The potential usefulness of human leukocyte antigen typing for celiac disease screening: a systematic review and meta-analysis

Directory of Open Access Journals (Sweden)

Alicia Díaz-Redondo

2015-07-01

Full Text Available Background and aim: The presence of specific human leukocyte antigen-DQ2 and DQ8 seems to be necessary for celiac disease development, but the real contribution of its typing for screening is still uncertain. We aim to conduct a systematic review and meta-analysis of the diagnostic performance of human leukocyte antigen typing tests for celiac disease screening. Methods: Systematic review of published studies assessing accuracy of human leukocyte antigen DQ2 and DQ8 typing for the detection of celiac disease were selected. MEDLINE and EMBASE were searched from 1st January 2004 until 31st December 2013. Two independent researchers carried out selection and classification of studies, data extraction and analysis. Meta-analysis combining sensitivities, specificities and likelihood ratios of HLA-DQ2 and DQ8 for the diagnosis of celiac disease were carried out. Results: 6 studies including 1303 individuals were finally evaluated. Pooled sensitivity was 98% (95% confidence interval: 97-99. Overall specificity was 45% (95% confidence interval: 41-48. Regarding specificity, studies were heterogeneous and a subgroup analysis was done according to the type of population included. Overall negative likelihood ratio was 0.05 (0.03-0.09. Conclusions: Due to its great sensitivity and low negative likelihood ratio, human leukocyte antigen-DQ2/DQ8 typing would be an appropriate test for ruling out celiac disease in the general population suffering related symptoms, and even more in at risk population.

Donor-recipient human leukocyte antigen matching practices in vascularized composite tissue allotransplantation: a survey of major transplantation centers.

Science.gov (United States)

Ashvetiya, Tamara; Mundinger, Gerhard S; Kukuruga, Debra; Bojovic, Branko; Christy, Michael R; Dorafshar, Amir H; Rodriguez, Eduardo D

2014-07-01

Vascularized composite tissue allotransplant recipients are often highly sensitized to human leukocyte antigens because of multiple prior blood transfusions and other reconstructive operations. The use of peripheral blood obtained from dead donors for crossmatching may be insufficient because of life support measures taken for the donor before donation. No study has been published investigating human leukocyte antigen matching practices in this field. A survey addressing human leukocyte antigen crossmatching methods was generated and sent to 22 vascularized composite tissue allotransplantation centers with active protocols worldwide. Results were compiled by center and compared using two-tailed t tests. Twenty of 22 centers (91 percent) responded to the survey. Peripheral blood was the most commonly reported donor sample for vascularized composite tissue allotransplant crossmatching [78 percent of centers (n=14)], with only 22 percent (n=4) using lymph nodes. However, 56 percent of the 18 centers (n=10) that had performed vascularized composite tissue allotransplantation reported that they harvested lymph nodes for crossmatching. Of responding individuals, 62.5 percent (10 of 16 individuals) felt that lymph nodes were the best donor sample for crossmatching. A slight majority of vascularized composite tissue allotransplant centers that have performed clinical transplants have used lymph nodes for human leukocyte antigen matching, and centers appear to be divided on the utility of lymph node harvest. The use of lymph nodes may offer a number of potential benefits. This study highlights the need for institutional review board-approved crossmatching protocols specific to vascularized composite tissue allotransplantation, and the need for global databases for sharing of vascularized composite tissue allotransplantation experiences.

Human leukocyte antigen-G polymorphism in relation to expression, function, and disease

DEFF Research Database (Denmark)

Larsen, Margit Hørup; Hviid, Thomas

2009-01-01

Human leukocyte antigen-G (HLA-G) is a nonclassical class Ib molecule belonging to the major histocompatibility complex. HLA-G appears to play a role in the suppression of immune responses and contribute to long-term immune escape or tolerance. The focus of this review is polymorphism in the HLA......-G gene and protein and its possible importance in expression, function, and disease associations....

The role of the human leukocyte antigen system in retinopathy of prematurity: a pilot study.

Science.gov (United States)

Flor-de-Lima, Filipa; Rocha, Gustavo; Proença, Elisa; Tafulo, Sandra; Freitas, Fátima; Guimarães, Hercília

2013-12-01

To assess the association between the human leukocyte antigen system and retinopathy of prematurity. Neonates of prematurity. A large-scale population-based study should be performed to clarify this association. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig

Science.gov (United States)

Morgan, Sophie B.; Attaf, Meriem; Szomolay, Barbara; Miles, John J.; Townsend, Alain; Bailey, Mick; Charleston, Bryan; Tchilian, Elma

2018-01-01

There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume. It may also be an important vector in the birds to human infection cycle. A major drawback of the current pig model is the inability to analyze antigen-specific CD8+ T-cell responses, which are critical to respiratory immunity. Here we address this knowledge gap using an established in-bred pig model with a high degree of genetic identity between individuals, including the MHC (Swine Leukocyte Antigen (SLA)) locus. We developed a toolset that included long-term in vitro pig T-cell culture and cloning and identification of novel immunodominant influenza-derived T-cell epitopes. We also generated structures of the two SLA class I molecules found in these animals presenting the immunodominant epitopes. These structures allowed definition of the primary anchor points for epitopes in the SLA binding groove and established SLA binding motifs that were used to successfully predict other influenza-derived peptide sequences capable of stimulating T-cells. Peptide-SLA tetramers were constructed and used to track influenza-specific T-cells ex vivo in blood, the lungs and draining lymph nodes. Aerosol immunization with attenuated single cycle influenza viruses (S-FLU) induced large numbers of CD8+ T-cells specific for conserved NP peptides in the respiratory tract. Collectively, these data substantially increase the utility of pigs as an effective model for studying protective local cellular immunity against respiratory

Arginine (Di)methylated Human Leukocyte Antigen Class I Peptides Are Favorably Presented by HLA-B*07

NARCIS (Netherlands)

Marino, Fabio; Mommen, Geert P M; Jeko, Anita; Meiring, Hugo D; van Gaans-van den Brink, Jacqueline A M; Scheltema, Richard A; van Els, Cécile A C M; Heck, Albert J R

Alterations in protein post-translational modification (PTM) are recognized hallmarks of diseases. These modifications potentially provide a unique source of disease-related human leukocyte antigen (HLA) class I-presented peptides that can elicit specific immune responses. While phosphorylated HLA

Human leukocyte antigen-G within the male reproductive system

DEFF Research Database (Denmark)

Hviid, Thomas Vauvert F

2015-01-01

by “priming” the woman’s immune system before conception and at conception. Recent studies have demonstrated the presence of the immunoregulatory and tolerance-inducible human leukocyte antigen (HLA)-G in the male reproductive organs. The expression of HLA-G in the blastocyst and by extravillous trophoblast......In sexual reproduction in humans, a man has a clear interest in ensuring that the immune system of his female partner accepts the semi-allogenic fetus. Increasing attention has been given to soluble immunomodulatory molecules in the seminal fluid as one mechanism of ensuring this, possibly...... plasma may even be associated with the chance of pregnancy in couples, where the male partner has reduced semen quality. More studies are needed to verify these preliminary findings....

Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition

Energy Technology Data Exchange (ETDEWEB)

Archbold, Julia K.; Macdonald, Whitney A.; Gras, Stephanie; Ely, Lauren K.; Miles, John J.; Bell, Melissa J.; Brennan, Rebekah M.; Beddoe, Travis; Wilce, Matthew C.J.; Clements, Craig S.; Purcell, Anthony W.; McCluskey, James; Burrows, Scott R.; Rossjohn, Jamie; (Monash); (Queensland Inst. of Med. Rsrch.); (Melbourne)

2009-07-10

Human leukocyte antigen (HLA) gene polymorphism plays a critical role in protective immunity, disease susceptibility, autoimmunity, and drug hypersensitivity, yet the basis of how HLA polymorphism influences T cell receptor (TCR) recognition is unclear. We examined how a natural micropolymorphism in HLA-B44, an important and large HLA allelic family, affected antigen recognition. T cell-mediated immunity to an Epstein-Barr virus determinant (EENLLDFVRF) is enhanced when HLA-B*4405 was the presenting allotype compared with HLA-B*4402 or HLA-B*4403, each of which differ by just one amino acid. The micropolymorphism in these HLA-B44 allotypes altered the mode of binding and dynamics of the bound viral epitope. The structure of the TCR-HLA-B*4405EENLLDFVRF complex revealed that peptide flexibility was a critical parameter in enabling preferential engagement with HLA-B*4405 in comparison to HLA-B*4402/03. Accordingly, major histocompatibility complex (MHC) polymorphism can alter the dynamics of the peptide-MHC landscape, resulting in fine-tuning of T cell responses between closely related allotypes.

Sequence-Based Genotyping of Expressed Swine Leukocyte Antigen Class I Alleles by Next-Generation Sequencing Reveal Novel Swine Leukocyte Antigen Class I Haplotypes and Alleles in Belgian, Danish, and Kenyan Fattening Pigs and Göttingen Minipigs

DEFF Research Database (Denmark)

Sørensen, Maria Rathmann; Ilsøe, Mette; Strube, Mikael Lenz

2017-01-01

for the prediction of epitope binding in pigs. The low number of known SLA class I alleles and the limited knowledge of their prevalence in different pig breeds emphasizes the need for efficient SLA typing methods. This study utilizes an SLA class I-typing method based on next-generation sequencing of barcoded PCR...

Maternal T-Cell Engraftment Interferes With Human Leukocyte Antigen Typing in Severe Combined Immunodeficiency.

Science.gov (United States)

Liu, Chang; Duffy, Brian; Bednarski, Jeffrey J; Calhoun, Cecelia; Lay, Lindsay; Rundblad, Barrett; Payton, Jacqueline E; Mohanakumar, Thalachallour

2016-02-01

To report the laboratory investigation of a case of severe combined immunodeficiency (SCID) with maternal T-cell engraftment, focusing on the interference of human leukocyte antigen (HLA) typing by blood chimerism. HLA typing was performed with three different methods, including sequence-specific primer (SSP), sequence-specific oligonucleotide, and Sanger sequencing on peripheral blood leukocytes and buccal cells, from a 3-month-old boy and peripheral blood leukocytes from his parents. Short tandem repeat (STR) testing was performed in parallel. HLA typing of the patient's peripheral blood leukocytes using the SSP method demonstrated three different alleles for each of the HLA-B and HLA-C loci, with both maternal alleles present at each locus. Typing results from the patient's buccal cells showed a normal pattern of inheritance for paternal and maternal haplotypes. STR enrichment testing of the patient's CD3+ T lymphocytes and CD15+ myeloid cells confirmed maternal T-cell engraftment, while the myeloid cell profile matched the patient's buccal cells. Maternal T-cell engraftment may interfere with HLA typing in patients with SCID. Selection of the appropriate typing methods and specimens is critical for accurate HLA typing and immunologic assessment before allogeneic hematopoietic stem cell transplantation. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Human leukocyte antigen genotypes and trial of desensitization in patients with oxcarbazepine-induced skin rash: a pilot study.

Science.gov (United States)

Lee, Bolyun; Yu, Hee Joon; Kang, Eun-Suk; Lee, Munhyang; Lee, Jeehun

2014-08-01

Skin rash associated with specific antiepileptic drugs occurs not infrequently and it usually necessitates discontinuation of the causative drugs. An alternative strategy is to desensitize the individual to the offending drug. We checked the human leukocyte antigen genotypes and conducted a pilot study to investigate the usefulness and safety of desensitization in pediatric patients with skin rash associated with oxcarbazepine. We enrolled 19 patients with epilepsy who had discontinued oxcarbazepine because of skin rash despite an initial good response and then became refractory to other antiepileptic drugs along with an individual with paroxysmal kinesigenic dyskinesia with a similar situation. High-resolution HLA-A and -B genotyping was performed to investigate the genetic risk. The desensitization began with 0.1 mg daily reaching 120 mg on the thirty-first day. Thereafter, the dose was increased at a rate of 12 mg/day. Nineteen patients completed the desensitization protocol to a target dosage over 2-5 months. Five patients developed itching and erythema during desensitization, but the symptoms disappeared after withholding a dose increment transiently. There were no human leukocyte antigen genotypes relevant to aromatic antiepileptic drug-induced severe hypersensitivity reactions. The seizure frequency was reduced to less than at baseline in 18 individuals. This study demonstrated 95% efficacy, including 42% seizure-free patients and the favorable tolerability of desensitization to oxcarbazepine in patients with intractable epilepsy and one patient with paroxysmal kinesigenic dyskinesia. Screening for sensitive human leukocyte antigen types and exclusion of severe hypersensitivity reactions should precede desensitization. Copyright © 2014 Elsevier Inc. All rights reserved.

Identification of swine influenza virus epitopes and analysis of multiple specificities expressed by cytotoxic T cell subsets

DEFF Research Database (Denmark)

Pedersen, Lasse Eggers; Breum, Solvej Østergaard; Riber, Ulla

2014-01-01

Background: Major histocompatibility complex (MHC) class I peptide binding and presentation are essential for antigen-specific activation of cytotoxic T lymphocytes (CTLs) and swine MHC class I molecules, also termed swine leukocyte antigens (SLA), thus play a crucial role in the process that leads...... to elimination of viruses such as swine influenza virus (SwIV). This study describes the identification of SLA-presented peptide epitopes that are targets for a swine CTL response, and further analyses multiple specificities expressed by SwIV activated CTL subsets. Findings: Four SwIV derived peptides were...

Human leukocyte antigen class II susceptibility conferring alleles among non-insulin dependent diabetes mellitus patients

International Nuclear Information System (INIS)

Tipu, H.N.; Ahmed, T.A.; Bashir, M.M.

2010-01-01

To determine the frequency of Human Leukocyte Antigen (HLA) class II susceptibility conferring alleles among type 2 Diabetes mellitus patients, in comparison with healthy controls. Cross-sectional comparative study. Patients with non-insulin dependent Diabetes mellitus meeting World Health Organization criteria were studied. These were compared with age and gender matched healthy control subjects. For each subject (patients as well as controls), DNA was extracted from ethylene diamine tetra-acetate sample and HLA class II DRB1 typing was carried out at allele group level (DRB1*01-DRB1*16) by sequence specific primers. Human leukocyte antigen DRB1 type was determined by agarose gel electrophoresis and results were recorded. Frequencies were determined as number of an allele divided by total number of alleles per group; p-value was computed using Pearson's chi-square test. Among the 100 patients, there were 63 males and 37 females with 68 controls. A total of 13 different HLA DRB1 alleles were detected, with DRB1*15 being the commonest in both the groups. The allele DRB1*13 had statistically significant higher frequency in patient group as compared to controls (p 0.005). HLA DRB1*13 was found with a significantly increased frequency in non-insulin dependent Diabetes mellitus. (author)

The expression and functional activity of membrane-bound human leukocyte antigen-G1 are influenced by the 3'-untranslated region

DEFF Research Database (Denmark)

Svendsen, Signe Goul; Hantash, Basil M; Zhao, Longmei

2013-01-01

Human Leukocyte Antigen (HLA)-G is an immunosuppressive molecule acting on both the innate and adaptive immune system. A 14 bp insertion/deletion polymorphism (rs66554220) in the 3'-untranslated region (3'UTR) of the HLA-G gene has been associated with a number of diseases, pregnancy complication...

Dynamic SLA Negotiation in Autonomic Federated Environments

Science.gov (United States)

Rubach, Pawel; Sobolewski, Michael

Federated computing environments offer requestors the ability to dynamically invoke services offered by collaborating providers in the virtual service network. Without an efficient resource management that includes Dynamic SLA Negotiation, however, the assignment of providers to customer's requests cannot be optimized and cannot offer high reliability without relevant SLA guarantees. We propose a new SLA-based SERViceable Metacomputing Environment (SERVME) capable of matching providers based on QoS requirements and performing autonomic provisioning and deprovisioning of services according to dynamic requestor needs. This paper presents the SLA negotiation process that includes on-demand provisioning and uses an object-oriented SLA model for large-scale service-oriented systems supported by SERVME. An initial reference implementation in the SORCER environment is also described.

From Viral genome to specific peptide epitopes - Methods for identifying porcine T cell epitopes based on in silico predictions, in vitro identification and ex vivo verification

DEFF Research Database (Denmark)

Pedersen, Lasse Eggers; Rasmussen, Michael; Harndahl, Mikkel

The affinity for and stability of peptides bound by major histocompatibility complex (MHC) class I molecules are instrumental factors in presentation of viral epitopes to cytotoxic T lymphocytes (CTLs). In swine, such peptide presentations by swine leukocyte antigens (SLA) are crucial for swine i...

Dicty_cDB: SLA117 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available SL (Link to library) SLA117 (Link to dictyBase) - - - Contig-U15540-1 - (Link to Or...iginal site) - - SLA117Z 649 - - - - Show SLA117 Library SL (Link to library) Clone ID SLA117 (Link to dicty...Base) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U15540-1 Original site URL http://dictycdb.b...--EPMHRNYYQPIQFKLPSFPDTSLPITQIDDKTGIFDSQRFLAFNNPQAMSKYESYRI YIHPSLGYSGNAKRFKQQPDVNEKALILDGNVYDGHLNPIYNCKICTE...SYRI YIHPSLGYSGNAKRFKQQPDVNEKALILDGNVYDGHLNPIYNCKICTEYYQTKSYFSANP HAKGKVLLVKNNILTRVKDGGFTLSLKPMCCSGHNSHIPLYF

Dicty_cDB: SLA529 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available SL (Link to library) SLA529 (Link to dictyBase) - - - Contig-U13922-1 SLA529F (Link... to Original site) SLA529F 670 - - - - - - Show SLA529 Library SL (Link to library) Clone ID SLA529 (Link to dic...1247( FM992688 |pid:none) Candida dubliniensis CD36 chrom... 35 2.6 EU565733_1( EU565733 |pid:none) Uncult...009385_2728( AP009385 |pid:none) Burkholderia multivorans ATCC 1... 33 5.8 AM260479_1383( AM260479 |pid:none...letal 8.0 %: mitochondrial 4.0 %: Golgi 4.0 %: vesicles of secretory system 4.0 %: endoplasmic reticul

Human leukocyte antigens in indigenous (mapuche) people in a regional renal transplantation program in chile.

Science.gov (United States)

Droguett, M A; Oyarzún, M J; Alruiz, P; Jerez, V; Mezzano, S; Ardiles, L

2005-10-01

An active regional transplantation program established in the southern region of Chile has allowed the incorporation of ethnic minorities particularly Mapuche living in this geographic area in the development of a histocompatibility database. To identify possible differences in the human leukocyte (HLA) antigen distribution in Chilean Mapuche compared with non-Mapuche, we reviewed 442 HLA tissue-typing studies. Seventy-eight of 309 recipients (25%) and 18 of 133 donors (13%) were Mapuche. Among recipients, Mapuche people showed a significantly higher frequency of the HLA antigens, A28, B16, DR4, and DR8, and a lower one for A19, B15, and DR1 (P Mapuche individuals. A particularly higher frequency of the haplotype A28, -B16, -DR4 was also evidenced in Mapuche. Besides, these recipients showed a higher frequency of the allele -DR4 when compared with Mapuche donors. A greater frequency of some histocompatibility antigens in patients with chronic renal disease might be attributed to allelic concentration due to a high index of endogamy, but a possible association with the development of progressive renal disease cannot be ignored, especially when a higher prevalence of DR4 was observed among Mapuche recipients.

Epidemiology of human leukocyte antigens among omani population.

Science.gov (United States)

Al Salmi, Issa; Metry, Abdul Massiah; Al Ismaili, Faisal; Hola, Alan; Shaheen, Faissal; Fakhoury, Hana; Hannawi, Suad

2017-01-01

Oman is located on the Southeastern coast of the Arabian Peninsula, and its population has high levels of consanguinity. Human leukocytic antigen (HLA) typing analysis in human population holds unexploited potential for elucidating the genetic causes of human disease and possibly leads to personalized medicine. This is a retrospective, descriptive study evaluating HLA frequencies of Omani individuals who underwent workup for kidney transplantation at the Royal Hospital (RH) from 2005 to 2016. Data on 870 subjects were collected from the Oman kidney transplant registry at RH as well from electronic medical record system. The mean age (standard deviation) years for the cohort were 33.2 (13.0). Males constituted 56.3% (490) while females constituted 43.7% (380). Seven HLA-A alleles accounted for more than 70% of the total alleles. Of which, HLA-A2 contributed the highest frequency (24%), followed by HLA A11 (9.4%), and A32 (8.1%). Ten alleles accounted for 70% of HLA-B alleles. Of which, HLA-B51 was the most common (18.9%), followed by HLA-B-35 (13.6%), and HLA-B8 (7.9%). Seven HLA-DRB1 alleles accounted for more than 70% of the total HLA DRB1 alleles, of which HLA- DRB1*16 contributed the highest frequency (29.56%). This was followed by HLA-DRB1*03 (14.57%) and HLA-DRB1*11 (9.48%). While three alleles accounted for more than 75% of the total HLA DQB1alleles. Of which, HLA-DQB1*05 contributed the highest frequency (37.56%). This was followed by allele HLA-DQB1*02 (26.48%) and HLA-DQB1*03 (17.18%). This study showed considerable heterogeneity in both HLA Class I and Class II antigens, which reflects admixture of our population with rest of old world countries. Despite the high levels of consanguinity, this population is genetically highly heterogeneous. These findings may be useful for transplantation programs, noncommunicable diseases, epidemiology of HLA linked diseases, pharmacogenomics, and anthropology.

Epidemiology of human leukocyte antigens among omani population

Directory of Open Access Journals (Sweden)

Issa Al Salmi

2017-01-01

Full Text Available Oman is located on the Southeastern coast of the Arabian Peninsula, and its population has high levels of consanguinity. Human leukocytic antigen (HLA typing analysis in human population holds unexploited potential for elucidating the genetic causes of human disease and possibly leads to personalized medicine. This is a retrospective, descriptive study evaluating HLA frequencies of Omani individuals who underwent workup for kidney transplantation at the Royal Hospital (RH from 2005 to 2016. Data on 870 subjects were collected from the Oman kidney transplant registry at RH as well from electronic medical record system. The mean age (standard deviation years for the cohort were 33.2 (13.0. Males constituted 56.3% (490 while females constituted 43.7% (380. Seven HLA-A alleles accounted for more than 70% of the total alleles. Of which, HLA-A2 contributed the highest frequency (24%, followed by HLA A11 (9.4%, and A32 (8.1%. Ten alleles accounted for 70% of HLA-B alleles. Of which, HLA-B51 was the most common (18.9%, followed by HLA-B-35 (13.6%, and HLA-B8 (7.9%. Seven HLA-DRB1 alleles accounted for more than 70% of the total HLA DRB1 alleles, of which HLA- DRB1*16 contributed the highest frequency (29.56%. This was followed by HLA-DRB1*03 (14.57% and HLA-DRB1*11 (9.48%. While three alleles accounted for more than 75% of the total HLA DQB1alleles. Of which, HLA-DQB1*05 contributed the highest frequency (37.56%. This was followed by allele HLA-DQB1*02 (26.48% and HLA-DQB1*03 (17.18%. This study showed considerable heterogeneity in both HLA Class I and Class II antigens, which reflects admixture of our population with rest of old world countries. Despite the high levels of consanguinity, this population is genetically highly heterogeneous. These findings may be useful for transplantation programs, noncommunicable diseases, epidemiology of HLA linked diseases, pharmacogenomics, and anthropology.

Dicty_cDB: SLA340 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available SL (Link to library) SLA340 (Link to dictyBase) - - - Contig-U16510-1 - (Link to Or...iginal site) - - SLA340Z 466 - - - - Show SLA340 Library SL (Link to library) Clone ID SLA340 (Link to dicty...Base) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U16510-1 Original site URL http://dictycdb.b.... 2 Translated Amino Acid sequence ---CGKPSPIPTCTRKLSPISICIIKLCPIFICITKLCSIYICTISICIIFICIICSNYS CNYNCNYSCNYN...qpqlqlqlqlqpqpqlqpqlqpq lplkfnqktffikyhynnffnnnsikk*y*kspffl Frame C: ---CGKPSPIPTCTRKLSPISICIIKLCPIFICITKLCSIYICT

A computational method for identification of vaccine targets from protein regions of conserved human leukocyte antigen binding

DEFF Research Database (Denmark)

Olsen, Lars Rønn; Simon, Christian; Kudahl, Ulrich J.

2015-01-01

Background: Computational methods for T cell-based vaccine target discovery focus on selection of highly conserved peptides identified across pathogen variants, followed by prediction of their binding of human leukocyte antigen molecules. However, experimental studies have shown that T cells often...... target diverse regions in highly variable viral pathogens and this diversity may need to be addressed through redefinition of suitable peptide targets. Methods: We have developed a method for antigen assessment and target selection for polyvalent vaccines, with which we identified immune epitopes from...... variable regions, where all variants bind HLA. These regions, although variable, can thus be considered stable in terms of HLA binding and represent valuable vaccine targets. Results: We applied this method to predict CD8+ T-cell targets in influenza A H7N9 hemagglutinin and significantly increased...

Associations among Epstein-Barr virus subtypes, human leukocyte antigen class I alleles, and the development of posttransplantation lymphoproliferative disorder in bone marrow transplant recipients

NARCIS (Netherlands)

Görzer, Irene; Puchhammer-Stöckl, Elisabeth; van Esser, Joost W J; Niesters, Hubert G M; Cornelissen, Jan J

2007-01-01

The association between Epstein-Barr virus subtype, human leukocyte antigen class I alleles, and the development of posttransplantation lymphoproliferative disorder was examined in a group of 25 bone marrow transplant recipients. A highly statistically significant correlation was observed between

Dendritic cells take up and present antigens from viable and apoptotic polymorphonuclear leukocytes.

Directory of Open Access Journals (Sweden)

Carlos Alfaro

Full Text Available Dendritic cells (DC are endowed with the ability to cross-present antigens from other cell types to cognate T cells. DC are poised to meet polymorphonuclear leukocytes (PMNs as a result of being co-attracted by interleukin-8 (IL-8, for instance as produced by tumor cells or infected tissue. Human monocyte-derived and mouse bone marrow-derived DC can readily internalize viable or UV-irradiated PMNs. Such internalization was abrogated at 4°C and partly inhibited by anti-CD18 mAb. In mice, DC which had internalized PMNs containing electroporated ovalbumin (OVA protein, were able to cross-present the antigen to CD8 (OT-1 and CD4 (OT-2 TCR-transgenic T cells. Moreover, in humans, tumor cell debris is internalized by PMNs and the tumor-cell material can be subsequently taken up from the immunomagnetically re-isolated PMNs by DC. Importantly, if human neutrophils had endocytosed bacteria, they were able to trigger the maturation program of the DC. Moreover, when mouse PMNs with E. coli in their interior are co-injected in the foot pad with DC, many DC loaded with fluorescent material from the PMNs reach draining lymph nodes. Using CT26 (H-2(d mouse tumor cells, it was observed that if tumor cells are intracellularly loaded with OVA protein and UV-irradiated, they become phagocytic prey of H-2(d PMNs. If such PMNs, that cannot present antigens to OT-1 T cells, are immunomagnetically re-isolated and phagocytosed by H-2(b DC, such DC productively cross-present OVA antigen determinants to OT-1 T cells. Cross-presentation to adoptively transferred OT-1 lymphocytes at draining lymph nodes also take place when OVA-loaded PMNs (H-2(d are coinjected in the footpad of mice with autologous DC (H-2(b. In summary, our results indicate that antigens phagocytosed by short-lived PMNs can be in turn internalized and productively cross-presented by DC.

TeSLA e-assessment workshop pilot 2

OpenAIRE

Janssen, José

2017-01-01

Presentatie ten behoeve van de e-assessment workshop voor docenten van de Open Universiteit Nederland betrokken in de tweede TeSLA pilot. Topics: toetsfraude, toetsdesign, technologie voor authenticatie en verificatie van auteurschap, TeSLA instrument.

File list: ALL.Bld.10.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: ALL.Bld.05.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: ALL.Bld.50.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: ALL.Bld.20.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

Lifescience Database Archive (English)

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TeSLA workshop betrouwbaar toetsen op afstand

NARCIS (Netherlands)

Brouns, Francis; Janssen, José

2017-01-01

Presentatie ten behoeve van workshop betrouwbaar toetsen op afstand voor docenten van de Open Universiteit Nederland betrokken in de derde TeSLA pilot. Topics: toetsfraude, toetsdesign, technologie voor authenticatie en verificatie van auteurschap, TeSLA instrumenten.

Factors associated with anti-human leukocyte antigen antibodies in patients supported with continuous-flow devices and effect on probability of transplant and post-transplant outcomes

DEFF Research Database (Denmark)

Alba, Ana C; Tinckam, Kathryn; Foroutan, Farid

2015-01-01

BACKGROUND: One major disadvantage of ventricular assist device (VAD) therapy is the development of human-leukocyte antigen (HLA) antibodies. We aimed to identify factors associated with HLA antibodies during continuous flow (CF)-VAD support and assess the effect on transplant probability...

VieSLAF Framework: Enabling Adaptive and Versatile SLA-Management

Science.gov (United States)

Brandic, Ivona; Music, Dejan; Leitner, Philipp; Dustdar, Schahram

Novel computing paradigms like Grid and Cloud computing demand guarantees on non-functional requirements such as application execution time or price. Such requirements are usually negotiated following a specific Quality of Service (QoS) model and are expressed using Service Level Agreements (SLAs). Currently available QoS models assume either that service provider and consumer have matching SLA templates and common understanding of the negotiated terms or provide public templates, which can be downloaded and utilized by the end users. On the one hand, matching SLA templates represent an unrealistic assumption in systems where service consumer and provider meet dynamically and on demand. On the other hand, handling of public templates seems to be a rather challenging issue, especially if the templates do not reflect users’ needs. In this paper we present VieSLAF, a novel framework for the specification and management of SLA mappings. Using VieSLAF users may specify, manage, and apply SLA mapping bridging the gap between non-matching SLA templates. Moreover, based on the predefined learning functions and considering accumulated SLA mappings, domain specific public SLA templates can be derived reflecting users’ needs.

The biocompatibility of SLA-treated titanium implants

International Nuclear Information System (INIS)

Kim, Hyeongil; Choi, Seong-Ho; Ryu, Jae-Jun; Koh, Seung-Yong; Park, Ju-Han; Lee, In-Seop

2008-01-01

The titanium implant surface was sandblasted with large grits and acid etched (SLA) to increase the implant surface for osseointegration. The topography of the titanium surface was investigated with scanning electron microscopy (SEM) and a profilometer. The SLA implant demonstrated uniform small micro pits (1-2 μm in diameter). The values of average roughness (R a ) and maximum height (R t ) were 1.19 μm and 10.53 μm respectively after sandblasting and the acid-etching treatment. In the cell-surface interaction study, the human osteoblast cells grew well in vitro. The in vivo evaluation of the SLA implant placed in rabbit tibia showed good bone-to-implant contact (BIC) with a mean value of 29% in total length of the implant. In the short-term clinical study, SLA implants demonstrated good clinical performance, maintaining good crestal bone height

A modern approach for epitope prediction: identification of foot-and-mouth disease virus peptides binding bovine leukocyte antigen (BoLA) class I molecules

DEFF Research Database (Denmark)

Pandya, Mital; Rasmussen, Michael; Hansen, Andreas

2015-01-01

Major histocompatibility complex (MHC) class I molecules regulate adaptive immune responses through the presentation of antigenic peptides to CD8+ T cells. Polymorphisms in the peptide binding region of class I molecules determine peptide binding affinity and stability during antigen presentation......, and different antigen peptide motifs are associated with specific genetic sequences of class I molecules. Understanding bovine leukocyte antigen (BoLA), peptide-MHC class I binding specificities may facilitate development of vaccines or reagents for quantifying the adaptive immune response to intracellular...... pathogens, such as foot-and-mouth disease virus (FMDV). Six synthetic BoLA class I (BoLA-I) molecules were produced, and the peptide binding motif was generated for five of the six molecules using a combined approach of positional scanning combinatorial peptide libraries (PSCPLs) and neural network...

Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 in Japanese patients with chronic hepatitis.

Science.gov (United States)

Nishioka, M; Morshed, S A; Parveen, S; Kono, K; Matsuoka, H; Manns, M P

1997-12-01

Auto-antibodies specific to various antigens in chronic hepatitis (CH) have been detected but their specificities and implications were uncertain. The aims of the present study were to investigate the frequency and the significance of seropositivity of antibodies to P450IID6 or liver/kidney microsome 1 (LKM1), soluble liver antigen (SLA), pyruvate dehydrogenase (PDH) and branched-chain keto acid dehydrogenase (BCKD) in 188 Japanese patients with different forms of CH by western blot or enzyme immunoassay (EIA). Anti-LKM1 was also measured by indirect immunofluorescent test. Anti-P450IID6 was found in 6/188 (3.2%) CH patients including 5/104 (4.8%) with hepatitis C virus (C) infection and 1/12 (8.3%) CH-C patients with antibodies to nuclear and smooth muscle antigens and hypergammaglobulinaemia (> 2.5 g/dL). This patient was the only one diagnosed with autoimmune hepatitis (AIH). All CH patients with hepatitis B (B), hepatitis non-B non-C (NBNC) and AIH were seronegative for anti-LKM1. Antibodies to soluble liver antigen were found in two of 188 (1%) patients, one with AIH and one with CH-B. Anti-BCKD-E2 but not anti-PDH-E2 was found in four patients (2.5%), one with AIH, two with CH-C, and one with NBNC. There was no obvious difference in age, sex ratio and laboratory findings in patients with or without anti-SLA and anti-BCKD-E2. Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 are uncommon in adult CH-C, CH-B, CH-NBNC and AIH patients in Japan. Some of these patients positive for auto-antibodies appear to have autoimmune features and might require a careful follow up. The heterogeneity of these antibodies in CH preclude further justification for subtyping of AIH by the presence of the distinct auto-antibodies.

TeSLA pilot 2 pedagogical & quality aspects

OpenAIRE

Janssen, José

2018-01-01

Presentation given at the TeSLA project meeting at the Open University of the Netherlands, addressing pedagogical aspects of pilot 2 and clarification of the scope and limitations of the TeSLA instruments with respect to pedagogy, assessment activity and type of academic dishonesty.

SlaVaComp: Konvertierungstool (= SlaVaComp Fonts Converter

Directory of Open Access Journals (Sweden)

Simon Skilevic

2013-12-01

Full Text Available Der vorliegende Beitrag informiert über ein Tool, das im Rahmen eines Freiburger Projekts zur historischen Korpuslinguistik entwickelt wurde und dazu dient, kirchenslavische Texte, die ohne Einsatz von Unicode digitalisiert wurden, ohne Verlust von Information bzw. Formatierung ins Unicode-Format zu überführen. Das Tool heißt SlaVaComp-Konvertierer. Es eignet sich für die Konvertierung aller idiosynkratischen Fonts und kann somit nicht nur in der Paläoslavistik, sondern in allen historisch arbeitenden Philologien eingesetzt werden. ____________________ This paper presents a fonts converter that was developed as a part of the Freiburg project on historical corpus linguistics. The tool named SlaVaComp-Konvertierer converts Church Slavonic texts digitized with non-Unicode fonts into the Unicode format without any loss of information contained in the original file and without damage to the original formatting. It is suitable for the conversion of all idiosyncratic fonts—not only Church Slavonic—and therefore can be used not only in Palaeoslavistic, but also in all historical and philological studies.

SLA Looks Globally.

Science.gov (United States)

Mark, Linda

1992-01-01

Summarizes the 1992 Special Libraries Association (SLA) Annual Conference. Topics discussed include emphasizing internationalism; competing in a global economy; the competitive importance of information; downsizing because of financial constraints; Internet and NREN (National Research and Education Network); recruitment; ethics; standards; and the…

Human Leukocyte Antigen-G Within the Male Reproductive System: Implications for Reproduction.

Science.gov (United States)

Hviid, Thomas Vauvert F

2015-01-01

In sexual reproduction in humans, a man has a clear interest in ensuring that the immune system of his female partner accepts the semi-allogenic fetus. Increasing attention has been given to soluble immunomodulatory molecules in the seminal fluid as one mechanism of ensuring this, possibly by "priming" the woman's immune system before conception and at conception. Recent studies have demonstrated the presence of the immunoregulatory and tolerance-inducible human leukocyte antigen (HLA)-G in the male reproductive organs. The expression of HLA-G in the blastocyst and by extravillous trophoblast cells in the placenta during pregnancy has been well described. Highly variable amounts of soluble HLA-G (sHLA-G) in seminal plasma from different men have been reported, and the concentration of sHLA-G is associated with HLA-G genotype. A first pilot study indicates that the level of sHLA-G in seminal plasma may even be associated with the chance of pregnancy in couples, where the male partner has reduced semen quality. More studies are needed to verify these preliminary findings.

Cryopreservation of Human Mucosal Leukocytes.

Directory of Open Access Journals (Sweden)

Sean M Hughes

Full Text Available Understanding how leukocytes in the cervicovaginal and colorectal mucosae respond to pathogens, and how medical interventions affect these responses, is important for developing better tools to prevent HIV and other sexually transmitted infections. An effective cryopreservation protocol for these cells following their isolation will make studying them more feasible.To find an optimal cryopreservation protocol for mucosal mononuclear leukocytes, we compared cryopreservation media and procedures using human vaginal leukocytes and confirmed our results with endocervical and colorectal leukocytes. Specifically, we measured the recovery of viable vaginal T cells and macrophages after cryopreservation with different cryopreservation media and handling procedures. We found several cryopreservation media that led to recoveries above 75%. Limiting the number and volume of washes increased the fraction of cells recovered by 10-15%, possibly due to the small cell numbers in mucosal samples. We confirmed that our cryopreservation protocol also works well for both endocervical and colorectal leukocytes. Cryopreserved leukocytes had slightly increased cytokine responses to antigenic stimulation relative to the same cells tested fresh. Additionally, we tested whether it is better to cryopreserve endocervical cells on the cytobrush or in suspension.Leukocytes from cervicovaginal and colorectal tissues can be cryopreserved with good recovery of functional, viable cells using several different cryopreservation media. The number and volume of washes has an experimentally meaningful effect on the percentage of cells recovered. We provide a detailed, step-by-step protocol with best practices for cryopreservation of mucosal leukocytes.

The Importance of Input and Interaction in SLA

Institute of Scientific and Technical Information of China (English)

党春花

2009-01-01

As is known to us, input and interaction play the crucial roles in second language acquisition (SLA). Different linguistic schools have different explanations to input and interaction Behaviorist theories hold a view that input is composed of stimuli and response, putting more emphasis on the importance of input, while mentalist theories find input is a necessary condition to SLA, not a sufficient condition. At present, social interaction theories, which is one type of cognitive linguistics, suggests that besides input, interaction is also essential to language acquisition. Then, this essay will discuss how input and interaction result in SLA.

Study of CD69 antigen expression and integrity of leukocyte cellular membrane in stored platelet concentrates following irradiation and treatment with Mirasol® PRT System.

Science.gov (United States)

Lachert, Elżbieta; Woźniak, Jolanta; Antoniewicz-Papis, Jolanta; Krzywdzińska, Agnieszka; Kubis, Jolanta; Mikołowska, Agata; Letowska, Magdalena

2017-01-01

Leukocytes in transfused blood components, particularly residual lymphocytes, have been shown to contribute to the occurrence of various adverse reactions. One of the most severe is transfusionassociated graft versus host disease (TA-GvHD) following transfusion of blood components contaminated with immunocompetent T lymphocytes. Irradiation is a routine method for protection against TA-GvHD. According to the literature, some pathogen reduction methods have also been proven effective for the inactivation of T lymphocytes, and so they may be considered as an alternative to irradiation. Comparison of CD69 antigen expression and the integrity of the leukocyte cellular membrane in stored platelet concentrates (PCs) following irradiation with the Gammacell 3000 Elan (Nordion Inc., Ottawa, Canada) and treatment with the Mirasol® Pathogen Reduction Technology (PRT) System (Terumo BCT, Lakewood, USA). The study included seven experiments. For each experiment we used 3 PCs, for Mirasol® PRT System treatment (M), for Gammacell 3000 Elan irradiation (R), and for the control (C). 7-amino-actinomycin D (7-AAD, Becton Dickinson, Franklin Lakes, USA) permeability was used to determine lymphocyte viability while CD69 antigen expression was the marker of lymphocyte activation. Analyses of 7-AAD and CD69 antigen expression were performed in a FACS Canto I flow cytometer (Becton Dickinson, USA). During 6 storage days, viable lymphocyte count decreased to 28% (p = 0.001) in the Mirasol® PRT System treated PCs and to 65% (p = 0.004) in the irradiated PCs. A statistically significant increase in CD69 expression in the irradiated PCs was observed; 1.3-fold on day 3 and 1.5-fold on day 6. In the Mirasol ® PRT System treated PCs, no statistically significant increase was observed. The in vitro results suggest that the Mirasol® PRT System is as effective as irradiation due to donor leukocyte inactivation capacity.

Microglial MHC antigen expression after ischemic and kainic acid lesions of the adult rat hippocampus

DEFF Research Database (Denmark)

Finsen, B.R.; Jørgensen, Martin Balslev; Diemer, Nils Henrik

1993-01-01

Leukocyte common antigen, macrophages, blood-brain barrier, neural degeneration, fascia dentata, neuropathology......Leukocyte common antigen, macrophages, blood-brain barrier, neural degeneration, fascia dentata, neuropathology...

A combined prediction strategy increases identification of peptides bound with high affinity and stability to porcine MHC class I molecules SLA-1*04:01, SLA-2*04:01, and SLA-3*04:01

DEFF Research Database (Denmark)

Pedersen, Lasse Eggers; Rasmussen, Michael; Harndahl, Mikkel

2016-01-01

constitute an attractive protocol to select target peptides from the vast pool of viral proteome peptides. We have earlier reported the peptide binding motif of the porcine MHC-I molecules SLA-1*04:01 and SLA-2*04:01, identified by an ELISA affinity-based positional scanning combinatorial peptide library...

Human leukocyte antigen genetics and clinical features of self-treated patients on a gluten-free diet.

Science.gov (United States)

Coburn, John A; Vande Voort, Jennifer L; Lahr, Brian D; Van Dyke, Carol T; Kroning, Cynthia M; Wu, Tsung-Teh; Gandhi, Manish J; Murray, Joseph A

2013-01-01

Increasingly, people start a gluten-free diet (GFD) without a clear celiac disease (CD) diagnosis. Human leukocyte antigen (HLA) genotyping is useful in ruling out CD in patients with equivocal results of serologic testing or small-bowel biopsy (SBB), but its utility and the clinical features of patients on self-treated GFD (ST-GFD) are largely unknown. Retrospective study of single tertiary care center cohort compared 137 patients on ST-GFD and 443 patients with well-defined CD. We compared HLA genotype, symptoms, serologic and SBB results, and response to GFD between the 2 groups. Analysis used univariate logistic regression modeling, adjusted for age and sex. Patients with ST-GFD presented more often with diarrhea (Pgluten sensitivity may play a role.

Distributed Trust Management for Validating SLA Choreographies

Science.gov (United States)

Haq, Irfan Ul; Alnemr, Rehab; Paschke, Adrian; Schikuta, Erich; Boley, Harold; Meinel, Christoph

For business workflow automation in a service-enriched environment such as a grid or a cloud, services scattered across heterogeneous Virtual Organizations (VOs) can be aggregated in a producer-consumer manner, building hierarchical structures of added value. In order to preserve the supply chain, the Service Level Agreements (SLAs) corresponding to the underlying choreography of services should also be incrementally aggregated. This cross-VO hierarchical SLA aggregation requires validation, for which a distributed trust system becomes a prerequisite. Elaborating our previous work on rule-based SLA validation, we propose a hybrid distributed trust model. This new model is based on Public Key Infrastructure (PKI) and reputation-based trust systems. It helps preventing SLA violations by identifying violation-prone services at service selection stage and actively contributes in breach management at the time of penalty enforcement.

Impact of Leukocyte Function-Associated Antigen-1 Blockade on Endogenous Allospecific T Cells to Multiple Minor Histocompatibility Antigen Mismatched Cardiac Allograft.

Science.gov (United States)

Kwun, Jean; Farris, Alton B; Song, Hyunjin; Mahle, William T; Burlingham, William J; Knechtle, Stuart J

2015-12-01

Blocking leukocyte function-associated antigen (LFA)-1 in organ transplant recipients prolongs allograft survival. However, the precise mechanisms underlying the therapeutic potential of LFA-1 blockade in preventing chronic rejection are not fully elucidated. Cardiac allograft vasculopathy (CAV) is the preeminent cause of late cardiac allograft failure characterized histologically by concentric intimal hyperplasia. Anti-LFA-1 monoclonal antibody was used in a multiple minor antigen-mismatched, BALB.B (H-2B) to C57BL/6 (H-2B), cardiac allograft model. Endogenous donor-specific CD8 T cells were tracked down using major histocompatibility complex multimers against the immunodominant H4, H7, H13, H28, and H60 minor Ags. The LFA-1 blockade prevented acute rejection and preserved palpable beating quality with reduced CD8 T-cell graft infiltration. Interestingly, less CD8 T cell infiltration was secondary to reduction of T-cell expansion rather than less trafficking. The LFA-1 blockade significantly suppressed the clonal expansion of minor histocompatibility antigen-specific CD8 T cells during the expansion and contraction phase. The CAV development was evaluated with morphometric analysis at postoperation day 100. The LFA-1 blockade profoundly attenuated neointimal hyperplasia (61.6 vs 23.8%; P < 0.05), CAV-affected vessel number (55.3 vs 15.9%; P < 0.05), and myocardial fibrosis (grade 3.29 vs 1.8; P < 0.05). Finally, short-term LFA-1 blockade promoted long-term donor-specific regulation, which resulted in attenuated transplant arteriosclerosis. Taken together, LFA-1 blockade inhibits initial endogenous alloreactive T-cell expansion and induces more regulation. Such a mechanism supports a pulse tolerance induction strategy with anti-LFA-1 rather than long-term treatment.

Association of canine juvenile generalized demodicosis with the dog leukocyte antigen system.

Science.gov (United States)

It, V; Barrientos, L; López Gappa, J; Posik, D; Díaz, S; Golijow, C; Giovambattista, G

2010-07-01

Demodectic mange is a well-known parasitic skin disease characterized by the presence of a larger than normal number of Demodex mites (Demodex canis) in the skin of dogs. Recent research has suggested that major histocompatibility complex (MHC) class II expression is higher in the skin of dogs suffering from demodicosis than in normal ones. We have investigated whether canine Dog Leukocyte Antigen (DLA) class II alleles are associated with canine juvenile generalized demodicosis (JGD). In the present study, the analysis of microsatellite markers (FH2202, FH2975 and FH2054) linked to DLA was made in Boxer, Argentinean Mastiff and mixed breed dogs. DNA samples from 56 dogs affected with the disease and 60 breed-matched controls collected in Argentina were analysed. A highly significant association, in some of the analysed markers, in all breeds with the presence of demodicosis was observed with P or =5. The results of this study suggest that an underlying DLA association exists with demodicosis in dogs and that this may represent an important immunological risk factor in the aetiology of this condition. This information could be used in the future to develop diagnostic tests to prevent canine JGD.

Human Leukocyte Antigen-G and Regulatory T Cells during Specific Immunotherapy for Pollen Allergy

DEFF Research Database (Denmark)

Sørensen, Anja Elaine; Johnsen, Claus R; Dalgaard, Louise Torp

2013-01-01

of the cytokine profile towards a TH1-polarized immune response. We investigated the effects of SIT on T cells, on immunomodulation of human leukocyte antigen (HLA)-G, which has been associated with allergy, on regulatory cytokine expression, and on serum allergen-specific antibody subclasses (IgE and IgG4......). Methods: Eleven birch and/or grass pollen-allergic patients and 10 healthy nonatopic controls were studied before and during SIT. Tregs, chemokine receptors, soluble HLA-G (sHLA-G), Ig-like transcript (ILT) 2, specific IgE, and IgG4 were studied. Peripheral blood mononuclear cells (PBMCs) were stimulated...... with pollen extract in vitro and immune factors were evaluated. Results: During SIT, the main changes in the peripheral blood were an increase in CXCR3+CD4+CD25+CD127low/- Tregs and a decrease in CCR4+CD4+CD25+CD127low/- Tregs, an increase in allergen-specific IgG4, and a decrease in sHLA-G during the first...

Protective Effect of Human Leukocyte Antigen (HLA Allele DRB1*13:02 on Age-Related Brain Gray Matter Volume Reduction in Healthy Women

Directory of Open Access Journals (Sweden)

Lisa M. James

2018-03-01

Full Text Available Background: Reduction of brain volume (brain atrophy during healthy brain aging is well documented and dependent on genetic, lifestyle and environmental factors. Here we investigated the possible dependence of brain gray matter volume reduction in the absence of the Human Leukocyte Antigen (HLA allele DRB1*13:02 which prevents brain atrophy in Gulf War Illness (James et al., 2017. Methods: Seventy-one cognitively healthy women (32–69 years old underwent a structural Magnetic Resonance Imaging (sMRI scan to measure the volumes of total gray matter, cerebrocortical gray matter, and subcortical gray matter. Participants were assigned to two groups, depending on whether they lacked the DRB1*13:02 allele (No DRB1*13:02 group, N = 60 or carried the DRB1*13:02 allele (N = 11. We assessed the change of brain gray matter volume with age in each group by performing a linear regression where the brain volume (adjusted for total intracranial volume was the dependent variable and age was the independent variable. Findings: In the No DRB1*13:02 group, the volumes of total gray matter, cerebrocortical gray matter, and subcortical gray matter were reduced highly significantly. In contrast, none of these volumes showed a statistically significant reduction with age in the DRB1*13:02 group. Interpretation: These findings document the protective effect of DRB1*13:02 on age-dependent reduction of brain gray matter in healthy individuals. Since the role of this allele is to connect to matching epitopes of external antigens for the subsequent production of antibodies and elimination of the offending antigen, we hypothesize that its protective effect may be due to the successful elimination of such antigens to which we are exposed during the lifespan, antigens that otherwise would persist causing gradual brain atrophy. In addition, we consider a possible beneficial role of DRB1*13:02 attributed to its binding to cathepsin S, a known harmful substance in brain

Human leukocyte antigen-G in the male reproductive system and in seminal plasma.

Science.gov (United States)

Larsen, Margit Hørup; Bzorek, Michael; Pass, Malene B; Larsen, Lise Grupe; Nielsen, Mette Weidinger; Svendsen, Signe Goul; Lindhard, Anette; Hviid, Thomas Vauvert F

2011-12-01

One of the non-classical human leukocyte antigen (HLA) class Ib proteins, HLA-G, is believed to exert important immunoregulatory functions, especially during pregnancy. The presence of HLA protein in paternal seminal fluid has been suggested to have an influence on the risk of developing pre-eclampsia. We have investigated whether HLA-G protein is present in human seminal plasma and in different tissue samples of the male reproductive system. Western blot technique and a soluble HLA-G (sHLA-G) assay were used to detect sHLA-G in human seminal plasma samples. Immunohistochemical staining was performed on paraffin-embedded tissue samples. We detected sHLA-G protein in seminal plasma, and HLA-G expression in normal testis and in epididymal tissue of the male reproductive system but not in the seminal vesicle. Furthermore, the results indicated a weak expression of HLA-G in hyperplastic prostatic tissue. In summary, several of the findings reported in this study suggest an immunoregulatory role of HLA-G in the male reproductive system and in seminal plasma.

Interleukin-6, C-reactive protein, and expression of human leukocyte antigen-DR on peripheral blood mononuclear cells in patients after laparoscopic vs. conventional bowel resection - A randomized study

NARCIS (Netherlands)

Dunker, M. S.; ten Hove, T.; Bemelman, W. A.; Slors, J. F. M.; Gouma, D. J.; van Deventer, S. J. H.

2003-01-01

PURPOSE: The aim of the study was to investigate the effect of surgical trauma in terms of approach (laparoscopic vs. conventional surgery) and extent of bowel resection (ileocolic resection vs. colectomy) on interleukin-6 level, C-reactive protein level, and expression of human leukocyte antigen-DR

Using high-resolution human leukocyte antigen typing of 11,423 randomized unrelated individuals to determine allelic varieties, deduce probable human leukocyte antigen haplotypes, and observe linkage disequilibria between human leukocyte antigen-B and-C and human leukocyte antigen-DRB1 and-DQB1 alleles in the Taiwanese Chinese population

Directory of Open Access Journals (Sweden)

Kuo-Liang Yang

2017-01-01

Full Text Available Objective: We report here the human leukocyte antigen (HLA allelic variety and haplotype composition in a cohort of the Taiwanese Chinese population and their patterns of linkage disequilibria on HLA-B: HLA-C alleles and HLA-DRB1: HLA-DQB1 alleles at a high-resolution level. Materials and Methods: Peripheral whole blood from 11,423 Taiwanese Chinese unrelated individuals was collected in acid citrate dextrose. Genomic DNA was extracted using the QIAamp DNA Blood Mini Kit. The DNA material was subjected to HLA genotyping for HLA-A,-B,-C,-DRB1, and-DQB1 loci using a commercial polymerase chain reaction-sequence-based typing (PCR-SBT kit, the SeCore® A/B/C/DRB1/DQB1 Locus Sequencing kit. High-resolution allelic sequencing was performed as previously described. Results: The number of individual HLA-B alleles detected was greater than the number of alleles recognized in the both the HLA-A and-DRB1 loci. Several novel alleles were discovered as a result of employing the SBT method and the high number of donors tested. In addition, we observed a genetic polymorphic feature of association between HLA-A and-B, HLA-B and-C, and HLA-DRB1 and-DQB1 alleles. Further, the homozygous haplotype frequencies of HLA-A and-B; HLA-A,-C, and-B; HLA-A,-C,-B, and-DRB1; and HLA-A,-C,-B,-DRB1, and-DQB1 in Taiwanese Chinese population are presented. Conclusion: As increasing number of HLA alleles are being discovered, periodic HLA profile investigation in a given population is essential to recognize the HLA complexity in that population. Population study can also provide an up-to-date strategic plan for future needs in terms of compatibility measurement for HLA matching between transplant donors and patients.

Altered expression of adhesion molecules on peripheral blood leukocytes in feline infectious peritonitis.

Science.gov (United States)

Olyslaegers, Dominique A J; Dedeurwaerder, Annelike; Desmarets, Lowiese M B; Vermeulen, Ben L; Dewerchin, Hannah L; Nauwynck, Hans J

2013-10-25

Feline infectious peritonitis (FIP) is a fatal, coronavirus-induced systemic disease in domestic and wild felids. The pathology associated with FIP (multifocal granulomatous vasculitis) is considered to be elicited by exaggerated activation and subsequent extravasation of leukocytes. As changes in the expression of adhesion molecules on circulating leukocytes precede their margination and emigration, we reasoned that the expression of leukocyte adhesion molecules may be altered in FIP. In present study, the expression of principal adhesion molecules involved in leukocyte transmigration (CD15s, CD11a, CD11b, CD18, CD49d, and CD54) on peripheral blood leukocytes from cats with naturally occurring FIP (n=15) and controls (n=12) was quantified by flow cytometry using a formaldehyde-based rapid leukocyte preparation technique. T- and B-lymphocytes from FIP patients exhibit higher expression of both subunits (CD11a and CD18) composing the β2 integrin lymphocyte function-associated antigen (LFA)-1. In addition, the expression of the α4 subunit (CD49d) of the β1 integrin very late antigen (VLA)-4 was elevated on B-lymphocytes from FIP patients. The expression of CD11b and CD18, that combine to form the β2 integrin macrophage-1 antigen (Mac-1), was elevated on monocytes, whereas the density of CD49d was reduced on this population in FIP. Granulocytes of FIP cats displayed an increased expression of the α chain of Mac-1 (CD11b). These observations suggest that leukocytes from FIP patients show signs of systemic activation causing them to extravasate into surrounding tissues and ultimately contribute to pyogranuloma formation seen in FIP. Copyright © 2013 Elsevier B.V. All rights reserved.

TeSLA e-assessment workshop

NARCIS (Netherlands)

Janssen, José

2016-01-01

Presentatie ten behoeve van de e-assessment workshop voor docenten van de Open Universiteit Nederland betrokken in de eerste TeSLA pilot. Topics: toetsfraude, toetsdesign, technologie voor authenticatie en verificatie van auteurschap.

Imputing amino acid polymorphisms in human leukocyte antigens.

Directory of Open Access Journals (Sweden)

Xiaoming Jia

Full Text Available DNA sequence variation within human leukocyte antigen (HLA genes mediate susceptibility to a wide range of human diseases. The complex genetic structure of the major histocompatibility complex (MHC makes it difficult, however, to collect genotyping data in large cohorts. Long-range linkage disequilibrium between HLA loci and SNP markers across the major histocompatibility complex (MHC region offers an alternative approach through imputation to interrogate HLA variation in existing GWAS data sets. Here we describe a computational strategy, SNP2HLA, to impute classical alleles and amino acid polymorphisms at class I (HLA-A, -B, -C and class II (-DPA1, -DPB1, -DQA1, -DQB1, and -DRB1 loci. To characterize performance of SNP2HLA, we constructed two European ancestry reference panels, one based on data collected in HapMap-CEPH pedigrees (90 individuals and another based on data collected by the Type 1 Diabetes Genetics Consortium (T1DGC, 5,225 individuals. We imputed HLA alleles in an independent data set from the British 1958 Birth Cohort (N = 918 with gold standard four-digit HLA types and SNPs genotyped using the Affymetrix GeneChip 500 K and Illumina Immunochip microarrays. We demonstrate that the sample size of the reference panel, rather than SNP density of the genotyping platform, is critical to achieve high imputation accuracy. Using the larger T1DGC reference panel, the average accuracy at four-digit resolution is 94.7% using the low-density Affymetrix GeneChip 500 K, and 96.7% using the high-density Illumina Immunochip. For amino acid polymorphisms within HLA genes, we achieve 98.6% and 99.3% accuracy using the Affymetrix GeneChip 500 K and Illumina Immunochip, respectively. Finally, we demonstrate how imputation and association testing at amino acid resolution can facilitate fine-mapping of primary MHC association signals, giving a specific example from type 1 diabetes.

Expression of Tac antigen component of bovine interleukin-2 receptor in different leukocyte populations infected with Theileria parva or Theileria annulata.

Science.gov (United States)

Dobbelaere, D A; Prospero, T D; Roditi, I J; Kelke, C; Baumann, I; Eichhorn, M; Williams, R O; Ahmed, J S; Baldwin, C L; Clevers, H

1990-01-01

The Tac antigen component of the bovine interleukin-2 receptor was expressed as a Cro-beta-galactosidase fusion protein in Escherichia coli and used to raise antibodies in rabbits. These antibodies were used for flow cytofluorimetric analysis to investigate the expression of Tac antigen in a variety of Theileria parva-infected cell lines and also in three Theileria annulata-infected cell lines. Cells expressing Tac antigen on their surface were found in all T. parva-infected cell lines tested whether these were of T- or B-cell origin. T cells expressing Tac antigen could be CD4- CD8-, CD4+ CD8-, CD4- CD8+, or CD4+ CD8+. Tac antigen expression was observed both in cultures which had been maintained in the laboratory for several years and in transformed cell lines which had recently been established by infection of lymphocytes in vitro with T. parva. Northern (RNA) blot analysis demonstrated Tac antigen transcripts in RNA isolated from all T. parva-infected cell lines. Three T. annulata-infected cell lines which were not of T-cell origin were also tested. Two of them expressed Tac antigen on their surface. Abundant Tac antigen mRNA was detected in these T. annulata-infected cell lines, but only trace amounts were demonstrated in the third cell line, which contained very few Tac antigen-expressing cells. In all cell lines tested, whether cloned or uncloned, a proportion of the cells did not express detectable levels of Tac antigen on their surface. This was also the case for a number of other leukocyte surface markers. In addition, we showed that the interleukin-2 receptors were biologically functional, because addition of recombinant interleukin-2 to cultures stimulated cell proliferation. Recombinant interleukin-2 treatment also resulted in increased amounts of steady-state Tac antigen mRNA. The relevance of interleukin-2 receptor expression on Theileria-infected cells is discussed. Images PMID:1979317

Evaluation of the Humoral Immune Response to Human Leukocyte Antigens in Brazilian Renal Transplant Candidates

Science.gov (United States)

Saito, Patricia Keiko; Yamakawa, Roger Haruki; Aparecida, Erica Pereira; da Silva Júnior, Waldir Verissimo; Borelli, Sueli Donizete

2014-01-01

Pre-transplant sensitization to human leukocyte antigens (HLA) is a risk factor for graft failure. Studies of the immunological profile related to anti-HLA antibodies in Brazilian renal transplant candidates are few. In this study, we evaluated the humoral immune response to HLA antigens in 269 renal transplant candidates, in Paraná State, Brazil. The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO) combined with Luminex technology, using an SSO-LABType commercial kit (One Lambda, Inc., Canoga Park, CA, USA). The percentages of panel-reactive antibodies (PRA) and the specificity of anti-HLA antibodies were determined using the LS1PRA and LS2PRA commercial kits (One Lambda, Inc.). The PRA-positive group consisted of 182 (67.7%) patients, and the PRA-negative group of 87 (32.3%) patients. The two groups differed significantly only with respect to gender. Females were the most sensitized. Among the 182 patients with PRA- positive, 62 (34.1%) were positive for class I and negative for class II, 39 (21.4%) were negative for class I and positive for class II, and 81 (44.5%) were positive for both classes I and II. The HLA-A*02, A*24, A*01, B*44, B*35, B*15, DRB1*11, DRB1*04 and DRB1*03 allele groups were the most frequent. The specificities of anti-HLA antibodies were more frequent: A34, B57, Cw15, Cw16, DR51, DQ8 and DP14. This study documented the profile of anti-HLA antibodies in patients with chronic renal failure who were on waiting lists for an organ in Paraná, and found high sensitization to HLA antigens in the samples. PMID:24927116

Evaluation of the humoral immune response to human leukocyte antigens in Brazilian renal transplant candidates.

Directory of Open Access Journals (Sweden)

Patricia Keiko Saito

Full Text Available Pre-transplant sensitization to human leukocyte antigens (HLA is a risk factor for graft failure. Studies of the immunological profile related to anti-HLA antibodies in Brazilian renal transplant candidates are few. In this study, we evaluated the humoral immune response to HLA antigens in 269 renal transplant candidates, in Paraná State, Brazil. The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO combined with Luminex technology, using an SSO-LABType commercial kit (One Lambda, Inc., Canoga Park, CA, USA. The percentages of panel-reactive antibodies (PRA and the specificity of anti-HLA antibodies were determined using the LS1PRA and LS2PRA commercial kits (One Lambda, Inc.. The PRA-positive group consisted of 182 (67.7% patients, and the PRA-negative group of 87 (32.3% patients. The two groups differed significantly only with respect to gender. Females were the most sensitized. Among the 182 patients with PRA- positive, 62 (34.1% were positive for class I and negative for class II, 39 (21.4% were negative for class I and positive for class II, and 81 (44.5% were positive for both classes I and II. The HLA-A*02, A*24, A*01, B*44, B*35, B*15, DRB1*11, DRB1*04 and DRB1*03 allele groups were the most frequent. The specificities of anti-HLA antibodies were more frequent: A34, B57, Cw15, Cw16, DR51, DQ8 and DP14. This study documented the profile of anti-HLA antibodies in patients with chronic renal failure who were on waiting lists for an organ in Paraná, and found high sensitization to HLA antigens in the samples.

Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

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Tilahun Alelign

2018-01-01

Full Text Available Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy.

Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

Science.gov (United States)

Ahmed, Momina M.; Bobosha, Kidist; Tadesse, Yewondwossen; Howe, Rawleigh; Petros, Beyene

2018-01-01

Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA) is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy. PMID:29693023

Increased Expression of Intercellular Adhesion Molecule-1, Vascular Cellular Adhesion Molecule-1 and Leukocyte Common Antigen in Diabetic Rat Retina

Institute of Scientific and Technical Information of China (English)

Ningyan Bai; Shibo Tang; Jing Ma; Yan Luo; Shaofeng Lin

2003-01-01

Purpose: To understand the expression and distribution of intercellular adhesion molecule- 1(ICAM- 1),vascular cellular adhesion molecule- 1 (VCAM- 1)and CD45 (Leukocyte Common Antigen) in the control nondiabetic and various courses of diabetic rats retina. To explore the role of adhesion molecules (Ams) and the adhesion of leukocytes to vascular endothelial cells via Ams in diabetic retinopathy(DR).Methods: Sixty healthy adult male Wistar rats were randomly divided into diabetic groups(induced by Streptozotocin, STZ) and normal control groups. Rats in these two groups were further randomly divided into 3, 7, 14, 30, 90 and 180 days-group,including 5 rats respectively. The immunohistochemical studies of ICAM-1, VCAM-1 and CD45 were carried out in the retinal digest preparations or retinal paraffin sections, and the results were analyzed qualitatively, semi-quantitatively.Results: No positive reaction of VCAM-1 was found, and weak reactions of ICAM-1,CD45 were found in nondiabetic rats retina. The difference of 6 control groups had no statistical significance(P ＞ 0.05). The increased ICAM-1 and CD45 staining pattern were detectable 3 days after diabetes induction, and a few VCAM-1 positive cells were observed in the retinal blood capillaries. The difference of diabetes and control is significant( P ＜ 0.05).Following the course, the expressions of ICAM-1, VCAM-1 and CD45 were increasingly enhanced, reaching a peak at the 14th day.Conclusion: Increased expression of ICAM-1, VCAM-1 and leukocytes adhering and stacking in retinal capillaries are the very early events in DR. Coherence of expression and distribution of the three further accounts for it is the key point for the onset of DR that Ams mediates leukocytes adhesion and endothelial cell injury.

