Aims/hypothesis Although the associations between obstructive sleep apnoea and type 2 diabetes mellitus have been reported in cross-sectional design studies, findings on the prospective association between the two conditions are limited. We examined prospectively the association between nocturnal intermittent hypoxia as a surrogate marker of obstructive sleep apnoea and risk of type 2 diabetes. Methods A total of 4,398 community residents aged 40 to 69 years who had participated in sleep investigation studies between 2001 and 2005 were enrolled. Nocturnal intermittent hypoxia was assessed by pulse-oximetry and defined by the number of oxygen desaturation measurements ≤3% per h, with five to <15 per h corresponding to mild and 15 events or more per h corresponding to moderate-to-severe nocturnal intermittent hypoxia, respectively. The development of type 2 diabetes was defined by: (1) fasting serum glucose ≥7.00 mmol/l (126 mg/dl); (2) non-fasting serum glucose ≥11.1 mmol/l (200 mg/dl); and/ or (3) initiation of glucose-lowering medication or insulin therapy. Multivariable model accounted for age, sex, BMI, smoking status, current alcohol intake, community, borderline type 2 diabetes, habitual snoring, excessive daytime sleepiness, sleep duration and (for women) menopausal status.Results By the end of 2007, 92.2% of participants had been followed up (median follow-up duration [interquartile range] 3.0 [2.9-4.0] years) and 210 persons identified as having developed diabetes. The multivariable-adjusted hazard ratio (95% CI) for developing type 2 diabetes was 1.26 (0.91-1.76) among those with mild nocturnal intermittent hypoxia and 1.69 (1.04-2.76) among those with moderate-to-severe nocturnal intermittent hypoxia (p=0.03 for trend). Conclusions/interpretation Nocturnal intermittent hypoxia was associated with increased risk of developing type 2 diabetes among middle-aged Japanese.

An effective method for the isolation and purification of exfoliatin which has been recently reported by Melish and others as the staphylococcal toxin responsible for the scalded skin syndrome and the physicochemical properties of the purified toxin were described. From an active crude toxin produced by one of the clinical isolates of phage group 2, four types of toxic proteins which were all capable of causing the typical Nikolsky sign in neonatal mice were obtained and designated A, B, C, and D toxins. They had a molecular weight of about 24,000 and showed the same serological features in neutralization and precipitation tests, but were different from each other in showing a different single band with their respective mobilities in polyacrylamide disk electrophoresis. They were precipitated between pH 4.0 and 4.5 and lost their exfoliative capabilities. The resulting precipitates, however, could be solubilized in acetate buffer containing 0.5% sodium dodecyl sulfate, restoring their toxicities to almost the same extent as before. They were all stable when heated at 60 C for 60 min and at 100 C for 20 min, but lost their toxicities when heated at 100 C for 40 min. Additionally, the present authors observed that some staphylococcal strains not belonging to the typical phage group 2, isolated from patients with the scalded skin syndrome, were also capable of producing a similar but serologically unrelated exfoliative toxin. Recently several groups of workers have pointed out the close association between Staphylococcus aureus of phage group 2 and the disease of infants known as toxic epidermal necrolysis of the Ritter's type (3, 4, 7-9, 12, 13). An experimental model with newborn mice for the study of the toxic epidermal necrolysis (TEN) has been reported by Melish and Glasgow (10). Subsequently, Arbuthnott et al. (1)

