bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLA class I expression and chromosomal deletions at 6p and 15q in head and neck squamous cell carcinomas
Authors: Feenstra M. , Veltkamp M. , Van Kuik J. , Wiertsema S. , Slootweg P. , Van Den Tweel J. , De Weger R. , Tilanus M. 
Published: March 2003

Abstract:Loss at the chromosomal region 6p21.3 is a frequent event in head and neck squamous cell carcinomas (HNSCC). Since the human leukocyte antigen (HLA) complex is located at 6p21.3, loss of heterozygosity (LOH) of this region may provide tumour cells with an immune‐escape tumour phenotype. In the present study, we have studied the correlation of HLA class I, TAP1 and TAP2 expression and LOH at 6p21.3. HLA class I and TAP1 and TAP2 protein expression was analysed by immunohistochemical procedures. A panel of 41 HNSCC with downregulated HLA class I expression was selected for LOH studies using 5 microsatellite markers located at 6p21.3 (D6S105, D6S265, D6S276, D6S273, D6S291) and 2 markers located at the chromosome 6 centromere (D6S473) and the 6p telomere (D6S277). In addition, LOH of the beta‐2‐microglobulin (β2m) gene was studied using 2 microsatellite markers flanking the β2m gene (D15S126 and D15S153) and was correlated with β2m and HLA class I expression. In 20/41 (49%) of the HNSCC, allelic loss for at least one locus at 6p21.3 was found. Loss at 15q was found in 4/10 (40%) HNSCC with downregulated β2m expression and in 12/41 (29%) HNSCC with downregulated HLA class I expression. Our data show that downregulation of HLA class I expression is correlated with loss of chromosomal regions at 6p21.3 in HNSCC. In addition, LOH at 6p21.3 and 15q in 10 paired samples of DNA derived from the primary HNSCC, the lymph node metastases and from peripheral blood lymphocytes (PBLs) was studied. Five (5/10) primary tumours contained the same deletion as the corresponding lymph node metastases. The other cases contained deletions either in the primary tumour (3 cases) or in the lymph node metastases (1 case) or no deletions at all (1 case).
A MAGE‐A1 peptide is recognized on HLA‐B7 human tumors by cytolytic T lymphocytes
Authors: Luiten R. , Van Der Bruggen P. 
Published: March 2003

Acknowledgments:We thank Ms. N. Krack and Mr. S. Mapp for their help in the preparation of the manuscript, Dr. V. Stroobant for the synthesis of the peptides, and Mrs. V. Ha Thi for processing the blood samples. We are grateful to Dr. D. Rimoldi (Ludwig Institute for Cancer Research, Lausanne) for providing us with several melanoma cell lines. R. Luiten was supported by a postdoctoral fellowship from the “Training and mobility of researchers” program of the European Commission.Abstract:Antigens encoded by MAGE genes are of particular interest for cancer immunotherapy because of their strict tumoral specificity and because they are shared by many tumors. MAGE antigenic peptides are currently used in therapeutic vaccination trials. The identification of additional antigenic peptides is likely to be important for the future of these clinical trials in order to increase the number of patients eligible for these vaccinations and to analyze in detail the T‐cell response of vaccinated patients. We describe here the isolation of a cytolytic T lymphocyte (CTL) clone which recognizes a new MAGE‐A1 peptide, RVRFFFPSL (MAGE‐A1289–297), which is presented by HLA‐B7. This CTL clone lysed HLA‐B7 tumor cells expressing MAGE‐A1. HLA‐B7 is expressed by approximately 20% of Caucasians.
Three novel MICB alleles
Authors: Fischer G. , Pérez‐Rodríguez M. , Argüello J.R. , Cox S.T. , McWhinnie A. , Travers P.J. , Madrigal J.A. 
Published: March 2003

Acknowledgments:This work is funded by the Anthony Nolan Bone Marrow Trust. M. P.‐R. is the recipient of a fellowship from Instituto Mexicano del Seguro Social.Abstract:The two members of the MHC class I chain‐related (MIC) gene family, MICA and MICB, have been shown by several investigators to be polymorphic. Most of the research effort so far has focussed on MICA, so less is known about the extent of polymorphism in the MICB gene. Here we report three novel MICB alleles, which had been detected in the course of an SSOP typing study on a large cohort of cell lines. Two of these alleles are formed by a non‐synonymous nucleotide variation. Our results confirm previous findings that most of the polymorphisms in the MICB gene, as in MICA, are coding and suggest that the extent of polymorphism in the two genes might be comparable.
HLA‐A*6817, identified in the Kolla Amerindians of North‐West Argentina possesses a novel nucleotide substitution
Authors: Ramon D. , Scott I. , Cox S.T. , Pesoa S. , Vullo C. , Little A.‐M. , Madrigal J.A. 
Published: March 2003

