The polymorphism of HLA-DR3 in South African populations

The polymorphism of HLA-DR3 was investigated in families and unrelated individuals of three population groups: South African (SA) Negroes, Cape Coloureds and SA Caucasoids. Serological and restriction fragment length polymorphism (RFLP) analysis indicated that DR3 could be subdivided into DRw17 (previously DR3.1) and DRw18 (previously DR3.2). In contrast, the two-dimensional (2-D) gel electrophoresis patterns could not distinguish between the DRB1 gene products of the HLA-DRw17 and DRw18 cells. Two DRB3 variants, correlating with the T-cell defined specificities Dw24 and Dw25 were identified at the genomic and product level. Of ten haplotypes studied with the newly defined HLA-DRw18 specificity, all had the DRB3 RFLP pattern associated with Dw24. HLA-DRw17 was found in all three population groups tested, although in the SA Negroes HLA-DRw18 was the prevalent DR3 subgroup. This subgroup was also present in the Cape Coloureds but was absent in the SA Caucasoid tested. HLA-DRw18 forms part of the most characteristic SA Negro haplotype, Bw42, DQw4, Dw“RSH,” while HLA-DRw17 is part of the classic Caucasoid haplotype, B8, DQw2, Dw3.     

Electrophoretic variants of human 6-phosphogluconate dehydrogenase: population and family studies and description of a new variant

Erythrocyte 6-phosphogluconate dehydrogenase (6-PGD) from 2603 individuals was observed on starch gel following electrophoresis and several genetic variants are described. Among them is a new variant (the Friendship variant) detectable only in the absence of NADP from the gel and presenting a triple pattern for erythrocyte enzyme but only a single band for leucocyte or fibroblast enzyme. Family studies indicate that all the variants are due to autosomal co-dominant alleles, and the population data suggest that the gene frequencies for the common alleles, PGD^A and PGD^C, are different between Negroes and whites.     

Effect of blood on the assay of 6-phosphogluconate dehydrogenase in vaginal fluid

The effect of blood in vaginal fluid on the assay of 6-phosphogluconate dehydrogenase has been studied. Alternative assay procedures have been investigated to overcome these effects.     

Implication of lysine residues in the loss of 6-phosphogluconate dehydrogenase activity in aging human erythrocytes

The activity of 6-phosphogluconate dehydrogenase (6-PGDH) decreases in aged human erythrocyte populations. The aged enzyme has 11 lysine residues less than the young enzyme, when they are measured with 2,4,6-trinitro-benzenesulfonic acid (TNBS). Treatment of young enzyme with ascorbate for 15 min produces the loss of 8 lysine residues and the diminution of enzymatic activity. These results suggest that there is a modification of lysine residue in human erythrocytes during senescence, probably caused by oxidation. This modification of lysine residue could imply the loss of enzymatic activity. This result is similar to that found in rat liver 6-PGDH during aging, described previously (Gordillo et al., J. Biol. Chem. 264 (1989) 17014-17019).     

The 6-phosphogluconate dehydrogenase from Trypanosoma cruzi: the absence of two inter-subunit salt bridges as a reason for enzyme instability

The third enzyme of the pentose phosphate pathway (PPP), 6-phosphogluconate dehydrogenase (6PGDH), is present in the four major stages of Trypanosoma cruzi, CL Brener clone. The enzyme was too unstable to be purified from epimastigote cell-free extracts. Two genes encoding 6PGDH were cloned and sequenced; the predicted amino acid sequences differ only in five non-essential residues. Since Southern blots suggested the presence of a single copy per haploid genome, the two genes found are probably alleles. One of these genes, encoding a protein with 78.6% identity with the Trypanosoma brucei 6PGDH, was expressed in Escherichia coli as an active recombinant enzyme, which was as unstable as the native 6PGDH. Modeling of the T. cruzi enzyme using the three-dimensional structure of the T. brucei 6PGDH as template suggested the lack of two out of five salt bridges proposed to strengthen subunit interactions in the active dimer. Restoring of these bridges by site-directed mutagenesis resulted in a more stable recombinant T. cruzi 6PGDH, which was used to determine the kinetic parameters. The K(m) value for 6-phosphogluconate (22.2+/-0.4 microM) was identical to the values reported for 6PGDHs from mammals, but the K(m) for NADP (5.9+/-0.2 microM) was significantly lower than the value reported for the human enzyme, and closer to that for the T. brucei enzyme. This suggests the possibility that inhibitors of the T. brucei 6PGDH, under development as potential drugs against African Trypanosomiasis, might also be successful for the chemotherapy of Chagas disease.     

Association of a single nucleotide polymorphism in the ubxn6 gene with long-term non-progression phenotype in HIV-positive individuals

ObjectivesThe long-term non-progressors (LTNPs) are a heterogeneous group of HIV-positive individuals characterized by their ability to maintain high CD4⁺ T-cell counts and partially control viral replication for years in the absence of antiretroviral therapy. The present study aims to identify host single nucleotide polymorphisms (SNPs) associated with non-progression in a cohort of 352 individuals.MethodsDNA microarrays and exome sequencing were used for genotyping about 240 000 functional polymorphisms throughout more than 20 000 human genes. The allele frequencies of 85 LTNPs were compared with a control population. SNPs associated with LTNPs were confirmed in a population of typical progressors. Functional analyses in the affected gene were carried out through knockdown experiments in HeLa–P4, macrophages and dendritic cells.ResultsSeveral SNPs located within the major histocompatibility complex region previously related to LTNPs were confirmed in this new cohort. The SNP rs1127888 (UBXN6) surpassed the statistical significance of these markers after Bonferroni correction (q = 2.11 × 10⁻⁶). An uncommon allelic frequency of rs1127888 among LTNPs was confirmed by comparison with typical progressors and other publicly available populations. UBXN6 knockdown experiments caused an increase in CAV1 expression and its accumulation in the plasma membrane. In vitro infection of different cell types with HIV-1 replication-competent recombinant viruses caused a reduction of the viral replication capacity compared with their corresponding wild-type cells expressing UBXN6.ConclusionsA higher prevalence of Ala31Thr in UBXN6 was found among LTNPs within its N-terminal region, which is crucial for UBXN6/VCP protein complex formation. UBXN6 knockdown affected CAV1 turnover and HIV-1 replication capacity.     

