Addition of exogenous cytokines in mixed lymphocyte culture for selecting related donors for bone marrow transplantation

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Jeane Eliete Laguila Visentainer

Full Text Available CONTEXT: Mixed lymphocyte culturing has led to conflicting opinions regarding the selection of donors for bone marrow transplantation. The association between a positive mixed lymphocyte culture and the development of graft-versus-host disease (GVHD is unclear. The use of exogenous cytokines in mixed lymphocyte cultures could be an alternative for increasing the sensitivity of culture tests. OBJECTIVE: To increase the sensitivity of mixed lymphocyte cultures between donor and recipient human leukocyte antigen (HLA identical siblings, using exogenous cytokines, in order to predict post-transplantation GVHD and/or rejection. TYPE OF STUDY: Prospective study. SETTING: Bone Marrow Transplantation Unit, Universidade Estadual de Campinas. PARTICIPANTS: Seventeen patients with hematological malignancies and their respective donors selected for bone marrow transplantation procedures. PROCEDURES: Standard and modified mixed lymphocyte culturing by cytokine supplementation was carried out using donor and recipient cells typed for HLA. MAIN MEASUREMENTS: Autologous and allogenic responses in mixed lymphocyte cultures after the addition of IL-4 or IL-2. RESULTS: In comparison with the standard method, average responses in the modified mixed lymphocyte cultures increased by a factor of 2.0 using IL-4 (p < 0.001 and 6.4 using IL-2 (p < 0.001, for autologous donor culture responses. For donor-versus-recipient culture responses, the increase was by a factor of 1.9 using IL-4 (p < 0.001 and 4.1 using IL-2 (p < 0.001. For donor-versus-unrelated culture responses, no significant increase was observed using IL-4, and a mean response inhibition of 20% was observed using IL-2 (p < 0.001. Neither of the cytokines produced a significant difference in the unrelated control versus recipient cell responses. CONCLUSION: IL-4 supplementation was the best for increasing the mixed lymphocyte culture sensitivity. However, IL-4 also increased autologous responses, albeit less

Apoptosis in peripheral blood lymphocytes of healthy donors and patients with laryngeal cancer after γ-irradiation in vitro

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Orlova, N.V.; Smirnova, S.G.; Zamulaeva, I.A.; Andreev, V.G.; Ryabchenko, N.I.; Saenko, A.S.

2001-01-01

Apoptosis in peripheral blood lymphocytes of healthy donors and cancer patients after γ-radiation with different doses is studied by the flow cytometry method. Wide intra- and interindividual variabilities of the lymphocyte radiosensitivity by different donors are observed. The radiosensitivity does not depend on the subpopulation composition of the lymphocyte pool. The persons with very low and high lymphocyte radiosensitivities are found significantly more often among the cancer patients than among the healthy donors. One can suggest that this method is useful to define risk groups with regard to radiogenic neoplasms and prognosis of radiotherapy efficiency [ru

Neonatal bone marrow transplantation of ADA-deficient SCID mice results in immunologic reconstitution despite low levels of engraftment and an absence of selective donor T lymphoid expansion.

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Carbonaro, Denise A; Jin, Xiangyang; Cotoi, Daniel; Mi, Tiejuan; Yu, Xiao-Jin; Skelton, Dianne C; Dorey, Frederick; Kellems, Rodney E; Blackburn, Michael R; Kohn, Donald B

2008-06-15

Adenosine deaminase (ADA)-deficient severe combined immune deficiency (SCID) may be treated by allogeneic hematopoietic stem cell transplantation without prior cytoreductive conditioning, although the mechanism of immune reconstitution is unclear. We studied this process in a murine gene knockout model of ADA-deficient SCID. Newborn ADA-deficient pups received transplants of intravenous infusion of normal congenic bone marrow, without prior cytoreductive conditioning, which resulted in long-term survival, multisystem correction, and nearly normal lymphocyte numbers and mitogenic proliferative responses. Only 1% to 3% of lymphocytes and myeloid cells were of donor origin without a selective expansion of donor-derived lymphocytes; immune reconstitution was by endogenous, host-derived ADA-deficient lymphocytes. Preconditioning of neonates with 100 to 400 cGy of total body irradiation before normal donor marrow transplant increased the levels of engrafted donor cells in a radiation dose-dependent manner, but the chimerism levels were similar for lymphoid and myeloid cells. The absence of selective reconstitution by donor T lymphocytes in the ADA-deficient mice indicates that restoration of immune function occurred by rescue of endogenous ADA-deficient lymphocytes through cross-correction from the engrafted ADA-replete donor cells. Thus, ADA-deficient SCID is unique in its responses to nonmyeloablative bone marrow transplantation, which has implications for clinical bone marrow transplantation or gene therapy.

Genetically enhanced T lymphocytes and the intensive care unit

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Tat, Tiberiu; Li, Huming; Constantinescu, Catalin-Sorin; Onaciu, Anca; Chira, Sergiu; Osan, Ciprian; Pasca, Sergiu; Petrushev, Bobe; Moisoiu, Vlad; Micu, Wilhelm-Thomas; Berce, Cristian; Tranca, Sebastian; Dima, Delia; Berindan-Neagoe, Ioana; Shen, Jianliang; Tomuleasa, Ciprian; Qian, Liren

2018-01-01

Chimeric antigen receptor-modified T cells (CAR-T cells) and donor lymphocyte infusion (DLI) are important protocols in lymphocyte engineering. CAR-T cells have emerged as a new modality for cancer immunotherapy due to their potential efficacy against hematological malignancies. These genetically modified receptors contain an antigen-binding moiety, a hinge region, a transmembrane domain, and an intracellular costimulatory domain resulting in lymphocyte T cell activation subsequent to antigen binding. In present-day medicine, four generations of CAR-T cells are described depending on the intracellular signaling domain number of T cell receptors. DLI represents a form of adoptive therapy used after hematopoietic stem cell transplant for its anti-tumor and anti-infectious properties. This article covers the current status of CAR-T cells and DLI research in the intensive care unit (ICU) patient, including the efficacy, toxicity, side effects and treatment. PMID:29662667

Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia

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Bo Cai

2016-11-01

Full Text Available Abstract Background Elderly patients with relapsed and refractory acute lymphoblastic leukemia (ALL have poor prognosis. Autologous CD19 chimeric antigen receptor-modified T (CAR-T cells have potentials to cure patients with B cell ALL; however, safety and efficacy of allogeneic CD19 CAR-T cells are still undetermined. Case presentation We treated a 71-year-old female with relapsed and refractory ALL who received co-infusion of haplo-identical donor-derived CD19-directed CAR-T cells and mobilized peripheral blood stem cells (PBSC following induction chemotherapy. Undetectable minimal residual disease by flow cytometry was achieved, and full donor cell engraftment was established. The transient release of cytokines and mild fever were detected. Significantly elevated serum lactate dehydrogenase, alanine transaminase, bilirubin and glutamic-oxalacetic transaminase were observed from days 14 to 18, all of which were reversible after immunosuppressive therapy. Conclusions Our preliminary results suggest that co-infusion of haplo-identical donor-derived CAR-T cells and mobilized PBSCs may induce full donor engraftment in relapsed and refractory ALL including elderly patients, but complications related to donor cell infusions should still be cautioned. Trial registration Allogeneic CART-19 for Elderly Relapsed/Refractory CD19+ ALL. NCT02799550

Age-related variation in the DNA-repair synthesis after UV-C irradiation in unstimulated lymphocytes of healthy blood donors

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Kovacs, E.; Weber, W.; Mueller, H.

1984-01-01

UV-C light-induced DNA-repair synthesis was studied in unstimulated lymphocytes of 51 healthy blood donors aged between 17 and 74 years. The evaluation included (1) the spontaneous DNA-synthesis in unirradiated lymphocytes with and without hydroxyurea, (2) the DNA-repair synthesis in lymphocytes irradiated with UV-light. The interindividual variation was significantly higher than the methodological variation ascertained in 24 persons in whom 2 determinations were carried out. In blood donors aged between 17 and 39 years, the spontaneous DNA synthesis, both with and without hydroxyurea, was significantly lower than in older individuals. The DNA-repair synthesis was dependent on the dose of UV-C light between 2 and 16 J/m 2 . There were no significant differences in DNA-repair synthesis in the age range 17-74 years. The variations in rate of DNA-repair synthesis were wider in older (44-74 years), than in younger individuals. (orig.)

Variability in the level of UV induced DNA damage in lymphocytes from unexposed and exposed to pesticides donors from Hungary

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Cebulska-Wasilewska, A.; Dyga, W.; Krasnowolski, S.; Florjan, D.; Siffel, C.

2000-01-01

In this study we investigated whether agrochemicals, which are in use among the farmers could show any genotoxic character in lymphocytes, change the radiosensitivity of cells or efficiency of their repair capacities. The potential influence of pesticides on the level of DNA damage and variation of the DNA damage repair capacity were investigated by use of the single cell gel-electrophoresis method (SCGE), also known as the Comet assay. Human lymphocytes were isolated from whole blood samples collected from 139 donors from Hungary and transported in dry ice for analysis into DERB laboratory. Among the donors 63 persons were treated as the reference group (no occupational exposure), average age was 45.1. Non exposed group consist mostly from males (86%) among that group 52 % of donors were recent or former smokers. The other 59 donors were occupationally exposed to pesticides, (61 % of males) average age was 42.5 years, and among them 56% were recent or former smokers. Additionally we have separated 17 males donors who was highly exposed to pesticides. Their average age was 42.3 y. and 88 % of them were recent or former smokers. Previously cryopreserved lymphocytes were defrosted and viability of the cells and DNA damage in lymphocytes prior to irradiation was investigated. It was found that due to cryopreservation or transportation process, the letter one was significantly lowered. Then cells were split into four parts. In one part SCGE was performed immediately, the other three were exposed to 6 J/m 2 of UVC radiation. In order to evaluate capacity of repair process, the levels of DNA damage were estimated immediately after exposure and after two hours of the incubation in presence or absence of phytohemoglutinin (PHA) cells division-stimulating agent. The same procedures were performed on the samples from people unexposed and exposed to pesticides. The majority of samples in both groups revealed much lower slope of curve describing increasing damage during

Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4+CD25+Foxp3+ regulatory T cells and down-regulates cardiac allograft rejection

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Zheng, De-Hua; Dou, Li-Ping; Wei, Yu-Xiang; Du, Guo-Sheng; Zou, Yi-Ping; Song, Ji-Yong; Zhu, Zhi-Dong; Cai, Ming; Qian, Ye-Yong; Shi, Bing-Yi

2010-01-01

Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-γ by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4 + CD25 high Foxp3 + regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

Biodistribution of radiolabeled lymphocytes

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Fawwaz, R.A.; Oluwole, S.; Wang, T.S.; Kuromoto, N.; Iga, C.; Hardy, M.A.; Alderson, P.O.

1985-01-01

Factors that might affect the biodistribution and clinical utility of radiolabeled lymphocytes were evaluated in experimental animals. Indium-111 (In-111) labeled lymphocytes obtained from peripheral blood, lymph node, or spleen were found in significant amounts in the lymphoid tissues of Lewis rats as early as 3 hours after infusion. A progressive increase in nodal activity with concomitant fall of activity in other organs followed, indicating active recirculation of the lymphocytes. In vitro irradiation of the In-111 labeled lymphocytes resulted in no detectable lymphocyte recirculation and/or reduced localization in lymphoid tissue. Splenectomized animals and those sensitized to an organ allograft before cell infusion showed increased activity in their bone marrow. These results suggest that the source of the injected cells, cell irradiation dose level and host sensitization should be considered when radiolabeled lymphocytes are being prepared for use in clinical diagnosis and therapy

Induction of MHC-mismatched Mouse Lung Allograft Acceptance with Combined Donor Bone Marrow: Lung Transplant using a 12-Hour Nonmyeloablative Conditioning Regimen

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Vulic, Ante; Panoskaltsis-Mortari, Angela; McDyer, John F.; Luznik, Leo

2016-01-01

Background Despite broad and intense conventional immunosuppression, long-term survival after lung transplantation lags behind that for other solid organ transplants, primarily because of allograft rejection. Therefore, new strategies to promote lung allograft acceptance are urgently needed. The purpose of the present study was to induce allograft tolerance with a protocol compatible with deceased donor organ utilization. Methods Using the MHC-mismatched mouse orthotopic lung transplant model, we investigated a conditioning regimen consisting of pretransplant T cell depletion, low dose total body irradiation and posttransplant (donor) bone marrow and splenocyte infusion followed by posttransplantation cyclophosphamide (PTTT-PTB/PTCy). Results Our results show that C57BL/6 recipients of BALB/c lung allografts undergoing this complete short-duration nonmyeloablative conditioning regimen had durable lung allograft acceptance. Mice that lacked 1 or more components of this regimen exhibited significant graft loss. Mechanistically, animals with lung allograft acceptance had established higher levels of donor chimerism, lymphocyte responses which were attenuated to donor antigens but maintained to third-party antigens, and clonal deletion of donor-reactive host Vβ T cells. Frequencies of Foxp3+ T regulatory cells were comparable in both surviving and rejected allografts implying that their perturbation was not a dominant cell-regulatory mechanism. Donor chimerism was indispensable for sustained tolerance, as evidenced by acute rejection of allografts in established chimeric recipients of PTTT-PTB/PTCy following a chimerism-ablating secondary recipient lymphocyte infusion. Conclusion Together, these data provide proof-of-concept for establishing lung allograft tolerance with tandem donor bone marrow transplantation (BMT) using a short-duration nonmyeloablative conditioning regimen and PTCy. PMID:27861294

Dicentric and ring chromosome yield in lymphocytes of in vitro irradiated blood of various donors

International Nuclear Information System (INIS)

Kubelka, D.; Horvat, D.; Svilicic, N.

1988-01-01

Results of in vitro irradiation of blood of nine human donors are presented. The blood irradiation doses were 0.1, 0.2, 0.5, 1, 2, and 3 Gy of X-ray exposure. The X-ray tube voltage was 250 kV. After irradiation, the standard 48-hours in vitro cultivation of lymphocytes was performed, with addition of BrdU, which enabled chromosome aberration analysis during the first in vitro division. Based on dicentric and ring yield, the dose-response curve has been generated for each donor. The tests on difference significance of obtained coefficients indicate there is no need for summary presentation of results. (author)

Frequency analysis of cytotoxic T lymphocyte precursors in search for donors in bone marrow transplantation

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Cukrova, V.; Dolezalova, L.; Loudova, M.; Matejkova, E.; Korinkova, P.; Lukasova, M.; Stary, J.

1995-01-01

The usefulness of cytotoxic T lymphocytes (CTLp) frequency analysis in the search for donors in bone marrow transplantation was studied. The frequency of anti-recipient CTLp was approached by limiting dilution assay in HLA matched unrelated, HLA partially matched related and HLA genotypically identical donors. The majority of patients examined were affected with different hematological malignancies. Allo-reactive CTLp recognizing non-HLA gene products were not detected in pre-transplant examination of two pairs of HLA identical siblings. However, an increase incidence of allo-specific CTLp was identified in HLA matched mixed lymphocyte culture (MLC) negative unrelated pairs. Thus, CTLp assay allowed to the residual Class I incompatibilities that remained hidden in standard serotyping. In two matched unrelated pairs with high pretranslant CTLp frequency the severe acute graft-versus-host diseases developed after bone marrow transplantation. Examination of other relatives in patients lacking an HLA identical sibling showed the importance of Class I incompatibility for CTLp generation as well. The lack of correlation between CTLp frequency and HLA-D disparity could suggest that Class II antigens do not participate in CTLp induction. With one exception we had good correlation between MLC and DNA analysis of Class II antigens demonstrating that MLC gives interpretable results even in unrelated pairs. Our results demonstrate the significance of CTLp frequency assay in detection of residual Class I incompatibilities in matched unrelated pairs and in assessment of Class I compatibility in related pairs. For that it should be used in the final selection of bone marrow transplantation donors. (author)

Transient hemolysis due to anti-D and anti-A1 produced by engrafted donor's lymphocytes after allogeneic unmanipulated haploidentical hematopoietic stem cell transplantation.

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Bailén, Rebeca; Kwon, Mi; Pérez-Corral, Ana María; Pascual, Cristina; Buño, Ismael; Balsalobre, Pascual; Serrano, David; Gayoso, Jorge; Díez-Martín, José Luis; Anguita, Javier

2017-10-01

Development of de novo alloantibodies against recipient's red blood cell (RBC) antigens by engrafted donor's lymphocytes is a known phenomenon in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). This situation is usually clinically insignificant. We report a case of early clinically relevant hemolytic anemia in a blood group A 1 D+ patient, due to a limited production of anti-D and anti-A 1 produced by nonpreviously sensitized newly engrafted donor's immune system. A 31-year-old Caucasian woman, blood group A 1 , D+, with Hodgkin's lymphoma, received an unmanipulated haploidentical allogeneic peripheral blood HSCT after a nonmyeloablative conditioning regimen. Donor blood group was A 2 B, D-. The patient had an uneventful course until Day +34, when she developed clinically significant hemolytic anemia with a positive direct antiglobulin test. Anti-D and anti-A 1 produced by the donor-engrafted lymphocytes were detected both in serum and in eluate. The hemolysis produced an accelerated group change, turning the patient's ABO group into A 2 B 2 weeks after the detection of the alloantibodies. As the residual patient's RBCs progressively disappeared, anti-D and anti-A 1 production decreased and were not detected in serum by Day +41. This case illustrates that de novo alloantibody production against ABO and D antigens by the newly engrafted donor's lymphocytes can occasionally cause clinically significant anemia. To our knowledge, this is the first case reported of clinically significant hemolytic anemia due to a transient anti-D anti-A 1 alloimmunization after T-cell-repleted haploidentical HSCT. © 2017 AABB.

CD4 T lymphocyte counts in patients undergoing splenectomy during living donor liver transplantation.

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Natsuda, Koji; Eguchi, Susumu; Takatsuki, Mistuhisa; Soyama, Akihiko; Hidaka, Masaaki; Hara, Takanobu; Kugiyama, Tota; Baimakhanov, Zhassulan; Ono, Shinichiro; Kitasato, Amane; Fujita, Fumihiko; Kanetaka, Kengo; Kuroki, Tamotsu

2016-02-01

The role of splenectomy in increasing the CD4-positive T lymphocyte counts (hereafter: CD4 counts) and the CD4 to CD8 ratio have not yet been fully investigated, especially in the case of HIV-positive patients undergoing liver transplantation (LT). The change in the total lymphocyte counts of 32 patients who underwent one-stage splenectomy with living donor (LD) LT with (n=13) or without rituximab (RTX, n=19) therapy were examined to validate our cohort of ABO-incompatible LDLT with RTX. Subsequently, perioperative changes in CD4 counts and the CD 4 to CD8 ratio were measured in 13 patients who underwent ABO-incompatible LDLT/RTX with splenectomy. (1) The administration of RTX did not significantly affect the total lymphocyte counts of patients after LDLT/splenectomy in any of the observation periods. (2) The CD4 counts were significantly higher at 2years after LDLT in comparison to the perioperative CD4 counts but not within the 3-month period (p=0.039). The CD4/CD8 ratio gradually decreased after LDLT/splenectomy under RTX treatment. An immediate increase in the CD4 counts therefore cannot be expected after LDLT with splenectomy. The total lymphocyte and CD4 counts were rather stable in the peritransplant period even in ABO incompatible LDLT with RTX. Copyright © 2015 Elsevier B.V. All rights reserved.

Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells and down-regulates cardiac allograft rejection

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Zheng, De-Hua [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China); Dou, Li-Ping [Department of Hematology, Chinese PLA General Hospital, No. 28 Fu-Xing Road, Beijing 100853 (China); Wei, Yu-Xiang; Du, Guo-Sheng; Zou, Yi-Ping; Song, Ji-Yong; Zhu, Zhi-Dong; Cai, Ming; Qian, Ye-Yong [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China); Shi, Bing-Yi, E-mail: shibingyi@medmail.com.cn [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China)

2010-05-14

Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-{gamma} by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4{sup +}CD25{sup high}Foxp3{sup +} regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

Variability in the susceptibility to UV induced DNA damage and repair capacity observed in lymphocytes from unexposed and exposed to pesticides Polish donors

International Nuclear Information System (INIS)

Cebulska-Wasilewska, A.; Dyga, W.; Drag, Z.

2000-01-01

The aim of this study was to find out whether occupational exposure to pesticides may affect the individual susceptibility to the induction of the DNA damage by genotoxic agents. Differences in sensitivity of human lymphocytes to UV and variability of the DNA damage repair capacity were investigated by use of the single cell gel-electrophoresis method (SCGE), also known as the Comet assay. Human lymphocytes were isolated from whole blood samples collected from 100 male donors from Poland. Among the donors 50 males were treated as reference group (no occupational exposure), average age was 38.7, and among them 68 % were recent or former smokers, the other 50 males were occupationally exposed to pesticides, average age was 39.1, and among them 58 % were recent or former smokers. Previously cryopreserved lymphocytes were defrosted and viability of the cells and DNA damage in lymphocytes prior to any in vitro studies was investigated. On the average the DNA damage detected in lymphocytes and expressed as the mean Comet tail moment was significantly higher in the exposed group than in the reference group. In order to evaluate sensitivity of human lymphocytes to UV and variability of the DNA damage repair capacity, defrosted cells were irradiated with 6 J/m 2 of UVC radiation and the DNA damages were estimated immediately after exposure to UV and after two hours of the incubation in presence or absence of phytohemoglutinin (PHA) cells division-stimulating agent. The same procedures were performed on the samples from aloud exposed an unexposed to pesticides. Comet assay detectable levels of the DNA damage were increasing during the incubation of cells following UVC exposure. Average levels of damage detected after incubation in presence of PHA of exposed to UV lymphocytes were lower than without PHA. In presence of phytohemoglutinin (PHA) results showed statistically significant (p=0.001) repair of the DNA damage for both reference and exposed group. No difference due to

DNA damages induced in human lymphocytes by UV or X-rays and repair capacities of healthy donors and skin cancer patients

International Nuclear Information System (INIS)

Cebulska-Wasilewska, A.; Dyga, W.; Budzanowska, E.

1999-01-01

The aim of this study was to compare variation in the individual susceptibility of various donors to the induction of the DNA damage by genotoxic agents and their cellular capabilities to repair induced damage. DNA damages induced by UV or X-rays in lymphocytes and cellular repair capability of healthy donors and persons bearing various categories of skin cancer cells were investigated. Fresh blood was collected by venipuncture from 35 individuals (including nine prior to skin cancer treatment). All cancer patients were nonsmoking males, however 42.3 % of them were former smokers. All healthy donors were also males, an average age was 38.6 y and among them 68% were recent or former smokers. Immediately after collecting samples, lymphocytes were isolated and stored at -70 o C for further studies in vitro. Previously cryopreserved lymphocytes were defrosted and viability of the cells was investigated. The single cell gel electrophoresis assay (SCGE), known as a Comet assay, was performed in defrozen lymphocytes to evaluate individual DNA damage levels presented in lymphocytes at the time of sample's collection. To compare individual susceptibility to the induction of DNA damage by UV and ionizing radiation, lymphocytes were exposed to dose of 6 J/m 2 of UV or 2 Gy of X-rays and DNA damages were detected again with an application of the Comet assay. Additionally, to study variation in the individuals cellular capability to repair damages induced, prior to the DNA damage analysis an incubation of cells exposed was also done in presence or absence of phytohemagglutinin (cell divisions processes starting agent). Results showed in untreated lymphocytes of skin cancer patients significantly higher than in the reference group levels of the DNA damages. Significantly different responses to UV and significantly lower capabilities to repair UV induced damage in skin cancer patients were observed. On the average, no differences between reference group and skin cancer patients

Effects of radiolabelled monoclonal antibody infusion on blood leukocytes in cancer patients

International Nuclear Information System (INIS)

Gridley, D.S.; Slater, J.M.; Stickney, D.R.

1990-01-01

This study was undertaken to investigate the effects of a single infusion of radiolabelled murine monoclonal antibody (MAb) on peripheral blood leukocytes in cancer patients. Eleven patients with disseminated colon cancer, malignant melanoma, or lung adenocarcinoma were infused with 111In-labelled anti-ZCE 025, anti-p97 type 96.5c, or LA 20207 MAb, respectively. Blood samples were obtained before infusion, immediately after infusion (1 hr), and at 4 and 7 days postinfusion. Flow cytometry analysis of CD3+, CD4+, CD8+, CD16+, and CD19+ lymphocytes showed increasing CD4:CD8 ratios in seven patients after infusion. This phenomenon was not restricted to antibody subclass or to type of cancer. Two of the remaining patients exhibited a marked post-infusion increase in CD8+ cells. In all three patients with malignant melanoma, decreasing levels of CD16+ lymphocytes were noted after infusion and natural killer cell cytotoxicity showed fluctuations which paralleled the changes in the CD16+ subpopulation. Oxygen radical production by phagocytic cells was markedly affected in three subjects. These results suggest that a single infusion of radiolabelled murine MAb may alter the balance of critical lymphocyte subpopulations and modulate other leukocyte responses in cancer patients

The In Vivo Granulopoietic Response to Dexamethasone Injection Is Abolished in Perforin-Deficient Mutant Mice and Corrected by Lymphocyte Transfer from Nonsensitized Wild-Type Donors

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Pedro Xavier-Elsas

2015-01-01

Full Text Available Exogenously administered glucocorticoids enhance eosinophil and neutrophil granulocyte production from murine bone-marrow. A hematological response dependent on endogenous glucocorticoids underlies bone-marrow eosinophilia induced by trauma or allergic sensitization/challenge. We detected a defect in granulopoiesis in nonsensitized, perforin-deficient mice. In steady-state conditions, perforin- (Pfp- deficient mice showed significantly decreased bone-marrow and blood eosinophil and neutrophil counts, and colony formation in response to GM-CSF, relative to wild-type controls of comparable age and/or weight. By contrast, peripheral blood or spleen total cell and lymphocyte numbers were not affected by perforin deficiency. Dexamethasone enhanced colony formation by GM-CSF-stimulated progenitors from wild-type controls, but not Pfp mice. Dexamethasone injection increased bone-marrow eosinophil and neutrophil counts in wild-type controls, but not Pfp mice. Because perforin is expressed in effector lymphocytes, we examined whether this defect would be corrected by transferring wild-type lymphocytes into perforin-deficient recipients. Short-term reconstitution of the response to dexamethasone was separately achieved for eosinophils and neutrophils by transfer of distinct populations of splenic lymphocytes from nonsensitized wild-type donors. Transfer of the same amount of splenic lymphocytes from perforin-deficient donors was ineffective. This demonstrates that the perforin-dependent, granulopoietic response to dexamethasone can be restored by transfer of innate lymphocyte subpopulations.

The devil is in the details: retention of recipient group A type 5 years after a successful allogeneic bone marrow transplant from a group O donor.

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Cooling, Laura L W; Herrst, Michelle; Hugan, Sherri L

2018-01-01

ABO-incompatible (ABOi) hematopoietic stem cell transplants (HSCTs) can present challenges in the blood bank. During transplantation, patients receive components that are ABO-compatible with both the donor graft and recipient; this practice can strain group O red blood cell (RBC) inventories.1 In addition, there are risks for acute hemolysis at the time of infusion and in the early post-transplant period.1,2 In ABO major-incompatible bone marrow HSCTs, which contain significant quantities of donor RBCs that are ABOi with recipient plasma, it is common to perform a RBC depletion of the bone marrow in an effort to minimize hemolysis at the time of infusion.2 Furthermore, patients with high-titer ABO antibodies may undergo a prophylactic, pre-transplant plasma exchange to further reduce the risk of acute hemolysis, delayed RBC engraftment, and pure RBC aplasia.2-4 ABO minor-incompatible HSCTs, in which donor plasma is ABOi with the recipient, have less risk for hemolysis at the time of infusion but can result in transient hemolysis approximately 10-21 days post-transplant, especially in patients undergoing nonmyeloablative HSCT and/or patients who have not received methotrexate for graft-versus-host-disease (GVHD) prophylaxis.1-4 In these patients, viable donor B-lymphocytes in the graft may expand and produce ABO antibodies capable of hemolyzing patient RBCs.

Organ distribution of 111In-oxine labeled lymphocytes in normal subjects and in patients with chronic lymphocytic leukemia and malignant lymphoma

International Nuclear Information System (INIS)

Matsuda, Shin; Uchida, Tatsumi; Yui, Tokuo; Kariyone, Shigeo

1982-01-01

T and B lymphocyte survival and organ distribution were studied by using 111 In-oxine labeled autologous lymphocytes in 3 normal subjects, 3 patients with chronic lymphocytic leukemia (CLL) and 9 with malignant lymphoma (ML).FDisappearance curves of the labeled lymphocytes showed two exponential components in all cases. The half time of the first component was within 1 hour in all cases. That of the second one was 50.7 +- 6.4 hours for all lymphocytes, 52.0 +- 5.5 hours for T lymphocytes and 31.6 +- 4.9 hours for B lymphocytes in normal subjects, 192.6 hours for T-CLL and 57.7 +- 46.9 hours for B-CLL, and 60.2 +- 30.7 hours for T cell type of malignant lymphoma (T-ML) and 63.7 +- 24.5 hours for B cell type of malignant lymphoma (B-ML). These data might suggest that all lymphocyte disappearance curve reflected T lymphocyte disappearance curve chiefly, and the half time of B lymphocytes was shorter than that of T lymphocytes. In the T-CLL, the half time of the second component prolonged extremely in comparison with that of normal T lymphocytes. The labeled cells were accumulated in the lungs, spleen and liver immediately after the infusion, then in the spleen most remarkably 1 hour after the infusion in all cases. The radioactivity over the bone marrow was observed from 1 hour in all cases and that of lymph nodes were first noticed 18 hours after the infusion in T-CLL and T-ML, 68 hours in B-CLL but were not noticed in normal subjects and B-ML. The recovery of labeled cells in the blood was 28.5 +- 7.9% for all lymphocytes, 19.7 +- 1.9% for T lymphocytes and 11.0 +- 5.1% for B lymphocytes in normal subjects, 25.8 +- 1.6% for CLL, and 17.6 +- 11.0% for T-ML, 7.7 +- 5.2% for B-ML, respectively. (J.P.N.)

Responses to recipient and donor B cells by genetically donor T cells from human haploidentical chimeras

International Nuclear Information System (INIS)

Schiff, S.; Sampson, H.; Buckley, R.

1986-01-01

Following administration of haploidentical stem cells to infants with severe combined immunodeficiency (SCID), mature T cells of donor karyotype appear later in the recipient without causing graft-versus-host disease. To investigate the effect of the host environment on the responsiveness of these genetically donor T cells, blood B and T lymphocytes from 6 SCID recipients, their parental donors and unrelated controls were purified by double SRBC rosetting. T cells were stimulated by irradiated B cells at a 1:1 ratio in 6 day cultures. Engrafted T cells of donor karyotype gave much smaller responses to irradiated genetically recipient B cells than did fresh donor T cells. Moreover, engrafted T cells of donor karyotype from two of the three SCIDs who are longest post-transplantation responded more vigorously (14,685 and 31,623 cpm) than fresh donor T cells (5141 and 22,709 cpm) to donor B cells. These data indicate that T lymphocytes which have matured from donor stem cells in the recipient microenvironment behave differently from those that have matured in the donor

Prolongation of rat heart allografts by donor-specific blood transfusion treated with ultraviolet irradiation

International Nuclear Information System (INIS)

Oluwole, S.F.; Iga, C.; Lau, H.; Hardy, M.A.

1985-01-01

The effect of donor-specific blood transfusion was compared to that of UVB-irradiated donor-specific blood transfusion on heart allograft survival in inbred rats with major histocompatibility differences. In one series ACI rats received heterotopic heart grafts from Lewis rats and 1 mL transfusion of donor-type blood at 1, 2, and 3 weeks prior to the transplantation. Fifty percent of the grafts were permanently accepted (survival greater than 200 days). Following UVB-irradiated donor-specific blood transfusion, 55% of the grafts survived indefinitely. In a mixed lymphocyte reaction ACI lymphocytes are weak responders to Lewis lymphocytes. In another series, Lewis rats received ACI hearts. Donor-specific transfusions at 1, 2, and 3 weeks prior to transplantation did not significantly alter the survival of heart allografts. Lewis lymphocytes react strongly to ACI stimulator cells in a mixed lymphocyte reaction. However, when the donor blood was UVB-irradiated prior to transfusion, the ACI allograft survival was significantly prolonged in this ACI-to-Lewis strain combination. When Lewis rats received W/F hearts following either donor-specific or UVB-irradiated donor-specific transfusions, the hearts' survival was similarly and significantly prolonged, but did not become permanent. Mixed lymphocyte reaction reveals that the stimulation index of Lewis lymphocytes against W/F lymphocytes is greater than that of ACI versus Lewis, but is less than that between Lewis responder cells against ACI stimulators

Donor T cells primed on leukemia lysate-pulsed recipient APCs mediate strong graft-versus-leukemia effects across MHC barriers in full chimeras.

Science.gov (United States)

Ghosh, Arnab; Koestner, Wolfgang; Hapke, Martin; Schlaphoff, Verena; Länger, Florian; Baumann, Rolf; Koenecke, Christian; Cornberg, Markus; Welte, Karl; Blazar, Bruce R; Sauer, Martin G

2009-04-30

Antigen-presenting cells (APCs) of host origin drive graft-versus-leukemia (GVL) effects but can also trigger life-threatening graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) across major histocompatibility complex (MHC) barriers. We show that in vitro priming of donor lymphocytes can circumvent the need of recipient-derived APCs in vivo for mediating robust GVL effects and significantly diminishes the risk of severe GVHD. In vitro, generated and expanded T cells (ETCs) mediate anti-leukemia effects only when primed on recipient-derived APCs. Loading of APCs in vitro with leukemia cell lysate, chimerism status of the recipient, and timing of adoptive transfer after HCT are important factors determining the outcome. Delayed transfer of ETCs resulted in strong GVL effects in leukemia-bearing full chimera (FC) and mixed chimera (MC) recipients, which were comparable with the GVL/GVHD rates observed after the transfer of naive donor lymphocyte infusion (DLI). Upon early transfer, GVL effects were more pronounced with ETCs but at the expense of significant GVHD. The degree of GVHD was most severe in MCs after transfer of ETCs that had been in vitro primed either on nonpulsed recipient-derived APCs or with donor-derived APCs.

Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study.

Science.gov (United States)

Cruz, Conrad Russell Y; Micklethwaite, Kenneth P; Savoldo, Barbara; Ramos, Carlos A; Lam, Sharon; Ku, Stephanie; Diouf, Oumar; Liu, Enli; Barrett, A John; Ito, Sawa; Shpall, Elizabeth J; Krance, Robert A; Kamble, Rammurti T; Carrum, George; Hosing, Chitra M; Gee, Adrian P; Mei, Zhuyong; Grilley, Bambi J; Heslop, Helen E; Rooney, Cliona M; Brenner, Malcolm K; Bollard, Catherine M; Dotti, Gianpietro

2013-10-24

Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19.CAR) are active against B-cell malignancies, but it is unknown whether allogeneic CD19.CAR T cells are safe or effective. After allogeneic hematopoietic stem cell transplantation (HSCT), infused donor-derived virus-specific T cells (VSTs) expand in vivo, persist long term, and display antiviral activity without inducing graft-vs-host disease; therefore, we determined whether donor VSTs, engineered to express CD19.CAR, retained the characteristics of nonmanipulated allogeneic VSTs while gaining antitumor activity. We treated 8 patients with allogeneic (donor-derived) CD19.CAR-VSTs 3 months to 13 years after HSCT. There were no infusion-related toxicities. VSTs persisted for a median of 8 weeks in blood and up to 9 weeks at disease sites. Objective antitumor activity was evident in 2 of 6 patients with relapsed disease during the period of CD19.CAR-VST persistence, whereas 2 patients who received cells while in remission remain disease free. In 2 of 3 patients with viral reactivation, donor CD19.CAR-VSTs expanded concomitantly with VSTs. Hence CD19.CAR-VSTs display antitumor activity and, because their number may be increased in the presence of viral stimuli, earlier treatment post-HSCT (when lymphodepletion is greater and the incidence of viral infection is higher) or planned vaccination with viral antigens may enhance disease control.

Bone marrow cells from allogeneic bone marrow chimeras inhibit the generation of cytotoxic lymphocyte responses against both donor and recipient cells

International Nuclear Information System (INIS)

Ogasawara, M.; Iwabuchi, K.; Good, R.A.; Onoe, K.

1988-01-01

When added to a mixed lymphocyte culture, bone marrow cells suppress the generation of CTL activity against H-2 Ag shared by the BM cells and the stimulator cells. These cells have been referred to as veto cells and are thought to play a role in maintaining self-tolerance. We analyzed the H-2 specificity of the suppression expressed by the veto cells from H-2 incompatible bone marrow chimeras, because lymphocytes of such chimeras had been shown to be tolerant to both donor and recipient Ag when tested by CTL responses. We found that the bone marrow cells of such chimeras which were featured by non-T and non-B cell characteristics inhibited the generation of CTL directed against either donor or recipient Ag, but not against third-party Ag. These observations suggest that in allogeneic chimeras the veto or veto-like cells alter the inhibitory specificity exhibited in the recipient microenvironment and indicate that these cells are directly involved in the induction and maintenance of self-tolerance

Immunostimulation by cytomegalovirus (CMV): helper T cell-dependent activation of immunoglobulin production in vitro by lymphocytes from CMV-immune donors

International Nuclear Information System (INIS)

Yachie, A.; Tosato, G.; Straus, S.E.; Blaese, R.M.

1985-01-01

Cytomegalovirus (CMV) is the cause of a number of different diseases ranging from self-limited benign infections in healthy adults to life threatening illnesses among immunocompromised hosts and newborns. Suppression of cell-mediated immunity is often found in cases of acute CMV infection, and in addition, the virus may also be a potent stimulant of lymphoid cells in vivo. The authors studied cellular proliferation and immunoglobulin (Ig) production induced by CMV to determine its effect on human lymphocytes in vitro. The CMV that was added to cultures of lymphocytes from CMV-seronegative donors failed to induce either significant cellular proliferation or Ig production. By contrast, CMV-stimulated cultures from CMV-seropositive donors induced both prominent cellular proliferation and Ig production. B cell differentiation into Ig-secreting cells required the presence of T cells, and this T cell help was sensitive to irradiation with 2000 rad and to treatment with cyclosporin A. When T cells were depleted of OKT4+ cells with monoclonal antibody and complement, the co-cultured B cells failed to produce Ig, whereas the depletion of OKT8+ cells had no effect on the Ig-secreting cell response. Inactivation of CMV before culture did not result in a reduction of either cellular proliferation or Ig production. Thus, infection of target cells is not required for in vitro lymphocyte activation by CMV. These results demonstrate that CMV is a potent activator of B cells inducing Ig production in vitro, and that this process requires the presence of virus-specific memory T cells

Postoperative neutrophil-to-lymphocyte ratio of living-donor liver transplant: Association with graft size

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Hironori Hayashi

2016-04-01

Full Text Available Issues related to small-for-size grafts in living donor liver transplantation (LDLT are highly important. The neutrophil lymphocyte ratio (NLR has been reported to be an inexpensive index of systemic inflammation for various diseases. We retrospectively evaluated the relationship between NLR and clinical course of 61 adult LDLT recipients in our institute until post-operative day 14. Patients were classified into two groups based on the graft volume divided by standard liver volume, as over 35% of graft volume divided by standard liver volume (GV/SLV (Group L; n = 55 and under 35% of GV/SLV (Group S; n = 6. No differences were seen in background of the patients between the two groups. Also, absolute neutrophil, lymphocyte and platelet counts in both the groups showed no significant differences. In contrast, the NLR between the groups differed significantly from post-operative day 3 to 10, being higher in the Group S. In addition, the incidence of prolonged hyperbilirubinemia and small for size graft syndrome differed significantly between the two groups. Therefore, the elevation of post-operative NLR in the smaller graft group reflect suggestive pathophysiology of endothelial injuries that related to small for size graft syndrome in LDLT.

Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial.

Science.gov (United States)

Strug, Michael R; Su, Renwei; Young, James E; Dodds, William G; Shavell, Valerie I; Díaz-Gimeno, Patricia; Ruíz-Alonso, Maria; Simón, Carlos; Lessey, Bruce A; Leach, Richard E; Fazleabas, Asgerally T

2016-07-01

Does a single intrauterine infusion of human chorionic gonadotropin (hCG) at the time corresponding to a Day 3 embryo transfer in oocyte donors induce favorable molecular changes in the endometrium for embryo implantation? Intrauterine hCG was associated with endometrial synchronization between endometrial glands and stroma following ovarian stimulation and the induction of early decidual markers associated with stromal cell survival. The clinical potential for increasing IVF success rates using an intrauterine hCG infusion prior to embryo transfer remains unclear based on previously reported positive and non-significant findings. However, infusion of CG in the non-human primate increases the expression of pro-survival early decidual markers important for endometrial receptivity, including α-smooth muscle actin (α-SMA) and NOTCH1. Oocyte donors (n=15) were randomly assigned to receive an intrauterine infusion of 500 IU hCG (n=7) or embryo culture media vehicle (n=8) 3 days following oocyte retrieval during their donor stimulation cycle. Endometrial biopsies were performed 2 days later, followed by either RNA isolation or tissue fixation in formalin and paraffin embedding. Reverse transcription of total RNA from endometrial biopsies generated cDNA, which was used for analysis in the endometrial receptivity array (ERA; n = 5/group) or quantitative RT-PCR to determine relative expression of ESR1, PGR, C3 and NOTCH1. Tissue sections were stained with hematoxylin and eosin followed by blinded staging analysis for dating of endometrial glands and stroma. Immunostaining for ESR1, PGR, α-SMA, C3 and NOTCH1 was performed to determine their tissue localization. Intrauterine hCG infusion was associated with endometrial synchrony and reprograming of stromal development following ovarian stimulation. ESR1 and PGR were significantly elevated in the endometrium of hCG-treated patients, consistent with earlier staging. The ERA did not predict an overall positive impact of

MAJOR AND LYMPHOCYTE POPULATIONS OF HUMAN PERIPHERAL BLOOD LYMPHOCYTES AND THEIR REFERENCE VALUES, AS ASSAYED BY MULTI-COLOUR CYTOMETRY

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S. V. Khaidukov

2009-01-01

Full Text Available Abstract. Determination of lymphocyte subpopulations and their phenotypes is an important diagnostic feature, in order to elucidate some disturbances connected with immune system functioning. However, insufficient data are obtained when analyzing only major populations of peripheral lymphocytes. In order to perform clinical diagnostics, the data about minor lymphocytic populations and activated cellular pools seem to be more pertinent.Studies of peripheral blood cell subpopulations of healthy donors performed in different Russian regions allowed to assess quantitative distribution intervals for both major and minor immune cell subpopulations in humans. The results obtained, as compared with data from literature, provide an evidence for similar reference intervals for main immune cell subpopulations in healthy donors, independent on their habitation area.Present work has resulted into development of algorithms for cytometric studies and generation of certain panels of monoclonal antibodies enabling evaluation of all main lymphocyte subpopulations, as well as their minor subsets participating in emerging immune response. The distribution intervals have been estimated for such minor subpopulations, as B1- and B2-lymphocytes, memory B-cells, γδ- and αβT-cells, regulatory and naїve T-cells, cytotoxic and secretory NK-cell polupations.The results of present study, while been performed with peripheral blood of healthy donors, may provide a basis of reference values when studying subpopulation profile of immune cells.

Biological dosimetry of heavy ion induced chromosome lesions in human peripheral blood lymphocytes of different healthy donors

International Nuclear Information System (INIS)

Groesser, T.; Rydberg, B.; Ritter, S.; Hessel, P.; Kraft, G.

2003-01-01

Full text: In the presented work the effect of sparsely ionizing X-rays or densely ionizing carbon ions on human peripheral blood lymphocytes (PBL) from healthy donors regarding the fluctuations in radiosensitivity within the same donor and between different donors was examined. This is not only of special interest for physicians and radiation biologists but also plays an important role in space flights because such fluctuations in the radiation response would reduce the accuracy of the biological dosimetry. In this context, biological changes in the aberration rate of metaphase cells as well as in cell proliferation and the mitotic index were measured. Since chromosome analyses are presently the most powerful biological method to quantify radiation exposure, the study focused on the measurements of chromosome aberrations in first-metaphase cells. The investigations showed that the aberration yield after 400 MeV/u carbon ion exposure (LET = 11 keV/micrometer) was higher than after X-irradiation. The aberration yield in first mitotic cells as well as the proportion of damaged cells was stable over the examined period up to 72h after exposure to X-rays or carbon ions. Furthermore, the results of the presented work revealed pronounced fluctuations in the measured parameters in the same donor as well as between different donors. If the dose effect curves of such parameters were used as calibration curves for radiation dose assessment these fluctuations will decrease their potential of use for dose estimation. This demonstrates that a general calibration curve for dose assessment might not be sufficiently precise and individual calibration curves might improve the accuracy of the biological dosimetry

Bone marrow-derived T lymphocytes responsible for allograft rejection

International Nuclear Information System (INIS)

Senjanovic, M.; Marusic, M.

1984-01-01

Lethally irradiated mice reconstituted with syngeneic bone marrow cells were grafted with allogeneic skin grafts 6-7 weeks after irradiation and reconstitution. Mice with intact thymuses rejected the grafts whereas the mice thymectomized before irradiation and reconstitution did not. Thymectomized irradiated mice (TIR mice) reconstituted with bone marrow cells from donors immune to the allografts rejected the grafts. Bone marrow cells from immunized donors, pretreated with Thy 1.2 antibody and C', did not confer immunity to TIR recipients. To determine the number of T lymphocytes necessary for the transfer of immunity by bone marrow cells from immunized donors, thymectomized irradiated mice were reconstituted with nonimmune bone marrow cells treated with Thy 1.2 antibody and C' and with various numbers of splenic T lymphocytes from nonimmune and immune donors. Allogeneic skin graft rejection was obtained with 10(6) nonimmune or 10(4) immune T cells. The effect of immune T cells was specific: i.e., immune T cells accelerated only rejection of the relevant skin grafts whereas against a third-party skin grafts acted as normal T lymphocytes

Monitoring of genotoxic effects in lymphocytes of people exposed to pesticides

International Nuclear Information System (INIS)

Panek, A.; Marcos, R.; Cebulska-Wasilewska, A.

2002-01-01

The aim of this study was to assess the potential genotoxic risk of occupational exposure to pesticides. The DNA damage and the repair capacities of lymphocytes, in four groups of the people of various countries were assessed by the use of single cell gel electrophoresis (SCGE) also known as the Comet assay. The results from the analysis performed in the Spanish group are presented in this paper. Statistical analysis of the results shows a slightly higher level of the DNA damage in the untreated lymphocytes of donors from the group exposed to pesticides; however, only for donors below 30 years old are these differences significant (p<0.05). Although, comparison of the efficiency of the UV-C induced dimmers excision process did not indicate differences between exposed and referent groups, though lymphocytes for donors exposed to pesticides have shown a statistically lower repair rate (p<0.01) than lymphocytes from the unexposed group. (author)

Evaluation of radioinduced damage and repair capacity in blood lymphocytes of breast cancer patients

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P.A. Nascimento

2001-02-01

Full Text Available Genetic damage caused by ionizing radiation and repair capacity of blood lymphocytes from 3 breast cancer patients and 3 healthy donors were investigated using the comet assay. The comets were analyzed by two parameters: comet tail length and visual classification. Blood samples from the donors were irradiated in vitro with a 60Co source at a dose rate of 0.722 Gy/min, with a dose range of 0.2 to 4.0 Gy and analyzed immediately after the procedure and 3 and 24 h later. The basal level of damage and the radioinduced damage were higher in lymphocytes from breast cancer patients than in lymphocytes from healthy donors. The radioinduced damage showed that the two groups had a similar response when analyzed immediately after the irradiations. Therefore, while the healthy donors presented a considerable reduction of damage after 3 h, the patients had a higher residual damage even 24 h after exposure. The repair capacity of blood lymphocytes from the patients was slower than that of lymphocytes from healthy donors. The possible influence of age, disease stage and mutations in the BRCA1 and BRCA2 genes are discussed. Both parameters adopted proved to be sensitive and reproducible: the dose-response curves for DNA migration can be used not only for the analysis of cellular response but also for monitoring therapeutic interventions. Lymphocytes from the breast cancer patients presented an initial radiosensitivity similar to that of healthy subjects but a deficient repair mechanism made them more vulnerable to the genotoxic action of ionizing radiation. However, since lymphocytes from only 3 patients and 3 normal subjects were analyzed in the present paper, additional donors will be necessary for a more accurate evaluation.

TH1/TH2 cytokines and soluble CD30 levels in kidney allograft patients with donor bone marrow cell infusion.

Science.gov (United States)

Solgi, G; Amirzagar, A A; Pourmand, G; Mehrsai, A R; Taherimahmoudi, M; Baradaran, N; Nicknam, M H; Ebrahimi Rad, M R; Saraji, A; Asadpoor, A A; Moheiydin, M; Nikbin, B

2009-09-01

We investigated the relevance of donor bone marrow cell infusion (DBMI) and serum levels of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and soluble CD30 (sCD30) in kidney recipients. We analyzed the allograft outcomes correlated with sCD30, IFN-gamma, and IL-10 levels using pre- and posttransplantation sera from 40 live donor renal transplants (20 patients with DBMI [2.1 x 10(9) +/- 1.3 x 10(9) mononuclear cells/body] and 20 controls). Patients with acute rejection episodes (ARE)-3/20 DBMI and 6/20 controls-showed increased sCD30 and IFN-gamma as well as decreased IL-10 posttransplantation compared with nonrejectors. Significant differences were observed for sCD30 and IFN-gamma levels: 59.54 vs 30.92 ng/mL (P = .02) and 11.91 vs 3.01 pg/mL (P = .01), respectively. Comparison of pre- and posttransplant levels of IFN-gamma, IL-10, and sCD30 in ARE patients showed higher levels in posttransplant sera except for IFN-gamma in controls (6.37 vs 11.93; P = .01). Increased IFN-gamma and IL-10 were correlated with rejection (r = .93; P = .008). sCD30 correlated with serum creatinine among ARE patients in control and DBMI groups (r = .89; P = .019; and r = 1.00; P sCD30, IFN-gamma, and IL-10 posttransplantation in rejecting patients provided evidence for coexistence of cellular and humoral responses in ARE. There appeared to be a down-regulatory effect of infusion on alloresponses.

Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes.

Science.gov (United States)

Naik, Swati; Nicholas, Sarah K; Martinez, Caridad A; Leen, Ann M; Hanley, Patrick J; Gottschalk, Steven M; Rooney, Cliona M; Hanson, I Celine; Krance, Robert A; Shpall, Elizabeth J; Cruz, Conrad R; Amrolia, Persis; Lucchini, Giovanna; Bunin, Nancy; Heimall, Jennifer; Klein, Orly R; Gennery, Andrew R; Slatter, Mary A; Vickers, Mark A; Orange, Jordan S; Heslop, Helen E; Bollard, Catherine M; Keller, Michael D

2016-05-01

Viral infections are a leading fatal complication for patients with primary immunodeficiencies (PIDs) who require hematopoietic stem cell transplantation (HSCT). Use of virus-specific T lymphocytes (VSTs) has been successful for the treatment and prevention of viral infections after HSCT for malignant and nonmalignant conditions. Here we describe the clinical use of VSTs in patients with PIDs at 4 centers. We sought to evaluate the safety and efficacy of VSTs for treatment of viral infections in patients with PIDs. Patients with PIDs who have received VST therapy on previous or current protocols were reviewed in aggregate. Clinical information, including transplantation details, viral infections, and use of antiviral and immunosuppressive pharmacotherapy, were evaluated. Data regarding VST production, infusions, and adverse reactions were compared. Thirty-six patients with 12 classes of PID diagnoses received 37 VST products before or after HSCT. Twenty-six (72%) patients had received a diagnosis of infection with cytomegalovirus, EBV, adenovirus, BK virus, and/or human herpesvirus 6. Two patients were treated before HSCT because of EBV-associated lymphoproliferative disease. Partial or complete responses against targeted viruses occurred in 81% of patients overall. Time to response varied from 2 weeks to 3 months (median, 28 days). Overall survival at 6 months after therapy was 80%. Four patients had graft-versus-host disease in the 45 days after VST infusion, which in most cases was therapy responsive. VSTs derived from either stem cell donors or third-party donors are likely safe and effective for the treatment of viral infections in patients with PIDs. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Activation of human T lymphocytes by Leishmania lipophosphoglycan

DEFF Research Database (Denmark)

Kemp, M; Theander, T G; Handman, E

1991-01-01

This study describes Leishmania antigen-induced activation of lymphocytes isolated from Kenyan donors, previously treated for visceral leishmaniasis, and from Danish and Kenyan controls. Peripheral blood mononuclear cells (PBMC) from cured Kala-Azar patients proliferated and produced Interferon......, the results suggest that human T lymphocytes can respond to glycolipid antigens....

Repair of x-ray induced chromosomal damage in trisomy 2- and normal diploid lymphocytes

International Nuclear Information System (INIS)

Countryman, P.I.; Heddle, J.A.; Crawford, E.

1977-01-01

The frequency of chromosomal aberrations produced by x-rays is greater in lymphocytes cultured from trisomy 21 patients (Down's syndrome) than from normal diploid donors. This increase, which can be detected by a micronucleus assay for chromosomal damage, was postulated by us to result from a defect in the rejoining system which repairs chromosomal breaks. The postulated defect would result in a longer rejoining time, therapy permitting more movement of broken ends and thus enhancing the frequency of exchanges. To test this possibility, the time required for the rejoining (repair) of chromosome breaks was measured in lymphocytes from five Down's syndrome (four trisomy 21 and one D/G translocation partial trisomy 21) donors, from a monosomy 21 donor, and from five diploid donors. The rejoining time was reduced in the Down's syndrome lymphocytes in comparison to the normal diploid and monosomy 21 lymphocytes. Thus the repair of chromosome breaks, far from being defective as evidenced by a longer rejoining time in Down's syndrome cells, occurred more rapidly than in normal cells

Chromosome aberrations frequencies in peripheral blood lymphocytes from patients with larynx cancer

International Nuclear Information System (INIS)

Lisowska, H.; Lankoff, A.; Banasik, A.; Padjas, A.; Wieczorek, A.; Kuszewski, T.; Gozdz, A.; Wojcik, A.

2005-01-01

There is data suggesting that the sensitivity to ionising radiation of peripheral blood lymphocytes of cancer patients is higher than in healthy donors. This effect is especially prominent when chromosomal aberrations induced in S/G2 phase of the cell cycle are analysed. The aim of our study was to investigate if the S/G2- aberration frequencies in lymphocytes of patients with larynx cancer were higher than in control individuals. In addition, the multiple fixation regimen was applied in lymphocytes of the cancer patients. The aim of this was to check if the aberration frequencies scored in cells harvested at one time point were representative for a larger fraction of the cell cycle. Peripheral blood of 40 patients was collected before the onset of radiotherapy, cultured and irradiated with Co-60 (2 Gy) after 67 hours of culture time. Irradiation was performed in the Swietokrzyskie Oncology Center. Chromosome specimens were prepared from cells fixed at three time points after irradiation: 5, 7 and 9 hours. Colcemide was always added for 2 hours before harvest. Lymphocytes of 40 healthy donors were cultured and irradiated in the same way like in the case of patients with cancer, however, they were only harvested at one time point (5 hours p.r.). No statistically significant differences in aberration frequencies were observed between lymphocytes harvested at the 3 time points. In both donor groups, individual differences in aberration frequencies were observed. Despite this, the aberration frequencies in lymphocytes of patients were in average higher than in the healthy donors. This suggests, that the radiation sensitivity of lymphocytes of patients with larynx cancer may be a marker of cancer predisposition. More patients must be analysed to confirm this hypothesis. (author)

Labelling of human resting lymphocytes by continuous infusion of (/sup 3/H)thymidine. 1. Characterization of cytoplasmic label

Energy Technology Data Exchange (ETDEWEB)

Schick, P; Trepel, F; Maisel, K H; Past, W; Reisert, I; Begemann, H; Pilgrim, C [Ulm Univ. (Germany, F.R.)

1978-01-01

After continuous /sup 3/H-TdR infusion in vivo or incubation with /sup 3/H-TdR in vitro human blood lymphocytes were examined by light-microscopic and electron-microscopic autoradiography. Using relatively long autoradiographic exposure times (50-300 days) not only nuclear but also cytoplasmic labelling was visualized, the cytoplasmic label being present in up to 96% of the cells. The cytoplasmic label was predominantly associated with the mitochondria and was removed from the cells nearly completely by treatment with DNase but not with RNase or cold perchloric acid. It is concluded that this cytoplasmic label mainly represents /sup 3/H-TdR incorporated into mitochondrial DNA which is continuously renewed in an average turnover time of 14 days or less. This value is compatible with a turnover time of 11 days for mitochondrial DNA in mammalian cells reported in the literature.

Phenotypic complexity of T regulatory subsets in patients with B-chronic lymphocytic leukemia.

Science.gov (United States)

Biancotto, Angélique; Dagur, Pradeep K; Fuchs, John C; Wiestner, Adrian; Bagwell, C Bruce; McCoy, J Philip

2012-02-01

Increased numbers of T regulatory (T(reg)) cells are found in B-chronic lymphocytic leukemia, but the nature and function of these T(regs) remains unclear. Detailed characterization of the T(regs) in chronic lymphocytic leukemia has not been performed and the degree of heterogeneity of among these cells has not been studied to date. Using 15-color flow cytometry we show that T(reg) cells, defined using CD4, CD25, and forkhead box P3 (FOXP3), can be divided into multiple complex subsets based on markers used for naïve, memory, and effector delineation as well as markers of T(reg) activation. Furthermore FOXP3(+) cells can be identified among CD4(+)CD25(-) as well as CD8(+)CD4(-) populations in increased proportions in patients with chronic lymphocytic leukemia compared with healthy donors. Significantly different frequencies of naïve and effector T(regs) populations are found in healthy donor controls compared with donors with chronic lymphocytic leukemia. A population of CCR7(+)CD39(+) T(regs) was significantly associated with chronic lymphocytic leukemia. This population demonstrated slightly reduced suppressive activity compared with total T(regs) or T(regs) of healthy donors. These data suggest that FOXP3-expressing cells, particularly in patients with chronic lymphocytic leukemia are much more complex for T(reg) sub-populations and transitions than previously reported. These findings demonstrate the complexity of regulation of T-cell responses in chronic lymphocytic leukemia and illustrate the use of high-dimensional analysis of cellular phenotypes in facilitating understanding of the intricacies of cellular immune responses and their dysregulation in cancer.

Psychosocial factors and T lymphocyte counts in Brazilian peacekeepers.

Science.gov (United States)

Silva, Angela M Monteiro da; Speranza, Francisco A B; Ishii, Solange Kiyoko; Hirata, Raphael; Mattos-Guaraldi, Ana Luíza; Milagres, Lucimar Gonçalves

2015-02-01

To investigate the associations between psychosocial factors and peripheral blood CD4 and CD8 T lymphocyte numbers in Brazilian peacekeepers. Venous blood was collected from 759 peacekeepers who had just returned from a peace mission in Haiti. Among the 759 soldiers, 642 individuals completed the psychosocial measures. CD4 and CD8 T lymphocyte counts were measured by flow cytometry using a commercially available kit. Psychosocial factors, including military peace force stressors, clinical stress, anxiety and depression, were recorded. As a reference for T lymphocyte numbers, we measured T lymphocyte counts in 75 blood donors from the Instituto de Biologia do Exército, Rio de Janeiro. The median numbers of CD4 and CD8 T lymphocytes in the blood donors were 819 cells/µl and 496 cells/µl, respectively, with a CD4:CD8 ratio of 1.6. Significantly (p<0.05) lower CD4 T cell counts (759 cells/µl) were recorded for peacekeepers, with similar CD8 levels (548 cells/µl) and smaller CD4:CD8 ratios (1.3, p<0.001) compared to blood donors. These differences were due to a group of 14 military personnel with CD4 and CD8 medians of 308 and 266 cells/µl, respectively. Only one (7.1%) of these 14 individuals was diagnosed with clinical stress compared with 13.5% of the individuals with normal levels of CD4 T lymphocytes. One individual out of 628 (0.16%) had a Lipp's Stress Symptom Inventory score of 3, indicating near exhaustion. The prevalence of psychological disorders was low and there were no associations with CD4 or CD8 T cell numbers.

Allograft immunity in vitro. I. Cultivation conditions and mixed lymphocyte interaction of mouse peripheral lymphocytes

Science.gov (United States)

Häyry, P.; Defendi, V.

1970-01-01

We have adapted mouse peripheral lymphocytes to culture as a preliminary step in designing a model for the study of allograft immunity in vitro. The isolation of peripheral leucocytes is facilitated by using Plasmagel® as an erythrocyte-agglutinating agent. The yield of leucocytes can be considerably increased by intravenous injection of the donor animals with supernatant fluid from Bordetella pertussis cultures and the lymphocytes thus mobilized react both to phytohaemagglutinin (PHA) and allogeneic stimulus, as do lymphocytes from untreated animals. Preparations which contain more than 25–50 RBC/WBC are refractory in the mixed lymphocyte interaction (MLI). The optimum cell density for the proliferative response is approximately 1–3 × 106 lymphocytes/ml. Various nutritive milieu were tested and found to have little influence on the MLI; both normal and suspension media behaved in a similar manner. PHA causes a vigorous proliferative response in mouse peripheral lymphocytes, the 3H–TdR incorporation values in PHA-containing cultures at peak point of stimulation (3rd day) being up to 1000 times those observed for control cultures. The allogeneic response in the MLI takes place later (6th to 7th day) and is weaker, about one-tenth the PHA response, when strains differing at the H-2 locus are used as cell donors. Because the specific proliferative response to allogeneic stimulus in mixed culture, regardless of the way it is measured, is indistinguishable from the response produced by other non-specific factors, these other factors must be critically excluded. It appears that supplementing the culture medium with low concentrations of certain lots of foetal calf or agamma-newborn-calf serum permits the study of the specific response at an optimum sensitivity. PMID:4315207

Inactivation of hemopoietic stem cells by lymphocytes as related to genotype of interacting cells

Energy Technology Data Exchange (ETDEWEB)

Petrov, R V; Seslavina, L S; Panteleev, E I; Egorova, O S

1975-05-01

Inoculation of a mixture of bone marrow cells with allogeneic lymphocytes into irradiated mice of inbred strains or into F/sub 1/ hybrids results in the depression of bone marrow cell proliferation in the spleen of the recipient: the effect of inactivation of nonsyngeneic stem cells. The inactivation of stem cells by allogeneic lymphocytes can be detected in all tested combinations of mice strains - donors of lymphocytes and bone marrow cells and mice - recipients but the degree of inactivation differs and depends on the genotype of cell donors rather than on the genotype of the recipient. Lymphocytes of some mice strains (haplotypes H-2sup(k) and H-2sup(a)) are more active killers of bone marrow cells as compared with lymphocytes of other strains (hyplotypes H-2sup(b) and H-2sup(d)). Probably, the degree of stem cells inactivation by lymphocytes depends on the differences of their histocompatibility in H-2 system.

Intra-osseous injection of donor mesenchymal stem cell (MSC) into the bone marrow in living donor kidney transplantation; a pilot study.

Science.gov (United States)

Lee, Hyunah; Park, Jae Berm; Lee, Sanghoon; Baek, Soyoung; Kim, HyunSoo; Kim, Sung Joo

2013-04-11

Mesenchymal stem cells (MSCs) are multi-potent non-hematopoietic progenitor cells possessing an immune-regulatory function, with suppression of proliferation of activated lymphocytes. In this study, adult living donor kidney transplantation (LDKT) recipients were given MSCs derived from the donor bone marrow to evaluate the safety and the feasibility of immunological changes related to the intra-osseous injection of MSC into the bone marrow. MSCs were derived from negative HLA cross-match donors. Donor bone marrow was harvested 5 weeks prior to KT. At the time of transplantation, 1 x 106 cell/kg of donor MSC was directly injected into the bone marrow of the recipient's right iliac bone. Patients' clinical outcomes, presence of mixed chimerism by short tandem repeat polymerase chain reaction, analysis of plasma FoxP3 mRNA and cytokine level, and mixed lymphocyte reaction (MLR) were performed. Seven patients enrolled in this study and received donor MSC injections simultaneously with LDKT. The median age of recipients was 36 years (32 ~ 48). The number of HLA mismatches was 3 or less in 5 and more than 3 in 2. No local complications or adverse events such as hypersensitivity occurred during or after the injection of donor MSC. There was no graft failure, but the biopsy-proven acute rejections were observed in 3 recipients during the follow-up period controlled well with steroid pulse therapy (SPT). The last serum creatinine was a median of 1.23 mg/dL (0.83 ~ 2.07). Mixed chimerism was not detected in the peripheral blood of the recipients at 1 and 8 week of post-transplantation. Donor-specific lymphocyte or T cell proliferation and Treg priming responses were observed in some patients. Plasma level of IL-10, a known mediator of MSC-induced immune suppression, increased in the patients with Treg induction. Donor MSC injection into the iliac bone at the time of KT was feasible and safe. A possible correlation was observed between the induction of inhibitory

Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation.

Science.gov (United States)

Bryant, Jane; Hlavaty, Kelan A; Zhang, Xiaomin; Yap, Woon-Teck; Zhang, Lei; Shea, Lonnie D; Luo, Xunrong

2014-10-01

Human islet cell transplantation is a promising treatment for type 1 diabetes; however, long-term donor-specific tolerance to islet allografts remains a clinically unmet goal. We have previously shown that recipient infusions of apoptotic donor splenocytes chemically treated with 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (donor ECDI-SP) can mediate long-term acceptance of full major histocompatibility complex (MHC)-mismatched murine islet allografts without the use of immunosuppression. In this report, we investigated the use of poly(lactide-co-glycolide) (PLG) particles in lieu of donor ECDI-SP as a synthetic, cell-free carrier for delivery of donor antigens for the induction of transplant tolerance in full MHC-mismatched murine allogeneic islet transplantation. Infusions of donor antigen-coupled PLG particles (PLG-dAg) mediated tolerance in ∼20% of recipient mice, and the distribution of cellular uptake of PLG-dAg within the spleen was similar to that of donor ECDI-SP. PLG-dAg mediated the contraction of indirectly activated T cells but did not modulate the direct pathway of allorecognition. Combination of PLG-dAg with a short course of low dose immunosuppressant rapamycin at the time of transplant significantly improved the tolerance efficacy to ∼60%. Furthermore, altering the timing of PLG-dAg administration to a schedule that is more feasible for clinical transplantation resulted in equal tolerance efficacy. Thus, the combination therapy of PLG-dAg infusions with peritransplant rapamycin represents a clinically attractive, biomaterials-based and cell-free method for inducing long-term donor-specific tolerance for allogeneic cell transplantation, such as for allogeneic islet transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

The mitogenic response of cryopreserved human lymphocytes in a microculture system.