Detection of human leukocyte antigen compatibility and antibodies in liver transplantation in China

Institute of Scientific and Technical Information of China (English)

Xue-Qin Meng; Xuan Zhang; Jun Fan; Lin Zhou; Bing Hao; Xiao-Ming Chen; Wei-Hang Ma; Shu-Sen Zheng

2009-01-01

BACKGROUND: The exact roles of human leukocyte antigen (HLA) compatibility, HLA antibodies and underlying diseases in acute rejection of liver transplants are not clear. Moreover, cytomegalovirus (CMV) infection, one of the most common infections after transplantation, is related to HLA genotype and the incidence of acute rejection. METHODS: Since there are controversial reports, we analyzed the impact of HLA matching, HLA antibodies and underlying diseases in 38 liver transplant recipients in China, and assessed the association of CMV infection and HLA compatibility. RESULTS: The frequency of no HLA compatibility was high in patients without antigenemia (P=0.019). All 17 patients with HLA-A matching developed antigenemia (P0.05). In patients with acute rejection, no differences were found in the incidence of acute rejection in transplants for hepatitis B, tumors, or combined hepatitis B and tumors (P>0.05).CONCLUSIONS: There are fewer acute rejections in transplants with more HLA compatibilities. Speciifc investigations of underlying diseases and HLA typing may be necessary in liver transplantation. The mechanisms of CMV infection and HLA matching should be further studied. HLA before transplantation should be examined for the prevention of acute rejection and CMV infection.

Accurate Typing of Human Leukocyte Antigen Class I Genes by Oxford Nanopore Sequencing.

Science.gov (United States)

Liu, Chang; Xiao, Fangzhou; Hoisington-Lopez, Jessica; Lang, Kathrin; Quenzel, Philipp; Duffy, Brian; Mitra, Robi David

2018-04-03

Oxford Nanopore Technologies' MinION has expanded the current DNA sequencing toolkit by delivering long read lengths and extreme portability. The MinION has the potential to enable expedited point-of-care human leukocyte antigen (HLA) typing, an assay routinely used to assess the immunologic compatibility between organ donors and recipients, but the platform's high error rate makes it challenging to type alleles with accuracy. We developed and validated accurate typing of HLA by Oxford nanopore (Athlon), a bioinformatic pipeline that i) maps nanopore reads to a database of known HLA alleles, ii) identifies candidate alleles with the highest read coverage at different resolution levels that are represented as branching nodes and leaves of a tree structure, iii) generates consensus sequences by remapping the reads to the candidate alleles, and iv) calls the final diploid genotype by blasting consensus sequences against the reference database. Using two independent data sets generated on the R9.4 flow cell chemistry, Athlon achieved a 100% accuracy in class I HLA typing at the two-field resolution. Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Introducing positive psychology to SLA

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Sarah Mercer

2014-01-01

Full Text Available Positive psychology is a rapidly expanding subfield in psychology that has important implications for the field of second language acquisition (SLA. This paper introduces positive psychology to the study of language by describing its key tenets. The potential contributions of positive psychology are contextualized with reference to prior work, including the humanistic movement in language teaching, models of motivation, the concept of an affective filter, studies of the good language learner, and the concepts related to the self. There are reasons for both encouragement and caution as studies inspired by positive psychology are undertaken. Papers in this special issue of SSLLT cover a range of quantitative and qualitative methods with implications for theory, research, and teaching practice. The special issue serves as a springboard for future research in SLA under the umbrella of positive psychology.

Comprehensive Analysis of Cytomegalovirus pp65 Antigen-Specific CD8+ T Cell Responses According to Human Leukocyte Antigen Class I Allotypes and Intraindividual Dominance

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Seung-Joo Hyun

2017-11-01

Full Text Available To define whether individual human leukocyte antigen (HLA class I allotypes are used preferentially in human cytomegalovirus (CMV-specific cytotoxic T lymphocyte responses, CD8+ T cell responses restricted by up to six HLA class I allotypes in an individual were measured in parallel using K562-based artificial antigen-presenting cells expressing both CMV pp65 antigen and one of 32 HLA class I allotypes (7 HLA-A, 14 HLA-B, and 11 HLA-C present in 50 healthy Korean donors. The CD8+ T cell responses to pp65 in the HLA-C allotypes were lower than responses to those in HLA-A and -B allotypes and there was no difference between the HLA-A and HLA-B loci. HLA-A*02:01, -B*07:02, and -C*08:01 showed the highest magnitude and frequency of immune responses to pp65 at each HLA class I locus. However, HLA-A*02:07, -B*59:01, -B*58:01, -B*15:11, -C*03:02, and -C*02:02 did not show any immune responses. Although each individual has up to six different HLA allotypes, 46% of the donors showed one allotype, 24% showed two allotypes, and 2% showed three allotypes that responded to pp65. Interestingly, the frequencies of HLA-A alleles were significantly correlated with the positivity of specific allotypes. Our results demonstrate that specific HLA class I allotypes are preferentially used in the CD8+ T cell immune response to pp65 and that a hierarchy among HLA class I allotypes is present in an individual.

The effect of HLA mismatches, shared cross-reactive antigen groups, and shared HLA-DR antigens on the outcome after pediatric liver transplantation

NARCIS (Netherlands)

Sieders, E; Hepkema, BG; Peeters, PMJG; Ten Vergert, EM; De Jong, KP; Porte, RJ; Bijleveld, CMA; van den Berg, AP; Lems, SPM; Gouw, ASH; Slooff, MJH

2005-01-01

The aim of this study was to analyze the effect of human leukocyte antigen (HLA) class I and HLA-DR mismatching, sharing cross-reactive antigen groups (CREGs), and sharing HLA-DR antigens on the outcome after pediatric liver transplantation. Outcome parameters were graft survival, acute rejection,

Human Leukocyte Antigen (HLA) Class I Restricted Epitope Discovery in Yellow Fewer and Dengue Viruses: Importance of HLA Binding Strength

DEFF Research Database (Denmark)

Lund, Ole; Nascimento, Eduardo J. M.; Maciel, Milton, Jr

2011-01-01

Epitopes from all available full-length sequences of yellow fever virus (YFV) and dengue fever virus (DENV) restricted by Human Leukocyte Antigen class I (HLA-I) alleles covering 12 HLA-I supertypes were predicted using the NetCTL algorithm. A subset of 179 predicted YFV and 158 predicted DENV...... inoculated twice with the 17DD YFV vaccine strain. Three of the YFV A*02:01 restricted peptides activated T-cells from the infected mice in vitro. All three peptides that elicited responses had an HLA binding affinity of 2 nM or less. The results indicate the importance of the strength of HLA binding...

A viral, transporter associated with antigen processing (TAP)-independent, high affinity ligand with alternative interactions endogenously presented by the nonclassical human leukocyte antigen E class I molecule.

Science.gov (United States)

Lorente, Elena; Infantes, Susana; Abia, David; Barnea, Eilon; Beer, Ilan; García, Ruth; Lasala, Fátima; Jiménez, Mercedes; Mir, Carmen; Morreale, Antonio; Admon, Arie; López, Daniel

2012-10-12

The transporter associated with antigen processing (TAP) enables the flow of viral peptides generated in the cytosol by the proteasome and other proteases to the endoplasmic reticulum, where they complex with nascent human leukocyte antigen (HLA) class I. Later, these peptide-HLA class I complexes can be recognized by CD8(+) lymphocytes. Cancerous cells and infected cells in which TAP is blocked, as well as individuals with unusable TAP complexes, are able to present peptides on HLA class I by generating them through TAP-independent processing pathways. Here, we identify a physiologically processed HLA-E ligand derived from the D8L protein in TAP-deficient vaccinia virus-infected cells. This natural high affinity HLA-E class I ligand uses alternative interactions to the anchor motifs previously described to be presented on nonclassical HLA class I molecules. This octameric peptide was also presented on HLA-Cw1 with similar binding affinity on both classical and nonclassical class I molecules. In addition, this viral peptide inhibits HLA-E-mediated cytolysis by natural killer cells. Comparison between the amino acid sequences of the presenting HLA-E and HLA-Cw1 alleles revealed a shared structural motif in both HLA class molecules, which could be related to their observed similar cross-reactivity affinities. This motif consists of several residues located on the floor of the peptide-binding site. These data expand the role of HLA-E as an antigen-presenting molecule.

SLA-aware differentiated QoS in elastic optical networks

Science.gov (United States)

Agrawal, Anuj; Vyas, Upama; Bhatia, Vimal; Prakash, Shashi

2017-07-01

The quality of service (QoS) offered by optical networks can be improved by accurate provisioning of service level specifications (SLSs) included in the service level agreement (SLA). A large number of users coexisting in the network require different services. Thus, a pragmatic network needs to offer a differentiated QoS to a variety of users according to the SLA contracted for different services at varying costs. In conventional wavelength division multiplexed (WDM) optical networks, service differentiation is feasible only for a limited number of users because of its fixed-grid structure. Newly introduced flex-grid based elastic optical networks (EONs) are more adaptive to traffic requirements as compared to the WDM networks because of the flexibility in their grid structure. Thus, we propose an efficient SLA provisioning algorithm with improved QoS for these flex-grid EONs empowered by optical orthogonal frequency division multiplexing (O-OFDM). The proposed algorithm, called SLA-aware differentiated QoS (SADQ), employs differentiation at the level of routing, spectrum allocation, and connection survivability. The proposed SADQ aims to accurately provision the SLA using such multilevel differentiation with an objective to improve the spectrum utilization from the network operator's perspective. SADQ is evaluated for three different CoSs under various traffic demand patterns and for different ratios of the number of requests belonging to the three considered CoSs. We propose two new SLA metrics for the improvement of functional QoS requirements, namely, security, confidentiality and survivability of high class of service (CoS) traffic. Since, to the best of our knowledge, the proposed SADQ is the first scheme in optical networks to employ exhaustive differentiation at the levels of routing, spectrum allocation, and survivability in a single algorithm, we first compare the performance of SADQ in EON and currently deployed WDM networks to assess the

Technique of leukocyte harvesting and labeling: problems and perspectives

International Nuclear Information System (INIS)

McAfee, J.G.; Subramanian, G.; Gagne, G.

1984-01-01

Mixed leukocyte suspensions obtained after gravity sedimentation of red cells and labeled with 111 In lipophilic chelates are now widely used clinically for abscess localization at many medical centers. So far, labeling with 111 In-oxine or tropolone has been more successful than any 99 mTc method. More sophisticated approaches are available for isolation and labeling of specific leukocyte cell types, to study their migration in vivo. The most significant advances in cell harvesting include newer density gradients for isopyknic centrifugation, centrifugal elutriation, and flow cytometry. Unlike current radioactive agents which label many cell types indiscriminately, more selective ligands are being developed which bind to specific cell surface receptors. These will label certain leukocyte populations or subtypes while not reacting with others, thereby avoiding laborious separation techniques. Monoclonal antibodies against leukocyte cell-surface antigens appear particularly promising as agents for selective cell labeling

Current Issues in the Teaching of Grammar: An SLA Perspective

Science.gov (United States)

Ellis, Rod

2006-01-01

The study of how learners acquire a second language (SLA) has helped to shape thinking about how to teach the grammar of a second language. There remain, however, a number of controversial issues. This paper considers eight key questions relating to grammar pedagogy in the light of findings from SLA. As such, this article complements…

On the Nature of Interaction in SLA: A Philosophical Stream

Science.gov (United States)

Maftoon, Parviz; Shakouri, Nima

2013-01-01

Researchers have long grappled with situating the stance of interaction in SLA, but it is only recently that interaction has begun to receive consideration from SLA quarters. Delving into the nature of interaction and the prerequisite of interaction in real world, in general, and in classroom, in particular, the authors hold that based on…

Strong human leukocyte antigen matching effect in nonsensitized kidney recipients with high pretransplant soluble CD30.

Science.gov (United States)

Süsal, Caner; Pelzl, Steffen; Opelz, Gerhard

2003-10-27

The influence of human leukocyte antigen (HLA) matching on graft survival is greater in patients with preformed lymphocytotoxic antibodies than in nonsensitized patients. Pretransplant serum soluble CD30 (sCD30) affects graft outcome independently of presensitization status. The impact of HLA compatibility on kidney transplant survival was analyzed in 3980 nonsensitized first cadaveric kidney recipients in relation to the pretransplant serum sCD30 content. Although HLA compatibility influenced graft outcome only marginally in nonsensitized recipients with low sCD30 (at 3 years: P=0.0095; at 5 years: P=0.1033), a strong HLA matching effect was observed in nonsensitized recipients with high sCD30 (at 3 years: PsCD30 benefit from an HLA well-matched kidney. Patients should be tested for sCD30 while on the waiting list for a kidney transplant, and HLA well-matched kidneys should be allocated to patients with high sCD30.

Optimisation of the CT h4S bioassay for detection of human interleukin-4 secreted by mononuclear cells stimulated by phytohaemaglutinin or by human leukocyte antigen mismatched mixed lymphocyte culture

DEFF Research Database (Denmark)

Petersen, Søren Lykke; Russell, Charlotte Astrid; Bendtzen, Klaus

2002-01-01

S bioassay detects 5 pg/ml of human recombinant IL-4 with no detection of IL-2 in concentrations below 500 pg/ml. We have found 72 h of culture optimal for detection of IL-2 and IL-4 produced by human mononuclear cells (MNC) in response to stimulation with phytohaemaglutinin and for detection of IL......-2 in human leukocyte antigen (HLA)-mismatched mixed leukocyte culture (MLC). An interindividual variation in cytokine accumulation was demonstrated for IL-4 but not for IL-2. With the use of 5x10(4) responder cells/well no IL-4 could be detected in HLA-mismatched MLC between days 1 and 16. The lack...

DDA/TDB liposomes containing soluble Leishmania major antigens induced a mixed Th1/Th2 immune response in BALB/c mice

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Mansure Hojatizade

2017-04-01

Full Text Available Objective(s: Leishmaniasis is a complex parasitic disease that represents a major public health problem. Despite numerous attempts over the past decades, yet there is no effective vaccine against human leishmaniasis probably due to the lack of suitable adjuvants. In this study, a first generation liposomal-based Leishmania vaccine was developed using soluble Leishmania major antigens (SLA and á, Ü-trehalose6, 6'-dibehenat (TDB as an immunostimulatory adjuvant. In this liposome structure, the cationic lipid Dimethyldioctadecylammonium (DDA provides intrinsic adjuvant activity and cholesterol was added as a membrane stabilizer. Liposomes containing SLA were prepared.Materials and Methods: BALB/c mice were subcutaneously (sc immunized with Lip (DDA/TDB/CHOL-SLA+, Lip (DDA/TDB-SLA+, Lip (DDA-SLA+, Lip (DDA/CHOL-SLA+, SLA or Tris-HCl buffer. Immunization was done every two weeks for three weeks. The immunized mice were then challenged sc in the left footpad with 1×106 stationary phase L. major promastigotes (50 ìl, at 2 weeks after last booster injection.Results: mice immunized with any of the liposomal formulations containing SLA (Lip-SLA+, substantially increased footpad swelling and parasite loads of foot and spleen with no significant difference compared to Tris-HCl buffer or SLA alone. Lip-SLA+ formulations induced a mixed Th1/Th2 immune response characterized by IFN-ã and IL-4 production as well as high levels of IgG1 anti-Leishmania antibody. Conclusion: immunization with liposomes containing DDA and/or TDB in combination with SLA induces a mixed Th1/Th2 immune response and is not an appropriate strategy for preferential induction of a Th1 response and protection against leishmaniasis.

The future (r)evolution of preimplantation genetic diagnosis/human leukocyte antigen testing: ethical reflections.

Science.gov (United States)

de Wert, Guido; Liebaers, Inge; Van de Velde, Hilde

2007-09-01

There has been increasing support for combining preimplantation genetic diagnosis (PGD) for specific diseases with a test for human leukocyte antigens (HLA) because the generation of HLA-matched umbilical cord blood cells may save the life of a diseased sibling. To date, this procedure has taken place in the context of conceiving another child--PGD/HLA testing type 1. However, it may well become possible to perform PGD/HLA testing outside this context, that is, to select matched embryos from which embryonic stem cells could be derived and used in cell therapy--PGD/HLA testing type 2. A proactive ethical analysis is needed and is presented in this article. Although PGD/HLA testing type 1 can be morally justified, the risks, pitfalls, and practical limitations of this procedure make it necessary to develop alternative strategies. PGD/HLA testing type 2 may provide an alternative strategy. From an ethical point of view, the controversial issue is that this procedure creates embryos purely for instrumental use. However, given the dominant view that the preimplantation embryo has only limited moral value, this alternative may be as morally justified as PGD/HLA testing type 1.

Introducing Positive Psychology to SLA

Science.gov (United States)

MacIntyre, Peter D.; Mercer, Sarah

2014-01-01

Positive psychology is a rapidly expanding subfield in psychology that has important implications for the field of second language acquisition (SLA). This paper introduces positive psychology to the study of language by describing its key tenets. The potential contributions of positive psychology are contextualized with reference to prior work,…

Relating SLA Research to Language Teaching Materials

Directory of Open Access Journals (Sweden)

Vivian J. Cook

1998-12-01

Full Text Available Abstract This article discusses applications of Second Language Acquisition (SLA research to the preparation of language coursebooks. The author suggests a number of ways in which SLA research findings can help improve coursebooks and thereby enhance the learning of large numbers of students. Research leads us to consider learners as genuine speakers of the L2, as bilinguals who still have an L1 present in their minds and who do not all go about learning the L2 in the same way. Few coursebooks take into account these and other findings of SLA research, for example: that the acquisition of basic syntax precedes the acquisition of inflectional morphology, that most of the syntax to be learned is really part of the lexicon, or that vocabulary needs to be encountered in a structural and semantic context in order to be effectively acquired. Coursebook authors also need to bear in mind that pronunciation is necessary not only for communication but also for the actual learning of L2 forms, and that some aspects of the L2 writing system need to be explicitly taught. The author provides two sample lessons to illustrate how these research findings might be applied to the writing of a coursebook.

Modeling the Structural Response of Reinforced Glass Beams using an SLA Scheme

NARCIS (Netherlands)

Louter, P.C.; Graaf, van de Anne; Rots, J.G.; Bos, Freek; Louter, Pieter Christiaan; Veer, Fred

2010-01-01

This paper investigates whether a novel computational sequentially linear analysis (SLA) technique, which is especially developed for modeling brittle material response, is applicable for modeling the structural response of metal reinforced glass beams. To do so, computational SLA results are

Correlation between Leukocyte Numbers and Body Size of Rainbow Trout

DEFF Research Database (Denmark)

Mohammad, Rezkar Jaafar; Otani, Maki; Kania, Per Walter

2016-01-01

wild and cultured fish and we show that the size of the leukocyte population increases exponentially with body size of rainbow trout. Four groups (5 fish/group) of naive rainbow trout (Oncorhynchus mykiss) with a mean body weight of 2 - 4 g (group I), 4 - 6 g (group II), 25 - 30 g (group III), and 650...... towards an antigen to be initiated even in fry. The number of leukocytes in individual fish at different developmental stages is likely to influence the capacity of the fish to respond simultaneously to several antigens (pathogens and vaccine components). This parameter may therefore be crucial for both...... - 780 g (group IV) were investigated. The number of lymphocytes was generally higher in head kidney compared to blood and spleen but they dominated in all samples (blood, head kidney and spleen) and their numbers increased exponentially with fish size. Percentages of lymphocytes in relation...

Monoclonal antibodies and coupling reagents to cell membrane proteins for leukocyte labeling

International Nuclear Information System (INIS)

McAfee, J.G.; Gagne, G.; Subramanian, G.; Schneider, R.F.

1984-01-01

Current gamma-emitting agents for tagging leukocytes, In-111 oxine or tropolone, label all cell types indiscriminantly, and nuclear localization in lymphocytes results in radiation damage. Coupling reagents and murine monoclonal antibodies (Mab) specific for cell surface antigens of human leukocytes were tried as cell labeling agents to avoid nuclear localization. 10/sup 8/ mixed human leukocytes in Hepes buffer were added to tubes coated with 5 mg of dry cyclic dianhydride of DTPA for 15 minutes at room temperature. After washing, 0.1 ml of In-111 Cl in ACD (pH 6.8) was added. After 30 minutes, a cell labeling yield of 23% was obtained. Washing the cells in an elutriation centrifuge showed that this label was irreversible. Mab for cell surface antigens of human granulocytes were labeled with 300 μCi of I-125 using the Iodobead technic and unbound activity was removed by gel column chromatography. 1-10 μg were added to 10/sup 8/ mixed leukocytes in 0.5 ml plasma or saline for 1 hr. With Mab anti-leu M4 (clone G7 E11), an IgM, the cell labeling yield was 21%, irreversible, and specific for granulocytes. With anti-human leukocyte Mab NEI-042 (clone 9.4), and IgG2a, and anti-granulocyte Mab MAS-065 (clone FMCl1) an IgG1, the cell labeling was relatively unstable. Labeling of leukocyte subpopulations with Mab is feasible, and the binding of multivalent IgM is stronger than that of other immunoglobulins. DTPA cyclic anhydride is firmly bound to cell membranes, but the labeling is non-specific

Human Leukocyte Antigen Typing Using a Knowledge Base Coupled with a High-Throughput Oligonucleotide Probe Array Analysis

Science.gov (United States)

Zhang, Guang Lan; Keskin, Derin B.; Lin, Hsin-Nan; Lin, Hong Huang; DeLuca, David S.; Leppanen, Scott; Milford, Edgar L.; Reinherz, Ellis L.; Brusic, Vladimir

2014-01-01

Human leukocyte antigens (HLA) are important biomarkers because multiple diseases, drug toxicity, and vaccine responses reveal strong HLA associations. Current clinical HLA typing is an elimination process requiring serial testing. We present an alternative in situ synthesized DNA-based microarray method that contains hundreds of thousands of probes representing a complete overlapping set covering 1,610 clinically relevant HLA class I alleles accompanied by computational tools for assigning HLA type to 4-digit resolution. Our proof-of-concept experiment included 21 blood samples, 18 cell lines, and multiple controls. The method is accurate, robust, and amenable to automation. Typing errors were restricted to homozygous samples or those with very closely related alleles from the same locus, but readily resolved by targeted DNA sequencing validation of flagged samples. High-throughput HLA typing technologies that are effective, yet inexpensive, can be used to analyze the world’s populations, benefiting both global public health and personalized health care. PMID:25505899

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

Science.gov (United States)

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

Immunochip analysis identifies novel susceptibility loci in the human leukocyte antigen region for acquired thrombotic thrombocytopenic purpura.

Science.gov (United States)

Mancini, I; Ricaño-Ponce, I; Pappalardo, E; Cairo, A; Gorski, M M; Casoli, G; Ferrari, B; Alberti, M; Mikovic, D; Noris, M; Wijmenga, C; Peyvandi, F

2016-12-01

Essentials Genetic predisposition to acquired thrombotic thrombocytopenic purpura (aTTP) is mainly unknown. Genetic risk factors for aTTP were studied by Immunochip analysis and replication study. Human leukocyte antigen (HLA) variant rs6903608 conferred a 2.5-fold higher risk of developing aTTP. rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in aTTP. Click to hear Dr Cataland's presentation on acquired thrombotic thrombocytopenic purpura SUMMARY: Background Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy associated with the development of autoantibodies against the von Willebrand factor-cleaving protease ADAMTS-13. Similarly to what has been found for other autoimmune disorders, there is evidence of a genetic contribution, including the association of the human leukocyte antigen (HLA) class II complex with disease risk. Objective To identify novel genetic risk factors in acquired TTP. Patients/Methods We undertook a case-control genetic association study in 190 European-origin TTP patients and 1255 Italian healthy controls by using the Illumina Immunochip. Replication analysis in 88 Italian cases and 456 controls was performed with single-nucleotide polymorphism (SNP) TaqMan assays. Results and conclusion We identified one common variant (rs6903608) located within the HLA class II locus that was independently associated with acquired TTP at genome-wide significance and conferred a 2.6-fold increased risk of developing a TTP episode (95% confidence interval [CI] 2.02-3.27, P = 1.64 × 10 -14 ). We also found five non-HLA variants mapping to chromosomes 2, 6, 8 and X that were suggestively associated with the disease: rs9490550, rs115265285, rs5927472, rs7823314, and rs1334768 (nominal P-values ranging from 1.59 × 10 -5 to 7.60 × 10 -5 ). Replication analysis confirmed the association of HLA variant rs6903608 with acquired TTP (pooled P = 3.95 × 10 -19 ). Imputation of classic

From viral genome to specific peptide epitopes: methods for identifying porcine T cell epitopes based on in silico predictions, in vitro identification and ex vivo verification

DEFF Research Database (Denmark)

Pedersen, Lasse Eggers; Rasmussen, Michael; Harndah, Mikkel

2013-01-01

to predict likely candidates for peptide-SLA binding. These results were combined with binding predictions generated by the algorithm, NetMHCpan (http://www.cbs.dtu.dk/services/NetMHCpan/) in order to select peptide candidates for in vitro analysis. The correlation between high affinity and high stability.......000 peptides. T cell epitopes were identified using peptide-SLA complexes assembled into fluorescent tetramers to stain swine influenza specific CTLs derived from immunized animals and MHC-defined pigs vaccinated against foot-and-mouth disease virus. These results demonstrate the broad applicability of methods...... originally developed for analysis of human leukocyte antigen (HLA) presentation of peptides. The methods presented provide a timely and cost-effective approach to CTL epitope discovery that can be applied to diseases of swine and of other mammalian species of interest....

Human leukocyte antigen in the allocation of kidneys from cadaveric donors in the United States.

Science.gov (United States)

Ting, Alan; Edwards, Leah Bennett

2004-02-27

Minorities wait longer for a cadaveric donor kidney transplant than whites. For example, the median waiting time to transplant for candidates listed from 1997 to 1998 was 874 days for whites, 1,493 days for blacks, 1,281 days for Hispanics, 1,491 days for Asians, and 1,466 days for others. The current allocation algorithm has been criticized as contributing to decreased access to transplants for racial minorities. There are two levels in the current algorithm: The first is mandatory national sharing between donors and patients with zero human leukocyte antigen (HLA)-A, B, and DR mismatches. The second occurs if there are no candidates and local placement is accomplished based on an algorithm with an HLA component that assigns seven, five, and two points to zero, one, and two HLA-B and DR mismatches, respectively. An analysis of the data shows that a higher percentage of white recipients (21%) received zero antigen mismatched kidneys compared with other races: blacks (7%), Hispanics (14%), and Asians (7%). Whites also received the highest percentage of kidneys with zero B and DR mismatches and one B and DR mismatch compared with the other races. These data indicate that the current algorithm favors whites over minorities, and it is most likely that giving points for HLA-B matching is a strong contributory factor. To address this inequity, the Organ Procurement and Transplantation Network and United Network for Organ Sharing Board of Directors approved a recommendation in November 2002 to change the HLA points to award two points for zero DR mismatches and one point for one DR mismatch. Obviously it will take some time to gather sufficient data to allow meaningful analysis of the effect of the policy change.

Association of human cytomegalovirus viremia with human leukocyte antigens in liver transplantation recipients

Institute of Scientific and Technical Information of China (English)

Jianhua Hu; Jun Fan; Xueqin Meng; Hong Zhao; Xuan Zhang; Hainv Gao; Meifang Yang; Yadan Ma; Minhuan Li; Weihang Ma

2011-01-01

Human cytomegalovirus (HCMV) reactivation is a common complication after liver transplantation (LT).Here, we investigated whether human leukocyte antigen (HLA)-matching was related to HCMV infection and subsequent graft failure after LT for hepatitis B virus cirrhosis. This retrospective study reviewed 91 LT recipients.All the patients were grouped according to HLA-A, HLA-B, and HLA-DR locus matching. Clinical data were collected, including complete HLA-typing, HCMV viremia, graft failure, and the time of HCMV viremia.HLA typing was performed using a sequence-specific primer-polymerase chain reaction kit. HCMV was detected by pp65 antigenemia using a commercial kit.The incidence of HCMV infection post-LT was 81.32%.Graft failure was observed in 16 of 91 (17.6%) patients during the 4-year study. The incidence of HCMV viremia was 100% (5/5), 91.4% (32/35), and 72.5% (37/51) in HLA-A two locus, one locus, and zero locus compatibility,respectively. Nevertheless, the degree of the HLA-A,HLA-B, or HLA-DR match did not influence the time of HCMV viremia, graft failure, or the time of graft failure after a diagnosis of HCMV viremia (all P＞ 0.05). An interesting discovery was that the risk of HCMV viremia tended to be higher in patients with better HLA-A compatibility. Graft failure, time of HCMV viremia, and graft failure after a diagnosis of HCMV viremia appear to be independent of HLA allele compatibility.

Analytical Review of Universal Grammar (UG) Approach on Second Language Acquisition (SLA)

Science.gov (United States)

Irwandy

2015-01-01

The aim of this paper is to explore the analysis of Universal Grammar (UG) approach on Second Language Acquisition (SLA). This paper is significant as the sources for teacher or researcher of the second language since this elaboration is deeply focusing on the use of UG on SLA. The method used in this academic writing is inductive method of…

Relative impact of human leukocyte antigen mismatching and graft ischemic time after lung transplantation.

Science.gov (United States)

Brugière, Olivier; Thabut, Gabriel; Suberbielle, Caroline; Reynaud-Gaubert, Martine; Thomas, Pascal; Pison, Christophe; Saint Raymond, Christel; Mornex, Jean-François; Bertocchi, Michèle; Dromer, Claire; Velly, Jean-François; Stern, Marc; Philippe, Bruno; Dauriat, Gaëlle; Biondi, Giuseppina; Castier, Yves; Fournier, Michel

2008-06-01

Recent data strongly suggest that human leukocyte antigen (HLA) mismatching has a negative impact on development of bronchiolitis obliterans syndrome (BOS) and survival after lung transplantation (LTx). Because HLA matching is sometimes achieved by extending ischemic time in other solid-organ transplantation models and ischemic time is a risk factor per se for death after LTx, we sought to compare the theoretical benefit of HLA matching with the negative impact of lengthened ischemic time. In this collaborative study we compared the relative impact of HLA mismatching and ischemic time on BOS and survival in 182 LTx recipients. Using multivariate analyses, we observed a lower incidence of BOS (hazard ratio [HR] = 1.70, 95% confidence interval [CI]: 1.1 to 2.7, p = 0.03) and enhanced survival (HR = 1.91, 95% CI: 1.24 to 2.92, p = 0.01) in patients with zero or one HLA-A mismatch compared with those having two HLA-A mismatches. This beneficial effect on survival was equivalent to a reduction of ischemic time of 168 minutes. We observed a reduced incidence of BOS and a better survival rate in patients well-matched at the HLA-A locus, associated with an opposite effect of an enhanced ischemic time. This suggests that graft ischemic time should be taken into account in future studies of prospective HLA matching in LTx.

TeSLA presentatie voor medewerkers van AMN

NARCIS (Netherlands)

Janssen, José

2017-01-01

Presentatie over Online toetsen voor medewerkers van AMN (www.amn.nl). Topics: assessment onderzoek Welten-instituut en meer in het bijzonder het TeSLA project waarin instrumenten voor authenticatie en auteurschap verificatie worden gecombineerd om betrouwbaar toetsen op afstand mogelijk te maken.

Persistence of hepatitis C virus in a white population: associations with human leukocyte antigen class 1.

LENUS (Irish Health Repository)

Fanning, Liam J

2012-02-03

The aim of this study was to define novel associations between human leukocyte antigen (HLA) class 1 alleles and persistence or clearance of the hepatitis C virus (HCV) in a white population. All individuals in the study were seropositive for anti-HCV antibodies. Viral status was determined by the Roche HCV Amplicor test. HLA-A, -B, -C allelic group profile was molecularly defined by reverse line probe hybridization. The strongest individual allelic group associations with persistent HCV infection were HLA A*11 (p = 0.044) and Cw*04 (p = 0.006). However, only the HLA C*04 association survived correction for multiple comparisons. Further analysis of alleles in linkage with HLA Cw*04 revealed that the haplotype HLA A*11, Cw*04 was present in 11 individuals, 10 of whom were viremic (p = 0.05). No gene dosage effect was observed. No association between HLA class 1 allelic groups and aviremia and virus load was evident in this white population. HLA B*44 is associated with low virus load in human immunodeficiency virus disease, but this association was not evident in this HCV-infected population. Novel HLA class 1 alleles associated with persistence of HCV have been identified.

77 FR 38884 - Sisseton Milbank Railroad Company-Acquisition and Operation Exemption-SLA Property Management...

Science.gov (United States)

2012-06-29

... DEPARTMENT OF TRANSPORTATION Surface Transportation Board [Docket No. FD 35641] Sisseton Milbank Railroad Company--Acquisition and Operation Exemption--SLA Property Management Limited Partnership and... verified notice of exemption under 49 CFR 1150.31 to acquire from SLA Property Management Limited...

The cost for meeting SLA dependability requirements; implications for customers and providers

International Nuclear Information System (INIS)

Følstad, Eirik L.; Helvik, Bjarne E.

2016-01-01

A Service Level Agreement (SLA) describes the service, the service-level objectives (SLOs), the price the customer should pay and the compensation if the SLOs are not met. There is a trade-off for the provider between the costs for improving the deployed service quality vs. probability of paying compensation. We propose how to estimate the provider's optimal service deployment. We show that the optimal deployed service quality is dependent on the SLOs, deployment cost, compensation and observation interval. A service deployment based on cost optimization results in targeted dependability objective values that are significantly better than stated in the SLOs. The proposed approach provides valuable insight for an aggregator, who buys services from other providers, to negotiate adequate SLOs, price and compensation from the providers to make a valuable offer for its own customers. - Highlights: • SLA with availability, number of failures, down time criteria and observation period. • Analysis of compound service delivery in the SLA context by a semi-Markov model. • SLA non-conformance risk dependent on the inherent/steady state system parameters. • Cost optimal service operation under non-conformance penalties (the safety margin).

Discriminating between Interstitial and Circulating Leukocytes in Tissues of the Murine Oral Mucosa Avoiding Nasal-Associated Lymphoid Tissue Contamination.

Science.gov (United States)

Bittner-Eddy, Peter D; Fischer, Lori A; Tu, Andy A; Allman, Daniel A; Costalonga, Massimo

2017-01-01

Periodontitis is a chronic inflammatory response to a microbial biofilm that destroys bone and soft tissues supporting the teeth. Murine models of periodontitis based on Porphyromonas gingivalis ( Pg ) colonization have shown that extravasation of leukocytes into oral tissue is critical to driving alveolar bone destruction. Identifying interstitial leukocytes is key to understanding the immunopathogenesis of periodontitis. Here, we describe a robust flow cytometry assay based on intravenous FITC-conjugated anti-mouse CD45 mAb that distinguishes interstitial leukocytes in the oral mucosa of mice from those circulating within the vasculature or in post-dissection contaminating blood. Unaccounted circulating leukocytes skewed the relative frequency of B cells and granulocytes and inflated the numbers of all leukocyte cell types. We also describe a dissection technique that avoids contamination of oral mucosal tissues with nasal-associated lymphoid tissues (NALT), a B cell rich organ that can inflate leukocyte numbers at least 10-fold and skew the assessment of interstitial CD4 T cell phenotypes. Unlike circulating CD4 T cells, interstitial CD4 T cells were almost exclusively antigen-experienced cells (CD44 hi ). We report for the first time the presence of antigen-experienced Pg -specific CD4 T cells in NALT following oral feeding of mice with Pg . This new combined flow cytometry and dissection approach allows identification of leukocytes infiltrating the connective tissues of the murine oral mucosa and avoids confounding analyses of leukocytes not recruited to inflamed oral mucosal tissues in disease conditions like periodontitis, candidiasis, or sialadenitis.

Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens

International Nuclear Information System (INIS)

Szala, S.; Kasai, Yasushi; Steplewski, Z.; Rodeck, U.; Koprowski, H.; Linnenbach, A.J.

1990-01-01

The human tumor-associated antigen CO-029 is a monoclonal antibody-defined cell surface glycoprotein of 27-34 kDa. By using the high-efficiency COS cell expression system, a full-length cDNA clone for CO-029 was isolated. When transiently expressed in COS cells, the cDNA clone directed the synthesis of an antigen reactive to monoclonal antibody CO-029 in mixed hemadsorption and immunoblot assays. Sequence analysis revealed that CO-029 belongs to a family of cell surface antigens that includes the melanoma-associated antigen ME491, the leukocyte cell surface antigen CD37, and the Sm23 antigen of the parasitic helminth Schistosoma mansoni. CO-029 and ME491 antigen expression and the effect of their corresponding monoclonal antibodies on cell growth were compared in human tumor cell lines of various histologic origins

Focal epithelial hyperplasia associated with human papillomavirus 13 and common human leukocyte antigen alleles in a Turkish family.

Science.gov (United States)

Akoğlu, Gülşen; Metin, Ahmet; Ceylan, Gülay Güleç; Emre, Selma; Akpolat, Demet; Süngü, Nuran

2015-02-01

Focal epithelial hyperplasia (FEH) is a rare and benign papillomatous disease of the oral cavity, which is closely associated with human papillomavirus (HPV) type 13 and 32. Genetic susceptibility to HPV infections are supported by recent studies involving the human leukocyte antigen system (HLA). In this report, we aimed to determine the clinicopathological features of a Turkish family with FEH and to detect the shared HLA DR and DQ types. HPV DNA typing of tissue samples and HLA determination from blood samples of four family members were performed by polymerase chain reaction. Histopathological examination of all patients revealed acanthotic papillomatous epidermis, koilocytes, apoptotic keratinocytes, and mitosoid bodies. HPV13 was detected by polymerase chain reaction. HLA DQA1*0501, HLA DQB1*0302, and HLA DRB1*11 alleles were common in all family members. HLA DRB1*04 was detected in three of them. This report is the first step for the investigation of involvement of HLA types in the pathogenesis of Turkish patients with FEH. © 2014 The International Society of Dermatology.

Polymorphism of leukocyte and erythrocyte antigens in chronic kidney disease patients in southern Brazil.

Directory of Open Access Journals (Sweden)

Roger Haruki Yamakawa

Full Text Available We investigated the polymorphism of human leukocyte antigens (HLA and Duffy erythrocyte antigens in chronic kidney disease (CKD patients in southern Brazil. One hundred and eighty-three CKD patients, over 18 years old, on hemodialysis, were included. HLA-A, -B and -DRB1 typing was performed using the LABType®SSO (One Lambda, Inc.. Duffy phenotypes were determined by gel column agglutination using anti-Fy(a and anti-Fy(b monoclonal anti-sera. The patients' predominant ages ranged between 51 and 70 years (43% and the predominant gender, ethnic group and dialysis period were, respectively, male (62%, white (62% and 1-3 years (40%. The highest and lowest frequencies of Duffy phenotypes were Fy(a+b+ and Fy(a-b-, respectively. Nineteen HLA-A, 30 HLA-B and 13 HLA-DRB1 allele groups were identified. The most frequent HLA allele groups were HLA-A*01, -A*02, -A*03, -A*11, -A*24; HLA-B*07, -B*15, -B*35, -B*44, -B*51; HLA-DRB1*03, -DRB1*04, -DRB1*07, -DRB1*11 and -DRB1*13. Statistically significant differences were observed in the Duffy and HLA polymorphisms compared between CKD patients and healthy subjects. The Fy(a+b- phenotype (p<0.0001, OR = 2.56, 95% CI = 1.60-4.07 was the most frequent in the patients (p<0.05, and the Fy(a+b+ phenotype (p = 0.0039, OR = 1.71, 95% CI = 1.18-2.51 was the most frequent in the healthy subjects in the same region of Paraná state (p<0.05. Regarding HLA, the HLA-B*42, -B*45, -B*51 and -DRB1*03 allele groups were the most frequent in the patients (p<0.05, and the HLA-B*44 allele group was the most frequent in the healthy subjects in the same region of Brazil (p<0.05. The polymorphism of these two markers among CKD patients in southern Brazil and healthy subjects of other studies, suggests that these markers might be involved with CKD development. Further studies should be undertaken to analyze the markers' influence on CKD and the long-term results from kidney transplantation.

Ionizing radiation modulates the surface expression of human leukocyte antigen-G in a human melanoma cell line

Energy Technology Data Exchange (ETDEWEB)

Michelin, S.; Gallegos, C.E.; Dubner, D. [Radiopathology Laboratory, Nuclear Regulatory Authority, Buenos Aires (Argentina); Favier, B.; Carosella, E.D. [CEA, I2BM, Hopital Saint-Louis, IUH, Service de Recherches en Hemato-Immunologie, Paris (France)

2009-07-01

Human leukocyte antigen G (HLA-G) is a nonclassical HLA class I molecule involved in fetus protection from the maternal immune system, transplant tolerance, and viral and tumoral immune escape. Tumor-specific HLA-G expression has been described for a wide variety of malignancies, including melanomas. The aim of this study was to evaluate whether ionizing radiation (IR) could modulate the surface expression of HLA-G1 in a human melanoma cell line that expresses endogenously membrane-bound HLA-G1. For this purpose, cells were exposed to increasing doses of {gamma}-irradiation (0-20 Gy) and HLA-G1 levels at the plasma membrane were analyzed at different times postirradiation by flow cytometry. HLA-G total expression and the presence of the soluble form of HLA-G1 (sHLA-G1) in the culture medium of irradiated cells were also evaluated. IR was capable of down regulating cell surface and total HLA-G levels, with a concomitant increase of sHLA-G1 in the medium. These results could indicate that {gamma}-irradiation decreases HLA-G1 surface levels by enhancing the proteolytic cleavage of this molecule. (authors)

Ionizing radiation modulates the surface expression of human leukocyte antigen-G in a human melanoma cell line

International Nuclear Information System (INIS)

Michelin, S.; Gallegos, C.E.; Dubner, D.; Favier, B.; Carosella, E.D.

2009-01-01

Human leukocyte antigen G (HLA-G) is a nonclassical HLA class I molecule involved in fetus protection from the maternal immune system, transplant tolerance, and viral and tumoral immune escape. Tumor-specific HLA-G expression has been described for a wide variety of malignancies, including melanomas. The aim of this study was to evaluate whether ionizing radiation (IR) could modulate the surface expression of HLA-G1 in a human melanoma cell line that expresses endogenously membrane-bound HLA-G1. For this purpose, cells were exposed to increasing doses of γ-irradiation (0-20 Gy) and HLA-G1 levels at the plasma membrane were analyzed at different times postirradiation by flow cytometry. HLA-G total expression and the presence of the soluble form of HLA-G1 (sHLA-G1) in the culture medium of irradiated cells were also evaluated. IR was capable of down regulating cell surface and total HLA-G levels, with a concomitant increase of sHLA-G1 in the medium. These results could indicate that γ-irradiation decreases HLA-G1 surface levels by enhancing the proteolytic cleavage of this molecule. (authors)

Transformation of ATLA-negative leukocytes by blood components from anti-ATLA-positive donors in vitro.

Science.gov (United States)

Miyamoto, K; Tomita, N; Ishii, A; Nishizaki, T; Kitajima, K; Tanaka, T; Nakamura, T; Watanabe, S; Oda, T

1984-06-15

Anti-ATLA-positive blood components transformed healthy human leukocytes in vitro. Blood components examined were packed red cells, whole blood, platelet concentrate and fresh frozen plasma. Leukocytes present in anti-ATLA-positive blood components such as packed red cells, whole blood and platelet concentrate easily transformed anti-ATLA-negative leukocytes. Co-culture in fresh frozen plasma, however, did not transform recipient leukocytes, and leukocytes of anti-ATLA-positive recipients proved refractory to transformation. The transformed cells were morphologically lymphoid, grew in suspension, and possessed normal recipient karyotypes except in the case of three platelet concentrates. A high proportion of all the transformed populations formed E-rosettes with neuraminidase-treated sheep erythrocytes. The cytoplasm of over 90% of each recipient was stained brilliantly with antibodies against ATLV-determined antigens. Electron microscopy of these transformed cells revealed many C-type virus particles in the extracellular space. Blood components, such as packed red cells, whole blood and platelet concentrate, containing leukocytes from anti-ATLA-positive donors, should be used cautiously to prevent the transmission on ATLV to anti-ATLA-negative recipients.

Second Language Writing Research and Written Corrective Feedback in SLA: Intersections and Practical Applications

Science.gov (United States)

Ferris, Dana R.

2010-01-01

For more than a decade now, a great deal of research has been done on the topic of written corrective feedback (CF) in SLA and second language (L2) writing. Nonetheless, what those research efforts really have shown as well as the possible implications for practice remain in dispute. Although L2 writing and SLA researchers often examine similar…

Discovery and development of 5-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-yl-methyl]-3-thiophenecarboxylic acid (BMS-587101)--a small molecule antagonist of leukocyte function associated antigen-1.

Science.gov (United States)

Potin, Dominique; Launay, Michele; Monatlik, Francoise; Malabre, Patrice; Fabreguettes, Maud; Fouquet, Andre; Maillet, Magali; Nicolai, Eric; Dorgeret, Loïc; Chevallier, François; Besse, Dominique; Dufort, Monique; Caussade, François; Ahmad, Syed Z; Stetsko, Dawn K; Skala, Stacey; Davis, Patricia M; Balimane, Praveen; Patel, Karishma; Yang, Zheng; Marathe, Punit; Postelneck, Jennifer; Townsend, Robert M; Goldfarb, Valentina; Sheriff, Steven; Einspahr, Howard; Kish, Kevin; Malley, Mary F; DiMarco, John D; Gougoutas, Jack Z; Kadiyala, Pathanjali; Cheney, Daniel L; Tejwani, Ravindra W; Murphy, Denette K; Mcintyre, Kim W; Yang, Xiaoxia; Chao, Sam; Leith, Leslie; Xiao, Zili; Mathur, Arvind; Chen, Bang-Chi; Wu, Daugh-Rurng; Traeger, Sarah C; McKinnon, Murray; Barrish, Joel C; Robl, Jeffrey A; Iwanowicz, Edwin J; Suchard, Suzanne J; Dhar, T G Murali

2006-11-30

LFA-1 (leukocyte function-associated antigen-1), is a member of the beta2-integrin family and is expressed on all leukocytes. This letter describes the discovery and preliminary SAR of spirocyclic hydantoin based LFA-1 antagonists that culminated in the identification of analog 8 as a clinical candidate. We also report the first example of the efficacy of a small molecule LFA-1 antagonist in combination with CTLA-4Ig in an animal model of transplant rejection.

Soluble human leukocyte antigen G5 polarizes differentiation of macrophages toward a decidual macrophage-like phenotype.

Science.gov (United States)

Lee, Cheuk-Lun; Guo, YiFan; So, Kam-Hei; Vijayan, Madhavi; Guo, Yue; Wong, Vera H H; Yao, YuanQing; Lee, Kai-Fai; Chiu, Philip C N; Yeung, William S B

2015-10-01

What are the actions of soluble human leukocyte antigen G5 (sHLAG5) on macrophage differentiation? sHLAG5 polarizes the differentiation of macrophages toward a decidual macrophage-like phenotype, which could regulate fetomaternal tolerance and placental development. sHLAG5 is a full-length soluble isoform of human leukocyte antigen implicated in immune tolerance during pregnancy. Low or undetectable circulating level of sHLAG5 in first trimester of pregnancy is associated with pregnancy complications such as pre-eclampsia and spontaneous abortion. Decidual macrophages are located in close proximity to invasive trophoblasts, and are involved in regulating fetomaternal tolerance and placental development. Human peripheral blood monocytes were differentiated into macrophages by treatment with granulocyte macrophage colony-stimulating factor in the presence or absence of recombinant sHLAG5 during the differentiation process. The phenotypes and the biological activities of the resulting macrophages were compared. Recombinant sHLAG5 was produced in Escherichia coli BL21 and the protein identity was verified by tandem mass spectrometry. The expression of macrophage markers were analyzed by flow cytometry and quantitative PCR. Phagocytosis was determined by flow cytometry. Indoleamine 2,3-dioxygenase 1 expression and activity were measured by western blot analysis and kynurenine assay, respectively. Cell proliferation and cell cycling were determined by fluorometric cell proliferation assay and flow cytometry, respectively. Cytokine secretion was determined by cytokine array and ELISA kits. Intracellular cytokine expression was measured by flow cytometry. Cell invasion and migration were determined by trans-well invasion and migration assay, respectively. sHLAG5 drove the differentiation of macrophages with 'immuno-modulatory' characteristics, including reduced expression of M1 macrophage marker CD86 and increased expression of M2 macrophage marker CD163. sHLAG5-polarized

The pig as a model for therapeutic human anti-cancer vaccine development, elucidating the T-cell reactivity against IDO and RhoC

DEFF Research Database (Denmark)

Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon

is important. Previous development of therapeutic cancer vaccines has largely been based on studies in mice and the majority of these candidate vaccines failed to establish therapeutic responses in subsequent human clinical trials. Since the porcine immunome is more closely related to the human counterpart, we...... here introduce pigs as a superior large animal model for human cancer vaccine development via the use of our unique technology for swine leukocyte antigen (SLA) production. IDO and RhoC, both known to be important in human cancer development and progression, were used as vaccine targets. Pigs were......, and peptide-SLA complex stability measurements revealed 89 stable (t½ ≥ 0.5 hour) complexes. Vaccine-induced peptide-specific CTL responses were monitored using IFN-γ release as a read out. We found responses to IDO- and RhoC-derived peptides across all groups; surprisingly non-stably binding peptides also...

SlaVaComp Fonts Converter

Directory of Open Access Journals (Sweden)

Simon Skilevic

2013-12-01

Full Text Available This paper presents a fonts converter that was developed as a part of the Freiburg project on historical corpus linguistics. The tool named SlaVaComp-Konvertierer converts Church Slavonic texts digitized with non-Unicode fonts into the Unicode format without any loss of information contained in the original file and without damage to the original formatting. It is suitable for the conversion of all idiosyncratic fonts—not only Church Slavonic—and therefore can be used not only in Palaeoslavistic, but also in all historical and philological studies.

Association of human leukocyte A, B, and DR antigens in Colombian patients with diagnosis of spondyloarthritis.

Science.gov (United States)

Santos, Ana M; Peña, Paola; Avila, Mabel; Briceño, Ignacio; Jaramillo, Carlos; Vargas-Alarcon, Gilberto; Rueda, Juan C; Saldarriaga, Eugenia-Lucia; Angarita, Jose-Ignacio; Martinez-Rodriguez, Nancy; Londono, John

2017-04-01

There is substantial evidence that non-B27 major histocompatibility complex (MHC) genes are associated with spondyloarthritis (SpA). Studies in Mexican and Tunisian populations demonstrated the association of SpA and human leukocyte antigen (HLA) B15. The purpose of this study was to evaluate the association of HLA-A, B, and DR antigens in a group of Colombian patients with a diagnosis of SpA. A total of 189 patients and 100 healthy subjects were included in the present study. All subjects underwent a complete characterization of HLA alleles A, B, and DR. Of the 189 studied patients, 35 were reactive arthritis (ReA), 87 were ankylosing spondylitis (AS), and 67 undifferentiated SpA (uSpA). According to the Assessment of Spondyloarthritis International Society (ASAS) criteria, 167 were axial SpA (axSpA) and 171 were peripheral SpA (pSpA). 63.8% were men, with a mean age of 35.9 ± 12.7 years. 40.7% (77/189) of patients were HLA-B27 positive of which 52.9% had AS and 42.5% axSpA. 23.2% (44/189) of patients were HLA-B15 positive: 23.8% were uSpA, 12.57% were axSpA, and 11.7% were pSpA. In addition, HLA-DRB1*01 was associated with AS (58.6%) and axSpA (42.5%). Also, HLA-DRB1*04 was present in 62 patients with AS (71.2%) and in 26 with axSpA (15.5%). In this population, we found a strong association between the presence of HLA-B27 and the diagnosis of axSpA and AS, but the HLA-B15 is also significantly associated with all subtypes of the disease, predominantly with pSpA. Additionally, HLA-DR1 and DR4 were associated in a cohort of patients with SpA from Colombia.

Classification and Implication of Motivation Research in SLA

Institute of Scientific and Technical Information of China (English)

温泉

2015-01-01

<正>Introduction The author of this essay does not intend to clarify the controversy about motivation in Second Language Acquisition(SLA)as a critical social-psychological element in the field,because the research of motivation is such a complex process which requires some degree of expertise in three scholarly

An Analysis on the Contextual Factors Affecting Motivation in SLA

Institute of Scientific and Technical Information of China (English)

2007-01-01

<正>For us Chinese,a foreign language is something to be acquired as a kind of communicative tool,so we can infer that an effective way in SLA(Second Language Acquisition) must be learning the target language in a communicative context.A communicative context certainly concerns not only the interactional classroom activities designed in accordance with some stated curriculum tasks to lead the L2 students to learning swimming by swimming,but also other relevant elements which have a lot to do with all the situational,interactional and cultural contexts.In order to lessen some potential sources of conflict between L2 teacher and L2 learner,this article is an attempt to urge a careful study on the contextual factors affecting motivation in SLA.

Radiolabeled leukocytes

International Nuclear Information System (INIS)

Datz, F.L.; Taylor, A.T.

1986-01-01

Leukocytes are a heterogeneous group of nucleated cells that follow similar patterns of differentiation in the bone marrow. Although the various leukocyte cell types perform somewhat different functions, they act as a group to protect the host from hazards of the internal and external environment, such as infection and neoplasia, and they assist in the repair of damaged tissue. Leukocytes spend a small fraction of their life in the peripheral blood, using it only for transportation to sites where they are needed to perform their defensive functions. In adults, the mature types of leukocytes are neutrophils (59 percent of the leukocyte population), lymphocytes (34 percent), monocytes (four percent), eosinophils (three percent), and basophils (0.5 percent). Neutrophils, eosinophils, and basophils all contain nuclei with finitely granular, evenly distributed chromatin and are collectively called granulocytes. In addition to the main categories of leukocytes listed above, there are subsets of many of these classes of cells; for example, natural killer cells are a subset of lymphocytes

Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation

Science.gov (United States)

Viswanathan, Kavitha; Dhabhar, Firdaus S.

2005-04-01

Effective immunoprotection requires rapid recruitment of leukocytes into sites of surgery, wounding, infection, or vaccination. In contrast to immunosuppressive chronic stressors, short-term acute stressors have immunoenhancing effects. Here, we quantify leukocyte infiltration within a surgical sponge to elucidate the kinetics, magnitude, subpopulation, and chemoattractant specificity of an acute stress-induced increase in leukocyte trafficking to a site of immune activation. Mice acutely stressed before sponge implantation showed 200-300% higher neutrophil, macrophage, natural killer cell, and T cell infiltration than did nonstressed animals. We also quantified the effects of acute stress on lymphotactin- (LTN; a predominantly lymphocyte-specific chemokine), and TNF-- (a proinflammatory cytokine) stimulated leukocyte infiltration. An additional stress-induced increase in infiltration was observed for neutrophils, in response to TNF-, macrophages, in response to TNF- and LTN, and natural killer cells and T cells in response to LTN. These results show that acute stress initially increases trafficking of all major leukocyte subpopulations to a site of immune activation. Tissue damage-, antigen-, or pathogen-driven chemoattractants subsequently determine which subpopulations are recruited more vigorously. Such stress-induced increases in leukocyte trafficking may enhance immunoprotection during surgery, vaccination, or infection, but may also exacerbate immunopathology during inflammatory (cardiovascular disease or gingivitis) or autoimmune (psoriasis, arthritis, or multiple sclerosis) diseases. chemokine | psychophysiological stress | surgical sponge | wound healing | lymphotactin

Effectiviteit van middelen tegen Rhizoctonia in sla en radijs

NARCIS (Netherlands)

Hofland-Zijlstra, J.D.; Paternotte, S.J.; Janse, J.; Slooten, van M.A.

2008-01-01

Rhizoctonia is een veelvoorkomend probleem in sla en radijs en kan veel opbrengstverlies geven. Uit eerder onderzoek van Wageningen UR Glastuinbouw in radijs werd gevonden dat het enige toegelaten fungicide tegen Rhizoctonia in de praktijk niet voldoende werkt. Door het kleine middelenpakket in de

Impact of SLA assimilation in the Sicily Channel Regional Model: model skills and mesoscale features

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A. Olita

2012-07-01

Full Text Available The impact of the assimilation of MyOcean sea level anomalies along-track data on the analyses of the Sicily Channel Regional Model was studied. The numerical model has a resolution of 1/32° degrees and is capable to reproduce mesoscale and sub-mesoscale features. The impact of the SLA assimilation is studied by comparing a simulation (SIM, which does not assimilate data with an analysis (AN assimilating SLA along-track multi-mission data produced in the framework of MyOcean project. The quality of the analysis was evaluated by computing RMSE of the misfits between analysis background and observations (sea level before assimilation. A qualitative evaluation of the ability of the analyses to reproduce mesoscale structures is accomplished by comparing model results with ocean colour and SST satellite data, able to detect such features on the ocean surface. CTD profiles allowed to evaluate the impact of the SLA assimilation along the water column. We found a significant improvement for AN solution in terms of SLA RMSE with respect to SIM (the averaged RMSE of AN SLA misfits over 2 years is about 0.5 cm smaller than SIM. Comparison with CTD data shows a questionable improvement produced by the assimilation process in terms of vertical features: AN is better in temperature while for salinity it gets worse than SIM at the surface. This suggests that a better a-priori description of the vertical error covariances would be desirable. The qualitative comparison of simulation and analyses with synoptic satellite independent data proves that SLA assimilation allows to correctly reproduce some dynamical features (above all the circulation in the Ionian portion of the domain and mesoscale structures otherwise misplaced or neglected by SIM. Such mesoscale changes also infer that the eddy momentum fluxes (i.e. Reynolds stresses show major changes in the Ionian area. Changes in Reynolds stresses reflect a different pumping of eastward momentum from the eddy to

Modeling leukocyte-leukocyte non-contact interactions in a lymph node.

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Nicola Gritti

Full Text Available The interaction among leukocytes is at the basis of the innate and adaptive immune-response and it is largely ascribed to direct cell-cell contacts. However, the exchange of a number of chemical stimuli (chemokines allows also non-contact interaction during the immunological response. We want here to evaluate the extent of the effect of the non-contact interactions on the observed leukocyte-leukocyte kinematics and their interaction duration. To this aim we adopt a simplified mean field description inspired by the Keller-Segel chemotaxis model, of which we report an analytical solution suited for slowly varying sources of chemokines. Since our focus is on the non-contact interactions, leukocyte-leukocyte contact interactions are simulated only by means of a space dependent friction coefficient of the cells. The analytical solution of the Keller-Segel model is then taken as the basis of numerical simulations of interactions between leukocytes and their duration. The mean field interaction force that we derive has a time-space separable form and depends on the chemotaxis sensitivity parameter as well as on the chemokines diffusion coefficient and their degradation rate. All these parameters affect the distribution of the interaction durations. We draw a successful qualitative comparison between simulated data and sets of experimental data for DC-NK cells interaction duration and other kinematic parameters. Remarkably, the predicted percentage of the leukocyte-leukocyte interactions falls in the experimental range and depends (~25% increase upon the chemotactic parameter indicating a non-negligible direct effect of the non-contact interaction on the leukocyte interactions.

Modeling leukocyte-leukocyte non-contact interactions in a lymph node.

Science.gov (United States)

Gritti, Nicola; Caccia, Michele; Sironi, Laura; Collini, Maddalena; D'Alfonso, Laura; Granucci, Francesca; Zanoni, Ivan; Chirico, Giuseppe

2013-01-01

The interaction among leukocytes is at the basis of the innate and adaptive immune-response and it is largely ascribed to direct cell-cell contacts. However, the exchange of a number of chemical stimuli (chemokines) allows also non-contact interaction during the immunological response. We want here to evaluate the extent of the effect of the non-contact interactions on the observed leukocyte-leukocyte kinematics and their interaction duration. To this aim we adopt a simplified mean field description inspired by the Keller-Segel chemotaxis model, of which we report an analytical solution suited for slowly varying sources of chemokines. Since our focus is on the non-contact interactions, leukocyte-leukocyte contact interactions are simulated only by means of a space dependent friction coefficient of the cells. The analytical solution of the Keller-Segel model is then taken as the basis of numerical simulations of interactions between leukocytes and their duration. The mean field interaction force that we derive has a time-space separable form and depends on the chemotaxis sensitivity parameter as well as on the chemokines diffusion coefficient and their degradation rate. All these parameters affect the distribution of the interaction durations. We draw a successful qualitative comparison between simulated data and sets of experimental data for DC-NK cells interaction duration and other kinematic parameters. Remarkably, the predicted percentage of the leukocyte-leukocyte interactions falls in the experimental range and depends (~25% increase) upon the chemotactic parameter indicating a non-negligible direct effect of the non-contact interaction on the leukocyte interactions.

Ekspresi Human Leukocyte Antigen-G (HLA-G dan Heat-Shock Protein-70 (Hsp-70 pada Pertumbuhan Janin Terhambat

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Sri Sulistyowati

2014-03-01

Full Text Available Intra uterine growth retardation (IUGR is one of the leading causes of higher morbidity and mortality in perinatal. Immune maladaptation affects trophoblast invasion and spiralis arteria remodeling that will cause placental tissue hypoxia. This research aimed to analyze human leukocyte antigen-G (HLA-G and heat-shock protein-70 (Hsp-70 expression on the IUGR trophoblast and normal pregnancy, by applying analytical observational method and cross sectional approach. This research was conducted at the Obstetric and Gynecology Department of Dr. Moewardi Hospital Surakarta from November to December 2011. The total samples were 30, divided into two groups. There were 15 samples trophoblast on IUGR and 15 samples trophoblast from normal pregnancy. All samples were tested for HLA-G and Hsp-70 using immunohistochemistry. The data were analyzed by using t-test. The mean of HLA-G expression on the IUGR groups was 32.42±8.90 and on the normal pregnancy groups was 43.92±14.91 (p=0.016. Heat-shock protein70 expression on the IUGR groups was 2.4355+0.26647 and on the normal pregnancy groups was 1.5920+0.17142 with p=0.008. In conclusion, in IUGR, the HLA-G expression is lower and the Hsp-70 expression is higher than in normal pregnancy.

Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis.

Science.gov (United States)

Singh, Om Prakash; Stober, Carmel B; Singh, Abhishek Kr; Blackwell, Jenefer M; Sundar, Shyam

2012-01-01

There are no effective vaccines for visceral leishmaniasis (VL), a neglected parasitic disease second only to malaria in global mortality. We previously identified 14 protective candidates in a screen of 100 Leishmania antigens as DNA vaccines in mice. Here we employ whole blood assays to evaluate human cytokine responses to 11 of these antigens, in comparison to known defined and crude antigen preparations. Whole blood assays were employed to measure IFN-γ, TNF-α and IL-10 responses to peptide pools of the novel antigens R71, Q51, L37, N52, L302.06, J89, M18, J41, M22, M63, M57, as well as to recombinant proteins of tryparedoxin peroxidase (TRYP), Leishmania homolog of the receptor for activated C kinase (LACK) and to crude soluble Leishmania antigen (SLA), in Indian patients with active (n = 8) or cured (n = 16) VL, and in modified Quantiferon positive (EHC(+ve), n = 20) or modified Quantiferon negative (EHC(-ve), n = 9) endemic healthy controls (EHC). Active VL, cured VL and EHC(+ve) groups showed elevated SLA-specific IFN-γ, but only active VL patients produced IL-10 and EHC(+ve) did not make TNF-α. IFN-γ to IL-10 and TNF-α to IL-10 ratios in response to TRYP and LACK antigens were higher in cured VL and EHC(+ve) exposed individuals compared to active VL. Five of the eleven novel candidates (R71, L37, N52, J41, and M22) elicited IFN-γ and TNF-α, but not IL-10, responses in cured VL (55-87.5% responders) and EHC(+ve) (40-65% responders) subjects. Our results are consistent with an important balance between pro-inflammatory IFNγ and TNFγ cytokine responses and anti-inflammatory IL-10 in determining outcome of VL in India, as highlighted by response to both crude and defined protein antigens. Importantly, cured VL patients and endemic Quantiferon positive individuals recognise 5 novel vaccine candidate antigens, confirming our recent data for L. chagasi in Brazil, and their potential as cross-species vaccine candidates.

Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis.

Directory of Open Access Journals (Sweden)

Om Prakash Singh

Full Text Available There are no effective vaccines for visceral leishmaniasis (VL, a neglected parasitic disease second only to malaria in global mortality. We previously identified 14 protective candidates in a screen of 100 Leishmania antigens as DNA vaccines in mice. Here we employ whole blood assays to evaluate human cytokine responses to 11 of these antigens, in comparison to known defined and crude antigen preparations.Whole blood assays were employed to measure IFN-γ, TNF-α and IL-10 responses to peptide pools of the novel antigens R71, Q51, L37, N52, L302.06, J89, M18, J41, M22, M63, M57, as well as to recombinant proteins of tryparedoxin peroxidase (TRYP, Leishmania homolog of the receptor for activated C kinase (LACK and to crude soluble Leishmania antigen (SLA, in Indian patients with active (n = 8 or cured (n = 16 VL, and in modified Quantiferon positive (EHC(+ve, n = 20 or modified Quantiferon negative (EHC(-ve, n = 9 endemic healthy controls (EHC.Active VL, cured VL and EHC(+ve groups showed elevated SLA-specific IFN-γ, but only active VL patients produced IL-10 and EHC(+ve did not make TNF-α. IFN-γ to IL-10 and TNF-α to IL-10 ratios in response to TRYP and LACK antigens were higher in cured VL and EHC(+ve exposed individuals compared to active VL. Five of the eleven novel candidates (R71, L37, N52, J41, and M22 elicited IFN-γ and TNF-α, but not IL-10, responses in cured VL (55-87.5% responders and EHC(+ve (40-65% responders subjects.Our results are consistent with an important balance between pro-inflammatory IFNγ and TNFγ cytokine responses and anti-inflammatory IL-10 in determining outcome of VL in India, as highlighted by response to both crude and defined protein antigens. Importantly, cured VL patients and endemic Quantiferon positive individuals recognise 5 novel vaccine candidate antigens, confirming our recent data for L. chagasi in Brazil, and their potential as cross-species vaccine candidates.

Granulocytes: New Members of the Antigen-Presenting Cell Family

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Ang Lin

2017-12-01

Full Text Available Granulocytes, the most abundant types of leukocytes, are the first line of defense against pathogen invasion. However, the plasticity and diversity of granulocytes have been increasingly revealed, especially with regard to their versatile functions in orchestrating adaptive immune responses. A substantial body of recent evidence demonstrates that granulocytes can acquire the function as antigen-presenting cells under pathological or inflammatory conditions. In addition, they can acquire surface expression of MHC class II and costimulatory molecules as well as T cell stimulatory behavior when cultured with selected cytokines. The classic view of granulocytes as terminally differentiated, short-lived phagocytes is therefore changing to phenotypically and functionally heterogeneous cells that are engaged in cross-talk with other leukocyte populations and provide an additional link between innate and adaptive immunity. In this brief review, we summarize the current knowledge on the antigen-presenting capacity of granulocyte subsets (neutrophils, eosinophils, and basophils. Underlying mechanisms, relevant physiological significance and potential controversies are also discussed.

