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Biomedical subjects

S Isogai

Publications and source records attributed to S Isogai.

At least 37 records · Page 2Linked to original sources

The fibronectin production is increased by thrombospondin via activation of TGF-beta in cultured human mesangial cells.

Thrombospondin (TSP) is a multifunctional glycoprotein that is synthesized by a variety of cells including mesangial cells (MCs). To clarify the effect of TSP on the pathogenesis of diabetic nephropathy, we studied the effect of glucose concentrations on TSP synthesis in cultured human MCs. Thereafter, the effects of TSP on the activation of transforming growth factor beta (TGF-beta) and fibronectin production were investigated in MCs. Incubating MCs with elevated glucose levels for 6 days resulted in an increase in TSP synthesis, measured by an enzyme-linked immunosorbent assay, both in culture media and cell layers. Treatment of MCs with TSP (final concentrations 1 and 5 microg/ml) for 24 h resulted in an increase (1.3- and 2.1-fold, respectively) in active TGF-beta, which was determined with an enzyme-linked immunosorbent assay using TGF-beta-soluble receptor type II, in the culture media without having any effect on the production of total TGF-beta. Exposure of MCs to TSP caused enhancement of fibronectin production in both media and cell layers in a TSP dose-dependent manner with the maximum at a TSP concentration of 1 microg/ml. The TSP-induced increase in fibronectin production from MCs was completely prevented by concomitant treatment with 10 microg/ml anti-TGF-beta neutralizing antibody. These results indicate that the TSP production is promoted by a high ambient glucose concentration in human MCs and that TSP, in turn, causes an increase in fibronectin production via activation of TGF-beta.

Antibodies↗

Pulmonary pseudallescherioma associated with systemic lupus erythematosus.

We report a case of fungus ball due to Pseudallescheria boydii (pseudallescherioma) associated with systemic lupus erythematosus. Direct microscopical examination revealed a fungus with broad septate hyphae resembling Aspergillus and the fungus was identified as P. boydii on culture. Surgical resection was required to control episodes of hemoptysis. Cases of pulmonary pseudallescheriasis are rare, especially in Japan. However, some cases previously diagnosed as pulmonary aspergillosis may have been found to be caused by P. boydii, if adequate culture studies had been conducted. Unlike Aspergillus, P. boydii is resistant to amphotericin B. Therefore, we emphasize the importance of a correct diagnosis based on culture examination.

Adult↗

Technique for arterial-phase contrast-enhanced three-dimensional MR angiography of the carotid and vertebral arteries.

Our goal was to evaluate whether contrast-enhanced three-dimensional MR angiography using the MR Smartprep technique would enable us to obtain arterial-phase MR angiograms of the carotid and vertebral arteries. The study included 35 patients with suspected lesions of the neck in whom the MR Smartprep technique was used for MR angiography performed with a 1.5-T superconducting system. The tracker volume was placed primarily in the middle part of the right common carotid artery. The imaging volume was placed in a coronal direction to include the carotid and vertebral arteries from the aortic arch to the skull base. A centric phase-ordering scheme was used. Imaging times were 20 to 38 seconds for 14 patients and 11 to 16 seconds for 21 patients. By using a smaller tracker volume and an imaging time of less than 16 seconds, we were able to achieve a 100% successful triggering rate and to delineate selectively arterial-phase carotid and vertebral arteries with almost no venous contamination. Contract-enhanced 3-D MR angiography with the MR Smartprep technique was useful for showing arterial-phase carotid and vertebral arteries selectively.

Aorta, Thoracic↗

[Dynamic magnetic resonance dacryocystography using half Fourier single shot fast spin echo sequence].

Dynamic magnetic resonance dacryocystography (MRD) was implemented using 1.5T superconductive imager with a standard head coil. Prior to MRD, a pair of polyethylene microcatheters were inserted into the lower lacrimal canaliculi. Injecting a mixture of 6 ml of saline and 4 ml of xylocaine (0.5%) as a substitute for contrast medium, repeated measurement of thick section heavily T2 weighted image using half Fourier single shot fast spin echo (SSFSE) sequence was performed. MRD could well depict the pathologies of the lacrimal sac and the lacrimal duct in five cases of epiphora. It pinpointed the level of lacrimal duct obstruction, which was confirmed by both X-ray dacryocystography and intraoperative findings. Dynamic MRD is a reliable method of diagnosing nasolacrimal duct obstruction without using ionizing radiation or chemical contrast medium.

Aged↗

[Maximum intensity projection (MIP) and multiplanar reformation (MPR) for post-processing cholangiopancreatographic data set--clinical application and pitfalls].