Science.gov (United States)

Steel, C M; Ennis, M; Levin, A G; Wasunna, A

1977-01-01

Fresh blood lymphocytes from nine health donors have been compared with samples from the same donors, recovered after period of 2 to 21 months storage in liquid nitrogen, for the capacity to respond to a range of mitogens in vitro. A microculture assay was used, requireing aliquots of only 25,000 cells. The mean levels of 14C-thymidine uptake for fresh and frozen samples were closely comparable when the cells had been stimulated by PHA, Pokeweed or mitomycin-C-treated allogeneic lymphoblastoid cells. Lymphocytes from six East African donors, frozen by a very simple technique, were recovered after 3 or more years storage in liquid nitrogen. Five of the samples were in good condition as judged by cell viability and the capacity to form spontaneous 'E' rosettes with sheep erythrocytes. These five samples also responded extremely well to PHA, PWM and mitomycin-C-treated allogeneic lymphoblastoid cells using the microculture assay. This study extends the range of applications of cell banks in which small aliquots of blood lymphocytes are stored in liquid nitrogen for periods of several years.

The role of regulatory T cells during the attenuation of graft-versus-leukemia activity following donor leukocyte infusion in mice.

Science.gov (United States)

Choi, Mi-Sun; Lim, Ji-Young; Cho, Byung-Sik; Kim, Yoo-Jin; Chung, Nack-Gyun; Jeong, Dae Chul; Youn, Hyewon; Lee, Chulbom; Choi, Eun Young; Min, Chang-Ki

2011-12-01

We investigated how the graft-versus-leukemia (GVL) effect is attenuated in the tumor microenvironment using a murine model of non-myeloablative allo-HSCT (NM-HSCT) plus delayed donor leukocyte infusion (DLI) in a haploidentical B6→F1 strain combination. In-line with aggravated leukemia growth, the proportions of effector T cells expressing IFN-γ (Teffs) in spleen were reduced and attenuated GVL activity was found to be accompanied by a rebound in CD4(+)Foxp3(+) regulatory T cells (Tregs) in tumor-draining lymph nodes and tumor tissues. DLI-derived Tregs and Teffs may be potential indicators of presence of leukemic progression after DLI in this GVL model. Copyright © 2011 Elsevier Ltd. All rights reserved.

Eomesodermin(lo) CTLA4(hi) Alloreactive CD8+ Memory T Cells Are Associated With Prolonged Renal Transplant Survival Induced by Regulatory Dendritic Cell Infusion in CTLA4 Immunoglobulin-Treated Nonhuman Primates.

Science.gov (United States)

Ezzelarab, Mohamed B; Lu, Lien; Guo, Hao; Zahorchak, Alan F; Shufesky, William F; Cooper, David K C; Morelli, Adrian E; Thomson, Angus W

2016-01-01

Memory T cells (Tmem), particularly those resistant to costimulation blockade (CB), are a major barrier to transplant tolerance. The transcription factor Eomesodermin (Eomes) is critical for Tmem development and maintenance, but its expression by alloactivated T cells has not been examined in nonhuman primates. We evaluated Eomes and coinhibitory cytotoxic T lymphocyte antigen-4 (CTLA4) expression by alloactivated rhesus monkey T cells in the presence of CTLA4 immunoglobulin, both in vitro and in renal allograft recipients treated with CTLA4Ig, with or without regulatory dendritic cell (DCreg) infusion. In normal monkeys, CD8+ T cells expressed significantly more Eomes than CD4+ T cells. By contrast, CD8+ T cells displayed minimal CTLA4. Among T cell subsets, central Tmem (Tcm) expressed the highest levels of Eomes. Notably, Eomes(lo)CTLA4(hi) cells displayed higher levels of CD25 and Foxp3 than Eomes(hi)CTLA4(lo) CD8+ T cells. After allostimulation, distinct proliferating Eomes(lo)CTLA4(hi) and Eomes(hi)CTLA4(lo) CD8+ T cell populations were identified, with a high proportion of Tcm being Eomes(lo)CTLA4(hi). CB with CTLA4Ig during allostimulation of CD8+ T cells reduced CTLA4 but not Eomes expression, significantly reducing Eomes(lo)CTLA4(hi) cells. After transplantation with CB and rapamycin, donor-reactive Eomes(lo)CTLA4(hi) CD8+ T cells were reduced. However, in monkeys also given DCreg, absolute numbers of these cells were elevated significantly. Low Eomes and high CTLA4 expression by donor-reactive CD8+ Tmem is associated with prolonged renal allograft survival induced by DCreg infusion in CTLA4Ig-treated monkeys. Prolonged allograft survival associated with DCreg infusion may be related to maintenance of donor-reactive Eomes(lo)CTLA4(hi) Tcm.

Eomesoderminlo CTLA4hi Alloreactive CD8+ Memory T Cells Are Associated With Prolonged Renal Transplant Survival Induced by Regulatory Dendritic Cell Infusion in CTLA4Ig-Treated Non-Human Primates

Science.gov (United States)

Ezzelarab, Mohamed B.; Lu, Lien; Guo, Hao; Zahorchak, Alan F.; Shufesky, William F.; Cooper, David K.C.; Morelli, Adrian E.; Thomson, Angus W.

2015-01-01

Background Memory T cells (Tmem), particularly those resistant to costimulation blockade (CB), are a major barrier to transplant tolerance. The transcription factor Eomesodermin (Eomes) is critical for Tmem development and maintenance, but its expression by alloactivated T cells has not been examined in non-human primates. Methods We evaluated Eomes and co-inhibitory cytotoxic T lymphocyte antigen-4 (CTLA4) expression by alloactivated rhesus monkey T cells in the presence of CTLA4 immunoglobulin (Ig), both in vitro and in renal allograft recipients treated with CTLA4Ig, with or without regulatory dendritic cell (DCreg) infusion. Results In normal monkeys, CD8+ T cells expressed significantly more Eomes than CD4+T cells. By contrast, CD8+T cells displayed minimal CTLA4. Among T cell subsets, central Tmem (Tcm) expressed the highest levels of Eomes. Notably, EomesloCTLA4hi cells displayed higher levels of CD25 and Foxp3 than EomeshiCTLA4lo CD8+ T cells. Following allostimulation, distinct proliferating EomesloCTLA4hi and EomeshiCTLA4lo CD8+ T cell populations were identified, with a high proportion of Tcm being EomesloCTLA4hi. CB with CTLA4Ig during allostimulation of CD8+T cells reduced CTLA4 but not Eomes expression, significantly reducing EomesloCTLA4hi cells. After transplantation with CB and rapamycin, donor-reactive EomesloCTLA4hi CD8+T cells were reduced. However, in monkeys also given DCreg, absolute numbers of these cells were elevated significantly. Conclusions Low Eomes and high CTLA4 expression by donor-reactive CD8+ Tmem is associated with prolonged renal allograft survival induced by DCreg infusion in CTLA4Ig-treated monkeys. Prolonged allograft survival associated with DCreg infusion may be related to maintenance of donor-reactive EomesloCTLA4hi Tcm. PMID:26680373

The prognostic value of peripheral CD4+CD25+ T lymphocytes among early stage and triple negative breast cancer patients receiving dendritic cells-cytokine induced killer cells infusion.

Science.gov (United States)

Song, Qing-Kun; Ren, Jun; Zhou, Xin-Na; Wang, Xiao-Li; Song, Guo-Hong; Di, Li-Jun; Yu, Jing; Hobeika, Amy; Morse, Michael A; Yuan, Yan-Hua; Yang, Hua-Bing; Lyerly, Herbert Kim

2015-12-01

This study aimed to assess the prognostic value of CD4+CD25+ T lymphocyte in peripheral blood among breast cancer patients treated with adoptive T lymphocytes immunotherapy. 217 patients participated in the follow-up study. CD4+CD25+ proportion was measured by flow cytometry in peripheral T cells. The median survival was estimated by Kaplan-Meier curve, Log-rank test and Cox hazard proportion regression model, between groups of CD4+CD25+ proportion more than 5% and less than or equal to 5% in peripheral T cells. Peripheral CD4+CD25+ T lymphocytes had not a relationship with progression-free survival. It was featured that above 5% peripheral CD4+CD25+ proportion of T cells was related with the median overall survival by a shorten of 51 months (p < 0.05) with the HR 1.65 (95%CI 1.04, 2.62). Above 5% CD4+CD25+proportion of T cells produced the HR to be 1.76 (95%CI 1.07, 2.87) In stage 0-II patients, and 3.59 (95%CI 1.05, 12.29) in triple negative breast cancer patients. Cellular immunity restoration recovered by adoptive T cell infusions which resulted in less proportion of peripheral CD4+CD25+T lymphocytes could be a potential prognostic indicator among early stage and triple negative patients.

No evidence of transmission of chronic lymphocytic leukemia through blood transfusion

DEFF Research Database (Denmark)

Hjalgrim, Henrik; Rostgaard, Klaus; Vasan, Senthil K

2015-01-01

Monoclonal B-cell lymphocytosis (MBL) is a precursor of chronic lymphocytic leukemia (CLL). Observations of MBL in blood donors raise concern that transmitted MBL may cause recipient CLL. Using a database with health information on 1.5 million donors and 2.1 million recipients, we compared CLL...... of 0.94 (95% confidence interval, 0.52-1.71). Analyses using the entire database showed no evidence of CLL clustering among recipients of blood from individual donors. In conclusion, when donor MBL was approximated by subsequent donor CLL diagnosis, data from 2 countries' entire computerized...

Graft versus host disease in a rat small bowel transplant model after T-cell depleted donor specific bone marrow infusion

Directory of Open Access Journals (Sweden)

Bakonyi Neto Alexandre

2003-01-01

Full Text Available Low cytoreductive regimen of irradiation associated to unmodified bone marrow infusion (UBM does not prevent the occurrence of graft versus host disease (GVHD after transplant. PURPOSE: In this study we evaluated the potential advantages of a long-term immunossupression and T-cell depleted bone marrow infusion (TCDBMI in preventing the occurrence of GVHD after small bowel transplantation (SBTx. METHODS: Heterotopic SBTX was performed with Lewis rats as recipients and DA as donors and distributed into 5 groups according to the irradiation, duration of immunossupression and the use of UBM or TCDBMI: G1 (n=6, without irradiation and G2 (n=9, G3 (n=4, G4 (n=5 and G5 (n=6 was given 250 rd of irradiation. Groups 1,2,4 and G3 and 5 were infused with 100 x 10(6 UBM and TCDBM respectively. Animals in G1, 2, 3 were immunossupressed with 1mg/ FK506/Kg/IM for 5 days and G4 and G5 for 15 days. Anti CD3 monoclonal antibodies and immunomagnetic beads were used for T-cell depletion.Animals were examined for rejection, GVHD, chimerism characterization and ileal and skin biopsies. RESULTS: Minimal to mild rejection was observed in all groups; however, GVHD were present only in irradiated groups. Long-term immunossupression changed the severity of GVHD in G4 and G5. Rejection was the cause of death in G1 while GVHD in G2, 3, 4 and 5, not avoided by the use of TCDBMI. Total chimerism and T-cell chimerism was statistically higher in irradiated groups when compared to G1. CONCLUSION: Extended immunossupression associated to low dose of irradiation decrease the severity of GVHD, not avoided by the use of TCDBMI.

Intra-osseous injection of donor mesenchymal stem cell (MSC) into the bone marrow in living donor kidney transplantation; a pilot study

OpenAIRE

Lee, Hyunah; Park, Jae Berm; Lee, Sanghoon; Baek, Soyoung; Kim, HyunSoo; Kim, Sung Joo

2013-01-01

Background Mesenchymal stem cells (MSCs) are multi-potent non-hematopoietic progenitor cells possessing an immune-regulatory function, with suppression of proliferation of activated lymphocytes. In this study, adult living donor kidney transplantation (LDKT) recipients were given MSCs derived from the donor bone marrow to evaluate the safety and the feasibility of immunological changes related to the intra-osseous injection of MSC into the bone marrow. Methods MSCs were derived from negative ...

Application of rosula-formation tests for determining man lymphocyte radiosensitivity

International Nuclear Information System (INIS)

Shchilik, Ts.; Krushevskij, E.; Endrzhejchak, V.

1982-01-01

Radiosensitivity of subpopulation of lymphocytes-T-lymphocytes and B-lymphocytes was studied to diagnose acute radiation disease as well as if radiosensitivity of any of them is more effective indication of irradiation as compared with absolute lymphocyte quantity. The investigations were carried on in vitro using blood of healthy men-donors at the age of 21-25. It is shown that absolute quantity of cells forming AE rosette in perapheral blood is a much better indication of irradiation as compared with absolute quantity of lymphocytes. Considerable significance of tests of rosette formation especially AE test is underlined. High test sensitivity and relative simplicity of accomplishment permit authors to recommend it for diagnostic purposes when revealing acute radiation disease including the stages of medicinal evacuation

An Algorithm Measuring Donor Cell-Free DNA in Plasma of Cellular and Solid Organ Transplant Recipients That Does Not Require Donor or Recipient Genotyping

Directory of Open Access Journals (Sweden)

Paul MK Gordon

2016-09-01

Full Text Available Cell-free DNA (cfDNA has significant potential in the diagnosis and monitoring of clinical conditions but accurately and easily distinguishing the relative proportion of DNA molecules in a mixture derived from two different sources (i.e. donor and recipient tissues after transplantation is challenging. In human cellular transplantation there is currently no useable method to detect in vivo engraftment and blood-based non-invasive tests for allograft rejection in solid organ transplantation are either non-specific (e.g. creatinine in kidney transplantation, liver enzymes in hepatic transplantation or absent (i.e. heart transplantation. Elevated levels of donor cfDNA have been shown to correlate with solid organ rejection but complex methodology limits implementation of this promising biomarker. We describe a cost-effective method to quantify donor cfDNA in recipient plasma using a panel of high-frequency single nucleotide polymorphisms, next-generation (semiconductor sequencing and a novel mixture model algorithm. In vitro, our method accurately and rapidly determined donor/recipient DNA admixture. For in vivo testing, donor cfDNA was serially quantified in an infant with a urea cycle disorder after receiving six daily infusions of donor liver cells. Donor cfDNA isolated from 1-2 ml of recipient plasma was detected as late as 24 weeks after infusion suggesting engraftment. The percentage of circulating donor cfDNA was also assessed in pediatric and adult heart transplant recipients undergoing routine endomyocardial biopsy with levels observed to be stable over time and generally measuring <1% in cases without moderate or severe cellular rejection. Unlike existing non-invasive methods used to define the proportion of donor cfDNA in solid organ transplant patients, our assay does not require sex mismatch, donor genotyping or whole-genome sequencing and potentially has broad application to detect cellular engraftment or allograft injury after

Phenotypic and functional properties of murine thymocytes. II. Quantitation of host- and donor-derived cytolytic T lymphocyte precursors in regenerating radiation bone marrow chimeras

International Nuclear Information System (INIS)

Ceredig, R.; McDonald, H.R.

1982-01-01

Thymocytes from radiation bone marrow chimeras, in which donor bone marrow and irradiated recipient differed at the Thy-1 locus, were stained by indirect immunofluorescence with monoclonal anti-Thy-1 antibodies and analyzed by flow microfluorometry (FMF). Kinetic studies indicated an early appearance of host-derived (CBA, Thy-1.2 + ) thymocytes, which reaches maximum number of 10 to 20 x 10 6 cells at 12 to 16 days after bone marrow reconstitution. Donor-derived (AKR, Thy-1.1 + ) cells were not detectable until 10 to 12 days after reconstitution; subsequently, they increased exponentially in number until 28 days, when they accounted for essentially all cells in the thymus (50 x 10 6 ). Concomitant with the appearance and disappearance of host-derived cells was a change in their Thy-1 surface phenotype. In particular, the proportion of host cells having a ''mature'' phenotype (weakly Thy-1.2 staining) increased progressively with time after irradiation. Functional studies using a sensitive mixed leukocyte microculture system to quantitate cytolytic T lymphocyte precursors (CTL-P) were also carried out in regenerating chimeric thymuses. Initially, the regenerating thymus contained few CTL-P, but by 4 wk after reconstitution, frequencies similar to control adult thymuses were obtained. Analysis of the CTL-P content of host and donor-derived subpopulations, separated either by appropriate anti-Thy-1 antibody plus complement or by direct cell sorting, indicated that both host- and donor-derived cells contained appreciable numbers of CTL-P. Furthermore, increases in CTL-P frequency of both host and donor subpopulations correlated with changes in their surface Thy-1 phenotype

Regulatory dendritic cell infusion prolongs kidney allograft survival in nonhuman primates.

Science.gov (United States)

Ezzelarab, M B; Zahorchak, A F; Lu, L; Morelli, A E; Chalasani, G; Demetris, A J; Lakkis, F G; Wijkstrom, M; Murase, N; Humar, A; Shapiro, R; Cooper, D K C; Thomson, A W

2013-08-01

We examined the influence of regulatory dendritic cells (DCreg), generated from cytokine-mobilized donor blood monocytes in vitamin D3 and IL-10, on renal allograft survival in a clinically relevant rhesus macaque model. DCreg expressed low MHC class II and costimulatory molecules, but comparatively high levels of programmed death ligand-1 (B7-H1), and were resistant to pro-inflammatory cytokine-induced maturation. They were infused intravenously (3.5-10 × 10(6) /kg), together with the B7-CD28 costimulation blocking agent CTLA4Ig, 7 days before renal transplantation. CTLA4Ig was given for up to 8 weeks and rapamycin, started on Day -2, was maintained with tapering of blood levels until full withdrawal at 6 months. Median graft survival time was 39.5 days in control monkeys (no DC infusion; n = 6) and 113.5 days (p DCreg-treated animals (n = 6). No adverse events were associated with DCreg infusion, and there was no evidence of induction of host sensitization based on circulating donor-specific alloantibody levels. Immunologic monitoring also revealed regulation of donor-reactive memory CD95(+) T cells and reduced memory/regulatory T cell ratios in DCreg-treated monkeys compared with controls. Termination allograft histology showed moderate combined T cell- and Ab-mediated rejection in both groups. These findings justify further preclinical evaluation of DCreg therapy and their therapeutic potential in organ transplantation. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Use of ATG-Fresenius as an Induction Agent in Deceased-Donor Kidney Transplantation.

Science.gov (United States)

Yilmaz, M; Sezer, T Ö; Kir, O; Öztürk, A; Hoşcoşkun, C; Töz, H

2017-04-01

Anti-T-lymphocyte globulins (ATG) are most commonly used as induction agents in kidney transplantation (KT). In this study, we investigated the use of ATG as induction therapy in deceased-donor KT. Among 152 deceased-donor KT recipients transplanted between January 2009 and December 2003, 147 with exact data were enrolled in this study. Delayed graft function was defined as dialysis requirement after KT. Greater than 10% panel-reactive antibody (PRA) was considered as positive. Total ATG (rATG-Fresenius) dosage and induction duration was evaluated. Mean age was 45 ± 10 years; 91 patients were male and 56 patients were female. Class I and class II PRA-positive patient numbers were 20 (13.6%) and 17 (11.5%), respectively. Pre-transplant dialysis vintage was 108 ± 63 months. Mean donor age was 42 ± 17, and cold ischemia time was 16 ± 5 hours. Eighty-nine patients (60%) had delayed graft function and needed at least one session of hemodialysis after transplantation. Cumulative ATG-F dosage was 676 ± 274 mg. The mean ATG-F cumulative dosage was 10.6 ± 3.8 mg/kg. At the end of first year, mean creatinine and proteinuria levels were 1.4 ± 1.0 mg/dL and 0.3 ± 0.4 g/d, respectively. Mean follow-up time was 32 ± 20 months. During follow-up, there were 14 graft failures and 11 patients died. Patient survival for 1 and 2 years were 93% and 92.3%, respectively. Death-censored graft survival rates for 1 and 2 years were 94.8% and 90.8%, respectively. ATG-F induction provides acceptable graft and patient survival in deceased-donor KT. ATG-F infusion is well tolerated. Infection rates seem to be acceptable compared with all transplantation populations. Copyright © 2017 Elsevier Inc. All rights reserved.

Cross-reactivity of human nickel-reactive T-lymphocyte clones with copper and palladium

NARCIS (Netherlands)

Pistoor, F. H.; Kapsenberg, M. L.; Bos, J. D.; Meinardi, M. M.; von Blomberg, M. E.; Scheper, R. J.

1995-01-01

Twenty Ni-reactive T-lymphocyte clones were obtained from eight different donors and analyzed for their ability to cross-react with other metals. All Ni-reactive T-lymphocyte clones were CD4+CD8- and recognized Ni in association with either HLA-DR or -DQ molecules. Based on the periodic table of the

Continuous DC-CIK infusions restore CD8+ cellular immunity, physical activity and improve clinical efficacy in advanced cancer patients unresponsive to conventional treatments.

Science.gov (United States)

Zhao, Yan-Jie; Jiang, Ni; Song, Qing-Kun; Wu, Jiang-Ping; Song, Yu-Guang; Zhang, Hong-Mei; Chen, Feng; Zhou, Lei; Wang, Xiao-Li; Zhou, Xin-Na; Yang, Hua-Bing; Ren, Jun; Lyerly, Herbert Kim

2015-01-01

There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients. A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits. An average of 5.7±2.94x10(9) induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic CD8+CD28+T lymphocytes were increased by 74% and suppressive CD8+CD28-T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of CD8+CD28- T cell proportion reflecting a 5% higher risk of progression (p<0.05). In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.

A comparison of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratios in schizophrenia and bipolar disorder patients - a retrospective file review.

Science.gov (United States)

Özdin, Selçuk; Sarisoy, Gökhan; Böke, Ömer

2017-10-01

Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) have recently been used as indicators of inflammation. Higher MLR and PLR values have been determined in the euthymic and manic periods in patients with bipolar disorder compared to a control group. High NLR values were determined in the only study investigating this ratio in schizophrenia patients. The purpose of this study was to compare NLR, PLR and MLR values and complete blood count elements in patients receiving treatment and hospitalized due to schizophrenic psychotic episode and bipolar disorder manic episode. All patients meeting the inclusion criteria among subjects receiving treatment and hospitalized due to schizophrenia-psychotic episode and bipolar affective disorder-manic episode at the Ondokuz Mayıs University Medical Faculty Psychiatry Department, Turkey, in 2012-2016 were included in our study. A total of 157 healthy donors were included as a control group. White blood cell (WBC), neutrophil, lymphocyte, platelet and monocyte numbers were noted retrospectively from complete blood counts at time of admission, and NLR, PLR and MLR were calculated from these. NLR, PLR and MLR values and platelet numbers in this study were higher and lymphocyte numbers were lower in bipolar disorder patients compared to the controls. Elevation in NLR, MLR and PLR values and neutrophil numbers and lower lymphocyte numbers were determined in schizophrenia patients compared to the controls. Higher NLR and MLR values were found in schizophrenia patients compared to bipolar disorder. Findings of our study supported the inflammation hypothesis for schizophrenia and bipolar disorder.

Phenotypic and functional properties of murine thymocytes. II. Quantitation of host- and donor-derived cytolytic T lymphocyte precursors in regenerating radiation bone marrow chimeras

Energy Technology Data Exchange (ETDEWEB)

Ceredig, R.; McDonald, H.R.

1982-02-01

Thymocytes from radiation bone marrow chimeras, in which donor bone marrow and irradiated recipient differed at the Thy-1 locus, were stained by indirect immunofluorescence with monoclonal anti-Thy-1 antibodies and analyzed by flow microfluorometry (FMF). Kinetic studies indicated an early appearance of host-derived (CBA, Thy-1.2/sup +/) thymocytes, which reaches maximum number of 10 to 20 x 10/sup 6/ cells at 12 to 16 days after bone marrow reconstitution. Donor-derived (AKR, Thy-1.1/sup +/) cells were not detectable until 10 to 12 days after reconstitution; subsequently, they increased exponentially in number until 28 days, when they accounted for essentially all cells in the thymus (50 x 10/sup 6/). Concomitant with the appearance and disappearance of host-derived cells was a change in their Thy-1 surface phenotype. In particular, the proportion of host cells having a ''mature'' phenotype (weakly Thy-1.2 staining) increased progressively with time after irradiation. Functional studies using a sensitive mixed leukocyte microculture system to quantitate cytolytic T lymphocyte precursors (CTL-P) were also carried out in regenerating chimeric thymuses. Initially, the regenerating thymus contained few CTL-P, but by 4 wk after reconstitution, frequencies similar to control adult thymuses were obtained. Analysis of the CTL-P content of host and donor-derived subpopulations, separated either by appropriate anti-Thy-1 antibody plus complement or by direct cell sorting, indicated that both host- and donor-derived cells contained appreciable numbers of CTL-P. Furthermore, increases in CTL-P frequency of both host and donor subpopulations correlated with changes in their surface Thy-1 phenotype.

Regulatory dendritic cell infusion prolongs kidney allograft survival in non-human primates

Science.gov (United States)

Ezzelarab, M.; Zahorchak, A.F.; Lu, L.; Morelli, A.E.; Chalasani, G.; Demetris, A.J.; Lakkis, F.G.; Wijkstrom, M.; Murase, N.; Humar, A.; Shapiro, R.; Cooper, D.K.C.; Thomson, A.W.

2014-01-01

We examined the influence of regulatory dendritic cells (DCreg), generated from cytokine-mobilized donor blood monocytes in vitamin D3 and IL-10, on renal allograft survival in a clinically-relevant rhesus macaque model. DCreg expressed low MHC class II and costimulatory molecules, but comparatively high levels of programmed death ligand-1 (B7-H1), and were resistant to pro-inflammatory cytokine-induced maturation. They were infused intravenously (3.5–10×106/kg), together with the B7-CD28 costimulation blocking agent CTLA4Ig, 7 days before renal transplantation. CTLA4Ig was given for up to 8 weeks and rapamycin, started on day −2, was maintained with tapering of blood levels until full withdrawal at 6 months. Median graft survival time was 39.5 days in control monkeys (no DC infusion; n=6) and 113.5 days (pDCreg-treated animals (n=6). No adverse events were associated with DCreg infusion, and there was no evidence of induction of host sensitization based on circulating donor-specific alloantibody levels. Immunologic monitoring also revealed regulation of donor-reactive memory CD95+ T cells and reduced memory/regulatory T cell ratios in DCreg-treated monkeys compared with controls. Termination allograft histology showed moderate combined T cell- and Ab-mediated rejection in both groups. These findings justify further pre-clinical evaluation of DCreg therapy and their therapeutic potential in organ transplantation. PMID:23758811

Association of Donor and Recipient Telomere Length with Clinical Outcomes following Lung Transplantation.

Science.gov (United States)

Courtwright, Andrew M; Fried, Sabrina; Villalba, Julian A; Moniodis, Anna; Guleria, Indira; Wood, Isabelle; Milford, Edgar; Mallidi, Hari H; Hunninghake, Gary M; Raby, Benjamin A; Agarwal, Suneet; Camp, Philip C; Rosas, Ivan O; Goldberg, Hilary J; El-Chemaly, Souheil

2016-01-01

Patients with short telomere syndromes and pulmonary fibrosis have increased complications after lung transplant. However, the more general impact of donor and recipient telomere length in lung transplant has not been well characterized. This was an observational cohort study of patients who received lung transplant at a single center between January 1st 2012 and January 31st 2015. Relative donor lymphocyte telomere length was measured and classified into long (third tertile) and short (other tertiles). Relative recipient lung telomere length was measured and classified into short (first tertile) and long (other tertiles). Outcome data included survival, need for modification of immunosuppression, liver or kidney injury, cytomegalovirus reactivation, and acute rejection. Recipient lung tissue telomere lengths were measured for 54 of the 79 patients (68.3%) who underwent transplant during the study period. Donor lymphocyte telomeres were measured for 45 (83.3%) of these recipients. Neither long donor telomere length (hazard ratio [HR] = 0.58, 95% confidence interval [CI], 0.12-2.85, p = 0.50) nor short recipient telomere length (HR = 1.01, 95% CI = 0.50-2.05, p = 0.96) were associated with adjusted survival following lung transplant. Recipients with short telomeres were less likely to have acute cellular rejection (23.5% vs. 58.8%, p = 0.02) but were not more likely to have other organ dysfunction. In this small cohort, neither long donor lymphocyte telomeres nor short recipient lung tissue telomeres were associated with adjusted survival after lung transplantation. Larger studies are needed to confirm these findings.

Genotoxic damage in cultured human peripheral blood lymphocytes ...

African Journals Online (AJOL)

Falaq Naz

2012-06-29

Jun 29, 2012 ... Genotoxic damage in cultured human peripheral blood lymphocytes of oral ... catechol estrogens and quinines, via redox reactions causes oxidative damage to .... volume was prepared for each donor. About, 0.8 ml of cell sus .... duce the adverse effects of OCs, such as the reduction in the estrogen content.

In vitro sensitization of human lymphocytes to a myeloma cell-related antigen

International Nuclear Information System (INIS)

Whitson, M.E.; Griffin, G.D.; Novelli, G.D.; Solomon, A.

1981-01-01

Peripheral blood lymphocytes from normal human donors were cocultivated with cells from two established human multiple myeloma cell lines, RPMI 8226 and K-737, and with lymphoblastoid cells from a third B cell line, RAMM. After a comparison of three methods of lymphocyte sensitization, a 6-day incubation protocol with equal numbers of normal lymphocytes and mitomycin C-treated tumor cells was selected. Cells fom the RPMI 8226 myeloma line stimulated the differentiation of lymphocytes into cytotoxic effector cells as measured by 51 Cr release from labeled target cells. The RPMI 8226-sensitized lymphocytes were cytotoxic for myeloma cells (RPMI 8226 and K-737) and for lymphoblastoid cells (RAMM) but not for cells from human lung tumor lines (A549, A427, MB9812), a breast carcinoma line (ALAB), a normal diploid fibroblast line (HSBP), or normal lymphocytes

In vitro sensitization of human lymphocytes to a myeloma cell-related antigen

Energy Technology Data Exchange (ETDEWEB)

Whitson, M.E. (Univ. of South Carolina, Columbia); Griffin, G.D.; Novelli, G.D.; Solomon, A.

1981-01-01

Peripheral blood lymphocytes from normal human donors were cocultivated with cells from two established human multiple myeloma cell lines, RPMI 8226 and K-737, and with lymphoblastoid cells from a third B cell line, RAMM. After a comparison of three methods of lymphocyte sensitization, a 6-day incubation protocol with equal numbers of normal lymphocytes and mitomycin C-treated tumor cells was selected. Cells fom the RPMI 8226 myeloma line stimulated the differentiation of lymphocytes into cytotoxic effector cells as measured by /sup 51/Cr release from labeled target cells. The RPMI 8226-sensitized lymphocytes were cytotoxic for myeloma cells (RPMI 8226 and K-737) and for lymphoblastoid cells (RAMM) but not for cells from human lung tumor lines (A549, A427, MB9812), a breast carcinoma line (ALAB), a normal diploid fibroblast line (HSBP), or normal lymphocytes.

Lung allograft rejection in the rat. I. Accelerated rejection caused by graft lymphocytes

International Nuclear Information System (INIS)

Prop, J.; Nieuwenhuis, P.; Wildevuur, C.R.

1985-01-01

To find out to what extent rejection of lungs differs from that of other organs, functional rejection of lung allografts was studied in five combinations of inbred rat strains. Rejection could be monitored accurately by perfusion scintigraphy, and equally well by chest roentgenography. The rejection of lung grafts was found to proceed remarkably fast, when compared with heart grafts, in combinations with strong RT1-incompatibilities. This accelerated rejection pattern could be converted into rejection at a normal pace by pretreatment of the donor with 10 Gy roentgen irradiation one day before transplantation. Donor pretreatment depleted the lung graft's bronchus-associated lymphoid tissue (BALT) of lymphocytes. When grafts were depleted of all other passenger cells as well--by retransplantation from a cyclosporine-treated intermediate host--they showed an even more reduced immunogenicity, probably because of the loss of donor-type dendritic cells. These results indicate that lymphocytes from the BALT of lung grafts are capable of accelerating the rejection response

The effect of the cytoskeletal inhibitors on the splenic lymphocyte traffic and homing in rats

International Nuclear Information System (INIS)

Yang Huibin

1989-01-01

The rat splenic lymphocyte traffic and homing in vivo and the effect of cytoskeletal inhibitors on this process were investigated using the technique of γ-counting of 51 Cr-labelled lymphocytes. The results suggests that:(1) After 2 of intravenous injection, the 51 Cr-labelled lymphocytes from donor rat spleen mainly home to recipient rat spleen, liver, lungs, mesenteric lymph modes (MLN) and gut-associated lymphoid tissues. (2) A significant inhibiting effect on the ability of preferential homing of splenic lymphocytes treated with sodium azide, cytochalasin B or colchicine shows that microtubles and microfilaments play an important role in the lymphocyte traffic and homing

Preoperative selective desensitization of live donor liver transplant recipients considering the degree of T lymphocyte cross-match titer, model for end-stage liver disease score, and graft liver volume.

Science.gov (United States)

Hong, Geun; Yi, Nam-Joon; Suh, Suk-won; Yoo, Tae; Kim, Hyeyoung; Park, Min-Su; Choi, YoungRok; Lee, Kyungbun; Lee, Kwang-Woong; Park, Myoung Hee; Suh, Kyung-Suk

2014-05-01

Several studies have suggested that a positive lymphocyte cross-matching (XM) is associated with low graft survival rates and a high prevalence of acute rejection after adult living donor liver transplantations (ALDLTs) using a small-for-size graft. However, there is still no consensus on preoperative desensitization. We adopted the desensitization protocol from ABO-incompatible LDLT. We performed desensitization for the selected patients according to the degree of T lymphocyte cross-match titer, model for end-stage liver disease (MELD) score, and graft liver volume. We retrospectively evaluated 230 consecutive ALDLT recipients for 5 yr. Eleven recipients (4.8%) showed a positive XM. Among them, five patients with the high titer (> 1:16) by antihuman globulin-augmented method (T-AHG) and one with a low titer but a high MELD score of 36 were selected for desensitization: rituximab injection and plasmapheresis before the transplantation. There were no major side effects of desensitization. Four of the patients showed successful depletion of the T-AHG titer. There was no mortality and hyperacute rejection in lymphocyte XM-positive patients, showing no significant difference in survival outcome between two groups (P=1.000). In conclusion, this desensitization protocol for the selected recipients considering the degree of T lymphocyte cross-match titer, MELD score, and graft liver volume is feasible and safe.

Chronic administration of the HNO donor Angeli's salt does not lead to tolerance, cross-tolerance, or endothelial dysfunction: comparison with GTN and DEA/NO.

Science.gov (United States)

Irvine, Jennifer C; Kemp-Harper, Barbara K; Widdop, Robert E

2011-05-01

Nitroxyl (HNO) displays distinct pharmacology to its redox congener nitric oxide (NO(•)) with therapeutic potential in the treatment of heart failure. It remains unknown if HNO donors are resistant to tolerance development following chronic in vivo administration. Wistar-Kyoto rats received a 3-day subcutaneous infusion of one of the NO(•) donors, glyceryl trinitrate (GTN) or diethylamine/NONOate (DEA/NO), or the HNO donor Angeli's salt (AS). GTN infusion (10 μg/kg/min) resulted in significantly blunted depressor responses to intravenous bolus doses of GTN, demonstrating tolerance development. By contrast, infusion with AS (20 μg/kg/min) or DEA/NO (2 μg/kg/min) did not alter their subsequent depressor responses. Similarly, ex vivo vasorelaxation responses in isolated aortae revealed that GTN infusion elicited a significant 6-fold decrease in the sensitivity to GTN and reduction in the maximum response to acetylcholine (ACh). Chronic infusion of AS or DEA/NO had no effect on subsequent vasorelaxation responses to themselves or to ACh. No functional cross-tolerance between nitrovasodilators was evident, either in vivo or ex vivo, although an impaired ability of a nitrovasodilator to increase tissue cGMP content was not necessarily indicative of a reduced functional response. In conclusion, HNO donors may represent novel therapies for cardiovascular disease with therapeutic potential over clinically used organic nitrates.

The immunodeficiency of bone marrow-transplanted patients. The effect of patient lymphocytes on the response of donor lymphocytes to mitogens and allogeneic cells

DEFF Research Database (Denmark)

Ødum, Niels; Hofmann, B; Platz, P

1985-01-01

Lymphocytes from patients after bone marrow transplantation (BMT) are in most cases predominantly of the Leu-2+ (cytotoxic/suppressor) phenotypes and are almost unresponsive to mitogens. In contrast, normal Leu-3+-depleted, Leu-2+-enriched lymphocyte suspensions retain approximately 50...

Kinetics of human lymphocyte division and chromosomal radiosensitivity

Energy Technology Data Exchange (ETDEWEB)

Bianchi, N O; Bianchi, M S; Larramendy, M [Instituto Multidisciplinario de Biologia Celular, La Plata (Argentinia)

1979-12-01

Human blood from normal donors was irradiated with 200 R during the G/sub 0/ phase, and the X-ray sensitivity of early and late dividing lymphocytes in culture was expressed as percentage of induced dicentrics. Cells in first or subsequent divisions were individualized by BrdU-Giemsa techniques. Lymphocytes in the first division at 40, 44 and 72 h after the start of culture had a lower sensitivity to radiation than lymphocytes making their first division at 48, 52 and 56 h. It was observed that: (a) the combination of radiation followed by BrdU did not increase the clastoyenic action of X-rays, (b)X-rays in the dose and duration used in our cultures did not increase the frequency of SCEs, and (c) minor changes in culture conditions probably influenced the frequency of SCEs.

A nitric oxide donor (nitroglycerin) triggers genuine migraine attacks

DEFF Research Database (Denmark)

Thomsen, L L; Kruuse, C; Iversen, Helle Klingenberg

1994-01-01

Supersensitivity to induction of headache and arterial dilatation by a donor of nitric oxide (nitroglycerin) has recently been demonstrated in migraine sufferers. The aims of the present study were to examine whether the nitric oxide donor nitroglycerin may induce a typical migraine attack......, to exclude placebo-related effects and to describe the relation between middle cerebral artery dilatation and provoked migraine. Nitroglycerin (0.5 μg/kg/min for 20 min) or placebo was infused into 12 migraine patients in a double-blind cross-over trial. Blood velocity in the middle cerebral artery...

Trends in organ donor management: 2002 to 2012.

Science.gov (United States)

Callahan, Devon S; Kim, Dennis; Bricker, Scott; Neville, Angela; Putnam, Brant; Smith, Jennifer; Bongard, Frederic; Plurad, David

2014-10-01

Refinements in donor management have resulted in increased numbers and quality of grafts after neurologic death. We hypothesize that the increased use of hormone replacement therapy (HRT) has been accompanied by improved outcomes over time. Using the Organ Procurement and Transplant Network donor database, all brain-dead donors procured from July 1, 2001 to June 30, 2012 were studied. Hormone replacement therapy was identified by an infusion of thyroid hormone. An expanded criteria donor was defined as age 60 years or older. Incidence of HRT administration and number of donors and organs recovered were calculated. Using the Organ Procurement and Transplant Network thoracic recipient database transplant list, wait times were examined. There were 74,180 brain-dead donors studied. Hormone replacement therapy use increased substantially from 25.6% to 72.3% of donors. However, mean number of organs procured per donor remained static (3.51 to 3.50; p = 0.083), and the rate of high-yield donors decreased (46.4% to 43.1%; p donors decreased (42.1% to 33.9%; p donors (22.1% to 26%). Despite this, there has been an increase in the raw number of donors (20,558 to 24,308; p organs (5,857 to 6,945; p organs per traumatic brain injury donor (4.02 to 4.12; p = 0.002) and a decrease in days on the waiting list (462.2 to 170.4 days; p donors has been accompanied by increased organ availability overall. Potential mechanisms might include successful conversion of previously unacceptable donors and improved recovery in certain subsets of donors. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

γδ T lymphocytes from cystic fibrosis patients and healthy donors are high TNF-α and IFN-γ-producers in response to Pseudomonas aeruginosa

Directory of Open Access Journals (Sweden)

Martínez Natalia

2003-09-01

Full Text Available Abstract Background γδ T cells have an important immunoregulatory and effector function through cytokine release. They are involved in the responses to Gram-negative bacterium and in protection of lung epithelium integrity. On the other hand, they have been implicated in airway inflammation. Methods The aim of the present work was to study intracytoplasmic IL-2, IL-4, IFN-γ and TNF-α production by γδ and αβ T lymphocytes from cystic fibrosis patients and healthy donors in response to Pseudomonas aeruginosa (PA. Flow cytometric detection was performed after peripheral blood mononuclear cells (PBMC culture with a cytosolic extract from PA and restimulation with phorbol ester plus ionomycine. Proliferative responses, activation markers and receptor usage of γδ T cells were also evaluated. Results The highest production of cytokine was of TNF-α and IFN-γ, γδ being better producers than αβ. No differences were found between patients and controls. The Vγ9δ2 subset of γδ T cells was preferentially expanded. CD25 and CD45RO expression by the αβ T subset and PBMC proliferative response to PA were defective in cystic fibrosis lymphocytes. Conclusion Our results support the hypothesis that γδ T lymphocytes play an important role in the immune response to PA and in the chronic inflammatory lung reaction in cystic fibrosis patients. They do not confirm the involvement of a supressed Th1 cytokine response in the pathogenesis of this disease.

Lymphocyte cytotoxicity induced by preincubation with serum from patients with Hashimoto thyroiditis

Science.gov (United States)

Calder, Elizabeth A.; McLeman, Dena; Irvine, W. J.

1973-01-01

Lymphocytes from healthy donors were incubated with serum samples from nine patients with Hashimoto thyroiditis and subsequently shown to be cytotoxic to chicken red blood cells (Ch. RBC) coated with thyroglobulin. Target cell death was estimated using a standard 51Cr release assay system. Lymphocytes pre-incubated with Hashimoto serum caused a mean% 51Cr release of 13·11±2·83 (SEM) from thyroglobulin-coated Ch. RBC and a mean% 51Cr release of 1·22±0·65 from uncoated Ch. RBC. Untreated lymphocytes caused no significant isotope release from either uncoated or thyroglobulin coated target cells. PMID:4800956

Radiation induced chromosomal instability in lymphocytes of cancer patients

International Nuclear Information System (INIS)

Sudo, H.; Sagara, M.; Ban, S.; Noda, S.; Iwakawa, M.; Harada, Y.; Imai, T.; Cologne, J.B.

2003-01-01

Full text: Cytokinesis-blocked micronucleus (CBMN) assay has been extensively used to evaluate the radiation sensitivity of human individuals. Using the CBMN assay, Scott et al (1998, 1999) demonstrated that a fraction of radiosensitive individuals in breast cancer case population was larger than in normal individual population. However, Vral et al were very skeptical about the Scott et al's findings (2002). Under the approval from the ethical committee of NIRS, peripheral blood was obtained from 46 normal healthy females, 131 breast cancer patients, 32 cervical cancer patients and 7 female head and neck cancer patients. Radiosensitivity of T-lymphocytes was assessed by using a CBMN assay. The frequencies of MN per binucleated cell in healthy donors were 0.031(±0.010) and 0.151(±0.066) for cells treated before and after X-ray-irradiation (2Gy), respectively. Spontaneous MN frequencies in cancer patients were significantly higher than healthy donors (p < 0.001). Radiation sensitivities of breast- and head and neck-cancer patients were significantly higher than normal individuals (p < 0.001). Cervical cancer patients were more resistant to irradiation than healthy donors, though the number of cases for statistical analysis was small. (p < 0.001). We are considering that the HPV infection affected the radiosensitivity of cervical cancer cases. Because it is widely believed that one key mechanism which leads to spontaneous micronucleus formation involves an imbalance of chromosomal segregation and a chromosomal instability in patients' lymphocytes might be greater than that in normal individuals' lymphocytes. Recently, Kuschel et al (2002) demonstrated that ratios in two SNPs on XRCC3 were significantly different between cancer patients and healthy females. Then, we can suppose that the radiation-related genes with low penetrance may be involved in tumorigenesis of mammary- and head and neck-cells, and also, in patients' radiation susceptibility

Studies of variability in response to UV in lymphocytes of people exposed to pesticides and reference group from Spain

International Nuclear Information System (INIS)

Cebulska-Wasilewska, A.; Panek, A.; Dyga, W.; Marcos, R.

2000-01-01

Pesticides, which are appertained to a group of the modern agrochemicals, create a potential risk to the environment and human health. As a result of their dangerous action, DNA damage may be produced in the cell and as a consequence, may lead to the cancer. The aim of this study was to assess potential genotoxic risk of occupational exposure to pesticides. The DNA damages and repair capacities of lymphocytes in four groups of people from various countries were assessed by the use of single cell gel electrophoresis (SCGE) also known as the Comet assay. All groups of donors had a similar age, sex and occupation. The results from the analysis performed in the Spanish group are presented in this paper. Among the donors 44 of them belonged to the control and 49 belonged to the exposed to pesticides groups. Average age in the control group was 37.8 and in the exposed group 33,5. In general, all donors were free of major health problems. In the control group there were 66% smokers, 23% non-smokers and 11% were former smokers. In the group exposed to pesticides 51% were smokers, 45% non-smokers and 4% former smokers. Lymphocytes were collected in Spain, whole blood samples were isolated and frozen, then were transported in dry ice to Poland for DNA damage analysis. Part of the defrosted lymphocytes were tested for viability and presence of DNA damage. Results did not show statistically significant differences in the level of DNA damages between the control and the exposed to pesticides groups. Another part of defrosted lymphocytes was irradiated with 6 J/m 2 of UV-C and incubated for 2 hours with or without the presence of phytohemoglutinin (PHA). Comparison of the efficiency of the UV induced dimmers excision process did not indicate differences between these groups. However, lymphocytes from exposed to pesticides donors have shown a statistically lower repair rate than lymphocytes from unexposed group.(author)

Single-donor islet transplantation and long-term insulin independence in select patients with type 1 diabetes mellitus.

Science.gov (United States)

Al-Adra, David P; Gill, Richdeep S; Imes, Sharleen; O'Gorman, Doug; Kin, Tatsuya; Axford, Sara J; Shi, Xinzhe; Senior, Peter A; Shapiro, A M James

2014-11-15

Islet transplantation is a recognized treatment option for select patients with type I diabetes mellitus. However, islet infusions from multiple donors are often required to achieve insulin independence. Ideally, insulin independence would be achieved routinely with only a single donor. Identification of factors associated with insulin independence after single-donor islet transplantation may help to select recipient-donor combinations with the highest probability of success. Subjects undergoing islet transplantation at a single center (Edmonton, Canada) between March 1999 and August 2013 were included. Recipient, donor, and transplant characteristics were collected and compared between recipients who became insulin independent after one islet transplantation and those who did not. Thirty-one patients achieved insulin independence after a single-donor islet transplantation, and 149 did not. Long-term insulin-free survival was not different between the groups. Factors significantly associated with single-donor success included recipient age, insulin requirement at baseline, donor weight, donor body mass index, islet transplant mass, and peritransplant heparin and insulin administration. On multivariate analysis, pretransplantation daily insulin requirements, the use of peritransplantation heparin and insulin infusions, and islet transplant mass remained significant. We have identified clinically relevant differences defining the achievement of insulin independence after single-donor transplantation. Based on these differences, a preoperative insulin requirement of less than 0.6 U/kg per day and receiving more than 5,646 islet equivalents (IEQ)/kg have a sensitivity of 84% and 71% and specificity of 50% and 50%, respectively, for insulin independence after single-donor islet transplantation. With ideal patient selection, this finding could potentially increase single-donor transplantation success and may be especially relevant for presensitized subjects or those who

Efficient clinical-scale enrichment of lymphocytes for use in adoptive immunotherapy using a modified counterflow centrifugal elutriation program.

Science.gov (United States)

Powell, Daniel J; Brennan, Andrea L; Zheng, Zhaohui; Huynh, Hong; Cotte, Julio; Levine, Bruce L

2009-01-01

Clinical-scale lymphocyte enrichment from a leukapheresis product has been performed most routinely using costly magnetic bead separation systems that deplete monocytes, but this procedure may leave behind residual beads or antibodies in the enriched cell product. Counterflow centrifugal elutriation has been demonstrated previously to enrich monocytes efficiently for generation of dendritic cells. This study describes a modified elutriation procedure for efficient bead-free economical enrichment of lymphocytes from leukapheresis products from healthy donors and study subjects with human immunodeficiency virus (HIV) infection or malignancy. Modified program settings and conditions for the CaridianBCT Elutra device were investigated to optimize lymphocyte enrichment and recovery. Lymphocyte enrichment was measured using a novel approach utilizing cell sizing analysis on a Beckman Coulter Multisizer and confirmed by flow cytometry phenotypic analysis. Efficient enrichment and recovery of lymphocytes from leukapheresis cell products was achieved using modified elutriation settings for flow rate and fraction volume. Elutriation allowed for enrichment of larger numbers of lymphocytes compared with depletion of monocytes by bead adherence, with a trend toward increased lymphocyte purity and yield via elutriation, resulting in a substantial reduction in the cost of enrichment per cell. Importantly, significant lymphocyte enrichment could be accomplished using leukapheresis samples from healthy donors (n=12) or from study subjects with HIV infection (n=15) or malignancy (n=12). Clinical-scale closed-system elutriation can be performed efficiently for the selective enrichment of lymphocytes for immunotherapy protocols. This represents an improvement in cost, yield and purity over current methods that require the addition of monocyte-depleting beads.

Pet Rodents and Fatal Lymphocytic Choriomeningitis in Transplant Patients

Centers for Disease Control (CDC) Podcasts

Three organ transplant recipients died from infection with lymphocytic choriomeningitis virus (LCMV), which was traced back to a hamster owned by the daughter of the organ donor. Dr. Brian Amman, a mammalogist with the Special Pathogens Branch at CDC, discusses the dangers LCMV may pose to people with immune disorders, as well as to pregnant women.

Air Pump-Assisted Graft Centration, Graft Edge Unfolding, and Graft Uncreasing in Young Donor Graft Pre-Descemet Endothelial Keratoplasty.

Science.gov (United States)

Jacob, Soosan; Narasimhan, Smita; Agarwal, Amar; Agarwal, Athiya; A I, Saijimol

2017-08-01

To assess an air pump-assisted technique for graft centration, graft edge unfolding, and graft uncreasing while performing pre-Descemet endothelial keratoplasty (PDEK) using young donor grafts. Continuous pressurized air infusion was used for graft centration, graft edge unfolding, and graft unwrinkling. Ten eyes of 10 patients underwent PDEK with donors aged below 40 years. In all eyes, the donor scrolled into tight scrolls. In all cases, the air pump-assisted technique was effective in positioning and centering the graft accurately and in straightening infolded graft edges and smoothing out graft creases and wrinkles. Endothelial cell loss was 38.6%. Postoperative best-corrected visual acuity at 6 months was 0.66 ± 0.25 in decimal equivalent. Continuous pressurized air infusion acted as a third hand providing a continuous pressure head that supported the graft and prevented graft dislocation as well as anterior chamber collapse during intraocular maneuvering. Adequate maneuvering space was available in all cases, and bleeding, if any, was tamponaded successfully in all cases. Although very young donor grafts may be used for PDEK, they are difficult to center and unroll completely before floating against host stroma. An air pump-assisted technique using continuous pressurized air infusion allows successful final graft positioning even with very young donor corneas. It thus makes surgery easier as several key steps are made easier to handle. It additionally helps in tamponading hemorrhage during peripheral iridectomy, increasing surgical space, preventing fluctuations in the anterior chamber depth, and promoting graft adherence.

Humoral and cellular CMV responses in healthy donors; identification of a frequent population of CMV-specific, CD4+ T cells in seronegative donors

DEFF Research Database (Denmark)

Loeth, Nina; Assing, Kristian; Madsen, Hans O

2012-01-01

.e., T lymphocyte) assays. Here, we have analyzed the CMV status of 100 healthy blood bank donors using both serology and cellular assays. About half (56%) were found to be CMV seropositive, and they all mounted strong CD8+ and/or moderate CD4+ T cell responses ex vivo against the immunodominant CMV...... protein, pp65. Of the 44 seronegative donors, only five (11%) mounted ex vivo T cell responses; surprisingly, 33 (75%) mounted strong CD4+ T cell responses after a brief in vitro peptide stimulation culture. This may have significant implications for the analysis and selection of HCT donors.......CMV status is an important risk factor in immune compromised patients. In hematopoeitic cell transplantations (HCT), both donor and recipient are tested routinely for CMV status by serological assays; however, one might argue that it might also be of relevance to examine CMV status by cellular (i...

Ontogeny of B lymphocyte function. IV. Kinetics of maturation of B lymphocytes from fetal and neonatal mice when transferred into adult irradiated hosts

International Nuclear Information System (INIS)

Sherr, D.; Szewczuk, M.R.; Siskind, G.W.

1977-01-01

Lethally irradiated mice reconstituted with adult T cells and neonatal or fetal B cells produce an anti-DNP response of restricted heterogeneity of affinity when compared with the response of mice reconstituted with T and B cells from adult donors. The capacity to reconstitute adult mice to give a heterogeneous response matures between 7 and 10 days after birth. The maturation of B cells from day-15 fetal or neonatal donors to produce a heterogeneous response was followed in the adult, cell transfer recipient by immunizing them at different times after cell transfer. It was found that B cells both from day-15 fetal mice and from neonatal mice acquire the capacity to produce a heterogeneous response within 3 days in the adult, cell transfer recipient. Thus, the B cell population matures more rapidly in the cell transfer recipient than in the intact donor. The kinetics of maturation in the adult recipient is the same for B cells from day-15 fetal and neonatal donors. The data imply that all information required to produce a fully heterogeneous response is already present in the day-15 fetus. In addition, the data strongly support the hypothesis that a factor in the adult mouse acts to induce this step in the maturation of the B lymphocyte population. Thus, the data seem to be inconsistent with the view that the timing of the occurrence of this differentiation event is precoded in an internal cell clock in the B lymphocyte line. Clearly, B cells from day-15 fetal mice are already capable of differentiating in response to the inducing factor which is present in the adult animal

Apoptotic response of irradiated T-Lymphocytes. An epidemiologic study in canine radiotherapy patients

International Nuclear Information System (INIS)

Stankeova, S.; Kaser-Hotz, B.; Crompton, N.E.A.; Blattmann, H.; Theiler, P.; Emery, G.C.; Roos, M.

2003-01-01

Background: Evaluation of radiation-induced apoptosis in T-lymphocytes was developed for human medicine in order to predict the sensitivity of individual patients to radiation therapy and has regular use in cases of suspected hypersensitivity. A major goal of the present study was to evaluate the usefulness of the apoptosis assay in veterinary medicine for application in radiation sensitivity testing. The main goal was to examine potential changes in sensitivity of T-lymphocytes to radiation-induced apoptosis during the course of radiation treatment. This is a clear example of the advantageous use of spontaneous canine tumors to augment human cancer research. Material and Methods: Blood was collected in heparin tubes, diluted 1:10 in RPMI medium, irradiated with X-rays and incubated for 48 h. T-lymphocytes were labeled using FITC-conjugated antibodies, erythrocytes were lysed, and DNA stained with propidium iodide. For cell analysis, a Becton Dickinson FACScan flow cytometer was used. Radiation-induced apoptosis in T-lymphocytes was quantified. Blood samples from tumor-bearing dogs were taken before the first fraction and at the end of radiation therapy. Results: Apoptosis in lymphocytes is dependent on donor age and donor weight. Tumor-bearing dogs when compared with healthy dogs showed no significant differences in levels of induced apoptosis. No significant changes were seen in the levels of radiation-induced apoptosis in blood taken before, during, or after radiation therapy. Conclusion: The leukocyte apoptosis assay can be successfully applied to canine patients, and a wide spectrum of sensitivities to radiation-induced apoptosis is observed. The sensitivity of a patient's peripheral blood T-lymphocytes to radiation-induced apoptosis does not change as a result of the trauma of radiotherapy during the course of tumor treatment. (orig.)

Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial

Directory of Open Access Journals (Sweden)

Chongsheng Qian

2017-05-01

Full Text Available Abstract Background Allogeneic hematopoietic stem cell transplantation (HSCT, the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB. Methods Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9% or a third party haploidentical donor (57.1%. One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. Results One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%. Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. Conclusions Adoptive transfer of rapidly isolated ADV

A game-theoretic approach to donor kidney sharing.

Science.gov (United States)

O'Brien, B J

1988-01-01

Graft survival in renal transplantation is a function, amongst other things, of the degree of histocompatibility lymphocyte-A (HLA) tissue matching achieved between donor and recipient. Yet a donor procured at centre A might match a transplant candidate at centre B and vice versa. This raises the question of whether, and under what circumstances, surgeons will offer and exchange donor kidneys and gain from such trade in terms of graft survival. We analyse the problem in a game-theoretic framework where the choice of strategy 'to offer or not?' is evaluated in the context of the uncertainty of reciprocation by the other player(s) in the game. The equilibrium solution to a number of variations of the game is predicted to be non-cooperation resulting in collectively sub-optimal graft survival rates. Some policy options for improving cooperation are considered including exchange incentives and coercive measures.

The relative biological effectiveness of a high energy neutron beam for micronuclei induction in T-lymphocytes of different individuals

Energy Technology Data Exchange (ETDEWEB)

Slabbert, J.P., E-mail: jps@tlabs.ac.z [NRF iThemba LABS (Laboratory for Accelerated Based Sciences), Somerset West (South Africa); Dept. of Medical Imaging and Clinical Oncology, University of Stellenbosch (South Africa); August, L. [NRF iThemba LABS (Laboratory for Accelerated Based Sciences), Somerset West (South Africa); Vral, A. [Dept. of Basic Medical Sciences, Ghent University (Belgium); Symons, J. [NRF iThemba LABS (Laboratory for Accelerated Based Sciences), Somerset West (South Africa)

2010-12-15

In assessing the radiation risk of personnel exposed to cosmic radiation fields as it pertains to radiological damage during travel in civilian aircrafts, it is particularly important to know the relative biological effectiveness (RBE) for high energy neutrons. It has been the subject of numerous investigations in recent years using different neutron energies and cytogenetic examinations. Variations in the radiosensitivity of white blood cells for different individuals are likely to influence the estimate of the relative biological effectiveness for high energy neutrons. This as such observations have been noted in the response of different cancer cell lines with varying inherent sensitivities. In this work the radiosensitivities of T-lymphocytes of different individuals to the p(66)/Be neutron beam at iThemba LABS were measured using micronuclei formations and compared to that noted following exposure to {sup 60}Co {gamma}-rays. The principle objective of this investigation was to establish if a relationship between neutron RBE and variation in biological response to {sup 60}Co {gamma}-rays for lymphocytes from different individuals could be determined. Peripheral blood samples were collected from four healthy donors and isolated lymphocytes were exposed to different doses of {sup 60}Co {gamma}-rays (1-5 Gy) and p(66)/Be neutrons (0.5-2.5 Gy). One sample per donor was not exposed to radiation and served as a control. Lymphocytes were stimulated using PHA and cultured to induce micronuclei in cytokinesis-blocked cells. Micronuclei yields were numerated using fluorescent microscopy. Radiosensitivities and RBE values were calculated from the fitted parameters describing the micronuclei frequency dose response data. Dissimilar dose response curves for different donors were observed reflecting varying inherent sensitivities to both neutron and gamma radiation. A clear reduction in the dose limiting RBE{sub M} is noted for donors with lymphocytes more sensitive to

Is Efficacy of the Anti-Cd20 Antibody Rituximab Preventing Hemolysis Due to Passenger Lymphocyte Syndrome?

Science.gov (United States)

Tsujimura, Kazuma; Ishida, Hideki; Tanabe, Kazunari

2017-02-01

Passenger lymphocyte syndrome (PLS) often occurs after ABO-mismatched solid organ and/or bone marrow transplantation between a donor and recipient. Viable donor B-lymphocytes transferred during organ transplantation produce antibodies against recipient red cell antigens, leading to hemolysis. The incidence of PLS has been reported to be around 9% after renal transplantation. A previous report showed that rituximab (Rit) was useful for treatment of PLS in allogeneic stem cell transplantation, bowel transplant and severe cases of hemolysis. However, the effectiveness of Rit in preventing PLS after renal transplantation has not yet been evaluated. The participants in this study were 85 patients who had undergone ABO-mismatched renal transplantation from January 2005 to April 2013. Rit was administered to these patients before transplantation. None of the patients that received Rit treatment developed PLS. Thus administration of Rit before transplantation effectively controlled the production of antibodies by B-lymphocytes, which probably prevented the development of PLS. © 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

A simple bedside approach to therapeutic goals achievement during the management of deceased organ donors--An adapted version of the "VIP" approach.

Science.gov (United States)

Westphal, Glauco Adrieno

2016-02-01

The disproportion between the supply and demand of transplant organs could be alleviated by improving the quality of clinical management of deceased potential donors. As a large number of donor losses by cardiac arrest occur due to hemodynamic instability, without instituting all essential maintenance measures, it is likely that the application of simplified potential donor maintenance protocols will help to decrease potential donor losses and increase the supply of organs for transplantation. The Ventilation, Infusion and Pumping (VIP) strategy is a mnemonic method that brings together key aspects of the restoration of oxygen delivery to tissues during hemodynamic instability: adequate mechanical Ventilation, volume Infusion and evaluation of heart Pump effectiveness. The inclusion of the additional initials, "P" and "S," refers to Pharmacological treatment and Specificities involved in the etiology of shock. The use of simplified care standards can assist in adhering to essential potential donor management measures. Therefore, using a simplified method as the adapted VIP approach can contribute to improving management standards of potential organ donors and increasing the supply of organs for transplantation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent graft-versus-host disease in children with haematological malignancies transplanted from an unrelated donor: a multicentre, randomised, open-label, phase 3 trial

OpenAIRE

Locatelli, Franco; Bernardo, Maria Ester; Bertaina, Alice; Rognoni, Carla; Comoli, Patrizia; Rovelli, Attilio; Pession, Andrea; Fagioli, Franca; Favre, Claudio; Lanino, Edoardo; Giorgiani, Giovanna; Merli, Pietro; Pagliara, Daria; Prete, Arcangelo; Zecca, Marco

2017-01-01

Background Although rabbit anti-T-lymphocyte globulin (ATLG) is largely used for the prevention of immunemediated complications in patients given allogeneic haemopoietic stem-cell transplantation (HSCT) from an unrelated donor, the optimum dose of this drug in children is still undefined. We aimed to test whether a higher dose of ATLG was superior to a lower dose for prevention of grade II–IV acute graft-versus-host disease (GVHD). Methods We conducted a multicentre, randomised, open-label, p...

Cytogenetic effects of tritium incorporated into DNA of human lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Beno, M [Inst. of Preventive and Clinical Medicine, 83301 Bratislava (Slovakia)

1996-12-31

In the reported in vitro experiments the numbers of chromosomal aberrations (CA) in correlation to the physical dose as assessed by determining the specific radioactivity of DNA have been followed in vitro human lymphocytes from adult donors. Lymphocytes from healthy adult donors of age from 20 to 59 of both sexes (24 males and 20 females) were isolated from blood by centrifugation. After washing the cells were irradiated from tritium incorporated during in vitro incubation in phytohemagglutinin containing medium with tritium labelled thymidine. Slides for standard CA counting have been done from every sample 48 hours after the begin cultivation. The CA were counted in at least 200 metaphases on each slide. Parallel samples of lymphocytes served for preparation smears for autoradiography to determine the labeling index. Other parallel samples were used for the determination of tritium concentration in DNA by the diphenylamine method, as well as determination of the specific radioactivity in lymphocyte DNA by scintillation counting. The dose absorbed in DNA was estimated using the conversion factor implicating that 37 kBq of tritium uniformly distributed per gram of tissue of unit density delivers a dose rate of 121.4 {sup m}i{sup G}y/hour. The contamination of cells by precursors of nucleic acids - like tritiated thymidine - causes an uneven distribution of doses in the cell population. A proportion of the population of cells remains unlabelled. The dose-response curve is flat showing signs of loss of heavily damaged cells and signs of repair of damage. Both these signs are based on the nature of biological processes which lead to internal contamination of cells and to expression of effects in terms of numbers of CA. (J.K.) 5 figs., 4 refs.

Albumin infusion after reperfusion prevents gut ischemia-reperfusion-induced gut-associated lymphoid tissue atrophy.

Science.gov (United States)

Ikezawa, Fumie; Fukatsu, Kazuhiko; Moriya, Tomoyuki; Maeshima, Yoshinori; Okamoto, Koichi; Hara, Etsuko; Hiraide, Hoshio; Compher, Charlene W

2006-01-01

Our recent study clarified that gut ischemia-reperfusion (I/R) causes gut-associated lymphoid tissue (GALT) mass atrophy, a possible mechanism for increased morbidity of infectious complications after severe surgical insults. Because albumin administration reportedly reduces hemorrhagic shock-induced lung injury, we hypothesized that albumin treatment prevents GALT atrophy due to gut I/R. Male mice (n = 37) were randomized to albumin, normal saline, and sham groups. All groups underwent jugular vein catheter insertion. The albumin and normal saline groups underwent 75-minute occlusion of the superior mesenteric artery. During gut ischemia, all mice received normal saline infusions at 1.0 mL/h. The albumin group was given 5% bovine serum albumin in normal saline at 1.0 mL/h for 60 minutes after reperfusion, whereas the normal saline group received 0.9% sodium chloride at 1.0 mL/h. The sham group underwent laparotomy only. Mice were killed on day 1 or 7, and the entire small intestine was harvested. GALT lymphocytes were isolated and counted. Their phenotypes (alphabetaTCR, gammadeltaTCR, CD4, CD8, B220) were determined by flow cytometry. On day 1, the gut I/R groups showed significantly lower total lymphocyte and B cell numbers in Peyer's patches and the lamina propria than the sham group. However, the albumin infusion partially but significantly restored these cell numbers. On day 7, there were no significant differences in any of the parameters measured among the 3 groups. Albumin infusion after a gut ischemic insult may maintain gut immunity by preventing GALT atrophy.

