, exposure to room air causes the plasma gel to disappear within 1 month. In our animal study, the autologous plasma gel remained in situ for 6 months in animals with minimal inflammation. Clinical study showed that vocal cord palsy was well compensated for with the plasma gel in all patients at two months after injection with no significant complications. Jitter, shimmer, maximum, maximum phonation time (MPT) and mean voice handicap index (VHI) also improved significantly after plasma gel injection. However, because the injected plasma gel was gradually absorbed, 6 patients needed another injection, while the gel remained in place in 2 patients. Injection laryngoplasty with autologous plasma gel may be a useful and safe treatment option for temporary vocal cord palsy.

  17. Autologous Fat Transfer in a Patient with Lupus Erythematosus Profundus

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    Jimi Yoon


    Full Text Available Lupus erythematosus profundus, a form of chronic cutaneous lupus erythematosus, is a rare inflammatory disease involving in the lower dermis and subcutaneous tissues. It primarily affects the head, proximal upper arms, trunk, thighs, and presents as firm nodules, 1 to 3 cm in diameter. The overlying skin often becomes attached to the subcutaneous nodules and is drawn inward to produce deep, saucerized depressions. We present a rare case of lupus erythematosus profundus treated with autologous fat transfer.





    ABSTRACT Introduction: Cervical myelopathy is a degenerative pathology of spinal and/or root involvement. Caused by hypertrophy of the yellow ligament, osteophytes in the medullary canal and disc herniation. It affects the upper and lower motor neurons. The treatment of myelopathy diagnosed by magnetic resonance and electromyography consists of decompression by corpectomy. Methods: Autologous graft integration with cervical plate placement was evaluated in 31 patients, from January 1, 2013 ...

  19. Controlled clinical trial of adjuvant immunotherapy with BCG and neuraminidase-treated autologous tumour cells in large bowel cancer. (United States)

    Gray, B N; Walker, C; Andrewartha, L; Freeman, S; Bennett, R C


    A controlled, randomised clinical trial of immunotherapy was performed in 301 patients with stage B or C colorectal cancer. The immunotherapy treatment consisted of 18 vaccinations over a 2 year period following surgery with a combination of BCG given by scarification plus subcutaneous injection of Vibrio cholera neuraminidase (VCN)-modified autologous tumour cells. Five year follow-up has now been completed in all patients. The immunotherapy did not alter either the disease-free interval or the overall survival of patients in comparison with a control group of patients not receiving immunotherapy.

  20. Complete mitochondrial genomes of the human follicle mites Demodex brevis and D. folliculorum: novel gene arrangement, truncated tRNA genes, and ancient divergence between species. (United States)

    Palopoli, Michael F; Minot, Samuel; Pei, Dorothy; Satterly, Alicia; Endrizzi, Julie


    Follicle mites of the genus Demodex are found on a wide diversity of mammals, including humans; surprisingly little is known, however, about the evolution of this association. Additional sequence information promises to facilitate studies of Demodex variation within and between host species. Here we report the complete mitochondrial genome sequences of two species of Demodex known to live on humans--Demodex brevis and D. folliculorum--which are the first such genomes available for any member of the genus. We analyzed these sequences to gain insight into the evolution of mitochondrial genomes within the Acariformes. We also used relaxed molecular clock analyses, based on alignments of mitochondrial proteins, to estimate the time of divergence between these two species. Both Demodex genomes shared a novel gene order that differs substantially from the ancestral chelicerate pattern, with transfer RNA (tRNA) genes apparently having moved much more often than other genes. Mitochondrial tRNA genes of both species were unusually short, with most of them unable to encode tRNAs that could fold into the canonical cloverleaf structure; indeed, several examples lacked both D- and T-arms. Finally, the high level of sequence divergence observed between these species suggests that these two lineages last shared a common ancestor no more recently than about 87 mya. Among Acariformes, rearrangements involving tRNA genes tend to occur much more often than those involving other genes. The truncated tRNA genes observed in both Demodex species would seem to require the evolution of extensive tRNA editing capabilities and/or coevolved interacting factors. The molecular machinery necessary for these unusual tRNAs to function might provide an avenue for developing treatments of skin disorders caused by Demodex. The deep divergence time estimated between these two species sets a lower bound on the time that Demodex have been coevolving with their mammalian hosts, and supports the

  1. Clinical outcome of autologous cultivated limbal epithelium transplantation

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    Sangwan Virender


    Full Text Available Purpose: To report the clinical outcome of autologous cultivated limbal epithelial transplantation. Methods: Eighty-six patients′ records and their clinical photographs were reviewed for demographics, primary etiology, type of limbal transplantation, ocular surface stability, visual acuity, final outcome, and possible factors affecting outcome and complications. Results: Eighty-eight eyes of 86 patients with limbal stem cell deficiency (LSCD underwent autologous cultivated limbal epithelium transplantation between March 2001 and May 2003, with a mean follow-up of 18.3 months. The etiology of LSCD was alkali burns in 64% patients. Sixty-one eyes had total LSCD. Thirty-two of the 88 eyes had undergone amniotic membrane transplantation and 10 eyes had previously undergone limbal transplantation with unfavorable outcome. Nineteen eyes underwent penetrating keratoplasty, of which 11 grafts survived at the final follow-up. Finally, 57 eyes (73.1%, 95% CI: 63.3-82.9 had a successful outcome with a stable ocular surface without conjunctivalization, 21 eyes (26.9%, 95%CI: 17.1-36.7 were considered failures, and 10 patients were lost to follow-up. Conclusion: LSCD can be successfully treated by autologous cultivated limbal epithelium transplantation in majority of the cases.

  2. [Functional results after autologous rotational keratoplasty. A retrospective study]. (United States)

    Birnbaum, F; Reinhard, T; Ulbricht, T; Hausser, J; Sundmacher, R


    Autologous rotational keratoplasty is a therapeutic option in patients with central corneal scars. Its advantage compared to allogeneic procedures is the absence of immunologic destruction. In this retrospective analysis, long-term results are presented. Since 1988, autologous rotational keratoplasty was performed in 19 patients. The trephine size varied between 7.0 mm and 9.0 mm. Mean follow-up was 7.1+/-4.6 years. In 16 of the patients, the graft center remained clear during the entire follow-up period. Visual acuity improved from 0.25+/-0.16 preoperatively to 0.34+/-0.27 postoperatively with spectacles and to 0.43+/-0.3 with contact lenses. The mean postoperative astigmatism was 6.41+/-3.87 dpt with irregular components in six patients. Only a few postoperative graft complications were observed. Especially in patients with a markedly elevated risk for immune reactions (e.g., small infants), autologous rotational keratoplasty is a safe alternative to allogenic procedures.

  3. Autologous fat grafting in lip reconstruction following hemangioma treatment. (United States)

    Yin, Jiapeng; Li, Haidong; Yin, Ningbei; Wu, Di; Wang, Yongqian; Tong, Haizhou; Li, Yan; Yan, Wei; Fang, Ling; Zhao, Zhenmin


    Autologous fat grafting has been successfully used in lip cosmetic surgery. However, little supportive evidence exists for its use in lip reconstruction following hemangioma treatment. Patients with lip deformity following hemangioma treatment at the Plastic Surgery Hospital in Beijing between September 2010 and July 2012 were retrospectively investigated. Twelve patients underwent autologous fat grafting. Aesthetic appearance and texture and volume persistence of the graft were measured preoperatively and postoperatively, and the presence of infection and hematoma was recorded. After a series of 3 to 4 injections and a mean 24 months of follow-up, all 12 patients were satisfied with their aesthetic appearance and the texture and volume persistence of the graft. There were no complications such as infection or hematoma. The current study demonstrates that autologous fat transplantation is a viable option for correction of lip deformities. It is beneficial not only for correction of the tissue defect themselves, but also in terms of its effect on surrounding tissues and its long-lasting results without major complications in the management of this difficult problem.

  4. Combined thrombin and autologous blood for repair of lumbar durotomy. (United States)

    Moussa, Wael Mohamed Mohamed; Aboul-Enein, Hisham A


    Lumbar durotomy can be intended or unintended and can result in persistent cerebrospinal fluid (CSF) leak. Several methods are used to manage this complication including bed rest and CSF diversion. In this study, we theorize that the use of thrombin-soaked gel foam together with autologous blood laid on the sutured dural tear can prevent persistent CSF leak. A retrospective review of the records of patients who underwent lumbar surgery and had an unintended dural tear with CSF leak, comparing the outcome of patients who were submitted to thrombin-soaked gel foam together with autologous blood (group A) to patients treated by subfacial drain, tight bandage, and bed rest (group B). A total of 1371 patients had lumbar surgery, of whom 131 had dural tear. Group A included 62 patients, while group B included 69 patients. 8.1 % of group A patients had CSF leak as compared to 17.4 % of group B patients at postoperative day 14. The incidence of postoperative CSF leak and duration of postoperative hospital stay were statistically lower in group A than in group B (p thrombin and autologous blood for repair of lumbar durotomy is an effective and a relatively cheap way to decrease CSF leak in the early postoperative period as well as decreasing postoperative hospital stay. It also resulted in decreased complications rate in the late postoperative period.

  5. Complete Microbiota Engraftment Is Not Essential for Recovery from Recurrent Clostridium difficile Infection following Fecal Microbiota Transplantation

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    Christopher Staley


    Full Text Available Bacterial communities from subjects treated for recurrent Clostridium difficile infection (rCDI by fecal microbiota transplantation (FMT, using either heterologous donor stool samples or autologous stool samples, were characterized by Illumina next-generation sequencing. As previously reported, the success of heterologous FMT (90% was superior to that of autologous FMT (43% (P = 0.019, and post-FMT intestinal bacterial communities differed significantly between treatment arms (P < 0.001. Subjects cured by autologous FMT typically had greater abundances of the Clostridium XIVa clade and Holdemania bacteria prior to treatment, and the relative abundances of these groups increased significantly after FMT compared to heterologous FMT and pre-FMT samples. The typical shift to post-FMT, donor-like assemblages, featuring high relative abundances of genera within the Bacteroidetes and Firmicutes phyla, was not observed in the autologous FMT subjects. Autologous FMT patient bacterial communities were significantly different in composition than those for heterologous FMT patients and donors (P < 0.001. The SourceTracker program, which employs a Bayesian algorithm to determine source contributions to sink communities, showed that patients initially treated by heterologous FMT had significantly higher percentages of engraftment (i.e., similarity to donor communities, mean value of 74% compared to those who suffered recurrence following autologous FMT (1% (P ≤ 0.013. The findings of this study suggest that complete donor engraftment may be not necessary if functionally critical taxa are present in subjects following antibiotic therapy.

  6. Complete Nucleotide Sequence and Genetic Organization of Aichi Virus, a Distinct Member of the Picornaviridae Associated with Acute Gastroenteritis in Humans (United States)

    Yamashita, Teruo; Sakae, Kenji; Tsuzuki, Hideaki; Suzuki, Yasumoto; Ishikawa, Naohisa; Takeda, Naokazu; Miyamura, Tatsuo; Yamazaki, Shudo


    The complete nucleotide sequence of a novel enteric virus, Aichi virus, associated with nonbacterial acute gastroenteritis in humans was determined. The Aichi virus genome proved to be a single-stranded positive-sense RNA molecule with 8,251 bases excluding a poly(A) tail; it contains a large open reading frame with 7,302 nucleotides that encodes a potential polyprotein precursor of 2,433 amino acids. The genome contains a 5′ nontranslated region (NTR) with 712 bases and a 3′ NTR with 240 bases followed by a poly(A) tail. The structure of the genome, VPg–5′ NTR–leader protein–structural proteins–nonstructural proteins–3′ NTR–poly(A), was found to be typical of a picornavirus. The VP0-VP3 and VP3-VP1 cleavage sites were determined to be Q-H and Q-T, respectively, by N-terminal amino acid sequence analyses using purified virion proteins. Possible cleavage sites, Q-G, Q-A, and Q-S, which cleave P2 and P3 polyproteins were found to be similar to those of picornaviruses. A dendrogram based on 3Dpol proteins indicated that Aichi virus is genetically distinct from the known six genera of picornaviruses including entero-, rhino-, cardio-, aphtho-, and hepatovirus and echovirus 22. Considering this together with other properties of the virus (T. Yamashita, S. Kobayashi, K. Sakae, S. Nakata, S. Chiba, Y. Ishihara, and S. Isomura, J. Infect. Dis. 164:954–957, 1991), we propose that Aichi virus be regarded as a new genus of the family Picornaviridae. PMID:9733894

  7. The complete cosmicomics

    CERN Document Server

    Calvino, Italo


    The definitive edition of Calvino’s cosmicomics, bringing together all of these enchanting stories—including some never before translated—in one volume for the first time. In Italo Calvino’s cosmicomics, primordial beings cavort on the nearby surface of the moon, play marbles with atoms, and bear ecstatic witness to Earth’s first dawn. Exploring natural phenomena and the origins of the universe, these beloved tales relate complex scientific concepts to our common sensory, emotional, human world. Now, The Complete Cosmicomics brings together all of the cosmicomic stories for the first time. Containing works previously published in Cosmicomics, t zero, and Numbers in the Dark, this single volume also includes seven previously uncollected stories, four of which have never been published in translation in the United States. This “complete and definitive collection” (Evening Standard) reconfirms the cosmicomics as a crowning literary achievement and makes them available to new generations of reader...

  8. Macrophage pro-inflammatory cytokine secretion is enhanced following interaction with autologous platelets

    Directory of Open Access Journals (Sweden)

    Fischer Thomas H


    Full Text Available Abstract Background Macrophages are the dominant phagocyte at sites of wound healing and inflammation, and the cellular and acellular debris encountered by macrophages can have profound effects on their inflammatory profile. Following interaction with apoptotic cells, macrophages are known to switch to an anti-inflammatory phenotype. Activated platelets, however, are also a major component of inflammatory lesions and have been proposed to be pro-inflammatory mediators. In the present study, we tested the hypothesis that macrophage interaction with activated platelets results in an inflammatory response that differs from the response following phagocytosis of apoptotic cells. Methods Human monocyte-derived macrophages (hMDMs were co-incubated with autologous activated platelets (AAPs and the platelet-macrophage interaction was examined by electron microscopy and flow cytometry. The cytokines TNF-α, IL-6, and IL-23 were also measured during LPS-activated hMDM co-incubation with AAPs, which was compared to co-incubation with apoptotic lymphocytes. Cytokine secretion was also compared to platelets pre-treated with the gluococorticoid dexamethasone. Results Macrophages trapped and phagocytized AAPs utilizing a mechanism that was significantly inhibited by the scavenger receptor ligand fucoidan. LPS-induced macrophage secretion of TNF-α, IL-6, and IL-23 was inhibited by co-incubation with apoptotic cells, but enhanced by co-incubation with AAPs. The platelet-dependent enhancement of LPS-induced cytokines could be reversed by pre-loading the platelets with the glucocorticoid dexamethasone. Conclusions The interaction of human macrophages with autologous platelets results in scavenger-receptor-mediated platelet uptake and enhancement of LPS-induced cytokines. Therefore, the presence of activated platelets at sites of inflammation may exacerbate pro-inflammatory macrophage activation. The possibility of reversing macrophage activation with

  9. Reconstruction of beagle hemi-mandibular defects with allogenic mandibular scaffolds and autologous mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    ChangKui Liu

    Full Text Available Massive bone allografts are frequently used in orthopedic reconstructive surgery, but carry a high failure rate of approximately 25%. We tested whether treatment of graft with mesenchymal stem cells (MSCs can increase the integration of massive allografts (hemi-mandible in a large animal model.Thirty beagle dogs received surgical left-sided hemi-mandibular defects, and then divided into two equal groups. Bony defects of the control group were reconstructed using allografts only. Those of the experimental group were reconstructed using allogenic mandibular scaffold-loaded autologous MSCs. Beagles from each group were killed at 4 (n = 4, 12 (n = 4, 24 (n = 4 or 48 weeks (n = 3 postoperatively. CT and micro-CT scans, histological analyses and the bone mineral density (BMD of transplants were used to evaluate defect reconstruction outcomes.Gross and CT examinations showed that the autologous bone grafts had healed in both groups. At 48 weeks, the allogenic mandibular scaffolds of the experimental group had been completely replaced by new bone, which has a smaller surface area to that of the original allogenic scaffold, whereas the scaffold in control dogs remained the same size as the original allogenic scaffold throughout. At 12 weeks, the BMD of the experimental group was significantly higher than the control group (p<0.05, and all micro-architectural parameters were significantly different between groups (p<0.05. Histological analyses showed almost all transplanted allogeneic bone was replaced by new bone, principally fibrous ossification, in the experimental group, which differed from the control group where little new bone formed.Our study demonstrated the feasibility of MSC-loaded allogenic mandibular scaffolds for the reconstruction of hemi-mandibular defects. Further studies are needed to test whether these results can be surpassed by the use of allogenic mandibular scaffolds loaded with a combination of MSCs and osteoinductive growth

  10. Arthritic periosteal tissue from joint replacement surgery: a novel, autologous source of stem cells. (United States)

    Chang, Hana; Docheva, Denitsa; Knothe, Ulf R; Knothe Tate, Melissa L


    The overarching aim of this study is to assess the feasibility of using periosteal tissue from the femoral neck of arthritic hip joints, usually discarded in the normal course of hip replacement surgery, as an autologous source of stem cells. In addition, the study aims to characterize intrinsic differences between periosteum-derived cell (PDC) populations, isolated via either enzymatic digestion or a migration assay, including their proliferative capacity, surface marker expression, and multipotency, relative to commercially available human bone marrow-derived stromal cells (BMSCs) cultured under identical conditions. Commercial BMSCs and PDCs were characterized in vitro, using a growth assay, flow cytometry, as well as assay of Oil Red O, alizarin red, and Safranin O/Fast Green staining after respective culture in adipo-, osteo-, and chondrogenic media. Based on these outcome measures, PDCs exhibited proliferation rate, morphology, surface receptor expression, and multipotency similar to those of BMSCs. No significant correlation was observed between outcome measures and donor age or diagnosis (osteoarthritis [OA] and rheumatoid arthritis [RA], respectively), a profound finding given recent rheumatological studies indicating that OA and RA share not only common biomarkers and molecular mechanisms but also common pathophysiology, ultimately resulting in the need for joint replacement. Furthermore, PDCs isolated via enzymatic digestion and migration assay showed subtle differences in surface marker expression but otherwise no significant differences in proliferation or multipotency; the observed differences in surface marker expression may indicate potential effects of isolation method on the population of cells isolated and/or the behavior of the respective isolated cell populations. This study demonstrates, for the first time to our knowledge, the feasibility of using arthritic tissue resected during hip replacement as a source of autologous stem cells. In sum

  11. Repair of segmental radial defect with autologous bone marrow aspirate and hydroxyapatite in rabbit radius: A clinical and radiographic evaluation

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    Kalbaza Ahmed Yassine


    Full Text Available Aim: Finding an ideal bone substitute to treat large bone defects, delayed union and nonunions remain a challenge for orthopedic surgeons and researchers. Several studies have been conducted on bone regeneration; each has its own advantages and disadvantages. The aim of this study was to evaluate the effect of a combination of hydroxyapatite (HA powder with autologous bone marrow (BM aspirate on the repair of segmental radial defect in a rabbit model. Materials and Methods: A total of 36 male and adult New Zealand rabbit with a mean weight of 2.25 kg were used in this study. Approximately, 5 mm defect was created in the mid-shaft of the radius to be filled with HA powder in the control group "HA" (n=18 and with a combination of HA powder and autologous BM aspirate in the test group "HA+BM" (n=18. Animals were observed daily for healing by inspection of the surgical site, and six rabbits of each group were sacrificed at 30, 60, and 90 post-operative days to perform a radiographic evaluation of defect site. Results: Obtained results revealed a better and more rapid bone regeneration in the test group: Since the defect was rapidly and completely filled with mature bone tissue after 90 days. Conclusion: Based on these findings, we could infer that adding a BM aspirate to HA is responsible of a better regeneration process leading to a complete filling of the defect.

  12. Fetal subcutaneous cells have potential for autologous tissue engineering. (United States)

    Ekblad, Åsa; Westgren, Magnus; Fossum, Magdalena; Götherström, Cecilia


    Major congenital malformations affect up to 3% of newborns. Infants with prenatally diagnosed soft tissue defects should benefit from having autologous tissue readily available for surgical implantation in the perinatal period. In this study, we investigate fetal subcutaneous cells (fSC) as cellular source for tissue engineering. Fetal subcutaneous biopsies were collected from elective terminations at gestational week 20-21. Cells were isolated, expanded and characterized in vitro. To determine cell coverage, localization, viability and proliferation in different constructs, the cells were seeded onto a matrix (small intestine submucosa (SIS)) or in collagen gel with or without poly(ε-caprolactone) (PCL) mesh and were kept in culture for up to 8 weeks before analysis. Angiogenesis was analyzed through a tube-forming assay. fSC could be expanded until 43±3 population doublings, expressed mesenchymal markers and readily differentiate into adipogenic and osteogenic lineages. The cells showed low adherence to SIS and did not migrate deep into the matrix. However, in collagen gels the cells migrated into the gel and proliferated with sustained viability for up to 8 weeks. The cells in the matrices expressed Ki67, CD73 and α-smooth muscle actin but not cytokeratin or CD31. Fetal cells derived from subcutaneous tissue demonstrated favorable characteristics for preparation of autologous tissue transplants before birth. Our study supports the theory that cells could be obtained from the fetus during pregnancy for tissue engineering purposes after birth. In a future clinical situation, autologous transplants could be used for reconstructive surgery in severe congenital malformations. This article is protected by copyright. All rights reserved.

  13. Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

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    Afonso José Pereira Cortez


    Full Text Available BACKGROUND: Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. OBJECTIVES: To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. METHODS: A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. RESULTS: The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. CONCLUSION: Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not

  14. Autologous Fat Transfer: An Aesthetic and Functional Refinement for Parotidectomy

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    Pierre G. Vico


    Full Text Available Parotidectomy is a surgical procedure associated to functional (Frey’s syndrome as well as aesthetic (facial asymmetry complications that can be very disturbing for the patient. Several procedures have been described to primarily avoid or secondarily reconstruct the facial defect and treat the neurological iatrogenic syndrome. Autologous fat transfer was primarily used in 10 cases to avoid such complications. It is an easy technique widely used in cosmetic and reconstructive surgery. This technique gives very satisfying long-term results on the cosmetic as well as on the physiological point of view.

  15. Facial fat necrosis following autologous fat transfer and its management

    Directory of Open Access Journals (Sweden)

    Sweta Rai


    Full Text Available Autologous fat transfer (AFT is an increasingly popular cosmetic procedure practiced by dermatologic surgeons worldwide. As this is an office based procedure performed under local or tumescent anaesthesia with fat transferred within the same individual and limited associated down time its is considered relatively safe and risk free in the cosmetic surgery arena. We describe a case of AFT related fat necrosis causing significant facial dysmorphia and psychosocial distress. We also discuss the benefits and risks of AFT highlighting common causes of fat graft failure.

  16. Immunisation of colorectal cancer patients with autologous tumour cells

    DEFF Research Database (Denmark)

    Diederichsen, Axel Cosmus Pyndt; Stenholm, A C; Kronborg, O


    Patients with colorectal cancer were entered into a clinical phase I trial of immunotherapy with an autologous tumour cell/bacillus Calmette-Guerin (BCG) vaccine. We attempted to describe the possible effects and side effects of the immunisation, and further to investigate whether expression...... of immune-response-related surface molecules on the tumour cells in the vaccine correlated with survival. The first and second vaccine comprised of 107 irradiated tumour cells mixed with BCG, the third of irradiated tumour cells only. Thirty-nine patients were considered, but only 6 patients fulfilled...

  17. Autologous fat grafting for cosmetic enhancement of the perioral region. (United States)

    Glasgold, Mark; Lam, Samuel M; Glasgold, Robert


    The role of volume loss in the progression of facial aging is widely accepted as an important cause. The aging appearance of the perioral region and lower face is significantly affected by this volume loss, which contributes to the development of labiomental folds, the loss of definition of the jawline, and worsening of skin texture, among other manifestations. Autologous fat transfer can effectively replace this lost volume and contribute to any facial rejuvenation plan. Fat can replace larger volumes than off-the-shelf fillers and provides a potentially permanent solution.

  18. Cost effectiveness of autologous blood transfusion – A developing ...

    African Journals Online (AJOL)

    Igbobi - Lagos en 1992 suite à l'augmentation de zéro prévalence de VIH remarquée chez nos donateurs “remplacement relatif”. une analyse lot rétrospectif des patients qui ont reçus une transfusion autologous et ceux qui ont reçu du sang homologous dans notre hôpital en 1997, a été effectuée. D'après le frais prélevé ...

  19. Transplantation of autologous synovial mesenchymal stem cells promotes meniscus regeneration in aged primates. (United States)

    Kondo, Shimpei; Muneta, Takeshi; Nakagawa, Yusuke; Koga, Hideyuki; Watanabe, Toshifumi; Tsuji, Kunikazu; Sotome, Shinichi; Okawa, Atsushi; Kiuchi, Shinji; Ono, Hideo; Mizuno, Mitsuru; Sekiya, Ichiro


    Transplantation of aggregates of synovial mesenchymal stem cells (MSCs) enhanced meniscus regeneration in rats. Anatomy and biological properties of the meniscus depend on animal species. To apply this technique clinically, it is valuable to investigate the use of animals genetically close to humans. We investigated whether transplantation of aggregates of autologous synovial MSCs promoted meniscal regeneration in aged primates. Chynomolgus primates between 12 and 13 years old were used. After the anterior halves of the medial menisci in both knees were removed, an average of 14 aggregates consisting of 250,000 synovial MSCs were transplanted onto the meniscus defect. No aggregates were transplanted to the opposite knee for the control. Meniscus and articular cartilage were analyzed macroscopically, histologically, and by MRI T1rho mapping at 8 (n = 3) and 16 weeks (n = 4). The medial meniscus was larger and the modified Pauli's histological score for the regenerated meniscus was better in the MSC group than in the control group in each primate at 8 and 16 weeks. Mankin's score for the medial femoral condyle cartilage was better in the MSC group than in the control group in all primates at 16 weeks. T1rho value for both the regenerated meniscus and adjacent articular cartilage in the MSC group was closer to the normal meniscus than in the control group in all primates at 16 weeks. Transplantation of aggregates of autologous synovial MSCs promoted meniscus regeneration and delayed progression of degeneration of articular cartilage in aged primates. This is the first report dealing with meniscus regeneration in primates. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1274-1282, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  20. Feasibility of arthroscopic placement of autologous matrix-induced chondrogenesis grafts in the cadaver hip joint

    Directory of Open Access Journals (Sweden)

    Fritz Thorey


    Full Text Available An assortment of clinical trials have been done presenting the effectiveness of autologous matrix-induced chondrogenesis (AMIC for the regeneration of chondral leasions. The purpose of the study was to underline the accessability of the acetabulum and the femoral head through the known portals and prove i the feasibility of placing the AMIC in the different zones of the hip joint and ii check for dislocation after joint movement. Six human cadavers underwent hip arthroscopy on both hips. Two chondral lesions were set on each femoral head and two in the acetabulum to evaluate a total of 48 defects. After microfracturing an autologous matrix-induced chondrogenesis graft was placed on these lesions arthroscopically. After repeated joint movement the dislocation of the graft was checked. It was possible to place the AMIC graft in all 48 chondral lesions. The time needed for placing the graft was 8±2.9 minutes. A trend of time reduction could be detected throughout this study as the surgeon gained more experience. For the femoral head, after twenty cycles of joint movement 18/24 spots showed no displacement, 4/24 showed minor displacement (<3 mm and 2/24 showed major displacement (>3 mm. None showed total displacement. For the acetabulum 22/24 spots showed no displacement and 2/24 showed minor displacement. A combined microfracturing and placing of an AMIC graft of focal chondral lesions of the hip joint can be done arthroscopically. Prospective randomized in vivo studies should compare the results of arthroscopilally placed AMIC grafts with microfracturing and microfracturing alone.

  1. Pulmonary heart valve replacement using stabilized acellular xenogeneic scaffolds; effects of seeding with autologous stem cells

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    Harpa Marius Mihai


    Full Text Available Background: We hypothesized that an ideal heart valve replacement would be acellular valve root scaffolds seeded with autologous stem cells. To test this hypothesis, we prepared porcine acellular pulmonary valves, seeded them with autologous adipose derived stem cells (ADSCs and implanted them in sheep and compared them to acellular valves.

  2. Persistent seropositivity for yellow fever in a previously vaccinated autologous hematopoietic stem cell transplantation recipient

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    Kayoko Hayakawa


    Full Text Available The duration of a protective level of yellow fever antibodies after autologous hematopoietic stem cell transplantation in a previously vaccinated person is unclear. The case of a patient who had previously been vaccinated for yellow fever and who remained seropositive for 22 months after autologous peripheral blood stem cell transplantation for malignant lymphoma is described herein.