Validation of celiac disease diagnoses recorded in the Danish National Patient Register using duodenal biopsies, celiac disease-specific antibodies, and human leukocyte-antigen genotypes

DEFF Research Database (Denmark)

Dydensborg Sander, Stine; Størdal, Ketil; Plato Hansen, Tine

2016-01-01

PURPOSE: The purpose of this study was to validate the celiac disease diagnoses recorded in the Danish National Patient Register. To validate the diagnoses, we used information on duodenal biopsies from a national register of pathology reports (the Patobank) and information on celiac disease......-specific antibodies and human leukocyte antigen (HLA) genotypes obtained from patient medical records. PATIENTS AND METHODS: We included all the children who were born from 1995 to 2012 and who were registered as having celiac disease in the Danish National Patient Register. We reviewed all the pathology reports...... on duodenal biopsies in the Patobank and the information in the medical records on celiac disease-specific antibodies (ie, anti-tissue transglutaminase 2 IgA and IgG, endomysial antibodies IgA, and anti-deamidated gliadin peptide IgG) and HLA genotypes. RESULTS: We identified 2,247 children who were...

The link between some alleles on human leukocyte antigen system and autism in children.

Science.gov (United States)

Mostafa, Gehan A; Shehab, Abeer A; Al-Ayadhi, Laila Y

2013-02-15

The reason behind the initiation of autoimmunity to brain in some patients with autism is not well understood. There is an association between some autoimmune disorders and specific alleles of human leukocyte antigen (HLA) system. Thus, we examined the frequency of some HLA-DRB1 alleles in 100 autistic children and 100 healthy matched-children by differential hybridization with sequence-specific oligonucleotide probes. The risk of association between acquisition or absence of these alleles and autism and also a history of autoimmune diseases in autistic relatives was studied. Autistic children had significantly higher frequency of HLA-DRB1*11 allele than controls (P<0.001). In contrast, autistic children had significantly lower frequency of HLA-DRB1*03 allele than controls (P<0.001). Acquisition of HLA-DRB1*011 and absence of HLA-DRB1*3 had significant risk for association with autism (odds ratio: 3.21 and 0.17, respectively; 95% CI: 1.65-6.31 and 0.06-0.45, respectively). HLA-DRB1*11 had a significant risk for association with a family history of autoimmunity in autistic children (odds ratio: 5.67; 95% CI: 2.07-16.3). In conclusions, the link of some HLA alleles to autism and to family history of autoimmunity indicates the possible contributing role of these alleles to autoimmunity in some autistic children. Despite a relatively small sample size, we are the first to report a probable protective association of HLA-DRB1*03 allele with autism. It warrants a replication study of a larger sample to validate the HLA-DRB1 genetic association with autism. This is important to determine whether therapeutic modulations of the immune function are legitimate avenues for novel therapy in selected cases of autism. Copyright © 2012 Elsevier B.V. All rights reserved.

Leukocyte adhesion deficiencies

NARCIS (Netherlands)

van de Vijver, Edith; van den Berg, Timo K.; Kuijpers, Taco W.

2013-01-01

During inflammation, leukocytes play a key role in maintaining tissue homeostasis through elimination of pathogens and removal of damaged tissue. Leukocytes migrate to the site of inflammation by crawling over and through the blood vessel wall, into the tissue. Leukocyte adhesion deficiencies (ie,

Marginal Bone Loss Around Early-Loaded SLA and SLActive Implants: Radiological Follow-Up Evaluation Up to 6.5 Years.

Science.gov (United States)

Şener-Yamaner, Işil Damla; Yamaner, Gökhan; Sertgöz, Atilla; Çanakçi, Cenk Fatih; Özcan, Mutlu

2017-08-01

The aim of this study was to compare marginal bone loss around early-loaded SLA and SLActive tissue-level implants (Straumann Dental Implants; Institut Straumann AG, Basel, Switzerland) after a mean of 81-month follow-up period. One hundred seven SLA and 68 SLActive implants were placed in 55 patients and loaded with final restoration after 8 and 3 weeks of healing time, respectively. Marginal bone loss around implants was determined radiographically at initial and after a mean observation time ranging between 20 and 81 months. The effect of location (mandible vs maxilla), smoking habit, sex, implant length and diameter, and the type of prosthesis on the marginal bone loss was evaluated. The overall cumulative survival rate was 98.2% being 99% for SLA implants and 97% for SLActive implants. After 20-month follow-up period, mean marginal bone loss values for the SLA and SLActive implants were 0.24 and 0.17 mm, respectively. After 81 months, mean marginal bone loss for the SLA and SLActive implants reached 0.71 and 0.53 mm, respectively. Marginal bone loss was affected by the length and type of implant and patients' smoking habit after a mean observation time of 20 months. However, none of the parameters had any significant effect on the marginal bone loss after a follow-up period of 81 months. With both SLA and SLActive implants, successful clinical results could be achieved up to 6.5 years of follow-up period.

Leishmania mexicana Gp63 cDNA Using Gene Gun Induced Higher Immunity to L. mexicana Infection Compared to Soluble Leishmania Antigen in BALB/C

Science.gov (United States)

Rezvan, H; Rees, R; Ali, SA

2011-01-01

Background Leishmaniasis is a worldwide disease prevalent in tropical and sub tropical countries. Many attempts have been made and different strategies have been approached to develop a potent vaccine against Leishmania. DNA immunisation is a method, which is shown to be effective in Leishmania vaccination. Leishmania Soluble Antigen (SLA) has also recently been used Leishmania vaccination. Methods The immunity generated by SLA and L. mexicana gp63 cDNA was compared in groups of 6 mice, which were statistically analysed by student t- test with the P-value of 0.05. SLA was administered by two different methods; intramuscular injection and injection of dendritic cells (DCs) loaded with SLA. L. mexicana gp63 cDNA was administered by the gene gun. Results Immunisation of BALB/c mice with L. mexicana gp63 resulted in high levels of Th1-type immune response and cytotoxic T lymphocytes (CTL) activity, which were accompanied with protection induced by the immunisation against L. mexicana infection. In contrast, administration of SLA, produced a mixed Th1/Th2-type immune responses as well as a high level of CTL activity but did not protect mice from the infection. Conclusion The results indicate higher protection by DNA immunisation using L. mexicana gp63 cDNA compared to SLA, which is accompanied by a high level of Th1 immune response. However, the CTL activity does not necessarily correlate with the protection induced by the vaccine. Also, gene gun immunisation is a potential approach in Leishmania vaccination. These findings would be helpful in opening new windows in Leishmania vaccine research. PMID:22347315

Leukocyte Ig-Like Receptors – a model for MHC class I disease associations

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Rachel Louise Allen

2016-07-01

Full Text Available MHC class I (MHC-I polymorphisms are associated with the outcome of some viral infections and autoimmune diseases. MHC-I proteins present antigenic peptides and are recognised by receptors on Natural Killer cells and Cytotoxic T lymphocytes, thus enabling the immune system to detect self-antigens and eliminate targets lacking self or expressing foreign antigens. Recognition of MHC-I, however, extends beyond receptors on cytotoxic leukocytes. Members of the Leukocyte Ig-like receptor (LILR family are expressed on monocytic cells and can recognise both classical and non-classical MHC-I alleles. Despite their relatively broad specificity when compared to the T Cell Receptor or Killer Ig-like Receptors, variations in the strength of LILR binding between different MHC-I alleles have recently been shown to correlate with control of HIV infection. We suggest that LILR recognition may mediate MHC-I disease association in a manner that does not depend on a binary discrimination of self/non-self by cytotoxic cells. Instead, the effects of LILR activity following engagement by MHC-I may represent a degrees of self model, whereby strength of binding to different alleles determines the degree of influence exerted by these receptors on immune cell functions. LILR are expressed by myelomonocytic cells and lymphocytes, extending their influence across antigen presenting cell subsets including dendritic cells, macrophages and B cells. They have been identified as important players in the response to infection, inflammatory diseases and cancer, with recent literature to indicate that MHC-I recognition by these receptors and consequent allelic effects could extend an influence beyond the immune system.

Common tree shrews and primates share leukocyte membrane antigens.

Science.gov (United States)

Palley, L S; Schlossman, S F; Letvin, N L

1984-01-01

Monoclonal antibodies reactive with human peripheral blood lymphocyte and myeloid cell surface antigens were utilized to study the phylogeny of the common tree shrew. Blood cells from the common tree shrew, but not the bat or short-tailed shrew, react with certain of these antibodies. These data strengthen the argument that the Tupaiidae are primitive primates rather than insectivores. They also indicate that this approach should be useful for further work in taxonomic systemization.

Complex preimplantation genetic diagnosis for beta-thalassaemia, sideroblastic anaemia, and human leukocyte antigen (HLA)-typing.

Science.gov (United States)

Kakourou, Georgia; Vrettou, Christina; Kattamis, Antonis; Destouni, Aspasia; Poulou, Myrto; Moutafi, Maria; Kokkali, Georgia; Pantos, Konstantinos; Davies, Stephen; Kitsiou-Tzeli, Sophia; Kanavakis, Emmanuel; Traeger-Synodinos, Joanne

2016-01-01

Preimplantation genetic diagnosis (PGD) to select histocompatible siblings to facilitate curative haematopoeitic stem-cell transplantation (HSCT) is now an acceptable option in the absence of an available human leukocyte antigen (HLA) compatible donor. We describe a case where the couple who requested HLA-PGD, were both carriers of two serious haematological diseases, beta-thalassaemia and sideroblastic anaemia. Their daughter, affected with sideroblastic anaemia, was programmed to have HSCT. A multiplex-fluorescent-touchdown-PCR protocol was optimized for the simultaneous amplification of: the two HBB-gene mutated regions (c.118C> T, c.25-26delAA), four short tandem repeats (STRs) in chr11p15.5 linked to the HBB gene, the SLC25A38 gene mutation (c.726C > T), two STRs in chr3p22.1 linked to the SLC25A38 gene, plus eleven informative STRs for HLA-haplotyping (chr6p22.1-21.3). This was followed by real-time nested PCR and high-resolution melting analysis (HRMA) for the detection of HBB and SLC25A38 gene mutations, as well as the analysis of all STRs on an automatic genetic analyzer (sequencer). The couple completed four clinical in vitro fertilization (IVF)/PGD cycles. At least one matched unaffected embryo was identified and transferred in each cycle. A twin pregnancy was established in the fourth PGD cycle and genotyping results at all loci were confirmed by prenatal diagnosis. Two healthy baby girls were delivered at week 38 of pregnancy. The need to exclude two familial disorders for HLA-PGD is rarely encountered. The methodological approach described here is fast, accurate, clinically-validated, and of relatively low cost.

Initial afferent lymphatic vessels controlling outbound leukocyte traffic from skin to lymph nodes.

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Ignacio eMelero

2013-12-01

Full Text Available Tissue drains fluid and macromolecules through lymphatic vessels, which are lined by a specialized endothelium that expresses peculiar differentiation proteins, not found in blood vessels (i.e: LYVE-1, Podoplanin, PROX-1 and VEGFR-3. Lymphatic capillaries are characteristically devoid of a continuous basal membrane and are anchored to the ECM by elastic fibers that act as pulling ropes which open the vessel to avoid oedema if tissue volume increases, as it occurs upon inflammation. Lymphatic vessels are also crucial for the transit of T lymphocytes and antigen presenting cells from tissue to draining lymph nodes. Importantly, cell traffic control across lymphatic endothelium is differently regulated under resting and inflammatory conditions. Under steady-state non-inflammatory conditions, leukocytes enter into the lymphatic capillaries through basal membrane gaps (portals. This entrance is integrin-independent and seems to be mainly guided by CCL21 chemokine gradients acting on leukocytes expressing CCR7. In contrast, inflammatory processes in lymphatic capillaries involve a plethora of cytokines, chemokines, leukocyte integrins and other adhesion molecules. Importantly, under inflammation a role for integrins and their ligands becomes apparent and, as a consequence, the number of leukocytes entering the lymphatic capillaries multiplies several-fold. Enhancing transmigration of dendritic cells en route to lymph nodes is conceivably useful for vaccination and cancer immunotherapy, whereas interference with such key mechanisms may ameliorate autoimmunity or excessive inflammation. Recent findings illustrate how, transient cell-to-cell interactions between lymphatic endothelial cells and leukocytes contribute to shape the subsequent behaviour of leukocytes and condition the lymphatic vessel for subsequent trans-migratory events.

Q methodology for post-social-turn research in SLA

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Kay Irie

2014-01-01

Full Text Available Q methodology, an approach to inquiry on the subjective views about a complex phenomenon/issue which has been increasingly employed in a wide range of social science fields has not yet been applied in language learning and teaching research. It is a unique approach that has characteristics of both qualitative and quantitative research methods. The purpose of the present paper is to introduce Q methodology as an alternative approach and demonstrate its potential to respond to the needs of the field that has been expanding in its epistemological diversity since the social turn (Block, 2003; Ortega, 2012. The relevance of the methodology for SLA research will be discussed with a particular focus on the parallels between the development of the methodology in the 1930s and current criticisms towards the traditional cognitive approach in SLA. Using a published study (Irie & Ryan, 2014, the author explains how the focus on the holistic understanding of subjectivity is built into the procedure. Suggestions for possible areas of research and teaching in which Q methodology could be applied are discussed.

Cell surface expression level variation between two common Human Leukocyte Antigen alleles, HLA-A2 and HLA-B8, is dependent on the structure of the C terminal part of the alpha 2 and the alpha 3 domains

DEFF Research Database (Denmark)

Dellgren, Christoffer; Nehlin, Jan O; Barington, Torben

2015-01-01

Constitutive cell surface expression of Human Leukocyte Antigen (HLA) class I antigens vary extremely from tissue to tissue and individual antigens may differ widely in expression levels. Down-regulation of class I expression is a known immune evasive mechanism used by cancer cells and viruses....... Moreover, recent observations suggest that even minor differences in expression levels may influence the course of viral infections and the frequency of complications to stem cell transplantation. We have shown that some human multipotent stem cells have high expression of HLA-A while HLA-B is only weakly...... expressed, and demonstrate here that this is also the case for the human embryonic kidney cell line HEK293T. Using quantitative flow cytometry and quantitative polymerase chain reaction we found expression levels of endogenous HLA-A3 (median 71,204 molecules per cell) 9.2-fold higher than the expression of...

Optimizing virtual machine placement for energy and SLA in clouds using utility functions

Directory of Open Access Journals (Sweden)

Abdelkhalik Mosa

2016-10-01

Full Text Available Abstract Cloud computing provides on-demand access to a shared pool of computing resources, which enables organizations to outsource their IT infrastructure. Cloud providers are building data centers to handle the continuous increase in cloud users’ demands. Consequently, these cloud data centers consume, and have the potential to waste, substantial amounts of energy. This energy consumption increases the operational cost and the CO2 emissions. The goal of this paper is to develop an optimized energy and SLA-aware virtual machine (VM placement strategy that dynamically assigns VMs to Physical Machines (PMs in cloud data centers. This placement strategy co-optimizes energy consumption and service level agreement (SLA violations. The proposed solution adopts utility functions to formulate the VM placement problem. A genetic algorithm searches the possible VMs-to-PMs assignments with a view to finding an assignment that maximizes utility. Simulation results using CloudSim show that the proposed utility-based approach reduced the average energy consumption by approximately 6 % and the overall SLA violations by more than 38 %, using fewer VM migrations and PM shutdowns, compared to a well-known heuristics-based approach.

Balancing selection and heterogeneity across the classical human leukocyte antigen loci: a meta-analytic review of 497 population studies.

Science.gov (United States)

Solberg, Owen D; Mack, Steven J; Lancaster, Alex K; Single, Richard M; Tsai, Yingssu; Sanchez-Mazas, Alicia; Thomson, Glenys

2008-07-01

This paper presents a meta-analysis of high-resolution human leukocyte antigen (HLA) allele frequency data describing 497 population samples. Most of the datasets were compiled from studies published in eight journals from 1990 to 2007; additional datasets came from the International Histocompatibility Workshops and from the AlleleFrequencies.net database. In all, these data represent approximately 66,800 individuals from throughout the world, providing an opportunity to observe trends that may not have been evident at the time the data were originally analyzed, especially with regard to the relative importance of balancing selection among the HLA loci. Population genetic measures of allele frequency distributions were summarized across populations by locus and geographic region. A role for balancing selection maintaining much of HLA variation was confirmed. Further, the breadth of this meta-analysis allowed the ranking of the HLA loci, with DQA1 and HLA-C showing the strongest balancing selection and DPB1 being compatible with neutrality. Comparisons of the allelic spectra reported by studies since 1990 indicate that most of the HLA alleles identified since 2000 are very-low-frequency alleles. The literature-based allele-count data, as well as maps summarizing the geographic distributions for each allele, are available online.

Probability of Finding Marrow Unrelated Donor (MUD) for an Indian patient in a Multi-national Human Leukocyte Antigen (HLA) Registry.

Science.gov (United States)

Tiwari, Aseem K; Bhati-Kushwaha, Himakshi; Kukreja, Pooja; Mishra, Vikash C; Tyagi, Neetu; Sharma, Ashish; Raina, Vimarsh

2015-06-01

With an increase in the number of transplants happening globally, hematopoietic stem cells (HSC) transplantation from matched unrelated donor (MUD) has begun. The increasing trend of MUD transplants across countries has been largely facilitated with the conspicuous growth of volunteer HSC donor noted in the last decade i.e. 8 million HSC donors in 2002 to more than 22 million in 2013 registered in 71 member registries of the Bone Marrow Donor Worldwide (BMDW). Some populations of the world are still very poorly represented in these registries. Since, the chances of successful engraftment and disease free survival are directly proportional to the HLA compatibility between the recipient and the prospective donor, the diversity of the HLA system at the antigenic and allelic level and the heterogeneity of HLA data of the registered donors has a bearing on the probability of finding a volunteer unrelated HSC donor for patients from such populations. In the present study 126 patients were identified suffering from hematological diseases requiring MUD transplant. Their HLA typing was performed and search was done using BMDW database. The search results for these Indian patients in the multinational registry as well as in the Indian Registries were analyzed using mean, range, standard deviation and finally evaluated in terms of probability for finding matched donor (MUD). Total Asian population is only 11 % in the BMDW making it difficult to find a MUD for an Asian patient. The current study supports this, experimentally; revealing that the probability of finding an allele match for an Indian patient in the multinational Human Leukocyte Antigen (HLA) registries is 16 % and a dismal 0.008 % in the Indian registries (donors in Indian registries is just 33,678 as compared to 22.5 million in BMDW). This greatly, emphasizes on enhancing the number of Indian donors in Indian and multi-national registries.

A leukocyte antigen, Leu-13, is involved in induction of resistance of human cells to x-ray cell killing by interferon-α

International Nuclear Information System (INIS)

Kita, Kazuko; Zhai, Ling; Sugaya, Shigeru; Suzuki, Nobuo

2003-01-01

We previously reported on human interferon (HuIFN)-induced resistance of human cells to X-ray and UV cell killing. In this study, we searched for the genes whose expression is responsible for the resistance, using a PCR-based mRNA differential display method and Northern blotting analysis. RSa cells were used for this analysis, because they show increased resistance to X-ray- and UV-caused cell killing by HuIFN-α treatment prior to irradiation. Messenger RNA expression levels for Leu-13, a leukocyte antigen, were markedly up-regulated in RSa cells after HuIFN-α treatment. Furthermore, pretreatment of RSa cells with antisense oligonucleotides for Leu-13 mRNA resulted in the suppression of the HuIFN-α-induced resistance of the cells to X-ray cell killing, but did not modulate HuIFN-α-induced resistance to UV cell killing. These results suggest that Leu-13 is involved in HuIFN-α-induced resistance of human cells to X-ray cell killing, but not to UV cell killing. (author)

Distribution of cytoskeletal proteins, integrins, leukocyte adhesion molecules and extracellular matrix proteins in plastic-embedded human and rat kidneys

NARCIS (Netherlands)

van Goor, H; Coers, W; van der Horst, MLC; Suurmeijer, AJH

2001-01-01

OBJECTIVE: To study the distribution of cytoskeletal proteins (actin, alpha -actinin, vinculin, beta -tubulin, keratin, vimentin, desmin), adhesion molecules for cell-matrix interations (very later antigens [VLA1-6], beta1, beta2 [CD18], vitronectin receptor [alphav beta3], CD 11b), leukocyte

Epistemological Diversity and Moral Ends of Research in Instructed SLA

Science.gov (United States)

Ortega, Lourdes

2012-01-01

In this article I explore epistemological diversity in the field of second language acquisition (SLA) from the perspective that obtains if we examine the moral ends of research, and we ask: In what ways does epistemological diversity relate to enhancing the social value and educational relevance of the research generated by the instructed SLA…

An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity

Directory of Open Access Journals (Sweden)

Marcela V Maus

2016-01-01

Full Text Available Chimeric antigen receptors (CARs are synthetic receptors that usually redirect T cells to surface antigens independent of human leukocyte antigen (HLA. Here, we investigated a T cell receptor-like CAR based on an antibody that recognizes HLA-A*0201 presenting a peptide epitope derived from the cancer-testis antigen NY-ESO-1. We hypothesized that this CAR would efficiently redirect transduced T cells in an HLA-restricted, antigen-specific manner. However, we found that despite the specificity of the soluble Fab, the same antibody in the form of a CAR caused moderate lysis of HLA-A2 expressing targets independent of antigen owing to T cell avidity. We hypothesized that lowering the affinity of the CAR for HLA-A2 would improve its specificity. We undertook a rational approach of mutating residues that, in the crystal structure, were predicted to stabilize binding to HLA-A2. We found that one mutation (DN lowered the affinity of the Fab to T cell receptor-range and restored the epitope specificity of the CAR. DN CAR T cells lysed native tumor targets in vitro, and, in a xenogeneic mouse model implanted with two human melanoma lines (A2+/NYESO+ and A2+/NYESO−, DN CAR T cells specifically migrated to, and delayed progression of, only the HLA-A2+/NY-ESO-1+ melanoma. Thus, although maintaining MHC-restricted antigen specificity required T cell receptor-like affinity that decreased potency, there is exciting potential for CARs to expand their repertoire to include a broad range of intracellular antigens.

Frequency of null allele of Human Leukocyte Antigen-G (HLA-G locus in subjects to recurrent miscarriage

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Nazila Alizadeh

2016-07-01

Full Text Available Background: Human leukocyte antigen-G (HLA-G is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. Objective: This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Materials and Methods: Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR. Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Results: Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. Conclusion: The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele.

Frequency of null allele of Human Leukocyte Antigen-G (HLA-G) locus in subjects to recurrent miscarriage

Science.gov (United States)

Alizadeh, Nazila; Mosaferi, Elnaz; Farzadi, Laya; Majidi, Jafar; Monfaredan, Amir; Yousefi, Bahman; Baradaran, Behzad

2016-01-01

Background: Human leukocyte antigen-G (HLA-G) is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM) subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. Objective: This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Materials and Methods: Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR). Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Results: Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. Conclusion: The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele. PMID:27525330

The perivascular phagocyte of the mouse pineal gland: An antigen-presenting cell

DEFF Research Database (Denmark)

Møller, Morten; Rath, Martin F; Klein, David C

2006-01-01

The perivascular space of the rat pineal gland is known to contain phagocytic cells that are immunoreactive for leukocyte antigens, and thus they appear to belong to the macrophage/microglial cell line. These cells also contain MHC class II proteins. We investigated this cell type in the pineal g...... for MHC class II protein and for CD68, a marker of monocytes/phagocytes. This study verifies that perivascular phagocytes with antigen-presenting properties are present in the mouse pineal gland....

The production and crystallization of the human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 complexed with deamidated gliadin peptides implicated in coeliac disease

Energy Technology Data Exchange (ETDEWEB)

Henderson, Kate N.; Reid, Hugh H.; Borg, Natalie A.; Broughton, Sophie E.; Huyton, Trevor [The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800 (Australia); Anderson, Robert P. [Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3050 (Australia); Department of Gastroenterology, The Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050 (Australia); McCluskey, James [Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010 (Australia); Rossjohn, Jamie, E-mail: jamie.rossjohn@med.monash.edu.au [The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800 (Australia)

2007-12-01

The production and crystallization of human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 in complex with deamidated gliadin peptides is reported. Crystals of HLA-DQ2{sup PQPELPYPQ} diffracted to 3.9 Å, while the HLA-DQ8{sup EGSFQPSQE} crystals diffracted to 2.1 Å, allowing structure determination by molecular replacement. The major histocompatibility complex (MHC) class II molecules HLA-DQ2 and HLA-DQ8 are key risk factors in coeliac disease, as they bind deamidated gluten peptides that are subsequently recognized by CD4{sup +} T cells. Here, the production and crystallization of both HLA-DQ2 and HLA-DQ8 in complex with the deamidated gliadin peptides DQ2 α-I (PQPELPYPQ) and DQ8 α-I (EGSFQPSQE), respectively, are reported.

Positive Psychology in SLA: An Agenda for Learner and Teacher Wellbeing

Science.gov (United States)

Mercer, Sarah

2017-01-01

This article begins with an outline of the developments in Positive Psychology (PP) generally and specifically within SLA focusing on theoretical, empirical and practical developments. It moves on to consider PP's potential contribution to language teaching focusing on how it can help promote emotional, social and psychological wellbeing for…

Alloactivated HLA class II-positive T-cell lines induce IL-2 reactivity but lack accessory cell function in mixed leukocyte culture

DEFF Research Database (Denmark)

Odum, N; Dickmeiss, E; Hofmann, B

1989-01-01

in the primary mixed leukocyte reaction (median counts per minute (cpm) 5.5 x 10(3] was significantly lower than that of peripheral blood mononuclear cells (cpm: 44.0 x 10(3]. The stimulation by Ta was almost only seen when the Ta were specifically directed against the class II antigens of the responder...... peripheral blood mononuclear cells (i.e., in combinations with "backstimulation") (median cpm: 21,000). In mixed leukocyte reaction combinations without backstimulation, significantly weaker reactions were seen (median cpm: 1,000). This observation may explain previous controversies concerning...

A molecular basis for the presentation of phosphorylated peptides by HLA-B antigens

NARCIS (Netherlands)

Alpízar, Adán; Marino, Fabio; Ramos-Fernández, Antonio; Lombardía, Manuel; Jeko, Anita; Pazos, Florencio; Paradela, Alberto; Santiago, César; Heck, Albert J R; Marcilla, Miguel

2017-01-01

As aberrant protein phosphorylation is a hallmark of tumor cells, the display of tumor-specific phosphopeptides by Human Leukocyte Antigen (HLA) class I molecules can be exploited in the treatment of cancer by T-cell-based immunotherapy. Yet, the characterization and prediction of HLA-I

Demonstration of tumor-associated antigens in dogs

International Nuclear Information System (INIS)

Warren, R.P.; Tsoi, M.S.; Henderson, B.H.; Weiden, P.L.; Storb, R.

1975-01-01

Procedures for the 51 Cr release assay using labeled L cells or lymphocytes and the indirect leukocyte migration test are described. These assays appear capable of detecting cellular immunity against tumor associated antigens in dogs. In 8 of 14 instances, lymphocyte-mediated cytotoxicity to autochthonous L cells was found as measured by 51 Cr release, and lymphocytes from 12 of 24 dogs produced the migration inhibition factor (MIF) when cultured with autochthonous tumor cells. Chromium-51 release occurred with 4 h of exposure of effector cells to target cells, suggesting that the immunity detected in the tumor dogs against their tumors is also present in vivo. With the leukocyte migration test, however, consistent MIF production was achieved only after 3 to 6 days in culture, suggesting that in vitro sensitization may result in increased MIF production

Towards Cloud Computing SLA Risk Management: Issues and Challenges

OpenAIRE

Morin, Jean-Henry; Aubert, Jocelyn; Gateau, Benjamin

2012-01-01

Cloud Computing has become mainstream technology offering a commoditized approach to software, platform and infrastructure as a service over the Internet on a global scale. This raises important new security issues beyond traditional perimeter based approaches. This paper attempts to identify these issues and their corresponding challenges, proposing to use risk and Service Level Agreement (SLA) management as the basis for a service level framework to improve governance, risk and compliance i...

Current trends in platelet transfusions practice: The role of ABO-RhD and human leukocyte antigen incompatibility

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Serena Valsami

2015-01-01

Full Text Available Platelet transfusions have contributed to the revolutionary modern treatment of hypoproliferative thrombocytopenia. Despite the long-term application of platelet transfusion in therapeutics, all aspects of their optimal use (i.e., in cases of ABO and/or Rh (D incompatibility have not been definitively determined yet. We reviewed the available data on transfusion practices and outcome in ABO and RhD incompatibility and platelet refractoriness due to anti-human leukocyte antigen (HLA antibodies. Transfusion of platelets with major ABO-incompatibility is related to reduced posttransfusion platelet (PLT count increments, compared to ABO-identical and minor, but still are equally effective in preventing clinical bleeding. ABO-minor incompatible transfusions pose the risk of an acute hemolytic reaction of the recipient that is not always related to high anti-A, B donor titers. ABO-identical PLT transfusion seems to be the most effective and safest therapeutic strategy. Exclusive ABO-identical platelet transfusion policy could be feasible, but alternative approaches could facilitate platelet inventory management. Transfusion of platelets from RhD positive donors to RhD negative patients is considered to be effective and safe though is associated with low rate of anti-D alloimmunization due to contaminating red blood cells. The prevention of D alloimmunization is recommended only for women of childbearing age. HLA alloimmunization is a major cause of platelet refractoriness. Managing patients with refractoriness with cross-matched or HLA-matched platelets is the current practice although data are still lacking for the efficacy of this practice in terms of clinical outcome. Leukoreduction contributes to the reduction of both HLA and anti-D alloimmunization.

Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens

Science.gov (United States)

Under physiological conditions the gut-associated lymphoid tissues not only prevent the induction of a local inflammatory immune response, but also induce systemic tolerance to fed antigens. A notable exception is coeliac disease, where genetically susceptible individuals expressing human leukocyte...

A genomic study on distribution of human leukocyte antigen (HLA-A and HLA-B alleles in Lak population of Iran

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Farhad Shahsavar

2017-03-01

Full Text Available Anthropological studies based on the highly polymorphic gene, human leukocyte antigen (HLA, provide useful information for bone marrow donor registry, forensic medicine, disease association studies, as well as infertility treatment, designing peptide vaccines against tumors, and infectious or autoimmune diseases. The aim of this study was to determine HLA-A and HLA-B allele frequencies in 100 unrelated Lak/lᴂk/individuals from Lorestan province of Iran. Finally, we compared the results with that previously described in Iranian population. Commercial HLA-Type kits from BAG (Lich, Germany company were used for determination of the HLA-A and HLA-B allele frequencies in genomic DNA, based on polymerase chain reaction with sequence specific primer (PCR-SSP assay. The differences between the populations in distribution of HLA-A and HLA-B alleles were estimated by chi-squared test with Yate's correction. The most frequent HLA-A alleles were *24 (20%, *02 (18%, *03 (12% and *11 (10%, and the most frequent HLA-B alleles were *35 (24%, *51 (16%, *18 (6% and *38 (6% in Lak population. HLA-A*66 (1%, *74(1% and HLA-B*48 (1%, *55(1% were the least observed frequencies in Lak population. Our results based on HLA-A and HLA-B allele frequencies showed that Lak population possesses the previously reported general features of Iranians but still with unique.

Autoimmune hepatitis-specific antibodies against soluble liver antigen and liver cytosol type 1 in patients with chronic viral hepatitis

OpenAIRE

Rigopoulou, Eirini I; Mytilinaiou, Maria; Romanidou, Ourania; Liaskos, Christos; Dalekos, George N

2007-01-01

Background Non-organ specific autoantibodies are highly prevalent in patients with chronic hepatitis C (HCV). Among them, anti-liver kidney microsomal type 1 (LKM1) antibody – the serological marker of type 2 autoimmune hepatitis (AIH-2)- is detected in up to 11% of the HCV-infected subjects. On the other hand, anti-liver cytosol type 1 antibodies (anti-LC1) – either in association with anti-LKM1, or in isolation- and anti-soluble liver antigen antibodies (anti-SLA) have been considered as us...

Návrh na slaďování pracovního a soukromého života ve vybraném podniku

OpenAIRE

Švejdíková, Romana

2013-01-01

Diplomová práce se zabývá problematikou slaďování práce a soukromého života ve zvolené organizaci. Detailně popisuje nástroje slaďování práce a soukromého života, srovnává teoretické poznatky se skutečností. Práce identifikuje možnosti a překážky slaďování práce a soukromého života u zaměstnanců zkoumané firmy. Na základě semistrukturovaného rozhovoru a dotazníkového šetření jsou navržena opatření pro optimální slaďování práce a života v organizaci. The diploma thesis deals with the issue ...

The African buffalo parasite Theileria. sp. (buffalo can infect and immortalize cattle leukocytes and encodes divergent orthologues of Theileria parva antigen genes

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R.P. Bishop

2015-12-01

Full Text Available African Cape buffalo (Syncerus caffer is the wildlife reservoir of multiple species within the apicomplexan protozoan genus Theileria, including Theileria parva which causes East coast fever in cattle. A parasite, which has not yet been formally named, known as Theileria sp. (buffalo has been recognized as a potentially distinct species based on rDNA sequence, since 1993. We demonstrate using reverse line blot (RLB and sequencing of 18S rDNA genes, that in an area where buffalo and cattle co-graze and there is a heavy tick challenge, T. sp. (buffalo can frequently be isolated in culture from cattle leukocytes. We also show that T. sp. (buffalo, which is genetically very closely related to T. parva, according to 18s rDNA sequence, has a conserved orthologue of the polymorphic immunodominant molecule (PIM that forms the basis of the diagnostic ELISA used for T. parva serological detection. Closely related orthologues of several CD8 T cell target antigen genes are also shared with T. parva. By contrast, orthologues of the T. parva p104 and the p67 sporozoite surface antigens could not be amplified by PCR from T. sp. (buffalo, using conserved primers designed from the corresponding T. parva sequences. Collectively the data re-emphasise doubts regarding the value of rDNA sequence data alone for defining apicomplexan species in the absence of additional data. ‘Deep 454 pyrosequencing’ of DNA from two Theileria sporozoite stabilates prepared from Rhipicephalus appendiculatus ticks fed on buffalo failed to detect T. sp. (buffalo. This strongly suggests that R. appendiculatus may not be a vector for T. sp. (buffalo. Collectively, the data provides further evidence that T. sp. (buffalo. is a distinct species from T. parva.

In vitro and in vivo evaluation of SLA titanium surfaces with further alkali or hydrogen peroxide and heat treatment

International Nuclear Information System (INIS)

Zhang, E W; Wang, Y B; Zheng, Y F; Shuai, K G; Gao, F; Bai, Y J; Cheng, Y; Xiong, X L; Wei, S C

2011-01-01

The present study aimed to evaluate the bioactivity of titanium surfaces sandblasted with large-grit corundum and acid etched (SLA) plus further alkali or hydrogen peroxide and heat treatment for dental implant application. Pure titanium disks were mechanically polished as control surface (Ti-control) and then sandblasted with large-grit corundum and acid etched (SLA). Further chemical modifications were conducted using alkali and heat treatment (ASLA) and hydrogen peroxide and heat treatment (HSLA) alternatively. The surface properties were characterized by scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS), and contact angle and roughness measurements. Further evaluation of surface bioactivity was conducted by MC3T3-E1 cell attachment, proliferation, morphology, alkaline phosphatase (ALP) activity and calcium deposition on the sample surfaces. After insertion in the beagle's mandibula for a specific period, cylindrical implant samples underwent micro-CT examination and then histological examination. It was found that ASLA and HSLA surfaces significantly increased the surface wettability and MC3T3-E1 cell attachment percentage, ALP activity and the quality of calcium deposition in comparison with simple SLA and Ti-control surfaces. Animal studies showed good osseointegration of ASLA and HSLA surfaces with host bone. In conclusion, ASLA and HSLA surfaces enhanced the bioactivity of the traditional SLA surface by integrating the advantages of surface topography, composition and wettability.

In vitro and in vivo evaluation of SLA titanium surfaces with further alkali or hydrogen peroxide and heat treatment

Energy Technology Data Exchange (ETDEWEB)

Zhang, E W; Wang, Y B; Zheng, Y F [State Key Laboratory for Turbulence and Complex System, Department of Advanced Materials and Nanotechnology, College of Engineering, Peking University, Beijing 100871 (China); Shuai, K G; Gao, F; Bai, Y J; Cheng, Y; Xiong, X L [Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Wei, S C, E-mail: enwei@pku.edu.cn, E-mail: yanbo.pku@pku.edu.cn, E-mail: shuaikegang@gmail.com, E-mail: soarfgoal@gmail.com, E-mail: norice86@163.com, E-mail: chengyan@pku.edu.cn, E-mail: xxiaoling11@hotmail.com, E-mail: yfzheng@pku.edu.cn, E-mail: weishicheng99@163.com [Department of Oral and Maxillofacial Surgery, School of Stomatology, Peking University, Beijing 100081 (China)

2011-04-15

The present study aimed to evaluate the bioactivity of titanium surfaces sandblasted with large-grit corundum and acid etched (SLA) plus further alkali or hydrogen peroxide and heat treatment for dental implant application. Pure titanium disks were mechanically polished as control surface (Ti-control) and then sandblasted with large-grit corundum and acid etched (SLA). Further chemical modifications were conducted using alkali and heat treatment (ASLA) and hydrogen peroxide and heat treatment (HSLA) alternatively. The surface properties were characterized by scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS), and contact angle and roughness measurements. Further evaluation of surface bioactivity was conducted by MC3T3-E1 cell attachment, proliferation, morphology, alkaline phosphatase (ALP) activity and calcium deposition on the sample surfaces. After insertion in the beagle's mandibula for a specific period, cylindrical implant samples underwent micro-CT examination and then histological examination. It was found that ASLA and HSLA surfaces significantly increased the surface wettability and MC3T3-E1 cell attachment percentage, ALP activity and the quality of calcium deposition in comparison with simple SLA and Ti-control surfaces. Animal studies showed good osseointegration of ASLA and HSLA surfaces with host bone. In conclusion, ASLA and HSLA surfaces enhanced the bioactivity of the traditional SLA surface by integrating the advantages of surface topography, composition and wettability.

Prevention of alloimmunization by ultraviolet-B irradiation. Inactivation of leukocytes and the generation of active oxygen and radicals

International Nuclear Information System (INIS)

Takahashi, Tsuneo; Mogi, Yuko; Sekiguchi, Sadayoshi; Akasaka, Junichi; Kamo, Naoki; Kuwabara, Mikinori.

1994-01-01

UV-B irradiation of platelet concentrates (PC) has been tried in several institutes to inactivate leukocytes in PC and prevent alloimmunization on platelet transfusion. However, the mechanism of inactivation of leukocytes contaminating PC has not been fully understood. It is known that UV-B light is absorbed by photosensitizers in cells and produces active oxygen and radicals, such as singlet oxygen, superioxide anions and hydroxyl radicals. These active oxygen or radicals should injure cellular components and this could cause the suppression of cellular functions. In this study, we investigated the relationships among UV-B irradiation, free radical generation and leukocyte inactivation. We found the evidence that active oxygen and radicals were produced in peripheral blood mononuclear cells by UV-B irradiation. UV-B irradiation suppressed the stimulatory function of leukocytes in a mixed lymphocyte reaction (MLR), and the suppression depended on the dosage of UV-B. Even a low dosage of UV-B, 10 J/m 2 , could inhibit the MLR if the irradiated cells were incubated at 37degC for 24 hours before co-culture with responder cells. Treatments of cells with the exogenous singlet oxygen or superoxide anions also caused suppression of the stimulatory function in the MLR, inhibition of capping formation of HLA-DR antigens, and an increase of intracellular free Ca 2+ levels as did the UV-B treatment. These results indicate that the active oxygen or radicals generated in UV-B-irradiated leukocytes could be one of the causes of leukocyte inactivation. (author0

Construction and application of a Korean reference panel for imputing classical alleles and amino acids of human leukocyte antigen genes.

Science.gov (United States)

Kim, Kwangwoo; Bang, So-Young; Lee, Hye-Soon; Bae, Sang-Cheol

2014-01-01

Genetic variations of human leukocyte antigen (HLA) genes within the major histocompatibility complex (MHC) locus are strongly associated with disease susceptibility and prognosis for many diseases, including many autoimmune diseases. In this study, we developed a Korean HLA reference panel for imputing classical alleles and amino acid residues of several HLA genes. An HLA reference panel has potential for use in identifying and fine-mapping disease associations with the MHC locus in East Asian populations, including Koreans. A total of 413 unrelated Korean subjects were analyzed for single nucleotide polymorphisms (SNPs) at the MHC locus and six HLA genes, including HLA-A, -B, -C, -DRB1, -DPB1, and -DQB1. The HLA reference panel was constructed by phasing the 5,858 MHC SNPs, 233 classical HLA alleles, and 1,387 amino acid residue markers from 1,025 amino acid positions as binary variables. The imputation accuracy of the HLA reference panel was assessed by measuring concordance rates between imputed and genotyped alleles of the HLA genes from a subset of the study subjects and East Asian HapMap individuals. Average concordance rates were 95.6% and 91.1% at 2-digit and 4-digit allele resolutions, respectively. The imputation accuracy was minimally affected by SNP density of a test dataset for imputation. In conclusion, the Korean HLA reference panel we developed was highly suitable for imputing HLA alleles and amino acids from MHC SNPs in East Asians, including Koreans.

Construction and application of a Korean reference panel for imputing classical alleles and amino acids of human leukocyte antigen genes.

Directory of Open Access Journals (Sweden)

Kwangwoo Kim

Full Text Available Genetic variations of human leukocyte antigen (HLA genes within the major histocompatibility complex (MHC locus are strongly associated with disease susceptibility and prognosis for many diseases, including many autoimmune diseases. In this study, we developed a Korean HLA reference panel for imputing classical alleles and amino acid residues of several HLA genes. An HLA reference panel has potential for use in identifying and fine-mapping disease associations with the MHC locus in East Asian populations, including Koreans. A total of 413 unrelated Korean subjects were analyzed for single nucleotide polymorphisms (SNPs at the MHC locus and six HLA genes, including HLA-A, -B, -C, -DRB1, -DPB1, and -DQB1. The HLA reference panel was constructed by phasing the 5,858 MHC SNPs, 233 classical HLA alleles, and 1,387 amino acid residue markers from 1,025 amino acid positions as binary variables. The imputation accuracy of the HLA reference panel was assessed by measuring concordance rates between imputed and genotyped alleles of the HLA genes from a subset of the study subjects and East Asian HapMap individuals. Average concordance rates were 95.6% and 91.1% at 2-digit and 4-digit allele resolutions, respectively. The imputation accuracy was minimally affected by SNP density of a test dataset for imputation. In conclusion, the Korean HLA reference panel we developed was highly suitable for imputing HLA alleles and amino acids from MHC SNPs in East Asians, including Koreans.

A model of acute renal allograft rejection in outbred Yorkshire piglets.

Science.gov (United States)

Lassiter, Randi; Wang, Youli; Fang, Xuexiu; Winn, Matt; Ghaffari, Arina; Ho, Chak-Sum; Helman, Sandra; Jajosky, Ryan; Kleven, Daniel; Stanley Nahman, N; Merchen, Todd D

2017-06-01

Pigs represent a desirable animal model for the study of rejection in kidney transplantation with inbred Yucatan miniature swine (YMS) the most commonly studied strain due to well defined swine leukocyte antigen (SLA) genotypes. However, limitations to YMS may include cost and availability. Outbred Yorkshire pigs are widely available and significantly cheaper than YMS. Recent advances in SLA genotyping have allowed its application to outbred strains. On this basis, we theorized that Yorkshire pigs would be a viable alternative to YMS for the study of rejection in kidney transplantation. To address this question, we performed auto (Auto) and allotransplants (Allo) in 24 Yorkshire pigs, and assessed SLA genotypes and acute rejection after 72h. At sacrifice, and when compared to autotransplants, allotransplants had significant elevations in serum creatinine (8.4±1.3 vs 2.8±2.0mg/dL for Allo vs autotransplants, respectively) and BUN (61±9 vs 19.2±15mg/dL for Allo vs autotransplants, respectively). Warm ischemia times between the two groups did not differ (24±2.3 vs 26.4±1.4min for Auto vs Allo, respectively). There were 16 distinct SLA haplotypes identified from pigs undergoing allotransplantion, no matched donor-recipient pairs, and all allografts demonstrated rejection. Type IIA cellular rejection (Banff) was the most common. One allograft demonstrated hyperacute rejection due a blood group incompatibility. Histologically, the expression of regulatory Tcells and dendritic cells was increased in allografts. These data suggest that Yorkshire pigs may be a useful model for the study of acute rejection in experimental kidney transplantation. Copyright © 2017. Published by Elsevier B.V.

Effect of human leukocyte antigen-C and -DQ matching on pediatric heart transplant graft survival.

Science.gov (United States)

Butts, Ryan J; Savage, Andrew J; Nietert, Paul J; Kavarana, Minoo; Moussa, Omar; Burnette, Ali L; Atz, Andrew M

2014-12-01

A higher degree of human leukocyte antigen (HLA) matching at the A, B, and DR loci has been associated with improved long-term survival after pediatric heart transplantation in multiple International Society for Heart and Lung Transplantation registry reports. The aim of this study was to investigate the association of HLA matching at the C and DQ loci with pediatric graft survival. The United Network of Organ Sharing database was queried for isolated heart transplants that occurred from 1988 to 2012 with a recipient age of 17 or younger and at least 1 postoperative follow-up encounter. When HLA matching at the C or DQ loci were analyzed, only transplants with complete typing of donor and recipient at the respective loci were included. Transplants were divided into patients with at least 1 match at the C locus (C-match) vs no match (C-no), and at least 1 match at the DQ (DQ-match) locus vs no match (DQ-no). Primary outcome was graft loss. Univariate analysis was performed with the log-rank test. Cox regression analysis was performed with the following patient factors included in the model: recipient age, ischemic time; recipient on ventilator, extracorporeal membrane oxygenation, ventricular assist device, or inotropes at transplant; recipient serum bilirubin and creatinine closest to transplant, ratio of donor weight to recipient weight, underlying cardiac diagnosis, crossmatch results, transplant year, and HLA matching at the A, B, and DR loci. Complete typing at the C locus occurred in 2,429 of 4,731 transplants (51%), and complete typing at the DQ locus occurred in 3,498 of 4,731 transplants (74%). Patient factors were similar in C-match and C-no, except for year of transplant (median year, 2007 [interquartile range, 1997-2010] vs year 2005 [interquartile range, 1996-2009], respectively; p = 0.03) and the degree of HLA matching at the A, B, and DR loci (high level of HLA matching in 11.9% vs 3%, respectively; p HLA matching at the C locus or the DQ locus

New CALL-SLA Research Interfaces for the 21st Century: Towards Equitable Multilingualism

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Ortega, Lourdes

2017-01-01

The majority of the world is multilingual, but inequitably multilingual, and much of the world is also technologized, but inequitably so. Thus, researchers in the fields of computer-assisted language learning (CALL) and second language acquisition (SLA) would profit from considering multilingualism and social justice when envisioning new CALL-SLA…

Autoantibodies and their antigens in autoimmune hepatitis.

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Bogdanos, Dimitrios P; Mieli-Vergani, Giorgina; Vergani, Diego

2009-08-01

Autoantibody detection assists in the diagnosis and allows differentiation of autoimmune hepatitis (AIH) type 1 (AIH-1), characterized by antinuclear antibody (ANA) and/or smooth muscle antibody (SMA), and type 2 (AIH-2), distinguished by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) and/or antibodies to liver cytosol type 1 (anti-LC1). Detection of atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-soluble liver antigen (SLA) antibodies can act as an additional pointer toward the diagnosis of AIH, particularly in the absence of the conventional autoantibodies. Routine autoantibody testing by indirect immunofluorescence has been recently complemented by molecular assays based on purified or recombinant antigens. Although the AIH-1-specific ANA and SMA targets need better definition, those of anti-LKM1 and anti-LC1 in AIH-2 have been clearly identified; the fine specificity of antibody reactivity and its clinical relevance to disease pathogenesis are the focus of ongoing investigation. This article critically discusses the current knowledge of the diagnostic and clinical significance of AIH-related autoantibody reactivities, focusing on key issues that the physician needs to be aware of to be able to request the appropriate testing and to interpret correctly the laboratory results within the clinical context of the patient. Copyright Thieme Medical Publishers.

Biomimetic carriers mimicking leukocyte plasma membrane to increase tumor vasculature permeability

Science.gov (United States)

Palomba, R.; Parodi, A.; Evangelopoulos, M.; Acciardo, S.; Corbo, C.; De Rosa, E.; Yazdi, I. K.; Scaria, S.; Molinaro, R.; Furman, N. E. Toledano; You, J.; Ferrari, M.; Salvatore, F.; Tasciotti, E.

2016-10-01

Recent advances in the field of nanomedicine have demonstrated that biomimicry can further improve targeting properties of current nanotechnologies while simultaneously enable carriers with a biological identity to better interact with the biological environment. Immune cells for example employ membrane proteins to target inflamed vasculature, locally increase vascular permeability, and extravasate across inflamed endothelium. Inspired by the physiology of immune cells, we recently developed a procedure to transfer leukocyte membranes onto nanoporous silicon particles (NPS), yielding Leukolike Vectors (LLV). LLV are composed of a surface coating containing multiple receptors that are critical in the cross-talk with the endothelium, mediating cellular accumulation in the tumor microenvironment while decreasing vascular barrier function. We previously demonstrated that lymphocyte function-associated antigen (LFA-1) transferred onto LLV was able to trigger the clustering of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Herein, we provide a more comprehensive analysis of the working mechanism of LLV in vitro in activating this pathway and in vivo in enhancing vascular permeability. Our results suggest the biological activity of the leukocyte membrane can be retained upon transplant onto NPS and is critical in providing the particles with complex biological functions towards tumor vasculature.

KSAC, a defined Leishmania antigen, plus adjuvant protects against the virulence of L. major transmitted by its natural vector Phlebotomus duboscqi.

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Regis Gomes

Full Text Available Recombinant KSAC and L110f are promising Leishmania vaccine candidates. Both antigens formulated in stable emulsions (SE with the natural TLR4 agonist MPL® and L110f with the synthetic TLR4 agonist GLA in SE protected BALB/c mice against L. major infection following needle challenge. Considering the virulence of vector-transmitted Leishmania infections, we vaccinated BALB/c mice with either KSAC+GLA-SE or L110f+GLA-SE to assess protection against L. major transmitted via its vector Phlebotomus duboscqi.Mice receiving the KSAC or L110f vaccines were challenged by needle or L. major-infected sand flies. Weekly disease progression and terminal parasite loads were determined. Immunological responses to KSAC, L110f, or soluble Leishmania antigen (SLA were assessed throughout vaccination, three and twelve weeks after immunization, and one week post-challenge.Following sand fly challenge, KSAC-vaccinated mice were protected while L110f-vaccinated animals showed partial protection. Protection correlated with the ability of SLA to induce IFN-γ-producing CD4(+CD62L(lowCCR7(low effector memory T cells pre- and post-sand fly challenge.This study demonstrates the protective efficacy of KSAC+GLA-SE against sand fly challenge; the importance of vector-transmitted challenge in evaluating vaccine candidates against Leishmania infection; and the necessity of a rapid potent Th1 response against Leishmania to attain true protection.

Human Leukocyte Antigen Class II Alleles (DQB1 and DRB1 as Predictors for Response to Interferon Therapy in HCV Genotype 4

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Olfat Shaker

2013-01-01

Full Text Available Human leukocyte antigens class II play an important role in immune response against HCV. We investigated whether HLA class II alleles influence susceptibility to HCV infection and response to interferon therapy. HLA-DRB1 and -DQB1 loci were genotyped using PCR-SSO Luminex technology. According to our regimen, 41 (66% of patients achieved sustained virological response to combined treatment of IFN and ribavirin. Frequencies of DQB1*0313 allele and DRB1*04-DRB1*11, DQB1*0204-DQB1*0313, DQB1*0309-DQB1*0313, and DQB1*0313-DQB1*0319 haplotypes were significantly more frequent in nonresponders than in responders. In contrast, DQB1*02, DQB1*06, DRB1*13, and DRB1*15 alleles were significantly more frequent in responders than in nonresponders. Similarly, DRB1*1301, DRB1*1361, and DRB1*1369 alleles and DRB1*1301-DRB1*1328, DRB1*1301-DRB1*1361, DRB1*1301-DRB1*1369, DRB1*1328-DRB1*1361, and DRB1*1328-DRB1*1369 haplotypes were significantly found only in responders. Some alleles and linkages showed significantly different distributions between patient and healthy groups. These alleles may be used as predictors for response to treatment or to susceptibility to HCV infection in the Egyptian population.

Enhancing Information Security in Cloud Computing Services using SLA based metrics

OpenAIRE

, Nia; Mganga, Ramadianti Putri;; Charles, Medard

2011-01-01

Context: Cloud computing is a prospering technology that most organizations are considering for adoption as a cost effective strategy for managing IT. However, organizations also still consider the technology to be associated with many business risks that are not yet resolved. Such issues include security, privacy as well as legal and regulatory risks. As an initiative to address such risks, organizations can develop and implement SLA to establish common expectations and goals between the clo...

Human Leukocyte Antigen-G Is Frequently Expressed in a Multicentric Study on Glioblastoma and May Be Induced in Vitro by Combined 5-aza-2'-deoxycytidine and Interferon-γ Treatments

DEFF Research Database (Denmark)

Wastowski, Isabela J; Simões, Renata T; Yaghi, Layale

2012-01-01

-G protein expression was associated with a better long-term survival rate. The mechanisms underlying HLA-G gene expression were investigated in glioma cell lines U251MG, D247MG, and U138MG. Induction of HLA-G transcriptional activity was dependent of 5-aza-2'-deoxycytidine treatment and enhanced......Human leukocyte antigen-G (HLA-G) is a nonclassical major histocompatibility complex (MHC) class I molecule involved in immune tolerance processes, playing an important role in the maintenance of the semi-allogeneic fetus. Although HLA-G expression is restricted in normal tissues, it is broadly...... expressed in malignant tumors and may favor tumor immune escape. We analyzed HLA-G protein and mRNA expression in tumor samples from patients with glioblastoma collected in France, Denmark, and Brazil. We found HLA-G protein expression in 65 of 108 samples and mRNA in 20 of 21 samples. The absence of HLA...

Autoimmune hepatitis-specific antibodies against soluble liver antigen and liver cytosol type 1 in patients with chronic viral hepatitis.

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Rigopoulou, Eirini I; Mytilinaiou, Maria; Romanidou, Ourania; Liaskos, Christos; Dalekos, George N

2007-02-04

Non-organ specific autoantibodies are highly prevalent in patients with chronic hepatitis C (HCV). Among them, anti-liver kidney microsomal type 1 (LKM1) antibody--the serological marker of type 2 autoimmune hepatitis (AIH-2)--is detected in up to 11% of the HCV-infected subjects. On the other hand, anti-liver cytosol type 1 antibodies (anti-LC1)--either in association with anti-LKM1, or in isolation--and anti-soluble liver antigen antibodies (anti-SLA) have been considered as useful and specific diagnostic markers for AIH. However, their specificity for AIH has been questioned by some recent studies, which have shown the detection of anti-LC1 and anti-SLA by immunoprecipitation assays in HCV patients irrespective of their anti-LKM1 status. The aim of the present study was to test the anti-LC1 and anti-SLA presence by specific enzyme linked immunosorbent assays (ELISAs), in a large group of Greek HCV-infected patients with or without anti-LKM1 reactivity as firstly, immunoprecipitation assays are limited to few specialized laboratories worldwide and cannot be used routinely and secondly, to assess whether application of such tests has any relevance in the context of patients with viral hepatitis since antibody detection based on such ELISAs has not been described in detail in large groups of HCV patients. One hundred and thirty eight consecutive HCV patients (120 anti-LKM1 negative and 18 anti-LKM1 positive) were investigated for the presence of anti-LC1 and anti-SLA by commercial ELISAs. A similar number (120) of chronic hepatitis B virus (HBV) infected patients seronegative for anti-LKM1 was also tested as pathological controls. Six out of 18 (33%) anti-LKM(pos)/HCV(pos) patients tested positive for anti-LC1 compared to 1/120 (0.83%) anti-LKM(neg)/HCV(pos) patients and 0/120 (0%) of the anti-LKM1(neg)/HBV(pos) patients (p LKM1) or HBV-infected patients. We showed that anti-LC1 and anti-SLA autoantibodies are not detected by conventional assays in a large group of

Regulation of T cell response to leishmania antigens by determinants of histocompatibility leukocyte class I and II molecules

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Bacellar O.

1998-01-01

Full Text Available It has been shown that HLA class I molecules play a significant role in the regulation of the proliferation of T cells activated by mitogens and antigens. We evaluated the ability of mAb to a framework determinant of HLA class I molecules to regulate T cell proliferation and interferon gamma (IFN-g production against leishmania, PPD, C. albicans and tetanus toxoid antigens in patients with tegumentary leishmaniasis and healthy subjects. The anti-major histocompatibility complex (MHC mAb (W6/32 suppressed lymphocyte proliferation by 90% in cultures stimulated with aCD3, but the suppression was variable in cultures stimulated with leishmania antigen. This suppression ranged from 30-67% and was observed only in 5 of 11 patients. IFN-g production against leishmania antigen was also suppressed by anti-HLA class I mAb. In 3 patients IFN-g levels were suppressed by more than 60%, while in the other 2 cultures IFN-g levels were 36 and 10% lower than controls. The suppression by HLA class I mAb to the proliferative response in leishmaniasis patients and in healthy controls varied with the antigens and the patients or donors tested. To determine whether the suppression is directed at antigen presenting cells (APCs or at the responding T cells, experiments with antigen-primed non-adherent cells, separately incubated with W6/32, were performed. Suppression of proliferation was only observed when the W6/32 mAb was added in the presence of T cells. These data provide evidence that a mAb directed at HLA class I framework determinants can suppress proliferation and cytokine secretion in response to several antigens.

De nonklassiske humant leukocyt-antigen (HLA)-vaevstyper--fra implantation til transplantation

DEFF Research Database (Denmark)

Hviid, Thomas Vauvert F

2006-01-01

), other functional HLA genes have been detected, the so-called non-classical HLA class Ib genes: HLA-E, -G and -F. They resemble the HLA class Ia antigens in many ways, but several major differences have been described. They are almost monomorphic and generally have a restricted pattern of expression. One...... has a role in implantation. A very strong expression of HLA-G is observed in the invasive trophoblast cells in the placenta. HLA-G may be involved in certain complications of pregnancy and the genetic predisposition to these. Finally, HLA-G expression has been associated with a reduced risk...

Scintigraphy with In-111 labeled leukocytes

International Nuclear Information System (INIS)

Itoh, Kazuo; Tsukamoto, Eriko; Furudate, Masayori; Saito, Chihoko.

1987-01-01

With increasing necessity for In-111 labeled leukocyte scintigraphy (ILLS) as a routine examination, a problem of complicated labeling of leukocytes has arisen. In this study, simplified labeling of leukocytes was examined with respect to its ability to detect abscesses. Simplified labeling method yielded significantly satisfactory results for recovery and labeling rates of leukocytes, as compared with conventional recommended method. Therefore, ILLS by simplified technique was clinically applied in 58 patients with suppurative or non-suppurative diseases who gave informed consent. In an analysis of ILLS for detecting suppurative region, the sensitivity, specificity, and corrected specificity were found to be 81 %, 75 %, and 82 %, respectively. (Namekawa, K.)

Preimplantation diagnosis: efficient tool for human leukocyte antigen matched bone marrow transplantation for thalassemia

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Anver Kuliev

2011-08-01

Full Text Available Thalassemia is among the most frequent indications for preimplantation genetic diagnosis (PGD to allow at risk couples reproducing without fear of having an affected child. In addition, those already having the affected child, have also the option to produce an unaffected offspring that may be also a complete human leukocyte antigen (HLA match to affected child to ensure successful bone marrow transplantation. We present here the results of retrospective analysis of 293 PGD cycles for thalassemia, including 144cases of simultaneous HLA typing, resulting in birth of 70 thalassemia-free children and 12 unaffected HLA matched ones, providing their cord blood and/or bone marrow for transplantation treatment of their affected siblings. The present overall experience includes successful cord blood or bone marrow transplantation in more than three dozens of cases with HLA matched stem cells obtained from children born after PGD, demonstrating that PGD is an efficient approach for improving success of bone marrow transplantation treatment for thalassemia.   植入前遗传学诊断（PGD）是地中海贫血（地贫）最常用的疗法，该病患者夫妇无须担心孕儿受到感染。此外，如果已经怀上受到感染的宝宝，他们也可有选择性再生育一个未受感染的后代，提供完全匹配的HLA，来确保骨髓成功移植。本文将提供293个地贫病例的PGD周期诊断结果，包括144例HLA同时配型，有70例宝宝无地贫出生和12例未受感染的HLA配型宝宝出生。将这些健康宝宝的脐带血和/或骨髓取出以完成对他们同胞的移植手术，通过使用经诊断后的，出生宝宝身上取出的HLA配型干细胞，成功完成36例宝宝的脐带或骨髓移植手术。结果表明PGD能有效提高地贫患儿骨髓移植手术的成功率。

Efficiency of Direct Microscopy of Stool Samples Using an Antigen-Specific Adhesin Test for Entamoeba Histolytica

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Arzu İrvem

2016-10-01

Full Text Available Background: E. histolytica is among the common causes of acute gastroenteritis. The pathogenic species E. histolytica and the nonpathogenic species E. dispar cannot be morphologically differentiated, although correct identification of these protozoans is important for treatment and public health. In many laboratories, the screening of leukocytes, erythrocytes, amoebic cysts, trophozoites and parasite eggs is performed using Native-Lugol’s iodine for pre-diagnosis. Aims: In this study, we aimed to investigate the frequency of E. histolytica in stool samples collected from 788 patients residing in the Anatolian region of İstanbul who presented with gastrointestinal complaints. We used the information obtained to evaluate the effectiveness of microscopic examinations when used in combination with the E. histolytica adhesin antigen test. Study Design: Retrospective cross-sectional study Methods: Preparations of stool samples stained with Native-Lugol’s iodine were evaluated using the E. histolytica adhesin test and examined using standard light microscopy at ×40 magnification. Pearson’s Chi-square and Fisher’s exact tests were used for statistical analysis. Logistic regression analysis was used for multivariate analysis. Results: Of 788 samples, 38 (4.8% were positive for E. histolytica adhesin antigens. When evaluated together with the presences of erythrocytes, leukocytes, cysts, and trophozoites, respectively, using logistic regression analysis, leukocyte positivity was significantly higher. The odds ratio of leukocyte positivity increased adhesin test-positivity by 2,530-fold (95% CI=1.01–6.330. Adhesin test-positivity was significant (p=0.047. Conclusion: In line with these findings, the consistency between the presence of cysts and erythrocytes and adhesin test-positivity was found to be highly significant, but that of higher levels of leukocytes was found to be discordant. It was concluded that leukocytes and trophozoites were

Human leukocyte antigen (HLA class I restricted epitope discovery in yellow fewer and dengue viruses: importance of HLA binding strength.

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Ole Lund

Full Text Available Epitopes from all available full-length sequences of yellow fever virus (YFV and dengue fever virus (DENV restricted by Human Leukocyte Antigen class I (HLA-I alleles covering 12 HLA-I supertypes were predicted using the NetCTL algorithm. A subset of 179 predicted YFV and 158 predicted DENV epitopes were selected using the EpiSelect algorithm to allow for optimal coverage of viral strains. The selected predicted epitopes were synthesized and approximately 75% were found to bind the predicted restricting HLA molecule with an affinity, K(D, stronger than 500 nM. The immunogenicity of 25 HLA-A*02:01, 28 HLA-A*24:02 and 28 HLA-B*07:02 binding peptides was tested in three HLA-transgenic mice models and led to the identification of 17 HLA-A*02:01, 4 HLA-A*2402 and 4 HLA-B*07:02 immunogenic peptides. The immunogenic peptides bound HLA significantly stronger than the non-immunogenic peptides. All except one of the immunogenic peptides had K(D below 100 nM and the peptides with K(D below 5 nM were more likely to be immunogenic. In addition, all the immunogenic peptides that were identified as having a high functional avidity had K(D below 20 nM. A*02:01 transgenic mice were also inoculated twice with the 17DD YFV vaccine strain. Three of the YFV A*02:01 restricted peptides activated T-cells from the infected mice in vitro. All three peptides that elicited responses had an HLA binding affinity of 2 nM or less. The results indicate the importance of the strength of HLA binding in shaping the immune response.

Long-Term Effects of Antibodies Against Human Leukocyte Antigens Detected by Flow Cytometry in the First Year After Renal Transplantation

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Tülay Kılıçaslan Ayna

2013-03-01

Full Text Available Objective: In this study, we aimed to investigate the incidence, dynamics and profiles of human leukocyte antigen (HLA-directed antibodies developed after transplantation and their impact on graft rejection and outcome in kidney recipients. Study Design: Prospective follow-up study. Material and Methods: A total of 56 kidney recipients were monitored at 1st, 6th and 12th months for the development of anti-HLA antibodies using bead based flow-cytometry assays (Flow PRA tests. Results: In 21 (37.5% patients, panel reactive antibodies (PRA was positive after transplantation, however, in 35 (62.5% patients PRA was found negative. Twelve (57.1% patients with post-transplantation HLA-reactive antibodies [PRA (+] and 8 (22.9% patients with no detectable alloantibodies [PRA (-] were developed allograft rejection (p=0.010. In the PRA positive patient group the rates of early period infection and delayed graft function (DGF were higher than the PRA negative patient group. Serum creatinine levels of PRA positive group at 6. and 12. months after transplantation were significantly higher than the PRA negative group (p=0.015 and p=0.048, respectively. The rejection rates of patients who had class I and II HLA antibodies were significantly higher than the patients who had either class I or II HLA antibodies (p=0.011. Acute rejection rates were significantly higher in patients who had class I and II HLA antibodies at the first month (p=0.007. Conclusion: Higher occurrence of rejection episodes in PRA positive group may show the importance of anti-HLA antibody monitoring using Flow-PRA after renal transplantation as a prognostic marker in terms of graft survival.