A polymorphism in the splice donor site of ZNF419 results in the novel renal cell carcinoma-associated minor histocompatibility antigen ZAPHIR.

Directory of Open Access Journals (Sweden)

Kelly Broen

Full Text Available Nonmyeloablative allogeneic stem cell transplantation (SCT can induce remission in patients with renal cell carcinoma (RCC, but this graft-versus-tumor (GVT effect is often accompanied by graft-versus-host disease (GVHD. Here, we evaluated minor histocompatibility antigen (MiHA-specific T cell responses in two patients with metastatic RCC who were treated with reduced-intensity conditioning SCT followed by donor lymphocyte infusion (DLI. One patient had stable disease and emergence of SMCY.A2-specific CD8+ T cells was observed after DLI with the potential of targeting SMCY-expressing RCC tumor cells. The second patient experienced partial regression of lung metastases from whom we isolated a MiHA-specific CTL clone with the capability of targeting RCC cell lines. Whole genome association scanning revealed that this CTL recognizes a novel HLA-B7-restricted MiHA, designated ZAPHIR, resulting from a polymorphism in the splice donor site of the ZNF419 gene. Tetramer analysis showed that emergence of ZAPHIR-specific CD8+ T cells in peripheral blood occurred in the absence of GVHD. Furthermore, the expression of ZAPHIR in solid tumor cell lines indicates the involvement of ZAPHIR-specific CD8+ T cell responses in selective GVT immunity. These findings illustrate that the ZNF419-encoded MiHA ZAPHIR is an attractive target for specific immunotherapy after allogeneic SCT.

Isolating peripheral lymphocytes by density gradient centrifugation and magnetic cell sorting.

Science.gov (United States)

Brosseron, Frederic; Marcus, Katrin; May, Caroline

2015-01-01

Combining density gradient centrifugation with magnetic cell sorting provides a powerful tool to isolate blood cells with high reproducibility, yield, and purity. It also allows for subsequent separation of multiple cell types, resulting in the possibility to analyze different purified fractions from one donor's sample. The centrifugation step divides whole blood into peripheral blood mononuclear cells (PBMC), erythrocytes, and platelet-rich plasma. In the following, lymphocyte subtypes can be consecutively isolated from the PBMC fraction. This chapter describes enrichment of erythrocytes, CD14-positive monocytes and CD3-positive T lymphocytes. Alternatively, other cell types can be targeted by using magnetic beads specific for the desired subpopulation.

Antibody-mediated suppression of grafted lymphoma. III. Evaluation of the role of thymic function, non-thymus-derived lymphocytes, macrophages, platelets, and polymorphonuclear leukocytes in syngeneic and allogeneic hosts

International Nuclear Information System (INIS)

Shin, H.S.; Hayden, M.; Langley, S.; Kaliss, N.; Smith, M.R.

1975-01-01

Syngeneic or allogeneic mice pretreated with sublethal whole-body irradiation were rendered incapable of suppressing the growth of grafted tumor cells sensitized with alloantibody. The growth of sensitized tumor cells was suppressed when they were mixed with donor effector cells from mice syngeneic or allogeneic to the recipients and then were inoculated in irradiated recipients. Three donor-host combinations were used to study the suppression of the murine lymphoma 6C3HED indigenous to C3H mice. These were C3H donor cells in C3H recipients, C57BL/6 donor cells in C3H recipients, or C57BL/6 donor cells in C57BL/6 recipients. In all three combinations, macrophages obtained from an inflammatory exudate, exudate lymphocytes not bearing theta antigen, and platelets were, in descending order of effectiveness, consistently active in restoring antibody-mediated suppression of tumor growth in irradiated hosts. Prior irradiation of the transferred lymphocytes somewhat diminished their effectiveness. Freeze-thawed or heat-killed macrophages (but not freeze-thawed platelets or lymphocytes) were effective in restoration. Peripheral blood mononuclear leukocytes and splenic lymphoid cells were not active in the recipients syngeneic to the donor cells but were active in recipients allogeneic to the donor cells. Polymorphonuclear leukocytes isolated from peripheral blood or an inflammatory exudate were not active. Intact thymic function seems unimportant since antibody-mediated suppression took place as effectively in thymectomized mice as in normal controls. (U.S.)

[Amplification of γδ T cells in PBMCs of healthy donors and osteosarcoma patients stimulated by zoledronate].

Science.gov (United States)

Li, Zhao-xu; Sun, Ling-ling; Cheng, Rui-lin; Sun, Zheng-wang; Ye, Zhao-ming

2012-08-01

To investigate the amplification and cytotoxicity of γδ T cells in peripheral blood mononuclear cells (PBMCs) of healthy donors and osteosarcoma patients stimulated by zoledronate (Zol) and IL-2. PBMCs from healthy donors and osteosarcoma patients were stimulated with IL-2 and Zol+IL-2, respectively. After 14-day culture, the purity of γδ T cells was assessed by flow cytometry. The cytotoxicity of γδ T cells against target cells was analyzed using a standard lactate dehydrogenase release assay with γδ T lymphocyte-sensitive Daudi cells, γδ T lymphocyte-resistant Raji cells and human osteoblast cell line, hFOB, as the target cells. After 2-week culture ex vivo of PBMCs from healthy donors and osteosarcoma patients, compared with stimulation of IL-2, Zol+IL-2 significantly promoted the amplification of γδ T cells. In addition, γδ T cells showed the higher cytotoxicity against Daudi cells, but no cytotoxic effect on normal cells like hFOB. γδ T cells of high purity and high cytotoxicity can be obtained by the stimulation of Zol combined with IL-2 on PBMCs from healthy donors and osteosarcoma patients.

Immunogenetic analysis of cellular interactions governing the recruitment of T lymphocytes and monocytes in lymphocytic choriomeningitis virus-induced immunopathology

International Nuclear Information System (INIS)

Doherty, P.C.; Ceredig, R.; Allan, J.E.

1988-01-01

The Lyt2+ class I major histocompatibility complex (MHC)-restricted virus-immune T cells that induce murine lymphocytic choriomeningitis (LCM) are targeted onto radiation-resistant cells in the central nervous system of virus-infected mice. The use of appropriate bone marrow radiation chimeras as LCM virus-infected, (immunosuppressed recipients for immune T-cell transfer has established that, though bone marrow-derived cells can stimulate virus-specific cytotoxic T lymphocytes (CTL) in spleen, they do not reconstitute the barrier to T-cell recruitment from blood to cerebrospinal fluid. This is true for chimeras made up to 8 months previously, even though the inflammatory monocytes and macrophages in such chimeras are all of donor bone marrow origin. Radiation-resistant cells in the spleens of these chimeras are also still able to further stimulate virus-immune CTL. There is no requirement for H-2 compatibility between virus-immune T lymphocytes and secondarily recruited monocytes, or T cells of an inappropriate specificity. The key event in LCM immunopathology may thus be localization of T cells to the antigen-presenting endothelium in brain, leading to the secretion of mediators that promote the nonspecific recruitment of monocytes and other T cells

Immunoglobulin production in human mixed lymphocyte cultures: implications for co-cultures of cells from patients and healthy donors

International Nuclear Information System (INIS)

Ruemke, H.C.; Terpstra, F.G.; Huis, B.; Out, T.A.; Zeijlemaker, W.P.

1982-01-01

When human peripheral blood lymphocytes (PBL) are cultured in the presence of irradiated allogeneic lymphocytes, the resulting mixed lymphocyte reaction (MLR) leads to the secretion into the supernatant of substantial amounts of IgM and IgG, derived from nonirradiated responder B lymphocytes. Our data indicate that stimulation to Ig production by responder B cells may result from different types of of interactions. First, B cells and monocytes among the irradiated stimulator cells activate T responder B cells to produce Ig; second, ''responder'' B cells activate irradiated ''stimulator'' T cells, leading to a ''helper'' signal, back to the responder B cells and leading to Ig production. The latter system is radiosensitive, because allogeneic T cells, irradiated at a dose of 4000 rad or more, failed to induce Ig production by responder B cells. In some combinations of human allogeneic lymphocytes, the co-culture of the cells leads to inhibition of Ig production, both in the presence and in the absence of PWM. Thus, co-culture of allogeneic cells may cause ''positive'' as well as ''negative'' allogeneic effects. The implications of these findings for the interpretation of co-cultures that are aimed at establishing defects in lymphocytes from patients with, for example, immunodeficiencies, who fail to produce Ig in the presence of PWM are discussed

Mixed allogeneic reconstitution (A+B----A) to induce donor-specific transplantation tolerance. Permanent acceptance of a simultaneous donor skin graft

International Nuclear Information System (INIS)

Ildstad, S.T.; Wren, S.M.; Oh, E.; Hronakes, M.L.

1991-01-01

Mixed allogeneic reconstitution, in which a mixture of T-cell-depleted bone marrow of syngeneic host and allogeneic donor type is transplanted into a lethally irradiated recipient (A+B----A), results in mixed lymphopoietic chimerism with engraftment of a mixture of both host and donor bone marrow elements. Recipients are specifically tolerant to donor both in vitro and in vivo. Donor-specific skin grafts survive indefinitely when they are placed after full bone marrow repopulation at 28 days, while third-party grafts are rapidly rejected. To determine whether a delay of a month or more for full bone marrow repopulation is required before a donor-specific graft can be placed, we have now examined whether tolerance induction can be achieved if a graft is placed at the time of bone marrow transplantation. Permanent acceptance of donor-specific B10.BR skin grafts occurred when mixed allogeneic chimerism (B10+B10.BR----B10) was induced and a simultaneous allogeneic donor graft placed. In vitro, mixed reconstituted recipients were specifically tolerant to the B10.BR donor lymphoid cells but fully reactive to MHC-disparate third-party (BALB/c; H-2dd) when assessed by mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays. These data therefore indicate that a donor-specific graft placed at the time of mixed allogeneic reconstitution is permanently accepted without rejection. To determine whether an allogeneic skin graft alone without allogeneic bone marrow would be sufficient to induce tolerance, syngeneic reconstitution (B10----B10) was carried out, and a simultaneous B10.BR allogeneic skin graft placed. Although skin grafts were prolonged in all recipients, all grafts rejected when full lymphopoietic repopulation occurred at 28 days

The determination of lymphoid cell chimerism using peripheral blood lymphocytes from murine bone marrow chimeras

International Nuclear Information System (INIS)

Skidmore, B.J.; Miller, L.S.

1978-01-01

A simple, rapid and accurate method was devised for determining lymphoid cell chimerism in bone marrow-reconstituted mice. Chimeras were produced by reconstituting lethally irradiated mice with semi-allogeneic bone marrow cells. Lymphocytes from the peripheral blood of individual chimeric mice were purified by sedimentation in dextran solution and differential flotation in Ficoll-Hypaque gradients. From 250-500 μl of blood, 1-7 x 10 5 cells were routinely obtained. The extent of chimerism was determined serologically by using peripheral blood lymphocytes as target cells in a dye exclusion microcytotoxicity assay. Using this new technique, approximately 80% of the reconstituted mice were found to be repopulated with lymphocytes of the donor type. (Auth.)

Phytohemagglutinin (PHA) stimulation of peripheral-blood lymphocytes and stem cell take

Energy Technology Data Exchange (ETDEWEB)

Astaldi, G [Blood Research Foundation Center, Tortona, Italy; Karanovic, D; Vettori, P P; Karanovic, J; Piletic, O

1974-01-01

The effect of PHA-stimulation of peripheral-blood lymphocytes on the spleen-colony formation in irradiated rats was examined. 25-day old Wistar rats underwent total-body irradiation (600 R), and they were used as recipients. On the other hand, 2 and /sup 1///sub 2/ month old untreated Wistar rats were used as donors of peripheral-blood lymphocytes, which were obtained by sedimentation with Dextraven from defibrinated blood. Four rat lots were used. The 1st one did not receive irradiation, and was kept as ''blank control.'' The 2nd one was just irradiated and kept as ''radiated control.'' The 3rd and the 4th rat lots of the series were irradiated, but the former lot was injected i.v. with 5 x 10/sup 7/ peripheral-blood untreated lymphocytes, whereas the fourth lot was injected i.v. with the same amount of lymphocytes, which were previously incubated in vitro for 24 hrs with PHA-M (Difco). The results showed that the PHA-incubation of transplanted peripheral-blood lymphocytes significantly increases the number and size of the macroscopic spleen colonies, in relationship to the colonies which occurs after transplantation of untreated lymphocytes. Histo-cytological observation clearly showed that the colonies formed after injection of mitogen-pretreated peripheral-blood lymphocytes were predominantly of erythroid type and, then, of non-differentiated cells. Only a few of them were of a mixed type, consisting of both undifferentiated cells and erythroid cells.

Increased uracil misincorporation in lymphocytes from folate-deficient rats

OpenAIRE

Duthie, S J; Grant, G; Narayanan, S

2000-01-01

The development of certain human cancers has been linked with inadequate intake of folates. The effects of folate deficiency in vivo on DNA stability (strand breakage, misincorporated uracil and oxidative base damage) in lymphocytes isolated from rats fed a diet deficient in folic acid was determined. Because the metabolic pathways of folate and other methyl donors are closely coupled, the effects of methionine and choline deficiency alone or in combination with folate deficiency were determi...

Pet Rodents and Fatal Lymphocytic Choriomeningitis in Transplant Patients

Centers for Disease Control (CDC) Podcasts

2007-05-16

Three organ transplant recipients died from infection with lymphocytic choriomeningitis virus (LCMV), which was traced back to a hamster owned by the daughter of the organ donor. Dr. Brian Amman, a mammalogist with the Special Pathogens Branch at CDC, discusses the dangers LCMV may pose to people with immune disorders, as well as to pregnant women.  Created: 5/16/2007 by CDC, Office of the Director.   Date Released: 5/16/2007.

Genomic instability after targeted irradiation of human lymphocytes: Evidence for inter-individual differences under bystander conditions

International Nuclear Information System (INIS)

Kadhim, Munira A.; Lee, Ryonfa; Moore, Stephen R.; Macdonald, Denise A.; Chapman, Kim L.; Patel, Gaurang; Prise, Kevin M.

2010-01-01

Environmental 222 radon exposure is a human health concern, and many studies demonstrate that very low doses of high LET α-particle irradiation initiate deleterious genetic consequences in both irradiated and non-irradiated bystander cells. One consequence, radiation-induced genomic instability (RIGI), is a hallmark of tumorigenesis and is often assessed by measuring delayed chromosomal aberrations. We utilised a technique that facilitates transient immobilization of primary lymphocytes for targeted microbeam irradiation and have reported that environmentally relevant doses, e.g. a single 3 He 2+ particle traversal to a single cell, are sufficient to induce RIGI. Herein we sought to determine differences in radiation response in lymphocytes isolated from five healthy male donors. Primary lymphocytes were irradiated with a single particle per cell nucleus. We found evidence for inter-individual variation in radiation response (RIGI, measured as delayed chromosome aberrations). Although this was not highly significant, it was possibly masked by high levels of intra-individual variation. While there are many studies showing a link between genetic predisposition and RIGI, there are few studies linking genetic background with bystander effects in normal human lymphocytes. In an attempt to investigate inter-individual variation in the induction of bystander effects, primary lymphocytes were irradiated with a single particle under conditions where fractions of the population were traversed. We showed a marked genotype-dependent bystander response in one donor after exposure to 15% of the population. The findings may also be regarded as a radiation-induced genotype-dependent bystander effect triggering an instability phenotype.

Genomic instability after targeted irradiation of human lymphocytes: Evidence for inter-individual differences under bystander conditions

Energy Technology Data Exchange (ETDEWEB)

Kadhim, Munira A., E-mail: mkadhim@brookes.ac.uk [School of Life Sciences, Oxford Brookes University, Oxford OX3 0BP (United Kingdom); Lee, Ryonfa [Biophysics, GSI Helmholtzzentrum fuer Schwerionenforschung GmbH, Planckstrasse 1, D-64291 Darmstadt (Germany); Moore, Stephen R.; Macdonald, Denise A. [Radiation and Genome Stability Unit, Medical Research Council, Harwell, Oxfordshire OX11 0RD (United Kingdom); Chapman, Kim L. [School of Life Sciences, Oxford Brookes University, Oxford OX3 0BP (United Kingdom); Patel, Gaurang; Prise, Kevin M. [Centre for Cancer Research and Cell Biology, Queen' s University Belfast, Belfast BT9 7BL (United Kingdom)

2010-06-01

Environmental {sup 222}radon exposure is a human health concern, and many studies demonstrate that very low doses of high LET {alpha}-particle irradiation initiate deleterious genetic consequences in both irradiated and non-irradiated bystander cells. One consequence, radiation-induced genomic instability (RIGI), is a hallmark of tumorigenesis and is often assessed by measuring delayed chromosomal aberrations. We utilised a technique that facilitates transient immobilization of primary lymphocytes for targeted microbeam irradiation and have reported that environmentally relevant doses, e.g. a single {sup 3}He{sup 2+} particle traversal to a single cell, are sufficient to induce RIGI. Herein we sought to determine differences in radiation response in lymphocytes isolated from five healthy male donors. Primary lymphocytes were irradiated with a single particle per cell nucleus. We found evidence for inter-individual variation in radiation response (RIGI, measured as delayed chromosome aberrations). Although this was not highly significant, it was possibly masked by high levels of intra-individual variation. While there are many studies showing a link between genetic predisposition and RIGI, there are few studies linking genetic background with bystander effects in normal human lymphocytes. In an attempt to investigate inter-individual variation in the induction of bystander effects, primary lymphocytes were irradiated with a single particle under conditions where fractions of the population were traversed. We showed a marked genotype-dependent bystander response in one donor after exposure to 15% of the population. The findings may also be regarded as a radiation-induced genotype-dependent bystander effect triggering an instability phenotype.

Influence of occupational exposure to pesticides on the level of DNA damage induced in human lymphocytes (Polish group) by UV-C and X-rays

International Nuclear Information System (INIS)

Dyga, W.; Drag, Z.; Cebulska-Wasilewska, A.

2002-01-01

The aim of this study was to find out whether occupational exposure to pesticides might affect the individual susceptibility of various donors to the induction of DNA damage by genotoxic agents (UV-C, X-rays) and the efficiency of cellular repair. Previously cryo preserved lymphocytes were defrosted, and DNA damage in the lymphocytes prior to any in vitro studies was investigated with the application of the Comet assay. In order to evaluate the susceptibilities of human lymphocytes to genotoxic agents and the variability of repair capacities, the DNA migrations were estimated immediately after exposure to UV-C light or X-rays and after two hours. On average, the DNA damage detected in untreated lymphocytes was significantly higher in the group exposed to pesticides than in reference group. UV-C treated lymphocytes from group exposed to pesticides shows a greater statistically significant level of DNA migration compared to the reference group, detected after 2 hours incubation in the absence of PHA. Significantly lower responses to X-rays and higher levels of residual DNA damage were detected in the lymphocytes of donors from the group exposed to pesticides compared with the reference group. In conclusion, our results suggest that occupational exposure to pesticides influences the level of induced DNA damage, and the cellular capabilities of repair. (author)

Achievements and challenges of adoptive T cell therapy with tumor-infiltrating or blood-derived lymphocytes for metastatic melanoma

DEFF Research Database (Denmark)

Svane, Inge Marie; Verdegaal, Els M

2014-01-01

Adoptive cell therapy (ACT) based on autologous T cell derived either from tumor as tumor-infiltrating lymphocytes (TILs) or from peripheral blood is developing as a key area of future personalized cancer therapy. TIL-based ACT is defined as the infusion of T cells harvested from autologous fresh...

Role of donor lymphoid cells in the transfer of allograft tolerance

International Nuclear Information System (INIS)

Pierce, G.E.; Watts, L.M.

1985-01-01

Tolerance to murine skin allografts across a MHC disparity was induced by conditioning primary hosts with sublethal fractionated total-body irradiation (FTBI) and transfusion of allogeneic bone marrow (BM). Tolerance could be adoptively transferred to secondary hosts conditioned by FTBI with infusion of spleen cells from hosts bearing intact skin allografts greater than 60 days. Tolerance could not be transferred by tolerant host spleen (THS) preparations from which cells of the donor genotype had been deleted by cytotoxic alloantisera. Deletion of host genotype cells, however, did not diminish the capability of THS to transfer tolerance. All of the tolerizing activity of THS appeared to reside within cells of the donor genotype. Small numbers of normal donor spleen cells could induce tolerance in FTBI hosts but only at the expense of very high mortality, in contrast to the low mortality observed with tolerizing injections of allogeneic donor cells from THS or injections of normal semiallogeneic F1 hybrid spleen cells. If an active immune response is responsible for tolerance induction/transfer in this model, allogeneic donor lymphoid cells derived from BM, in contrast to donor spleen cells, must be capable of mounting this response without concomitant severe GVHD. In future experiments, cells of donor genotype can be isolated from THS and purified in sufficient numbers to compare their tolerizing efficiency vs. that of normal donor cells, detect possible suppression of normal host cell alloreactivity in vitro and identify the donor cell phenotypes involved

Expression of a single, viral oncoprotein in skin epithelium is sufficient to recruit lymphocytes.

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Allison Choyce

Full Text Available Established cancers are frequently associated with a lymphocytic infiltrate that fails to clear the tumour mass. In contrast, the importance of recruited lymphocytes during premalignancy is less well understood. In a mouse model of premalignant skin epithelium, transgenic mice that express the human papillomavirus type 16 (HPV16 E7 oncoprotein under a keratin 14 promoter (K14E7 mice display epidermal hyperplasia and have a predominant infiltrate of lymphocytes consisting of both CD4 and CD8 T cells. Activated, but not naïve T cells, were shown to preferentially traffic to hyperplastic skin with an increased frequency of proliferative CD8+ T cells and CD4+ T cells expressing CCR6 within the tissue. Disruption of the interaction between E7 protein and retinoblastoma tumour suppressor protein (pRb led to reduced epithelial hyperplasia and T cell infiltrate. Finally, while K14E7 donor skin grafts are readily accepted onto syngeneic, non-transgenic recipients, these same skin grafts lacking skin-resident lymphocytes were rejected. Our data suggests that expression of a single oncoprotein in the epidermis is sufficient for lymphocyte trafficking (including immunosuppressive lymphocytes to premalignant skin.

Infusion cisternography

International Nuclear Information System (INIS)

Magnaes, B.; Rootwelt, K.; Sjaastad, O.

1976-01-01

A source of error in cerebrospinal fluid (CSF) infusion tests is leakage at the dural puncture site. The addition of a bolus of radionuclide to the infusion fluid was helpful in detecting the existence of leakage as shown by increased infusion pressure in six of eight patients studied with and without scintigraphic evidence of leakage. Comparison of CSF dynamics in 26 patients studied by infusion cisternography and conventional cisternography showed similar patterns, suggesting no alteration of CSF dynamics by the artificial CSF infusion. Combining the two tests, therefore, resulted in simple identification of the leakage and saved the patient time and discomfort

[Variability of the sensitivity of human lymphocytes to the antiproliferative action of alkylating agents].

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Veremko, L N; Telegin, L Iu; Pevnitskii, L A

1983-05-01

A study was made of variability of the sensitivity of peripheral blood lymphocytes from different donors to an antiproliferative action of cyclophosphamide and thiophosphamide. A similar degree of the sensitivity was revealed to alkylating agents differing in the action mode, with this degree being independent of the "stimulation index" magnitude.

Phytohemagglutinin (PHA) stimulation of peripheral-blood lymphocytes and stem cell take

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Astaldi, G. (Blood Research Foundation Center, Tortona, Italy); Karanovic, D.; Vettori, P.P.; Karanovic, J.; Piletic, O.

1974-01-01

The effect of PHA-stimulation of peripheral-blood lymphocytes on the spleen-colony formation in irradiated rats was examined. 25-day old Wistar rats underwent total-body irradiation (600 R), and they were used as recipients. On the other hand, 2 and /sup 1///sub 2/ month old untreated Wistar rats were used as donors of peripheral-blood lymphocytes, which were obtained by sedimentation with Dextraven from defibrinated blood. Four rat lots were used. The 1st one did not receive irradiation, and was kept as ''blank control.'' The 2nd one was just irradiated and kept as ''radiated control.'' The 3rd and the 4th rat lots of the series were irradiated, but the former lot was injected i.v. with 5 x 10/sup 7/ peripheral-blood untreated lymphocytes, whereas the fourth lot was injected i.v. with the same amount of lymphocytes, which were previously incubated in vitro for 24 hrs with PHA-M (Difco). The results showed that the PHA-incubation of transplanted peripheral-blood lymphocytes significantly increases the number and size of the macroscopic spleen colonies, in relationship to the colonies which occurs after transplantation of untreated lymphocytes. Histo-cytological observation clearly showed that the colonies formed after injection of mitogen-pretreated peripheral-blood lymphocytes were predominantly of erythroid type and, then, of non-differentiated cells. Only a few of them were of a mixed type, consisting of both undifferentiated cells and erythroid cells.

Role of mobile passenger lymphocytes in the rejection of renal and cardiac allografts in the rat. A passenger lymphocyte-mediated graft-versus-host reaction amplifies the host response

International Nuclear Information System (INIS)

van Vrieshilfgaarde, R.; Hermans, P.; Terpstra, J.L.; van Breda Viresman, P.J.

1980-01-01

It is demonstrated that passenger lymphocytes migrate out of rat renal allografts into host spleens in a radioresistant fashion. These mobile passenger lymphocytes within BN kidney and heart transplants are immunocompetent, since they elicit a graft-versus-host (GVH) reaction in the spleens of (LEW x BN)F2 hybrid hosts. The greater GVH reaction in (LEW x BN)F1 recipients of BN kidneys reflects the greater number of mobile passenger lymphocytes in the kidney when compared to the heart. The mobile passenger lymphocytes within BN renal allografts also cause a proliferative response in the spleens of the LEW hosts as well as an accelerated rejection of BN renal allografts when compared to BN cardiac allografts, for the differences between BN kidney and heart, both in terms of splenomegaly elicited in LEW as well as tempo of rejection, are abolished by total body x-irradiation of the donor with 900 rad. Results indicate that a mobile passenger lymphocyte mediated GVH reaction in the central lymphoid organs of the host augments the host response to allogenic kidneys and contributes materially to first-set renal allograft rejection; this GVH reaction on the other hand is not conspicuously present in LEW recipients of BN cardiac allografts and has therefore little effect on first-set cardiac allograft rejection

Reference ranges for lymphocyte subsets in healthy adult male Oman is

International Nuclear Information System (INIS)

Al-Jabri, Ali A.; Al-Shukaili, Ahmed K.; Al-Rashdi, Zowaina T.; Ganguly, Shyam S.

2008-01-01

Objective was to determine the reference ranges of lymphocyte subsets in serologically HIV-seronegative healthy male adults in Oman. A cohort, of 118 healthy male blood donors ranging in age from 18-51 years, was included in the study. The average was 25 years. Blood samples collected into tubes containing ethylene-diamine-tetra acetic acid were investigated for lymphocyte subsets using flow cytometer. This study was conducted in the Immunology Laboratory of Sultan Qaboos University, College of Medicine and Health Sciences, Muscat, Oman during the year 2006. For the 118 males investigated, the mean percentage and absolute values of the lymphocyte subsets were as follows: Cd3: 68.53+-7.5%, 1701+-489 cells/ul; CD8: 25.8+-5.9%, 638+-225 cells/ul; CD19: 13.7+-4.7%, 349+-158 cells/ul, CD56: 12.2+-6.7%, 308+-204 cells/ul. The ratio of CD4/CD8 was 1.6. Immunophenotyping has been used to establish reference values of lymphocyte subsets in normal healthy adult males in Oman. The Omani male reference values obtained in this study show wide variations compared with kits values previously used as reference. (author)

Infusion Extractor

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Chang-Diaz, Franklin R.

1988-01-01

Apparatus and method of removing desirable constituents from an infusible material by infusion extraction, where a piston operating in a first chamber draws a solvent into the first chamber where it may be heated, and then moves the heated solvent into a second chamber containing the infusible material, and where infusion extraction takes place. The piston then moves the solvent containing the extract through a filter into the first chamber, leaving the extraction residue in the second chamber.

Cytogenetic effects of near ultraviolet radiation in normal and systemic lupus erythematosus lymphocytes

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Caporossi, D.; Sebastiani, G.; Nicoletti, B. (Rome 2 University (Italy). Department of Public Health and Cellular Biology); Masala, C. (' La Sapienza' University, rome (Italy). Institute of Infectious and Tropical Diseases)

1990-03-01

The authors conducted a study on the spontaneous and UV-A induced frequency of chromosomal breaks and sister-chromatid exchanges (SCE) in purified lymphocytes from normal donors and from systemic lupus erythematosus (SLE) patients who were in clinical remission at the time of the study. Our results show that although SLE lymphocytes exhibit a higher frequency of spontaneous SCEs than controls, the rate of chromosomal breakage is comparable in the 2-groups. In both controls and patients, irradiation with UV-A (320-400 nm) increases the SCE values but does not significantly affect the frequency of chromosomal aberrations. (author). 14 refs.; 1 fig.; 3 tabs.

Cytogenetic effects of near ultraviolet radiation in normal and systemic lupus erythematosus lymphocytes

International Nuclear Information System (INIS)

Caporossi, D.; Sebastiani, G.; Nicoletti, B.; Masala, C.

1990-01-01

The authors conducted a study on the spontaneous and UV-A induced frequency of chromosomal breaks and sister-chromatid exchanges (SCE) in purified lymphocytes from normal donors and from systemic lupus erythematosus (SLE) patients who were in clinical remission at the time of the study. Our results show that although SLE lymphocytes exhibit a higher frequency of spontaneous SCEs than controls, the rate of chromosomal breakage is comparable in the 2-groups. In both controls and patients, irradiation with UV-A (320-400 nm) increases the SCE values but does not significantly affect the frequency of chromosomal aberrations. (author). 14 refs.; 1 fig.; 3 tabs

Effect of cortisol infusion patterns and castration on metabolic and immunological indices of stress response in cattle.

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Ting, S T L; Earley, B; Crowe, M A

2004-05-01

This study tested the hypotheses that: (1) either acute stress induced by Burdizzo castration, or cortisol infusion would modulate plasma glucose, insulin and growth hormone (GH) concentrations; and (2) immune modulation induced by cortisol would be dependent on the pattern, intensity and duration of circulating cortisol concentrations. Fifty 9.2-month-old Holstein x Friesian bulls (232 +/- 2.0 kg) were blocked by weight and randomly assigned to one of five treatments (n = 10 per treatment): (1) sham handled control; (2) Burdizzo castration; (3) hydrocortisone infusion to mimic the castration-induced secretion pattern of cortisol; (4) hourly pulse infusion of hydrocortisone; and (5) sustained infusion of hydrocortisone for 8h. Blood samples were collected intensively on day 0, and weekly from days 1 to 35. Castration acutely increased plasma cortisol, GH and haptoglobin concentrations, suppressed lymphocyte in vitro interferon-gamma (IFN-gamma) production, but had no effect on plasma glucose and insulin concentrations. Cortisol infusion to simulate the castration-induced secretion pattern of cortisol, and pulse infusion of cortisol did not suppress the IFN-gamma production. A sustained infusion of cortisol resulted in the transient suppression of IFN-gamma production. Moreover, the sustained cortisol infusion resulted in increased plasma glucose, insulin and GH concentrations. The overall 14-day feed intakes and 35-day growth rates were not affected by treatments. In conclusion, cortisol infusion to induce immune suppression in vivo occurred only at pharmacological doses. Within physiological ranges, cortisol was not associated with the suppression of immune function, indicating that during castration cortisol per se is not responsible for the suppression of in vitro IFN-gamma production.

Hematopoietic stem cell transplantation for chronic lymphocytic leukemia.

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Gladstone, Douglas E; Fuchs, Ephraim

2012-03-01

Although hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many aggressive hematologic malignancies, the role of HSCT in chronic lymphocytic leukemia (CLL) has remained controversial. Now in the era of improved conventional treatment and better prognostication of long-term outcome, a review of autologous and allogeneic HSCT in CLL treatment is warranted. Despite an improved disease-free survival in some patients, multiple, prospective, randomized autologous HSCT CLL trials fail to demonstrate an overall survival benefit as compared to conventional therapy. Allogeneic bone marrow transplantation, although limited by donor availability, can successfully eradicate CLL with adverse prognostic features. In the older CLL patients, nonmyeloablative allogeneic transplants are better tolerated than myeloablative transplants. Nonmyeloablative allogeneic transplants are less effective in heavily diseased burdened patients. Outside of a clinical protocol, autologous HSCT for CLL cannot be justified. Nonmyeloablative allogeneic transplantation should be considered in high-risk populations early in the disease process, when disease burden is most easily controlled. Alternative donor selection using haploidentical donors and posttransplantation cyclophosphamide has the potential to vastly increase the availability of curative therapy in CLL while retaining a low treatment-related toxicity.

Generation of B-cell chronic lymphocytic leukemia (B-CLL)-reactive T-cell lines and clones from HLA class I-matched donors using modified B-CLL cells as stimulators: implications for adoptive immunotherapy.

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Hoogendoorn, M; Wolbers, J Olde; Smit, W M; Schaafsma, M R; Barge, R M Y; Willemze, R; Falkenburg, J H F

2004-07-01

Allogeneic stem cell transplantation following reduced-intensity conditioning is being evaluated in patients with advanced B-cell chronic lymphocytic leukemia (B-CLL). The curative potential of this procedure is mediated by donor-derived alloreactive T cells, resulting in a graft-versus-leukemia effect. However, B-CLL may escape T-cell-mediated immune reactivity since these cells lack expression of costimulatory molecules. We examined the most optimal method to transform B-CLL cells into efficient antigen-presenting cells (APC) using activating cytokines, by triggering toll-like receptors (TLRs) using microbial pathogens and by CD40 stimulation with CD40L-transfected fibroblasts. CD40 activation in the presence of IL-4 induced strongest upregulation of costimulatory and adhesion molecules on B-CLL cells and induced the production of high amounts of IL-12 by the leukemic cells. In contrast to primary B-CLL cells as stimulator cells, these malignant APCs were capable of inducing the generation of B-CLL-reactive CD8(+) CTL lines and clones from HLA class I-matched donors. These CTL lines and clones recognized and killed primary B-CLL as well as patient-derived lymphoblasts, but not donor cells. These results show the feasibility of ex vivo generation of B-CLL-reactive CD8(+) CTLs. This opens new perspectives for adoptive immunotherapy, following allogeneic stem cell transplantation in patients with advanced B-CLL.

[The Influence of UV-Light on the Sub-Populational Composition and Expression of Membrane Markers of Lymphocytes of Donor Blood].

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Artyukhov, V G; Basharina, O V; Zemchenkova, O V; Ryazantsev, S V

2016-01-01

The influence of UV-light (240-390 nm) at dozes of 151 and 755 J/m2 on the content of membrane markers of lymphocytes using the method of flow cytometry was investigated. It was demonstrated that during incubation of UV-irradiated lymphocytes the change of their populational and sub-populational composition occurs. Expression of complexes of CD3, CD 19,.CD8, CD 16, CD25 and CD95 increased. This increase was caused mainly by de novo synthesis. UV-light had immunostimulating effect on CD8+ T-lymphocyte population. Together with the increase of cytotoxic cells and NK-cells, activation of lymphocytes (increased amount of CD25+ and CD95+ cells) took place. Amount of cells undergone apoptosis or necrosis increased proportionally to the dosage. These changes were more expressed during incubation of lymphocytes in nutrition medium without autological blood serum, e.g. under deficiency of growth factors and antioxidants.

Unilateral Dependant Pulmonary Edema During Laparoscopic Donor Nephrectomy: Report of Three Cases

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Manisha Modi

2009-01-01

Full Text Available Unilateral pulmonary edema of the dependant lung was observed in three patients during laparoscopic donor nephrectomy. Patients were treated with 02 supplementation by face mask, fluid restriction and diuretic. All the patients were relieved of symptoms with radiological improvement. The possible causes of this unusual complication following laparoscopic surgery appear to be prolonged lateral decubitus position and high intraoperative fluid infusion.

Donor exosomes rather than passenger leukocytes initiate alloreactive T cell responses after transplantation

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Marino, Jose; Babiker-Mohamed, Mohamed H.; Crosby-Bertorini, Patrick; Paster, Joshua T.; LeGuern, Christian; Germana, Sharon; Abdi, Reza; Uehara, Mayuko; Kim, James I.; Markmann, James F.; Tocco, Georges; Benichou, Gilles

2016-01-01

Transplantation of allogeneic organs and tissues represents a lifesaving procedure for a variety of patients affected with end-stage diseases. Although current immunosuppressive therapy prevents early acute rejection, it is associated with nephrotoxicity and increased risks for infection and neoplasia. This stresses the need for selective immune-based therapies relying on manipulation of lymphocyte recognition of donor antigens. The passenger leukocyte theory states that allograft rejection is initiated by recipient T cells recognizing donor major histocompatibility complex (MHC) molecules displayed on graft leukocytes migrating to the host’s lymphoid organs. We revisited this concept in mice transplanted with allogeneic skin, heart, or islet grafts using imaging flow cytometry. We observed no donor cells in the lymph nodes and spleen of skin-grafted mice, but we found high numbers of recipient cells displaying allogeneic MHC molecules (cross-dressed) acquired from donor microvesicles (exosomes). After heart or islet transplantation, we observed few donor leukocytes (100 per million) but large numbers of recipient cells cross-dressed with donor MHC (>90,000 per million). Last, we showed that purified allogeneic exosomes induced proinflammatory alloimmune responses by T cells in vitro and in vivo. Collectively, these results suggest that recipient antigen-presenting cells cross-dressed with donor MHC rather than passenger leukocytes trigger T cell responses after allotransplantation. PMID:27942611

Donor leucocyte imaging in patients with AIDS: A preliminary report

International Nuclear Information System (INIS)

O'Doherty, M.J.; Kent and Canterbury Hospital; Revell, P.; Page, C.J.; Nunan, T.O.; Lee, S.; Mountford, P.J.

1990-01-01

Four patients with the acquired immunodeficiency syndrome (AIDS) and fever were investigated using donor leucocyte scans. The lung/liver and lung/spleen uptake ratios in these patients were compared with the uptake ratios in donor leucocyte scans in seven neutropenic (non-AIDS) patients and five patients who had autologous leucocyte scans performed over the same time period. All scans used indium oxine In 111 labelled leucocytes except that for one AIDS patient which used technetium hexamethyl-propylene amine oxide Tc99m labelled donor leucocytes. There were no adverse reactions to the donor cell infusions. Two patients had repeat studies 8 weeks apart (from different donors) without ill effect. There were no differences in the 111 In uptake ratios between the three groups. There were three positive studies in the patients with AIDS, and these elucidated the cause of the pyrexia in all three. The negative case is more difficult to confirm, but the clinical course and the absence of focal disease on post-mortem have been taken to support the scan findings. There was no difference in the acceptibility of the technique or the distribution of the labelled leucocytes between the AIDS and non-AIDS patients. Donor leucocyte imaging of patients with AIDS is probably more effective and considerably less hazardous for technical staff than autologous leucocyte methods. This study demonstrates that the technique can be applied successfully to patients with AIDS. (orig.)

The impact of donor characteristics on the immune cell composition of mixture allografts of granulocyte-colony-stimulating factor-mobilized marrow harvests and peripheral blood harvests.

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Wang, Yu-Tong; Zhao, Xiang-Yu; Zhao, Xiao-Su; Xu, Lan-Ping; Zhang, Xiao-Hui; Wang, Yu; Liu, Kai-Yan; Chang, Ying-Jun; Huang, Xiao-Jun

2015-12-01

The association of donor characteristics with immune cell composition in allografts remains poorly understood. In this retrospective study, the effects of donor characteristics on immune cell composition in allografts were investigated. The correlations of donor characteristics with the immune cell composition in mixture allografts of granulocyte-colony-stimulating factor-mobilized marrow harvests and peripheral blood harvests of 390 healthy donors (male, 240; female, 150; median age, 40 years old) were analyzed. The median doses of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD3+CD4-CD8- T cells, and monocytes in mixture allografts were 160.57 × 10(6), 89.29 × 10(6), 56.16 × 10(6), 10.87 × 10(6), and 137.94 × 10(6)/kg, respectively. Multivariate analysis showed that younger donor age was associated with a higher dose of CD3+ T cells (p = 0.006), CD3+CD8+ T cells (p donor weight with CD3+ T cells (p blood lymphocyte pre-peripheral blood apheresis was correlated with the yield of CD3+ T cells (p blood monocyte count before marrow harvest predicted the monocyte dose (p = 0.002). The results suggested that older and overweight donors should not be chosen. The monocyte and lymphocyte counts before harvest could predict the yield of immune cells in allografts. © 2015 AABB.

Long-term engraftment, graft-vs.-host disease, and immunologic reconstitution after experimental transplantation of allogeneic peripheral blood cells from G-CSF-treated donors.

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Pan, L; Bressler, S; Cooke, K R; Krenger, W; Karandikar, M; Ferrara, J L

1996-10-01

Peripheral blood cells (PBPC) are an alternative source of bone marrow for allogeneic transplantation. Reports from recent clinical trials granulocyte colony-stimulating factor (G-CSF)-mobilized PBPC for allogeneic transplantation show incidence and severity of graft-vs.-host disease (GVHD) similar to those observed in conventional bone marrow transplantation (BMT), despite the presence of 10- to 20-fold more T cell in the PBPC inoculum. In the present study, we examined the effects of pretreatment of donors with G-CSF on GVHD, long-term engraftment, and lymphocyte reconstitution in a murine parent-->F1 model (B6.Ly-5a-->B6d2F1) using splenocytes as a source of peripheral progenitor cells. Recipients of splenocytes from G-CSF-treated donors experienced less mortality from acute GVHD and showed sustained weight gain by day 100 after transplantation. At that time, there was no histological evidence od GVHD in either liver or gut. Recipients of splenocytes from G-CSF-treated donors showed complete donor engraftment within 1 month, which was sustained until the end of the observation period. In contrast, recipients of T cell-depleted splenocytes showed slower donor engraftment and persistent donor/host chimerism. In addition, lymphocyte phenotype and function in mice receiving splenocytes from G-CSF-treated donors was significantly restored by day 100 after transplantation. Thus, the use of G-CSF-mobilized PBPC may provide significant advantages to conventional BMT by reducing GVHD without impairing long-term engraftment and immunologic reconstruction.

Genetic modification of T cells improves the effectiveness of adoptive tumor immunotherapy.

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Jakóbisiak, Marek; Gołab, Jakub

2010-10-01

Appropriate combinations of immunotherapy and gene therapy promise to be more effective in the treatment of cancer patients than either of these therapeutic approaches alone. One such treatment is based on the application of patients' cytotoxic T cells, which can be activated, expanded, and genetically engineered to recognize particular tumor-associated antigens (TAAs). Because T cells recognizing TAAs might become unresponsive in the process of tumor development as a result of tumor evasion strategies, immunogenic viral antigens or alloantigens could be used for the expansion of cytotoxic T cells and then redirected through genetic engineering. This therapeutic approach has already demonstrated promising results in melanoma patients and could be used in the treatment of many other tumors. The graft-versus-leukemia, or more generally graft-versus-tumor, reaction based on the application of a donor lymphocyte infusion can also be ameliorated through the incorporation of suicide genes into donor lymphocytes. Such lymphocytes could be safely and more extensively used in tumor patients because they could be eliminated should a severe graft-versus-host reaction develop.

Descriptive evaluation of chromosome aberrations in blood lymphocytes due to gamma-irradiation

International Nuclear Information System (INIS)

Medina III, F.S.; Gregorio, J.S.; Vinoya, P.C.; Panlaque, C.A.

1983-01-01

To induce and evaluate the effect of radiation among Filipinos, frequencies and types of ν-ray induced chromosome aberrations were studied with peripheral lymphocytes from 19 donors. Peripheral blood samples were irradiated at 0 Gray, 500 mGy, 1 Gy, 2 Gy, 3 Gy and 4 Gy. Irradiated blood samples were cultured by the same standard technique as that commonly used for human blood lymphocytes. Our observations showed that irradiation causes chromosomal aberration similar to effects observed in Caucasians. Our study confirm that irradiation causes an increase of the chromosome aberrations types normally found in the control (gaps, chromatid breaks and chromosome fragments) and can induce aberrations which are rarely observed in non-exposed individual (deletions, translocations, polycentrics, rings, and despiralizations). (author)

CHARACTERISTICS OF SIGNALING PATHWAYS MEDIATING A CYTOTOXIC EFFECT OF DENDRITIC CELLS UPON ACTIVATED Т LYMPHOCYTES AND NK CELLS

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T. V. Tyrinova

2012-01-01

Full Text Available Abstract. Cytotoxic/pro-apoptogenic effects of IFNα-induced dendritic cells (IFN-DCs directed against Т-lymphocytes and NK cells were investigated in healthy donors. Using an allogenic MLC system, it was revealed that IFN-DCs induce apoptosis of both activated CD4+ and CD8+ T-lymphocytes, and NK cells. Apoptosis of CD4+ and CD8+ T-lymphocytes induced by their interaction with IFN-DCs was mediated by various signaling pathways. In particular, activated CD4+Т-lymphocytes were most sensitive to TRAIL- и Fas/ FasL-transduction pathways, whereas activated CD8+ T-lymphocytes were induced to apoptosis via TNFα-mediated pathway. PD-1/B7-H1-signaling pathway also played a distinct role in cytotoxic activity of IFNDCs towards both types of T lymphocytes and activated NK cells. The pro-apoptogenic/cytotoxic activity of IFN-DC against activated lymphocytes may be regarded as a mechanism of a feedback regulation aimed at restriction of immune response and maintenance of immune homeostasis. Moreover, upregulation of proapoptogenic molecules on DCs under pathological conditions may lead to suppression of antigen-specific response, thus contributing to the disease progression.

Chromosomal aberrations induced by low-dose γ-irradiation: Study of R-banded chromosomes of human lymphocytes

International Nuclear Information System (INIS)

Al-Achkar, W.; Lefrancois, D.; Aurias, A.

1991-01-01

The effect of low-dose (0-0.5 Gy) γ-radiations was studied on R-banded chromosomes from lymphocytes of healthy donors of various ages. In cells from newborns, an increase of chromosome damage roughly proportional to the dose was found. In lymphocytes from young adults chromosomal aberrations were not detected at doses of 0.05 and 0.1 Gy, and in lymphocytes from old adults not even at 0.2 Gy. The difficulty in detecting aberrations in lymphocytes from adults is largely due to a considerable background of chromosomal anomalies which should be borne in mind in dosimetry studies. The rate of induction largely depends on the types of rearrangements. One-break terminal deletions are efficiently induced at 0.1 and 0.2 Gy and are the best indicators of exposure at these doses. At 0.5 Gy, the frequencies of 2-break lesions, i.e., dicentrics and reciprocal translocations, increase, whereas the of deletions decreases. (author). 6 refs., 3 figs., 2 tabs

Improved survival and marrow engraftment of mice transplanted with bone marrov of GM-CSF-treated donors

International Nuclear Information System (INIS)

Ballin, A.; Sagi, O.; Schiby, G.; Meytes, D.

1993-01-01

Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) administered to bone marrow (BM) transplant recipients is associated with earlier recovery. We have investigated the possibility of stimulating normal donor mice in vivo with GM-CSF. Donor balb/c mice were injected i.p. with GM-CSF (5000 u) or saline. Seventy-two hours later 5 x 105 BM cells from either GM-CSF-treated or control donors were infused into lethally irradiated (850 R) recipients. In the recipients of BM from GM-CSF-treated donors, significantly higher CFU-S and significantly higher survival rate (57% [n = 65]; vs. 30% [n = 63]; p < 0.05) were noted. Donor mice of the GM-CSF group did not differ in bone-marrow cellularity and composition from their controls. However, recipients of BM from GM-CSF-treated mice had higher blood counts of haemoglobin, Leukocytes and platelets compared to controls. These data demonstrate that pretreatment of BM donors with GM-CSF may be of benefit in improving survival and marrow engraftment in mice. (au) (13 refs.)

Adaptive response in human blood lymphocytes exposed to non-ionizing radiofrequency fields: resistance to ionizing radiation-induced damage.

Science.gov (United States)

Sannino, Anna; Zeni, Olga; Romeo, Stefania; Massa, Rita; Gialanella, Giancarlo; Grossi, Gianfranco; Manti, Lorenzo; Vijayalaxmi; Scarfì, Maria Rosaria

2014-03-01

The aim of this preliminary investigation was to assess whether human peripheral blood lymphocytes which have been pre-exposed to non-ionizing radiofrequency fields exhibit an adaptive response (AR) by resisting the induction of genetic damage from subsequent exposure to ionizing radiation. Peripheral blood lymphocytes from four healthy donors were stimulated with phytohemagglutinin for 24 h and then exposed for 20 h to 1950 MHz radiofrequency fields (RF, adaptive dose, AD) at an average specific absorption rate of 0.3 W/kg. At 48 h, the cells were subjected to a challenge dose (CD) of 1.0 or 1.5 Gy X-irradiation (XR, challenge dose, CD). After a 72 h total culture period, cells were collected to examine the incidence of micronuclei (MN). There was a significant decrease in the number of MN in lymphocytes exposed to RF + XR (AD + CD) as compared with those subjected to XR alone (CD). These observations thus suggested a RF-induced AR and induction of resistance to subsequent damage from XR. There was variability between the donors in RF-induced AR. The data reported in our earlier investigations also indicated a similar induction of AR in human blood lymphocytes that had been pre-exposed to RF (AD) and subsequently treated with a chemical mutagen, mitomycin C (CD). Since XR and mitomycin-C induce different kinds of lesions in cellular DNA, further studies are required to understand the mechanism(s) involved in the RF-induced adaptive response.

Bone Marrow Stromal Cells Contribute to Bone Formation Following Infusion into Femoral Cavities of a Mouse Model of Osteogenesis Imperfecta

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Li, Feng; Wang, Xujun; Niyibizi, Christopher

2010-01-01

Currently, there are conflicting data in literature regarding contribution of bone marrow stromal cells (BMSCs) to bone formation when the cells are systemically delivered in recipient animals. To understand if BMSCs contribute to bone cell phenotype and bone formation in osteogenesis imperfecta bones (OI), MSCs marked with GFP were directly infused into the femurs of a mouse model of OI (oim). The contribution of the cells to the cell phenotype and bone formation was assessed by histology, immunohistochemistry and biomechanical loading of recipient bones. Two weeks following infusion of BMSCs, histological examination of the recipient femurs demonstrated presence of new bone when compared to femurs injected with saline which showed little or no bone formation. The new bone contained few donor cells as demonstrated by GFP fluorescence. At six weeks following cell injection, new bone was still detectable in the recipient femurs but was enhanced by injection of the cells suspended in pepsin solublized type I collagen. Immunofluorescence and immunohistochemical staining showed that donor GFP positive cells in the new bone were localized with osteocalcin expressing cells suggesting that the cells differentiated into osteoblasts in vivo. Biomechanical loading to failure in thee point bending, revealed that, femurs infused with BMSCs in PBS or in soluble type I collagen were biomechanically stronger than those injected with PBS or type I collagen alone. Taken together, the results indicate that transplanted cells differentiated into osteoblasts in vivo and contributed to bone formation in vivo; we also speculate that donor cells induced differentiation or recruitment of endogenous cells to initiate reparative process at early stages following transplantation. PMID:20570757

Post-thaw non-cultured and post-thaw cultured equine cord blood mesenchymal stromal cells equally suppress lymphocyte proliferation in vitro.

Directory of Open Access Journals (Sweden)

Lynn B Williams

Full Text Available Multipotent mesenchymal stromal cells (MSC are receiving increased attention for their non-progenitor immunomodulatory potential. Cryopreservation is commonly used for long-term storage of MSC. Post-thaw MSC proliferation is associated with a lag-phase in vitro. How this lag-phase affect MSC immunomodulatory properties is unknown. We hypothesized that in vitro there is no difference in lymphocyte suppression potential between quick-thawed cryopreserved equine cord blood (CB MSC immediately included in mixed lymphocyte reaction (MLR and same MSC allowed post-thaw culture time prior to inclusion in MLR. Cryopreserved CB-MSC from five unrelated foals were compared using two-way MLR. For each of the five unrelated MSC cultures, paired MLR assays of MSC allowed five days of post-thaw culture and MSC included in MLR assay immediately post-thawing were evaluated. We report no difference in the suppression of lymphocyte proliferation by CB-MSC that had undergone post-thaw culture and MSC not cultured post-thaw (p<0.0001. Also, there was no inter-donor variability between the lymphocyte suppressive properties of MSC harvested from the five different donors (p = 0.13. These findings suggest that cryopreserved CB-MSC may have clinical utility immediately upon thawing. One implication hereof is the possibility of using cryopreserved CB-MSC at third party locations without the need for cell culture equipment or competencies.

Low central venous pressure with milrinone during living donor hepatectomy.

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Ryu, H-G; Nahm, F S; Sohn, H-M; Jeong, E-J; Jung, C-W

2010-04-01

Maintaining a low central venous pressure (CVP) has been frequently used in liver resections to reduce blood loss. However, decreased preload carries potential risks such as hemodynamic instability. We hypothesized that a low CVP with milrinone would provide a better surgical environment and hemodynamic stability during living donor hepatectomy. Thirty-eight healthy adult liver donors were randomized to receive either milrinone (milrinone group, n = 19) or normal saline (control group, n = 19) infusion during liver resection. The surgical field was assessed using a four-point scale. Intraoperative vital signs, blood loss, the use of vasopressors and diuretics and postoperative laboratory data were compared between groups. The milrinone group showed a superior surgical field (p milrinone group required smaller amounts of vasopressors and less-frequent diuretics to maintain a low CVP. The milrinone group also showed a more rapid recovery pattern after surgery. Milrinone-induced low CVP improves the surgical field with less blood loss during living donor hepatectomy and also has favorable effects on intraoperative hemodynamics and postoperative recovery.

Study of the radioprotective effect of flavonoid quercetin on human lymphocytes

International Nuclear Information System (INIS)

Siqueira, Williams Nascimento de

2013-01-01

Ionizing radiation has been used in various fields of study, as medicine, industry, energy production, surgical materials sterilization, preservation and sterilization of foods, among others. These radiations may be responsible for adverse effects at molecular level in living organisms, where most important damage occurs in deoxyribonucleic acid molecule, DNA. These harmful effects caused by radiation highlights the importance of acquiring knowledge about radioprotector substances because they can act as protector of living tissue of those effects. In this research was investigated the possible radioprotective effect 'in vitro' of the flavonoid quercetin in human lymphocytes exposed to gamma radiation. At first, test was performed to evaluate the antioxidant activity of quercetin by capturing DPPH free radical molecules. Then, it was collected peripheral blood of volunteers donors. Then the samples were irradiated from linear accelerator (Siemens Primus - energy of 6 MeV and dose rate of 200 cGy/min from IMIP-PE). After samples irradiation, lymphocytes were isolated from whole blood and then the culture was carried out to obtain lymphocyte in metaphases and subsequent, analysis of chromosomal abnormalities were done at optical microscope. Statistical analysis was used Student 't' test. The results showed that quercetin at a concentration of 37.5 μM presented radioprotective against damage from gamma radiation on human lymphocytes in vitro. Have been also observed that the irradiated lymphocytes showed morphologically unchanged after undergoing the presence of the flavonoid quercetin. (author)

Factors affecting the autologous mixed lymphocyte reaction in kidney transplantation

International Nuclear Information System (INIS)

Fuller, L.; Flaa, C.; Jaffe, D.; Strauss, J.; Kyriakides, G.K.; Miller, J.

1983-01-01

In long-term well adapted kidney transplant recipients we have found a close correlation between the T helper (TH):T suppressor/cytotoxic (TS/C) subset ratios and the presence of T cells that respond in the autologous mixed lymphocyte reaction (AMLR). In 21 recipients with T cell E rosette levels ranging between 53 and 86% and TH:TS/C ratios between 0.15 to 2.10, ratios of greater than 0.8 correlated with AMLR responses (13/13), and ratios of less than 0.8 with AMLR nonreactivity (7/7). By contrast, the allogeneic MLR showed no apparent correlation with the TH:TS/C ratios or with the AMLR pre- or postoperatively. It was found that the AMLR in 22 of 23 normal individuals was markedly inhibited by autologous T cells obtained from peripheral blood lymphocytes, exposed to 3,000 rad (Tx) and added as a third component to the cultures. In contrast, 13 of 13 kidney transplant recipients failed to exhibit this Tx AMLR inhibitory cell population. The ''naturally occurring'' T inhibitory cells, fractionated by an affinity column chromatography procedure into x-irradiated TH and TS/C subsets, inhibited the AMLR to the same extent as unseparated Tx cells. In cell interchange studies performed in four of five HLA identical donor-recipient pairs the Tx cells of the (normal) donor inhibited the recipient AMLR (immunosuppressed), but recipient Tx cells failed to inhibit the donor AMLR. Finally T cells, primed in AMLR and allogeneic MLR for 10 d were tested for AMLR or allogeneic MLR inhibitory activity. Allogeneic MLR primed x-irradiated cells, inhibited both the AMLR and allogeneic MLR while AMLR x-irradiated primed cells inhibited neither reaction. The Tx AMLR inhibitor found in normal peripheral blood, appears to be a cell that is highly sensitive to the effects of biologic or pharmacologic immunosuppressive agents

Regulatory dendritic cell infusion prolongs kidney allograft survival in non-human primates

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Ezzelarab, M.; Zahorchak, A.F.; Lu, L.; Morelli, A.E.; Chalasani, G.; Demetris, A.J.; Lakkis, F.G.; Wijkstrom, M.; Murase, N.; Humar, A.; Shapiro, R.; Cooper, D.K.C.; Thomson, A.W.

2013-01-01

We examined the influence of regulatory dendritic cells (DCreg), generated from cytokine-mobilized donor blood monocytes in vitamin D3 and IL-10, on renal allograft survival in a clinically-relevant rhesus macaque model. DCreg expressed low MHC class II and costimulatory molecules, but comparatively high levels of programmed death ligand-1 (B7-H1), and were resistant to pro-inflammatory cytokine-induced maturation. They were infused intravenously (3.5–10×106/kg), together with the B7-CD28 cos...

Peripheral lymphocyte subpopulations in recurrent aphthous ulceration

DEFF Research Database (Denmark)

Pedersen, A; Klausen, B; Hougen, H P

1991-01-01

Peripheral lymphocyte subsets--T-helper (CD4+), T-suppressor/cytotoxic (CD8+), and naive/virgin T cells/natural killer cells (CD45RA)--were studied quantitatively in 30 patients with recurrent aphthous ulceration (RAU) and 29 sex- and age-matched RAU-free control donors. The CD4+ percentage...... was significantly lower in the patients than in the control group (P less than 0.0001), whereas CD8+ and CD4/CD8 ratio figures did not differ significantly between patients and controls. The CD45RA+ counts were significantly higher in the patient group (P less than 0.01). The study supports previous investigations...

T-lymphocyte dependency of B-lymphocyte blastogenic response to phytomitogens

International Nuclear Information System (INIS)

Han, T.; Dadey, B.

1978-01-01

Human peripheral blood T and B lymphocytes were separated by a method based on the stable rosette formation of T lymphocytes with neuraminidase-treated sheep erythrocytes, followed by centrifugation over a Ficoll-Hypaque gradient. Monocytes were isolated from the T-depleted B lymphocyte preparation by allowing the monocytes to ingest iron particles and by subsequent centrifugation over a Ficoll-Hypaque gradient. The T lymphocytes responded extremely well to PHA and very well to PWM, while the B lymphocytes were unresponsive to either PHA or PWM. However, when the B lymphocytes were cultured together with irradiated autologous or allogeneic T lymphocytes (1 : 1,1:2 or 1 : 4 ratio), both PHA and PWM became mitogenic to B lymphocytes. Irradiated T lymphocytes alone did not respond to either PHA or PWM, indicating that the 3 H-thymidine incorporation seen in the mixed-cell culture was due to the activation of unirradiated B lymphocytes. The B lymphocytes failed to respond to these phytomitogens in the presence of lower concentrations of irradiated T lymphocytes. The monocytes were found to be incapable of helping the B lymphocytes to respond to PHA or PWM. (author)

Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes.

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Toor, Amir A; Sabo, Roy T; Roberts, Catherine H; Moore, Bonny L; Salman, Salman R; Scalora, Allison F; Aziz, May T; Shubar Ali, Ali S; Hall, Charles E; Meier, Jeremy; Thorn, Radhika M; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B; McCarty, John M; Chung, Harold M; Manjili, Masoud H; Neale, Michael C

2015-07-01

Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3(+) cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3(+) at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The healthy donor profile of immunoregulatory soluble mediators is altered by stem cell mobilization and apheresis.

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Melve, Guro Kristin; Ersvaer, Elisabeth; Paulsen Rye, Kristin; Bushra Ahmed, Aymen; Kristoffersen, Einar K; Hervig, Tor; Reikvam, Håkon; Hatfield, Kimberley Joanne; Bruserud, Øystein

2018-05-01

Peripheral blood stem cells from healthy donors mobilized by granulocyte colony-stimulating factor (G-CSF) and thereafter harvested by leukapheresis are commonly used for allogeneic stem cell transplantation. Plasma levels of 38 soluble mediators (cytokines, soluble adhesion molecules, proteases, protease inhibitors) were analyzed in samples derived from healthy stem cell donors before G-CSF treatment and after 4 days, both immediately before and after leukapheresis. Donors could be classified into two main subsets based on their plasma mediator profile before G-CSF treatment. Seventeen of 36 detectable mediators were significantly altered by G-CSF; generally an increase in mediator levels was seen, including pro-inflammatory cytokines, soluble adhesion molecules and proteases. Several leukocyte- and platelet-released mediators were increased during apheresis. Both plasma and graft mediator profiles were thus altered and showed correlations to graft concentrations of leukocytes and platelets; these concentrations were influenced by the apheresis device used. Finally, the mediator profile of the allotransplant recipients was altered by graft infusion, and based on their day +1 post-transplantation plasma profile our recipients could be divided into two major subsets that differed in overall survival. G-CSF alters the short-term plasma mediator profile of healthy stem cell donors. These effects together with the leukocyte and platelet levels in the graft determine the mediator profile of the stem cell grafts. Graft infusion also alters the systemic mediator profile of the recipients, but further studies are required to clarify whether such graft-induced alterations have a prognostic impact. Copyright © 2018. Published by Elsevier Inc.

A mathematical model resolving normal human blood lymphocyte population X-ray survival curves into six components: radiosensitivity, death rate and size of two responding sub-populations

International Nuclear Information System (INIS)

Thomson, A.E.R.; Vaughan-Smith, S.; Peel, W.E.

1982-01-01

The analysis was based on observations of survival decrease as a function of dose (range 0-5 Gy (= 500 rad)) and time after irradiation in vitro. Since lymphocyte survival is also sensitive to culture conditions the effects of radiation were examined daily up to 3 days only, while survival of control cells remained ca. 90 per cent. The time-dependent changes were resolved as the death rates (first-order governed) of lethally-hit cells (apparent survivors), so rendering these distinguishable from the morphologically identical, true (ultimate) survivors. For 12 blood donors the estimated dose permitting 37 per cent ultimate survival (D 37 value) averaged 0.72 +- 0.18 (SD) Gy for the more radiosensitive lymphocyte fraction and 2.50 +- 0.67 Gy for the less radiosensitive, each fraction proving homogeneously radiosensitive and the latter identifying substantially in kind with T-type (E-rosetting lymphocytes). The half-life of lethally-hit members of either fraction varied widely among the donors (ranges, 25-104 hours and 11-40 hours, respectively). Survival curves reconstructed by summating the numerical estimates of the six parameters according to the theoretical model closely matched those observed experimentally (ranged in multiple correlation coefficient, 0.9709-0.9994) for all donors). This signified the absence of any additional, totally radioresistant cell fraction. (author)

Use of radiolabeled monoclonal anti-B1 antibody for B lymphocyte imaging in Rhesus monkeys

International Nuclear Information System (INIS)

Letvin, N.L.; Zalutsky, M.R.; Chalifoux, L.V.; Atkins, H.L.

1987-01-01

Imaging tissues rich in B lymphocytes in man using a radiolabeled monoclonal anti-B cell antibody would be extremely useful in the clinical staging of non-Hodgkins lymphomas. Studies were done in rhesus monkeys using radiolabeled monoclonal anti-B1 antibody to determine the feasibility of such an approach. Immunohistologic studies demonstrated that infused monoclonal anti-B1 binds in vivo with specificity to B cells in lymph nodes and spleen. The kinetics of clearance of 131 I-labeled anti-B1 were determined. The B lymphocyte-rich spleen could be readily visualized by gamma camera scanning without significant background and without the need for image intensification or blood background subtraction techniques. These data support the feasibility of using anti-B1 for staging B cell lymphomas in man. (author)

Rapid assay of intrinsic radiosensitivity based on apoptosis in human CD4 and CD8 T-lymphocytes

International Nuclear Information System (INIS)

Ozsahin, Mahmut; Ozsahin, Huelya; Yuquan, Shi; Larsson, Boerje; Wuergler, Friedrich E.; Crompton, Nigel E. A.