  3. Extra-anatomic transplantations in autologous adult cell therapies aiding anatomical regeneration and physiological recovery – An insight and categorization

    Directory of Open Access Journals (Sweden)



    analysis of the functional uniqueness of the source vs target across these criteria of germ layers, organs, tissues and sites have to be thoroughly studied. Until pluripotent stem cell-derived clinical applications come into regular practice, such extra-anatomic adult cell therapies either IECT or TECT are worth studying as novel solutions to tissue regeneration. These are likely to evolve in the coming years and existing solutions could be enhanced using the principles behind IECT or TECT for diseases that do not have a definitive treatment. References Knutsen G, Drogset JO, Engebretsen L, Grøntvedt T, Isaksen V, Ludvigsen TC, Roberts S, Solheim E, Strand T, Johansen O. A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. J Bone Joint Surg Am. 2007;89(10:2105-12. Tsai RJ, Li LM, Chen JK. Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells. N Engl J Med. 2000;343(2:86-93. Siltanen A, Nuutila K, Imanishi Y, Uenaka H, Mäkelä J, Pätilä T, Vento A, Miyagawa S, Sawa Y, Harjula A, Kankuri E. The paracrine effect of skeletal myoblasts is cardioprotective against oxidative stress and involves EGFR-ErbB4 signaling, cystathionase, and the unfolded protein response. Cell Transplant.2015. [Epub ahead of print] Burman S, Sangwan V. Cultivated limbal stem cell transplantation for ocular surface reconstruction. Clin Ophthalmol. 2008;2(3:489-502. Tabakow P, Jarmundowicz W, Czapiga B, Fortuna W, Miedzybrodzki R, Czyz M, Huber J, Szarek D, Okurowski S, Szewczyk P, Gorski A, Raisman G. Transplantation of autologous olfactory ensheathing cells in complete human spinal cord injury.Cell Transplant. 2013;22(9:1591-612. Vaddi S, Godala C, Reddy V, Senthilkumar R, Srinivasan T, Reena H, Preethy S, Abraham S. Role of tissue engineered buccal mucosa for treatment of urethral stricture. Proceedings of the Annual Symposium & Plenary Session on Regenerative Medicine (PASRM. J Stem Cells Regen Med. 2013

  4. Shaping of the Unaffected Breast with Brava-Assisted Autologous Fat Grafting to Obtain Symmetry after Breast Reconstruction. (United States)

    Uda, Hirokazu; Tomioka, Yoko K; Sugawara, Yasusih; Sarukawa, Syunji; Sunaga, Ataru


    In breast reconstruction, symmetry is a vital issue. However, when the original breast is unusually shaped or the patient desires augmentation at the time of reconstruction, obtaining symmetrical breasts becomes difficult. The authors performed shaping of unaffected breasts by Brava-assisted autologous fat grafting to enhance breast symmetry, and evaluated the clinical results to validate this new approach. Brava-assisted autologous fat grafting was performed to the unaffected breasts of 12 patients who had undergone unilateral breast reconstruction. The procedure was used for augmentation in six patients and to correct ptosis, volume, and tuberous breast deformity in three, two, and one patient, respectively. Clinical outcomes were assessed in all 12 patients. All patients could complete fat grafting within two sessions (one session in nine patients and two sessions in three patients). The mean volume of grafted fat per session was 211 cc in all patients. The mean retention rate of grafted fat was 58.9% in the 10 patients for whom the retention rate could be calculated using preoperative and postoperative magnetic resonance imaging (MRI). Postoperative MRI revealed small benign foci in two patients (16.7%), which were not palpable and did not become a clinical problem. A postoperative mammography revealed a small agglutinate calcification in one patient, which was determined to be benign through biopsy. Shaping the unaffected breast by autologous fat grafting combined with Brava is predictable, effective, and feasible as an aesthetic adjunct to unilateral breast reconstruction to achieve breast symmetry. 4 Therapeutic. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission:

  5. A study of autologous melanocyte transfer in treatment of stable vitiligo

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    Pandya Vishvabhavan


    Full Text Available Background: Replenishing melanocytes selectively in vitiliginous macules by autologous melanocytes is a promising treatment. With expertise in culturing melanocytes, it has now become possible to treat larger recipient areas with smaller skin samples. Aim: To study the extent of repigmentation after autologous melanocyte transplantation in patients with stable vitiligo. Methods: The melanocytes were harvested as an autologous melanocyte rich cell suspension from a donor split thickness graft. Melanocyte culture was performed in selected cases where the melanocyte cell count was insufficient to meet the requirement of the recipient area. These cells were then transplanted to the recipient area that had been superficially dermabraded. Results: An excellent response was seen in 52.17% cases with the autologous melanocyte rich cell suspension (AMRCS technique and in 50% with the melanocyte culture (MC technique. Conclusion: Autologous melanocyte transplantation can be an effective form of surgical treatment in stable but recalcitrant lesions of vitiligo.

  6. Orthognathic Surgery with Simultaneous Autologous Fat Transfer for Correction of Facial Asymmetry. (United States)

    Wang, Yu-Ching; Wallace, Christopher Glenn; Pai, Betty Chien-Jung; Chen, Hui-Ling; Lee, Yueh-Tse; Hsiao, Yen-Chang; Chang, Chun-Shin; Liao, Yu-Fang; Chen, Philip Kuo-Ting; Chen, Yu-Ray


    Most patients treated with orthognathic surgery for facial asymmetry would value improvement in residual soft-tissue asymmetry. Autologous fat transfer is widely used to augment facial soft tissue. The authors assessed the effect of combining orthognathic surgery with autologous fat transfer for treating patients with facial asymmetry. In this retrospective study, 15 consecutive adults underwent combined orthognathic surgery and autologous fat transfer between January of 2013 and December of 2015. Lower facial profile symmetry was assessed using postoperative standard frontal photographs. Lower facial symmetry was much improved by combining orthognathic surgery and autologous fat injection. The combined use of orthognathic surgery and autologous fat transfer is a promising technique for improving facial symmetry in patients with facial asymmetry. Therapeutic, IV.

  7. A Randomized Study of Intraoperative Autologous Retropubic Urethral Sling on Urinary Control after Robotic Assisted Radical Prostatectomy. (United States)

    Nguyen, Hao G; Punnen, Sanoj; Cowan, Janet E; Leapman, Michael; Cary, Clint; Welty, Christopher; Weinberg, Vivian; Cooperberg, Matthew R; Meng, Maxwell V; Greene, Kirsten L; Garcia, Maurice; Carroll, Peter R


    We evaluated whether placement of a retropubic urethral sling fashioned from autologous vas deferens during robotic assisted radical prostatectomy would improve recovery of continence. In a phase 2, single blind trial age stratified patients were randomized to undergo robotic assisted radical prostatectomy by multiple surgeons with or without sling placement. The outcomes were complete continence (0 urinary pads of any type) and near continence (0, an occasional or 1 pad per day) at 6 months, which was assessed by the Fisher exact test and logistic regression. The Kaplan-Meier method and the log rank test were used to evaluate time to continence. EPIC-UIN (Expanded Prostate Cancer Index Composite-Urinary Inventory) and I-PSS (International Prostate Symptom Score) 1, 3 and 6 months after catheter removal were evaluated by mixed models for repeated measures. Of 203 patients who were recruited 95 and 100 were randomized to undergo sling and no sling placement, respectively, and completed postoperative interviews. Six months after surgery the proportions reporting complete and near continence (66% and 87%, respectively) and times to complete and near continence were similar in the groups. Younger age was associated with a higher likelihood of complete continence (OR 1.74 per decreasing 5-year interval, 95% CI 1.23-2.48, p <0.01) and near continence (OR 2.18 per decreasing 5-year interval, 95% CI 1.21-3.92, p <0.01) adjusting for clinical, urinary and surgical factors. Adjusted EPIC-UIN and I-PSS scores changed with time but did not differ between the groups. No serious adverse events were observed. This trial failed to demonstrate a benefit of autologous urethral sling placement at robotic assisted radical prostatectomy on early return of continence at 6 months. Continence was related to patient age in adjusted models. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  8. Twente spine model : A complete and coherent dataset for musculo-skeletal modeling of the lumbar region of the human spine

    NARCIS (Netherlands)

    Bayoglu, Riza; Geeraedts, Leo; Groenen, Karlijn; Verdonschot, N.J.J.; Koopman, H.F.J.M.; Homminga, Jasper Johan

    Musculo-skeletal modeling can greatly help in understanding normal and pathological functioning of the spine. For such models to produce reliable muscle and joint force estimations, an adequate set of musculo-skeletal data is necessary. In this study, we present a complete and coherent dataset for

  9. Twente spine model: A complete and coherent dataset for musculo-skeletal modeling of the lumbar region of the human spine.

    NARCIS (Netherlands)

    Bayoglu, R.; Geeraedts, L.; Groenen, K.H.J.; Verdonschot, N.J.; Koopman, B.; Homminga, J.


    Musculo-skeletal modeling can greatly help in understanding normal and pathological functioning of the spine. For such models to produce reliable muscle and joint force estimations, an adequate set of musculo-skeletal data is necessary. In this study, we present a complete and coherent dataset for

  10. Twente spine model: A complete and coherent dataset for musculo-skeletal modeling of the lumbar region of the human spine

    NARCIS (Netherlands)

    Bayoglu, R.; Geeraedts, L.; Groenen, K.H.J.; Verdonschot, N.J.; Koopman, B.; Homminga, J.


    Musculo-skeletal modeling can greatly help in understanding normal and pathological functioning of the spine. For such models to produce reliable muscle and joint force estimations, an adequate set of musculo-skeletal data is necessary. In this study, we present a complete and coherent dataset for

  11. Twente spine model : A complete and coherent dataset for musculo-skeletal modeling of the thoracic and cervical regions of the human spine

    NARCIS (Netherlands)

    Bayoglu, Riza; Geeraedts, Leo; Groenen, Karlijn H.J.; Verdonschot, Nico; Koopman, Bart; Homminga, Jasper


    Musculo-skeletal modeling could play a key role in advancing our understanding of the healthy and pathological spine, but the credibility of such models are strictly dependent on the accuracy of the anatomical data incorporated. In this study, we present a complete and coherent musculo-skeletal

  12. Twente spine model: A complete and coherent dataset for musculo-skeletal modeling of the thoracic and cervical regions of the human spine.

    NARCIS (Netherlands)

    Bayoglu, R.; Geeraedts, L.; Groenen, K.H.J.; Verdonschot, N.J.; Koopman, B.; Homminga, J.


    Musculo-skeletal modeling could play a key role in advancing our understanding of the healthy and pathological spine, but the credibility of such models are strictly dependent on the accuracy of the anatomical data incorporated. In this study, we present a complete and coherent musculo-skeletal

  13. Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman's syndrome and endometrial atrophy: a pilot cohort study. (United States)

    Santamaria, Xavier; Cabanillas, Sergio; Cervelló, Irene; Arbona, Cristina; Raga, Francisco; Ferro, Jaime; Palmero, Julio; Remohí, Jose; Pellicer, Antonio; Simón, Carlos


    Could cell therapy using autologous peripheral blood CD133+ bone marrow-derived stem cells (BMDSCs) offer a safe and efficient therapeutic approach for patients with refractory Asherman's syndrome (AS) and/or endometrial atrophy (EA) and a wish to conceive? In the first 3 months, autologous cell therapy, using CD133+ BMDSCs in conjunction with hormonal replacement therapy, increased the volume and duration of menses as well as the thickness and angiogenesis processes of the endometrium while decreasing intrauterine adhesion scores. AS is characterized by the presence of intrauterine adhesions and EA prevents the endometrium from growing thicker than 5 mm, resulting in menstruation disorders and infertility. Many therapies have been attempted for these conditions, but none have proved effective. This was a prospective, experimental, non-controlled study. There were 18 patients aged 30-45 years with refractory AS or EA were recruited, and 16 of these completed the study. Medical history, physical examination, endometrial thickness, intrauterine adhesion score and neoangiogenesis were assessed before and 3 and 6 months after cell therapy. After the initial hysteroscopic diagnosis, BMDSC mobilization was performed by granulocyte-CSF injection, then CD133+ cells were isolated through peripheral blood aphaeresis to obtain a mean of 124.39 million cells (range 42-236), which were immediately delivered into the spiral arterioles by catheterization. Subsequently, endometrial treatment after stem cell therapy was assessed in terms of restoration of menses, endometrial thickness (by vaginal ultrasound), adhesion score (by hysteroscopy), neoangiogenesis and ongoing pregnancy rate. The study was conducted at Hospital Clínico Universitario of Valencia and IVI Valencia (Spain). All 11 AS patients exhibited an improved uterine cavity 2 months after stem cell therapy. Endometrial thickness increased from an average of 4.3 mm (range 2.7-5) to 6.7 mm (range 3.1-12) ( ITALIC! P = 0

  14. Autologous Bone Marrow Mononuclear Cells Intrathecal Transplantation in Chronic Stroke

    Directory of Open Access Journals (Sweden)

    Alok Sharma


    Full Text Available Cell therapy is being widely explored in the management of stroke and has demonstrated great potential. It has been shown to assist in the remodeling of the central nervous system by inducing neurorestorative effect through the process of angiogenesis, neurogenesis, and reduction of glial scar formation. In this study, the effect of intrathecal administration of autologous bone marrow mononuclear cells (BMMNCs is analyzed on the recovery process of patients with chronic stroke. 24 patients diagnosed with chronic stroke were administered cell therapy, followed by multidisciplinary neurorehabilitation. They were assessed on functional independence measure (FIM objectively, along with assessment of standing and walking balance, ambulation, and hand functions. Out of 24 patients, 12 improved in ambulation, 10 in hand functions, 6 in standing balance, and 9 in walking balance. Further factor analysis was done. Patients of the younger groups showed higher percentage of improvement in all the areas. Patients who underwent cell therapy within 2 years after the stroke showed better changes. Ischemic type of stroke had better recovery than the hemorrhagic stroke. This study demonstrates the potential of autologous BMMNCs intrathecal transplantation in improving the prognosis of functional recovery in chronic stage of stroke. Further clinical trials are recommended. This trial is registered with NCT02065778.

  15. Calculation of size and location of autologous ipsilateral rotating keratoplasty. (United States)

    Jonas, J B; Panda-Jonas, S


    Autologous ipsilateral rotating keratoplasty is a special form of keratoplasty in which a nonprogressive opacification of the centre of the cornea is rotated towards the limbus and the clear peripheral cornea is rotated into the optical axis of the eye. This study was performed to find an equation for calculating the best size and location of the trephine for this special kind of keratoplasty. Geometrical calculations were used to derive the formula. We arrived at the following equation for the best diameter of the trephine: diameter(trephine) = 3/4 diameter(cornea)-1/2e(e = preoperative distance between corneal centre and nearest edge of opacity covering corneal centre). The postoperative diameter of the optical zone is: 2 x diameter(trephine)-diameter(cornea). A postoperative clear optical zone of half the corneal diameter is achieved if the opacity just touches but does not extend beyond the corneal centre. For a postoperative optical zone of at least 30% (40%) of the corneal diameter, the opacity is preoperatively not allowed to extend beyond the corneal centre for more than 20% (10%) of the corneal diameter. This equation can be used for calculating the optimum size and location of the trephine for autologous ipsilateral rotational keratoplasty. For that purpose it is advisable to take photographs preoperatively.

  16. Biomaterial Implants Mediate Autologous Stem Cell Recruitment In Mice (United States)

    Nair, Ashwin; Shen, Jinhui; Lotfi, Parisa; Ko, Cheng-Yu; Zhang, Cheng Cheng; Tang, Liping


    Autologous stem cells, recognized as the best cells for stem cell therapy, are associated with difficult extraction procedures that often lead to more traumas for the patients and time consuming laboratory work that delays their subsequent application. To combat such challenges, we have recently uncovered that shortly after biomaterial implantation, following the recruitment of inflammatory cells, substantial numbers of mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC) were recruited to the implantation sites. These multipotent MSCs could be differentiated into various lineages in vitro. Inflammatory signals may be responsible for the gathering of stem cells, since there is a good relationship between biomaterial-mediated inflammatory responses and stem cell accumulation in vivo. In addition, the treatment with anti-inflammatory drug – dexamethasone – substantially reduced the recruitment of both MSC and HSC. The results from this work support that such strategies could be further developed towards localized recruitment and differentiation of progenitor cells. This may permit the future development of autologous stem cell therapies without the need for tedious cell isolation, culture and transplantation. PMID:21784181

  17. Assessment of autologous serum skin test in chronic idiopathic urticaria

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    Mohammad Kazem Nooh pisheh


    Full Text Available Background: In the vast majority of patients with chronic urticaria , the etiology is unknown. It has been noted that in one third of such patients it has an autoimmune base. Autologous serum skin test (ASST is currently the best in vivo test for the detection of such patients. Our aim was to identify the prevalence of positive ASST among patients with chronic idiopathic urticaria (CIU and to compare features of ASST + and ASST – groups. Methods: this study was done on 79 patients with CIU. Samples of 0.05ml of autologous serum and normal saline were separately injected intradermaly into the volar aspect of right and left forearm respectively. ASST Was deemed to be positive if a serum induced weal had a diameter bigger than a sailin induced response by < 1.5 mm was seen at 30min. Also we compare the clinical and laboratory parameters of ASST+ and ASST - groups.Results: Out of 79 patients with CIU, 39 patients (39% had positive ASST and it was found that the frequency of attacks was higher in these patients (P=0.04. Conclusion: Significant percent of patients with CIU showed positive response to ASST which is most likely an autoimmune source for them. ASST can be used as a simple and cost - effective test for the detection of these patients, which has proven to be a therapeutic challenge to the treating physician.

  18. Subcutaneous autologous serum therapy in chronic spontaneous urticaria

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    Kiran Vasant Godse


    Full Text Available Background: There is a felt need for trying newer therapeutic modalities in patients with chronic spontaneous urticaria, especially in the subset of patients classified as non-responders to antihistamines. Autologous serum therapy is an upcoming modality of treatment, and we decided to study its efficacy by subcutaneous route. Aims: To evaluate the effectiveness of subcutaneous autologous serum therapy (AST in CSU. Methods: This was a single blind, placebo-controlled parallel group, randomized, controlled study. Twenty-four patients with CSU (11M: 13 F were given subcutaneous AST and seventeen patients (7 M: 10F patients were given subcutaneous injection normal saline (placebo, along with levocetirizine in an on-demand basis in both groups. Results: Urticaria activity score (UAS came down from 35.74 to 7 at the end of 9 weeks and the patients' requirement of antihistamines also reduced remarkably from 5.8 to 1.7 per week in the serum group. Sub-cutaneous saline group did not show statistically significant fall in UAS. Saline group showed UAS 32.8 at zero week to 22.1 at the end of 9 weeks. DLQI showed significant fall in serum group, from 14.26 to 4 at the end of 9 weeks. Conclusion: Subcutaneous autoserum therapy is effective in treatment of CSU.

  19. Alteration of Skin Properties with Autologous Dermal Fibroblasts

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    Rajesh L. Thangapazham


    Full Text Available Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound healing and skin repair. Preclinical studies suggest wider applications of dermal fibroblasts ranging from skin based indications to non-skin tissue regeneration in tendon repair. One clinical application for autologous dermal fibroblasts has been approved by the Food and Drug Administration (FDA while others are in preclinical development or various stages of regulatory approval. In this context, we outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous dermal fibroblasts. The microanatomic and phenotypic differences of fibroblasts occupying particular locations within the skin are reviewed, emphasizing the therapeutic relevance of attributes exhibited by subpopulations of fibroblasts. Special focus is provided to fibroblast characteristics that define regional differences in skin, including the thick and hairless skin of the palms and soles as compared to hair-bearing skin. This regional specificity and functional identity of fibroblasts provides another platform for developing regional skin applications such as the induction of hair follicles in bald scalp or alteration of the phenotype of stump skin in amputees to better support their prosthetic devices.

  20. Cytokine-rich autologous serum system for cartilaginous tissue engineering. (United States)

    Isogai, Noritaka; Nakagawa, Yumiko; Suzuki, Koji; Yamada, Ryo; Asamura, Shinichi; Hayakawa, Sumio; Munakata, Hiroshi


    Animal serum used for tissue engineering approaches has unacceptable risk for contamination with infectious agents. In this study, a cytokine-rich autologous serum (CRAS) system was developed. Canine auricular chondrocytes were cultured in medium supplemented with either fetal bovine serum (FBS) or autologous canine serum, alone or supplemented with basic fibroblast growth factor (b-FGF). Cell proliferative capacity was higher in the CRAS cultures than in those cultured in FBS, with greater expression of aggrecan and type II collagen in the b-FGF-supplemented CRAS group. The chondrocytes were seeded onto an ear-shaped biodegradable polymer (poly-L-lactide:epsilon-caprolactone, 50:50) and cultured in a Bioflow reactor for 1 week, using the 3 different culture media indicated above, and subsequently implanted into nude mice. The best outcome (cartilage gene expression and morphologic properties) was seen with tissue-engineered constructs precultured in the b-FGF-supplemented CRAS media. These findings indicate a clinically realizable approach for tissue engineering of cartilaginous structures.

  1. Isolated congenital complete heart block in a five-year-old seronegative girl born to a woman seropositive for human immunodeficiency virus: a case report. (United States)

    Pallangyo, Pedro; Mawenya, Isaac; Nicholaus, Paulina; Mayala, Henry; Kalombola, Amida; Sharau, Godwin; Majani, Naiz; Janabi, Mohamed


    Congenital complete heart block is a life-threatening condition which is highly associated with autoimmune and connective tissue disorders. Presence of maternal autoantibodies for associated conditions increases the risk of delivering a child with congenital complete heart block, however, less than a half of all women with such antibodies are symptomatic even after delivery. Mortality rate is highest during the neonatal period (45 %) and about two-thirds of all cases will require permanent pacing at some point in their lives. We report a case of isolated complete heart block in a 5-year-old HIV-free girl of African descent born to an HIV-infected woman with no prior history of autoimmune disorders. She was referred to us with chief complaints of recurrent syncopal attacks and effort intolerance since birth. A physical examination was unremarkable except for her being small for her age (body mass index 16.3 kg/m2) and bradycardia. Her vital signs were within acceptable range with the exception of her pulse rate, which ranged between 22 and 34 beats/minute. An echocardiogram revealed a sinus bradycardia, otherwise a structurally normal heart. An electrocardiogram showed atrioventricular dissociation in keeping with third-degree atrioventricular block. The child underwent a permanent epicardial pacemaker insertion and has been symptom-free following pacing. Despite its infrequency and life-threatening potential, patients with congenital complete heart block have an excellent survival rate with timely diagnosis and intervention. An incidental detection of bradycardia in a fetus during routine obstetrical ultrasound examination should increase the index of suspicion for congenital complete heart block and warrant a screening for associated maternal autoantibodies.

  2. Cellular Reprogramming Allows Generation of Autologous Hematopoietic Progenitors From AML Patients That Are Devoid of Patient-Specific Genomic Aberrations (United States)

    Salci, Kyle R; Lee, Jong-Hee; Laronde, Sarah; Dingwall, Steve; Kushwah, Rahul; Fiebig-Comyn, Aline; Leber, Brian; Foley, Ronan; Dal Cin, Arianna; Bhatia, Mickie


    Current treatments that use hematopoietic progenitor cell (HPC) transplantation in acute myeloid leukemia (AML) patients substantially reduce the risk of relapse, but are limited by the availability of immune compatible healthy HPCs. Although cellular reprogramming has the potential to provide a novel autologous source of HPCs for transplantation, the applicability of this technology toward the derivation of healthy autologous hematopoietic cells devoid of patient-specific leukemic aberrations from AML patients must first be evaluated. Here, we report the generation of human AML patient-specific hematopoietic progenitors that are capable of normal in vitro differentiation to myeloid lineages and are devoid of leukemia-associated aberration found in matched patient bone marrow. Skin fibroblasts were obtained from AML patients whose leukemic cells possessed a distinct, leukemia-associated aberration, and used to create AML patient-specific induced pluripotent stem cells (iPSCs). Through hematopoietic differentiation of AML patient iPSCs, coupled with cytogenetic interrogation, we reveal that AML patient-specific HPCs possess normal progenitor capacity and are devoid of leukemia-associated mutations. Importantly, in rare patient skin samples that give rise to mosaic fibroblast cultures that continue to carry leukemia-associated mutations; healthy hematopoietic progenitors can also be generated via reprogramming selection. Our findings provide the proof of principle that cellular reprogramming can be applied on a personalized basis to generate healthy HPCs from AML patients, and should further motivate advances toward creating transplantable hematopoietic stem cells for autologous AML therapy. Stem Cells 2013;33:1839–1849 PMID:25764124

  3. Effects of autologous platelet transfusion on platelet inhibition in ticagrelor-treated and clopidogrel-treated subjects. (United States)

    Teng, R; Carlson, G F; Nylander, S; Andersson, T L G


    Essentials Limited data on hemostatic benefits of platelet transfusion (PT) exist. 44 healthy subjects had a single dose of ticagrelor or clopidogrel ± autologous PT post-dosing. PT did not reverse ticagrelor's antiplatelet effects and had minimal impact post clopidogrel. Post-ticagrelor, PT is unlikely to be beneficial, and the benefits post-clopidogrel are unknown. Background Antiplatelet agents increase bleeding risk. Few data on hemostatic benefits of platelet transfusion exist. Objective To assess the effect of autologous platelet transfusion on ticagrelor-mediated and clopidogrel-mediated platelet inhibition in a single-center, open-label, randomized, cross-over study (NCT01744288). Methods Forty-four healthy subjects received ticagrelor (180 mg) or clopidogrel (600 mg; two functional CYP2C19 alleles [*1 or *17] required) with or without platelet transfusion (14-day washout). Subjects received one autologous platelet apheresis unit (approximately six pooled donor platelet units) 24 h (n = 15) or 48 h (n = 13) after ticagrelor or 48 h after clopidogrel (n = 16). Platelet apheresis was conducted 72 h before transfusion. Aspirin (81 mg per day) was taken from after apheresis until 24 h before transfusion. P2Y12 reaction units (PRUs) and inhibition of platelet aggregation (IPA) induced by ADP were measured. Results Mean age and body mass index were 30 years (standard deviation [SD] 6 years) and 26.9 kg m(-2) (SD 4.0 kg m(-2) ), respectively; 98% of subjects were men, and 39 of 44 completed treatment. Platelet transfusion 24 h after ticagrelor had minimal effects on IPA or PRU values within 48 h after transfusion. Platelet transfusion 48 h after ticagrelor also had minimal effects on IPA or PRU values at most post-transfusion times. Platelet transfusion 48 h after clopidogrel, versus no transfusion, had a small reversing effect on IPA (24 h, 36 h, and 48 h) and PRU values (12 h, 24 h, and 36 h) after transfusion. Conclusions Autologous platelet transfusion is

  4. Deletion of the steroid-binding domain of the human androgen receptor gene in one family with complete androgen insensitivity syndrome: Evidence for further genetic heterogeneity in this syndrome

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    Brown, T.R.; Lubahn, D.B.; Wilson, E.M.; Joseph, D.R.; French, F.S.; Migeon, C.J. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))


    The cloning of a cDNA for the human androgen receptor gene has resulted in the availability for cDNA probes that span various parts of the gene, including the entire steroid-binding domain and part of the DNA-binding domain, as well as part of the 5' region of the gene. The radiolabeled probes were used to screen for androgen receptor mutations on Southern blots prepared by restriction endonuclease digestion of genomic DNA from human subjects with complete androgen insensitivity syndrome (AIS). In this investigation, the authors considered only patients presenting complete AIS and with the androgen receptor (-) form as the most probably subjects to show a gene deletion. One subject from each of six unrelated families with the receptor (-) form of complete AIS and 10 normal subjects were studied. In the 10 normal subjects and in 5 of the 6 patients, identical DNA restriction fragment patterns were observed with EcoRI and BamHI. Analysis of other members of this family confirmed the apparent gene deletion. The data provide direct proof that complete AIS in some families can result from a deletion of the androgen receptor structural gene. However, other families do not demonstrate such a deletion, suggesting that point mutations may also result in the receptor (-) form of complete AIS, adding further to the genetic heterogeneity of this syndrome.

  5. Dynamics of Acute Local Inflammatory Response after Autologous Transplantation of Muscle-Derived Cells into the Skeletal Muscle

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    Anna Burdzinska


    Full Text Available The vast majority of myoblasts transplanted into the skeletal muscle die within the first week after injection. Inflammatory response to the intramuscular cell transfer was studied in allogeneic but not in autologous model. The aim of this study was to evaluate immune reaction to autotransplantation of myogenic cells and to assess its dynamics within the first week after injection. Muscle-derived cells or medium alone was injected into the intact skeletal muscles in autologous model. Tissue samples were collected 1, 3, and 7 days after the procedure. Our analysis revealed the peak increase of the gene expression of all evaluated cytokines (Il-1α, Il-1β, Il-6, Tgf-β, and Tnf-α at day 1. The mRNA level of analyzed cytokines normalized in subsequent time points. The increase of Il-β gene expression was further confirmed at the protein level. Analysis of the tissue sections revealed rapid infiltration of injected cell clusters with neutrophils and macrophages. The inflammatory infiltration was almost completely resolved at day 7. The survived cells were able to participate in the muscle regeneration process. Presented results demonstrate that autotransplanted muscle-derived cells induce classical early immune reaction in the site of injection which may contribute to cellular graft elimination.


    Todorich, Bozho; Sharma, Sumit; Vajzovic, Lejla


    To describe vitreoretinal surgical technique of using autologous platelet-rich plasma to aid in surgical repair of optic pit maculopathy refractive to previous vitrectomy. A case of an 18-year-old woman presenting with serous macular detachment secondary to optic pit is reported. Patient had previously undergone vitrectomy and peripapillary laser, but had recurrence of subretinal fluid and worsening visual acuity. Autologous platelet-rich plasma was harvested from the patient's blood and purified using Arthrex ACP kit (Arthrex, Inc, Naples, FL). Repeat pars plana vitrectomy was performed with internal limiting membrane peeling extending to the optic nerve. Platelet-rich plasma was layered over the pit and long-acting gas tamponade performed with face-down positioning. At 8 months of follow-up, subretinal fluid was resolved, the connection between optic pit and subretinal space collapsed and the ellipsoid zone near completely reconstituted on optical coherence tomography. The patient's vision improved significantly from 20/100 to 20/50, which is largely limited by posterior subcapsular cataract. Platelet-rich plasma can augment anatomical and visual outcomes in surgical repair of optic pit maculopathy.

