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Biomedical subjects

T Shinzato

Publications and source records attributed to T Shinzato.

At least 73 records · Page 4Linked to original sources
PubMed1996

Thy-1 antigen mediates apoptosis of rat glomerular cells in vitro and in vivo.

Injection of anti-Thy-1 antibody into a rat induces immediate glomerular cell death and subsequent development of glomerulonephritis. Whether the immediate cell death in this model is apoptotic has yet to be determined. Recent in vivo studies on thymocyte death have elucidated that the Thy-1 molecule can activate intracellular signaling for apoptosis. This observation prompted us to re-examine whether stimulation with anti-Thy-1 antibody can provoke apoptosis in the rat glomerulus. We found that anti-Thy-1 antibody could induce laddered DNA fragmentation of isolated glomeruli and mesangial cells in culture, definite biochemical evidence for random double-stranded breaks through apoptosis. Such DNA laddering was also demonstrated in the isolated glomeruli of rats that had been infused with anti-Thy-1 antibody several hours before. Furthermore, the terminal deoxynucleotidyl-transferase-mediated oligonucleotide nick end labeling technique stained a cell in the mesangium. Although apoptosis may be considered a candidate mechanism mediating resolution of hypercellularity in the anti-Thy-1 model, we propose that it is also involved in the immediate cell death in this model.

Animals↗
PubMed1996

Accumulation of albumin-linked and free-form pentosidine in the circulation of uremic patients with end-stage renal failure: renal implications in the pathophysiology of pentosidine.

Pentosidine is an advanced glycation end product and its formation is shown to be closely related to oxidative processes. Recent studies have shown that pentosidine levels are increased not only in plasma and matrix proteins from diabetic patients, but also markedly in nondiabetic hemodialysis patients. Currently, the mechanism of accumulation and kinetics of pentosidine formation in hemodialysis patients remain unknown. Gel filtration of uremic plasma revealed that plasma pentosidine exists in the albumin fraction (approximately 90%) and, interestingly, in free form (approximately 5%) as well. Plasma free pentosidine was undetectable in subjects with normal renal function. There was a significant correlation between the plasma levels of albumin-linked and free pentosidine in hemodialysis patients. Kinetic studies indicated that dietary pentosidine was absorbed into the circulation and that, after either oral or intravenous administration of pentosidine to intact or nephrectomized rats, the plasma free pentosidine level was closely linked to the level of renal function. These findings demonstrate that: (1) Pentosidine accumulates as albumin-linked and in free form in the circulation of uremic patients; (2) dietary pentosidine can be absorbed into the circulation, thus being one possible origin of circulating free pentosidine; (3) free pentosidine may accumulate as a result of decreased glomerular filtration; and (4) the mechanism of accumulation of albumin-linked pentosidine is not related to high glucose levels. It suggests the simultaneous accumulation, during renal failure, of either unknown pentosidine precursor(s) or catalyst(s) of glycoxidation, independent of glucose.

Animals↗
PubMed1996

[Clinical evaluation on causes of death in patients with active pulmonary tuberculosis].

Seventy one patients with active pulmonary tuberculosis who died during the past 5 years (1989 to 1993) were evaluated on their causes of death. Twenty two patients (31%) died directly of tuberculosis, and among them, 18 patients (81%) of 22 patients who died of tuberculosis) had very advanced tuberculosis. The majority of them (64%) were old age over 70 years and were bedridden due mostly to cerebrovascular injuries. The serum level of albumin was low in all 17 patients in whom it was measured. Establishment of diagnosis of tuberculosis was delayed over one month after the onset of symptoms in 59% of patients who died of severe disease. Sixty one percent (11/18) of patients died within the first month after the initiation of chemotherapy and about 90% (16/18) died within 3 months. Two patients died from massive hemoptysis and other patients died of either respiratory failure or tuberculosis meningitis. From these observations it was found that very advanced tuberculosis was the major cause of death in patients who died of tuberculosis and that the advanced disease was chiefly caused by the delay on the establishment of diagnosis, and it was most important to detect tuberculosis as early as possible, with regular check up of chest X-ray and frequent examination for AFB (acid-fast bacilli) for tuberculosis suspected patients. On the other hand, the majority of patients (49/71) died of complicating medical problem unrelated to tuberculosis. Seventeen patients died from malignancy (seven lung cancer, four lymphoma, two laryngeal cancer, etc). Ten deaths were the result of bacterial superinfection. Other patients died from respiratory failure due to COPD, arteiosclerotic heart disease, or cerebrovascular injuries, etc. Two patients of old age died of hepatic failure possibly caused by adverse reaction of TB chemotherapy. It was found that diseases unrelated to tuberculosis were the cause of death in approximately 70% of patients with active tuberculosis, and it should be emphasized to detect early and to treat these diseases, in particular malignancy. And it is also imperative that the chemotherapy for TB must be instituted very carefully with frequent monitoring of liver function in patients with old age.