Maximum intensity projection (MIP) and multiplanar reformation (MPR) are the most frequently used algorithms for MR cholangiopancreatography (MRCP). The MIP allows three dimensional overview of the pancreatic and biliary system. Because of its resemblance to ERCP images, MIP reconstruction is widely accepted by clinicians. In spite of its usefulness, MIP may be misleading without a proper reference to source images or a guidance of MPR. Opacification defects that reflect intra-ductal or intra-cystic pathologies are notably erased through the process of MIP reconstruction. Diagnosis based only on MIP images is therefore not clinically feasible. A combined use either of multisection images, or at least source images, is essential. The MPR on the other hand, enables an investigation of the details of the intra-ductal or intra-cystic pathologies. Detailing with MPR and surveying with MIP work together in interpreting MRCP data set.

Biliary Tract↗

Protective effect of D-alpha-tocopherol on the function of human mesangial cells exposed to high glucose concentrations.

Altered functions of mesangial cells (MCs) induced by high glucose levels are thought to play an important role in the pathogenesis of diabetic nephropathy. We investigate whether D-alpha-tocopherol (Toc), an antioxidant, can prevent malfunction of cultured human MCs induced by high-glucose media. Incubating MCs with 33 mmol/L glucose caused increased lipid peroxide (LPO) levels, disturbed cell replication, enhanced cytotoxicity, enhanced activity of the diacylglycerol (DAG)-protein kinase C (PKC) pathway, and overproduction of fibronectin and eicosanoids (6-keto prostaglandin F1 alpha [PGF1 alpha] and thromboxane B2 [TXB2]). The amount of LPO in MCs grown in 5 mmol/L glucose was reduced by the addition of Toc in a dose-dependent manner. Since the maximum effect of Toc on decreasing LPO was achieved at a concentration of 100 mumol/L, this dose was selected for the following experiments. Addition of Toc prevented increased LPO levels and [51Cr]-release from MCs induced by high-glucose media without affecting cell number. Toc decreased the total DAG level and PKC activity in membrane fractions in MCs cultured at both 5 and 33 mmol/L glucose. Furthermore, glucose-induced overproduction of fibronectin and eicosanoids from MCs was completely abolished by Toc. These results strongly suggest that Toc ameliorates glucose-induced malfunctions of MCs in vitro.

Cell Count↗

Persistent primitive sciatic artery associated with other various anomalies of vessels.

A left persistent primitive sciatic artery was observed in a Japanese male cadaver. The sciatic artery arose from the internal iliac artery and perforated the ventral division of the sacral plexus. The sciatic artery did not anastomose with the perforating arteries nor the popliteal artery. The left femoral artery was incompletely developed, attenuating and terminating as the saphenous artery. Instead of the femoral artery, direct continuation of the profunda femoris artery, which probably corresponded to the fourth perforating artery, became the popliteal artery. Other vessel anomalies were observed in various regions. They included; (1) the retroesophageal right subclavian artery; (2) the left vertebral artery entering the transverse foramen of the 4th cervical vertebra; (3) bilateral occurrence of the superficial brachial artery; (4) the left gastric artery independently arising from the abdominal aorta; (5) a hepatolienomesenteric trunk; (6) three accessory renal arteries; (7) double testicular arteries; (8) the arteria intermesenterica; (9) a venous ring termed the 'renal collar', and (10) paired thoracic ducts. The present cadaver was considered to be a very rare case in which many primitive vascular systems had extensively persisted in various parts of the body.

Abnormalities, Multiple↗

[A case of Sjögren's syndrome complicated by membranous nephropathy].

A case of Sjögren's syndrome (SjS) complicated by membranous nephropathy (MN) is presented. A 50-year-old female was admitted to Toho University Hospital because of overt proteinuria (5g/day). She had xerotic keratitis in addition to a renal disorder, and laboratory data showed positive anti-nuclear antibody (ANA) and anti-SSA antibody. The specimens from renal biopsy revealed mild thickening of the glomerular basement membrane under light microscopy, positive IgG along the capillary walls revealed by immunofluorescence, and sparse and irregular subepithelial electron dense deposits seen under electron microscopy. No interstitial changes were observed. From these findings, she was diagnosed as having SjS complicated by MN. Proteinuria gradually decreased with a reduction in serum levels of ANA and anti-SSA antibody following corticosteroid therapy. Although renal interstitial lesions occasionally develop in patients with SjS, glomerular changes, especially MN, are very rare. We suspect that immunocomplexes, such as anti-SSA antibody, revealed in SjS patients could be responsible for the glomerular lesions, leading to MN.