  7. Autologous platelet concentrate in surgery for macular detachment associated with congenital optic disc pit

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    Nadal J


    Full Text Available Jeroni Nadal,1,2 Marta S Figueroa,3 Elisa Carreras,2,4 Patricia Pujol,2,4 Maria Isabel Canut,2,4,5 Rafael Ignacio Barraquer2,6 1Vitreoretinal Surgery Department at Centro de Oftalmología Barraquer, 2Universitat autónoma de Barcelona, Barcelona, 3Vissum Madrid, Madrid, 4Instituto Barraquer, 5Glaucoma Department at Centro de Oftalmología Barraquer, 6Cornea and Cataract Surgery Department at Centro de Oftalmología Barraquer, Barcelona, Spain Purpose: To evaluate the anatomical and functional results obtained with pars plana vitrectomy (PPV plus autologous platelet concentrate (APC as a treatment for macular detachment associated with optic disc pit (ODP.Methods: We performed a prospective interventional study of 19 eyes of 19 consecutive patients with posterior macular detachment due to ODP. All patients underwent PPV, posterior hyaloid peeling, fluid–air exchange, injection of 0.05 mL of APC over the ODP and 15% perfluoropropane (C3F8 endotamponade. Postoperative measures included face-up positioning for 2 hours and then avoidance of the face-up position during the ensuing 10 days. All patients underwent complete ophthalmologic examination and optical coherence tomography preoperatively at 1 month, 3 months, 6 months, 9 months, and 12 months postoperatively and then annually. Outcome measures were best corrected visual acuity (BCVA by logMAR, improvement of quality of vision, macular attachment, and resolution of intraretinal schisis-like separation.Results: Preoperatively, the median BCVA was 0.70 (range: 0.30–1.70 and all patients showed improved visual acuity after surgery; BCVA was 0.22 (range: 0.07–0.52 at 12 months follow-up. All patients showed complete reabsorption of intraretinal fluid (median time: 3.5 months [range: 2–8 months] and macular attachment at the end of follow-up (median: 60 months [range: 12–144 months], with stable or improved visual acuity. No reoperations were needed and no major adverse events were

  8. Long term results in refractory tennis elbow using autologous blood

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    Naseem ul Gani


    Full Text Available Tennis elbow (TE is one of the commonest myotendinosis. Different treatment options are available and autologous blood injection has emerged as the one of the acceptable modalities of treatment. Long term studies over a larger group of patients are however lacking. The purpose of this study was to evaluate these patients on longer durations. One-hundred and twenty patients of TE, who failed to respond to conventional treatment including local steroid injections were taken up for this prospective study over the period from year 2005 to 2011 and were followed up for the minimum of 3 years (range 3-9 years. Two mL of autologous blood was taken from the ipsilateral limb and injected into the lateral epicondyle. The effectiveness of the procedure was assessed by Pain Rating Sscale and Nirschl Staging, which was monitored before the procedure, at first week, monthly for first three months, at 6 months and then 3 monthly for first year, six monthly for next 2 years and then yearly. Statistical analysis was done and a P value of <0.05 was taken as significant. The patients (76 females and 44 males were evaluated after procedure. The mean age group was 40.67±8.21. The mean follow up was 5.7±1.72 (range 3 to 9 years. The mean pain score and Nirschl stage before the procedure was 3.3±0.9 and 6.2±0.82 respectively. At final follow up the pain score and Nirschl were 1.1±0.9 and 1.5±0.91 respectively. Autologous blood injection was found to be one of the modalities for treatment of TE. Being cheap, available and easy method of treatment, it should be considered as a treatment modality before opting for the surgery. Universal guidelines for the management of tennis elbow should be made as there is lot of controversy regarding the treatment.

  9. Effect of hyperbaric oxygen therapy combined with autologous platelet concentrate applied in rabbit fibula fraction healing

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    Paulo Cesar Fagundes Neves


    Full Text Available OBJECTIVES: The purpose is to study the effects of hyperbaric oxygen therapy and autologous platelet concentrates in healing the fibula bone of rabbits after induced fractures. METHODS: A total of 128 male New Zealand albino rabbits, between 6-8 months old, were subjected to a total osteotomy of the proximal portion of the right fibula. After surgery, the animals were divided into four groups (n = 32 each: control group, in which animals were subjected to osteotomy; autologous platelet concentrate group, in which animals were subjected to osteotomy and autologous platelet concentrate applied at the fracture site; hyperbaric oxygen group, in which animals were subjected to osteotomy and 9 consecutive daily hyperbaric oxygen therapy sessions; and autologous platelet concentrate and hyperbaric oxygen group, in which animals were subjected to osteotomy, autologous platelet concentrate applied at the fracture site, and 9 consecutive daily hyperbaric oxygen therapy sessions. Each group was divided into 4 subgroups according to a pre-determined euthanasia time points: 2, 4, 6, and 8 weeks postoperative. After euthanasia at a specific time point, the fibula containing the osseous callus was prepared histologically and stained with hematoxylin and eosin or picrosirius red. RESULTS: Autologous platelet concentrates and hyperbaric oxygen therapy, applied together or separately, increased the rate of bone healing compared with the control group. CONCLUSION: Hyperbaric oxygen therapy and autologous platelet concentrate combined increased the rate of bone healing in this experimental model.

  10. Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas

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    Torres-Trejo Alejandro


    Full Text Available Abstract Background The prognosis for malignant gliomas remains dismal. We addressed the safety, feasibility and preliminary clinical activity of the vaccinations using autologous glioma cells and interleukin (IL-4 gene transfected fibroblasts. Methods In University of Pittsburgh Cancer Institute (UPCI protocol 95-033, adult participants with recurrent glioblastoma multiforme (GBM or anaplastic astrocytoma (AA received gross total resection (GTR of the recurrent tumors, followed by two vaccinations with autologous fibroblasts retrovirally transfected with TFG-IL4-Neo-TK vector admixed with irradiated autologous glioma cells. In UPCI 99-111, adult participants with newly diagnosed GBM or AA, following GTR and radiation therapy, received two intradermal vaccinations with the TFG-IL4-Neo-TK-transfected fibroblasts admixed with type-1 dendritic cells (DC loaded with autologous tumor lysate. The participants were evaluated for occurrence of adverse events, immune response, and clinical response by radiological imaging. Results and Discussion In UPCI 95-033, only 2 of 6 participants received the vaccinations. Four other participants were withdrawn from the trial because of tumor progression prior to production of the cellular vaccine. However, both participants who received two vaccinations demonstrated encouraging immunological and clinical responses. Biopsies from the local vaccine sites from one participant displayed IL-4 dose-dependent infiltration of CD4+ as well as CD8+ T cells. Interferon (IFN-γ Enzyme-Linked Immuno-SPOT (ELISPOT assay in another human leukocyte antigen (HLA-A2+ participant demonstrated systemic T-cell responses against an HLA-A2-restricted glioma-associated antigen (GAA epitope EphA2883–891. Moreover, both participants demonstrated clinical and radiological improvement with no evidence of allergic encephalitis, although both participants eventually succumbed with the tumor recurrence. In 99-111, 5 of 6 enrolled participants

  11. Analysis of complete genome sequences of G9P[19] rotavirus strains from human and piglet with diarrhea provides evidence for whole-genome interspecies transmission of nonreassorted porcine rotavirus. (United States)

    Yodmeeklin, Arpaporn; Khamrin, Pattara; Chuchaona, Watchaporn; Kumthip, Kattareeya; Kongkaew, Aphisek; Vachirachewin, Ratchaya; Okitsu, Shoko; Ushijima, Hiroshi; Maneekarn, Niwat


    Whole genomes of G9P[19] human (RVA/Human-wt/THA/CMH-S070-13/2013/G9P[19]) and porcine (RVA/Pig-wt/THA/CMP-015-12/2012/G9P[19]) rotaviruses concurrently detected in the same geographical area in northern Thailand were sequenced and analyzed for their genetic relationships using bioinformatic tools. The complete genome sequence of human rotavirus RVA/Human-wt/THA/CMH-S070-13/2013/G9P[19] was most closely related to those of porcine rotavirus RVA/Pig-wt/THA/CMP-015-12/2012/G9P[19] and to those of porcine-like human and porcine rotaviruses reference strains than to those of human rotavirus reference strains. The genotype constellation of G9P[19] detected in human and piglet were identical and displayed as the G9-P[19]-I5-R1-C1-M1-A8-N1-T1-E1-H1 genotypes with the nucleotide sequence identities of VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4, and NSP5 at 99.0%, 99.5%, 93.2%, 97.7%, 97.7%, 85.6%, 89.5%, 93.2%, 92.9%, 94.0%, and 98.1%, respectively. The findings indicate that human rotavirus strain RVA/Human-wt/THA/CMH-S070-13/2013/G9P[19] containing the genome segments of porcine genetic backbone is most likely a human rotavirus of porcine origin. Our data provide an evidence of interspecies transmission and whole-genome transmission of nonreassorted G9P[19] porcine RVA to human occurring in nature in northern Thailand. Copyright © 2016. Published by Elsevier B.V.

  12. Autologous mesenchymal stem cells or meniscal cells: what is the best cell source for regenerative meniscus treatment in an early osteoarthritis situation? (United States)

    Zellner, Johannes; Pattappa, Girish; Koch, Matthias; Lang, Siegmund; Weber, Johannes; Pfeifer, Christian G; Mueller, Michael B; Kujat, Richard; Nerlich, Michael; Angele, Peter


    Treatment of meniscus tears within the avascular region represents a significant challenge, particularly in a situation of early osteoarthritis. Cell-based tissue engineering approaches have shown promising results. However, studies have not found a consensus on the appropriate autologous cell source in a clinical situation, specifically in a challenging degenerative environment. The present study sought to evaluate the appropriate cell source for autologous meniscal repair in a demanding setting of early osteoarthritis. A rabbit model was used to test autologous meniscal repair. Bone marrow and medial menisci were harvested 4 weeks prior to surgery. Bone marrow-derived mesenchymal stem cells (MSCs) and meniscal cells were isolated, expanded, and seeded onto collagen-hyaluronan scaffolds before implantation. A punch defect model was performed on the lateral meniscus and then a cell-seeded scaffold was press-fit into the defect. Following 6 or 12 weeks, gross joint morphology and OARSI grade were assessed, and menisci were harvested for macroscopic, histological, and immunohistochemical evaluation using a validated meniscus scoring system. In conjunction, human meniscal cells isolated from non-repairable bucket handle tears and human MSCs were expanded and, using the pellet culture model, assessed for their meniscus-like potential in a translational setting through collagen type I and II immunostaining, collagen type II enzyme-linked immunosorbent assay (ELISA), and gene expression analysis. After resections of the medial menisci, all knees showed early osteoarthritic changes (average OARSI grade 3.1). However, successful repair of meniscus punch defects was performed using either meniscal cells or MSCs. Gross joint assessment demonstrated donor site morbidity for meniscal cell treatment. Furthermore, human MSCs had significantly increased collagen type II gene expression and production compared to meniscal cells (p cell-based tissue engineering approach was shown

  13. Ductal-lobar organisation of human breast tissue, its relevance in disease and a research objective: vector mapping of parenchyma in complete breasts (the Astley Cooper project)


    Going, James J.


    A human breast has many lobes, which are highly variable in size and shape, each with one central duct, its peripheral branches and their associated glandular tissues. Realising the potential of new endoductal approaches to breast diagnosis and improving our understanding of breast cancer precursors will require greatly improved knowledge of this ductal-lobar anatomy and the distribution of cancer precursors within it. This architecture is very challenging to study in its entirety: whole-brea...

  14. Poor man’s 1000 genome project: Recent human population expansion confounds the detection of disease alleles in 7,098 complete mitochondrial genomes

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    Hie Lim eKim


    Full Text Available Rapid growth of the human population has caused the accumulation of rare genetic variants that may play a role in the origin of genetic diseases. However, it is challenging to identify those rare variants responsible for specific diseases without genetic data from an extraordinarily large population sample. Here we focused on the accumulated data from the human mitochondrial (mt genome sequences because this data provided 7,098 whole genomes for analysis. In this dataset we identified 6,110 single nucleotide variants (SNVs and their frequency and determined that the best-fit demographic model for the 7,098 genomes included severe population bottlenecks and exponential expansions of the non-African population. Using this model, we simulated the evolution of mt genomes in order to ascertain the behavior of deleterious mutations. We found that such deleterious mutations barely survived during population expansion. We derived the threshold frequency of a deleterious mutation in separate African, Asian, and European populations and used it to identify pathogenic mutations in our dataset. Although threshold frequency was very low, the proportion of variants showing a lower frequency than that threshold was 82%, 83%, and 91% of the total variants for the African, Asian, and European populations, respectively. Within these variants, only 18 known pathogenic mutations were detected in the 7,098 genomes. This result showed the difficulty of detecting a pathogenic mutation within an abundance of rare variants in the human population, even with a large number of genomes available for study.

  15. Sustained complete remission of human epidermal growth factor receptor 2-positive metastatic breast cancer in the liver during long-term trastuzumab (Herceptin maintenance therapy in a woman: a case report

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    Tsavaris Nicolas


    Full Text Available Abstract Introduction This case report and short review discusses how long trastuzumab should be continued in metastatic breast cancer, the safety issues in case of pregnancy and the risk of relapse with trastuzumab cessation. Case presentation We present the case of a 34-year-old Caucasian woman with human epidermal growth factor receptor 2-positive metastatic breast cancer in the liver who achieved prolonged complete remission within six months of receiving trastuzumab (Herceptin in combination with vinorelbine and gemcitabine. The patient remains in complete remission seven years later and continues to receive trastuzumab as maintenance therapy. Conclusion Trastuzumab-based therapies have greatly improved the survival rates of patients with human epidermal growth factor receptor 2- positive metastatic breast cancer. Despite such improvements, the safety of trastuzumab administration during pregnancy is yet to be defined.

  16. Intraluminal instillation of urokinase and autologous plasma: a method to unblock occluded central venous ports

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    Henze Guenter


    Full Text Available Abstract Background Therapeutic use and effective function of recombinant urokinase (r-UK for occluded ports need the presence of plasminogen. Methods As a therapeutic proof of principle, we demonstrate that the use of r-UK and autologous plasma effectively reestablishes the function of occluded central venous ports (CVP resistant to routine management of catheter occlusion. Five patients with occluded ports resistant to the routine management were treated. Results All patients were successfully treated with thrombolytic therapy using intraluminal instillation of r-UK and autologous plasma. Conclusion Instillation of r-UK and autologous plasma is a safe and effective method for management of CVP occlusion.

  17. [Sarcoidosis flare after autologous stem cell transplantation: An immune paradox? (United States)

    Marchal, A; Charlotte, F; Maksud, P; Haroche, J; Lifferman, F; Miyara, M; Choquet, S; Amoura, Z; Cohen Aubart, F


    Sarcoidosis is a systemic granulomatous disorder of unknown cause. Apparition or flare of previously diagnosed sarcoidosis following hematopoietic stem cell transplantation (HSCT) has rarely been reported. We report a 62-year-old woman who presented a radiological flare of sarcoidosis post-autologous stem cell transplantation for a POEMS syndrome. Imaging findings and lymph node histology, which revealed non-caseating granuloma, were consistent with the sarcoidosis diagnosis. The patient was asymptomatic and was kept free of treatment. Sarcoidosis must be considered ahead of compatible clinicoradiological presentation occurring after HSCT. Sarcoidosis can mimic metastatic cancer or lymphatic relapse. Tissue biopsies and exclusion of differential diagnosis of granuloma diseases are warranted to confirm sarcoidosis diagnosis. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  18. Autologous osteochondral graft for traumatic defects of finger joints. (United States)

    Wu, W C; Fok, M W M; Fung, K Y; Tam, K H


    Finger joint defects in 16 adults were treated with an autologous osteochondral graft from the base of the second metacarpal, the radial styloid, the base of the third metacarpal or the trapezoid and these patients were followed up from between 12 and 62 months. There was no donor site morbidity. One patient had resorption of the graft and developed pain. The joint was subsequently fused. The mean range of movement was 55.8% of the opposite normal joint. At follow up, 15 patients had no discomfort or mild discomfort. Three had mild narrowing of the joint space and two had slight joint subluxation. Only two patients with concomitant severe injury to the same limb had difficulty performing daily activities. Ten were open injuries and these had poorer outcomes. A hemicondylar defect of a finger joint can be treated using an osteochondral graft obtained from the same hand.

  19. MR imaging of autologous chondrocyte implantation of the knee

    Energy Technology Data Exchange (ETDEWEB)

    James, S.L.J.; Connell, D.A.; Saifuddin, A.; Skinner, J.A.; Briggs, T.W.R. [RNOH Stanmore, Department of Radiology, Stanmore, Middlesex (United Kingdom)


    Autologous chondrocyte implantation (ACI) is a surgical technique that is increasingly being used in the treatment of full-thickness defects of articular cartilage in the knee. It involves the arthroscopic harvesting and in vitro culture of chondrocytes that are subsequently implanted into a previously identified chondral defect. The aim is to produce a repair tissue that closely resembles hyaline articular cartilage that gradually becomes incorporated, restoring joint congruity. Over the long term, it is hoped that this will prevent the progression of full-thickness articular cartilage defects to osteoarthritis. This article reviews the indications and operative procedure performed in ACI. Magnetic resonance imaging (MRI) sequences that provide optimal visualization of articular cartilage in the post-operative period are discussed. Normal appearances of ACI on MRI are presented along with common complications that are encountered with this technique. (orig.)

  20. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma

    DEFF Research Database (Denmark)

    Mellqvist, Ulf-Henrik; Gimsing, Peter; Hjertner, Oyvind


    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370...... patients were centrally randomly assigned 3 months after ASCT to receive 20 doses of bortezomib given during 21 weeks or no consolidation. The hypothesis was that consolidation therapy would prolong progression-free survival (PFS). The PFS after randomization was 27 months for the bortezomib group compared......-reported quality-of-life (QOL) questionnaires, whereas no other major differences in QOL were recorded between the groups. Consolidation therapy seemed to be beneficial for patients not achieving at least a very good partial response (VGPR) but not for patients in the ≥ VGPR category at randomization...

  1. The Effect of Autologous Serum Eye Drop Application on Epithelization in the Treatment of Various Ocular Surface Disorders and its Safety

    Directory of Open Access Journals (Sweden)

    Fatma Selin Kaya


    Full Text Available Pur po se: To evaluate the effect of autologous serum application on epithelization in the treatment of ocular surface disorders in hard cases and its safety. Ma te ri al and Met hod: Patients with serious ocular surface disorders, unresponsive to conventional treatment were recruited. Clinical features of retrospective cohort of patients who were prescribed serum drops are presented. From July 2007 to January 2010, 31 eyes of 21 patients, who were given autologous serum eye drops, were included into the study. Clinical examination included epithelial changes, rose bengal/lissamine green staining, fluorescein staining, and tear film break-up time. A history of systemic disease was recorded together with systemic medications used. A complete ocular history was also obtained. Re sults: Autologous serum was used in 7 patients with delayed epithelization after penetrating keratoplasty, in 4 patients with epithelial disturbances secondary to keratitis, in 2 patients with alkali burns, in 3 patients with Stevens-Johnson syndrome, in 1 patient with ligneous conjunctivitis, in 1 patient with epidermolysis bullosa, in 1 patient with corneal burn with hot water, and in 2 patients with Sjogren syndrome. The female:male ratio was 13:8. The mean age was 36.23±24.80 standard deviation (range: 7 months-87 years. No significant sight-threatening complication has been observed with the use of serum drops. Dis cus si on: Autologous serum application is safe and efficient additional therapy in the treatment of serious ocular surface problems in difficult cases. (Turk J Ophthalmol 2012; 42: 336-41

  2. Regenerative Repair of Damaged Meniscus with Autologous Adipose Tissue-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Jaewoo Pak


    Full Text Available Mesenchymal stem cells (MSCs are defined as pluripotent cells found in numerous human tissues, including bone marrow and adipose tissue. Such MSCs, isolated from bone marrow and adipose tissue, have been shown to differentiate into bone and cartilage, along with other types of tissues. Therefore, MSCs represent a promising new therapy in regenerative medicine. The initial treatment of meniscus tear of the knee is managed conservatively with nonsteroidal anti-inflammatory drugs and physical therapy. When such conservative treatment fails, an arthroscopic resection of the meniscus is necessary. However, the major drawback of the meniscectomy is an early onset of osteoarthritis. Therefore, an effective and noninvasive treatment for patients with continuous knee pain due to damaged meniscus has been sought. Here, we present a review, highlighting the possible regenerative mechanisms of damaged meniscus with MSCs (especially adipose tissue-derived stem cells (ASCs, along with a case of successful repair of torn meniscus with significant reduction of knee pain by percutaneous injection of autologous ASCs into an adult human knee.

  3. Tear trough – Anatomy and treatment by autologous fat grafting

    Directory of Open Access Journals (Sweden)

    Chang Yung Chia


    Full Text Available Tear trough is the main irregularity at midface, of which treatment is difficult. There is no agreement in literature about its anatomy and best treatment. The author presented an anatomical study and personal autologous fat grafting technique for tear trough treatment. Anatomical dissections were done on two fresh cadavers to examine the skin, subcutaneous, muscle and bone layers, spaces, and attachments. Safety and efficacy were evaluated via retrospective analysis of the last 200 consecutive procedures performed by the author. Tear trough is caused by the abrupt transition of the palpebral orbicular oculi muscle (OOM (i.e., thin skin without subcutaneous fat compartment to the orbital OOM (i.e., thicker skin with malar fat compartment. The tear trough region is located at the OOM bony origin at the medial canthus where no specific ligament was found. The grafted fat volume stabilized at two or three months after the procedure, instead of six months as stated in literature, with excellent results and no severe complications. Tear trough is a personal characteristic, a natural anatomical depression caused by subcutaneous irregularity and can worsen with age. The lack of volume is not effectively corrected by surgeries and thus it must be filled. Fat grafting has several advantages over alloplastic fillers, although it may be more difficult. Fat graft is autologous and abundant, and tissue transplantation could enhance skin quality. Fat grafting is a simple, safe, and effective solution for adding extra volume to correct the deflation phenomenon of the midface aging process. There is no specific anatomical plane for volume injection; the fat graft must be evenly distributed in the deep and superficial plane for uniformity.

  4. A new nose tip-defining technique for Asians using autologous cartilage prefabricated with octyl-2-cyanoacrylate adhesive. (United States)

    Seo, Jeong-Ok; Kwon, Jang-Woo; Kim, Sung-Kyun; Lim, Joo-Sin; Park, Dong-Joon


    To form and test a prefabricated, 3-dimensional tip graft structure from autologous cartilage pieces and octyl-2-cyanoacrylate adhesive (Dermabond). Displacement and instability of grafted cartilage are common drawbacks of endonasal tip surgery, and we evaluated the feasibility and efficacy of octyl-2-cyanoacrylate adhesive for clinical use. Three New Zealand rabbits were examined in this study. We cut auricular cartilage into pieces of approximately 1 x 2 cm and glued them together with octyl-2-cyanoacrylate. Three months after subcutaneous implantation in the rabbits, we histopathologically analyzed foreign body reactions, histotoxic effects, and the structure of the regenerative tissue in the implanted cartilage. Furthermore, from human patients we harvested small pieces of autologous cartilage and cemented them together with octyl-2-cyanoacrylate adhesive to prefabricate 3-dimensional tip grafts, which we then inserted into the nasal tips of patients via an endonasal approach to project and contour the nasal tip. The changes in tip definition of 42 Asian patients were analyzed. Octyl-2-cyanoacrylate adhesive interacts well with cartilage tissues with no systemic or local adverse effects. Its ability to bond cartilage instantaneously allows for the fabrication of intricate cartilage implant components. The aesthetic results in 42 cases were excellent, and the implants were both safe and effective. Our results demonstrate that octyl-2-cyanoacrylate can be safely used in endonasal tip surgery to produce excellent cosmetic outcomes in Asian subjects.

  5. Platelet-rich plasma-enriched autologous fat graft in regenerative and aesthetic facial surgery: Technical note. (United States)

    Picard, F; Hersant, B; La Padula, S; Meningaud, J-P


    The goal of adding platelet-rich plasma (PRP) to autologous fat graft is to increase the survival rate of the graft. After their activation, platelets release some important growth factors. As a result, PRP may increase the proliferation and differentiation of Adipose-derived stem cells (ASCs) into adipocytes, improve fat graft vascularisation, and may block the apoptosis of grafted adipocytes. The other benefit expected from the addition of PRP to fat graft is the improvement of cutaneous trophicity above the grafted areas. An exhaustive review of the literature retrieved 11 clinical studies on humans and 7 on animals. A statistically significant increase of the survival rate of fat grafts has been found in 9 comparative studies. Our synthesis allowed us to set up the following protocol: addition of 20% of PRP activated with calcium hydrochloride to fat grafts. It may enhance the results of autologous facial fat graft in regenerative and aesthetic facial surgery. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Autologous Cell Delivery to the Skin-Implant Interface via the Lumen of Percutaneous Devices in vitro

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    Antonio Peramo


    Full Text Available Induced tissue regeneration around percutaneous medical implants could be a useful method to prevent the failure of the medical device, especially when the epidermal seal around the implant is disrupted and the implant must be maintained over a long period of time. In this manuscript, a novel concept and technique is introduced in which autologous keratinocytes were delivered to the interfacial area of a skin-implant using the hollow interior of a fixator pin as a conduit. Full thickness human skin explants discarded from surgeries were cultured at the air-liquid interface and were punctured to fit at the bottom of hollow cylindrical stainless steel fixator pins. Autologous keratinocytes, previously extracted from the same piece of skin and cultured separately, were delivered to the specimens thorough the interior of the hollow pins. The delivered cells survived the process and resembled undifferentiated epithelium, with variations in size and shape. Viability was demonstrated by the lack of morphologic evidence of necrosis or apoptosis. Although the cells did not form organized epithelial structures, differentiation toward a keratinocyte phenotype was evident immunohistochemically. These results suggest that an adaptation of this technique could be useful for the treatment of complications arising from the contact between skin and percutaneous devices in vivo.

  7. Ductal-lobar organisation of human breast tissue, its relevance in disease and a research objective: vector mapping of parenchyma in complete breasts (the Astley Cooper project) (United States)

    Going, James J


    A human breast has many lobes, which are highly variable in size and shape, each with one central duct, its peripheral branches and their associated glandular tissues. Realising the potential of new endoductal approaches to breast diagnosis and improving our understanding of breast cancer precursors will require greatly improved knowledge of this ductal-lobar anatomy and the distribution of cancer precursors within it. This architecture is very challenging to study in its entirety: whole-breast lobe mapping has only been achieved for two human breasts. Clearly, much more efficient techniques are required. Streamlined data capture and visualisation of breast parenchymal anatomy from thin and thick sections in a vector format would allow integrated mapping of whole-breast structure with conventional histology and molecular data. The 'Astley Cooper digital breast mapping project' is proposed as a name for this achievable research objective. Success would offer new insights into the development of breast cancer precursor lesions, allow testing of the important 'sick lobe' hypothesis, improve correlation with imaging studies and provide 'ground truth' for mathematical modelling of breast growth. PMID:16879731

  8. HOCOMOCO: towards a complete collection of transcription factor binding models for human and mouse via large-scale ChIP-Seq analysis

    KAUST Repository

    Kulakovskiy, Ivan V.


    We present a major update of the HOCOMOCO collection that consists of patterns describing DNA binding specificities for human and mouse transcription factors. In this release, we profited from a nearly doubled volume of published in vivo experiments on transcription factor (TF) binding to expand the repertoire of binding models, replace low-quality models previously based on in vitro data only and cover more than a hundred TFs with previously unknown binding specificities. This was achieved by systematic motif discovery from more than five thousand ChIP-Seq experiments uniformly processed within the BioUML framework with several ChIP-Seq peak calling tools and aggregated in the GTRD database. HOCOMOCO v11 contains binding models for 453 mouse and 680 human transcription factors and includes 1302 mononucleotide and 576 dinucleotide position weight matrices, which describe primary binding preferences of each transcription factor and reliable alternative binding specificities. An interactive interface and bulk downloads are available on the web: and In this release, we complement HOCOMOCO by MoLoTool (Motif Location Toolbox, that applies HOCOMOCO models for visualization of binding sites in short DNA sequences.

