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Biomedical subjects

K Funabiki

Publications and source records attributed to K Funabiki.

53 records · Page 3Linked to original sources
PubMed1992

Increased remission of early stage membranous nephropathy on long-term treatment with corticosteroid.

Sixty-five patients with primary membranous nephropathy were examined in order to assess the effects of long-term treatment with corticosteroid. The observation period varied from 8 to 279 months (average, 95 months). The patients were treated with corticosteroid alone or with combinations of corticosteroid and immunosuppressants, nonsteroidal anti-inflammatory drugs (NSAID) and/or dipyridamole. At 6 months after treatment, only 14% of the patients had achieved complete remission. At 24 months after treatment, 46% of the patients showed complete remission. The rate of clinical remission, i.e. complete and incomplete remission, was markedly increased in stage I and II patients with membranous nephropathy by Ehrenreich and Churg's classification but not in stage III patients. The actuarial survival curve indicated that 84% of the patients were alive at 10 years after onset. These data suggest that active treatment with corticosteroid is beneficial for patients with primary membranous nephropathy.

Adolescent↗
PubMed1991

Altered steady-state levels of mRNA coding for extracellular matrices in renal tissues of ddY mice, an animal model for IgA nephropathy.

Correlations between the steady-state mRNA levels of extracellular matrices using specific cDNA probes for the alpha 1 chain of type IV collagen (alpha 1 (IV) chain); laminin A, B1, and B2 chains; and heparan sulfate proteoglycan (HSPG); and glomerular injuries in ddY mice were evaluated. Eight-, sixteen- and forty-week-old ddY mice were used in this study. ICR mice of the same age served as control. Extracted total RNA of pooled kidneys was fixed on a filter and then hybridized with the cDNA probes. Renal cryostat sections were incubated with rabbit anti-mouse type IV collagen, laminin, and HSPG antisera and then stained with FITC-labeled goat anti-rabbit IgG antiserum. The sections were also stained with FITC-labeled goat anti-mouse IgA, IgM, IgG, and C3 antisera. In light microscopy, the average number of glomerular cells was calculated at each age. Increased expression of extracellular matrices genes for the alpha 1(IV) chain; laminin A, B1, and B2 chains; and HSPG was found in renal tissues of ddY mice. Staining of type IV collagen, laminin, and HSPG was observed in renal tissues of ddY mice at each age. Increased proteinuria in 40-week-old ddY mice might be related to the decrease in glomerular basement membrane HSPG which acts as the anionic sites in such areas. Marked proliferation and or expansion of glomerular cells and mesangial matrices were observed in 40 week-old-ddY mice. The intensity of IgA and C3 deposits in the glomeruli was parallel to the levels of mRNA for such components.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Computer imaging analysis of the correlation between intensities of glomerular immune-deposits and histopathology in patients with IgA nephropathy.

The relationship between the intensities of IgA, C3c, and C9 deposition in renal glomeruli and the severity of histopathologic injuries in patients with IgA nephropathy was examined using Microscope-Photometer 01K and a computer. Percentages of glomerular adhesion to Bowman's capsules, crescent formation, and glomerular sclerosis were calculated in the renal specimens. There was a significant correlation between the intensity of each C3c and C9 deposition in glomeruli and the degree of glomerular adhesion to Bowman's capsules and crescent formation in patients with IgA nephropathy. There was no significant correlation between the intensity of C3c or C9 deposition in glomeruli and the degree of glomerular sclerosis. No relationship was found between the intensity of IgA deposition in glomeruli and the degree of histopathologic injuries. The patients with negative or trace amounts of glomerular C3c deposits showed less severe glomerular injuries. Thus, the intensity of C3c and C9 deposition in glomeruli appears to be one of the critical factors responsible for the active progression of glomerular inflammatory process in patients with IgA nephropathy.

Complement C3c↗
PubMed1991

Urinary levels of interleukin-6 and disease activity in patients with IgA nephropathy.

We studied, using ELISA, 27 patients with IgA nephropathy to determine if levels of urinary interleukin-6 (IL-6) might reflect the disease activity. The levels of urinary IL-6 in patients with the advanced stage were significantly higher than those in patients with the mild stage of the disease or in healthy adults. The results showed a significant correlation between the levels of urinary IL-6 and the disease activity, i.e., levels of urinary cast and urinary protein. It was thus suggested that the measurement of urinary IL-6 is useful in evaluating the degree of glomerular injuries and/or prognosis in patients with IgA nephropathy.