1997-01-01

Purpose: An assay for radiosensitivity has numerous applications in the clinic. Avoidance of acute responses, prediction of normal tissue toxicity, and individualization of patient radiotherapy are included among these. We have developed a rapid assay (about 24 h) able to predict intrinsic radiosensitivity of CD4 and CD8 T-lymphocytes based on radiation-induced apoptosis. Methods and Materials: Fresh blood samples (1-2 ml in heparinized tubes) were irradiated with 0-, 2-, and 8-Gy X rays at a dose rate of approximately 3 Gy/min. Following irradiation, the cells were collected and prepared for flow-cytometric analysis and cell sorting. In conjunction with the CellQuest software available with the FACSVantage cell sorter (Becton-Dickinson), two T-lymphocyte types were analyzed on the basis of their cell-specific antigens (CD4 and CD8), and DNA was stained with DAPI. Following the separation of these cell types, radiation-induced cell death was assessed. Cytotoxicity was characterized by gradual degradation of internucleosomal DNA which results in a sub-G1 peak on the DNA histogram, and by the associated loss of surface antigens causing an intermediate positive peak in the antibody histogram. Using the assay, we investigated the interdonor variation in a cohort of 45 healthy adult blood donors and 5 children [one had immunodeficiency, centromeric instability, and facial anomalies syndrome (ICF), and one had ataxia telangiectasia (AT)]. Intradonor variation was assessed with 10 different experiments from a single donor. Results: CD4 and CD8 T-lymphocyte radiosensitivities were correlated (r 0.63 and 0.65 for 2 and 8 Gy, respectively) in 45 adult donors. Both for CD4 and CD8 cells, 2 and 8 Gy irradiation responses showed a good correlation (r 0.77 for both). Interdonor variation was significantly higher than intradonor variation (p < 0.0005) for all CD4 and CD8 data. We observed a decrease in the antigen fluorescence of dying cells, a phenomenon referred to as antigen

Sensitivity of cultured lymphocytes from patients with nevoid basal cell carcinoma syndrome to ultraviolet light and phytohemagglutinin stimulation

International Nuclear Information System (INIS)

Ferraro, P.; Celotti, L.; Furlan, D.; Pattarello, I.; Peserico, A.

1990-01-01

DNA repair and replication after in vitro UV irradiation were determined in cultured peripheral blood lymphocytes from 6 patients with nevoid basal cell carcinoma syndrome (NBCCS) and from a group of control donors. DNA repair synthesis (UDS) was measured in unstimulated lymphocytes by incubation with 3H-TdR in the presence of hydroxyurea for 3 and 6 h after UV irradiation (6-48 J/m2). DNA replication was measured in PHA-stimulated lymphocytes, UV-irradiated or mock-irradiated, by incubation with 3H-TdR for 24 h. The effect of the mitogen was followed during 5 days after stimulation by determining the incorporation of 3H-TdR, the increase of cell number, and the mitotic index. NBCCS and control lymphocytes showed equal sensitivity to UV light in terms of UDS and reduced response to PHA. On the contrary, the mitotic index and the number of cells in stimulated cultures were significantly lower in the affected subjects. These data suggest an altered progression along the cell cycle, which could be characteristic of stimulated NBCCS lymphocytes

Fish Lymphocytes: An Evolutionary Equivalent of Mammalian Innate-Like Lymphocytes?

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Giuseppe Scapigliati

2018-05-01

Full Text Available Lymphocytes are the responsible of adaptive responses, as they are classically described, but evidence shows that subpopulations of mammalian lymphocytes may behave as innate-like cells, engaging non-self rapidly and without antigen presentation. The innate-like lymphocytes of mammals have been mainly identified as γδT cells and B1-B cells, exert their activities principally in mucosal tissues, may be involved in human pathologies and their functions and tissue(s of origin are not fully understood. Due to similarities in the morphology and immunobiology of immune system between fish and mammals, and to the uniqueness of having free-living larval stages where the development can be precisely monitored and engineered, teleost fish are proposed as an experimental model to investigate human immunity. However, the homology between fish lymphocytes and mammalian innate-like lymphocytes is an issue poorly considered in comparative immunology. Increasing experimental evidence suggests that fish lymphocytes could have developmental, morphological, and functional features in common with innate-like lymphocytes of mammals. Despite such similarities, information on possible links between conventional fish lymphocytes and mammalian innate-like lymphocytes is missing. The aim of this review is to summarize and describe available findings about the similarities between fish lymphocytes and mammalian innate-like lymphocytes, supporting the hypothesis that mammalian γδT cells and B1-B cells could be evolutionarily related to fish lymphocytes.

Nitric oxide selectively decreases interferon-gamma expression by activated human T lymphocytes via a cGMP-independent mechanism

NARCIS (Netherlands)

Roozendaal, R; Vellenga, E; Postma, DS; De Monchy, JGR; Kauffman, HF

1999-01-01

The role of exogenous nitric oxide (NO) on the expression of interleukin (IL)-2, IL-4, IL-5 and interferon-gamma (IFN-gamma) by freshly isolated human T lymphocytes was investigated. The presence of NO, generated from any of the NO-donor compounds, S-nitroso-N-acetyl-D,L-penicillamine (NAP),

Human T Lymphocytes Are Permissive for Dengue Virus Replication.

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Silveira, Guilherme F; Wowk, Pryscilla F; Cataneo, Allan H D; Dos Santos, Paula F; Delgobo, Murilo; Stimamiglio, Marco A; Lo Sarzi, Maria; Thomazelli, Ana Paula F S; Conchon-Costa, Ivete; Pavanelli, Wander R; Antonelli, Lis R V; Báfica, André; Mansur, Daniel S; Dos Santos, Claudia N Duarte; Bordignon, Juliano

2018-05-15

Dengue virus (DV) infection can cause either a self-limiting flu-like disease or a threatening hemorrhage that may evolve to shock and death. A variety of cell types, such as dendritic cells, monocytes, and B cells, can be infected by DV. However, despite the role of T lymphocytes in the control of DV replication, there remains a paucity of information on possible DV-T cell interactions during the disease course. In the present study, we have demonstrated that primary human naive CD4 + and CD8 + T cells are permissive for DV infection. Importantly, both T cell subtypes support viral replication and secrete viable virus particles. DV infection triggers the activation of both CD4 + and CD8 + T lymphocytes, but preactivation of T cells reduces the susceptibility of T cells to DV infection. Interestingly, the cytotoxicity-inducing protein granzyme A is highly secreted by human CD4 + but not CD8 + T cells after exposure to DV in vitro Additionally, using annexin V and polycaspase assays, we have demonstrated that T lymphocytes, in contrast to monocytes, are resistant to DV-induced apoptosis. Strikingly, both CD4 + and CD8 + T cells were found to be infected with DV in acutely infected dengue patients. Together, these results show that T cells are permissive for DV infection in vitro and in vivo , suggesting that this cell population may be a viral reservoir during the acute phase of the disease. IMPORTANCE Infection by dengue virus (DV) causes a flu-like disease that can evolve to severe hemorrhaging and death. T lymphocytes are important cells that regulate antibody secretion by B cells and trigger the death of infected cells. However, little is known about the direct interaction between DV and T lymphocytes. Here, we show that T lymphocytes from healthy donors are susceptible to infection by DV, leading to cell activation. Additionally, T cells seem to be resistant to DV-induced apoptosis, suggesting a potential role as a viral reservoir in humans. Finally, we show

Detection of adult T-cell leukemia virus (ATLV) bearing lymphocytes in concentrated red blood cells derived from ATL associated antibody (ATLA-Ab) positive donors.

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Morishima, Y; Ohya, K; Ueda, R; Fukuda, T

1986-01-01

Adult T cell leukemia associated antibody (ATLA-Ab) positive persons were screened by indirect immunofluorescence (IF) testing. Their lymphocytes were collected from concentrated red blood cells (CRC), and cultured in vitro with and without phytohemagglutinin (PHA) for 10 days. The expression of ATL virus (ATLV) positive lymphocytes during the in vitro culture was then analyzed by IF assay using mouse monoclonal antibody ATL-19 reactive to p19 core protein of ATLV. 97% of ATLA-Ab positive CRC (36 cases) demonstrated ATLV positive lymphocytes after being cultured for more than 10 days with PHA, whereas, none of ATLA-Ab negative CRC (22 cases) demonstrated ATLV positive lymphocytes. All of the 10 ATLA-Ab positive CRC that were stored for 2, 4, and 7 days contained lymphocytes which expressed ATLV after in vitro culture, while 7 of 10 CRC stored for 14 days and only 1 of 10 CRCs stored for 20 days, expressed ATLV positive lymphocytes. This data indicates that almost all of the ATLA-Ab positive blood contained ATLV positive lymphocytes, and that the in vitro appearance of these ATLV positive lymphocytes was reduced by storing the CRC for more than 14 days.

Defective G2 repair in Down syndrome; Effect of caffeine, adenosine and niacinamide in control and X-ray irradiated lymphocytes

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Pincheira, J.; Rodriguez, M. (Department of Cellular Biology and Genetics, University of Chile, Santiago (Chile)); Bravo, M. (Department of Pediatrics, University of Chile, Santiago (Chile)); Navarrete, M.H.; Lopez-Saez, J.F. (Department of Biology, Faculty of Science, Universidad Autonoma y CCIC, Madrid (Spain))

1994-01-01

Lymphocytes from both Down syndrome (DS) patients and age-matched control donors have been investigated to identify a possible disturbance in chromosomal G2 repair. Analyses of caffeine treatments during G2 have shown that the frequency of chromosomal aberrations is higher in DS lymphocytes than in normal lymphocytes. Likewise, G2 duration is longer in DS cells than in normal cells. In both control and DS lymphocytes, caffeine treatments increase the frequencies of chromatid breakages and decrease the average of G2 duration. The reversal of the caffeine potentiation effect by adenosine and niacinamide is higher in DS cells than in normal cells. Furthermore, ATP content per cell in DS lymphocytes is one third of that estimated in normal lymphocytes. The increase of ATP level produced by adenosine or niacinamide generally correlates with the reversal of the caffeine effect on chromosome aberrations. Under the experimental conditions tested, a good negative exponential correlation between ATP level and chromosome aberrations has been detected in both normal and DS lymphocytes which were or were not X-irradiated. Finally, we postulate a decrease in G2 repair capability of DS lymphocytes caused by a low availability of ATP and/or some other factor correlating with it. (au).

Pharmacokinetics and pharmacokinetic/pharmacodynamic associations of ofatumumab, a human monoclonal CD20 antibody, in patients with relapsed or refractory chronic lymphocytic leukaemia: a phase 1-2 study

DEFF Research Database (Denmark)

Coiffier, Bertrand; Losic, Nedjad; Rønn, Birgitte Biilmann

2010-01-01

The purpose of this phase 1-2 study was to investigate the association between the pharmacokinetic properties of ofatumumab, a human monoclonal CD20 antibody, and outcomes in 33 patients with relapsed/refractory chronic lymphocytic leukaemia receiving 4 weekly infusions of ofatumumab. The ofatumu...

Copper-associated hepatitis in a patient with chronic myeloid leukemia following hematopoietic stem cell transplantation: A case report.

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Lee, Ching-Fen; Chen, Chi-Hua; Wen, Yu-Chuan; Chang, Tsung-Yen; Lai, Ming-Wei; Jaing, Tang-Her

2017-12-01

We report a complicated case of cholestatic hepatitis with suspected autoimmune hemolytic anemia (AIHA) and copper toxicity syndrome after HSCT and donor lymphocyte infusion (DLI). A 19-year-1-month-old girl presented with a history of CML. She underwent matched unrelated donor HSCT and donor lymphocyte infusion subsequently. Three months later, yellowish discoloration of the skin was found, which was accompanied by progressive itchy skin, easy fatigability, insomnia, and dark urine output. After admission, liver function disorders were observed. Methylprednisolone was administered for suspected hepatic GVHD. Although abdominal sonography revealed no evidence of biliary tract obstruction and the viral hepatitis survey disclosed unremarkable findings; silymarin and ursodeoxycholic acid were administered to preserve the liver function. In addition, rituximab was prescribed for suspected AIHA. Because hyperbilirubinemia was progressive, mycophenolate and high-dose intravenous immunoglobulin were accordingly administered. As drug-induced liver injury cannot be excluded, all potential unconfirmed causes of drug-related hepatoxicity were discontinued. In this case, the patient's history of shrimps and chocolate consumption led us to strongly suspect cholestatic hepatitis associated with copper toxicity syndrome. High 24-hour urine copper excretion and low serum zinc levels were also confirmed. Accordingly, D-penicillamine and zinc gluconate were administered. She succumbed to progressive hepatic failure and eventual multisystem organ failure 14 months after HSCT. No autopsy was performed. This report described the combined effects of hepatic GVHD, AIHA, drugs, and copper toxicity on liver damage, and demonstrated the potential diagnostic challenges and treatment dilemmas associated with this disease.

Induction of adaptive response in human blood lymphocytes exposed to radiofrequency radiation.

Science.gov (United States)

Sannino, Anna; Sarti, Maurizio; Reddy, Siddharth B; Prihoda, Thomas J; Vijayalaxmi; Scarfì, Maria Rosaria

2009-06-01

The incidence of micronuclei was evaluated to assess the induction of an adaptive response to non-ionizing radiofrequency (RF) radiation in peripheral blood lymphocytes collected from five different human volunteers. After stimulation with phytohemagglutinin for 24 h, the cells were exposed to an adaptive dose of 900 MHz RF radiation used for mobile communications (at a peak specific absorption rate of 10 W/kg) for 20 h and then challenged with a single genotoxic dose of mitomycin C (100 ng/ml) at 48 h. Lymphocytes were collected at 72 h to examine the frequency of micronuclei in cytokinesis-blocked binucleated cells. Cells collected from four donors exhibited the induction of adaptive response (i.e., responders). Lymphocytes that were pre-exposed to 900 MHz RF radiation had a significantly decreased incidence of micronuclei induced by the challenge dose of mitomycin C compared to those that were not pre-exposed to 900 MHz RF radiation. These preliminary results suggested that the adaptive response can be induced in cells exposed to non-ionizing radiation. A similar phenomenon has been reported in cells as well as in animals exposed to ionizing radiation in several earlier studies. However, induction of adaptive response was not observed in the remaining donor (i.e., non-responder). The incidence of micronuclei induced by the challenge dose of mitomycin C was not significantly different between the cells that were pre-exposed and unexposed to 900 MHz RF radiation. Thus the overall data indicated the existence of heterogeneity in the induction of an adaptive response between individuals exposed to RF radiation and showed that the less time-consuming micronucleus assay can be used to determine whether an individual is a responder or non-responder.

The dependence of the magnitude of induced adaptive responseon on the dose of pre-irradiation of cultured human lymphocytes under the optimum irradiation time scheme

International Nuclear Information System (INIS)

Mortazavi, S.M.J.; Mozdarani, H.

2000-01-01

Human lymphocytes exposed to low doses of X-rays, become less susceptible to the induction of chromosome aberrations by subsequent exposure to high doses of X-rays. This has been termed the radioadaptive response. One of the most important questions in the adaptive response studies was that of the possible existence of an optimum adapting dose. Early experiments indicated that this response could be induced by low doses of X-rays from 1 cGy to 20 cGy. Recently, it has been interestingly shown that the time scheme of exposure to adapting and challenge doses plays an important role in determination of the magnitude of the induced adaptive response. In this study, using the optimum irradiation time scheme (24-48), we have monitored the cytogenetic endpoint of chromosome aberrations to assess the magnitude of adaptation to ionizing radiation in the cultured human lymphocytes. Lymphocytes were pre-exposed to an adapting dose of 1-20 cGy at 24 hours, before an acute challenge dose of 1 or 2 Gy at 48 hours. Cells were fixed at 54 hours. Lymphocytes, which were pretreated with 5 as well as 10 cGy adapting doses, had significantly fewer chromosome aberrations. In spite of the fact that lymphocytes of some of our blood donors which were pre-treated with 1 or 20 cGy adapting doses, showed an adaptive response, the pooled data (all donors) indicated that such an induction of adaptive response can not be observed in these lymphocytes. The overall pattern of the induced adaptive response, indicated that in human lymphocyte (at least under the above mentioned irradiation scheme), 5 cGy and 10 cGy adapting doses are the optimum doses. (author)

Comparative Peripheral Blood T Cells Analysis Between Adult Deceased Donor Liver Transplantation (DDLT) and Living Donor Liver Transplantation (LDLT).

Science.gov (United States)

Kim, Jong Man; Kwon, Choon Hyuck David; Joh, Jae-Won; Choi, Gyu-Seong; Kang, Eun-Suk; Lee, Suk-Koo

2017-08-08

BACKGROUND T lymphocytes are an essential component of allograft rejection and tolerance. The aim of the present study was to analyze and compare the characteristics of T cell subsets in patients who underwent deceased donor liver transplantation (DDLT) versus living donor liver transplantation (LDLT). MATERIAL AND METHODS Between April 2013 and June 2014, 64 patients underwent adult liver transplantation. The distribution of peripheral blood T lymphocyte subsets before transplantation and at 4, 8, 12, and 24 weeks post-transplantation were monitored serially. RESULTS In the serial peripheral blood samples, the absolute CD3+ T cell counts in the LDLT group were higher than those in the DDLT group (p=0.037). The CD4+, CD8+, CD4/CD8, Vδ1, Vδ2, and γδ T cell counts did not change significantly over time in either group. The Vδ1/Vδ2 ratio was higher in patients with cytomegalovirus (CMV) infection than in patients without CMV infection (0.12 versus 0.26; p=0.033). The median absolute CD3+ and CD8+ T cell counts in patients with biopsy-proven acute rejection (BPAR) were 884 (range, 305-1,320) and 316 (range, 271-1,077), respectively, whereas they were 320 (range, 8-1,167) and 257 (range, 58-1,472) in patients without BPAR. The absolute CD3+ and CD8 T cell counts were higher in patients with BPAR than in patients without BPAR (p=0.007 and p=0.039, respectively). CONCLUSIONS With the exception of CD3+ T cells, T cell populations did not differ significantly between patients who received DDLT versus LDLT. In liver transplantation patients, CMV infection and BPAR were closely associated with T cell population changes.

Recruitment of feces donors among blood donors

DEFF Research Database (Denmark)

Dahl Jørgensen, Simon Mark; Erikstrup, Christian; Dinh, Khoa Manh

2018-01-01

As the use of fecal microbiota transplantation (FMT) has gained momentum, an increasing need for continuous access to healthy feces donors has developed. Blood donors constitute a healthy subset of the general population and may serve as an appropriate group for recruitment. In this study, we...... investigated the suitability of blood donors as feces donors. In a prospective cohort study, we recruited blood donors onsite at a public Danish blood bank. Following their consent, the blood donors underwent a stepwise screening process: First, blood donors completed an electronic pre-screening questionnaire...... to rule out predisposing risk factors. Second, eligible blood donors had blood and fecal samples examined. Of 155 blood donors asked to participate, 137 (88%) completed the electronic pre-screening questionnaire, 16 declined, and 2 were excluded. Of the 137 donors who completed the questionnaire, 79 (58...

The absence of radiation-induced adaptive response in lymphocytes of patients with Down's syndrome

International Nuclear Information System (INIS)

Khandogina, E.K.; Mutovin, G.R.; Zvereva, S.V.; Zverev, D.O.; Neudakhin, E.V.; Arkhipov, B.A.; Akif'ev, A.P.; AN SSSR, Moscow

1991-01-01

The adaptive syndrome and response (AR) in lymphocytes from 6 patients with Down syndrome (DS) were investigated. No AR was found to occur in all cases in DS cells pre-exposed to 3 rad of X-rays in S phase of cell cycle and then irradiated with 150 rad of gamma rays in G2 whereas the chromosome aberrations yield in cells from control donors was decreased twice under such conditions of the experiment

Combination of Ipilimumab and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma

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John E. Mullinax

2018-03-01

Full Text Available PurposeAdoptive cell therapy (ACT using tumor-infiltrating lymphocytes (TIL for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL.Experimental designThirteen patients with metastatic melanoma were enrolled. Patients received four doses of ipilimumab (3 mg/kg beginning 2 weeks prior to tumor resection for TIL generation, then 1 week after resection, and 2 and 5 weeks after preconditioning chemotherapy and TIL infusion followed by interleukin-2. The primary endpoint was safety and feasibility. Secondary endpoints included of clinical response at 12 weeks and at 1 year after TIL transfer, progression free survival (PFS, and overall survival (OS.ResultsAll patients received at least two doses of ipilimumab, and 12 of the 13 (92% received TIL. A median of 6.5 × 1010 (2.3 × 1010 to 1.0 × 1011 TIL were infused. At 12 weeks following infusion, there were five patients who experienced objective response (38.5%, four of whom continued in objective response at 1 year and one of which became a complete response at 52 months. Median progression-free survival was 7.3 months (95% CI 6.1–29.9 months. Grade ≥ 3 immune-related adverse events included hypothyroidism (3, hepatitis (2, uveitis (1, and colitis (1.ConclusionIpilimumab plus ACT for metastatic melanoma is feasible, well tolerated, and associated with a low rate of attrition due to progression during cell expansion. This combination approach serves as a model for future efforts to improve the efficacy of ACT.

Combination of Ipilimumab and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma.

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Mullinax, John E; Hall, MacLean; Prabhakaran, Sangeetha; Weber, Jeffrey; Khushalani, Nikhil; Eroglu, Zeynep; Brohl, Andrew S; Markowitz, Joseph; Royster, Erica; Richards, Allison; Stark, Valerie; Zager, Jonathan S; Kelley, Linda; Cox, Cheryl; Sondak, Vernon K; Mulé, James J; Pilon-Thomas, Shari; Sarnaik, Amod A

2018-01-01

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience) remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL. Thirteen patients with metastatic melanoma were enrolled. Patients received four doses of ipilimumab (3 mg/kg) beginning 2 weeks prior to tumor resection for TIL generation, then 1 week after resection, and 2 and 5 weeks after preconditioning chemotherapy and TIL infusion followed by interleukin-2. The primary endpoint was safety and feasibility. Secondary endpoints included of clinical response at 12 weeks and at 1 year after TIL transfer, progression free survival (PFS), and overall survival (OS). All patients received at least two doses of ipilimumab, and 12 of the 13 (92%) received TIL. A median of 6.5 × 10 10 (2.3 × 10 10 to 1.0 × 10 11 ) TIL were infused. At 12 weeks following infusion, there were five patients who experienced objective response (38.5%), four of whom continued in objective response at 1 year and one of which became a complete response at 52 months. Median progression-free survival was 7.3 months (95% CI 6.1-29.9 months). Grade ≥ 3 immune-related adverse events included hypothyroidism (3), hepatitis (2), uveitis (1), and colitis (1). Ipilimumab plus ACT for metastatic melanoma is feasible, well tolerated, and associated with a low rate of attrition due to progression during cell expansion. This combination approach serves as a model for future efforts to improve the efficacy of ACT.

Mechanisms of immunologic unresponsiveness induced by ultraviolet-irradiated donor-specific blood transfusions and peritransplant cyclosporine

Energy Technology Data Exchange (ETDEWEB)

Oluwole, S.F.; Chabot, J.; Pepino, P.; Reemtsma, K.; Hardy, M.A.

1988-09-01

Recipient pretreatment with UV-B irradiated donor-specific blood transfusions (UV-DST) combined with peritransplant cyclosporine on days 0, +1, and +2 leads to permanent cardiac allograft survival in the ACI-to-Lewis rat strain combination. This study investigates the mechanisms of immunologic unresponsiveness induced by UV-DST and CsA by examining several in vitro and in vivo parameters in long-term cardiac allograft recipients. The results of the in vitro studies demonstrate that thoracic duct lymphocytes (TDL) of treated and allografted Lewis rats respond less in a mixed lymphocyte reaction to donor splenic lymphocytes (SpL) by 69%, 75%, and 73% (P less than 0.001) at 30, 50, and 100 days after transplantation, respectively, compared with controls, while the response to a third-party (W/F) SpL is unimpaired. In coculture experiments, the TDL from treated recipients specifically suppressed the response of unmodified Lewis TDL to ACI SpL by 59% and 40% (P less than 0.01) at 30 and 50 days after transplantation, respectively, while responses to W/F SpL were suppressed by only 3-6%. The sera obtained from ungrafted rats transfused with UV-DST suppressed the MLR between unmodified Lewis TDL and ACI SpL by 31% (P less than 0.05) while the sera from UV-DST and CsA-treated and allografted rats specifically suppressed the MLR by 75%, 80% (P less than 0.001) and 37% (P less than 0.01) at 10, 30, and 50 days after transplantation, respectively. In vivo adoptive transfer of 10(4) donor-type dendritic cells (DC) into recipients of beating cardiac allografts at 40 or 60 days after transplantation led to rapid and acute allograft rejection, while the adoptive transfer of 10(8) unseparated SpL obtained at 50 days after transplantation from treated Lewis recipients to syngeneic naive hosts led to a modest but significant prolongation of ACI test cardiac allografts.

Manifestation of radiaton injury of human lymphocytes using PHA mitogenic stimulation in different culture systems

International Nuclear Information System (INIS)

Horky, J.

1986-01-01

The proliferative response of human lymphocytes to phytohemagglutinin in vitro is affected by X-irradiation. Dose-related changes in mitogenic stimulation of irradiated lymphocytes were compared for two culture systems - the cultivation of separated lymphocytes and the cultivation of whole blood. In the whole blood cultures, the proliferative activity of stimulated lyphocytes was markedly and reproducibly depressed by irradiation. An exponential curve could be fitted to the values of mitogenic response within a dose range from 0 to 2.5 Gy with high correlation. In a modified test where the mitogenic stimulus was given after a 24 h delay, depression in the response was even more pronounced. Radiosensitivity of human lymphocytes as determined by means of mitogenic stimulation in the whole blood cultures appears to be a characteristic individual feature. The mean D 37 value of the radiation-induced depression in mitogenic response in a group of 20 healthy donors was 2.5 Gy in the standard test and 2.0 Gy in the test with a delayed mitogenic stimulus. In contrast, the data obtained from separated lymphocyte cultures were characterized by a high degree of test-to-test variability and by much lower radiosensitivity. The possible mechanisms of these distinctive manifestations of the same primary radiation injury are discussed. (author) 3 tabs., 2 figs., 12 refs

Infusion volume control and calculation using metronome and drop counter based intravenous infusion therapy helper.

Science.gov (United States)

Park, Kyungnam; Lee, Jangyoung; Kim, Soo-Young; Kim, Jinwoo; Kim, Insoo; Choi, Seung Pill; Jeong, Sikyung; Hong, Sungyoup

2013-06-01

This study assessed the method of fluid infusion control using an IntraVenous Infusion Controller (IVIC). Four methods of infusion control (dial flow controller, IV set without correction, IV set with correction and IVIC correction) were used to measure the volume of each technique at two infusion rates. The infused fluid volume with a dial flow controller was significantly larger than other methods. The infused fluid volume was significantly smaller with an IV set without correction over time. Regarding the concordance correlation coefficient (CCC) of infused fluid volume in relation to a target volume, IVIC correction was shown to have the highest level of agreement. The flow rate measured in check mode showed a good agreement with the volume of collected fluid after passing through the IV system. Thus, an IVIC could assist in providing an accurate infusion control. © 2013 Wiley Publishing Asia Pty Ltd.

Preservation of Antigen-Specific Functions of αβ T Cells and B Cells Removed from Hematopoietic Stem Cell Transplants Suggests Their Use As an Alternative Cell Source for Advanced Manipulation and Adoptive Immunotherapy.

Science.gov (United States)

Li Pira, Giuseppina; Di Cecca, Stefano; Biagini, Simone; Girolami, Elia; Cicchetti, Elisabetta; Bertaina, Valentina; Quintarelli, Concetta; Caruana, Ignazio; Lucarelli, Barbarella; Merli, Pietro; Pagliara, Daria; Brescia, Letizia Pomponia; Bertaina, Alice; Montanari, Mauro; Locatelli, Franco

2017-01-01

Hematopoietic stem cell transplantation is standard therapy for numerous hematological diseases. The use of haploidentical donors, sharing half of the HLA alleles with the recipient, has facilitated the use of this procedure as patients can rely on availability of a haploidentical donor within their family. Since HLA disparity increases the risk of graft-versus-host disease, T-cell depletion has been used to remove alloreactive lymphocytes from the graft. Selective removal of αβ T cells, which encompass the alloreactive repertoire, combined with removal of B cells to prevent EBV-related lymphoproliferative disease, proved safe and effective in clinical studies. Depleted αβ T cells and B cells are generally discarded as by-products. Considering the possible use of donor T cells for donor lymphocyte infusions or for generation of pathogen-specific T cells as mediators of graft-versus-infection effect, we tested whether cells in the discarded fractions were functionally intact. Response to alloantigens and to viral antigens comparable to that of unmanipulated cells indicated a functional integrity of αβ T cells, in spite of the manipulation used for their depletion. Furthermore, B cells proved to be efficient antigen-presenting cells, indicating that antigen uptake, processing, and presentation were fully preserved. Therefore, we propose that separated αβ T lymphocytes could be employed for obtaining pathogen-specific T cells, applying available methods for positive selection, which eventually leads to indirect allodepletion. In addition, these functional T cells could undergo additional manipulation, such as direct allodepletion or genetic modification.

Preservation of Antigen-Specific Functions of αβ T Cells and B Cells Removed from Hematopoietic Stem Cell Transplants Suggests Their Use As an Alternative Cell Source for Advanced Manipulation and Adoptive Immunotherapy

Science.gov (United States)

Li Pira, Giuseppina; Di Cecca, Stefano; Biagini, Simone; Girolami, Elia; Cicchetti, Elisabetta; Bertaina, Valentina; Quintarelli, Concetta; Caruana, Ignazio; Lucarelli, Barbarella; Merli, Pietro; Pagliara, Daria; Brescia, Letizia Pomponia; Bertaina, Alice; Montanari, Mauro; Locatelli, Franco

2017-01-01

Hematopoietic stem cell transplantation is standard therapy for numerous hematological diseases. The use of haploidentical donors, sharing half of the HLA alleles with the recipient, has facilitated the use of this procedure as patients can rely on availability of a haploidentical donor within their family. Since HLA disparity increases the risk of graft-versus-host disease, T-cell depletion has been used to remove alloreactive lymphocytes from the graft. Selective removal of αβ T cells, which encompass the alloreactive repertoire, combined with removal of B cells to prevent EBV-related lymphoproliferative disease, proved safe and effective in clinical studies. Depleted αβ T cells and B cells are generally discarded as by-products. Considering the possible use of donor T cells for donor lymphocyte infusions or for generation of pathogen-specific T cells as mediators of graft-versus-infection effect, we tested whether cells in the discarded fractions were functionally intact. Response to alloantigens and to viral antigens comparable to that of unmanipulated cells indicated a functional integrity of αβ T cells, in spite of the manipulation used for their depletion. Furthermore, B cells proved to be efficient antigen-presenting cells, indicating that antigen uptake, processing, and presentation were fully preserved. Therefore, we propose that separated αβ T lymphocytes could be employed for obtaining pathogen-specific T cells, applying available methods for positive selection, which eventually leads to indirect allodepletion. In addition, these functional T cells could undergo additional manipulation, such as direct allodepletion or genetic modification. PMID:28386262

Comparison of two different techniques on the human lymphocytes morphology and sensitivity to gamma radiation

International Nuclear Information System (INIS)

Kol, R.

1985-02-01

The lymphocytes in the peripheral blood are divided into two main subclasses: T cells and B cells. These differ from each other in function and in their sensitivity to radiation. The effort to study which group is more sensitive to radiation has resulted in many contradictory results. In the present study we examined whether the methods that are used to separate the lymphocytes from the whole blood, before their separation into subclasses, have an effect on the cells and whether this might contribute to the contradictory results. Blood samples were taken from several normal donors and each sample was devided into two fractions. Lymphocytes in each fraction were separated by one of the two following methods: a) sedimentation of erythrocytes by gravitation; b) separation on Ficoll-Paque density gradient. For cells obtained by these two methods, the ultrastructure was examined by electron microscopy and their ability to incorporate radioactive thymidine was measured. Samples separated on Ficoll-Paque showed a subpopulation with morphological changes similar to those occuring in lymphocytes undergoing stimulation. Unstimulated cells separated on Ficoll-Paque showed greater sensitivity to radiation. The effect of gamma radiation on the capability of lymphocytes to undergo transformation in response to three mitogens; PHA, PWM and Con A was examined. Different mitogens stimulate different lymphocytes subpopulations. There was no difference between the two separation methods regarding the sensitivity to gamma radiation of stimulation by PAH and PWM. The transformation by Con A of lymphocytes separated on Ficoll-Paque was more radiosensitive. This could indicate that the separation by Ficoll-Paque density gradient causes a selective depletion of T lymphocytes that react with Con A and are considered more radioresistant. The use of different methods for separating lymphocytes from whole blood- each has a different influence on the cells- can contribute to contradictory

Better Clinical Efficiency of TILs for Malignant Pleural Effusion and Ascites than Cisplatin Through Intrapleural and Intraperitoneal Infusion.

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Chu, Hongjin; Du, Fengcai; Gong, Zhaohua; Lian, Peiwen; Wang, Zhixin; Li, Peng; Hu, Baohong; Chi, Cheng; Chen, Jian

2017-08-01

To evaluate the clinical efficiency of tumor-infiltrating lymphocytes (TILs) compared to cisplatin for malignant pleural effusion and ascites through intrapleural and intraperitoneal infusion. Thirteen patients with malignant pleural effusion and ascites were divided into a TIL-treated group and a cisplatin-treated group. Patients were given TILs or cisplatin, through intrapleural and intraperitoneal infusion respectively, after drainage of the malignant serous effusion by thoracentesis or abdominocentesis. The overall response rate and disease control rate of the TIL-treated group (33.33% and 83.33%) were higher than that of the cisplatin-treated group (28.57% and 71.43%). The progression-free survival for the TIL-treated group was significantly longer (p=0.002) and better than that of the cisplatin-treated group (66.67% vs. 28.57%). Quality of life apparently improved in the TIL-treated group and was clearly higher than that in the cisplatin-treated group. The use of TILs has a better clinical efficiency for malignant pleural effusion and ascites than cisplatin through intrapleural and intraperitoneal infusion without severe adverse effects. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Effects of mercury on the proliferation of human peripheral lymphocytes in vitro

International Nuclear Information System (INIS)

Piwecka, K.; Poniedzialek, B.; Rzymski, P.; Karczewski, J.; Zurawski, J.; Wiktorowicz, K.

2011-01-01

Our project aimed to investigate the effects of mercury on the proliferation of human peripheral lymphocytes in vitro. The lymphocytes were isolated from the blood collected from healthy donors at Regionalne Centrum Krwiodawstwa i Krwiolecznictwa in Poznan, Poland. For the purpose of cell culture, the lymphocyte suspension (25 · 10 4 cells/ml) in Eagle's medium supplemented with 10% fetal calf serum was prepared. Phytohaemagglutinin-L (PHA-L) was used in a concentration of 2.5 mg/ml to stimulate cell proliferation. Mercuric chloride (HgCl 2 ) in four different concentrations (1 μM, 10 μM, 50 μM, 100 μM) and [3H]-thymidine were added after 48 hours of incubation and the cell culture was continued for the next 24 hours. The rate of lymphocyte proliferation was measured by [3H]-thymidine incorporation method with a liquid scintillation counter. Results indicate that higher concentrations of mercury (50 μM, 100 μM) inhibit the [3H]-thymidine incorporation of human peripheral lymphocytes in vitro. The incorporation was lower than the control sample by 65% at a concentration of 50 μM, while at a concentration of 100 μM it fell to virtually zero. Moreover, the phase of lymphocyte proliferation cycle affected by mercuric chloride was also investigated. For this purpose HgCl 2 in 2 concentrations (10 μM, 50 μM) was added to the cell culture in 4 different time points: at the start of the cell culture and after 4, 24, and 48 hours of incubation. After 48 hours, [3H]-thymidine was added and the cell culture was continued for an additional 24 hours. The rate of cell proliferation was estimated by [3H]-thymidine incorporation using a liquid scintillation counter. The inhibition effect was observed in samples with metal added at the start of the cell culture and after 4 h of incubation, i.e. at the initial phase of the lymphocyte proliferation cycle. (authors)

Evaluation of radio-induced DNA damage and their repair in human lymphocytes by comet assay or single cell gel electrophoresis

International Nuclear Information System (INIS)

Nascimento, Patricia A. do; Suzuki, Miriam F.; Okazaki, Kayo

1997-01-01

The comet assay, also called single cell gel electrophoresis technique, permits to evaluate quantitatively DNA breakage induced by chemical and physical agents at the level of the single cell. The present paper refers to the construction of dose-response curves to DNA damage and repair studies in human peripheral lymphocytes, utilizing the comet assay for the radiosensitivity analysis. So, the blood samples were obtained from healthy donors (40-50 year old), irradiated in a 60 Co source (GAMMACEL 220) with doses of 0.17, 0.25, 0.57, 1.10, 2.12 and 4.22 Gy (0.59 Gy/min.) and processed 1 and 24 hours after the exposition. Results obtained showed a increase in the total lenght of comet (DNA migration) as a function of radiation dose in samples processed 1 and 24 hours after the treatment. The DNA lesion in irradiated lymphocytes with 4.22 Gy (means value of 101.4 μm) were 3.4 times higher than in the untreated lymphocytes (mean value of 30 μm) instead of 24 hours after the irradiation were 1.5 times higher (mean value of 46.3 μm). This reduction on DNA repair occurred in these cells. It was also possible visualized the presence of subpopulations of the cells with different sensitivity and repair capacity to ionizing radiation in these donors. (author). 8 refs., 3 figs

Radiation effects on lymphocytes

International Nuclear Information System (INIS)

Roser, B.

1976-01-01

This review of the ontogeny of lymphocyte populations concentrates on sites of production, rates of production, and the factors governing the differentiation and longevity of the various lymphocyte pools. The physiology of the lymphocyte pools is described with particular emphasis on recirculation from blood to lymph through lymphoid tissues. The separate routes of recirculation of both thymus-derived and nonthymus-derived lymphocytes and the possible anatomical sites and mechanisms of lymphocyte cooperation are discussed. Radiation effects on lymphocyte populations are divided into two sections. First, the effects of whole-body irradiation on the total lymphocyte pools are discussed including the differential effects of irradiation on T lymphocytes, B lymphocytes, lymphoblasts, and plasma cells. The differential sensitivity of various types of immune response is correlated, where possible, with the differential sensitivity of the lymphocyte types involved. Second, experimental attempts to selectively deplete discrete subpopulations of the total lymphocyte pools, e.g., recirculating cells, are briefly discussed with particular emphasis on studies on the effects of the localization of radionuclides in lymphoid tissue

Human umbilical cord derived mesenchymal stem cells promote interleukin-17 production from human peripheral blood mononuclear cells of healthy donors and systemic lupus erythematosus patients.

Science.gov (United States)

Ren, S; Hu, J; Chen, Y; Yuan, T; Hu, H; Li, S

2016-03-01

Inflammation instigated by interleukin (IL)-17-producing cells is central to the development and pathogenesis of several human autoimmune diseases and animal models of autoimmunity. The expansion of IL-17-producing cells from healthy donors is reportedly promoted by mesenchymal stem cells derived from fetal bone marrow. In the present study, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were examined for their effects on lymphocytes from healthy donors and from patients with systemic lupus erythematosus (SLE). Significantly higher levels of IL-17 were produced when CD4(+) T cells from healthy donors were co-cultured with hUC-MSCs than those that were cultured alone. Blocking experiments identified that this effect might be mediated partially through prostaglandin E2 (PGE2 ) and IL-1β, without IL-23 involvement. We then co-cultured hUC-MSCs with human CD4(+) T cells from systemic lupus erythematosus patients. Ex-vivo inductions of IL-17 by hUC-MSCs in stimulated lymphocytes were significantly higher in SLE patients than in healthy donors. This effect was not observed for IL-23. Taken together, our results represent that hUC-MSCs can promote the IL-17 production from CD4(+) T cells in both healthy donor and SLE patients. PGE2 and IL-1β might also be partially involved in the promotive effect of hUC-MSCs. © 2015 British Society for Immunology.

Radiation injuries to chromosomes in lymphocytes of patients with hereditary diseases

Energy Technology Data Exchange (ETDEWEB)

Khandogina, E K; Mutovin, G R; Filyushkin, I V; Akif' ev, A P

1980-02-01

The authors studied dose dependences of the output of choromosomal aberrations in peripheral blood lymphocytes during ..gamma..-irradiation in vitro in patients with Parkinson's syndrome, in a patient with progeria, in a child with translocational Down's syndrome and his mother, phenotypically normal woman, with translocation, and also in control donors. Irradiation was conducted up to the stimulation with PHA (stage Go) from the source /sup 60/Co in the dose range of 0.25-3.0 Gy. It was established that the output of metabolic aberrations is depicted by the linear-quadratic function of the dose better than by the grade one. The lymphocytes of one of the female patients with Parkinson's syndrome suffering from papilloma of the larynx showed an increase in the spontaneous level of chromosomal abberrations and also a tendency to an increase in the fragment output in comparison with the control. The lymphocytes of the patient with progeria showed an insignificantly increased spontaneous level of chromosomal aberrations and a considerable increase in the output of radiation-induced exchanges. In the child with translocational Down's syndrome the output of radiation-induced exchanges was increased in comparison with control, mainly with doses less than 1 Gy and in the lymphocytes of the woman with translocation the output of fragments was increased. In both cases the increase in the spontaneous level of aberrations was observed. A relationship between increased radiosensitivity and the inclusion of patients into a high risk group with reference to a relative increase in the incidence of malignant neoplasms and reduced life span is discussed.

Radiation injuries to chromosomes in lymphocytes of patients with hereditary diseases

International Nuclear Information System (INIS)

Khandogina, E.K.; Mutovin, G.R.; Filyushkin, I.V.; Akif'ev, A.P.

1980-01-01

The authors studied dose dependences of the output of choromosomal aberrations in peripheral blood lymphocytes during γ-irradiation in vitro in patients with Parkinson's syndrome, in a patient with progeria, in a child with translocational Down's syndrome and his mother, phenotypically normal woman, with translocation, and also in control donors. Irradiation was conducted up to the stimulation with PHA (stage Go) from the source 60 Co in the dose range of 0.25-3.0 Gy. It was established that the output of metabolic aberrations is depicted by the linear-quadratic function of the dose better than by the grade one. The lymphocytes of one of the female patients with Parkinson's syndrome suffering from papilloma of the larynx showed an increase in the spontaneous level of chromosomal abberrations and also a tendency to an increase in the fragment output in comparison with the control. The lymphocytes of the patient with progeria showed an insignificantly increased spontaneous level of chromosomal aberrations and a considerable increase in the output of radiation-induced exchanges. In the child with translocational Down's syndrome the output of radiation-induced exchanges was increased in comparison with control, mainly with doses less than 1 Gy and in the lymphocytes of the woman with translocation the output of fragments was increased. In both cases the increase in the spontaneous level of aberrations was observed. A relationship between increased radiosensitivity and the inclusion of patients into a high risk group with reference to a relative increase in the incidence of malignant neoplasms and reduced life span is discussed

Differences in genotoxic activity of alpha-Ni3S2 on human lymphocytes from nickel-hypersensitized and nickel-unsensitized donors.

Science.gov (United States)

Arrouijal, F Z; Marzin, D; Hildebrand, H F; Pestel, J; Haguenoer, J M

1992-05-01

The genotoxic activity of alpha-Ni3S2 was assessed on human lymphocytes from nickel-hypersensitized (SSL) and nickel-unsensitized (USL) subjects. Three genotoxicity tests were performed: the sister chromatid exchange (SCE) test, the metaphase analysis test and the micronucleus test. (i) The SCE test (3-100 micrograms/ml) showed a weak but statistically significant increase in the number of SCE in both lymphocyte types with respect to controls, USL presenting a slightly higher SCE incidence but only at one concentration. (ii) The metaphase analysis test demonstrated a high dose-dependent clastogenic activity of alpha-Ni3S2 in both lymphocyte types. The frequency of chromosomal anomalies was significantly higher in USL than in SSL for all concentrations applied. (iii) The micronucleus test confirmed the dose-dependent clastogenic activity of alpha-Ni3S2 and the differences already observed between USL and SSL, i.e. the number of cells with micronuclei was statistically higher in USL. Finally, the incorporation study with alpha-63Ni3S2 showed a higher uptake of its solubilized fraction by USL. This allows an explanation of the different genotoxic action of nickel on the two cell types. In this study we demonstrated that hypersensitivity has an influence on the incorporation of alpha-Ni3S2 and subsequently on the different induction of chromosomal aberrations in human lymphocytes.

Adoptive Immunotherapy for Hematological Malignancies Using T Cells Gene-Modified to Express Tumor Antigen-Specific Receptors

Directory of Open Access Journals (Sweden)

Hiroshi Fujiwara

2014-12-01

Full Text Available Accumulating clinical evidence suggests that adoptive T-cell immunotherapy could be a promising option for control of cancer; evident examples include the graft-vs-leukemia effect mediated by donor lymphocyte infusion (DLI and therapeutic infusion of ex vivo-expanded tumor-infiltrating lymphocytes (TIL for melanoma. Currently, along with advances in synthetic immunology, gene-modified T cells retargeted to defined tumor antigens have been introduced as “cellular drugs”. As the functional properties of the adoptive immune response mediated by T lymphocytes are decisively regulated by their T-cell receptors (TCRs, transfer of genes encoding target antigen-specific receptors should enable polyclonal T cells to be uniformly redirected toward cancer cells. Clinically, anticancer adoptive immunotherapy using genetically engineered T cells has an impressive track record. Notable examples include the dramatic benefit of chimeric antigen receptor (CAR gene-modified T cells redirected towards CD19 in patients with B-cell malignancy, and the encouraging results obtained with TCR gene-modified T cells redirected towards NY-ESO-1, a cancer-testis antigen, in patients with advanced melanoma and synovial cell sarcoma. This article overviews the current status of this treatment option, and discusses challenging issues that still restrain the full effectiveness of this strategy, especially in the context of hematological malignancy.

Nonmyeloablative and reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation: a clinical review.

Science.gov (United States)

Pollack, Seth M; O'Connor, Thomas P; Hashash, Jana; Tabbara, Imad A

2009-12-01

Allogeneic hematopoietic stem cell transplantation provides many patients, with hematological and malignant diseases, hope of remission and in some cases cure. Because the toxicities of this approach are severe, its use has been limited to younger healthier patients. Nonmyeloablative and reduced intensity conditioning regimens depend more on donor cellular immune effects and less on the cytotoxic effects of the conditioning regimen to eradicate the underlying disease. This approach is based on the induction of host tolerance to donor cells followed by the administration of scheduled donor T-lymphocytes infusions. Accumulated clinical data have been encouraging, and prospective studies are underway to compare this approach to conventional myeloablative allogeneic stem cell transplantation with regard to outcome, durability of responses, effects on the immune system, and the consequences of late complications such as chronic graft-versus-host disease.

Effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function in healthy humans

DEFF Research Database (Denmark)

Madsen, Jan Lysgård; Fuglsang, Stefan; Graff, J

2006-01-01

of glyceryl trinitrate 1 microg/kg x min or saline. A gamma camera technique was used to measure gastric emptying and small intestinal transit after a 1600-kJ mixed liquid and solid meal. Furthermore, duodenal motility was assessed by manometry. RESULTS: Glyceryl trinitrate did not change gastric mean......BACKGROUND: Glyceryl trinitrate is a donor of nitric oxide that relaxes smooth muscle cells of the gastrointestinal tract. Little is known about the effect of glyceryl trinitrate on gastric emptying and no data exist on the possible effect of glyceryl trinitrate on small intestinal transit. AIM......: To examine the effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function after a meal in healthy humans. METHODS: Nine healthy volunteers participated in a placebo-controlled, double-blind, crossover study. Each volunteer was examined during intravenous infusion...

Impact of HLA diversity on donor selection in organ and stem cell transplantation.

Science.gov (United States)

Tiercy, Jean-Marie; Claas, Frans

2013-01-01

The human major histocompatibility complex is a multigene system encoding polymorphic human leucocyte antigens (HLA) that present peptides derived from pathogens to the immune system. The high diversity of HLA alleles and haplotypes in the worldwide populations represents a major barrier to organ and allogeneic hematopoietic stem cell transplantation, because HLA incompatibilities are efficiently recognized by T and B lymphocytes. In organ transplantation, pre-transplant anti-HLA antibodies need to be taken into account for organ allocation. Although HLA-incompatible transplants can be performed thanks to immunosuppressive drugs, the de novo production of anti-HLA antibodies still represents a major cause of graft failure. The HLAMatchmaker computer algorithm determines the immunogenicity of HLA mismatches and allows to define HLA antigens that will not induce an antibody response. Because of the much higher stringency of HLA compatibility criteria in stem cell transplantation, the best donor is a HLA genotypically identical sibling. However, more than 50% of the transplants are now performed with hematopoietic stem cells from volunteer donors selected from the international registry. The development of European national registries covering populations with different HLA haplotype frequencies is essential for optimizing donor search algorithms and providing the best chance for European patients to find a fully compatible donor.

Continuous-infusion adriamycin

International Nuclear Information System (INIS)

Benjamin, R.S.; Chawla, S.P.; Ewer, M.S.; Hortobagyi, G.N.

1986-01-01

This chapter discusses the diminished cardiotoxicity as well as diminished nausea and vomiting with continuous infusions of adriamycin to patients undergoing radiation therapy, particularly with infusions of 48 hours or longer, and best with 96-hour infusions, the longest duration that has been studied systematically. In breast cancer, data show that more adriamycin is better, but only for a selected subgroup of patients: those with complete remission. The diminished cardiotoxicity makes the use of adriamycin more attractive in the adjuvant situation, where increased safety will decrease the chances of long-term complications and make retreatment easy for cured patients who develop second malignancies

Type of homogenization and fat loss during continuous infusion of human milk.

Science.gov (United States)

García-Lara, Nadia Raquel; Escuder-Vieco, Diana; Alonso Díaz, Clara; Vázquez Román, Sara; De la Cruz-Bértolo, Javier; Pallás-Alonso, Carmen Rosa

2014-11-01

Substantial fat loss may occur during continuous feeding of human milk (HM). A decrease of fat loss has been described following homogenization. Well-established methods of homogenization of HM for routine use in the neonatal intensive care unit (NICU) would be desirable. We compared the loss of fat based on the use of 3 different methods for homogenizing thawed HM during continuous feeding. Sixteen frozen donor HM samples were thawed, homogenized with ultrasound and separated into 3 aliquots ("baseline agitation," "hourly agitation," and "ultrasound"), and then frozen for 48 hours. Aliquots were thawed again and a baseline agitation was applied. Subsequently, aliquots baseline agitation and hourly agitation were drawn into a syringe, while ultrasound was applied to aliquot ultrasound before it was drawn into a syringe. The syringes were loaded into a pump (2 mL/h; 4 hours). At hourly intervals the hourly agitation infusion was stopped, the syringe was disconnected and gently shaken. During infusion, samples from the 3 groups were collected hourly for analysis of fat and caloric content. The 3 groups of homogenization showed similar fat content at the beginning of the infusion. For fat, mean (SD) hourly changes of -0.03 (0.01), -0.09 (0.01), and -0.09 (0.01) g/dL were observed for the hourly agitation, baseline agitation, and ultrasound groups, respectively. The decrease was smaller for the hourly agitation group (P homogenization is used. © The Author(s) 2014.

Somatic mutation in peripheral blood lymphocytes among Metro Manila residents: indicator of exposure to environmental pollution

International Nuclear Information System (INIS)

Yulo-Nazarea, Teresa; Cobar, Ma. Lucia C.; Nato, Alejandro Q.; Nazarea, Apolinario D.

2001-01-01

Results of a four-year study on somatic mutation in peripheral blood lymphocytes among Metro Manila residents as an indicator of exposure to environmental pollution conducted by the Philippine Nuclear Research Institute (PNRI) is presented. The study which involves mutation indexing of 200 blood donors demonstrated very strong correlation between high levels of ambient air pollution and increase incidence of mutation at the specific gene locus in peripheral blood lymphocytes among residents of specific areas in Metro Manila. Using the PNRI adapted protocol to determine incidence of mutation at a specific gene marker, hypoxanthine guanine phosphoribosyl transferase (HGPRT), our database analysis indicated a statistically significant difference between mean mutation index of blood donors residing in an area with lower level of pollution (Las Pinas) compared to those residents living in areas with the highest estimated pollution level (Valenzuela). The results of the statistical analyses should provide regulators the direction in incorporating the data into their pollution abatement program to maximize health impact. Biomarker analysis should play a greater role in the future in the formulation of national environment policies. The temporal variation of these ''aseline data'' as the Philippine moves forward through the next several years in its industrialization program should in itself be a very valuable source of environmental policy instruments. (Author)

Directional migration of recirculating lymphocytes through lymph nodes via random walks.

Directory of Open Access Journals (Sweden)

Niclas Thomas

Full Text Available Naive T lymphocytes exhibit extensive antigen-independent recirculation between blood and lymph nodes, where they may encounter dendritic cells carrying cognate antigen. We examine how long different T cells may spend in an individual lymph node by examining data from long term cannulation of blood and efferent lymphatics of a single lymph node in the sheep. We determine empirically the distribution of transit times of migrating T cells by applying the Least Absolute Shrinkage & Selection Operator (LASSO or regularised S-LASSO to fit experimental data describing the proportion of labelled infused cells in blood and efferent lymphatics over time. The optimal inferred solution reveals a distribution with high variance and strong skew. The mode transit time is typically between 10 and 20 hours, but a significant number of cells spend more than 70 hours before exiting. We complement the empirical machine learning based approach by modelling lymphocyte passage through the lymph node insilico. On the basis of previous two photon analysis of lymphocyte movement, we optimised distributions which describe the transit times (first passage times of discrete one dimensional and continuous (Brownian three dimensional random walks with drift. The optimal fit is obtained when drift is small, i.e. the ratio of probabilities of migrating forward and backward within the node is close to one. These distributions are qualitatively similar to the inferred empirical distribution, with high variance and strong skew. In contrast, an optimised normal distribution of transit times (symmetrical around mean fitted the data poorly. The results demonstrate that the rapid recirculation of lymphocytes observed at a macro level is compatible with predominantly randomised movement within lymph nodes, and significant probabilities of long transit times. We discuss how this pattern of migration may contribute to facilitating interactions between low frequency T cells and antigen

Cytotoxic T lymphocyte responses by chimeric thymocytes. Self-recognition is determined early in T cell development

International Nuclear Information System (INIS)

Kruisbeek, A.M.; Hodes, R.J.; Singer, A.

1981-01-01

In this study the cytotoxic T lymphocyte (CTL) recognition pattern of thymocytes from recently reconstituted parent leads to F1 and F1 leads to parent radiation bone marrow chimeras was investigated. Chimeric thymocytes were entirely of donor origin approximately 4 weeks after irradiation and reconstitution but were not capable of autonomously generating either alloreactive or trinitrophenyl (TNP)-modified-self-reactive CTL responses. These experiments demonstrte that even at the earliest time CTL effectors of donor origin from the thymuses of chimeras can be studied, their self-receptor repertoire has already been restricted to recognition of host MHC determinants. These results support the cocept that the host environment influences the self-recognition capacity of T cells at the pre- or intrathymic stage of differentation

Thrombolytic treatment for acute ischemic cerebral stroke: intraarterial urokinase infusion vs. intravenous heparin and urokinase infusion

International Nuclear Information System (INIS)

Ko, Gi Young; Suh, Dae Chul; Lee, Jae Hong; Kim, Jun Hyoung; Choi, Choong Gon; Lee, Ho Kyu; Lee, Myoung Chong

1996-01-01

To evaluate the efficacy and limitation of intra-arterial urokinase (IAUK) infusion for treatment of acute cerebral stroke. Twenty-seven acute cerebral stroke patients treated with IAUK infusion within six hours of stroke onset were reviewed. All patients showed normal initial brain findings on CT. In 21 patients, urokinase(5-15 x 10 5 IU) was administered through a microcatheter placed into or proximal to occluded segment. Mechanical disruption of thrombus by guidewire was performed in 17 patients. Angiographic and clinical responses and complications after IAUK infusion, were evaluated and the results were compared with those of intravenous heparin(N=19) and urokinase infusion(N=19). Complete or partial angiographic recanalization of occluded segment was found in 18 patients (67%), and neurologic improvement was followed in 14 patients(52%). The degree of improvement on the stroke scale score after IAUK infusion was statistically more significant(p<0.05) than that shown after intravenous heparin and urokinase infusion. Complications after IAUK infusion were large(15%) and small amount intracerebral hemorrhage(15%), contrast leakage into brain parenchyma(11%), and gastrointestinal bleeding(4%). Between the IAVK and the intravenous urokinase infusion group, differences in extent and types of complications were statistically insignificant, but were significantly higher in those two groups than in the intravenous heparin infusion group. IAUK infusion may be effective for the treatment of acute cerebral stroke

Short-term effects of regional irradiation on lymphocytes, T lymphocytes and eosinophils

International Nuclear Information System (INIS)

Chazarin, C.; Roche, H.; Bugat, R.; Pris, F.

1983-01-01

Twenty-three cancer patients treated only by regional irradiation were studied. Radiotherapy was delivered to the pelvis in 14 patients and to the mediastinum in 9. T lymphocytes were evaluated with the Jondal technique. Before treatment, lymphocyte counts were identical in patients and control. Decreases in total lymphocytes and T lymphocytes became significant in both groups after 40 Gy. Significant rises in eosinophil counts were found only after abdominal irradiation and seemed unrelated to variations in lymphocyte counts [fr

Subcutaneous insulin infusion: change in basal infusion rate has no immediate effect on insulin absorption rate

International Nuclear Information System (INIS)

Hildebrandt, P.; Birch, K.; Jensen, B.M.; Kuehl, C.

1986-01-01

Eight insulin-dependent diabetic patients were simultaneously given subcutaneous infusions (1.12 IU/h each) of 125 I-labeled Actrapid insulin in each side of the abdominal wall. After 24 h of infusion, the size of the infused insulin depots was measured by external counting for 5 h. The basal infusion rate was then doubled in one side and halved in the other for the next 4 h. Finally, 1.12 IU/h of insulin was given in both sides of the abdominal wall for an additional 3 h. The changes in the size of the depots were measured, and the absorption rates for each hour were calculated. During the first 5 h of infusion, the depot size was almost constant (approximately 5 IU) with an absorption rate that equaled the infusion rate. Doubling the infusion rate led to a significant increase in depot size, but the absorption rate remained unchanged for the first 3 h, and only thereafter was a significant increase seen. When the infusion rate was reduced to the initial 1.12 IU/h, the absorption rate remained elevated during the next 3 h. Correspondingly, when the infusion rate was decreased, the depot size also decreased, but the absorption rate remained unchanged for the first 3 h. The results show that a change in the basal insulin infusion rate does not lead to any immediate change in the insulin absorption rate. This should be considered when planning an insulin-infusion program that includes alteration(s) in the basal-rate setting

Age and smoking habit influence on the spontaneous and radiation induced frequencies of the micronucleus in human lymphocytes

International Nuclear Information System (INIS)

Di Giorgio, M.; Nasazzi, N.; Heredia, M.L.

1996-01-01

Several endpoints have been used for monitoring human population that have been exposed at work or in the environment to genotoxic agents, particularly to ionizing radiation. The cytokinesis-block micronucleus (MN) assay in peripheral lymphocytes is a reliable method for evaluating radiation induced chromosomal damage (DNA breaks and mitotic spindle disturbances) and thus, a suitable dosimeter for estimating in vivo whole body exposures. A research to determine the influence of age, sex and life style factors (smoking habits) on the MN spontaneous and radiation induced frequencies was carried out in order to define the use of this assay in Biological Dosimetry. The estimation of MN frequencies was analyzed in lymphocytes cultures from 50 health donors aged between 4 and 60 years. Based on the smoking habits, they were divided into 2 groups. A fraction of the sample was irradiated in vitro with γ-rays in the range of 0.35 Gy to 4 Gy. A statistically significant influence on the spontaneous MN frequency was observed (R 2 = 0.59) when the variables age and smoking habit were analyzed, and a statistically significant influence on the radiation induced MN frequency was also obtained (R 2 = 0.86) when dose, age and smoking habit were studied. Sex did not influence significantly MN variability, but there was a greater dispersion in the results obtained from female donors, when compared to males, possibly due to the loss of X chromosomes. The comparison of the data from smoking donors to the data from non smoking donors supports the convenience of taking into account the smoking habit for estimating in vivo whole body exposure to γ-rays for doses below 2 Gy. (authors). 8 refs., 3 figs., 2 tabs

Role of reactive oxygen species and Bcl-2 family proteins in TNF-α-induced apoptosis of lymphocytes.

Science.gov (United States)

Ryazanceva, N V; Novickiy, V V; Zhukova, O B; Biktasova, A K; Chechina, O E; Sazonova, E V; Belkina, M V; Chasovskih, N Yu; Khaitova, Z K

2010-08-01

We studied the in vitro apoptosis-inducing effect of recombinant TNF-α (rTNF-α) on blood lymphocytes from healthy donors. rTNF-α-induced apoptosis was accompanied by an increase in the number of cells with low mitochondrial transmembrane potential, increased intracellular content of reactive oxygen species, reduced content of Bcl-2, Bcl-xL, and Bax proteins, and elevated Bad content. The molecular mechanisms of these changes are discussed.

Treatment of blastic transformation of chronic granulocytic leukemia by chemotherapy, total body irradiation and infusion of cryopreserved autologous marrow

Energy Technology Data Exchange (ETDEWEB)

Buckner, C D; Stewart, P; Clift, R A; Fefer, A; Neiman, P E; Singer, J; Storb, R; Thomas, E D [Washington Univ., Seattle (USA). School of Medicine; The United States Public Health Service Hospital; Providence Medical Center, and the Fred Hutchinson Cancer Research Center, Seattle, Washington, USA)

1978-01-01

We have previously reported attempts to reestablish the chronic phase of chronic granulocytic leukemia (CGL), in two patients with blastic transrormation, utilizing intensive therapy followed by the infusion of cryopreserved autologous marrow. This approach has now been attempted in a total of seven patients. Marrow was harvested on single or multiple occasions during the chronic phase of CGL and cryopreserved in 10% dimethylsulfoxide. All patients were treated with cyclophosphamide, 120 mg/kg, plus 1,000 rad of total body irradiation followed by infusion of stored marrow. Two patients failed to achieve marrow repopulation and died of infection after 29 and 48 days. Three patients had partial marrow recovery. Two of these achieved repopulation of myeloid, erythroid, and lymphoid elements but did not recover platelet function; one died of hemorrhage on day 55, and one died of cytomegalovirus interstitial pneumonitis on day 58. A third patient had delayed engraftment of all cell elements, most prominently lymphocytes, and died after 84 days of an iodopathic interstitial pneumonitis. Two patients achieved prompt and complete reestablishment of the chronic phase of CGL. One died on day 72 with a fungal pheumonitis and one developed blastic transformation within 4 months. These preliminary results indicate that this approach to the treatment of blastic transformation of CGL is feasible but difficult. Improvements in results may be achieved by more frequent storage of marrow and pheripheral blood stem cells and lymphocytes and further advances in pretransplant therapy.

Individual radiosensitivity does not correlate with radiation-induced apoptosis in lymphoblastoid cell lines or CD{sup 3+} lymphocytes

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Wistop, A.; Keller, U.; Grabenbauer, G.G.; Sauer, R.; Distel, L.V.R. [Dept. of Radiation Oncology, Friedrich Alexander Univ. Erlangen-Nuremberg, Erlangen (Germany); Sprung, C.N. [Div. of Research, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia)

2005-05-01

Background and purpose: spontaneous and radiation-induced apoptosis of lymphoblastoid cell lines (LCLs) derived from healthy donors, cancer patients and donors with radiosensitivity syndromes as well as CD{sup 3+} lymphocytes from patients with {>=} grade 3 late toxicity were investigated as a possible marker for the detection of individual radiosensitivity. These investigations are based on the hypothesis that hypersensitive patients have reduced levels of apoptosis after in vitro irradiation as a result of a defect in the signaling pathway. Material and methods: Epstein-Barr virus-(EBV-)transformed LCLs derived from five healthy donors, seven patients with heterozygous or homozygous genotype for ataxia-telangiectasia or Nijmegen breakage syndrome and five patients with {>=} grade 3 late toxicity (RTOG) were investigated. In addition, CD{sup 3+} lymphocytes from 21 healthy individuals and 18 cancer patients including five patients with a proven cellular hypersensitivity to radiation were analyzed. Cells were irradiated in vitro with a dose of 2 and 5 Gy and were incubated for 48 h. Apoptotic rates were measured by the TUNEL assay followed by customized image analysis. Results: four out of seven radiosensitivity syndrome patients were identified to have an increased cellular radiosensitivity as determined by reduced apoptotic rates after irradiation of their respective LCLs. Comparatively, only two of the five hypersensitive cancer patients were clearly identified by reduced apoptotic rates. Spontaneous apoptotic rates were very homogeneous among all 39 samples from controls and patients, while lymphocytes of all cancer patients showed significantly lower radiation-induced rates. Conclusion: only a subgroup of hypersensitive patients may be identified by reduction of radiation-induced apoptotic rate. It is concluded that the hypothesis according to which hypersensitive cells have reduced levels of apoptosis is only conditionally true. The authors suggest that this

HLA-C is necessary for optimal human immunodeficiency virus type 1 infection of human peripheral blood CD4 lymphocytes.

Science.gov (United States)

Baroni, Miriam; Matucci, Andrea; Scarlatti, Gabriella; Soprana, Elisa; Rossolillo, Paola; Lopalco, Lucia; Zipeto, Donato; Siccardi, Antonio G; De Santis, Claudio

2010-01-01

The hypothesis that open conformers of HLA-C on target cells might directly exert an effect on their infectability by human immunodeficiency virus (HIV) has been suggested previously. This was tested by exploiting the peculiar specificity of monoclonal antibody (mAb) L31 for HLA-C open conformers to show that normal levels of Env-driven fusion were restored in HLA-C transfectants of a major histocompatibility complex-deleted (fusion-incompetent) cell line. The physiological relevance of this finding is now confirmed in this report, where small interfering RNA (siRNA) technology was used to silence HLA-C expression in peripheral blood lymphocytes (PBLs) from 11 healthy donors. Infectability by HIV (strains IIIB and Bal and primary isolates) was significantly reduced (P=0.016) in silenced cells compared with cells that maintained HLA-C expression in 10 of the 11 PBL donors. Normal infectability was resumed, together with HLA-C expression, when the effect of siRNA interference waned after several days in culture. Additional confirmation of the HLA-C effect was obtained in several assays employing HLA-C-positive and -negative cell lines, a number of HIV strains and also pseudoviruses. In particular, viruses pseudotyped with env genes from HIV strains AC10 and QH0692.42 were assayed on siRNA-silenced lymphocytes from three healthy donors: the differences in infection with pseudoviruses were even higher than those observed in infections with normal viruses.

Development of a coordinated allo T cell and auto B cell response against autosomal PTK2B after allogeneic hematopoietic stem cell transplantation.

