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Biomedical subjects

R Karasawa

Publications and source records attributed to R Karasawa.

At least 19 recordsLinked to original sources
PubMed2000

Treatment of membranoproliferative glomerulonephritis associated with hepatitis C virus infection. Niigata Research Group of Glomerulonephritis and Nephrotic Syndrome.

OBJECTIVE: Interferon has been used as a new therapeutic agent for glomerulonephritis since a manifest relationship between membranoproliferative glomerulonephritis (MPGN) and hepatitis C virus (HCV) infection was documented. However, several side effects and rebound phenomenon have been significant problems. We retrospectively evaluated the therapeutic effect and safety of the standard treatment with steroids and/or immunosuppressive agents for MPGN patients with an HCV infection. METHODS: Remission and renal survival rates as well as clinical and histological data were compared between MPGN groups with or without an HCV infection. In addition, the hepatic function was followed-up after the treatment. PATIENTS: The subjects were 42 biopsy proven MPGN patients. Seven were positive for an HCV infection. Secondary causes of MPGN excluding an HCV infection were omitted. Most patients were treated with steroids and/or immunosuppressive agents. RESULTS: The mean age of the MPGN patients with an HCV infection was significantly higher than that of those without an HCV infection. The renal function and the interstitial change of the former group were significantly worse than those of the latter. Nevertheless, remission and renal survival rates were not significantly different between the two groups. None in the HCV positive MPGN group showed an impairment of hepatic function during the clinical course. However, 2 subjects died from severe pneumonia during the treatment. CONCLUSION: The standard treatment with steroids and/or immunosuppressive agents did not reveal a statistical difference in the therapeutic efficacy between MPGN patients with or without an HCV infection. However, some in the former group showed a poor prognosis.

Adult↗
PubMed1998

Apolipoprotein E4 reduces risk of diabetic nephropathy in patients with NIDDM.

Hypercholesterolemia is a major determinant of the decline of renal function in patients with diabetes. Apolipoprotein E polymorphism may influence the metabolism of lipoprotein in diabetic patients. The purpose of this study was to investigate the association between genetic polymorphisms in apolipoprotein E and the progression of diabetic nephropathy in patients with non-insulin-dependent diabetes mellitus over a 10-year period (13 to 37 years; median, 20 years). Subjects with a stable renal function without overt proteinuria had a higher cholesterol level, lower incidences of hypertension and proliferative diabetic retinopathy, and a higher frequency of the E4 allele than subjects with a decline in renal function (end-stage renal failure requiring dialysis treatment). In the diabetic patients, the apolipoprotein E4 carriers had a higher cholesterol level than did the noncarriers. The survival rate from renal disease in the apolipoprotein E4 carriers was higher than in the noncarriers among the diabetic patients. Apolipoprotein E polymorphism and hypertension were identified as independent risk factors for the progression to renal failure. Results indicate that apolipoprotein E polymorphism is associated with the progression of diabetic nephropathy. Presence of the apolipoprotein E4 allele is a protective factor, and other alleles are risk factors.

Adult↗
PubMed1997

Early increase of chondroitin sulfate glycosaminoglycan in the glomerular basement membrane of rats with diabetic glomerulopathy.

A decrease in anionic change and the loss of heparan sulfate proteoglycan have previously been observed in the glomerular basement membrane (GBM) during diabetic glomerulosclerosis. We studied the chronological changes in the anionic character and the glycosaminoglycan content in the GBM of WBN/ Kob rats with spontaneous diabetes. Two types of cationic probes were used: polyethyleneimine (PEI) and cationic colloidal gold (CCG). Immunogold labeling was performed with anti-monoclonal-heparan-sulfate-glycosaminoglycan (HS-GAG) and anti-chondroitin-sulfate-glycosaminoglycan (CS-GAG) antibodies. The GBM width, the anionic sites and the GAG sites were investigated in diabetic WBN/Kob rats at 2, 10 and 19 months, compared with control rats. Diabetes was confirmed in WBN/Kob rats after 8 months in this study. The GBM width gradually thickened with age. The PEI anionic sites significantly decreased in the lamina rara externa (LRE) at 19 months (vs. 2 and 10 months). The HS-GAG sites also significantly decreased in the LRE at 10 and 19 months (vs. 2 months). However, the CCG anionic sites and the CS-GAG sites significantly increased in the LRE and the lamina densa at 10 months (vs. 2 months) and, after 19 months, returned to the level seen at 2 months. Results indicate that there is an early transient increase in CS-GAG in the GBM while HS-GAG decreases. We noticed a transient increase in the CCG anionic sites at this early stage of diabetic glomerulosclerosis as well. The increase in CS-GAG may provide a marker for early diabetic changes in the GBM.