Adult↗
PubMed1991

Immunohistochemical studies of glomerular extracellular components in repeated renal biopsies of patients with IgA nephropathy.

Immunohistochemical and light microscopic examinations were carried out to assess the correlation between the progression of glomerular lesions and changes in the intensity of glomerular extracellular components such as type IV and I collagens, laminin and fibronectin, and of IgA deposits in repeated renal biopsies of patients with IgA nephropathy. By light microscopy, the percentage of glomeruli showing glomerular mesangial expansion or sclerosis was found to be significantly higher in the second renal biopsy. Type IV collagen, laminin and fibronectin were also marked in the expanded glomerular mesangium in the second biopsy. Although these components were not observed in the global sclerotic glomeruli, type I collagen was detected in such areas of patients with IgA nephropathy. Patients who revealed high percentages of glomerular sclerosis associated with marked type IV collagen, laminin, fibronectin and/or type I collagen, had high levels of proteinuria and progressive deterioration of renal function. It is concluded that hyperproduction of the above extracellular components mainly in the glomerular mesangium is closely linked to the progression of glomerular lesions in patients with IgA nephropathy.

Adolescent↗
PubMed1990

[Serum concentration of laminin in transitional cell carcinoma].

The concentration of laminin in the serum was determined for 45 patients with urinary tract transitional cell carcinoma, and the clinical significance of the findings was considered. The difference between the serum laminin concentrations in the control group and the transitional cell carcinoma patient group was not statistically significant, but the serum laminin level was highest in the transitional cell carcinoma patients with metastatic foci. In many of the patients who had metastatic foci and showed clearly progressive disease, the serum laminin concentration was found to increase with the passage of time. When the transitional cell carcinoma tissues were stained by the fluorescent antibody technique, there was little distribution of laminin in the tumor tissues, contrary to our earlier-reported findings regarding the staining of laminin in renal cell carcinoma tissues. In renal cell carcinoma patients, the serum concentration of laminin had been found to be high even when there were no metastatic foci, and consideration of this fact strongly suggests the possibility that the mechanism for laminin synthesis in urinary tract transitional cell carcinoma is different from that in renal cell carcinoma. It was surmised that the serum laminin concentration has potential for use as a diagnostic indicator of metastasis in patients with urinary tract transitional cell carcinoma.

Carcinoma, Transitional Cell↗
PubMed1990

Immunohistochemical analysis of extracellular components in the glomerular sclerosis of patients with glomerulonephritis.

Immunofluorescence and immunoperoxidase staining was carried out to determine correlations between the progression of glomerular sclerosis and changes in the amount or distribution of glomerular extracellular components, including type I, III, IV, and VI collagens, laminin and fibronectin, in patients with IgA nephropathy, membranoproliferative glomerulonephritis and rapidly progressive glomerulonephritis. Staining of type I and III collagens was not observed in glomeruli from normal individuals or patients with mild glomerulonephritis. In the advanced stages of glomerulonephritis, the staining of type IV and VI collagens, laminin and fibronectin was marked in the glomerular mesangium, and the distribution of fibronectin extended to the glomerular capillary walls in the sclerotic lesions of glomeruli. However, the staining intensity of type IV collagen, laminin and fibronectin was gradually decreased during the progression of glomerular sclerosis. On the other hand, the staining of type I and III collagens was observed focally in sclerotic or hyalinotic glomeruli and around such glomeruli in those patients. Light microscopic examination revealed that patients who showed marked staining of type I and III collagens by immunofluorescence had severe damage of Bowman's capsules. These results suggest that the hyperproduction and/or invasion of interstitial collagens, i.e., types I and III, are closely linked to the progression of glomerular sclerosis and hyalinosis in patients with various types of glomerulonephritis.

Antibodies, Monoclonal↗
PubMed1989

Computer imaging analysis of glomerular extracellular components in patients with IgA nephropathy.

Computer imaging analysis was used for quantitative evaluation of the extents, amounts and distributions of glomerular extracellular components, such as the 7S and NC-1 domains of type IV collagen, laminin (LN), fibronectin (FN) and IgA, in glomeruli from patients with IgA nephropathy. Renal biopsy specimens from 13 patients with IgA nephropathy were incubated with mouse monoclonal antibodies against the FN or non-collagenous (NC-1) domain of type IV collagen or polyclonal antiserum against the LN or 7S domain of human type IV collagen, and then stained with appropriate dilutions of FITC-labeled anti-mouse Ig antisera. Marked staining of the 7S or NC-1 domain of type IV collagen, LN or FN was detected in the glomerular capillary walls and/or mesangial areas in patients with IgA nephropathy. In particular, a prominent increase of FN was observed in the subendothelial regions of glomerular capillary walls, i.e. mesangial interposition, in the moderate or advanced stage of IgA nephropathy. Therefore, computer imaging analysis was shown to be useful for the quantitative determination of such components distributed in glomeruli from patients with IgA nephropathy.

