Complete remission in idiopathic membranous glomerulonephritis.
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Publications and source records attributed to S Takebayashi.
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In reflux nephropathy both interstitial and glomerular damage advances with an increase in the scarring grade even in macroscopically normal regions. Based on various histologic findings, sclerosis and the enlargement of glomeruli rapidly accelerate between stages c-a and c-b, as shown by the combined Smellie's scarring grade of the bilateral kidneys. These two steep histologic changes in stage c-b are followed by a remarkable reduction in renal function (DTPA-GFR) and an increase in the amount of urinary protein. These clinicopathological changes thus suggest that hemodynamic changes or overloading in the functional remnant nephrons possibly start in stage c-a. It is also suggested that glomerular enlargement is an index of progressive disease in reflux nephropathy. Among our specimens, most cases of glomerular sclerosis were global while focal segmental glomerulosclerosis was very rare. These findings thus suggest that the global sclerosis observed in our specimens is clearly different from focal segmental glomerulosclerosis.
We previously found that type V collagen repressed the attachment and spread of aortic smooth muscle cells. The present study was carried out to investigate the effects of type V collagen on the formation of fibronectin and F-actin filaments of human dermal fibroblasts in relation to cell attachment and spread, using an immunofluorescent technique and morphometry. The number and area of the cells attached to type V collagen at 1 and 3 hours after seeding were significantly lower than those of cells on other substrates, including collagen types I, III and IV, and bovine serum albumin. However, there was no significant difference in the attachment and spread among the cells on these substrates after 24 hours. Cultured fibroblasts exhibited two patterns of fibronectin; one was a clear, linear fibronectin localized mainly in the cellular margins, and the other was a granular or flocculent fibronectin found in the perinuclear areas. The former was stained in non-permeabilized cells, but not in trypsin-treated cells (cell surface fibronectin). In contrast, the latter was not detected in nonpermeabilized cells, but was found in trypsin-treated cells (perinuclear fibronectin). Most of the cells cultured on type V collagen did not form either linear cell surface fibronectin or F-actin filaments at 3 hours. In contrast, many cells on collagen types I, III, and IV developed both cell surface fibronectin and F-actin filaments, the distributions of which were partially coincident. Colocalization of linear cell surface fibronectin and F-actin filaments was found in cells on all of the substrates after 24 hours. Perinuclear fibronectin showed similar patterns, and was not colocalized with F-actin filaments on different substrates at 3 and 24 hours of culture. Solid-phase substrates induced a better cellular attachment at 3 hours than serum adhesive factors. The administration of monensin, which inhibits the secretion of protein products, decreased the intensity of the fluorescence of cell surface fibronectin in fibroblasts, which was observed in a clear line. These results suggest that the retardation of the initial attachment and spread of fibroblasts on type V collagen is related to an inhibition in the formation of the fibronexus, a close transmembranous association of individual fibronectin fibers and F-actin filaments.
Cell degeneration and collagenosis are the main features in atherosclerotic plaque. We examined the effects of human low density lipoprotein (LDL) on cultured rabbit aortic smooth muscle cells (SMCs). Copper oxidized LDL (LDL+Cu) injured the SMCs more than did native LDL. Cytotoxicity of oxidized LDL was prevented by the simultaneous addition of butylated hydroxytoluene (BHT) and ethylenediamine tetraacetic acid. Collagen synthesis increased up to 6 fold after incubation with 200 micrograms protein/ml of both native and oxidized LDL compared with that incubated in bovine serum albumin. Noncollagen protein synthesis was significantly reduced by oxidized LDL when compared to that by native LDL. Therefore, oxidized LDL increased the relative collagen synthesis (3.33%) to a greater extent than did native LDL (0.72%). By adding BHT to LDL+Cu, the elevated relative collagen synthesis was reversed due to the restoration of noncollagen protein synthesis while it also inhibited LDL peroxidation as evaluated by the formation of malondialdehyde (MDA). However, sodium MDA (up to 200 microM) did not induce either cytotoxicity or an increase of relative collagen synthesis. We therefore conclude that oxidized human LDL enhanced the relative collagen synthesis coinciding with the induction of injury in cultured aortic SMCs, however free MDA may not be the component responsible for these effects.