Animals↗
PubMed1997

Histological localization of advanced glycosylation end products in the progression of diabetic nephropathy.

We studied the immunohistochemical localization of advanced glycosylation end products (AGEs) in the progression of diabetic nephropathy. Fourteen NIDDM patients with diabetic nephropathy were evaluated: 2 patients with normoalbuminuria, 4 with microalbuminuria (MA) and 8 with overt proteinuria (OP). Three patients with minor glomerular abnormalities were used as nondiabetic controls. Immunoreactivity to a monoclonal anti-AGE antibody (6D12) was recognized on the internal elastic membranes of arterial walls in every diabetic group. Hyaline lesions of arterioles of the MA and OP groups demonstrated strong reactions with 6D12. A portion of the nodular and exudative lesions in glomeruli of OP group patients also revealed immunoreactivity to 6D12. No immunoreactivity to 6D12 was observed in nondiabetic control specimens. We confirm that the accumulation of AGEs began in arterial walls of the early stage and presented in glomerular lesions of the late stage of the progression of diabetic nephropathy.

Adult↗
PubMed1997

Prognosis of Japanese membranous nephropathy patients with nephrotic syndrome.

We retrospectively investigated the prognosis and efficacy of various treatments in 58 Japanese patients with primary membranous nephropathy (MN). Patients were treated with prednisolone (PSL) + immunosuppressive (IS) agents (N = 22). PSL alone (N = 23), IS agents alone (N = 5) and aspirin or dipyridamole (N = 8). Overall, 25 patients (43.1%) achieved complete remission (CR), 11 (18.9%) achieved partial remission (PR) and 22 (37.9%) were non-responders (NR). The 10-year survival rate was 90% and the 10-year CR rate was 61.8% as determined by Kaplan-Meier analysis. There was no significant difference in the CR among treatment groups. Of the 22 patients in the PSL + IS group, 3 progressed to end-stage renal disease and 2, who were more than 65 years old, died of pneumonia. The clinical and histological data at renal biopsy did not significantly differ among the treatment groups. In conclusion, the overall prognosis of MN was excellent. Treatment with PSL and/or IS agents did not appear to be superior to treatment with aspirin or dipyridamole.

Disease Progression↗
PubMed1997

Tubulointerstitial lesions in non-insulin dependent diabetes mellitus.

The clinical features and quantitative renal morphometry, including the index of mesangial expansion (IME), the index of arteriolar hyalinous change (IAHC), the percentage of globally sclerosed glomeruli (%GS), and interstitial volume fraction for total renal cortex (Vv int/T) of 67 Japanese non-insulin dependent diabetes mellitus (NIDDM) patients were examined. For the total subject population, Vv int/T correlated with urine protein, creatinine clearance, blood pressure, IME, IAHC and %GS, but not with duration of NIDDM. No significant difference in interstitial expansion between normo- and microalbuminuric patients was observed, and Vv int/T did not correlate with urine albumin excretion rate in those patients. However, in the area without hyalinized glomeruli and atrophic tubules, we found significant interstitial expansion and thickening of the tubular basement membrane (TBM) in patients without overt proteinuria as compared with those in the age-matched minimal change control group. This study confirmed that interstitial expansion in NIDDM progresses in parallel with glomerular and arteriolar lesions and that the expansion occurs concurrently with TBM thickening before the appearance of proteinuria.

Adult↗
PubMed1995

An ultrastructural study of glomerular basement membrane in rheumatoid arthritis patients with urinary abnormalities.

We measured the thickness of the glomerular basement membrane (GBM) in 48 rheumatoid arthritis (RA) patients with proteinuria and/or hematuria and studied its relationship to clinical features of RA. Ten cases with minor glomerular abnormalities, renal cancer, donor of renal transplantation, were studied as controls. Secondary glomerular diseases and hereditary thin basement membrane disease (TBMD) were excluded. Mean GBM thickness was 289 +/- 74 nm (mean +/- SD) in RA patients, which was significantly thinner than that of control group (342 +/- 38 nm) (p < 0.01). Mean GBM thickness were 276 +/- 72 nm and 336 +/- 68 nm in RA patients with and without gold sodium thiomalate (GST) treatment, respectively (p < 0.05). Mean GBM thickness of RA patients without GST and controls were not different statistically, but RA patients with GST had significantly thinner GBM, compared with controls (p < 0.01). The mean thickness of GBM were also 274 +/- 69 nm and 344 +/- 72 nm in RA patients with and without hematuria, respectively (p < 0.01). According to these results, we suspect that the thinning of GBM in RA patients may be related to GST treatment.