Antibodies, Antinuclear↗

Changes in carnitine metabolism with ketone body production in obese glucose-intolerant patients.

To elucidate the relationship between carnitine metabolism and plasma ketone body concentrations in moderately obese patients with mild glucose intolerance, the ketone body and carnitine levels in the basal state were determined in 72 obese patients: 20 with normal glucose tolerance (NGT), 29 with impaired glucose tolerance (IGT), and 23 with non-insulin-dependent diabetes mellitus (NIDDM) having a fasting plasma glucose (FPG) level of less than 200 mg/dl. Total ketone body (TKB) levels significantly (P < 0.05) increased in the order of NGT, IGT, NIDDM, while the FPG and free fatty acid (FFA) concentrations were significantly (P < 0.05) higher in the NIDDM group than in the other two groups. In contrast, the insulin, glucagon and glycerol levels were comparable in the three groups. The plasma short-chain acylcarnitine (SCAC) concentration and the acylcarnitine/free carnitine (AC/FC) ratio were similar in the IGT and NIDDM groups, and significantly (P < 0.05) greater than those in the NGT group. The AC/FC ratio correlated significantly with the FPG and FFA, but not with the TKB. These results suggest that the combination of IGT with simple obesity may trigger the acceleration of hepatic ketogenesis in conjunction with an elevated SCAC and an increased AC/FC ratio. In addition, the data also imply that, in patients with mild NIDDM, factors other than the carnitines may play a greater role in enhancing ketonemia.

Acylation↗

Effect of an aldose reductase inhibitor on glomerular basement membrane anionic sites in streptozotocin-induced diabetic rats.

The present study was conducted in order to determine whether an aldose reductase inhibitor (ARI), epalrestat, prevents the progression of diabetic nephropathy in rats. Rats were made diabetic by intravenous injection of streptozotocin (STZ 50 mg/kg) and epalrestat (100 mg/kg) was administered orally through a gastric tube once daily for 4 weeks. Examination by electron microscope revealed that the number of anionic sites (AS) in the lamina rara externa per 1000 nm of glomerular basement membrane (GBM) was significantly decreased in diabetic rats compared to control values (17.6 + or - 0.4 vs. 21.9 + or -0.4, P < 0.01), whereas, significant recovery (20.3 + or - 0.7, P < 0.05) was observed after 4 weeks of epalrestat treatment. Urinary albumin excretion (UAE) rate was markedly increased in diabetic rats and the treatment resulted in its significant suppression from diabetic rats. In conclusion, administration of epalrestat to diabetic rats is capable of preventing a reduction in the number of AS in GBM which would ameliorate an increased permeability of the basement membrane leading to albuminuria.

Administration, Oral↗

Thrombospondin modulates adhesion, proliferation and production of extracellular matrix in mesangial cells.

Thrombospondin (TSP) is produced by glomerular mesangial cells and one of the extracellular matrix in the mesangium, whereas the physiological role of TSP in mesangial cells is poorly understood. In order to know whether TSP modulates mesangial cell functions, we investigated the effects of TSP on cell adhesion, proliferation, synthesis of extracellular matrix and serine proteinases in cultured human mesangial cells. The substratum of TSP inhibited cell attachment and spreading in a TSP-dose-dependent manner in mesangial cells. Soluble TSP (50 micrograms/ml) also caused the detachment of fully adherent mesangial cells, whereas TSP less than 10 micrograms/ml did not. [3H]-thymidine incorporation into mesangial cells was dose-dependently reduced by TSP. On the other hand, the production of both fibronectin and type IV collagen from mesangial cells was enhanced by TSP. The incubation of mesangial cells with TSP increased the secretion of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), while plasminogen activator inhibitor-type 1 (PAI-1) decreased. These observations indicate that TSP inhibits cell adhesion and proliferation in cultured human mesangial cells. It is also suggested that TSP influences the metabolism of mesangial matrix by modulating both synthesis and degradation of matrix components. Thus, TSP, may be an important mediator of mesangial cell functions in an autocrine fashion.

Cell Adhesion↗

Clinical effect of the anti-platelet drug, dilazep dihydrochloride, in patients at the microalbuminuric stage of diabetic nephropathy--a multi-center study.