Science.gov (United States)

Kremer, Anita N; van der Griendt, Judith C; van der Meijden, Edith D; Honders, M Willy; Ayoglu, Burcu; Schwenk, Jochen M; Nilsson, Peter; Falkenburg, J H Frederik; Griffioen, Marieke

2014-02-01

It is well known that allo-reactive T cells play a crucial role in graft-versus-leukemia and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (alloSCT). Allo-reactive CD4(+) T cells can mediate direct cytolysis, but may also stimulate production of IgG antibodies as helper cells. Immune complexes may subsequently be processed and presented by professional antigen presenting cells and stimulate induction of specific CD8(+) T cells. As such, proteins targeted in coordinated T- and B-cell responses may represent a class of immunodominant antigens in clinical responses after alloSCT. We previously identified LB-PTK2B-1T as HLA class II restricted polymorphic antigen in a patient treated with donor lymphocyte infusion for relapsed chronic myeloid leukemia after HLA-matched alloSCT. Since PTK2B has also been described as antibody target, we here investigated whether a coordinated T- and B-cell response against PTK2B was induced. Patient serum before and after alloSCT and donor lymphocyte infusion (DLI) was screened for antibodies, and we indeed observed development of a humoral immune response against PTK2B. Antibodies against PTK2B were only found after DLI and, in contrast to the CD4(+) T cells, recognized a monomorphic region of the protein. To our knowledge, this is the first description of a coordinated allo-reactive CD4(+) T-cell and auto-reactive antibody response against an autosomal antigen.

Infusion MR arteriography during hepatic arterial infusion chemotherapy. Evaluation of clinical usefulness

International Nuclear Information System (INIS)

Uchino, Minako; Takizawa, Kenji

2003-01-01

We developed a new method of infusion MR arteriography (IMRA) via an implantable port system using an infusion pump for the evaluation of drug distribution during hepatic arterial infusion chemotherapy. The purposes of this study were to optimize the method and evaluate its clinical usefulness. We used 3D-T1 turbo field echo (TFE) as the most suitable sequence for IMRA according to the results of a phantom model experiment. We examined 33 cases of liver cancer that had been treated by arterial infusion chemotherapy via the port system. The following investigations were performed: degree of tumor enhancement, intra- and extra- hepatic perfusion abnormality, and related toxicity. The evaluation of images was performed separately by two radiologists. IMRA provided good images of contrast enhancement, to reveal the perfusion patterns. The treatment response rate in the tumor group with well enhancement was higher than that of the group with poor enhancement (p<0.0001). Extrahepatic perfusion was well visualized and was correlated with toxicity (p<0.0001). IMRA is a useful method to evaluate drug perfusion for the optimization of arterial infusion chemotherapy. (author)

Induction of micronuclei in human and mouse lymphocytes irradiated with gamma radiation and effect of panax ginseng C. A. Meyer

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Kim, Sung Ho; Oh, Heon; Lee, Song Eun [Chonnam National Univ., Kwangju (Korea, Republic of); Lee, Yun Sil; Kim, Tae Hwan [Korea Cancer Center Hospital, Seoul (Korea, Republic of); Jeong, Kyu Sik [Korea Research Institute of Bioscience and Biotechnology, Taejon (Korea, Republic of); Ryu, Si Yun [Chungnam National Univ., Taejon (Korea, Republic of)

1997-09-01

The frequencies of {gamma}-ray-induced micronuclei (MN) in Cytokinesis-Blocked (CB) lymphocytes at several doses were measured in three donors of human and C57BL/6 mice. Measurements performed after irradiation showed a dose-related increases in MN frequency in each of the donors studied. The relative sensitivity of mouse in Spleen Lymphocytes (SLs) compared with human Peripheral Blood Lymphocytes (PBLs) was estimated by best fitting linear-quadratic model based on the radiation-induced MN data over the range from 0 cGy to 400 cGy. In the case of MN frequency with 0.2 per CB cell, the relative sensitivity of mouse SLs was 1.67. Compared with the radiation-induced MN formation in the PBLs of human, the SLs of mouse were more radiosensitive. Using this MN assay with human PBLs and mouse SLs, studies were performed to determine whether the water fraction of ginseng (Panax ginseng C.A.Meyer)against radiation-induced MN in human PBLs after in vitro irradiation (3Gy) and in SLs of C57BL/6 mice after in vivo irradiation (3Gy). The frequency of MN in human PBLs was reduced by water fraction of ginseng (0.5mg/ml of medium) both pre-and post treatment (p<0.01) in vitro. In addition, the frequency of MN in mouse SLs was also reduced by pretreatment of ginseng (2mg/ml of drinking water for 7 days) in vivo.

An audit of hospital based outpatient infusions and a pilot program of community-based monoclonal antibody infusions.

LENUS (Irish Health Repository)

Doran, J-P

2012-02-01

INTRODUCTION: Infliximab, a chimeric monoclonal antibody to tumour necrosis factor alpha, is administered as an intravenous infusion requiring a costly hospital day case or inpatient admission. METHODS: An audit of all current therapies given by intravenous infusions in an outpatient setting in St Vincent\\'s University Hospital (SVUH) was undertaken. Furthermore, in conjunction with TCP homecare, we established in a general practise health clinic, the first Irish community infusion centre for the administration of infliximab in August 2006. RESULTS: All outpatient departments indicated that they would favour a centralized hospital infusion unit. There were no adverse events and the mean global satisfaction improved in the community infliximab infusion pilot programme of seven patients. CONCLUSION: This study suggests efficiencies in providing centralized infusion facilities, while the community based infusion of infliximab is feasible and safe in this small cohort and identifies the community infusion unit as a viable and cost efficient alternative for administration of infliximab.

Adoptive infusion of tolerogenic dendritic cells prolongs the survival of pancreatic islet allografts: a systematic review of 13 mouse and rat studies.

Directory of Open Access Journals (Sweden)

Guixiang Sun

Full Text Available OBJECTIVE: The first Phase I study of autologous tolerogenic dendritic cells (Tol-DCs in Type 1 diabetes (T1D patients was recently completed. Pancreatic islet transplantation is an effective therapy for T1D, and infusion of Tol-DCs can control diabetes development while promoting graft survival. In this study, we aim to systematically review islet allograft survival following infusion of Tol-DCs induced by different methods, to better understand the mechanisms that mediate this process. METHODS: We searched PubMed and Embase (from inception to February 29(th, 2012 for relevant publications. Data were extracted and quality was assessed by two independent reviewers. We semiquantitatively analyzed the effects of Tol-DCs on islet allograft survival using mixed leukocyte reaction, Th1/Th2 differentiation, Treg induction, and cytotoxic T lymphocyte activity as mechanisms related-outcomes. We discussed the results with respect to possible mechanisms that promote survival. RESULTS: Thirteen articles were included. The effects of Tol-DCs induced by five methods on allograft survival were different. Survival by each method was prolonged as follows: allopeptide-pulsed Tol-DCs (42.14 ± 44 days, drug intervention (39 days, mesenchymal stem cell induction (23 days, genetic modification (8.99 ± 4.75 days, and other derivation (2.61 ± 6.98 days. The results indicate that Tol-DC dose and injection influenced graft survival. Single-dose injections of 10(4 Tol-DCs were the most effective for allograft survival, and multiple injections were not superior. Tol-DCs were also synergistic with immunosuppressive drugs or costimulation inhibitors. Possible mechanisms include donor specific T cell hyporesponsiveness, Th2 differentiation, Treg induction, cytotoxicity against allograft reduction, and chimerism induction. CONCLUSIONS: Tol-DCs induced by five methods prolong MHC mismatched islet allograft survival to different degrees, but allopeptide-pulsed host DCs

Bronchial arterial infusion versus bronchial combined pulmonary arterial infusion for pulmonary metastatic tumors

International Nuclear Information System (INIS)

Dong Sheng; Dong Weihua; Jia Ningyang; Zhang Dianbo; Xiao Xiangsheng

2008-01-01

Objective: To evaluate the pulmonary metastatic tumor response to different ways of transcatheter arterial infusion. Methods: Thirty-five patients with pulmonary metastatic tumors were randomized divided into two groups: 15 patients with 49 lesions treated with bronchial arterial infusion (BAI) and 20 patients with 65 lesions treated with bronchial arterial infusion (BM)combined with pulmonary arterial infusion (PAI). The therapeutic response was assessed by the WHO evaluation criteria. Results: The total effective rate(CR + PR) of BAI was 65.3% (32/49), PAI + BAI was 61.5%(40/65) showing no statistical difference. The median survival time of BAI was 9 mo, BAI + PAI was 11.5 mo, demonstrating no statistical significance. Conclusions: BAI should be the primary treatment for pulmonary metastatic tumor. (authors)

Cytogenetic Low-Dose Hyperradiosensitivity Is Observed in Human Peripheral Blood Lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Seth, Isheeta [Department of Biological Sciences, Wayne State University, Detroit, Michigan (United States); Joiner, Michael C. [Department of Radiation Oncology, Wayne State University, Detroit, Michigan (United States); Tucker, James D., E-mail: jtucker@biology.biosci.wayne.edu [Department of Biological Sciences, Wayne State University, Detroit, Michigan (United States)

2015-01-01

Purpose: The shape of the ionizing radiation response curve at very low doses has been the subject of considerable debate. Linear-no-threshold (LNT) models are widely used to estimate risks associated with low-dose exposures. However, the low-dose hyperradiosensitivity (HRS) phenomenon, in which cells are especially sensitive at low doses but then show increased radioresistance at higher doses, provides evidence of nonlinearity in the low-dose region. HRS is more prominent in the G2 phase of the cell cycle than in the G0/G1 or S phases. Here we provide the first cytogenetic mechanistic evidence of low-dose HRS in human peripheral blood lymphocytes using structural chromosomal aberrations. Methods and Materials: Human peripheral blood lymphocytes from 2 normal healthy female donors were acutely exposed to cobalt 60 γ rays in either G0 or G2 using closely spaced doses ranging from 0 to 1.5 Gy. Structural chromosomal aberrations were enumerated, and the slopes of the regression lines at low doses (0-0.4 Gy) were compared with doses of 0.5 Gy and above. Results: HRS was clearly evident in both donors for cells irradiated in G2. No HRS was observed in cells irradiated in G0. The radiation effect per unit dose was 2.5- to 3.5-fold higher for doses ≤0.4 Gy than for doses >0.5 Gy. Conclusions: These data provide the first cytogenetic evidence for the existence of HRS in human cells irradiated in G2 and suggest that LNT models may not always be optimal for making radiation risk assessments at low doses.

Proliferation of Peripheral Blood Lymphocytes and Mesenchymal Stromal Cells Derived from Wharton's Jelly in Mixed and Membrane-Separated Cultures.

Science.gov (United States)

Poltavtsev, A M; Poltavtseva, R A; Yushina, M N; Pavlovich, S V; Svirshchevskaya, E V

2017-08-01

We studied the effect of mesenchymal stromal cells on proliferation of CFSE-stained T cells in mixed and membrane-separated (Transwell) cultures and in 3D culture of mesenchymal stromal cells from Wharton's jelly. The interaction of mesenchymal stromal cells with mitogen-activated peripheral blood lymphocytes from an allogeneic donor was followed by suppression of T-cell proliferation in a wide range of cell proportions. Culturing in the Transwell system showed the absence of suppression assessed by the fraction of proliferating cells and by the cell cycle analysis. In 3D cultures, contact interaction of mesenchymal stromal cells and lymphocytes was demonstrated that led to accumulation of G2/M phase lymphocytes and G0/G1 phase mesenchymal stromal cells. The suppressive effect of mesenchymal stromal cells from Wharton's jelly is mediated by two mechanisms. The effects are realized within 6 days, which suggests that the therapeutic effects of mesenchymal stromal cells persist until their complete elimination from the body.

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

Directory of Open Access Journals (Sweden)

Anne M. Dickinson

2017-06-01

Full Text Available The success of hematopoietic stem cell transplantation (HSCT lies with the ability of the engrafting immune system to remove residual leukemia cells via a graft-versus-leukemia effect (GvL, caused either spontaneously post-HSCT or via donor lymphocyte infusion. GvL effects can also be initiated by allogenic mismatched natural killer cells, antigen-specific T cells, and activated dendritic cells of leukemic origin. The history and further application of this GvL effect and the main mechanisms will be discussed and reviewed in this chapter.

Donor Outcomes in Living Donor Liver Transplantation-Analysis of 275 Donors From a Single Centre in India.

Science.gov (United States)

Narasimhan, Gomathy; Safwan, Mohamed; Kota, Venugopal; Reddy, Mettu S; Bharathan, Anand; Dabora, Abderrhaim; Kaliamoorthy, Ilankumaran; Kanagavelu, Rathnavel G; Srinivasan, Vijaya; Rela, Mohamed

2016-06-01

Live donor liver transplantation is the predominant form of liver transplantation in India and in most Asian countries. Donor outcome reports are an important source of information to be shared with prospective donors at the time of informed consent. This is the first donor outcome series from India. Analysis of donor characteristics and morbidity of 275 live donors from a single large volume center is documented. Two hundred seventy-five patients donated from November 2009 to October 2014, 144 were women and 131 were men, 180 donated to adults and 95 donated to children. Right lobe donors were majority at 62.2% followed by left lateral segment 28%. Two thirds of the live donors did not have any morbidity; 114 complications were encountered in 85 patients. The complications were graded as per Clavien 5 tier grading and major morbidity (grade III b, grade IV grade V) was 4.36%. Postoperative biliary complication was seen in 3 donors. This large single-center study is the first donor outcome report from India, and the results are comparable to other published donor series. Documentation and regular audit of donor outcomes is important to help improve the safety of donor hepatectomy and to provide a database for informed consent of prospective donors.

UVB pretreatment of rat bone marrow allografts. Prevention of GVHD and induction of allochimerism and donor-specific unresponsiveness

International Nuclear Information System (INIS)

Chabot, J.A.; Pepino, P.; Wasfie, T.; Stegall, M.D.; Marboe, C.; Hardy, M.A.

1990-01-01

Ultraviolet B irradiation has been used to pretreat blood and islets to prevent subsequent graft rejection. In this study the optimal dose of UVB irradiation of bone marrow was determined in syngeneic recipients and was subsequently applied to in-vitro treatment of bone marrow allografts. UVB pretreatment of donor bone marrow inoculum led to complete prevention of GVHD in allogeneic rat recipients without major marrow or other toxicity. Long-standing recipients of allogeneic UVB-BM became stable adult chimeras. The recipients of allogeneic BM were populated by donor-type peripheral blood lymphocytes and did not reject host or donor-type heart grafts. The BM allograft recipients were immunocompetent as measured by their ability to normally reject third-party cardiac allografts. We suggest that the prevention of GVHD and induction of stable chimerism in adult recipients of allogeneic UVB-BM may be mediated by suppressor mechanisms

UVB pretreatment of rat bone marrow allografts. Prevention of GVHD and induction of allochimerism and donor-specific unresponsiveness

Energy Technology Data Exchange (ETDEWEB)

Chabot, J.A.; Pepino, P.; Wasfie, T.; Stegall, M.D.; Marboe, C.; Hardy, M.A. (Columbia Univ. College of Physicians and Surgeons, New York, NY (USA))

1990-05-01

Ultraviolet B irradiation has been used to pretreat blood and islets to prevent subsequent graft rejection. In this study the optimal dose of UVB irradiation of bone marrow was determined in syngeneic recipients and was subsequently applied to in-vitro treatment of bone marrow allografts. UVB pretreatment of donor bone marrow inoculum led to complete prevention of GVHD in allogeneic rat recipients without major marrow or other toxicity. Long-standing recipients of allogeneic UVB-BM became stable adult chimeras. The recipients of allogeneic BM were populated by donor-type peripheral blood lymphocytes and did not reject host or donor-type heart grafts. The BM allograft recipients were immunocompetent as measured by their ability to normally reject third-party cardiac allografts. We suggest that the prevention of GVHD and induction of stable chimerism in adult recipients of allogeneic UVB-BM may be mediated by suppressor mechanisms.

Reduction and repopulation of recipient T4+ and T8+ T-lymphocytes in allogeneic bone marrow transplantation

International Nuclear Information System (INIS)

Gratama, J.W.; van den Bergh, R.L.; Naipal, A.; D'Amaro, J.; Zwaan, F.E.; Jansen, J.; de Gast, G.C.

1986-01-01

In eight recipients of allogeneic bone marrow grafts who had sex-mismatched donors, the reduction and subsequent repopulation of T4+ and T8+ T-lymphocytes of recipient origin were studied. The origin of the donor-recipient T4+ and T8+ T cells was studied using quinacrine staining of Y chromatin combined with T-cell typing for T4 and T8. Following chemoradiotherapy and bone marrow transplantation (BMT), T cells reached their nadir at a median of five (range 1-8) days after BMT. T8+ T cells decreased at a faster rate from the peripheral blood than T4+ T cells. The first T cells that appeared in the circulation at day 12 were predominantly T4+, and a large number of them were of recipient origin. Thereafter, they gradually decreased, and the numbers of T cells of donor origin increased. In the patients who had no or only minor complications, T4+ and T8+ T cells of donor origin repopulated the blood at similar rates. This pattern, however, was modified by severe graft-versus-host disease or by cytomegalovirus infection

Effect of steel and teflon infusion catheters on subcutaneous adipose tissue blood flow and infusion counter pressure in humans

DEFF Research Database (Denmark)

Højbjerre, Lise; Skov-Jensen, Camilla; Kaastrup, Peter

2009-01-01

BACKGROUND: Subcutaneous tissue is an important target for drug deposition or infusion. A local trauma may induce alterations in local microcirculation and diffusion barriers with consequences for drug bioavailability. We examined the influence of infusion catheters' wear time on local...... microcirculation and infusion counter pressure. METHODS: One steel catheter and one Teflon (Dupont, Wilmington, DE) catheter were inserted in subcutaneous, abdominal adipose tissue (SCAAT) in 10 healthy, lean men. The catheters were infused with isotonic saline at a rate of 10 microL/h for 48 h. Another steel...... catheter and a Teflon catheter were inserted contralateral to the previous catheters after 48 h. The infusion counter pressure was measured during a basal infusion rate followed by a bolus infusion. The measurements during a basal rate infusion were repeated after the bolus infusion. Adipose tissue blood...

The Japan Marrow Donor Program, 25 years of experience in achieving 20,000 bone marrow transplantations: organization structure, activity, and financial basis.

Science.gov (United States)

Saito, Hidehiko; Ito, Masaharu; Kato, Shunichi; Kodera, Yoshihisa; Okamoto, Shinichiro; Taniguchi, Shuichi; Takanashi, Minoko; Kanamori, Heiwa; Masaoka, Toru; Takaku, Fumimaro

2018-01-24

The Japan Marrow Donor Program (JMDP), established in 1991, has continued to grow in its capacity to facilitate unrelated bone marrow (BMT) and peripheral blood stem cell transplantation (PBSCT) for the past 25 years in Japan. The current donor pool is 463,465 (as of 31 December 2016) and 20,237 transplants were performed with the help of the Japanese Red Cross, government, and supporters. As JMDP introduced PBSCT in 2010, the vast majority of transplants are BMT. All donors are fully typed for HLA-A, B, C, and DR. The peak age of registered donors is around 40 years. The 8/8 HLA-matched donors are found in our registry for 96% of the patients and 54% of the patients receive a transplant. The median time between the initiation of donor search and the transplantation is approximately 122 days. The median interval between the initiation of donor search and identification of the first potential donor is 40 days. The most common diseases for which unrelated BMT/PBSCT is indicated are acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS), and malignant lymphoma. In recent years we have seen a marked increase in elderly patients who received BMT.

Activation of NK Cells in Mixed Cultures of Wharton's Jelly Mesenchymal Stromal Cells and Peripheral Blood Lymphocytes.

Science.gov (United States)

Svirshchevskaya, E V; Poltavtsev, A M; Os'mak, G Zh; Poltavtseva, R A

2018-01-01

Mesenchymal stromal cells possess immunosuppressive properties that might be used for the therapy of inflammatory diseases of various geneses. The effects of mesenchymal stromal cells depend on their lifetime in the recipient tissues. During heterologous transplantation, mesenchymal stromal cells are eliminated by NK cells. We studied NK cell formation in mixed cultures of Wharton's jelly mesenchymal stromal cells and peripheral blood lymphocytes from an autologous donor. Lymphocytes were activated by a mitogen or IL-2. The lifetime of mesenchymal stromal cells was estimated by MTT test. Cytotoxic activity and phenotype of NK cells were evaluated by flow cytometry. It was found that activation of NK cells depended on IL-2 and was registered on day 2 of incubation with IL-2. In cultures with mitogen-activated lymphocytes, cytotoxicity was observed after 5-6 days. Cytotoxicity of NK correlated with significant decrease in CD16+ and increase in CD56+ NK and with reduction of mesenchymal stromal cell viability. Thus, the main mechanism of elimination of mesenchymal stromal cells is cytotoxicity of NK cells that depended on IL-2 production.

Hippocampal infusions of glucose reverse memory deficits produced by co-infusions of a GABA receptor agonist.

Science.gov (United States)

Krebs-Kraft, Desiree L; Parent, Marise B

2008-02-01

Although septal infusions of glucose typically have positive effects on memory, we have shown repeatedly that this treatment exacerbates memory deficits produced by co-infusions of gamma-aminobutyric acid (GABA) receptor agonists. The present experiments tested whether this negative interaction between glucose and GABA in the medial septum would be observed in the hippocampus, a brain region where glucose typically has positive effects on memory. Specifically, we determined whether hippocampal infusions of glucose would reverse or exacerbate memory deficits produced by hippocampal co-infusions of the GABA receptor agonist muscimol. Fifteen minutes prior to either assessing spontaneous alternation (SA) or continuous multiple trial inhibitory avoidance (CMIA) training, male Sprague-Dawley-derived rats were given bilateral hippocampal infusions of vehicle (phosphate-buffered saline [PBS], 1 microl/2 min), glucose (33 or 50 nmol), muscimol (0.3 or 0.4 microg, SA or 3 microg, CMIA) or muscimol and glucose combined in one solution. The results indicated that hippocampal infusions of muscimol alone decreased SA scores and CMIA retention latencies. More importantly, hippocampal infusions of glucose, at doses that had no effect when infused alone, attenuated (33 nmol) or reversed (50 nmol) the muscimol-induced memory deficits. Thus, although co-infusions of glucose with muscimol into the medial septum impair memory, the present findings show that an opposite effect is observed in the hippocampus. Collectively, these findings suggest that the memory-impairing interaction between glucose and GABA in the medial septum is not a general property of the brain, but rather is brain region-dependent.

Subcutaneous infusion in palliative care: a focus on the neria soft 90 infusion set.

Science.gov (United States)

Gabriel, Janice

2014-11-01

Subcutaneous administration of medications and/or fluids can play a crucial part in supporting patients at home and thereby avoiding the need for hospitalisation. It is an area of patient care that has received little attention compared with other types of parenteral therapies. However, it is an effective and safe route for continuous administration for individuals requiring palliative care. Technological advancements have led to improved subcutaneous infusion devices, such as fine-gauge cannulae with integral sharps protection, as well as integral hypoallergenic dressings. These design features not only help to increase patient comfort but also minimise the potential for needlestick injuries, as well as providing the health professional with one sterile package containing all of the components needed to establish subcutaneous infusion. However, technological developments alone are insufficient to improve patient outcomes. Knowledge of the individual patient, together with their diagnosis and intended treatment, will influence the choice of subcutaneous infusion device, with the overall aim of minimising the potential for complications and improving comfort. This paper provides an overview of subcutaneous infusion, including the importance of patient assessment and the education and training needs of health professionals, and then focuses on one specific subcutaneous infusion device: the neria soft 90 infusion set.

Specific tolerance induction across a xenogeneic barrier: Production of mixed rat/mouse lymphohematopoietic chimeras using a nonlethal preparative regimen

International Nuclear Information System (INIS)

Sharabi, Y.; Aksentijevich, I.; Sundt, T.M. III; Sachs, D.H.; Sykes, M.

1990-01-01

The development of safe methods for inducing donor-specific tolerance across xenogeneic barriers could potentially relieve the critical shortage of allograft donors that currently limits the applicability of organ transplantation. We report here that such tolerance can be induced in a xenogeneic combination (rat----mouse) using a nonmyeloablative and nonlethal preparative regimen. Successful induction of chimerism and donor-specific transplantation tolerance required pretreatment of recipients with monoclonal antibodies (mAbs) against NK1.1, Thy-1.2, CD4 and CD8, followed by administration of 3 Gy whole body radiation (WBI), 7 Gy thymic irradiation, and infusion of T cell-depleted rat bone marrow cells (BMC). Rat cells appeared among peripheral blood lymphocytes (PBL) of such recipients by 2-3 wk, and rat T cells by 2-5 wk following bone marrow transplantation (BMT). Donor-type rat skin grafts placed 4 mo after BMT were accepted, while simultaneously placed non-donor-type rat skin grafts were promptly rejected. In addition to its clinical potential, the ability to induce donor-specific tolerance across xenogeneic barriers using such a nonlethal preparative regimen provides a valuable model for the study of mechanisms of xenogeneic transplantation tolerance

In vivo assessment of 111In labelled lymphocyte gut homing in a TNBS colitis mouse model determined by dedicated animal pinhole SPECT

International Nuclear Information System (INIS)

Bennink, R.J.; Bruin, C.M. de; Montfrans, C. van; Jonge, W.J. de; Deventer, S.J. van; Velde, A.A. te

2002-01-01

Aims: The increasing knowledge of the molecular basis of leukocyte trafficking results in the development of novel anti-inflammatory strategies for inflammatory bowel disease (IBD). For optimal evaluation of therapy efficacy, information about inflammatory activity in bowel segments or lymphocyte recirculation and kinetics in the follow-up of experimental treatment for IBD is needed. The aim of this study was to evaluate a non-invasive scintigraphic technique, able to assess lymphocyte trafficking in a trinitrobenzene sulfonic acid (TNBS) induced mouse colitis model of IBD. Materials and Methods: TNBS sensitised and non-sensitised murine total splenocytes, isolated from donor TNBS colitis or placebo treated BALB/c mice, were labelled in vitro with 111 In-oxine and injected intravenously into recipient BALB/c mice with TNBS-induced colitis or healthy BALB/c mice instilled with saline. Biodistribution and specific radioactive uptake, representing transferred cells, was determined by serial dedicated animal planar scintigraphy and pinhole SPECT of the abdomen 4, 24 and 48h post injection of labelled cells. Moreover, the severity of inflammation in recipient mice was determined by histological scoring. Results: Lymphocyte migration to the inflamed colon of recipient mice increased in time and was maximal at 48h after administration of the 111 In-oxine labelled donor splenocytes. The highest specific radioactive uptake ratio in the colon after 48h was observed in recipient mice with TNBS colitis that received TNBS sensitised lymphocytes (saline vs. TNBS colitis resp. 0.22 ± 0.035 and 0.51 ± 0.033 mean ± SEM p<0.01). Histological scoring confirmed colitis in the TNBS colitis recipient groups and excluded colitis in the saline instilled recipient groups. TNBS colitis recipient mice that received sensitised lymphocytes had a more severe colitis upon histological evaluation as compared with TNBS colitis recipient mice receiving non-sensitised cells (mean histological

Radiation-induced micronucleus frequencies in female peripheral blood lymphocytes collected during the first and second half of the menstrual cycle

International Nuclear Information System (INIS)

Krol, M.; Lankoff, A.; Buraczewska, I.; Derezinska, E.; Wojcik, A.

2007-01-01

Biological dosimetry relies on the assessment of dose in peripheral blood lymphocytes (PBL) of a victim. Variability in the individual radiosensitivity of PBL has an impact on the precision of dose estimate and radiation-induced micronuclei show a strong individual variability. A factor which can influence the radiosensitivity of PBL is the hormonal status of female donors, which shows a regular pattern during the menstrual cycle. The aim of the present investigation was to verify whether the position within the menstrual cycle has an impact on the level of micronuclei in PBL. Blood was collected from 19 donors during the first and second half of the menstrual cycle and exposed to 2 Gy. Although statistically significant differences between the MN frequencies in PBL collected during the different time points were observed in the case of some donors, no reproducible trend that could find application in biological dosimetry could be detected. (authors)

Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: potential for group housing

DEFF Research Database (Denmark)

Jensen, Vivi Flou Hjorth; Molck, Anne-Marie; Martensson, Martin

2017-01-01

compound in these studies, and a comparator model of persistent exposure by HI infusion from external pumps has recently been developed to support toxicological evaluation of long-acting insulin analogues. However, this model requires single housing of the animals. Developing an insulin-infusion model...... which allows group housing would therefore greatly improve animal welfare. The aim of the present study was to investigate the suitability of implantable infusion pumps for HI infusion in group-housed rats. Group housing of rats implanted with a battery-driven pump proved to be possible. Intravenous...... infusion of HI lowered blood glucose levels persistently for two weeks, providing a comparator model for use in two-week repeated-dose toxicity studies with new long-acting insulin analogues, which allows group housing, and thereby increasing animal welfare compared with an external infusion model....

Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients

Directory of Open Access Journals (Sweden)

Ellebaek Eva

2012-08-01

Full Text Available Abstract Background Adoptive cell therapy may be based on isolation of tumor-specific T cells, e.g. autologous tumor infiltrating lymphocytes (TIL, in vitro activation and expansion and the reinfusion of these cells into patients upon chemotherapy induced lymphodepletion. Together with high-dose interleukin (IL-2 this treatment has been given to patients with advanced malignant melanoma and impressive response rates but also significant IL-2 associated toxicity have been observed. Here we present data from a feasibility study at a Danish Translational Research Center using TIL adoptive transfer in combination with low-dose subcutaneous IL-2 injections. Methods This is a pilot trial (ClinicalTrials.gov identifier: NCT00937625 including patients with metastatic melanoma, PS ≤1, age Results Low-dose IL-2 considerably decreased the treatment related toxicity with no grade 3–4 IL-2 related adverse events. Objective clinical responses were seen in 2 of 6 treated patients with ongoing complete responses (30+ and 10+ months, 2 patients had stable disease (4 and 5 months and 2 patients progressed shortly after treatment. Tumor-reactivity of the infused cells and peripheral lymphocytes before and after therapy were analyzed. Absolute number of tumor specific T cells in the infusion product tended to correlate with clinical response and also, an induction of peripheral tumor reactive T cells was observed for 1 patient in complete remission. Conclusion Complete and durable responses were induced after treatment with adoptive cell therapy in combination with low-dose IL-2 which significantly decreased toxicity of this therapy.

Immunoregulatory activities of human immunodeficiency virus (HIV) proteins: Effect of HIV recombinant and synthetic peptides on immunoglobulin synthesis and proliferative responses by normal lymphocytes

International Nuclear Information System (INIS)

Nair, M.P.N.; Pottathil, R.; Heimer, E.P.; Schwartz, S.A.

1988-01-01

Recombinant and synthetic peptides corresponding to envelope proteins of the human immunodeficiency virus (HIV) were examined for their effects on the activities of lymphocytes from normal donors in vitro. Although lymphocytes cultured with env-gag peptides produced significant amounts of IgG, addition of env-gag peptides to a pokeweed mitogen-induced B-cell activation system resulted in suppression of immunoglobulin synthesis by normal lymphocytes. Recombinant antigens, env-gag and env-80 dihydrofolate reductase (DHFR), produced a substantial proliferative response by peripheral blood mononuclear cells (PBMC) as determined by [ 3 H]thymidine incorporation. PBMC precultured with HIV synthetic peptide env 578-608 also manifested significant proliferative responses as compared to control cultures. CD3 + lymphocytes precultured with recombinant HIV antigens, env-gag and env-80 DHFR, and synthetic HIV peptide, env 487-511, showed moderate but significant proliferative responses. Both recombinant antigens and synthetic peptides also produced a dose-dependent stimulatory effect on proliferation by CD3 - lymphocytes. These studies demonstrate that recombinant and synthetic peptides of the HIV genome express immunoregulatory T- and B-cell epitopes. Identification of unique HIV epitopes with immunogenic and immunoregulatory activities is necessary for the development of an effective vaccine against HIV infection

Assessment of Impact of HLA Type on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia.

Science.gov (United States)

Hill, Brian T; Ahn, Kwang Woo; Hu, Zhen-Huan; Aljurf, Mahmoud; Beitinjaneh, Amer; Cahn, Jean-Yves; Cerny, Jan; Kharfan-Dabaja, Mohamed A; Ganguly, Siddhartha; Ghosh, Nilanjan; Grunwald, Michael R; Inamoto, Yoshihiro; Kindwall-Keller, Tamila; Nishihori, Taiga; Olsson, Richard F; Saad, Ayman; Seftel, Matthew; Seo, Sachiko; Szer, Jeffrey; Tallman, Martin; Ustun, Celalettin; Wiernik, Peter H; Maziarz, Richard T; Kalaycio, Matt; Alyea, Edwin; Popat, Uday; Sobecks, Ronald; Saber, Wael

2018-03-01

Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplantation (allo-HCT) for medically fit patients. Although the use of allo-HCT has declined since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT, the only known curative treatment for CLL. The potential benefit of transplantation is most likely due to the presence of alloreactive donor T cells that mediate the graft-versus-leukemia (GVL) effect. The recognition of potentially tumor-specific antigens in the context of class I and II major histocompatibility complex on malignant B lymphocytes by donor T cells may be influenced by subtle differences in the highly polymorphic HLA locus. Given previous reports of specific HLA alleles impacting the incidence of CLL and the clinical outcomes of allo-HCT for CLL, we sought to study the overall survival and progression-free survival of a large cohort of patients with CLL who underwent allo-HCT from fully HLA-matched related and unrelated donors at Center for International Blood and Marrow Transplant Research transplantation centers. We found no statistically significant association of allo-HCT outcomes in CLL based on previously reported HLA combinations. Additional study is needed to further define the immunologic features that portend a more favorable GVL effect after allo-HCT for CLL. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Thoracic epidural analgesia in donor hepatectomy: An analysis.

Science.gov (United States)

Koul, Archna; Pant, Deepanjali; Rudravaram, Swetha; Sood, Jayashree

2018-02-01

The purpose of this study is to analyze whether supplementation of general anesthesia (GA) with thoracic epidural analgesia (TEA) for right lobe donor hepatectomy is a safe modality of pain relief in terms of changes in postoperative coagulation profile, incidence of epidural catheter-related complications, and timing of removal of epidural catheter. Retrospective analysis of the record of 104 patients who received TEA for right lobe donor hepatectomy was done. Platelet count, international normalized ratio, alanine aminotransferase, and aspartate aminotransferase were recorded postoperatively until the removal of the epidural catheter. The day of removal of the epidural catheter and visual analogue scale (VAS) scores were also recorded. Any complication encountered was documented. Intraoperatively, central venous pressure (CVP), hemodynamic variables, and volume of intravenous fluids infused were also noted. Statistical analysis was performed by using SPSS statistical package, version 17.0 (SPSS Inc. Chicago, IL). Continuous variables were presented as mean ± standard deviation. A total of 90% of patients had mean VAS scores between 1 and 4 in the postoperative period between days 1 and 5. None of the patients had a VAS score above 5. Although changes in coagulation status were encountered in all patients in the postoperative period, these changes were transient and did not persist beyond postoperative day (POD) 5. There was no delay in removal of the epidural catheter, and the majority of patients had the catheter removed by POD 4. There was no incidence of epidural hematoma. Aside from good intraoperative and postoperative analgesia, TEA in combination with balanced GA and fluid restriction enabled maintenance of low CVP and prevention of hepatic congestion. In conclusion, vigilant use of TEA appears to be safe during donor hepatectomy. Living liver donors should not be denied efficient analgesia for the fear of complications. Liver Transplantation 24 214

Strontium-rubidium infusion pump with in-line dosimetry

International Nuclear Information System (INIS)

Barker, S.L.; Loberg, M.D.

1986-01-01

A strontium-rubidium infusion system is described which consists of: (a) means for generating rubidium 82 in a solution which can be infused into a patient; (b) means for infusing the solution into a patient; (c) means for measuring the radioactivity present in the solution as it is infused into the patient; and (d) means for controlling the means for infusing in response to the amount of radioactivity which has been infused into the patient

In Utero Exposure to Exosomal and B-Cell Alloantigens Lessens Alloreactivity of Recipients’ Lymphocytes Rather than Confers Allograft Tolerance

Directory of Open Access Journals (Sweden)

Jeng-Chang Chen

2018-03-01

Full Text Available According to actively acquired tolerance, antigen exposure before full immune development in fetal or early neonatal life will cause tolerance to this specific antigen. In this study, we aimed to examine whether allogeneic tolerance could be elicited by in utero exposure to surface MHC antigens of allogenic cells or soluble form of MHC exosomes. Gestational day 14 FVB/N fetuses were subjected to intraperitoneal injection of allogeneic major histocompatibility complex (MHC exosomes or highly enriched B-cells. Postnatally, the recipients were examined for the immune responses to donor alloantigens by lymphocyte proliferative reactions and skin transplantation. In utero exposure to allogeneic MHC exosomes abolished the alloreactivity of recipients’ lymphocytes to the alloantigens, but could not confer skin allograft tolerance. In utero transplantation of highly enriched allogeneic B-cells generated low-level B-cell chimerism in the recipients. However, it only extended the survivals of skin allograft by a few days despite the lack of donor-specific alloreactivity of recipients’ lymphocyte. Thus, an early in utero contact with exosomal or B-cell alloantigens did not lead to full skin tolerance but rather, at best, only to delayed skin rejection in the presence of microchimerism made by B-cell inocula. These results argued against the theory of actively acquired tolerance, and implicated that in utero exposure to marrow cells in previous studies was a unique model of allo-tolerance induction that involved the establishment of significant hematopoietic chimerism. Taken together with the discovery of in utero sensitization to ovalbumin in our previous studies, the immunological consequences of fetal exposure to foreign antigens might vary according to the type or nature of antigens introduced.

In Utero Exposure to Exosomal and B-Cell Alloantigens Lessens Alloreactivity of Recipients' Lymphocytes Rather than Confers Allograft Tolerance.

Science.gov (United States)

Chen, Jeng-Chang; Ou, Liang-Shiou; Chan, Cheng-Chi; Kuo, Ming-Ling; Tseng, Li-Yun; Chang, Hsueh-Ling

2018-01-01

According to actively acquired tolerance, antigen exposure before full immune development in fetal or early neonatal life will cause tolerance to this specific antigen. In this study, we aimed to examine whether allogeneic tolerance could be elicited by in utero exposure to surface MHC antigens of allogenic cells or soluble form of MHC exosomes. Gestational day 14 FVB/N fetuses were subjected to intraperitoneal injection of allogeneic major histocompatibility complex (MHC) exosomes or highly enriched B-cells. Postnatally, the recipients were examined for the immune responses to donor alloantigens by lymphocyte proliferative reactions and skin transplantation. In utero exposure to allogeneic MHC exosomes abolished the alloreactivity of recipients' lymphocytes to the alloantigens, but could not confer skin allograft tolerance. In utero transplantation of highly enriched allogeneic B-cells generated low-level B-cell chimerism in the recipients. However, it only extended the survivals of skin allograft by a few days despite the lack of donor-specific alloreactivity of recipients' lymphocyte. Thus, an early in utero contact with exosomal or B-cell alloantigens did not lead to full skin tolerance but rather, at best, only to delayed skin rejection in the presence of microchimerism made by B-cell inocula. These results argued against the theory of actively acquired tolerance, and implicated that in utero exposure to marrow cells in previous studies was a unique model of allo-tolerance induction that involved the establishment of significant hematopoietic chimerism. Taken together with the discovery of in utero sensitization to ovalbumin in our previous studies, the immunological consequences of fetal exposure to foreign antigens might vary according to the type or nature of antigens introduced.

The U.S. home infusion market.

Science.gov (United States)

Monk-Tutor, M R

1998-10-01

Medicare legislation stimulated the development of home care services but also resulted in fragmentation of service components. In the 1980s, prospective pricing and diagnosis-related groups, and resulting pressures to reduce inpatient length of stay, prompted additional growth of the industry. Even so, in 1995 home care represented only 3% of total national expenditures on health care. The annual growth rate of the home infusion industry dropped from 64% in 1982-86 to 24% in 1986-93. While revenue per patient for home infusion is expected to decrease under managed care, an increasing number of patients will support continued market growth. The home infusion market is highly competitive, with only a few large national providers and many small local providers. In 1996, 29% of acute care hospitals provided or were developing a home care program. Community pharmacists' options in the home infusion area include independent services, partnerships, joint ventures, contracts with hospitals, and franchises. The home infusion market is being integrated into alternative sites, such as ambulatory infusion centers (AICs), as providers attempt to diversify to maintain managed care contracts. AICs provide infusion therapy and nursing to noninstitutionalized, nonhome-bound patients. Untapped sources for future growth of the infusion market include long-term-care facilities. More consistent studies of the home care market are needed. Despite slowed growth in recent years, home care has a strong market in the United States.

Early mechanism of action of arterially infused ethanol: an experimental study on the influence of infusion speed

International Nuclear Information System (INIS)

Han, Joon Koo

1988-01-01

Abdominal aortography and histopathologic examination after absolute ethanol infusion at fast (0.4cc/sec) and slow speed (0.04cc/sec) were performed on 16 rats (2 controls. 7 fast infusion group. 7 slow infusion group). Angiographic and histopathologic findings were correlated and the findings of slow and fast infusion groups were studied. The results are as follows: 1. Histopathologic findings of the fast infusion group revealed wide area of glomerular and tubular collapses, obliteration of the free space between the Bowmann's capsule and glomerulus, sloughing and loss of the endothelium, fresh thrombi attached to the wall, and cleavage of the muscle layer of the arteries. 2. Angiographic findings of the fast infusion group revealed luminal irregularity, early obstruction of the aorta and the renal arteries, and delayed circulation time. 3. Histopathologic findings of the slow infusion group revealed degenerated, coalesced red blood cell packed in the glomeruli, focal areas of severe glomerular and tubular damage on relatively normal background, endothelial and muscular damage of the arteries. 4. Angiographic findings of the slow infusion group revealed focal perfusion defect of the kidney, delayed circulation time, and mild luminal irregularity, but there was no obstruction of the major arteries. 5. In conclusion, author believes that endothelial damage and thrombus formation from the damaged vessel wall, as well as direct cytotoxicity and in situ emboli formation play a significant role in the embolic effect of absolute ethanol.

Effect of Vibrio cholerae neuraminidase on the mitogen response of T lymphocytes. I. Enhancement of macrophage T-lymphocyte cooperation in concanavalin-A-induced lymphocyte activation.

Science.gov (United States)

Knop, J

1980-12-01

Vibrio cholerae neuraminidase (VCN) enhances the immune response of lymphocytes in various systems, such as antigen- and mitogen-induced blastogenesis, mixed lymphocyte culture (MLC) and tumor-cell response. We used macrophage-depleted and reconstituted murine lymph-node T-cells to investigate the effect of VCN on macrophage-T-lymphocyte co-operation in Con-A-induced lymphocyte activation. In unfractionated lymph-node cells VCN enhanced the Con-A-induced lymphocyte activation as measured by 3H-thymidine (3H-dThd) incorporation. Removing macrophages from the cells resulted in a significantly diminished response. In addition the enhancing effect of VCN was greatly reduced. Reconstitution of the lymphocyte cultures with macrophages in increasing numbers and from various sources rstored the lymphocyte response and the enhancing effect of VCN. VCN proved to be most efficient in cultures reconstituted with normal peritoneal macrophages. Some effect was also observed using bone-marrow-derived (BM) macrophages. However, higher numbers of normal PE macrophages in the presence of VCN inhibited lymphocyte activation, and inhibition by thioglycollate-broth-induced macrophages was considerably increased by VCN. These results suggest that VCN acts by increasing the efficiency of macrophage-T lymphocyte interaction.

Are drowned donors marginal donors? A single pediatric center experience.

Science.gov (United States)

Kumm, Kayla R; Galván, N Thao N; Koohmaraie, Sarah; Rana, Abbas; Kueht, Michael; Baugh, Katherine; Hao, Liu; Yoeli, Dor; Cotton, Ronald; O'Mahony, Christine A; Goss, John A

2017-09-01

Drowning, a common cause of death in the pediatric population, is a potentially large donor pool for OLT. Anecdotally, transplant centers have deemed these organs high risk over concerns for infection and graft dysfunction. We theorized drowned donor liver allografts do not portend worse outcomes and therefore should not be excluded from the donation pool. We reviewed our single-center experience of pediatric OLTs between 1988 and 2015 and identified 33 drowned donor recipients. These OLTs were matched 1:2 to head trauma donor OLTs from our center. A chart review assessed postoperative peak AST and ALT, incidence of HAT, graft and recipient survival. Recipient survival at one year between patients with drowned donor vs head trauma donor allografts was not statistically significant (94% vs 97%, P=.63). HAT incidence was 6.1% in the drowned donor group vs 7.6% in the control group (P=.78). Mean postoperative peak AST and ALT was 683 U/L and 450 U/L for drowned donors vs 1119 U/L and 828 U/L in the matched cohort. These results suggest drowned donor liver allografts do not portend worse outcomes in comparison with those procured from head trauma donors. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identification of TP53 as an Acute Lymphocytic Leukemia Susceptibility Gene Through Exome Sequencing

Science.gov (United States)

Powell, Bradford C.; Jiang, Lichun; Muzny, Donna M.; Treviño, Lisa R.; Dreyer, ZoAnn E.; Strong, Louise C.; Wheeler, David A.; Gibbs, Richard A.; Plon, Sharon E.

2014-01-01

Although acute lymphocytic leukemia (ALL) is the most common childhood cancer, genetic predisposition to ALL remains poorly understood. Whole-exome sequencing was performed in an extended kindred in which five individuals had been diagnosed with leukemia. Analysis revealed a nonsense variant of TP53 which has been previously reported in families with sarcomas and other typical Li Fraumeni syndrome-associated cancers but never in a familial leukemia kindred. This unexpected finding enabled identification of an appropriate sibling bone marrow donor and illustrates that exome sequencing will reveal atypical clinical presentations of even well-studied genes. PMID:23255406

Inhibition of DNA repair by whole body irradiation induced nitric oxide leads to higher radiation sensitivity in lymphocytes

International Nuclear Information System (INIS)

Sharma, Deepak; Santosh Kumar, S.; Raghu, Rashmi; Maurya, D.K.; Sainis, K.B.

2007-01-01

Full text: It is well accepted that the sensitivity of mammalian cells is better following whole body irradiation (WBI) as compared to that following in vitro irradiation. However, the underlying mechanisms are not well understood. Following WBI, the lipid peroxidation and cell death were significantly higher in lymphocytes as compared to that in vitro irradiated lymphocytes. Further, WBI treatment of tumor bearing mice resulted in a significantly higher inhibition of EL-4 cell proliferation as compared to in vitro irradiation of EL-4 cells. The DNA repair was significantly slower in lymphocytes obtained from WBI treated mice as compared to that in the cells exposed to same dose of radiation in vitro. Generation of nitric oxide following irradiation and also its role in inhibition of DNA repair have been reported, hence, its levels were estimated under both WBI and in vitro irradiation conditions. Nitric oxide levels were significantly elevated in the plasma of WBI treated mice but not in the supernatant of in vitro irradiated cells. Addition of sodium nitroprusside (SNP), a nitric oxide donor to in vitro irradiated cells inhibited the repair of DNA damage and sensitized cells to undergo cell death. It also enhanced the radiation-induced functional impairment of lymphocytes as evinced from suppression of mitogen-induced IL-2, IFN-γ and bcl-2 mRNA expression. Administration of N G -nitro-L-arginine-methyl-ester(L-NAME), a nitric oxide synthase inhibitor, to mice significantly protected lymphocytes against WBI-induced DNA damage and inhibited in vivo radiation-induced production of nitric oxide. Our results indicated that nitric oxide plays a role in the higher radiosensitivity of lymphocytes in vivo by inhibiting repair of DNA damage

Influence of a transfusion of donor leukocytes treated with 8-methoxypsoralen and long-wave ultraviolet light (PUVA) on skin allograft survival in mice

International Nuclear Information System (INIS)

Gruner, S.; Noack, F.; Meffert, H.

1989-01-01

The influence of pretransplant donor spleen cell infusions on murine skin graft survival was studied. In dependence on the time interval between transplantation and transfusion an accelerated or delayed rejection of the grafts was observed. If the donor spleen cells were treated with the photosensitizer 8-methoxypsoralen and UVA light (PUVA) a graft prolongation was achieved at all time intervals. Furthermore, the survival of antigenically unrelated grafts was also prolonged. An additional immunosuppressive treatment of the recipients with antilymphocyte serum, but not cyclophosphamide, led to a further prolongation of graft survival. The survival of PUVA treated skin grafts was not longer in recipients preinfused with PUVA treated donor cells compared with untreated hosts. The results presented in this work may have implications in clinical organ transplantation to prevent sensitizing reactions by sparing protective mechanisms for the graft. (author)

Imaging evaluation of potential donors in living-donor liver transplantation

International Nuclear Information System (INIS)

Low, G.; Wiebe, E.; Walji, A.H.; Bigam, D.L.

2008-01-01

Liver transplants, originally obtained from deceased donors, can now be harvested from living donors as well. This technique, called living-donor liver transplantation (LDLT), provides an effective alternative means of liver transplantation and is a method of expanding the donor pool in light of the demand and supply imbalance for organ transplants. Imaging plays an important role in LDLT programmes by providing robust evaluation of potential donors to ensure that only anatomically suitable donors with no significant co-existing pathology are selected and that crucial information that allows detailed preoperative planning is available. Imaging evaluation helps to improve the outcome of LDLT for both donors and recipients, by improving the chances of graft survival and reducing the postoperative complication rate. In this review, we describe the history of LDLT and discuss in detail the application of imaging in donor assessment with emphasis on use of modern computed tomography (CT) and magnetic resonance imaging (MRI) techniques

Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors

DEFF Research Database (Denmark)

Arendrup, M; Hansen, J E; Clausen, H

1991-01-01

Three virus isolates HTLV-IIIB/lyA, HTLV-IIIB/lyB and HTLV-IIIB/lyO, obtained by passaging and propagating the HTLV-IIIB/H9 isolate in three separate cultures of mixed peripheral blood mononuclear cells (PBMC) from donors of blood type A, B or O, respectively, were tested for susceptibility...... for virus neutralization by the monoclonal antibody (MAb) AH16 directed against the blood group A epitope. MAb AH16 was previously shown to inhibit cell-free virus infection using HTLV-IIIB propagated in H9 cells. AH16 showed a concentration-dependent inhibition of the HTLV-IIIB/lyA isolate but did...... not inhibit the HTLV-IIIB/lyB or the HTLV-IIIB/lyO isolate. Specificity of the MAb-mediated inhibition was shown using A-antigen (tetrasaccharide). Thus, HIV infection of PBMC from donors with blood type A appears to induce expression of host-cell-encoded carbohydrate blood group A epitope on HIV which can...

Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors

DEFF Research Database (Denmark)

Arendrup, M; Hansen, J E; Clausen, H

1991-01-01

Three virus isolates HTLV-IIIB/lyA, HTLV-IIIB/lyB and HTLV-IIIB/lyO, obtained by passaging and propagating the HTLV-IIIB/H9 isolate in three separate cultures of mixed peripheral blood mononuclear cells (PBMC) from donors of blood type A, B or O, respectively, were tested for susceptibility...... not inhibit the HTLV-IIIB/lyB or the HTLV-IIIB/lyO isolate. Specificity of the MAb-mediated inhibition was shown using A-antigen (tetrasaccharide). Thus, HIV infection of PBMC from donors with blood type A appears to induce expression of host-cell-encoded carbohydrate blood group A epitope on HIV which can...... for virus neutralization by the monoclonal antibody (MAb) AH16 directed against the blood group A epitope. MAb AH16 was previously shown to inhibit cell-free virus infection using HTLV-IIIB propagated in H9 cells. AH16 showed a concentration-dependent inhibition of the HTLV-IIIB/lyA isolate but did...

21 CFR 880.5725 - Infusion pump.

Science.gov (United States)

2010-04-01

... Infusion pump. (a) Identification. An infusion pump is a device used in a health care facility to pump fluids into a patient in a controlled manner. The device may use a piston pump, a roller pump, or a... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Infusion pump. 880.5725 Section 880.5725 Food and...

Gamete donation: parents' experiences of searching for their child's donor siblings and donor.

Science.gov (United States)

Freeman, T; Jadva, V; Kramer, W; Golombok, S

2009-03-01

This study investigates the new phenomenon of parents of donor offspring searching for and contacting their child's 'donor siblings' (i.e. donor offspring conceived by the same donor) and donor. Online questionnaires were completed by 791 parents (39% lone-mother, 35% lesbian-couple, 21% heterosexual-couple, 5% non-specified) recruited via the Donor Sibling Registry; a US-based international registry that facilitates contact between donor conception families who share the same donor. Data were collected on parents' reasons for searching for their child's donor siblings and/or donor, the outcome of these searches and parents' and their child's experiences of any resulting contact. Parents' principal motivation for searching for their child's donor siblings was curiosity and for their donor, enhancing their child's sense of identity. Some parents had discovered large numbers of donor siblings (maximum = 55). Most parents reported positive experiences of contacting and meeting their child's donor siblings and donor. This study highlights that having access to information about a child's donor origins is important for some parents and has potentially positive consequences. These findings have wider implications because the removal of donor anonymity in the UK and elsewhere means that increasing numbers of donor offspring are likely to seek contact with their donor relations in the future.

Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Science.gov (United States)

2018-01-26

Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

Establishment and operation of a Good Manufacturing Practice-compliant allogeneic Epstein-Barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease.

Science.gov (United States)

Vickers, Mark A; Wilkie, Gwen M; Robinson, Nicolas; Rivera, Nadja; Haque, Tanzina; Crawford, Dorothy H; Barry, Jacqueline; Fraser, Neil; Turner, David M; Robertson, Victoria; Dyer, Phil; Flanagan, Peter; Newlands, Helen R; Campbell, John; Turner, Marc L

2014-11-01

Epstein-Barr virus (EBV) is associated with several malignancies, including post-transplant lymphoproliferative disorder (PTLD). Conventional treatments for PTLD are often successful, but risk organ rejection and cause significant side effects. EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from peripheral blood lymphocytes provide an alternative treatment modality with few side effects, but autologous CTLs are difficult to use in clinical practice. Here we report the establishment and operation of a bank of EBV-specific CTLs derived from 25 blood donors with human leucocyte antigen (HLA) types found at high frequency in European populations. Since licensure, there have been enquiries about 37 patients, who shared a median of three class I and two class II HLA types with these donors. Cells have been infused into ten patients with lymphoproliferative disease, eight of whom achieved complete remission. Neither patient with refractory disease was matched for HLA class II. Both cases of EBV-associated non-haematopoietic sarcoma receiving cells failed to achieve complete remission. Thirteen patients died before any cells could be issued, emphasizing that the bank should be contacted before patients become pre-terminal. Thus, this third party donor-derived EBV-specific CTL cell bank can supply most patients with appropriately matched cells and most recipients have good outcomes. © 2014 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

[A Case of HPN, In Which QOL Improvement Was Achieved by Combining Continuous Infusion with Once-Weekly Intermittent Infusion - Contribution of Pharmacists to Health Promotion among Home Patients Receiving Infusion Therapy].

Science.gov (United States)

Takeda, Namihiro; Hamana, Tomoko; Oka, Toyoka; Hirohara, Masayoshi; Kushida, Kazuki

2016-12-01

Patients receiving parenteral nutrition at home have the following two options: 24-h continuous or intermittent infusion. To date, for patients with impaired glucose tolerance and/or other metabolic disorders or for those with decreased cardiac/ pulmonary/renal function, it is desirable to opt for continuous infusion to minimize the variance in the body's metabolic rate as much as possible. Furthermore, it should be noted that continuous infusion evokes a stronger feeling among patients of being constrained because it restricts their everyday activities. This case witnesses collaborations among the patient's doctor, dispensary's pharmacy, and patient's family. Because ofthe use ofintermittent infusion more or less once per week in addition to continuous infusion, significant improvement in quality of life was achieved, and the patient was able to enjoy taking a short trip. To assist a home patient receiving infusion therapy, it is essential that the pharmacist be equipped with skills to manage risks associated with infusion therapy and have knowledge about insurance to cover incidents concerning infusion fluids or medical materials. It will certainly depend on the degree ofindependence ofpatients and the level ofcare their families can provide; however, should we manage to use a similar medical procedure in at least a few cases in the future, we may be able to contribute to "joie de vivre" in home patients receiving infusion therapy.

Discrimination of human cytotoxic lymphocytes from regulatory and B-lymphocytes by orthogonal light scattering

NARCIS (Netherlands)

Terstappen, Leonardus Wendelinus Mathias Marie; de Grooth, B.G.; ten Napel, C.H.H.; van Berkel, W.; Greve, Jan

1986-01-01

Light scattering properties of human lymphocyte subpopulations selected by immunofluorescence were studied with a flow cytometer. Regulatory and B-lymphocytes showed a low orthogonal light scatter signal, whereas cytotoxic lymphocytes identified with leu-7, leu-11 and leu-15 revealed a large

Associations of health status with subsequent blood donor behavior-An alternative perspective on the Healthy Donor Effect from Donor InSight

NARCIS (Netherlands)

van den Hurk, Katja; Zalpuri, Saurabh; Prinsze, Femmeke J.; Merz, Eva-Maria; de Kort, Wim L. A. M.

2017-01-01

In donor health research, the 'Healthy Donor Effect' (HDE) often biases study results and hampers their interpretation. This refers to the fact that donors are a selected 'healthier' subset of a population due to both donor selection procedures and self-selection. Donors with long versus short donor

Desensitization Protocol in Recipients of Deceased Kidney Donor With Donor-Specific Antibody-Low Titers.

Science.gov (United States)

Kanter Berga, J; Sancho Calabuig, A; Gavela Martinez, E; Puig Alcaraz, N; Avila Bernabeu, A; Crespo Albiach, J; Molina Vila, P; Beltrán Catalan, S; Pallardó Mateu, L

2016-11-01

Kidney transplantation is the better option for end-stage renal disease (ESRD), but for patients with human leukocyte antigen (HLA) sensitization, the wait times are significantly longer than for patients without antibodies. Many desensitization protocols have been described involving strong immunosuppression, the use of apheresis, and B-cell-modulating therapies. We have designed a desensitization protocol from day 0 for deceased donor kidney transplantation. Our aim was to present our initial experience with five kidney transplant patients. All patients had a negative complement-dependent cytotoxicity cross-match. The desensitization protocol included five to seven doses of thymoglobulin (1.25 mg/kg) and three sessions of plasmapheresis (PP) within the first week after transplantation, with intravenous immunoglobulin (500 mg/kg) after each PP session and one dose of rituximab on day 8. The presence of donor-specific antibodies (DSA) was analyzed by use of Luminex technology; levels between 1000 and 3000 mean fluorescence intensity were considered for desensitization. The median age was 44 years and median renal replacement therapy time was 9 years. All recipients presented 1 to 3 DSA specificities. There were no severe side effects related to PP, infusion of intravenous immunoglobulin, or rituximab. The median follow-up period was 19.3 months. Median serum creatinine level at last follow-up was 1.7 mg/dL. A kidney biopsy was performed in all patients. Graft and patient survival was 100%. Until now, few data are available concerning whether HLA-incompatible kidney transplantation after desensitization would benefit patients with ERSD. The desensitization strategy using the combination of PP, low doses of intravenous immunoglobulin, and rituximab at our center resulted in a satisfactory clinical outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantification of newly produced B and T lymphocytes in untreated chronic lymphocytic leukemia patients

Directory of Open Access Journals (Sweden)

Caimi Luigi

2010-11-01

Full Text Available Abstract Background The immune defects occurring in chronic lymphocytic leukemia are responsible for the frequent occurrence of infections and autoimmune phenomena, and may be involved in the initiation and maintenance of the malignant clone. Here, we evaluated the quantitative defects of newly produced B and T lymphocytes. Methods The output of B and T lymphocytes from the production and maturation sites was analyzed in chronic lymphocytic leukemia patients and healthy controls by quantifying kappa-deleting recombination excision circles (KRECs and T-cell receptor excision circles (TRECs by a Real-Time PCR assay that simultaneously detects both targets. T-lymphocyte subsets were analyzed by six-color flow cytometric analysis. Data comparison was performed by two-sided Mann-Whitney test. Results KRECs level was reduced in untreated chronic lymphocytic leukemia patients studied at the very early stage of the disease, whereas the release of TRECs+ cells was preserved. Furthermore, the observed increase of CD4+ lymphocytes could be ascribed to the accumulation of CD4+ cells with effector memory phenotype. Conclusions The decreased number of newly produced B lymphocytes in these patients is likely related to a homeostatic mechanism by which the immune system balances the abnormal B-cell expansion. This feature may precede the profound defect of humoral immunity characterizing the later stages of the disease.

Infusion-related reactions to infliximab in patients with rheumatoid arthritis in a clinical practice setting: relationship to dose, antihistamine pretreatment, and infusion number.

Science.gov (United States)

Wasserman, Michael J; Weber, Deborah A; Guthrie, Judith A; Bykerk, Vivian P; Lee, Peter; Keystone, Edward C

2004-10-01

We describe infusion-related reactions to infliximab (during infusion or within 1 hour postinfusion) in patients with active rheumatoid arthritis (RA) treated in a quaternary care center. We followed 113 patients for a mean of 60.6 +/- 28.9 weeks, obtaining 10.5 +/- 4.9 infusions per patient. We observed 1183 infusions resulting in 104 infusion reactions (8.8%). All reactions resolved within several hours following cessation of the infusion and none was serious enough to warrant hospitalization. Reactions included allergic reactions (pruritus, urticaria) in 4.2% of infusions, cardiopulmonary (hypotension, hypertension, tachycardia) in 3.0%, and miscellaneous reactions (headache, nausea, vomiting) in 2.0%. Reactions occurred in 8.0% of 3 mg/kg infusions and in 10.3% of 5 mg/kg infusions. Reactions occurred in 13.2% of infusions that involved antihistamine pretreatment compared to only 7.5% of infusions that involved no pretreatment. At both infliximab doses, there was a similar frequency of infusion reactions in patients pretreated due to a previous infusion (12.6%) compared to those pretreated strictly based on infusion number (14.7%). A number of the reactions involving antihistamine pretreatment may be explained by known side effects of diphenhydramine, including headache, dizziness, nausea, and palpitations. Infusion-related reactions to infliximab were infrequent, rarely severe, and easily manageable. The frequency of reactions was equivalent in patients treated with 3 mg/kg compared to 5 mg/kg. Reactions were significantly more frequent in infusions where patients were pretreated with the antihistamine diphenhydramine, compared to those not involving pretreatment.

Extended infusion versus intermittent infusion of imipenem in the treatment of ventilator-associated pneumonia.

Science.gov (United States)

Ibrahim, Mohamed M; Tammam, Tarek Fouad; Ebaed, Mohy El Deen; Sarhan, Hatem A; Gad, Gamal F; Hussein, Amal K

2017-01-01

Mechanical ventilation support can be the main source of ventilator-associated pneumonia (VAP). VAP is a serious infection that may be associated with dangerous gram-negative bacteria mainly, and it leads to an increase in the mortality in the intensive care unit (ICU). Imipenem is one of the strongest antibiotics now available for treating VAP which is associated with gram-negative and gram-positive bacteria, and it belongs to beta-lactam antibiotic group (carbapenem). This study tried to investigate the efficacy of imipenem against VAP when it was infused within 180 min versus the efficacy when it was infused within 30-60 min. This study was conducted in main ICU in general hospital which consists of surgical and medical beds within 2 years. One hundred and eighty-seven patients were enrolled on it. This study is a retrospective cohort which was conducted within 2 years. The efficacy of imipenem which was administered by intermittent infusion (30-60 min) within first year was compared with the efficacy of imipenem which was administered by extended infusion (180 min) within second year in the field of VAP curing and cost reduction. All data were collected retrospectively from patient medical files and were statistically analyzed by SPSS version 20. The study was designed to measure clinical and cost reduction outcomes, mortality and hospital stay. The results indicated that there is a significant decrease in mortality, number of recurrent infection, and ICU stay length, and the number of mechanical ventilator days was associated with extended imipenem infusion during the second year of the study. The use of imipenem with extended infusion over 3 hours enhances its clinical outcomes in the treatment of VAP.

Understanding Infusion Pumps.

Science.gov (United States)

Mandel, Jeff E

2018-04-01

Infusion systems are complicated electromechanical systems that are used to deliver anesthetic drugs with moderate precision. Four types of systems are described-gravity feed, in-line piston, peristaltic, and syringe. These systems are subject to a number of failure modes-occlusion, disconnection, siphoning, infiltration, and air bubbles. The relative advantages of the various systems and some of the monitoring capabilities are discussed. A brief example of the use of an infusion system during anesthetic induction is presented. With understanding of the functioning of these systems, users may develop greater comfort.

Combined cord blood and bone marrow transplantation from the same human leucocyte antigen-identical sibling donor for children with malignant and non-malignant diseases.

Science.gov (United States)

Tucunduva, Luciana; Volt, Fernanda; Cunha, Renato; Locatelli, Franco; Zecca, Marco; Yesilipek, Akif; Caniglia, Maurizio; Güngör, Tayfun; Aksoylar, Serap; Fagioli, Franca; Bertrand, Yves; Addari, Maria Carmen; de la Fuente, Josu; Winiarski, Jacek; Biondi, Andrea; Sengeloev, Henrik; Badell, Isabel; Mellgren, Karin; de Heredia, Cristina Díaz; Sedlacek, Petr; Vora, Ajay; Rocha, Vanderson; Ruggeri, Annalisa; Gluckman, Eliane

2015-04-01

Umbilical cord blood (UCB) from an human leucocyte antigen (HLA)-identical sibling can be used for transplantation of patients with malignant and non-malignant diseases. However, the low cellular content of most UCB units represents a limitation to this approach. An option to increase cell dose is to harvest bone marrow (BM) cells from the same donor and infuse them along with the UCB. We studied 156 children who received such a combined graft between 1992 and 2011. Median age was 7 years and 78% of patients (n = 122) were transplanted for non-malignant diseases, mainly haemoglobinopathies. Acute leukaemia (n = 26) was the most frequent malignant diagnosis. Most patients (91%) received myeloablative conditioning. Median donor age was 1·7 years, median infused nucleated cell dose was 24·4 × 10(7) /kg and median follow-up was 41 months. Sixty-days neutrophil recovery occurred in 96% of patients at a median of 17 d. The probabilities of grade-II-IV acute and chronic graft-versus-host disease (GVHD) were 19% and 10%, respectively. Four-year overall survival was 90% (68% malignant; 97% non-malignant diseases) with 3% probability of death. In conclusion, combined UCB and BM transplantation from an HLA-identical sibling donor is an effective treatment for children with malignant and non-malignant disorders with high overall survival and low incidence of GVHD. © 2014 John Wiley & Sons Ltd.