Adolescent↗
PubMed1995

Nephrotic syndrome in a bone marrow transplant recipient with chronic graft-versus-host disease.

A 21-year-old male developed massive proteinuria and microscopic hematuria, 1 year after allogeneic BMT for acute lymphoblastic leukemia. These symptoms occurred during an exacerbation of chronic cutaneous graft-versus-host disease (GVHD). Renal biopsy revealed granular deposits of IgG and IgM along the glomerular basement membrane, and subepithelial electron dense deposits. A diagnosis of membranous nephropathy was made. With prednisolone therapy proteinuria decreased gradually, and amelioration of cutaneous lesions was also noted. It was speculated that the disordered immune regulation of chronic GVHD resulted in the development of immune complex nephritis.

Adult↗
PubMed1994

A light microscopic study of glomerulosclerosis in Japanese patients with noninsulin-dependent diabetes mellitus: the relationship between clinical and histological features.

We studied the relationships of renal lesions with clinical features and renal prognosis in 128 Japanese patients with noninsulin-dependent diabetes mellitus (NIDDM). Diabetic glomerulosclerosis (DMGS) was found in 108 cases (84.4%), and DM-associated glomerulonephritis (GN), IgA nephropathy and membranous nephropathy, was in 20 cases (15.6%). There was no significant difference in age at renal biopsy, age at DM onset, DM duration, glomerular filtration rate (GFR), urine protein and serum IgA level between patients with DMGS and DM-associated GN. With respect to histological parameters, the increase in mesangial matrix was more closely related to DM duration, GFR and urine protein than to the degree of glomerular sclerosis. The index of glomerular lesion (IGL), which was calculated by combining these two lesions, had a more significant correlation with the clinical features than the tubulo-interstitial lesions. We suggested that the mesangial change was an initiating reaction, and the interstitial one was secondary in NIDDM patients. The prognosis of renal function after renal biopsy of the patients whose serum creatinine level was less than 1.2 mg/dl, was poorer in cases with nodular lesion than in those with diffuse lesion. The grade of tubulo-interstitial lesion was also more severe in these patients with nodular lesion. However, the controls of blood glucose, blood pressure, serum total cholesterol were not different among the two groups. On the other hand, serum creatinine level of most patients with associated GN did not change for a long period, up to 10 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1993

Localization of apolipoprotein(a) and B-100 in various renal diseases.

Recently it has become clear that abnormalities of lipid metabolism play a large role in the progression of renal diseases. To investigate the relationship between lipids and kidney tissue, we employed an immunofluorescent technique to determine the localization pattern of apolipoprotein(a) [apo(a)], apoB-100, and low-density lipoprotein receptor in the glomeruli, and analyzed the relationship between their presence and the clinical and histological findings of a total 92 patients with glomerular diseases. Immunostaining showed co-localization of apo(a) and apoB-100 in glomeruli. The patients were divided into three groups, as follows: both apo(a) and apoB-100 positive (Group 1; 38 cases), apo(a) positive only (Group 2; 19 cases) and apo(a) negative (Group 3; 35 cases). Group 1 had more severe proteinuria, higher levels of lipoprotein(a) [Lp(a)], and lower total protein levels than Group 3. Group 1 had a higher prevalence of glomerulosclerosis and interstitial changes than Group 3. Group 2 had more severe proteinuria and a higher prevalence of glomerulosclerosis than Group 3. Although apo(a) and apoB-100 are almost absent in normal controls, these apoproteins [and presumably lipoproteins Lp(a)] are present in the glomeruli of patients with glomerular diseases. The data support the view that these apoproteins play a significant role in progressive renal diseases.

Adolescent↗
PubMed1993

Glomerulonephritis with various crystalline deposits.

