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Biomedical subjects

T Shinzato

Publications and source records attributed to T Shinzato.

At least 19 recordsLinked to original sources

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

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

[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

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

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

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

Role of adenosine in dialysis-induced hypotension.

First, this investigation showed that plasma levels of inosine, hypoxanthine, and xanthine, which are metabolites of adenosine, rose sharply when blood pressure dropped suddenly along with symptoms during a hemodialysis session (sudden hypotension), but not when it decreased gradually with eventual symptoms (gradual hypotension). Because adenosine has an action to dilate vessels, this result indicates the possibility that the increased release of adenosine would be a cause of sudden hypotension. Second, it was found that the frequency of sudden hypotension decreases with the administration of caffeine, which is an adenosine-receptor antagonist, whereas the frequency of gradual hypotension did not change. This result supports the above-mentioned hypothesis that adenosine may well be a mediator of sudden hypotension, but not of gradual hypotension. Third, our investigation demonstrated no significant differences in plasma norepinephrine level, in plasma renin activity, or in mean blood pressure between the hemodialysis session in which caffeine was administered and the session in which a placebo was given. These findings suggest that the effect of caffeine administration to prevent sudden hypotension is not mediated by the stimulation of the sympathetic nervous system or activation of the renin-angiotensin system, but by the adenosine-receptor antagonism.

Adenosine

Basic fibroblast growth factor-binding domain of heparan sulfate in the human glomerulosclerosis and renal tubulointerstitial fibrosis.

BACKGROUND: The saccharide side chains of heparan sulfate (HS) proteoglycans show enormous complexity. These polysaccharides can interact specifically with cytokines such as basic fibroblast growth factor (bFGF). The understanding of HS expression in glomerulosclerosis and interstitial fibrosis, which is still rudimentary, could provide some insight about the role of bFGF in kidney diseases. EXPERIMENTAL DESIGN: Kidney sections were exposed to exogenous bFGF and then to a monoclonal anti-bFGF antibody. Specificity of the interaction between HS and bFGF was established by monitoring concomitant loss of bFGF during selective removal of HS with heparitinase and competitive inhibition studies. To further characterize regional changes in saccharide sequences, heparitinase-generated unsaturated disaccharides, N-sulfated glucosamine-enriched but O-sulfate-scarce portions characteristics of native HS, and such portions characteristic of Engelbreth-Holm-Swarm tumor HS were studied. RESULTS: HS was detected in interstitial fibrosis and in advanced glomerulosclerosis, whereas bFGF-binding domains were found only in the fibrosis: The distributional pattern of the N-sulfate-enriched and O-sulfate-scarce portions of native HS was similar to that of bFGF-binding domains. Moreover, a small population of parenchymal cells in advanced tubulointerstitial fibrosis with marked cellular infiltration were especially rich in the bFGF-binding domains. CONCLUSIONS: In fibrotic lesions of the peritubular interstitium, HS shows enrichment of bFGF-binding domains. These regions may play an important role in the fibrogenesis through their interaction with endogenous bFGF.

Adult

Phenotypic expressions of type I, III, IV, V, and VI collagens in patients with diabetic nephropathy: immunohistochemical comparison between HD and non-HD patients.

Molecular organization of extracellular matrix (ECM) in the kidney may change as impairment of renal function progresses. The present immunohistochemical study of the kidney was designed to compare localization of type I, III, IV, V, and VI collagens between "Group A" (13 patients on maintenance hemodialysis due to diabetic nephropathy) and "Group B" (13 patients with diabetic nephropathy and massive proteinuria whose serum creatinine levels were 1.3 +/- 0.5 mg/dl, mean +/- SD). Nodular scleroses that were commonly observed both in Group A (87.8 +/- 10.1%) and B (80.5 +/- 17.0%) were stained in a very similar way with antibodies against collagen types IV, V, and VI. On the contrary, thickened Bowman's capsules that were observed exclusively in Group A (80.7 +/- 10.4% in Group A versus 5.7 +/- 6.2% in Group B) were stained intensely with antibodies against collagen types I and III. Normal and expanded peritubular interstitium from every group was stained with all of the above antibodies in an identical manner. Taken together, these results indicated a close relationship between severe impairment of residual renal function and a high incidence of thickened Bowman's capsule rich in type I and III collagens.