Adult↗
PubMed1995

Relationship between susceptibility to apoptosis and Fas expression in peripheral blood T cells from uremic patients: a possible mechanism for lymphopenia in chronic renal failure.

Chronic renal failure (CRF) is often complicated by lymphopenia, which may be partly responsible for immune deficiency. We hypothesized that lymphopenia in CRF might result from apoptosis of T cells in vivo. To elucidate the involvement of Fas antigen which mediates apoptosis, we analyzed Fas expression on peripheral blood T cells in uremic non-dialyzed (non-HD) patients and hemodialysis (HD) patients. T cells from both uremic groups expressed Fas with higher intensity than control T cells. When two uremic groups were compared, Fas intensity on T cells was significantly higher in non-HD patients than in patients on HD. Moreover, uremic T cells were shown to undergo accelerated apoptosis when cultured in vitro, in correlation with Fas expression. Our results suggest that T cells in CRF may undergo apoptosis by the Fas system and that hemodialysis treatment has beneficial effects in the light of the inhibition of T cell apoptosis.

Apoptosis↗
PubMed1995

Basic fibroblast growth factor-heparan sulphate complex in the human dialysis-related amyloidosis.

A major constituent of the amyloid fibrils in dialysis-related amyloidosis is beta 2-microglobulin (beta 2-MG). Heparan sulphates (HS) co-localize with the amyloid fibrils and monocytes/macrophages are commonly found around amyloid deposits, but the role of HS in amyloidogenesis is not yet defined. HS have variable saccharide sequences and can interact specifically with basic fibroblast growth factor (bFGF), a potent chemotactic factor for the monocyte/macrophage. The present investigation was undertaken to look for a functional link between co-localized HS and the pathogenesis of dialysis-related amyloidosis. Using amyloid-enriched ligament, immunohistochemical localization was tested for beta 2-MG, endogenous bFGF, and bFGF-binding portions of HS. For the detection of bFGF-binding portions of HS, the ligament sections were incubated with exogenous bFGF and then with anti-bFGF antibody. The specificity of the interaction between bFGF and HS was established by confirming a concomitant loss of immunoreactivity during selective removal of HS with heparitinase. beta 2-MG, endogenous bFGF, and bFGF-binding portions of HS were detected between bundles of collagen. Endogenous bFGF and bFGF-binding portions of HS were not detected in more advanced amyloid lesions, whereas beta 2-MG and other portions of HS were detected. We propose that beta 2-MG, endogenous bFGF, and bFGF-binding portions of HS form a complex and localize in the early amyloid lesions of dialysis-related amyloidosis.

Amyloidosis↗
PubMed1995

Long-term nifedipine treatment reduces calcium overload in isolated reperfused hearts of diabetic rats.

1. Streptozotocin-induced diabetic rats showed poor post-ischemic recovery in isolated working rat hearts. 2. Diabetic rats showed myocardial Na+ accumulation after ischemia, and Ca2+ level and water content elevation after reperfusion. 3. A 6-wk nifedipine treatment improved post-ischemic recovery of cardiac parameters and prevented myocardial Na+ accumulation after ischemia and myocardial Ca2+ level and water content elevation after reperfusion of diabetic rats. 4. Results suggest that nifedipine treatment improves cardiac dysfunction in the reperfused ischemic hearts of diabetic rats through normalization of the Na+-Ca2+ imbalance and water content.

Animals↗
PubMed1995

Enhanced insulin response relates to acetylcholine-induced vasoconstriction in vasospastic angina.