Human leukocyte antigen-A, -B, and -DRB1 haplotypes of cord blood units in the Tzu Chi Taiwan Cord Blood Bank.

Science.gov (United States)

Wen, Shu-Hui; Lai, Meng-Jiun; Yang, Kuo-Liang

2008-07-01

Cord blood (CB) is considered an alternative resource to bone marrow and peripheral blood stem cells (PBSC) for allogeneic stem cell transplantation. In this study, human leukocyte antigen (HLA)-A, -B, and -DRB1 high-resolution allele types were analyzed from a total of 710 CB units in the Tzu Chi Taiwan Cord Blood Bank. We observed 21 HLA-A alleles, 59 HLA-B alleles, and 28 HLA-DRB1 alleles, whereas 19 unique alleles were present in the CB units of 2,023 individuals selected for confirmatory testing in the Tzu Chi Taiwan Marrow Donor Registry (TCTMDR). The allelic associations between the HLA-A and -B locus were stronger than that of either the HLA-B and -DRB1 loci or the HLA-A and -DRB1 loci. The most common haplotype of CB units in the general Taiwanese population was A*3303-B*5801-DRB1*0301 (6.59%), followed by A*0207-B*4601-DRB1*0901 (3.47%) and then A*1101-B*4001-DRB1*0901 (2.11%). Moreover, two haplotypes, A*2402-B*5201-DRB1*1502 and A*0201-B*1301-DRB1*1202, existed uniquely in the CB units but were not observed in the data of TCTMDR. Although the number of CB units studied for high-resolution of HLA typing in the current study is small, we believe our data should provide useful information to increase the chances of obtaining acceptable HLA-A-, -B-, and -DRB1-matched CB units for patients.

Outcome of recipients of human leukocyte antigen incompatible kidney transplants who underwent desensitization at King Fahad Specialist Hospital, Dammam, Saudi Arabia

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Mohammed Abdulrahim Idris

2017-01-01

Full Text Available In patients whom are highly sensitized immunologically, the benefit of kidney transplantation can be extended to this population through the utilization of organs from human leukocyte antigen incompatible (HLAi donors. This retrospective observational study was designed to identify the incidence and predictors of acute antibody-mediated rejection/acute cellular rejection (AMR/ACR in our kidney recipients from living kidney donors (sensitized and those with low immunologic risk. This single-center study has been conducted at King Fahad Specialist Hospital, Dammam (KFSH-D, Saudi Arabia; during the period of September 2008- August 2013. All eligible recipients of living donor kidneys during the study period were included (n = 213 in the study. Over 60% of patients in the study were females. Thirty of the 213 kidneys were from HLAi donors. During the follow-up period (median follow-up time = 16 months; 3–27 months, the incidence rate of ACR among HLA compatible (HLAc and HLAi groups was 22.2% and 16.7%, respectively (P >0.05. The incidence rate of AMR was 2.6% in HLAc group and 16.7%in the HLAi group (P<0.05. The significantly higher incidence of AMR in HLAi group can be explained by the presence of the donor-specific antibodies in weak titers. These results are consistent with studies from similar populations in published literature. However, the relatively small number and short duration of the study are considered, and longer follow-up of this population will be needed for conclusions on the sustainability of our findings.

Differences in leukocyte differentiation molecule abundances on domestic sheep (Ovis aries) and bighorn sheep (Ovis canadensis) neutrophils identified by flow cytometry.

Science.gov (United States)

Highland, Margaret A; Schneider, David A; White, Stephen N; Madsen-Bouterse, Sally A; Knowles, Donald P; Davis, William C

2016-06-01

Although both domestic sheep (DS) and bighorn sheep (BHS) are affected by similar respiratory bacterial pathogens, experimental and field data indicate BHS are more susceptible to pneumonia. Cross-reactive monoclonal antibodies (mAbs) for use in flow cytometry (FC) are valuable reagents for interspecies comparative immune system analyses. This study describes cross-reactive mAbs that recognize leukocyte differentiation molecules (LDMs) and major histocompatibility complex antigens on DS and BHS leukocytes. Characterization of multichannel eosinophil autofluorescence in this study permitted cell-type specific gating of granulocytes for evaluating LDMs, specifically on neutrophils, by single-label FC. Evaluation of relative abundances of LDMs by flow cytometry revealed greater CD11a, CD11b, CD18 (β2 integrins) and CD 172a (SIRPα) on DS neutrophils and greater CD14 (lipopolysaccharide receptor) on BHS neutrophils. Greater CD25 (IL-2) was identified on BHS lymphocytes following Concavalin A stimulation. While DS and BHS have similar total peripheral blood leukocyte counts, BHS have proportionately more neutrophils. Published by Elsevier Ltd.

Chemokines in the corpus luteum: Implications of leukocyte chemotaxis

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Liptak Amy R

2003-11-01

Full Text Available Abstract Chemokines are small molecular weight peptides responsible for adhesion, activation, and recruitment of leukocytes into tissues. Leukocytes are thought to influence follicular atresia, ovulation, and luteal function. Many studies in recent years have focused attention on the characterization of leukocyte populations within the ovary, the importance of leukocyte-ovarian cell interactions, and more recently, the mechanisms of ovarian leukocyte recruitment. Information about the role of chemokines and leukocyte trafficking (chemotaxis during ovarian function is important to understanding paracrine-autocrine relationships shared between reproductive and immune systems. Recent advances regarding chemokine expression and leukocyte accumulation within the ovulatory follicle and the corpus luteum are the subject of this mini-review.

[Mechanisms of leukocyte formation of endogenous pyrogen].

Science.gov (United States)

Rybakina, E G; Sorokin, A V

1982-06-01

A study was made of the kinetics of endogenous pyrogen production by rabbit blood and exudate leukocytes and possible role played by the products of activated leukocytes in autoregulation of the process. It was established that accumulation of endogenous pyrogen in the cell precedes its release by stimulated cells. Then the processes of active pyrogen formation and release gel interdependent: pyrogen formed releases from the cell; the lowering of pyrogen concentration in the cell is accompanied by the decrease of its content in the medium. No stimulating effect of the products activated during leukocyte inflammation on pyrogen formation by blood leukocytes was discovered.

Diversity of natural self-derived ligands presented by different HLA class I molecules in transporter antigen processing-deficient cells.

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Elena Lorente

Full Text Available The transporter associated with antigen processing (TAP translocates the cytosol-derived proteolytic peptides to the endoplasmic reticulum lumen where they complex with nascent human leukocyte antigen (HLA class I molecules. Non-functional TAP complexes and viral or tumoral blocking of these transporters leads to reduced HLA class I surface expression and a drastic change in the available peptide repertoire. Using mass spectrometry to analyze complex human leukocyte antigen HLA-bound peptide pools isolated from large numbers of TAP-deficient cells, we identified 334 TAP-independent ligands naturally presented by four different HLA-A, -B, and -C class I molecules with very different TAP dependency from the same cell line. The repertoire of TAP-independent peptides examined favored increased peptide lengths and a lack of strict binding motifs for all four HLA class I molecules studied. The TAP-independent peptidome arose from 182 parental proteins, the majority of which yielded one HLA ligand. In contrast, TAP-independent antigen processing of very few cellular proteins generated multiple HLA ligands. Comparison between TAP-independent peptidome and proteome of several subcellular locations suggests that the secretory vesicle-like organelles could be a relevant source of parental proteins for TAP-independent HLA ligands. Finally, a predominant endoproteolytic peptidase specificity for Arg/Lys or Leu/Phe residues in the P(1 position of the scissile bond was found for the TAP-independent ligands. These data draw a new and intricate picture of TAP-independent pathways.

Mg ion implantation on SLA-treated titanium surface and its effects on the behavior of mesenchymal stem cell

International Nuclear Information System (INIS)

Kim, Beom-Su; Kim, Jin Seong; Park, Young Min; Choi, Bo-Young; Lee, Jun

2013-01-01

Magnesium (Mg) is one of the most important ions associated with bone osseointegration. The aim of this study was to evaluate the cellular effects of Mg implantation in titanium (Ti) surfaces treated with sand blast using large grit and acid etching (SLA). Mg ions were implanted into the surface via vacuum arc source ion implantation. The surface morphology, chemical properties, and the amount of Mg ion release were evaluated by scanning electron microscopy (SEM), Auger electron spectroscopy (AES), Rutherford backscattering spectroscopy (RBS), and inductively coupled plasma-optical emission spectrometer (ICP-OES). Human mesenchymal stem cells (hMSCs) were used to evaluate cellular parameters such as proliferation, cytotoxicity, and adhesion morphology by MTS assay, live/dead assay, and SEM. Furthermore, osteoblast differentiation was determined on the basis of alkaline phosphatase (ALP) activity and the degree of calcium accumulation. In the Mg ion-implanted disk, 2.3 × 10 16 ions/cm 2 was retained. However, after Mg ion implantation, the surface morphology did not change. Implanted Mg ions were rapidly released during the first 7 days in vitro. The MTS assay, live/dead assay, and SEM demonstrated increased cell attachment and growth on the Mg ion-implanted surface. In particular, Mg ion implantation increased the initial cell adhesion, and in an osteoblast differentiation assay, ALP activity and calcium accumulation. These findings suggest that Mg ion implantation using the plasma source ion implantation (PSII) technique may be useful for SLA-treated Ti dental implants to improve their osseointegration capacity. - Highlights: ► Mg ion was coated onto surface of SLA treated titanium via vacuum arc source ion implantation method. ► The morphological characteristics did not change after Mg ion implantation. ► Mg ion implanted SLA Ti is highly cytocompatible. ► Initial cell adhesion of MSCs is improved by Mg ion implantation. ► Mg ion implantation improved

Leukocyte integrins and their ligand interactions

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Hyun, Young-Min; Lefort, Craig T.; Kim, Minsoo

2010-01-01

Although critical for cell adhesion and migration during normal immune-mediated reactions, leukocyte integrins are also involved in the pathogenesis of diverse clinical conditions including autoimmune diseases and chronic inflammation. Leukocyte integrins therefore have been targets for anti-adhesive therapies to treat the inflammatory disorders. Recently, the therapeutic potential of integrin antagonists has been demonstrated in psoriasis and multiple sclerosis. However, current therapeutics broadly affect integrin functions and, thus, yield unfavorable side effects. This review discusses the major leukocyte integrins and the anti-adhesion strategies for treating immune diseases. PMID:19184539

Leukocyte telomere dynamics in the elderly

DEFF Research Database (Denmark)

Steenstrup, Troels; Hjelmborg, Jacob V B; Mortensen, Laust H

2013-01-01

Limited data suggest that leukocytes of the elderly display ultra-short telomeres. It was reported that in some elderly persons leukocyte telomere length (LTL) shows age-dependent elongation. Using cross-sectional and longitudinal models, we characterized LTL dynamics in participants...

Correlation and agreement between eplet mismatches calculated using serological, low-intermediate and high resolution molecular human leukocyte antigen typing methods.

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Fidler, Samantha; D'Orsogna, Lloyd; Irish, Ashley B; Lewis, Joshua R; Wong, Germaine; Lim, Wai H

2018-03-02

Structural human leukocyte antigen (HLA) matching at the eplet level can be identified by HLAMatchmaker, which requires the entry of four-digit alleles. The aim of this study was to evaluate the agreement between eplet mismatches calculated by serological and two-digit typing methods compared to high-resolution four-digit typing. In a cohort of 264 donor/recipient pairs, the evaluation of measurement error was assessed using intra-class correlation to confirm the absolute agreement between the number of eplet mismatches at class I (HLA-A, -B, C) and II loci (HLA-DQ and -DR) calculated using serological or two-digit molecular typing compared to four-digit molecular typing methods. The proportion of donor/recipient pairs with a difference of >5 eplet mismatches between the HLA typing methods was also determined. Intra-class correlation coefficients between serological and four-digit molecular typing methods were 0.969 (95% confidence intervals [95% CI] 0.960-0.975) and 0.926 (95% CI 0.899-0.944), respectively; and 0.995 (95% CI 0.994-0.996) and 0.993 (95% CI 0.991-0.995), respectively between two-digit and four-digit molecular typing methods. The proportion of donor/recipient pairs with a difference of >5 eplet mismatches at class I and II loci was 4% and 16% for serological versus four-digit molecular typing methods, and 0% and 2% for two-digit versus four-digit molecular typing methods, respectively. In this small predominantly Caucasian population, compared with serology, there is a high level of agreement in the number of eplet mismatches calculated using two-compared to four-digit molecular HLA-typing methods, suggesting that two-digit typing may be sufficient in determining eplet mismatch load in kidney transplantation.

Soluble CD30 and ELISA-detected human leukocyte antigen antibodies for the prediction of acute rejection in pediatric renal transplant recipients.

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Billing, Heiko; Sander, Anja; Süsal, Caner; Ovens, Jörg; Feneberg, Reinhard; Höcker, Britta; Vondrak, Karel; Grenda, Ryszard; Friman, Stybjorn; Milford, David V; Lucan, Mihai; Opelz, Gerhard; Tönshoff, Burkhard

2013-03-01

Biomarker-based post-transplant immune monitoring for the prediction of impending graft rejection requires validation in specific patient populations. Serum of 28 pediatric renal transplant recipients within the framework of a well-controlled prospective randomized trial was analyzed pre- and post-transplant for soluble CD30 (sCD30), a biomarker reflecting mainly T-cell reactivity, and anti-human leukocyte antigen (anti-HLA) antibody reactivity, a biomarker for B-cell activation. A sCD30 concentration ≥40.3 U/ml on day 14 was able to discriminate between patients with or without biopsy-proven acute rejection (BPAR) with a sensitivity of 100% and a specificity of 76%. Six of seven patients (86%) with BPAR showed a sCD30 above this cut-off, whereas only 3/21 patients (14%) without BPAR had a sCD30 above this cut-off (P = 0.004). For pre- and post-transplant anti-HLA class II reactivities by enzyme-linked immunosorbent assay, a cut-off value of 140 optical density was able to discriminate rejecters from nonrejecters with a sensitivity of 86% or 71% and a specificity of 81% or 90%, respectively. Withdrawal of steroids was associated with a approximately twofold higher serum sCD30 compared to controls, but did not affect anti-HLA reactivities. An increased post-transplant sCD30 serum concentration and positive pre- and post-transplant anti-HLA class II reactivities are informative biomarkers for impending BPAR in pediatric renal transplant recipients. (TWIST, Clinical Trial No: FG-506-02-43). © 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.

Effect of the human leukocyte antigen HLA-DRB1 and anti-cyclic citrullinated peptide on the outcome of rheumatoid arthritis patients.

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Farouk, H M; Mansour, H E; Rahman, S A; Mostafa, A A; Shamy, H A; Zarouk, W A

2009-09-01

Our objective was to determine whether the presence of the human leukocyte antigen HLA-DRB1 locus is associated with production of anti-cyclic citrullinated peptide antibodies (anti-CCP Abs) and to what extent they are associated with increased susceptibility to and severity of rheumatoid arthritis (RA) in Egyptian patients. Twenty-nine RA patients gave informed consent to participate in a case-control study that was approved by the Ain Shams University Medical Ethics Committee. RA disease activity and severity were determined using the simplified disease activity index and Larsen scores, respectively. We used a wide scale national study on the pattern of HLA typing in normal Egyptians as a control study. Anti-CCP Abs and HLA-DRB1 typing were determined for all subjects. The alleles most strongly associated with RA were HLA-DRB1 [*01 , *04 and *06] (41.4%). RA patients with serum anti-CCP Ab titers above 60 U/mL had a significantly higher frequency of HLA-DRB1*01 (58.3%) and HLA-DRB1*04 alleles (83.3%). Significant positive correlations were found between serum and synovial anti-CCP Ab titer, RA disease activity, and severity (r = 0.87, 0.66 and 0.63, respectively; P < 0.05). HLA-DRB1 SE+ alleles [*01 and *04] were highly expressed among Egyptian RA patients. The presence of these alleles was associated with higher anti-CCP Ab titer, active and severe RA disease. Early determination of HLA-DRB1 SE+ alleles and serum anti-CCP Ab could facilitate the prediction of the clinical course and prognosis of RA when first evaluated leading to better disease control.

Effect of the human leukocyte antigen HLA-DRB1 and anti-cyclic citrullinated peptide on the outcome of rheumatoid arthritis patients

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H.M. Farouk

2009-09-01

Full Text Available Our objective was to determine whether the presence of the human leukocyte antigen HLA-DRB1 locus is associated with production of anti-cyclic citrullinated peptide antibodies (anti-CCP Abs and to what extent they are associated with increased susceptibility to and severity of rheumatoid arthritis (RA in Egyptian patients. Twenty-nine RA patients gave informed consent to participate in a case-control study that was approved by the Ain Shams University Medical Ethics Committee. RA disease activity and severity were determined using the simplified disease activity index and Larsen scores, respectively. We used a wide scale national study on the pattern of HLA typing in normal Egyptians as a control study. Anti-CCP Abs and HLA-DRB1 typing were determined for all subjects. The alleles most strongly associated with RA were HLA-DRB1 [*01 , *04 and *06] (41.4%. RA patients with serum anti-CCP Ab titers above 60 U/mL had a significantly higher frequency of HLA-DRB1*01 (58.3% and HLA-DRB1*04 alleles (83.3%. Significant positive correlations were found between serum and synovial anti-CCP Ab titer, RA disease activity, and severity (r = 0.87, 0.66 and 0.63, respectively; P < 0.05. HLA-DRB1 SE+ alleles [*01 and *04] were highly expressed among Egyptian RA patients. The presence of these alleles was associated with higher anti-CCP Ab titer, active and severe RA disease. Early determination of HLA-DRB1 SE+ alleles and serum anti-CCP Ab could facilitate the prediction of the clinical course and prognosis of RA when first evaluated leading to better disease control.

In-111-labeled leukocyte scintigraphy in postoperative joint infection

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Ogawa, Yoji; Uetani, Masataka; Aziz, A.; Hayashi, Kuniaki

2000-01-01

To evaluate the role of In-111-labeled leukocyte scintigraphy in the patients with suspected postoperative joint infection, 41 scintigraphic examinations were performed in 24 patients. Scintigrams were interpreted by the degree of accumulation of labeled leukocytes, and were classified into 3 groups: positive, intermediate, and negative. In the cases of positive leukocyte scans, definite diagnosis of infection was made in all cases except one. In the cases of negative scans, there was no evidence of infection. In 13 cases, leukocyte scintigrams were interpreted in conjunction with bone scintigrams. Definite diagnosis of infection was made in all of the cases with positive combined leukocyte/bone scan, and there was no evidence of infection in cases with negative combined leukocyte/bone scan. This study demonstrates that In-111-labeled leukocyte scintigraphy is a useful method in diagnosis of postoperative joint infection, and accuracy of the examination improves when combined with bone scintigraphy. (author)

Genomic signatures characterize leukocyte infiltration in myositis muscles

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2012-01-01

Background Leukocyte infiltration plays an important role in the pathogenesis and progression of myositis, and is highly associated with disease severity. Currently, there is a lack of: efficacious therapies for myositis; understanding of the molecular features important for disease pathogenesis; and potential molecular biomarkers for characterizing inflammatory myopathies to aid in clinical development. Methods In this study, we developed a simple model and predicted that 1) leukocyte-specific transcripts (including both protein-coding transcripts and microRNAs) should be coherently overexpressed in myositis muscle and 2) the level of over-expression of these transcripts should be correlated with leukocyte infiltration. We applied this model to assess immune cell infiltration in myositis by examining mRNA and microRNA (miRNA) expression profiles in muscle biopsies from 31 myositis patients and 5 normal controls. Results Several gene signatures, including a leukocyte index, type 1 interferon (IFN), MHC class I, and immunoglobulin signature, were developed to characterize myositis patients at the molecular level. The leukocyte index, consisting of genes predominantly associated with immune function, displayed strong concordance with pathological assessment of immune cell infiltration. This leukocyte index was subsequently utilized to differentiate transcriptional changes due to leukocyte infiltration from other alterations in myositis muscle. Results from this differentiation revealed biologically relevant differences in the relationship between the type 1 IFN pathway, miR-146a, and leukocyte infiltration within various myositis subtypes. Conclusions Results indicate that a likely interaction between miR-146a expression and the type 1 IFN pathway is confounded by the level of leukocyte infiltration into muscle tissue. Although the role of miR-146a in myositis remains uncertain, our results highlight the potential benefit of deconvoluting the source of

Immunohistochemical detection of SWC3, CD2, CD3, CD4 and CD8 antigens in paraformaldehyde fixed and paraffin embedded porcine lymphoid tissue

DEFF Research Database (Denmark)

Tingstedt, Jens Erik; Tornehave, Ditte; Lind, Peter

2003-01-01

Identification of the different cell types of the immune system is important for in situ studies on the pathogenesis of infectious diseases in various animals, including the pig. Unfortunately, many monoclonal anti-leukocyte antibodies are only useful for staining frozen tissue sections with inhe......Identification of the different cell types of the immune system is important for in situ studies on the pathogenesis of infectious diseases in various animals, including the pig. Unfortunately, many monoclonal anti-leukocyte antibodies are only useful for staining frozen tissue sections...... with inherent poor tissue morphology, and are not readily adapted to formaldehyde fixed and paraffin embedded tissue with well preserved morphology. Seven well characterised monoclonal antibodies against porcine leukocyte antigens were tested on neutral buffered paraformaldehyde fixed and paraffin embedded...

ImmunoChip study implicates antigen presentation to T cells in narcolepsy.

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Juliette Faraco

Full Text Available Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip. Three loci located outside the Human Leukocyte Antigen (HLA region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@, variants in two additional narcolepsy loci, Cathepsin H (CTSH and Tumor necrosis factor (ligand superfamily member 4 (TNFSF4, also called OX40L, attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells in the pathophysiology of this autoimmune disease.

Radioisotopic 51Cr-leukocyte adherence inhibition (LAI) assay. I

International Nuclear Information System (INIS)

Tsang, P.H.; Tangnavarad, K.; Lesnick, G.; Holland, J.F.; Bekesi, J.G.; Perloff, M.

1980-01-01

A simplified radioisotopic leukocyte adherence inhibition assay ( 51 Cr-LAI assay) was used to determine tumor-directed immune responses in patients with cancer of the breast. Essential steps in development of this assay are the standardization of conditions for optimal 51 Cr uptake by peripheral blood lymphocytes (PBL) and the inclusion of autologous or normal AB serum in the incubation media. A dextrose salt mixture (GNK) was found to enhance intracellular uptake of 51 Cr significantly (8-fold) without affecting viability of the cells or without causing selective loss of lymphocyte subpopulations. The presence of 10% autologous or normal AB serum prevented non-specific LAI responses to unrelated tumor antigens. Experimental results are presented and it is seen that this short term (4 h) 51 Cr-LAI assay provides reproducible and specific results analogous to those using tube-LAI assay. The test has the advantages of being accurate, sensitive and free from technical bias. (Auth.)

Detection of intracellular canine distemper virus antigen in mink inoculated with an attenuated or a virulent strain of canine distemper virus.

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Blixenkrone-Møller, M

1989-09-01

Using an indirect immunofluorescence technique, the distribution of viral antigen in various tissues and blood mononuclear leukocytes was studied in wild mink, either vaccinated with an attenuated vaccine strain of canine distemper virus (CDV) or experimentally inoculated with the virulent Snyder-Hill strain of CDV. Viral antigen was detected in cells of the lymphoid system 6 to 12 days after vaccination. From 2 to 3 days after inoculation with the virulent strain, CDV antigen was demonstrated in cells of the lymphoid system and, during the incubation period, the antigen had spread to the epithelia and brain at days 6 and 12, respectively. In clinical cases of acute fatal canine distemper, the viral antigen was detected in a wide variety of tissues, including the cells of the lymphoid system, epithelial cells of skin, mucous membranes, lung, kidney, and cells of the CNS. The diagnostic importance of CDV antigen detection is discussed on the basis of these findings.

Human Leukocyte Antigen (HLA and Immune Regulation: How Do Classical and Non-Classical HLA Alleles Modulate Immune Response to Human Immunodeficiency Virus and Hepatitis C Virus Infections?

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Nicole B. Crux

2017-07-01

Full Text Available The genetic factors associated with susceptibility or resistance to viral infections are likely to involve a sophisticated array of immune response. These genetic elements may modulate other biological factors that account for significant influence on the gene expression and/or protein function in the host. Among them, the role of the major histocompatibility complex in viral pathogenesis in particular human immunodeficiency virus (HIV and hepatitis C virus (HCV, is very well documented. We, recently, added a novel insight into the field by identifying the molecular mechanism associated with the protective role of human leukocyte antigen (HLA-B27/B57 CD8+ T cells in the context of HIV-1 infection and why these alleles act as a double-edged sword protecting against viral infections but predisposing the host to autoimmune diseases. The focus of this review will be reexamining the role of classical and non-classical HLA alleles, including class Ia (HLA-A, -B, -C, class Ib (HLA-E, -F, -G, -H, and class II (HLA-DR, -DQ, -DM, and -DP in immune regulation and viral pathogenesis (e.g., HIV and HCV. To our knowledge, this is the very first review of its kind to comprehensively analyze the role of these molecules in immune regulation associated with chronic viral infections.

Human peripheral blood monocytes display surface antigens recognized by monoclonal antinuclear antibodies

International Nuclear Information System (INIS)

Holers, V.M.; Kotzin, B.L.

1985-01-01

The authors used monoclonal anti-nuclear autoantibodies and indirect immunofluorescence to examine normal human peripheral blood mononuclear leukocytes for the presence of cell surface nuclear antigens. Only one monoclonal anti-histone antibody (MH-2) was found to bind to freshly isolated PBL, staining approximately 10% of large cells. However, after cells were placed into culture for 16-24 h, a high percentage (up to 60%) of large-sized cells were recognized by an anti-DNA (BWD-1) and several different antihistone monoclonal antibodies (BWH-1, MH-1, and MH-2). These antibodies recognize separate antigenic determinants on chromatin and histones extracted from chromatin. The histone antigen-positive cells were viable, and the monoclonal antibodies could be shown to be binding to the cell surface and not to the nucleus. Using monoclonal antibodies specific for monocytes and T cells, and complement-mediated cytotoxicity, the cells bearing histone antigens were shown to be primarily monocytes. The appearance of histone and DNA antigen-positive cells was nearly completely inhibited by the addition of low concentrations of cycloheximide at initiation of the cultures. In contrast, little effect on the percentage of positive cells was detected if cells were exposed to high doses of gamma irradiation before culture. These data further support the existence of cell surface nuclear antigens on selected cell subsets, which may provide insight into the immunopathogenesis of systemic lupus erythematosus and related autoimmune diseases

Indium-111 leukocyte imaging in patients with rheumatoid arthritis

International Nuclear Information System (INIS)

Uno, K.; Matsui, N.; Nohira, K.

1986-01-01

This study evaluates the usefulness of labeled leukocyte imaging in patients with rheumatoid arthritis. In 33 patients, the incidence of pain and swelling in 66 wrist joints and 66 knee joints was compared with the accumulation of [ 111 In]leukocytes. No accumulation of [ 111 In]leukocytes was seen in any of the patients' wrists (0/12) or knee joints (0/14) when both pain and swelling were absent. In contrast, 93% (25/27) of wrist joints and 80% (24/30) of knee joints with both pain and swelling were positive by [ 111 In]leukocyte scintigraphy. There was little correlation between the stage of the disease, as determined by radiography, and [ 111 In]leukocyte accumulation. This study suggests that [ 111 In]leukocyte imaging may be a reliable procedure for monitoring the activity of rheumatoid arthritis, especially for confirming the lack of an ongoing inflammatory response

Inflammation Scan Using {sup 99m}Tc-HMPAO Labelled Leukocytes

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Yang, Woo Jin; Chung, Soo Kyo; Shinn, Kyung Sub; Bahk, Yong Whee; Kim, Hoon Kyo [Catholic University College of Medicine, Seoul (Korea, Republic of)

1989-07-15

Inflammation scan using radiolabelled leukocytes has high sensitivity and specificity. Several methods for labelling leukocytes have been evaluated using P-32 diisopropyl fluorophosphate (DFP -32), H-3 thymidine, Cr-51 chromate, Ga-67 citrate and {sup 99m}Tc-sulfur colloid. In-111-oxine has proved so far to be the most reliable agent for labelling leukocytes. In-111-oxine is, however, expensive, not easily available when needed, and its radiation dose to leukocytes is relatively high. Moreover, resolution of the resultant image is relatively poor. {sup 99m}Tc is still the agent of choice because of, as compared with the indium, its favorable physical characteristics, lower cost and availability. Now the technique for labelling the leukocytes with technetium is successfully obtained using the lipophilic HMPAO with higher efficiency for granulocytes than for other cells. With this technique it is possible to label leukocytes in plans to improve the viability of the leukocytes. Inflammation scan using {sup 99m}Tc-HMPAO has been evaluated in several laboratories, and difference in methods for separation and labelling accounts for difference in efficiency, viability and biodistribution of the labelled leukocytes. We performed inflammation scan using leukocytes labelled with {sup 99m}Tc-HMPAO in three dogs 24 hours after inoculation of live E. Coli and S. Aureus in their right abdominal wall. We separated mixed leukocytes by simple sedimentation using 6% hetastarch (HES) and labelled the leukocytes with {sup 99m}Tc-HMPAO in 20% cell free plasma diluted with phosphate buffer solution. Uptake was high in the liver and spleen but is was minimal in the lungs on whole body scan. Kidneys and intestine showed minimal activity although it was high in the urinary bladder. Uptake of labelled leukocytes in the inflammation site was definite on 2 hour-postinjection scan and abscess was clearly delineated on 24 hour-delayed scan with high target-to-nontarget ratio. 4). Inflammation

Synthesis of endogenous pyrogen by rabbit leukocytes.

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Moore, D M; Murphy, P A; Chesney, P J; Wood, W B

1973-05-01

Rabbit ieukocytes from peritoneal exudates and from blood were stimulated to form leukocyte pyrogen in the presence of radiolabeled amino acids. The stimuli used were endotoxin, phagocytosis, and tuberculin. The crude leukocyte pyrogen samples were purified; pyrogen from exudate cells was rendered homogeneous; pyrogen from blood cells was still contaminated with other proteins. All the purified pyrogens were radioactive; and for all it was shown that radioactivity and pyrogenic activity coincided on electrophoresis at pH 3.5 and pH 9 in acrylamide and on isoelectric focusing in acrylamide. Furthermore, pyrogens obtained from exudate cells stimulated in different ways, or from blood cells and exudate cells stimulated with endotoxin, appeared to be identical. These results suggest that leukocyte pyrogen was synthesized de novo from amino acid precursors and that leukocytes made the same pyrogen whatever the stimulus used to activate them.

Use of flow cytometry to identify monoclonal antibodies that recognize conserved epitopes on orthologous leukocyte differentiation antigens in goats, llamas, and rabbits

Czech Academy of Sciences Publication Activity Database

Davis, W. C.; Drbal, Karel; El-Aziz, A.; Mosaad, A.E.; Elbagory, A.R.M.; TIbary, A.; Barrington, G.M.; Park, Y.H.; Hamilton, M.J.

2007-01-01

Roč. 119, 1-2 (2007), s. 123-130 ISSN 0165-2427 Institutional research plan: CEZ:AV0Z50520514 Keywords : flow cytometry * monoclonal antibodies * leukocytes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.957, year: 2007

Advances in RNAi therapeutic delivery to leukocytes using lipid nanoparticles.

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Ramishetti, Srinivas; Landesman-Milo, Dalit; Peer, Dan

2016-11-01

Small interfering RNAs (siRNAs) therapeutics has advanced into clinical trials for liver diseases and solid tumors, but remain a challenge for manipulating leukocytes fate due to lack of specificity and safety issues. Leukocytes ingest pathogens and defend the body through a complex network. They are also involved in the pathogeneses of inflammation, viral infection, autoimmunity and cancers. Modulating gene expression in leukocytes using siRNAs holds great promise to treat leukocyte-mediated diseases. Leukocytes are notoriously hard to transduce with siRNAs and are spread throughout the body often located deep in tissues, therefore developing an efficient systemic delivery strategy is still a challenge. Here, we discuss recent advances in siRNA delivery to leukocyte subsets such as macrophages, monocytes, dendritic cells and lymphocytes. We focus mainly on lipid-based nanoparticles (LNPs) comprised of new generation of ionizable lipids and their ability to deliver siRNA to primary or malignant leukocytes in a targeted manner. Special emphasis is made on LNPs targeted to subsets of leukocytes and we detail a novel microfluidic mixing technology that could aid in changing the landscape of process development of LNPs from a lab tool to a potential novel therapeutic modality.

A Measure of Proficiency or Short-Term Memory? Validation of an Elicited Imitation Test for SLA Research

Science.gov (United States)

Kim, Youjin; Tracy-Ventura, Nicole; Jung, Yeonjoo

2016-01-01

Elicited imitation requires listeners to listen and repeat sentences as accurately as possible. In second language acquisition (SLA) research it has been used for a variety of purposes. Recently, versions of the same elicited imitation test (EIT) have been created in 6 languages with the purpose of measuring second language proficiency (Ortega…

Electrophoretic detection of protein p53 in human leukocytes

International Nuclear Information System (INIS)

Paponov, V.D.; Kupsik, E.G.; Shcheglova, E.G.; Yarullin, N.N.

1986-01-01

The authors have found an acid-soluble protein with mol. wt. of about 53 kD in peripheral blood leukocytes of persons with Down's syndrome. It was present in different quantities in all 20 patients tested, but was virtually not discovered in 12 healthy blood donors. This paper determines the possible identity of this protein with protein p53 from mouse ascites carcinoma by comparing their electrophoretic mobilities, because the accuracy of electrophoretic determination of the molecular weight of proteins is not sufficient to identify them. The paper also describes experiments to detect a protein with electrophoretic mobility identical with that of a protein in the leukocytes of patients with Down's syndrome in leukocytes of patients with leukemia. To discover if protein p53 is involved in cell proliferation, the protein composition of leukocytes from healthy blood donors, cultured in the presence and absence of phytohemagglutinin (PHA), was compared. Increased incorporation of H 3-thymidine by leukocytes of patients with Down's syndrome is explained by the presence of a population of immature leukocytes actively synthesizing DNA in the peripheral blood of these patients, and this can also explain the presence of protein p53 in the leukocytes of these patients

The Effect of Hemiscorpius lepturus (Scorpionida: Hemiscorpiidae Venom on Leukocytes and the Leukocyte Subgroups in Peripheral Blood of Rat

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Mehri Ghafourian

2016-01-01

Full Text Available Background: The aim of this study was to investigate the effect of Hemiscorpius lepturus venom on leukocytes and the leukocyte subgroups in peripheral blood of rat.Methods: In this experimental study, sixty N-Mari rats were divided into three groups of 20 rats. Then the rats in each group were divided into four subgroups based on the blood sampling time that was 2, 6, 24 and 48 hours after the venom injection, respectively. The control group did not receive anything, however, the first and the second ex­perimental groups received 0.1 and 0.01mg/kg of venom, subcutaneously. In accordance with a designated four sam­pling times, the blood sampling was carried out in three groups. After RBC lysis, the leukocytes and leukocyte sub­populations were determined and counted using appropriate hematological standard methods.Results: The leukocyte and the neutrophil count at two (P<0.05, six (P<0.01 and 24 (P<0.05 hours after the venom injection showed a significant decline compared with the control group, this decrease was significant at the dose of 0.1 mg/kg until 48 hours after the venom injection (P<0.05. The lymphocyte count showed a significant decline throughout the all hours of the experiment, compared with the control group (P<0.05.Conclusion: Leukocytes are probably affected by the cytotoxicity effect of the H. lepturus venom in a dose-dependent manner. This could be a wakeup call for the medical staff to perform quick and accurate treatment in the least time possible.

Influence of Human Leukocyte Antigen (HLA) Alleles and Killer Cell Immunoglobulin-Like Receptors (KIR) Types on Heparin-Induced Thrombocytopenia (HIT).

Science.gov (United States)

Karnes, Jason H; Shaffer, Christian M; Cronin, Robert; Bastarache, Lisa; Gaudieri, Silvana; James, Ian; Pavlos, Rebecca; Steiner, Heidi E; Mosley, Jonathan D; Mallal, Simon; Denny, Joshua C; Phillips, Elizabeth J; Roden, Dan M

2017-09-01

Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT. HIT cases and heparin-exposed controls were identified in BioVU, an electronic health record coupled to a DNA biobank. HLA sequencing and KIR type imputation using Illumina OMNI-Quad data were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR interactions using conditional logistic regressions were determined in the overall population and by race/ethnicity. Analysis was restricted to KIR types and HLA alleles with a frequency greater than 0.01. The p values for HLA and KIR association were corrected by using a false discovery rate qHIT cases and 350 matched controls were identified. No statistical differences in baseline characteristics were observed between cases and controls. The HLA-DRB3*01:01 allele was significantly associated with HIT in the overall population (odds ratio 2.81 [1.57-5.02], p=2.1×10 -4 , q=0.02) and in individuals with European ancestry, independent of other alleles. No KIR types were associated with HIT, although a significant interaction was observed between KIR2DS5 and the HLA-C1 KIR binding group (p=0.03). The HLA-DRB3*01:01 allele was identified as a potential risk factor for HIT. This class II HLA gene and allele represent biologically plausible candidates for influencing HIT pathogenesis. We found limited evidence of the role of KIR types in HIT pathogenesis. Replication and further study of the HLA-DRB3*01:01 association is necessary. © 2017 Pharmacotherapy Publications, Inc.

Leukocyte scintigraphy with 99mTc-exametazime-labeled leukocytes is not useful for follow-up of systemic vasculitis

International Nuclear Information System (INIS)

Staudenherz, A.; Kletter, K.; Deicher, R.; Haas, M.; Hoerl, W.H.; Jilma, B.; Becherer, A.; Dudczak, R.

2002-01-01

Background: The prognosis of systemic vasculitis, for instance Wegener's granulomatosis (WG), was greatly improved by the introduction of immunosuppressive treatment. However, relapses are frequent and predictors are scarce. 111 In-leukocytes have been found to indicate unknown manifestations of WG and to predict later relapse. We prospectively investigated the value of 99m Tc-Exametazime ( 99m Tc-HMPAO)-labeled leukocytes with regard to specific patterns and for their usefulness in the follow-up of patients with WG. Methods: The vasculitis group consisted of 8 patients with WG and 2 with idiopathic necrotizing glomerulonephritis (ING). Seven patients with different inflammatory diseases served as controls. Leukocyte labeling with 99m Tc-HMPAO was done using a slightly modified Hammersmith protocol. Cell viability after labeling was verified in vivo by the exclusion of early lung and splenic uptake and in vitro by means of propidium iodide and FACS analysis. Static gamma camera images from the head, chest, abdomen, and pelvis were obtained up to 18 hours after injection of approximately 300 MBq 99m Tc-HMPAO-labeled leukocytes. Scintigrams were analyzed visually; for semiquantitative analysis ROIs were drawn over the nasal region, the right lung, kidneys, and liver. Results: Increased nasal leukocyte accumulation was found in 7/8 patients with WG and in 2/2 patients with ING. Of 2 patients who had a relapse 6 months later, one presented with, and one without nasal uptake. The kidney/liver ratio was higher in controls (0.24 ± 0.07 vs. 0.37 ± 0.11, p 99m Tc-HMPAO leukocyte scintigraphy failed to indicate or exclude a later relapse and is therefore not suitable as a diagnostic tool in the management of patients with systemic vasculitis. (author)

Leukocyte scintigraphy with 99mTc-exametazime-labeled leukocytes is not useful for follow-up of systemic vasculitis

International Nuclear Information System (INIS)

Becherer, A.; Dudczak, R.; Deicher, R.; Haas, M.; Hoerl, W.H.; Jilma, B.; Staudenherz, A.; Kletter, K.

2002-01-01

The prognosis of systemic vasculitis, for instance Wegener's granulomatosis (WG), was greatly improved by the introduction of immunosuppressive treatment. However, relapses are frequent and predictors are scarce. 111 In-leukocytes have been found to indicate unknown manifestations of WG and to predict later relapse. We prospectively investigated the value of 99m Tc-Exametazime ( 99m Tc-HMPAO)-labeled leukocytes with regard to specific patterns and for their usefulness in the follow-up of patients with WG. The vasculitis group consisted of 8 patients with WG and 2 with idiopathic necrotizing glomerulonephritis (ING). Seven patients with different inflammatory diseases served as controls. Leukocyte labeling with 99m Tc-HMPAO was done using a slightly modified Hammersmith protocol. Cell viability after labeling was verified in vivo by the exclusion of early lung and splenic uptake and in vitro by means of propidium iodide and FACS analysis. Static gamma camera images from the head, chest, abdomen, and pelvis were obtained up to 18 hours after injection of approximately 300 MBq 99m Tc-HMPAO-labeled leukocytes. Scintigrams were analyzed visually; for semiquantitative analysis ROls were drawn over the nasal region, the right lung, kidneys, and liver. Increased nasal leukocyte accumulation was found in 7/8 patients with WG and in 2/2 patients with ING. Of 2 patients who had a relapse 6 months later, one presented with, and one without nasal uptake. The kidney/liver ratio was higher in controls (0.24 ± 0.07 vs. 0.37 ± 0.11, p 99m Tc-HMPAO leukocyte scintigraphy failed to indicate or exclude a later relapse and is therefore not suitable as a diagnostic tool in the management of patients with systemic vasculitis. (author)

21 CFR 864.7675 - Leukocyte peroxidase test.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Leukocyte peroxidase test. 864.7675 Section 864.7675 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7675 Leukocyte...

Impact of cyclophosphamide dose of conditioning on the outcome of allogeneic hematopoietic stem cell transplantation for aplastic anemia from human leukocyte antigen-identical sibling.

Science.gov (United States)

Mori, Takehiko; Koh, Hideo; Onishi, Yasushi; Kako, Shinichi; Onizuka, Makoto; Kanamori, Heiwa; Ozawa, Yukiyasu; Kato, Chiaki; Iida, Hiroatsu; Suzuki, Ritsuro; Ichinohe, Tatsuo; Kanda, Yoshinobu; Maeda, Tetsuo; Nakao, Shinji; Yamazaki, Hirohito

2016-04-01

The standard conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia from a human leukocyte antigen (HLA)-identical sibling has been high-dose cyclophosphamide (CY 200 mg/kg). In the present study, results for 203 patients with aplastic anemia aged 16 years or older who underwent allogeneic HSCT from HLA-identical siblings were retrospectively analyzed using the registry database of Japan Society for Hematopoietic Cell Transplantation. Conditioning regimens were defined as a (1) high-dose CY (200 mg/kg or greater)-based (n = 117); (2) reduced-dose CY (100 mg/kg or greater, but less than 200 mg/kg)-based (n = 38); and (3) low-dose CY (less than 100 mg/kg)-based (n = 48) regimen. Patient age and the proportion of patients receiving fludarabine were significantly higher in the reduced- and low-dose CY groups than the high-dose CY group. Engraftment was comparable among the groups. Five-year overall survival (OS) tended to be higher in the low-dose CY group [93.0 % (95 % CI 85.1-100.0 %)] than the high-dose CY [84.2 % (95 % CI 77.1-91.3 %)] or reduced-dose CY groups [83.8 % (95 % CI 71.8-95.8 %); P = 0.214]. Age-adjusted OS was higher in the low-dose CY group than the high- and reduced-dose CY groups with borderline significance (P = 0.067). These results suggest that CY dose can safely be reduced without increasing graft rejection by adding fludarabine in allogeneic HSCT for aplastic anemia from an HLA-identical sibling.

First systematic experience of preimplantation genetic diagnosis for single-gene disorders, and/or preimplantation human leukocyte antigen typing, combined with 24-chromosome aneuploidy testing.

Science.gov (United States)

Rechitsky, Svetlana; Pakhalchuk, Tatiana; San Ramos, Geraldine; Goodman, Adam; Zlatopolsky, Zev; Kuliev, Anver

2015-02-01

To study the feasibility, accuracy, and reproductive outcome of 24-chromosome aneuploidy testing (24-AT), combined with preimplantation genetic diagnosis (PGD) for single-gene disorders (SGDs) or human leukocyte antigen (HLA) typing in the same biopsy sample. Retrospective study. Preimplantation genetic diagnosis center. A total of 238 PGD patients, average age 36.8 years, for whom 317 combined PGD cycles were performed, involving 105 different conditions, with or without HLA typing. Whole-genome amplification product, obtained in 24-AT, was used for PGD and/or HLA typing in the same blastomere or blastocyst biopsy samples. Proportion of the embryos suitable for transfer detected in these blastomere or blastocyst samples, and the resulting pregnancy and spontaneous abortion rates. Embryos suitable for transfer were detected in 42% blastocyst and 25.1% blastomere samples, with a total of 280 unaffected, HLA-matched euploid embryos detected for transfer in 212 cycles (1.3 embryos per transfer), resulting in 145 (68.4%) unaffected pregnancies and birth of 149 healthy, HLA-matched children. This outcome is significantly different from that of our 2,064 PGD cycle series without concomitant 24-AT, including improved pregnancy (68.4% vs. 45.4%) and 3-fold spontaneous abortion reduction (5.5% vs. 15%) rates. The introduced combined approach is a potential universal PGD test, which in addition to achieving extremely high diagnostic accuracy, significantly improves reproductive outcomes of PGD for SGDs and HLA typing in patients of advanced reproductive age. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Scintigraphy with /sup 111/In-labeled leukocytes. Simplified procedure for labeling

Energy Technology Data Exchange (ETDEWEB)

Terada, Hitoshi; Shiire, Yasushi; Koizumi, Kiyoshi; Aburano, Tamio; Tonami, Norihisa; Hisada, Kin-ichi

1987-12-01

To utilize /sup 111/In leukocytes in a routine work, simplified procedure for sterile leukocytes preparation and labeling with water soluble oxine sulfate was performed. Viability and chemotaxis of leukocytes were maintained during separation and labeling. Chelated rate of /sup 111/In with oxine sulfate was 93.5 %. Labeling efficiency of /sup 111/In leukocytes was 93.8 %. Obvious blood pool images due to remaind erythrocytes were not observed. /sup 111/In labeled leukocytes showed good migration into inflammatory focci.

On the Danger of Exogenous Theory in CA-for-SLA: A Response to Hellermann and Cole (2009)

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Hauser, Eric

2011-01-01

Within the growing body of work that is sometimes labeled CA-for-SLA, there is a need for more research with longitudinal data. Hellermann and Cole (2009) provide a valuable contribution in this area. However, in doing so, they also make use of an exogenous theory of learning, situated learning theory (Lave and Wenger 1991), and its associated…

Human leukocyte antigen typing using buccal swabs as accurate and non-invasive substitute for venipuncture in children at risk for celiac disease.

Science.gov (United States)

Adriaanse, Marlou P M; Vreugdenhil, Anita C E; Vastmans, Véronique; Groeneveld, Lisette; Molenbroeck, Stefan; Schott, Dina A; Voorter, Christina E M; Tilanus, Marcel G J

2016-10-01

Human leukocyte antigen (HLA) typing is an important step in the diagnostic algorithm for celiac disease (CD) and is also used for screening purposes. Collection of blood is invasive and accompanied with emotional impact especially in children. Genetic technological progress now enables HLA typing from buccal cell samples. This study evaluated the reliability and feasibility of HLA typing for CD-associated HLA polymorphisms using buccal swabs as routine test in high-risk individuals. Blood and buccal swabs of 77 children and adolescents with high risk for CD were prospectively collected in this cohort study. Buccal swab collection was performed either by the investigator at the outpatient clinic or by the patient or its parents at home. To evaluate the possibility of self-administration, three families performed the test at home. DNA was extracted using an adapted QIAamp method. Quantity, quality, and purity of DNA were recorded. HLA-DRB1, HLA-DQA1, and HLA-DQB1 typing was examined on buccal cell-derived and blood-derived DNA at low and, if necessary, high resolution level, using sequence-specific oligonucleotide and sequence-based typing, respectively. DNA isolation using buccal swabs yielded a good quality and sufficient quantity of DNA to perform HLA-DQ typing in all individuals. HLA typing results on buccal cell-derived DNA were identical to typing on blood-derived DNA, also for the self-administered samples. Introduction of the buccal swab test for HLA typing of CD risk in routine diagnostics can omit the current venipuncture and enables self-administration at home. Therefore, the buccal swab test is beneficial for individuals with a clinical suspicion for CD, as well as for screening purposes in high-risk populations. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Radio (111In) capillary tube leukocyte adherence inhibition assay for the detection of specific tumor-associated immunity

International Nuclear Information System (INIS)

Peng, R.; Myers, W.L.

1984-01-01

The specific tumor-associated immune response of C3H/HeJ mice was determined at various times after subcutaneous injection with a transplantable mammary adenocarcinoma (H2712) using a radio ( 111 In) leukocyte adherence inhibition (LAI) assay carried out in capillary tubes. Solubilized tumor-associated antigen prepared by a single phase 1-butanol extraction of the specific tumor and other transplantable tumors of different histological origin were used in the evaluation of LAI reactivity. The assay was found to be capable of detecting a significant antitumor response before the subcutaneous tumors became detectable by palpation. The response remained significant until the tumors were greater than 20 mm in diameter

An agent-based model of leukocyte transendothelial migration during atherogenesis.

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Rita Bhui

2017-05-01

Full Text Available A vast amount of work has been dedicated to the effects of hemodynamics and cytokines on leukocyte adhesion and trans-endothelial migration (TEM and subsequent accumulation of leukocyte-derived foam cells in the artery wall. However, a comprehensive mechanobiological model to capture these spatiotemporal events and predict the growth and remodeling of an atherosclerotic artery is still lacking. Here, we present a multiscale model of leukocyte TEM and plaque evolution in the left anterior descending (LAD coronary artery. The approach integrates cellular behaviors via agent-based modeling (ABM and hemodynamic effects via computational fluid dynamics (CFD. In this computational framework, the ABM implements the diffusion kinetics of key biological proteins, namely Low Density Lipoprotein (LDL, Tissue Necrosis Factor alpha (TNF-α, Interlukin-10 (IL-10 and Interlukin-1 beta (IL-1β, to predict chemotactic driven leukocyte migration into and within the artery wall. The ABM also considers wall shear stress (WSS dependent leukocyte TEM and compensatory arterial remodeling obeying Glagov's phenomenon. Interestingly, using fully developed steady blood flow does not result in a representative number of leukocyte TEM as compared to pulsatile flow, whereas passing WSS at peak systole of the pulsatile flow waveform does. Moreover, using the model, we have found leukocyte TEM increases monotonically with decreases in luminal volume. At critical plaque shapes the WSS changes rapidly resulting in sudden increases in leukocyte TEM suggesting lumen volumes that will give rise to rapid plaque growth rates if left untreated. Overall this multi-scale and multi-physics approach appropriately captures and integrates the spatiotemporal events occurring at the cellular level in order to predict leukocyte transmigration and plaque evolution.

Penetration of equine leukocytes by merozoites of Sarcocystis neurona.

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Lindsay, David S; Mitchell, Sheila M; Yang, Jibing; Dubey, J P; Gogal, Robert M; Witonsky, Sharon G

2006-06-15

Horses are considered accidental hosts for Sarcocystis neurona and they often develop severe neurological disease when infected with this parasite. Schizont stages develop in the central nervous system (CNS) and cause the neurological lesions associated with equine protozoal myeloencephalitis. The present study was done to examine the ability of S. neurona merozoites to penetrate and develop in equine peripheral blood leukocytes. These infected host cells might serve as a possible transport mechanism into the CNS. S. neurona merozoites penetrated equine leukocytes within 5 min of co-culture. Infected leukocytes were usually monocytes. Infected leukocytes were present up to the final day of examination at 3 days. Up to three merozoites were present in an infected monocyte. No development to schizont stages was observed. All stages observed were in the host cell cytoplasm. We postulate that S. neurona merozoites may cross the blood brain barrier hidden inside leukocytes. Once inside the CNS these merozoites can egress and invade additional cells and cause encephalitis.

Tenocytes, pro-inflammatory cytokines and leukocytes: a relationship?

OpenAIRE

Al-Sadi, Onays; Schulze-Tanzil, Gundula; Kohl, Benjamin; Lohan, Anke; Lemke, Marion; Ertel, Wolfgang; John, Thilo

2012-01-01

Leukocyte derived pro-inflammatory mediators could be involved in tendon healing and scar formation. Hence, the effect of autologous leukocytes (PBMCs, peripheral blood mononuclear cells and neutrophils) on primary rabbit Achilles tenocytes gene expression was tested in insert assisted co-cultures.

Human leukocyte antigen class I and II alleles and cervical adenocarcinoma: a pooled analysis of two epidemiologic studies

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Mahboobeh eSafaeian

2014-06-01

Full Text Available Associations between human leukocyte antigens (HLA alleles and cervical cancer are largely representative of squamous cell carcinoma (SCC, the major histologic subtype. We evaluated the association between HLA class I (A, B, and C and class II (DRB1 and DQB1 loci and risk of cervical adenocarcinoma (ADC, a less common but aggressive histologic subtype.We pooled data from the Eastern and Western US cervical cancer studies, and evaluated the association between individual alleles and allele combinations and ADC (n=630 ADC; n=775 controls. Risk estimates were calculated for 11 a priori (based on known associations with cervical cancer regardless of histologic type and 38 non a priori common alleles, as odds ratios (OR and 95% confidence intervals (CI, adjusted for age and study. In exploratory analysis, we compared the risk associations between subgroups with HPV16 or HPV18 DNA in ADC tumor tissues in the Western US study cases and controls. Three of the a priori alleles were significantly associated with decreased risk of ADC (DRB1*13:01 (OR=0.61; 95%CI:0.41-0.93, DRB1*13:02 (OR=0.49; 95%CI:0.31-0.77, and DQB1*06:03 (OR=0.64; 95%CI:0.42-0.95; one was associated with increased risk (B*07:02(OR=1.39; 95%CI:1.07-1.79. Among alleles not previously reported, DQB1*06:04 (OR=0.46; 95%CI: 0.27-0.78 was associated with decreased risk of ADC and C*07:02 (OR=1.41; 95%CI:1.09-1.81 was associated with increased risk. We did not observe a difference by histologic subtype. ADC was most strongly associated with increased risk with B*07:02/C*07:02 alleles (OR=1.33; 95%CI:1.01-1.76 and decreased risk with DRB1*13:02/DQB1*06:04 (OR=0.41; 95%CI:0.21-0.80. Results suggest that HLA allele associations with cervical ADC are similar to those for cervical SCC. An intriguing finding was the difference in risk associated with several alleles restricted to HPV16 or HPV18 related tumors, consistent with the hypothesis that HLA recognition is HPV type specific.

Characteristics of Rheumatoid Arthritis relative to HLA-DR in Saudi Arabia

International Nuclear Information System (INIS)

Al-Arfaj, Abdurhman S.

2001-01-01

The objective was to determine the clinical characteristics of rheumatoid arthritis in Saudi Arabia in relation to human leukocyte antigen type. A group of 91 rheumatoid arthritis patients, 72 females and 19 males were studied for the various clinical, laboratory and radiological parameters along with human leukocyte antigen-DR phenotypes. Since human leukocyte antigen-DR10 was most commonly associated with rheumatoid arthritis in our population, we compared those patients with human leukocyte antigen-DR10 to those without. The comparison yielded differences in the presence of rheumatoid nodules, erosions, corticosteroid treatment, and joint involvement at presentation, hemoglobin levels, and white cell count. Only the last 3 parameters showed a statistical significance. Human leukocyte antigen type of Saudi patients with rheumatoid arthritis influenced the course of the disease but only to a limited extent. (author)

Clumping of labeled leukocyte suspension. A simple measure for avoiding it

International Nuclear Information System (INIS)

Goedemans, W.T.; Hardeman, M.R.; State Univ., Amsterdam

1988-01-01

Leukocytes in mixed suspensions can clump together, resulting in cell clusters which are responsible for false positive hot spots in lungs of patients, in the case of abscess localization studies using 111 In labeled leukocytes. Addition of extra ACD (acid-citrate-dextrose) in those labeled leukocyte suspensions prevented cell clumping and avoided occurrence of focal radioactivity accumulation in lungs. The acidification did not interfere in leukocyte migration under agar. (author)

On the Relationship Between Input and Interaction Psycholinguistic, Cognitive, and Ecological Perspectives in SLA

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Parisa Daftarifard

2010-09-01

Full Text Available Input is one of the most important elements in the process of second language acquisition (SLA. As Gass (1997 points out, second language learning simply cannot take place without input of some sort. Since then, specific issues have been actively debated in SLA on the nature of input and input processing, such as the amount of input that is necessary for language acquisition, various attributes of input and how they may facilitate or hinder acquisition, and instructional method that may enhance input. In this paper, four hypotheses and paradigms of input processing have been described. It is delineated that although the three paradigms of triggering, input hypothesis, and interaction hypothesis have been widely used and accepted, they lack the ability to account for the dynamic nature of language. Affordance, on the other hand, can account for such a nature of language.
Therefore, affordance replaces fixed-eye vision by mobile-eye vision; an active learner establishes relationships with and within the environment. The learner can directly perceive and act on the ambient language without having to route everything through a pre-existing mental apparatus of schemata and representation, while this is not true in the fixed-code theory. In the fixed-eye theory of communication it is assumed that ready-made messages are coded at one end, transmitted,
and then decoded in identical form at the other end. We need in its place a constructivist theory of message construction and interpretation.

Relationships between leukocytes and Hepatozoon spp. In green frogs, Rana clamitans.

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Shutler, Dave; Smith, Todd G; Robinson, Stephen R

2009-01-01

There are few published data on amphibian leukocyte profiles, and relationships between amphibian leukocytes and parasites are even less well known. Using counts from 35 pairs of blood smears taken 2 days apart, we tested for correlations between leukocyte proportions and infection intensities of Hepatozoon spp. (either Hepatozoon catesbianae or Hepatozoon clamatae) in green frogs (Rana clamitans). On average (SE), we counted 65.4 (1.7) lymphocytes, 14.0 (1.3) neutrophils, 19.3 (1.6) eosinophils, 0.9 (0.1) monocytes, and 0.4 (0.1) basophils per 100 leukocytes. All frogs harbored Hepatozoon spp. (median seven parasites per 100 leukocytes; range 1-250). Significant relationships were not observed between numbers of leukocytes and infection intensities of Hepatozoon spp. Among the possible explanations for these null results are that Hepatozoon spp. is benign, that Hepatozoon spp. is able to evade detection by the immune system, that Hepatozoon spp. is able to manipulate leukocyte investment, or that other unmeasured or undetected parasites were more important in affecting immune response.

Disintegrins: integrin selective ligands which activate integrin-coupled signaling and modulate leukocyte functions

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Barja-Fidalgo C.

2005-01-01

Full Text Available Extracellular matrix proteins and cell adhesion receptors (integrins play essential roles in the regulation of cell adhesion and migration. Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. Once leukocytes are guided to sites of infection, inflammation, or antigen presentation, integrins can participate in the initiation, maintenance, or termination of the immune and inflammatory responses. The modulation of neutrophil activation through integrin-mediated pathways is important in the homeostatic control of the resolution of inflammatory states. In addition, during recirculation, T lymphocyte movement through distinct microenvironments is mediated by integrins, which are critical for cell cycle, differentiation and gene expression. Disintegrins are a family of low-molecular weight, cysteine-rich peptides first identified in snake venom, usually containing an RGD (Arg-Gly-Asp motif, which confers the ability to selectively bind to integrins, inhibiting integrin-related functions in different cell systems. In this review we show that, depending on the cell type and the microenvironment, disintegrins are able to antagonize the effects of integrins or to act agonistically by activating integrin-mediated signaling. Disintegrins have proven useful as tools to improve the understanding of the molecular events regulated by integrin signaling in leukocytes and prototypes in order to design therapies able to interfere with integrin-mediated effects.

Dynamic properties of blood flow and leukocyte mobilization in infected flaps

International Nuclear Information System (INIS)

Feng, L.J.; Price, D.C.; Mathes, S.J.; Hohn, D.

1990-01-01

Two aspects of the inflammatory response to infection--blood flow alteration and leukocyte mobilization--are investigated in the canine model. The elevation of paired musculocutaneous (MC) and random pattern (RP) flaps allowed comparison of healing flaps with significant differences in blood flow (lower in random pattern flaps) and resistance to infection (greater in musculocutaneous flaps). Blood flow changes as determined by radioactive xenon washout were compared in normal skin and distal flap skin both after elevation and following bacterial inoculation. Simultaneous use of In-111 labeled leukocytes allowed determination of leukocyte mobilization and subsequent localization in response to flap infection. Blood flow significantly improved in the musculocutaneous flap in response to infection. Although total leukocyte mobilization in the random pattern flap was greater, the leukocytes in the musculocutaneous flap were localized around the site of bacterial inoculation within the dermis. Differences in the dynamic blood flow and leukocyte mobilization may, in part, explain the greater reliability of musculocutaneous flaps when transposed in the presence of infection

Efficacy of standard (SLA) and modified sandblasted and acid-etched (SLActive) dental implants in promoting immediate and/or early occlusal loading protocols: a systematic review of prospective studies.

Science.gov (United States)

Chambrone, Leandro; Shibli, Jamil Awad; Mercúrio, Carlos Eduardo; Cardoso, Bruna; Preshaw, Philip M

2015-04-01

To assess the survival percentage, clinical and radiographic outcomes of sandblasted and acid-etched (SLA) dental implants and its modified surface (SLActive) in protocols involving immediate and early occlusal loading. MEDLINE, EMBASE and the Cochrane Oral Health Group's Trials Register CENTRAL were searched in duplicate up to, and including, June 2013 to include randomised controlled trials (RCTs) and prospective observational studies of at least 6-month duration published in all languages. Studies limited to patients treated with SLA and/or SLActive implants involving a treatment protocol describing immediate and early loading of these implants were eligible for inclusion. Data on clinical and/or radiographic outcomes following implant placement were considered for inclusion. Of the 447 potentially eligible publications identified by the search strategy, seven RCTs comprising a total of 853 implants (8% titanium plasma-sprayed, 41.5% SLA and 50.5% SLActive) and 12 prospective observational studies including 1394 SLA and 145 SLActive implants were included in this review. According to the Cochrane Collaboration's tool for assessing risk of bias, one of the studies was considered to be at a low risk of bias, whereas the remaining studies were considered to be at an unclear risk. Regarding the observational studies, all of them presented a medium methodological quality based on the Modified Newcastle-Ottawa scale. There were no significant differences reported in the studies in relation to implant loss or clinical parameters between the immediate/early loading and delayed loading protocols. Overall, 95% of SLA and 97% of SLActive implants still survive at the end of follow-up. Despite of the positive findings achieved by the included studies, few RCTs were available for analysis for SLActive implants. Study heterogeneity, scarcity of data and the lack of pooled estimates represent a limitation between studies' comparisons and should be considered when interpreting

How the definition of acceptable antigens and epitope analysis can facilitate transplantation of highly sensitized patients with excellent long-term graft survival.

Science.gov (United States)

Heidt, Sebastiaan; Haasnoot, Geert W; Claas, Frans H J

2018-05-24

Highly sensitized patients awaiting a renal transplant have a low chance of receiving an organ offer. Defining acceptable antigens and using this information for allocation purposes can vastly enhance transplantation of this subgroup of patients, which is the essence of the Eurotransplant Acceptable Mismatch program. Acceptable antigens can be determined by extensive laboratory testing, as well as on basis of human leukocyte antigen (HLA) epitope analyses. Within the Acceptable Mismatch program, there is no effect of HLA mismatches on long-term graft survival. Furthermore, patients transplanted through the Acceptable Mismatch program have similar long-term graft survival to nonsensitized patients transplanted through regular allocation. Although HLA epitope analysis is already being used for defining acceptable HLA antigens for highly sensitized patients in the Acceptable Mismatch program, increasing knowledge on HLA antibody - epitope interactions will pave the way toward the definition of acceptable epitopes for highly sensitized patients in the future. Allocation based on acceptable antigens can facilitate transplantation of highly sensitized patients with excellent long-term graft survival.

Effects of testosterone on blood leukocytes in plasmodium berghei-infected mice.

Science.gov (United States)

Kamis, A B; Ibrahim, J B

1989-01-01

Gonadectomized male mice aged 5 weeks were given 5 mg testosterone propionate daily for 14 days. The treatment significantly decreased the number of blood leukocytes. The number of all individual types of leukocytes except basophils in vehicle-treated gonadectomized mice was increased. Testosterone-treated mice consistently had a lower number of leukocytes after being infected with Plasmodium berghei than did vehicle-treated mice. The results suggest that testosterone suppresses the production of leukocytes and that testosterone-treated mice become more susceptible to parasite infection.

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Human leukocytic pyrogen: purification and development of a radioimmunoassay.

Science.gov (United States)

Dinarello, C A; Renfer, L; Wolff, S M

1977-10-01

Leukocytic pyrogen is a small endogenous protein that mediates fever. Because of the limitations of bioassays, circulating leukocytic pyrogen has not been demonstrated during fever in humans. The pyrogen was produced in vitro after phagocytosis of staphylococci by blood monocytes. Antibody against the pyrogen was obtained from rabbits immunized with leukocytic pyrogen and the antiserum was purified by solid-phase immunoadsorbants. Purified antibody to the pyrogen was attached to activated Sepharose 4B and used in conjunction with gel filtration to purify the pyrogen. The pyrogen was labeled with 125I and further purified by gel filtration and ion-exchange chromatography. The final preparation of 125I-labeled pyrogen demonstrated a homogeneous band during isoelectric focusing and other separation procedures. With antibody to pyrogen attached to Sepharose, less than 0.1 of a rabbit pyrogenic dose of human leukocytic pyrogen inhibited the binding of 125I-labeled pyrogen to this immunoadsorbant, and this inhibition was not affected by the presence of human serum. Thus, a radioimmunoassay for human leukocytic pyrogen has been developed that may be used to detect circulating pyrogen during fever in humans.

