Familial multiple myeloma. Two more families

The authors report on two multiple myeloma sibling pairs. In the absence of a known disease-specific marker one can only speculate on an explanation: is it because of inherited errors or is it related to the same environmental exposure, or both? In this study HLA typing and metabolizing enzyme polymorphism studies have been carried out with the aim of finding inherited similarities in the siblings or characteristics that might differ from the average population. Sibling pair 1 shared an HLA haplotype. Sibling pair 2 shared only HLA-B51, DR4, DRw53, DQ3. Sibling 1/1 was GSTT1/GSTM1 null and GSTP1 Ile105Val; sibling 1/2 was a GSTT1/GSTM1 heterozygote and GSTP1 Ile105Val; sibling 2/1 and 2/2 were GSTT1 heterozygotes and shared GSTM1 null/GSTP1 Ile105Ile. The siblings had identical light chain or heavy chain secretion, or both. The similarities found in the inherited factors together with the same environmental exposure in the siblings' first 20 years of life imply that the development of the same disease cannot be a coincidence

De novo malignant melanoma occurred in renal allograft: DNA typing to determine the origin of the tumour

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Strength and volume consistency of aluminium piston castings

26.00; Translated from Polish (Banyasz. Kohasz. Lapok (Oentoede) 1986 v. 37(3) p. 53-57)SIGLEAvailable from British Library Document Supply Centre- DSC:9022.0602(BISI-NF-Trans--169)T / BLDSC - British Library Document Supply CentreGBUnited Kingdo

HLA genetic diversity in Hungarians and Hungarian Gypsies: complementary differentiation patterns and demographic signals revealed by HLA-A, -B and -DRB1 in Central Europe

Systematic analyses of human leukocyte antigen (HLA) profiles in different populations may increase the efficiency of bone marrow donor selection and help reconstructing human peopling history. We typed HLA-A, -B, and -DRB1 allele groups in two bone marrow donor cohorts of 2402 Hungarians and 186 Hungarian Gypsies and compared them with several Central-European, Spanish Gypsy, and Indian populations. Our results indicate that different European Gypsy populations share a common origin but diverged genetically as a consequence of founder effect and rapid genetic drift, whereas other European populations are related genetically in relation to geography. This study also suggests that while HLA-A accurately depicts the effects of genetic drift, HLA-B, and -DRB1 conserve more signatures of ancient population relationships, as a result of balancing selection

Differences in the genetic background of latent autoimmune diabetes in adults (LADA) and type 1 diabetes mellitus

Objectives: According to the recent classification of diabetes mellitus the Latent Autoimmune Diabetes in Adults (LADA) belongs to the group of type 1 autoimmune diabetes, as a slowly progressive form. Our aim was to determine (i) the prevalence of HLA-DRB1 and DQB1 genotypes, and (ii) to determine the tumor necrosis factor (TNF) α promoter polymorphism at position -308 (the G→A substitution, designated the TNF2 allele) in patients with type 1 diabetes and with LADA compared with the healthy population. Methods: The major histocompatibility complex (MHC) II genotypes and the TNF α promoter polymorphism were determined by PCR method. We examined 69 type 1 diabetic and 42 LADA patients. As control samples of 336 cadaver kidney donors and 138 volunteers were used. Results: Both type 1 diabetes mellitus and LADA were positively associated with the DRB1*04-DQB1*0302 (DR4/DQ8) haplotype (P=0.00001, and P=0.0005, respectively), and negatively associated with the DRB1*11-DQB1*0301 (DR11/DQ7) haplotype (P=0.00006, and P=0.007, respectively) compared with control population. There were differences between the two disease entities in the frequency of the DRB1*03-DQB1*02 (DR3/DQ2) haplotype (P=0.00008 vs. P=0.177) compared with control group. The presence of the TNF2 allele was significantly lower in LADA than type I diabetes (P=0.022) or control group (P=0.017). Conclusion: Our findings indicate that there are marked differences in the genetic background of type 1 diabetes and LADA. The low presence of TNF2 allele (known to be associated with high amount of TNF α production) in LADA could be one of the factors responsible for the relatively slow progression. © 2002 Elsevier Science B.V. All rights reserved

Sex-specific survival difference in association with HLA-DRB1 *04 following allogeneic haematopoietic stem cell transplantation for lymphoid malignancies

The role of HLA system in allogeneic haematopoietic stem cell transplantation (allo-HSCT) outcome is unarguable. In this study we investigated association of HLA-A,-B and-DRB1 alleles with overall survival (OS) in 186 patients undergoing allo-HSCT for lymphoid malignancies. Analyses confirmed significantly better OS for HLA-DRB1 *04 carriers compared with non-carriers (p=0.01). Survival benefit was confined to male patients (in multivariate analyses p=0.034, hazard ratio 0.35, 95% confidence interval 0.13-0.92), whereas in females no difference was noted (p=0.82). Furthermore, donor gender also affected outcome and transplantation from female HLA-DRB1 *04 carrier donors resulted in superior survival compared with female non-carrier donors (p=0.01). Combined analyses including recipient/donor gender and HLA-DRB1 *04 showed that survival of male patients varied significantly according to donor gender and HLA-DRB1 *04 carriership (p=0.04) with best survival among HLA-DRB1 *04 carriers transplanted from female donors. Of relevance to our results, HLA-DRB1 *04 has been documented as risk allele group for lymphoid malignancies, and studies described a male-specific risk. We believe that our findings provide further supporting evidence for sex-specific alterations secondary to HLA-DRB1 *04 or related genes. Further studies are warranted to evaluate whether in contrast to general favour of male donors HLA-DRB1 *04 carrier patients with lymphoid malignancies could benefit from transplantation from female donors