Abstract:Analysis of HLA polymorphism of the indigenous populations of Central and South America has identified many alleles not seen previously in other populations. We have described a novel allele, B*5113, previously in a Kolla Amerindian individual from North‐West Argentina. Here we present a second novel allele from this population: A*6817, which differs from its closest neighbour A*68012 by a single substitution at nucleotide 419. This substitution of adenosine 419 A*68012 for thymidine in A*6817 results in a novel amino acid change (aspartate to valine) at residue 116 ( Note).
Polymorphism of the ABO blood group genes in Han, Kazak and Uygur populations in the Silk Route of northwestern China
Authors: Iwasaki M. , Kobayashi K. , Suzuki H. , Anan K. , Ohno S. , Geng Z. , Li G. , Inoko H. 
Published: March 2003

Abstract:Genetic polymorphism in the ABO blood group gene of Han, Kazak and Uygur populations inhabiting the most northwestern part of China was investigated using polymerase chain reaction‐based techniques. The present study enrolled 43 healthy unrelated Han, 37 Kazak and 59 Uygur volunteers. The allele in A1 blood group is distinguished A0101 and A0102 in difference of nucleotide position 467. The A0101 allele is more frequent in Caucasian and the A0102 allele is characteristic in Mongoloid. It must be notable that A0201 in the A2 group (with a single base deletion at nucleotides 1059 to 1061) which was characteristic of Caucasian was observed in Kazak and Uygur populations but not in Han. Further, O0201 (with no nucleotide deletion at 261 and three nucleotide differences), which is frequent in different races including Caucasian except for Mongoloid, was detected also in Kazak and Uygur populations. The frequencies of B0101 in Kazak, Uygur and Han were comparable to those of other Asian populations but higher than those of Caucasian populations. Collectively, these results reveal that the allele frequencies of Kazak and Uygur at the ABO blood group locus are an intermediate between those of Mongoloid and Caucasian, suggesting the admixed feature of Kazak and Uygur with Mongoloid and Caucasian.
Characterization of HLA‐B*3921 and confirmation of HLA‐B*4415, two variant HLA‐B alleles identified in the Omani population
Authors: Williams F. , Curran M.D. , Leheny W.A. , Daar A.S. , Middleton D. 
Published: March 2003

Abstract:We describe a variant HLA‐B*39 allele present in two individuals from Oman, which has been officially named HLA‐B*3921. In addition we confirm the existence of HLA‐B*4415, an allele closely related to HLA‐B*4501 differing only at the Bw4/Bw6 epitope ( Note).
Sequence analysis of a new HLA‐DR11 allele in a Caucasian Italian family: DRB1*11272
Authors: Canossi A. , Piancatelli D. , Papola F. , Di Rocco M. , Del Beato T. , Liberatore G. , Casciani C.U. , Adorno D. 
Published: March 2003

Acknowledgments:This research was supported in part by funding from the C.N.R., P.F. “Biotecnologie”. We wish to acknowledge and thank Dr. Maria Teresa Vicentini, Dr. Lorena Pompucci and Dr. Anna Aureli for their support with HLA typing.Abstract:This communication describes a new DRB1*11 allele identified in a familial group of Caucasian individuals from central Italy. The new sequence has been officially named DRB1*11272 by the World Health Organization (WHO) Nomenclature Committee (February 2000). It encodes an HLA antigen serologically recognized as DR11. The sequence variation of this new allele was localized to codon 77 of exon 2. It differs at position 230 from DRB1*11011 allele (A replacing C), and at position 231 from DRB1*1127 (C replacing T). At the amino acid level, the DRB1*11272 mutation is silent with respect to the DRB*1127 phenotype, coding for a synonymous asparagine.
HLA‐DRB1*03, DRB1*11 or DRB1*12 and their respective DRB3 specificities in clinical variants of sarcoidosis
Authors: Bogunia‐Kubik K. , Tomeczko J. , Suchnicki K. , Lange A. 
Published: March 2003