Evaluation of Activated Leukocyte Cell Adhesion Molecule as a Biomarker for Breast Cancer in Egyptian Patients

International Nuclear Information System (INIS)

El-Shepiny, M.S.E.M.

2013-01-01

In this study, serum activated leukocyte cell adhesion molecule (ALCAM) levels were evaluated in 41 primary breast cancer patients and 20 healthy females, and its diagnostic value was quantified, and compared with those of carbohydrate antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA). Also, its prognostic value was examined. Serum ALCAM levels were also evaluated before and after surgical treatment. Serum levels of ALCAM and CA 15-3 were significantly higher in breast cancer patients than healthy controls (P=0.002, P=0.043 respectively), but the difference in serum CEA levels did not reach statistical significance. Serum ALCAM levels had significant area under the curve (AUC) (P=0.002), but serum levels of CA 15-3 and CEA had nonsignificant AUCs, and various combinations between them did not result in any improvement. A significant association was found between serum levels of ALCAM and CEA with age and menopausal status in breast cancer patients. Non-significant difference was shown in serum levels of ALCAM, CA 15-3 and CEA before and after surgical treatment. In conclusion, this study suggests that serum ALCAM may represent a novel diagnostic bio marker for breast cancer

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Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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CD44 antibody stimulates adhesion of peripheral blood T cells to keratinocytes through the leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway

NARCIS (Netherlands)

Bruynzeel, I.; Koopman, G.; van der Raaij, L. M.; Pals, S. T.; Willemze, R.

1993-01-01

Close contact between T lymphocytes and keratinocytes is an important feature of many inflammatory skin diseases. In vitro studies showed that stimulation of keratinocytes with interferon-gamma or tumor necrosis factor-alpha and of T cells with phorbol esters results in a leukocyte

Kinetics of reversible-sequestration of leukocytes by the isolated perfused rat lung

Energy Technology Data Exchange (ETDEWEB)

Goliaei, B.

1980-08-01

The kinetics and morphology of sequestration and margination of rat leukocytes were studied using an isolated perfused and ventilated rat lung preparation. Whole rat blood, bone marrow suspension, or leukocyte suspensions, were used to perfuse the isolated rat lung. The lung was also perfused with latex particle suspensions and the passage of particles through the lung capillaries was studied. When a leukocyte suspension was perfused through the lung in the single-pass mode, the rate of sequestration decreased as more cells were perfused. In contrast, latex particles of a size comparable to that of leukocytes were totally stopped by the lung. When the leukocyte suspension was recirculated through the lung, cells were rapidly removed from circulation until a steady state was reached, after which no net removal of cells by the lung occurred. These results indicate that leukocytes are reversibly sequestered from circulation. The sequestered cells marginated and attached to the luminal surface of the endothelium of post-capillary venules and veins. A mathematical model was developed based on the assumption that the attachment and detachment of leukocytes to blood vessel walls follows first-order kinetics. The model correctly predicts the following characteristics of the system: (a) the kinetics of the sequestration of leukocytes by the lung; (b) the existence of a steady state when a suspension of leukocytes is recirculated through the lung; and (c) the independence of the fraction of cells remaining in circulation from the starting concentration for all values of starting concentration. (ERB)

Antigen Expression on Blast Cells and Hematological Parameters at Presentation in Acute Lymphoblastic Leukemia Patients

International Nuclear Information System (INIS)

Naeem, S.; Bukhari, M. H.

2015-01-01

Objective: To analyze the expression of various antigens on the leukemic blasts and to determine the hematological parameters, in Acute Lymphoblastic Leukemia (ALL) patients at presentation. Study Design: Observational study. Place and Duration of Study: King Edward Medical University, Lahore and Hameed Latif Hospital, Lahore, from February 2013 to March 2014. Methodology: A total of 50 newly diagnosed and untreated patients of ALL were selected from Mayo Hospital and Hameed Latif Hospital. These patients included both genders and all age groups. Hemoglobin, total leukocyte count and platelet count were determined on hematology analyser-Sysmex-Kx-2I. Blast cell percentage was estimated on Giemsa stained blood smears. Immuno phenotyping was done on bone marrow samples by 5 colour flow cytometery on Beckman Counter Navious Flow cytometer. An acute leukemia panel of 23 antibodies was used. The data was entered and analyzed in SPSS version 22. Results: Of the 50 ALL patients, 36 (72 percentage) were B-ALL and 14 (28 percentage) T-ALL. There were 18 (36 percentage) children and 32 (64 percentage) adults. T-ALL included 22 percentage of the childhood and 31 percentage of the adult cases. Immuno phenotypic analysis showed that CD19, CD79a and CD20 were B-lineage specific markers whereas cCD3, CD3 and CD5 were T-lineage specific. CD10 was the most sensitive marker for B-ALL and CD7 was the most sensitive marker of T-ALL. TdT was expressed in 92 percentage B-ALL and 71 percentage T-ALL cases, CD34 in 58 percentage and 43 percentage cases and CD45 in 83 percentage and 100 percentage respectively. High leukocyte count (> 50 x 109/L) was present in 58 percentage cases. Hemoglobin was < 10 g/dl in 74 percentage patients and platelet count was below 20 x 109/Lin 12 percentage patients. Leukocyte count, hemoglobin, platelet count and blast cell percentage did not show a significant difference in the two ALL immuno types. Conclusion: The frequency of T-ALL is higher in childhood

A robust automatic leukocyte recognition method based on island-clustering texture

Directory of Open Access Journals (Sweden)

Xiaoshun Li

2016-01-01

Full Text Available A leukocyte recognition method for human peripheral blood smear based on island-clustering texture (ICT is proposed. By analyzing the features of the five typical classes of leukocyte images, a new ICT model is established. Firstly, some feature points are extracted in a gray leukocyte image by mean-shift clustering to be the centers of islands. Secondly, the growing region is employed to create regions of the islands in which the seeds are just these feature points. These islands distribution can describe a new texture. Finally, a distinguished parameter vector of these islands is created as the ICT features by combining the ICT features with the geometric features of the leukocyte. Then the five typical classes of leukocytes can be recognized successfully at the correct recognition rate of more than 92.3% with a total sample of 1310 leukocytes. Experimental results show the feasibility of the proposed method. Further analysis reveals that the method is robust and results can provide important information for disease diagnosis.

Observing a fictitious stressful event: haematological changes, including circulating leukocyte activation.

Science.gov (United States)

Mian, Rubina; Shelton-Rayner, Graham; Harkin, Brendan; Williams, Paul

2003-03-01

The aim of this study was to assess the effect of watching a psychological stressful event on the activation of leukocytes in healthy human volunteers. Blood samples were obtained from 32 healthy male and female subjects aged between 20 and 26 years before, during and after either watching an 83-minute horror film that none of the subjects had previously seen (The Texas Chainsaw Massacre, 1974) or by sitting quietly in a room (control group). Total differential cell counts, leukocyte activation as measured by the nitroblue tetrazolium (NBT) test, heart rate and blood pressure (BP) measurements were taken at defined time points. There were significant increases in peripheral circulating leukocytes, the number of activated circulating leukocytes, haemoglobin (Hb) concentration and haematocrit (Hct) in response to the stressor. These were accompanied by significant increases in heart rate, systolic and diastolic BP (P<0.05 from baseline). This is the first reported study on the effects of observing a psychologically stressful, albeit fictitious event on circulating leukocyte numbers and the state of leukocyte activation as determined by the nitrotetrazolium test.

Human leukocyte antigen-e alleles are associated with hepatitis c virus, torque teno virus, and toxoplasma co-infections but are not associated with hepatitis b virus, hepatitis d virus, and GB virus c co-infections in human immunodeficiency virus patients

Directory of Open Access Journals (Sweden)

Afiono Agung Prasetyo

2016-01-01

Full Text Available Context: Data regarding the distribution of Human Leukocyte Antigen (HLA-E alleles and their association with blood-borne pathogen infections/co-infections are limited for many populations, including Indonesia. Aims: The aim of this study was to analyze the association between HLA-E allelic variants and infection with blood-borne pathogens such as hepatitis B virus (HBV, hepatitis C virus (HCV, hepatitis D virus (HDV, torque teno virus (TTV, GB virus C (GBV-C, and Toxoplasma gondii (T. gondii in Indonesian Javanese human immunodeficiency virus (HIV patients. Settings and Design: A total of 320 anti-HIV-positive blood samples were analyzed for HBV, HCV, HDV, TTV, GBV-C, and T. gondii infection status and its association with HLA-E allelic variants. Materials and Methods: Nucleic acid was extracted from plasma samples and used for the molecular detection of HBV DNA, HCV RNA, HDV RNA, TTV DNA, and GBV-C RNA, whereas hepatitis B surface antigen, anti-HCV, immunoglobulin M and G (IgM and IgG anti-T. gondii were detected through serological testing. The blood samples were genotyped for HLA-E loci using a sequence-specific primer-polymerase chain reaction. Statistical Analysis Used: Either the Chi-square or Fisher′s exact test was performed to analyze the frequency of HLA-E alleles and blood-borne pathogen infections in the population. Odds ratios (ORs were calculated to measure the association between the antibodies found and the participants′ possible risk behaviors. A logistic regression analysis was used to assess the associations. Results: HLA-EFNx010101/0101 was associated with HCV/TTV co-infection (adjusted OR [aOR]: 3.5; 95% confidence interval [CI]: 1.156-10.734; P = 0.027 and IgM/IgG anti-Toxo positivity (aOR: 27.0; 95% CI: 3.626-200.472; P = 0.001. HLA-EFNx010103/0103 was associated with TTV co-infection (aOR: 2.7; 95% CI: 1.509-4.796; P = 0.001. Conclusions: HLA-E alleles in Indonesian Javanese HIV patients were found to be associated

Breed differences in development of anti-insulin antibodies in diabetic dogs and investigation of the role of dog leukocyte antigen (DLA) genes.

Science.gov (United States)

Holder, Angela L; Kennedy, Lorna J; Ollier, William E R; Catchpole, Brian

2015-10-15

Administration of insulin for treatment of diabetes mellitus in dogs can stimulate an immune response, with a proportion of animals developing anti-insulin antibodies (AIA). For an IgG antibody response to occur, this would require B cell presentation of insulin peptides by major histocompatibility complex (MHC) class II molecules, encoded by dog leukocyte antigen (DLA) genes, in order to receive T-cell help for class switching. DLA genes are highly polymorphic in the dog population and vary from breed to breed. The aim of the present study was to evaluate AIA reactivity in diabetic dogs of different breeds and to investigate whether DLA genes influence AIA status. Indirect ELISA was used to determine serological reactivity to insulin in diabetic dogs, treated with either a porcine or bovine insulin preparation. DLA haplotypes for diabetic dogs were determined by sequence-based typing of DLA-DRB1, -DQA1 and -DQB1 loci. Significantly greater insulin reactivity was seen in treated diabetic dogs (n=942) compared with non-diabetic dogs (n=100). Relatively few newly diagnosed diabetic dogs (3/109) were found to be AIA positive, although this provides evidence that insulin autoantibodies might be involved in the pathogenesis of the disease in some cases. Of the diabetic dogs treated with a bovine insulin preparation, 52.3% (182/348) were AIA positive, compared with 12.6% (75/594) of dogs treated with a porcine insulin preparation, suggesting that bovine insulin is more immunogenic. Breeds such as dachshund, Cairn terrier, miniature schnauzer and Tibetan terrier were more likely to develop AIA, whereas cocker spaniels were less likely to develop AIA, compared with crossbreed dogs. In diabetic dogs, DLA haplotype DRB1*0015--DQA1*006--DQB1*023 was associated with being AIA positive, whereas the haplotype DLA-DRB1*006--DQA1*005--DQB1*007 showed an association with being AIA negative. These research findings suggest that DLA genes influence AIA responses in treated diabetic

Significance of leukocyte scanning in infected endoprostheses

Energy Technology Data Exchange (ETDEWEB)

Becker, W.; Pasurka, B.; Boerner, W.

1989-03-01

31 patients with suspected septic loosening of an endoprosthesis (hip endoprosthesis n=30; knee endoprosthesis n=1) were examined with leukocyte scans (10 MBq /sup 111/In-oxine: n=22; 300 MBq /sup 99m/Tc-HMPAO: n=9). The results were compared with results of the bacterial growth (n=22), the histology (n=12) and of the bone scans (/sup 99m/Tc-MDP: n=20) which were performed within 4 days. The sensitivity of the bone scan was 100%, the specificity 30% and the diagnostic accuracy regarding a septic loosening of the arthroplasty was 55%. For the leukocyte scans a comparable sensitivity of 100%, but a higher specificity (86%) and accuracy (91%) could be calculated. A false positive leukocyte scan could be observed in a periprosthetic granuloma, an ossifying periarthritis and in a patient with negative bacterial growth with the histological proof of an inflammation.

(Re) Constructing Gender in a New Voice: the Role of Gender Identity in Sla, the Case of Malaysia

OpenAIRE

Cheng, Karen Kow Yip

2004-01-01

This study is a qualitative study of Malaysian children aged between four and six years engaged in a story-telling task. The question posed in this piece of research then: Is the role played by gender in SLA? If it does play a role, what then is the nature of this role? The path taken by this study is to analyze discourse in story-telling.

Návrh slaďování pracovního a soukromého života ve vybrané organizaci

OpenAIRE

Majerčíková, Andrea

2014-01-01

Cílem diplomové práce je analyzovat strategii vybrané soukromé organizace v oblasti slaďování pracovního a osobního života a navrhnout opatření ke zlepšení stávajícího stavu. Práce specifikuje pojmy jako konflikt rolí v rámci pracovního a osobního života, gender a politika rovných příležitostí, koncept „flexicurity“ a dále nastiňuje různorodá opatření napomáhající slaďování pracovního a soukromého života. V rámci analýzy bylo využito dotazníkového šetření a rozhovoru s manažerkou vybrané orga...

The human leukocyte antigen G promotes trophoblast fusion and β-hCG production through the Erk1/2 pathway in human choriocarcinoma cell lines

Energy Technology Data Exchange (ETDEWEB)

Wang, Ji-meng [School of Medicine, Nankai University, Tianjin 300071 (China); State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China); Zhao, Hong-xi [Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038 (China); Wang, Li [Department of Obstetrics and Gynecology, General Hospital of Chinese People’s Liberation Army, Beijing 100853 (China); Gao, Zhi-ying, E-mail: gaozy301@yahoo.com.cn [Department of Obstetrics and Gynecology, General Hospital of Chinese People’s Liberation Army, Beijing 100853 (China); Yao, Yuan-qing, E-mail: yqyao@126.com [Department of Obstetrics and Gynecology, General Hospital of Chinese People’s Liberation Army, Beijing 100853 (China)

2013-05-10

Highlights: •HLA-G expression promotes BeWo cells fusion and fusogenic gene expression. •HLA-G is capable of inducing β-hCG production in human choriocarcinoma cell lines. •Up-regulation of β-hCG production by HLA-G is mediated via the Erk1/2 pathway. -- Abstract: The human leukocyte antigen G (HLA-G) is expressed on the fetal–maternal interface and plays a role in protecting fetal-derived trophoblasts from the maternal immune response, allowing trophoblasts to invade the uterus. However, HLA-G also possesses immune suppressing-independent functions. We found that HLA-G expressing BeWo choriocarcinoma cells increased cell–cell fusion compared to control BeWo cells under forskolin treatment. Regardless of forskolin treatment, the expression of fusogenic gene mRNAs, including syncytin-1, the transcription factor glial cell missing 1 (Gcm1), and beta human chorionic gonadotropin (β-hCG) were elevated. HLA-G up-regulates β-hCG production in human choriocarcinoma cells because HLA-G knockdown in JEG-3 cells induces a dramatic decrease in β-hCG compared with control cells. The defect in β-hCG production in HLA-G knocked-down cells could not be completely overcome by stimulating hCG production through increasing intracellular cAMP levels. HLA-G expressing cells have increased phosphorylation levels for extracellular signal-regulated kinase1/2 (Erk1/2) in BeWo cells. The Erk1/2 pathway is inactivated after the inhibition of HLA-G expression in JEG-3 cells. Finally, Erk1/2 inhibition was able to suppress the increased hCG production induced by HLA-G expression. Together, these data suggest novel roles for HLA-G in regulating β-hCG production via the modulation of the Erk1/2 pathway and by inducing trophoblast cell fusion.

Peripheral blood leukocyte count as an index of defense status in the leukopenic host

International Nuclear Information System (INIS)

Cawley, S.; Findon, G.; Miller, T.E.

1988-01-01

These experimental studies have investigated the reliability of the peripheral blood leukocyte count to predict whether the leukopenic host can contain or eliminate infection. Additionally, we have investigated the possibility that determination of leukocyte recruitment, supplementary to peripheral blood leukocyte counts, might allow individuals with neutropenia at risk from serious infection to be distinguished with greater certainty. Varying doses of radiation, cyclophosphamide, and methylprednisolone were used to induce distinct levels of leukopenia in rats. Leukocyte recruitment was measured by quantifying the response of neutropenic animals to evocative, subcutaneous stimuli, and the results of this assay were then compared with circulating leukocyte counts in the same individuals. Six models of experimentally induced infection were used to compare circulating and recruitable leukocytes as indicators of the susceptibility of the leukopenic host to infection. Response curves relating leukocyte numbers to host resistance were similar when circulating or recruitable leukocytes were used as an index of defense capability. These findings support the use of peripheral blood leukocyte numbers as an index of resistance to infection in individuals with leukopenia and suggest that functional analyses such as leukocyte recruitment are unlikely to provide additional information

Efficiency and safety of leukocyte filtration during cardiopulmonary bypass for cardiac surgery

NARCIS (Netherlands)

Smit, JJJ; de Vries, AJ; Gu, YJ; van Oeveren, W

Background. Leukocyte filtration of systemic blood during cardiopulmonary bypass surgery to reduce post-operative morbidity has not yet been established because of the enormous leukocyte release from the third space. This study was designed to examine the efficiency and safety of leukocyte

Human Leukocyte Antigen-A, B, C, DRB1, and DQB1 Allele and Haplotype Frequencies in a Subset of 237 Donors in the South African Bone Marrow Registry

Directory of Open Access Journals (Sweden)

Mqondisi Tshabalala

2018-01-01

Full Text Available Human leukocyte antigen- (HLA- A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele and haplotype frequencies were studied in a subset of 237 volunteer bone marrow donors registered at the South African Bone Marrow Registry (SABMR. Hapl-o-Mat software was used to compute allele and haplotype frequencies from individuals typed at various resolutions, with some alleles in multiple allele code (MAC format. Four hundred and thirty-eight HLA-A, 235 HLA-B, 234 HLA-DRB1, 41 HLA-DQB1, and 29 HLA-C alleles are reported. The most frequent alleles were A∗02:02g (0.096, B∗07:02g (0.082, C∗07:02g (0.180, DQB1∗06:02 (0.157, and DRB1∗15:01 (0.072. The most common haplotype was A∗03:01g~B∗07:02g~C∗07:02g~DQB1∗06:02~DRB1∗15:01 (0.067, which has also been reported in other populations. Deviations from Hardy-Weinberg equilibrium were observed in A, B, and DRB1 loci, with C~DQB1 being the only locus pair in linkage disequilibrium. This study describes allele and haplotype frequencies from a subset of donors registered at SABMR, the only active bone marrow donor registry in Africa. Although the sample size was small, our results form a key resource for future population studies, disease association studies, and donor recruitment strategies.

Ischemia-reperfusion injury in the isolated rat lung. Role of flow and endogenous leukocytes.

Science.gov (United States)

Seibert, A F; Haynes, J; Taylor, A

1993-02-01

Microvascular lung injury caused by ischemia-reperfusion (IR) may occur via leukocyte-dependent and leukocyte-independent pathways. Leukocyte-endothelial adhesion may be a rate-limiting step in IR lung injury. Leukocyte adhesion to microvascular endothelium occurs when the attractant forces between leukocyte and endothelium are greater than the kinetic energy of the leukocyte and the vascular wall shear rate. We hypothesized (1) that isolated, buffer-perfused rat lungs are not free of endogenous leukocytes, (2) that endogenous leukocytes contribute to IR-induced microvascular injury as measured by the capillary filtration coefficient (Kfc), and (3) that a reduction of perfusate flow rate would potentiate leukocyte-dependent IR injury. Sixty lungs were divided into four groups: (1) low-flow controls, (2) high-flow controls, (3) low-flow IR, and (4) high-flow IR. Microvascular injury was linearly related to baseline perfusate leukocyte concentrations at both low (r = 0.78) and high (r = 0.82) flow rates. Kfc in the high-flow IR group (0.58 +/- 0.03 ml/min/cm H2O/100 g) was less (p Kfc in the low-flow IR group (0.82 +/- 0.07), and in both groups Kfc values were significantly greater than low-flow (0.34 +/- 0.03) and high-flow (0.31 +/- 0.01) control Kfc values after 75 min. Retention of leukocytes in the lung, evaluated by a tissue myeloperoxidase assay, was greatest in the low-flow IR group. We conclude (1) that isolated, buffer-perfused rat lungs contain significant quantities of leukocytes and that these leukocytes contribute to IR lung injury, and (2) that IR-induced microvascular injury is potentiated by low flow.

In silico and cell-based analyses reveal strong divergence between prediction and observation of T-cell-recognized tumor antigen T-cell epitopes.

Science.gov (United States)

Schmidt, Julien; Guillaume, Philippe; Dojcinovic, Danijel; Karbach, Julia; Coukos, George; Luescher, Immanuel

2017-07-14

Tumor exomes provide comprehensive information on mutated, overexpressed genes and aberrant splicing, which can be exploited for personalized cancer immunotherapy. Of particular interest are mutated tumor antigen T-cell epitopes, because neoepitope-specific T cells often are tumoricidal. However, identifying tumor-specific T-cell epitopes is a major challenge. A widely used strategy relies on initial prediction of human leukocyte antigen-binding peptides by in silico algorithms, but the predictive power of this approach is unclear. Here, we used the human tumor antigen NY-ESO-1 (ESO) and the human leukocyte antigen variant HLA-A*0201 (A2) as a model and predicted in silico the 41 highest-affinity, A2-binding 8-11-mer peptides and assessed their binding, kinetic complex stability, and immunogenicity in A2-transgenic mice and on peripheral blood mononuclear cells from ESO-vaccinated melanoma patients. We found that 19 of the peptides strongly bound to A2, 10 of which formed stable A2-peptide complexes and induced CD8 + T cells in A2-transgenic mice. However, only 5 of the peptides induced cognate T cells in humans; these peptides exhibited strong binding and complex stability and contained multiple large hydrophobic and aromatic amino acids. These results were not predicted by in silico algorithms and provide new clues to improving T-cell epitope identification. In conclusion, our findings indicate that only a small fraction of in silico -predicted A2-binding ESO peptides are immunogenic in humans, namely those that have high peptide-binding strength and complex stability. This observation highlights the need for improving in silico predictions of peptide immunogenicity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Uptake of radiolabeled leukocytes in prosthetic graft infection

International Nuclear Information System (INIS)

Serota, A.I.; Williams, R.A.; Rose, J.G.; Wilson, S.E.

1981-01-01

The utility of radionuclide labeled leukocytes in the demonstration of infection within vascular prostheses was examined. The infrarenal aorta was replaced with a 3 cm Dacron graft in 12 dogs. On the third postoperative day, six of the animals received an intravenous injection of 10(8) Staphylococcus aureus. Labeled leukocyte scans were performed at postoperative days one and three, and then weekly for 8 weeks with indium-111 and technetium-99 labeled autologous leukocytes. When scans showed focal uptake of isotope in the area of prosthetic material, the grafts were aseptically excised and cultured on mannitol-salt agar. Both control and infected animals had retroperitoneal isotope activity in the immediate postoperative period that disappeared by the end of the first week. By the eighth postoperative week, all of the animals that received the bacteremic challenge had both radionuclide concentration in the region of the vascular prosthesis and S. aureus cultured subsequently from the perigraft tissues. None of the control animals had either radionuclide or bacteriologic evidence of infection at the eighth postoperative week. The radiolabeled leukocyte scan is a highly sensitive and specific technique, clinically applicable for the diagnosis of vascular prosthetic infections

Insulin radioreceptor assay on murine splenic leukocytes and peripheral erythrocytes

International Nuclear Information System (INIS)

Shimizu, F.; Kahn, R.

1982-01-01

Insulin radioreceptor assays were developed using splenic leukocytes and peripheral erythrocytes from individual mice. Splenic leukocytes were prepared using an NH 4 Cl buffer which did not alter insulin binding, but gave much higher yields than density gradient methods. Mouse erythrocytes were isolated from heparinized blood by three passages over a Boyum gradient, and a similar buffer was used to separate cells from free [ 125 I]iodoinsulin at the end of the binding incubation. Insulin binding to both splenic leukocytes and peripheral erythrocytes had typical pH, temperature, and time dependencies, and increased linearly with an increased number of cells. Optimal conditions for the splenic leukocytes (6 x 10 7 /ml) consisted of incubation with [ 125 I]iodoinsulin at 15 C for 2 h in Hepes buffer, pH 8.0. In cells from 20 individual mice, the specific [ 125 I]iodoinsulin binding was 2.6 +/- 0.1% (SEM), and nonspecific binding was 0.3 +/- 0.04% (10.6% of total binding). Erythrocytes (2.8 x 10 9 /ml) were incubated with [ 125 ]iodoinsulin at 15 C for 2 h in Hepes buffer, pH 8.2. In cells from 25 individual mice, the specific [ 125 I]iodoinsulin binding was 4.5 +/- 0.2%, and nonspecific binding was 0.7 +/- 0.03% (13.6% of total binding). In both splenic leukocytes and peripheral erythrocytes, analysis of equilibrium binding data produced curvilinear Scatchard plots with approximately 3500 binding sites/leukocyte and 20 binding sites/erythrocyte. These data demonstrate that adequate numbers of splenic leukocytes and peripheral erythrocytes can be obtained from individual mice to study insulin binding in a precise and reproducible manner

Lym-1 Chimeric Antigen Receptor T Cells Exhibit Potent Anti-Tumor Effects against B-Cell Lymphoma

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Long Zheng

2017-12-01

Full Text Available T cells expressing chimeric antigen receptors (CARs recognizing CD19 epitopes have produced remarkable anti-tumor effects in patients with B-cell malignancies. However, cancer cells lacking recognized epitopes can emerge, leading to relapse and death. Thus, CAR T cells targeting different epitopes on different antigens could improve immunotherapy. The Lym-1 antibody targets a conformational epitope of Human Leukocyte Antigen-antigen D Related (HLA-DR on the surface of human B-cell lymphomas. Lym-1 CAR T cells were thus generated for evaluation of cytotoxic activity towards lymphoma cells in vitro and in vivo. Human T cells from healthy donors were transduced to express a Lym-1 CAR, and assessed for epitope-driven function in culture and towards Raji xenografts in NOD-scidIL2Rgammanull (NSG mice. Lym-1 CAR T cells exhibited epitope-driven activation and lytic function against human B-cell lymphoma cell lines in culture and mediated complete regression of Raji/Luciferase-Green fluorescent protein (Raji/Luc-GFP in NSG mice with similar or better reactivity than CD19 CAR T cells. Lym-1 CAR transduction of T cells is a promising immunotherapy for patients with Lym-1 epitope positive B-cell malignancies.

Leukocyte scintiscanning for the diagnosis of inflammations

International Nuclear Information System (INIS)

Becker, W.

1988-01-01

The value of leukocyte scintiscanning for clinical diagnostics is examined with regard to various areas of indications, and as a method of first examination, or as an alternative to, or additional method to be combined with, the other usual techniques. Leukocyte scintiscanning is indicated as a good first examination method in case of chronic enteritis in a highly active stage, stenosis of the colon, or when abscess is suspected, or infected renal cysts, or infection of angioplasty, osteomyelitis, or in case of fiever of unknown origin and impossible focal diagnosis. It also is applicable for follow-up diagnostics in chronic enteritis, suspected abdominal abscess, prosthetic valvular endocarditis, and infection of hip joint prothesis. The method also may yield additional information in case of renal graft rejection, coronary inflammations, for differential diagnosis of brain tumor or abcess, edematous or antodigestive pancreatitis, and in chronic polyarthritis. For leukocyte labelling, indium-111 and Tc-99m are primarily used. (ECB) [de

In vivo imaging of leukocyte recruitment to glomeruli in mice using intravital microscopy.

Science.gov (United States)

Kitching, A Richard; Kuligowski, Michael P; Hickey, Michael J

2009-01-01

Leukocytes mediate some forms of glomerulonephritis, particularly severe proliferative and crescentic forms. The renal glomerulus is one of the few sites within the microvasculature in which leukocyte recruitment occurs in capillaries. However, due to the difficulty of directly visualising the glomerulus, the mechanisms of leukocyte recruitment to glomerular capillaries are poorly understood. To overcome this, a murine kidney can be rendered hydronephrotic, by ligating one ureter, and allowing the mouse to rest for 12 weeks. This allows the visualisation of the glomerular microvasculature during inflammatory responses. In inflammation, in this example induced by anti-glomerular basement membrane (GBM) antibody, leukocytes can be observed undergoing adhesion in glomerular capillaries using intravital microscopy. Leukocyte adhesion can be quantitated using this approach. An observation protocol involving few, limited periods of epifluorescence avoids phototoxicity-induced leukocyte recruitment. The process of hydronephrosis does not alter the ability of anti-GBM-antibody to induce a glomerular inflammatory response. This approach allows detailed investigation of the mechanisms of leukocyte recruitment within glomeruli.

The Viral Transcription Group Determines the HLA Class I Cellular Immune Response Against Human Respiratory Syncytial Virus*

Science.gov (United States)

Johnstone, Carolina; Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Infantes, Susana; Lemonnier, François A.; David, Chella S.; Admon, Arie; López, Daniel

2015-01-01

The cytotoxic T-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class I molecules that are exposed on the surface of infected cells. The cytotoxic T-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. In this study, naturally processed viral human leukocyte antigen class I ligands were identified with mass spectrometry analysis of complex human leukocyte antigen-bound peptide pools isolated from large amounts of human respiratory syncytial virus-infected cells. Acute antiviral T-cell response characterization showed that viral transcription determines both the immunoprevalence and immunodominance of the human leukocyte antigen class I response to human respiratory syncytial virus. These findings have clear implications for antiviral vaccine design. PMID:25635267

Lymphatic pump treatment mobilizes leukocytes from the gut associated lymphoid tissue into lymph.

Science.gov (United States)

Hodge, Lisa M; Bearden, Melissa K; Schander, Artur; Huff, Jamie B; Williams, Arthur; King, Hollis H; Downey, H Fred

2010-06-01

Lymphatic pump techniques (LPT) are used clinically by osteopathic practitioners for the treatment of edema and infection; however, the mechanisms by which LPT enhances lymphatic circulation and provides protection during infection are not understood. Rhythmic compressions on the abdomen during LPT compress the abdominal area, including the gut-associated lymphoid tissues (GALT), which may facilitate the release of leukocytes from these tissues into the lymphatic circulation. This study is the first to document LPT-induced mobilization of leukocytes from the GALT into the lymphatic circulation. Catheters were inserted into either the thoracic or mesenteric lymph ducts of dogs. To determine if LPT enhanced the release of leukocytes from the mesenteric lymph nodes (MLN) into lymph, the MLN were fluorescently labeled in situ. Lymph was collected during 4 min pre-LPT, 4 min LPT, and 10 min following cessation of LPT. LPT significantly increased lymph flow and leukocytes in both mesenteric and thoracic duct lymph. LPT had no preferential effect on any specific leukocyte population, since neutrophil, monocyte, CD4+ T cell, CD8+ T cell, IgG+B cell, and IgA+B cell numbers were similarly increased. In addition, LPT significantly increased the mobilization of leukocytes from the MLN into lymph. Lymph flow and leukocyte counts fell following LPT treatment, indicating that the effects of LPT are transient. LPT mobilizes leukocytes from GALT, and these leukocytes are transported by the lymphatic circulation. This enhanced release of leukocytes from GALT may provide scientific rationale for the clinical use of LPT to improve immune function.

(RE CONSTRUCTING GENDER IN A NEW VOICE: THE ROLE OF GENDER IDENTITY IN SLA, THE CASE OF MALAYSIA

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Karen Kow Yip Cheng

2004-01-01

Full Text Available This study is a qualitative study of Malaysian children aged between four and six years engaged in a story-telling task. The question posed in this piece of research then: Is the role played by gender in SLA? If it does play a role, what then is the nature of this role? The path taken by this study is to analyze discourse in story-telling.

Association of Human Leukocyte Antigen DRB1*15 and DRB1*15:01 Polymorphisms with Response to Immunosuppressive Therapy in Patients with Aplastic Anemia: A Meta-Analysis

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Liu, Shan; Li, Qing; Zhang, Ying; Li, Qiushuang; Ye, Baodong; Wu, Dijiong; Wu, Li; Lu, Hanti; Ji, Conghua

2016-01-01

This study aimed to review and quantitatively analyze (1) the association of aplastic anemia (AA) with human leukocyte antigen (HLA)-DRB1*15 and HLA-DRB1*15:01 polymorphisms and (2) the association of HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms with response to immunosuppressive therapy (IST) in AA. Published studies have reported conflicting and heterogeneous results regarding the association of HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms with response to IST in AA. The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical Literature, Wangfang and Chinese Social Sciences Citation Index databases were searched. All relevant publications were searched through December 2015. Odds ratio (OR), risk ratio (RR), and 95% confidence intervals (CI) for the comparison between case–control or cohort studies were evaluated. Finally, 24 articles were identified. For HLA-DRB1*15 and HLA-DRB1*15:01, the OR (95% CI) was 2.24(1.33–3.77), P 0.05). Sensitivity analyses revealed that the results were statistically robust. The meta-analysis suggested that HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms might be associated with increased AA risk in Asians. IST might be more effective in HLA-DRB1*15+ and HLA-DRB1*15:01+ Asian patients with AA than in HLA-DRB1*15− and HLA-DRB1*15:01− Asian patients with AA. Future studies with adequate methodological quality on gene–gene and gene–environment interactions and gene treatment may yield valid results. PMID:27611583

PET/CT with 18F-FDG- and 18F-FBEM-labeled leukocytes for metabolic activity and leukocyte recruitment monitoring in a mouse model of pulmonary fibrosis.

Science.gov (United States)

Bondue, Benjamin; Sherer, Félicie; Van Simaeys, Gaetan; Doumont, Gilles; Egrise, Dominique; Yakoub, Yousof; Huaux, François; Parmentier, Marc; Rorive, Sandrine; Sauvage, Sébastien; Lacroix, Simon; Vosters, Olivier; De Vuyst, Paul; Goldman, Serge

2015-01-01

Idiopathic pulmonary fibrosis is characterized by a progressive and irreversible respiratory failure. Validated noninvasive methods able to assess disease activity are essential for prognostic purposes as well as for the evaluation of emerging antifibrotic treatments. C57BL/6 mice were used in a murine model of pulmonary fibrosis induced by an intratracheal instillation of bleomycin (control mice were instilled with a saline solution). At different times after instillation, PET/CT with (18)F-FDG- or (18)F-4-fluorobenzamido-N-ethylamino-maleimide ((18)F-FBEM)-labeled leukocytes was performed to assess metabolic activity and leukocyte recruitment, respectively. In bleomycin-treated mice, a higher metabolic activity was measured on (18)F-FDG PET/CT scans from day 7 to day 24 after instillation, with a peak of activity measured at day 14. Of note, lung mean standardized uptake values correlated with bleomycin doses, histologic score of fibrosis, lung hydroxyproline content, and weight loss. Moreover, during the inflammatory phase of the model (day 7), but not the fibrotic phase (day 23), bleomycin-treated mice presented with an enhanced leukocyte recruitment as assessed by (18)F-FBEM-labeled leukocyte PET/CT. Autoradiographic analysis of lung sections and CD45 immunostaining confirm the higher and early recruitment of leukocytes in bleomycin-treated mice, compared with control mice. (18)F-FDG- and (18)F-FBEM-labeled leukocyte PET/CT enable monitoring of metabolic activity and leukocyte recruitment in a mouse model of pulmonary fibrosis. Implications for preclinical evaluation of antifibrotic therapy are expected. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

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Fine-grained leukocyte classification with deep residual learning for microscopic images.

Science.gov (United States)

Qin, Feiwei; Gao, Nannan; Peng, Yong; Wu, Zizhao; Shen, Shuying; Grudtsin, Artur

2018-08-01

Leukocyte classification and cytometry have wide applications in medical domain, previous researches usually exploit machine learning techniques to classify leukocytes automatically. However, constrained by the past development of machine learning techniques, for example, extracting distinctive features from raw microscopic images are difficult, the widely used SVM classifier only has relative few parameters to tune, these methods cannot efficiently handle fine-grained classification cases when the white blood cells have up to 40 categories. Based on deep learning theory, a systematic study is conducted on finer leukocyte classification in this paper. A deep residual neural network based leukocyte classifier is constructed at first, which can imitate the domain expert's cell recognition process, and extract salient features robustly and automatically. Then the deep neural network classifier's topology is adjusted according to the prior knowledge of white blood cell test. After that the microscopic image dataset with almost one hundred thousand labeled leukocytes belonging to 40 categories is built, and combined training strategies are adopted to make the designed classifier has good generalization ability. The proposed deep residual neural network based classifier was tested on microscopic image dataset with 40 leukocyte categories. It achieves top-1 accuracy of 77.80%, top-5 accuracy of 98.75% during the training procedure. The average accuracy on the test set is nearly 76.84%. This paper presents a fine-grained leukocyte classification method for microscopic images, based on deep residual learning theory and medical domain knowledge. Experimental results validate the feasibility and effectiveness of our approach. Extended experiments support that the fine-grained leukocyte classifier could be used in real medical applications, assist doctors in diagnosing diseases, reduce human power significantly. Copyright © 2018 Elsevier B.V. All rights reserved.

Crossing the Vascular Wall: Common and Unique Mechanisms Exploited by Different Leukocyte Subsets during Extravasation

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Michael Schnoor

2015-01-01

Full Text Available Leukocyte extravasation is one of the essential and first steps during the initiation of inflammation. Therefore, a better understanding of the key molecules that regulate this process may help to develop novel therapeutics for treatment of inflammation-based diseases such as atherosclerosis or rheumatoid arthritis. The endothelial adhesion molecules ICAM-1 and VCAM-1 are known as the central mediators of leukocyte adhesion to and transmigration across the endothelium. Engagement of these molecules by their leukocyte integrin receptors initiates the activation of several signaling pathways within both leukocytes and endothelium. Several of such events have been described to occur during transendothelial migration of all leukocyte subsets, whereas other mechanisms are known only for a single leukocyte subset. Here, we summarize current knowledge on regulatory mechanisms of leukocyte extravasation from a leukocyte and endothelial point of view, respectively. Specifically, we will focus on highlighting common and unique mechanisms that specific leukocyte subsets exploit to succeed in crossing endothelial monolayers.

In vitro phagocytosis of several Candida berkhout species by murine leukocytes.

Science.gov (United States)

Fontenla de Petrino, S E; Bibas Bonet de Jorrat, M E; Sirena, A

1985-03-01

In vitro phagocytosis of thirteen Candida berkhout species by rat leukocytes was studied to assess a possible correlation between pathogenicity and phagocytosis Yeast-leukocyte suspensions were mixed up for 3 h and phagocytic index, germ-tube formation and leukocyte candidacidal activity were evaluated. Highest values for phagocytosis were reached in all cases at the end of the first hour. Leukocyte candidacidal activity was absent. Only C. albicans produced germ-tubes. The various phagocytosis indices were determined depending on the Candida species assayed. Under these conditions, the more pathogenic species presented the lower indices of phagocytosis. It is determined that the in vitro phagocytic index may bear a close relationship with the pathogenicity of the Candida berkhout.

Improved survival of newborns receiving leukocyte transfusions for sepsis

International Nuclear Information System (INIS)

Cairo, M.S.; Rucker, R.; Bennetts, G.A.; Hicks, D.; Worcester, C.; Amlie, R.; Johnson, S.; Katz, J.

1984-01-01

To determine the role of polymorphonuclear (PMN) leukocyte transfusions in neonates with sepsis, 23 consecutive newborns were prospectively randomly selected during an 18-month period in a treatment plan to receive polymorphonuclear leukocyte transfusions with supportive care or supportive care alone. Thirteen neonates received transfusions every 12 hours for a total of five transfusions. Each transfusion consisting of 15 mL/kg of polymorphonuclear leukocytes was subjected to 1,500 rads of radiation. The polymorphonuclear leukocytes were obtained by continuous-flow centrifugation leukapheresis and contained 0.5 to 1.0 X 10(9) granulocytes per 15 mL with less than 10% lymphocytes. Positive findings on blood cultures were obtained in 14/23 patients and seven were randomly selected for each treatment group. Absolute granulocyte counts were less than 1,500/microL in 13 patients but tibial bone marrow examinations revealed that the neutrophil supply pool was depleted in only three patients. The survival was significantly greater in the treatment group compared with the group that did not receive transfusions

The viral transcription group determines the HLA class I cellular immune response against human respiratory syncytial virus.

Science.gov (United States)

Johnstone, Carolina; Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Infantes, Susana; Lemonnier, François A; David, Chella S; Admon, Arie; López, Daniel

2015-04-01

The cytotoxic T-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class I molecules that are exposed on the surface of infected cells. The cytotoxic T-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. In this study, naturally processed viral human leukocyte antigen class I ligands were identified with mass spectrometry analysis of complex human leukocyte antigen-bound peptide pools isolated from large amounts of human respiratory syncytial virus-infected cells. Acute antiviral T-cell response characterization showed that viral transcription determines both the immunoprevalence and immunodominance of the human leukocyte antigen class I response to human respiratory syncytial virus. These findings have clear implications for antiviral vaccine design. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Anti-Thyroid Peroxidase Reactivity Is Heightened in Pemphigus Vulgaris and Is Driven by Human Leukocyte Antigen Status and the Absence of Desmoglein Reactivity

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Kristina Seiffert-Sinha

2018-04-01

Full Text Available Pemphigus vulgaris (PV belongs to an autoimmune disease cluster that includes autoimmune thyroid disease (AITD, suggesting common mechanisms driving autoimmune susceptibility. Our group has shown that PV patients exhibit significant reactivity to AITD-related anti-thyroid peroxidase (anti-TPO, and anti-TPO antibodies affect signaling pathways in keratinocytes similar to anti-desmoglein (Dsg 3 antibodies. To further assess the relevance of anti-TPO reactivity in PV, we analyzed anti-TPO levels in 280 PV and 167 healthy control serum samples across a comprehensive set of variable and static parameters of disease activity and etiopathogenesis. PV patients have significantly higher activity rates (A.R.s for anti-TPO than healthy controls, but levels do not differ between phases of clinical activity and remission. Patients that carry both the PV-associated human leukocyte antigen (HLA alleles DRB1*0402 and DQB1*0503, or DQB1*0503 alone show a low prevalence of anti-TPO (A.R. 9.5 and 4.8%, respectively, while patients that lack expression of these alleles or carry DRB1*0402 alone have a much higher prevalence of anti-TPO (A.R. 23.1 and 15.8%, respectively, suggesting that the absence of DQB1*0503 may predispose patients to the development of anti-TPO antibodies. Similarly, anti-Dsg1−/3− patients have a higher anti-TPO A.R. (26.9% than anti-Dsg1−/3+ (18.8%, anti-Dsg1+/3− (14.3%, and anti-Dsg1+/3+ (3.9% patients. Our data suggest that anti-TPO reactivity in PV is driven by genetic markers that may be in linkage disequilibrium with the established PV-susceptibility alleles and that this association drives the selection of a combination of anti-Dsg and anti-TPO antibodies, with anti-TPO filling the gap in active patients that do not carry the established PV-associated autoantibodies and/or are lacking the established PV-HLA-susceptibility alleles.

Anti-Thyroid Peroxidase Reactivity Is Heightened in Pemphigus Vulgaris and Is Driven by Human Leukocyte Antigen Status and the Absence of Desmoglein Reactivity

Science.gov (United States)

Seiffert-Sinha, Kristina; Khan, Shahzaib; Attwood, Kristopher; Gerlach, John A.; Sinha, Animesh A.

2018-01-01

Pemphigus vulgaris (PV) belongs to an autoimmune disease cluster that includes autoimmune thyroid disease (AITD), suggesting common mechanisms driving autoimmune susceptibility. Our group has shown that PV patients exhibit significant reactivity to AITD-related anti-thyroid peroxidase (anti-TPO), and anti-TPO antibodies affect signaling pathways in keratinocytes similar to anti-desmoglein (Dsg) 3 antibodies. To further assess the relevance of anti-TPO reactivity in PV, we analyzed anti-TPO levels in 280 PV and 167 healthy control serum samples across a comprehensive set of variable and static parameters of disease activity and etiopathogenesis. PV patients have significantly higher activity rates (A.R.s) for anti-TPO than healthy controls, but levels do not differ between phases of clinical activity and remission. Patients that carry both the PV-associated human leukocyte antigen (HLA) alleles DRB1*0402 and DQB1*0503, or DQB1*0503 alone show a low prevalence of anti-TPO (A.R. 9.5 and 4.8%, respectively), while patients that lack expression of these alleles or carry DRB1*0402 alone have a much higher prevalence of anti-TPO (A.R. 23.1 and 15.8%, respectively), suggesting that the absence of DQB1*0503 may predispose patients to the development of anti-TPO antibodies. Similarly, anti-Dsg1−/3− patients have a higher anti-TPO A.R. (26.9%) than anti-Dsg1−/3+ (18.8%), anti-Dsg1+/3− (14.3%), and anti-Dsg1+/3+ (3.9%) patients. Our data suggest that anti-TPO reactivity in PV is driven by genetic markers that may be in linkage disequilibrium with the established PV-susceptibility alleles and that this association drives the selection of a combination of anti-Dsg and anti-TPO antibodies, with anti-TPO filling the gap in active patients that do not carry the established PV-associated autoantibodies and/or are lacking the established PV-HLA-susceptibility alleles. PMID:29675021

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Hug tightly and say goodbye: role of endothelial ICAM-1 in leukocyte transmigration.

Science.gov (United States)

Rahman, Arshad; Fazal, Fabeha

2009-04-01

Stable adhesion of leukocytes to endothelium is crucial for transendothelial migration (TEM) of leukocytes evoked during inflammatory responses, immune surveillance, and homing and mobilization of hematopoietic progenitor cells. The basis of stable adhesion involves expression of intercellular adhesion molecule-1 (ICAM-1), an inducible endothelial adhesive protein that serves as a counter-receptor for beta(2)-integrins on leukocytes. Interaction of ICAM-1 with beta(2)-integrins enables leukocytes to adhere firmly to the vascular endothelium and subsequently, to migrate across the endothelial barrier. The emerging paradigm is that ICAM-1, in addition to firmly capturing leukocytes, triggers intracellular signaling events that may contribute to active participation of the endothelium in facilitating the TEM of adherent leukocytes. The nature, duration, and intensity of ICAM-1-dependent signaling events may contribute to the determination of the route (paracellular vs. transcellular) of leukocyte passage; these aspects of ICAM-1 signaling may in turn be influenced by density and distribution of ICAM-1 on the endothelial cell surface, the source of endothelial cells it is present on, and the type of leukocytes with which it is engaged. This review summarizes our current understanding of the "ICAM-1 paradigm" of TEM with an emphasis on the signaling events mediating ICAM-1 expression and activated by ICAM-1 engagement in endothelial cells.

Identifying the rules of engagement enabling leukocyte rolling, activation, and adhesion.

Directory of Open Access Journals (Sweden)

Jonathan Tang

2010-02-01

Full Text Available The LFA-1 integrin plays a pivotal role in sustained leukocyte adhesion to the endothelial surface, which is a precondition for leukocyte recruitment into inflammation sites. Strong correlative evidence implicates LFA-1 clustering as being essential for sustained adhesion, and it may also facilitate rebinding events with its ligand ICAM-1. We cannot challenge those hypotheses directly because it is infeasible to measure either process during leukocyte adhesion following rolling. The alternative approach undertaken was to challenge the hypothesized mechanisms by experimenting on validated, working counterparts: simulations in which diffusible, LFA1 objects on the surfaces of quasi-autonomous leukocytes interact with simulated, diffusible, ICAM1 objects on endothelial surfaces during simulated adhesion following rolling. We used object-oriented, agent-based methods to build and execute multi-level, multi-attribute analogues of leukocytes and endothelial surfaces. Validation was achieved across different experimental conditions, in vitro, ex vivo, and in vivo, at both the individual cell and population levels. Because those mechanisms exhibit all of the characteristics of biological mechanisms, they can stand as a concrete, working theory about detailed events occurring at the leukocyte-surface interface during leukocyte rolling and adhesion experiments. We challenged mechanistic hypotheses by conducting experiments in which the consequences of multiple mechanistic events were tracked. We quantified rebinding events between individual components under different conditions, and the role of LFA1 clustering in sustaining leukocyte-surface adhesion and in improving adhesion efficiency. Early during simulations ICAM1 rebinding (to LFA1 but not LFA1 rebinding (to ICAM1 was enhanced by clustering. Later, clustering caused both types of rebinding events to increase. We discovered that clustering was not necessary to achieve adhesion as long as LFA1 and

Early events in the pathogenesis of foot-and-mouth disease in pigs; identification of oropharyngeal tonsils as sites of primary and sustained viral replication.

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Carolina Stenfeldt

Full Text Available A time-course study was performed to elucidate the early events of foot-and-mouth disease virus (FMDV infection in pigs subsequent to simulated natural, intra-oropharyngeal, inoculation. The earliest detectable event was primary infection in the lingual and paraepiglottic tonsils at 6 hours post inoculation (hpi characterized by regional localization of viral RNA, viral antigen, and infectious virus. At this time FMDV antigen was localized in cytokeratin-positive epithelial cells and CD172a-expressing leukocytes of the crypt epithelium of the paraepiglottic tonsils. De novo replication of FMDV was first detected in oropharyngeal swab samples at 12 hpi and viremia occurred at 18-24 hpi, approximately 24 hours prior to the appearance of vesicular lesions. From 12 through 78 hpi, microscopic detection of FMDV was consistently localized to cytokeratin-positive cells within morphologically characteristic segments of oropharyngeal tonsil crypt epithelium. During this period, leukocyte populations expressing CD172a, SLA-DQ class II and/or CD8 were found in close proximity to infected epithelial cells, but with little or no co-localization with viral proteins. Similarly, M-cells expressing cytokeratin-18 did not co-localize with FMDV proteins. Intra-epithelial micro-vesicles composed of acantholytic epithelial cells expressing large amounts of structural and non-structural FMDV proteins were present within crypts of the tonsil of the soft palate during peak clinical infection. These findings inculpate the paraepiglottic tonsils as the primary site of FMDV infection in pigs exposed via the gastrointestinal tract. Furthermore, the continuing replication of FMDV in the oropharyngeal tonsils during viremia and peak clinical infection with no concurrent amplification of virus occurring in the lower respiratory tract indicates that these sites are the major source of shedding of FMDV from pigs.

Traffic of leukocytes in microfluidic channels with rectangular and rounded cross-sections.

Science.gov (United States)

Yang, Xiaoxi; Forouzan, Omid; Burns, Jennie M; Shevkoplyas, Sergey S

2011-10-07

Traffic of leukocytes in microvascular networks (particularly through arteriolar bifurcations and venular convergences) affects the dynamics of capillary blood flow, initiation of leukocyte adhesion during inflammation, and localization and development of atherosclerotic plaques in vivo. Recently, a growing research effort has been focused on fabricating microvascular networks comprising artificial vessels with more realistic, rounded cross-sections. This paper investigated the impact of the cross-sectional geometry of microchannels on the traffic of leukocytes flowing with human whole blood through a non-symmetrical bifurcation that consisted of a 50 μm mother channel bifurcating into 30 μm and 50 μm daughter branches. Two versions of the same bifurcation comprising microchannels with rectangular and rounded cross-sections were fabricated using conventional multi-layer photolithography to produce rectangular microchannles that were then rounded in situ using a recently developed method of liquid PDMS/air bubble injection. For microchannels with rounded cross-sections, about two-thirds of marginated leukocytes traveling along a path in the top plane of the bifurcation entered the smallest 30 μm daughter branch. This distribution was reversed in microchannels with rectangular cross-sections--the majority of leukocytes traveling along a similar path continued to follow the 50 μm microchannels after the bifurcation. This dramatic difference in the distribution of leukocyte traffic among the branches of the bifurcation can be explained by preferential margination of leukocytes towards the corners of the 50 μm mother microchannels with rectangular cross-sections, and by the additional hindrance to leukocyte entry created by the sharp transition from the 50 μm mother microchannel to the 30 μm daughter branch at the intersection. The results of this study suggest that the trajectories of marginated leukocytes passing through non-symmetrical bifurcations are

Selective suppression of leukocyte recruitment in allergic inflammation

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CL Weller

2005-03-01

Full Text Available Allergic diseases result in a considerable socioeconomic burden. The incidence of allergic diseases, notably allergic asthma, has risen to high levels for reasons that are not entirely understood. With an increasing knowledge of underlying mechanisms, there is now more potential to target the inflammatory process rather than the overt symptoms. This focuses attention on the role of leukocytes especially Th2 lymphocytes that regulate allergic inflammation and effector cells where eosinophils have received much attention. Eosinophils are thought to be important based on the high numbers that are recruited to sites of allergic inflammation and the potential of these cells to effect both tissue injury and remodelling. It is hoped that future therapy will be directed towards specific leukocyte types, without overtly compromising essential host defence responses. One obvious target is leukocyte recruitment. This necessitates a detailed understanding of underlying mechanisms, particularly those involving soluble che-moattractants signals and cell-cell adhesion molecules.

In vitro evaluation of canine leukocytes radiolabeled in whole blood with 99mTc stannous colloid

International Nuclear Information System (INIS)

Abushhiwa, Mohamed H.; Salehi, Nouria S.; Whitton, Robert C.; Charles, Jennifer A.; Finnin, Peter J.; Lording, Peter M.; Caple, Ivan W.; Parry, Bruce W.

2008-01-01

Introduction: Technetium-99m stannous colloid ( 99m TcSnC)-labeled leukocytes are used to investigate a variety of inflammatory diseases in human medicine. The present study investigates the in vitro behavior of canine leukocytes labeled in whole blood with 99m TcSnC. Methods: Blood samples from 10 healthy dogs were labeled with 99m TcSnC using a standard procedure. The distribution of radioactivity among blood components (plasma, leukocyte layers and erythrocytes) was measured following separation of the radiolabeled samples across Histopaque density gradients. Phagocytic function of labeled and unlabeled leukocytes was estimated using zymosan particles. Labeling retention by leukocytes was determined at 1, 3, 4 and 7 h postlabeling. Results: The mean±standard error percentage of radioactivity associated with plasma, erythrocyte and leukocyte fractions was 2.0±0.21%, 55.5±0.60% and 42.5±0.54%, respectively (the last comprising 70.2±0.83% in polymorphonuclear leukocytes and 29.8±0.83% in mononuclear leukocytes). Labeled canine leukocytes had a phagocytic activity of 91.3±0.28% (control, 91.7±0.26%). The radiolabeled canine leukocytes retained 94.1±0.30% of radioactivity at 7 h postlabeling. Conclusions: Radiolabeling of canine leukocytes in whole blood with 99m TcSnC has minor adverse effect on their phagocytic function. The radiolabeled canine leukocytes retained a large percentage of radioactivity for at least 7 h postlabeling

Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency

DEFF Research Database (Denmark)

Qasim, Waseem; Cavazzana-Calvo, Marina; Davies, E Graham

2009-01-01

OBJECTIVES: Leukocyte adhesion deficiency is a rare primary immune disorder caused by defects of the CD18 beta-integrin molecule on immune cells. The condition usually presents in early infancy and is characterized by deep tissue infections, leukocytosis with impaired formation of pus, and delayed...... of leukocyte adhesion deficiency who underwent hematopoietic stem-cell transplantation between 1993 and 2007 was retrospectively analyzed. Data were collected by the registries of the European Society for Immunodeficiencies/European Group for Blood and Marrow Transplantation, and the Center for International......, with full donor engraftment in 17 cases, mixed multilineage chimerism in 7 patients, and mononuclear cell-restricted chimerism in an additional 3 cases. CONCLUSIONS: Hematopoietic stem-cell transplantation offers long-term benefit in leukocyte adhesion deficiency and should be considered as an early...

SLA mechanism in wireless Mesh network%无线Mesh网络环境下的SLA机制

Institute of Scientific and Technical Information of China (English)

赵耀培; 杨扬

2015-01-01

SLA mechanism in wireless Mesh network was studied .A collision avoidance mechanism based on different service levels in wireless network was presented .The collision avoidance algorithm based on multiple service levels in MAC was de‐signed ,named as multipriority collision avoidance (MPCA) .Considering the data stream with different strategies of SLA ,MP‐CA adopted different retreating algorithms .M PCA supported the transmission of sudden business flow ,and assured the instan‐taneity of business with high service level .The simulation results show that MPCA can effectively improve service quality of cus‐tomers’ perception ,service reliability ,usability and stability .%对无线Mesh网络环境中SLA机制进行研究，建立一套无线Mesh环境下基于不同服务等级的冲突避免机制，在M AC层设计基于多服务等级的冲突避免算法（multipriority collision avoidance ， M PCA ），针对不同SLA策略的数据流采用不同退避算法。该算法支持突发业务流传输，能够保证高服务等级业务的实时性。仿真结果表明， M PC A能有效提高用户感知服务质量、服务可靠性以及可用性和稳定性。

Appearance of acute gouty arthritis on indium-111-labeled leukocyte scintigraphy

International Nuclear Information System (INIS)

Palestro, C.J.; Vega, A.; Kim, C.K.; Swyer, A.J.; Goldsmith, S.J.

1990-01-01

Indium-111-labeled leukocyte scintigraphy was performed on a 66-yr-old male with polyarticular acute gouty arthritis. Images revealed intense labeled leukocyte accumulation in a pattern indistinguishable from septic arthritis, in both knees and ankles, and the metatarsophalangeal joint of both great toes, all of which were involved in the acute gouty attack. Joint aspirate as well as blood cultures were reported as no growth; the patient was treated with intravenous colchicine and ACTH for 10 days with dramatic improvement noted. Labeled leukocyte imaging, repeated 12 days after the initial study, revealed near total resolution of joint abnormalities, concordant with the patient's clinical improvement. This case demonstrates that while acute gouty arthritis is a potential pitfall in labeled leukocyte imaging, in the presence of known gout, it may provide a simple, objective, noninvasive method of evaluating patient response to therapy

In vitro studies of leukocyte labeling with /sup 99m/Tc

International Nuclear Information System (INIS)

Uchida, T.; Vincent, P.C.

1976-01-01

A method for labeling leukocytes in vitro with /sup 99m/Tc is described. Separated leukocytes are incubated with /sup 99m/Tc, followed by reduction with stannous chloride and washing with acid citrate dextrose solution. Maximum labeling occurs after at least 5 min incubation with pertechnetate, followed by at least 10 min incubation with stannous chloride. Labeling is similar at room temperature and at 37 0 C. The labeled leukocytes are viable, and reutilization of label does not occur in vitro. In acid conditions (pH 5.2), the elution of /sup 99m/Tc from leukocytes is comparable with that of 32 P-diisopropylfluorophosphate, but /sup 99m/Tc elution is greater at pH 7.2 to 7.4. Neutrophils label more heavily with /sup 99m/Tc than do monocytes, lymphocytes, erythrocytes, or platelets

Effect of antibiotic therapy on the sensitivity of indium-111-labeled leukocyte scans

International Nuclear Information System (INIS)

Datz, F.L.; Thorne, D.A.

1986-01-01

Although 111 In-labeled leukocytes have been shown to be a useful technique for detecting infection, it has been postulated that antibiotic therapy may reduce the sensitivity of the leukocyte scan. Many patients with suspected bacterial infections are placed on antibiotics before a definite site of infection has been identified. Three hundred twelve leukocyte scans on 271 patients were retrospectively reviewed and classified as positive or negative, and as to whether or not they were being treated with antibiotics at the time the leukocyte scan was performed. The overall sensitivity, considering all 312 studies, was 90%. One hundred sixty-nine patient studies were on patients receiving antibiotics; 143 studies were on patients not on antibiotics. The sensitivity of the leukocyte scan was 88.7% in patients on antibiotic therapy; it was 92.1% in those who were not receiving antibiotics. The differences in sensitivity between the two groups were not significantly different (p less than 0.05). We conclude that antibiotic therapy does not affect the sensitivity of the 111 In-labeled leukocyte scan

Study of terahertz-radiation-induced DNA damage in human blood leukocytes

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Angeluts, A A; Esaulkov, M N; Kosareva, O G; Solyankin, P M; Shkurinov, A P [International Laser Center, M. V. Lomonosov Moscow State University, Moscow (Russian Federation); Gapeyev, A B; Pashovkin, T N [Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region (Russian Federation); Matyunin, S N [Section of Applied Problems at the Presidium of the Russian Academy of Sciences, Moscow (Russian Federation); Nazarov, M M [Institute on Laser and Information Technologies, Russian Academy of Sciences, Shatura, Moscow Region (Russian Federation); Cherkasova, O P [Institute of Laser Physics, Siberian Branch, Russian Academy of Sciences, Novosibirsk (Russian Federation)

2014-03-28

We have carried out the studies aimed at assessing the effect of terahertz radiation on DNA molecules in human blood leukocytes. Genotoxic testing of terahertz radiation was performed in three different oscillation regimes, the blood leukocytes from healthy donors being irradiated for 20 minutes with the mean intensity of 8 – 200 μW cm{sup -2} within the frequency range of 0.1 – 6.5 THz. Using the comet assay it is shown that in the selected regimes such radiation does not induce a direct DNA damage in viable human blood leukocytes. (biophotonics)

Posttransplant chimeric antigen receptor therapy.

Science.gov (United States)

Smith, Melody; Zakrzewski, Johannes; James, Scott; Sadelain, Michel

2018-03-08

Therapeutic T-cell engineering is emerging as a powerful approach to treat refractory hematological malignancies. Its most successful embodiment to date is based on the use of second-generation chimeric antigen receptors (CARs) targeting CD19, a cell surface molecule found in most B-cell leukemias and lymphomas. Remarkable complete remissions have been obtained with autologous T cells expressing CD19 CARs in patients with relapsed, chemo-refractory B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. Allogeneic CAR T cells may also be harnessed to treat relapse after allogeneic hematopoietic stem cell transplantation. However, the use of donor T cells poses unique challenges owing to potential alloreactivity. We review different approaches to mitigate the risk of causing or aggravating graft-versus-host disease (GVHD), including CAR therapies based on donor leukocyte infusion, virus-specific T cells, T-cell receptor-deficient T cells, lymphoid progenitor cells, and regulatory T cells. Advances in CAR design, T-cell selection and gene editing are poised to enable the safe use of allogeneic CAR T cells without incurring GVHD. © 2018 by The American Society of Hematology.

Cytolytic T lymphocyte responses to metabolically inactivated stimulator cells. I. Metabolic inactivation impairs both CD and LD antigen signals

International Nuclear Information System (INIS)

Kelso, A.; Boyle, W.

1982-01-01

The effects of metabolic inactivation of spleen cells on antigen presentation to precursors of alloreactive cytolytic T lymphocytes (T/sub c/) were examined. By serological methods, populations inactivated by ultraviolet irradiation, glutaraldehyde fixation or plasma membrane isolation were found to retain normal levels of H-2K/D and Ia antigens. However, comparison of the antigen doses required to stimulate secondary T/sub c/ responses in mixed leukocyte culture showed that the inactivated preparations were approximately 10-fold less immunogenic than X-irradiated spleen cells. Their total inability to stimulate primary cytolytic responses pointed to at least a 100-fold impairment of immunogenicity for unprimed T/sub c/ precursors in the case of uv-irradiated and glutaraldehyde-treated stimulator cells, and at least a 10-fold impairment for membrane fragments. Experiments showing that the capacity of cell monolayers to absorb precursor T/sub c/ from unprimed spleen populations was reduced following uv-irradiation or glutaraldehyde treatment provided direct evidence that this loss of immunogenicity was due in part to suboptimal antigen presentation to precursor T/sub c/. It is concluded that, in addition to the traditional view that these treatments damage the ''LD'' signal to helper T lymphocytes, metabolic inactivation also impairs recognition of ''CD'' determinants by precursor T/sub c/

Meisoindigo, but not its core chemical structure indirubin, inhibits zebrafish interstitial leukocyte chemotactic migration.

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Ye, Baixin; Xiong, Xiaoxing; Deng, Xu; Gu, Lijuan; Wang, Qiongyu; Zeng, Zhi; Gao, Xiang; Gao, Qingping; Wang, Yueying

2017-12-01

Inflammatory disease is a big threat to human health. Leukocyte chemotactic migration is required for efficient inflammatory response. Inhibition of leukocyte chemotactic migration to the inflammatory site has been shown to provide therapeutic targets for treating inflammatory diseases. Our study was designed to discover effective and safe compounds that can inhibit leukocyte chemotactic migration, thus providing possible novel therapeutic strategy for treating inflammatory diseases. In this study, we used transgenic zebrafish model (Tg:zlyz-EGFP line) to visualize the process of leukocyte chemotactic migration. Then, we used this model to screen the hit compound and evaluate its biological activity on leukocyte chemotactic migration. Furthermore, western blot analysis was performed to evaluate the effect of the hit compound on the AKT or ERK-mediated pathway, which plays an important role in leukocyte chemotactic migration. In this study, using zebrafish-based chemical screening, we identified that the hit compound meisoindigo (25 μM, 50 μM, 75 μM) can significantly inhibit zebrafish leukocyte chemotactic migration in a dose-dependent manner (p = 0.01, p = 0.0006, p migration (p = 0.43). Furthermore, our results unexpectedly showed that indirubin, the core structure of meisoindigo, had no significant effect on zebrafish leukocyte chemotactic migration (p = 0.6001). Additionally, our results revealed that meisoindigo exerts no effect on the Akt or Erk-mediated signalling pathway. Our results suggest that meisoindigo, but not indirubin, is effective for inhibiting leukocyte chemotactic migration, thus providing a potential therapeutic agent for treating inflammatory diseases.