  9. HOCOMOCO: towards a complete collection of transcription factor binding models for human and mouse via large-scale ChIP-Seq analysis. (United States)

    Kulakovskiy, Ivan V; Vorontsov, Ilya E; Yevshin, Ivan S; Sharipov, Ruslan N; Fedorova, Alla D; Rumynskiy, Eugene I; Medvedeva, Yulia A; Magana-Mora, Arturo; Bajic, Vladimir B; Papatsenko, Dmitry A; Kolpakov, Fedor A; Makeev, Vsevolod J


    We present a major update of the HOCOMOCO collection that consists of patterns describing DNA binding specificities for human and mouse transcription factors. In this release, we profited from a nearly doubled volume of published in vivo experiments on transcription factor (TF) binding to expand the repertoire of binding models, replace low-quality models previously based on in vitro data only and cover more than a hundred TFs with previously unknown binding specificities. This was achieved by systematic motif discovery from more than five thousand ChIP-Seq experiments uniformly processed within the BioUML framework with several ChIP-Seq peak calling tools and aggregated in the GTRD database. HOCOMOCO v11 contains binding models for 453 mouse and 680 human transcription factors and includes 1302 mononucleotide and 576 dinucleotide position weight matrices, which describe primary binding preferences of each transcription factor and reliable alternative binding specificities. An interactive interface and bulk downloads are available on the web: and In this release, we complement HOCOMOCO by MoLoTool (Motif Location Toolbox, that applies HOCOMOCO models for visualization of binding sites in short DNA sequences. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Autologous valve replacement-CD133+ stem cell-plus-fibrin composite-based sprayed cell seeding for intraoperative heart valve tissue engineering. (United States)

    Kaminski, Alexander; Klopsch, Christian; Mark, Peter; Yerebakan, Can; Donndorf, Peter; Gäbel, Ralf; Eisert, Friederike; Hasken, Stefan; Kreitz, Sebastian; Glass, Aenne; Jockenhövel, Stefan; Ma, Nan; Kundt, Guenther; Liebold, Andreas; Steinhoff, Gustav


    The development of biological valve prostheses with lifetime native-like performance and optimal host engraftment is an ultimate goal of heart valve tissue engineering. We describe a new concept for autologous graft coating based on a CD133(+)-stem-cells-plus-fibrin (SC+F) complex processed from bone marrow and peripheral blood of a single patient. CD133(+)-SC (1 × 10(6) cells/mL) from human bone marrow and autologous fibrin (20 mg/mL) were administered simultaneously via spray administration using the novel Vivostat Co-Delivery System. During static cultivation, SC+F performance was monitored for 20 days after delivery and compared with controls. For dynamic testing SC+F-composite was sprayed on a decellularized porcine pulmonary valve and transferred to a bioreactor under pulsatile flow conditions for 7 days. Static cultivation of SC+F-composite induced significant improvements in stem cell proliferation as compared with controls. For dynamic testing, microscopic analyses on a smooth engineered heart valve surface detected homogenous distribution of stem cells. Ultrasonic analysis revealed native-like valve performance. Applied CD133(+) stem cells differentiated into endothelial-like cells positive for CD31 and vascular endothelial growth factor receptor 2 and engrafted the valve. However, occasional delamination was observed. SC+F serves as an excellent autologous matrix for intraoperative tissue engineering of valve prostheses promising optimal in vivo integration. However, stability remains an issue.

  11. Cloning and expression of a cDNA covering the complete coding region of the P32 subunit of human pre-mRNA splicing factor SF2

    DEFF Research Database (Denmark)

    Honoré, B; Madsen, Peder; Rasmussen, H H


    We have cloned and expressed a cDNA encoding the 32-kDa subunit (P32) of the human pre-mRNA splicing factor, SF2. This cDNA extends beyond the 5'-end of a previously reported cDNA [Krainer et al., Cell 66 (1991) 383-394]. Importantly, our fragment includes an ATG start codon which was absent from...... the previously reported cDNA, where it was suggested that translation might initiate at a CTG codon instead of at an ATG codon. Using the vaccinia virus (Vv) expression system, we demonstrate that translation starts at the conventional ATG start codon and not at the CTG codon. The protein is synthesized as a pro...

  12. Development of a complete human IgG monoclonal antibody to transferrin receptor 1 targeted for adult T-cell leukemia/lymphoma. (United States)

    Shimosaki, Shunsuke; Nakahata, Shingo; Ichikawa, Tomonaga; Kitanaka, Akira; Kameda, Takuro; Hidaka, Tomonori; Kubuki, Yoko; Kurosawa, Gene; Zhang, Lilin; Sudo, Yukio; Shimoda, Kazuya; Morishita, Kazuhiro


    Iron is an essential nutrient for normal cell growth, and reprogramming of iron metabolism is essential to tumor cell survival and progression. HTLV-1-associated adult T-cell leukemia/lymphoma (ATLL) has no effective therapy and high levels of cell surface transferrin receptor 1 (TFR1) expression have been reported in ATLL by us and other groups. In this study, to develop a novel molecular-targeted therapy against TFR1 to modulate iron metabolism, we initially determined the expression pattern of several iron-related genes along with TFR1 and found that ATLL cells presented characteristic of an iron-deficiency state such as high expression of iron-regulatory protein 2 (IRP2) and low expression of its E3 ubiquitin-ligase, FBXL5. Therefore, we developed human IgG monoclonal antibodies to human TFR1 using a phage display method (ICOS method) to block the incorporation of the transferrin (TF)-iron complex into ATLL cells for inhibiting cell growth. One of the mAbs, JST-TFR09, presented its greater affinity to TFR1 on ATLL cells in flow cytometry (FCM) analysis than those of commercially available anti-TFR1 antibodies and identified high expression of TFR1 in most of the acute-type ATLL cells. Moreover, JST-TFR09 could interfere with binding between TFR1 and TF, which resulted in effective blockade of TFR1 internalization and induction of cell apoptosis by the treatment of ATLL cells with JST-TFR09. JST-TFR09 showed dual activities through direct cell cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC), and the treatment of JST-TFR09 significantly suppressed cell growth of ATLL cells with induction of apoptosis in in vitro and in vivo experiments. Thus, JST-TFR09 described here may become a promising therapeutic antibody for the treatment of ATLL. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates. (United States)

    Sha, Jian; Kirtley, Michelle L; Klages, Curtis; Erova, Tatiana E; Telepnev, Maxim; Ponnusamy, Duraisamy; Fitts, Eric C; Baze, Wallace B; Sivasubramani, Satheesh K; Lawrence, William S; Patrikeev, Igor; Peel, Jennifer E; Andersson, Jourdan A; Kozlova, Elena V; Tiner, Bethany L; Peterson, Johnny W; McWilliams, David; Patel, Snehal; Rothe, Eric; Motin, Vladimir L; Chopra, Ashok K


    Currently, no plague vaccine exists in the United States for human use. The capsular antigen (Caf1 or F1) and two type 3 secretion system (T3SS) components, the low-calcium-response V antigen (LcrV) and the needle protein YscF, represent protective antigens of Yersinia pestis We used a replication-defective human type 5 adenovirus (Ad5) vector and constructed recombinant monovalent and trivalent vaccines (rAd5-LcrV and rAd5-YFV) that expressed either the codon-optimized lcrV or the fusion gene designated YFV (consisting of ycsF, caf1, and lcrV). Immunization of mice with the trivalent rAd5-YFV vaccine by either the intramuscular (i.m.) or the intranasal (i.n.) route provided protection superior to that with the monovalent rAd5-LcrV vaccine against bubonic and pneumonic plague when animals were challenged with Y. pestis CO92. Preexisting adenoviral immunity did not diminish the protective response, and the protection was always higher when mice were administered one i.n. dose of the trivalent vaccine (priming) followed by a single i.m. booster dose of the purified YFV antigen. Immunization of cynomolgus macaques with the trivalent rAd5-YFV vaccine by the prime-boost strategy provided 100% protection against a stringent aerosol challenge dose of CO92 to animals that had preexisting adenoviral immunity. The vaccinated and challenged macaques had no signs of disease, and the invading pathogen rapidly cleared with no histopathological lesions. This is the first report showing the efficacy of an adenovirus-vectored trivalent vaccine against pneumonic plague in mouse and nonhuman primate (NHP) models. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. Impact of Autologous and Allogeneic Stem Cell Transplantation in Peripheral T-Cell Lymphomas

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    Peter Reimer


    Full Text Available Peripheral T/NK-cell lymphomas (PTCLs are rare malignancies characterized by poor prognosis. So far, no standard therapy has been established, due to the lack of randomised studies. High-dose therapy and autologous stem cell transplantation (HDT-autoSCT have shown good feasibility with low toxicity in retrospective studies. In relapsing and refractory PTCL several comparison analyses suggest similar efficacy for PTCL when compared with aggressive B-cell lymphoma. In the upfront setting, prospective data show promising results with a long-lasting overall survival in a relevant subset of patients. Achieving a complete remission at transplantation seems to be the most important prognostic factor. Allogeneic stem cell transplantation (alloSCT has been investigated only as salvage treatment. Especially when using reduced intensity conditioning regimen, eligible patients seem to benefit from this approach. To define the role for upfront stem cell transplantation a randomised trial by the German High-Grade Non-Hodgkin Lymphoma Study Group comparing HDT-autoSCT and alloSCT will be initiated this year.

  15. Predictors of non-compliance in autologous hematopoietic SCT patients undergoing out-patient transplants. (United States)

    Mumby, P B; Hurley, C; Samsi, M; Thilges, S; Parthasarathy, M; Stiff, P J


    Non-compliance has received significant attention in medicine, yet few studies have examined its correlates in autologous hematopoietic SCT (AHSCT) patients. This study examined predictors of non-compliance in a sample of 151 AHSCT patients treated in an outpatient setting. Before AHSCT, participants completed a validated measure of mood and retrospective chart reviews were conducted to assess non-compliance during AHSCT, defined as refusal of oral hygiene, prescribed exercise programs, oral nutrition and/or prescribed medications. We found 121 patients (80%) were non-compliant with an aspect of the AHSCT regimen on 1 or more days; mean percentage of non-compliant days was 16.6 (s.d. 15.6). Men were more likely than women to be non-compliant (Pnon-compliance: gender, depression, global distress and nausea and vomiting severity (P-values all non-compliance (Prisk factors for non-compliance and the importance of assessing patient barriers to compliance to ensure optimal treatment outcome.

  16. [Effects of intracoronary autologous bone marrow mononuclear cells transplantation in patients with anterior myocardial infarction]. (United States)

    Wang, Wei-min; Sun, Ning-ling; Liu, Jian; Zhang, Ping; Liu, Kai-yan; Wang, Qian; Yang, Song-na; Wang, Su-qin; Zang, Yue; Guo, Ji-hong


    To investigate the efficacy of intracoronary transfer of autologous bone marrow mononuclear cells (ABMMNCs) to patients with myocardial infarction (MI) on left ventricular function and myocardial perfusion. Thirty-five patients with MI (> 4 weeks) were enrolled in this prospective, open-labeled study (20 patients in cell transplantation group; 15 patients in control group). All patients were treated by standard drug therapy and percutaneous coronary intervention (PCI). Baseline and 3 months follow-up evaluations included complete clinical and laboratory examinations, six minutes walk test, echocardiography, Dual-isotope simultaneous acquisition single photon emission computed tomography (DISA-SPECT) and cardiac magnetic resonance imaging (MRI). Baseline parameters were similar between the two groups. NYHA classification and six minutes walk test at 3 months follow-up were also similar between the two groups. However, left ventricular ejection fraction (LVEF) determined by echocardiography and DISA-SPECT was significantly higher; regional wall motion measured by echocardiography and cardiac MRI, myocardial viability and myocardial perfusion in the infarct zone assessed by DISA-SPECT were all significantly improved than before transplantation and than that in control group at 3 months follow-up. Our results indicate that intracoronary transplantation of ABMMNCs could improve the left ventricular systolic function and beneficially affect myocardial perfusion up to 3 months post transplantation in patients with myocardial infarction.

  17. Sequential, autologous hematopoietic stem cell transplant followed by renal transplant in multiple myeloma

    Directory of Open Access Journals (Sweden)

    D Bhowmik


    Full Text Available A 30-year-old female was symptomatic with headache, fatigue, and weakness since October 2011 and was told to have anemia. In January 2012, she was admitted outside with pulmonary edema. Investigations revealed advanced azotemia, anemia, and hypercalcemia. Urine showed 2 + proteins and 30–35 red blood cells. There was no history of oral ulcers, rash, Raynaud's phenomenon, or hemoptysis. She was evaluated for causes of rapidly progressive “renal failure.” Hemolytic work-up; antinuclear antibody, double-stranded DNA, and anti-neutrophil cytoplasmic antibody were negative. Kidney biopsy was done and interpreted as acute interstitial nephritis with hyaline casts. She was started on hemodialysis and treated with steroids and cyclophosphamide. She came to our institute in January 2012. Investigations showed evidence of paraproteinemia with kappa restriction. Bone marrow showed 15% plasma cells. Kidney biopsy was reviewed and was diagnostic of cast nephropathy. She was treated with 6 monthly cycles of dexamethasone and bortezomib. She achieved complete remission in July 2012. Maintenance doses of bortezomib were continued until May 2014. Autologous bone marrow transplantation was performed on June 06, 2014. Monthly, bortezomib was continued till April 2015. Subsequently, workup for renal transplantation was started with her father as her donor. Test for sensitization was negative. Renal transplantation was done on January 1, 2016, with prednisolone, mycophenolate, and tacrolimus. She achieved a serum creatinine of 0.6 mg% on the 4th postoperative day. Thereafter, she continues to remain stable.

  18. Thymidine Kinase Suicide Gene-mediated Ganciclovir Ablation of Autologous Gene-modified Rhesus Hematopoiesis (United States)

    Barese, Cecilia N; Krouse, Allen E; Metzger, Mark E; King, Connor A; Traversari, Catia; Marini, Frank C; Donahue, Robert E; Dunbar, Cynthia E


    Despite the genotoxic complications encountered in clinical gene therapy trials for primary immunodeficiency diseases targeting hematopoietic cells with integrating vectors; this strategy holds promise for the cure of several monogenic blood, metabolic and neurodegenerative diseases. In this study, we asked whether the inclusion of a suicide gene in a standard retrovirus vector would allow elimination of vector-containing stem and progenitor cells and their progeny in vivo following transplantation, using our rhesus macaque transplantation model. Following stable engraftment with autologous CD34+ cells transduced with a retrovirus vector encoding a highly sensitive modified Herpes simplex virus thymidine kinase SR39, the administration of the antiviral prodrug ganciclovir (GCV) was effective in completely eliminating vector-containing cells in all hematopoietic lineages in vivo. The sustained absence of vector-containing cells over time, without additional GCV administration, suggests that the ablation of TkSR39 GCV-sensitive cells occurred in the most primitive hematopoietic long-term repopulating stem or progenitor cell compartment. These results are a proof-of-concept that the inclusion of a suicide gene in integrating vectors, in addition to a therapeutic gene, can provide a mechanism for later elimination of vector-containing cells, thereby increasing the safety of gene transfer. PMID:22910293

  19. Knee Osteochondral Autologous Transplantation: Long-term MR findings and clinical correlations

    Energy Technology Data Exchange (ETDEWEB)

    Tetta, Cecilia, E-mail: cecilia.tetta@ior.i [Radiology, Rizzoli Orthopedic Institute, Bologna (Italy); Busacca, Maurizio; Moio, Antonio; Rinaldi, Raffaella [Radiology, Rizzoli Orthopedic Institute, Bologna (Italy); Delcogliano, Marco; Kon, Elizaveta; Filardo, Giuseppe; Marcacci, Maurilio [Biomechanics Laboratory, Rizzoli Orthopedic Institute, Bologna (Italy); Albisinni, Ugo [Radiology, Rizzoli Orthopedic Institute, Bologna (Italy)


    We evaluated long-term magnetic resonance imaging (MRI) features of Knee Osteochondral Autologous Transplantation (OAT)-Mosaicplasty and correlated MRI findings and clinical outcome. Twenty-four patients (mean age 29.9 {+-} 8.7, 70.8% male) undergoing arthroscopic OAT between 1997 and 2000 were prospectively enrolled. The International Cartilage Repair Society (ICRS)/International Knee Documentation Committee (IKDC) scores and Tegner scores were employed for clinical evaluation. The magnetic resonance observation of cartilage repair tissue (MOCART) was utilized for description and assessment of the repair tissue. Median follow up was 113 months (interquartile range [IQR] 106-122). MRI showed good survival of grafted cartilage in 62.5% of patients. The integration of the graft was complete in 75% of cases, while the repaired tissue was intact in 62.5% and had an homogeneous structure in 70.8%. The MOCART score significantly correlated with objective and subjective scores (p = 0.003 and p = 0.002). Contrastingly, overall MOCART showed no correlation with the Tegner score. MRI revealed to be a powerful tool for non-invasive long-term assessment of OAT.

  20. Phase 1 Trial of Autologous Bone Marrow Stem Cell Transplantation in Patients with Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Zurab Kakabadze


    Full Text Available Introduction. A total of 18 patients, with complete motor deficits and paraplegia caused by thoracic and lumbar spine trauma without muscle atrophy or psychiatric problems, were included into this study. Materials and Methods. The bone marrow was aspirated from the anterior iliac crest under local anesthesia and the mononuclear fraction was isolated by density gradient method. At least 750 million mononuclear-enriched cells, suspended in 2 mL of saline, were infused intrathecally. Results and Discussion. The study reports demonstrated improvement of motor and sensory functions of various degrees observed in 9 of the 18 (50% cases after bone marrow stem cell transplantation. Measured by the American Spinal Injury Association (ASIA scale, 7 (78% out of the 9 patients observed an improvement by one grade, while two cases (22% saw an improvement by two grades. However, there were no cases in which the condition was improved by three grades. Conclusions. Analysis of subsequent treatment results indicated that the transplantation of mononuclear-enriched autologous BMSCs is a feasible and safe technique. However, successful application of the BMSCs in the clinical practice is associated with the necessity of executing more detailed examinations to evaluate the effect of BMSCs on the patients with spinal cord injury.

  1. Phase 1 Trial of Autologous Bone Marrow Stem Cell Transplantation in Patients with Spinal Cord Injury (United States)

    Kakabadze, Zurab; Mardaleishvili, Konstantine; Chutkerashvili, Gocha; Chelishvili, Irakli; Harders, Albrecht; Loladze, George; Shatirishvili, Gocha; Kipshidze, Nodar; Chakhunashvili, David; Chutkerashvili, Konstantine


    Introduction. A total of 18 patients, with complete motor deficits and paraplegia caused by thoracic and lumbar spine trauma without muscle atrophy or psychiatric problems, were included into this study. Materials and Methods. The bone marrow was aspirated from the anterior iliac crest under local anesthesia and the mononuclear fraction was isolated by density gradient method. At least 750 million mononuclear-enriched cells, suspended in 2 mL of saline, were infused intrathecally. Results and Discussion. The study reports demonstrated improvement of motor and sensory functions of various degrees observed in 9 of the 18 (50%) cases after bone marrow stem cell transplantation. Measured by the American Spinal Injury Association (ASIA) scale, 7 (78%) out of the 9 patients observed an improvement by one grade, while two cases (22%) saw an improvement by two grades. However, there were no cases in which the condition was improved by three grades. Conclusions. Analysis of subsequent treatment results indicated that the transplantation of mononuclear-enriched autologous BMSCs is a feasible and safe technique. However, successful application of the BMSCs in the clinical practice is associated with the necessity of executing more detailed examinations to evaluate the effect of BMSCs on the patients with spinal cord injury. PMID:27433165

  2. Autologous adipocyte derived stem cells favour healing in a minipig model of cutaneous radiation syndrome.

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    Fabien Forcheron

    Full Text Available Cutaneous radiation syndrome (CRS is the delayed consequence of localized skin exposure to high doses of ionizing radiation. Here we examined for the first time in a large animal model the therapeutic potential of autologous adipose tissue-derived stroma cells (ASCs. For experiments, Göttingen minipigs were locally gamma irradiated using a (60Co source at the dose of 50 Gy and grafted (n = 5 or not (n = 8. ASCs were cultured in MEM-alpha with 10% fetal calf serum and basic fibroblast growth factor (2 ng.mL(-1 and post irradiation were intradermally injected on days 25, 46, 67 and finally between days 95 and 115 (50 × 10(6 ASCs each time into the exposed area. All controls exhibited a clinical evolution with final necrosis (day 91. In grafted pigs an ultimate wound healing was observed in four out of five grafted animals (day 130 +/- 28. Immunohistological analysis of cytokeratin expression showed a complete epidermis recovery. Grafted ASCs accumulated at the dermis/subcutis barrier in which they attracted numerous immune cells, and even an increased vasculature in one pig. Globally this study suggests that local injection of ASCs may represent a useful strategy to mitigate CRS.

  3. Outcome of autologous hematopoietic stem cell transplantation in refractory multiple myeloma. (United States)

    Veltri, Lauren W; Milton, Denái R; Delgado, Ruby; Shah, Nina; Patel, Krina; Nieto, Yago; Kebriaei, Partow; Popat, Uday R; Parmar, Simrit; Oran, Betul; Ciurea, Stefan; Hosing, Chitra; Lee, Hans C; Manasanch, Elisabet; Orlowski, Robert Z; Shpall, Elizabeth J; Champlin, Richard E; Qazilbash, Muzaffar H; Bashir, Qaiser


    Despite the introduction of effective, novel agents, the outcome of patients with refractory multiple myeloma remains poor, particularly those who are refractory to both proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs). Limited data are available on the role of autologous hematopoietic stem cell transplantation in this population. Patients with refractory myeloma who underwent first autologous hematopoietic stem cell transplantation (auto-HCT) between March 2000 and October 2015 were retrospectively analyzed. Those who had primary refractory disease and those with relapsed and refractory disease were included. Disease that was refractory to at least 1 PI and at least 1 IMiD was classified as double-refractory multiple myeloma (DR-MM). In total, 233 patients were identified, including 105 (45%) classified with DR-MM and 128 (55%) classified with nondouble-refractory myeloma (NDR-MM). At a median follow-up of 42 months for surviving patients, at least a partial response was observed in 188 patients (81%; 83 patients in the DR-MM group [79%] and 105 patients in the NDR-MM [82%]; P = .77). A near complete response or better was observed in 52 patients (22%; 25 patients in the DR-MM group [24%] and 27 patients in the NDR-MM group [21%]; P = .77). The median progression-free survival was 17.6 months (14.4 months in the DR-MM group and 18.2 months in the NDR-MM group), and the 2-year progression-free survival rate was 38% (35% in the DR-MM group and 40% in the NDR-MM group; P = .40). The median overall survival was 48 months (38.9 months in the DR-MM group and 56.6 months in the NDR-MM group), and the 2-year overall survival rate was 74% (71% in the DR-MM group and 76% in the NDR-MM group; P = .27). The current findings indicate that auto-HCT is an effective and safe therapy in patients with refractory multiple myeloma, including those who are refractory to IMiDs and PIs. Cancer 2017;123:3568-75. © 2017 American Cancer Society. © 2017

  4. Autologous Stem Cell Injection for Spinal Cord Injury - A Clinical Study from India.

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    Ravikumar R


    Full Text Available We studied 100 patients with Spinal Cord injury (SCI after Autologous Stem cell Injection in the Spinal fluid with a Follow up of 6 months post Stem cell injection. There were 69 males and 31 females; age ranging from 8 years to 55 years.? Time after Spinal Injury ranged from 11 years - 3 months (Average: 4.5 years. The Level of Injury ranged from Upper Thoracic (T1-T7 - 34 pts, Lower thoracic (T7-T12 -45 pts, Lumbar -12, Cervical-9 pts. All patients had an MRI Scan, urodynamic study and SSEP (somatosensory Evoked Potential tests before and 3 months after Stem cell Injection.80% of patients had Grade 0 power in the Lower limbs and rest had grade 1-2 power before stem cell injections. 70% of cases had complete lack of Bladder control and 95% had reduced detrusor function.We Extracted CD34 and CD 133 marked Stem cells from 100 ml of Bone marrow Aspirate using Ficoll Gradient method with Cell counting done using flowcytometry.15 ml of the Stem cell concentrate was injected into the Lumbar spinal fluid in aseptic conditions. The CD 34/CD45 counts ranged from 120-400 million cells in the total volume.6 months after Injection, 8 patients had more than 2 grades of Motor power improvement, 3 are able to walk with support. 1 patient with T12/L1 injury was able to walk without support. 12 had sensory tactile and Pain perception improvement and 8 had objective improvement in bladder control and Bladder Muscle contractility. A total of 18 patients had reported or observed improvement in Neurological status. 85% of patients who had motor Improvement had Lesions below T8. MRI, SSEP and Urodynamic Study data are gathered at regular intervals. Conclusion: This study shows that Quantitative and qualitative Improvement in the Neurological status of paralyzed patients after Spinal cord injury is possible after autologous bone marrow Stem cell Injections in select patients. There was no report of Allodynia indicating the safety of the procedure. Further studies to

  5. High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS (United States)

    Hutton, George J.; Racke, Michael K.; Popat, Uday; Devine, Steven M.; Steinmiller, Kaitlyn C.; Griffith, Linda M.; Muraro, Paolo A.; Openshaw, Harry; Sayre, Peter H.; Stuve, Olaf; Arnold, Douglas L.; Wener, Mark H.; Georges, George E.; Wundes, Annette; Kraft, George H.; Bowen, James D.


    Objective: To evaluate the safety, efficacy, and durability of multiple sclerosis (MS) disease stabilization after high-dose immunosuppressive therapy (HDIT) and autologous hematopoietic cell transplantation (HCT). Methods: High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT-MS) is a phase II clinical trial of HDIT/HCT for patients with relapsing-remitting (RR) MS who experienced relapses with disability progression (Expanded Disability Status Scale [EDSS] 3.0–5.5) while on MS disease-modifying therapy. The primary endpoint was event-free survival (EFS), defined as survival without death or disease activity from any one of: disability progression, relapse, or new lesions on MRI. Participants were evaluated through 5 years posttransplant. Toxicities were reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (AE). Results: Twenty-five participants were evaluated for transplant and 24 participants underwent HDIT/HCT. Median follow-up was 62 months (range 12–72). EFS was 69.2% (90% confidence interval [CI] 50.2–82.1). Progression-free survival, clinical relapse-free survival, and MRI activity-free survival were 91.3% (90% CI 74.7%–97.2%), 86.9% (90% CI 69.5%–94.7%), and 86.3% (90% CI 68.1%–94.5%), respectively. AE due to HDIT/HCT were consistent with expected toxicities and there were no significant late neurologic adverse effects noted. Improvements were noted in neurologic disability with a median change in EDSS of −0.5 (interquartile range −1.5 to 0.0; p = 0.001) among participants who survived and completed the study. Conclusion: HDIT/HCT without maintenance therapy was effective for inducing long-term sustained remissions of active RRMS at 5 years. identifier: NCT00288626. Classification of evidence: This study provides Class IV evidence that participants with RRMS experienced sustained remissions with toxicities as expected from HDIT/HCT. PMID:28148635

  6. Clinical Trials Using Adenovirus Encoding Tyrosinase/MART-1/MAGEA6-transduced Autologous Dendritic Cell Vaccine (United States)

    NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying adenovirus encoding tyrosinase/mart-1/magea6-transduced autologous dendritic cell vaccine.

  7. Rapid deterioration of preexisting renal insufficiency after autologous mesenchymal stem cell therapy

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    Jun-Seop Kim


    Full Text Available Administration of autologous mesenchymal stem cells (MSCs has been shown to improve renal function and histological findings in acute kidney injury (AKI models. However, its effects in chronic kidney disease (CKD are unclear, particularly in the clinical setting. Here, we report our experience with a CKD patient who was treated by intravenous infusion of autologous MSCs derived from adipose tissue in an unknown clinic outside of Korea. The renal function of the patient had been stable for several years before MSC administration. One week after the autologous MSC infusion, the preexisting renal insufficiency was rapidly aggravated without any other evidence of AKI. Hemodialysis was started 3 months after MSC administration. Renal biopsy findings at dialysis showed severe interstitial fibrosis and inflammatory cell infiltration, with a few cells expressing CD34 and CD117, 2 surface markers of stem cells. This case highlights the potential nephrotoxicity of autologous MSC therapy in CKD patients.

  8. Infusion of Autologous Lysed Plasma Into the Baboon: Assessment of Coagulation, Platelet, and Pulmonary Function

    National Research Council Canada - National Science Library

    Morse, D


    .... Eight baboons were infused with 250 cc of autologous plasma treated with urokinase in doses of 3000 IU/ml or 5000 IU/ml, creating a fibrinolytic state in which plasmin was generated and fibrinogen...

  9. Local administration of autologous platelet-rich plasma in a female patient with skin ulcer defect

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    S M Noskov


    Full Text Available The paper describes a clinical observation of the efficiency of local therapy with autologous platelet-rich plasma for .skin ulcer defect in a female with chronic lymphocytic leukemia

  10. Use of autologous platelet - Rich plasma in the treatment of intrabony defects

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    Sharath K Shetty


    Treatment of intrabony defects by autologous PRP gel alone caused significant soft tissue clinical improvement as well as hard tissue defect fill as evidenced by SSD view in spiral computed tomography.

  11. The role of autologous bone graft in surgical treatment of hypertrophic nonunion of midshaft clavicle fractures

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    Hui-Kuang Huang


    Conclusion: LC-DCP fixation is an effective method for treating hypertrophic nonunion of mid-shaft clavicle fracture. Local bone graft is sufficient to achieve necessary union, and autologous bone graft from other sites of the body appears unnecessary.

  12. Comparison of immune reconstitution after allogeneic vs. autologous stem cell transplantation in 182 pediatric recipients

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    V. Wiegering


    Conclusion: Children undergoing a HSCT show a different pattern of immune reconstitution in the allogeneic and autologous setting. This might influence the outcome and should affect the clinical handling of infectious prophylaxis and re-vaccinations.

  13. Chemokine receptor polymorphism and autologous neutralizing antibody response in long-term HIV-1 infection

    DEFF Research Database (Denmark)

    Schønning, Kristian; Joost, Mette; Gram, G J


    We have previously reported that slowly progressing HIV infection (SPI) was associated with the presence of contemporaneous autologous neutralizing antibodies. In contrast, a group of individuals with more rapidly progressing infection (RPI) generally lacked these antibodies. To understand the im...