Micronuclei Frequencies in Lymphocytes of Nuclear Malaysia Radiation Workers

International Nuclear Information System (INIS)

Mohd Rodzi Ali; Aisyah Mohd Yusof; Rahimah Abdul Rahim; Juliana Mahamat Napiah; Yahaya Talib; Shafii Khamis

2016-01-01

The objective of the study is to investigate the frequency of cell aberration in lymphocytes of the Nuklear Malaysia radiation workers. A total of 58 blood samples were collected from the radiation workers during their routine medical examination. The donor age range is between 23 to 58 years, 31 male and 27 female. Blood samples were cultured according to the standard protocol recommended by the International Atomic Energy Agency. The mean micronuclei (MN) is 23.5 ± 0.9 MN/ 1000 binucleate, with the median value of 24 MN/ 1000 binucleate. The lowest number of MN was 9, and the highest was 43. There is no correlation between the number of MN in blood and yearly cumulative dose for radiation workers. The results indicate the MN expression due to small radiation exposure is almost negligible in Nuclear Malaysia radiation workers. (author)

Control of charge transfer by conformational and electronic effects: Donor-donor and donor-acceptor phenyl pyrroles

International Nuclear Information System (INIS)

Neubauer, Antje; Bendig, Juergen; Rettig, Wolfgang

2009-01-01

Derivatives of N-pyrrolobenzene with a para-donor and a para-acceptor substituent on the benzene ring are compared. It is shown that by a suitable increase of the donor strength of the pyrrolo group, CT fluorescence can be achieved even for donor-donor-substituted benzenes. The ICT emission for sterically hindered compounds is more forbidden than that of unhindered phenyl pyrroles. This suggests conformational effects which induce a narrower twist angle distribution around a perpendicular minimum in the excited state.

Swelling and infusion of tea in tea bags.

Science.gov (United States)

Yadav, Geeta U; Joshi, Bhushan S; Patwardhan, Ashwin W; Singh, Gurmeet

2017-07-01

The present study deals with swelling and infusion kinetics of tea granules in tea bags. The swelling and infusion kinetics of tea bags differing in tea loading and tea bag shapes were compared with loose tea. Increment in temperature and dipping frequency of tea bag in hot water increased the infusion kinetics of tea bags. Reduction in particle size enhanced the swelling and infusion kinetics of tea in a tea bag. The effects of tea particle size, tea bag dipping rate, loading of tea granules in tea bag and tea bag shapes on infusion kinetics were investigated. Increase in tea loading in tea bags resulted in reduced infusion kinetics. Double chambered tea bag showed the highest swelling (30%) and infusion kinetics (8.30% Gallic acid equivalence) while single chambered tea bags showed the lowest kinetics, amongst the various bags studied. The swelling and infusion kinetics of loose tea was always faster and higher than that of tea bags. It was found that overall effect of percentage filling of tea granules and height of tea bed in a tea bag affects tea infusion kinetics the most. Weibull model was found to be in good agreement with the swelling data.

Progranulin Inhibits Human T Lymphocyte Proliferation by Inducing the Formation of Regulatory T Lymphocytes

Directory of Open Access Journals (Sweden)

Kyu Hwan Kwack

2017-01-01

Full Text Available We have examined the effect of progranulin (PGRN on human T cell proliferation and its underlying mechanism. We show that PGRN inhibits the PHA-induced multiplication of T lymphocytes. It increases the number of iTregs when T lymphocytes are activated by PHA but does not do so in the absence of PHA. PGRN-mediated inhibition of T lymphocyte proliferation, as well as the induction of iTregs, was completely reversed by a TGF-β inhibitor or a Treg inhibitor. PGRN induced TGF-β secretion in the presence of PHA whereas it did not in the absence of PHA. Our findings indicate that PGRN suppresses T lymphocyte proliferation by enhancing the formation of iTregs from activated T lymphocytes in response to TGF-β.

Experiences of offspring searching for and contacting their donor siblings and donor.

Science.gov (United States)

Jadva, Vasanti; Freeman, Tabitha; Kramer, Wendy; Golombok, Susan

2010-04-01

This study investigates a new phenomenon whereby individuals conceived by donor insemination are searching for and contacting their donor and/or 'donor siblings' (i.e. donor offspring conceived by the same donor who are their genetic half siblings). On-line questionnaires were completed by members of the Donor Sibling Registry (DSR), a US-based registry that facilitates contact between donor conception families who share the same donor. Of the 165 donor offspring who completed the survey, 15% were searching for their donor siblings, 13% were searching for their donor, and 64% were searching for both. Differences were found according to family type and age of disclosure. Fewer offspring from heterosexual couple families had told their father about their search when compared with offspring from lesbian couple families who had told their co-parent. Offspring who had found out about their conception after age 18 were more likely to be searching for medical reasons, whereas those who had found out before age 18 tended to be searching out of curiosity. Some offspring had discovered large numbers of half siblings (maximum=13). The majority of offspring who had found their donor relations reported positive experiences and remained in regular contact with them. Copyright (c) 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Flow cytometric analysis of lymphocytes and lymphocyte subpopulations in induced sputum from patients with asthma

Directory of Open Access Journals (Sweden)

Yutaro Shiota

2000-01-01

Full Text Available Study objectives were to compare the numbers of lymphocytes and lymphocyte subpopulations in induced sputum from asthmatic patients and from healthy subjects, and to determine the effect of inhaled anti-asthmatic steroid therapy on these cell numbers. Hypertonic saline inhalation was used to non-invasively induce sputum samples in 34 patients with bronchial asthma and 21 healthy subjects. The sputum samples were reduced with dithioerythritol and absolute numbers of lymphocytes and lymphocyte subpopulations were assessed by direct immunofluorescence and flow cytometry. To assess the effect of beclomethasone dipropionate (BDP on induced sputum, numbers of lymphocytes and lymphocyte subpopulations in sputum also were evaluated after 4 weeks of BDP inhalation treatment in seven asthmatic patients. An adequate sample was obtained in 85.3% of patients with asthma and in 79.2% of the healthy subjects. Induced sputum from patients with asthma had increased numbers of lymphocytes (P = 0.009; CD4+ cells (P = 0.044; CD4+ cells-bearing interleukin-2 receptor (CD25; P = 0.016; and CD4+ cells bearing human histocompatibility leukocyte antigen (HLA-DR (P = 0.033. CD8+ cells were not increased in asthmatic patients. In patients treated with inhaled steroids, numbers of lymphocytes, CD4+ cells, CD25-bearing CD4+ cells and HLA-DR-bearing CD4+ cells in sputum decreased from pretreatment numbers (P = 0.016, 0.002, 0.003 and 0.002, respectively. Analysis of lymphocytes in induced sputum by flow cytometry is useful in assessing bronchial inflammation, and activated CD4+ lymphocytes may play a key role in the pathogenesis of airway inflammation in bronchial asthma.

Donor hematopoiesis in mice following total lymphoid irradiation requires host T-regulatory cells for durable engraftment

Science.gov (United States)

Müller, Antonia M. S.; Poyser, Jessica; Küpper, Natascha J.; Burnett, Cassandra; Ko, Rose M.; Kohrt, Holbrook E.K.; Florek, Mareike; Zhang, Pei; Negrin, Robert S.

2014-01-01

Total lymphoid irradiation (TLI) with antithymocyte globulin (ATG) is a unique regimen that prepares recipients for allogeneic hematopoietic cell transplantation by targeting lymph nodes, while sparing large areas of the bone marrow. TLI is reported to increase the frequency of CD4+CD25+FoxP3+ T-regulatory cells (Treg) relative to conventional T cells. In this study, barriers to hematopoietic stem cell (HSC) engraftment following this nonmyeloablative conditioning were evaluated. TLI/ATG resulted in profound lymphoablation but endogenous host HSC remained. Initial donor HSC engraftment occurred only in radiation exposed marrow sites, but gradually distributed to bone marrow outside the radiation field. Sustained donor engraftment required host lymphoid cells insofar as lymphocyte deficient Rag2γc−/− recipients had unstable engraftment compared with wild-type. TLI/ATG treated wild-type recipients had increased proportions of Treg that were associated with increased HSC frequency and proliferation. In contrast, Rag2γc−/− recipients who lacked Treg did not. Adoptive transfer of Treg into Rag2γc−/− recipients resulted in increased cell cycling of endogenous HSC. Thus, we hypothesize that Treg influence donor engraftment post-TLI/ATG by increasing HSC cell cycling, thereby promoting the exit of host HSC from the marrow niche. Our study highlights the unique dynamics of donor hematopoiesis following TLI/ATG, and the effect of Treg on HSC activity. PMID:24591203

Infusion's greenfield subsidiary in Poland

NARCIS (Netherlands)

Williams, C.; van Eerde, W.; The, D.

2012-01-01

The president of Infusion Development Corporation was reviewing the progress of the new subsidiary the company had set up 15 months earlier in Krakow, Poland. The purpose of the subsidiary was to work with other Infusion offices around the world to provide innovative software development services to

Cryopreservation of adult unrelated donor products in hematopoietic cell transplantation: the OneMatch experience and systematic review of the literature.

Science.gov (United States)

Aziz, Joseph; Morris, Gail; Rizk, Mina; Shorr, Risa; Mercer, Dena; Young, Kimberly; Allan, David

2017-11-01

The frequency of cryopreserving blood stem or progenitor products from unrelated donors is not known and the underlying reasons are poorly documented. Greater insight is needed to develop policies on cryopreservation that balance donor safety with patient needs. Cryopreservation requests between January 1, 2014, and May 31, 2016, at the OneMatch Stem Cell and Marrow Network at Canadian Blood Services were reviewed and a systematic review of the literature was performed. Thirty products of 719 (4.2%) unrelated donor collections facilitated by OneMatch were cryopreserved. Patient-related reasons were most common and included the need to delay transplant for continued antimicrobial treatment (six patients), patient too deconditioned to proceed with scheduled transplant (five patients), and/or need for more treatment for relapsed disease (three patients). Donor-related issues leading to cryopreservation requests were less common (five cases), mainly due to lack of donor availability after attempting to reschedule. Cryopreservation of a product that was never infused occurred infrequently (two cases, 7%). In our systematic review of the literature, 993 cases were identified in 32 published reports. Both patient-related and donor-related reasons were cited but not specifically reported, precluding quantitative insight regarding the relative frequency of causes. The impact of cryopreservation on hematopoietic engraftment appears negligible when compared to controls in a subset of studies; however, reporting of outcomes was inconsistent. Future studies with standard outcome measures are needed to clarify the impact of cryopreservation on engraftment and other transplant outcomes. International guidelines that consider the ethical framework surrounding requests for donor product cryopreservation are needed. © 2017 AABB.

Mercuric dichloride induces DNA damage in human salivary gland tissue cells and lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Schmid, Katharina; Kroemer, Susanne [University of Regensburg, Regensburg (Germany); Sassen, Andrea [University of Regensburg, Department of Pathology, Regensburg (Germany); Staudenmaier, Rainer [Technical University of Munich, Department of Otorhinolaryngology, Head and Neck Surgery, Munich (Germany); Reichl, Franz-Xaver [University of Munich, Institute of Pharmacology and Toxicology, Munich (Germany); Harreus, Ulrich [University of Munich, Department of Otorhinolaryngology, Head and Neck Surgery, Munich (Germany); Hagen, Rudolf; Kleinsasser, Norbert [University of Wuerzburg, Department of Otorhinolaryngology, Head and Neck Surgery, Wuerzburg (Germany)

2007-11-15

Amalgam is still one of the most frequently used dental filling materials. However, the possible adverse effects especially that of the mercuric component have led to continued controversy. Considering that mercury may be released from amalgam fillings into the oral cavity and also reach the circulating blood after absorption and resorption, it eventually may contribute to tumorigenesis in a variety of target cells. The present investigation focuses on genotoxic effects below a cytotoxic dose level of mercuric dichloride (HgCl{sub 2}) in human samples of salivary glands and lymphocytes to elucidate a possible role in tumor initiation. DNA migration due to single strand breaks, alkali labile sites and incomplete excision repair was quantified with the aid of the single cell microgel electrophoresis (Comet) assay. The concepts of Olive Tail Moment, percentage of DNA in the Tail and Tail Length were used as measures of DNA damage. To control for cytotoxic effects, the trypan blue exclusion test was applied. Human samples of the parotid salivary gland and lymphocytes of ten donors were exposed to HgCl{sub 2} concentrations from 1 to 50 {mu}M. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and dimethyl sulfoxide (DMSO) served as controls. Increasing dose-dependent DNA migration could be demonstrated after exposure to HgCl{sub 2} in cells of the salivary glands and lymphocytes. In both cell types a significant increase in DNA migration could be shown starting from HgCl{sub 2} concentrations of 5 {mu}M in comparison to the negative control. The viability of the cell systems was not affected except at the highest concentration (50 {mu}M) tested. These data indicate genotoxic effects of mercuric dichloride in human salivary glands and lymphocytes at concentrations not leading to cytotoxic effects or cell death. Consequently, a contributory role in oral salivary gland tumor initiation warrants further investigation. (orig.)

Increase of lymphocytes with Fc receptors for IgE in patients with allergic rhinitis during the grass pollen season.

OpenAIRE

Spiegelberg, H L; Simon, R A

1981-01-01

Peripheral blood lymphocytes from 10 nonallergic donors and 7 patients suffering from seasonal allergic rhinitis and receiving desensitization therapy were analyzed by rosette assays for Fc receptors for IgE (Fc epsilon R) and IgG (Fc gamma R) before, during and after the grass pollen season. Six of seven patients had moderately elevated IgE levels (330 +/- 268 IU/ml), all had high titers of skin sensitizing antibodies to grass pollens and serum IgE antibodies as measured by radio-allergosorb...

Adaptive response induced by low doses of ionizing radiation in human lymphocytes

International Nuclear Information System (INIS)

Frati, Diego Libkind; Bunge, Maria M.

2001-01-01

The term adaptive response (AR) applies to the phenomenon of protection or enhanced repair induced by a small dose of a mutagenic agent. In order to determine the existence of AR in human lymphocytes for two different irradiation schemes, microcultures of blood from 4 donors were irradiated. Samples were exposed 24 hours (hr) after phytohemagglutinin stimulation to an adapting dose of 0,01 Gy and to a challenging dose of 1,5 Gy either 6 or 24 hr later (irradiation scheme 24+30 or 24+48, respectively). Gamma radiation from a 2,5 MeV Linac was used in all experiments. A cytogenetic analysis of unstable chromosome aberrations was applied as the endpoint. High inter-individual variability was found for the first irradiation scheme: one expressed AR, two did not and the last showed an apparent synergistic response. For the second irradiation scheme, low mitotic indices (MI) were found, suggesting a G2 arrest. When a series of harvesting times were applied for the last donor, normal MI were obtained only harvesting after 58 hr. An AR was found when harvesting at 72 hr but not at 58 hr. (author)

Lymphocyte development in irradiated thymuses: dynamics of colonization by progenitor cells and regeneration of resident cells

International Nuclear Information System (INIS)

Mehr, R.; Fridkis-Hareli, M.; Abel, L.; Segel, L.; Globerson, A.

1995-01-01

Lymphocyte development in irradiated thymuses was analyzed using two complementary strategies: an in vitro experimental model and computer simulations. In the in vitro model, fetal thymus lobes were irradiated and the regeneration of cells that survived irradiation were examined, with the results compared to those of reconstitution of the thymus by donor bone marrow cells and their competition with the thymic resident cells. In vitro measurements of resident cell kinetics showed that cell proliferation is slowed down significantly after a relatively low (10Gy) irradiation dose. Although the number of thymocytes that survived irradiation remained low for several days post-irradiation, further colonization by donor cells was not possible, unless performed within 6 h after irradiation. These experimental results, coupled with the analysis by computer simulations, suggest that bone marrow cell engraftment in the irradiated thymus may be limited by the presence of radiation-surviving thymic resident cells and the reduced availability of seeding niches. (Author)

Pharmacokinetics and toxicology of continuously infused nitroimidazoles

International Nuclear Information System (INIS)

Eifel, P.J.; Brown, J.M.

1984-01-01

The pharmacokinetics and toxicology of misonidazole (MISO) and SR-2508 given by continuous intraperitoneal infusion were studied in female C 3 H mice. The survival (time to death) of animals receiving continuous infusions of SR-2508 and MISO was compared and related to plasma concentration, rate of infusion and total amount of drug delivered. Brain and plasma concentrations were determined by HPLC. For SR-2508, plasma concentration was directly proportional to the infusion rate. However, as the infusion rate of MISO was doubled, the plasma concentration of MISO increased approximately 6-fold, reflecting a substantial increase in the apparent half-life. The brain/plasma concentration ratio in animals infused for up to 6 days with SR-2508 remained constant, at approximately 0.09. At plasma concentrations of 0.08-1.5 mM, animals receiving SR-2508 survived approximately 3 times as long as animals exposed to a comparable plasma concentration of MISO. Even at the lowest infusion rates employed in this study, the survival of mice receiving SR-2508 was much shorter than would have been predicted if the toxicity of these two drugs were solely related to the integral brain exposure. The low brain/plasma concentration ratio of SR-2508 was maintained throughout long continuous exposures

MONITORING TETESAN INFUS BERBASIS MIKROKONTROLER ATMEGA16

Directory of Open Access Journals (Sweden)

Ardiyanto Iqbal Nugroho

2015-09-01

Penelitian ini menghasilkan suatu alat monitoring tetesan infus yang dapat memberikan informasi mengenai laju kecepatan tetesan dan kondisi cairan pada infus. Sistem yang secara realtime dimonitoring oleh perawat ini dapat mengurangi permasalahan yang timbul karena kelalaian petugas. Sehingga perawat tidak secara manual dalam mengatur kecepatan tetesan infus dan meningkatkan pelayanan kepada pasien.

B and T lymphocytes in man. I. Effect of infant thymic irradiation on the circulating B and T lymphocytes

International Nuclear Information System (INIS)

Reddy, M.M.; Goh, K.; Hempelmann, L.H.

1976-01-01

B and T lymphocytes were studied in a group of adults whose thymic glands were irradiated in infancy for alleged thymic enlargement. Two independent methods were used to determine the B and T lymphocytes from each peripheral blood specimen: (1) the relative proportion of cells with surface immunoglobulins (B lymphocytes) and cells forming rosettes with sheep erythrocytes (T lymphocytes); and (2) the relative mitogenic response to phytohemagglutinin (T lymphocytes) and to pokeweed mitogen (B lymphocytes). All specimens were coded. The results obtained indicate: (1) a reduction of B and T lymphocytes; and (2) a decreased mitogenic response of lymphocytes to phytohemagglutinin and pokeweed mitogen in this group of patients as compared with the controls. These observations suggest that (1) the effect of irradiation to the thymus gland on lymphocytes is long lasting and (2) both B and T lymphocytes are affected by irradiation to the thymus gland

Determination of 24-hour insulin infusion pattern by an artificial endocrine pancreas for intravenous insulin infusion with a miniature pump

DEFF Research Database (Denmark)

Kølendorf, K; Christiansen, J S; Bojsen, J

1981-01-01

UNLABELLED: Intravenous insulin infusion with a glucose controlled insulin infusion system (GCIIS) is known to restore glucose homeostasis. A simpler approach to improve blood glucose regulation is preprogrammed intravenous insulin infusion with portable pumps without sensor-mediated feedback. We...... report a study designed to evaluate whether the preprogrammed insulin infusion pattern to be used in the miniature insulin infusion pump (MIIP) could be optimized by concomitant employment of the GCIIS for blood glucose control. Six juvenile-onset insulin-dependent diabetics (mean age 31 yrs) were...... studied. Mean blood glucose (MBG) was 6.2 mmol/l +/- 0.5 (SD) during glucose controlled infusion and 5.3 +/- 0.6 during the combined MIIP + GCIIS-day. The insulin requirements calculated from the s.c. regimen (56 U +/- 10 SD) were identical to the GCIIS-measured (51 U +/- 14) and to the amounts delivered...

Islet transplantation using donors after cardiac death: report of the Japan Islet Transplantation Registry.

Science.gov (United States)

Saito, Takuro; Gotoh, Mitsukazu; Satomi, Susumu; Uemoto, Shinji; Kenmochi, Takashi; Itoh, Toshinori; Kuroda, Yoshikazu; Yasunami, Youichi; Matsumoto, Shnichi; Teraoka, Satoshi

2010-10-15

This report summarizes outcomes of islet transplantation employing donors after cardiac death (DCD) between 2004 and 2007 as reported to the Japan Islet Transplantation Registry. Sixty-five islet isolations were performed for 34 transplantations in 18 patients with insulin-dependent diabetes mellitus, including two patients who had prior kidney transplantation. All but one donor (64/65) was DCD at the time of harvesting. Factors influencing criteria for islet release included duration of low blood pressure of the donor, cold ischemic time, and usage of Kyoto solution for preservation. Multivariate analysis selected usage of Kyoto solution as most important. Of the 18 recipients, 8, 4, and 6 recipients received 1, 2, and 3 islet infusions, respectively. Overall graft survival defined as C-peptide level more than or equal to 0.3 ng/mL was 76.5%, 47.1%, and 33.6% at 1, 2, and 3 years, respectively, whereas corresponding graft survival after multiple transplantations was 100%, 80.0%, and 57.1%, respectively. All recipients remained free of severe hypoglycemia while three achieved insulin independence for 14, 79, and 215 days. HbA1c levels and requirement of exogenous insulin were significantly improved in all patients. Islet transplantation employing DCD can ameliorate severe hypoglycemic episodes, significantly improve HbA1c levels, sustain significant levels of C-peptide, and achieve insulin independence after multiple transplantations. Thus, DCD can be an important resource for islet transplantation if used under strict releasing criteria and in multiple transplantations, particularly in countries where heart-beating donors are not readily available.

Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells.

Science.gov (United States)

Withers, Barbara; Blyth, Emily; Clancy, Leighton E; Yong, Agnes; Fraser, Chris; Burgess, Jane; Simms, Renee; Brown, Rebecca; Kliman, David; Dubosq, Ming-Celine; Bishop, David; Sutrave, Gaurav; Ma, Chun Kei Kris; Shaw, Peter J; Micklethwaite, Kenneth P; Gottlieb, David J

2017-11-14

Donor-derived adoptive T-cell therapy is a safe and effective treatment of viral infection posttransplant, but it is limited by donor serostatus and availability and by its personalized nature. Off-the-shelf, third-party virus-specific T cells (VSTs) appear promising, but the long-term safety and durability of responses have yet to be established. We conducted a prospective study of 30 allogeneic hemopoietic stem cell transplant (HSCT) patients with persistent or recurrent cytomegalovirus (CMV) (n = 28), Epstein-Barr virus (n = 1), or adenovirus (n = 1) after standard therapy. Patients were treated with infusions of partially HLA-matched, third-party, ex vivo-expanded VSTs (total = 50 infusions) at a median of 75 days post-HSCT (range, 37 to 349 days). Safety, viral dynamics, and immune recovery were monitored for 12 months. Infusions were safe and well tolerated. Acute graft versus host disease occurred in 2 patients, despite a median HLA match between VSTs and the recipient of 2 of 6 antigens. At 12 months, the cumulative incidence of overall response was 93%. Virological control was durable in the majority of patients; the reintroduction of antiviral therapy after the final infusion occurred in 5 patients. CMV-specific T-cell immunity rose significantly and coincided with a rise in CD8 + terminal effector cells. PD-1 expression was elevated on CD8 + lymphocytes before the administration of third-party T cells and remained elevated at the time of viral control. Third-party VSTs show prolonged benefit, with virological control achieved in association with the recovery of CD8 + effector T cells possibly facilitated by VST infusion. This trial was registered at www.clinicaltrials.gov as #NCT02779439 and www.anzctr.org.au as #ACTRN12613000603718.

Infusing PDA technology into nursing education.

Science.gov (United States)

White, Ann; Allen, Patricia; Goodwin, Linda; Breckinridge, Daya; Dowell, Jeffery; Garvy, Ryan

2005-01-01

Use of the personal digital assistant (PDA) has been infused into the accelerated baccalaureate program at Duke University to help prepare nursing students for professional practice. The authors provide an overview of the use of PDAs in the classroom, laboratory, and clinical setting. Technical aspects of PDA infusion and steps to ensure regulatory compliance are explored. Benefits of PDA use by both faculty and students in the program and challenges met with the infusion of this technology are also described.

Donor, dad, or…? Young adults with lesbian parents' experiences with known donors.

Science.gov (United States)

Goldberg, Abbie E; Allen, Katherine R

2013-06-01

In this exploratory qualitative study of 11 young adults, ages 19-29 years, we examine how young people who were raised by lesbian parents make meaning out of and construct their relationships with known donors. In-depth interviews were conducted to examine how participants defined their family composition, how they perceived the role of their donors in their lives, and how they negotiated their relationships with their donors. Findings indicate that mothers typically chose known donors who were family friends, that the majority of participants always knew who their donors were, and that their contact with donors ranged from minimal to involved. Further, participants perceived their donors in one of three ways: as strictly donors and not members of their family; as extended family members but not as parents; and as fathers. The more limited role of donors in participants' construction of family relationships sheds light on how children raised in lesbian, gay, and bisexual families are contributing to the redefinition and reconstruction of complex kinship arrangements. Our findings hold implications for clinicians who work with lesbian-mother families, and suggest that young adulthood is an important developmental phase during which interest in and contact with the donor may shift, warranting a transfer of responsibility from mother to offspring in terms of managing the donor-child relationship. © FPI, Inc.

Characterization of CD4 T Cell Epitopes of Infliximab and Rituximab Identified from Healthy Donors

Directory of Open Access Journals (Sweden)

Moustafa Hamze

2017-05-01

Full Text Available The chimeric antibodies anti-CD20 rituximab (Rtx and anti-TNFα infliximab (Ifx induce antidrug antibodies (ADAs in many patients with inflammatory diseases. Because of the key role of CD4 T lymphocytes in the initiation of antibody responses, we localized the CD4 T cell epitopes of Rtx and Ifx. With the perspective to anticipate immunogenicity of therapeutic antibodies, identification of the CD4 T cell epitopes was performed using cells collected in healthy donors. Nine T cell epitopes were identified in the variable chains of both antibodies by deriving CD4 T cell lines raised against either Rtx or Ifx. The T cell epitopes often exhibited a good affinity for human leukocyte antigen (HLA-DR molecules and were part of the peptides identified by MHC-associated peptide proteomics assay from HLA-DR molecules of dendritic cells (DCs loaded with the antibodies. Two-third of the T cell epitopes identified from the healthy donors stimulated peripheral blood mononuclear cells from patients having developed ADAs against Rtx or Ifx and promoted the secretion of a diversity of cytokines. These data emphasize the predictive value of evaluating the T cell repertoire of healthy donors and the composition of peptides bound to HLA-DR of DCs to anticipate and prevent immunogenicity of therapeutic antibodies.

Vincristine-induced bystander effect in human lymphocytes

International Nuclear Information System (INIS)

Testi, Serena; Azzarà, Alessia; Giovannini, Caterina; Lombardi, Sara; Piaggi, Simona; Facioni, Maria Sole; Scarpato, Roberto

2016-01-01

Highlights: • We studied whether or not vincristine induced a bystander response in human lymphocytes. • Vincristine significantly increased MN frequencies in mononucleated recipient cells. • ROS or soluble proteins (IL-32 and TGF-β) may account for the observed response. - Abstract: Bystander effect is a known radiobiological effect, widely described using ionizing radiations and which, more recently, has also been related to chemical mutagens. In this study, we aimed to assess whether or not a bystander response can be induced in cultured human peripheral lymphocytes by vincristine, a chemotherapeutic mutagen acting as spindle poison, and by mitomycin-C, an alkylating agent already known to induce this response in human lymphoblastoid cells. Designing a modified ad hoc protocol for the cytokinesis blocked micronucleus (MN) assay, we detected the presence of a dose-dependent bystander response in untreated cultures receiving the conditioned medium (CM) from mitomycin-C (MMC) or vincristine (VCR) treated cultures. In the case of MMC, MN frequencies, expressed as micronucleated binucleates, were: 13.5 ± 1.41 at 6 μM, 22 ± 2.12 at 12 μM or 28.25 ± 5.13 at 15 μM vs. a control value of 4.75 ± 1.59. MN levels for VCR, expressed as micronucleated mononucleates were: 2.75 ± 0.88 at 0.0 μM, 27.25 ± 2.30 at 0.4 μM, 46.25 ± 1.94 at 0.8 μM, 98.25 ± 7.25 at 1.6 μM. To verify that no mutagen residual was transferred to recipient cultures together with the CM, we evaluated MN levels in cultures receiving the medium immediately after three washings following the chemical treatment (unconditioned medium). We further confirmed these results using a cell-mixing approach where untreated lymphocytes were co-cultured with donor cells treated with an effect-inducing dose of MMC or VCR. A distinct production pattern of both reactive oxygen species and soluble mediator proteins by treated cells may account for the differences observed in the manifestation of the

Vincristine-induced bystander effect in human lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Testi, Serena; Azzarà, Alessia; Giovannini, Caterina; Lombardi, Sara [Unità di Genetica, Dipartimento di Biologia, Pisa University, Via Derna 1, 56126 Pisa (Italy); Piaggi, Simona [Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Pisa University, Via Savi 10, 56126 Pisa (Italy); Facioni, Maria Sole [Unità di Genetica, Dipartimento di Biologia, Pisa University, Via Derna 1, 56126 Pisa (Italy); Scarpato, Roberto, E-mail: roberto.scarpato@unipi.it [Unità di Genetica, Dipartimento di Biologia, Pisa University, Via Derna 1, 56126 Pisa (Italy); Research Center of Nutraceuticals and Food for Health, University of Pisa, Pisa (Italy)

2016-07-15

Highlights: • We studied whether or not vincristine induced a bystander response in human lymphocytes. • Vincristine significantly increased MN frequencies in mononucleated recipient cells. • ROS or soluble proteins (IL-32 and TGF-β) may account for the observed response. - Abstract: Bystander effect is a known radiobiological effect, widely described using ionizing radiations and which, more recently, has also been related to chemical mutagens. In this study, we aimed to assess whether or not a bystander response can be induced in cultured human peripheral lymphocytes by vincristine, a chemotherapeutic mutagen acting as spindle poison, and by mitomycin-C, an alkylating agent already known to induce this response in human lymphoblastoid cells. Designing a modified ad hoc protocol for the cytokinesis blocked micronucleus (MN) assay, we detected the presence of a dose-dependent bystander response in untreated cultures receiving the conditioned medium (CM) from mitomycin-C (MMC) or vincristine (VCR) treated cultures. In the case of MMC, MN frequencies, expressed as micronucleated binucleates, were: 13.5 ± 1.41 at 6 μM, 22 ± 2.12 at 12 μM or 28.25 ± 5.13 at 15 μM vs. a control value of 4.75 ± 1.59. MN levels for VCR, expressed as micronucleated mononucleates were: 2.75 ± 0.88 at 0.0 μM, 27.25 ± 2.30 at 0.4 μM, 46.25 ± 1.94 at 0.8 μM, 98.25 ± 7.25 at 1.6 μM. To verify that no mutagen residual was transferred to recipient cultures together with the CM, we evaluated MN levels in cultures receiving the medium immediately after three washings following the chemical treatment (unconditioned medium). We further confirmed these results using a cell-mixing approach where untreated lymphocytes were co-cultured with donor cells treated with an effect-inducing dose of MMC or VCR. A distinct production pattern of both reactive oxygen species and soluble mediator proteins by treated cells may account for the differences observed in the manifestation of the

Calibration curves for biological dosimetry by drug-induced prematurely condensed chromosomes in human lymphocytes

International Nuclear Information System (INIS)

Kang, C. M.; Chung, H. C.; Cho, C. K.

2002-01-01

To develop the cytogenetic tool to detect chromosome damages after high dose exposure with 60 Coγ- rays, dose-response curves were measured for induction of prematurely condensed chromosomes (PCC) in peripheral lymphocytes. Blood was obtained from 10 different healthy donors, and given okadaic acid (OA) 500nM in cultured lymphocytes 1h after radiation exposure. Cells were analyzed by the frequencies of OA-induced PCC rings because it is difficult to obtain mitotic chromosomes using a conventional chromosome aberration (CA). PCC-rings were scored in cells exposed in the dose range of 0.2-16Gy. The frequency of the cells with PCC and the dose-response relationship for the yield of PCC rings were examined in the irradiated lymphocytes. The yield of PCC-rings increased with dose dependent-manner up to 16Gy. The observed dose-effect relationship for the percentage of cells with PCC-rings was calculated by linear-quadratic model. This technique can be applied to biological dosimetry of radiation exposures involving whole body irradiation to allow damaged chromosomes to be detected with great sensitivity. Detection of okadaic acid-induced PCC rings is a useful method up to 16Gy or more doses in estimating the absorbed doses of victims after high dose exposure. Calibration curves described in this paper will be used in our laboratory for biological dosimetry by PCC-ring after a high dose exposure

Disparate rates of acute rejection and donor-specific antibodies among high-immunologic risk renal transplant subgroups receiving antithymocyte globulin induction.

Science.gov (United States)

Patel, Samir J; Suki, Wadi N; Loucks-DeVos, Jennifer; Graviss, Edward A; Nguyen, Duc T; Knight, Richard J; Kuten, Samantha A; Moore, Linda W; Teeter, Larry D; Gaber, Lillian W; Gaber, A Osama

2016-08-01

Lymphocyte-depleting induction lowers acute rejection (AR) rates among high-immunologic risk (HIR) renal transplant recipients, including African Americans (AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dnDSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin (ATG) induction and triple maintenance immunosuppression. A total of 464 HIR recipients from 2007 to 2014 were reviewed. AR and dnDSA rates at 1 year for the entire population were 14% and 27%, respectively. AR ranged from 6.7% among living donor (LD) recipients to 30% in younger AA deceased donor (DD) recipients. De novo donor-specific antibody at 1 year ranged from 7% in older non-AA LD recipients to 32% in AAs. AA race remained as an independent risk factor for AR among DD recipients and for dnDSA among all HIR recipients. Development of both AR and dnDSA within the first year was associated with a 54% graft survival at 5 years and was an independent risk factor for graft loss. Despite utilization of recommended immunosuppression for HIR recipients, substantial disparities exist among subgroups, warranting further consideration of individualized immunosuppression in certain HIR subgroups. © 2016 Steunstichting ESOT.

NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells

Directory of Open Access Journals (Sweden)

Mauro Di Ianni

2018-04-01

Full Text Available To investigate chronic lymphocytic leukemia (CLL-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs. In NOTCH1-mutated CLL, we detected subclonal mutations in 57% CD34+/CD38− HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an increased mutational burden compared to HSCs. Flow cytometric analysis revealed significantly higher NOTCH1 activation in CD34+/CD38− and CD34+/CD38+ cells from CLL patients, regardless NOTCH1 mutation compared to healthy donors. Activated NOTCH1 resulted in overexpression of the NOTCH1 target c-MYC. We conclude that activated NOTCH1 is an early event in CLL that may contribute to aberrant HSCs in this disease.

NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells.

Science.gov (United States)

Di Ianni, Mauro; Baldoni, Stefano; Del Papa, Beatrice; Aureli, Patrizia; Dorillo, Erica; De Falco, Filomena; Albi, Elisa; Varasano, Emanuela; Di Tommaso, Ambra; Giancola, Raffaella; Accorsi, Patrizia; Rotta, Gianluca; Rompietti, Chiara; Silva Barcelos, Estevão Carlos; Campese, Antonio Francesco; Di Bartolomeo, Paolo; Screpanti, Isabella; Rosati, Emanuela; Falzetti, Franca; Sportoletti, Paolo

2018-01-01

To investigate chronic lymphocytic leukemia (CLL)-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs). In NOTCH1- mutated CLL, we detected subclonal mutations in 57% CD34+/CD38- HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an increased mutational burden compared to HSCs. Flow cytometric analysis revealed significantly higher NOTCH1 activation in CD34+/CD38- and CD34+/CD38+ cells from CLL patients, regardless NOTCH1 mutation compared to healthy donors. Activated NOTCH1 resulted in overexpression of the NOTCH1 target c-MYC. We conclude that activated NOTCH1 is an early event in CLL that may contribute to aberrant HSCs in this disease.

Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Human C1q Deficiency: The Karolinska Experience.

Science.gov (United States)

Olsson, Richard F; Hagelberg, Stefan; Schiller, Bodil; Ringdén, Olle; Truedsson, Lennart; Åhlin, Anders

2016-06-01

Human C1q deficiency is associated with systemic lupus erythematosus (SLE) and increased susceptibility to severe bacterial infections. These patients require extensive medical therapy and some develop treatment-resistant disease. Because C1q is produced by monocytes, it has been speculated that allogeneic hematopoietic stem cell transplantation (allo-HSCT) may cure this disorder. We have so far treated 5 patients with C1q deficiency. In 3 cases, SLE symptoms remained relatively mild after the start of medical therapy, but 2 patients developed treatment-resistant SLE, and we decided to pursue treatment with allo-HSCT. For this purpose, we chose a conditioning regimen composed of treosulfan (14 g/m) and fludarabine (30 mg/m) started on day -6 and given for 3 and 5 consecutive days, respectively. Thymoglobulin was given at a cumulative dose of 8 mg/kg, and graft-versus-host disease prophylaxis was composed of cyclosporine and methotrexate. A 9-year-old boy and a 12-year-old girl with refractory SLE restored C1q production after allo-HSCT. This resulted in normal functional properties of the classical complement pathway followed by reduced severity of SLE symptoms. The boy developed posttransplant lymphoproliferative disease, which resolved after treatment with rituximab and donor lymphocyte infusion. Unfortunately, donor lymphocyte infusion induced severe cortisone-resistant gastrointestinal graft-versus-host disease, and the patient died from multiple organ failure 4 months after transplantation. The girl is doing well 33 months after transplantation, and clinically, all signs of SLE have resolved. Allo-HSCT can cure SLE in human C1q deficiency and should be considered early in subjects resistant to medical therapy.

The effect of glucagon on infusion cholangiography

International Nuclear Information System (INIS)

Evans, A.F.; Whitehouse, G.H.

1979-01-01

An assessment has been made of the effects of glucagon on biliary tract opacification during intravenous cholangiography. Two series of infusion cholangiograms were obtained at two investigating centres designated A and B. In series A, 41 patients had ioglycamide infusions at a rate of 0.2833 g min -1 over 1 h. In series B, 31 patients had ioglycamide infusions at a rate of 0.3886 g min -1 over 30 min. Radiographs were taken in both series immediately at the end of the infusion, 10 min later and 30 min after the infusion. Two mg of intravenous glucagon was injected into alternate cases in both series A and B immediately after the first radiograph was taken at the completion of the ioglycamide infusion. Two observers in each series then assessed the radiographic opacification of the biliary system without prior knowledge of which patients had received the glucagon. Delineation of the biliary system was considered better in both series in those patients who received glucagon when compared with the controls. Gallbladder opacification was definitely increased in series A in those receiving glucagon, and a similar tendency was shown in series B. The amount of contrast in the upper intestine was increased in series A in the glucagon group, but not in series B. It is concluded that glucagon improves visualisation of the biliary tract, especially the gallbladder at infusion cholangiography. (author)

Laparoscopic donor nephrectomy

Directory of Open Access Journals (Sweden)

Gupta Nitin

2005-01-01

Full Text Available Of the various options for patients with end stage renal disease, kidney transplantation is the treatment of choice for a suitable patient. The kidney for transplantation is retrieved from either a cadaver or a live donor. Living donor nephrectomy has been developed as a method to address the shortfall in cadaveric kidneys available for transplantation. Laparoscopic living donor nephrectomy (LLDN, by reducing postoperative pain, shortening convalescence, and improving the cosmetic outcome of the donor nephrectomy, has shown the potential to increase the number of living kidney donations further by removing some of the disincentives inherent to donation itself. The technique of LLDN has undergone evolution at different transplant centers and many modifications have been done to improve donor safety and recipient outcome. Virtually all donors eligible for an open surgical procedure may also undergo the laparoscopic operation. Various earlier contraindications to LDN, such as right donor kidney, multiple vessels, anomalous vasculature and obesity have been overcome with increasing experience. Laparoscopic live donor nephrectomy can be done transperitoneally or retroperitoneally on either side. The approach is most commonly transperitoneal, which allows adequate working space and easy dissection. A review of literature and our experience with regards to standard approach and the modifications is presented including a cost saving model for the developing countries. An assessment has been made, of the impact of LDN on the outcome of donor and the recipient.

Pulsatile versus steady infusions for hepatic artery chemotherapy

International Nuclear Information System (INIS)

Kim, E.E.; Haynie, T.P.; Wright, K.C.; Chaynsangavej, C.; Gianturco, C.; Lamki, L.; Wallace, S.

1984-01-01

Hepatic artery chemotherapy for unresectable liver tumors requires an even distribution of the drugs in the tumor or vascular bed. This cannot be determined angiographically because the drugs are infused at a much lower rate than the contrast media. It is easy, however, to determine the quality of the perfusion by injecting a small volume of Tc-99m MAA in one of the side ports while chemotherapeutic agent is being infused at the same rate. Usually this shows a uniform, satisfactory distribution of isotope. Occasionally, however, some areas fail to receive Tc-99m in spite of what appears to be a good position of the catheter tip. Since ''streaming'' of the infused drugs has been blamed for their uneven distribution, the authors decided to compare the usual steady flow infusions with infusions made pulsatile by the addition of a pulsing device (Gianturco Pump) attached to the infusion tubing. Eighty-three patients were studied with steady as well as pulsatile infusions. In 16 of these patients the perfusion pattern was definitely changed by the pulsatile infusion. In one patient the pulsatile mode resulted in an unwanted gastric perfusion. In 5 patients the distribution was improved in one hepatic lobe and in 10 patients it was improved in both lobes. These results show that hepatic artery perfusions can occasionally be improved by pulsing the infusate. However, pulsing can produce the unwanted perfusion of extra-hepatic areas

Lymphocyte-platelet crosstalk in Graves' disease.

Science.gov (United States)

Kuznik, Boris I; Vitkovsky, Yuri A; Gvozdeva, Olga V; Solpov, Alexey V; Magen, Eli

2014-03-01

Platelets can modulate lymphocytes' role in the pathophysiology of thyroid autoimmune diseases. The present study was performed to clarify the status of platelet-lymphocyte subpopulations aggregation in circulating blood in patients with Graves' disease (GD). One hundred and fifty patients with GD (GD group) and 45 hyperthyroid patients with toxic multinodular goiter (TMG group) were recruited in the study. Control group consisted 150 healthy subjects. Immunophenotyping of lymphocytes was performed by flow cytometry. Detection of lymphocyte-platelet aggregates (LPAs) was done using light microscope after Ficoll-gradient centrifugation. The group of GD patients exhibited reduced CD8 lymphocyte and higher CD19 cell counts compared with TMG group and healthy controls. A greater number of activated CD3, HLA-DR+ lymphocytes were observed in GD than in TMG group and control group. GD group was characterized by lower blood platelet count (232 ± 89 × 10 cells/µL) than TMG group (251 ± 97 × 10 cells/µL; P TMG group (116 ± 67/µL, P < 0.005) and control group (104 ± 58 /µL; P < 0.001). GD is associated with higher levels of activated lymphocytes and lymphocyte-platelet aggregates.

Liquid-liquid displacement in slippery liquid-infused membranes (SLIMs)

OpenAIRE

Bazyar, Hanieh; Lv, Pengyu; Wood, Jeffery A.; Porada, Slawomir; Lohse, Detlef; Lammertink, Rob G. H.

2018-01-01

Liquid-infused membranes inspired by slippery liquid-infused porous surfaces (SLIPS) have been recently introduced to membrane technology. The gating mechanism of these membranes is expected to give rise to anti-fouling properties and multi-phase transport capabilities. However, the long-term retention of the infusion liquid has not yet been explored. To address this issue, we investigate the retention of the infusion liquid in slippery liquid-infused membranes (SLIMs) via liquid-liquid displ...

Cytological and cytochemical effects of sodium benzoate and gamma irradiation on human peripheral lymphocytes

International Nuclear Information System (INIS)

Mohamed, N.A.F.

1981-01-01

In vitro studies of human peripheral lymphocytes were conducted to elucidate and compare the effects of a suspected chemical clastogen, sodium benzoate, widely used in the food industry as an antimicrobial food additive, to that of a well-known physical mutagen, gamma rays. Blood from ten normal donors, five males and five females, was collected and treated with various doses of the two agents independently and in combination during G 0 or G 1 phase. Induction of structural chromosomal aberrations, sister chromatid exchanges (SCEs) and unscheduled DNA synthesis were used as parameters to monitor the effects of the two agents. Sodium benzoate at the same concentrations used in the food industry (0.05% and 0.10%) caused inhibition of mitosis and induced chromatid-type aberrations (gaps and breaks). The frequency of aberrations increased as the concentration of sodium benzoate increased. No increase in SCEs over the control level was observed as either concentration tested. The relative amount of DNA damage inflicted in the treated lymphocytes estimated as 3 H-tritiated thymidine incorporation (unscheduled DNA synthesis) was highly significant. In contrast, blood irradiated with 300, 600, or 900 rad 60 Co gamma rays produced chromatid and chromosome aberrations in cultured lymphocytes, dicentrics being the most frequent exchange event. The aberration yield was found to be dose-dependent and to fit the quadratic model. Unscheduled DNA synthesis as measured by lymphocyte 3 H-TdR incorporation following gamma irradiation was highly significantly increased with the largest uptake occurring during the first hour of incubation. The combined treatment of gamma irradiation plus 0.05% sodium benzoate did not increase the aberration frequencies over the independent irradiation treatments and had no effect on SCEs frequencies

Financial analysis for the infusion alliance.

Science.gov (United States)

Perucca, Roxanne

2010-01-01

Providing high-quality, cost-efficient care is a major strategic initiative of every health care organization. Today's health care environment is transparent; very competitive; and focused upon providing exceptional service, safety, and quality. Establishing an infusion alliance facilitates the achievement of organizational strategic initiatives, that is, increases patient throughput, decreases length of stay, prevents the occurrence of infusion-related complications, enhances customer satisfaction, and provides greater cost-efficiency. This article will discuss how to develop a financial analysis that promotes value and enhances the financial outcomes of an infusion alliance.

Donor T cells primed on leukemia lysate-pulsed recipient APCs mediate strong graft-versus-leukemia effects across MHC barriers in full chimeras

OpenAIRE

Ghosh, Arnab; Koestner, Wolfgang; Hapke, Martin; Schlaphoff, Verena; Länger, Florian; Baumann, Rolf; Koenecke, Christian; Cornberg, Markus; Welte, Karl; Blazar, Bruce R.; Sauer, Martin G.

2009-01-01

Antigen-presenting cells (APCs) of host origin drive graft-versus-leukemia (GVL) effects but can also trigger life-threatening graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) across major histocompatibility complex (MHC) barriers. We show that in vitro priming of donor lymphocytes can circumvent the need of recipient-derived APCs in vivo for mediating robust GVL effects and significantly diminishes the risk of severe GVHD. In vitro, generated and expanded T cel...

Optimized choice of method for determining proliferation response of peripheral lymphocytes to mitogens in low dose irradiation with cyclotron fast neutrons

International Nuclear Information System (INIS)

Refka, Z.; Svec, M.; Aganov, P.; Svoboda, V.; Podzimek, F.

1989-01-01

Heparinized venous blood sampled from seven donors was irradiated with doses of 0.1; 0.25; 0.5; 1.0; 2.0 and 3.0 Gy of fast neutrons of a mean energy of 7.6 MeV using the U 120 M isochronous cyclotron. A non-irradiated control sample was also prepared. A lymphoblastic transformation test was conducted with both the intact and irradiated samples. The samples were cultivated in the RPMI-1640 medium with and without a mitogen addition, this in five time variants, viz., for 48, 72, 90, 96 and 120 hours. The proliferation was monitored of lymphocytes stimulated with mitogens PHA, CON-A and PWM in dependence on the time of cultivation and on the radiation dose. The dose dependent relative response was also studied of the irradiated lymphocytes. (E.J.). 8 figs., 1 tab., 18 refs

Homing of bone marrow lymphoid cells

International Nuclear Information System (INIS)

Yoshida, Y.; Osmond, D.G.

1978-01-01

DNA labeling, bone marrow fractionation, and radioautography were used to follow the fate of transfused, newly formed marrow lymphocytes in irradiated hosts. After infusing donor Hartley guinea pigs with 3 H-thymidine for 3 to 5 days, high concentrations of labeled small lymphocytes and large lymphoid cells were separated from marrow by sedimentation in sucrose-serum gradients and injected into lethally x-irradiated syngeneic recipients. Most labeled small lymphocytes and large lymphoid cells rapidly left the circulation. They appeared to be mainly in the marrow and spleen, increasing in incidence from 1 to 3 days, but declining in mean grain count. Labeled cells were scattered throughout the recipient marrow; in the spleen they localized initially in the red pulp, and subsequently in peripheral areas of white pulp, often in clusters. Labeled small lymphocytes showed a delayed migration into the mesenteric lymph node, mainly in the superficial cortex and medulla; they also appeared in small numbers in Peyer's patches, but rarely in the thymus or thoracic duct lymph. It is concluded that a rapid selective homing of newly formed marrow lymphoid cells occurs in both the marrow and certain areas of the spleen of irradiated hosts, followed by a continuing proliferation of large lymphoid cells and production of small lymphocytes. The results are discussed with respect to the life history of marrow lymphocytes and the use of adoptive immune assays of marrow cells to characterize B lymphocyte maturation

Results of investigation of trace element content in nucleic acids and histones, isolated from human leucaemic cells

International Nuclear Information System (INIS)

Andronikashvili, Eh.L.; Mosulishvili, L.M.; Belokobyl'skij, A.I.; Kharabadze, N.E.; Desai, A.S.; Foley, G.E.; Harvard Cancer Commission, Boston, MA

1977-01-01

Trace metals in purified nucleic acids and histones, extracted from lymphocyte cell culture of patients with acute lymphocytic leukemia or infections mononucleosis and healthy donors were determined with the activation analysis method. In the lymphocyte DNA of patients with infections mononucleosis and healthy donors the content of Co ++ , Sb ++ , Fe +++ , Zn ++ , turned out to be high, while in the lymphoblast DNA of patients with acute lymphocytic leukemia lower concentrations of these metals were detected, with the exception of Co ++ , the content of which is 20 times higher than in the DNA, extracted from the lymphocytes of healthy donors. In the general histone of the leukemic cells the content of the most of trace metals is higher than in the general lymphocyte histone of healthy donors. The exception is Zn ++ , the content of which is lower

Marginal kidney donor

Directory of Open Access Journals (Sweden)

Ganesh Gopalakrishnan

2007-01-01

Full Text Available Renal transplantation is the treatment of choice for a medically eligible patient with end stage renal disease. The number of renal transplants has increased rapidly over the last two decades. However, the demand for organs has increased even more. This disparity between the availability of organs and waitlisted patients for transplants has forced many transplant centers across the world to use marginal kidneys and donors. We performed a Medline search to establish the current status of marginal kidney donors in the world. Transplant programs using marginal deceased renal grafts is well established. The focus is now on efforts to improve their results. Utilization of non-heart-beating donors is still in a plateau phase and comprises a minor percentage of deceased donations. The main concern is primary non-function of the renal graft apart from legal and ethical issues. Transplants with living donors outnumbered cadaveric transplants at many centers in the last decade. There has been an increased use of marginal living kidney donors with some acceptable medical risks. Our primary concern is the safety of the living donor. There is not enough scientific data available to quantify the risks involved for such donation. The definition of marginal living donor is still not clear and there are no uniform recommendations. The decision must be tailored to each donor who in turn should be actively involved at all levels of the decision-making process. In the current circumstances, our responsibility is very crucial in making decisions for either accepting or rejecting a marginal living donor.

Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios as independent predictors of cervical stromal involvement in surgically treated endometrioid adenocarcinoma

Directory of Open Access Journals (Sweden)

Wang D

2013-03-01

Full Text Available Dan Wang, Jia-Xin Yang, Dong-Yan Cao, Xi-Run Wan, Feng-Zhi Feng, Hui-Fang Huang, Keng Shen, Yang Xiang Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China Background: The purpose of this study was to evaluate the relationship between preoperative inflammatory markers (neutrophil-lymphocyte ratio and platelet-lymphocyte ratio and cervical stromal involvement in patients with endometrioid adenocarcinoma. Methods: We studied 318 patients with endometrioid adenocarcinoma who underwent comprehensive surgical staging. We used univariate and multivariate analyses of cervical stromal involvement and receiver-operating curves to calculate optimal cutoff values for neutrophil-lymphocyte and platelet-lymphocyte ratios to predict cervical stromal involvement. Results: The presence of cervical stromal involvement was associated with neutrophil-lymphocyte ratio and platelet-lymphocyte ratio (P = 0.009 and P = 0.031, respectively. Multivariate analysis showed that higher neutrophil-lymphocyte and platelet-lymphocyte ratios independently predicted cervical stromal involvement (odds ratio 3.10, 95% confidence interval 1.10–8.76, P = 0.032, and odds ratio 5.27, 95% confidence interval 1.94–14.35, P = 0.001, respectively. At a threshold of 2.01, the neutrophil-lymphocyte ratio was 71.0% sensitive and 63.8% specific for stromal involvement; at a 172.24 threshold, the platelet-lymphocyte ratio was 48.4% sensitive and 88.9% specific. Conclusion: Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios can help identify the risk of cervical stromal involvement in patients with endometrial cancer. Evaluating these ratios may help select patients who should be particularly watched and tested for cervical stromal involvement. Keywords: neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, endometrioid adenocarcinoma

Chronic lymphocytic leukemia (CLL)

Science.gov (United States)

... is used for painful and enlarged lymph nodes. Blood transfusions or platelet transfusions may be required if blood ... unexplained fatigue, bruising, excessive sweating, or weight loss. Alternative ... Leukemia - chronic lymphocytic (CLL); Blood cancer - chronic lymphocytic leukemia; Bone marrow cancer - chronic ...

Evolution and phylogeny of B lymphocytes

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Fabiola Claudio-Piedras

2016-05-01

Full Text Available B lymphocytes are one of the most important cell types involved in the immune response of mammals. The origin and evolution of this cellular type is unknown, but the B lymphocyte bona fide appeared first in fish. In this review we analize the principal components of the immune response of invertebrates, their phylogenetic distribution and the permancence of some properties that allowed the emergence of the B lymphocyte. We started from the idea that many of the components that characterize the B lymphocyte are found distributed among the invertebrates, however, it is in the B lymphocyte, where all these components that give this type of cell its identity, converged. The actual knowledge we have in regards of the lymphocytes comes, in the most part, from physiological studies in mammals, being the mice the more representative. The origin of the B lymphocyte, its alternative mechanisms for generating receptor diversity, its immune effector response, and the generation of memory, require an evolutionary and multidisiplinary approach for its study.

Donor Retention in Online Crowdfunding Communities: A Case Study of DonorsChoose.org.

Science.gov (United States)

Althoff, Tim; Leskovec, Jure

2015-05-01

Online crowdfunding platforms like DonorsChoose.org and Kick-starter allow specific projects to get funded by targeted contributions from a large number of people. Critical for the success of crowdfunding communities is recruitment and continued engagement of donors. With donor attrition rates above 70%, a significant challenge for online crowdfunding platforms as well as traditional offline non-profit organizations is the problem of donor retention. We present a large-scale study of millions of donors and donations on DonorsChoose.org, a crowdfunding platform for education projects. Studying an online crowdfunding platform allows for an unprecedented detailed view of how people direct their donations. We explore various factors impacting donor retention which allows us to identify different groups of donors and quantify their propensity to return for subsequent donations. We find that donors are more likely to return if they had a positive interaction with the receiver of the donation. We also show that this includes appropriate and timely recognition of their support as well as detailed communication of their impact. Finally, we discuss how our findings could inform steps to improve donor retention in crowdfunding communities and non-profit organizations.

MicroRNA expression profiling identifies activated B cell status in chronic lymphocytic leukemia cells.

Directory of Open Access Journals (Sweden)

Shuqiang Li

2011-03-01

Full Text Available Chronic lymphocytic leukemia (CLL is thought to be a disease of resting lymphocytes. However, recent data suggest that CLL cells may more closely resemble activated B cells. Using microRNA (miRNA expression profiling of highly-enriched CLL cells from 38 patients and 9 untransformed B cells from normal donors before acute CpG activation and 5 matched B cells after acute CpG activation, we demonstrate an activated B cell status for CLL. Gene set enrichment analysis (GSEA identified statistically-significant similarities in miRNA expression between activated B cells and CLL cells including upregulation of miR-34a, miR-155, and miR-342-3p and downregulation of miR-103, miR-181a and miR-181b. Additionally, decreased levels of two CLL signature miRNAs miR-29c and miR-223 are associated with ZAP70(+ and IgV(H unmutated status and with shorter time to first therapy. These data indicate an activated B cell status for CLL cells and suggest that the direction of change of individual miRNAs may predict clinical course in CLL.

The effect of gamma ray on total leukocytes, lymphocytes and neutrophils on blood samples of smokers compared to non-smoker donors

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Baydaa Taher Sih

2017-01-01

Conclusions: By increases the doses of γ-ray, the declining in the values of WBCs, lymphocytes, and neutrophils in the smokers blood is greater than of nonsmokers and this confirms that these cells are more fragile, weak, and less tolerant to external stimuli.

Ex vivo measurement of calpain activation in human peripheral blood lymphocytes by detection of immunoreactive products of calpastatin degradation.

Directory of Open Access Journals (Sweden)

Jacek M Witkowski

2008-01-01

Full Text Available Limited proteolysis of multiple intracellular proteins by endogenous Ca-dependent cysteine proteases--calpains--is an important regulatory mechanism for cell proliferation, apoptosis etc. Its importance for cellular functions is stressed by existence of endogenous calpain inhibitors--calpastatins. The calpain-calpastatin system within living cells is in a fragile balance, which depends on both partners. The interdependence of calpain--a protease--and calpastatin--an endogenous inhibitor and at the same time a substrate for this enzyme makes any assessment of actual activity of this enzyme in the cells very difficult. In this work we made an attempt to estimate and compare the activity of calpain in human peripheral blood lymphocytes by assessing the levels of limited proteolysis of calpastatin in these cells by western blot, while at the same time the levels of calpain protein inside these cells was measured by flow cytometry. Our results indicate that it is possible to compare (semi-quantitatively the activities of calpain in peripheral blood CD4+ and CD19+ lymphocytes from various donors that way. Preliminary results showed that calpain activity is increased in the CD4+ T cells isolated from peripheral blood of rheumatoid arthritis patients as compared to control lymphocytes. Extremely high intrinsic activity of calpain was detected in chronic lymphocytic leukemia (CD19+ cells. All this confirms the detection of immunoreactive products of calpastatin as a good maker of endogenous calpain activity.

ABO-Incompatible Adult Living Donor Liver Transplantation Under the Desensitization Protocol With Rituximab.

Science.gov (United States)

Song, G-W; Lee, S-G; Hwang, S; Kim, K-H; Ahn, C-S; Moon, D-B; Ha, T-Y; Jung, D-H; Park, G-C; Kim, W-J; Sin, M-H; Yoon, Y-I; Kang, W-H; Kim, S-H; Tak, E-Y

2016-01-01

ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the largest single-center experience of ABO-incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in-hospital mortality. The cumulative 3-year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO-compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody-mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Infusion Antihypoxants in Children with Critical Conditions

Directory of Open Access Journals (Sweden)

Yu. S. Aleksandrovich

2014-01-01

Full Text Available Hypoxia and mitochondrial damage are a key component of the pathogenesis and tanatogenesis of a critical condition, suggesting the need for its prevention and maximally rapid elimination. Objective: to analyze the efficacy and safety of infusion antihypoxants used in critically ill children from the results of researches. Materials and methods. Available investigations dealing with infusion therapy in children and papers on the use of infusion antihypoxants in adults in 2005 to 2013 were sought in the medical databases PubMed and Cochrane Library with their free availability and analyzed. Results. The analysis included 70 trials. The pathophysiology and pathobiochemistry of hypoxia in critically ill children are given; the current principles of its correction by infusion therapy are considered in detail. Particular emphasis is placed on trials evaluating the efficacy and safety of succinic acid solutions in children. Main indications for and contraindications to their use are demonstrated. Conclusion. The use of Krebs cycle substrate-based infusion antihypoxants (malate, succinate is an effective and promising procedure for the intensive therapy and correction of hypoxia in both adults and children with critical conditions. Considering the fact that papers on the use of infusion antihypoxants in children are scanty, there is a need for further investigations. 

Nyretransplantation med levende donor

DEFF Research Database (Denmark)

Kamper, A L; Løkkegaard, H; Rasmussen, F

2000-01-01

In recent years transplantation from living donors has accounted for 25-30% of all kidney transplants in Denmark corresponding to 40-45 per year. Most of these living donors are parents or siblings, although internationally an increasing number are unrelated donors. Donor nephrectomy is associate...... in cadaver transplantation. The ethical and psychological aspects related to transplantation from a living donor are complex and need to be carefully evaluated when this treatment is offered to the patients....

The History of Target-Controlled Infusion

NARCIS (Netherlands)

Struys, Michel M. R. F.; De Smet, Tom; Glen, John (Iain) B.; Vereecke, Hugo E. M.; Absalom, Anthony R.; Schnider, Thomas W.

Target-controlled infusion (TCI) is a technique of infusing IV drugs to achieve a user-defined predicted (target) drug concentration in a specific body compartment or tissue of interest. In this review, we describe the pharmacokinetic principles of TCI, the development of TCI systems, and technical

The role of stem cell mobilization regimen on lymphocyte collection yield in patients with multiple myeloma.

Science.gov (United States)

Hiwase, D K; Hiwase, S; Bailey, M; Bollard, G; Schwarer, A P

2008-01-01

The lymphocyte dose (LY-DO) infused during an autograft influences absolute lymphocyte (ALC) recovery and survival following autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. Factors influencing lymphocyte yield (LY-C) during leukapheresis have been poorly studied. Factors that could influence survival, LY-C and CD34(+) cell yield were analyzed in 122 MM patients. Three mobilization regimens were used, granulocyte-colony-stimulating factor (G-CSF) alone (n=13), cyclophosphamide 1-2 g/m(2) plus G-CSF (LD-CY, n=62) and cyclophosphamide 3-4 g/m(2) and G-CSF (ID-CY, n=47). Using multivariate analysis, age, LY-C, ALC on day 30 (ALC-30) and International Staging System stage significantly influenced overall (OS) and progression-free survival (PFS) following ASCT. PFS (56 versus 29 months, P=0.05) and OS (72 versus 49 months; P=0.07) were longer in the LY-C>or=0.12x10(9)/kg group than the LY-Cradiotherapy and number of leukaphereses significantly influenced LY-C. Significantly higher LY-C was obtained with G-CSF alone compared with the LD-CY and ID-CY groups. CD34(+) count on the day of leukapheresis, prior chemotherapy with prednisone, cyclophosphamide, adriamycin and BCNU or melphalan, and stem cell mobilization regimen significantly influenced CD34(+) cell yield. LY-C influenced ALC-15 and survival following ASCT. Factors that influenced CD34(+) cell yield and LY-C during leukapheresis were different. Mobilization should be tailored to maximize the LY-C and CD34(+) cell yield.

To the nucleolar bodies (nucleoli) in cells of the lymphocytic lineage in patients suffering from B - chronic lymphocytic leukemia.

Science.gov (United States)

Smetana, K; Karban, J; Trneny, M

2010-01-01

The present study was undertaken to provide more information on nucleoli in lymphocytes of B - chronic lymphocytic leukemia. The computer assisted nucleolar and cytoplasmic RNA image densitometry, reflecting the nucleolar and cytoplasmic RNA concentration at the single cell level, demonstrated a remarkable stability during the differentiation and maturation of B- lymphocytes. In contrast, as it was expected, the nucleolar diameter during the lymphocytic development markedly decreased. Thus the nucleolar RNA content of leukemic B-lymphocytes was apparently related to the nucleolar size. In both immature and mature lymphocytes, the cytostatic treatment increased the incidence of micronucleoli, which represent the "inactive" type of nucleoli. However, the decreased values of the nucleolar diameter were statistically significant only in mature lymphocytes of treated patients. On the other hand, despite such observation, it must be mentioned that "large active" and "ring shaped resting" nucleoli were still present in immature and mature lymphocytes after the cytostatic therapy and such cells might represent a potential pool of proliferating cells. As it is generally accepted "large active nucleoli" with multiple fibrillar centers are known to be characteristic for proliferating cells. "Ring shaped resting nucleoli" are present in sleeping cells, which may be stimulated to return to the cell cycle and to proliferate again. In addition, the nucleolar RNA distribution also indicated that Gumprecht ghosts mostly originated from mature lymphocytes. Increased ratio of the nucleolar to cytoplasmic RNA density in Gumprecht ghosts or apoptotic cells and apoptotic bodies of the lymphocytic origin was related to the decreased cytoplasmic RNA concentration. The increased nucleolar size together with the markedly decreased cytoplasmic RNA concentration characteristic for Gumprecht ghosts just reflected the spreading of lymphocytes during smear preparations. In apoptotic cells or

Low-dose factor VIII infusion in Chinese adult haemophilia A patients: pharmacokinetics evidence that daily infusion results in higher trough level than with every-other-day infusion with similar factor VIII consumption.