HLA Typing and Histopathologic Features of Patients with Celiac Disease-A Retrospective Study

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Gulay Ceylan

2014-12-01

Full Text Available Aim: Celiac disease is the most common defect of nutrition intolerance. There is an increased sensitivity to the glutene. It is inherited multifactorial, because of this, genetic and enviromental factors are important in the evaluation. The existence of specific human leukocyte antigen alleles coding especially DQ2 and DQ8 are important at the diagnosis of celiac disease. In this study, it is aimed to determine human leukocyte antigens allel distribution for celiac disease in patients with chronic diarrhea, abdominal pain and similar symptomes. Material and Method: The prevalance of human leukocyte antigens of 40 patients applied to our laboratory were searched using polimerase chain reaction-sequence specific primer method. Marsh classification of the patients were also performed by a pathologist. Results: We determined human leukocyte antigens in 95% of the patients. The most common antigens were DQA1*0501 and DQB1*0201. The combination of DQA1*0501 and DRB1*04 was the least. According to Marsh classification, Grade 2 Marsh Type 4 hypoplastic was the most common type. Discussion: The human leukocyte antigen typing is helpful for the clinicians at the progression of the celiac disease and at the prediction of the tendency to the disease.

Bacterial metabolism of human polymorphonuclear leukocyte-derived arachidonic acid.

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Sorrell, T C; Muller, M; Sztelma, K

1992-05-01

Evidence for transcellular bacterial metabolism of phagocyte-derived arachidonic acid was sought by exposing human blood polymorphonuclear leukocytes, prelabelled with [3H]arachidonic acid, to opsonized, stationary-phase Pseudomonas aeruginosa (bacteria-to-phagocyte ratio of 50:1) for 90 min at 37 degrees C. Control leukocytes were stimulated with the calcium ionophore A23187 (5 microM) for 5 min. Radiochromatograms of arachidonic acid metabolites, extracted from A23187-stimulated cultures and then separated by reverse-phase high-performance liquid chromatography, revealed leukotriene B4, its omega-oxidation products, and 5-hydroxy-eicosatetraenoic acid. In contrast, two major metabolite peaks, distinct from known polymorphonuclear leukocyte arachidonic acid products by high-performance liquid chromatography or by thin-layer chromatography, were identified in cultures of P. aeruginosa with [3H]arachidonic acid-labelled polymorphonuclear leukocytes. Respective chromatographic characteristics of these novel products were identical to those of two major metabolite peaks produced by incubation of stationary-phase P. aeruginosa with [3H]arachidonic acid. Production of the metabolites was dependent upon pseudomonal viability. UV spectral data were consistent with a conjugated diene structure. Metabolism of arachidonic acid by P. aeruginosa was not influenced by the presence of catalase, superoxide dismutase, nordihydroguaiaretic acid, ethanol, dimethyl sulfoxide, or ferrous ions but was inhibited by carbon monoxide, ketoconazole, and 1,2-epoxy-3,3,3-trichloropropane. Our data suggest that pseudomonal metabolism of polymorphonuclear leukocyte-derived arachidonic acid occurs during phagocytosis, probably by enzymatic epoxidation and hydroxylation via an oxygenase. By this means, potential proinflammatory effects of arachidonic acid or its metabolites may be modulated by P. aeruginosa at sites of infection in vivo.

Shorter leukocyte telomere length is associated with higher risk of infections

DEFF Research Database (Denmark)

Helby, Jens; Nordestgaard, Børge G; Benfield, Thomas

2017-01-01

In the general population, older age is associated with short leukocyte telomere length and with high risk of infections. In a recent study of allogeneic hematopoietic cell transplantation for severe aplastic anemia, long donor leukocyte telomere length was associated with improved survival...

Use of an Interferon Gamma Release Assay (IGRA) to test T-cell responsiveness to soluble Leishmania infantum antigen in whole blood of dogs from endemic areas.

Science.gov (United States)

Zribi, Lilia; El-Goulli, Amel F; Ben-Abid, Meriem; Gharbi, Mohamed; Ben-Sghaier, Ines; Boufaden, Imed; Aoun, Karim; Bouratbine, Aïda

2017-11-15

Interferon-Gamma (IFN-γ) Release Assays (IGRAs) are easy tests that allow rapid screening of primed memory T-cells immunity in response to antigen. The aim of this study was to use IGRA to assess IFN-γ release in response to Soluble Leishmania infantum antigen (SLA) in whole blood of dogs living in endemic area of visceral leishmaniasis and to interpret IGRA results according to clinical examination, specific anti-Leishmania humoral response and presence of L. infantum DNA in blood. The study was carried out on 56 dogs living in greater Tunis area. Physical examination, quantitative serology and PCR on blood were used to characterize dogs' status in relation to Leishmania infection and disease. IGRA consisted on testing by ELISA for IFN-γ-secretion in whole blood after a 20-h challenge with SLA. PBS and Phytohemagglutinin (PHA) stimulations were used as controls. Four groups of dogs were characterized: 31 were negative by both serology and PCR, two had doubtful serology, 10 presented no to mild clinical signs but low antibodies levels and 13 were affected by Canine Leishmaniasis (CanL). In seronegative dogs, IGRA was little contributory in 4 puppies (age dogs (median age=72months, IQR: 45-84 months) that didn't respond to PHA stimulation, IGRA was negative in 19 and positive in three animals with lymph node enlargement. In dogs with doubtful serology, IGRA was positive in one dog and negative in the other. In infected dogs with no to mild clinical signs, one dog exhibited high level of IFN-γ in absence of antigenic stimulation and all the other were positive by IGRA. CanL dogs showed variable IGRA results. Negative IGRAs (n=4) were shown in animals with the highest parasitic burden whereas positive IGRAs (n=5) were shown in dogs with negative PCR or low parasitic load. The 4 remaining dogs either didn't respond to PHA (n=2) or showed non-specific secretion in PBS tube (n=2). The results of this study showed that IGRA is a useful new tool that can assess

A high-throughput microfluidic approach for 1000-fold leukocyte reduction of platelet-rich plasma

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Xia, Hui; Strachan, Briony C.; Gifford, Sean C.; Shevkoplyas, Sergey S.

2016-10-01

Leukocyte reduction of donated blood products substantially reduces the risk of a number of transfusion-related complications. Current ‘leukoreduction’ filters operate by trapping leukocytes within specialized filtration material, while allowing desired blood components to pass through. However, the continuous release of inflammatory cytokines from the retained leukocytes, as well as the potential for platelet activation and clogging, are significant drawbacks of conventional ‘dead end’ filtration. To address these limitations, here we demonstrate our newly-developed ‘controlled incremental filtration’ (CIF) approach to perform high-throughput microfluidic removal of leukocytes from platelet-rich plasma (PRP) in a continuous flow regime. Leukocytes are separated from platelets within the PRP by progressively syphoning clarified PRP away from the concentrated leukocyte flowstream. Filtrate PRP collected from an optimally-designed CIF device typically showed a ~1000-fold (i.e. 99.9%) reduction in leukocyte concentration, while recovering >80% of the original platelets, at volumetric throughputs of ~1 mL/min. These results suggest that the CIF approach will enable users in many fields to now apply the advantages of microfluidic devices to particle separation, even for applications requiring macroscale flowrates.

Monitoring of benzene-induced hematotoxicity in mice by serial leukocyte counting using a microcavity array.

Science.gov (United States)

Hosokawa, Masahito; Asami, Marie; Yoshino, Tomoko; Tsujimura, Noriyuki; Takahashi, Masayuki; Nakasono, Satoshi; Tanaka, Tsuyoshi; Matsunaga, Tadashi

2013-02-15

Monitoring of hematotoxicity, which requires serial blood collection, is difficult to carry out in small animals due to a lack of non-invasive, individual animal-appropriate techniques that enable enumeration of leukocyte subsets from limited amounts of whole blood. In this study, a microfluidic device equipped with a microcavity array that enables highly efficient separation of leukocytes from submicroliters of whole blood was applied for hematotoxicity monitoring in mice. The microcavity array can specifically separate leukocytes from whole blood based on differences in the size and deformability between leukocytes and other blood cells. Mouse leukocytes recovered on aligned microcavities were continuously processed for image-based immunophenotypic analysis. Our device successfully recovered almost 100% of mouse leukocytes in 0.1 μL of whole blood without the effect of serial blood collection such as changes in body weight and total leukocyte count. We assessed benzene-associated hematotoxicity in mice using this system. Mice were administered with benzene once daily and the depression of leukocyte numbers induced in individual mice was successfully monitored from tail vein blood collected every other day for 2 weeks. Serial monitoring of the leukocyte number in individual mice will contribute to the understanding of hematotoxicity and reduction of the number of animal experiment trials. Copyright © 2012 Elsevier B.V. All rights reserved.

Production of fibrogenic cytokines by interleukin-2-treated peripheral blood leukocytes

DEFF Research Database (Denmark)

Kovacs, E J; Brock, B; Silber, I E

1993-01-01

OBJECTIVE: To assess the production of fibrogenic cytokines by interleukin-2 (IL-2)-stimulated peripheral blood leukocytes and to examine their ability to stimulate the production of connective tissue. METHODS: Culture medium from human peripheral blood leukocytes incubated with or without IL-2 w...

Inhibition of nitric oxide synthesis enhances leukocyte rolling and adhesion in human microvasculature

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Hossain Mokarram

2012-07-01

Full Text Available Abstract Background Nitric oxide (NO is a multifunctional signaling molecule that regulates important cellular events in inflammation including leukocyte recruitment. Previous studies have shown that pharmacological inhibition of NO synthesis induces leukocyte recruitment in various in vitro and animal models. However, it is not known whether NO modulation has similar effects on leukocyte-endothelial cell interactions within the human microvasculature. The present study explored the effect of systemic L-NAME treatment on leukocyte recruitment in the SCID-hu mouse model. Methods Human skin xenografts were transplanted in SCID mice to study human leukocyte dynamics in human vasculature. Early events of human leukocyte recruitment in human vasculature were studied using intravital microscopy. NO synthesis was pharmacologically inhibited using NG-nitro-L-arginine methyl ester (L-NAME. Immunohistochemical analysis was performed to elucidate E-selectin expression in human xenograft skin. Human neutrophil-endothelial cell interactions were also studied in an in vitro flow chamber assay system. P- and E-selectin expression on cultured human umbilical vein endothelial cells (HUVECs was measured using ELISA. Platelet-activating factor (PAF synthesis was detected using a TLC-based assay. Results L-NAME treatment significantly enhanced the rolling and adhesion of human leukocytes to the human vasculature. Functional blocking of P- and E-selectins significantly inhibited rolling but not adhesion induced by inhibition of NO synthesis. Systemic L-NAME treatment enhanced E-selectin expression in human xenograft skin. L-NAME treatment significantly enhanced P- and E-selectin expression on HUVECs. L-NAME treatment did not significantly modify neutrophil rolling or adhesion to HUVECs indicating that L-NAME−induced subtle P- and E-selectin expression was insufficient to elicit dynamic neutrophil-HUVEC interactions in vitro. Moreover, synthesis of endothelial

Uptake of apoptotic leukocytes by synovial lining macrophages inhibits immune complex-mediated arthritis.

Science.gov (United States)

van Lent, P L; Licht, R; Dijkman, H; Holthuysen, A E; Berden, J H; van den Berg, W B

2001-11-01

Previously we have shown that synovial lining macrophages (SLMs) determine the onset of experimental immune complex-mediated arthritis (ICA). During joint inflammation, many leukocytes undergo apoptosis, and removal of leukocytes by SLMs may regulate resolution of inflammation. In this study we investigated binding and uptake of apoptotic leukocytes by SLMs and its impact on the onset of murine experimental arthritis. We used an in vitro model to evaluate phagocytosis of apoptotic cells on chemotaxis. Phagocytosis of apoptotic thymocytes resulted in a significant decrease (58%) of chemotactic activity for polymorphonuclear neutrophils (PMNs). If apoptotic cells were injected directly into a normal murine knee joint, SLMs resulted in a prominent uptake of cells. After ICA induction, electron micrographs showed that apoptotic leukocytes were evidently present in SLMs on days 1 and 2. Injection of apoptotic leukocytes into the knee joint 1 h before induction of ICA significantly inhibited PMN infiltration into the knee joint at 24 h (61% decrease). This study indicates that uptake of apoptotic leukocytes by SLM reduces chemotactic activity and inhibits the onset of experimental arthritis. These findings indicate an important mechanism in the resolution of joint inflammation.

Short fetal leukocyte telomere length and preterm prelabor rupture of the membranes.

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Ramkumar Menon

Full Text Available BACKGROUND: Rupture of the fetal membranes is a common harbinger of imminent labor and delivery. Telomere shortening is a surrogate for oxidative stress (OS and senescence. Fetal leukocyte and placental membrane DNA telomere lengths were evaluated to determine their association with preterm prelabor rupture of the membranes (pPROM or spontaneous preterm births with intact membranes (PTB, compared to term birth. METHODS: Telomere lengths were quantified in cord blood leukocytes (n = 133 from three major groups: 1 pPROM (n = 28, 2 PTB (n = 69 and 3 uncomplicated full term births (controls, n = 35, using real-time quantitative PCR. Placental membrane specimens (n = 18 were used to correlate fetal leukocyte and placental telomere lengths. Telomere length differences among the groups were analyzed by ANOVA. Pearson correlation coefficients determined relationships between leukocyte and placental membrane telomere lengths. RESULTS: In pregnancies with intact membranes, fetal leukocyte telomere length was inversely proportional to gestational age. The mean telomere length decreased as gestation progressed, with the shortest at term. pPROM had telomere lengths (9962 ± 3124 bp that were significantly shorter than gestational age-matched PTB (11546 ± 4348 bp, p = 0.04, but comparable to term births (9011 ± 2497 bp, p = 0.31. Secondary analyses revealed no effects of race (African American vs. Caucasian or intraamniotic infection on telomere length. A strong Pearson's correlation was noted between fetal leukocyte and placental membrane telomere lengths (ρ = 0.77; p<0.01. CONCLUSIONS: Fetal leukocyte telomere length is reduced in pPROM compared to PTB but is similar to term births. pPROM represents a placental membrane disease likely mediated by OS-induced senescence.

Effect of leukocyte hydrolases on bacteria

International Nuclear Information System (INIS)

Cohen, D.; Michel, J.; Ferne, M.; Bergner-Rabinowitz, S.; Ginsburg, I.

1979-01-01

Leukocyte extracts, trypsin, and lysozyme are all capable of releasing the bulk of the LPS from S. typhi, S. typhimurium, and E. coli. Bacteria which have been killed by heat, ultraviolet irradiation, or by a variety of metabolic inhibitors and antibiotics which affect protein, DNA, RNA, and cell wall synthesis no longer yield soluble LPS following treatment with the releasing agents. On the other hand, bacteria which are resistant to certain of the antibiotics yield nearly the full amount of soluble LPS following treatment, suggesting that certain heatabile endogenous metabolic pathways collaborate with the releasing agents in the release of LPS from the bacteria. It is suggested that some of the beneficial effects of antibiotics on infections with gram-negative bacteria may be the prevention of massive release of endotoxin by leukocyte enzymes in inflammatory sites

Total hip and knee replacement surgery results in changes in leukocyte and endothelial markers

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Maclean Kirsty M

2010-01-01

Full Text Available Abstract Background It is estimated that over 8 million people in the United Kingdom suffer from osteoarthritis. These patients may require orthopaedic surgical intervention to help alleviate their clinical condition. Investigations presented here was to test the hypothesis that total hip replacement (THR and total knee replacement (TKR orthopaedic surgery result in changes to leukocyte and endothelial markers thus increasing inflammatory reactions postoperatively. Methods During this 'pilot study', ten test subjects were all scheduled for THR or TKR elective surgery due to osteoarthritis. Leukocyte concentrations were measured using an automated full blood count analyser. Leukocyte CD11b (Mac-1 and CD62L cell surface expression, intracellular production of H2O2 and elastase were measured as markers of leukocyte function. Von Willebrand factor (vWF and soluble intercellular adhesion molecule-1 (sICAM-1 were measured as markers of endothelial activation. Results The results obtained during this study demonstrate that THR and TKR orthopaedic surgery result in similar changes of leukocyte and endothelial markers, suggestive of increased inflammatory reactions postoperatively. Specifically, THR and TKR surgery resulted in a leukocytosis, this being demonstrated by an increase in the total leukocyte concentration following surgery. Evidence of leukocyte activation was demonstrated by a decrease in CD62L expression and an increase in CD11b expression by neutrophils and monocytes respectively. An increase in the intracellular H2O2 production by neutrophils and monocytes and in the leukocyte elastase concentrations was also evident of leukocyte activation following orthopaedic surgery. With respect to endothelial activation, increases in vWF and sICAM-1 concentrations were demonstrated following surgery. Conclusion In general it appeared that most of the leukocyte and endothelial markers measured during these studies peaked between days 1

Association of selected human leukocyte antigen alleles (HLA-DQA1*0102, HLA-DQA1*0103 and HLA–DQB1*0301 with Helicobacter pylori infection among dyspeptic patients

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Piyumali Sandareka Arachchi

2016-11-01

Full Text Available Background: Helicobacter pylori has been identified as a group I carcinogenic bacteria that infect the gastric mucosa leading to gastritis, peptic ulcer disease, lymphoma and gastric cancer. Pathogenesis of H. pylori depends on the virulence of the strain, host immune response and modulating factors like smoking and diet. Objective: This study aimed to assess the association of selected HLA (Human Leukocyte Antigen alleles; HLA-DQA1*0102, HLA-DQA1*0103 and HLA-DQB1*0301, with the presence of H. pylori infection and disease severity among dyspeptic patients. Methods: Gastric tissue samples from 100 dyspeptic patients, who underwent upper gastrointestinal endoscopy at a tertiary care hospital, were collected. Presence of HLA alleles was confirmed using Polymerase Chain Reaction (PCR. H. pylori infection was determined using PCR and Histology. The histological interpretation was done according to the ‘Sydney classification’. Statistical analysis was done with the Statistical Package of Social Sciences (SPSS (version 22; SPSS, Inc., Chicago, Illinois, USA. Results: Respective percentages of HLA-DQA1*0102, HLA-DQA1*0103 and HLA-DQB1*0301 were 39%, 31% and 20%. Of the 25 samples positive for H. pylori infection respectively 56% (14/25, 36% (9/25 and 12% (3/25 were positive for HLA-DQA1*0102, HLA-DQA1*0103 and HLA-DQB1*0301 alleles. Considering the association with H. pylori infection, only HLA-DQA1*0102 showed significant association (p=0.044. No significant association was found between the HLA alleles and the histological severity among the H. pylori infected patients. Conclusion: In conclusion, HLA-DQA1*0102 allele has a significant association with H. pylori infection while HLA-DQA1*0103 and HLA-DQB1*0301 shows no significant association in a Sri Lankan dyspeptic patient population.

Evaluation of possible hip prosthesis infection with In-111 leukocyte scintigraphy

International Nuclear Information System (INIS)

Noto, R.B.; Alavi, A.; Star, A.M.; Cuckler, J.M.; Eisenberg, B.

1987-01-01

To evaluate the utility of In-111 leukocyte scintigraphy in patients with possible hip prosthesis infection, the authors retrospectively reviewed 44 such scans without clinical history. The results of In-111 leukocyte scans were compared with intraoperative cultures obtained at the time of prosthesis revision in 34 patients, with hip aspirates and/or clinical follow-up obtained in the remaining ten patients. This comparison yielded a 71% sensitivity, 78% specificity, and 77% overall accuracy. They conclude that In-111 leukocyte scans can be helpful in the evaluation of suspected hip prosthesis infection, but they are not as accurate as has been previously reported elsewhere

Correlation of 111In-labeled leukocyte scintigraphy with clinical and laboratory findings

International Nuclear Information System (INIS)

Uchida, Yoshitaka; Kitakata, Yuusuke; Uno, Kimiichi; Minoshima, Satoshi; Arimizu, Noboru.

1993-01-01

This study evaluated the relationship between 111 In-labeled leukocyte scintigraphy and clinical information and laboratory findings in 24 patients with bone infection and 35 patients with abdominal infection. Fifty-nine scintigrams were retrospectively reviewed and classified into positive or negative results. As the laboratory findings, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR) at 60 minutes, and peripheral blood leukocyte counts (WBCC) were evaluated. Clinical information such as presence of fever and administration of antibiotics was also compared. No significant relationship between the scintigraphic results and clinical as well as laboratory findings was observed in bone infection patients. CRP levels in positive scintigraphic patients were significantly higher than those in negative scintigraphic patients in the abdominal infection group, otherwise the other indices were not correlated with the scintigraphic results. A few patients with slightly increased CRP (mostly chronic cases) did not show positive scintigrams, suggesting an increased false negative rate of leukocyte scintigraphy in such circumstances. These results suggest that it is inappropriate to determine the application of leukocyte scintigraphy depending on clinical as well as laboratory findings, and leukocyte scintigraphy would yield additional information different from other indices when evaluating inflammatory foci. (author)

Comprehensive evaluation of leukocyte lineage derived from human hematopoietic cells in humanized mice.

Science.gov (United States)

Takahashi, Masayuki; Tsujimura, Noriyuki; Otsuka, Kensuke; Yoshino, Tomoko; Mori, Tetsushi; Matsunaga, Tadashi; Nakasono, Satoshi

2012-04-01

Recently, humanized animals whereby a part of the animal is biologically engineered using human genes or cells have been utilized to overcome interspecific differences. Herein, we analyzed the detail of the differentiation states of various human leukocyte subpopulations in humanized mouse and evaluated comprehensively the similarity of the leukocyte lineage between humanized mice and humans. Humanized mice were established by transplanting human CD34(+) cord blood cells into irradiated severely immunodeficient NOD/Shi-scid/IL2Rγ(null) (NOG) mice, and the phenotypes of human cells contained in bone marrow, thymus, spleen and peripheral blood from the mice were analyzed at monthly intervals until 4 months after cell transplantation. The analysis revealed that transplanted human hematopoietic stem cells via the caudal vein homed and engrafted themselves successfully at the mouse bone marrow. Subsequently, the differentiated leukocytes migrated to the various tissues. Almost all of the leukocytes within the thymus were human cells. Furthermore, analysis of the differentiation states of human leukocytes in various tissues and organs indicated that it is highly likely that the human-like leukocyte lineage can be developed in mice. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Dark chocolate consumption improves leukocyte adhesion factors and vascular function in overweight men.

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Esser, Diederik; Mars, Monica; Oosterink, Els; Stalmach, Angelique; Müller, Michael; Afman, Lydia A

2014-03-01

Flavanol-enriched chocolate consumption increases endothelium-dependent vasodilation. Most research so far has focused on flow-mediated dilation (FMD) only; the effects on other factors relevant to endothelial health, such as inflammation and leukocyte adhesion, have hardly been addressed. We investigated whether consumption of regular dark chocolate also affects other markers of endothelial health, and whether chocolate enrichment with flavanols has additional benefits. In a randomized double-blind crossover study, the effects of acute and of 4 wk daily consumption of high flavanol chocolate (HFC) and normal flavanol chocolate (NFC) on FMD, augmentation index (AIX), leukocyte count, plasma cytokines, and leukocyte cell surface molecules in overweight men (age 45-70 yr) were investigated. Sensory profiles and motivation scores to eat chocolate were also collected. Findings showed that a 4 wk chocolate intake increased FMD by 1%, which was paralleled by a decreased AIX of 1%, decreased leukocyte cell count, decreased plasma sICAM1 and sICAM3, and decreased leukocyte adhesion marker expression (Peffect), with no difference between HFC and NFC consumption. Flavanol enrichment did affect taste and negatively affected motivation to consume chocolate. This study provides new insights on how chocolate affects endothelial health by demonstrating that chocolate consumption, besides improving vascular function, also lowers the adherence capacity of leukocytes in the circulation.

The hemostatic agent ethamsylate promotes platelet/leukocyte aggregate formation in a model of vascular injury.

Science.gov (United States)

Hernandez, Maria Rosa; Alvarez-Guerra, Miriam; Escolar, Ginés; Chiavaroli, Carlo; Hannaert, Patrick; Garay, Ricardo P

2004-08-01

The hemostatic agent ethamsylate enhances membrane expression of P-selectin in human platelets, but whether this promotes platelet-leukocyte aggregate formation is unknown. Here we investigated this point by flow cytometry determination of human platelet-leukocyte aggregates under basal conditions and after whole-blood perfusion through a damaged rabbit aorta segment. Actions of ethamsylate on adhesive molecules of platelets and leukocytes were investigated in parallel. Under basal conditions, ethamsylate was unable to modify whole-blood platelet-leukocyte aggregation, but following whole-blood perfusion through a damaged vessel, ethamsylate produced a modest, but significant increase in platelet-leukocyte aggregates (48+/-21 and 45+/-26% above control levels at ethamsylate 20 and 40 microm respectively). In isolated leukocyte plasma membranes, 14C-ethamsylate specifically bound up to an amount of 660 pmol/mg protein. Moreover, at concentrations > or =1 microm, ethamsylate induced an important (100-200%) and significant increase in the P-selectin glycoprotein ligand 1 (PSGL-1) fluorescence signal in isolated leukocytes and was unable to significantly modify the percentage of CD11b-positive cells. However, no significant changes in aggregate formation were found when ethamsylate was incubated with isolated leukocytes and blood was reconstituted and perfused. In isolated platelet cell membranes, anti-P-selectin antibody and the anti-integrin RGD-containing pentapeptide (GRDGS) were unable to displace 14C-ethamsylate binding. In conclusion, ethamsylate specifically binds to plasma membranes of leukocytes, enhances membrane PSGL-1 expression and promotes leukocyte-platelet aggregation in whole-blood perfused through a damaged vascular segment. These results together with the previously observed enhancement of platelet P-selectin membrane expression [Thromb. Res. (2002)107:329-335] confirms and extends the view that ethamsylate acts on the first step of hemostasis, by

Technetium-99m HMPAO labeled leukocytes in inflammation imaging

International Nuclear Information System (INIS)

Uno, Kimiichi; Yoshikawa, Kyousan; Imazeki, Keiko; Minoshima, Satoshi; Arimizu, Noboru

1991-01-01

Technetium-99m-HMPAO (Tc-99m-HMPAO) labeled leukocyte imaging was carried out in 19 patients at 3-5 hr after reinjection. There were no side effects noted. Tc-99m leukocyte images showed gall bladder, colon, kidney, and urinary bladder activity in normal distribution as a result of excretion of the eluted Tc-99m complex. They yielded a sensitivity of 93%, a specificity of 100% and an accuracy of 95%. They were correctly positive in 14 out of 19 cases. But one false negative case was seen in a patient with pyonephrosis showing a lack of renal function with decreased renal blood flow. It was concluded that they have some advantages over In-111 leukocyte images, but we have to consider the fact that the ureteral obstruction or the lack of renal function with decreased renal blood flow may result in a false positive or a false negative case. (author)

Detection of acute synthetic vascular graft infection with IN-111 labeled leukocyte imaging

International Nuclear Information System (INIS)

Alazraki, N.; Dries, D.; Lawrence, P.; Murphy, K.; Kercher, J.; Datz, F.; Christian, P.; Taylor, A.

1985-01-01

Synthetic vascular graft infection is characterized by late diagnosis due to indolent and nonspecific symptoms. Reported data on accuracy of In-111 labeled leukocyte imaging to identify vascular graft infection is sparse and conflicting. The purpose of this animal study was to clarify the accuracy of detection of early graft infection using a mixed population of In-111 labeled leukocytes. Twelve mongrel dogs received dacron aortic interposition grafts. Seven grafts were contaminated at surgery by topical ATCC S. aureus, 10/sup 8/ organisms per ml. Six control animals received no graft contamination Mixed population In-111 homologous leukocyte labeling was performed followed by imaging at 24 and 48 hours following intravenous injection of 250 μCi In-111 leukocytes. Scans were done on Day 2 post-surgery. Infected dogs were sacrificed following Indium imaging; control dogs were rescanned at 3 weeks postop and sacrificed thereafter. Autopsy results were correlated with scans, yielding sensitivity 71%, specificity 100%, accuracy 85% for In-111 leukocyte imaging to detect early graft infection. False positive leukocyte imaging in the early postop period was not a problem. At autopsy all 5 dogs with infected grafts and positive scans had gross pus. The 2 dogs with false negative scans showed no gross pus at autopsy; cultures were positive for S. aureus in all 7 dogs. Scans at 2 days and 3 weeks post-surgery were true negatives in all 6 control dogs. These data suggest a high level of clinical reliability of leukocyte imaging for early graft infection detection

Towards understanding the impact of assimilating along-track SLA data on simulated eddy characteristics in the Agulhas System

CSIR Research Space (South Africa)

De Vos, M

2016-10-01

Full Text Available understanding the impact of assimilating along-track SLA data on simulated eddy characteristics in the Agulhas System Marc de Vos1, 3, Björn Backeberg2, 3, 4 and François Counillon4 Marine Research Unit, South African Weather Service, South Africa1 Coastal... and 1 Tel: +27 21 935 5764; Email: marc.devos@weathersa.co.za dipoles reach the Agulhas Current frequently and on occasion propagate all the way to the retroflection, influencing its position and modulating ring shedding events there (Schouten et al...

Identification of a second putative receptor of platelet activating factor on human polymorphonuclear leukocytes

International Nuclear Information System (INIS)

Hwang, S.B.

1987-01-01

Due to multiple molecular species of platelet activating factor (PAF) and the existence of high affinity binding sites in a variety of cells and tissues, possible existence of PAF receptor subtypes has been suggested. This report shows differences between specific PAF receptors on human leukocytes and platelets. Human PMN leukocyte membranes showed high affinity binding sites for PAF with an equilibrium dissociation constant (Kd) of 4.7 (+/- 1.4) x 10 -10 M. The maximal number (B/sub max/) of receptor sites was estimated to be 3.13 (+/- 1.4) x 10 -13 mol/mg protein. They compared the relative potencies of several PAF agonists and receptor antagonists between human platelet and human leukocyte membranes. One antagonist (Ono-6240) was found to be 8 times less potent at inhibiting the [ 3 H]PAF specific receptor binding to human leukocytes than to human platelets. Mg 2+ , Ca 2+ and K + ions potentiated the [ 3 H]PAF specific binding in both systems. Na + ions inhibited the [ 3 H]PAF specific binding to human platelets but showed no effects in human leukocytes. K + ions decreased the Mg 2+ -potentiated [ 3 H]PAF binding in human leukocytes but showed no effects in human platelets. These results suggest that the PAF specific receptors in human leukocytes are different structurally and possibly functionally from the receptors identified in human platelets

Colonic localization of indium-111 labeled leukocytes in active Behcet's disease

International Nuclear Information System (INIS)

Harre, R.G.; Conrad, G.R.; Seabold, J.E.

1988-01-01

A patient with known Behcet's disease demonstrated intense colonic localization of In-111 labeled leukocytes. Gastrointestinal involvement had not been previously manifested, but extensive colonic inflammation was documented by endoscopy. This case illustrates the utility of In-111 labeled leukocyte imaging for detecting active bowel disease in a debilitated patient with documented Behcet's vasculitis

Use of 99mTc-Mononuclear Leukocyte Scintigraphy in Nosocomial Fever

International Nuclear Information System (INIS)

Gutfilen, B.; Lopes de Souza, S.A.; Martins, F.P.P.; Cardoso, L.R.; Pinheiro Pessoa, M.C.; Fonseca, L.M.B.

2006-01-01

Purpose: To determine the overall diagnostic accuracy of mononuclear leukocyte- 99m Tc scintigraphy in the routine detection of infectious lesions and fever of unknown origin (FUO) in inpatients. Material and Methods: The use of mononuclear leukocyte 99m Tc scintigraphy is presented in 87 patients who fulfilled the Durack and Street diagnostic criteria of nosocomial FUO; 66 patients were suspected of having infectious lesions (myocarditis, endocarditis, infected catheters, diabetic foot, and osteomyelitis) and 21 patients presented with unknown causes of FUO. Scans were carried out 1, 3, and 24 h after injection of labeled leukocytes. Results: In three cases (3/27) where scintigraphs were negative, biopsies were positive. There were two (2/87) false-positive scintigrams. We found a 95.8% sensitivity and 92.3% specificity. PPV was 93.8%, PPN 94.7%, and accuracy 94.2%. Conclusion: Mononuclear leukocyte 99m Tc scintigraphy showed high sensitivity, specificity, positive and negative predictive values in patients with nosocomial FUO. These results suggest an important role for nuclear medicine in the management of patients with infection/inflammation

Subacute Low Dose Nerve Agent Exposure Causes DNA Fragmentation in Guinea Pig Leukocytes

Science.gov (United States)

2005-10-01

1 SUBACUTE LOW DOSE NERVE AGENT EXPOSURE CAUSES DNA FRAGMENTATION IN GUINEA PIG LEUKOCYTES. Jitendra R. Dave1, John R. Moffett1, Sally M...DNA fragmentation in blood leukocytes from guinea pigs by ‘Comet’ assay after exposure to soman at doses ranging from 0.1LD50 to 0.4 LD50, once per...computer. Data obtained for exposure to soman demonstrated significant increases in DNA fragmentation in circulating leukocytes in CWNA treated guinea pigs as

Evaluation of polyacrylonitrile electrospun nano-fibrous mats as leukocyte removal filter media.

Science.gov (United States)

Pourbaghi, Raha; Zarrebini, Mohammad; Semnani, Dariush; Pourazar, Abbasali; Akbari, Nahid; Shamsfar, Reihaneh

2017-09-13

Removal of leukocytes from blood products is the most effective means for elimination of undesirable side effects and prevention of possible reactions in recipients. Micro-fibrous mats are currently used for removal of leukocytes from blood. In this study, samples of electrospun nano-fibrous mats were produced. The performance of the produced electrospun nano-fibrous mats as means of leukocytes removal from fresh whole blood was both evaluated and compared with that of commercially available micro-fibrous mats. In order to produce the samples, polyacrylonitrile (PAN) nano-fibrous mats were made under different electrospinning conditions. Mean fiber diameter, pore characterization and surface roughness of the PAN nano-fibrous mats were determined using image processing technique. In order to evaluate the surface tension of the fabricated mats, water contact angle was measured. The leukocyte removal performance, erythrocytes recovery percent and hemolysis rate of the nano-fibrous mats were compared. The effectiveness of nano-fibrous mats in removing leukocyte was established using both scanning electron microscope and optical microscope. Results showed that for given weight, the fabricated nano-fibrous mats were not only more efficient but also more cost-effective than their commercial counterparts. Results confirmed that changes in mean fiber diameter, the number of layer and weight of each layer in the absence of any chemical reaction or physical surface modification, the fabricated nano-fibrous mats were able to remove 5-log of leukocytes. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

Development of a T7 Phage Display Library to Detect Sarcoidosis and Tuberculosis by a Panel of Novel Antigens

Directory of Open Access Journals (Sweden)

Harvinder Talwar

2015-04-01

Full Text Available Sarcoidosis is a granulomatous inflammatory disease, diagnosed through tissue biopsy of involved organs in the absence of other causes such as tuberculosis (TB. No specific serologic test is available to diagnose and differentiate sarcoidosis from TB. Using a high throughput method, we developed a T7 phage display cDNA library derived from mRNA isolated from bronchoalveolar lavage (BAL cells and leukocytes of sarcoidosis patients. This complex cDNA library was biopanned to obtain 1152 potential sarcoidosis antigens and a microarray was constructed to immunoscreen two different sets of sera from healthy controls and sarcoidosis. Meta-analysis identified 259 discriminating sarcoidosis antigens, and multivariate analysis identified 32 antigens with a sensitivity of 89% and a specificity of 83% to classify sarcoidosis from healthy controls. Additionally, interrogating the same microarray platform with sera from subjects with TB, we identified 50 clones that distinguish between TB, sarcoidosis and healthy controls. The top 10 sarcoidosis and TB specific clones were sequenced and homologies were searched in the public database revealing unique epitopes and mimotopes in each group. Here, we show for the first time that immunoscreenings of a library derived from sarcoidosis tissue differentiates between sarcoidosis and tuberculosis antigens. These novel biomarkers can improve diagnosis of sarcoidosis and TB, and may aid to develop or evaluate a TB vaccine.

Autoantibodies in Autoimmune Hepatitis.

Science.gov (United States)

Muratori, Luigi; Deleonardi, Gaia; Lalanne, Claudine; Barbato, Erica; Tovoli, Alessandra; Libra, Alessia; Lenzi, Marco; Cassani, Fabio; Muratori, Paolo

2015-01-01

The detection of diagnostic autoantibodies such as antinuclear antibodies (ANA), anti-smooth muscle antibodies (SMA), anti-liver/kidney microsomal type 1 (anti-LKM1), anti-liver cytosol type 1 (anti-LC1) and anti-soluble liver antigen (anti-SLA) is historically associated with the diagnosis of autoimmune hepatitis. When autoimmune hepatitis is suspected, the detection of one or any combination of diagnostic autoantibodies, by indirect immunofluorescence or immuno-enzymatic techniques with recombinant antigens, is a pivotal step to reach a diagnostic score of probable or definite autoimmune hepatitis. Diagnostic autoantibodies (ANA, SMA, anti-LKM1, anti-LC1, anti-SLA) are a cornerstone in the diagnosis of autoimmune hepatitis. Other ancillary autoantibodies, associated with peculiar clinical correlations, appear to be assay-dependent and institution-specific, and validation studies are needed. © 2015 S. Karger AG, Basel.

Leukocyte Reference Intervals for Free-Ranging Hummingbirds in Northern California.

Science.gov (United States)

Safra, Noa; Christopher, Mary M; Ernest, Holly B; Bandivadekar, Ruta; Tell, Lisa A

2018-04-04

  Hummingbirds are specialized nectarivores and important ecological pollinators that are the focus of conservation efforts as well as scientific investigations of metabolism and flight dynamics. Despite their importance, basic information is lacking about hummingbird blood cells. We aimed to establish reference intervals for total and differential leukocyte counts from healthy free-ranging hummingbirds in northern California. Hummingbirds were captured in five counties in spring and summer of 2012. A drop of blood was used to prepare smears for total white blood cell estimate and 200-cell differential leukocyte counts. Reference Value Advisor was used for descriptive statistics and calculation of reference intervals. Blood smears from 42 Anna's Hummingbirds ( Calypte anna) and 33 Black-chinned Hummingbirds ( Archilochus alexandri) were included. The only significant differences in leukocyte counts were due to age, and juvenile hummingbirds had significantly higher lymphocyte counts than adult hummingbirds ( Phummingbirds.

Exposure to Sodium Fluoride Produces Signs of Apoptosis in Rat Leukocytes

Directory of Open Access Journals (Sweden)

Sigrit Suástegui-Domínguez

2010-09-01

Full Text Available Fluoride is naturally present in the earth's crust and can be found in rocks, coal, and clay; thus, it can be found in small quantities in water, air, plants, and animals. Therefore, humans are exposed to fluoride through food, drinking water, and in the air they breathe. Flouride is essential to maintain bone strength and to protect against dental decay, but if it is absorbed too frequently, it can cause tooth decay, osteoporosis, and damage to kidneys, bones, nerves, and muscles. Therefore, the present work was aimed at determining the effect of intake of sodium fluoride (NaF as an apoptosis inducer in leukocytes of rats treated for eight weeks with 1 or 50 parts per million (ppm NaF. Expression of p53, bcl-2, and caspade-3 were used as apoptotic and general metabolism indicators of leukocyte-like indicators of the (INT oxidation system. Male rats were exposed to NaF (1 and 500 ppm for eight weeks, and then sacrificed weekly to obtain blood samples. Expression of p53, bcl-2, and caspase-3 were determined in leukocytes by Western blot, and general metabolism of leukocytes was analyzed with a commercial kit. We found changes in the expression of the proteins described, especially when the animals received 50 ppm of NaF. These results indicate that NaF intoxication can be an apoptosis inducer in rat leukocytes treated with the compound for eight weeks.

Measurement of leukocyte rheology in vascular disease: clinical rationale and methodology. International Society of Clinical Hemorheology.

Science.gov (United States)

Wautier, J L; Schmid-Schönbein, G W; Nash, G B

1999-01-01

The measurement of leukocyte rheology in vascular disease is a recent development with a wide range of new opportunities. The International Society of Clinical Hemorheology has asked an expert panel to propose guidelines for the investigation of leukocyte rheology in clinical situations. This article first discusses the mechanical, adhesive and related functional properties of leukocytes (especially neutrophils) which influence their circulation, and establishes the rationale for clinically-related measurements of parameters which describe them. It is concluded that quantitation of leukocyte adhesion molecules, and of their endothelial receptors may assist understanding of leukocyte behaviour in vascular disease, along with measurements of flow resistance of leukocytes, free radical production, degranulation and gene expression. For instance, vascular cell adhesion molecule (VCAM-1) is abnormally present on endothelial cells in atherosclerosis, diabetes mellitus and inflammatory conditions. Soluble forms of intercellular adhesion molecule (ICAM-1) or VCAM can be found elevated in the blood of patients with rheumatoid arthritis or infections disease. In the second part of the article, possible technical approaches are presented and possible avenues for leukocyte rheological investigations are discussed.

Detection of occult abscesses with 111In-labeled leukocytes

International Nuclear Information System (INIS)

Martin, W.R.; Gurevich, N.; Goris, M.L.; McDougall, I.R.

1979-01-01

Clinicians are frequently faced with the problem of a patient in whom they suspect an occult abscess. In such a situation, there may be no clinical signs to localize the site of the abscess and often extensive investigations do not provide additional useful information. This report illustrates the efficacy of autologous leukocytes labeled with 111 In oxine in detecting the site and extent of occult abscesses in two patients. The technique of in vitro lebeling of leukocytes is simple and has been mastered by all of our nuclear medicine technologists

Analysis of leukocyte binding to depletion filters: role of passive binding, interaction with platelets, and plasma components.

Science.gov (United States)

Henschler, R; Rüster, B; Steimle, A; Hansmann, H L; Walker, W; Montag, T; Seifried, E

2005-08-01

Since limited knowledge exists on the mechanisms which regulate cell binding to leukocyte removal filter surfaces, we investigated the binding patterns of leukocytes to individual layers of leukocyte depletion filters. After passage of 1 unit of whole blood, blotting of isolated filter layers on glass slides or elution of cells from filter layers revealed that most leukocytes were located within the first 10 of a total of 28 filter layers, peaking at layers 6 to 8, with granulocytes binding on average to earlier filter layers than lymphocytes. Leukocytes preincubated with inhibitors of actin activation showed unchanged distribution between filter layers, suggesting that cytoskeletal activation does not significantly contribute to their binding. When leukocytes were directly incubated with single filter layers, binding of up to 30% of input cells was recorded in the absence of Ca(2+). Immunohistological analyses showed colocalization of platelets and leukocytes, with co-clustering of platelets and leukocytes. Monocytes and to some degree lymphocytes but not granulocytes competed with platelets for filter binding. Precoating of filter layers with individual plasma components showed that hyaluronic acid, plasma type fibronectin, and fibrinogen all increased the binding of leukocytes compared with albumin coating. In conclusion, leukocytes can bind passively to filters in a process which does not require Ca(2+), which is independent of cytoskeletal activation and which may depend on individual plasma components. These results are of importance when new selective cell enrichment or depletion strategies through specific filters are envisaged.

Comparison of Plasmagel with LeucoPREP-Macrodex methods for separation of leukocytes for virus isolation.

Science.gov (United States)

Woods, G L; Proffitt, M R

1987-10-01

Plasmagel (Cellular Products, Inc., Buffalo, NY), which can separate both polymorphonuclear leukocytes (PMN) and mononuclear cells from other blood components, and LeucoPREP (Becton Dickinson Immunocytometry Systems, Mountain View, CA), which can separate mononuclear cells from other blood components, were used to harvest leukocytes from whole blood for the purpose of virus isolation. Macrodex was combined with the later, in a second step, for recovery of PMN. Of 90 peripheral blood specimens examined, cytomegalovirus was recovered from 10: in six by both methods, in three from Plasmagel prepared cells only, and in one from cells from the LeucoPREP-Macrodex preparation only. Total leukocyte counts, differential counts, and leukocyte viability did not differ significantly for the two methods. Plasmagel provided an efficient, inexpensive means of harvesting leukocytes from whole blood for virus isolation.

NOG-hIL-4-Tg, a new humanized mouse model for producing tumor antigen-specific IgG antibody by peptide vaccination.

Directory of Open Access Journals (Sweden)

Yoshie Kametani

Full Text Available Immunodeficient mice transplanted with human peripheral blood mononuclear cells (PBMCs are promising tools to evaluate human immune responses to vaccines. However, these mice usually develop severe graft-versus-host disease (GVHD, which makes estimation of antigen-specific IgG production after antigen immunization difficult. To evaluate antigen-specific IgG responses in PBMC-transplanted immunodeficient mice, we developed a novel NOD/Shi-scid-IL2rγnull (NOG mouse strain that systemically expresses the human IL-4 gene (NOG-hIL-4-Tg. After human PBMC transplantation, GVHD symptoms were significantly suppressed in NOG-hIL-4-Tg compared to conventional NOG mice. In kinetic analyses of human leukocytes, long-term engraftment of human T cells has been observed in peripheral blood of NOG-hIL-4-Tg, followed by dominant CD4+ T rather than CD8+ T cell proliferation. Furthermore, these CD4+ T cells shifted to type 2 helper (Th2 cells, resulting in long-term suppression of GVHD. Most of the human B cells detected in the transplanted mice had a plasmablast phenotype. Vaccination with HER2 multiple antigen peptide (CH401MAP or keyhole limpet hemocyanin (KLH successfully induced antigen-specific IgG production in PBMC-transplanted NOG-hIL-4-Tg. The HLA haplotype of donor PBMCs might not be relevant to the antibody secretion ability after immunization. These results suggest that the human PBMC-transplanted NOG-hIL-4-Tg mouse is an effective tool to evaluate the production of antigen-specific IgG antibodies.

Inhibition of leukocyte-type 12-lipoxygenase by guava tea leaves prevents development of atherosclerosis.

Science.gov (United States)

Takahashi, Yoshitaka; Otsuki, Akemi; Mori, Yoshiko; Kawakami, Yuki; Ito, Hideyuki

2015-11-01

Oxidation of low-density lipoprotein (LDL) is one of the crucial steps for atherosclerosis development, and an essential role of leukocyte-type 12-lipoxygenase expressed in macrophages in this process has been demonstrated. The biochemical mechanism of the oxidation of circulating LDL by leukocyte-type 12-lipoxygenase in macrophages has been proposed. The major ingredients in guava tea leaves which inhibited the catalytic activity of leukocyte-type 12-lipoxygenase were quercetin and ethyl gallate. Administration of extracts from guava tea leaves to apoE-deficient mice significantly attenuated atherogenic lesions in the aorta and aortic sinus. We recently showed that Qing Shan Lu Shui inhibited the catalytic activity of leukocyte-type 12-lipoxygenase. The major components inhibiting the enzyme contained in Qing Shan Lu Shui were identified to be novel monoterpene glycosides. The anti-atherogenic effect of the tea leaves might be attributed to the inhibition of leukocyte-type 12-lipoxygenase by these components. Copyright © 2015 Elsevier Ltd. All rights reserved.

Carcinoma-associated antigens

International Nuclear Information System (INIS)

Bartorelli, A.; Accinni, R.

1981-01-01

This invention relates to novel antigens associated with breast carcinoma, anti-sera specific to said antigens, 125 I-labeled forms of said antigens and methods of detecting said antigens in serum or plasma. The invention also relates to a diagnostic kit containing standardised antigens or antisera or marked forms thereof for the detection of said antigens in human blood, serum or plasma. (author)

High resolution human leukocyte antigen (HLA) class I and class II allele typing in Mexican mestizo women with sporadic breast cancer: case-control study

International Nuclear Information System (INIS)

Cantú de León, David; Yu, Neng; Yunis, Edmond J; Granados, Julio; Pérez-Montiel, Delia; Villavicencio, Verónica; Carranca, Alejandro García; Betancourt, Alejandro Mohar; Acuña-Alonzo, Victor; López-Tello, Alberto; Vargas-Alarcón, Gilberto; Barquera, Rodrigo

2009-01-01

The development of breast cancer is multifactorial. Hormonal, environmental factors and genetic predisposition, among others, could interact in the presentation of breast carcinoma. Human leukocyte antigen (HLA) alleles play an important role in immunity (cellular immunity) and may be important genetic traits. HLAAllele-specific interaction has not been well established. Recently, several studies had been conducted in order to do so, but the results are controversial and in some instances contradictory. We designed a case-control study to quantify the association of HLA class I and II genes and breast cancer. HLA typing was performed by high resolution sequence-specific oligotyping after DNA amplification (PCR-SSOP) of 100 breast cancer Mexican mestizo patients and 99 matched healthy controls. HLA-A frequencies that we were able to observe that there was no difference between both groups from the statistical viewpoint. HLA-B*1501 was found three times more common in the case group (OR, 3.714; p = 0.031). HLA-Cw is not a marker neither for risk, nor protection for the disease, because we did not find significant statistical differences between the two groups. DRB1*1301, which is expressed in seven cases and in only one control, observing an risk increase of up to seven times and DRB1*1602, which behaves similarly in being present solely in the cases (OR, 16.701; 95% CI, 0.947 – 294.670). DQ*0301-allele expression, which is much more common in the control group and could be protective for the presentation of the disease (OR, 0.078; 95% CI, 0.027–0.223, p = 0.00001). Our results reveal the role of the MHC genes in the pathophysiology of breast cancer, suggesting that in the development of breast cancer exists a disorder of immune regulation. The triggering factor seems to be restricted to certain ethnic groups and certain geographical regions since the relevant MHC alleles are highly diverse. This is the first study in Mexican population where high resolutions HLA

Peripheral blood film review. The demise of the eyecount leukocyte differential.

Science.gov (United States)

Pierre, Robert V

2002-03-01

initiate blood film review based on findings of the CBC and automated differential is a more sensitive and accurate method of detecting patients with blood film abnormalities than routine blood film review of all specimens by technologists. Clinicians need to recognize that daily differential results or differentials at intervals of less than a week are not medically necessary in most patients. The laboratory, however, must provide opportunities for the clinician to request differentials at any time for specific medical reasons. The laboratory must establish the validity of screening criteria for detection of distribution and morphologic abnormalities of leukocytes by clinical correlation studies or adopt criteria established by laboratories with the same instrumentation and which have conducted clinical evaluations. A final observation on the eyecount differential is that it was the only way to identify cell types and their relative proportion for nearly 100 years. Cells were identified by their shape, intracellular structures, and staining characteristics. Many studies were able eventually to correlate some aspect of each cell type's function with their morphologic appearance. It has also been learned that the bone marrow is the source of production of most circulating cells and a great deal of the controls of cell production and release into the peripheral blood have been learned. But leukocytes have many functions, almost none of which are performed in the peripheral blood. The peripheral blood is mainly a conduit from the bone marrow to the tissues where the leukocytes perform their function in the case of the neutrophils and monocytes. It is mainly a recirculation and redistribution system for lymphocytes that usually receive their instructions from antigen processing cells in the tissues and allow these modified cells to home to sites where their functions occur. Cellular morphology and staining characteristics tell little about the maturation stage and functional

Immunity to tumour antigens.

Science.gov (United States)

Li, Geng; Ali, Selman A; McArdle, Stephanie E B; Mian, Shahid; Ahmad, Murrium; Miles, Amanda; Rees, Robert C

2005-01-01

During the last decade, a large number of human tumour antigens have been identified. These antigens are classified as tumour-specific shared antigens, tissue-specific differentiation antigens, overexpressed antigens, tumour antigens resulting from mutations, viral antigens and fusion proteins. Antigens recognised by effectors of immune system are potential targets for antigen-specific cancer immunotherapy. However, most tumour antigens are self-proteins and are generally of low immunogenicity and the immune response elicited towards these tumour antigens is not always effective. Strategies to induce and enhance the tumour antigen-specific response are needed. This review will summarise the approaches to discovery of tumour antigens, the current status of tumour antigens, and their potential application to cancer treatment.

Healthy lifestyle and leukocyte telomere length in U.S. women.

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Qi Sun

Full Text Available Whether a healthy lifestyle may be associated with longer telomere length is largely unknown.To examine healthy lifestyle practices, which are primary prevention measures against major age-related chronic diseases, in relation to leukocyte telomere length.Cross-sectional analysis in the Nurses' Health Study (NHS.The population consisted of 5,862 women who participated in multiple prospective case-control studies within the NHS cohort. Z scores of leukocyte telomere length were derived within each case-control study. Based on prior work, we defined low-risk or healthy categories for five major modifiable factors assessed in 1988 or 1990: non-current smoking, maintaining a healthy body weight (body mass index in 18.5-24.9 kg/m(2, engaging in regular moderate or vigorous physical activities (≥150 minutes/week, drinking alcohol in moderation (1 drink/week to <2 drinks/day, and eating a healthy diet (Alternate Healthy Eating Index score in top 50%. We calculated difference (% of the z scores contrasting low-risk groups with reference groups to evaluate the association of interest.Although none of the individual low-risk factors was significantly associated with larger leukocyte telomere length z scores, we observed a significant, positive relationship between the number of low-risk factors and the z scores. In comparison with women who had zero low-risk factors (1.9% of the total population and were, therefore, considered the least healthy group, the leukocyte telomere length z scores were 16.4%, 22.1%, 28.7%, 22.6%, and 31.2% (P for trend = 0.015 higher for women who had 1 to 5 low-risk factors, respectively.Adherence to a healthy lifestyle, defined by major modifiable risk factors, was associated with longer telomere length in leukocytes.

IMMUNITY STATE IN THE OFFSPRING OF RATS EXPOSED ANTIGENS TOXOPLASMA GONDII

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T. F. Sokolova

2014-01-01

Full Text Available Today the questions about possibility of development disturbances in the immune system of the fetus and the newborn in chronic toxoplasmosis are poorly understood. Aim of research: to detect immunological disturbances in the offspring of rats which have been administered antigens T. gondii.Two series of experiments was performed. In these experiments white female Wistar rats in the III trimester of pregnancy have been administered corpuscular antigen T. gondii. The 60 days-old offspring of these rats have been included in study group of 137 animals. CD3+ cells count was performed in peripherical blood and standard suspension of splenocytesrats offspring. Peripherical blood cells count was performed in the blood of the rats offspring. In the second experiment rats offspring have been administered sheep erythrocytes in 5 days, before euthanasia. In spleen of this rats antigen-produced cells was counted.In control group was included 118 animals, which was born from white female Wistar rats have been administered 0,9% NaCl solution. CD3+ cells was detected in Cytomics FC500 flow cytometry analyzer (Beckman Coulter,USA by use rats origne-specifed monoclonal antibodies Anti-Rat CD3-FITC (Beckman Coulter,USA. Hematological parameters was assessed by use hematological analyzer Excell-22 (USA.We observed, that CD3+ lymphocytes and antigen-produced cells was decreased in test group (degress of decrease CD3+ cells was 17,2%; р = 0,003 in spleen vs. control group, degress of decrease antigen-produced cells was 27,3%; р = 0,03 vs. control group. Number of leukocytes was increased in in test group (34,5%; р = 0,009 vs. control group. Power and strength correlation pleiades between studied blood and spenal markers were higher in in test group vs. control group (∑Gi = 16; ∑Di = 4,38 vs. ∑Gi = 13; ∑Di = 2,28. This phenomenon is probably due to the development adaptive reactions disruption in the immune system and development

Leukocyte count, systemic inflammation, and health status in older adults: a narrative review

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Chmielewski Piotr

2018-03-01

Full Text Available Epidemiological and clinical studies suggest that elevated leukocyte count within the normal range can predict cardiovascular and total mortality in older adults. These findings are remarkable because this simple and common laboratory test is included in routine medical check-ups. It is well known that chronic systemic inflammation (inflammaging is one of the hallmarks of aging and an important component of obesity-associated insulin resistance that can lead to type 2 diabetes and other health problems in both overweight individuals and elderly people. To understand the molecular mechanisms linking increased systemic inflammation with aging-associated diseases and elevated leukocyte counts in the elderly is to unravel the multiplicity of molecular factors and mechanisms involved in chronic low-grade systemic inflammation, the gradual accumulation of random molecular damage, age-related diseases, and the process of leukopoiesis. There are several possible mechanisms through which chronic low-grade systemic inflammation is associated with both higher leukocyte count and a greater risk of aging-associated conditions in older adults. For example, the IL-6 centric model predicts that this biomediator is involved in chronic systemic inflammation and leukopoiesis, thereby suggesting that elevated leukocyte count is a signal of poor health in older adults. Alternatively, an increase in neutrophil and monocyte counts can be a direct cause of cardiovascular events in the elderly. Interestingly, some authors assert that the predictive ability of elevated leukocyte counts with regard to cardiovascular and allcause mortality among older adults surpass the predictive value of total cholesterol. This review reports the recent findings on the links between elevated but normal leukocyte counts and the increased risks of all-cause, cardiovascular, and cancer mortality. The possible molecular mechanisms linking higher but normal leukocyte counts with increased

Effect of 30-Gy irradiation in conjunction with leukocyte reduction filter on platelet and transfusion efficiency

International Nuclear Information System (INIS)

Shimojima, Hiromi; Sawada, Umihiko; Horie, Takashi; Itoh, Takeyoshi

2001-01-01

To evaluate the effect of 30-Gy irradiation in conjunction with leukocyte reduction filter on platelet and transfusion efficiency, we studied platelet recovery, leukocyte reduction rate, content of platelet factor 4 and β-thromboglobulin in platelet products, platelet functions, and positive rates of platelet surface membranes CD42 and CD62, prior to and after treatment. We also evaluated the efficiency of platelet transfusion by estimating post- transfusion (1 and 24 hour) corrected count increment (CCI), and transfusion side effects. Recovery of platelets was 91.8±6.5% and depletion rate of leukocytes was 1.7±1.1 log. There was no significant difference in platelet activation markers or function tests prior to and after the procedure. The mean post-transfusion CCI and 1 and 24 hours were 16,550 (n=114) and 13,310 (n=93), respectively, with 30-Gy irradiation and leukocyte reduction filter. Those treated solely with leukocyte reduction filter were 14,970 (n=114) and 10,880 (n=118), respectively. There was no increase in transfusion side effects after the treatment of platelet concentrate with 30-Gy irradiation combined with leukocyte reduction filter compared with treatment by leukocyte reduction filter alone. These results indicate that treatment with 30 Gy irradiation in conjunction with leukocyte reduction filter is safe and effective in platelet transfusion. (author)

Accumulative effects of indoor air pollution exposure on leukocyte telomere length among non-smokers

International Nuclear Information System (INIS)

Lin, Nan; Mu, Xinlin; Wang, Guilian; Ren, Yu'ang; Su, Shu; Li, Zhiwen; Wang, Bin; Tao, Shu

2017-01-01

Indoor air pollution is an important environmental factor that contributes to the burden of various diseases. Long-term exposure to ambient air pollution is associated with telomere shortening. However, the association between chronic indoor air pollution from household fuel combustion and leukocyte telomere length has not been studied. In our study, 137 cancer-free non-smokers were recruited. Their exposure levels to indoor air pollution from 1985 to 2014 were assessed using a face-to-face interview questionnaire, and leukocyte telomere length (LTL) was measured using a monochrome multiplex quantitative PCR method. Accumulative exposure to solid fuel usage for cooking was negatively correlated with LTL. The LTL of residents who were exposed to solid fuel combustion for three decades (LTL = 0.70 ± 0.17) was significantly shorter than that of other populations. In addition, education and occupation were related to both exposure to solid fuel and LTL. Sociodemographic factors may play a mediating role in the correlation between leukocyte telomere length and environmental exposure to indoor air pollution. In conclusion, long-term exposure to indoor air pollution may cause LTL dysfunction. - Highlights: • This is the first study to investigate a clear association between indoor air pollution and leukocyte telomere length. • Chronic exposure to household solid fuel combustion and leukocyte telomere length presented a negative correlation. • Shortest leukocyte telomere length belonged to population cooking for longest time. • Education and occupation were remarkably associated with leukocyte telomere length via relating with indoor air pollution. - Long-term exposure to household solid fuel combustion is negatively associated with LTL.

Blocking of leukocyte accumulation in the cerebrospinal fluid augments bacteremia and increases lethality in experimental pneumococcal meningitis

DEFF Research Database (Denmark)

Brandt, Christian T; Lundgren, Jens D; Frimodt-Møller, Niels

2005-01-01

, blocking leukocyte entry to the central nervous system in experimental pneumococcal meningitis compromises the survival prognosis but does not affect the risk of brain damage or level of infection in this compartment. Conversely, poorer prognosis was associated with an increase in bacterial load in blood......The role of leukocyte accumulation in the cerebrospinal fluid (CSF) in the evolution of the pathophysiological changes that occur in bacterial meningitis is unclear. Here, we investigate how leukocyte recruitment to the CSF, modulated by the leukocyte blocker fucoidin, affects the extent of brain......, suggesting that leukocyte blockage affects the host's ability to control systemic infection....

Effect of human polymorphonuclear and mononuclear leukocytes on chromosomal and plasmid DNA of Escherichia coli. Role of acid DNase

International Nuclear Information System (INIS)

Rozenberg-Arska, M.; van Strijp, J.A.; Hoekstra, W.P.; Verhoef, J.

1984-01-01

Phagocytosis and killing by polymorphonuclear and mononuclear leukocytes are important host resistance factors against invading microorganisms. Evidence showing that killing is rapidly followed by degradation of bacterial components is limited. Therefore, we studied the fate of Escherichia coli DNA following phagocytosis of E. coli by polymorphonuclear and mononuclear leukocytes. [ 3 H]Thymidine-labeled, unencapsulated E. coli PC2166 and E. coli 048K1 were incubated in serum, washed, and added to leukocytes. Uptake and killing of the bacteria and degradation of DNA were measured. Although phagocytosis and killing by mononuclear leukocytes was less efficient than that by polymorphonuclear leukocytes, only mononuclear leukocytes were able to degrade E. coli PC2166 DNA. Within 2 h, 60% of the radioactivity added to mononuclear leukocytes was released into the supernate, of which 40% was acid soluble. DNA of E. coli 048K1 was not degraded. To further analyze the capacity of mononuclear leukocytes to degrade E. coli DNA, chromosomal and plasmid DNA was isolated from ingested bacteria and subjected to agarose gel-electrophoresis. Only chromosomal DNA was degraded after phagocytosis. Plasmid DNA of E. coli carrying a gene coding for ampicillin resistance remained intact for a 2-h period after ingestion, and was still able to transform recipient E. coli cells after this period. Although we observed no DNA degradation during phagocytosis by polymorphonuclear leukocytes, lysates of both polymorphonuclear and mononuclear leukocytes contained acid-DNase activity with a pH optimum of 4.9. However, the DNase activity of mononuclear leukocytes was 20 times higher than that of polymorphonuclear leukocytes. No difference was observed between DNase activity from polymorphonuclear and mononuclear leukocytes from a chronic granulomatous disease patient with DNase activity from control polymorphonuclear and mononuclear leukocytes

Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from Chikungunya 6K protein.

Science.gov (United States)

Lorente, Elena; Barriga, Alejandro; García-Arriaza, Juan; Lemonnier, François A; Esteban, Mariano; López, Daniel

2017-10-01

The adaptive cytotoxic T lymphocyte (CTL)-mediated immune response is critical for clearance of many viral infections. These CTL recognize naturally processed short viral antigenic peptides bound to human leukocyte antigen (HLA) class I molecules on the surface of infected cells. This specific recognition allows the killing of virus-infected cells. The T cell immune T cell response to Chikungunya virus (CHIKV), a mosquito-borne Alphavirus of the Togaviridae family responsible for severe musculoskeletal disorders, has not been fully defined; nonetheless, the importance of HLA class I-restricted immune response in this virus has been hypothesized. By infection of HLA-A*0201-transgenic mice with a recombinant vaccinia virus that encodes the CHIKV structural polyprotein (rVACV-CHIKV), we identified the first human T cell epitopes from CHIKV. These three novel 6K transmembrane protein-derived epitopes are presented by the common HLA class I molecule, HLA-A*0201. One of these epitopes is processed and presented via a complex pathway that involves proteases from different subcellular locations. Specific chemical inhibitors blocked these events in rVACV-CHIKV-infected cells. Our data have implications not only for the identification of novel Alphavirus and Togaviridae antiviral CTL responses, but also for analyzing presentation of antigen from viruses of different families and orders that use host proteinases to generate their mature envelope proteins.

Indium-111 labeled leukocyte images demonstrating a lung abscess with prominent fluid level

International Nuclear Information System (INIS)

Massie, J.D.; Winer-Muram, H.

1986-01-01

In-111 labeled leukocyte images show an abscess cavity with a fluid level on 24-hour upright images. Fluid levels, frequently seen on radiographs, are uncommon on nuclear images. This finding demonstrates rapid migration of labeled leukocytes into purulent abscess fluid

Impact of sex, MHC, and age of recipients on the therapeutic effect of transferred leukocytes from cancer-resistant SR/CR mice

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Adams Jonathan M

2009-09-01

Full Text Available Abstract Background Spontaneous Regression/Complete Resistant (SR/CR mice are resistant to cancer through a mechanism that is mediated entirely by leukocytes of innate immunity. Transfer of leukocytes from SR/CR mice can confer cancer resistance in wild-type (WT recipients in both preventative and therapeutic settings. In the current studies, we investigated factors that may impact the efficacy and functionality of SR/CR donor leukocytes in recipients. Results In sex-mismatched transfers, functionality of female donor leukocytes was not affected in male recipients. In contrast, male donor leukocytes were greatly affected in the female recipients. In MHC-mismatches, recipients of different MHC backgrounds, or mice of different strains, showed a greater negative impact on donor leukocytes than sex-mismatches. The negative effects of sex-mismatch and MHC-mismatch on donor leukocytes were additive. Old donor leukocytes performed worse than young donor leukocytes in all settings including in young recipients. Young recipients were not able to revive the declining function of old donor leukocytes. However, the function of young donor leukocytes declined gradually in old recipients, suggesting that an aged environment may contain factors that are deleterious to cellular functions. The irradiation of donor leukocytes prior to transfers had a profound suppressive effect on donor leukocyte functions, possibly as a result of impaired transcription. The cryopreserving of donor leukocytes in liquid nitrogen had no apparent effect on donor leukocyte functions, except for a small loss of cell number after revival from freezing. Conclusion Despite the functional suppression of donor leukocytes in sex- and MHC-mismatched recipients, as well as old recipients, there was a therapeutic time period during the initial few weeks during which donor leukocytes were functional before their eventual rejection or functional decline. The eventual rejection of donor

Passive acquisition of leukocyte proteins is associated with changes in phosphorylation of cellular proteins and cell-cell adhesion properties.