Complement C3↗
PubMed1989

[Serum concentration of laminin in renal cell carcinoma].

Serum concentration of laminin was measured radioimmunologically in 19 patients with renal cell carcinoma and 71 normal controls. The serum laminin levels of renal cell carcinoma patients were significantly higher than those of normal controls. After nephrectomy the elevated serum levels of laminin showed marked decreases in most of the patients without metastasis. By the immunofluorescent technique with LAM-1, a monoclonal antibody which is specific to laminin A and B chains , strong fluorescence was found in the extracellular matrix in renal cancer tissue. Taken all these facts together, renal cell carcinoma may be a laminin synthetic tumor. The average serum laminin level of the patients with a disseminated disease were significantly higher than that of the patients with a localized disease. The elevated serum level of laminin may play an important role in the process of tumor metastasis. Furthermore, our data suggest that elevated laminin levels may predict the subsequent course of a tumor condition. The monitoring of serum laminin level may be valuable for following-up of the course of renal cell carcinoma.

Adult↗
PubMed1989

[An elderly patient with IgD myeloma associated with renal amyloidosis and acute renal failure].

A 83-year-old male patient with IgD myeloma associated with renal amyloidosis and acute renal failure is described. We also reviewed the clinicopathological findings of IgD myeloma in the literature. Although hemodialysis was performed 36 times for acute renal failure, he died of severe gastrointestinal bleeding. Renal necropsy specimens revealed typical features of amyloidosis in light microscopic, electron microscopic and immunofluorescent examinations. The levels of serum IgD (755 mg/dl), immunoelectrophoresis, and immunofluorescence of bone marrow and renal specimens were consistent with IgD myeloma (lambda type). IgD myeloma is generally considered to be a rare disease of juvenile onset and is complicated with extramyelogenic tumors according to previous reports. However, IgD myeloma without extramyelogenic tumors occurred in a 83-year-old patient reported here. It appears that advanced age onset IgD myeloma associated with renal amyloidosis and acute renal failure is rare. This was the oldest case of IgD myeloma we examined.

Acute Kidney Injury↗
PubMed1989

[Comparative studies of clinicopathological findings in patients with adult and juvenile onset of IgA nephropathy].

Comparative studies of clinicopathological findings were carried out in 89 patients with adult and juvenile onset of IgA nephropathy. Among 89 patients with IgA nephropathy, there were 42 patients with juvenile onset, i.e less than 19 years old, and 47 patients with adult onset, i.e. more than 35 years old. Clinical activities of both groups were examined as follows; urinary protein, mean blood pressure renal function (PSP 15 min, Ccr) and serum IgA (s-IgA). The histology of renal tissues was also examined by light microscopy and immunofluorescence in both groups. The levels of mean blood pressure or s-IgA in patients with adult onset group were significantly higher than those in patients with juvenile onset group (p less than 0.001). The levels of Ccr in patients with adult onset group were markedly decreased. The patients with more than 1.0g/day of proteinuria and more than 110 mmHg of mean blood pressure showed severe proliferative glomerular injuries by light microscopy. It is suggested that the patients with adult onset of IgA nephropathy show severe progressive and/or exacerbating factors during the clinical course.

Adolescent↗
PubMed1989

[Immunohistochemical analysis of extracellular components on the glomerular sclerosis in patients with glomerulonephritis and diabetic nephropathy].

Immunofluorescence and immunoperoxidase staining were carried out to determine the correlations between the progression of glomerular sclerosis and changes in the amount and distribution of glomerular extracellular components, such as Type I, III, IV, V, VI collagen, laminin (LN) and fibronectin (FN) in patients with various types of glomerulonephritis and diabetic nephropathy. Six patients with IgA nephropathy, four patients with membrano-proliferative glomerulonephritis, four patients with rapidly progressive glomerulonephritis and six patients with diabetic nephropathy were examined. The intensity and distribution of Type IV collagen, LN and FN were similar between the glomeruli from normal individuals and patients with mild stages of glomerulonephritis and diabetic nephropathy. However, staining of Type I, III or V collagen was not observed in the glomeruli from normal individuals and such patients. In more advanced stages of glomerulonephritis and diabetic nephropathy, the amounts of Types IV and VI collagen, LN and FN were increased markedly in the mesangium, and their distribution extended along the glomerular capillary walls. The intensity of Type IV collagen, LN or FN in the nodular sclerotic lesions of glomeruli was decreased significantly in patients with glomerulonephritis and diabetic nephropathy. On the other hand, staining of Types I, III and V collagen was observed focally in the sclerotic or hyalinotic glomeruli and around such glomeruli in these patients. In light microscopic examinations, the patients who had marked staining of Type I, III or V collagen by immunofluorescence showed severe damage of the basement membrane in Bowman's capsules. It is concluded that hyperproduction and/or infiltration of interstitial collagens, i.e. Types I, III and V collagen, is closely linked to the progression of glomerular sclerosis and hyalinosis in patients with various types of glomerulonephritis and diabetic nephropathy.