Abstract:Determination of DRB1 and DRB3 specificities in sarcoidosis patients identified that the presence of DRB1*03 and the absence of DRB1*11 and/or DRB1*12 favors a course of disease that is associated positively with Löfgren’s syndrome (DRB1*03) and negatively with stage I disease (DRB1*11 and/or 12). In common with normal controls, DRB1*03 was associated with DRB3*0101 and DRB1*11/12 with DRB3*0201/2. An analysis of DRB1 and DRB3 associations in variants of sarcoidosis revealed that DRB1*03 and DRB3*0101 were associated with Löfgren’s syndrome in a combined association fashion. Conversely, a lack of DRB1*11 and/or DRB1*12 but not DRB3*0201/2 favored the clinical course of sarcoidosis.
ANALYSIS OF THE RESULTS OF PAIRED CADAVERIC KIDNEYS WITH SIMILAR DONOR‐RECIPIENT HLA MATCHINGS
Authors: Yaǧmurdur MC , Emiroğlu R , Basaran O , Karakayalı H , Tezel E , Haberal M 
Published: March 2003

In this study, we aimed to clarify the factors that may effect long‐term graft and patient survivals. We retrospectively evaluated the outcome of 112 renal transplant recipients who shared paired cadaveric kidneys between 1985 and July 2001.There were two study groups, each with 56 patients, according to the timing of the operations. The operations were performed by the same transplant team, so Group 1 represents the recipients of the first kidney and Group 2, the second. The same low‐dose triple drug immunosuppression protocol with prednisolone, azathioprine and cyclosporine A was used in both groups. Cyclosporine A was converted to tacrolimus in seven patients in Group 1 and in five patients in Group 2. Demographic properties, number of acute‐rejection episodes, serum creatinine levels, creatinine clearance values, graft and patient survival rates, postoperative complications, recipient body weights, cold ischemia times, and de novo malignancies were studied. To analyze our results the Chi‐square and Wilcoxon Signed Ranks tests were used, differences, with P<0.05 were accepted as significant.Regarding the HLA matchings, the groups were similar. Mean cold ischemia times were 22.1±8.7 and 23.3±9.1 h in Groups 1 and 2, respectively (P>0.05). Acute‐rejection rates within the first month following the transplantation were also similar in both groups. Serum creatinine levels and creatinine clearance values at 30 days post‐transplantation showed no significant difference between the groups (P>0.05). One, 2 and 5 years' graft survival rates (Group 1 vs. Group 2) were 97% vs. 92%, 74% vs. 77% and 27% vs. 24%, respectively. No statistically significant difference was observed on returning to the hemodialysis rates (10/56 vs. 13/56). In Group 2, the rate of proteinuria (over 200 mg/day) throughout the follow‐up period was significantly higher than that in Group 1 (Chi‐square, P=0.03). Three patients underwent re‐transplantation: one in Group 1 and two in Group 2. Three post‐transplant malignancies were detected: one in Group 1 and two in Group 2. An interesting observation was the post‐transplantation T‐cell lymphoma diagnosis in both recipients of the same donor. Also, when compared, the patients were not significantly statistically different according to their body weights, rejection rates and graft survival rates.In conclusion, the short‐ and long‐term outcomes of consecutive‐paired cadaveric kidney transplantations are comparable with similar cold ischemia times, HLA matching and immunosuppressive protocols.
Nickel and copper tolerance and toxicity in three Tuscan populations of Silene paradoxa
Authors: Gonnelli Cristina , Galardi Francesca , Gabbrielli Roberto 
Published: March 2003

Three Tuscan ecotypes of Silene paradoxa L. were studied to evaluate the occurrence of multiple tolerance or co‐tolerance mechanisms and to underline some tolerance strategies in plants naturally adapted to toxic concentrations of heavy metals. Seeds were collected from non‐toxic calcareous soil, a serpentine outcrop with high nickel content and a copper mine dump. The evaluation of the toxic effects of the metals on root growth showed the copper‐tolerant population as nickel co‐tolerant, whereas the opposite was not the case. This suggests the occurrence of a non‐reciprocal co‐tolerance mechanism.The nickel‐tolerant population seemed able to tolerate nickel by limiting its inhibiting effect on the peroxisomal H2O2 scavenging enzymes since, in the sensitive population, this inhibition revealed itself as one of the causes of nickel‐induced oxidative stress. A very low copper root and shoot concentration seemed to be characteristic of the copper‐tolerant population, combined with a low susceptibility to metal‐induced oxidative stress.
The dose–response curve of the gravitropic reaction: a re‐analysis
Authors: Perbal Gérald , Jeune Bernard , Lefranc Agnès , Carnero‐Diaz Eugénie , Driss‐Ecole Dominique 
Published: March 2003