OBJECTIVES: This study investigated whether insulin response to an oral glucose load correlates to acetylcholine-induced coronary vasoconstriction in subjects with vasospastic angina. BACKGROUND: It has been suggested that coronary vasospasm is caused by augmented vascular responsiveness possibly exerted by atherosclerosis. Recently, insulin resistance syndrome has been proposed as a major promotor of atherosclerotic disease, potentially enhancing vascular smooth muscular tone. METHODS: Among subjects with angiographically smooth coronary arteries, we selected 14 subjects with vasospastic angina and 14 age- and gender-matched subjects with atypical chest pain. We compared coronary vasomotor response to acetylcholine infusion, glucose and insulin responses to an oral glucose load (75 g), serum lipid concentrations, obesity, heart rate, blood pressure and smoking habits in both groups. RESULTS: Fasting serum insulin concentrations and insulin response were higher in subjects with vasospastic angina than in those with atypical chest pain; however, glucose tolerance, obesity, heart rate, blood pressure and smoking habits did not differ between groups. In subjects with vasospastic angina, nearly all coronary segments, except distal segments of the left circumflex coronary artery, were constricted at peak acetylcholine infusion (20 to 100 micrograms), whereas all segments were dilated in subjects with atypical chest pain. Regression analysis for both groups demonstrated a correlation between coronary vasoconstriction and fasting serum insulin concentrations (r = 0.52, p < 0.01), insulin response (r = 0.71, p < 0.001), serum triglyceride concentrations (r = 0.51, p < 0.05) and atherogenic index (r = 0.44, p < 0.05). CONCLUSIONS: Results show that acetylcholine-induced coronary vasoconstriction in subjects with vasospastic angina correlates with hyperinsulinemia and enhanced insulin response, suggesting insulin resistance syndrome as a feature of vasospastic angina.

Acetylcholine↗
PubMed1995

The Streptococcus milleri group as a cause of pulmonary infections.

Streptococci that colonize the mouth and upper respiratory tract tend to be considered harmless commensals. In 45 cases of acute pneumonia and/or pulmonary abscess and 25 cases of thoracic empyema, the predominant species recovered were anaerobic bacteria and the Streptococcus milleri group, which encompasses the oral species Streptococcus anginosus, Streptococcus constellatus, and Streptococcus intermedius. The isolation of most S. milleri organisms along with oral anaerobes indicated synergy between these groups. Studies in a mouse model of pneumonia demonstrated this synergy; mortality was higher, histopathologic abnormalities were more marked (reflecting acute pneumonia followed by pulmonary abscess or empyema), and viable bacteria were more numerous in the lungs of mice with mixed infections caused by the S. milleri group and anaerobes than in the lungs of those with monomicrobial infection. In vitro studies elucidated a possible mechanism of this synergistic effect: anaerobes may enhance the growth of the S. milleri group and/or inhibit the bactericidal activity of the host. We conclude that the S. milleri group is more important in pulmonary infections than has previously been recognized.

Animals↗
PubMed1995

Impaired mechanical response to calcium of diabetic rat hearts: reversal by nifedipine treatment.

Streptozotocin-induced diabetic and age-matched control rats were treated with 0.03% nifedipine-containing chow for 6 weeks, and mechanical response to Ca2+ was studied using isolated working hearts. At 14 weeks of age, 7 weeks after a streptozotocin injection, diabetic rats had a lower body weight and heart weight than controls, and an increase in heart weight-to-body weight ratio. Nifedipine treatment did not alter these parameters of controls, but decreased the heart weight and heart weight-to-body weight ratio of diabetic rats without affecting the body weight. In diabetic rats, systolic blood pressure was decreased compared to controls (124 +/- 5 vs. 137 +/- 6 mm Hg, p < 0.01), and reduced more by nifedipine treatment (111 +/- 4 mm Hg, p < 0.01). In control rats, LV developed pressure, LV +/- dP/dt, and cardiac work were unchanged regardless of the increment in preload at 1.25, 1.88, and 2.50 mM Ca2+. However, the responses of diabetic rats were decreased with an increment in preload at 2.5 mM Ca2+. Nifedipine treatment produced a partial recovery of all four parameters at 2.5 mM Ca2+ in diabetic rats. The myocardial Ca2+ content and sarcolemmal lipid peroxidation were similar in hearts from control and diabetic rats at all Ca2+ concentrations and nifedipine treatment did not affect these values. Results suggest that chronic nifedipine treatment improve the contractility of diabetic rat hearts under high Ca2+ conditions.