Science.gov (United States)

Hua, B; Lee, A; Fan, L; Li, K; Zhang, Y; Poon, M-C; Zhao, Y

2017-05-01

Pharmacokinetics (PK) modelling suggests improvement of trough levels are achieved by using more frequent infusion strategy. However, no clinical study data exists to confirm or quantify improvement in trough level, particularly for low-dose prophylaxis in patients with haemophilia A. To provide evidence that low dose daily (ED) prophylaxis can increase trough levels without increasing FVIII consumption compared to every-other-day (EOD) infusion. A cross-over study on 5 IU kg -1 FVIII daily vs. 10 IU kg -1 EOD infusions, each for 14 days was conducted at the PUMCH-HTC. On the ED schedule, trough (immediate prior to infusion), and peak FVIII:C levels (30 min after infusion) were measured on days 1-5; and trough levels alone on days 7, 9, 11 and 13. For the EOD schedule, troughs, peaks and 4-h postinfusion were measured on day 1; troughs and peaks on days 3, 5, and 7; troughs alone on days 9, 11 and 13 and 24-h postinfusion on days 2, 4 and 6. FVIII inhibitors were assessed on days 0 and 14 during both infusion schedules. Six patients were enrolled. PK evidence showed that daily prophylaxis achieved higher (~2 times) steady-state FVIII trough levels compared to EOD with the same total factor consumption. The daily prophylaxis had good acceptability among patients and reduced chronic pain in the joints in some patients. Our PK study shows low-dose factor VIII daily infusion results in higher trough level than with EOD infusion with similar factor VIII consumption in Chinese adult haemophilia A patients. © 2017 John Wiley & Sons Ltd.

Radiation sensitivity of human malignant lymphocytes

International Nuclear Information System (INIS)

Seshadri, R.; Matthews, C.; Morley, A.A.

1985-01-01

A simple and rapid in vitro technique to assess the sensitivity of human malignant lymphocytes to roentgen irradiation is described. A variety of established malignant lymphocyte cell lines were cloned in microwells and clone survival was used as the end-point. The survival of the clonogenic malignant lymphocyte down to a fraction of approximately 0.001 could be measured accurately. Except for a T-cell line, the radiation sensitivities of the cell lines were similar to that of normal T-lymphocytes. (orig.)

An experimental study on the influence of infusion speed on the early mechanism of embolic effect of arterially infused absolute Ethanol in the rat

International Nuclear Information System (INIS)

Han, Joon Koo; Kim, Woo Ho; Lee, Byung Hee; Park, Kil Sun; Park, Jae Hyung; Kim, Chu Wan; Han, Man Chung

1990-01-01

In order to clarify the early mechanism of action of the tissue necrosis induced by intraarterially infused absolute ethanol, abdominal aortography and histopathologic examination after absolute ethanol infusion into aorta at fast (0.4ml/sec) and slow speed (0.04ml/sec) were performed on 22 rats (2 controls, 7 in fast infusion group, 7 in slow infusion group, 3 in fast and 3 in slow infusion groups during aorta compression, respectively). Histopathologic features under the light and scanning electron microscope were correlated with the angiographic findings within 30 minutes after ethanol infusion. The results are as follows : 1. In fast infusion group, histopathologic examination of the kidney showed severe glomerular and tubular damage. Extensive damage on endothelial and medial layer was noted in arteries, and fresh thrombi originated from the damaged arterial wall were seen. 2. Angiographic findings in the fast infusion group were luminal irregularity and early obstruction of large arteries. And circulation time was prolonged. 3. In slow infusion group, histopathologic examination of the kidney showed focal area of severe glomerular and tubular damage on relatively normal background. Endothelial and muscular damage was noted in arteries, but the degree of the damage was less severe than that of the fast infusion group. 4. Angiographic findings in the slow infusion group were focal perfusion defect of the kidney, delayed circulation time, and mild luminal irregularity, but obstruction of the major arteries was not seen

Inflammatory markers as selection criteria of hepatocellular carcinoma in living-donor liver transplantation.

Science.gov (United States)

Na, Gun Hyung; Kim, Dong Goo; Han, Jae Hyun; Kim, Eun Young; Lee, Soo Ho; Hong, Tae Ho; You, Young Kyoung

2014-06-07

To investigate that inflammatory markers can predict accurately the prognosis of hepatocelluar carcinoma (HCC) patients in living-donor liver transplantation (LDLT). From October 2000 to November 2011, 224 patients who underwent living donor liver transplantation for HCC at our institution were enrolled in this study. We analyzed disease-free survival (DFS) and overall survival (OS) after LT in patients with HCC and designed a new score model using pretransplant neutrophil-lymphocyte ratio (NLR) and C-reactive protein (CRP). The DFS and OS in patients with an NLR level ≥ 6.0 or CRP level ≥ 1.0 were significantly worse than those of patients with an NLR level < 6.0 or CRP level < 1.0 (P = 0.049, P = 0.003 for NLR and P = 0.010, P < 0.001 for CRP, respectively). Using a new score model using the pretransplant NLR and CRP, we can differentiate HCC patients beyond the Milan criteria with a good prognosis from those with a poor prognosis. Combined with the Milan criteria, new score model using NLR and CRP represent new selection criteria for LDLT candidates with HCC, especially beyond the Milan criteria.

Infusing Systems Thinking into Career Counseling

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Ryan, Charles W.; Tomlin, James H.

2010-01-01

This study examined the role of career counselors in infusing systems thinking into occupational advising. The authors conducted a qualitative review and analysis of selected literature on systems thinking and analyzed trends for adaptation to career counseling practice. This analysis suggests that career counselors need to infuse systems…

Is continuous infusion of imipenem always the best choice?

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Suchánková, Hana; Lipš, Michal; Urbánek, Karel; Neely, Michael N; Strojil, Jan

2017-03-01

Monte Carlo simulations allow prediction and comparison of concentration-time profiles arising from different dosing regimens in a defined population, provided a population pharmacokinetic model has been established. The aims of this study were to evaluate the population pharmacokinetics of imipenem in critically ill patients with hospital-acquired pneumonia (HAP) and to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) using EUCAST data. A two-compartment model based on a data set of 19 subjects was employed. Various dosage regimens at 0.5-h and 3-h infusion rates and as continuous infusion were evaluated against the pharmacodynamic targets of 20%fT >MIC , 40%fT >MIC and 100%fT >MIC . For the target of 40%fT >MIC , all 0.5-h infusion regimens achieved optimal exposures (CFR ≥ 90%) against Escherichia coli and Staphylococcus aureus, with nearly optimal exposure against Klebsiella pneumoniae (CFR ≥ 89.4%). The 3-h infusions and continuous infusion exceeded 97% CFR against all pathogens with the exception of Pseudomonas aeruginosa and Acinetobacter spp., where the maximum CFRs were 85.5% and 88.4%, respectively. For the 100%fT >MIC target, only continuous infusion was associated with nearly optimal exposures. Higher PTAs for the targets of 40%fT >MIC and 100%fT >MIC were achieved with 3-h infusions and continuous infusion in comparison with 0.5-h infusions; however, continuous infusion carries a risk of not reaching the MIC of less susceptible pathogens in a higher proportion of patients. In critically ill patients with HAP with risk factors for Gram-negative non-fermenting bacteria, maximum doses administered as extended infusions may be necessary. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Influence of kinship on donors' mental burden in living donor liver transplantation.

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Erim, Yesim; Beckmann, Mingo; Kroencke, Sylvia; Sotiropoulos, Georgios C; Paul, Andreas; Senf, Wolfgang; Schulz, Karl-Heinz

2012-08-01

In the context of living donor liver transplantation (LDLT), German transplantation law stipulates that donor candidates should primarily be relatives of the recipients or persons with distinct and close relationships. In this study, we investigated the influence of the relationship between the donor and the recipient on the donor's emotional strain before transplantation. Donors were categorized according to the following subgroups: (1) parents donating for their children, (2) children donating for their parents, (3) siblings, (4) spouses, (5) other relatives, and (6) nonrelatives. The sample consisted of 168 donor candidates. Anxiety (F = 2.8, P = 0.02), depression (F = 2.6, P = 0.03), and emotional quality of life (F = 3.1, P = 0.01) differed significantly according to the relationship between the donor and the recipient. In comparison with healthy controls, parents donating for their children were significantly less stressed before LDLT and demonstrated fewer anxiety (P depression symptoms (P < 0.05). Adult children donating for their parents demonstrated the highest mental burden and the lowest emotional quality of life. However, this was not due to the responsibility of these children for their own families because differences between donors with children and donors without children could not be ascertained. This group should be given special attention before LDLT and during follow-up visits, and psychological help should be provided when it is necessary. Copyright © 2012 American Association for the Study of Liver Diseases.

Antigen-Specific Polyclonal Cytotoxic T Lymphocytes Induced by Fusions of Dendritic Cells and Tumor Cells

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Shigeo Koido

2010-01-01

Full Text Available The aim of cancer vaccines is induction of tumor-specific cytotoxic T lymphocytes (CTLs that can reduce the tumor mass. Dendritic cells (DCs are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Thus, DCs-based vaccination represents a potentially powerful strategy for induction of antigen-specific CTLs. Fusions of DCs and whole tumor cells represent an alternative approach to deliver, process, and subsequently present a broad spectrum of antigens, including those known and unidentified, in the context of costimulatory molecules. Once DCs/tumor fusions have been infused back into patient, they migrate to secondary lymphoid organs, where the generation of antigen-specific polyclonal CTL responses occurs. We will discuss perspectives for future development of DCs/tumor fusions for CTL induction.

Biological dosimetry: the potential use of radiation-induced apoptosis in human T-lymphocytes

International Nuclear Information System (INIS)

Menz, R.; Andres, R.; Larsson, B.; Ozsahin, M.; Crompton, N.E.A.; Trott, K.

1997-01-01

An assay for biological dosimetry based on the induction of apoptosis in human T-lymphocytes is described. Radiation-induced apoptosis was assessed by flow cytometric identification of cells displaying apoptosis-associated DNA condensation. CD4 and CD8 T-lymphocytes were analysed. They were recognized on the basis of their cell-surface antigens. Four parameters were measured for both cell types: cell size, granularity, antigen immunofluorescence and DNA content. Apoptosis was quantified as the fraction of CD4-, or CD8-positive cells with a characteristic reduction of cell size and DNA content. At doses below 1 Gy, levels of radiation-induced apoptosis increased for up to 5 days after irradiation. Optimal dose discrimination was observed 4 days after irradiation, at which time the dose-response curves were linear, with a slope of 8% ± 0.5% per 0.1 Gy. In controlled, dose-response experiments the lowest dose level at which the radiation-induced apoptosis frequency was still significantly above control was 0.05 Gy. After 5 days post-irradiation incubation, intra- and interdonor variations were measured and found to be similar; thus, apoptotic levels depend more on the dose than on the donor. The results demonstrate the potential of this assay as a biological dosimeter. (orig.)

Spontaneous Apoptosis, Oxidative Status and Immunophenotype Markers in Blood Lymphocytes of AIDS Patients

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Gabriele A. Losa

2000-01-01

Full Text Available Peripheral blood mononuclear cells (PBMC from 251 HIV‐positive drug abusers of known clinical stage and from 40 healthy donors were tested for conventional immunologic markers (CD3, CD4, CD8, CD19, CD14, CD16/CD56, CD45 and HLA‐DR. Additional cell parameters and the occurrence of spontaneous apoptosis (programmed cell death were investigated on freshly isolated PBMC by flow cytometric measurement of either annexin‐V bound to plasma membrane phosphatidylserine or propidium iodide uptake. The activity of γ‐glutamyltransferase (γ‐GT, an ectoenzyme contributing to the synthesis of the intracellular antioxidant glutathione (GSH and involved in early apoptosis, was also determined in these cells. Immunocompetent T‐cell counts were lower in HIV+ patients, with the exception of CD8+ and HLA‐DR+ lymphocytes. The external binding of annexin‐V was significantly higher in HIV+ PBMC and occurred in both CD8+ and CD4+ T‐lymphocyte subsets. The activity of γ‐GT, was significantly lower in the PBMC from HIV+ patients, indicating that the redox status of PBMC may be affected in HIV+ individuals. Finally, the most dominant features characterising patients receiving antiretroviral therapy were greater long‐term stability in the distribution of various cell parameters excepted the level of apoptosis.

Iron deficiency in blood donors

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Rodolfo Delfini Cançado

Full Text Available CONTEXT: Blood donation results in a substantial loss of iron (200 to 250 mg at each bleeding procedure (425 to 475 ml and subsequent mobilization of iron from body stores. Recent reports have shown that body iron reserves generally are small and iron depletion is more frequent in blood donors than in non-donors. OBJECTIVE: The aim of this study was to evaluate the frequency of iron deficiency in blood donors and to establish the frequency of iron deficiency in blood donors according to sex, whether they were first-time or multi-time donors, and the frequency of donations per year. DESIGN: From September 20 to October 5, 1999, three hundred blood donors from Santa Casa Hemocenter of São Paulo were studied. DIAGNOSTIC TESTS: Using a combination of biochemical measurements of iron status: serum iron, total iron-binding capacity, transferrin saturation index, serum ferritin and the erythrocyte indices. RESULTS: The frequency of iron deficiency in blood donors was 11.0%, of whom 5.5% (13/237 were male and 31.7% (20/63 female donors. The frequency of iron deficiency was higher in multi-time blood donors than in first-time blood donors, for male blood donors (7.6% versus 0.0%, P < 0.05 and female ones (41.5% versus 18.5%, P < 0.05. The frequency of iron deficiency found was higher among the male blood donors with three or more donations per year (P < 0.05 and among the female blood donors with two or more donations per year (P < 0.05. CONCLUSIONS: We conclude that blood donation is a very important factor for iron deficiency in blood donors, particularly in multi-time donors and especially in female donors. The high frequency of blood donors with iron deficiency found in this study suggests a need for a more accurate laboratory trial, as hemoglobin or hematocrit measurement alone is not sufficient for detecting and excluding blood donors with iron deficiency without anemia.

Correlation between donor age and organs transplanted per donor: our experience in Japan.

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Ashikari, J; Omiya, K; Konaka, S; Nomoto, K

2014-05-01

The shortage of available organs for transplantation is a worldwide issue. To maximize the number of transplantations, increasing the number of organs transplanted per donor (OTPD) is widely recognized as an important factor for improving the shortage. In Japan, we have had 211 donors, 1112 organs transplanted, and 924 recipients receiving the transplants, resulting in 4.4 ± 1.4 recipients receiving transplants per donor and 5.3 ± 1.6 OTPD as of February 2013. Because donor age is a well-recognized factor of donor suitability, we analyzed the correlation between donor age group and OTPD. Only the age group 60 to 69 years and the age group 70 to 79 years were significantly different (P donor under age 70 years has the potential to donate 4.6 to 6.7 organs. Copyright © 2014 Elsevier Inc. All rights reserved.

Achieving donor management goals before deceased donor procurement is associated with more organs transplanted per donor.

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Malinoski, Darren J; Daly, Michael C; Patel, Madhukar S; Oley-Graybill, Chrystal; Foster, Clarence E; Salim, Ali

2011-10-01

There is a national shortage of organs available for transplantation. Implementation of preset donor management goals (DMGs) to improve outcomes is recommended, but uniform practices and data are lacking. We hypothesized that meeting DMGs before organ procurement would result in more organs transplanted per donor (OTPD). The eight organ procurement organization in United Network for Organ Sharing Region 5 selected 10 critical care end points as DMGs. Each organ procurement organization submitted retrospective data from 40 standard criteria donors. "DMGs met" was defined as achieving any eight DMGs before procurement. The primary outcome was ≥4 OTPD. Binary logistic regression was used to determine independent predictors of ≥4 OTPD with a pdonors had 3.6±1.6 OTPD. Donors with DMGs met had more OTPD (4.4 vs. 3.3, p50% (OR=4.0), Pao2:FIO2>300 (OR=4.6), and serum sodium 135 to 160 mEq/L (OR=3.4). Meeting DMGs before procurement resulted in more OTPD. Donor factors and critical care end points are independent predictors of organ yield. Prospective studies are needed to determine the true impact of each DMG on the number and function of transplanted organs.

Effect of Piper chaba Hunter, Piper sarmentosum Roxb. and Piper interruptum Opiz. on natural killer cell activity and lymphocyte proliferation.

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Panthong, Sumalee; Itharat, Arunporn

2014-08-01

Immune system is the most important system ofhuman body. Thaifolk doctors have used some medicinal plants as an adaptogenic drug or immunomodulatory agent. Piper chaba Hunter, Piper sarmentosum Roxb. and Piper interruptum Opiz. are used by folk doctors to activate immune response in cancer patients. To investigate the effect on natural killer cell activity and on lymphocyte proliferation activity of water extract of P chaba Hunter P. sarmentosum Roxb. and P interruptum Opiz. MATERIAL ANDMETHOD: Plant materials were extracted by decoction method. All extracts were testedfor an immunomodulatory effect using PBMCs from twelve healthy donors by chromium release assay. Lymphocyte proliferation was also determined by 3H-thymidine uptake assay. The degree of activation was expressed as the stimulation index. The water extract of P chaba Hunter significantly increased lymphocyte proliferation at concentrations ofl ng/ml, 10 ng/ml, 1 μg/ml, 5 μg/ml, 10 μg/ml and 100 μg/ml. P sarmentosum Roxb., and P interruptum Opiz. extracts at those concentrations significantly stimulated lymphocyteproliferation. P sarmentosum Roxb. extractsignificantly increased natural killer (NK) cell activity at a concentration of 100 μg/ml but P chaba Hunter and P interruptum Opiz. extracts did not significantly stimulate natural killer cell activity. P chaba Hunter, P interruptum Opiz. andP sarmentosum Roxb. have an immunomodulatory effect especially for P sarmentosum Roxb. extract which can activate both lymphocyte proliferation and NK cell activity.

Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients

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Mélanie Saint-Jean

2018-01-01

Full Text Available Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs. This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2 regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous metastasis, TILs were produced according to a previously described method and then infused into the patient who also received a complementary subcutaneous IL-2 regimen. Nine women and 1 man were treated for unresectable stage IIIC (n=4 or IV (n=6 melanoma. All but 1 patient with unresectable stage III melanoma (1st line had received at least 2 previous treatments, including anti-CTLA-4 antibody for 4. The number of TILs infused ranged from 0.23 × 109 to 22.9 × 109. Regarding safety, no serious adverse effect was reported. Therapeutic responses included a complete remission, a partial remission, 2 stabilizations, and 6 progressions. Among these 4 patients with clinical benefit, 1 is still alive with 9 years of follow-up and 1 died from another cause after 8 years of follow-up. Notably, patients treated with high percentages of CD4 + CD25 + CD127lowFoxp3+ T cells among their TILs had significantly shorter OS. The therapeutic effect of combining TILs with new immunotherapies needs further investigation.

A Novel Technique for Split-Thickness Skin Donor Site Pain Control: Subcutaneous Catheters for Continuous Local Anesthetic Infusion

Science.gov (United States)

2012-01-01

the new: a novel approach to treating pain associated with rib fractures . World J Surg 2010;34:2359–62. 3. Wheatley GH III, Rosenbaum DH, Paul MC, et...has been described after laparotomy, tho- racotomy, inguinal hernia repair, and rib fractures .2–4 We describe our experience at the U.S. Army Insti...JAN 2012 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE A novel technique for split-thickness skin donor site pain control

Krypton 81m infusion studies. Chapter 18

International Nuclear Information System (INIS)

Kaplan, E.; Mayron, L.W.; Friedman, A.M.; Gindler, J.E.

1978-01-01

A technique is described to give a continuous, constant-rate, intravascular infusion of 81 Krsup(m). Modifications of earlier generators included production of sodium-free 81 Rb, the use of a solution of commercial sterile isotonic non-ionic 5% dextrose-in-water as an eluant, the incorporation of a constant-rate infusion pump, and the miniaturization of the generator column and catheter system. Results are presented of studies of 81 Krsup(m) distribution in dogs, using both intravenous and intra-arterial infusion. (author)

A simplified donor risk index for predicting outcome after deceased donor kidney transplantation.

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Watson, Christopher J E; Johnson, Rachel J; Birch, Rhiannon; Collett, Dave; Bradley, J Andrew

2012-02-15

We sought to determine the deceased donor factors associated with outcome after kidney transplantation and to develop a clinically applicable Kidney Donor Risk Index. Data from the UK Transplant Registry on 7620 adult recipients of adult deceased donor kidney transplants between 2000 and 2007 inclusive were analyzed. Donor factors potentially influencing transplant outcome were investigated using Cox regression, adjusting for significant recipient and transplant factors. A United Kingdom Kidney Donor Risk Index was derived from the model and validated. Donor age was the most significant factor predicting poor transplant outcome (hazard ratio for 18-39 and 60+ years relative to 40-59 years was 0.78 and 1.49, respectively, Pinformed consent.

Opinion: Interactions of innate and adaptive lymphocytes

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Gasteiger, Georg; Rudensky, Alexander Y.

2015-01-01

Innate lymphocytes, including natural killer (NK) cells and the recently discovered innate lymphoid cells (ILCs) have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. Less well understood is the contribution of the adaptive immune system to the orchestration of innate lymphocyte responses. We review our current understanding of the interactions between adaptive and innate lymphocytes, and propose a model in which adaptive T cells function as antigen-specific sensors for the activation of innate lymphocytes to amplify and instruct local immune responses. We highlight the potential role of regulatory and helper T cells in these processes and discuss major questions in the emerging area of crosstalk between adaptive and innate lymphocytes. PMID:25132095

The impact of disclosure on donor gamete participants: donors, intended parents and offspring.

Science.gov (United States)

Greenfeld, Dorothy A

2008-06-01

The present review examines recent publications that provide insight into how the trend toward nonanonymity and disclosure in gamete donation impacts donors, intended parents, and their donor-conceived children. Recent findings show an increase in donor programs that offer open-identity between donors and offspring. The psychological needs of gamete donors and their attitudes toward disclosure are increasingly given consideration. Qualitative research on how parents of donor gamete offspring make decisions about disclosure reveals that even when couples initially disagree about disclosing to offspring, most ultimately come to a united disclosure decision. The literature on the impact of disclosure on donor gamete offspring has extended to include children conceived through embryo donation and children born as a result of surrogacy. The absence of genetic or gestational link between parents and their child does not have a negative impact on parent-child relationships. Parents through surrogacy tend to disclose the method of family creation to their child, whereas parents through embryo donation tend to be secretive about their child's origins. The trend toward greater openness in gamete donation has been accompanied by an increase in programs offering open-identity donation. In addition, the psychological needs of gamete donors and their attitudes toward disclosure are increasingly being given consideration. Parents of donor gamete offspring give careful thought to their disclosure decisions, and the psychological well being of donor-conceived children does not seem to be impacted by those decisions.

Differences in social representation of blood donation between donors and non-donors: an empirical study.

Science.gov (United States)

Guarnaccia, Cinzia; Giannone, Francesca; Falgares, Giorgio; Caligaris, Aldo Ozino; Sales-Wuillemin, Edith

2015-11-04

Both donors and non-donors have a positive image of blood donation, so donors and non-donors do not differ regarding their views on donation but do differ in converting their opinion into an active deed of donation. Several studies have identified altruism and empathy as the main factors underlying blood donation. However, a mixture of various motivational factors mould the complex behaviour of donation. This paper presents an exploratory study on differences of social representations of blood donation between blood donors and non-donors, in order to understand the reasons that bring someone to take the decision to become a blood donor. Participants filled in the Adapted Self-Report Altruism Scale, Toronto Empathy Questionnaire and answered a test of verbal association. Descriptive and correlation analyses were carried out on quantitative data, while a prototypic analysis was used for qualitative data. The study was carried out on a convenience sample of 786 individuals, 583 donors (mean age: 35.40 years, SD: 13.01 years; 39.3% female) and 203 non-donors (mean age: 35.10 years, SD: 13.30 years; 67.5% female). Social representations of donors seem to be more complex and articulated than those of non-donors. The terms that appear to be central were more specific in donors (life, needle, blood, help, altruism were the words most associated by non-donors; life, aid, altruism, solidarity, health, love, gift, generosity, voluntary, control, needed, useful, needle were the words most associated by donors). Furthermore, non-donors associated a larger number of terms referring to negative aspects of blood donation. Aspects related to training and the accuracy of any information on blood donation seem to be important in the decision to become a donor and stabilise the behaviour of donation over time, thus ensuring the highest levels of quality and safety in blood establishments.

Clinical applications of continuous infusion chemotherapy ahd concomitant radiation therapy

International Nuclear Information System (INIS)

Rosenthal, C.J.; Rotman, M.

1986-01-01

This book presents information on the following topics: theoretical basis and clinical applications of 5-FU as a radiosensitizer; treatment of hepatic metastases from gastro intestingal primaries with split course radiation therapy; combined modality therapy with 5-FU, Mitomycin-C and radiation therapy for sqamous cell cancers; treatment of bladder carcinoma with concomitant infusion chemotherapy and irradiation; a treatment of invasiv bladder cancer by the XRT/5FU protocol; concomitant radiation therapy and doxorubicin by continuous infusion in advanced malignancies; cis platin by continuous infusion with concurrent radiation therapy in malignant tumors; combination of radiation with concomitant continuous adriamycin infusion in a patient with partially excised pleomorphic soft tissue sarcoma of the lower extremeity; treatment of recurrent carcinoma of the paranasal sinuses using concomitant infusion cis-platinum and radiation therapy; hepatic artery infusion for hepatic metastases in combination with hepatic resection and hepatic radiation; study of simultaneous radiation therapy, continuous infusion, 5FU and bolus mitomycin-C; cancer of the esophagus; continuous infusion VP-16, bolus cis-platinum and simultaneous radiation therapy as salvage therapy in small cell bronchogenic carcinoma; and concomitant radiation, mitomycin-C and 5-FU infusion in gastro intestinal cancer

Donor lung derived myeloid and plasmacytoid dendritic cells differentially regulate T cell proliferation and cytokine production

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Benson Heather L

2012-03-01

Full Text Available Abstract Background Direct allorecognition, i.e., donor lung-derived dendritic cells (DCs stimulating recipient-derived T lymphocytes, is believed to be the key mechanism of lung allograft rejection. Myeloid (cDCs and plasmacytoid (pDCs are believed to have differential effects on T cell activation. However, the roles of each DC type on T cell activation and rejection pathology post lung transplantation are unknown. Methods Using transgenic mice and antibody depletion techniques, either or both cell types were depleted in lungs of donor BALB/c mice (H-2d prior to transplanting into C57BL/6 mice (H-2b, followed by an assessment of rejection pathology, and pDC or cDC-induced proliferation and cytokine production in C57BL/6-derived mediastinal lymph node T cells (CD3+. Results Depleting either DC type had modest effect on rejection pathology and T cell proliferation. In contrast, T cells from mice that received grafts depleted of both DCs did not proliferate and this was associated with significantly reduced acute rejection scores compared to all other groups. cDCs were potent inducers of IFNγ, whereas both cDCs and pDCs induced IL-10. Both cell types had variable effects on IL-17A production. Conclusion Collectively, the data show that direct allorecognition by donor lung pDCs and cDCs have differential effects on T cell proliferation and cytokine production. Depletion of both donor lung cDC and pDC could prevent the severity of acute rejection episodes.

Quality of harvested autologous platelets compared with stored donor platelets for use after cardiopulmonary bypass procedures.

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Crowther, M; Ford, I; Jeffrey, R R; Urbaniak, S J; Greaves, M

2000-10-01

Platelet dysfunction has a major contribution in bleeding after cardiopulmonary bypass (CPB) and transfusion of platelets is frequently used to secure haemostasis. Allogeneic platelets prepared for transfusion are functionally impaired. Autologous platelets harvested preoperatively require a shorter storage time before transfusion and their use also avoids the risks associated with transfusion of allogeneic blood products. For the first time, we have compared the functional quality of autologous platelets with allogeneic platelets prepared by two methods, immediately before infusion. Platelet activation was assessed by P-selectin expression and fibrinogen binding using flow cytometry. We also monitored the effects of CPB surgery and re-infusion of autologous platelets on platelet function. Autologous platelet-rich plasma (PRP) contained a significantly lower (P platelets compared with allogeneic platelet preparations, and also contained a significantly higher (P platelets. Allogeneic platelets prepared by donor apheresis were more activated and less responsive than those produced by centrifugation of whole blood. In patients' blood, the percentage of platelets expressing P-selectin or binding fibrinogen increased significantly after CPB (P platelets responsive to in vitro agonists was decreased (P platelet activation during the procedure. The percentage of activated platelets decreased (statistically not significant) after re-infusion of autologous PRP. P-selectin expression had returned to pre-CPB levels 24 h post-operatively. Autologous platelet preparations display minimal activation, but remain responsive. Conservation of platelet function may contribute to the potential clinical benefits of autologous transfusion in cardiopulmonary bypass.

Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors.

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Taniguchi, K; Yoshihara, S; Maruya, E; Ikegame, K; Kaida, K; Hayashi, K; Kato, R; Inoue, T; Fujioka, T; Tamaki, H; Okada, M; Onuma, T; Fujii, N; Kusunoki, Y; Soma, T; Saji, H; Ogawa, H

2012-10-01

Pre-existing donor-specific HLA antibodies in patients undergoing HLA-mismatched SCT have increasingly been recognized as a risk factor for primary graft failure. However, the clinical implications of the presence of HLA antibodies in donors remain unknown. We prospectively examined 123 related donors for the presence of HLA antibodies by using a Luminex-based single antigen assay. Of these, 1/57 (1.8%) male, 6/27 (22%) parous female and 0/39 (0%) nonparous female donors were HLA antibody-positive. Then, we determined the presence of HLA antibodies in seven patients who received SCT from antibody-positive donors. Of these, four became HLA antibody-positive after SCT. The specificities of the antibodies that emerged in the patients closely resembled those of the antibodies found in the donors, indicating their production by donor-derived plasma cells. Moreover, the kinetics of the HLA antibody levels were similar in all four patients: levels started increasing within 1 week after SCT and peaked at days 10-21, followed by a gradual decrease. These results suggest that donor-derived HLA antibody production frequently occurs in patients undergoing SCT from antibody-positive donors. Further studies are warranted for clarifying the clinical significance of donor-derived HLA antibodies, including the role of these antibodies in post transplant platelet transfusion refractoriness.

Fas expression on peripheral blood lymphocytes in systemic lupus erythematosus (SLE) : relation to lymphocyte activation and disease activity

NARCIS (Netherlands)

Bijl, M; Horst, G; Limburg, PC; Kallenberg, CGM

2001-01-01

Levels of apoptotic lymphocytes have been found to be increased in SLE and persistence of apoptotic cells has been associated with autoantibody production, Increased lymphocyte Fas (CD95) expression due to lymphocyte activation may account for increased Susceptibility to Fas-mediated apoptosis in

Canadian Palliative Community Milrinone Infusions: A Case Series.

Science.gov (United States)

Reimche, Ruthanne; Salcedo, Daniel

2016-01-01

Abstract Symptom managementfor end-of-life heartfailure (HF) patients is a significant concern. Currently, Canadian practice does not support community milrinone therapy in end-of-life HF patients. Two patients had severe HF that was unresponsive to optimal medications. Further optimization and furosemide infusions were ineffective for symptom management. Both patients' symptoms were better controlled with optimal medication, furosemide, and milrinone infusions. A tailored discharge plan was developed to assist with community milrinone infusions. We discuss the challenges and successes of transitioning two patients to the community. By providing symptom management and meaningful patient and family experience, both patients were able to die in a setting of their choosing. Milrinone infusions as a bridge to end of life may improve symptoms and quality of life. Select patients may benefit from milrinone infusions with resources put in place; these end-of-life HF patients can be supported in the community.

Systematic donor blood qualification by flow cytometry would have been able to avoid CLL-type MBL transmission after unrelated hematopoietic stem cell transplantation.

Science.gov (United States)

Ferrand, Christophe; Garnache-Ottou, Francine; Collonge-Rame, Marie Agnès; Larosa, Fabrice; Blanc, Michel; Behar, Catherine; Giannoli, Catherine; Garnier, Frédérico; Tiberghien, Pierre; Deconinck, Eric; Rohrlich, Pierre Simon

2012-03-01

The current screening for eligibility of unrelated volunteer marrow donors comprises a complete clinical check-up, a blood CBC and serum protein immunoelectrophoresis. This allows to eliminate acute leukemias, myeloproliferative and myelodysplastic disorders, myelomas and MGUS. To date, the risk of transmission of chronic lymphocytic leukemia (CLL) disease is only evaluated by the clinical evaluation and CBC. We report here the case of a CLL-type MBL disease occurring in a 12-year-old boy after unrelated BMT. Deep biological investigations, as Immunophenotyping, cytogenetic and molecular biology allow us to determine the donor origin of the CLL clone. In 2010, 14.2% donor (105/737) for unrelated hematopoietic stem cell transplantation were over 45y. It is currently estimated (USA) that 1 in 210 men and women will be diagnosed with CLL during their lifetime. Given the long asymptomatic phase of CLL, this raises the case for a detection strategy analog to that used for MGUS and myeloma through serum protein electrophoresis. This case-report, to our knowledge, of a CLL-type MBL unrelated donor-to-recipient transmission through BMT raises ethical and practical questions, such as the proper information about disease transmission risk. The cost-effectiveness of a systematic peripheral blood Immunophenotyping in donors elder than 40y at time of stem cell donation should be evaluated. © 2012 John Wiley & Sons A/S.

The effect of whole-blood donor adverse events on blood donor return rates.

Science.gov (United States)

Newman, Bruce H; Newman, Daniel T; Ahmad, Raffat; Roth, Arthur J

2006-08-01

Some blood donation-related adverse events (AEs) can negatively impact the blood donor return rate (BDRR) and decrease donor retention. One-thousand randomly selected whole-blood donors were interviewed 3 weeks after a 525-mL index whole-blood donation for seven AEs. The number of return visits and duration of follow-up were recorded for each of the 1000 donors. A negative binomial regression analysis was used to determine the contribution of the four most common AEs to the BDRR, and interactions between these AEs were also evaluated. The four most common AEs were bruise alone (15.1%), sore arm "alone" (7.0%), fatigue "alone" (5.1%), and donor reaction "alone" (4.2%), where "alone" is defined to also include donors who had a bruise but no other AE. The estimated BDRR for donations without AEs was 1.32 visits per year. The estimated BDRRs for the four most common AEs were: bruise alone, 1.32 visits per year; sore arm alone, 1.30 visits per year (2% reduction in BDRR); fatigue alone, 1.06 visits per year (20% reduction in BDRR); and donor reaction alone, 0.87 visits per year (34% reduction in BDRR). The BDRR for donor reaction, fatigue, and sore arm together was 0.20 visits per year (85% reduction in BDRR). Donor reaction had the most negative impact on the BDRR. There appears to be a synergistic effect between donor reaction, fatigue, and sore arm. Theoretically, amelioration of some AEs has the potential to improve BDRRs.

A new infusion pathway intactness monitoring system.

Science.gov (United States)

Ogawa, Hidekuni; Yonezawa, Yoshiharu; Maki, Hiromichi; Ninomiya, Ishio; Sata, Koji; Hamada, Shingo; Caldwell, W Morton

2006-01-01

A new infusion pathway monitoring system has been developed for hospital and home use. The system consists of linear integrated circuits and a low-power 8-bit single chip microcomputer which constantly monitors the infusion pathway intactness. An AC (alternating current) voltage is induced on the patient's body by electrostatic coupling from the normal 100 volt, 60 Hz AC power line wiring field in the patient's room. The induced AC voltage can be recorded by a main electrode wrapped around the infusion polyvinyl chloride tube. A reference electrode is wrapped on the electrode to monitor the AC voltage around the main electrode. If the injection needle or infusion tube becomes detached, then the system detects changes in the induced AC voltages and alerts the nursing station, via the nurse call system or PHS (personal handy phone system).

ِAnalysis of donor motivations in living donor liver transplantation

Directory of Open Access Journals (Sweden)

Hesham eAbdeldayem

2014-07-01

Full Text Available Objectives: The introduction of the living donor liver transplantation (LDLT in Egypt as in elsewhere, has raised important psychological conflicts and ethical questions. The objective of this study was to get better understanding of the potential donors’ motives towards LDLT.Methods:This study was conducted on consecutive 193 living –liver donors who underwent partial hepatectomy as donors for LDLT during the period between April 2003 and January 2013, at the National Liver Institute Menoufeyia University, Egypt. Potential donors were thoroughly evaluated preoperatively through a screening questionnaire and interviews as regard their demographic data, relationship to the potential recipient and motives towards proceeding to surgery. They were assured that the information shared between them and the transplant centre is confidential. Results.The donors’ mean age was 25.53± 6.39 years with a range of 18-45 years. Males represented 64.7 % and females were 35.3%. The most common donors (32.1%, n_62, were sons and daughters to their parents (sons: n_43, daughters: n_19 while parents to their offsprings represent 15% (mothers: n_21, fathers: n_8. Brothers and sisters represent 16.5 % (brothers: n_22, sisters: n_10. Nephews & nieces giving their uncles or aunts were 14%. The number of wives donating to their husbands was 11 (5.7%. Interestingly, there was no single husband who donated his wife. Among the remaining donors, there were 11 cousins & one uncle. Unrelated donors were 20 (10.4%. Several factors seemed to contribute to motivation for donation: the seriousness of the potential recipient condition, the relationship and personal history of the donor to the potential recipient, the religious beliefs, the trust in the health care system, and family dynamics and obligations.Conclusions. Absolute absence of coercion on the living-liver donor’s motives may not be realistic because of the serious condition of the potential recipient. It is

Comparison of the intracoronary continuous infusion method using a microcatheter and the intravenous continuous adenosine infusion method for inducing maximal hyperemia for fractional flow reserve measurement.

Science.gov (United States)

Yoon, Myeong-Ho; Tahk, Seung-Jea; Yang, Hyoung-Mo; Park, Jin-Sun; Zheng, Mingri; Lim, Hong-Seok; Choi, Byoung-Joo; Choi, So-Yeon; Choi, Un-Jung; Hwang, Joung-Won; Kang, Soo-Jin; Hwang, Gyo-Seung; Shin, Joon-Han

2009-06-01

Inducing stable maximal coronary hyperemia is essential for measurement of fractional flow reserve (FFR). We evaluated the efficacy of the intracoronary (IC) continuous adenosine infusion method via a microcatheter for inducing maximal coronary hyperemia. In 43 patients with 44 intermediate coronary lesions, FFR was measured consecutively by IC bolus adenosine injection (48-80 microg in left coronary artery, 36-60 microg in the right coronary artery) and a standard intravenous (IV) adenosine infusion (140 microg x min(-1) x kg(-1)). After completion of the IV infusion method, the tip of an IC microcatheter (Progreat Microcatheter System, Terumo, Japan) was positioned at the coronary ostium, and FFR was measured with increasing IC continuous adenosine infusion rates from 60 to 360 microg/min via the microcatheter. Fractional flow reserve decreased with increasing IC adenosine infusion rates, and no further decrease was observed after 300 microg/min. All patients were well tolerated during the procedures. Fractional flow reserves measured by IC adenosine infusion with 180, 240, 300, and 360 microg/min were significantly lower than those by IV infusion (P < .05). Intracoronary infusion at 180, 240, 300, and 360 microg/min was able to shorten the times to induction of optimal and steady-stable hyperemia compared to IV infusion (P < .05). Functional significances were changed in 5 lesions by IC infusion at 240 to 360 microg/min but not by IV infusion. The results of this study suggest that an IC adenosine continuous infusion method via a microcatheter is safe and effective in inducing steady-state hyperemia and more potent and quicker in inducing optimal hyperemia than the standard IV infusion method.

AID protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma is associated with poor prognosis and complex genetic alterations.

Science.gov (United States)

Leuenberger, Mona; Frigerio, Simona; Wild, Peter J; Noetzli, Franziska; Korol, Dimitri; Zimmermann, Dieter R; Gengler, Carole; Probst-Hensch, Nicole M; Moch, Holger; Tinguely, Marianne

2010-02-01

The biological behavior of chronic lymphocytic leukemia and small lymphocytic lymphoma is unpredictable. Nonetheless, non-mutated IgV(H) gene rearrangement, ATM (11q22-23) and p53 (17p13) deletion are recognized as unfavorable prognosticators in chronic lymphocytic leukemia. The mRNA expression of activation-induced cytidine deaminase (AID), an enzyme indispensable for somatic hypermutation processes, was claimed to be predictive of non-mutated chronic lymphocytic leukemia cells in blood. Here, we evaluated AID protein expression compared with known molecular and immunohistochemical prognostic indicators in 71 chronic lymphocytic leukemia/small lymphocytic lymphoma patients using a tissue microarray approach. We found AID heterogeneously expressed in tumor cells as shown by colocalization analysis for CD5 and CD23. Ki-67 positive paraimmunoblasts of the proliferation centers displayed the highest expression. This observation is reflected by a significant association of AID positivity with a high proliferation rate (P=0.012). ATM deletion was detected in 10% (6/63) of patients and p53 deletion in 19% (13/67) of patients. Moreover, both ATM (P=0.002) and p53 deletion (P=0.004) were significantly associated with AID. IgV(H) gene mutation was seen in 45% (27/60) of patients. Twenty-five percent (17/69) of patients with AID-positive chronic lymphocytic leukemia/small lymphocytic lymphoma displayed a shorter survival than AID-negative chronic lymphocytic leukemia/small lymphocytic lymphoma patients (61 vs 130 months, P=0.001). Although there was a trend, we could not show an association with the IgV(H) gene mutation status. Taken together, our study shows that AID expression is an indicator of an unfavorable prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma patients, although it is not a surrogate marker for the IgV(H) status. Furthermore, the microenvironment of proliferation centers seems to influence AID regulation and might be an initiating factor

Inhibition of endogenous lactate turnover with lactate infusion in humans

International Nuclear Information System (INIS)

Searle, G.L.; Feingold, K.R.; Hsu, F.S.; Clark, O.H.; Gertz, E.W.; Stanley, W.C.

1989-01-01

The extent to which lactate infusion may inhibit endogenous lactate production, though previously considered, has never been critically assessed. To examine this proposition, single injection tracer methodology (U- 14 C Lactate) has been used for the estimation of lactate kinetics in 12 human subjects under basal conditions and with the infusion of sodium lactate. The basal rate of lactate turnover was measured on a day before the study with lactate infusion, and averaged 63.7 + 5.5 mg/kg/h. Six of these individuals received a stable lactate infusion at an approximate rate of 160 mg/kg/h, while the remaining six individuals were infused at the approximate rate of 100 mg/kg/h. It has been found that stable lactate infused at rates approximating 160 mg/kg/h consistently produced a complete inhibition of endogenous lactate production. Infusion of lactate at 100 mg/kg/h caused a lesser and more variable inhibition of endogenous lactate production (12% to 64%). In conclusion, lactate infusion significantly inhibits endogenous lactate production

Síndrome da infusão do propofol Síndrome de la infusión del propofol Propofol infusion syndrome

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Fabiano Timbó Barbosa

2007-10-01

Full Text Available JUSTIFICATIVA E OBJETIVOS: A síndrome da infusão do propofol tem sido descrita como uma síndrome rara e quase sempre fatal que ocorre após infusão prolongada desse fármaco. Ela pode resultar em acidose metabólica grave, rabdomiólise, colapso cardiovascular e morte. O objetivo deste artigo foi mostrar aspectos relacionados com a síndrome da infusão do propofol por meio da revisão de literatura. CONTEÚDO: Estão definidas as características da síndrome da infusão do propofol quanto à fisiopatologia, características clínicas, tratamento e recomendações de dose para pacientes gravemente enfermos. CONCLUSÕES: O propofol deve ser usado com cautela quando se planeja seu uso sob regime de infusão contínua por períodos prolongados. O surgimento de sinais sugestivos da síndrome da infusão do propofol indica a suspensão imediata do fármaco e início de medidas de suporte.JUSIFICATIVA Y OBJETIVOS: El síndrome de la infusión del propofol ha sido descrito como un síndrome raro y frecuentemente fatal que ocurre después de la infusión prolongada de ese fármaco. Puede resultar en acidez metabólica grave, rabdomiólisis, colapso cardiovascular y deceso. El objetivo de este artículo fue mostrar aspectos relacionados al síndrome de la infusión del propofol a través de la revisión de la literatura. CONTENIDO: Están definidas las características del síndrome de la infusión del propofol en cuanto a la fisiopatología, características clínicas, tratamiento y recomendaciones de dosis para pacientes gravemente enfermos. CONCLUSIONES: El propofol debe ser usado con cautela cuando se planea su uso bajo el régimen de infusión continua por períodos prolongados. El aparecimiento de señales sugestivas del síndrome de la infusión del propofol indica la suspensión inmediata del fármaco y el inicio de medidas de soporte.BACKGROUND AND OBJECTIVES: Propofol infusion syndrome has been described as a rare, and frequently fatal

Effect of Insulin Infusion on Liver Protein Synthesis during Hemodialysis

DEFF Research Database (Denmark)

Reinhard, Mark; Frystyk, Jan; Jespersen, Bente

2011-01-01

Background Hemodialysis (HD) is a catabolic procedure that may contribute to the high frequency of protein-energy wasting among patients receiving maintenance HD. The present study investigated the additional effect of glucose and glucose-insulin infusion on liver protein synthesis during HD...... compared with a meal alone. Methods In a randomized cross-over study with three arms, 11 non-diabetic HD patients were assigned to receive a conventional HD session with either: • no treatment (NT) • IV infusion of glucose (G) • IV infusion of glucose-insulin (GI) During infusions blood glucose levels were...... maintained at 8.0-10.0 mmol/L by additional glucose infusion. Glucose and glucose-insulin infusions were commenced 2 h prior to HD and continued throughout the HD session. Fasting blood samples were collected at baseline before infusion and followed by the only meal allowed during the study. Results Blood...

Combined strategy of endothelial cells coating, Sertoli cells coculture and infusion improves vascularization and rejection protection of islet graft.

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Yang Li

Full Text Available Improving islet graft revascularization and inhibiting rejection become crucial tasks for prolonging islet graft survival. Endothelial cells (ECs are the basis of islet vascularization and Sertoli cells (SCs have the talent to provide nutritional support and exert immunosuppressive effects. We construct a combined strategy of ECs coating in the presence of nutritious and immune factors supplied by SCs in a co-culture system to investigate the effect of vascularization and rejection inhibition for islet graft. In vivo, the combined strategy improved the survival and vascularization as well as inhibited lymphocytes and inflammatory cytokines. In vitro, we found the combinatorial strategy improved the function of islets and the effect of ECs-coating on islets. Combined strategy treated islets revealed higher levels of anti-apoptotic signal molecules (Bcl-2 and HSP-32, survival and function related molecules (PDX-1, Ki-67, ERK1/2 and Akt and demonstrated increased vascular endothelial growth factor receptor 2 (KDR and angiogenesis signal molecules (FAk and PLC-γ. SCs effectively inhibited the activation of lymphocyte stimulated by islets and ECs. Predominantly immunosuppressive cytokines could be detected in culture supernatants of the SCs coculture group. These results suggest that ECs-coating and Sertoli cells co-culture or infusion synergistically enhance islet survival and function after transplantation.

Radiosensitivity of lymphocytes in vitro

International Nuclear Information System (INIS)

Albrecht, S.

1979-01-01

The radiation-induced impairment of human T-lymphocytes was studied after in vitro exposure to 25.8 - 825.6 mC/kg (100 - 3200 R) of 60 Co γ-radiation by ascertaining the change in lymphocyte response to phytohaemagglutin stimulation. Following methods were used: (1) measurement of 3 H-thymidine uptake, (2) E-rosette test, and (3) morphological examination of transformed T-cells. The results revealed a dose-dependent decline in T-cell number which was still somewhat more marked with lymphocytes purified over Ficoll-Isopaque prior to irradiation. (author)

GENERATION OF CYTOTOXIC LYMPHOCYTES IN MIXED LYMPHOCYTE REACTIONS

Science.gov (United States)

Forman, James; Möller, Göran

1973-01-01

Generation of cytotoxic effector cells by a unidirectional mixed lymphocyte reaction (MLR) in the mouse H-2 system was studied using labeled YAC (H-2a) leukemia cells as targets. The responding effector cell displayed a specific cytotoxic effect against target cells of the same H-2 genotype as the stimulating cell population. Killing of syngeneic H-2 cells was not observed, even when the labeled target cells were "innocent bystanders" in cultures where specific target cells were reintroduced. Similar results were found with spleen cells taken from mice sensitized in vivo 7 days earlier. The effector cell was not an adherent cell and was not activated by supernatants from MLR. The supernatants were not cytotoxic by themselves. When concanavalin A or phytohemagglutinin was added to the cytotoxic test system, target and effector cells were agglutinated. Under these conditions, killing of H-2a target cells was observed in mixed cultures where H-2a lymphocytes were also the effector cells. These findings indicate that specifically activated, probably thymus-derived lymphocytes, can kill nonspecifically once they have been activated and providing there is close contact between effector and target cells. Thus, specificity of T cell killing appears to be restricted to recognition and subsequent binding to the targets, the actual effector phase being nonspecific. PMID:4269560

Human leukaemic cells

International Nuclear Information System (INIS)

Andronikashvili, E.L.; Mosulishvili, L.M.; Belokobil'skiy, A.I.; Kharabadze, N.E.; Shonia, N.I.; Desai, L.S.; Foley, G.E.

1976-01-01

Trace metals were measured by neutron-activation analyses in purified nucleic acids and histone(s) of lymphocytes from patients with acute lymphocytic leukaemia or infectious mononucleosis, and from normal donors. DNA isolated from lymphocytes of a patient with infectious mononucleosis and a normal donor showed a high content of Cr 2+ , Sb 2+ , Fe 2+ , Zn 2+ , whereas DNA of lymphoblasts from a patient with acute lymphocytic leukaemia had a lower content of these trace metals, but the Co 2+ content was 20-fold higher than in DNA of normal donor lymphocytic cells. Total histones from leukaemic cells had higher contents of most of the trace metals except for Zn 2+ , which was present in lesser concentration than in histones from normal donor lymphocytic cells. Lysine-rich (F1) histones showed lower contents of Cr 2+ , Sb 2+ and Co 2+ , whereas arginine-rich (F3) histones had significantly higher contents of these trace metals. These observations may be of interest in that F3 histones more effectively inhibit RNA synthesis in human lymphocytic cells than do other species of histones. (author)

Lipolytic response to glucose infusion in human subjects

International Nuclear Information System (INIS)

Wolfe, R.R.; Peters, E.J.

1987-01-01

The authors have determined the effect of various rates of glucose infusion on the rates of release of glycerol (R/sub a/ glycerol), free fatty acids (R/sub a/ FFA), and on energy metabolism in normal human volunteers. Plasma kinetics were determined with use of the stable isotopic tracers D-5-glycerol and [1- 13 C]palmitate, and energy metabolism was determined by indirect calorimetry. The effect of glucose infusion on R/sub a/ glycerol and R/sub a/ FFA was dose-dependent. At 4 mg x kg -1 x min -1 , both R/sub a/ glycerol and R/sub a/ FFA were suppressed; at 8 mg x kg -1 x min -1 , R/sub a/ FFA was even more depressed, but R/sub a/ glycerol was similar to the value during the 4 mg x kg -1 x min -1 infusion. At all infusion rates tested, the amount of potential energy available from the sum of the glucose infusion and endogenously mobilized fat was always greater than when no glucose was infused. Glucose decreased fat mobilization by both inhibiting lipolysis and stimulating reesterification, thus causing a significant increase in triglyceride-fatty acid substrate cycling within the adipose tissue. Plasma insulin was determined by radioimmunoassay

Transfer of unstable chromosomal aberrations in human peripheral lymphocytes at cell division and their significance for the aberration frequency

International Nuclear Information System (INIS)

Stephan, G.; Chang Tsangpi.

1986-04-01

In 48 h cultures, the fraction of human lymphocytes in 2nd mitosis was found to be between 0 and 42.5% (mean value 8.7%). The X-ray exposure from irradiating with 2 Gy resulted in a cell cycle delay which varied from donor to donor. A loss of nearly 50% of dicentric chromosomes and acentric fragments from unstable chromosomes occurred at cell division, while centric rings were not impeded. When dicentric chromosomes, or acentric fragments are found in 2nd mitosis, they show a characteristic differential staining, which means that chromatides at cell division fall free and are replicated in daughter cells. When plotting dose effect curves of dicentric chromosomes, up to 20% of 2nd mitosis fractions have little influence on the aberration rate. This may be additionally verified as part of the 'biological dosimetry' in a person with 24% of 2nd mitosis. When the rates of dicentric chromosomes exclusively evaluated from 1st mitosis after irradiation with 2.0 Gy were related to the donors age, no age-dependent sensitivity to radiation could be observed. Aberration rates which deviate from person to person are comparable to the results achieved by conventional staining methods. (orig./MG) [de

Expansion of donor-reactive host T cells in primary graft failure after allogeneic hematopoietic SCT following reduced-intensity conditioning.

Science.gov (United States)

Koyama, M; Hashimoto, D; Nagafuji, K; Eto, T; Ohno, Y; Aoyama, K; Iwasaki, H; Miyamoto, T; Hill, G R; Akashi, K; Teshima, T

2014-01-01

Graft rejection remains a major obstacle in allogeneic hematopoietic SCT following reduced-intensity conditioning (RIC-SCT), particularly after cord blood transplantation (CBT). In a murine MHC-mismatched model of RIC-SCT, primary graft rejection was associated with activation and expansion of donor-reactive host T cells in peripheral blood and BM early after SCT. Donor-derived dendritic cells are at least partly involved in host T-cell activation. We then evaluated if such an expansion of host T cells could be associated with graft rejection after RIC-CBT. Expansion of residual host lymphocytes was observed in 4/7 patients with graft rejection at 3 weeks after CBT, but in none of the 17 patients who achieved engraftment. These results suggest the crucial role of residual host T cells after RIC-SCT in graft rejection and expansion of host T cells could be a marker of graft rejection. Development of more efficient T cell-suppressive conditioning regimens may be necessary in the context of RIC-SCT.

Comparison of infusion pumps calibration methods

Science.gov (United States)

Batista, Elsa; Godinho, Isabel; do Céu Ferreira, Maria; Furtado, Andreia; Lucas, Peter; Silva, Claudia

2017-12-01

Nowadays, several types of infusion pump are commonly used for drug delivery, such as syringe pumps and peristaltic pumps. These instruments present different measuring features and capacities according to their use and therapeutic application. In order to ensure the metrological traceability of these flow and volume measuring equipment, it is necessary to use suitable calibration methods and standards. Two different calibration methods can be used to determine the flow error of infusion pumps. One is the gravimetric method, considered as a primary method, commonly used by National Metrology Institutes. The other calibration method, a secondary method, relies on an infusion device analyser (IDA) and is typically used by hospital maintenance offices. The suitability of the IDA calibration method was assessed by testing several infusion instruments at different flow rates using the gravimetric method. In addition, a measurement comparison between Portuguese Accredited Laboratories and hospital maintenance offices was performed under the coordination of the Portuguese Institute for Quality, the National Metrology Institute. The obtained results were directly related to the used calibration method and are presented in this paper. This work has been developed in the framework of the EURAMET projects EMRP MeDD and EMPIR 15SIP03.

Continuous indomethacin infusion may be less effective than bolus infusions for ductal closure in very low birth weight infants

NARCIS (Netherlands)

de Vries, NKS; Jagroep, FK; Jaarsma, AS; Elzenga, NJ; Bos, AF

The effectiveness of continuous indomethacin (INDO) infusion versus bolus infusions for closure of patent ductus arteriosus (PDA) was investigated. The study design was an open-label case series (continuous INDO) with historic controls matched for gestational age (bolus INDO). Ductal closure rates

Inter- and Intrapersonal Barriers to Living Donor Kidney Transplant among Black Recipients and Donors.

Science.gov (United States)

Davis, LaShara A; Grogan, Tracy M; Cox, Joy; Weng, Francis L

2017-08-01

End-stage renal disease (ESRD) is more common among Blacks, but Blacks are less likely to receive a live donor kidney transplant (LDKT). The objective of this study is to identify barriers and coping mechanisms that Black LDKT recipients and donors experienced while receiving or donating a kidney. A qualitative study was conducted using structured interviews. Thematic analysis was used for data interpretation. All 20 participants identified as Black, with two participants identifying themselves as multiracial. The mean age for the 14 recipients was 60, and the average age for the 6 living donors was 47. Themes emerging from the data suggest both recipients and donors faced barriers in the LDKT experience. Recipients faced barriers associated with their denial and avoidance of the severity of their ESRD, their desire to maintain the privacy of their health status, and their refusal to approach potential donors. Donors encountered negative responses from others about the donors' desire to donate and the initial refusal of recipients to accept a LDKT offer. Recipients identified faith as a coping mechanism, while donors identified normalization of donation as their method of coping. Various types of social support helped donors and recipients navigate the transplant process. Black LDKT recipients and donors must overcome barriers prior to receiving or donating a kidney. Most of these barriers arise from communication and interactions with others that are either lacking or undesirable. Future interventions to promote LDKT among Blacks may benefit by specifically targeting these barriers.

Alternative allogeneic donor sources for transplantation for childhood diseases: unrelated cord blood and haploidentical family donors.

Science.gov (United States)

Cairo, Mitchell S; Rocha, Vanderson; Gluckman, Eliane; Hale, Gregory; Wagner, John

2008-01-01

Allogeneic stem cell transplantation has been demonstrated to be curative in a wide variety of pediatric malignant and nonmalignant diseases, and can be traced back over 50 years ago to the original report of Thomas et al. HLA matched sibling donors have been the gold standard for pediatric recipients requiring allogeneic donors for both nonmalignant and malignant conditions. However, only 25% of potential pediatric recipients possesses an HLA-matched sibling donor, and the frequency is even less in those with genetic nonmalignant conditions because of genetically affected other siblings within the family. Therefore, 75% to 90% of potential pediatric recipients require alternative allogeneic donor cells for treatment of their underlying conditions. Potential alternative allogeneic donor sources include unrelated cord blood donors, unrelated adult donors, and haploidentical family donors. In this article we review the experience of both unrelated cord blood donor and haploidentical family donor transplants in selected pediatric malignant and nonmalignant conditions.

Vocal fold submucosal infusion technique in phonomicrosurgery.

Science.gov (United States)

Kass, E S; Hillman, R E; Zeitels, S M

1996-05-01

Phonomicrosurgery is optimized by maximally preserving the vocal fold's layered microstructure (laminae propriae). The technique of submucosal infusion of saline and epinephrine into the superficial lamina propria (SLP) was examined to delineate how, when, and why it was helpful toward this surgical goal. A retrospective review revealed that the submucosal infusion technique was used to enhance the surgery in 75 of 152 vocal fold procedures that were performed over the last 2 years. The vocal fold epithelium was noted to be adherent to the vocal ligament in 29 of the 75 cases: 19 from previous surgical scarring, 4 from cancer, 3 from sulcus vocalis, 2 from chronic hemorrhage, and 1 from radiotherapy. The submucosal infusion technique was most helpful when the vocal fold epithelium required resection and/or when extensive dissection in the SLP was necessary. The infusion enhanced the surgery by vasoconstriction of the microvasculature in the SLP, which improved visualization during cold-instrument tangential dissection. Improved visualization facilitated maximal preservation of the SLP, which is necessary for optimal pliability of the overlying epithelium. The infusion also improved the placement of incisions at the perimeter of benign, premalignant, and malignant lesions, and thereby helped preserve epithelium uninvolved by the disorder.

[An analysis of immunophenotyping of peripheral lymphocytes in adult patients with infectious mononucleosis and chronic active Epstein-Barr virus infection].

Science.gov (United States)

Xie, J; Wang, H L; Qiu, Z F; Li, T S

2016-06-01

To determine the immunophenotypic features of peripheral lymphocytes in adult patients with Epstein-Barr virus(EBV)-associated infectious mononucleosis(IM) and chronic active EBV infection (CAEBV). Eighteen IM patients, 12 CAEBV patients and 18 healthy donors were included. Lymphocyte subsets including CD3(-)CD19(+) B cells, CD3(-)CD16/56(+) NK cells, CD4(+) and CD8(+) T cells in peripheral blood were measured by flow cytometry. The expression of activation markers (HLA-DR and CD38) on CD8(+) T cells and CD28 expression on T cells were also determined. Kruskal-Wallis H and Mann-Whitney U tests were used to compare variables among groups. IM patients had dramatically increased CD8(+) T cell counts than healthy donors (5.22×10(9)/L vs 0.54×10(9)/L, P<0.001). B cell counts moderately reduced in patients with IM than in healthy donors. No difference was found in absolute CD4(+) T cell and NK cell counts between IM and healthy donors. The levels of HLA-DR and CD38 on CD8(+) T cells significantly increased in IM patients compared with those in healthy controls. The intensity of CD28 on CD8(+) T cells significantly decreased, which was not seen on CD4(+) T cells. The median cell counts of B, NK, CD4(+) T and CD8(+) T subsets in CAEBV patients were 0.02×10(9)/L, 0.06×10(9)/L, 0.26×10(9)/L and 0.21×10(9)/L respectively, which were significantly lower than those in healthy donors (0.22×10(9)/L, 0.38×10(9)/L, 0.78×10(9)/L, 0.54×10(9)/L)and IM patients (0.12×10(9)/L, 0.40×10(9)/L, 0.91×10(9)/L, 5.22×10(9)/L). The positive rates of HLA-DR and CD38 on CD8(+) T cells in CAEBV patients were higher than those in healthy controls, but lower than those in IM patients. The immunophenotypic pattern in adult patients with IM is characterized by a dramatic increase of extensively activated CD8(+) T cells, a moderate reduction of CD19(+) B cells and no significant change of CD4(+) T cells and CD16/56(+) NK cells. CAEBV is featured by an immunosuppression status as

Phosphodiesterase profile of human B lymphocytes from normal and atopic donors and the effects of PDE inhibition on B cell proliferation

Science.gov (United States)

Gantner, Florian; Götz, Christine; Gekeler, Volker; Schudt, Christian; Wendel, Albrecht; Hatzelmann, Armin

1998-01-01

CD19+ B lymphocytes were purified from the peripheral blood of normal and atopic subjects to analyse and compare the phosphodiesterase (PDE) activity profile, PDE mRNA expression and the importance of PDE activity for the regulation of B cell function.The majority of cyclic AMP hydrolyzing activity of human B cells was cytosolic PDE4, followed by cytosolic PDE7-like activity; marginal PDE3 activity was found only in the particulate B cell fraction. PDE1, PDE2 and PDE5 activities were not detected.By cDNA-PCR analysis mRNA of the PDE4 subtypes A, B (splice variant PDE4B2) and D were detected. In addition, a weak signal for PDE3A was found.No differences in PDE activities or mRNA expression of PDE subtypes were found in B cells from either normal or atopic subjects.Stimulation of B lymphocytes with the polyclonal stimulus lipopolysaccharide (LPS) induced a proliferative response in a time- and concentration-dependent manner, which was increased in the presence of interleukin-4 (IL-4). PDE4 inhibitors (rolipram, piclamilast) led to an increase in the cellular cyclic AMP concentration and to an augmentation of proliferation, whereas a PDE3 inhibitor (motapizone) was ineffective, which is in accordance with the PDE profile found. The proliferation enhancing effect of the PDE4 inhibitors was partly mimicked by the cyclic AMP analogues dibutyryl (db) cyclic AMP and 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole-3′,5′-cyclic monophosphorothioate, Sp-isomer (dcl-cBIMPS), respectively. However, at concentrations exceeding 100 μM db-cyclic AMP suppressed B lymphocyte proliferation, probably as a result of cytotoxicity. Prostaglandin E2 (PGE2, 1 μM) and forskolin (10 μM) did not affect B cell proliferation, even when given in combination with rolipram.Inhibition of protein kinase A (PKA) by differentially acting selective inhibitors (KT 5720, Rp-8-Br-cyclic AMPS) decreased the proliferative response of control cells and reversed the proliferation enhancing effects

Donor-Derived Myeloid Sarcoma in Two Kidney Transplant Recipients from a Single Donor

Directory of Open Access Journals (Sweden)

Amudha Palanisamy

2015-01-01

Full Text Available We report the rare occurrence of donor-derived myeloid sarcoma in two kidney transplant patients who received organs from a single deceased donor. There was no evidence of preexisting hematologic malignancy in the donor at the time of organ recovery. Both recipients developed leukemic involvement that appeared to be limited to the transplanted organ. Fluorescence in situ hybridization (FISH and molecular genotyping analyses confirmed that the malignant cells were of donor origin in each patient. Allograft nephrectomy and immediate withdrawal of immunosuppression were performed in both cases; systemic chemotherapy was subsequently administered to one patient. Both recipients were in remission at least one year following the diagnosis of donor-derived myeloid sarcoma. These cases suggest that restoration of the immune system after withdrawal of immunosuppressive therapy and allograft nephrectomy may be sufficient to control HLA-mismatched donor-derived myeloid sarcoma without systemic involvement.

Effect of a single intraoperative high-dose ATG-Fresenius on delayed graft function in donation after cardiac-death donor renal allograft recipients: a randomized study.

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van den Hoogen, Martijn W F; Kho, Marcia M L; Abrahams, Alferso C; van Zuilen, Arjan D; Sanders, Jan-Stephan; van Dijk, Marja; Hilbrands, Luuk B; Weimar, Willem; Hoitsma, Andries J

2013-04-01

Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with depleting anti-T-lymphocyte antibodies is coupled with a reduction of the dosage of the calcineurin inhibitor. The separate effect of anti-T-cell therapy on the incidence and duration of delayed graft function is therefore difficult to assess. We performed a randomized study to evaluate the effect of a single intraoperative high-dose of anti-T-lymphocyte immunoglobulin (ATG)-Fresenius (9 mg/kg body weight) on the incidence of delayed graft function. Eligible adult recipients of a first donation after cardiac death donor renal allograft were randomly assigned to ATG-Fresenius or no induction therapy. Maintenance immunosuppression consisted of tacrolimus, in an unadjusted dose, mycophenolate mofetil, and steroids. The study was prematurely terminated because of a lower-than-anticipated inclusion rate. Baseline characteristics were comparable in the ATG-Fresenius group (n=28) and the control group (n=24). Twenty-two patients in the ATG-Fresenius group (79%) had delayed graft function, compared with 13 in the control group (54%; P = .06). Allograft and patient survival were comparable in both groups. Serious adverse events occurred more frequently in the ATG-Fresenius group than they did in the control group (57% vs 29%; P Fresenius in donation after cardiac death donor renal allograft recipients, followed by triple immunosuppression with an unadjusted tacrolimus dose, seems ineffective to reduce the incidence of delayed graft function. Moreover, this was associated with a higher rate of serious adverse events (EudraCT-number, 2007-000210-36.).

Minimal contribution of severe hypertriglyceridemia in L-asparaginase-associated pancreatitis developed in a child with acute lymphocytic leukemia.