Squamous cell carcinoma of skin with a rhabdoid phenotype: a case report

A 67 year old man presented with a polypoid lesion on the temple that had all the light microscopic, immunohistochemical, and ultrastructural features of a rhabdoid tumour. There was an area of intraepidermal carcinoma and invasive squamous carcinoma at the base of the polyp. The tumour progressed aggressively and the patient died five months after primary excision. Cutaneous tumours with a rhabdoid morphology have been described previously and tend to have a very poor prognosis. No previously published report describes a clear squamous histogenesis.     

The first case of the p phenotype in a Gurkha Nepalese

A serum sample from a Gurkha Nepalese soldier, residing in Hong Kong, was found to cause hemolysis of reagent ABO red cells (RBCs) in the reverse blood grouping test. Subsequent follow-up studies revealed that he was of the p phenotype, with potent anti-PP1Pk that was strongly hemolytic both at room temperature and 37 degrees C. The anti-PP1Pk was composed of IgG and IgM, and its various components were separable.     

The level of 6-phosphogluconate dehydrogenase (6-PGD) activity in a patient with a 1p terminal deletion suggests that the gene locus is not distal to sub-band p36.3 on chromosome 1

A rare case of chromosome 1p deletion is reported in a mentally retarded male infant with a derived chromosome: 45,XY,-1,-13,tdic(1;13)(1qter----1p36.2::13p11.2----++ +13qter). Parental chromosomes were normal. Since the patient's 6-PGD specific activity was in the normal range, it is probable that he retained both 6-PGD alleles. Consequently, if a dosage affect exists, then the locus for 6-PGD must be proximal to 1p36.3.     

Juberg-Hayward syndrome: report of a new patient with severe phenotype and novel clinical features

We studied the distribution of GSTM1 phenotypes in 611 individuals from an ethnically mixed sample of the Brazilian population who died from various causes. No influence of age, gender, or ethnicity was detected on the phenotypic distribution. In a sub-sample of 66 alcoholic individuals compared with 399 non-alcoholics there was almost a doubling of the odds ratio for GSTM1(0) individuals in the alcoholic category. The incidence of hepatopathies was higher in this group as well, and we observed a significant association of the null phenotype with cirrhosis. An excess of null phenotypes (374/611) was observed, and the allelic distribution was: GSTM1*A = 0.168, *B = 0.089, and *0 (null) = 0.743.     

Detection of 1311 polymorphism in the glucose-6-phosphate dehydrogenase gene by microarray technique

Introduction

Nucleotide 1311 polymorphism at exon 11 of the glucose-6-phosphate dehydrogenase (G6PD) gene is fairly common in various populations worldwide, especially among Mediterranean populations. In this study, 1311 polymorphism in G6PD-deficient cases was identified by microarray technique.

Material and methods

Four hundred and fifty clinically healthy subjects were screened and 32 cases were found to have G6PD deficiency (7.11%). Our analysis of genomic DNA samples from 32 G6PD-deficient individuals revealed that the number and percentage of subjects who had a C-to-T alteration at nucleotide 1311 were 21 and 4.7% respectively. Given that the frequency of 1311 polymorphism has been reported in previous studies to be fairly high among G6PD-deficient people with the Mediterranean mutation, our data seem to be inconsistent with what we would expect for this particular region.

Results

The highly diverse ethnic background of the Adana population which probably results from the high level of immigration into this part of Turkey may be one of the most sensible explanations for this unexpected finding. Nevertheless, it seems that our results need to be confirmed in larger studies.

Conclusions

The polymorphism studies in the G6PD gene may help us to illuminate the genetic basis of the G6PD deficiency in different regions and in various ethnic groups, and also to discover the influence of a specific polymorphism on the clinical course of the deficiency.     

Translocation 10;17 in clear cell sarcoma of the kidney. A first report

This is the first report of a t(10;17) as the unique cytogenetic finding in one case of a rare childhood tumor, clear cell sarcoma of the kidney (CCSK). This observation is discussed in relation to the cytogenetics of Wilms' tumors, of which CCSK is a variant.     

The first report of Angiostrongylus vasorum (Nematoda; Metastrongyloidea) in Poland,in red foxes (Vulpes vulpes)

Angiostrongylus vasorum belongs to the superfamily of Metastrongyloidea. This nematode occurs in foxes, dogs and other predators. The Nematode A. vasorum place themselves in the pulmonary artery and its branches, and in the right ventricle and atrium of the heart. Numerous species of land snails are the intermediate hosts of the parasite. In 2013, lungs and hearts of 76 foxes shot in the Forest District G??boki Bród in Augustowska Primeval Forest were parasitologically necropsied. Four of the examined foxes were infected with the nematode A. vasorum, a prevalence of 5.2%. In one fox pericardium there were 6 male and 6 female nematodes. In the remaining three foxes nematodes were localized in the pulmonary artery. In two foxes 2 specimens of nematodes were detected (male and female, and two females) while 1 female was detected in the other fox. This is the first report of the presence of the nematode A. vasorum in fox in Poland.