  14. Artificial Polymeric Scaffolds as Extracellular Matrix Substitutes for Autologous Conjunctival Goblet Cell Expansion. (United States)

    He, Min; Storr-Paulsen, Thomas; Wang, Annie L; Ghezzi, Chiara E; Wang, Siran; Fullana, Matthew; Karamichos, Dimitrios; Utheim, Tor P; Islam, Rakibul; Griffith, May; Islam, M Mirazul; Hodges, Robin R; Wnek, Gary E; Kaplan, David L; Dartt, Darlene A


    We fabricated and investigated polymeric scaffolds that can substitute for the conjunctival extracellular matrix to provide a substrate for autologous expansion of human conjunctival goblet cells in culture. We fabricated two hydrogels and two silk films: (1) recombinant human collagen (RHC) hydrogel, (2) recombinant human collagen 2-methacryloylxyethyl phosphorylcholine (RHC-MPC) hydrogel, (3) arginine-glycine-aspartic acid (RGD) modified silk, and (4) poly-D-lysine (PDL) coated silk, and four electrospun scaffolds: (1) collagen, (2) poly(acrylic acid) (PAA), (3) poly(caprolactone) (PCL), and (4) poly(vinyl alcohol) (PVA). Coverslips and polyethylene terephthalate (PET) were used for comparison. Human conjunctival explants were cultured on scaffolds for 9 to 15 days. Cell viability, outgrowth area, and the percentage of cells expressing markers for stratified squamous epithelial cells (cytokeratin 4) and goblet cells (cytokeratin 7) were determined. Most of cells grown on all scaffolds were viable except for PCL in which only 3.6 ± 2.2% of the cells were viable. No cells attached to PVA scaffold. The outgrowth was greatest on PDL-silk and PET. Outgrowth was smallest on PCL. All cells were CK7-positive on RHC-MPC while 84.7 ± 6.9% of cells expressed CK7 on PDL-silk. For PCL, 87.10 ± 3.17% of cells were CK7-positive compared to PET where 67.10 ± 12.08% of cells were CK7-positive cells. Biopolymer substrates in the form of hydrogels and silk films provided for better adherence, proliferation, and differentiation than the electrospun scaffolds and could be used for conjunctival goblet cell expansion for eventual transplantation once undifferentiated and stratified squamous cells are included. Useful polymer scaffold design characteristics have emerged from this study.

  15. Investigation of postoperative satisfaction of facial autologous fat grafting with platelet-rich plasma


    Xiangdong Qi; Jie Zhou


    Objectives: This single-center prospective, case-controlled study investigated satisfaction and esthetic results as rated by the physician and patient, respectively, by following up thirty patients with aging face, who underwent facial autologous fat grafting with platelet-rich plasma (PRP). Materials and Methods: A retrospective review of thirty patients, who were suffering from facial sagging or partial depression and requiring autologous fat grafting between February 2012 and September 201...

  16. Autologous conjunctiva transplantation with stem cells on edge of cornea for recurrent pterygium


    Yun Wang


    AIM: To observe the clinical effectiveness and practicality the autologous conjunctiva transplantation with stem cells on edge of cornea for recurrent pterygium.METHODS: Of the 53 recurrent pterygium patients(57 eyes), after all pathological tissues were removed, underwent the autologous conjunctiva transplantation with stem cells on edge of cornea which were locked above conjunctival transplantation of the operated eye.RESULTS: Postopretive follow-up was 1-12 months for all 57 eyes, of which...

  17. Rapid deterioration of preexisting renal insufficiency after autologous mesenchymal stem cell therapy


    Jun-Seop Kim; Jong-Hak Lee; Owen Kwon; Jang-Hee Cho; Ji-Young Choi; Sun-Hee Park; Chan-Duck Kim; Yong-Jin Kim; Yong-Lim Kim


    Administration of autologous mesenchymal stem cells (MSCs) has been shown to improve renal function and histological findings in acute kidney injury (AKI) models. However, its effects in chronic kidney disease (CKD) are unclear, particularly in the clinical setting. Here, we report our experience with a CKD patient who was treated by intravenous infusion of autologous MSCs derived from adipose tissue in an unknown clinic outside of Korea. The renal function of the patient had been stable for ...

  18. The composite of bone marrow concentrate and PRP as an alternative to autologous bone grafting.

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    Mohssen Hakimi

    Full Text Available One possible alternative to the application of autologous bone grafts represents the use of autologous bone marrow concentrate (BMC. The purpose of our study was to evaluate the potency of autologous platelet-rich plasma (PRP in combination with BMC. In 32 mini-pigs a metaphyseal critical-size defect was surgically created at the proximal tibia. The animals were allocated to four treatment groups of eight animals each (1. BMC+CPG group, 2. BMC+CPG+PRP group, 3. autograft group, 4. CPG group. In the BMC+CPG group the defect was filled with autologous BMC in combination with calcium phosphate granules (CPG, whereas in the BMC+CPG+PRP group the defect was filled with the composite of autologous BMC, CPG and autologous PRP. In the autograft group the defect was filled with autologous cancellous graft, whereas in the CPG group the defect was filled with CPG solely. After 6 weeks radiological and histomorphometrical analysis showed significantly more new bone formation in the BMC+CPG+PRP group compared to the BMC+CPG group and the CPG group. There were no significant differences between the BMC+CPG+PRP group and the autograft group. In the PRP platelets were enriched significantly about 4.7-fold compared to native blood. In BMC the count of mononuclear cells increased significantly (3.5-fold compared to the bone marrow aspirate. This study demonstrates that the composite of BMC+CPG+PRP leads to a significantly higher bone regeneration of critical-size defects at the proximal tibia in mini-pigs than the use of BMC+CPG without PRP. Furthermore, within the limits of the present study the composite BMC+CPG+PRP represents a comparable alternative to autologous bone grafting.

  19. Persistent seropositivity for yellow fever in a previously vaccinated autologous hematopoietic stem cell transplantation recipient. (United States)

    Hayakawa, Kayoko; Takasaki, Tomohiko; Tsunemine, Hiroko; Kanagawa, Shuzo; Kutsuna, Satoshi; Takeshita, Nozomi; Mawatari, Momoko; Fujiya, Yoshihiro; Yamamoto, Kei; Ohmagari, Norio; Kato, Yasuyuki


    The duration of a protective level of yellow fever antibodies after autologous hematopoietic stem cell transplantation in a previously vaccinated person is unclear. The case of a patient who had previously been vaccinated for yellow fever and who remained seropositive for 22 months after autologous peripheral blood stem cell transplantation for malignant lymphoma is described herein. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Intense immunosuppression followed by autologous haematopoietic stem cell transplantation as a therapeutic strategy in aggressive forms of multiple sclerosis. (United States)

    Mancardi, Gianluigi; Sormani, Maria Pia; Muraro, Paolo A; Boffa, Giacomo; Saccardi, Riccardo


    In the majority of relapsing multiple sclerosis patients, the disease can be quite easily controlled by already available, approved therapies. There are, however, some aggressive cases who continue to have clinical and magnetic resonance imaging (MRI) activity in spite of the treatment. These are the cases who may now receive benefit from intense immunosuppression followed by autologous haematopoietic stem cell transplantation (aHSCT). In this review, we describe the method and the rationale of aHSCT, the more recently published studies that demonstrate its efficacy in selected multiple sclerosis cases, the problems related to safety and the transplant-related mortality risk of the procedure. A description of the ideal patient who can take advantage of aHSCT is outlined and, finally, the ongoing studies which are near to completion or are close to starting are briefly reported.

  1. Cell Based Autologous Immune Enhancement Therapy (AIET after Radiotherapy in a Locally Advanced Carcinoma of the Cervix

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    Sumana Premkumar


    Full Text Available Radiotherapy is the primary form of treatment in patients with locally advanced cervical carcinoma. However for residual disease in the form of the persistent lymph nodes, surgery or chemotherapy is recommended. As surgery is not acceptable by every patient and chemotherapy has associated side effects, we hereby report the positive outcome of in vitro expanded natural killer cell and activated T lymphocyte based autologous immune enhancement therapy (AIET for the residual lymphadenopathy in a patient with locally advanced cervical cancer after radiation. After six transfusions of AIET, there was complete resolution of residual lymph nodes and there was no evidence of local lesion. The patient also reported improvement in quality of life. As AIET has been reported as the least toxic among the available therapies for cancer, combining AIET with conventional forms of therapy in similar patients might not only improve the outcome but may also help the patients achieve a good quality of life.

  2. Subantral bone grafts, a comparative study of the degree of resorption of alloplastic versus autologous grafts. (United States)

    Onişor-Gligor, Florin; Juncar, Mihai; Câmpian, Radu Septimiu; BăciuŢ, Grigore; Bran, Simion; BăciuŢ, Mihaela Felicia


    The placement of dental implants in the posterior region of the maxillary may pose some difficulties caused by the quality and particularly, the quantity of the subantral bone reserve, which are overcome by subantral bone augmentation. The current study performs a comparative evaluation of the quality and especially, of the stability of alloplastic and autologous materials used for subantral bone augmentation. This study included 21 patients who underwent subantral bone augmentation with alloplastic and autologous material. The patients were followed-up over a 24-month period after bone augmentation, during which the osseointegration rate of dental implants and the stability of subantral grafts were evaluated. The rate of failure of dental implants placed in autologous material grafts was 1.89% (0.036±9.398), while the rate of failure of those placed in alloplastic material was 7.69% (1.960±19.194). Bone resorption was higher within 12 months of dental implant placement both for the alloplastic material (9.87±3.76%) and the autologous material (18.87±3.25%), while 12-24 months after bone augmentation it diminished. The implants placed in the autologous bone grafts had a lower rate of failure compared to those placed in the alloplastic material grafts; in contrast, alloplastic material had a lower resorption rate compared to autologous material.

  3. Complete Mapping of a Cystine Knot and Nested Disulfides of Recombinant Human Arylsulfatase A by Multi-Enzyme Digestion and LC-MS Analysis Using CID and ETD (United States)

    Ni, Wenqin; Lin, Melanie; Salinas, Paul; Savickas, Philip; Wu, Shiaw-Lin; Karger, Barry L.


    Cystine knots or nested disulfides are structurally difficult to characterize, despite current technological advances in peptide mapping with high-resolution liquid chromatography coupled with mass spectrometry (LC-MS). In the case of recombinant human arylsulfatase A (rhASA), there is one cystine knot at the C-terminal, a pair of nested disulfides at the middle, and two out of three unpaired cysteines in the N-terminal region. The statuses of these cysteines are critical structure attributes for rhASA function and stability that requires precise examination. We used a unique approach to determine the status and linkage of each cysteine in rhASA, which was comprised of multi-enzyme digestion strategies (from Lys-C, trypsin, Asp-N, pepsin, and PNGase F) and multi-fragmentation methods in mass spectrometry using electron transfer dissociation (ETD), collision induced dissociation (CID), and CID with MS3 (after ETD). In addition to generating desired lengths of enzymatic peptides for effective fragmentation, the digestion pH was optimized to minimize the disulfide scrambling. The disulfide linkages, including the cystine knot and a pair of nested cysteines, unpaired cysteines, and the post-translational modification of a cysteine to formylglycine, were all determined. In the assignment, the disulfide linkages were Cys138-Cys154, Cys143-Cys150, Cys282-Cys396, Cys470-Cys482, Cys471-Cys484, and Cys475-Cys481. For the unpaired cysteines, Cys20 and Cys276 were free cysteines, and Cys51 was largely converted to formylglycine (>70 %). A successful methodology has been developed, which can be routinely used to determine these difficult-to-resolve disulfide linkages, ensuring drug function and stability.

  4. Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial. (United States)

    Tan, Jianming; Wu, Weizhen; Xu, Xiumin; Liao, Lianming; Zheng, Feng; Messinger, Shari; Sun, Xinhui; Chen, Jin; Yang, Shunliang; Cai, Jinquan; Gao, Xia; Pileggi, Antonello; Ricordi, Camillo


    Antibody-based induction therapy plus calcineurin inhibitors (CNIs) reduce acute rejection rates in kidney recipients; however, opportunistic infections and toxic CNI effects remain challenging. Reportedly, mesenchymal stem cells (MSCs) have successfully treated graft-vs-host disease. To assess autologous MSCs as replacement of antibody induction for patients with end-stage renal disease who undergo ABO-compatible, cross-match-negative kidney transplants from a living-related donor. One hundred fifty-nine patients were enrolled in this single-site, prospective, open-label, randomized study from February 2008-May 2009, when recruitment was completed. Patients were inoculated with marrow-derived autologous MSC (1-2 x 10(6)/kg) at kidney reperfusion and two weeks later. Fifty-three patients received standard-dose and 52 patients received low-dose CNIs (80% of standard); 51 patients in the control group received anti-IL-2 receptor antibody plus standard-dose CNIs. The primary measure was 1-year incidence of acute rejection and renal function (estimated glomerular filtration rate [eGFR]); the secondary measure was patient and graft survival and incidence of adverse events. Patient and graft survival at 13 to 30 months was similar in all groups. After 6 months, 4 of 53 patients (7.5%) in the autologous MSC plus standard-dose CNI group (95% CI, 0.4%-14.7%; P = .04) and 4 of 52 patients (7.7%) in the low-dose group (95% CI, 0.5%-14.9%; P = .046) compared with 11 of 51 controls (21.6%; 95% CI, 10.5%-32.6%) had biopsy-confirmed acute rejection. None of the patients in either autologous MSC group had glucorticoid-resistant rejection, whereas 4 patients (7.8%) in the control group did (95% CI, 0.6%-15.1%; overall P = .02). Renal function recovered faster among both MSC groups showing increased eGFR levels during the first month after surgery than the control group. Patients receiving standard-dose CNI had a mean difference of 6.2 mL/min per 1.73 m(2) (95% CI, 0.4-11.9; P=.04

  5. Cell therapy of hip osteonecrosis with autologous bone marrow grafting

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    Hernigou Philippe


    Full Text Available Background: One of the reasons for bone remodeling leading to an insufficient creeping substitution after osteonecrosis in the femoral head may be the small number of progenitor cells in the proximal femur and the trochanteric region. Because of this lack of progenitor cells, treatment modalities should stimulate and guide bone remodeling to sufficient creeping substitution to preserve the integrity of the femoral head. Core decompression with bone graft is used frequently in the treatment of osteonecrosis of the femoral head. In the current series, grafting was done with autologous bone marrow obtained from the iliac crest of patients operated on for early stages of osteonecrosis of the hip before collapse with the hypothesis that before stage of subchondral collapse, increasing the number of progenitor cells in the proximal femur will stimulate bone remodeling and creeping substitution and thereby improve functional outcome. Materials and Methods: Between 1990 and 2000, 342 patients (534 hips with avascular osteonecrosis at early stages (Stages I and II were treated with core decompression and autologous bone marrow grafting obtained from the iliac crest of patients operated on for osteonecrosis of the hip. The percentage of hips affected by osteonecrosis in this series of 534 hips was 19% in patients taking corticosteroids, 28% in patients with excessive alcohol intake, and 31% in patients with sickle cell disease. The mean age of the patients at the time of decompression and autologous bone marrow grafting was 39 years (range: 16-61 years. The aspirated marrow was reduced in volume by concentration and injected into the femoral head after core decompression with a small trocar. To measure the number of progenitor cells transplanted, the fibroblast colony forming unit was used as an indicator of the stroma cell activity. Results: Patients were followed up from 8 to 18 years. The outcome was determined by the changes in the Harris hip score

  6. Efficacy and Safety of a Novel Autologous Wound Matrix in the Management of Complicated, Chronic Wounds: A Pilot Study. (United States)

    Kushnir, Igal; Kushnir, Alon; Serena, Thomas E; Garfinkel, Doron


    The objective of this pilot study was to evaluate the efficacy and safety of a novel method using an autologous whole blood clot formed with the RedDress Wound Care System (RD1, RedDress Ltd, Israel), a provisional whole blood clot matrix used in the treatment of chronic wounds of various etiologies. Patients were treated at the bedside with the whole blood clot matrix. Blood was withdrawn from each patient using citrate, mixed with a calcium gluconate/kaolin suspension, and injected into an RD1 clotting tray. Within 10 minutes, a clot was formed, placed upon the wound, and fixed with primary and secondary dressings. Wounds were redressed weekly with a whole blood clot matrix. Treatment was terminated when complete healing was achieved, or when the clinician determined that the wound could not further improve without additional invasive procedures. Seven patients with multiple and serious comorbidities and 9 chronic wounds were treated with 35 clot matrices. Complete healing was achieved in 7 of 9 wounds (78%). In 1 venous ulcer with a nonhealing fistula, 77% healing was achieved. Treatment was terminated in 1 pressure ulcer at 82% closure, because an unexpected mechanical trauma resulted in deterioration; this was the only adverse event reported, unrelated to the product. No systemic adverse events occurred. This pilot study demonstrates the in vitro autologous whole blood clot matrix is effective and safe for treating patients with chronic wounds of different etiologies. A larger clinical trial is needed to assess the relative success rate of the matrix in different types of wounds in a diverse population with comorbidities.

  7. Adaptive Immune Response Impairs the Efficacy of Autologous Transplantation of Engineered Stem Cells in Dystrophic Dogs (United States)

    Sitzia, Clementina; Farini, Andrea; Jardim, Luciana; Razini, Paola; Belicchi, Marzia; Cassinelli, Letizia; Villa, Chiara; Erratico, Silvia; Parolini, Daniele; Bella, Pamela; da Silva Bizario, Joao Carlos; Garcia, Luis; Dias-Baruffi, Marcelo; Meregalli, Mirella; Torrente, Yvan


    Duchenne muscular dystrophy is the most common genetic muscular dystrophy. It is caused by mutations in the dystrophin gene, leading to absence of muscular dystrophin and to progressive degeneration of skeletal muscle. We have demonstrated that the exon skipping method safely and efficiently brings to the expression of a functional dystrophin in dystrophic CD133+ cells injected scid/mdx mice. Golden Retriever muscular dystrophic (GRMD) dogs represent the best preclinical model of Duchenne muscular dystrophy, mimicking the human pathology in genotypic and phenotypic aspects. Here, we assess the capacity of intra-arterial delivered autologous engineered canine CD133+ cells of restoring dystrophin expression in Golden Retriever muscular dystrophy. This is the first demonstration of five-year follow up study, showing initial clinical amelioration followed by stabilization in mild and severe affected Golden Retriever muscular dystrophy dogs. The occurrence of T-cell response in three Golden Retriever muscular dystrophy dogs, consistent with a memory response boosted by the exon skipped-dystrophin protein, suggests an adaptive immune response against dystrophin. PMID:27506452

  8. Technetium-99m-Labeled Autologous Serum Albumin: A Personal-Exclusive Source of Serum Component

    Directory of Open Access Journals (Sweden)

    Yuh-Feng Wang


    Full Text Available Technetium-99m human serum albumin (99mTc-HSA is an important radiopharmaceutical required in nuclear medicine studies. However, the risk of transfusion-transmitted infection remains a major safety concern. Autopreparation of serum component acquired from patient provides a “personal-exclusive” source for radiolabeling. This paper is to evaluate the practicality of on-site elusion and subsequent radiolabeling efficacy for serum albumin. Results showed that the autologous elute contained more albumin fraction than serum without extraction procedure. Good radiochemical purity and stability were demonstrated after radiolabeling. Biodistribution study showed that labeled albumin accumulated immediately in the lung, liver, and kidney. It was cleared steadily and excreted in the urine. The biologic half-life was defined, and all samples passed the pyrogenicity and sterility tests. In conclusion, autoalbumin could be extracted and radiolabeled properly in a nuclear medicine setting. Moreover, the risk of transfusion-transmitted infection associated with nonautologous, multisource 99mTc-HSA agents can be reduced.

  9. Biological and mechanical evaluation of a Bio-Hybrid scaffold for autologous valve tissue engineering. (United States)

    Jahnavi, S; Saravanan, U; Arthi, N; Bhuvaneshwar, G S; Kumary, T V; Rajan, S; Verma, R S


    Major challenge in heart valve tissue engineering for paediatric patients is the development of an autologous valve with regenerative capacity. Hybrid tissue engineering approach is recently gaining popularity to design scaffolds with desired biological and mechanical properties that can remodel post implantation. In this study, we fabricated aligned nanofibrous Bio-Hybrid scaffold made of decellularized bovine pericardium: polycaprolactone-chitosan with optimized polymer thickness to yield the desired biological and mechanical properties. CD44+, αSMA+, Vimentin+ and CD105- human valve interstitial cells were isolated and seeded on these Bio-Hybrid scaffolds. Subsequent biological evaluation revealed interstitial cell proliferation with dense extra cellular matrix deposition that indicated the viability for growth and proliferation of seeded cells on the scaffolds. Uniaxial mechanical tests along axial direction showed that the Bio-Hybrid scaffolds has at least 20 times the strength of the native valves and its stiffness is nearly 3 times more than that of native valves. Biaxial and uniaxial mechanical studies on valve interstitial cells cultured Bio-Hybrid scaffolds revealed that the response along the axial and circumferential direction was different, similar to native valves. Overall, our findings suggest that Bio-Hybrid scaffold is a promising material for future development of regenerative heart valve constructs in children. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Characterization of complete particles (VSV-G/SIN-GFP) and empty particles (VSV-G/EMPTY) in human immunodeficiency virus type 1-based lentiviral products for gene therapy: potential applications for improvement of product quality and safety. (United States)

    Zhao, Yuan; Keating, Kenneth; Dolman, Carl; Thorpe, Robin


    Lentiviral vectors persist in the host and are therefore ideally suited for long-term gene therapy. To advance the use of lentiviral vectors in humans, improvement of their production, purification, and characterization has become increasingly important and challenging. In addition to cellular contaminants derived from packaging cells, empty particles without therapeutic function are the major impurities that compromise product safety and efficacy. Removal of empty particles is difficult because of their innate similarity in particle size and protein composition to the complete particles. We propose that comparison of the properties of lentiviral products with those of purposely expressed empty particles may reveal potential differences between empty and complete particles. For this, three forms of recombinant lentiviral samples, that is, recombinant vesicular stomatitis virus glycoprotein (VSV-G) proteins, empty particles (VSV-G/Empty), and complete particles (VSV-G/SIN-GFP) carrying viral RNA, were purified by size-exclusion chromatography (SEC). The SEC-purified samples were further analyzed by immunoblotting with six antibodies to examine viral and cellular proteins associated with the particles. This study has demonstrated, for the first time, important differences between VSV-G/Empty particles and complete VSV-G/SIN-GFP particles. Differences include the processing of Gag protein and the inclusion of cellular proteins in the particles. Our findings support the development of improved production, purification, and characterization methods for lentiviral products.

  11. Electrolyte and acid/base changes in dogs undergoing autologous blood transfusion via a cell salvage device. (United States)

    Lamb, Jodie L; Thieman Mankin, Kelley M; Levine, Gwendolyn J; Thompson, James


    This study reports electrolyte and acid/base disturbances observed in clinical cases receiving autologous transfusion of blood processed by a cell salvage device. The records of 12 client-owned dogs that received an autologous transfusion via a cell salvage device with pre- and post-autologous transfusion blood work available were reviewed. Blood work from the 12 case dogs was compared to blood work from 12 control dogs with similar diseases. Control dogs received similar surgical treatment and were administered a similar volume per kg of packed red blood cells as case dogs, but did not undergo autologous transfusion. Case dogs that received autologous transfusion via a cell salvage device were significantly more likely to experience a decrease in ionized calcium and magnesium levels post-transfusion than were control dogs. Calcium and magnesium levels should be closely monitored during and after autologous transfusion. Calcium and/or magnesium supplementation may be required.

  12. Breast reconstruction de novo by water-jet assisted autologous fat grafting – a retrospective study

    Directory of Open Access Journals (Sweden)

    Hoppe, Delia Letizia


    Full Text Available [english] Background: Autologous fat grafting has become a frequent, simple, reproducible and low-risk technique for revisional or partial breast reconstruction. The presented European multicenter study describes an optimized treatment and follow-up protocol for the de novo breast reconstruction after total mastectomy by lipotransfer alone.Methods: A retrospective European multicenter trial included 135 procedures on 28 (35 breasts postmastectomy patients (mean 52.4 years. All women were treated with the water-jet assisted fat grafting method (BEAULI™ combined with additional procedures (NAC reconstruction, contralateral mastoplasty and evaluated with at least 6 months follow-up (mean 2.6 years. Sonography or mammography, clinical examination, patient questionnaire (10-point Likert scale and digital photographs were carried out.Results: On average the patients received 4 to 6 procedures each with a single volume of 159 ml (±61 ml over 21 months (range 9 months to 2.5 years. In total 1,020 ml (±515 ml fat were grafted till a complete breast reconstruction was achieved. Irradiated patients needed a significantly higher volume than non-irradiated (p<0.041. Main treatment complications were liponecrosis (2.59%, infection (0.74% and granuloma (0.74%. Patient satisfaction was overall high to very high (96% and confirmed the good aesthetic results (68% and the natural softness, contour and shape of the reconstructed breast.Conclusions: A complete breast reconstruction with large volume fat grafting is alternatively possible to standard techniques in selected cases. It takes at least 4 to 6 lipotransfers in the course of 2 years. Patients with prior radiotherapy may require even up to 8 sessions over nearly 3 years of treatment.

  13. Complete amino acid sequence of the human alpha 5 (IV) collagen chain and identification of a single-base mutation in exon 23 converting glycine 521 in the collagenous domain to cysteine in an Alport syndrome patient

    DEFF Research Database (Denmark)

    Zhou, J; Hertz, Jens Michael; Leinonen, A


    We have generated and characterized cDNA clones providing the complete amino acid sequence of the human type IV collagen chain whose gene has been shown to be mutated in X chromosome-linked Alport syndrome. The entire translation product has 1,685 amino acid residues. There is a 26-residue signal...... alleles. The mutation which was located to exon 23 was sequenced from a polymerase chain reaction-amplified product, and shown to be a G----T change in the coding strand. The mutation changed the GGT codon of glycine 521 to cysteine. The same mutation was found in one allele of the female cousin...

  14. Matrix-induced autologous chondrocyte implantation for a large chondral defect in a professional football player: a case report


    Beyzadeoglu Tahsin; Onal Ayberk; Ivkovic Alan


    Abstract Introduction Matrix-assisted autologous chondrocyte implantation is a well-known procedure for the treatment of cartilage defects, which aims to establish a regenerative milieu and restore hyaline cartilage. However, much less is known about third-generation autologous chondrocyte implantation application in high-level athletes. We report on the two-year follow-up outcome after matrix-assisted autologous chondrocyte implantation to treat a large cartilage lesion of the lateral femora...

  15. Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Francesco Orio


    Full Text Available Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo- and autologous- (auto- stem cell transplant (HSCT. This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90–99% of women and 60–90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40–50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma, gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT.

  16. Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis. (United States)

    Muraro, Paolo A; Martin, Roland; Mancardi, Giovanni Luigi; Nicholas, Richard; Sormani, Maria Pia; Saccardi, Riccardo


    Autologous haematopoietic stem cell transplantation (AHSCT) is a multistep procedure that enables destruction of the immune system and its reconstitution from haematopoietic stem cells. Originally developed for the treatment of haematological malignancies, the procedure has been adapted for the treatment of severe immune-mediated disorders. Results from ∼20 years of research make a compelling case for selective use of AHSCT in patients with highly active multiple sclerosis (MS), and for controlled trials. Immunological studies support the notion that AHSCT causes qualitative immune resetting, and have provided insight into the mechanisms that might underlie the powerful treatment effects that last well beyond recovery of immune cell numbers. Indeed, studies have demonstrated that AHSCT can entirely suppress MS disease activity for 4-5 years in 70-80% of patients, a rate that is higher than those achieved with any other therapies for MS. Treatment-related mortality, which was 3.6% in studies before 2005, has decreased to 0.3% in studies since 2005. Current evidence indicates that the patients who are most likely to benefit from and tolerate AHSCT are young, ambulatory and have inflammatory MS activity. Clinical trials are required to rigorously test the efficacy, safety and cost-effectiveness of AHSCT against highly active MS drugs.

  17. Immune re-education following autologous hematopoietic stem cell transplantation. (United States)

    Abrahamsson, Sofia; Muraro, Paolo A


    The encounter with different environmental antigens during immune maturation from childhood through early adulthood could play a role in the development of autoimmune disease in individuals with a susceptible genetic background. Autologous haematopoietic stem cell transplantation (HSCT) is an experimental treatment for autoimmunity that could offer a second possibility to correct for an aberrant immune reactivity. The premise is that eradication of the existing and pathogenic immune repertoire, in combination with the reinfusion of precursor cells, could reset the immunological clock to an earlier, latent phase of disease. Re-education of the adaptive immune system would occur during the reconstitution of cells under extreme lymphopenia, in which the antigenic priming takes place with a different sequence and timing than during the previous immunological history of the individual, resulting in a different immune repertoire. In this article, we discuss different mechanisms that could contribute to the development of tolerance during immune re-education and address the role of immune renewal and the qualitative reshaping of immunological memory.

  18. PET studies of parkinsonian patients treated with autologous adrenal implants. (United States)

    Guttman, M; Burns, R S; Martin, W R; Peppard, R F; Adam, M J; Ruth, T J; Allen, G; Parker, R A; Tulipan, N B; Calne, D B


    Transplantation of autologous adrenal medulla tissue into the striatum has recently been proposed as a treatment for Parkinson's disease. We report the use of positron emission tomography (PET) to evaluate patients who had adrenal implants placed into the right caudate. 6-[18F] fluoro-L-dopa (6-FD) scans were performed to study the integrity and activity of the implant, and the nigrostriatal dopamine system before and six weeks after transplantation surgery. [68Ga] Gallium-ethylenediaminetetraacetate (Ga) scans were also performed to assess the blood brain barrier. The Ga scans performed on two patients showed increased permeability of the blood brain barrier at the surgical site. 6-FD PET scans in five patients did not show a consistent change in striatal uptake following adrenal medullary implantation after six weeks. Further assessment of implant viability with 6-FD PET scans after longer follow up may provide useful information if the blood-brain barrier becomes re-established with the passage of time.