To clarify the clinical and pathological significance of thin glomerular basement membranes (Thin-GBM) appearing in evident diabetics, we examined the renal biopsies from 179 diabetes mellitus (DM) patients with urinary abnormalities in which the number of non insulin dependent diabetes mellitus cases was 140 cases while the remaining 39 cases had insulin dependent diabetes mellitus. In addition, 17 of these cases were found to have either segmental or diffuse Thin-GBM by electron microscopy. The clinical and morphological parameters between the diabetics with Thin-GBM (DM-Thin-GBM) and the diabetics without Thin-GBM (the controls) were significantly different regarding DM duration (DM-Thin-GBM vs control: 5.3 +/- 5.5 vs 9.8 +/- 6.5 years, p < 0.01), Ccr (67.0 +/- 25.5 ml/min vs 45.6 +/- 24.4 ml/min, p < 0.01), the incidence of hematuria (52.9% vs 24.5%, p < 0.05) and hypertension (13.3% vs 51.3%, p < 0.05). The severity of glomerular damage was mild in the DM-Thin-GBM group as compared to the control. The renal survival rate from the onset of urinary abnormalities was higher in the DM-Thin-GBM group than in the control (p < 0.01). In the case of DM-Thin-GBM, the grade of proteinuria correlated with the mean width of the thickened GBM (p < 0.01) and the spread of the thickened GBM which was more than 500 nm in width (p < 0.001). The severity of microscopic hematuria correlated with the spread of the Thin-GBM (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
A cell line derived from medial smooth muscle cells (SMC) was established from the porcine coronary artery by transfection with ori-defective simian virus 40 plasmid DNA (SV40 DNA). The characteristics of transfected cells (SV40-SMC) such as cell growth, collagen and non-collagen syntheses were investigated. SV40-SMC expressed SV40 large T antigen, c-myc and c-myb encoded proteins in the nuclei. SV40-SMC demonstrated a 'hills and valleys'-like arrangement in overconfluence and actin filaments upon immunofluorescent staining. Under electron microscopic observation, SV40-SMC had larger amounts of synthetic organelles and smaller amounts of filament bundles than those of SMC. SV40-SMC demonstrated three times higher growth activity and 4.4 times greater cellular density than SMC. Smooth muscle cells did not grow in media containing 5% plasma derived serum (PDS) instead of normal serum, whereas SV40-SMC proliferated in this medium. SV40-SMC did not grow in soft agar gel, while HeLa S3 cells, a cell line of human cervical carcinoma, formed colonies in this gel. By immunofluorescent (IF) staining, collagen phenotypes I, III, IV and V were detected in both SV40-SMC and SMC. However, protein synthesis including collagen and non-collagen was higher in SV40-SMC than in the control sample. It was concluded that SV40-SMC were a continuous cell line for vascular SMC regarding morphological characteristics, and demonstrated a higher growth activity, with increased collagen and non-collagen syntheses. This cell line is useful for the investigation of atherogenesis in relation to a proliferation of SMC and an accumulation of extracellular matrices in vascular intima.
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The different types of collagen including Types I, III, IV, V, VI and VIII are distributed in the artery. The atherosclerotic lesions, such as fatty streaks and atheromatous plaques, are characterised by an increase in types V and VI, which are localized in the region with a deposition of LDL and an infiltration of macrophages. Vascular smooth muscle cells interact with various types of collagen. Collagen matrices induce an enhancement of differentiation and suppression of cellular proliferation of "normal" smooth muscle cells. However, transformed smooth muscle cells fail to interact with various types of collagen. These results suggest that the interaction between vascular cells, including smooth muscle cells, macrophages and endothelial cells and collagen matrices is important in atherogenesis.
