Heparan sulfate proteoglycans in the human sclerosing and scarring kidney. Changes in heparan sulfate moiety.
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Biomedical subjects
Publications and source records attributed to T Shinzato.
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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.
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.
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.
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.
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.
The bacteriology of empyema fluid and the clinical background of 23 cases from July 1987 through July 1992 were studied. Nineteen cases were male and 4 female, with a mean age of 59.6 years (range; 33 to 84 y.o.). There were 15 cases of community-acquired infection and 8 of nosocomial infection. Acute pneumonia and/or lung abscess developed into empyema in 19 cases. Sixteen cases had associated predisposing conditions, such as diabetes, chronic bronchitis, disorders with dysphagia, and excess alcohol intake. Forty-one strains were isolated from empyema in 22 cases. The predominant organisms, in order of prevalence, were "Streptococcus milleri" group (11 strains), Peptostreptococcus spp. (6), Prevotella spp. (6), Fusobacterium spp. (5) and other viridans streptococci (3). The majority of streptococcal infections, which were primarily caused by "S. milleri" group, were mixed with anaerobes and/or aerobes/facultatives. These results demonstrate that oral streptococci, especially "S. milleri" group, and anaerobes play a significant role as pathogens in empyema.
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.
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.
An interesting case of hereditary angioedema in a 26-year-old female is reported, with a finding of transient effusion of fluid into the peritoneal cavity during the attacks. The patient suffered from recurrent abdominal pain for several years, but no family members had any similar symptoms. In spite of repeated hospital admissions and many examinations, accurate diagnosis was not made until the most recent admission. The recognition of hereditary angioedema as a cause of acute and/or recurrent abdominal pain may avoid useless invasive procedures and lead to adequate treatment in other similar cases.
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Dialysis-induced hypotension, the sharp decrease in blood pressure occurring during hemodialysis, remains one of the most difficult problems associated with hemodialysis even today. However, there is yet no established theory to explain the mechanism triggering dialysis-induced hypotension. This review attempts to offer a consistent and cohesive source of information on the hemodynamics during dialysis-induced hypotension, and then analyzes etiologic factors in such hypotension reported by various investigators. Finally, three hypotheses concerning the mechanism of dialysis-induced hypotension including our own are introduced.
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The present study was undertaken to examine the effects of excess factor D build-up in the body of end-stage renal disease (ESRD) patients upon the activation of the alternative pathway and the terminal pathway in the fluid phase. First, to clarify the effect of excess factor D on the alternative pathway, purified factor D from an ESRD patient was added to normal serum and the changes in concentrations of C3a-des-Arg and C5a-des-Arg were investigated. The results showed that once the serum factor D level reached a concentration corresponding to 15 micrograms/ml in the serum of the ESRD patient, the C3a-des-Arg and C5a-des-Arg levels had climbed to about 1.7-fold the concentration in normal serum. Next, in order to clarify the effect of excess factor D on the terminal pathway, purified factor D was added to normal serum, and the changes in C5b6 generation were examined. The results indicated that as the factor D level increased in the serum, the C5b6 level rose gradually also; and when the factor D concentration reached 15 micrograms/ml, the C5b6 generation had risen to approximately 1.5-fold the level in normal serum. The present results therefore suggest that factor D build-up in ESRD patients provides a uremic toxin that can cause abnormal activation of the whole complement cascade.
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