The dose–response curve of the gravitropic reaction is often used to evaluate the gravisensing of plant organs. It has been proposed (Larsen 1957) that the response (curvature) varies linearly as a function of the logarithm of the dose of gravistimulus. As this model fitted correctly most of the data obtained in the literature, the presentation time (tp, minimal duration of stimulation in the gravitational field to induce a response) or the presentation dose (dp, minimal quantity in g.s of stimulation to induce a response) were estimated by extrapolating down to zero curvature the straight line representing the response as a function of the logarithm of the stimulus. This method was preferred to a direct measurement of dp or tp with minute stimulations, since very slight gravitropic response cannot be distinguished from the background oscillations of the extremity of the organs. In the present review, it is shown that generally the logarithmic model (L) does not fit the experimental data published in the literature as well as the hyperbolic model (H). The H model in its simplest form is related to a response in which a ligand‐receptor system is the limiting phase in the cascade of events leading to the response (Weyers et al. 1987). However, it is demonstrated that the differential growth, responsible for the curvature (and the angle of curvature), would vary as a hyperbolic function of the dose of stimulation, even if several steps involving ligand‐receptor systems are responsible for the gravitropic curvature. In the H model, there is theoretically no presentation time (or presentation dose) since the curve passes through the origin. The value of the derivative of the H function equals a/b and represents the slope of the cune at the origin. It could be therefore used to estimate gravisensitivity. This provides a measurement of graviresponsiveness for threshold doses of stimulation. These results imply that the presentation time (or presentation dose) derived from the L model cannot be used anymore as an estimate of gravisensitivity. On the contrary, the perception time (minimal duration of a repeated stimulation which induces a response), which is less than 1 s, should be related to the perception of gravity. The consequences of these results on the mode of action and the nature of graviperception are discussed.
Effect of pig‐specific cytokines on mobilization of hematopoietic progenitor cells in pigs and on pig bone marrow engraftment in baboons
Authors: Kozlowski Tomasz , Monroy Rodney , Giovino Maria , Hawley Robert J. , Glaser Roseann , Li Zhifang , Meshulam Deborah H. , Spitzer Thomas R. , Cooper David K. C. , Sachs David H. 
Published: March 2003

Kozlowski T, Monroy R, Giovino M, Hawley RJ, Glaser R, Li Z, Meshulam DH, Spitzer TR, Cooper DKC and Sachs DH Effect of pig specific cytokines on mobilization of hematopoietic progenitor cells in pigs and on pig bone marrow engraftment in baboons. Xenotransplantation 1999; 6: 00‐00. ©Munksgaard, Copenhagen.Abstract: Mixed hematopoietic chimerism has been found to be a requirement for achieving specific immunologic hyporesponsiveness. Some of the requirements for in vitro and in vivo coexistence of discordant hematopoietic systems in the pig‐to‐baboon (or human) model have been investigated. We have tested the efficacy of pig‐specific cytokines (PSC) (IL3, SCF, GM‐CSF) in the mobilization of porcine bone marrow (BM) progenitors in vivo (i) in the pig and (ii) in baboons that underwent a conditioning regimen and porcine BM transplantation. In a preliminary in vitro study, porcine BM cells were incubated in various media to assess the effect of human plasma on pig progenitors in a colony‐forming unit (CFU) assay. In in vivo studies, four pigs received PSC and one control pig did not. Six baboons underwent natural antibody removal, with subsequent pig BM transplantation. Four of these six underwent nonmyeloablative (n=2) or myeloablative (n=2) conditioning and all received PSC treatment. Two baboons did not receive PSC, one of which underwent a nonmyeloablative regimen. Sequential blood samples and BM biopsies in pigs and baboons were analyzed by CFU assay for the detection of porcine cells. Baboon samples were analyzed by polymerase chain reaction (PCR) to detect porcine DNA.In the case of the in vitro tests, colony forming by porcine progenitors was not inhibited by media containing human plasma and for the in vivo tests, PSC increased the number of progenitors in pig BM; mobilization of progenitors into the peripheral blood was observed. PSC‐treated baboons which experienced transient depletion of leukocytes < 1,000/ml (as an effect of the conditioning regimen) had porcine BM cells detectable by PCR for as long as day 316 after BM transplantation. In conclusion we found that: (i) under the conditions of these studies, in vitro porcine progenitor cell growth was not inhibited by human plasma containing natural antibody and complement; (ii) PSC treatment led to an increased number of progenitors in pig BM and peripheral blood; (iii) the combination of an effective conditioning regimen and treatment with PSC was capable of inducing long‐term survival of pig progenitors in baboons, although only a low level of engraftment was achieved.
The role of chemokines and their receptors in the rejection of pig islet tissue xenografts
Authors: Solomon Michelle F. , Kuziel William A. , Mann David A. , Simeonovic Charmaine J. 
Published: March 2003