We attempted to clarify the effects of various purified extracellular components, including types I, III, IV, and V collagen and fibronectin on attachment, spread, growth, and DNA synthesis of porcine aortic smooth muscle cells (SMCs) in vitro. The number, area and shape index (SI = 4 pi S/L2) of cells attached to different substrates were determined at various intervals of incubation. The cell number and [3H]thymidine incorporation into DNA were measured on the 1st and 6th days of culture. SMCs showed the largest number of attached cells on fibronectin, but the smallest number of attached cells on type V collagen. There was no evidence of effects of the serum in media on the attachment of SMCs to the substrates. The areas of attached SMCs were the largest on fibronectin and the smallest on type V collagen. The shape index of SMCs on fibronectin decreased relative to those on other substrates. On the 6th day in culture, the number and population doubling of SMCs on type V collagen were significantly fewer than those on other substrates. Both the incorporation rate of [3H]thymidine into DNA and the percentage of nuclei labeled with [3H]thymidine were significantly less in the SMCs on type V collagen on the 1st day than those on other substrates. SMCs on types I, III, and IV collagen showed intermediate levels of cell attachment, spread, and growth. These results suggest that attachment, spread, and growth of SMCs are affected mainly by solid phase purified extracellular components and are most strongly suppressed by type V collagen. When DNA synthesis of growth-arrested SMCs was reinitiated by the addition of serum, type V collagen most intensively inhibited the rate and amount of [3H]thymidine incorporation. Flow cytometric analysis demonstrated an increased in the proportion of cells in G0/G1 phase on type V collagen in comparison with that on other substrates. Thus, the antiproliferative effect of type V collagen may relate to inhibition of transition of SMCs from the G0/G1 into the S phase.
To clarify the morphological changes in renal proximal tubules at the onset of diabetic nephropathy, we observed 177 biopsy samples from patients with Non-Insulin-Dependent Diabetics (NIDDM) using light and electron microscopy. Group I had no proteinuria (p.u.), group II had p.u. < or = 0.5 g/day, group III had p.u. > 0.5 g/day, group IV had serum creatine level (Cr) > 1.5 mg/dl. Twenty age-matched normal patients and 80 patients with IgA nephropathy were used as controls. In groups I and II, the following features were significantly different from those in the controls: spherical enlargement of mitochondria (MT) in proximal tubule cells, hypertrophy of proximal tubule cells and their nuclei, and thickening of both the proximal tubule basement membrane (TBM) and the glomerular basement membrane (GBM). Among the histological changes observed in group I, the thickness of the GBM and TBM indicated that the disease would lead to diabetic nephropathy. MT enlargement was positively correlated with nuclear and cytoplasmic enlargement of the proximal tubule cells in diabetic patients (p < 0.05), but was not correlated with other morphological changes or disease prognosis. Glomerular nodular lesions, glomerular sclerotic change, and cortical tubulointerstitial fibrosis became evident in groups III and IV. From the above, we concluded that MT enlargement and thickening of the TBM are possible causes of reduced active transport in the proximal tubules, causing microalbuminuria in diabetics, and initial impairment of post-tubule transport.
To clarify the ultrastructural changes in renal proximal tubules causing microalbuminuria in the early stage of diabetic nephropathy, three different groups of rats were prepared: rats with streptozotocin (STZ)-induced diabetes given no treatment (DMut; n = 7), rats with STZ-induced diabetes treated with insulin (DMt; n = 7), and non-diabetic rats injected with citrate buffer (control; n = 7). In each group, the laboratory findings, ATP content of the renal cortex, and the size of proximal tubule cells and their nuclei and mitochondria (MT) were determined. In two weeks after the start of the study, MT in renal proximal tubules showed diffuse enlargement in the DMut group as compared with those in the control group. Renal cortical ATP content, fractional sodium excretion (FENa), urinary excretion of beta 2-microglobulin and albumin were also increased significantly in the DMut group relative to the controls. In the DMt group, most of the examined parameters returned almost to normal. There were positive correlations between each of the following parameters: hyperglycemia and MT enlargement, MT enlargement and increased cortical ATP content, increased cortical ATP content and increased FENa, increased FENa and increased urinary excretion of beta 2-microglobulin and albumin. On the basis of these results, we conclude that mitochondrial enlargement, resulting from disturbed metabolism of ATP, may reduce active transport in renal proximal tubules, which, in turn, may impair reabsorption in the tubules. This would cause urinary excretion of low-molecular-weight proteins and microalbumin in the early stage of diabetic nephropathy.