A 60-year-old Japanese male was admitted with nephrotic syndrome complaining of facial and pedal edema. Renal biopsy revealed mesangial and endocapillary proliferation with massive mesangial and subendothelial deposits. Deposits of IgA, IgG, IgM, C3 and fibrinogen were identified by immunofluorescence technique in both mesangial and subendothelial areas. Deposits of kappa and lambda light chains were also recognized in similar patterns. Electron microscopy revealed crystalline structures of various appearance in these deposits. A large deposit consisted of various small triangular, quadrilateral and polygonal shapes of deposits with crystalline structures. These crystalline structures exhibited lattice or parallel lamellar lines with different periodic distances. Although a disease producing paraproteinemia was suspected, no immunoglobulin disorder or light chain abnormality could be detected on clinical and laboratory examinations. On the second biopsy, a faint reaction for cryoglobulin was recognized. However, the crystalline deposits observed in this case were absolutely different from the tubular structures seen in cryoglobulinemic nephropathy. This was a very rare and unclassified case.

Crystallization↗
PubMed1993

Clinico-pathological studies of Amyloid-P component in human glomerulopathies.

Renal tissues from 171 patients with different glomerulopathies and 6 normal controls were examined by an immunofluorescent technique. Specimens were stained in particular with anti-Amyloid P (AP) antisera, and were also stained for immunoglobulins and complement. The intensity and distribution pattern of AP staining were studied. The AP staining revealed a faint/linear pattern in normal controls, and was granular and linear in pathological specimens. The distribution of AP was found to be mesangial, capillary and mesangiocapillary. According to the degree of AP intensity, the patients were divided into two groups: group I (56 patients) exhibiting a faint intensity as seen in the normal controls, and group II (115 patients) with a strong intensity. The histological findings and laboratory data were compared between the two groups as well as among patients with different diseases. The incidence of sclerotic lesions and the amount of proteinuria were significantly higher in group II than in group I. Increased amounts of AP deposition in different glomerular diseases thus appear to be related to a diminished renal function or glomerular damage.

Adolescent↗
PubMed1992

An electron microscopic study of glomeruli in Japanese patients with non-insulin dependent diabetes mellitus.

Renal biopsy specimens of 29 Japanese non-insulin dependent diabetes mellitus (NIDDM) patients were examined by quantitative electron microscopic morphometry. In NIDDM the relative increase of percent total mesangium and mesangial capillary surface density (S/Vb) and the relative decrease of peripheral capillary surface density (S/Va) were compared with disease controls. However, mesangial-GBM-epithelial surface density (S/Vc) was not different between both groups. These results suggest that the increased mesangial matrix expands directly towards the capillary lumen as well as along the inner surface of GBM, and narrows the capillary lumen and filtration surface. The duration of diabetes mellitus (DM) did not correlate with all morphological parameters. The mesangial expansion correlated with urinary protein excretion and decreased creatinine clearance (CCr). GBM thickening correlated with proteinuria, but not with CCr. The degree of these morphological changes could be the indicators of hypertension of NIDDM patients. Areas of thin GBM were occasionally noticed in glomeruli which revealed thick GBM extensively, although the mechanism of GBM thinning is not known at the present time.

Adult↗
PubMed1991

[Clinicopathological studies of renal disorders in patients with progressive systemic sclerosis].

The renal impairments were studied clinicopathologically in 57 patients with progressive systemic sclerosis (scleroderma). Proteinuria, hematuria, azotemia and hypertension, used as markers for renal involvements, were observed in 3 (5.3%), 4 (7.0%), 2 (3.5%) and 6 patients (10.5%) respectively, at the initial examination. Hypertension was increased 2.6 times at the last observation, although the incidence of other three markers have not changed during the follow-up period. Finally, 17 out of 57 patients (29.8) revealed more than one of these clinical markers throughout the study. The decrease of GFR (CThio) was noticed in 3 out of 36 cases (8.3%), however that of RPF (CPAH) in 11 of 36 patients (30.6%), including 5 without abnormal clinical markers. Histological studies were performed in 12 patients. One showed crescentic glomerulonephritis, two membranous nephropathy, and the remaining 9 minor glomerular abnormalities. On the other hand, the vascular changes such as intimal proliferation of interlobular arteries were frequently observed. The frequency of pulmonary involvements, skin ulcer and gastro-intestinal involvement in the patients with renal lesions were not significantly different from that of the non-renal group. The level of RPF was significantly lower in the patients with skin ulcer than that of those without skin ulcer. No significant difference was noticed in the frequency of renal involvements between the patients with or without anti-Scl-70 antibody.

Adult↗