Clinical effects of an anti-platelet drug (dilazep dihydrochloride) in the microalbuminuric stage of diabetic nephropathy were investigated in a multi-center study. Thirty-seven patients with at the microalbuminuric stage of diabetic nephropathy were examined in the present study. They were administered 300 mg/day of dilazep dihydrochloride (Comelian-Kowa) orally for 6 months. Mean values of albuminuria after the administration of dilazep dihydrochloride were significantly decreased compared with the pre-administration values. Urinary NAG activity was improved after this treatment in the microalbuminuric stage of diabetic nephropathy. Furthermore, impairment of renal function was not observed at that stage. It appears that administration of dilazep dihydrochloride from the early stage of diabetic nephropathy may be useful for the improvement of albuminuria and prevention of renal dysfunction.

Adult↗

Protective effect of heparin on renal glomerular anionic sites of streptozotocin-injected rats.

Albuminuria at the rate of 500 micrograms/24 h was observed in rats treated with 50 mg/kg body wt. i.v. streptozotocin (STZ). When STZ was combined with heparin, administered twice daily (250 IU/kg subcutaneous injection) after 24 h following STZ injection, the daily urinary albumin excretion (U-AE) was less than half the amount found in non-heparinized rats (280.3 micrograms/24 h). The observation period in both instances was 8 weeks. When animals were permitted to develop albuminuria over the first 4 weeks, subsequent heparin administration for another 4 weeks lowered U-AE from 500 micrograms/24 h to less than half the amount (227.8 micrograms/24 h). A significantly negative correlation (P < 0.001) existed between U-AE and the number of anionic sites (AS) in the lamina rara externa of glomerular basement membranes, as visualized by electron microscopy. The number of AS per 1000 nm in STZ-injected rats (15.5 +/- 0.2) was lower than that in control rats (23.1 +/- 0.6); however, in heparinized animals, regardless of STZ, the values were not significantly different from normal. Heparin by itself had no effect on the number of AS in normal rats. All STZ-injected animals became hyperglycemic (400-550 mg/dl), but received no insulin. Heparin had no effect on plasma glucose levels. From these results, it is concluded that heparin suppressed both of an increase in U-AE and a decrease in AS count of glomerular basement membranes in STZ-injected rats.

Albuminuria↗

A high concentration of glucose alters the production of tPA, uPA and PAI-1 antigens from human mesangial cells.

To elucidate a role of tPA, uPA and PAI-1 for the development of diabetic glomerulosclerosis, the effect of high glucose concentration on the production of both basal and thrombin-mediated tPA, uPA and PAI-1 antigens from human mesangial cells was investigated. The culture of mesangial cells in the presence of high glucose (33 mM) for 11 days resulted in an increase in the synthesis of tPA and uPA when compared with that in normal glucose concentration (5 mM). In contrast, the cells grown in high glucose produced less PAI-1 than those in normal glucose. Thrombin stimulated dose-dependently the production of tPA, uPA and PAI-1 from the cells grown in either 5 or 33 mM glucose. However, the magnitude of the increase in tPA, uPA and PAI-1 from the cells grown in high glucose was less than that in normal glucose. These results suggest that the plasmin activity in mesangial cells may increase under a high glucose condition, leading to increased proteolysis of mesangial matrix. In addition, either fibrinolysis or proteolysis mediated by thrombin may be altered by high glucose concentration. Therefore, it is postulated that the turnover of mesangial matrix may be increased in diabetic nephropathy.

Cells, Cultured↗

Relationship between urinary excretion of fibronectin degradation products and proteinuria in diabetic patients, and their suppression after continuous subcutaneous heparin infusion.

To explore the possibility that the excretion of urinary fibronectin degradation products (U-FnDP) can be an indicator of the progression of diabetic nephropathy, U-FnDP and urinary protein(U-P) were determined in 64 diabetic patients and 11 healthy volunteers. Moreover, to determine whether continuous subcutaneous heparin infusion (CSHI) reduces elevated U-FnDP and U-P in diabetic patients with persistent proteinuria, heparin sodium was administered as a bolus subcutaneous injection of 5000 IU, followed by subcutaneous infusion of 250 IU/kg per 24 h heparin sodium for 7 days. U-FnDP excretion rate elevated proportionally to the degree of U-P. CSHI reduced significantly elevated U-FnDP from 172.68 +/- 15.79 to 100.04 +/- 14.93 micrograms/24 h (P < 0.01) and U-P from 1.76 +/- 0.13 to 1.20 +/- 0.12 g/24 h (P < 0.01). No significant changes in blood pressure and diurnal mean plasma glucose levels were found. APTT was prolonged with a decrease of AT-III activity during the treatment. These findings suggest that U-FnDP can be one of the indicators which reflects the degree of progression of diabetic nephropathy, and that CSHI may be useful for the normalization of elevated U-FnDP and reduction in U-P in diabetic nephropathy.

Adult↗