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Goto, Yoshinori; Nishimura, Ryosei; Nohara, Atsushi; Mase, Shintaro; Fujiki, Toshihiro; Irabu, Hitoshi; Kuroda, Rie; Araki, Raita; Ikawa, Yasuhiro; Maeba, Hideaki; Yachie, Akihiro

2016-08-01

A 10-year-old girl developed L-asparaginase (ASP)-associated pancreatitis during chemotherapy for acute lymphocytic leukemia. Her symptoms showed alleviation with continuous regional arterial infusion of protease inhibitor and systemic somatostatin analog therapy. She had intermittent and marked hypertriglyceridemia, an initial trigger for pancreatitis, probably as a side effect of ASP and steroids. However, we considered the pancreatitis to have developed mainly because of factors other than hypertriglyceridemia as lipoprotein analysis confirmed chylomicron levels to be nearly undetectable. Extremely large chylomicrons contribute directly to the onset of pancreatitis by causing blockage of small vessels. Although it is necessary to examine patients for dyslipidemia developing as a side effect of ASP, therapeutic intervention for hypertriglyceridemia is not considered to prevent the onset of ASP-associated pancreatitis.

Energy status of pig donor organs after ischemia is independent of donor type.

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Stadlbauer, Vanessa; Stiegler, Philipp; Taeubl, Philipp; Sereinigg, Michael; Puntschart, Andreas; Bradatsch, Andrea; Curcic, Pero; Seifert-Held, Thomas; Zmugg, Gerda; Stojakovic, Tatjana; Leopold, Barbara; Blattl, Daniela; Horki, Vera; Mayrhauser, Ursula; Wiederstein-Grasser, Iris; Leber, Bettina; Jürgens, Günther; Tscheliessnigg, Karlheinz; Hallström, Seth

2013-04-01

Literature is controversial whether organs from living donors have a better graft function than brain dead (BD) and non-heart-beating donor organs. Success of transplantation has been correlated with high-energy phosphate (HEP) contents of the graft. HEP contents in heart, liver, kidney, and pancreas from living, BD, and donation after cardiac death in a pig model (n=6 per donor type) were evaluated systematically. BD was induced under general anesthesia by inflating a balloon in the epidural space. Ten hours after confirmation, organs were retrieved. Cardiac arrest was induced by 9V direct current. After 10min of ventricular fibrillation without cardiac output, mechanical and medical reanimation was performed for 30min before organ retrieval. In living donors, organs were explanted immediately. Freeze-clamped biopsies were taken before perfusion with Celsior solution (heart) or University of Wisconsin solution (abdominal organs) in BD and living donors or with Histidine-Tryptophan-Ketoglutaric solution (all organs) in non-heart-beating donors, after perfusion, and after cold ischemia (4h for heart, 6h for liver and pancreas, and 12h for kidney). HEPs (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, and phosphocreatine), xanthine, and hypoxanthine were measured by high-performance liquid chromatography. Energy charge and adenosine triphosphate-to-adenosine diphosphate ratio were calculated. After ischemia, organs from different donor types showed no difference in energy status. In all organs, a decrease of HEP and an increase in hypoxanthine contents were observed during perfusion and ischemia, irrespective of the donor type. Organs from BD or non-heart-beating donors do not differ from living donor organs in their energy status after average tolerable ischemia. Copyright © 2013 Elsevier Inc. All rights reserved.

Frequency and risk factors for donor reactions in an anonymous blood donor survey.

Science.gov (United States)

Goldman, Mindy; Osmond, Lori; Yi, Qi-Long; Cameron-Choi, Keltie; O'Brien, Sheila F

2013-09-01

Adverse donor reactions can result in injury and decrease the likelihood of donor return. Reaction reports captured in the blood center's database provide an incomplete picture of reaction rates and risk factors. We performed an anonymous survey, mailed to 40,000 donors in 2008, including questions about symptoms, height, weight, sex, and donation status. Reaction rates were compared to those recorded in our database. Possible risk factors were assessed for various reactions. The response rate was 45.5%. A total of 32% of first-time and 14% of repeat donors reported having any adverse symptom, most frequently bruising (84.9 per 1000 donors) or feeling faint or weak (66.2 per 1000). Faint reactions were two to eight times higher than reported in our database, although direct comparison was difficult. Younger age, female sex, and first-time donation status were risk factors for systemic and arm symptoms. In females, low estimated blood volume (EBV) was a risk factor for systemic symptoms. Only 51% of donors who consulted an outside physician also called Canadian Blood Services. A total of 10% of first-time donors with reactions found adverse effects information inadequate. This study allowed us to collect more information about adverse reactions, including minor symptoms and delayed reactions. Based on our findings of the risk factors and frequency of adverse reactions, we are implementing more stringent EBV criteria for younger donors and providing more detailed information to donors about possible adverse effects and their management. © 2012 American Association of Blood Banks.

Molecular Characterization of Chronic Lymphocytic Leukemia Patients with a High Number of Losses in 13q14

Science.gov (United States)

Rodríguez, Ana Eugenia; Hernández, Jose Ángel; Benito, Rocío; Gutiérrez, Norma C.; García, Juan Luis; Hernández-Sánchez, María; Risueño, Alberto; Sarasquete, M. Eugenia; Fermiñán, Encarna; Fisac, Rosa; de Coca, Alfonso García; Martín-Núñez, Guillermo; de las Heras, Natalia; Recio, Isabel; Gutiérrez, Oliver; De Las Rivas, Javier; González, Marcos; Hernández-Rivas, Jesús M.

2012-01-01

Background Patients with chronic lymphocytic leukemia and 13q deletion as their only FISH abnormality could have a different outcome depending on the number of cells displaying this aberration. Thus, cases with a high number of 13q- cells (13q-H) had both shorter overall survival and time to first therapy. The goal of the study was to analyze the genetic profile of 13q-H patients. Design and Methods: A total of 102 samples were studied, 32 of which served as a validation cohort and five were healthy donors. Results Chronic lymphocytic leukemia patients with higher percentages of 13q- cells (>80%) showed a different level of gene expression as compared to patients with lower percentages (<80%, 13q-L). This deregulation affected genes involved in apoptosis and proliferation (BCR and NFkB signaling), leading to increased proliferation and decreased apoptosis in 13q-H patients. Deregulation of several microRNAs, such as miR-15a, miR-155, miR-29a and miR-223, was also observed in these patients. In addition, our study also suggests that the gene expression pattern of 13q-H cases could be similar to the patients with 11q- or 17p-. Conclusions This study provides new evidence regarding the heterogeneity of 13q deletion in chronic lymphocytic leukemia patients, showing that apoptosis, proliferation as well as miRNA regulation are involved in cases with higher percentages of 13q- cells. PMID:23152777

Infusion of radionuclides throughout pregnancy

International Nuclear Information System (INIS)

Mountford-Lister, P.G.; Lambert, B.E.; Milner, A.C.; Kang, X.Z.

1992-01-01

This work is part of a long-term study to examine the cancer incidence in the offspring of mice exposed to 239 Pu or 147 Pm throughout pregnancy. The need to model the human intake scenario and the possibility of a critical period during uterine development necessitates constant availability of radionuclides throughout pregnancy. Various methods (multiple daily injections, infusion by external cannula and infusion by indwelling osmotic pump) have been examined and osmotic infusion pumps chosen. These pumps result in a near-constant blood concentration for up to 21 days. Part of the study is the estimation of dose to the critical haemopoietic tissues of the pup from a knowledge of the radionuclide distribution and kinetics. At present the distribution has been followed from birth to 180 days. Activity in the suckling pups at 7 days old is around 1 percent of the infused activity, though most of this is accounted for by the contents of the stomach and gastrointestinal tract. The liver and femur account for around 0.025 percent and 0.012 percent respectively per pup. Activity increases in both liver and femur during lactation after which both concentration and activity fall with time. Long-term studies with the pups of dams exposed to a range of 239 Pu concentrations between 0-70 kBq/kg are underway. Correlation of average organ dose with tumour incidence will be determined at completion of the life-span study. (Author) 39 refs., 5 tabs., 6 figs

Alternative Donor Graft Sources for Adults with Hematologic Malignancies: A Donor for All Patients in 2017!

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Kindwall-Keller, Tamila L; Ballen, Karen K

2017-09-01

Hematopoietic stem cell transplant (HSCT) is potentially curative for a wide variety of malignant diseases, including acute and leukemias, lymphoma, and myelodysplasia. Choice of a stem cell donor is dependent on donor availability, donor compatibility and health, recipient disease type, and recipient condition. Current sources of stem cell donation for HSCT are matched sibling donors (MSDs), matched unrelated donors (MUDs), 1-antigen mismatched unrelated donors (MMUDs), haploidentical donors (haplo), and umbilical cord blood (UCB) units. Historically, preferred donors for HSCT have been human leukocyte antigen (HLA)-matched sibling donors; however, only about 30% of U.S. patients will have a MSD available. The majority of patients referred for HSCT will require an alternative donor graft: MUD, MMUD, UCB, or haplo. The likelihood of finding a MUD varies depending on the ethnicity of the recipient. White Caucasians of European descent have the greatest chance of finding a MUD. Chances of finding a MUD are significantly less for African-American or Hispanic recipients due to HLA polymorphisms. Therefore, MMUD, UCB, and haplo donor graft sources expand the donor pool for recipients who do not have a MSD or MUD available. Given the variety of different donor stem cell sources available today, nearly every patient who needs an allogeneic HSCT has a potential donor in 2017. All transplant-eligible patients with hematologic malignancies should be evaluated by a transplant center to determine if HSCT is a viable treatment option for their underlying disease process. The goal of this review is to increase the awareness of oncology practitioners to the availability of alternative donor stem cell transplants for patients with hematologic malignancies. Despite new agents, stem cell transplant remains the only curative therapy for many patients with acute and chronic leukemia, myelodysplasia, and lymphoma. Given the variety of different donor stem cell sources available today

Chemokines, lymphocytes, and HIV

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Farber J.M.

1998-01-01

Full Text Available Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-g and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3a, and STRL22 has been re-named CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit

SHARPIN Regulates Uropod Detachment in Migrating Lymphocytes

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Jeroen Pouwels

2013-11-01

Full Text Available SHARPIN-deficient mice display a multiorgan chronic inflammatory phenotype suggestive of altered leukocyte migration. We therefore studied the role of SHARPIN in lymphocyte adhesion, polarization, and migration. We found that SHARPIN localizes to the trailing edges (uropods of both mouse and human chemokine-activated lymphocytes migrating on intercellular adhesion molecule-1 (ICAM-1, which is one of the major endothelial ligands for migrating leukocytes. SHARPIN-deficient cells adhere better to ICAM-1 and show highly elongated tails when migrating. The increased tail lifetime in SHARPIN-deficient lymphocytes decreases the migration velocity. The adhesion, migration, and uropod defects in SHARPIN-deficient lymphocytes were rescued by reintroducing SHARPIN into the cells. Mechanistically, we show that SHARPIN interacts directly with lymphocyte-function-associated antigen-1 (LFA-1, a leukocyte counterreceptor for ICAM-1, and inhibits the expression of intermediate and high-affinity forms of LFA-1. Thus, SHARPIN controls lymphocyte migration by endogenously maintaining LFA-1 inactive to allow adjustable detachment of the uropods in polarized cells.

Laboratorial diagnosis of lymphocytic meningitis

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Sérgio Monteiro de Almeida

Full Text Available Meningitis is the main infectious central nervous system (CNS syndrome. Viruses or bacteria can cause acute meningitis of infectious etiology. The term "Aseptic Meningitis" denotes a clinical syndrome with a predominance of lymphocytes in the cerebrospinal fluid (CSF, with no common bacterial agents identified in the CSF. Viral meningitis is considered the main cause of lymphocyte meningitis. There are other etiologies of an infectious nature. CSF examination is essential to establish the diagnosis and to identify the etiological agent of lymphocytic meningitis. We examined CSF characteristics and the differential diagnosis of the main types of meningitis.

Dual-energy CT-cholangiography in potential donors for living-related liver transplantation: Improved biliary visualization by intravenous morphine co-medication

International Nuclear Information System (INIS)

Sommer, C.M.; Schwarzwaelder, C.B.; Stiller, W.; Schindera, S.T.; Heye, T.; Stampfl, U.; Bellemann, N.; Holzschuh, M.; Schmidt, J.; Weitz, J.; Grenacher, L.; Kauczor, H.U.; Radeleff, B.A.

2012-01-01

Purpose: To prospectively evaluate whether intravenous morphine co-medication improves bile duct visualization of dual-energy CT-cholangiography. Materials and methods: Forty potential donors for living-related liver transplantation underwent CT-cholangiography with infusion of a hepatobiliary contrast agent over 40 min. Twenty minutes after the beginning of the contrast agent infusion, either normal saline (n = 20 patients; control group [CG]) or morphine sulfate (n = 20 patients; morphine group [MG]) was injected. Forty-five minutes after initiation of the contrast agent, a dual-energy CT acquisition of the liver was performed. Applying dual-energy post-processing, pure iodine images were generated. Primary study goals were determination of bile duct diameters and visualization scores (on a scale of 0 to 3: 0—not visualized; 3—excellent visualization). Results: Bile duct visualization scores for second-order and third-order branch ducts were significantly higher in the MG compared to the CG (2.9 ± 0.1 versus 2.6 ± 0.2 [P < 0.001] and 2.7 ± 0.3 versus 2.1 ± 0.6 [P < 0.01], respectively). Bile duct diameters for the common duct and main ducts were significantly higher in the MG compared to the CG (5.9 ± 1.3 mm versus 4.9 ± 1.3 mm [P < 0.05] and 3.7 ± 1.3 mm versus 2.6 ± 0.5 mm [P < 0.01], respectively). Conclusion: Intravenous morphine co-medication significantly improved biliary visualization on dual-energy CT-cholangiography in potential donors for living-related liver transplantation

Dual-energy CT-cholangiography in potential donors for living-related liver transplantation: Improved biliary visualization by intravenous morphine co-medication

Energy Technology Data Exchange (ETDEWEB)

Sommer, C.M., E-mail: christof.sommer@med.uni-heidelberg.de [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg (Germany); Schwarzwaelder, C.B.; Stiller, W. [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg (Germany); Schindera, S.T. [Department of Diagnostic, Interventional, and Pediatric Radiology, University Hospital and University of Berne, Berne (Switzerland); Heye, T.; Stampfl, U.; Bellemann, N.; Holzschuh, M. [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg (Germany); Schmidt, J.; Weitz, J. [Department of General, Abdominal and Transplantation Surgery, University Hospital Heidelberg, Heidelberg (Germany); Grenacher, L.; Kauczor, H.U.; Radeleff, B.A. [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg (Germany)

2012-09-15

Purpose: To prospectively evaluate whether intravenous morphine co-medication improves bile duct visualization of dual-energy CT-cholangiography. Materials and methods: Forty potential donors for living-related liver transplantation underwent CT-cholangiography with infusion of a hepatobiliary contrast agent over 40 min. Twenty minutes after the beginning of the contrast agent infusion, either normal saline (n = 20 patients; control group [CG]) or morphine sulfate (n = 20 patients; morphine group [MG]) was injected. Forty-five minutes after initiation of the contrast agent, a dual-energy CT acquisition of the liver was performed. Applying dual-energy post-processing, pure iodine images were generated. Primary study goals were determination of bile duct diameters and visualization scores (on a scale of 0 to 3: 0—not visualized; 3—excellent visualization). Results: Bile duct visualization scores for second-order and third-order branch ducts were significantly higher in the MG compared to the CG (2.9 ± 0.1 versus 2.6 ± 0.2 [P < 0.001] and 2.7 ± 0.3 versus 2.1 ± 0.6 [P < 0.01], respectively). Bile duct diameters for the common duct and main ducts were significantly higher in the MG compared to the CG (5.9 ± 1.3 mm versus 4.9 ± 1.3 mm [P < 0.05] and 3.7 ± 1.3 mm versus 2.6 ± 0.5 mm [P < 0.01], respectively). Conclusion: Intravenous morphine co-medication significantly improved biliary visualization on dual-energy CT-cholangiography in potential donors for living-related liver transplantation.

Differences in Expansion Potential of Naive Chimeric Antigen Receptor T Cells from Healthy Donors and Untreated Chronic Lymphocytic Leukemia Patients

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Jean-Marc Hoffmann

2018-01-01

Full Text Available IntroductionTherapy with chimeric antigen receptor T (CART cells for hematological malignancies has shown promising results. Effectiveness of CART cells may depend on the ratio of naive (TN vs. effector (TE T cells, TN cells being responsible for an enduring antitumor activity through maturation. Therefore, we investigated factors influencing the TN/TE ratio of CART cells.Materials and methodsCART cells were generated upon transduction of peripheral blood mononuclear cells with a CD19.CAR-CD28-CD137zeta third generation retroviral vector under two different stimulating culture conditions: anti-CD3/anti-CD28 antibodies adding either interleukin (IL-7/IL-15 or IL-2. CART cells were maintained in culture for 20 days. We evaluated 24 healthy donors (HDs and 11 patients with chronic lymphocytic leukemia (CLL for the composition of cell subsets and produced CART cells. Phenotype and functionality were tested using flow cytometry and chromium release assays.ResultsIL-7/IL-15 preferentially induced differentiation into TN, stem cell memory (TSCM: naive CD27+ CD95+, CD4+ and CXCR3+ CART cells, while IL-2 increased effector memory (TEM, CD56+ and CD4+ T regulatory (TReg CART cells. The net amplification of different CART subpopulations derived from HDs and untreated CLL patients was compared. Particularly the expansion of CD4+ CARTN cells differed significantly between the two groups. For HDs, this subtype expanded >60-fold, whereas CD4+ CARTN cells of untreated CLL patients expanded less than 10-fold. Expression of exhaustion marker programmed cell death 1 on CARTN cells on day 10 of culture was significantly higher in patient samples compared to HD samples. As the percentage of malignant B cells was expectedly higher within patient samples, an excessive amount of B cells during culture could account for the reduced expansion potential of CARTN cells in untreated CLL patients. Final TN/TE ratio stayed <0.3 despite stimulation condition for patients

Circulating Lymphocyte Subsets 
in Patients with Lung Cancer and Their Prognostic Value

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Jun LUO

2011-08-01

Full Text Available Background and objective Lung cancer is one of the most common malignancies. The aim of this study is to investigate the relationship between the change of lymphocyte subsets in the peripheral blood of lung cancer patients and the survival rate. Methods Flow cytometry was used to measure the percentages of lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, CD25+, CD44+, and NK cells in peripheral blood obtained from 221 patients with primary lung cancer without any treatment and from 96 healthy blood donors as the control group. The result was combined with clinical and follow-up data and statistical analysis was conducted. Results The levels of CD3+ and CD8+ in the patient group are significantly lower compared with the control group, whereas the levels of CD4+/CD8+, CD19+, CD25+, CD44+, and NK cells are significantly higher (P<0.05. CD8+ is significantly higher in the small cell lung cancer (SCLC group compared with the non-small cell lung cancer (NSCLC group. However, CD4+ and CD4+/CD8+ are lower in SCLC (P<0.05. There were no significant differences in different stages and differentiation (P>0.05 in the NSCLC group. The level of CD3+ was significantly higher compared with the pre-chemotherapy group, but NK cell, CD19+, and CD44+ were distinctly lower in the post-chemotherapy group (P<0.05. More survival opportunities will be obtained for patients with no increase in CD44+ after chemotherapy (P=0.021, but the other three indices have no obvious influence on survival. Conclusion Widespread changes of lymphocyte occur in the peripheral blood of patients with lung cancer. There is a significant correlation between the change of CD44+ and the prognosis after chemotherapy.

Promoting Organ Donor Registries Through Public Education: What Is the Cost of Securing Organ Donors?

Science.gov (United States)

Razdan, Manik; Smith, Kenneth J; Bryce, Cindy L; Degenholtz, Howard B

2016-06-01

Transplant medicine's impact on America's public health is seriously limited by acute shortage of transplantable organs. Consequently, the United Sates has witnessed considerable investment in the promotion of organ donor registries. Although there is no evidence to support that donor registry promotion alleviates organ shortage, this belief continues to drive investments into registry promotion. In this study, return on investment in donor registry promotion was examined using cost-outcomes analysis. Cost of promoting the donor registry was estimated in US dollars whereas the outcome was measured as the number of individuals who join the registry (registrants) and their value in terms of organ donors. The study was conducted from the perspective of a regional Organ Procurement Organization (OPO). Costs were directly obtained from the OPO. The number of new registrants was obtained from the OPO and the departments of motor vehicles that maintain the donor registry. The value of registrants in terms of organ donors was computed based on a registrant's age-dependent risk of dying and age-dependent probability of becoming an organ donor. Six thousand seven hundred eight individuals joined the organ donor registry (95% confidence interval [95% CI], 5429-7956) at a cost of $455 per registrant (95% CI, US $383-US $562). These individuals result in 4.2 present-day donors (95% CI, 2.5-6.6) at a cost of US $726 000 (95% CI, US $462000-US $1.2 million). Because the cost per registrant and cost per donor is less than society's willingness to pay, donor registry promotion offers positive return on investment. Investment in registry promotion should at the minimum be maintained at current levels.

Design of Infusion Schemes for Neuroreceptor Imaging

DEFF Research Database (Denmark)

Feng, Ling; Svarer, Claus; Madsen, Karine

2016-01-01

for bolus infusion (BI) or programmed infusion (PI) experiments. Steady-state quantitative measurements can be made with one short scan and venous blood samples. The GABAA receptor ligand [(11)C]Flumazenil (FMZ) was chosen for this purpose, as it lacks a suitable reference region. Methods. Five bolus [(11)C...... state was attained within 40 min, which was 8 min earlier than the optimal BI (B/I ratio = 55 min). Conclusions. The system can design both BI and PI schemes to attain steady state rapidly. For example, subjects can be [(11)C]FMZ-PET scanned after 40 min of tracer infusion for 40 min with venous...

Does prolonged β-lactam infusions improve clinical outcomes compared to intermittent infusions? A meta-analysis and systematic review of randomized, controlled trials

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Van Arendonk Kyle J

2011-06-01

Full Text Available Abstract Background The emergence of multi-drug resistant Gram-negatives (MDRGNs coupled with an alarming scarcity of new antibiotics has forced the optimization of the therapeutic potential of available antibiotics. To exploit the time above the minimum inhibitory concentration mechanism of β-lactams, prolonging their infusion may improve outcomes. The primary objective of this meta-analysis was to determine if prolonged β-lactam infusion resulted in decreased mortality and improved clinical cure compared to intermittent β-lactam infusion. Methods Relevant studies were identified from searches of MEDLINE, EMBASE, and CENTRAL. Heterogeneity was assessed qualitatively, in addition to I2 and Chi-square statistics. Pooled relative risks (RR and 95% confidence intervals (CI were calculated using Mantel-Haenszel random-effects models. Results Fourteen randomized controlled trials (RCTs were included. Prolonged infusion β-lactams were not associated with decreased mortality (n= 982; RR 0.92; 95% CI:0.61-1.37 or clinical cure (n = 1380; RR 1.00 95% CI:0.94-1.06 compared to intermittent infusions. Subgroup analysis for β-lactam subclasses and equivalent total daily β-lactam doses yielded similar results. Most studies had notable methodological flaws. Conclusions No clinical advantage was observed for prolonged infusion β-lactams. The limited number of studies with MDRGNs precluded evaluation of prolonged infusion of β-lactams for this subgroup. A large, multicenter RCT with critically ill patients infected with MDRGNs is needed.

Donor selection criteria and procurement

International Nuclear Information System (INIS)

Agcaoili, N.R.

1999-01-01

Donor selection is one of the most important aspects of tissue banking practice. Without a good donor selection criteria, the results of any effort of trying to preserve tissues will have disastrous outcome for the recipient of these tissues. While with a very good and strict donor selection the Tissue Bank can guarantee safe and effective tissue allografts. There are significant aspects in the history and physical examination of the donor that must be emphasized. A donor exclusion criteria has also been formulated together with a list of all the needed laboratory examinations to eliminate possible diseases that may be transferred from the donor. The methods of procurement of tissue allografts from living and cadaver donors will be described. The limitations and advantages of each will be taken.There are also special restrictions that are important in the practice of removing the tissues from the donors. All the necessary equipment should be ready and the potential risk on the personnel should be known to all doing Tissue Banking

[Survey of blood donors on the topic of "reimbursement for blood donors"].

Science.gov (United States)

Zeiler, T; Kretschmer, V

1995-02-01

Remuneration for blood donors, in the way as presently handled by governmental and communal blood transfusion services in Germany, is not generally accepted. It is feared that donors are recruited with increased risk to transmit infectious diseases, especially AIDS. Alternative incentives are discussed. After the so-called AIDS scandal in Germany, a change in the donor motivation was to be expected, associated with an increased willingness to renounce remuneration. Therefore, we performed the present survey, in which we evaluated the donor's willingness to renounce remuneration, possibilities of cashless remuneration and other alternative incentives. During March and April 1994, a total of 1,157 blood donors of the University Blood Bank Marburg were questioned anonymously by a questionnaire in the framework of whole-blood donations. Beside the above-mentioned aspects demoscopic data were included (age, sex, profession, journey). Cutting of remuneration without any other compensation was refused by 86.1% of the donors, 77% would not want to further donate blood in this case. Transfer of money to a bank account instead of cash payment was accepted by 78.6%, the use of non-negotiable cheques by 68.7%. Alternative compensation by tickets for theater, concert, cinema or coupons for restaurants met with the approval of only 27.3%; under these circumstances, 36.9% would be willing to continue blood donation. With increasing age and number of donations, but largely independent of social status, donors attached greater importance to retention of remuneration. Cutting of remuneration would result in a considerable reduction of the willingness to donate blood within the population of donors of the governmental and communal blood transfusion services. However, an increase of virus safety of the blood products would not be reached in this way, since especially the long-term donors would be driven away. Considerable bottlenecks, particularly in the specific blood supply of

Intravenous lidocaine infusion--a new treatment of chronic painful diabetic neuropathy?

DEFF Research Database (Denmark)

Kastrup, J; Petersen, P; Dejgård, A

1987-01-01

after lidocaine infusion compared to after saline infusion (P less than 0.05 and P less than 0.02, respectively). The duration of the individual effect ranged from 3 to 21 days. Lidocaine infusion had no effect on the objective measurements of neuropathy. Intravenous lidocaine infusion seems to be a new...

Effect of radiotherapy on lymphocyte cytotoxicity in vitro

Energy Technology Data Exchange (ETDEWEB)

Wasserman, J; Melen, B [Central Microbiological Laboratory, Stockholm County Council (Sweden); Blomgren, H; Glas, U; Perlmann, P

1975-11-01

The cytotoxic functions of highly purified blood lymphocytes from patients with breast cancer were studied before and after radiotherapy. Addition of PHA or of rabbit antibodies to target cells (chicken erythrocytes) were chosen as two means of inducing lymphocyte cytotoxicity in vitro. The proportion of T and non-T lymphocytes was determined by means of E and EAC rosette tests. The antibody-induced cytotoxicity of lymphocytes decreased following radiotherapy while that mediated by PHA remained unchanged. There was some reduction in the percentage of EAC rosette-forming cells. These results, as well as earlier observations, suggest that the decrease in the peripheral blood of the proportion of lymphocytes with receptors for activated complement is responsible for changes in the antibody-mediated lymphocyte cytotoxicity.

Measurement of exercise-induced oxidative stress in lymphocytes.

Science.gov (United States)

Turner, James E; Bosch, Jos A; Aldred, Sarah

2011-10-01

Vigorous exercise is associated with oxidative stress, a state that involves modifications to bodily molecules due to release of pro-oxidant species. Assessment of such modifications provides non-specific measures of oxidative stress in human tissues and blood, including circulating lymphocytes. Lymphocytes are a very heterogeneous group of white blood cells, consisting of subtypes that have different functions in immunity. Importantly, exercise drastically changes the lymphocyte composition in blood by increasing the numbers of some subsets, while leaving other cells unaffected. This fact may imply that observed changes in oxidative stress markers are confounded by changes in lymphocyte composition. For example, lymphocyte subsets may differ in exposure to oxidative stress because of subset differences in cell division and the acquisition of cytotoxic effector functions. The aim of the present review is to raise awareness of interpretational issues related to the assessment of oxidative stress in lymphocytes with exercise and to address the relevance of lymphocyte subset phenotyping in these contexts.

A human monoclonal antibody drug and target discovery platform for B-cell chronic lymphocytic leukemia based on allogeneic hematopoietic stem cell transplantation and phage display

OpenAIRE

Baskar, Sivasubramanian; Suschak, Jessica M.; Samija, Ivan; Srinivasan, Ramaprasad; Childs, Richard W.; Pavletic, Steven Z.; Bishop, Michael R.; Rader, Christoph

2009-01-01

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only potentially curative treatment available for patients with B-cell chronic lymphocytic leukemia (B-CLL). Here, we show that post-alloHSCT antibody repertoires can be mined for the discovery of fully human monoclonal antibodies to B-CLL cell-surface antigens. Sera collected from B-CLL patients at defined times after alloHSCT showed selective binding to primary B-CLL cells. Pre-alloHSCT sera, donor sera, and control sera w...

The impact of meeting donor management goals on the number of organs transplanted per donor: results from the United Network for Organ Sharing Region 5 prospective donor management goals study.

Science.gov (United States)

Malinoski, Darren J; Patel, Madhukar S; Daly, Michael C; Oley-Graybill, Chrystal; Salim, Ali

2012-10-01

Many organ procurement organizations have implemented critical care end points as donor management goals in efforts to increase organs transplanted per donor after neurologic determination of death. Although retrospective studies have demonstrated an association between meeting donor management goals and organ yield, prospective studies are lacking. In June 2008, nine donor management goals were prospectively implemented as a checklist and every donor after neurologic determination of death was managed to meet them. The donor management goals represented normal cardiovascular, pulmonary, renal, and endocrine end points. Data were collected for 7 months. Donor management goals "met" was defined a priori as achieving any seven of the nine donor management goals, and this was recorded at the time of consent, 12-18 hrs later, and prior to organ recovery. The primary outcome measure was ≥4 organs transplanted per donor, and binary logistic regression was used to identify independent predictors of this outcome with a porgan procurement organizations in the five Southwestern United States (United Network for Organ Sharing Region 5). All standard criteria donors after neurologic determination of deaths. Prospective implementation of a donor management goal checklist. There were 380 standard criteria donors with 3.6±1.7 organs transplanted per donor. Fifteen percent had donor management goals met at the time of consent, 33% at 12-18 hrs, and 38% prior to organ recovery. Forty-eight percent had ≥4 organs transplanted per donor. Donors with ≥4 organs transplanted per donor had significantly more individual donor management goals met at all three time points. Independent predictors of ≥4 organs transplanted per donor were age (odds ratio=0.95 per year), final creatinine (odds ratio=0.75 per 1-unit increase), donor management goals "met" at consent (odds ratio=2.03), donor management goals "met" prior to organ recovery (odds ratio=2.34), and a change in the number of

Development of Organ-Specific Donor Risk Indices

Science.gov (United States)

Akkina, Sanjeev K.; Asrani, Sumeet K.; Peng, Yi; Stock, Peter; Kim, Ray; Israni, Ajay K.

2012-01-01

Due to the shortage of deceased donor organs, transplant centers accept organs from marginal deceased donors, including older donors. Organ-specific donor risk indices have been developed to predict graft survival using various combinations of donor and recipient characteristics. We will review the kidney donor risk index (KDRI) and liver donor risk index (LDRI) and compare and contrast their strengths, limitations, and potential uses. The Kidney Donor Risk Index has a potential role in developing new kidney allocation algorithms. The Liver Donor Risk Index allows for greater appreciation of the importance of donor factors, particularly for hepatitis C-positive recipients; as the donor risk index increases, rates of allograft and patient survival among these recipients decrease disproportionately. Use of livers with high donor risk index is associated with increased hospital costs independent of recipient risk factors, and transplanting livers with high donor risk index into patients with Model for End-Stage Liver Disease scores Donor Risk Index has limited this practice. Significant regional variation in donor quality, as measured by the Liver Donor Risk Index, remains in the United States. We also review other potential indices for liver transplant, including donor-recipient matching and the retransplant donor risk index. While substantial progress has been made in developing donor risk indices to objectively assess donor variables that affect transplant outcomes, continued efforts are warranted to improve these indices to enhance organ allocation policies and optimize allograft survival. PMID:22287036

Forearm metabolism during infusion of adrenaline

DEFF Research Database (Denmark)

Simonsen, L; Stefl, B; Bülow, J

2000-01-01

Human skeletal muscle metabolism is often investigated by measurements of substrate fluxes across the forearm. To evaluate whether the two forearms give the same metabolic information, nine healthy subjects were studied in the fasted state and during infusion of adrenaline. Both arms were...... catheterized in a cubital vein in the retrograde direction. A femoral artery was catheterized for blood sampling, and a femoral vein for infusion of adrenaline. Forearm blood flow was measured by venous occlusion strain-gauge plethysmography. Forearm subcutaneous adipose tissue blood flow was measured...... by the local 133Xe washout method. Metabolic fluxes were calculated as the product of forearm blood flow and a-v differences of metabolite concentrations. After baseline measurements, adrenaline was infused at a rate of 0.3 nmol kg-1 min-1. No difference in the metabolic information obtained in the fasting...

ArtsIN: Arts Integration and Infusion Framework

Science.gov (United States)

Hartle, Lynn C.; Pinciotti, Patricia; Gorton, Rebecca L.

2015-01-01

Teaching to meet the diverse learning needs of twenty-first century, global learners can be challenging, yet a growing body of research points to the proved successes of arts-infused and integrated curricula, especially for building capacity for learning and motivation. This article presents the ArtsIN: Arts Integration and Infusion framework, a…

Bupivacaine constant continuous surgical wound infusion versus continuous epidural infusion for post cesarean section pain, randomized placebo-controlled study

Directory of Open Access Journals (Sweden)

Hossam A. ELShamaa

2016-10-01

Conclusion: The current study demonstrated that bupivacaine administered by continuous epidural infusion provided a significantly lower pain scores with mobilization, and hence better analgesia for post cesarean section pain in the first postoperative day compared to continuous bupivacaine wound infusion through fenestrated catheter using the constant flow PainFusor system.

Metal ion levels and lymphocyte counts

DEFF Research Database (Denmark)

Penny, Jeannette Ø; Varmarken, Jens-Erik; Ovesen, Ole

2013-01-01

BACKGROUND AND PURPOSE: Wear particles from metal-on-metal arthroplasties are under suspicion for adverse effects both locally and systemically, and the DePuy ASR Hip Resurfacing System (RHA) has above-average failure rates. We compared lymphocyte counts in RHA and total hip arthroplasty (THA) an....../ppb. INTERPRETATION: Circulating T-lymphocyte levels may decline after surgery, regardless of implant type. Metal ions-particularly cobalt-may have a general depressive effect on T- and B-lymphocyte levels. Registered with ClinicalTrials.gov under # NCT01113762.......BACKGROUND AND PURPOSE: Wear particles from metal-on-metal arthroplasties are under suspicion for adverse effects both locally and systemically, and the DePuy ASR Hip Resurfacing System (RHA) has above-average failure rates. We compared lymphocyte counts in RHA and total hip arthroplasty (THA....... RESULTS: The T-lymphocyte counts for both implant types declined over the 2-year period. This decline was statistically significant for CD3(+)CD8(+) in the THA group, with a regression coefficient of -0.04 × 10(9)cells/year (95% CI: -0.08 to -0.01). Regression analysis indicated a depressive effect...

Chronic lymphocytic leukemia/small lymphocytic lymphoma presenting as septic arthritis of the shoulder

Energy Technology Data Exchange (ETDEWEB)

Donovan, Andrea; Schweitzer, Mark E.; Nomikos, George [NYU Hospital for Joint Diseases, New York, NY (United States); Garcia, Roberto A. [Bellevue Hospital Center, New York, NY (United States)

2008-11-15

We report a case of a 53-year-old man presenting with shoulder pain mimicking septic arthritis. Laboratory findings were atypical. Biopsy performed to assess for possible osteomyelitis demonstrated chronic lymphocytic leukemia/small lymphocytic lymphoma. Intra-articular lymphoma is a rare but important consideration in patients with atypical clinical presentation. Imaging alone may be insufficient to render diagnosis as lymphoma can mimic infection, synovial hypertrophic processes, and depositional arthropathy. (orig.)

Evaluation of radio-induced DNA damage and their repair in human lymphocytes by comet assay or single cell gel electrophoresis; Avaliacao do dano radioinduzido no DNA e reparo em linfocitos humanos pelo metodo do cometa (single cell gel electrophoresis)

Energy Technology Data Exchange (ETDEWEB)

Nascimento, Patricia A. do; Suzuki, Miriam F.; Okazaki, Kayo [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil)

1997-12-01

The comet assay, also called single cell gel electrophoresis technique, permits to evaluate quantitatively DNA breakage induced by chemical and physical agents at the level of the single cell. The present paper refers to the construction of dose-response curves to DNA damage and repair studies in human peripheral lymphocytes, utilizing the comet assay for the radiosensitivity analysis. So, the blood samples were obtained from healthy donors (40-50 year old), irradiated in a {sup 60} Co source (GAMMACEL 220) with doses of 0.17, 0.25, 0.57, 1.10, 2.12 and 4.22 Gy (0.59 Gy/min.) and processed 1 and 24 hours after the exposition. Results obtained showed a increase in the total lenght of comet (DNA migration) as a function of radiation dose in samples processed 1 and 24 hours after the treatment. The DNA lesion in irradiated lymphocytes with 4.22 Gy (means value of 101.4 {mu}m) were 3.4 times higher than in the untreated lymphocytes (mean value of 30 {mu}m) instead of 24 hours after the irradiation were 1.5 times higher (mean value of 46.3 {mu}m). This reduction on DNA repair occurred in these cells. It was also possible visualized the presence of subpopulations of the cells with different sensitivity and repair capacity to ionizing radiation in these donors. (author). 8 refs., 3 figs.

Human decellularized bone scaffolds from aged donors show improved osteoinductive capacity compared to young donor bone.

Directory of Open Access Journals (Sweden)

Christopher A Smith

Full Text Available To improve the safe use of allograft bone, decellularization techniques may be utilized to produce acellular scaffolds. Such scaffolds should retain their innate biological and biomechanical capacity and support mesenchymal stem cell (MSC osteogenic differentiation. However, as allograft bone is derived from a wide age-range, this study aimed to determine whether donor age impacts on the ability an osteoinductive, acellular scaffold produced from human bone to promote the osteogenic differentiation of bone marrow MSCs (BM-MSC. BM-MSCs from young and old donors were seeded on acellular bone cubes from young and old donors undergoing osteoarthritis related hip surgery. All combinations resulted in increased osteogenic gene expression, and alkaline phosphatase (ALP enzyme activity, however BM-MSCs cultured on old donor bone displayed the largest increases. BM-MSCs cultured in old donor bone conditioned media also displayed higher osteogenic gene expression and ALP activity than those exposed to young donor bone conditioned media. ELISA and Luminex analysis of conditioned media demonstrated similar levels of bioactive factors between age groups; however, IGF binding protein 1 (IGFBP1 concentration was significantly higher in young donor samples. Additionally, structural analysis of old donor bone indicated an increased porosity compared to young donor bone. These results demonstrate the ability of a decellularized scaffold produced from young and old donors to support osteogenic differentiation of cells from young and old donors. Significantly, the older donor bone produced greater osteogenic differentiation which may be related to reduced IGFBP1 bioavailability and increased porosity, potentially explaining the excellent clinical results seen with the use of allograft from aged donors.

Delivery interaction between co-infused medications: an in vitro modeling study of microinfusion.

Science.gov (United States)

Tsao, Amy C; Lovich, Mark A; Parker, Michael J; Zheng, Hui; Peterfreund, Robert A

2013-01-01

To test the hypothesis that steady-state drug delivery by continuous infusion is predictably affected by a second drug infusion in the same lumen. Clinicians commonly administer two drugs by continuous infusion through one central venous catheter lumen (co-infusion). To limit fluid delivery, low flow rate carriers transport concentrated drug solutions; a method called microinfusion. How microinfusion delivery of one drug is affected by a second drug infusion has not been explored. Two water-soluble dyes, tartrazine and erioglaucine, infused at 3 ml · h(-1), modeled drug delivery through a four stopcock linear manifold and catheter lumen. A pump drove a carrier fluid (10 ml · h(-1)). After tartrazine reached steady-state delivery, erioglaucine entered downstream or upstream of the tartrazine infusion. Quantitative spectrophotometry measured dye delivery. Starting erioglaucine's infusion upstream of tartrazine's entry caused a transient tartrazine bolus (duration 10 min, peak drug delivery 20% higher than target levels). Starting erioglaucine's infusion downstream produced a similar amplitude, briefer, bolus. Stopping the erioglaucine infusion caused a transient reduction in tartrazine delivery. Measured delivery profiles were comparable to prediction models. We confirmed the hypothesis that delivery of one infused drug is transiently affected by starting or stopping a second drug infusion in the same line. The magnitude of the changes can be estimated quantitatively. The clinical impact depends on the drugs being co-infused and patient sensitivity, but could be clinically important; the findings have safety implications for infused medication delivery to critically ill or anesthetized children. We recommend minimizing infusion system dead volumes, connecting the most essential infusion(s) to the main fluid pathway as close as possible to the patient, and recognizing the potential for unintended alterations in delivery when multiple drugs co-infuse. © 2012

Continuous infusion of chemotherapy: focus on 5-fluorouracil and fluorodeoxyuridine

NARCIS (Netherlands)

Poorter, R. L.; Bakker, P. J.; Veenhof, C. H.

1998-01-01

Continuous infusion of chemotherapy is one of the developments to try to improve the treatment of metastatic cancer. There is a sound theoretical rationale to deliver cytotoxic drugs as a continuous infusion. Furthermore, the development of reliable venous access devices and portable infusion pumps

Genotoxic and cytotoxic effects of different types of dental cement on normal cultured human lymphocytes.

Science.gov (United States)

Bakopoulou, A; Mourelatos, D; Tsiftsoglou, A S; Giassin, N P; Mioglou, E; Garefis, P

2009-01-31

In this study we have investigated the genotoxic and cytotoxic effects of eluates derived from different types of commercially available dental cements, including glass ionomer cements (GICs) (Ketac Cem/3M ESPE and GC Fuji I/GC Corp), resin-modified glass ionomer cements (RM-GICs) (RelyX Luting/3M ESPE and Vitrebond/3M ESPE) and dual-cure resin cements (RCs) (Variolink II/ Ivoclar-Vivadent and Panavia F 2.0/Kuraray) on normal cultured human lymphocytes. Lymphocyte primary cultures obtained from blood samples of three healthy donors were exposed to serial dilutions of eluates derived from specimens of each material tested. Metaphases were induced with phytohaemagglutinin, collected after 72h treatment by use of colchicine and stained according to the fluorescence plus giemsa (FPG) procedure. Preparations were scored for sister chromatid exchange (SCE) and chromosomal aberrations (CAs), while the proliferation rate index (PRI) was also calculated. Our results show that eluates derived from the RM-GICs and RCs caused severe genotoxic effects by significantly increasing the frequencies of SCEs and CAs in cultures of peripheral blood lymphocytes and by decreasing the relevant PRI values in a dose-dependent manner, whereas the two GICs caused only minor cytogenetic effects. Eluates of the two RM-GICs (Vitrebond and RelyX) were also very cytotoxic, as the first serial dilutions of both materials caused a complete mitotic arrest in lymphocyte cultures. Overall, the degree of genotoxicity and cytotoxicity caused by dental cements decreased as follows: Viterbond>Rely X>Panavia F 2.0>Variolink II>Ketac Cem=GC Fuji I. These results indicate that different types of dental cement differ extensively in their genotoxic and cytotoxic potential and their ability to affect chromosomal integrity, cell-cycle progression, DNA replication and repair. Although these results cannot be directly extrapolated to the clinical situation, the potential occurrence of adverse effects caused by the

Outcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the société Francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

Science.gov (United States)

Roux, C; Tifratene, K; Socié, G; Galambrun, C; Bertrand, Y; Rialland, F; Jubert, C; Pochon, C; Paillard, C; Sirvent, A; Nelken, B; Vannier, J P; Freycon, C; Beguin, Y; Raus, N; Yakoub-Agha, I; Mohty, M; Dalle, J-H; Michel, G; Pradier, C; Peffault de Latour, R; Rohrlich, P-S

2017-05-01

Allogeneic hematopoietic stem cell transplantation (SCT) contributes to improved outcome in childhood acute leukemia (AL). However, therapeutic options are poorly defined in the case of post-transplantation relapse. We aimed to compare treatment strategies in 334 consecutive children with acute leukemia relapse or progression after SCT in a recent 10-year period. Data could be analyzed in 288 patients (157 ALL, 123 AML and 8 biphenotypic AL) with a median age of 8.16 years at transplantation. The median delay from first SCT to relapse or progression was 182 days. The treatment consisted of chemotherapy alone (n=108), chemotherapy followed by second SCT (n=70), supportive/palliative care (n=67), combination of chemotherapy and donor lymphocyte infusion (DLI; n=30), or isolated reinfusion of donor lymphocytes (DLI; n=13). The median OS duration after relapse was 164 days and differed according to therapy: DLI after chemotherapy=385 days, second allograft=391 days, chemotherapy=174 days, DLI alone=140 days, palliative care=43 days. A second SCT or a combination of chemotherapy and DLI yielded similar outcome (hazard ratio (HR)=0.85, P=0.53) unlike chemotherapy alone (HR=1.43 P=0.04), palliative care (HR=4.24, P<0.0001) or isolated DLI (HR=1,94, P<0.04). Despite limitations in this retrospective setting, strategies including immunointervention appear superior to other approaches, mostly in AML.

A microculture technique for rat lymphocyte transformation.

Science.gov (United States)

Lindsay, V J; Allardyce, R A

1979-01-01

We report the development of an economical microculture technique suitable for measuring rat lymphocyte response to mitogens and in mixed lymphocyte reactions. The effects of varying culture conditions, i.e. source of serum, addition and concentration of 2-mercaptoethanol, mitogen concentrations, culture incubation times, absorption of serum, lymphocyte numbers and microtitre plate well shape are described.

Damage of lymphocytes by ionizing irradiation

International Nuclear Information System (INIS)

Rose, H.; Moldenhauer, H.; Kehrberg, G.

1985-01-01

After a short review, how lymphocytes of the peripheral blood are influenced by radiotherapy, the damage of lymphocytes by whole-body irradiation is pointed out in animal experiments and after in vitro irradiation. The special sensibility of B-cells and their homogeneity in fields of radiobiology are opposed to the heterogeneity of T-cells. The radiosensibility of cytotoxic lymphocytes, suppressor cells, and helper cells are discussed. It appears, that within these functional criteria, there is a different radiosensibility, too. (author)

Safe and tolerable one-hour pamidronate infusion for multiple myeloma patients

Directory of Open Access Journals (Sweden)

Dimitrios Chantzichristos

2008-09-01

Full Text Available Dimitrios Chantzichristos, Andréasson Björn, Johansson PeterDepartment of Internal Medicine, Uddevalla Hospital, Uddevalla, SwedenBackground: Once a month, patients with multiple myeloma received an infusion of bisphosphonates, principally to reduce osteoclastic bone resorption. Recommended infusion time for pamidronate is 2 hours in the US and 4 hours in Europe because of its potential nephrotoxicity. From 2003, a 90 mg infusion of pamidronate was provided over 1 hour to patients with no pre-existing renal impairment, in the Daily Care Unit at Uddevalla Hospital.Method: Retrospective analysis of the renal deterioration, serum calcium, and adverse effects in patients with multiple myeloma treated with 1-hour pamidronate 90 mg infusion from January 2003 to April 2007.Results: Seventy-nine patients provided valuable data. A total number of 846 infusions were given and the median number of infusion to each patient was 11. Significant creatinine elevation was seen in 7 patients (8.9%, after 19 infusions (2.2%. Renal deterioration occurred in 5 of these 7 patients, which was related to progress of the myeloma or opportunistic infections. Prevalence of infusion-related events was 0.8% and the mean total S-Ca was 0.05 mmol/L lower than the baseline.Conclusion: Few events of renal deterioration, hypocalcemia, or other adverse effects resulted from a 1-hour pamidronate 90 mg infusion for multiple myeloma patients with no pre-existing renal impairment.Keywords: bisphosphonates, pamidronate, multiple myeloma, infusion time

Septal co-infusions of glucose with the benzodiazepine agonist chlordiazepoxide impair memory, but co-infusions of glucose with the opiate morphine do not.

Science.gov (United States)

Krebs-Kraft, Desiree L; Parent, Marise B

2010-03-30

We have found repeatedly that medial septal (MS) infusions of glucose impair memory when co-infused with the gamma-amino butyric acid (GABA) agonist muscimol. The present experiments sought to determine whether the memory-impairing effects of this concentration of glucose would generalize to another GABA(A) receptor agonist and to an agonist from another neurotransmitter system that is known to impair memory. Specifically, we determined whether the dose of glucose that produces memory deficits when combined with muscimol in the MS would also impair memory when co-infused with the GABA(A) receptor modulator chlordiazepoxide (CDP) or the opiate morphine. Male Sprague-Dawley rats were given MS co-infusions and then 15 min later tested for spontaneous alternation or given shock avoidance training (retention tested 48 h later). The results showed that MS infusions of the higher dose of glucose with morphine did not produce memory deficits, whereas, the performance of rats given MS co-infusions of CDP with glucose was impaired. These findings suggest that the memory-impairing effects of brain glucose administration may involve an interaction with the GABA(A) receptor. (c) 2009 Elsevier Inc. All rights reserved.

Autoimmune hepatitis in association with lymphocytic colitis.

LENUS (Irish Health Repository)

Cronin, Edmond M

2012-02-03

Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.

75 FR 21641 - Infusion Pumps; Public Meeting; Request for Comments

Science.gov (United States)

2010-04-26

...] Infusion Pumps; Public Meeting; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION... announcing a public meeting regarding external infusion pumps. The purpose of the meeting is to inform the public about current problems associated with external infusion pump use, to help the agency identify...

Compliance with donor age recommendations in oocyte donor recruitment advertisements in the USA.

Science.gov (United States)

Alberta, Hillary B; Berry, Roberta M; Levine, Aaron D

2013-04-01

IVF using donated oocytes offers benefits to many infertile patients, yet the technique also raises a number of ethical concerns, including worries about potential physical and psychological risks to oocyte donors. In the USA, oversight of oocyte donation consists of a combination of federal and state regulations and self-regulatory guidelines promulgated by the American Society for Reproductive Medicine. This study assesses compliance with one of these self-regulatory guidelines - specifically, ASRM's preferred minimum age for donors of 21. To assess compliance, 539 oocyte donor recruitment advertisements from two recruitment channels (Craigslist and college newspapers) were collected and evaluated. Of these, 61% in the Craigslist dataset and 43% in the college newspaper dataset listed minimum ages between 18 and 20, which is inconsistent with ASRM's preferred minimum age recommendation of 21. Advertisements placed by oocyte donor recruitment agencies were more likely than advertisements placed by clinics to specify minimum ages between 18 and 20. These results indicate that ASRM should evaluate and consider revising its donor age guidelines. IVF using donated human eggs can help many patients who have difficulty having children. However, the technique also raises ethical concerns, including concerns about potential physical and psychological harms to egg donors. In the USA, oversight of egg donation relies on a combination of federal and state regulation and professional self-regulation. Governmental regulations address only limited aspects of egg donation, such as the potential spread of infectious diseases and the reporting of success rates, leaving voluntary guidelines developed by an association of medical professionals to address most issues, including ethical concerns raised by the practice. One of these voluntary guidelines recommends that egg donors should be at least 21 years of age. In this article, we analysed 539 egg donor recruitment advertisements

Using higher doses to compensate for tubing residuals in extended-infusion piperacillin-tazobactam.

Science.gov (United States)

Lam, Wendy J; Bhowmick, Tanaya; Gross, Alan; Vanschooneveld, Trevor C; Weinstein, Melvin P

2013-06-01

To mathematically assess drug losses due to infusion line residuals and evaluate methods to compensate for drug loss due to residual volumes in intravenous pump tubing. Literature was accessed through Ovid MEDLINE (1996-February 2013), using combinations of the search terms tubing residuals, residual volume, residual medication, intravenous infusions, intravenous injections, piperacillin, piperacillin-tazobactam, β-lactams, equipment design, infusion pumps, extended infusion, extended administration, and prolonged infusion. In addition, select reference citations from publications identified were reviewed. All articles that involved extended-infusion piperacillin-tazobactam implementation strategies were included in the review. Infusion pump characteristics and tubing residuals can affect extended-infusion piperacillin-tazobactam dosing strategies. Two studies addressing tubing residuals were identified. Both studies recommended increasing infusion volumes to compensate for tubing residuals. One study also recommended decreasing infusion-line dead space by using alternative infusion pump systems. Study calculations suggest that higher doses of piperacillin-tazobactam may be used to account for medication left in tubing residuals if alternative infusion pump systems cannot be obtained, and increased infusion volumes are not an option. Extended-infusion piperacillin-tazobactam has been used as a method of maximizing pharmacodynamic target attainment. Use of higher doses of piperacillin-tazobactam may be a reasonable method to compensate for drug loss due to residual volumes in large-bore intravenous pump tubing.

Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses.

Science.gov (United States)

Kol, Amir; Wood, Joshua A; Carrade Holt, Danielle D; Gillette, Jessica A; Bohannon-Worsley, Laurie K; Puchalski, Sarah M; Walker, Naomi J; Clark, Kaitlin C; Watson, Johanna L; Borjesson, Dori L

2015-04-15

Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. In horses, MSCs are isolated primarily from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objective of this study was to determine the safety and lymphocyte response to multiple allogeneic IV injections of either AT-derived MSCs (AT-MSCs) or BM-derived MSCs (BM-MSCs) to healthy horses. We injected three doses of 25 × 10(6) allogeneic MSCs from either AT or BM (a total of 75 × 10(6) MSCs per horse) into five and five, respectively, healthy horses. Horses were followed up for 35 days after the first MSC infusion. We evaluated host inflammatory and immune response, including total leukocyte numbers, serum cytokine concentration, and splenic lymphocyte subsets. Repeated injection of allogeneic AT-MSCs or BM-MSCs did not elicit any clinical adverse effects. Repeated BM-MSC injection resulted in increased blood CD8(+) T-cell numbers. Multiple BM-MSC injections also increased splenic regulatory T cell numbers compared with AT-MSC-injected horses but not controls. These data demonstrate that multiple IV injections of allogeneic MSCs are well tolerated by healthy horses. No clinical signs or clinico-pathologic measurements of organ toxicity or systemic inflammatory response were recorded. Increased numbers of circulating CD8(+) T cells after multiple IV injections of allogeneic BM-MSCs may indicate a mild allo-antigen-directed cytotoxic response. Safety and efficacy of allogeneic MSC IV infusions in sick horses remain to be determined.

Development of Organ-Specific Donor Risk Indices

OpenAIRE

Akkina, Sanjeev K.; Asrani, Sumeet K.; Peng, Yi; Stock, Peter; Kim, Ray; Israni, Ajay K.

2012-01-01

Due to the shortage of deceased donor organs, transplant centers accept organs from marginal deceased donors, including older donors. Organ-specific donor risk indices have been developed to predict graft survival using various combinations of donor and recipient characteristics. We will review the kidney donor risk index (KDRI) and liver donor risk index (LDRI) and compare and contrast their strengths, limitations, and potential uses. The Kidney Donor Risk Index has a potential role in devel...

Iron deficiency among blood donors

DEFF Research Database (Denmark)

Rigas, A S; Pedersen, O B; Magnussen, K

2017-01-01

Blood components collected from blood donors are an invaluable part of modern-day medicine. A healthy blood donor population is therefore of paramount importance. The results from the Danish Blood Donor Study (DBDS) indicate that gender, number of previous donations, time since last donation...... and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood...... donors is not reflected in a reduced self-perceived mental and physical health. In general, the high proportion of iron-deficient donors can be alleviated either by extending the inter-donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark...

Suicidal hanging donors for lung transplantation

Science.gov (United States)

Ananiadou, Olga; Schmack, Bastian; Zych, Bartlomiej; Sabashnikov, Anton; Garcia-Saez, Diana; Mohite, Prashant; Weymann, Alexander; Mansur, Ashham; Zeriouh, Mohamed; Marczin, Nandor; De Robertis, Fabio; Simon, Andre Rüdiger; Popov, Aron-Frederik

2018-01-01

Abstract In the context of limited donor pool in cardiothoracic transplantation, utilization of organs from high risk donors, such as suicidal hanging donors, while ensuring safety, is under consideration. We sought to evaluate the outcomes of lung transplantations (LTx) that use organs from this group. Between January 2011 and December 2015, 265 LTx were performed at our center. Twenty-two recipients received lungs from donors after suicidal hanging (group 1). The remaining 243 transplantations were used as a control (group 2). Analysis of recipient and donor characteristics as well as outcomes was performed. No statistically significant difference was found in the donor characteristics between analyzed groups, except for higher incidence of cardiac arrest, younger age and smoking history of hanging donors (P donor cause of death is not associated with poor mid-term survival or chronic lung allograft dysfunction following transplantation. These results encourage assessment of lungs from hanging donors, and their consideration for transplantation. PMID:29620623

Mitochondrial DNA copy number and chronic lymphocytic leukemia/small lymphocytic lymphoma risk in two prospective studies

NARCIS (Netherlands)

Kim, Christopher; Bassig, Bryan A; Seow, Wei Jie; Hu, Wei; Purdue, Mark P; Huang, Wen-Yi; Liu, Chin-San; Cheng, Wen-Ling; Männistö, Satu; Vermeulen, Roel; Weinstein, Stephanie J; Lim, Unhee; Hosgood, H Dean; Bonner, Matthew R; Caporaso, Neil E; Albanes, Demetrius; Lan, Qing; Rothman, Nathaniel

BACKGROUND: Mitochondrial DNA copy number (mtDNA CN) may be modified by mitochondria in response to oxidative stress. Previously, mtDNA CN was associated with non-Hodgkin lymphoma (NHL) risk, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We conducted a replication

Effect and Outcome of Intraoperative Fluid Restriction in Living Liver Donor Hepatectomy.

Science.gov (United States)

Wang, Chih-Hsien; Cheng, Kwok-Wai; Chen, Chao-Long; Wu, Shao-Chun; Shih, Tsung-Hsiao; Yang, Sheng-Chun; Lee, Ying-En; Jawan, Bruno; Huang, Chiu-En; Juang, Sin-Ei; Huang, Chia-Jung

2017-11-10

BACKGROUND The purpose of this study was to evaluate the effect and outcome of intraoperative fluid restriction in living liver donor hepatectomy, regarding changes in intraoperative CVP levels, blood loss, and postoperative renal function. MATERIAL AND METHODS The charts of 167 patients were reviewed and analyzed retrospectively. Intraoperative central venous pressure levels, blood loss, fluids infused, and urine output per hour, before and after the liver allograft procurement, were calculated. Perioperative renal functions were also analyzed. RESULTS Fluid infused before and after liver allograft procurement was 3.21±1.5 and 9.0±3.9 mL/Kg/h and urine output was 1.5±0.7 and 1.8±1.4 mL/Kg/h, respectively. Intraoperative estimated blood loss was 91.3±78.9 mL. No patients required blood transfusion. Their preoperative and postoperative hemoglobin were 12.3±2.7 and 11.7±1.7 g/dL. CVP levels decreased gradually from 10.4±3.0 to a low of 8.1±1.9 mmHg at the time of transection of the liver parenchyma. Renal functions were not significantly affected based on the determination of BUN and creatinine levels. CONCLUSIONS The methods used to lower CVP are moderate and slow, with 2 main goals achieved: minimal blood loss (91.3±78.9 ml) and no blood transfusion. Furthermore, it did not have any negative effect on renal function.

Superselective intraarterial infusion therapy for head and neck carcinomas

International Nuclear Information System (INIS)

Nakatani, Hiroaki; Sawada, Shoichi; Takeda, Taizo

2004-01-01

We report the results of superselective intraarterial cisplatin (CDDP) infusion therapy combined with irradiation for 23 patients, mainly advanced head and neck carcinoma. All patients received intraarterial CDDP infusions with intravenous sodium thiosulfate (STS) neutralization. CDDP infusion was performed by the Seldinger's technique in 16 patients and by the implanted intraarterial reservoir system in 7 patients. STS was also infused by the reservoir system implanted at the forearm in most patients. An overall response was observed in 21 of the 23 (91.3%) patients. Complete and partial responses were achieved in 16 (69.6%) and 5 (21.7%) patients, respectively. There were no patients with worse than grade III complications. We concluded that superselective intraarterial infusion therapy with a high dose of CDDP and STS was very effective for the management of advanced head and neck carcinomas and we recommend the implantable reservoir system for both CDDP and STS administration as an easy and low-invasive method. (author)

[The lymphocyte transformation test in dermatology].

Science.gov (United States)

Zinn, K; Braun-Falco, O

1976-03-01

At first, immunologie and methodic basies of the lymphocyte transformation test are discussed. Then the results gained by this test in several dermatologic diseases are summarized. Finally, practice of the lymphocyte transformation test is critically reviewed.

Radiosensitivity of lymphocytes among Filipinos: final report

International Nuclear Information System (INIS)

Medina, F.I.S.; Gregorio, J.S.; Aguilar, C.P.; Poblete, E.E.

1996-01-01

This report is about the studies on the radiosensitivity of Filipino lymphocytes to radiation that can elucidate on the potential of blood chromosomes as biological dosimeters. The objective of this study is to determine the radiosensitivity of lymphocytes among Filipinos and to establish the radiation-induced chromosome anomaly standard curve in lymphocytes for radiological dosimetry. 47 refs., 9 figs., 1 tab

The Psychosocial and Independent Living Donor Advocate Evaluation and Post-surgery Care of Living Donors.

Science.gov (United States)

Rudow, Dianne LaPointe; Swartz, Kathleen; Phillips, Chelsea; Hollenberger, Jennifer; Smith, Taylor; Steel, Jennifer L

2015-09-01

Solid organ transplantation as a treatment for end stage organ failure has been an accepted treatment option for decades. Despite advances in medicine and technology, and increased awareness of organ donation and transplantation, the gap between supply and demand continues to widen. Living donation has been an option that has increased the number of transplants despite the continued shortage of deceased organs. In the early 2000s live donor transplantation reached an all-time high in the United States. As a result, a consensus meeting was convened in 2000 to increase the oversight of living donor transplantation. Both the Centers for Medicare and Medicaid Services and the United Network for Organ Sharing developed regulations that transplant programs performing live donor transplantation. These regulations and guidelines involve the education, evaluation, informed consent process and living donor follow-up care. Two areas in which had significant changes included the psychosocial and the independent living donor advocate (ILDA) evaluation. The purpose of this paper was to outline the current regulations and guidelines associated with the psychosocial and ILDA evaluation as well as provide further recommendations for the administration of a high quality evaluation of living donors. The goals and timing of the evaluation and education of donors; qualifications of the health care providers performing the evaluation; components of the evaluation; education provided to donors; documentation of the evaluation; participation in the selection committee meeting; post-decline and post-donation care of donors is described. Caveats including the paired donor exchange programs and non-directed and directed donation are also considered.

Infusion pressure and pain during microneedle injection into skin of human subjects

Science.gov (United States)

Gupta, Jyoti; Park, Sohyun; Bondy, Brian; Felner, Eric I.; Prausnitz, Mark R.

2011-01-01

Infusion into skin using hollow microneedles offers an attractive alternative to hypodermic needle injections. However, the fluid mechanics and pain associated with injection into skin using a microneedle have not been studied in detail before. Here, we report on the effect of microneedle insertion depth into skin, partial needle retraction, fluid infusion flow rate and the co-administration of hyaluronidase on infusion pressure during microneedle-based saline infusion, as well as on associated pain in human subjects. Infusion of up to a few hundred microliters of fluid required pressures of a few hundred mmHg, caused little to no pain, and showed weak dependence on infusion parameters. Infusion of larger volumes up to 1 mL required pressures up to a few thousand mmHg, but still usually caused little pain. In general, injection of larger volumes of fluid required larger pressures and application of larger pressures cause more pain, although other experimental parameters also played a significant role. Among the intradermal microneedle groups, microneedle length had little effect; microneedle retraction lowered infusion pressure but increased pain; lower flow rate reduced infusion pressure and kept pain low; and use of hyaluronidase also lowered infusion pressure and kept pain low. We conclude that microneedles offer a simple method to infuse fluid into the skin that can be carried out with little to no pain. PMID:21684001

Combined Treatment with Low Concentrations of Decitabine and SAHA Causes Cell Death in Leukemic Cell Lines but Not in Normal Peripheral Blood Lymphocytes

Directory of Open Access Journals (Sweden)

Barbora Brodská

2013-01-01

Full Text Available Epigenetic therapy reverting aberrant acetylation or methylation offers the possibility to target preferentially tumor cells and to preserve normal cells. Combination epigenetic therapy may further improve the effect of individual drugs. We investigated combined action of demethylating agent decitabine and histone deacetylase inhibitor SAHA (Vorinostat on different leukemic cell lines in comparison with peripheral blood lymphocytes. Large decrease of viability, as well as huge p21WAF1 induction, reactive oxygen species formation, and apoptotic features due to combined decitabine and SAHA action were detected in leukemic cell lines irrespective of their p53 status, while essentially no effect was observed in response to the combined drug action in normal peripheral blood lymphocytes of healthy donors. p53-dependent apoptotic pathway was demonstrated to participate in the wtp53 CML-T1 leukemic cell line response, while significant influence of reactive oxygen species on viability decrease has been detected in p53-null HL-60 cell line.

Associations between bolus infusion of hydrocortisone, glycemic variability and insulin infusion rate variability in critically Ill patients under moderate glycemic control

NARCIS (Netherlands)

van Hooijdonk, Roosmarijn T. M.; Binnekade, Jan M.; Bos, Lieuwe D. J.; Horn, Janneke; Juffermans, Nicole P.; Abu-Hanna, Ameen; Schultz, Marcus J.

2015-01-01

We retrospectively studied associations between bolus infusion of hydrocortisone and variability of the blood glucose level and changes in insulin rates in intensive care unit (ICU) patients. 'Glycemic variability' and 'insulin infusion rate variability' were calculated from and expressed as the

Q-FISH measurement of hepatocyte telomere lengths in donor liver and graft after pediatric living-donor liver transplantation: donor age affects telomere length sustainability.

Directory of Open Access Journals (Sweden)

Youichi Kawano