  19. Osteoarthritis treatment using autologous conditioned serum after placebo. (United States)

    Rutgers, Marijn; Creemers, Laura B; Auw Yang, Kiem Gie; Raijmakers, Natasja J H; Dhert, Wouter J A; Saris, Daniel B F


    Autologous conditioned serum (ACS) is a disease-modifying drug for treatment of knee osteoarthritis, and modest superiority over placebo was reported in an earlier randomized controlled trial (RCT). We hypothesized that when given the opportunity, placebo-treated patients from that RCT would now opt for ACS treatment, which would result in a greater clinical improvement than placebo. Of 74 patients treated with placebo in the previous trial, 20 opted for ACS treatment. Patients who did not choose further treatment were interviewed about their reasons. Clinical improvement of the 20 ACS-treated patients was measured using knee-specific clinical scores, as was "response shift" at 3 and 12 months. In the 20 patients who did opt for ACS, the visual analog scale (VAS) score for pain improved; but after 12 months, clinical results were similar to those after placebo treatment. Response shift measurement demonstrated that the 20 patients had adapted to their disabilities during treatment. Placebo-treated patients from an earlier trial were reluctant to undergo ACS treatment, in part due to the laborious nature of the therapy. In a subset of patients who opted for treatment, ACS treatment after placebo did not result in greater clinical improvement than placebo treatment only. However, due to the limited power of the current study and possible selection bias, definite advice on using or refraining from ACS cannot be given.

  20. Autologous miniature punch skin grafting in stable vitiligo

    Directory of Open Access Journals (Sweden)

    Savant S


    Full Text Available Autologous split thickness miniature punch skin grafting is one of the surgical modes of treatment of stable vitiligo. Out of 87 different sites, of stable vitiligo, occurring in 62 cases, (32 focal, 22 segmental and 8 generalised 75 sites showed total repigmentation with excellent cosmetic colour match. Out of the 62 cases, 46 cases who were treated postsurgically with PUVA therapy repigmented within 2 ½ to 3 months, 10 cases, who received no treatment postsurgically repigmented by 3 ½ to 6 months. In addition 6 cases in whom no treatment was given postsurgically had to be given PUVA therapy 3 months after surgery as there was poor repigmentation. The complications seen were graft rejection due to improper immobilization in 6 cases, graft rejection due to secondary infection in 1, contact allergic dermatitis to framycetin in 3, and reactivation of vitiligo in 2. Side effects seen were cobblestoning in 32, sinking pits in 12, variegated appearance in 4, and superficial scarring at donor site in all 62 cases.

  1. Sublabial Autologous Ear Cartilage Grafting for Increasing the Nasolabial Angle

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    Rajko Toncic


    Full Text Available BackgroundThe loss of nasal tip support is caused by many factors and eventually results in the collapse and eventual dropping of the nasal tip. This reduces the nasolabial (NL angle and negatively affects respiratory functions and one's appearance.MethodsThe aim of this retrospective study, which was conducted on 52 patients, was to present and popularize a simple and effective method for the reconstruction of a weakened columella by inserting an autologous ear cartilage graft using a sublabial approach.ResultsOf all the patients, three patients experienced transplant rejection. The period of follow-up observation was one to five years (mean, 27 months. The results were objectively evaluated by measuring the NL angle in standardized photos before and after the procedure at different time intervals over the follow-up period. We observed a significant increase of the NL angle (mean, 20°, and found these results to be durable over the long term. Of the 52 patients included in this study observed patients, three were dissatisfied (due to immediate infection and shifting of the strut, 28 were satisfied, and 21 were very satisfied.ConclusionsThe surgical method described here is simple and can be learned quickly. It has very good results with few complications, and is our method of choice for complex and serious cases seen in everyday rhinosurgical practice.

  2. Ethylene oxide sterilization of autologous bone flaps following decompressive craniectomy. (United States)

    Missori, P; Polli, F M; Rastelli, E; Baiocchi, P; Artizzu, S; Rocchi, G; Salvati, M; Paolini, S; Delfini, R


    In patients undergoing decompressive craniectomy, the bone flap is temporarily preserved either in the subcutaneous tissue of the patient or frozen. However, there are some drawbacks related to these methods. In 16 patients in whom the bone flap was removed for decompressive craniectomy, the bone was firstly washed in hydrogen peroxide and then placed in hermetically-sealed bags and sterilized using ethylene oxide. The bone was repositioned after an average period of 4.3 months. One patient sustained an infection of the surgical wound which required permanent exclusion of the bone flap. In all the others, esthetic and functional results were good after an average follow-up of 20 months. Control CT-scan of the bone flap demonstrated preservation of its structural features with fusion of the bone margins and revitalization of the flap. On MRI a subdural space was again visible. Sterilization of the bone flap with ethylene oxide in patients undergoing decompressive craniectomy avoids some of the drawbacks related to the techniques currently used. The easiness, low cost, good aesthetic and functional results of this procedure make it a valid alternative to other techniques for preservation of autologous bone in decompressive craniectomies.

  3. Cell Viability in Arthroscopic Versus Open Autologous Chondrocyte Implantation. (United States)

    Biant, Leela C; Simons, Michiel; Gillespie, Trudi; McNicholas, Michael J


    Autologous chondrocyte implantation (ACI) is an effective method of repair of articular cartilage defects. It is a 2-stage operation, with the second stage most commonly performed via mini-arthrotomy. Arthroscopic ACI is gaining popularity, as it is less invasive and may accelerate early rehabilitation. However, handling and manipulation of the implant have been shown to cause chondrocyte cell death. To assess the number and viability of cells delivered via an open versus arthroscopic approach in ACI surgery. Controlled laboratory study. Sixteen ACI surgeries were performed on young cadaveric knees by 2 experienced surgeons: 8 via mini-arthrotomy and 8 arthroscopically. Live and dead cells were stained and counted on implants after surgery. The cell number and viability were assessed using confocal laser scanning microscopy. Surgery was timed from knife to skin until the end of cycling the knee 10 times after implantation of the cell-membrane construct. On receipt of cell membranes after transportation from the laboratory, ≥92% of the cells were viable. There were significantly more remaining cells (8.47E+07 arthroscopic vs 1.41E+08 open; P arthroscopic vs 37.34% open; P arthroscopic technique. Open surgery was of a significantly shorter duration (6 vs 32 minutes; P arthroscopic technique. The viability of cells delivered for ACI via an arthroscopic approach was 16 times less than via an open approach. The mini-arthrotomy approach is recommended until long-term clinical comparative data are available.

  4. Latino College Completion: Hawaii (United States)

    Excelencia in Education (NJ1), 2012


    In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

  5. Latino College Completion: Alabama (United States)

    Excelencia in Education (NJ1), 2012


    In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

  6. Latino College Completion: Alaska (United States)

    Excelencia in Education (NJ1), 2012


    In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

  7. Design of a hybrid biomaterial for tissue engineering: Biopolymer-scaffold integrated with an autologous hydrogel carrying mesenchymal stem-cells. (United States)

    Weinstein-Oppenheimer, Caroline R; Brown, Donald I; Coloma, Rodrigo; Morales, Patricio; Reyna-Jeldes, Mauricio; Díaz, María J; Sánchez, Elizabeth; Acevedo, Cristian A


    Biologically active biomaterials as biopolymers and hydrogels have been used in medical applications providing favorable results in tissue engineering. In this research, a wound dressing device was designed by integration of an autologous clot hydrogel carrying mesenchymal stem-cells onto a biopolymeric scaffold. This hybrid biomaterial was tested in-vitro and in-vivo, and used in a human clinical case. The biopolymeric scaffold was made with gelatin, chitosan and hyaluronic acid, using a freeze-drying method. The scaffold was a porous material which was designed evaluating both physical properties (glass transition, melting temperature and pore size) and biological properties (cell viability and fibronectin expression). Two types of chitosan (120 and 300kDa) were used to manufacture the scaffold, being the high molecular weight the most biologically active and stable after sterilization with gamma irradiation (25kGy). A clot hydrogel was formulated with autologous plasma and calcium chloride, using an approach based on design of experiments. The optimum hydrogel was used to incorporate cells onto the porous scaffold, forming a wound dressing biomaterial. The wound dressing device was firstly tested in-vitro using human cells, and then, its biosecurity was evaluated in-vivo using a rabbit model. The in-vitro results showed high cell viability after one week (99.5%), high mitotic index (19.8%) and high fibronectin expression. The in-vivo application to rabbits showed adequate biodegradability capacity (between 1 and 2weeks), and the histological evaluation confirmed absence of rejection signs and reepithelization on the wound zone. Finally, the wound dressing biomaterial was used in a single human case to implant autologous cells on a skin surgery. The medical examination indicated high biocompatibility, partial biodegradation at one week, early regeneration capacity at 4weeks and absence of rejection signs. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Development and comparison of a minimally-invasive model of autologous clot pulmonary embolism in Sprague-Dawley and Copenhagen rats

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    Sanapareddy Nina


    Full Text Available Abstract Background Experimental models of pulmonary embolism (PE that produce pulmonary hypertension (PH employ many different methods of inducing acute pulmonary occlusion. Many of these models induce PE with intravenous injection of exogenous impervious objects that may not completely reproduce the physiological properties of autologous thromboembolism. Current literature lacks a simple, well-described rat model of autlogous PE. Objective: Test if moderate-severity autologous PE in Sprague-Dawley (SD and Copenhagen (Cop rats can produce persistent PH. Methods blood was withdrawn from the jugular vein, treated with thrombin-Ca++ and re-injected following pretreatment with tranexamic acid. Hemodynamic values, clot weights and biochemical measurements were performed at 1 and 5 days. Results Infusion of clot significantly increased the right ventricular peak systolic pressure to 45-55 mm Hg, followed by normalization within 24 hours in SD rats, and within 5 days in COP rats. Clot lysis was 95% (24 hours and 97% (5 days in SD rats and was significantly lower in COP rats (70%, 24 hours; 87% 5 days. Plasma D-dimer was elevated in surgical sham animals and was further increased 8 hours after pulmonary embolism. Neither strain showed a significant increase in bronchoalveolar chemotactic activity, myeloperoxidase activity, leukocyte infiltration, or chemokine accumulation, indicating that there was no significant pulmonary inflammation. Conclusions Both SD and COP rats exhibited near complete fibrinolysis of autologous clot PE within 5 days. Neither strain developed persistent PH. Experimental models of PE designed to induce sustained PH and a robust inflammatory response appear to require significant, persistent pulmonary vascular occlusion.

  9. Autologous Bone Marrow Stem Cells in Spinal Cord Injury; Our Experience in Clinical Studies, Animal Studies, Obstacles faced and steps for future

    Directory of Open Access Journals (Sweden)

    Ayyappan S


    Full Text Available BACKGROUND: Following traumatic vertebral injuries and resultant spinal cord injury, most patients are doomed to a life either of quadriplegia or paraplegia. Current treatment option is limited to the stabilization of the vertebral fracture along with medications to prevent secondary damage leading to further deterioration and wishful waiting for recovery. In most instances recovery is insignificant. Safety of intrathecal injection of autologous bone marrow stem cells is proven but its efficacy varies between patients (1. Intralesional application has been reported to be more efficacious than intrathecal application (2, 3, 4. We have analyzed our experience in human patients followed up for 3 year period and have found several grey areas in spinal cord injury(5 one of them is to explore the differences between Intrathecal and intralesional application of stem cells with and without scaffolds in the latter technique. Towards achieving this goal we started a pilot study in animals where instead of post-vertebral fixation intrathecal injection, we have performed intralesional application of autologous BMSC along with scaffolds (6. These scaffolds not only help retain the transplanted cells at the site of injury but also allow more neural precursors to grow compared to application without scaffolds (7. This study analyses the data retrospectively to plan further prospective studies with a view to improvise the results. MATERIALS AND METHODS: Study 1 : 100 to 120 ml of Bone marrow was tapped from the right posterior iliac crest under local anesthesia from human spinal injury victims (n=108; 76 males, 32 females about 3 weeks to 18 months after surgical fixation of the vertebrae. The Level of injury was varied- Cervical (13 patients. Upper Thorax- T1-T7 (35 patients Lower thorax T8-T12 (46 patients Lumbar (2 patients. Age Group Range: 8 yrs to 55 yrs. The bone marrow mononuclear cells were processed under cGMP SOP’s Class 10000 clean room and class

  10. Sports Activity After Reconstruction of Osteochondral Lesions of the Talus With Autologous Spongiosa Grafts and Autologous Matrix-Induced Chondrogenesis. (United States)

    Wiewiorski, Martin; Werner, Lorenzo; Paul, Jochen; Anderson, Andrew E; Barg, Alexej; Valderrabano, Victor


    For the treatment of osteochondral lesions of the talus (OCLTs), autologous matrix-induced chondrogenesis (AMIC) is a safe 1-step procedure with good clinical and radiological results. However, data regarding postoperative sports activity after AMIC are limited. To identify significant factors influencing the rate of postoperative sports and recreational activities. Case series; Level of evidence, 4. The sports and recreational activities of 60 patients (mean age, 34.9 ± 11.5 years) undergoing the AMIC procedure were retrospectively analyzed at a mean of 46.9 ± 17.8 months (range, 24.5-87.0 months) postoperatively. The visual analog scale (VAS) for pain score, Tegner activity scale score, activity rating scale (ARS) score, and satisfaction with surgery outcomes were assessed. Corrective calcaneal osteotomy was performed in 38 of 60 (63.3%) patients. Ligament repair was performed in 41 of 60 (68.3%) patients. The mean VAS score improved significantly from 6.9 ± 1.6 points (range, 5-10 points) preoperatively to 2.3 ± 1.9 points (range, 0-6 points) at latest follow-up (P sports activity before the onset of symptoms became significantly lower at the time of surgery (from 95.0% to 53.3%; P sports frequency and the duration of sports activity was found postoperatively. Patients undergoing AMIC repair of an OCLT participate at a similar low postoperative sports and recreational activity level compared with the preoperative level. © 2016 The Author(s).

  11. Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients (United States)

    Radvanyi, Laszlo G.; Bernatchez, Chantale; Zhang, Minying; Fox, Patricia S.; Miller, Priscilla; Chacon, Jessica; Wu, Richard; Lizee, Gregory; Mahoney, Sandy; Alvarado, Gladys; Glass, Michelle; Johnson, Valen E.; McMannis, John D.; Shpall, Elizabeth; Prieto, Victor; Papadopoulos, Nicholas; Kim, Kevin; Homsi, Jade; Bedikian, Agop; Hwu, Wen-Jen; Patel, Sapna; Ross, Merrick I.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Lucci, Anthony; Royal, Richard; Cormier, Janice N.; Davies, Michael A.; Mansaray, Rahmatu; Fulbright, Orenthial J.; Toth, Christopher; Ramachandran, Renjith; Wardell, Seth; Gonzalez, Audrey; Hwu, Patrick


    Purpose Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a promising treatment for metastatic melanoma unresponsive to conventional therapies. We report here on the results of an ongoing Phase II clinical trial testing the efficacy of ACT using TIL in metastatic melanoma patients and the association of specific patient clinical characteristics and the phenotypic attributes of the infused TIL with clinical response. Experimental Design Altogether, 31 transiently lymphodepleted patients were treated with their expanded TIL followed by two cycles of high-dose (HD) IL-2 therapy. The effects of patient clinical features and the phenotypes of the T-cells infused on clinical response were determined. Results Overall, 15/31 (48.4%) patients had an objective clinical response using immune-related response criteria (irRC), with two patients (6.5%) having a complete response. Progression-free survival of >12 months was observed for 9/15 (60%) of the responding patients. Factors significantly associated with objective tumor regression included a higher number of TIL infused, a higher proportion of CD8+ T-cells in the infusion product, a more differentiated effector phenotype of the CD8+ population and a higher frequency of CD8+ T-cells co-expressing the negative costimulation molecule “B- and T-lymphocyte attenuator” (BTLA). No significant difference in telomere lengths of TIL between responders and non-responders was identified. Conclusion These results indicate that immunotherapy with expanded autologous TIL is capable of achieving durable clinical responses in metastatic melanoma patients and that CD8+ T-cells in the infused TIL, particularly differentiated effectors cells and cells expressing BTLA, are associated with tumor regression. PMID:23032743

  12. Autologous bone marrow concentrate enriched in progenitor cells — An adjuvant in the treatment of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Vinay Sanghi


    Full Text Available Despite advances in revascularization techniques, acute myocardial infarction (AMI still carries significant morbidity and mortality. Over the past decade, the use of regenerative medicine methodologies, and specifically bone marrow derived progenitor cell therapy has been tested in more than 35 Phase I and Phase II clinical studies demonstrating overall safety and measurable clinical benefit, 12–61 months post-treatment as evaluated by improvement in the Left Ventricular Ejection Fraction (LVEF and changes in infarct size post AMI. Recent meta-analysis on the subject highlighted several important parameters that include timing of the cell therapy post AMI, the cell dose, and the baseline LVEF on enrollment. We further postulate that the mythologies and timing for cell handling and delivery including the specific devices are essential for clinical efficacy. Addressing this we have developed a rapid 60 to 90 minute process and integrated system which is carried out in the heart catheter lab, using a combination product (U.S. Food and Drug broadly defined as the combination of co-labeled optimized “cell friendly” devices, effective cell/biological formulation and dose for harvesting, processing, verifying, and delivering an autologous dose of bone marrow progenitor/stem cells via the intracoronary artery proximal to the infarct myocardial region. The methodology has been demonstrated to be safe and feasible for autologous in vivo use and presented by our groups' earlier studies1–3 and most recently used in a Phase Ib critical limb ischemia trial of 17 subjects (NCT01472289 (manuscript under preparation. This is the first case study prior to beginning the AMIRST trial [Acute Myocardial Infarction Rapid Stem cell Therapy], specific to our proprietary combination product kit for acute myocardial infarction, and was completed under the Independent Ethics Committee and Institutional Committee for Stem Cell Research and Therapy approval (TIEC

  13. Complete Ureteral Avulsion

    Directory of Open Access Journals (Sweden)

    V. Gupta


    Full Text Available Complete avulsion of the ureter is one of the most serious complications of ureteroscopy. It requires open or laparoscopic intervention for repair. This case report emphasizes its management and presents recommendations for prevention in current urological practice.

  14. The effect of topical autologous serum on graft re-epithelialization after penetrating keratoplasty. (United States)

    Chen, Yan-Ming; Hu, Fung-Rong; Huang, Jehn-Yu; Shen, Elizabeth P; Tsai, Tzu-Yun; Chen, Wei-Li


    To analyze factors influencing corneal graft re-epithelialization after penetrating keratoplasty (PK) and evaluate the effect of topical autologous serum in promoting graft re-epithelialization. Prospective interventional study. We analyzed 165 eyes of 165 patients who underwent PK between January 1, 2005 and December 31, 2007. Patients were divided into 2 groups according to routine use or non-use of postoperative 20% topical autologous serum. Postoperative slit-lamp examination after fluorescein staining was performed, and graft re-epithelialization time was recorded. Recipient/donor characteristics, surgical variables, and topical use of autologous serum were analyzed for their effects on post-PK graft re-epithelialization. Statistical analysis was performed by univariate and multivariate regression analysis using the ordinal logistic fit model to assess the potential risk factors influencing graft re-epithelialization after PK. In univariate analysis, diabetes mellitus (DM), longer death-to-storage time and death-to-surgery time of the donor, and larger recipient size significantly delayed graft re-epithelialization (P healing effect of autologous serum is particularly significant in diabetic recipients and larger grafts. Several factors may influence graft re-epithelialization after PK. Graft re-epithelialization time was longer in diabetic recipients and larger grafts. Use of autologous serum may be a beneficial strategy in these patients with potentially delayed epithelial healing. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  15. Preeclampsia in autologous and oocyte donation pregnancy: is there a different pathophysiology? (United States)

    Lashley, Lisa E E L O; Buurma, Aletta; Swings, Godelieve M J S; Eikmans, Michael; Anholts, Jacqueline D H; Bakker, Jaap A; Claas, Frans H J


    Oocyte donation (OD) is a specific method of artificial reproductive technology that is accompanied by a higher risk of preeclampsia during pregnancy. The pathophysiological mechanism underlying preeclampsia in OD pregnancies is thought to differ from preeclampsia in autologous pregnancies. As preeclampsia in autologous pregnancies is suggested to be associated with complement activation, we studied C4d deposition, circulating complement components and placental complement regulatory proteins in preeclamptic OD pregnancies. Women with uncomplicated and preeclamptic pregnancies after OD or spontaneous conception were selected. We stained the placentas for C4d, marker for complement activation, measured complement factors C1q, C3 and C4 in maternal sera and quantified the placental mRNA expression of complement regulatory proteins CD46, CD55 and CD59. A significantly (p preeclampsia compared with uncomplicated pregnancies, both OD and autologous. The level of complement factors in serum did not differ between the groups. Children born in the autologous preeclampsia group were significantly lower in birth weight (p preeclampsia pregnancies, there is excessive activation of complement in preeclamptic OD pregnancies. However, in contrast to autologous pregnancies this is not associated with counterbalancing upregulation of complement regulatory proteins. Furthermore, C4d deposition in OD pregnancies is not related to the severity of preeclampsia, suggesting another trigger or regulatory mechanism of placental C4d deposition in preeclamptic OD pregnancies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Decreased hernia recurrence using autologous platelet-rich plasma (PRP) with Strattice™ mesh in a rodent ventral hernia model. (United States)

    Van Eps, Jeffrey; Fernandez-Moure, Joseph; Cabrera, Fernando; Wang, Xin; Karim, Azim; Corradetti, Bruna; Chan, Paige; Dunkin, Brian; Tasciotti, Ennio; Weiner, Bradley; Ellsworth, Warren


    Recurrence after ventral hernia repair (VHR) remains a multifactorial problem still plaguing surgeons today. Some of the many contributing factors include mechanical strain, poor tissue-mesh integration, and degradation of matrices. The high recurrence rate witnessed with the use of acellular dermal matrices (ADM) for definitive hernia repair has reduced their use largely to bridging repair and breast reconstruction. Modalities that improve classic cellular metrics of successful VHR could theoretically result in improved rates of hernia recurrence; autologous platelet-rich plasma (PRP) may represent one such tool, but has been underinvestigated for this purpose. Lewis rats (32) had chronic ventral hernias created surgically and then repaired with Strattice™ mesh alone (control) or mesh + autologous PRP. Samples were harvested at 3 and 6 months postoperatively and compared for gross, histologic, and molecular outcomes of: neovascularization, tissue incorporation, peritoneal adhesions, hernia recurrence, and residual mesh thickness. Compared to control at 3 months postoperatively, PRP-treated rats displayed significantly more neovascularization of implanted mesh and considerable upregulation of both angiogenic genes (vEGF 2.73-fold, vWF 2.21-fold) and myofibroblastic genes (αSMA 9.68-fold, FSP-1 3.61-fold, Col1a1 3.32-fold, Col31a1 3.29-fold). Histologically, they also showed enhanced tissue deposition/ingrowth and diminished chronic immune cell infiltration. Peritoneal adhesions were less severe at both 3 (1.88 vs. 2.94) and 6 months (1.63 vs. 2.75) by Modified Hopkins Adhesion Scoring. PRP-treated rats experienced decreased hernia recurrence at 6 months (0/10 vs. 7/10) and had significantly improved ADM preservation as evidenced by quantification of residual mesh thickness. PRP is an autologous source of pro-regenerative growth factors and chemokines uniquely suited to soft tissue wound healing. When applied to a model of chronic VHR, it incites enhanced

  17. Therapeutic vaccination with an autologous mRNA electroporated dendritic cell vaccine in patients with advanced melanoma. (United States)

    Wilgenhof, Sofie; Van Nuffel, An M T; Corthals, Jurgen; Heirman, Carlo; Tuyaerts, Sandra; Benteyn, Daphné; De Coninck, Arlette; Van Riet, Ivan; Verfaillie, Guy; Vandeloo, Judith; Bonehill, Aude; Thielemans, Kris; Neyns, Bart


    The immunostimulatory capacity of dendritic cells is improved by co-electroporation with mRNA encoding CD40 ligand, constitutively active toll-like receptor 4, and CD70 (TriMix-DC). This pilot clinical trial evaluated the feasibility, safety, and immunogenicity of a therapeutic vaccination containing autologous TriMix-DC co-electroporated with mRNA encoding a human leukocyte antigen class II-targeting signal linked to 1 of 4 melanoma-associated antigens (MAGE-A3, MAGE-C2, tyrosinase, and gp100) in patients with advanced melanoma. Thirty-five American Joint Committee on Cancer stage III/IV melanoma patients received autologous TriMix-DC (4 administrations 2 weeks apart). Immune monitoring was performed by evaluating skin biopsies of delayed type IV hypersensitivity (DTH) reactions for presence of vaccinal antigen-specific DTH-infiltrating lymphocytes (DIL). Thereafter, patients could receive interferon-alpha-2b (IFN-α-2b) 5 MU subcutaneously 3 times weekly and additional TriMix-DC every 8 weeks. TriMix-DC-related adverse events comprised grade 2 local injection site reactions (all patients), and grade 2 fever and lethargy (2 patients). Vaccinal antigen-specific DIL were found in 0/6 patients tested at vaccine initiation and in 12/21 (57.1%) assessed after the fourth vaccine. A positive postvaccination DTH test correlated with IL-12p70 secretion capacity of TriMix-DC. No objective responses to TriMix-DC alone were seen according to RECIST. Twenty-nine patients received IFN-α-2b after the fourth vaccine without unexpected adverse events. During TriMix-DC/IFN-α-2b combination therapy, 1 partial response and 5 stable disease (disease control of >6 months with regression of metastases) were observed in 17 patients with evaluable disease at baseline. In conclusion, this study demonstrated that therapeutic vaccination with autologous TriMix-DC is feasible, safe, and immunogenic and can be combined with sequential IFN-α-2b.

  18. Autologous Intravenous Mononuclear Stem Cell Therapy in Chronic Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Bhasin A


    Full Text Available Background: The regenerative potential of brain has led to emerging therapies that can cure clinico-motor deficits after neurological diseases. Bone marrow mononuclear cell therapy is a great hope to mankind as these cells are feasible, multipotent and aid in neurofunctional gains in Stroke patients. Aims: This study evaluates safety, feasibility and efficacy of autologous mononuclear (MNC stem cell transplantation in patients with chronic ischemic stroke (CIS using clinical scores and functional imaging (fMRI and DTI. Design: Non randomised controlled observational study Study: Twenty four (n=24 CIS patients were recruited with the inclusion criteria as: 3 months–2years of stroke onset, hand muscle power (MRC grade at least 2; Brunnstrom stage of recovery: II-IV; NIHSS of 4-15, comprehendible. Fugl Meyer, modified Barthel Index (mBI and functional imaging parameters were used for assessment at baseline, 8 weeks and at 24 weeks. Twelve patients were administered with mean 54.6 million cells intravenously followed by 8 weeks of physiotherapy. Twelve patients served as controls. All patients were followed up at 24 weeks. Outcomes: The laboratory and radiological outcome measures were within normal limits in MNC group. Only mBI showed statistically significant improvement at 24 weeks (p<0.05 whereas the mean FM, MRC, Ashworth tone scores in the MNC group were high as compared to control group. There was an increased number of cluster activation of Brodmann areas BA 4, BA 6 post stem cell infusion compared to controls indicating neural plasticity. Cell therapy is safe and feasible which may facilitate restoration of function in CIS.