Aged

Continuous hematocrit monitoring method in an extracorporeal circulation system and its application for automatic control of blood volume during artificial kidney treatment.

A two-frequency electrical conductivity method for measuring hematocrit has been developed for use in the continuous monitoring of circulating blood volume during artificial kidney treatment. Using this method, an algorithm for programmed control of blood volume also has been developed. This hematocrit measurement method is based on the beta-dispersion of blood conductivity, and the values measured during hemodialysis are in good agreement with the laboratory hematocrit values obtained by a Coulter counter. Programmed control of blood volume was used 29 times on 11 patients undergoing long-term dialysis. In each case, the blood volume was maintained within 2.5% of the desired level, and stable control was achieved even with disturbances caused by eating, change in body position, and so on. These methods can be used to study the relationship between blood volume and dialysis-induced hypotension during artificial kidney treatment and to achieve adequate ultrafiltration without clinical adverse effects.

Blood Volume

Inhibitory effect of FUT-175 on complement activation and its application for glomerulonephritis with hypocomplementemia.

FUT-175 (6-amidino-2-naphthyl p-guanidinobenzoate dimethane-sulphonate), a potent serine protease inhibitor, has been reported to inhibit complement activity in vitro, and especially the classical complement pathway effectively. In the present study, we examined the inhibitory effect of FUT-175 on the classical complement pathway components by hemolytic assay using purified human complement components. As a result, 50% inhibition of the C1 protease activity for classical C3 convertase formation and for C2 was obtained with 3.0 x 10(-8) M and 7.0 x 10(-8) M of FUT-175, respectively. FUT-175 did not inhibit the C2 protease activity at all. We then administered FUT-175 to 5 glomerulonephritic patients with hypocomplementemia and proteinuria in order to assess the clinical effectiveness of this drug. When FUT-175 was administered intravenously and continuously at a rate of 0.1 to 0.2 mg/kg/hr for 2 weeks, the urinary protein excretion decreased significantly from 2.9 +/- 0.8 to 1.4 +/- 0.5 g/day (P < 0.025). In these patients, some of the serum complement markers (serum C3, C4 level and the hemolytic activity via the classical complement pathway (CH50)) were increased after FUT-175 administration. The above findings suggests that FUT-175 can exert beneficial effects on glomerulonephritis with hypocomplementemia by inhibiting complement activation.

Adult

[Detection of Legionella pneumophila using a nested polymerase chain reaction].

We evaluated the usefulness of a Nested PCR method for detecting Legionella pneumophila. This method resulted in L. pneumophila specific detection as far as we evaluated. The first and second step PCR achieved the sensitivity as small as 10 pg and 10 fg of the target DNA, respectively. In the detection from Legionella seeded sputa, the method could detect 0.1 cfu/ml of the bacteria, and it took about 12 hours to detect the target DNA. We demonstrated that the Nested PCR method was superior in sensitivity and rapidity for isolation of the bacteria to the conventional using low pH treatment and selective media for Legionella.

Base Sequence

Induction of irreversible glomerulosclerosis in the rat by repeated injections of a monoclonal anti-Thy-1.1 antibody.

The present experiment demonstrated that an irreversible glomerulosclerosis could be induced in the rat through repeated intravenous administrations of OX-7 (a monoclonal anti-Thy-1.1 antibody). Rats were injected with 0.2 mg of affinity-purified OX-7 at 1-week intervals for a period of 4 weeks. Glomerular damage was periodically examined at light-microscopic level. Thirty-five days after the initial injection (7 days after the final injection), capillary aneurysms and expansion of the mesangial areas with hypercellularity were frequently observed. Similar glomerular damage was also observed in rats 7 days after they received a single injection of either 1.0 or 0.2 mg of OX-7. After repeated injections, 112 days from the initial administration (84 days after the final injection), approximately 60% of the glomeruli had expanded mesangial areas with an apparent increase in the mesangial matrix. The result contrasts sharply with that obtained from a single injection of OX-7 in that more than 85% of the glomeruli showed no abnormalities 84 days after the injection. This chronic model, as a result of repeated injections of the antibody, could serve as a potential for further investigation of the mechanisms involved in the development of chronic glomerulonephritis.

Animals