Identification of a type 1 diabetes-associated CD4 promoter haplotype with high constitutive activity

CD4 is a candidate gene in autoimmune diseases, including Type 1 diabetes mellitus (T1DM), because the CD4 receptor is crucial for appropriate antigen responses of CD4(+) T cells. We previously found linkage between a CD4-1188(TTTTC)(5-14) promoter polymorphism and T1DM. In the present study, we screened the human CD4 promoter for mutations and identified three frequent single nucleotide polymorphisms (SNPs): CD4-181C/G, CD4-521C/G and CD4-1050T/C. The SNPs are in strong linkage disequilibrium (LD) and association with the CD4-1188(TTTTC)(5-14) alleles, and we observed nine CD4 promoter haplotypes, of which four are frequent. We genotyped the SNPs in 253 Danish T1DM families (1129 individuals) and found evidence for linkage and association of a CD4 (A4(-1188)T(-1050)G(-521)C(-181)) haplotype to T1DM. In reporter studies, we show that (1) the T1DM-associated CD4 haplotype encodes high constitutive promoter activity and (2) the CD4-181G variant encodes higher stimulated promoter activity than the CD4-181C variant. This difference is in part neutralized in the frequently occurring CD4 promoter haplotypes by the more upstream genetic variants. Thus, we report functional impact of a novel CD4-181C/G SNP on stimulated CD4 promoter activity and the identification of a novel CD4 haplotype with high constitutive promoter activity that is linked and associated with T1DM.     

Semen parameters and testicular pathology in men with testicular cancer and contralateral carcinoma in situ or bilateral testicular malignancies

We evaluated 14 patients with bilateral testicular tumour, one-sided tumour and contralateral carcinoma in situ (CIS) of the testis or testis tumour in single testis with respect to their fertility. We analysed semen parameters, serum hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone], testicular sonography, testicular volumes and testicular histology prior to further anti-cancer treatment. Ten out of 14 patients showed normal or reduced sperm concentrations, while 4/14 patients were azoospermic. Serum FSH levels showed a significant negative correlation with sperm concentrations in patients with testicular malignancies (r = -0.64, P = 0.025). Testicular volumes revealed a significant positive correlation with semen parameters in patients with testes that were affected by CIS (r = 0.733, P = 0.038). We conclude that even bilateral testicular cancer and/or CIS do not preclude fertility and, therefore, patients should be offered andrological investigation and therapy, including possibly surveillance strategy or the chance for cryopreservation of the semen prior to further treatment in order to preserve their chances for paternity.      

Chemical composition and morphology of welding fume particles and grinding dusts.

Elemental composition and morphology of pure manual metal arc (MMA) welding fumes, pure grinding dust, and combined fume/dust air samples were collected and determined separately under semilaboratory conditions. The base material was stainless steel. The purpose of the present study was to create a "synthetic" work situation under semilaboratory conditions by combining one grinding period and two MMA welding periods and comparing these results with results during welding in a workshop. The duty cycles of pure welding and of pure grinding were also observed. A comparison was also made between metal inert gas (MIG) and MMA welding on stainless steel as well as a nickel-rich alloy under regular conditions. The amount of collected material was determined by weighing the membrane filters before and after exposure, and the element contents were determined by atomic spectroscopy. Other transmission electron microscopy (TEM) filters were used for TEM and computer-image analysis, in which the amount of collected material and its morphological characteristics were observed. The arcing time and the consumption of filler material were estimated for different kinds of electrodes. Chemical analysis showed that the contents of manganese and total chromium were lower in grinding dust than in welding fumes. The contents of hexavalent chromium, Cr(VI), in grinding dust were undetectable. Samples collected in welding shops where concomitant grinding was performed contained about 30% less Cr(VI) than those collected under laboratory conditions during welding only. The sizes and shapes of the particles depend on the welding process and distance of collection from the plume of the fume. To compare laboratory experiments with regular welding situations, the experiment must resemble industrial welding.(ABSTRACT TRUNCATED AT 250 WORDS)     

Health related quality of life in Parkinson's disease: a prospective longitudinal study

OBJECTIVES: To examine the change over time in health related quality of life (HRQL) in a community based cohort of patients with Parkinson's disease. METHODS: One hundred and eleven patients were evaluated for HRQL in 1993 and then again in a follow up study 4 years later. The patients included in the study in 1993 were derived from a prevalence study of patients with Parkinson's disease in the county of Rogaland, Norway. The HRQL was measured by the Nottingham health profile (NHP). At both evaluations clinical and demographic variables were determined during semistructured interviews and by clinical examinations by a neurologist. RESULTS: During the 4 year follow up period there was a significant increase in NHP scores, reflecting a decreased HRQL, in the dimensions of physical mobility, emotional reactions, pain, and social isolation. In the same time period mean total NHP score increased from 120.0 (SD 102.6) to 176.0 (SD 119.4) (p<0.01). There were no clinical or demographic factors found in 1993 that identified patients at higher risk for developing decreased HRQL. Increased UPDRS score (unified Parkinson's disease rating scale) and Hoehn and Yahr stage during the 4 year study period correlated with increased NHP scores. Even though there was no increase in depressive symptoms or self reported insomnia, these symptoms, together with lower Schwab and England score, were the most important factors for a poor HRQL in 1997. CONCLUSIONS: Parkinson's disease has a substantial impact on HRQL. Despite modern care, we found a significantly increased distress during the 4 year follow up period. Increased parkinsonism, measured by UPDRS and Hoehn and Yahr stage, correlated with increased stress, not only in the dimension of physical mobility, but also in the areas of pain, social isolation, and emotional reactions. In addition to the clinical examination, HRQL scoring provides valuable information on the total health burden of Parkinson's disease in both cross sectional and longitudinal evaluations, and contributes to a more comprehensive picture of the total disease impact.     

Respiratory syncytial virus genotypes and disease severity among children in hospital

OBJECTIVES: To determine the spectrum of N and G genotypes of respiratory syncytial virus (RSV) causing respiratory tract infection and whether particular genotypes are associated with severity of infection. PATIENTS AND METHODS: Nasopharyngeal aspirates (NPAs) were obtained from 114 infants with acute respiratory tract infection due to RSV over two seasons. Viral mRNA was extracted from NPAs or cultured virus, reverse transcribed, and the cDNA amplified by the polymerase chain reaction using primers directed to parts of the N and G gene respectively. Amplicons were separately digested with four different restriction endonucleases for each gene. The fragments were separated by agarose gel, electrophoresis, and the electrophoretic patterns used to assign the various genotypes. Disease severity was assessed as very mild (upper respiratory tract signs only), mild (coryza and signs of lower respiratory tract infection), moderate (requiring nasogastric or intravenous fluids), and severe (requiring oxygen or ventilation). RESULTS: Five of the six known N genotypes were detected, but NP4 and NP2 were found most frequently. There was no association between N genotype and disease severity. Six G (SHL) genotypes were detected. Significantly (p = 0.04) more of the infants infected with the SHL2 genotype had severe or moderate disease. CONCLUSIONS: During the seasonal peaks of RSV respiratory tract infection at least 10 different RSV genotypes cocirculated. While there is no association between N genotypes and disease severity, infection with the SHL2 G genotype appears to result in moderate to severe disease.     

Aorto-Caval Fistula Due to Rupture of Abdominal Aneurysm

Abstract

Two operated cases of aorto-caval fistula due to ruptured abdominal aneurysm are reported. This is a rare and real surgical emergency and is fatal without operation. The classical symptoms of high-output failure occurring simultaneously with the findings of an expansible abdominal mass with thrill and bruit should facilitate clinical diagnosis.