Summary:but can also suggest the replicative potential remaining in each cell.14 Recovery of the hematopoietic system after hematopoTelomeres are responsible for keeping the stability not only of chromosomes but also of genes. To investigate ietic stem cell transplantation (HSCT) requires numerous replication cycles by HSCs. Such successive division of the effect of hematopoietic stem cell transplantation (HSCT) on telomeres, we studied telomere length in the HSCs may affect the telomere length of their descendant cells. Since telomeres are important not only for the stabperipheral blood mononuclear cells of 31 children who received HSCT. In the auto-HSCT groups telomere ility of chromosomes and genes, but also for determining the fate of cells [15][16][17][18][19] we became interested in the effect of length ranged from 8.6 to 12.0 kb and in the allo-HSCT groups from 8.4 to 12.0 kb. Comparison of the telomere HSCT on telomere length. In this study, we assessed the effect of HSCT on telolength between before and after auto-HSCT showed shorting up to 1.0 kb. Moreover, comparison between mere length in children. We found that the telomere length of the HSCT patients was not significantly shorter than that donors and recipients in allo-HSCT revealed that telomeres of recipients were up to 1.0 kb shorter than those of age-matched putative normal controls, but telomere length was affected by donor age. of the donors. Patients who received allo-HSCT from donors older than 18 years had significantly shorter telomeres than those transplanted from donors under 18 years old (P Ͻ 0.05), indicating that donor age is an Patients and methods important factor for recipient's telomere length. These findings suggest that the effects which might be induced Patients by shortening of telomeres in recipients are within the Thirty-one children who underwent HSCT from 1983 to biologically tolerable range. However, if hematopoietic 1996 at Jikei University Hospital were studied. Two stem cells from elderly donors are transplanted into patients were treated with autologous bone marrow transyounger patients, the telomere length may become too plantation (auto-BMT), 11 patients received autologous short for acceptable lifetime risks of genetic instability peripheral blood stem cell transplantation (auto-PBSCT), in the recipient.and 18 patients underwent allogenic bone marrow transKeywords: hematopoietic stem cell transplantation; plantation (allo-BMT). No T cell-depleted stem cells were children; telomere length; chromosomal instability transplanted. The conversion to donor blood type was confirmed in allo-HSCTs by studying one or two of the following factors: the sex chromosome, the types of red blood Telomeres are special protein/DNA structures that cap the cells, and the types of HLA. The clinical characteristics of ends of linear eukaryotic chromosomes, preventing end-tothe patients are listed in Tables 1 and 2. The follow-up perend fusion and exonucleotic degradation.

The liver enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are responsible for the oxidative metabolism of ethanol, are polymorphic in humans. Cytochrome P450IIE1, an ethanol-inducible isozyme of liver microsomal P450, is also important in ethanol metabolism. Genetic polymorphisms in the 5'-flanking region of the human cytochrome P450IIE1 gene have recently been reported. We hypothesized that the polymorphisms of ADH, ALDH, and P450IIE1 modify the susceptibility to development of alcoholism. We determined the genotypes of the ADH2, ALDH2, and P450IIE1 loci of 96 Japanese alcoholics and 60 healthy male subjects, using leukocyte DNA by the restriction fragment-length polymorphism by polymerase chain reaction. The alcoholics had significantly higher frequencies of the ADH2(1) and ALDH2(1) alleles than did the healthy subjects. No significant difference in the frequency of the P450IIE1 genotype was observed between the alcoholics and the healthy subjects. In conclusion, genetic polymorphisms of the ADH and ALDH genes, but not of the P450IIE1 gene, influence the risk of developing alcoholism in Japanese.

Summary.Although EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is of practical importance because failure to recognize this clinical entity may result in misdiagnosis and subsequent mismanagement of the patients, the pathophysiological nature of EDTA-PTCP remains unknown. To develop an effective way to evaluate the platelet counts in patients with EDTA-PTCP, we introduced aminoglycosidessupplemented anticoagulating agents. When kanamycin was pre-supplemented with EDTA for anticoagulating blood samples from EDTA-PTCP patients there was no significant change in the platelet counts and the morphology of blood cells after 150 min of incubation at room temperature. Furthermore, when kanamycin was added to EDTA-anticoagulated blood samples from EDTA-PTCP patients within 30 min after blood withdrawal, rapid dissociation of platelets without apparent morphological changes of blood cells was observed, and complete blood cell counts as well as the histogram patterns were almost the same as those examined immediately after blood sampling. The dissociation of aggregated platelets was also detected when other antibiotics were used, although it was associated with some extent of morphological changes of blood cells. These findings indicate that the supplementation of aminoglycosides either before or after blood sampling is a useful method for the diagnosis EDTA-PTCP and for the evaluation of platelet counts in patients with EDTA-PTCP.