Vacuoles in glomerular visceral epithelial cells were found in 149 of 254 patients with idiopathic membranous glomerulonephritis (IMGN). In the whole population studied, 115 patients were nephrotic, 88 (76.5%) of which were found to have intraepithelial vacuoles. Fifty (35.9%) of 139 non-nephrotic patients had vacuolated podocytes (p less than 0.01). Vacuolation occurred most frequently in stages II and III of IMGN. A few intraepithelial vacuoles were observed in stage IV. Increase in vacuolation tended to correlate with subepithelial deposits which were larger in size. From these results, we concluded that the appearance of epithelial vacuolation coincides with an increased filtration of protein in IMGN and that it is an important histological marker when diagnosing the level of severity of glomerular lesions. It was not, however, prognostic.
Clinicohistopathologically, we observed 109 patients with asymptomatic urinary abnormalities found via the Japanese school medical screening process. Follow-up was for a mean period of 9.3 +/- 4.0 years. More than 80% of the patients had either IgA nephropathy (IgAN, 47 cases, 43.1%), thin membrane disease (TMD; 21 cases, 19.3%) or normal glomerulus (NG; 20 cases, 18.3%). Complete remission appeared in 60.0% of the NG cases, 14.3% of the TMD cases and in 19.1% of the IgAN cases, and remission was significantly high in the NG group (p less than 0.01). No patient with TMD and NG ever progressed to the extent of pronounced proteinuria or renal failure. One patient deteriorated and required hemodialysis, and 2 patients developed renal insufficiency in IgAN. All of these cases possessed severe glomerular sclerotic change when the initial biopsies were performed. All IgAN cases that went into remission, however, had minor glomerular abnormalities. A positive family history of urinary abnormality was observed in 14.1% of both the IgAN group and the NG group, whereas we observed 71.4% in the TMD group, which was significantly high (p less than 0.01). Other cases included 4 each with non-IgA proliferative glomerulonephritis, focal segmental glomerular sclerosis, membranoproliferative glomerulonephritis and Alport's nephritis. It was concluded that the majority of patients (80.7%) with urinary abnormalities found via the school screening program had IgAN, NG or TMD. 74.5% of the IgAN group and 85.7% of the TMD group had long histories of urinary abnormalities extending into adulthood with no deterioration of the renal function.
Color Doppler sonographic findings on 38 lesions in 31 patients who had primary hepatocellular carcinoma were evaluated before and after transcatheter arterial embolization and compared with dynamic CT and hepatic arteriographic findings. All lesions that were observed with dynamic CT or arteriography were correctly identified on color Doppler sonography. Peritumoral pulsatile flow was the predominant color Doppler flow seen in all lesions. Mixed pulsatile and continuous flow were noted in larger tumors and in tumors with a higher degree of vascularity, as determined by arteriography. Two weeks after treatment, color Doppler flow was still identified in 18 lesions (47%), corresponding to dynamic CT or arteriographic findings documenting residual tumor. Histopathologic examination, performed in 10 other lesions, showed that the tumor was completely necrotic in five. These five necrotic tumors were not visible on color Doppler flow images after treatment. Viable tumor was observed in the five remaining lesions, all of which were shown on color Doppler flow images after treatment. During the 6- to 16-month follow-up period, color Doppler flow images showed recurrence of 13 (50%) of 26 lesions, corresponding to tumor recurrence as shown by CT and arteriography. We conclude that color Doppler sonography is useful for imaging hepatocellular carcinoma, for evaluating residual tumor after treatment, and for imaging tumor recurrence during follow-up.