OpenAIRE

Tabibzadeh, S. S.; Kong, Q. F.; Kapur, S.

1994-01-01

In this report, we show that interaction of neoplastic epithelial cells with vesicles derived from leukocytes results in passive acquisition by tumor cells of a diverse group of leukocyte proteins. Vesicles shed from leukocytes were heterogeneous and exhibited the specific proteins expressed on leukocyte subsets. Accordingly, epithelial cells differentially acquired leukocyte proteins associated with vesicles. Ultrastructural localization demonstrated that acquired proteins were associated wi...

In-111-labeled leukocyte imaging: false-positive study due to acute gastrointestinal bleeding

International Nuclear Information System (INIS)

Fisher, M.F.; Rudd, T.G.

1983-01-01

A case is reported in which In-111-labeled leukocytes accumulated in the left colon on a 24-hr delayed image. This was found to be secondary to an upper gastrointestinal bleed in progress at the time of injection of the radiolabeled leukocytes

TNFα promotes CAR-dependent migration of leukocytes across epithelial monolayers

Science.gov (United States)

Morton, Penny E.; Hicks, Alexander; Ortiz-Zapater, Elena; Raghavan, Swetavalli; Pike, Rosemary; Noble, Alistair; Woodfin, Abigail; Jenkins, Gisli; Rayner, Emma; Santis, George; Parsons, Maddy

2016-01-01

Trans-epithelial migration (TEpM) of leukocytes during inflammation requires engagement with receptors expressed on the basolateral surface of the epithelium. One such receptor is Coxsackie and Adenovirus Receptor (CAR) that binds to Junctional Adhesion Molecule-like (JAM-L) expressed on leukocytes. Here we provide the first evidence that efficient TEpM of monocyte-derived THP-1 cells requires and is controlled by phosphorylation of CAR. We show that TNFα acts in a paracrine manner on epithelial cells via a TNFR1-PI3K-PKCδ pathway leading to CAR phosphorylation and subsequent transmigration across cell junctions. Moreover, we show that CAR is hyper-phosphorylated in vivo in acute and chronic lung inflammation models and this response is required to facilitate immune cell recruitment. This represents a novel mechanism of feedback between leukocytes and epithelial cells during TEpM and may be important in controlling responses to pro-inflammatory cytokines in pathological settings. PMID:27193388

Use of {sup 99m}Tc-Mononuclear Leukocyte Scintigraphy in Nosocomial Fever

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Gutfilen, B.; Lopes de Souza, S.A.; Martins, F.P.P.; Cardoso, L.R.; Pinheiro Pessoa, M.C.; Fonseca, L.M.B. [Univ. Federal do Rio de Janeiro (Brazil). Dept. de Radiologia

2006-09-15

Purpose: To determine the overall diagnostic accuracy of mononuclear leukocyte-{sup 99m}Tc scintigraphy in the routine detection of infectious lesions and fever of unknown origin (FUO) in inpatients. Material and Methods: The use of mononuclear leukocyte {sup 99m}Tc scintigraphy is presented in 87 patients who fulfilled the Durack and Street diagnostic criteria of nosocomial FUO; 66 patients were suspected of having infectious lesions (myocarditis, endocarditis, infected catheters, diabetic foot, and osteomyelitis) and 21 patients presented with unknown causes of FUO. Scans were carried out 1, 3, and 24 h after injection of labeled leukocytes. Results: In three cases (3/27) where scintigraphs were negative, biopsies were positive. There were two (2/87) false-positive scintigrams. We found a 95.8% sensitivity and 92.3% specificity. PPV was 93.8%, PPN 94.7%, and accuracy 94.2%. Conclusion: Mononuclear leukocyte {sup 99m}Tc scintigraphy showed high sensitivity, specificity, positive and negative predictive values in patients with nosocomial FUO. These results suggest an important role for nuclear medicine in the management of patients with infection/inflammation.

Indium-111 leukocyte imaging in appendicitis

International Nuclear Information System (INIS)

Navarro, D.A.; Weber, P.M.; Kang, I.Y.; dos Remedios, L.V.; Jasko, I.A.; Sawicki, J.E.

1987-01-01

Indium- 111 -labeled leukocyte scintigraphy was applied to the diagnosis of acute appendicitis. Thirty-two patients observed in the hospital for possible appendicitis were prospectively studied. Scanning was done 2 hr after radiopharmaceutical injection. Thirteen scans were positive for acute appendicitis, and all but one were confirmed at laparotomy. In addition, two cases of colitis and two cases of peritonitis were detected. Of 15 negative studies, 11 had a benign course. Four patients with negative studies had laparotomy; two were found to have appendicitis and two had a normal appendix. Of 14 proven cases of appendicitis, 12 scans were positive for appendicitis with one false-positive scan, providing a sensitivity of 86%. Specificity was 93%: all negative cases except one had negative scans. Overall accuracy was 91% (29 of 32), comparing favorably with the accepted false-positive laparotomy rate of 25%. Use of In- 111 -labeled leukocyte scintigraphy serves to reduce the false-positive laparotomy rate and to shorten the clinical observation time in patients with acute appendicitis

Leukocyte scintigraphy compared to intraoperative small bowel enteroscopy and laparotomy findings in Crohn's disease

DEFF Research Database (Denmark)

Almen, Sven; Granerus, Göran; Ström, Magnus

2007-01-01

Background: Leukocyte scintigraphy is a noninvasive investigation to assess inflammation. We evaluated the utility of labeled leukocytes to detect small bowel inflammation and disease complications in Crohn's disease and compared it to whole small bowel enteroscopy and laparotomy findings. Methods......: Scintigraphy with technetium-99m exametazime-labeled leukocytes was prospectively performed in 48 patients with Crohn's disease a few days before laparotomy; 41 also had an intraoperative small bowel enteroscopy. The same procedures were performed in 8 control patients. Independent grading of scans...... was compared with the results of enteroscopy and with surgical, histopathologic, and clinical data. Results: In the 8 control patients leukocyte scan, endoscopy, and histopathology were all negative for the small bowel. In patients with Crohn's disease and small bowel inflammation seen at enteroscopy and...

Aberrant leukocyte telomere length in Birdshot Uveitis.

Science.gov (United States)

Vazirpanah, Nadia; Verhagen, Fleurieke H; Rothova, Anna; Missotten, Tom O A R; van Velthoven, Mirjam; Den Hollander, Anneke I; Hoyng, Carel B; Radstake, Timothy R D J; Broen, Jasper C A; Kuiper, Jonas J W

2017-01-01

Birdshot Uveitis (BU) is an archetypical chronic inflammatory eye disease, with poor visual prognosis, that provides an excellent model for studying chronic inflammation. BU typically affects patients in the fifth decade of life. This suggests that it may represent an age-related chronic inflammatory disease, which has been linked to increased erosion of telomere length of leukocytes. To study this in detail, we exploited a sensitive standardized quantitative real-time polymerase chain reaction to determine the peripheral blood leukocyte telomere length (LTL) in 91 genotyped Dutch BU patients and 150 unaffected Dutch controls. Although LTL erosion rates were very similar between BU patients and healthy controls, we observed that BU patients displayed longer LTL, with a median of log (LTL) = 4.87 (= 74131 base pair) compared to 4.31 (= 20417 base pair) in unaffected controls (PRTEL1. These findings suggest that BU is accompanied by significantly longer LTL.

Quantitative and qualitative changes in leukocytes of psoriatic patients

International Nuclear Information System (INIS)

Mahesar, S.M.; Khand, A.A.

2011-01-01

Background: Psoriasis is a disease concerned with inflammation and scaling of skin. In psoriasis, cells of the skin come on surface quickly before their complete maturation. In psoriatic patients, T-cells produce an abnormally large amount of toxic chemicals and cause inflammation. This study was undertaken to find out values of prognostic significance for worsening of the disease at early stage and to evaluate the changes (quantitative and qualitative) occurring in white blood cells of psoriatic patients. Methods: A total of 158 subjects, 79 psoriatic patients (44 males and 35 females) and same numbers of normal control volunteers were recruited. Total and Differential Leukocyte Counts (TLC and DLC) were determined. Morphological examination was also undertaken. All results of patients were compared with normal control volunteers. Results : In 47.7% male and 54.2% female patients TLC was higher than controls while variation in differential count was observed in 61.3% male and 62.8% female patients. Overall, neutrophils in 45% patients, basophils in 30.3%, eosinophils in 65.8%, and monocytes in 15% of patients were elevated. In 77.2% psoriatic patients, lymphocytes were decreased. In volunteers total and differential leukocyte counts were within normal range. Total leukocyte count in normal males was 5,136 +- 31, and in psoriatic male subjects it was 10,498 +- 43, and it was 5,023 +- 35 against 11,390 +- 31 in normal versus psoriatic females ( p<0.001). Conclusion: Total leukocyte count was elevated in psoriatics while on DLC neutrophils, eosinophils and neutrophils were significantly raised where as lymphocytes were significantly decreased in psoriatic patients. Morphological changes were also noted. (author)

Post Mortem Leukocyte Scintigraphy in Juvenile Pigs with Experimentally Induced Osteomyelitis

DEFF Research Database (Denmark)

Afzelius, P.; Nielsen, O. L.; Jensen, S. B.

2017-01-01

We have previously demonstrated that 111In-labeled autologous leukocyte scintigraphy is able to detect osteomyelitis in living juvenile pigs. In animal research studies, it may well be an advantage if the animals could be scanned after euthanasia. Applying traditional scanning of living animals...... for homing to the site of infections as usual while the pigs were alive. In this study, we demonstrate that it is possible to perform SPECT/CT with 111In-labelled autologous leukocytes almost 24 hrs after euthanasia with the same detectability of osteomyelitic lesions as in living pigs (78% versus 79......%). The pigs in this study had exactly the same experimental conditions as the living pigs and were examined in parallel with the living pigs except for euthanasia prior to the leukocyte scan and that no PET/CT scans were performed....

Signaling through MyD88 regulates leukocyte recruitment after brain injury

DEFF Research Database (Denmark)

Babcock, Alicia A; Toft-Hansen, Henrik; Owens, Trevor

2008-01-01

hippocampus. We now show that significant leukocyte entry into the EC occurs within 3-12 h of stab injury. Whereas T cells showed small, gradual increases over 8 days, macrophage infiltration was pronounced and peaked within 12-24 h. MyD88 deficiency significantly reduced macrophage and T cell recruitment...... for TNF-alpha, IL-1beta, and CCL2, which increased >50-fold after stab injury in C57BL/6 mice at the time of peak expression, were severely reduced in injured MyD88 knockout mice. Leukocyte recruitment and gene expression were unaffected in TLR2-deficient or TLR4 mutant mice. No significant differences...... in gene expression were observed in mice lacking IL-1R or IL-18R. These data show that MyD88-dependent signaling mediates proinflammatory gene expression and leukocyte recruitment after CNS injury....

Tracking flow of leukocytes in blood for drug analysis

Science.gov (United States)

Basharat, Arslan; Turner, Wesley; Stephens, Gillian; Badillo, Benjamin; Lumpkin, Rick; Andre, Patrick; Perera, Amitha

2011-03-01

Modern microscopy techniques allow imaging of circulating blood components under vascular flow conditions. The resulting video sequences provide unique insights into the behavior of blood cells within the vasculature and can be used as a method to monitor and quantitate the recruitment of inflammatory cells at sites of vascular injury/ inflammation and potentially serve as a pharmacodynamic biomarker, helping screen new therapies and individualize dose and combinations of drugs. However, manual analysis of these video sequences is intractable, requiring hours per 400 second video clip. In this paper, we present an automated technique to analyze the behavior and recruitment of human leukocytes in whole blood under physiological conditions of shear through a simple multi-channel fluorescence microscope in real-time. This technique detects and tracks the recruitment of leukocytes to a bioactive surface coated on a flow chamber. Rolling cells (cells which partially bind to the bioactive matrix) are detected counted, and have their velocity measured and graphed. The challenges here include: high cell density, appearance similarity, and low (1Hz) frame rate. Our approach performs frame differencing based motion segmentation, track initialization and online tracking of individual leukocytes.

Morphogen and proinflammatory cytokine release kinetics from PRGF-Endoret fibrin scaffolds: evaluation of the effect of leukocyte inclusion.

Science.gov (United States)

Anitua, E; Zalduendo, M M; Prado, R; Alkhraisat, M H; Orive, G

2015-03-01

The potential influence of leukocyte incorporation in the kinetic release of growth factors from platelet-rich plasma (PRP) may explain the conflicting efficiency of leukocyte platelet-rich plasma (L-PRP) scaffolds in tissue regeneration. To assess this hypothesis, leukocyte-free (PRGF-Endoret) and L-PRP fibrin scaffolds were prepared, and both morphogen and proinflammatory cytokine release kinetics were analyzed. Clots were incubated with culture medium to monitor protein release over 8 days. Furthermore, the different fibrin scaffolds were morphologically characterized. Results show that leukocyte-free fibrin matrices were homogenous while leukocyte-containing ones were heterogeneous, loose and cellular. Leukocyte incorporation produced a significant increase in the contents of proinflammatory cytokines interleukin (IL)-1β and IL-16 but not in the platelet-derived growth factors release (PRGF-Endoret, the inclusion of leukocytes induced a major increase in these cytokines, which was characterized by the presence of a latent period. The PRGF-Endoret matrices were stable during the 8 days of incubation. The inclusion of leukocytes alters the growth factors release profile and also increased the dose of proinflammatory cytokines. © 2014 Wiley Periodicals, Inc.

Chemotaxis of nurse shark leukocytes.

Science.gov (United States)

Obenauf, S D; Smith, S H

1985-01-01

Studies were conducted to determine the ability of leukocytes from the nurse shark to migrate in an in vitro micropore filter chemotaxis assay and to determine optimal assay conditions and suitable attractants for such an assay. A migratory response was seen with several attractants: activated rat serum, activated shark plasma, and a pool of shark complement components. Only the response to activated rat serum was chemotactic, as determined by the checkerboard assay.

Intratendon Delivery of Leukocyte-Poor Platelet-Rich Plasma Improves Healing Compared With Leukocyte-Rich Platelet-Rich Plasma in a Rabbit Achilles Tendinopathy Model.

Science.gov (United States)

Yan, Ruijian; Gu, Yanjia; Ran, Jisheng; Hu, Yejun; Zheng, Zefeng; Zeng, Mengfeng; Heng, Boon Chin; Chen, Xiao; Yin, Zi; Chen, Weishan; Shen, Weiliang; Ouyang, Hongwei

2017-07-01

Chronic tendinopathy is a commonly occurring clinical problem that affects both athletes and inactive middle-aged patients. Although some studies have shown that different platelet-rich plasma (PRP) preparations could exert various therapeutic effects in vitro, the role of leukocytes in PRP has not yet been defined under tendinopathy conditions in vivo. This study compared the effects of the intratendon delivery of leukocyte-poor PRP (Lp-PRP) versus leukocyte-rich PRP (Lr-PRP) in a rabbit chronic tendinopathy model in vivo. Controlled laboratory study. Four weeks after a local injection of collagenase in the Achilles tendon, the following treatments were randomly administered on the lesions: injections of (1) 200 μL of Lp-PRP (n = 8), (2) 200 μL of Lr-PRP (n = 8), or (3) 200 μL of saline (n = 8). Healing outcomes were assessed at 4 weeks after therapy with magnetic resonance imaging (MRI), cytokine quantification, real-time polymerase chain reaction analysis of gene expression, histology, and transmission electron microscopy (TEM). MRI revealed that the Lr-PRP and saline groups displayed higher signal intensities compared with the Lp-PRP group with T2 mapping. Histologically, the Lp-PRP group displayed significantly better general scores compared with the Lr-PRP ( P = .001) and saline ( P tendon healing and is a preferable option for the clinical treatment of tendinopathy. PRP is widely used in the clinical management of chronic tendinopathy. However, the clinical results are ambiguous. It is imperative to understand the influence of leukocytes on PRP-mediated tissue healing in vivo, which could facilitate the better clinical management of chronic tendinopathy. Further studies are needed to translate our findings to the clinical setting.

Palmitoylated transmembrane adaptor proteins in leukocyte signaling

Czech Academy of Sciences Publication Activity Database

Štěpánek, Ondřej; Dráber, Peter; Hořejší, Václav

2014-01-01

Roč. 26, č. 5 (2014), s. 895-902 ISSN 0898-6568 R&D Projects: GA ČR(CZ) GBP302/12/G101 Institutional support: RVO:68378050 Keywords : Leukocyte * Adaptor * Palmitoylation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.315, year: 2014

Commensal oral bacteria antigens prime human dendritic cells to induce Th1, Th2 or Treg differentiation.

Science.gov (United States)

Kopitar, A N; Ihan Hren, N; Ihan, A

2006-02-01

In various immunopathologic conditions, bacterial flora induce an immune response which results in inflammatory manifestations, e.g. periapical granuloma. Dendritic cells provide the main orchestration of specific immune responses. The aim of our study was to test the capacity of distinct oral bacterial antigens (prepared from Streptococcus mitis, Propionibacterium acnes, and Bacteroides spp.) to prime human dendritic cells for stimulation of the T-lymphocyte response. To assess the T-lymphocyte response, the expression of CD25, CD69, intracellular interferon gamma (cIFN-gamma), and intracellular interleukin 4 (cIL-4) was determined. Dendritic cells were prepared from leukocyte buffy coat from healthy blood donors. Monocytes were stimulated with IL-4 and GM-CSF and dendritic cells activated with bacterial lysates. Cell suspensions contained up to 90% dendritic cells, which represented 2-12% of the initial number of mononuclear cells. Lymphocyte subsets that developed in lymphocyte cultures after 1 week of stimulation were analyzed by flow cytometry. Dendritic cells, primed with antigens of Bacteroides fragilis have shown significantly higher activation and expression of intercellular IFN-gamma by T lymphocytes compared to negative controls. The dendritic cells primed with antigens of P. acnes had no effect on T-lymphocyte activation or cytokine production; instead they induced differentiation of T lymphocytes into CD25bright cells (regulatory T cells) with a potentially inhibitory effect on immune response. Dendritic cells primed with antigens of S. mitis induced increased expression of cIL-4. We conclude that commensal oral bacteria antigens prepared from B. fragilis, S. mitis, and P. acnes prime human dendritic cells to induce Th1, Th2, and T(reg) differentiation, respectively. This may advance our understanding of immunopathologic manifestations in the oral cavity and offer new possibilities for redirecting immune responses in mucosal vaccination.

Platelet transfusions can induce transplantation tolerance

International Nuclear Information System (INIS)

Claas, F.H.J.; Blankert, J.J.; Ruigrok, R.; Moerel, L.

1982-01-01

Recently it was shown that the induction of antibodies against the H-2 antigens after multiple platelet transfusions is due to leukocyte contamination of the platelet suspensions. Pure platelets are not able to induce a primary antibody response. The present study shows that the platelets, however, can be recognized by the immune system but they induce a suppression of the response. Mice pretreated with donor platelets will not give a primary antibody response upon a subsequent injection of donor leukocytes and the survival of donor skin grafts will be prolonged. Similar results were obtained by pretreatment of the responder mice with heat-treated donor leukocytes. Furthermore, repeated injections of heat-treated leukocytes of the recipient strain to the donor before bone marrow grafting, will graft-versus-host mortality. The recipient mice were irradiated and received spleen cell injections. These data show that cells which have only class I antigens on their surface and no activating class II antigens, induce a suppression of the response against class I antigens. (Auth.)

Clinical evaluation of {sup 99m}Tc-HMPAO labeled leukocyte imaging in ulcerative colitis

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Saitoh, Yasuhiro; Aburano, Tamio; Takashio, Tetsuya; Shuke, Noriyuki; Ayabe, Tokiyoshi; Nomura, Masashi; Kohgo, Yutaka; Ishikawa, Yukio; Satoh, Junichi [Asahikawa Medical Coll., Hokkaido (Japan)

1996-07-01

Inflammatory imaging using {sup 99m}Tc-HMPAO-labeled mixed leukocytes was assessed for use in treating 11 cases diagnosed as ulcerative colitis: 10 cases with total colitis and 1 with left-sided colitis. They consisted of 8 patients with relapse-remitting type and 3 with chronic continuous type. Radionuclide abdominal images were obtained at 1 hr, 4 hr and 24 hr after intravenous injection of 200 MBq prepared {sup 99m}Tc leukocytes. Obvious colonic activity noted at 4 hr served as the basis for positive comparative criterion in the present study. The diagnostic efficacy of radionuclide imaging was compared with endoscopic findings (based on Matts` classification) and the clinical manifestations as reference. The sensitivity and specificity of this imaging were 83.3% and 85.7%, respectively, these values being consistent with endoscopic findings and clinical manifestations at sites of disease activity. All of positive images changed to negative after treatment by leukocyte apheresis or glucocorticoid. Based on these results, {sup 99m}Tc leukocyte imaging can be used to accurately evaluate severity and treatment response in ulcerative colitis. Leukocytes may be closely related to the pathogenesis of ulcerative colitis. (author)

Leukocytes respiratory burst activity as indicator of innate immunity of pacu Piaractus mesopotamicus

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JD Biller-Takahashi

Full Text Available The present study evaluated the assay to quantify the respiratory burst activity of blood leukocytes of pacu as an indicator of the innate immune system, using the reduction of nitroblue tetrazolium (NBT to formazan as a measure of the production of reactive oxygen species (ROS. In order to assess the accuracy of the assay, fish were challenged by Aeromonas hydrophila and sampled one week after challenge. The A. hydrophila infection increased the leukocyte respiratory burst activity. The protocol showed a reliable and easy assay, appropriate to determine the respiratory burst activity of blood leukocytes of pacu, a neotropical fish, in the present experimental conditions.

Effects of electroacupuncture on leukocytes and plasma protein in the X-irradiated rats

International Nuclear Information System (INIS)

Hau, D.M.

1984-01-01

The effects of electroacupuncture on leukocytes and plasma protein on the X ray-irradiated rats were investigated in the present study. The results showed that X-irradiation had an evident inhibitory effect on the counts of total leukocytes, lymphocytes and neutrocytes, and the concentration of the total plasma protein, plasma albumin, globulin and alpha- and beta-globulin in X-irradiated rats. The electroacupuncture was able to help the X-irradiated rats to recover the counts of the total leukocyte, lymphocyte and neutrocyte. The electroacupuncture had a helpful tendency to recover the concentration of the total plasma protein, albumin, globulin, and alpha- and beta-globulin in the irradiated rats

Effects of electroacupuncture on leukocytes and plasma protein in the X-irradiated rats

Energy Technology Data Exchange (ETDEWEB)

Hau, D.M.

The effects of electroacupuncture on leukocytes and plasma protein on the X ray-irradiated rats were investigated in the present study. The results showed that X-irradiation had an evident inhibitory effect on the counts of total leukocytes, lymphocytes and neutrocytes, and the concentration of the total plasma protein, plasma albumin, globulin and alpha- and beta-globulin in X-irradiated rats. The electroacupuncture was able to help the X-irradiated rats to recover the counts of the total leukocyte, lymphocyte and neutrocyte. The electroacupuncture had a helpful tendency to recover the concentration of the total plasma protein, albumin, globulin, and alpha- and beta-globulin in the irradiated rats.

Comparative genome analysis of three eukaryotic parasites with differing abilities to transform leukocytes reveals key mediators of theileria-induced leukocyte transformation

KAUST Repository

Hayashida, Kyoko; Hara, Yuichiro; Abe, Takashi; Yamasaki, Chisato; Toyoda, Atsushi; Kosuge, Takehide; Suzuki, Yutaka; Sato, Yoshiharu; Kawashima, Shuichi; Katayama, Toshiaki; Wakaguri, Hiroyuki; Inoue, Noboru; Homma, Keiichi; Tada-Umezaki, Masahito; Yagi, Yukio; Fujii, Yasuyuki; Habara, Takuya; Kanehisa, Minoru; Watanabe, Hidemi; Ito, Kimihito; Gojobori, Takashi; Sugawara, Hideaki; Imanishi, Tadashi; Weir, William; Gardner, Malcolm; Pain, Arnab; Shiels, Brian; Hattori, Masahira; Nene, Vishvanath; Sugimoto, Chihiro

2012-01-01

. annulata. T. parva and T. annulata induce transformation of infected cells of lymphocyte or macrophage/monocyte lineages; in contrast, T. orientalis does not induce uncontrolled proliferation of infected leukocytes and multiplies predominantly within

In-111 labeled leukocyte scintigraphy in a case of multifocal candidiasis

Energy Technology Data Exchange (ETDEWEB)

Palestro, C.J.; Vega, A.; Kim, C.K.; Goldsmith, S.J. (Mount Sinai School of Medicine, New York, NY (USA))

1990-06-01

The value of indium-111 labeled leukocyte scintigraphy for the diagnosis of infection in the general population is well documented; there is less information available on its role in the evaluation of the immunocompromised patient. In this study, leukocyte scintigraphy was performed on a 31-year-old immunocompromised woman who had a possible intra-abdominal abscess. No abscess was detected, but intense oral, esophageal, gastric, and vaginal uptake was observed. Candida infection was histologically confirmed at all four sites.

In-111 labeled leukocyte scintigraphy in a case of multifocal candidiasis

International Nuclear Information System (INIS)

Palestro, C.J.; Vega, A.; Kim, C.K.; Goldsmith, S.J.

1990-01-01

The value of indium-111 labeled leukocyte scintigraphy for the diagnosis of infection in the general population is well documented; there is less information available on its role in the evaluation of the immunocompromised patient. In this study, leukocyte scintigraphy was performed on a 31-year-old immunocompromised woman who had a possible intra-abdominal abscess. No abscess was detected, but intense oral, esophageal, gastric, and vaginal uptake was observed. Candida infection was histologically confirmed at all four sites

Role of the eosinophil in serum-mediated adherence of equine leukocytes to infective larvae of Strongylus vulgaris.

Science.gov (United States)

Klei, T R; Chapman, M R; Dennis, V A

1992-06-01

The adherence of equine leukocytes to Strongylus vulgaris infective larvae (L3) in the presence of normal and immune sera was examined in vitro. Immune sera promoted adherence of buffy coat cells from ponies with S. vulgaris-induced eosinophilia (eosinophilic ponies) to S. vulgaris L3. However, eosinophils in the buffy coat cells were the predominant adherent cell type. Studies using leukocyte populations enriched for eosinophils, neutrophils, and mononuclear cells from eosinophilic ponies support the observations using buffy coat cells that eosinophils were the main effector cells. Adherent eosinophils from eosinophilic ponies immobilized L3. Neutrophils were less adherent and did not immobilize L3. Mononuclear cells failed to adhere. Normal eosinophils from strongly-naive ponies did not immobilize S. vulgaris L3 in the presence of immune serum, suggesting the in vivo activation of eosinophils in eosinophilic animals. Immune serum promoted less adherence of buffy coat cells to Strongylus edentatus or mixed species of Cyathostominae L3, suggesting that the serum-mediated cellular adherence phenomenon was species-specific. Normal serum promoted less cellular adherence to S. vulgaris L3 than immune serum. The adherence mediated by normal serum was removed by heat inactivation, suggesting that this nonspecific phenomenon was a complement-mediated reaction. Immune globulins promoted reactions similar to that seen using heat-inactivated immune serum, whereas normal globulins did not promote adherence. Immune globulins absorbed with pieces of S. vulgaris adult worms did not promote the adherence of buffy coat cells to S. vulgaris L3, suggesting that adult and L3 stages share antigens important in this phenomenon that resulted in the removal of specific adherence antibody during absorption.

Leukocyte depletion results in improved lung function and reduced inflammatory response after cardiac surgery

NARCIS (Netherlands)

Gu, YJ; Boonstra, PW; vanOeveren, W

Leukocyte depletion during cardiopulmonary bypass has been demonstrated in animal experiments to improve pulmonary function, Conflicting results have been reported, however, with clinical depletion by arterial line filter of leukocytes at the beginning of cardiopulmonary bypass. In this study, we

Leukocyte infiltration and tumor cell plasticity are parameters of aggressiveness in primary cutaneous melanoma.

NARCIS (Netherlands)

Hillen, F.; Baeten, C.I.M.; Winkel, van de A.; Creytens, D.; Schaft, van der D.W.J.; Winnepenninckx, V.; Griffioen, A.W.

2008-01-01

Various clinical and experimental observations detected an immunological host defense in cutaneous melanoma. In order to investigate the prognostic value of leukocyte effector mechanisms, we examined the presence of different subsets of leukocytes in tumor samples of 58 patients diagnosed with

Leukocyte removal efficiency of cell-washed and unwashed whole blood: an in vitro study.

NARCIS (Netherlands)

Brinke, M. ten; Weerwind, P.W.; Teerenstra, S.; Feron, JC; Meer, W. van der; Brouwer, René

2005-01-01

Leukocyte filtration of the cardiopulmonary bypass (CPB) perfusate after cardiac surgery has evolved as an important technique to prevent effector functions mediated by activated leukocytes. However, little is known about the filtration efficiency. Therefore, an in vitro study was conducted to

Chimeric Antigen Receptor Expressing Natural Killer Cells for the Immunotherapy of Cancer

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Rohtesh S. Mehta

2018-02-01

Full Text Available Adoptive cell therapy has emerged as a powerful treatment for advanced cancers resistant to conventional agents. Most notable are the remarkable responses seen in patients receiving autologous CD19-redirected chimeric antigen receptor (CAR T cells for the treatment of B lymphoid malignancies; however, the generation of autologous products for each patient is logistically cumbersome and has restricted widespread clinical use. A banked allogeneic product has the potential to overcome these limitations, yet allogeneic T-cells (even if human leukocyte antigen-matched carry a major risk of graft-versus-host disease (GVHD. Natural killer (NK cells are bone marrow-derived innate lymphocytes that can eliminate tumors directly, with their activity governed by the integration of signals from activating and inhibitory receptors and from cytokines including IL-15, IL-12, and IL-18. NK cells do not cause GVHD or other alloimmune or autoimmune toxicities and thus, can provide a potential source of allogeneic “off-the-shelf” cellular therapy, mediating major anti-tumor effects without inducing potentially lethal alloreactivity such as GVHD. Given the multiple unique advantages of NK cells, researchers are now exploring the use of CAR-engineered NK cells for the treatment of various hematological and non-hematological malignancies. Herein, we review preclinical data on the development of CAR-NK cells, advantages, disadvantages, and current obstacles to their clinical use.

Transepithelial activation of human leukocytes by probiotics and commensal bacteria: Role of Enterobacteriaceae-type endotoxin

DEFF Research Database (Denmark)

Baeuerlein, Annette; Ackermann, Stefanie; Parlesak, Alexandr

2009-01-01

The goal of the current study was to clarify whether commercially available probiotics induce greater trans-epithelial activation of human leukocytes than do commensal, food-derived and pathogenic bacteria and to identify the compounds responsible for this activation. Eleven different bacterial...... Escherichia coli K12, probiotic E. coli Nissle, EPEC) induced basolateral production of TNF-alpha, IFN-gamma, IL 6, 8, and 10. Gram-positive probiotics (Lactobacillus spp. and Bifidobacterium spp.) had virtually no effect. In addition, commensals (Enterococcus faecalis, Bacteroides vulgatus) and food...... (polymyxin, colistin) completely abrogated transepithelial activation of leukocytes. Enterobacteriaceae-type endotoxin is a crucial factor in transepithelial stimulation of leukocytes, regardless of whether it is produced by probiotics or other bacteria. Hence, transepithelial stimulation of leukocytes...

Antibiotic-Enhanced Phagocytosis of ’Borrelia recurrentis’ by Blood Polymorphonuclear Leukocytes.

Science.gov (United States)

1979-11-30

hours after Butler 7 institution of antibiotic treatment. Polymorphonuclear leukocytes are known to release endogenous pyrogen after phagocytosis of...other bacteria (6), and endogenous pyrogen may be one of the mediators of the rigor and temperature rise in the Jarisch-Herxheimer reaction (2). Release...the pathogenesis of fever. XII. The effect of phagocytosis on the release of endogenous pyrogen by polymorphonuclear leukocytes. J. Exp. Med. 119:715

Activation of human leukocytes on tantalum trabecular metal in comparison to commonly used orthopedic metal implant materials.

Science.gov (United States)

Schildhauer, T A; Peter, E; Muhr, G; Köller, M

2009-02-01

We analyzed leukocyte functions and cytokine response of human leukocytes toward porous tantalum foam biomaterial (Trabecular Metaltrade mark, TM) in comparison to equally sized solid orthopedic metal implant materials (pure titanium, titanium alloy, stainless steel, pure tantalum, and tantalum coated stainless steel). Isolated peripheral blood mononuclear cells (PBMC) and polymorphonuclear neutrophil leukocytes (PMN) were cocultured with equally sized metallic test discs for 24 h. Supernatants were analyzed for cytokine content by enzyme-linked immunosorbent assay. Compared to the other used test materials there was a significant increase in the release of IL (interleukin)-1ra and IL-8 from PMN, and of IL-1ra, IL-6, and TNF-alpha from PBMC in response to the TM material. The cytokine release correlated with surface roughness of the materials. In contrast, the release of IL-2 was not induced showing that mainly myeloid leukocytes were activated. In addition, supernatants of these leukocyte/material interaction (conditioned media, CM) were subjected to whole blood cell function assays (phagocytosis, chemotaxis, bacterial killing). There was a significant increase in the phagocytotic capacity of leukocytes in the presence of TM-conditioned media. The chemotactic response of leukocytes toward TM-conditioned media was significantly higher compared to CM obtained from other test materials. Furthermore, the bactericidal capacity of whole blood was enhanced in the presence of TM-conditioned media. These results indicate that leukocyte activation at the surface of TM material induces a microenvironment, which may enhance local host defense mechanisms.

Effect of radiographic contrast agents on leukocyte metabolic response

International Nuclear Information System (INIS)

Hernanz-Schulman, M.; Vanholder, R.; Waterloos, M.A.; Hakim, R.; Schulman, G.

2000-01-01

Barium, at clinical dilutions, causes a significant increase of baseline ''resting state'' phagocytic activity, which in turn leads to significant blunting of subsequent response to phagocytic challenge and adversely affects the response to all bacteria tested. There is no baseline activation of leukocytes by the water-soluble media, although there was some inhibition (rather than activation) of leukocyte metabolic activity. The effect of the water-soluble media in bacteria was more complex (although inhibition is minor compared to barium). Our data demonstrate that barium is a significant activator of phagocytic cells, which results in deactivation of phagocytic response when challenged; these data serve to explain the enhanced adverse effect of barium in cased of fecal peritonitis. (orig.)

Use of 8-methoxypsoralen and ultraviolet-A pretreated platelet concentrates to prevent alloimmunization against class I major histocompatibility antigens

International Nuclear Information System (INIS)

Grana, N.H.; Kao, K.J.

1991-01-01

The use of 8-methoxypsoralen (8-MOP) and UV-A irradiation to inactivate contaminating donor leukocytes in platelet concentrates and to prevent primary alloimmunization against donor class I major histocompatibility (MHC) antigens in mice was investigated. CBA/CaH-T6J mice with the H2k haplotype and BALB/cByJ mice with the H2d haplotype were used as donors and recipients, respectively. The mixed leukocyte reaction between these two strains of mice showed that treatment of spleen cells with 500 ng/mL 8-MOP and 5J/cm2 UV-A inhibited 99% of responder and 92% of stimulator function. There was no measurable loss of platelet aggregating activity after the treatment. After two weekly transfusions of platelets without any treatment, 93% of control mice (n = 15) developed anti-H2k antibody. In contrast, only 33% of mice (n = 15) receiving platelets treated with 8-MOP and UV-A became alloimmunized. After six weekly platelet transfusions, all mice became alloimmunized. Nevertheless, the mean titers of anti-H2k antibody in sera of the treated groups were significantly lower than the control groups. One hour posttransfusion recoveries of 51Cr-labeled donor platelets were also higher in mice transfused with the treated platelets. Thus, the pretreatment of platelet concentrates with 8-MOP and UV-A irradiation effectively reduced the alloantigenicity of class I MHC molecules. The implication of this finding in relation to the mechanism by which donor leukocytes allosensitize recipients is discussed

Human leukocyte mobilization and morphology in nickel contact allergy using a skin chamber technique

DEFF Research Database (Denmark)

Lerche, A; Bisgaard, H; Christensen, J D

1981-01-01

An improved skin chamber technique has been devised and used for quantitative evaluation of the leukocyte mobilization rate (LMR). The method was applied in 10 nickel-hypersensitive patients exposed to nickel sulphate. Each patient served as his own control and for additional control purpose, 5...... healthy individuals without nickel hypersensitivity were studied. The kinetics of the mobilized leukocytes were followed over a 48-hour period. After an initial lag phase of 2-4 hours, maximum migration was observed from the 24th to the 48th hour, with a wide interindividual variability in the number...... of mobilized cells at the time of maximum LMR response. The median cumulative leukocyte count was 1.412 x 10(6) leukocytes/cm2/48 h. In the same period a statistically significant increase in the basophils for all the nickel allergic patients was observed. In 8 out of 10 patients a statistically significant...

Monocyte Chemotactic Protein 1 in Plasma from Soluble Leishmania Antigen-Stimulated Whole Blood as a Potential Biomarker of the Cellular Immune Response to Leishmania infantum

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Ana V. Ibarra-Meneses

2017-09-01

Full Text Available New biomarkers are needed to identify asymptomatic Leishmania infection as well as immunity following vaccination or treatment. With the aim of finding a robust biomarker to assess an effective cellular immune response, monocyte chemotactic protein 1 (MCP-1 was examined in plasma from soluble Leishmania antigen (SLA-stimulated whole blood collected from subjects living in a Leishmania infantum-endemic area. MCP-1, expressed 110 times more strongly than IL-2, identified 87.5% of asymptomatic subjects and verified some asymptomatic subjects close to the cutoff. MCP-1 was also significantly elevated in all patients cured of visceral leishmaniasis (VL, unlike IL-2, indicating the specific memory response generated against Leishmania. These results show MCP-1 to be a robust candidate biomarker of immunity that could be used as a marker of cure and to both select and follow the population in vaccine phase I–III human clinical trials with developed rapid, easy-to-use field tools.

Increased oxidative DNA damage in mononuclear leukocytes in vitiligo

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Giovannelli, Lisa [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy)]. E-mail: lisag@pharm.unifi.it; Bellandi, Serena [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Pitozzi, Vanessa [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Fabbri, Paolo [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Dolara, Piero [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Moretti, Silvia [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy)

2004-11-22

Vitiligo is an acquired pigmentary disorder of the skin of unknown aetiology. The autocytotoxic hypothesis suggests that melanocyte impairment could be related to increased oxidative stress. Evidences have been reported that in vitiligo oxidative stress might also be present systemically. We used the comet assay (single cell alkaline gel electrophoresis) to evaluate DNA strand breaks and DNA base oxidation, measured as formamidopyrimidine DNA glycosylase (FPG)-sensitive sites, in peripheral blood cells from patients with active vitiligo and healthy controls. The basal level of oxidative DNA damage in mononuclear leukocytes was increased in vitiligo compared to normal subjects, whereas DNA strand breaks (SBs) were not changed. This alteration was not accompanied by a different capability to respond to in vitro oxidative challenge. No differences in the basal levels of DNA damage in polymorphonuclear leukocytes were found between patients and healthy subjects. Thus, this study supports the hypothesis that in vitiligo a systemic oxidative stress exists, and demonstrates for the first time the presence of oxidative alterations at the nuclear level. The increase in oxidative DNA damage shown in the mononuclear component of peripheral blood leukocytes from vitiligo patients was not particularly severe. However, these findings support an adjuvant role of antioxidant treatment in vitiligo.

Increased oxidative DNA damage in mononuclear leukocytes in vitiligo

International Nuclear Information System (INIS)

Giovannelli, Lisa; Bellandi, Serena; Pitozzi, Vanessa; Fabbri, Paolo; Dolara, Piero; Moretti, Silvia

2004-01-01

Vitiligo is an acquired pigmentary disorder of the skin of unknown aetiology. The autocytotoxic hypothesis suggests that melanocyte impairment could be related to increased oxidative stress. Evidences have been reported that in vitiligo oxidative stress might also be present systemically. We used the comet assay (single cell alkaline gel electrophoresis) to evaluate DNA strand breaks and DNA base oxidation, measured as formamidopyrimidine DNA glycosylase (FPG)-sensitive sites, in peripheral blood cells from patients with active vitiligo and healthy controls. The basal level of oxidative DNA damage in mononuclear leukocytes was increased in vitiligo compared to normal subjects, whereas DNA strand breaks (SBs) were not changed. This alteration was not accompanied by a different capability to respond to in vitro oxidative challenge. No differences in the basal levels of DNA damage in polymorphonuclear leukocytes were found between patients and healthy subjects. Thus, this study supports the hypothesis that in vitiligo a systemic oxidative stress exists, and demonstrates for the first time the presence of oxidative alterations at the nuclear level. The increase in oxidative DNA damage shown in the mononuclear component of peripheral blood leukocytes from vitiligo patients was not particularly severe. However, these findings support an adjuvant role of antioxidant treatment in vitiligo

Binding of C-reactive protein to human polymorphonuclear leukocytes: evidence for association of binding sites with Fc receptors

International Nuclear Information System (INIS)

Mueller, H.; Fehr, J.

1986-01-01

The functional similarities between C-reactive protein (CRP) and IgG raised the question as to whether human phagocytes are stimulated by CRP in the same way as by binding of antigen-complexes or aggregated IgG to their Fc receptors. Studies with the use of highly purified 125 I-labeled CRP showed specific and saturable binding to human polymorphonuclear leukocytes (PNM) with a K/sub D/ of 10.5 +/- 5.7 x 10 -8 M only when carried out in heat-inactivated plasma. The number of specific binding sites per cell was estimated at 1 to 3 x 10 6 . Competitive inhibition of CRP binding by antigen-complexed or aggregated IgG suggests CRP binding sites to be associated IgG suggests CRP binding sites to be associated with PMN Fc receptors. Only when assayed in heat-inactivated plasma did CRP binding induce adherence of cells to tissue culture dishes. However, no metabolic and potentially cytotoxic simulation of PMN was detected during CRP plasma-dependent attachment to surfaces: induction of aggregation, release of secondary granule constituents, and activation of the hexose monophosphate pathway were not observed. These results imply that CRP-PMN interactions is dependent on an additional factor present in heat-inactivated plasma and is followed only by a complement-independent increase in PMN attachment to surfaces. Because CRP was found to be deposits at sites of tissue injury, the CRP-mediated adherence of PMN may be an important step in localizing an inflammatory focus

Leukocyte counts in urine reflect the risk of concomitant sepsis in bacteriuric infants: A retrospective cohort study

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Harper Marvin B

2007-06-01

Full Text Available Abstract Background When urine infections are missed in febrile young infants with normal urinalysis, clinicians may worry about the risk – hitherto unverified – of concomitant invasion of blood and cerebrospinal fluid by uropathogens. In this study, we determine the extent of this risk. Methods In a retrospective cohort study of febrile 0–89 day old infants evaluated for sepsis in an urban academic pediatric emergency department (1993–1999, we estimated rates of bacteriuric sepsis (urinary tract infections complicated by sepsis after stratifying infants by urine leukocyte counts higher, or lower than 10 cells/hpf. We compared the global accuracy of leukocytes in urine, leukocytes in peripheral blood, body temperature, and age for predicting bacteruric sepsis. The global accuracy of each test was estimated by calculating the area under its receiver operating characteristic curve (AUC. Chi-square and Fisher exact tests compared count data. Medians for data not normally distributed were compared by the Kruskal-Wallis test. Results Two thousand two hundred forty-nine young infants had a normal screening dipstick. None of these developed bacteremia or meningitis despite positive urine culture in 41 (1.8%. Of 1516 additional urine specimens sent for formal urinalysis, 1279 had 0–9 leukocytes/hpf. Urine pathogens were isolated less commonly (6% vs. 76% and at lower concentrations in infants with few, compared to many urine leukocytes. Urine leukocytes (AUC: 0.94 were the most accurate predictors of bacteruric sepsis. Infants with urinary leukocytes Conclusion In young infants evaluated for fever, leukocytes in urine reflect the likelihood of bacteriuric sepsis. Infants with urinary tract infections missed because of few leukocytes in urine are at relatively low risk of invasive bacterial sepsis by pathogens isolated from urine.

99mTc-HMPAO Labelled WBC Scan in Experimental Abscess by Labelling Autologous Leukocytes with In-House-Synthesized HMPAO

International Nuclear Information System (INIS)

Lee, Dong Soo; Shin, Hyung Sik; Ahn, Curie; Chung, June Key; Lee, Myung Chul; Choi, Kang Won; Koh, Chang Soon; Jung, Jae Min; Chung, Eun Ju

1991-01-01

With HMPAO we have synthesized in our laboratory, we labelled 99m Tc to canine leukocytes. Experimental abscess made by subcutaneous injection with Staphylococcus aureus was imaged with these 99m Tc labelled leukocytes. Labelling efficiency of HMPAO with 99m Tc was 66.2% ± 14.6% (N=9). Labelling efficiency of leukocytes with 99m Tc-HMPAO was 54% ± 7.79 (N=7). Cell bound radio activity in 99m Tc-HMPAO labelled leukocytes was around 80%. when these cells were incubated in plasma in vitro at 37 .deg. C for 5 hours. In vivo cell bound activity was over 80% at 24 hours after injection. One day and four days after inoculation, uptake at the inflammatory focus was found with 99m Tc labelled leukocytes. Uptake showed up in 4 hour image, and the uptake at the lesion was most prominent in 24 hour image. These findings show that in-house-synthesized HMPAO could be used for labelling leukocytes with 99m Tc, and that 99m Tc-HMPAO-labelled leukocytes were so stable and viable that inflammatory focus could be visualized with these 99m Tc-labelled leukocytes.

Soft tissue regeneration using leukocyte-platelet rich fibrin after exeresis of hyperplastic gingival lesions: two case reports.

Science.gov (United States)

di Lauro, A E; Abbate, D; Dell'Angelo, B; Iannaccone, G A; Scotto, F; Sammartino, G

2015-11-02

Leukocyte-platelet rich fibrin belongs to a second generation of platelet concentrates that does not need biochemical blood manipulation. It is used for tissue healing and regeneration in periodontal and oral-maxillofacial surgery. We report two cases of hyperplastic gingival lesions treated by exeresis and application of leukocyte-platelet rich fibrin membranes in order to improve and accelerate tissue healing. Two patients (a 78-year-old Caucasian woman and a 30-year-old Caucasian man) were treated for hyperplastic gingival lesions. They underwent to exeresis of lesions and application of leukocyte-platelet rich fibrin membranes. Tissue healing was clinically evaluated after 1, 3, 7, 14 and 30 postoperative days. No recurrences were observed after 2 years of semi-annual follow up. We obtained rapid and good healing of soft tissues probably due to the elevated content of leukocytes, platelets and growth factors in the leukocyte-platelet rich fibrin. Based on our results we suggest the use of leukocyte-platelet rich fibrin to cover wounds after exeresis of oral neoformations such as hyperplastic gingival lesions.

Flow cytofluorometric assay of human whole blood leukocyte DNA degradation in response to Yersinia pestis and Staphylococcus aureus

Science.gov (United States)

Kravtsov, Alexander L.; Grebenyukova, Tatyana P.; Bobyleva, Elena V.; Golovko, Elena M.; Malyukova, Tatyana A.; Lyapin, Mikhail N.; Kostyukova, Tatyana A.; Yezhov, Igor N.; Kuznetsov, Oleg S.

2001-05-01

Human leukocytes containing less than 2C DNA per cell (damaged or dead cells) were detected and quantified by flow cytometry and DNA-specific staining with ethidium bromide and mithramycin in whole blood infected with Staphylococcus aureus or Yersinia pestis. Addition of live S. aureus to the blood (100 microbe cells per one leukocyte) resulted in rapid degradation of leukocyte DNA within 3 to 6 hours of incubation at 37 degree(s)C. However, only about 50 percent cells were damaged and the leukocytes with the intact genetic apparatus could be found in the blood for a period up to 24 hours. The leukocyte injury was preceded by an increase of DNA per cell content (as compared to the normal one) that was likely to be connected with the active phagocytosis of S. aureus by granulocytes (2C DNA of diploid phagocytes plus the all bacterial DNA absorbed). In response to the same dose of actively growing (at 37 degree(s)C) virulent Y. pestis cells, no increase in DNA content per cell could be observed in the human blood leukocytes. The process of the leukocyte DNA degradation started after a 6-hour incubation, and between 18 to 24 hours of incubation about 90 percent leukocytes (phagocytes and lymphocytes) lost their specific DNA fluorescence. These results demonstrated a high potential of flow cytometry in comparative analysis in vitro of the leukocyte DNA degradation process in human blood in response to bacteria with various pathogenic properties. They agree with the modern idea of an apoptotic mechanism of immunosuppression in plague.

Leukocyte telomere length and hippocampus volume: a meta-analysis [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Gustav Nilsonne

2015-10-01

Full Text Available Leukocyte telomere length has been shown to correlate to hippocampus volume, but effect estimates differ in magnitude and are not uniformly positive. This study aimed primarily to investigate the relationship between leukocyte telomere length and hippocampus gray matter volume by meta-analysis and secondarily to investigate possible effect moderators. Five studies were included with a total of 2107 participants, of which 1960 were contributed by one single influential study. A random-effects meta-analysis estimated the effect to r = 0.12 [95% CI -0.13, 0.37] in the presence of heterogeneity and a subjectively estimated moderate to high risk of bias. There was no evidence that apolipoprotein E (APOE genotype was an effect moderator, nor that the ratio of leukocyte telomerase activity to telomere length was a better predictor than leukocyte telomere length for hippocampus volume. This meta-analysis, while not proving a positive relationship, also is not able to disprove the earlier finding of a positive correlation in the one large study included in analyses. We propose that a relationship between leukocyte telomere length and hippocamus volume may be mediated by transmigrating monocytes which differentiate into microglia in the brain parenchyma.

De novo design, synthesis, and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold.

Science.gov (United States)

Potin, Dominique; Launay, Michele; Nicolai, Eric; Fabreguette, Maud; Malabre, Patrice; Caussade, François; Besse, Dominique; Skala, Stacey; Stetsko, Dawn K; Todderud, Gordon; Beno, Brett R; Cheney, Daniel L; Chang, Chiehying J; Sheriff, Steven; Hollenbaugh, Diane L; Barrish, Joel C; Iwanowicz, Edwin J; Suchard, Suzanne J; Dhar, T G Murali

2005-02-15

LFA-1 (leukocyte function-associated antigen-1), is a member of the beta(2)-integrin family and is expressed on all leukocytes. The LFA-1/ICAM interaction promotes tight adhesion between activated leukocytes and the endothelium, as well as between T cells and antigen-presenting cells. Evidence from both animal models and clinical trials provides support for LFA-1 as a target in several different inflammatory diseases. This paper describes the de novo design, synthesis and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold.

Altered mitochondrial function and oxidative stress in leukocytes of anorexia nervosa patients.

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Victor M Victor

Full Text Available CONTEXT: Anorexia nervosa is a common illness among adolescents and is characterised by oxidative stress. OBJECTIVE: The effects of anorexia on mitochondrial function and redox state in leukocytes from anorexic subjects were evaluated. DESIGN AND SETTING: A multi-centre, cross-sectional case-control study was performed. PATIENTS: Our study population consisted of 20 anorexic patients and 20 age-matched controls, all of which were Caucasian women. MAIN OUTCOME MEASURES: Anthropometric and metabolic parameters were evaluated in the study population. To assess whether anorexia nervosa affects mitochondrial function and redox state in leukocytes of anorexic patients, we measured mitochondrial oxygen consumption, membrane potential, reactive oxygen species production, glutathione levels, mitochondrial mass, and complex I and III activity in polymorphonuclear cells. RESULTS: Mitochondrial function was impaired in the leukocytes of the anorexic patients. This was evident in a decrease in mitochondrial O2 consumption (P<0.05, mitochondrial membrane potential (P<0.01 and GSH levels (P<0.05, and an increase in ROS production (P<0.05 with respect to control subjects. Furthermore, a reduction of mitochondrial mass was detected in leukocytes of the anorexic patients (P<0.05, while the activity of mitochondrial complex I (P<0.001, but not that of complex III, was found to be inhibited in the same population. CONCLUSIONS: Oxidative stress is produced in the leukocytes of anorexic patients and is closely related to mitochondrial dysfunction. Our results lead us to propose that the oxidative stress that occurs in anorexia takes place at mitochondrial complex I. Future research concerning mitochondrial dysfunction and oxidative stress should aim to determine the physiological mechanism involved in this effect and the physiological impact of anorexia.

Historical mapping reveals causes and temporal patterns of woodland contraction in Austur-Skaftafellssýsla from the 12th century AD to present

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Sigurmundsson, Friðþór S.; Gísladóttir, Guðrún; Erlendsson, Egill; Þorbjarnarson, Höskuldur

2016-04-01

Land-cover changes in Iceland over the last millennium encompass birch (Betula pubescens) woodland depletion and extensive soil erosion. Yet few studies have focused on spatial change of birch woodland coverage in Iceland over centuries and why and how the woodland depletion took place. The main objectives of this study are: (1) to map the woodland distribution today in Austur-Skaftafellssýsla (3041 km2) in southern Iceland; (2) to map woodland holdings over a period of 900 years from eleventh. AD 1100 to the early 20th century; (3) explain the relative impacts of socio-economic and natural forces on woodland cover over this period. We use a combined approach of historical reconstruction from diverse written archives, GIS techniques and field work. The woodland in Austur-Skaftafellssýsla now covers 73.2 km2 (2.5% of the study area). The woodland holdings, 44 in total, are regularly listed in the church inventories from 1179 to 1570 and are owned by the church. In the first complete register for the district in 1641 the woodland holdings were 73, owned and used by 58 estates, and distributed across Austur-Skaftafellssýsla. All the main patches of woodland remain today, with the exception of four minor woodlands which were exhausted near the end of the 19th century. The woodland was used for firewood and charcoal making as well as grazing during the study period but, crucially, in most cases only one estate had authority over each holding, none were commons. The main driving force behind the development of woodlands was socio-economic, rather than natural, where the form of ownership was fundamental for the fate of the woodland. Harsh climate and volcanism were not directly responsible for woodland depletion. The latter half of the 19th century was the period of greatest woodland loss. This period coincides with considerable expansion in livestock numbers, especially sheep and associated all year around grazing, at a time when the Little Ice Age culminated in

Diagnosis of osteomyelitis of the foot in diabetic patients: Value of 111In-leukocyte scintigraphy

International Nuclear Information System (INIS)

Larcos, G.; Brown, M.L.; Sutton, R.T.

1991-01-01

The noninvasive diagnosis of osteomyelitis of the foot in diabetic patients with currently available radiologic and radionuclide imaging techniques is often difficult. Recently, 111In-labeled leukocyte scintigraphy has been proposed as an attractive alternative. Accordingly, the authors retrospectively reviewed 51 111In-labeled leukocyte scans, 49 technetium-99m bone scans, and 49 plain radiographs obtained in 51 adults with diabetes in whom osteomyelitis of the foot was suspected. The sensitivity and specificity of these techniques were evaluated in all patients, as well as in a subgroup of 11 patients with neuroarthropathy. Results with 111In-labeled leukocyte scans were also examined in subsets of patients with soft-tissue ulcers (n = 35) and those receiving antibiotics during investigation (n = 20). Confirmation or exclusion of osteomyelitis was made surgically in 28 patients and clinically in 23. Fourteen patients had osteomyelitis. Bone scans were most sensitive (93%) but least specific (43%); plain radiographs were most specific (83%) but least sensitive (43%). 111In-labeled leukocyte scans were both sensitive (79%) and specific (78%), and remained useful in patients with neuroarthropathy, soft-tissue ulcers, and antibiotic treatment. Poor spatial resolution contributed to the false-negative and false-positive 111In-labeled leukocyte scans, suggesting that this technique should not be interpreted independent of other tests. 111In-labeled leukocyte scans are a valuable diagnostic tool for the diagnosis of pedal osteomyelitis in diabetic patients

10-year survival rate and the incidence of peri-implant disease of 374 titanium dental implants with a SLA surface: a prospective cohort study in 177 fully and partially edentulous patients

NARCIS (Netherlands)

van Velzen, F.J.J.; Ofec, R.; Schulten, E.A.J.M.; ten Bruggenkate, C.M.

2015-01-01

Purpose This prospective cohort study evaluates the 10-year survival and incidence of peri-implant disease at implant and patient level of sandblasted, large grid, and acid-etched titanium dental implants (Straumann, soft tissue level, SLA surface) in fully and partially edentulous patients.

Effect of radiographic contrast agents on leukocyte metabolic response

Energy Technology Data Exchange (ETDEWEB)

Hernanz-Schulman, M. [Dept. of Pediatric Radiology, Vanderbilt Children' s Hospital, Nashville, TN (United States); Vanholder, R.; Waterloos, M.A. [Dept. of Internal Medicine, Nephrology Section, University Hospital, Gent (Belgium); Hakim, R.; Schulman, G. [Department of Nephrology, Vanderbilt University Medical Center, Nashville, TN (United States)

2000-06-01

Barium, at clinical dilutions, causes a significant increase of baseline ''resting state'' phagocytic activity, which in turn leads to significant blunting of subsequent response to phagocytic challenge and adversely affects the response to all bacteria tested. There is no baseline activation of leukocytes by the water-soluble media, although there was some inhibition (rather than activation) of leukocyte metabolic activity. The effect of the water-soluble media in bacteria was more complex (although inhibition is minor compared to barium). Our data demonstrate that barium is a significat activator of phagocytic cells, which results in deactivation of phagocytic response when challenged; these dsata serve to explain the enhanced adverse effect of barium in cased of fecal peritonitis. (orig.)

The non-classical antigens of HLA-G and HLA-E as diagnostic and prognostic biomarkers and as therapeutic targets in transplantation and tumors.

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Seliger, Barbara

2013-01-01

The non-classical human leukocyte antigen (HLA) class I antigen HLA-G represents a tolerogenic molecule and is involved in the inhibition of natural killer cell and cytotoxic T lymphocyte-mediated cytotoxicity. Under physiological conditions, HLA-G expression is mainly restricted to immune-privileged tissues, whereas it is overexpressed in tumors and transplants as well as in virus-infected cells. Due to its immunosuppressive features, HLA-G is important for pregnancy or organ transplantation and autoimmune diseases as well as cancer immune escape. This review focusses on the expression, regulation, and function of HLA-G in tumor cells andlor in transplants as well as therapeutic tools for enhancing (transplantation) or avoiding (tumor) tolerance. Thus, HLA-G or HLA-G-derived synthetic molecules might be used as therapeutic agents in combination with immunosuppressive drugs to enhance organ tolerance upon transplantation. In addition, HLA-G neoexpressing tumor cells could be targeted by HLA-G-specific microRNAs in order to enhance tumor immunogenicity.

Maternal circulating leukocytes display early chemotactic responsiveness during late gestation

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Gomez-Lopez Nardhy

2013-01-01

Full Text Available Abstract Background Parturition has been widely described as an immunological response; however, it is unknown how this is triggered. We hypothesized that an early event in parturition is an increased responsiveness of peripheral leukocytes to chemotactic stimuli expressed by reproductive tissues, and this precedes expression of tissue chemotactic activity, uterine activation and the systemic progesterone/estradiol shift. Methods Tissues and blood were collected from pregnant Long-Evans rats on gestational days (GD 17, 20 and 22 (term gestation. We employed a validated Boyden chamber assay, flow cytometry, quantitative real time-polymerase chain reaction, and enzyme-linked immunosorbent assays. Results We found that GD20 maternal peripheral leukocytes migrated more than those from GD17 when these were tested with GD22 uterus and cervix extracts. Leukocytes on GD20 also displayed a significant increase in chemokine (C-C motif ligand 2 (Ccl2 gene expression and this correlated with an increase in peripheral granulocyte proportions and a decrease in B cell and monocyte proportions. Tissue chemotactic activity and specific chemokines (CCL2, chemokine (C-X-C motif ligand 1/CXCL1, and CXCL10 were mostly unchanged from GD17 to GD20 and increased only on GD22. CXCL10 peaked on GD20 in cervical tissues. As expected, prostaglandin F2α receptor and oxytocin receptor gene expression increased dramatically between GD20 and 22. Progesterone concentrations fell and estradiol-17β concentrations increased in peripheral serum, cervical and uterine tissue extracts between GD20 and 22. Conclusion Maternal circulating leukocytes display early chemotactic responsiveness, which leads to their infiltration into the uterus where they may participate in the process of parturition.

Leukocyte counts in urine reflect the risk of concomitant sepsis in bacteriuric infants: a retrospective cohort study.

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Bonsu, Bema K; Harper, Marvin B

2007-06-13

When urine infections are missed in febrile young infants with normal urinalysis, clinicians may worry about the risk--hitherto unverified--of concomitant invasion of blood and cerebrospinal fluid by uropathogens. In this study, we determine the extent of this risk. In a retrospective cohort study of febrile 0-89 day old infants evaluated for sepsis in an urban academic pediatric emergency department (1993-1999), we estimated rates of bacteriuric sepsis (urinary tract infections complicated by sepsis) after stratifying infants by urine leukocyte counts higher, or lower than 10 cells/hpf. We compared the global accuracy of leukocytes in urine, leukocytes in peripheral blood, body temperature, and age for predicting bacteruric sepsis. The global accuracy of each test was estimated by calculating the area under its receiver operating characteristic curve (AUC). Chi-square and Fisher exact tests compared count data. Medians for data not normally distributed were compared by the Kruskal-Wallis test. Two thousand two hundred forty-nine young infants had a normal screening dipstick. None of these developed bacteremia or meningitis despite positive urine culture in 41 (1.8%). Of 1516 additional urine specimens sent for formal urinalysis, 1279 had 0-9 leukocytes/hpf. Urine pathogens were isolated less commonly (6% vs. 76%) and at lower concentrations in infants with few, compared to many urine leukocytes. Urine leukocytes (AUC: 0.94) were the most accurate predictors of bacteruric sepsis. Infants with urinary leukocytes urinary tract infections complicated by bacteremia (N = 11) or bacterial meningitis (N = 1)--relative risk, 0 (CI:0-0.06) [RR, 0 (CI: 0-0.02), when including infants with negative dipstick]. Bands in peripheral blood had modest value for detecting bacteriuric sepsis (AUC: 0.78). Cases of sepsis without concomitant bacteriuria were comparatively rare (0.8%) and equally common in febrile young infants with low and high concentrations of urine leukocytes. In

Decline of blood leukocyte counts 1947-59, Hiroshima and Nagasaki

Energy Technology Data Exchange (ETDEWEB)

Ichimaru, Michito; Ueda, Shoichi; Blaisdell, R K

1963-03-03

Earlier reports of progressive decline in leukocyte counts in Hiroshima from about 1948 to 1954 have been confirmed. A similar phenomenon has been observed in Nagasaki. Analysis indicates that this decline in white cell count with time is not related to exposure to the 1945 atomic bombs, to sex, to age, to commonly diagnosed diseases, or to the disproportionate influence of a subgroup. The principal white cells affected were neutrophils, lymphocytes and eosinophils. The precise etiologic factors accounting for the decline, and the biological significance of the present lower range of leukocyte values in Hiroshima and Nagasaki remain to be determined. 16 references, 5 figures, 5 tables.

Role of β1 integrins and bacterial adhesins for Yop injection into leukocytes in Yersinia enterocolitica systemic mouse infection.

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Deuschle, Eva; Keller, Birgit; Siegfried, Alexandra; Manncke, Birgit; Spaeth, Tanja; Köberle, Martin; Drechsler-Hake, Doreen; Reber, Julia; Böttcher, Ralph T; Autenrieth, Stella E; Autenrieth, Ingo B; Bohn, Erwin; Schütz, Monika

2016-02-01

Injection of Yersinia outer proteins (Yops) into host cells by a type III secretion system is an important immune evasion mechanism of Yersinia enterocolitica (Ye). In this process Ye invasin (Inv) binds directly while Yersinia adhesin A (YadA) binds indirectly via extracellular matrix (ECM) proteins to β1 integrins on host cells. Although leukocytes turned out to be an important target of Yop injection by Ye, it was unclear which Ye adhesins and which leukocyte receptors are required for Yop injection. To explain this, we investigated the role of YadA, Inv and β1 integrins for Yop injection into leukocytes and their impact on the course of systemic Ye infection in mice. Ex vivo infection experiments revealed that adhesion of Ye via Inv or YadA is sufficient to promote Yop injection into leukocytes as revealed by a β-lactamase reporter assay. Serum factors inhibit YadA- but not Inv-mediated Yop injection into B and T cells, shifting YadA-mediated Yop injection in the direction of neutrophils and other myeloid cells. Systemic Ye mouse infection experiments demonstrated that YadA is essential for Ye virulence and Yop injection into leukocytes, while Inv is dispensable for virulence and plays only a transient and minor role for Yop injection in the early phase of infection. Ye infection of mice with β1 integrin-depleted leukocytes demonstrated that β1 integrins are dispensable for YadA-mediated Yop injection into leukocytes, but contribute to Inv-mediated Yop injection. Despite reduced Yop injection into leukocytes, β1 integrin-deficient mice exhibited an increased susceptibility for Ye infection, suggesting an important role of β1 integrins in immune defense against Ye. This study demonstrates that Yop injection into leukocytes by Ye is largely mediated by YadA exploiting, as yet unknown, leukocyte receptors. Copyright © 2015. Published by Elsevier GmbH.

Indium-111 leukocyte scintigraphic detection of myocardial abscess formation in patients with endocarditis

Energy Technology Data Exchange (ETDEWEB)

Cerqueira, M.D.; Jacobson, A.F.

1989-05-01

Myocardial abscess formation in patients with bacterial endocarditis in most clinical settings, especially in patients with prosthetic valves, is a primary indicator for surgical valve replacement. We report the detection of myocardial abscesses using /sup 111/In leukocyte scintigraphy in three patients with prosthetic or native valve endocarditis and nondiagnostic echocardiograms. Leukocyte scintigraphy may allow identification of myocardial abscess formation earlier than other imaging modalities.