Solomon MF, Kuziel WA, Mann DA, Simeonovic CJ. The role of chemokines and their receptors in the rejection of pig islet tissue xenografts. Xenotransplantation 2003; 10: 164–177. © Blackwell Munksgaard, 2003The mechanism by which inflammatory cells are recruited to pig islet tissue (proislet) xenografts was investigated by examining the intragraft mRNA expression of murine α‐ and β‐chemokines in CBA/H mice from days 3 to 10 post‐transplant. Xenograft rejection was associated with early intragraft transcript expression for monocyte chemotactic protein‐1 (MCP‐1) (3 to 5 days), IP‐10 (3 to 4 days) and macrophage inflammatory protein‐1α (MIP‐1α) (3 to 5 days) and subsequent expression of eotaxin (days 4 to 10), MIP‐1β (days 4 and 5) and regulated on activation, normal T cell expressed and secreted (RANTES) (days 4 to 6) mRNA. This pattern was consistent with the early recruitment of macrophages (MCP‐1, MIP‐1α), the influx of CD4 T cells (MCP‐1, MIP‐1α, MIP‐1β, IP‐10 and RANTES) and the characteristic infiltrate of eosinophils (eotaxin and RANTES) associated with islet xenograft rejection. Inhibition of β‐chemokine signaling in CCR2−/− mice (which lack the major co‐receptor for MCP‐1) resulted in retarded macrophage and CD4 T cell recruitment, enhanced eosinophil influx and a minor delay in rejection, compared with wildtype mice; there was little effect on leukocyte infiltration in xenografts harvested from CCR5−/− mice (lacking the co‐receptor for MIP‐1α, MIP‐1β and RANTES). The impeded migration of leukocytes into xenografts in CCR2−/− hosts was associated with delayed intragraft expression of MCP‐1 and RANTES mRNA; absence of MCP‐1/CCR2‐mediated signaling led to enhanced intragraft expression of MCP‐1, MIP‐1α and MIP‐1β mRNA. These findings suggest that MCP‐1 plays an important role in regulating macrophage and CD4 T cell infiltration to xenograft sites via the CCR2 signaling pathway. Additional treatment of xenografted CCR2−/− transplant recipients with anti‐interleukin‐(IL)‐4 and anti‐IL‐5 mAbs further delayed xenograft rejection demonstrating the potential for combined antirejection strategies in facilitating pig islet xenotransplantation.
Life, activation and death of intrahepatic lymphocytes in chronic hepatitis C
Authors: Valiante Nicholas M. , D'Andrea Annalisa , Crotta Stefania , Lechner Franziska , Klenerman Paul , Nuti Sandra , Wack Andreas , Abrignani Sergio 
Published: March 2003

Summary: The healthy liver of adult humans has little or no lymphocyte component and the histological finding of intrahepatic lymphocytes (IHL) is evidence of liver pathology. In a liver injured by chronic hepatitis C, the most common chronic liver disease, most IHL are activated/pro‐inflammatory cells, which are particularly enriched for effectors of innate immunity (natural killer (NK), natural T, and other NK‐like T cells). IHL do not undergo clonal expansion in the liver but migrate from extrahepatic sites to the chronically infected liver, where they display effector function and subsequently die, suggesting that maintenance of the IHL pool depends on continuous lymphocyte migration. The cytotoxic and inflammatory functions of these IHL have three potential outcomes: 1) they could be helpful in clearing the virus (a rare case in hepatitis C virus (HCV) infection); 2) they could be useless and have no effect on the infection; or 3) they could be harmful, whereby overaggressive lymphocyte responses destroy the liver in a continuous and unsuccessful attempt to clear the virus. Unfortunately, we do not know as of yet which of these possibilities is the case and, therefore, a more complete picture of the intrahepatic immune response will be relevant to the development of new therapeutic strategies against HCV. Additionally and from a more general perspective, due to the availability of biopsied material and the high prevalence (~3%) of HCV infection worldwide, studying the chronically inflamed liver of hepatitis C patients is an ideal model to investigate the poorly understood processes of lymphocyte trafficking, activation and death to non‐lymphoid sites of chronic inflammation in man.