Analysis of Variance↗
PubMed1995

[Tubulointerstitial changes in some hematological disorders].

This paper describes tubulointerstitial changes of the kidney in association with a) pathophysiology of paraproteinuria and related disorders, and b) the management of leukemia and malignant lymphoma. Various forms of tubulointerstitial changes might be provoked following the accumulation of "abnormal macromolecules" In a), multiple myeloma, light chain cast nephropathy (myeloma kidney), AL amyloidosis, light chain deposition disease, macroglobulinemia, cryoglobulinemia etc. are briefly reviewed. In the majority of cases, leukemia and lymphoma do not manifest themselves as tubulointerstitial disorders. However, a large number of patients suffer from tubulointerstitial abnormalities in the course of and/or after receiving chemotherapy. Thus it is explained, in b), why treatment for hematological malignancy is apt to induce tubulointerstitial complications. In this context, drugs responsible for the development of tubulitis and/or interstitial fibrosis are briefly reviewed.

Anti-Bacterial Agents↗
PubMed1994

Co-stimulation with LFA-1 triggers apoptosis in gamma delta T cells on T cell receptor engagement.

Stimulation of T cells through the T cell receptor (TcR) initiate activation pathways, and paradoxically can also result in activation-induced cell death. Many factors influence a stimulated cell's decision to manifest one or the other. Here we show that co-stimulation with LFA-1 plays a key role in the choice between the two fates, differentiating between alpha beta and gamma delta T cells. Peripheral gamma delta. T cells but not alpha beta T cells undergo apoptosis upon co-cross-linking of TcR and LFA-1 in MRL lpr/lpr mice as well as +/+ mice. Our results suggest that apoptosis of gamma delta T cells is inducible by combined stimuli independent of the Fas-mediated pathway.

Animals↗
PubMed1994

A mechanism of pathogenicity of "Streptococcus milleri group" in pulmonary infection: synergy with an anaerobe.

The relationship between Streptococcus constellatus, one of the species of the "Streptococcus milleri group", and Prevotella intermedia was studied in a model of pneumonia in mice and in vitro to elucidate mechanisms of pathogenicity in "S. milleri group"-associated pulmonary infection. Acute pneumonia with or without empyema and lung abscess in mice with mixed infection resulted in 60% mortality rate, but there was only 10% mortality and mild pneumonia in each separate infection. Bacterial clearance of organisms, especially S. constellatus, in mixed infection was delayed. Enhancement of growth of S. constellatus was demonstrated when cultured with P. intermedia; growth was also stimulated by a culture filtrate of P. intermedia which also inhibited bactericidal activity of human neutrophils. In an examination of infectivity and bacterial clearance of S. constellatus with P. intermedia culture filtrate in vivo, there was 20% mortality and delayed clearance of S. constellatus, although the infection was not as severe as that produced by the combination of both organisms. These results suggest that P. intermedia may act with S. constellatus in the production of pulmonary infections by stimulating its growth and suppressing bactericidal activity of the host.

Animals↗
PubMed1994

Determination of Kt/V and protein catabolic rate using pre- and postdialysis blood urea nitrogen concentrations.

We developed a new urea kinetic method for simultaneous determination of the Kt/V and protein catabolic rate (PCR) only from blood urea nitrogen (BUN) concentrations before and after a single dialysis session. Using this method, the parameters were calculated within 1.5 s even when a hand-held computer with a low central processing capacity is used. The total amount of urea eliminated during three dialysis sessions in 1 week is assumed to be equal to urea volume (Gw) generated over a 1-week period (Tw): [formula: see text]. Here, G is the generation rate, K is the dialyzer urea clearance, T is the dialysis time and C1, C2 and C3 are BUN during the respective dialysis session. If this equation and the equation expressing the urea kinetics during a single dialysis session are solved together, we have a solution for Kt/V and G. The thus-obtained Kt/V and G are corrected using the change in body weight. The corrected Kt/V showed a good correspondence with the parameter calculated with the classical method, and the midweek PCR derived from G determined by the present method being equivalent to the PCR averaged for a 1-week period determined by the classical methods.

Blood Urea Nitrogen↗