The T-cell receptor alpha, beta and gamma polymorphism in Japanese

Polymorphism in the genes encoding the alpha (alpha), beta (beta) and gamma (gamma) chains of the human T-cell receptors was analyzed both in population and family studies. Against twelve unrelated Japanese, several out of the 15 restriction endonucleases tested, revealed restriction fragment length polymorphism. The segregation of the polymorphic fragments were confirmed among 15 members of three families. In most of the cases paternal and/or maternal haplotypes could be assigned. By testing the polymorphic enzymes among the random healthy Japanese, the frequency of each polymorphic fragment was then determined. Although the polymorphism found in this study was similar to that reported in Caucasians, some differences were observed. Such differences are discussed. The restriction fragment length polymorphism in both population and family studies, derived from alpha, beta and gamma chains of the T-cell receptor found in this report, might be useful markers for genetic analysis of the T-cell function in relation to immunological disorders.     

Arthus-type nephritis. II. Glomerular clearing system against poorly soluble and insoluble immune complexes

The uptake and transport of immune complexes (IC) in glomeruli were studied in Arthus-type nephritis induced by ferritin anti-ferritin IC. This experimental nephritis was transient in nature, forming electron dense aggregates and deposits in glomeruli, and was considered to be suitable for the analysis of the glomerular defence against immune complex injury. The IC were taken up and removed from the glomerular circulation first by polymorphonuclear leukocytes and later by macrophages. The IC in the glomerular capillary walls and mesangium were seen to shift slowly from the peripheral part of the glomeruli to the more central and juxtaglomerular area. It is speculated that the glomerular integrity is maintained from the immune complex induced tissue injury through the handling and removal of phlogogenic IC by the blood derived phagocytic system and intrinsic glomerular clearing system.     

Histologic transformation in extranodal non-Hodgkin's lymphoma

Histologic transformation in the course of non-Hodgkin's lymphoma (NHL) has been reported to occur in 18 to 30% of the cases. Less favorable prognosis in cases with initial low grade malignancy followed by emergence of high grade malignancy has been previously described. In the previous literature, the histologic transformation has been examined mostly in nodal NHL. In the present study, histologic transformation in the course was investigated on 20 cases with early extranodal NHL. All these 20 cases were diffuse lymphomas, and were composed of 7 cases with low grade malignancy and 13 cases with high grade malignancy. Histologic transformation was not observed in any of these cases. These findings indicate that the frequency of histologic transformation is much lower in extranodal NHL than in nodal NHL. The prognostic significance of these findings is also discussed.     

Strain combination-dependent genesis of necrotizing arteritis in anti-ICAM-1 antibody-perfused renal allografts in the rat

Rat kidneys were perfused with anti-intercellular adhesion molecule-1 (anti-ICAM-1) monoclonal antibody prior to allo-transplantation. In the two strain combinations examined, LEJ-to-WKAH transplants resulted in accelerated graft loss, and no prolongation of graft survival. The accelerated graft logs was the resut of frequent occurrence of necrotizing arterttis wlthln the grafts. In contrast, TO-to-WKAH transplants resulted in no change In graft survival and no arteritis. Necratidng vasculitis in the LEJ-to-WKAH grafts was characterlzed by flbrinoid necrosis, collection of cellular infiltrates and serum macromolecular protein entrapment. The F(ab')² form of anti-ICAM-1 antlbody partially preserved the antibody's capacity to accelerate graft loss. Therefore, although endothelial injury by Fc-mediated cytotoxicity may be involved in vascular damage, other mechanisms also come into play. The amount and distribution pattern of ICAM-1 antigen were identical in both TO and LEJ strains. Intravenous anti-CAM-1 antibody administration combined with lipopolysaccharide, Poly(1)-Poly(C), warm ischemia to the kidney, or subcutaneous immunization with allogeneic spleen cells, but without renal transplantation, did not generate necrotizing vasculitis or proteinuria. These observations plus our previous data on the rat liver transplantation model clearly show that graft perfusion with anti-ICAM-1 monoclonal antibody invokes extensive vascular damage within allografts by Fc-mediated and Fc-independent mechanisms, depending on the donor-to-host combination.     

Serum magnesium concentration is a significant predictor of mortality in maintenance hemodialysis patients

A few studies have reported a correlation between magnesium and co-morbidity and mortality in end-stage renal disease. We investigated the prognostic value of serum magnesium concentration for mortality in 515 patients on maintenance hemodialysis (60 +/- 12 years, 306 males and 209 females; 24% diabetics). The patients underwent follow-up for 51 +/- 17 (mean +/- SD) months, and the relationship between the baseline magnesium concentration (mean of four months) and outcomes was analyzed statistically. During the follow-up period, there were 103 all-cause deaths, including 63 non-cardiovascular deaths. Kaplan-Meier analysis revealed that mortality was significantly higher in the lower magnesium group (< 2.77 mg/dL, i.e. < 1.14 mmol/L, n = 261), compared to that in the higher magnesium group (> or = 2.77 mg/dL, n = 254) (p < 0.001). Multivariate Cox proportional hazard analysis demonstrated that serum magnesium was a significant predictor for mortality (HR [per 1 mg/dL increase], 0.485 [95% CI, 0.241-0.975], p = 0.0424), particularly for non-cardiovascular mortality (HR 0.318 [95% CI, 0.132 to 0.769], p = 0.0110), after adjustment for other confounders, such as age, gender, hemodialysis duration, and the presence of diabetes. In conclusion, it is demonstrated that lower serum magnesium level is a significant predictor for mortality in hemodialysis patients, particularly for non-cardiovascular mortality, although the mechanisms remain to be explored in future studies. Factors affecting serum magnesium concentrations should be investigated in terms of better survival, including dietary magnesium intake. Further extensive studies may be also needed for possible reconsideration of the current dialysate magnesium concentration (1.0 mEq/L, i.e. 0.50 mmol/L used in most countries), one of the strong contributors to the serum magnesium concentrations of dialysis patients.     