  19. DIEAP flap for safe definitive autologous breast reconstruction. (United States)

    Seidenstuecker, Katrin; van Waes, Carl; Munder, Beatrix I; Claes, Karel E Y; Witzel, Christian; Roche, Nathalie; Stillaert, Filip; Mahajan, Ajay L; Andree, Christoph; Blondeel, Phillip N


    Breast cancer is the commonest form of cancer in women affecting almost a quarter of a million patients in the US annually. 30 percent of these patients and patients with genetic mutations undergo removal of the breast, as highlighted in a high profile celebrity patient. Although breast reconstruction with free microvascular transfer of a DIEAP flap from the abdomen is an ideal form of reconstruction, there have been misgivings about the complexity and potential complications. This study was aimed at clearing these misunderstandings and establishing the value of this form of breast reconstruction. 1036 DIEAP flap breast reconstructions carried out at the University Hospital, Gent (five year period) and at the Sana Kliniken, Düsseldorf (three year period) were included prospectively. Comorbid factors like chemotherapy, radiotherapy, patient age >65 years, BMI >30 and smoking were recorded. Outcomes were evaluated over a mean follow up of 2 years. Overall complication rate related to the reconstructed breast and donor abdominal area was 6.8 percent. Total flap loss was seen in only 0.8 percent. The mean operating time was less than five hours. Older age, higher BMI, chemotherapy and radiotherapy did not have a significant influence on complication rates, however smoking resulted in significant delay in wound healing in the breast (p = 0.025) and abdominal wounds (p = 0.019). The DIEAP flap is an excellent option for breast reconstruction, with a low level of donor site morbidity and complications. It is an autologous reconstruction that provides a stable long term result. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Regeneration of Tissues and Organs Using Autologous Cells

    Energy Technology Data Exchange (ETDEWEB)

    Anthony Atala, M D


    The proposed work aims to address three major challenges to the field of regenerative medicine: 1) the growth and expansion of regenerative cells outside the body in controlled in vitro environments, 2) supportive vascular supply for large tissue engineered constructs, and 3) interactive biomaterials that can orchestrate tissue development in vivo. Toward this goal, we have engaged a team of scientists with expertise in cell and molecular biology, physiology, biomaterials, controlled release, nanomaterials, tissue engineering, bioengineering, and clinical medicine to address all three challenges. This combination of resources, combined with the vast infrastructure of the WFIRM, have brought to bear on projects to discover and test new sources of autologous cells that can be used therapeutically, novel methods to improve vascular support for engineered tissues in vivo, and to develop intelligent biomaterials and bioreactor systems that interact favorably with stem and progenitor cells to drive tissue maturation. The Institute's ongoing programs are aimed at developing regenerative medicine technologies that employ a patient's own cells to help restore or replace tissue and organ function. This DOE program has provided a means to solve some of the vexing problems that are germane to many tissue engineering applications, regardless of tissue type or target disease. By providing new methods that are the underpinning of tissue engineering, this program facilitated advances that can be applied to conditions including heart disease, diabetes, renal failure, nerve damage, vascular disease, and cancer, to name a few. These types of conditions affect millions of Americans at a cost of more than $400 billion annually. Regenerative medicine holds the promise of harnessing the body's own power to heal itself. By addressing the fundamental challenges of this field in a comprehensive and focused fashion, this DOE program has opened new opportunities to treat

  1. Advances in autologous chondrocyte implantation and related techniques for cartilage repair. (United States)

    Foldager, Casper Bindzus


    Articular cartilage is a specialized tissue exhibiting low intrinsic capabilities of regeneration or healing after injury. Autologous chondrocyte implantation (ACI) and scaffold-supported ACI are often used for treatment of larger chondral defects (> 2 cm2). These utilize open surgery re-implantation of ex vivo cultured autologous chondrocytes harvested as a biopsy arthroscopically in a prior surgery. This two-step procedure is an advanced and expensive treatment that despite high expectations have failed to regenerate articular cartilage in a consistent and predictable fashion, and as many as 25% the operated of patients have dissatisfactory outcomes. The objective of the present thesis was to address and investigate methods for optimizing the steps involved in the ACI and scaffold-supported ACI treatment including chondrocyte culture environment, chondrocyte labeling and tracking, improved biomaterials, and cell seeding densities. We hypothesized that these areas were eligible for targeted optimization, which has been addressed in the five papers constituting the work performed in the present thesis. The first two studies address the in vitro cell expansion of chondrocytes before re-implantation. After validation of hypoxia-suitable housekeeping genes for quantitative gene expression analysis using previously validated algorithms (study 1) the effect of combined hypoxic- and 3D culture on human chondrocytes gene expression was investigated (study 2). An in vitro experiment was performed to determine the effect on gene expression of an intracellular superparamagnetic labeling agent for 1.5T MRI-tracking of alginate-embedded human chondrocytes (study 3). We further performed a literature study, reviewing the cell seeding densities of the implanted chondrocytes used in clinically available cell transplantation-based treatments for cartilage repair (study 4). Finally, we tested the addition of dermatan sulfate to a clinically approved methoxy-polyethen-glycol (MPEG

  2. Cost analysis and quality of life assessment comparing patients undergoing autologous peripheral blood stem cell transplantation or autologous bone marrow transplantation for refractory or relapsed non-Hodgkin's lymphoma or Hodgkin's disease : a prospective randomised trial

    NARCIS (Netherlands)

    van Agthoven, M; Vellenga, E; Fibbe, WE; Kingma, T; Uyl-de Groot, CA

    The cost-effectiveness of autologous peripheral blood stem cell transplantation (PBSCT) compared with autologous bone marrow transplantation (ABMT) for refractory or relapsed non-Hodgkin's lymphoma (NHL) or Morbus Hodgkin (MH) was assessed. Costs were determined from the induction chemotherapy

  3. Ocular Complications Following Autologous Fat Injections into Facial Area: Case Report of a Recovery from Visual Loss After Ophthalmic Artery Occlusion and a Review of the Literature. (United States)

    Szantyr, Aleksandra; Orski, Michał; Marchewka, Ida; Szuta, Mariusz; Orska, Małgorzata; Zapała, Jan


    With the increase in popularity of the use of cosmetic fillers in plastic and esthetic surgery, the possibility of severe ocular complications should not be neglected. Of the fillers used, autologous fat is the most common to cause permanent visual deterioration, one of the most severe complications associated with the use of cosmetic fillers. Here we present the first report of a complete recovery of visual acuity from an instance of visual loss with no light perception caused by ophthalmic artery occlusion of the right eye following autologous fat injection in the facial area. Immediate ophthalmological intervention and comprehensive therapy with prostaglandins and vinpocetine made it possible to restore retinal perfusion and achieve complete recovery of visual acuity. Awareness of the iatrogenic artery occlusions associated with facial fillers and the need for immediate treatment should be popularized among injectors to prevent devastating consequences, such as permanent vision loss. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors .

  4. High dose chemotherapy with autologous stem cell transplantation in diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Popp, Henning


    Full Text Available Background: High-dose chemotherapy (HDT with autologous stem cell transplantation (ASCT plays an important role in the treatment of aggressive non-Hodgkin’s lymphoma (NHL. We report on a retrospective analysis of all patients with diffuse large B-cell lymphoma who were consecutively treated with HDT followed by ASCT at the University Hospital of Bonn, Germany, between 1996 and 2004. Methods: A total of 25 patients were transplanted for biopsy-proven diffuse large B-cell lymphoma (DLBCL. Eight patients received up-front HDT as first-line therapy, four patients received HDT due to incomplete response to conventional induction chemotherapy, and six patients were treated for primary refractory disease. Seven patients had recurrent lymphoma. Results: A complete remission (CR was achieved in 14 of 25 patients (56%. Estimated 3-year survival for patients treated with upfront HDT, chemosensitive patients with incomplete response to first line therapy, and patients with chemosensitive relapsed disease was 87.5%, 50.0% and 60.0%, respectively. In contrast, no patient with primary refractory disease or relapsed disease lacking chemosensitivity lived longer than 8 months. Chemosensitivity was the only significant prognostic factor for overall survival (OS in multivariate analysis. Conclusions: Our results confirm that HDT and ASCT is a highly effective therapy in patients with DLBCL leading to long-term survival in a substantial proportion of patients. Patients treated upfront for high-risk disease, incomplete response to conventional first-line therapy, or for chemosensitive relapse have a good prognosis. In contrast, patients with primary chemorefractory disease and patients with relapsed disease lacking chemosensitivity do not benefit from HDT with ASCT.

  5. Autologous cartilage implantation for full thickness articular cartilage defects of the knee. (United States)

    Wasiak, J; Villanueva, E


    A variety of strategies have been employed for managing articular cartilage defects of the knee, including drilling and abrasion arthroplasty. These treatments are not always effective and when they are, the benefits may only be transitory. Unsuccessfully treated cartilage damage may progress to degenerative disease states and result in the need for a total knee replacement. In recent years the surgical implantation of healthy cartilage cells (autologous cartilage implantation [ACI] ) into damaged areas has been seen as an alternative option and is currently under investigation as a potential improvement over the current strategies for the management and treatment of articular cartilage defects. To determine the effectiveness of ACI in patients with full thickness articular cartilage defects of the knee. We searched the Cochrane Musculoskeletal Injuries Group specialised register (May 2002), Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2002), MEDLINE (1966 to June Week 4 2001), CINAHL (1982 to July Week 2 2001), EMBASE (1980 to 2001 Week 27), SPORTDiscus (1949 to June 2001), Current Contents (1993 Week 26 to 2001 Week 30) and the National Research Register (Issue 2, May 2002). Randomised and quasi-randomised trials comparing ACI with any other type of treatment (including no treatment or placebo) for symptomatic cartilage defects of the medial or lateral femoral condyle, trochlea or patella. Two independent reviewers applied the entry criteria to identified studies. No completed randomised controlled trials investigating this treatment were identified through the above searches. One possible trial has been placed in Studies Awaiting Assessment, awaiting translation of the full trial report. Ongoing trials currently underway will be incorporated in future updates of this review. No information is available from RCTs which can influence current practice. Therefore, since current evidence is subject to the inherent weaknesses of case series or

  6. The Complete Tutor. (United States)

    Gardner, Howard


    Explains the relationship between computers and multiple intelligences and explores its potential. Topics include behaviorism and cognitivism; constructivism; multiple representations in the human mind, including various forms of intelligence; individual differences; the challenge of altering early representations; and machine versus human tutors.…

  7. Site-directed in vitro immunization leads to a complete human monoclonal IgG4λ that binds specifically to the CDR2 region of CTLA-4 (CD152 without interfering the engagement of natural ligands

    Directory of Open Access Journals (Sweden)

    Hsu Shu-Ching


    Full Text Available Abstract Background The ability to acquire fully human monoclonal antibodies (mAbs with pre-defined specificities is critical to the development of molecular tags for the analysis of receptor function in addition to promising immunotherapeutics. Yet most of the arriving affinity maturated and complete human immunoglobulin G (IgG molecules, which are actually derived from single human B cells, have not widely been used to study the conserved self antigens (Ags such as CD152 (cytotoxic T lymphocyte antigen-4, CTLA-4 because proper hosts are lacking. Results Here we developed an optimized protocol for site-directed in vitro immunizing peripheral blood mononuclear cells (PBMC by using a selected epitope of human CD152, an essential receptor involved in down-regulation of T cell activation. The resultant stable trioma cell lines constantly produce anti-CD152 mAb (γ4λhuCD152, which contains variable (V regions of the heavy chain and the light chain derived from the VH3 and Vλ human germline genes, respectively, and yet displays an unusual IgG4 isotype. Interestingly, γ4λhuCD152 has a basic pI not commonly found in myeloid monoclonal IgG4λs as revealed by the isoelectric focusing (IEF analysis. Furthermore, γ4λhuCD152 binds specifically, with nanomolar affinity, to an extracellular constituency encompassing the putative second complementarity determining region (CDR2 of CD152, whereby it can react to activated CD3+ cells. Conclusion In a context of specific cell depletion and conditioned medium,in vitro induction of human Abs against a conserved self Ag was successfully acquired and a relatively basic mAb, γ4λhuCD152, with high affinity to CDR2 of CD152 was thus obtained. Application of such a human IgG4λ mAb with designated CDR2 specificity may impact upon and prefer for CD152 labeling both in situ and ex situ, as it does not affect the binding of endogenous B7 ligands and can localize into the confined immunological synapse which may


    Ozdek, Sengul; Ozdemir, Huseyin Baran


    To report the use of autologous fibrin for the treatment of persistent optic pit maculopathy. The authors report two patients with an optic pit-related serous macular detachment, which persisted after vitrectomy and internal limiting membrane peeling. Autologous fibrin was prepared from the patients' whole blood and injected over the optic disk pit area to seal the pit/coloboma area followed by fluid-air-gas exchange. Retina stayed attached starting from the first postoperative visit till the last visit at 27 (Case 1) and 14 (Case 2) months after surgery. The use of autologous fibrin for the treatment of optic disk pit-related serous macular detachment seems a worthy contribution to the treatment of persistent cases.

  9. Detecting autologous blood transfusions: a comparison of three passport approaches and four blood markers

    DEFF Research Database (Denmark)

    Mørkeberg, J; Sharpe, K; Belhage, B


    Blood passport has been suggested as an indirect tool to detect various kinds of blood manipulations. Autologous blood transfusions are currently undetectable, and the objective of this study was to examine the sensitivities of different blood markers and blood passport approaches in order...... to determine the best approach to detect autologous blood transfusions. Twenty-nine subjects were transfused with either one (n=8) or three (n=21) bags of autologous blood. Hemoglobin concentration ([Hb]), percentage of reticulocytes (%ret) and hemoglobin mass (Hbmass) were measured 1 day before reinfusion...... and six times after reinfusion. The sensitivity and specificity of a novel marker, Hbmr (based on Hbmass and %ret), was evaluated together with [Hb], Hbmass and OFF-hr by different passport methods. Our novel Hbmr marker showed superior sensitivity in detecting the highest dosage of transfused blood...


    Ricordi, Camillo; Tzakis, Anreas G.; Zeevi, Adriana; Rybka, Witold B.; Demetris, Anthony J.; Fontes, Paulo A.C.; Nalesnik, Michael A.; Trucco, Massimo; Ukah, Ferdinand O.; Ball, Edward D.; Mullen, Edward E.; Marino, Ignazio R.; Fung, John J.; Starzl, Thomas E.


    Graft-versus-host disease (GVHD) remains a major complication of bone marrow transplantation. This report describes reversal of GVHD by infusion of stored recipient bone marrow following combined liver-bone marrow allotransplantation. Graft-versus-host disease developed at the end of the first postoperative week. The skin involvement progressively spread to approximately 80% of the body surface and was not affected by modification of the immunosuppressive treatment. On the 42nd and 43rd postoperative day 1.23 × 108 and 1.6 × 108 autologous bone marrow cells per kg of recipient body weight were infused. The skin rush began to dramatically improve and resolved within 2 wk from the autologous marrow infusion. Autologous bone marrow storage previous to allogeneic bone marrow transplantation for tolerance induction could constitute a safety net in case of occurrence of GVHD. PMID:8012734

  11. Coculture of autologous limbal and conjunctival epithelial cells to treat severe ocular surface disorders: Long-term survival analysis (United States)

    Subramaniam, Sandhya V; Sejpal, Kunjal; Fatima, Anees; Gaddipati, Subhash; Vemuganti, Geeta K; Sangwan, Virender S


    Background: Cultivated limbal epithelium for reconstruction of corneal surface is a well-established procedure; however, it is not adequate for damage which also extensively involves the conjunctiva. In severe cases of ocular surface damage that warrant additional conjunctival transplantation apart from cultivated limbal stem cell transplantation, we describe the long-term survival of a novel method of cocultivating autologous limbal and conjunctival epithelium on a single substrate. Materials and Methods: Forty eyes of 39 patients with severe limbal stem cell deficiency and conjunctival scarring or symblepharon underwent transplantation of autologous cocultivated epithelium on human amniotic membrane. A ring barrier was used to segregate the central limbal and peripheral conjunctival epithelia in vitro. Patients were followed up at regular intervals to assess stability of the ocular surface, defined by absence of conjunctivalization into the central 4 mm of the cornea and absence of diffuse fluorescein staining. Penetrating keratoplasty (PKP) was subsequently performed, where indicated, in patients with surface stability. Results: The cumulative survival probability was 60% at 1 year and 45% at 4 years by Kaplan–Meier analysis (mean follow-up duration: 33 ± 29 months, range: 1–87 months). Best-corrected visual acuity improved to greater than 20/200 in 38% eyes at the last follow-up, compared with 5% eyes before surgery. Immunohistochemistry in five of the corneal buttons excised for PKP showed an epithelial phenotype similar to cornea in all five. Conclusions: Synchronous use of cultured limbal and conjunctival epithelium offers a feasible alternative and a simpler one-step surgical approach to treat severe ocular surface disorders involving limbus and conjunctiva. PMID:23552358

  12. Is there evidence that barrier membranes prevent bone resorption in autologous bone grafts during the healing period? A systematic review

    NARCIS (Netherlands)

    Gielkens, Pepijn F. M.; Bos, Ruud R. M.; Raghoebar, Gerry M.; Stegenga, Boudewijn


    Introduction: Autologous bone is considered the "reference standard" for bone-grafting procedures. A barrier membrane covering an autologous bone graft (guided bone regeneration [GBR]) is expected to prevent graft resorption. Good clinical results have been reported for GBR, although potential

  13. Loss of quiescence and impaired function of CD34(+)/CD38(low) cells one year following autologous stem cell transplantation

    NARCIS (Netherlands)

    Woolthuis, Carolien M.; Brouwers-Vos, Annet Z.; Huls, Gerwin; de Wolf, Joost Th. M.; Schuringa, Jan Jacob; Vellenga, Edo


    Patients who have undergone autologous stem cell transplantation are subsequently more susceptible to chemotherapy-induced bone marrow toxicity. In the present study, bone marrow primitive progenitor cells were examined one year after autologous stem cell transplantation and compared with normal

  14. Effectiveness of Autologous Fat Grafting in Adherent Scars: Results Obtained by a Comprehensive Scar Evaluation Protocol. (United States)

    Jaspers, Mariëlle E H; Brouwer, Katrien M; van Trier, Antoine J M; Groot, Marloes L; Middelkoop, Esther; van Zuijlen, Paul P M


    Nowadays, patients normally survive severe traumas such as burn injuries and necrotizing fasciitis. Large skin defects can be closed but the scars remain. Scars may become adherent to underlying structures when the subcutical fat layer is damaged. Autologous fat grafting provides the possibility of reconstructing a functional sliding layer underneath the scar. Autologous fat grafting is becoming increasingly popular for scar treatment, although large studies using validated evaluation tools are lacking. The authors therefore objectified the effectiveness of single-treatment autologous fat grafting on scar pliability using validated scar measurement tools. Forty patients with adherent scars receiving single-treatment autologous fat grafting were measured preoperatively and at 3-month follow-up. The primary outcome parameter was scar pliability, measured using the Cutometer. Scar quality was also evaluated by the Patient and Observer Scar Assessment Scale and the DSM II ColorMeter. To prevent selection bias, measurements were performed following a standardized algorithm. The Cutometer parameters elasticity and maximal extension improved 22.5 percent (p Scar Assessment Scale scores improved from 3.6 to 2.9 on the observer scale, and from 5.1 to 3.8 on the patient scale (both p scar and normal skin remained unaltered. For the first time, the effect of autologous fat grafting on functional scar parameters was ascertained using a comprehensive scar evaluation protocol. The improved scar pliability supports the authors' hypothesis that the function of the subcutis can be restored to a certain extent by single-treatment autologous fat grafting. Therapeutic, IV.

  15. Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection. (United States)

    Tweedy, Joshua; Spyrou, Maria Alexandra; Pearson, Max; Lassner, Dirk; Kuhl, Uwe; Gompels, Ursula A


    Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated "CiHHV-6A/B". These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, implying functional non-defective genomes. To further define the relationship between HHV-6A and CiHHV-6A we used next-generation sequencing to characterize genomes from three CiHHV-6A cardiac patients. Comparisons to known exogenous HHV-6A showed CiHHV-6A genomes formed a separate clade; including all 85 non-interrupted genes and necessary cis-acting signals for reactivation as infectious virus. Greater single nucleotide polymorphism (SNP) density was defined in 16 genes and the direct repeats (DR) terminal regions. Using these SNPs, deep sequencing analyses demonstrated superinfection with exogenous HHV-6A in two of the CiHHV-6A patients with recurrent cardiac disease. Characterisation of the integration sites in twelve patients identified the human chromosome 17p subtelomere as a prevalent site, which had specific repeat structures and phylogenetically related CiHHV-6A coding sequences indicating common ancestral origins. Overall CiHHV-6A genomes were similar, but distinct from known exogenous HHV-6A virus, and have the capacity to reactivate as emerging virus infections.

  16. Recovery of polyclonal immunoglobulins one year after autologous stem cell transplantation as a long-term predictor marker of progression and survival in multiple myeloma. (United States)

    González-Calle, Verónica; Cerdá, Seila; Labrador, Jorge; Sobejano, Eduardo; González-Mena, Beatriz; Aguilera, Carmen; Ocio, Enrique María; Vidriales, María Belén; Puig, Noemí; Gutiérrez, Norma Carmen; García-Sanz, Ramón; Alonso, José María; López, Rosa; Aguilar, Carlos; de Coca, Alfonso García; Hernández, Roberto; Hernández, José Mariano; Escalante, Fernando; Mateos, María-Victoria


    Immunoparesis or suppression of polyclonal immunoglobulins is a very common condition in newly diagnosed myeloma patients. However, the recovery of polyclonal immunoglobulins in the setting of immune reconstitution after autologous stem cell transplantation and its effect on outcome has not yet been explored. We conducted this study in a cohort of 295 patients who had undergone autologous transplantation. In order to explore the potential role of immunoglubulin recovery as a dynamic predictor of progression or survival after transplantation, conditional probabilities of progression-free survival and overall survival were estimated according to immunoglobulin recovery at different time points using a landmark approach. One year after transplant, when B-cell reconstitution is expected to be completed, among 169 patients alive and progression free, 88 patients (52%) showed immunoglobulin recovery and 81 (48%) did not. Interestingly, the group with immunoglobulin recovery had a significantly longer median progression-free survival than the group with persistent immunoparesis (median 60.4 vs. 27.9 months, respectively; Hazard Ratio: 0.45, 95%Confidence Interval: 0.31-0.66; P<0.001), and improved overall survival (11.3 vs. 7.3 years; Hazard Ratio: 0.45, 95%Confidence Interval: 0.27-0.74; P=0.002). Furthermore, the percentage of normal plasma cells detected by flow cytometry in the bone marrow assessed at day 100 after transplantation was associated with the immunoglobulin recovery at that time and may predict immunoglobulin recovery in the subsequent months: nine months and one year. In conclusion, the recovery of polyclonal immunoglobulins one year after autologous transplantation in myeloma patients is an independent long-term predictor marker for progression and survival. Copyright© Ferrata Storti Foundation.

  17. Follow-up of relapsed B-cell lymphoma patients treated with iodine-131-labeled anti-CD20 antibody and autologous stem-cell rescue

    Energy Technology Data Exchange (ETDEWEB)

    Liu, S Y.; Eary, Janet F.(Fred Hutchinson Cancer Research Center); Petersdorf, S H.; Martin, P J.(Fred Hutchinson Cancer Center); Maloney, D G.; Applebaum, F. R.(Fred Hutchinson Cancer Research Center); Matthews, D. C.(Fred Hutchinson Cancer Research Center); Bush, S A.; Durack, L. D.(Fred Hutchinson Cancer Research Center); Fisher, Darrell R.(BATTELLE (PACIFIC NW LAB)); Gooley, T A.; Bernstein, I. D.(Fred Hutchinson Cancer Research Center); Press, O. W.(Fred Hutchinson Cancer Research Center)


    Radioimmunotherapy (RIT) is a promising treatment approach for B-cell lymphomas. This is our first opportunity to report long-term follow-up data and late toxicities in 29 patients treated with myeloablative doses of iodine-131-anti-CD20 antibody (anti-B1) and autologous stem-cell rescue. PATIENTS AND METHODS: Trace-labeled biodistribution studies first determined the ability to deliver higher absorbed radiation doses to tumor sites than to lung, liver, or kidney at varying amounts of anti-B1 protein (0.35, 1.7, or 7 mg/kg). Twenty- nine patients received therapeutic infusions of single-agent (131)I- anti-B1, given at the protein dose found optimal in the biodistribution study, labeled with amounts of (131)I (280 to 785 mCi[10.4 to 29.0 GBq]) calculated to deliver specific absorbed radiation doses to the normal organs, followed by autologous stem-cell support. RESULTS: Major responses occurred in 25 patients (86%), with 23 complete responses (CRs; 79%). The nonhematopoietic do se-limiting toxicity was reversible cardiopulmonary insufficiency, which occurred in two patients at RIT doses that delivered > or = 27 Gy to the lungs. With a median follow-up time of 42 months, the estimated overall and progression-free survival rates are 68% and 42%, respectively. Currently, 14 of 29 patients remain in unmaintained remissions that range from 27+ to 87+ months after RIT. Late toxicities have been uncommon except for elevated thyroid-stimulating hormone (TSH) levels found in approximately 60% of the subjects. Two patients developed second malignancies, but none have developed myelodysplasia (MDS). CONCLUSION: Myeloablative (131)I-anti- B1 RIT is relatively well tolerated when given with autologous stem- cell support and often results in prolonged remission durations with few late toxicities.

  18. Autologous Blood and Platelet-Rich Plasma Injections for Treatment of Lateral Epicondylitis. (United States)

    Calandruccio, James H; Steiner, Murphy M


    Lateral epicondylitis (tennis elbow) is a frequent cause of elbow pain; most patients (80%-90%) are successfully treated with standard nonoperative methods (rest, nonsteroidal anti-inflammatory drugs, bracing, and physical therapy). Autologous blood injections and platelet-rich plasma injections are the two most frequently used orthobiologic techniques in the treatment of lateral epicondylitis. Studies of the effectiveness of autologous blood injections and platelet-rich plasma report varying outcomes, some citing significant clinical relief and others reporting no beneficial effect. More research is needed to determine how to best use orthobiologics in the treatment of lateral epicondylitis. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Morphological Analysis of Biocompatibility of Autologous Bone Marrow Mononuclear Cells with Synthetic Polyethylene Terephthalate Scaffold. (United States)

    Gilevich, I V; Polyakov, I S; Porkhanov, V A; Chekhonin, V P


    We studied the properties of a tissue-engineered trachea consisting of a polyethylene terephthalate scaffold populated with autologous bone marrow mononuclear cells. The tissue-engineered constructs were obtained before surgery, during the postoperative period, and during autopsy. Cytomorphological analysis during the postoperative period showed the presence of mesenchymal stem cells on the inner surface of the implant on day 3 after surgery and cells of the respiratory epithelium on day 10-14. In autopsy samples, single epithelial cells, endothelial cells, and basal cells were found. Biocompatibility of the tissue-engineered trachea with autologous mononuclear cells of the patient was demonstrated.

  20. Autologous Bone Marrow Stem Cell Infusion (AMBI therapy for Chronic Liver Diseases

    Directory of Open Access Journals (Sweden)

    Rajkumar JS


    Full Text Available Liver Cirrhosis is the end stage of chronic liver disease which may happen due to alcoholism, viral infections due to Hepatitis B, Hepatitis C viruses and is difficult to treat. Liver transplantation is the only available definitive treatment which is marred by lack of donors, post operative complications such as rejection and high cost. Autologous bone marrow stem cells have shown a lot of promise in earlier reported animal studies and clinical trials. We have in this study administered in 22 patients with chronic liver disease, autologous bone marrow stem cell whose results are presented herewith.

  1. Disposition of {sup 14}C-{beta}-carotene following delivery with autologous triacylglyceride-rich lipoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Dueker, Stephen R. [Department of Nutrition, University of California, Davis 95616 (United States) and Vitalea Science, Inc. 1233 East Beamer, Woodland, CA 95776 (United States)]. E-mail:; Le Thuy Vuong [Vitalea Science, Inc. 1233 East Beamer, Woodland, CA 95776 (United States); Faulkner, Brian [Vitalea Science, Inc. 1233 East Beamer, Woodland, CA 95776 (United States); Buchholz, Bruce A. [Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, Livermore, CA 94551 (United States); Vogel, John S. [Department of Nutrition, University of California, Davis 95616 (United States); Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, Livermore, CA 94551 (United States)


    Following ingestion, a fraction of {beta}-carotene is cleaved into vitamin A in the intestine, while another is absorbed intact and distributed among tissues and organs. The extent to which this absorbed {beta}-carotene serves as a source of vitamin A is unknown in vivo. In the present study we use the attomole sensitivity of accelerator mass spectrometry (AMS) for {sup 14}C to quantify the disposition of {sup 14}C-{beta}-carotene (930 ng; 60.4 nCi of activity) after intravenous injection with an autologous triacylglyceride-rich lipoprotein fraction in a single volunteer. Total {sup 14}C was quantified in serial plasma samples and also in triglyceride-rich, and low density lipoprotein, subfractions. The appearance of {sup 14}C-retinol, the circulating form of vitamin A in plasma, was determined by chromatographic separation of plasma retinol extracts prior to AMS analysis. The data showed that {sup 14}C concentrations rapidly decayed within the triglyceride-rich lipoprotein fractions after injection, whereas low density lipoprotein {sup 14}C began a significant rise in {sup 14}C 5 h post dose. Plasma {sup 14}C-retinol also appeared at 5 h post dose and its concentrations were maintained above baseline for >88 days. Based upon comparisons of {sup 14}C-retinol concentrations following an earlier study with orally dosed {sup 14}C-{beta}-carotene, a molar vitamin A value of the absorbed {beta}-carotene of 0.19 was derived, meaning that 1 mole of absorbed {beta}-carotene provides 0.19 moles of vitamin A. This is the first study to show that infused {beta}-carotene contributes to the vitamin A economy in humans in vivo.

  2. Autologous Graft versus Host Disease: An Emerging Complication in Patients with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Anu Batra


    Full Text Available Autologous graft versus host disease (autoGVHD is a rare transplant complication with significant morbidity and mortality. It has been hypothesized that patients with multiple myeloma might be predisposed to autoGVHD through dysregulation of the immune response resulting from either their disease, the immunomodulatory agents (IMiDs used to treat it, or transplant conditioning regimen. Hematopoietic progenitor cell (HPC products were available from 8 multiple myeloma patients with biopsy-proven autoGVHD, 16 matched multiple myeloma patients who did not develop autoGVHD, and 7 healthy research donors. The data on number of transplants prior to developing autoGVHD, mobilization regimens, exposure to proteasome inhibitors, use of IMiDs, and class I human leukocyte antigen types (HLA A and B were collected. The HPC products were analyzed by flow cytometry for expression of CD3, CD4, CD8, CD25, CD56, and FoxP3. CD3+ cell number was significantly lower in autoGVHD patients compared to unaffected controls (P=0.047. On subset analysis of CD3+ cells, CD8+ cells (but not CD4+ cells were found to be significantly lower in patients with autoGVHD (P=0.038. HLA-B55 expression was significantly associated with development of autoGVHD (P=0.032. Lower percentages of CD3+ and CD8+ T-cells and HLA-B55 expression may be predisposing factors for developing autoGVHD in myeloma.


    African Journals Online (AJOL)


    marketing boards (until their removal) have been responsible for the grading and the quality control of exported cocoa seeds. However, this function was completely out of place after the scrapping of the marketing boards in Nigeria. In the short – run cassava price. (lagged one year) has a positive and significant coefficient ...