Adult↗
PubMedDate not supplied

Expression of cysteine proteinases and their inhibitor, cystatin beta, in cultured rat mesangial cells.

Matrix expansion in the glomerular mesangial area is observed in diabetic nephropathy. Intracellular breakdown of long-lived proteins was lower in mesangial cells in the high glucose medium than that in the control medium. Enzymatic activity of cathepsin L increased 1.4-fold after 6 h of treatment with the high glucose, and then declined gradually to 72% of control cells after treatment for 36 h. Change in the enzyme activity of cathepsin B showed a similar time course but less magnitude than that of cathepsin L. Immunoblot analysis with anti-cathepsin L antibody showed that change in the enzyme activity of cathepsin L was due to the change in the amount of cathepsin L, and that with anti-cathepsin B antibody showed no change in the amount of cathepsin B in the mesangial cells treated with high glucose. Intracellular cathepsin activities were controlled not only by the amounts but also by the inhibitor cystatin beta. Immunoblot analysis with anti-cystatin beta antibody showed that intracellular levels of cystatin beta increased slightly after 24 h of treatment with high glucose. These changes were derived from changes in mRNA level. These results, therefore, demonstrated that the decrease of intracellular protein breakdown in mesangial cells treated with high glucose medium was due to both suppression of cathepsins and increase of cystatin beta.

Animals↗
PubMedDate not supplied

A case of IgM-associated mesangial proliferative glomerulonephritis with a giant paramesangial spherical deposit.

We report a case of IgM-associated mesangial proliferative glomerulonephritis with microscopic hematuria and renal tubular dysfunction. On electron microscopy, a giant spherical deposit was observed in the glomerular paramesangial area. Deposition of C3 in the glomerular mesangial areas was not observed by immunofluorescence. IgM-associated mesangial proliferative glomerulonephritis is clinically characterized by nephrotic syndrome, mild proteinuria and/or hematuria, tubular dysfunction or renal failure, suggesting that it is considered to be a heterogeneous disorder.

Female↗
PubMedDate not supplied

Antihypertensive effects of a new transdermal delivery system for clonidine (M-5041T) in spontaneously hypertensive rats.

The antihypertensive effects of a new transdermal delivery system for clonidine (clonidine tape; M-5041T) were investigated in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. In spontaneously hypertensive rats, M-5041T, at doses of 0.5-4.5 mg/kg (1.25-11.25 cm2/kg), produced a dose-dependent decrease of both systolic blood pressure and heart rate for 24 hr during transdermal application. These significant hypotensive effects lasted for 24 hr following the patching of M-5041T on the back of the animals at a dose of 4.5 mg/kg. In normotensive Wistar-Kyoto rats, the hypotensive and bradycardic effects of M-5041T were weak compared with those in spontaneously hypertensive rats. In both rat strains, M-5041T (4.5 mg/kg) caused behavioral changes such as sedation, piloerection and exophthalmos, accompanied by hypotensive effects. Both M-5041T (1.5 mg/kg) and clonidine (50 micrograms/kg, subcutaneously and 100 micrograms/kg, orally) induced similar hypotensive effects, accompanied by sedation. The hypotensive effects following transdermal M-5041T or systemic clonidine administrations were correlated with the time courses of the plasma clonidine concentration. In contrast to clonidine administered subcutaneously or orally, M-5041T produced a gradual increase in the plasma clonidine concentration, which persisted at a consistent level for at least 12 hr thereafter. Significant hypotensive effects lasted for 12 and 24 hr following M-5041T patching at 1.5 and 4.5 mg/kg, respectively. The present findings suggest that M-5041T can serve as an efficient and useful antihypertensive transdermal delivery system to achieve persistent blood pressure control.

Administration, Cutaneous↗