A 51-year-old man presented with a nonpulsatile anterior neck mass which suggested a thyroglossal duct cyst. At CT a small cystic mass was revealed. The mass contained a well-defined, crescent-shaped, low-density area with homogeneous contrast enhancement. On MR T2-weighted spin-echo and gradient-echo images the mass was as hyperintense as the neck vessels. Angiography and operation confirmed an aneurysm of the left superior thyroid artery with a mural thrombus.
We studied clinicopathologically 19 patients with abnormal urinary findings accompanying with persistent hypocomplementemia under age 15. They consisted of 6 patients with membranoproliferative glomerulonephritis (MPGN) type I, 2 with MPGN type II, 2 with focal MPGN, 8 with diffuse proliferative glomerulonephritis (DPGN), 1 with focal glomerulonephritis (FGN). 17 cases were treated with steroid. In 2 patients with MPGN type I and 1 patient with DPGN, the treatment resulted in normalization of serum C3 level and urinary abnormalities and improvement of histological findings. In 3 patients with DPGN, urinary abnormalities and hypocomplementemia have been persisted and histological findings changed to those of MPGN type I. Thus, DPGN with hypocomplementemia seems to be an early stage of MPGN type I.
We evaluated clinical and morphological findings in 254 patients (138 men and 116 women), with idiopathic membranous glomerulonephritis (IMGN). The mean age was 44 years. At time of biopsy proteinuria was found in 98%, nephrotic syndrome (NS) in 45.2%, hypertension in 10%, elevated serum creatinine concentration of greater than or equal to 1.4 g/dl in 24%, and markedly decreased Ccr (less than or equal to 40 ml/min) in 12.5% of the patients. Of 254 patients, 51 (20%) were classified as Stage I, 131 (52%) as Stage II, 52 (20.5%) as Stage III, 9 (3.5%) as Stage IV and 11 (4.3%) as Stage V, which was a relapsing form. Both intraglomerular, peripheral electron dense deposit-size and mean thickness of the glomerular basement membrane (GBMt) were analyzed by ultrastructural morphometric methods. In patients with NS, both the mean deposit-size and the mean GBMt were largest when compared to all others (p less than 0.01). The largest subepithelial deposits (SED), in mean, were observed in Stages II and V, while the largest incorporated deposits (ICD) were measured in Stages II and IV. The mean GBMt was largest in Stage III. Furthermore, there were strong correlations between the degree of proteinuria and the deposit-size (r = 0.603, p less than 0.001), and GBMt (r = 0.456, p less than 0.001). The GBMt showed a correlation with serum creatinine concentration (r = 0.476, p less than 0.001) and Ccr (r = 0.471, p less than 0.001). We concluded that the size of the electron dense deposits and GBM thickness play an important role in the clinical manifestation of IMGN.
A 30-year-old female with effusive-constrictive pericarditis was admitted to our hospital because of dyspnea, ascites and edema. On examination, her blood pressure was 118/94 mmHg and her pulse rate was 90 bpm. Physical examination revealed pulsus paradoxus, markedly raised venous pressure and pericardial knock sound. Chest X-ray showed marked cardiomegaly and bilateral pleural effusion. After cardiac catheterization there was elevation of mean right atrial pressure, right ventricular end-diastolic pressure, pulmonary-capillary-wedge pressure, and their pressures during diastole were approximately 30 mmHg. After successful pericardiocentesis, their diastolic pressures still remained at 15 mmHg. Additionally, pressure wave of the right ventricle showed distinct diastolic dip and plateau pattern, and that of the right atrium showed deep x and y descents. The pressure pattern suggested that not only pericardial effusion but also decreased compliance of the pericardium was the main factor contributing to the cardiac diastolic dysfunction. Histological examination of the pericardium showed diffuse lymphocyte infiltration and fibrosis. These findings strongly suggested that there might have been viral infection.