  4. Completeness of Lyapunov Abstraction

    Directory of Open Access Journals (Sweden)

    Rafael Wisniewski


    Full Text Available In this work, we continue our study on discrete abstractions of dynamical systems. To this end, we use a family of partitioning functions to generate an abstraction. The intersection of sub-level sets of the partitioning functions defines cells, which are regarded as discrete objects. The union of cells makes up the state space of the dynamical systems. Our construction gives rise to a combinatorial object - a timed automaton. We examine sound and complete abstractions. An abstraction is said to be sound when the flow of the time automata covers the flow lines of the dynamical systems. If the dynamics of the dynamical system and the time automaton are equivalent, the abstraction is complete. The commonly accepted paradigm for partitioning functions is that they ought to be transversal to the studied vector field. We show that there is no complete partitioning with transversal functions, even for particular dynamical systems whose critical sets are isolated critical points. Therefore, we allow the directional derivative along the vector field to be non-positive in this work. This considerably complicates the abstraction technique. For understanding dynamical systems, it is vital to study stable and unstable manifolds and their intersections. These objects appear naturally in this work. Indeed, we show that for an abstraction to be complete, the set of critical points of an abstraction function shall contain either the stable or unstable manifold of the dynamical system.

  5. Epispadias with complete prepuce

    African Journals Online (AJOL)


    Abstract. Epispadias with complete prepuce is a very rare anomaly. It is often associated with late presentation because it is a very rare condition and the penis appears grossly normal, thus, the diagnosis is easily missed during the neonatal period. We report a case of a boy presenting at seven years of age with epispadias.

  6. Completing lists of entities

    NARCIS (Netherlands)

    Fissaha Adafre, S.; de Rijke, M.; Tjong Kim Sang, E.


    We consider the list completion task, an entity retrieval task where, in return to a topic statement and a number of example entities, systems have to return further examples. For this task, we propose and evaluate several algorithms. One of the core challenges is to overcome the very limited amount

  7. Complete French Teach Yourself

    CERN Document Server

    Graham, Gaelle


    The best-selling complete course for a fun and effective way to learn French. This ISBN is for the paperback book. The corresponding audio support (ISBN: 9781444100068) is also available. The book and audio support can also be purchased as a pack (ISBN: 9781444100051).

  8. LEAR construction completed

    CERN Multimedia

    CERN PhotoLab


    In July 1982, LEAR construction was completed, the individual systems had been dry-tested. On 16 July, the first 50 MeV (309 MeV/c) protons from Linac 1 were injected and circulated. On 11 October, the first antiprotons from the AA, decelerated in the PS to 609 MeV/c, were injected. Also in 1982, acceleration, deceleration and stochastic cooling were successfully tested. See 9007366 for a more detailed description. See also 8201061, 8204131, 8309026.

  9. CMS Is Finally Completed

    CERN Multimedia


    Yet another step in the completion of the Large Hadron Collider was taken yesterday morning, as the final element of the Compact Muon Solenoid was lowered nearly 100 meters bellow ground. After more than eight years of work at the world's most powerful particle accelerator, scientists hope that they will be able to start initial experiments with the LHC until the end of this year.

  10. SCT Barrel Assembly Complete

    CERN Multimedia

    L. Batchelor

    As reported in the April 2005 issue of the ATLAS eNews, the first of the four Semiconductor Tracker (SCT) barrels, complete with modules and services, arrived safely at CERN in January of 2005. In the months since January, the other three completed barrels arrived as well, and integration of the four barrels into the entire barrel assembly commenced at CERN, in the SR1 building on the ATLAS experimental site, in July. Assembly was completed on schedule in September, with the addition of the innermost layer to the 4-barrel assembly. Work is now underway to seal the barrel thermal enclosure. This is necessary in order to enclose the silicon tracker in a nitrogen atmosphere and provide it with faraday-cage protection, and is a delicate and complicated task: 352 silicon module powertapes, 352 readout-fibre bundles, and over 400 Detector Control System sensors must be carefully sealed into the thermal enclosure bulkhead. The team is currently verifying the integrity of the low mass cooling system, which must be d...

  11. C1q Binding to and Uptake of Apoptotic Lymphocytes by Human Monocyte-derived Macrophages. (United States)

    Benoit, Marie E; Clarke, Elizabeth V; Tenner, Andrea J


    To characterize macrophage gene expression profiles during the uptake of autologous apoptotic cells, we developed a unique, more physiologic system using primary human monocyte derived macrophages purified via a nonactivating isolation procedure (and in the absence of contaminating platelets, which can release stimulating signals if activated) and autologous lymphocytes as a source of apoptotic cells. The use of autologous cells as the apoptotic target rather than transformed cell lines avoids antigenic stimulation from "nonself" structures at the HLA level but also from "altered self" signals due to the transformation inherent in cell lines.

  12. Technologies enabling autologous neural stem cell-based therapies for neurodegenerative disease and injury (United States)

    Bakhru, Sasha H.

    The intrinsic abilities of mammalian neural stem cells (NSCs) to self-renew, migrate over large distances, and give rise to all primary neural cell types of the brain offer unprecedented opportunity for cell-based treatment of neurodegenerative diseases and injuries. This thesis discusses development of technologies in support of autologous NSC-based therapies, encompassing harvest of brain tissue biopsies from living human patients; isolation of NSCs from harvested tissue; efficient culture and expansion of NSCs in 3D polymeric microcapsule culture systems; optimization of microcapsules as carriers for efficient in vivo delivery of NSCs; genetic engineering of NSCs for drug-induced, enzymatic release of transplanted NSCs from microcapsules; genetic engineering for drug-induced differentiation of NSCs into specific therapeutic cell types; and synthesis of chitosan/iron-oxide nanoparticles for labeling of NSCs and in vivo tracking by cellular MRI. Sub-millimeter scale tissue samples were harvested endoscopically from subventricular zone regions of living patient brains, secondary to neurosurgical procedures including endoscopic third ventriculostomy and ventriculoperitoneal shunt placement. On average, 12,000 +/- 3,000 NSCs were isolated per mm 3 of subventricular zone tissue, successfully demonstrated in 26 of 28 patients, ranging in age from one month to 68 years. In order to achieve efficient expansion of isolated NSCs to clinically relevant numbers (e.g. hundreds of thousands of cells in Parkinson's disease and tens of millions of cells in multiple sclerosis), an extracellular matrix-inspired, microcapsule-based culture platform was developed. Initial culture experiments with murine NSCs yielded unprecedented expansion folds of 30x in 5 days, from initially minute NSC populations (154 +/- 15 NSCs per 450 mum diameter capsule). Within 7 days, NSCs expanded as almost perfectly homogenous populations, with 94.9% +/- 4.1% of cultured cells staining positive for

  13. The Efficacy of Autologous Femoropopliteal Vein Reconstruction for Primary Aortic and Aortic Graft Infection

    NARCIS (Netherlands)

    Dirven, M.; Jagt, M.F.P. van der; Barendregt, W.B.; Vliet, D. van der


    BACKGROUND: The objective of our study was to analyze the efficacy of autologous superficial femoropopliteal vein reconstruction for primary aortic or aortic graft infection. METHODS: We performed a retrospective analysis of 14 patients treated for an infected aortic prosthesis or primary infected

  14. Effects of Autologous Fat and ASCs on Swine Hypertrophic Burn Scars: A Multimodal Quantitative Analysis

    Directory of Open Access Journals (Sweden)

    Scott J. Rapp, MD


    Conclusion:. Early results suggest that autologous fat and/or ASCs may improve healing of hypertrophic scarring by altering the cellular and structural components during wound remodeling up to 20 weeks after injury. This may have beneficial applications in early treatment of large or cosmetically sensitive immature burn scars.

  15. Autologous transplantation and management of younger patients with mantle cell lymphoma

    DEFF Research Database (Denmark)

    Geisler, Christian H


    Mantle cell lymphoma is traditionally conceived as one of the NHL subtypes with the worst prognosis and incurable. In responders to frontline induction with CHOP-like chemotherapy autologous stem cell transplantation (ASCT) is proven superior to interferon maintenance, but does not lead to long...

  16. Treatment of midshaft clavicular nonunion with plate fixation and autologous bone grafting

    DEFF Research Database (Denmark)

    Olsen, Bo Sanderhoff; Vaesel, M T; Søjbjerg, Jens Ole


    , and one had a failure. Thirteen of 16 patients were satisfied with the cosmetic outcome, assessing their cosmetic result as either good or excellent. Rigid plate fixation and restoration of clavicular length with autologous cancellous bone graft is recommended for the treatment of symptomatic clavicular...

  17. Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury (United States)

    Masuzawa, Akihiro; Black, Kendra M.; Pacak, Christina A.; Ericsson, Maria; Barnett, Reanne J.; Drumm, Ciara; Seth, Pankaj; Bloch, Donald B.; Levitsky, Sidney; Cowan, Douglas B.


    Mitochondrial damage and dysfunction occur during ischemia and modulate cardiac function and cell survival significantly during reperfusion. We hypothesized that transplantation of autologously derived mitochondria immediately prior to reperfusion would ameliorate these effects. New Zealand White rabbits were used for regional ischemia (RI), which was achieved by temporarily snaring the left anterior descending artery for 30 min. Following 29 min of RI, autologously derived mitochondria (RI-mitochondria; 9.7 ± 1.7 × 106/ml) or vehicle alone (RI-vehicle) were injected directly into the RI zone, and the hearts were allowed to recover for 4 wk. Mitochondrial transplantation decreased (P mitochondria (7.9 ± 2.9%) compared with RI-vehicle (34.2 ± 3.3%, P mitochondria hearts returned to normal contraction within 10 min after reperfusion was started; however, RI-vehicle hearts showed persistent hypokinesia in the RI zone at 4 wk of recovery. Electrocardiogram and optical mapping studies showed that no arrhythmia was associated with autologously derived mitochondrial transplantation. In vivo and in vitro studies show that the transplanted mitochondria are evident in the interstitial spaces and are internalized by cardiomyocytes 2–8 h after transplantation. The transplanted mitochondria enhanced oxygen consumption, high-energy phosphate synthesis, and the induction of cytokine mediators and proteomic pathways that are important in preserving myocardial energetics, cell viability, and enhanced post-infarct cardiac function. Transplantation of autologously derived mitochondria provides a novel technique to protect the heart from ischemia-reperfusion injury. PMID:23355340

  18. Reaming debris as a novel source of autologous bone to enhance healing of bone defects

    NARCIS (Netherlands)

    Bakker, A.D.; Kroeze, R.J.; Korstjens, C.; Kleine, R.H. de; Frolke, J.P.M.; Klein-Nulend, J.


    Reaming debris is formed when bone defects are stabilized with an intramedullary nail, and contains viable osteoblast-like cells and growth factors, and might thus act as a natural osteoinductive scaffold. The advantage of using reaming debris over stem cells or autologous bone for healing bone

  19. Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma

    DEFF Research Database (Denmark)

    Pettengell, Ruth; Schmitz, Norbert; Gisselbrecht, Christian


    The objective of this randomized trial was to assess the efficacy and safety of rituximab as in vivo purging before transplantation and as maintenance treatment immediately after high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT) in patients with relapsed follicular lymphoma...

  20. Pediatric tracheal reconstruction with pericardial patch and strips of autologous cartilage

    NARCIS (Netherlands)

    Hazekamp, Mark G.; Koolbergen, David R.; Kersten, Joost; Peper, Jacques; de Mol, Bas; König-Jung, Astrid


    OBJECTIVE: To analyze the results of pediatric tracheal reconstruction with autologous pericardial patch and strips of cartilage. METHODS: From September 2003 to February 2008 14 non-consecutive children were operated using pericardial patch augmentation of the trachea combined with external

  1. Outcome determinants for transformed indolent lymphomas treated with or without autologous stem cell transplantation

    DEFF Research Database (Denmark)

    Madsen, Charlotte; Pedersen, Martin Bjerregård; Vase, Maja Ølholm


    of autologous stem-cell transplantation (ASCT) is still debated. The purpose of this study was to determine whether the outcome of TIL patients improved if they, at transformation, also received ASCT. Furthermore, we investigated the outcome of cases with histologically low- and high-grade components diagnosed...

  2. Autologous blood injection for treatment of lateral epicondylosis: A meta-analysis of randomized controlled trials. (United States)

    Chou, Lin-Chuan; Liou, Tsan-Hon; Kuan, Yi-Chun; Huang, Yao-Hsien; Chen, Hung-Chou


    To appraise existing evidence of autologous blood injection in treating lateral epicondylosis. Meta-analysis of randomized controlled trials. A comprehensive search of the PubMed, Cochrane, SCOPUS, and CINAHL databases was performed to identify randomized controlled trials that reported the efficacy of autologous blood injection in treating lateral epicondylosis. The selected studies were subjected to a meta-analysis and risk of bias assessment. Patients with lateral epicondylosis. Pain-related measurement in each selected randomized controlled trial was pooled into meta-analysis. Nine randomized controlled trials were included in the analysis. The results of the meta-analysis including the pain scores indicated that autologous blood injection is more effective compared with corticosteroid injection (standard mean difference: -0.75; 95% confidence interval: -1.14 to -0.37) but not more effective compared with platelet-rich plasma injection (standard mean difference: 0.09; 95% confidence interval: -0.66 to 0.84). The risk of bias assessment indicated that all the included trials exhibited a moderate to high risk of bias. Autologous blood injection is more effective than corticosteroid injection but not more effective than platelet-rich plasma injection in treating lateral epicondylosis. However, this evidence is limited by the potential risk of bias. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Immediate reconstruction with autologous fat grafting: influence in loco regional recurrence in breast cancer


    STUMPF, CAMILE CESA; BIAZUS, JORGE VILLANOVA; ZUCATTO, FERNANDO SCHUH ÂNGELA ERGUY; Cericatto, Rodrigo; Cavalheiro, José Antônio Crespo; Damin, Andrea Pires Souto; Melo, Márcia Portela de


    ABSTRACT Objective: to evaluate local and systemic recurrence of breast cancer in patients submitted to autologous fat grafting in the immediate reconstruction after conservative surgery for breast cancer. Methods: this is a historical cohort study comparing 167 patients submitted to conservative surgery without reconstruction (conservative surgery group) with 27 patients submitted to conservative treatment with immediate graft reconstruction, following the Coleman's technique (lipofillin...

  4. Salmonella sepsis following posttraumatic splenectomy and implantation of autologous splenic tissue

    DEFF Research Database (Denmark)

    Schrøder, H M; Hovendal, C


    A severe complication following implantation of autologous splenic tissue occurred in a 51-year-old man. Indirect injury to abdomen resulted in a lesion of the splenic artery. Following splenectomy and reimplantation of splenic tissue into three pouches, a severe Salmonella sepsis developed within...

  5. Experimental results and clinical impact of using autologous rectus fascia sheath for vascular replacement

    NARCIS (Netherlands)

    Kobori, Laszlo; Nemeth, Tibor; Nagy, Peter; Dallos, Gabor; Sotonyi, Peter; Fehervari, Imre; Nemes, Balazs; Gorog, Denes; Patonai, Attila; Monostory, Katalin; Doros, Attila; Sarvary, Enikoe; Fazakas, Janos; Gerlei, Zsuzsanna; Benkoe, Tamas; Piros, Laszlo; Jaray, Jeno; De Jong, Koert P.

    Vascular complications are major causes of graft failure in liver transplantation. The use of different vascular grafts is common but the results are controversial. The aim of this study was to create an 'ideal' arterial interponate for vascular replacements in the clinical field. An autologous,

  6. Harvest of autologous clavipectoral fascia for use in duraplasty: cadaveric feasibility study. (United States)

    Louis, Robert G; Tubbs, R Shane; Mortazavi, Martin M; Shoja, Mohammadali M; Loukas, Marios; Cohen-Gadol, Aaron A


    Techniques and materials for repair of dural defects following neurosurgical procedures vary. Given higher complication rates with nonautologous duraplasty materials, most authors strongly recommend autologous grafts. To expand the arsenal of possible materials available to the neurosurgeon, we propose the use of autologous clavipectoral fascia as an alternative donor for duraplasty. Eight embalmed adult cadavers underwent dissection of the pectoral region. A 12-cm curvilinear skin incision was made 2 cm inferior to the nipple in males and along the inferior breast edge in females. Dissection was continued until the clavipectoral fascia was encountered, and a tissue plane was developed between this fascia and the deeper pectoralis major muscle. Sections of clavipectoral fascia were used for duraplasty in the same specimens. In all specimens, removal of clavipectoral fascia was easily performed with tissue separation between the overlying fascia and underlying muscle. Only small adhesions were found between the fascia and underlying muscle, and these were easily transected. No obvious gross neurovascular injuries were identified. Large portions of clavipectoral fascia were available, and at least a 10 × 10-cm piece (average thickness, 1.2 mm) was easily harvested for all specimens. Clavipectoral fascia shares characteristics with materials such as pericranium and fascia lata that have been used successfully in duraplasty, and most importantly, it is autologous. Theoretically, using clavipectoral fascia would reduce the risk of muscle herniation. It offers an alternative source for autologous dural grafting when other sources are unavailable or exhausted. Clinical experience with this fascia is warranted.

  7. Hemolytic uremic syndrome after high dose chemotherapy with autologous stem cell support

    NARCIS (Netherlands)

    van der Lelie, H.; Baars, J. W.; Rodenhuis, S.; Van Dijk, M. A.; de Glas-Vos, C. W.; Thomas, B. L.; van Oers, R. H.; von dem Borne, A. E.


    BACKGROUND: Chemotherapy intensification may lead to new forms of toxicity such as hemolytic uremic syndrome. METHODS: Three patients are described who developed this complication 4 to 6 months after high dose chemotherapy followed by autologous stem cell support. The literature on this subject is

  8. Autologous stem cell transplantation in treatment of aggressive non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Kluin-Nelemans, Hanneke


    There is no doubt that autologous stem cell transplantation is useful for patients with relapsed aggressive non-Hodgkin's lymphoma if they are responsive to the chemotherapy given before the transplantation. A small subset of patients with primary refractory disease still profits from this high dose

  9. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma

    DEFF Research Database (Denmark)

    d'Amore, Francesco; Relander, Thomas; Lauritzsen, Grete F


    Systemic peripheral T-cell lymphomas (PTCLs) respond poorly to conventional therapy. To evaluate the efficacy of a dose-dense approach consolidated by up-front high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in PTCL, the Nordic Lymphoma Group (NLG) conducted a large...

  10. Multiple myeloma related cells in patients undergoing autologous peripheral blood stem cell transplantation

    NARCIS (Netherlands)

    Guikema, JEJ; Vellenga, E; Veeneman, JM; Hovenga, S; Bakkus, MHC; Klip, H; Bos, NA

    A high incidence of oligoclonal serum M-components is observed in multiple myeloma (MM) patients treated with autologous Stem cell transplantation (ASCT). To determine whether these hi-components are produced by myeloma clonally related cells or caused by an aberrant B-cell regeneration we analysed

  11. Generating Peripheral Blood Derived Lymphocytes Reacting Against Autologous Primary AML Blasts. (United States)

    Mehta, Rohtesh S; Chen, Xiaohua; Antony, Jeyaraj; Boyiadzis, Michael; Szabolcs, Paul


    Expanding on our prior studies with cord blood T cells, we hypothesized that primary acute myeloid leukemia (AML)-reactive autologous T cells could be generated ex vivo under immunomodulatory conditions. We purified AML and T cells from 8 newly diagnosed high-risk patients. After 2 weeks expansion, T cells were stimulated with interferon-γ-treated autologous AML weekly × 3, interleukin-15, and agonistic anti-CD28 antibody. Cytotoxic T cells and ELISpot assays tested functionality; reverse transcriptase quantitative polymerase chain reaction tested AML and T-cell gene expression profiles. On the basis of combined positive ELIspot and cytotoxic T cells assays, T cells reactive against AML were generated in 5 of 8 patients. Treg proportion declined after cocultures in reactive T-cell samples. AML-reactive T cells displayed an activated gene expression profile. "Resistant" AML blasts displayed genes associated with immunosuppressive myeloid-derived suppressor cells. We discuss our approach to creating primary AML-reactive autologous T cell and limitations that require further work. Our study provides a platform for future research targeting on generating autologous leukemia-reactive T cells.

  12. Chondrocyte-seeded type I/III collagen membrane for autologous chondrocyte transplantation

    DEFF Research Database (Denmark)

    Niemeyer, Philipp; Lenz, Philipp; Kreuz, Peter C


    PURPOSE: We report the 2-year clinical results and identify prognostic factors in patients treated with autologous chondrocyte transplantation by use of a collagen membrane to seed the chondrocytes (ACT-CS). METHODS: This is a prospective study of 59 patients who were treated with ACT-CS and foll...

  13. In-vitro chondrogenic potential of synovial stem cells and chondrocytes allocated for autologous chondrocyte implantation

    DEFF Research Database (Denmark)

    Kubosch, Eva Johanna; Heidt, Emanuel; Niemeyer, Philipp


    Purpose: The use of passaged chondrocytes is the current standard for autologous chondrocyte implantation (ACI). De-differentiation due to amplification and donor site morbidity are known drawbacks highlighting the need for alternative cell sources. Methods: Via clinically validated flow cytometr...

  14. Influence of ex vivo purging with CliniMACS CD34(+) selection on outcome after autologous stem cell transplantation in non-Hodgkin lymphoma. (United States)

    Yahng, Seung-Ah; Yoon, Jae-Ho; Shin, Seung-Hwan; Lee, Sung-Eun; Cho, Byung-Sik; Eom, Ki-Seong; Kim, Yoo-Jin; Lee, Seok; Kim, Hee-Je; Min, Chang-Ki; Kim, Dong-Wook; Lee, Jong-Wook; Min, Woo-Sung; Park, Chong-Won; Kim, Yonggoo; Cho, Seok-Goo


    The major limitation of autologous stem cell transplantation (auto-SCT) in non-Hodgkin lymphoma (NHL) is relapse. Although autologous graft contamination may be a potential cause, prior purging of the autograft remains controversial. Therefore, we retrospectively analysed 56 consecutive patients with NHL receiving auto-SCT at complete (n = 41) or partial remission (n = 15). Among them, 24 patients underwent autograft manipulation with positive selection of CD34(+) cells using a CliniMACS device (purged group). Twenty-five patients had received ≥2 previous chemotherapy regimens before auto-SCT. After a median follow-up of 41·4 months, transplant-related mortality was observed only in unpurged group (n = 2; 3·6%). The 3-year overall survival (91·7% vs. 56·1%, P = 0·009) and progression-free survival (78·7% vs. 53·1%, P = 0·034) favoured CD34(+) purification. While neutrophil recovery was similar, platelet recovery was delayed in the purged group. Cytomegalovirus reactivation was predominantly observed in the purged group, although no other clinically unmanageable infectious complications occurred. Although this study has the inevitable limitations of heterogeneity in previous treatment and NHL subtypes, and a small number of patients analysed, the high survival rate in the purged group may suggest the need for prospective randomized trials to determine the role of CD34(+) purification in auto-SCT for NHL. © 2013 John Wiley & Sons Ltd.

  15. Repositioning of a pathologically migrated tooth using autologous platelet-rich plasma: a case report with 3-year follow-up. (United States)

    Karthikeyan, B V; Khanna, Divya; Prabhuji, M Lv


    An intricate balance between the periodontal tissues and the forces of occlusion, tongue, and lips helps to maintain a tooth in its physiologic position within the dental arch. Disturbances in the equilibrium can cause a tooth to migrate pathologically, often requiring multidisciplinary treatment approaches. The present case demonstrates, for the first time, the use of autologous platelet-rich plasma to aid in tooth repositioning after pathologic tooth migration. A 25-year-old woman presented with extrusion and labial migration of the maxillary left central incisor, a diastema of 3 mm, and grade II mobility. Radiographic evaluation showed a deep, angular bone defect, extending to the apical third of the root, on both the mesial and distal aspects of the maxillary left central incisor. Comprehensive treatment consisted of nonsurgical and surgical periodontal therapy with autologous platelet-rich plasma. Without orthodontic intervention, the unesthetic diastema had completely closed by the end of 3 months postoperatively, and the results were stable at a 3-year follow-up examination. This successful, novel approach can be adopted as a conservative and time-efficient modality for management of unesthetic spaces caused by pathologic tooth migration.

  16. Statistics a complete introduction

    CERN Document Server

    Graham, Alan


    Statistics: A Complete Introduction is the most comprehensive yet easy-to-use introduction to using Statistics. Written by a leading expert, this book will help you if you are studying for an important exam or essay, or if you simply want to improve your knowledge. The book covers all the key areas of Statistics including graphs, data interpretation, spreadsheets, regression, correlation and probability. Everything you will need is here in this one book. Each chapter includes not only an explanation of the knowledge and skills you need, but also worked examples and test questions.

  17. TestComplete cookbook

    CERN Document Server

    Alpaev, Gennadiy


    A practical cookbook, with a perfect package of simple, medium, and advanced recipes targeted at basic programmers as well as expert software testers, who will learn to create, manage, and run automated tests. It is packed with problem-solving recipes that are supported by simple examples.If you are a software tester or a programmer who is involved with testing automation using TestComplete, this book is ideal for you! You will be introduced to the very basics of using the tool, as well as polish any previously gained knowledge in using the tool. If you are already aware of programming basics,

  18. Penggunaan Tetes Telinga Serum Autologous dengan Amnion untuk Penutupan Perforasi Membran Timpani

    Directory of Open Access Journals (Sweden)

    Hidayatul Fitria


    Full Text Available Abstrak Latar Belakang: Gangguan pendengaran atau ketulian mempunyai dampak yang merugikan bagi penderita , keluarga, masyarakat maupun negara. Salah satu penyebab ketulian yang sering dijumpai adalah radang telinga tengah, terutama yang disertai perforasi membran timpani yang menetap. Penutupan perforasi membran timpani dapat dilakukan dengan operatif dan konservatif. Secara konservatif sudah banyak cara yang dilakukan. Salah satunya dengan mengkaustik tepi perforasi dengan menggunakan silver nitrat untuk membuat luka baru, kemudian digunakan amnion sebagai jembatan (bridge dan faktor regulasi yang terdapat pada tetes telinga serum autologous. Tujuan: Untuk menjelaskan gambaran penggunaan amnion sebagai jembatan dan tetes telinga serum autologous sebagai faktor regulasi. Tinjauan pustaka: Penutupan perforasi membran timpani dapat dilakukan secara konservatif salah satunya dengan menggunakan tetes telinga serum autologous sebagai faktor regulator, amnion sebagai jembatan dan penggunaan silver nitrat pada tepi perforasi untuk membuat luka baru. Serum autologous memiliki asselerator pertumbuhan yaitu epidermal growth factor (EGF , transforming growth factor β1 (TGF- β1 dan fibronektin. Asselerator pertumbuhan ini dapat kita temukan pada penyembuhan membran timpani normal. Sedangkan membran amnion adalah jaringan semi transparan tipis yang membentuk lapisan terdalam membran fetus dengan susunan membran basalis yang tebal dan jaringan stroma avaskuler. Membran amnion mempercepat pembentukan epitel normal dengan menekan pembentukan jaringan fibrosis. Sel epitel amnion memproduksi faktor pertumbuhan seperti fibroblast growth factor dan transforming growth factor beta. Faktor pertumbuhan akan membantu komunikasi antara epitel dan sel fibroblast stroma untuk menekan proliferasi dan diferensiasi jaringan fibrosis. Kesimpulan: Diperlukan tiga elemen pada penutupan perforasi membran timpani yaitu faktor regulasi, jembatan (bridge dan membuat luka baru

  19. Autologous whole blood versus corticosteroid local injection in treatment of plantar fasciitis: A randomized, controlled multicenter clinical trial. (United States)

    Karimzadeh, Afshin; Raeissadat, Seyed Ahmad; Erfani Fam, Saleh; Sedighipour, Leyla; Babaei-Ghazani, Arash


    Plantar fasciitis is the most common cause of heel pain. Local injection modalities are among treatment options in patients with resistant pain. The aim of the present study was to evaluate the effect of local autologous whole blood compared with corticosteroid local injection in treatment of plantar fasciitis. In this randomized controlled multicenter study, 36 patients with chronic plantar fasciitis were recruited. Patients were allocated randomly into three treatment groups: local autologous blood, local corticosteroid injection, and control groups receiving no injection. Patients were assessed with visual analog scale (VAS), pressure pain threshold (PPT), and plantar fasciitis pain/disability scale (PFPS) before treatment, as well as 4 and 12 weeks post therapy. Variables of pain and function improved significantly in both corticosteroid and autologous blood groups compared to control group. At 4 weeks following treatment, patients in corticosteroid group had significantly lower levels of pain than patients in autologous blood and control groups (higher PPT level, lower PFPS, and VAS). After 12 weeks of treatment, both corticosteroid and autologous blood groups had lower average levels of pain than control group. The corticosteroid group showed an early sharp and then more gradual improvement in pain scores, but autologous blood group had a steady gradual drop in pain. Autologous whole blood and corticosteroid local injection can both be considered as effective methods in the treatment of chronic plantar fasciitis. These treatments decrease pain and significantly improve function compared to no treatment.

  20. Complete atrioventricular canal

    Directory of Open Access Journals (Sweden)

    Limongelli Giuseppe


    Full Text Available Abstract Complete atrioventricular canal (CAVC, also referred to as complete atrioventricular septal defect, is characterised by an ostium primum atrial septal defect, a common atrioventricular valve and a variable deficiency of the ventricular septum inflow. CAVC is an uncommon congenital heart disease, accounting for about 3% of cardiac malform