Indium-111 leukocyte scintigraphic detection of myocardial abscess formation in patients with endocarditis

International Nuclear Information System (INIS)

Cerqueira, M.D.; Jacobson, A.F.

1989-01-01

Myocardial abscess formation in patients with bacterial endocarditis in most clinical settings, especially in patients with prosthetic valves, is a primary indicator for surgical valve replacement. We report the detection of myocardial abscesses using 111 In leukocyte scintigraphy in three patients with prosthetic or native valve endocarditis and nondiagnostic echocardiograms. Leukocyte scintigraphy may allow identification of myocardial abscess formation earlier than other imaging modalities

Channel catfish (Ictalurus punctatus) leukocytes express estrogen receptor isoforms ERα and ERβ2 and are functionally modulated by estrogens.

Science.gov (United States)

Iwanowicz, Luke R; Stafford, James L; Patiño, Reynaldo; Bengten, Eva; Miller, Norman W; Blazer, Vicki S

2014-09-01

Estrogens are recognized as modulators of immune responses in mammals and teleosts. While it is known that the effects of estrogens are mediated via leukocyte-specific estrogen receptors (ERs) in humans and mice, leucocyte-specific estrogen receptor expression and the effects of estrogens on this cell population is less explored and poorly understood in teleosts. Here in, we verify that channel catfish (Ictalurus punctaus) leukocytes express ERα and ERβ2. Transcripts of these isoforms were detected in tissue-associated leukocyte populations by PCR, but ERβ2 was rarely detected in PBLs. Expression of these receptors was temporally regulated in PBLs following polyclonal activation by concanavalin A, lipopolysaccharide or alloantigen based on evaluation by quantitative and end-point PCR. Examination of long-term leukocyte cell lines demonstrated that these receptors are differentially expressed depending on leukocyte lineage and phenotype. Expression of ERs was also temporally dynamic in some leukocyte lineages and may reflect stage of cell maturity. Estrogens affect the responsiveness of channel catfish peripheral blood leukocytes (PBLs) to mitogens in vitro. Similarly, bactericidal activity and phorbol 12-myristate 13-acetate induced respiratory burst was modulated by 17β-estradiol. These actions were blocked by the pure ER antagonist ICI 182780 indicating that response is, in part, mediated via ERα. In summary, estrogen receptors are expressed in channel catfish leukocytes and participate in the regulation of the immune response. This is the first time leukocyte lineage expression has been reported in teleost cell lines. Published by Elsevier Ltd.

Shorter preschool, leukocyte telomere length is associated with obesity at age 9 in Latino children

DEFF Research Database (Denmark)

Kjaer, Thora Wesenberg; Faurholt-Jepsen, D; Mehta, K M

2018-01-01

The aim of this study was to determine the potential role of leukocyte telomere length as a biomarker for development of childhood obesity in a low-income Latino population. A birth cohort of Latino children (N = 201) in San Francisco (recruited May 2006-May 2007) was followed until age 9...... and assessed annually for obesity and dietary intake. Leukocyte telomere length was measured at 4 and 5 years (n = 102) and assessed as a predictor for obesity at age 9, adjusting for known risk factors. Furthermore, leukocyte telomere length at age 4 and 5 was evaluated as a possible mediator...... of the relationship between excessive sugar-sweetened beverage consumption and obesity at age 9. Shorter leukocyte telomere length in preschoolers was associated with obesity at age 9 (adjusted odds ratio 0.35, 95% confidence interval 0.13-0.94) after adjustment for known risk factors. Telomere length mediated 11...

Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS

DEFF Research Database (Denmark)

Babcock, Alicia A; Kuziel, William A; Rivest, Serge

2003-01-01

Innate responses in the CNS are critical to first line defense against infection and injury. Leukocytes migrate to inflammatory sites in response to chemokines. We studied leukocyte migration and glial chemokine expression within the denervated hippocampus in response to axonal injury caused by e...

Shorter preschool, leukocyte telomere length is associated with obesity at age 9 in Latino children.

Science.gov (United States)

Kjaer, T W; Faurholt-Jepsen, D; Mehta, K M; Christensen, V B; Epel, E; Lin, J; Blackburn, E; Wojcicki, J M

2018-04-01

The aim of this study was to determine the potential role of leukocyte telomere length as a biomarker for development of childhood obesity in a low-income Latino population. A birth cohort of Latino children (N = 201) in San Francisco (recruited May 2006-May 2007) was followed until age 9 and assessed annually for obesity and dietary intake. Leukocyte telomere length was measured at 4 and 5 years (n = 102) and assessed as a predictor for obesity at age 9, adjusting for known risk factors. Furthermore, leukocyte telomere length at age 4 and 5 was evaluated as a possible mediator of the relationship between excessive sugar-sweetened beverage consumption and obesity at age 9. Shorter leukocyte telomere length in preschoolers was associated with obesity at age 9 (adjusted odds ratio 0.35, 95% confidence interval 0.13-0.94) after adjustment for known risk factors. Telomere length mediated 11% of the relationship between excessive sugar-sweetened beverage consumption and obesity. Shorter leukocyte telomere length may be an indicator of future obesity risk in high-risk populations as it is particularly sensitive to damage from oxidative stress exposure, including those from sugar-sweetened beverages. © 2017 World Obesity Federation.

MeReg: Managing Energy-SLA Tradeoff for Green Mobile Cloud Computing

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Rahul Yadav

2017-01-01

Full Text Available Mobile cloud computing (MCC provides various cloud computing services to mobile users. The rapid growth of MCC users requires large-scale MCC data centers to provide them with data processing and storage services. The growth of these data centers directly impacts electrical energy consumption, which affects businesses as well as the environment through carbon dioxide (CO2 emissions. Moreover, large amount of energy is wasted to maintain the servers running during low workload. To reduce the energy consumption of mobile cloud data centers, energy-aware host overload detection algorithm and virtual machines (VMs selection algorithms for VM consolidation are required during detected host underload and overload. After allocating resources to all VMs, underloaded hosts are required to assume energy-saving mode in order to minimize power consumption. To address this issue, we proposed an adaptive heuristics energy-aware algorithm, which creates an upper CPU utilization threshold using recent CPU utilization history to detect overloaded hosts and dynamic VM selection algorithms to consolidate the VMs from overloaded or underloaded host. The goal is to minimize total energy consumption and maximize Quality of Service, including the reduction of service level agreement (SLA violations. CloudSim simulator is used to validate the algorithm and simulations are conducted on real workload traces in 10 different days, as provided by PlanetLab.

Expression and Antigenic Evaluation of VacA Antigenic Fragment of Helicobacter Pylori

Science.gov (United States)

Hasanzadeh, Leila; Ghaznavi-Rad, Ehsanollah; Soufian, Safieh; Farjadi, Vahideh; Abtahi, Hamid

2013-01-01

Objective(s) : Helicobacter pylori, a human specific gastric pathogen is a causative agent of chronic active gastritis. The vacuolating cytotoxin (VacA) is an effective virulence factor involved in gastric injury. The aim of this study was to construct a recombinant protein containing antigenic region of VacA gene and determine its antigenicity. Materials and Methods: The antigenic region of VacA gene was detected by bioinformatics methods. The polymerase chain reaction method was used to amplify a highly antigenic region of VacA gene from chromosomal DNA of H. pylori. The eluted product was cloned into the prokaryotic expression vector pET32a. The target protein was expressed in the Escherichia coli BL21 (DE3) pLysS. The bacteria including pET32a-VacA plasmids were induced by IPTG. The antigenicity was finally studied by western blotting using sera of 15 H. pylori infected patients after purification. Results: Enzyme digestion analysis, PCR and DNA sequencing results showed that the target gene was inserted correctly into the recombinant vector. The expressed protein was purified successfully via affinity chromatography. Data indicated that antigenic region of VacA protein from Helicobacter pylori was recognized by all 15 patient’s sera. Conclusion : Our data showed that antigenic region of VacA protein can be expressed by in E. co.li. This protein was recognized by sera patients suffering from H. pylori infection. the recombinant protein has similar epitopes and close antigenic properties to the natural form of this antigen. Recombinant antigenic region of VacA protein also seems to be a promising antigen for protective and serologic diagnosis . PMID:23997913

Expression and Antigenic Evaluation of VacA Antigenic Fragment of Helicobacter Pylori

Directory of Open Access Journals (Sweden)

Leila Hasanzadeh

2013-07-01

Full Text Available Objective(s: Helicobacter pylori, a human specific gastric pathogen is a causative agent of chronic active gastritis. The vacuolating cytotoxin (VacA is an effective virulence factor involved in gastric injury. The aim of this study was to construct a recombinant protein containing antigenic region of VacA gene and determine its antigenicity.   Materials and Methods: The antigenic region of VacA gene was detected by bioinformatics methods. The polymerase chain reaction method was used to amplify a highly antigenic region of VacA gene from chromosomal DNA of H. pylori. The eluted product was cloned into the prokaryotic expression vector pET32a. The target protein was expressed in the Escherichia coli BL21 (DE3 pLysS. The bacteria including pET32a-VacA plasmids were induced by IPTG. The antigenicity was finally studied by western blotting using sera of 15 H. pylori infected patients after purification. Results: Enzyme digestion analysis, PCR and DNA sequencing results showed that the target gene was inserted correctly into the recombinant vector. The expressed protein was purified successfully via affinity chromatography. Data indicated that antigenic region of VacA protein from Helicobacter pylori was recognized by all 15 patient’s sera. Conclusion : Our data showed that antigenic region of VacA protein can be expressed by in E. co.li. This protein was recognized by sera patients suffering from H. pylori infection. the recombinant protein has similar epitopes and close antigenic properties to the natural form of this antigen. Recombinant antigenic region of VacA protein also seems to be a promising antigen for protective and serologic diagnosis .

Osteomyelitis in leukocyte adhesion deficiency type 1 syndrome

DEFF Research Database (Denmark)

Jabbari Azad, Farahzad; Ardalan, Maryam; H.Rafati, Ali

2010-01-01

Leukocyte adhesion deficiency type 1 (LAD-1) is a rare, inherited immunodeficiency that affects one per million people yearly and usually presents with recurrent, indolent bacterial infections of the skin, mouth, and respiratory tract and impaired pus formation and wound healing. A 13-year-old girl...

The molecular bases of δ/αβ T cell-mediated antigen recognition.

Science.gov (United States)

Pellicci, Daniel G; Uldrich, Adam P; Le Nours, Jérôme; Ross, Fiona; Chabrol, Eric; Eckle, Sidonia B G; de Boer, Renate; Lim, Ricky T; McPherson, Kirsty; Besra, Gurdyal; Howell, Amy R; Moretta, Lorenzo; McCluskey, James; Heemskerk, Mirjam H M; Gras, Stephanie; Rossjohn, Jamie; Godfrey, Dale I

2014-12-15

αβ and γδ T cells are disparate T cell lineages that can respond to distinct antigens (Ags) via the use of the αβ and γδ T cell Ag receptors (TCRs), respectively. Here we characterize a population of human T cells, which we term δ/αβ T cells, expressing TCRs comprised of a TCR-δ variable gene (Vδ1) fused to joining α and constant α domains, paired with an array of TCR-β chains. We demonstrate that these cells, which represent ∼50% of all Vδ1(+) human T cells, can recognize peptide- and lipid-based Ags presented by human leukocyte antigen (HLA) and CD1d, respectively. Similar to type I natural killer T (NKT) cells, CD1d-lipid Ag-reactive δ/αβ T cells recognized α-galactosylceramide (α-GalCer); however, their fine specificity for other lipid Ags presented by CD1d, such as α-glucosylceramide, was distinct from type I NKT cells. Thus, δ/αβTCRs contribute new patterns of Ag specificity to the human immune system. Furthermore, we provide the molecular bases of how δ/αβTCRs bind to their targets, with the Vδ1-encoded region providing a major contribution to δ/αβTCR binding. Our findings highlight how components from αβ and γδTCR gene loci can recombine to confer Ag specificity, thus expanding our understanding of T cell biology and TCR diversity. © 2014 Pellicci et al.

The molecular bases of δ/αβ T cell–mediated antigen recognition

Science.gov (United States)

Pellicci, Daniel G.; Uldrich, Adam P.; Le Nours, Jérôme; Ross, Fiona; Chabrol, Eric; Eckle, Sidonia B.G.; de Boer, Renate; Lim, Ricky T.; McPherson, Kirsty; Besra, Gurdyal; Howell, Amy R.; Moretta, Lorenzo; McCluskey, James; Heemskerk, Mirjam H.M.; Gras, Stephanie

2014-01-01

αβ and γδ T cells are disparate T cell lineages that can respond to distinct antigens (Ags) via the use of the αβ and γδ T cell Ag receptors (TCRs), respectively. Here we characterize a population of human T cells, which we term δ/αβ T cells, expressing TCRs comprised of a TCR-δ variable gene (Vδ1) fused to joining α and constant α domains, paired with an array of TCR-β chains. We demonstrate that these cells, which represent ∼50% of all Vδ1+ human T cells, can recognize peptide- and lipid-based Ags presented by human leukocyte antigen (HLA) and CD1d, respectively. Similar to type I natural killer T (NKT) cells, CD1d-lipid Ag-reactive δ/αβ T cells recognized α-galactosylceramide (α-GalCer); however, their fine specificity for other lipid Ags presented by CD1d, such as α-glucosylceramide, was distinct from type I NKT cells. Thus, δ/αβTCRs contribute new patterns of Ag specificity to the human immune system. Furthermore, we provide the molecular bases of how δ/αβTCRs bind to their targets, with the Vδ1-encoded region providing a major contribution to δ/αβTCR binding. Our findings highlight how components from αβ and γδTCR gene loci can recombine to confer Ag specificity, thus expanding our understanding of T cell biology and TCR diversity. PMID:25452463

[The use of programmed microcalculators for automation of leukocyte count].

Science.gov (United States)

Plykin, D L

1989-01-01

Soviet programmed microcalculators are recommended to be used for the calculation of the leukocytic formulae when making serial blood analyses at clinical laboratories. The suggested program helps completely automate the process of estimating the leukocyte types, detectable in microscopic examination of the blood smears; the results may be obtained as a per cent ratio of the cells (a form most prevalent nowadays) and as their quantity per microliter of blood. The presence of service elements in the program essentially simplifies the work, making it convenient for an untrained user of the microcalculator. Since commercial Soviet programmed microcalculators somewhat differ in the systems of program steps, two variants of the program are suggested, adapted to the two most prevalent designs.

Effect of Semen on Vaginal Fluid Cytokines and Secretory Leukocyte Protease Inhibitor

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Kathy J. Agnew

2008-01-01

Methods: 138 pregnant women had vaginal fluid collected for Gram stain, acid phosphatase detection by colorimetric assay, and interleukin 1-Beta, interleukin-6, interleukin-8, and secretory leukocyte protease inhibitor measurement by enzyme immunoassay. Results for women with and without acid phosphatase were compared by Mann-Whitney test. Results: of 138 subjects, 28 (20% had acid phosphatase detected; of these, only 19 (68% reported recent intercourse and 3 (11% had sperm seen on Gram stain. There were no significant differences in proinflammatory cytokine concentrations; however, secretory leukocyte protease inhibitor concentrations were significantly higher among women with acid phosphatase. Conclusions: proinflammatory cytokine measurement does not appear to be affected by the presence of semen, but secretory leukocyte protease inhibitor is significantly higher when semen is present. Detection of semen by acid phosphatase was associated with higher vaginal SLPI concentrations, however, the presence of semen did not appear to influence vaginal proinflammatory cytokine concentrations.

Leukocyte scintiscanning for the diagnosis of inflammations. Leukozytenszintigraphie zur Diagnostik entzuendlicher Erkrankungen

Energy Technology Data Exchange (ETDEWEB)

Becker, W

1988-01-01

The value of leukocyte scintiscanning for clinical diagnostics is examined with regard to various areas of indications, and as a method of first examination, or as an alternative to, or additional method to be combined with, the other usual techniques. Leukocyte scintiscanning is indicated as a good first examination method in case of chronic enteritis in a highly active stage, stenosis of the colon, or when abscess is suspected, or infected renal cysts, or infection of angioplasty, osteomyelitis, or in case of fiever of unknown origin and impossible focal diagnosis. It also is applicable for follow-up diagnostics in chronic enteritis, suspected abdominal abscess, prosthetic valvular endocarditis, and infection of hip joint prothesis. The method also may yield additional information in case of renal graft rejection, coronary inflammations, for differential diagnosis of brain tumor or abcess, edematous or antodigestive pancreatitis, and in chronic polyarthritis. For leukocyte labelling, indium-111 and Tc-99m are primarily used. (ECB).

Altered mitochondrial function and oxidative stress in leukocytes of anorexia nervosa patients.

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Victor, Victor M; Rovira-Llopis, Susana; Saiz-Alarcon, Vanessa; Sangüesa, Maria C; Rojo-Bofill, Luis; Bañuls, Celia; Falcón, Rosa; Castelló, Raquel; Rojo, Luis; Rocha, Milagros; Hernández-Mijares, Antonio

2014-01-01

Anorexia nervosa is a common illness among adolescents and is characterised by oxidative stress. The effects of anorexia on mitochondrial function and redox state in leukocytes from anorexic subjects were evaluated. A multi-centre, cross-sectional case-control study was performed. Our study population consisted of 20 anorexic patients and 20 age-matched controls, all of which were Caucasian women. Anthropometric and metabolic parameters were evaluated in the study population. To assess whether anorexia nervosa affects mitochondrial function and redox state in leukocytes of anorexic patients, we measured mitochondrial oxygen consumption, membrane potential, reactive oxygen species production, glutathione levels, mitochondrial mass, and complex I and III activity in polymorphonuclear cells. Mitochondrial function was impaired in the leukocytes of the anorexic patients. This was evident in a decrease in mitochondrial O2 consumption (Panorexia takes place at mitochondrial complex I. Future research concerning mitochondrial dysfunction and oxidative stress should aim to determine the physiological mechanism involved in this effect and the physiological impact of anorexia.

Photoperiod affects the expression of sex and species differences in leukocyte number and leukocyte trafficking in congeneric hamsters.

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Bilbo, S D; Dhabhar, F S; Viswanathan, K; Saul, A; Nelson, R J

2003-11-01

Sex differences in immune function are well documented. These sex differences may be modulated by social and environmental factors. Individuals of polygynous species generally exhibit more pronounced sex differences in immune parameters than individuals of monogamous species, often displaying an energetic trade-off between enhanced immunity and high mating success. During winter, animals contend with environmental conditions (e.g. low temperatures and decreased food availability) that evoke energetic-stress responses; many mammals restrict reproduction in response to photoperiod as part of an annual winter coping strategy. To test the hypothesis that extant sex and species differences in immune surveillance may be modulated by photoperiod, we examined leukocyte numbers in males and females of two closely related hamster species (Phodopus). As predicted, uniparental P. sungorus exhibited a robust sex difference, with total white blood cells, total lymphocytes, T cells, and B cells higher in females than males, during long days when reproduction occurs, but not during short days when reproduction usually stops. In contrast, biparental male and female P. campbelli exhibited comparable leukocyte numbers during both long and short days. To study sex differences in stress responses, we also examined immune cell trafficking in response to an acute (2 h) restraint stressor. During stressful challenges, it appears beneficial for immune cells to exit the blood and move to primary immune defense areas such as the skin, in preparation for potential injury or infection. Acute stress moved lymphocytes and monocytes out of the blood in all animals. Blood cortisol concentrations were increased in P. sungorus females compared to males at baseline (52%) and in response to restraint stress (38%), but only in long days. P. campbelli males and females exhibited comparable blood cortisol and stress responses during both long and short days. Our results suggest that interactions among

Reduced platelet-mediated and enhanced leukocyte-mediated fibrinolysis in experimentally induced diabetes in rats

International Nuclear Information System (INIS)

Winocour, P.D.; Colwell, J.A.

1985-01-01

Studies of fibrinolytic activity in diabetes mellitus have produced conflicting results. This may be a result of methodologic insensitivity or of variable contributions of the different blood components to whole blood fibrinolysis. To explore these two possibilities, the authors used a sensitive solid-phase radiometric assay to examine the fibrinolytic activity of whole blood, platelet-rich plasma, leukocytes, and platelet- and leukocyte-poor plasma prepared from control rats and rats with streptozocin-induced diabetes at various times after induction of diabetes. Fibrinolytic activity of whole blood from diabetic rats after 7 days was significantly reduced, and remained reduced after longer durations of diabetes up to 28 days. Platelet-rich plasma from diabetic rats had decreased fibrinolytic activity, which followed the same time course of changes as in whole blood. The platelet contribution to whole blood fibrinolysis was further reduced in vivo after 14 days of diabetes by a reduced whole blood platelet count. In contrast, fibrinolytic activity of leukocytes from diabetic rats became enhanced after 7 days of diabetes. After 49 days of diabetes, the whole blood leukocyte count was reduced, and in vivo would offset the enhanced activity. Plasma fibrinolytic activity was small compared with that of whole blood and was unaltered in diabetic rats. The authors conclude that altered platelet function contributes to decreased fibrinolytic activity of whole blood in diabetic rats, and that this may be partially offset by enhanced leukocyte-mediated fibrinolysis

High plasma folate is negatively associated with leukocyte telomere length in Framingham Offspring cohort.

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Paul, Ligi; Jacques, Paul F; Aviv, Abraham; Vasan, Ramachandran S; D'Agostino, Ralph B; Levy, Daniel; Selhub, Jacob

2015-03-01

Shortening of telomeres, the protective structures at the ends of eukaryotic chromosomes, is associated with age-related pathologies. Telomere length is influenced by DNA integrity and DNA and histone methylation. Folate plays a role in providing precursors for nucleotides and methyl groups for methylation reactions and has the potential to influence telomere length. We determined the association between leukocyte telomere length and long-term plasma folate status (mean of 4 years) in Framingham Offspring Study (n = 1,044, females = 52.1 %, mean age 59 years) using data from samples collected before and after folic acid fortification. Leukocyte telomere length was determined by Southern analysis and fasting plasma folate concentration using microbiological assay. There was no significant positive association between long-term plasma folate and leukocyte telomere length among the Framingham Offspring Study participants perhaps due to their adequate folate status. While the leukocyte telomere length in the second quintile of plasma folate was longer than that in the first quintile, the difference was not statistically significant. The leukocyte telomere length of the individuals in the fifth quintile of plasma folate was shorter than that of those in the second quintile by 180 bp (P folate concentrations in the upper four quintiles of plasma folate (P for trend = 0.001). Multivitamin use was associated with shorter telomeres in this cohort (P = 0.015). High plasma folate status possibly resulting from high folic acid intake may interfere with the role of folate in maintaining telomere integrity.

A Hybrid Multiobjective Discrete Particle Swarm Optimization Algorithm for a SLA-Aware Service Composition Problem

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Hao Yin

2014-01-01

Full Text Available For SLA-aware service composition problem (SSC, an optimization model for this algorithm is built, and a hybrid multiobjective discrete particle swarm optimization algorithm (HMDPSO is also proposed in this paper. According to the characteristic of this problem, a particle updating strategy is designed by introducing crossover operator. In order to restrain particle swarm’s premature convergence and increase its global search capacity, the swarm diversity indicator is introduced and a particle mutation strategy is proposed to increase the swarm diversity. To accelerate the process of obtaining the feasible particle position, a local search strategy based on constraint domination is proposed and incorporated into the proposed algorithm. At last, some parameters in the algorithm HMDPSO are analyzed and set with relative proper values, and then the algorithm HMDPSO and the algorithm HMDPSO+ incorporated by local search strategy are compared with the recently proposed related algorithms on different scale cases. The results show that algorithm HMDPSO+ can solve the SSC problem more effectively.

Mechanisms of the priming effect of low doses of lipopoly-saccharides on leukocyte-dependent platelet aggregation in whole blood.

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Montrucchio, Giuseppe; Bosco, Ornella; Del Sorbo, Lorenzo; Fascio Pecetto, Paolo; Lupia, Enrico; Goffi, Alberto; Omedè, Paola; Emanuelli, Giorgio; Camussi, Giovanni

2003-11-01

Several studies focused on the ability of bacterial lipopolysac-charides (LPS) in triggering platelet and/or leukocyte activation. The aim of this study was to investigate the molecular mechanisms involved in the aggregation of platelets and in their interaction with leukocytes in whole blood after stimulation with low doses of LPS. LPS did not directly induce platelet aggregation in whole blood, but they primed the aggregation of platelets induced by epinephrine, adenosine diphosphate and arachidonic acid. As shown by cytofluorimetry, platelets neither bind FITC-LPS, nor express the LPS-receptors CD14 and toll-like receptor 4 (TLR4). On the contrary, LPS primed monocytes and to a lesser extent polymorphonuclear neutrophils to adhere to platelets. Both platelet-leukocyte interaction and platelet aggregation in whole blood were inhibited by blockade of CD14 and TLR4. Moreover, the interaction between platelets and leukocytes was inhibited by P-selectin, and by blockade of PAF and reactive oxygen species, suggesting a role of P-selectin and of leukocyte-derived mediators. In conclusion, these results elucidate the mechanisms leading to platelet activation and interaction with leukocytes triggered by LPS. They suggest that the activation of platelets by LPS is mainly dependent on leukocytes and especially monocytes as a result of CD14 and TLR4 engagement. Moreover, we found that leukocyte-platelet interaction was triggered by the synthesis of PAF and the generation of oxygen radicals that induced upregulation of surface expression of P-selectin.

21 CFR 864.7660 - Leukocyte alkaline phosphatase test.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Leukocyte alkaline phosphatase test. 864.7660 Section 864.7660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7660...

LEUKOCYTE DIFFERENTIAL OF ANGUILLID EEL, Anguilla bicolor McClelland, EXPOSED TO VARIED SALINITIES

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Fita Fatimah

2017-06-01

Full Text Available The anguillid eel is a catadromous eel capable of inhabiting freshwater growth habitat and seawater spawning habitat throughout their life cycle. At the juvenile to mature stage, they inhabit freshwater then migrate to marine water to spawn. Changes in salinity, which is one of the stressful environmental factors for the eel, affect their physiological condition by increasing the leukocytes number. This increase is an adaptation method to improve their immune system as a response to salinity change. This study intended to evaluate the leukocyte differential of anguillid eel (Anguilla bicolor McClelland exposed to various salinities. This research applied a Completely Randomized Design. The treatment was three levels of saline media including 4 ppt, 15 ppt, and 30 ppt with five replicates. The independent variable was the different salinity, and the dependent variable was the leukocyte differential. The parameters measured consisted of the different percentage of neutrophils, lymphocytes, monocytes, and eosinophils in which the measurements administered after two months of the eel exposure. We analyzed the data with ANOVA at the confidence level of 95%. The results showed that exposure of salinity significantly affected the percentage of leukocyte differential (P < 0.05. The increase in salinity decreased the neutrophils and monocytes, but increased the lymphocytes, and showed no effect on eosinophils.

Immunoregulatory changes induced by total lymphoid irradiation. II. Development of thymus-leukemia antigen-positive and -negative suppressor T cells that differ in their regulatory function

International Nuclear Information System (INIS)

King, D.P.; Strober, S.

1981-01-01

BALB/c mice treated with total lymphoid irradiation (TLI) develop non-antigen-specific suppressor cells of the adoptive secondary antibody response and of the mixed leukocyte reaction. Suppressors of the adoptive anti-DNP response were eliminated by incubation of spleen cells with anti-Thy-1.2 or anti-thymus-leukemia (TL) antiserum and complement before cell transfer. Thymectomy before TLI prevented the appearance of the latter suppressor cells. On the other hand, suppressors of the MLR were eliminated by incubation of spleen cells with anti-Thy-1.2 but not anti-TL antiserum and complement. Thymectomy before TLI did not prevent their subsequent development. Thus, two subpopulations of suppressor T cells that differ in the expression of the TL surface antigen, dependence on the presence of the thymus, and in regulatory functions develop after TLI. The TL+, thymus-dependent cell suppresses the adoptive antibody response, and the TL-, thymus-independent cell suppresses the MLR

Activation of lysosomal cathepsins in pregnant bovine leukocytes.

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Talukder, Md Abdus Shabur; Balboula, Ahmed Zaky; Shirozu, Takahiro; Kim, Sung Woo; Kunii, Hiroki; Suzuki, Toshiyuki; Ito, Tsukino; Kimura, Koji; Takahashi, Masashi

2018-06-01

In ruminants, interferon-tau (IFNT) - mediated expression of interferon-stimulated genes in peripheral blood leukocytes (PBLs) can indicate pregnancy. Recently, type 1 IFN-mediated activation of lysosomes and lysosomal cathepsins (CTSs) was observed in immune cells. This study investigated the status of lysosomal CTSs and lysosomes in PBLs collected from pregnant (P) and non-pregnant (NP) dairy cows, and conducted in vitro IFNT stimulation of NP blood leukocytes. Blood samples were collected 0, 7, 14 and 18 days post-artificial insemination, and the peripheral blood mononuclear cells (PBMCs) and polymorphonuclear granulocytes (PMNs) separated. The fluorescent activity of CTSB and CTSK in PMNs significantly increased with the progress of pregnancy, especially on day 18. In vitro supplementation of IFNT significantly increased the activities of CTSB and CTSK in NP PBMCs and PMNs. CTSB expression was significantly higher in PBMCs and PMNs collected from P day-18 cows than from NP cows, whereas there was no difference in CTSK expression. IFNT increased CTSB expression but did not affect CTSK expression. Immunodetection showed an increase of CTSB in P day-18 PBMCs and PMNs. In vitro stimulation of IFNT increased CTSB in NP PBMCs and PMNs. Lysosomal acidification showed a significant increase in P day-18 PBMCs and PMNs. IFNT also stimulated lysosomal acidification. Expressions of lysosome-associated membrane protein (LAMP) 1 and LAMP2 were significantly higher in P day-18 PBMCs and PMNs. The results suggest that pregnancy-specific activation of lysosomal functions by CTS activation in blood leukocytes is highly associated with IFNT during maternal and fetal recognition of pregnancy. © 2018 Society for Reproduction and Fertility.

Visualization of a prosthetic vascular graft due to platelet contamination during 111Indium-labeled leukocyte scintigraphy

International Nuclear Information System (INIS)

Oates, E.; Ramberg, K.

1988-01-01

A prosthetic axillo-femoral bypass graft was visualized during 111 In-labeled leukocyte scintigraphy in a patient referred for possible abdominal abscess. The presence of significant cardiac blood-pool activity raised the possibility that this uptake was due to deposition of contaminating labeled platelets rather than labeled leukocytes. An analysis of a small sample of the patient's blood confirmed that the circulating activity was due to labeled platelets. Increased activity along prosthetic vascular grafts in patients undergoing 111 In-labeled leukocyte scintigraphy may be due to adherent platelet, and not indicative of infection

Studies for labelling of leukocytes with sup 99m Tc-HM-PAO in vitro and animal experiments

Energy Technology Data Exchange (ETDEWEB)

Zhaoxiang, Gu; Xiangtong, Lin [Shanghai Medical Univ. (China). Huashan Hospital

1989-05-01

A technigue for in vitro labelling of human leukocytes with {sup 99m}Tc-HM-PAO is described. The percentage of labelled leukocytes is 43.0 +- 5.0 (mean +- SD, n = 6). Cell function was not impaired by the labelling procedure. Sterility and exclusion of bacterial endotoxins in the final cell suspensions were demonstrated. In experiments on dogs with abscess, scintigraphic imaging showed accumulation of radioactivity in inflammation lesions, indicating the viability of the labelled leukocytes.

Ganglioside-specific IgG and IgA recruit leukocyte effector functions in Guillain-Barre syndrome

NARCIS (Netherlands)

Sorge, N.M. van; Yuki, N.; Koga, M.; Susuki, K.; Jansen, M.D.; Kooten, C. van; Wokke, J.H.; Winkel, J.G.J. van de; Pol, W.L. van der; Berg, L.H. van den

2007-01-01

The capacity of ganglioside-specific autoantibodies to recruit leukocyte effector functions was studied. Serum samples from 87 patients with Guillain–Barré (GBS) or Miller Fisher syndrome (MFS), containing GM1-, GQ1b-, or GD1b-specific IgG or IgA, were tested for leukocyte activating capacity.

Aberrant leukocyte telomere length in Birdshot Uveitis.

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Nadia Vazirpanah

Full Text Available Birdshot Uveitis (BU is an archetypical chronic inflammatory eye disease, with poor visual prognosis, that provides an excellent model for studying chronic inflammation. BU typically affects patients in the fifth decade of life. This suggests that it may represent an age-related chronic inflammatory disease, which has been linked to increased erosion of telomere length of leukocytes.To study this in detail, we exploited a sensitive standardized quantitative real-time polymerase chain reaction to determine the peripheral blood leukocyte telomere length (LTL in 91 genotyped Dutch BU patients and 150 unaffected Dutch controls.Although LTL erosion rates were very similar between BU patients and healthy controls, we observed that BU patients displayed longer LTL, with a median of log (LTL = 4.87 (= 74131 base pair compared to 4.31 (= 20417 base pair in unaffected controls (P<0.0001. The cause underpinning the difference in LTL could not be explained by clinical parameters, immune cell-subtype distribution, nor genetic predisposition based upon the computed weighted genetic risk score of genotyped validated variants in TERC, TERT, NAF1, OBFC1 and RTEL1.These findings suggest that BU is accompanied by significantly longer LTL.

Rescue from acute neuroinflammation by pharmacological chemokine-mediated deviation of leukocytes

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Berghmans Nele

2012-10-01

Full Text Available Abstract Background Neutrophil influx is an important sign of hyperacute neuroinflammation, whereas the entry of activated lymphocytes into the brain parenchyma is a hallmark of chronic inflammatory processes, as observed in multiple sclerosis (MS and its animal models of experimental autoimmune encephalomyelitis (EAE. Clinically approved or experimental therapies for neuroinflammation act by blocking leukocyte penetration of the blood brain barrier. However, in view of unsatisfactory results and severe side effects, complementary therapies are needed. We have examined the effect of chlorite-oxidized oxyamylose (COAM, a potent antiviral polycarboxylic acid on EAE. Methods EAE was induced in SJL/J mice by immunization with spinal cord homogenate (SCH or in IFN-γ-deficient BALB/c (KO mice with myelin oligodendrocyte glycoprotein peptide (MOG35-55. Mice were treated intraperitoneally (i.p. with COAM or saline at different time points after immunization. Clinical disease and histopathology were compared between both groups. IFN expression was analyzed in COAM-treated MEF cell cultures and in sera and peritoneal fluids of COAM-treated animals by quantitative PCR, ELISA and a bioassay on L929 cells. Populations of immune cell subsets in the periphery and the central nervous system (CNS were quantified at different stages of disease development by flow cytometry and differential cell count analysis. Expression levels of selected chemokine genes in the CNS were determined by quantitative PCR. Results We discovered that COAM (2 mg i.p. per mouse on days 0 and 7 protects significantly against hyperacute SCH-induced EAE in SJL/J mice and MOG35-55-induced EAE in IFN-γ KO mice. COAM deviated leukocyte trafficking from the CNS into the periphery. In the CNS, COAM reduced four-fold the expression levels of the neutrophil CXC chemokines KC/CXCL1 and MIP-2/CXCL2. Whereas the effects of COAM on circulating blood and splenic leukocytes were limited, significant

The effect of ibuprofen on accumulation of indium-111-labeled platelets and leukocytes in experimental myocardial infarction

International Nuclear Information System (INIS)

Romson, J.L.; Hook, B.G.; Rigot, V.H.; Schark, M.A.; Swanson, D.P.; Lucchesi, B.R.

1982-01-01

To assess the ability of ibuprofen to influence the extent of platelet aggregation and leukocyte infiltration during acute myocardial infarction, autologous indium-111 ( 111 In)-labeled platelets or leukocytes were injected before 60 minutes of left circumflex coronary artery (LCx) occlusion, followed by 24 hours of reperfusion in the canine heart. Myocardial infarct size, as a percent of the area at risk, was reduced in the ibuprofen-treated group (12.5 mg/kg i.v. every 4 hours beginning 30 minutes before LCx occulsion) by 40%, from 48 +/- 4% in control animals to 29 +/- 4% in ibuprofen-treated dogs (p=0.005). Quantification of the platelet-associated 111 In radioactivity in irreversibly injured myocardium indicated that ibuprofen did not alter the accumulation of platelets in infarcted myocardium. In contrast, leukocyte accumulation in infarcted tissue was reduced significantly. In tissue samples with 0.41-0.60 gram infarct, the infarcted/normal ratio of leukocyte radioactivity was 12 +/- 2 in control dogs and 4 +/- 1 in ibuprofen-treated dogs, which represents a 67% reduction in leukocyte accumulation in ibuprofen-treated compared with control dogs. Similar reductions were found in other gram-infarct-weight categories. Although both platelets and leukocytes acumulate in infarcted canine myocardium, ibuprofen may exert its beneficial effect on ischemic myocardium by suppressing the inflammatory response associated with myocardial ischemia and infarction

The effect of ibuprofen on accumulation of 111In-labeled platelets and leukocytes in experimental myocardial infarction

International Nuclear Information System (INIS)

Romson, J.L.; Hook, B.G.; Rigot, V.H.; Schork, M.A.; Swanson, D.P.; Lucchesi, B.R.

1982-01-01

To assess the ability of ibuprofen to influence the extent of platelet aggregation and leukocyte infiltration during acute myocardial infarction, autologous indium-111 ( 111 In)-labeled platelets or leukocytes were injected before 60 minutes of left circumflex coronary artery (LCx) occlusion, followed by 24 hours of reperfusion in the canine heart. Myocardial infarct size, as a percent of the area at risk, was reduced in the ibuprofen-treated group (12.5 mg/kg i.v. every 4 hours beginning 30 minutes before LCx occlusion) by 40%, from 48 +/- 4% in control animals to 29 +/- 4% in ibuprofen-treated dogs (p . 0.005). Quantification of the platelet-associated 111 In radioactivity in irreversibly injured myocardium indicated that ibuprofen did not alter the accumulation of platelets in infarcted myocardium. In contrast, leukocyte accumulation in infarcted tissue was reduced significantly. In tissue samples with 0.41-0.60 gram infarct, the infarcted/normal ratio of leukocyte radioactivity was 12 +/- 2 in control dogs and 4 +/- 1 in ibuprofen-treated dogs, which represents a 67% reduction in leukocyte accumulation in ibuprofen-treated compared with control dogs. Similar reductions were found in other gram-infarct-weight categories. Although both platelets and leukocytes accumulate in infarcted canine myocardium, ibuprofen may exert its beneficial effect on ischemic myocardium by suppressing the inflammatory response associated with myocardial ischemia and infarction

[In-line leukocyte depletion ov thrombocytapheresis concentrates with the Fresenius-AS-104 cell separator].

Science.gov (United States)

Zeiler, T; Kretschmer, V

1997-01-01

This study reports on in-line filtration of 72 platelet concentrates (PC) collected by the Fresenius AS 104 cell separator, using the new C4F sets with integrated leukocyte filters (Biofil P plus). 72 volunteer donors, automatic counts of platelets, microscopical counting of residual leukocytes with the Nageotte chamber, GMP-140 by flow cytometrie, beta-thromboglobulin release, platelet aggregation (ADP, collagen). Filtration reduced leukocytes by 98.5%. Residual leukocyte contamination remained clearly below 5 x 10(6) (mean 0.5 +/- 0.6 x 10(6), maximum 2.8 x 10(6). Platelet loss by filtration was found to be between 27.4 and 0.7% (median 8.5%). Filtration caused a significant decrease of platelet aggregability (p < 0.005), but no significant increase of beta-thromboglobulin release and only a slight decrease of GMP-140 expression. From these data can be concluded that in-line filtration was highly efficient with acceptable platelet retention. No significant platelet activation could be observed in the PC. The decrease of platelet aggregability have been due to the reduction of activated platelets which are believed to show reduced in vivo survival.

Rapid, high-efficiency labeling of leukocytes with In-111 after hemolytic removal of erythrocytes

International Nuclear Information System (INIS)

Karesh, S.M.; Henkin, R.E.

1985-01-01

During the labeling of leukocytes with Indium-111, conventional methodology involves separation and washing to remove red cells. This technique results in the loss of a significant number of leukocytes. Citrated whole blood of ten normal volunteers was studied for an alternate labeling method following sedimentation for 30 to 45 minutes and low speed centrifugation of the leukocyte-rich plasma. The average labeling for these ten volunteers by Indium-111 was 90% versus 60% by the older technique. Viability as measured by the trypan blue exclusion test was greater than 95%, WBC losses were essentially zero, and no WBC clumping was observed. Eighteen patients referred for leukocyte imaging were studied by this method. In this patient population, there was 91% labeling with viability greater than 95% and no evidence of clumping. Less than 5% RBC's were noted in any lot. Indium-111 WBC activity 20 minutes post injection averaged 79% of whole blood activity. This modification results in decreased losses of white cells, reduces preparation time to less than 2 hours, and significantly improves the labeling efficiency of the final product. Liver/spleen ratios and image quality were unchanged from the original method

Correlation of Leukocyte Count and Percentage of Segmented Neutrophils with Pathohistological Findings of Appendix in Children

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Marko Baskovic

2018-01-01

Full Text Available BackgroundAppendicitis is the most common indication for an emergency operation in children's age. Although none of the laboratory values has not high sensitivity and specificity for the diagnosis of appendicitis, leukocyte count and the percentage of segmented neutrophils are most commonly used. The aim of this study was to determine whether there is a statistically significant correlation between leukocyte count and the percentage of segmented neutrophils compared to the pathohistological finding of appendix in children. Materials and MethodsWe retrospectively analyzed the data in the period from 1 January 2016 to 31 December 2016. The analysis was made on 211 patients. Spearman's correlation coefficient (rs was calculated. We determined the specificity and sensitivity of leukocyte count and the percentage of segmented neutrophils used in the calculation of Alvorado and Pediatric Appendicitis score.ResultsThe results of the research have shown that the correlation between leukocyte count and the pathohistological findings is weak (rs = 0.29, p = 3.61*10-8, while there is no correlation between the percentage of segmented neutrophils and pathohistological findings (rs = 0.18, p = 7.08 *10-5. The sensitivity of leukocyte count is 93% and the specificity is 30%, while the sensitivity to the percentage of segmented neutrophils is 71% and the specificity is 50%. ROC analysis for leukocytes shows area under the curve of 0.648, while for segmented neutrophils of 0.574.ConclusionGiven the correlation results obtained, the clinical experience of physicians will still have one of the leading roles in diagnosing acute appendicitis in children.

Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells

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Isabel Correa

2018-03-01

Full Text Available Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1 specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires.

Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells.

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Correa, Isabel; Ilieva, Kristina M; Crescioli, Silvia; Lombardi, Sara; Figini, Mariangela; Cheung, Anthony; Spicer, James F; Tutt, Andrew N J; Nestle, Frank O; Karagiannis, Panagiotis; Lacy, Katie E; Karagiannis, Sophia N

2018-01-01

Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα) as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1) specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs) were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires.

Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells

Science.gov (United States)

Correa, Isabel; Ilieva, Kristina M.; Crescioli, Silvia; Lombardi, Sara; Figini, Mariangela; Cheung, Anthony; Spicer, James F.; Tutt, Andrew N. J.; Nestle, Frank O.; Karagiannis, Panagiotis; Lacy, Katie E.; Karagiannis, Sophia N.

2018-01-01

Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα) as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1) specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs) were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires. PMID:29628923

Impaired leukocyte influx in cervix of postterm women not responding to prostaglandin priming

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Masironi Britt

2008-09-01

Full Text Available Abstract Background Prolonged pregnancies are associated with increased rate of maternal and fetal complications. Post term women could be divided into at least two subgroups, one where parturition is possible to induce by prostaglandins and one where it is not. Our aim was to study parameters in cervical biopsies in women with spontaneous delivery at term (controls and compare to those that are successfully induced post term (responders, and those that are not induced (non-responders, by local prostaglandin treatment. Methods Stromal parameters examined in this study were the accumulation of leukocytes (CD45, CD68, mRNAs and/or proteins for the extracellular matrix degrading enzymes (matrix metalloproteinase (MMP-2, MMP-8 and MMP-9, their inhibitors (tissue inhibitor of MMP (TIMP-1 and TIMP-2, interleukin-8 (IL-8, the platelet activating factor-receptor (PAF-R, syndecan-1 and estrogen binding receptors (estrogen receptor (ERα, ERβ and G-coupled protein receptor (GPR 30 as well as the proliferation marker Ki-67. Results The influx of leukocytes as assessed by CD45 was strongest in the responders, thereafter in the controls and significantly lower in the non-responders. IL-8, PAF-R and MMP-9, all predominantly expressed in leukocytes, showed significantly reduced immunostaining in the group of non-responders, while ERα and GPR30 were more abundant in the non-responders, as compared to the controls. Conclusion The impaired leukocyte influx, as reflected by the reduced number of CD45 positive cells as well as decreased immunostaining of IL-8, PAF-R and MMP-9 in the non-responders, could be one explanation of the failed ripening of the cervix in post term women. If the decreased leukocyte influx is a primary explanation to absent ripening or secondary, as a result of other factors, is yet to be established.

Importance of killer immunoglobulin-like receptors in allogeneic hematopoietic stem cell transplantation

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Danilo Santana Alessio Franceschi

2011-01-01

Full Text Available Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein.

In-111-labeled leukocytes in the diagnosis of rejection and cytomegalovirus infection in renal transplant patients

International Nuclear Information System (INIS)

Forstrom, L.A.; Loken, M.K.; Cook, A.; Chandler, R.; McCullough, J.

1981-01-01

Indium-111-labeled (In-111) leukocytes have been shown to be useful in the localization of inflammatory processes, including renal transplant rejection. Using previously reported labeling methods, 63 studies with this agent have been performed in 53 renal transplant patients. Indications for study included suspected rejection or cytomegalovirus (CMV) infection. Studies were performed in 33 men and 20 women, with ages ranging from 6 to 68 years. Autologous cells were normally used for labeling, although leukocytes obtained from ABO-compatible donors were used in three subjects. Rectilinear scanner and/or scintillation camera images were obtained at 24 hours after intravenous administration of 0.1 to 0.6 mCi of In-111-leukocytes. There was abnormal uptake of In-111-leukocytes in the transplanted kidney in 11 of 15 cases of rejection. In three additional cases of increased transplant uptake, CMV infection was present in two. Abnormal lung uptake was present in 13 of 14 patients with CMV infection. In four additional cases, increased lung uptake was associated with other pulmonary inflammatory disease. Increased lung activity was not seen in patients with uncomplicated transplant rejection. These results suggest that In-111-leukocyte imaging may be useful in the differential diagnosis of rejection versus CMV infection in renal transplant patients

In-111-labeled leukocytes in the diagnosis of rejection and cytomegalovirus infection in renal transplant patients

International Nuclear Information System (INIS)

Forstrom, L.A.; Loken, M.K.; Cook, A.; Chandler, R.; McCullough, J.

1981-01-01

Indium-111-labelled (In-111) leukocytes have been shown to be useful in the localization of inflammatory processes, including renal transplant rejection. Using previously reported labelling methods, 63 studies with this agent have been performed in 53 renal transplant patients. Indications for study included suspected rejection or cytomegalovirus (CMV) infection. Studies were performed in 33 men and 20 women, with ages ranging from 6 to 68 years. Autologous cells were normally used for labeling, although leukocytes obtained from ABO-compatible donors were used in three subjects. Rectilinear scanner and/or scintillation camera images were obtained at 24 hours after intravenous administration of 0.1 to 0.6 mCi of In-111 leukocytes. There was abnormal uptake of In-111-leukocytes in the transplanted kidney in 11 of 15 cases of rejection. In three additional cases of increased transplant uptake, CMV infection was present in two. Abnormal lung uptake was present in 13 of 14 patients with CMV infection. In four additional cases, increased lung uptake was associated with other pulmonary inflammatory disease. Increased lung activity was not seen in patients with uncomplicated transplant rejection. These results suggest that In-111-leukocyte imaging may be useful in the differential diagnosis of rejection versus CMV infection in renal transplant patients

HLA class I is most tightly linked to levels of tapasin compared with other antigen-processing proteins in glioblastoma.

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Thuring, Camilla; Follin, Elna; Geironson, Linda; Freyhult, Eva; Junghans, Victoria; Harndahl, Mikkel; Buus, Søren; Paulsson, Kajsa M

2015-09-15

Tumour cells can evade the immune system by dysregulation of human leukocyte antigens (HLA-I). Low quantity and/or altered quality of HLA-I cell surface expression is the result of either HLA-I alterations or dysregulations of proteins of the antigen-processing machinery (APM). Tapasin is an APM protein dedicated to the maturation of HLA-I and dysregulation of tapasin has been linked to higher malignancy in several different tumours. We studied the expression of APM components and HLA-I, as well as HLA-I tapasin-dependency profiles in glioblastoma tissues and corresponding cell lines. Tapasin displayed the strongest correlation to HLA-I heavy chain but also clustered with β2-microglobulin, transporter associated with antigen processing (TAP) and LMP. Moreover, tapasin also correlated to survival of glioblastoma patients. Some APM components, for example, TAP1/TAP2 and LMP2/LMP7, showed variable but coordinated expression, whereas ERAP1/ERAP2 displayed an imbalanced expression pattern. Furthermore, analysis of HLA-I profiles revealed variable tapasin dependence of HLA-I allomorphs in glioblastoma patients. Expression of APM proteins is highly variable between glioblastomas. Tapasin stands out as the APM component strongest correlated to HLA-I expression and we proved that HLA-I profiles in glioblastoma patients include tapasin-dependent allomorphs. The level of tapasin was also correlated with patient survival time. Our results support the need for individualisation of immunotherapy protocols.

Transepithelial activation of human leukocytes by probiotics and commensal bacteria: role of Enterobacteriaceae-type endotoxin

DEFF Research Database (Denmark)

Bäuerlein, A.; Ackermann, S.; Parlesak, Alexandr

2009-01-01

The goal of the current study was to clarify whether commercially available probiotics induce greater trans-epithelial activation of human leukocytes than do commensal, food-derived and pathogenic bacteria and to identify the compounds responsible for this activation. Eleven different bacterial...... Escherichia coli K12, probiotic E. coli Nissle, EPEC) induced basolateral production of TNF-alpha, IFN-gamma, IL 6, 8, and 10. Gram-positive probiotics (Lactobacillus spp. and Bifidobacterium spp.) had virtually no effect. In addition, commensals (Enterococcus faecalis, Bacteroides vulgatus) and food...... (polymyxin, colistin) completely abrogated transepithelial activation of leukocytes. Enterobacteriaceae-type endotoxin is a crucial factor in transepithelial stimulation of leukocytes, regardless of whether it is produced by probiotics or other bacteria. Hence, transepithelial stimulation ofleukocytes...

Antigen processing and remodeling of the endosomal pathway: requirements for antigen cross-presentation.

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Compeer, Ewoud Bernardus; Flinsenberg, Thijs Willem Hendrik; van der Grein, Susanna Geertje; Boes, Marianne

2012-01-01

Cross-presentation of endocytosed antigen as peptide/class I major histocompatibility complex complexes plays a central role in the elicitation of CD8(+) T cell clones that mediate anti-viral and anti-tumor immune responses. While it has been clear that there are specific subsets of professional antigen presenting cells capable of antigen cross-presentation, identification of mechanisms involved is still ongoing. Especially amongst dendritic cells (DC), there are specialized subsets that are highly proficient at antigen cross-presentation. We here present a focused survey on the cell biological processes in the endosomal pathway that support antigen cross-presentation. This review highlights DC-intrinsic mechanisms that facilitate the cross-presentation of endocytosed antigen, including receptor-mediated uptake, maturation-induced endosomal sorting of membrane proteins, dynamic remodeling of endosomal structures and cell surface-directed endosomal trafficking. We will conclude with the description of pathogen-induced deviation of endosomal processing, and discuss how immune evasion strategies pertaining endosomal trafficking may preclude antigen cross-presentation.

Antigen processing and remodeling of the endosomal pathway: requirements for antigen cross-presentation.

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Ewoud Bernardus Compeer

2012-03-01

Full Text Available The cross-presentation of endocytosed antigen as peptide/class I MHC complexes plays a central role in the elicitation of CD8+ T cell clones that mediate anti-viral and anti-tumor immune responses. While it has been clear that there are specific subsets of professional antigen presenting cells (APC capable of antigen cross-presentation, description of mechanisms involved is still ongoing. Especially amongst dendritic cells (DC, there are specialized subsets that are highly proficient at antigen cross-presentation. We here present a focused survey on the cell biological processes in the endosomal pathway that support antigen cross-presentation. This review highlight DC-intrinsic mechanisms that facilitate the cross-presentation of endocytosed antigen, including receptor-mediated uptake, recycling and maturation including the sorting of membrane proteins, dynamic remodeling of endosomal structures and cell-surface directed endosomal trafficking. We will conclude with description of pathogen-induced deviation of endosomal processing, and discuss how immune evasion strategies pertaining endosomal trafficking may preclude antigen cross-presentation.

Leukocyte Adhesion Deficiency: Report of Two Family Related Newborn Infants

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Zohreh Kavehmanesh

2010-07-01

Full Text Available "nLeukocyte adhesion deficiency type 1 (LAD 1 is an autosomal recessive hereditary disorder resulting from deficiency of CD18, characterized by recurrent bacterial infections. We report two consanguineous patients with Leukocyte adhesion deficiency type 1( LAD1. These two infant boy patients were referred to us, within a short period of time, with the complaints of recurrent infections at the age of 38 and 75 days -old, respectively. Parents of two patients were first cousins and their grandmothers also were first cousins. The history of delayed umbilical cord separation was shown in both patients. Patient 1 had history of omphalitis, conjunctivitis, skin lesion of groin area and abscess formation of vaccination site, and had infective wound of eye-lid at the last admission. Patient 2 had history of omphalitis and soft tissue infection of right wrist at the last admission. Laboratory findings showed marked leukocytosis and low CD18 levels (6.6% in Patient 1 and 2.4 % in Patient 2. In Patient 1 recurrent infections were treated with antibiotic regimens and received bone marrow transplantation but Patient 2 died because of septicemia, generalized edema, ascites and progression to acute renal failure at 4 months of age. Due to considerable rate of consanguineous marriages in parents of Leukocyte adhesion deficiency patients, sequence analysis especially for prenatal diagnosis in subsequent pregnancies and genetic counseling is recommended.

Further comparisons of endogenous pyrogens and leukocytic endogenous mediators.

Science.gov (United States)

Kampschmidt, R F; Upchurch, H F; Worthington, M L

1983-07-01

It was recently shown (Murphy et al., Infect. Immun. 34:177-183), that rabbit macrophages produce two biochemically and immunologically distinct endogenous pyrogens. One of these has or copurifies with substances having a molecular weight of 13,000 and a pI of 7.3. This protein was produced by blood monocytes or inflammatory cells elicited in 16-h rabbit peritoneal exudates. These acute peritoneal exudates were produced by the intraperitoneal injection of large volumes of saline containing shellfish glycogen. When the leukocytes in these exudates were washed and incubated at 37 degrees C in saline, they released an endogenous pyrogen. The injection of this pyrogen into rabbits, rats, or mice caused the biological manifestations which have been attributed to leukocytic endogenous mediator. These effects were increases in blood neutrophils, the lowering of plasma iron and zinc levels, and the increased synthesis of the acute-phase proteins. The other rabbit endogenous pyrogen seems to be a family of proteins with isoelectric points between 4.5 and 5.0. These proteins are produced by macrophages in the lung, liver, or in chronic peritoneal exudates. In these experiments, the lower-isoelectric-point endogenous pyrogens were produced by macrophages from the peritoneal cavity of rabbits that had been injected 4 days earlier with 50 ml of light mineral oil. These rabbit pyrogens were found to have leukocytic endogenous mediator activity in mice but to be completely inactive in rats. When injected into rabbits, these proteins produced fever, lowered plasma iron, increased blood neutrophils, but failed to elevate plasma fibrinogen.

Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen

DEFF Research Database (Denmark)

Baldwin, Susan L; Roeffen, Will; Singh, Susheel K

2016-01-01

A subunit vaccine targeting both transmission and pathogenic asexual blood stages of Plasmodium falciparum, i.e., a multi-stage vaccine, could be a powerful tool to combat malaria. Here, we report production and characterization of the recombinant protein GMZ2.6C, which contains a fragment of the......-γ and TNF in response to GMZ2.6C. Both of these agonists have good safety records in humans....... of the sexual-stage protein Pfs48/45-6C genetically fused to GMZ2, an asexual vaccine antigen in advanced clinical development. To select the most suitable vaccine formulation for downstream clinical studies, GMZ2.6C was tested with various immune modulators in different adjuvant formulations (stable emulsions......, liposomes, and alum) in C57BL/6 mice. Some, but not all, formulations containing either the synthetic TLR4 agonist GLA or SLA elicited the highest parasite-specific antibody titers, the greatest IFN-γ responses in CD4+ TH1 cells, and the highest percentage of multifunctional CD4+ T cells expressing IFN...

Increased endothelial cell-leukocyte interaction in murine schistosomiasis: possible priming of endothelial cells by the disease.

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Suellen D S Oliveira

Full Text Available BACKGROUND AND AIMS: Schistosomiasis is an intravascular parasitic disease associated with inflammation. Endothelial cells control leukocyte transmigration and vascular permeability being modulated by pro-inflammatory mediators. Recent data have shown that endothelial cells primed in vivo in the course of a disease keep the information in culture. Herein, we evaluated the impact of schistosomiasis on endothelial cell-regulated events in vivo and in vitro. METHODOLOGY AND PRINCIPAL FINDINGS: The experimental groups consisted of Schistosoma mansoni-infected and age-matched control mice. In vivo infection caused a marked influx of leukocytes and an increased protein leakage in the peritoneal cavity, characterizing an inflamed vascular and cellular profile. In vitro leukocyte-mesenteric endothelial cell adhesion was higher in cultured cells from infected mice as compared to controls, either in the basal condition or after treatment with the pro-inflammatory cytokine tumor necrosis factor (TNF. Nitric oxide (NO donation reduced leukocyte adhesion to endothelial cells from control and infected groups; however, in the later group the effect was more pronounced, probably due to a reduced NO production. Inhibition of control endothelial NO synthase (eNOS increased leukocyte adhesion to a level similar to the one observed in the infected group. Besides, the adhesion of control leukocytes to endothelial cells from infected animals is similar to the result of infected animals, confirming that schistosomiasis alters endothelial cells function. Furthermore, NO production as well as the expression of eNOS were reduced in cultured endothelial cells from infected animals. On the other hand, the expression of its repressor protein, namely caveolin-1, was similar in both control and infected groups. CONCLUSION/SIGNIFICANCE: Schistosomiasis increases vascular permeability and endothelial cell-leukocyte interaction in vivo and in vitro. These effects are partially

Longitudinal evaluation of leukocyte transcripts in killer whales (Orcinus Orca)

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Sitt, Tatjana; Bowen, Lizabeth; Lee, Chia-Shan; Blanchard, Myra; McBain, James; Dold, Christopher; Stott, Jeffrey L.

2016-01-01

Early identification of illness and/or presence of environmental and/or social stressors in free-ranging and domestic cetaceans is a priority for marine mammal health care professionals. Incorporation of leukocyte gene transcript analysis into the diagnostic tool kit has the potential to augment classical diagnostics based upon ease of sample storage and shipment, inducible nature and well-defined roles of transcription and associated downstream actions. Development of biomarkers that could serve to identify “insults” and potentially differentiate disease etiology would be of great diagnostic value. To this end, a modest number of peripheral blood leukocyte gene transcripts were selected for application to a domestic killer whale population with a focus on broad representation of inducible immunologically relevant genes. Normalized leukocyte transcript values, longitudinally acquired from 232 blood samples derived from 26 clinically healthy whales, were not visibly influenced temporally nor by sex or the specific Park in which they resided. Stability in leukocyte transcript number during periods of health enhances their potential use in diagnostics through identification of outliers. Transcript levels of two cytokine genes, IL-4 and IL-17, were highly variable within the group as compared to the other transcripts. IL-4 transcripts were typically absent. Analysis of transcript levels on the other genes of interest, on an individual animal basis, identified more outliers than were visible when analyzed in the context of the entire population. The majority of outliers (9 samples) were low, though elevated transcripts were identified for IL-17 from 2 animals and one each for Cox-2 and IL-10. The low number of outliers was not unexpected as sample selection was intentionally directed towards animals that were clinically healthy at the time of collection. Outliers may reflect animals experiencing subclinical disease that is transient and self-limiting. The

Therapeutic relevance of penicillin-induced hypersensitivity of Staphylococcus aureus to killing by polymorphonuclear leukocytes.

OpenAIRE

Lam, C; Georgopoulos, A; Laber, G; Schütze, E

1984-01-01

There is an overwhelming body of evidence that certain Staphylococcus aureus strains become more sensitive to killing by polymorphonuclear leukocytes after their growth in media containing subinhibitory concentrations of penicillin. However, it is not clear to what extent this phenomenon contributes to the curative effect of penicillin in vivo. To explore its therapeutic relevance, we evaluated the interaction of staphylococci pretreated with penicillin in vitro with leukocytes in cell-proof ...

Using a split luciferase assay (SLA) to measure the kinetics of cell-cell fusion mediated by herpes simplex virus glycoproteins.

Science.gov (United States)

Saw, Wan Ting; Matsuda, Zene; Eisenberg, Roselyn J; Cohen, Gary H; Atanasiu, Doina

2015-11-15

Herpes simplex virus (HSV) entry and cell-cell fusion require the envelope proteins gD, gH/gL and gB. We propose that receptor-activated conformational changes to gD activate gH/gL, which then triggers gB (the fusogen) into an active form. To study this dynamic process, we have adapted a dual split protein assay originally developed to study the kinetics of human immunodeficiency virus (HIV) mediated fusion. This assay uses a chimera of split forms of renilla luciferase (RL) and green fluorescent protein (GFP). Effector cells are co-transfected with the glycoproteins and one of the split reporters. Receptor-bearing target cells are transfected with the second reporter. Co-culture results in fusion and restoration of RL, which can convert a membrane permeable substrate into a luminescent product, thereby enabling one to monitor initiation and extent of fusion in live cells in real time. Restoration of GFP can also be studied by fluorescence microscopy. Two sets of split reporters have been developed: the original one allows one to measure fusion kinetics over hours whereas the more recent version was designed to enhance the sensitivity of RL activity allowing one to monitor both initiation and rates of fusion in minutes. Here, we provide a detailed, step-by-step protocol for the optimization of the assay (which we call the SLA for split luciferase assay) using the HSV system. We also show several examples of the power of this assay to examine both the initiation and kinetics of cell-cell fusion by wild type forms of gD, gB, gH/gL of both serotypes of HSV as well as the effect of mutations and antibodies that alter the kinetics of fusion. The SLA can be applied to other viral systems that carry out membrane fusion. Copyright © 2015 Elsevier Inc. All rights reserved.

Accumulation of polymorphonuclear leukocytes in reperfused ischemic canine myocardium: relation with tissue viability assessed by fluorine-18-2-deoxyglucose uptake

International Nuclear Information System (INIS)

Wijns, W.; Melin, J.A.; Leners, N.

1988-01-01

Polymorphonuclear leukocytes may participate in reperfusion injury. Whether leukocytes affect viable or only irreversibly injured tissue is not known. Therefore, we assessed the accumulation of 111In-labeled leukocytes in tissue samples characterized as either ischemic but viable or necrotic by metabolic, histochemical, and ultrastructural criteria. Six open-chest dogs received left anterior descending coronary occlusion for 2 hr followed by 4 hr reperfusion. Myocardial blood flow was determined by microspheres and autologous 111In-labeled leukocytes were injected intravenously. Fluorine-18-2-deoxyglucose, a tracer of exogenous glucose utilization, was injected 3 hr after reperfusion. The dogs were killed 4 hr after reperfusion. The risk and the necrotic regions were assessed following in vivo dye injection and postmortem tetrazolium staining. Myocardial samples were obtained in the ischemic but viable, necrotic and normal zones, and counted for 111In and 18F activity. Compared to normal, leukocytes were entrapped in necrotic regions (111In activity: 207 +/- 73%) where glucose uptake was decreased (26 +/- 15%). A persistent glucose uptake, marker of viability, was mainly seen in risk region (135 +/- 85%) where leukocytes accumulation was moderate in comparison to normal zone (146 +/- 44%). Thus, the glucose uptake observed in viable tissue is mainly related to myocytes metabolism and not to leukocytes metabolism

Effect of leukocyte alteration on treatment outcomes following preoperative chemoradiotherapy in patients with rectal cancer

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Kim, Tae Gyu; Park, Won; Choi, Doo Ho [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); and others

2017-09-15

Hematotoxicity following anti-cancer treatment is known to be related to treatment efficacy in several malignancies. The purpose of this study was to examine the hematologic parameters related to the tumor response and survival in patients treated with curative surgery following preoperative chemoradiotherapy (CRT) for rectal cancer. Four hundred eighteen patients with rectal cancer who underwent preoperative CRT and curative surgery were analyzed, retrospectively. The main clinical factors and blood cell counts before and after CRT were investigated with respect to their relationships with tumor downstaging and patient survival. The post-CRT leukocyte count was significantly different between the tumor downstaging group and the nondownstaging group (median, 4740/uL vs. 5130/uL; p = 0.013). Multivariate analysis showed that histological grade, circumferential extent, and post-CRT leukocyte count were related to tumor downstaging. In addition, histological grade, post-CRT leukocyte count, and tumor downstaging were related to disease-free survival. The 5-year disease-free survival and overall survival in patients with post-CRT leukocyte count ≤3730/uL, which is the cut-off value derived from the receiver operation characteristic (ROC) curve analysis, were significantly higher than those with higher counts (88.0% vs. 71.6%, p = 0.001; 94.4% vs. 84.1%, p = 0.024). Post-CRT leukocyte count of ≤3730/uL could be regarded as a good prognostic factor for tumor response and survival in rectal cancer patients treated with preoperative CRT.

Enhancement of antitumor activity by using a fully human gene encoding a single-chain fragmented antibody specific for carcinoembryonic antigen