Association between HLA and Japanese patients with rheumatoid arthritis

Japanese patients with rheumatoid arthritis (RA) were observed to have a statistical association with HLA-DR4, MT3. Strong association between the clinical severity of RA and HLA was also observed. Male patients had a stronger association with HLA than female patients. Males are more resistant to RA than females. This suggested that the threshold of liability for RA is higher in males than in females. Japanese patients with RA with systemic vasculitis were negative for HLA-Bw44 and had antilymphocytotoxic autoantibody, indicating that RA with systemic vasculitis is different in etiology from RA without systemic vasculitis.     

In vitro early changes in intercellular junctions by treatment with a chemical carcinogen

To examine early intercellular junction changes caused by treatmentwith 9, 10-dimethyl-l, 2-benzanthracene (DMBA), rat lingualepithelium was cultivated in isolation and observed by electrophysiological,freeze-fracture and whole-mount electron microscopy. Electrophysiologicalmeasurements showed a transient decrease in membrane potentialof -10.2 mV 6 h after the treatment. It returned to almost thesame level as that of the control group 1 day later. Six hoursafter treatment, input resistance decreased rapidly to 5.3 Mbut increased to 18.0 M 12 h after treatment. Transient reductionof input resistance and membrane potential occurred prior tothe decrease in the coupling ratio 6 h after treatment withDMBA. In freeze-fracture replicas, the number of gap junctionsdecreased by 45% of the control value 6 h after treatment withDMBA. At 12 h and thereafter, the number and area of gap junctionssubsequently decreased by 60–80% of the control value.Alterations in the number and area of desmosomes were similarto those of the gap junctions. The formation of epithelial cytoskeletons,partially devoid of the 2–4 and 5–8 nm filamentswas also observed. A decrease in the density of filament networksbeneath the plasma membranes was especially apparent. Treatmentwith a carcinogen brought about morphological cellular changesas early as 6 h after treatment, and such early changes mighttrigger metabolic cellular abnormalities. Affected cells appearto move away from normal cells in a process of repeated destructionand revision of intercellular junctions, and cytoskeletons.     

Habitual Dietary Intake Affects the Altered Pattern of Gut Microbiome by Acarbose in Patients with Type 2 Diabetes

The aim of this research was to reveal the characteristics of gut microbiome altered by acarbose intervention in Japanese patients with type 2 diabetes (T2D) and its possible association with habitual dietary intake. Eighteen patients with T2D were administered acarbose for four weeks. The abundances of two major phyla, namely Actinobacteria and Bacteroidetes, were reciprocally changed accompanied by the acarbose intervention. There were also significant changes in the abundances of ten genera, including the greater abundance of Bifidobacterium, Eubacterium, and Lactobacillus and the lower abundance of Bacteroides in the group after the intervention than that before the intervention. Hierarchical clustering of habitual dietary intake was performed based on the pattern of changes in the gut microbiota and were classified into distinct three clusters. Cluster I consisted of sucrose, cluster II mainly included fat intake, and cluster III mainly included carbohydrate intake. Moreover, the amount of change in Faecalibacterium was positively correlated with the intake of rice, but negatively correlated with the intake of bread. The intake of potato was negatively correlated with the amount of change in Akkermansia and Subdoligranulum. Acarbose altered the composition of gut microbiome in Japanese patients with T2D, which might be linked to the habitual dietary intake.     

In Vitro Validation of Tissue Doppler Left Ventricular Regional Wall Velocities by Using a Novel Balloon Phantom

Velocity data from tissue Doppler imaging (TDI)can provide valuable information on regional leftventricular wallmotion. Validation of TDImyocardialvelocity measurements has been carried out indirectlyfrom gray- scale M- mode images,and discrepancieshave been reported.Mc Dicken[1] and Miyatake etal[2 ]have reported the accuracy and validity of the TDIsystem using a rotating sponge model.However theoverall motion of the heart should be considered.Inthe present study,we described a new TDI…     

Influence of popliteal vein thrombosis on subsequent ambulatory venous function measured by near-infrared spectroscopy

BACKGROUND: To determine the influence of the site affected by thrombi on the subsequent venous physiology, we examined patients with postthrombotic syndrome (PTS) with respect to ambulatory venous function using near-infrared spectroscopy (NIRS). METHODS: Fifty-one limbs of 45 patients, for whom more than 1 year had passed since an acute episode of deep vein thrombosis, were studied. Seventeen limbs were asymptomatic, 27 had mild symptoms (edema only), and 7 showed severe symptoms (skin changes). The mean duration of PTS was 8.2 years. All of the patients underwent a treadmill walking test with simultaneous NIRS. Deoxygenated hemoglobin was continuously measured during exercise. The ambulatory venous retention index (AVRI) obtained from the serial deoxygenated hemoglobin changes was calculated in each patient. The location of thrombi at the onset of deep vein thrombosis was identified by venography. RESULTS: The calculated AVRI was apparently related to the clinical symptoms of PTS. The limbs initially involved with popliteal vein thrombosis showed significantly higher AVRI values than those without popliteal vein thrombosis. CONCLUSIONS: The clinical severity of PTS is correlated well with the degree of venous retention during exercise. Initial involvement of the popliteal vein is an important factor determining subsequent venous hemodynamics in patients with PTS.