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Biomedical subjects

F Ishimoto

Publications and source records attributed to F Ishimoto.

At least 19 recordsLinked to original sources

Visual disturbance due to carotid artery thrombosis in a patient with familial hypercholesterolemia; response to surgical thrombotectomy.

A 48 years-old Japanese man suffered from marked xanthomas on ankles, knees, hand fingers, and foot joints due to insufficient control of serum hypercholesterolemia despite low density lipoprotein (LDL-C) absorptive therapy followed by treatment with potent anti-hypercholesterolemic agents. He had undergone surgical resection of xanthoma on the knee, foot and hand finger joints. Treatment with simvastatin returned the serum total cholesterol levels to nearly normal levels, followed by marked fluctuations. He subsequently experienced transient right-visual disturbance, and roentogenographic examination was performed. The patient was diagnosed as right-common carotid artery thrombosis. After the thrombotectomy of the right-common carotid artery, his visual power was markedly improved.

Carotid Artery Diseases↗

A case of renal amyloidosis associated with hepatic adenoma: the pathogenetic role of tumor necrosis factor-alpha.

We report a case of a 35-year-old man with secondary amyloidosis chiefly involving the kidney and heart. The patient showed severe proteinuria and ischemic heart damage and had hepatic adenoma at the age of 33. Biopsy specimens from the kidney, heart, stomach and rectum showed extensive deposition of amyloid. After the surgical resection of a 300-gram hepatic adenoma, highly elevated c-reactive protein (CRP) levels decreased and the serum amyloid A (SAA) level was completely normalized. Normal liver cells were immunostained with rabbit anti-SAA antibody, but the cells in adenoma tissue and kidney were not. Electron microscopic examination revealed extracellular deposition of amyloid fibrils in the hepatic adenoma and kidney tissue. The concentration of tumor necrosis factor-alpha (TNF-alpha) (312 pg/mg tissue protein) was 7-fold higher in adenoma tissue than in normal liver tissue. Moreover, SAA (2.8 ng/mg tissue protein) was 2-fold higher in normal liver tissue than in adenoma tissue. Since TNF-alpha has been known to induce SAA production in target cells, the present results suggest that the hepatic adenoma produced TNF-alpha, which then caused mainly secondary amyloidosis in the kidney and heart. Currently, 2 years after surgical resection, urinary excretion of protein has been markedly reduced (from 3.5 to 0.8 g/day) and renal and cardiac functions are normal without specific medical treatment.

Adenoma↗

Aminoglycoside-induced viability in cultured PtK1 proximal tubular cell lines.

The cell viability after aminoglycoside administration was evaluated by the determination of adenosine triphosphate (ATP) level and trypan blue exclusion of cultured PtK1 tubular cells. The assay in tubular cells was performed using luciferin-luciferase determined by a chemiluminator. The data are expressed as relative light units per milligram tissue protein. The standard curve of ATP showed a linearity from 0.5 to 2.5 mg/ml ATP as determined by the chemiluminator. The incubation time was steady for ATP production during 90 min after addition of ligand. The optimal incubation time was 60 min. The ATP production in PtK1 cells showed linearity within 10(3) to 5 x 10(6) cells in 200 microliters buffer. Although the magnitude of ATP production in Ptk1 cells was correlated with the cell viability as defined by trypan blue exclusion, the reproducibility of the former was better than that of the latter. The cell viability after application of aminoglycoside showed a decrement in a dose-dependent fashion. Our ATP assay is an excellent tool for determining the cell viability of renal proximal tubules in cases with tubular damage after administration of aminoglycoside antibiotics.

Adenosine Triphosphate↗

Effects of a hepato-protective agent and a hepato-secreting chelator on cadmium-induced nephrotoxicity in Syrian hamsters.

Cadmium (Cd)-induced nephropathy in male Syrian hamsters was treated with D/L-penicillamine (D/L-p) or neomynophagen C (NMC). The subcutaneous injection of CdCl(2), 3 mg/kg, three times a week led to marked renal damage, ie., increased proteinuria and the excretion of urinary N-acetyl-beta-D-glucosaminidase (NAG) as compared with the saline-injected controls. Cd-treated hamsters that were injected intraperitoneally with D/L-p, 0.1 mg/kg, five times a week, showed less renal damage, including a reduction in urinary protein from 3.60 + or - 0.42 to 1.77 + or - 0.7 mg/d. NMC-treated hamsters showed a reduced excretion of NAG (from 1.47 +/ - 0.34 to 0.91 + or - 0.68 u/d). The concentration of Cd in renal cortical tissue was reduced slightly (from 2.78 + or - 0.08 to 2.34 + or - 0.3 mg/g.prot) by NMC treatment, but not by D/L-p. The elevated malondialdehyde (MDA) in renal cortical tissue was unaffected by administering D/L-p or NMC. The concentration of glutathione (CSH) in the renal cortex was not elevated after administering Cd, but the ratio of the reduced to the oxidized GSH was elevated. The Cd induced liver dysfunction, as compared with untreated controls. The dysfunction was improved slightly by NMC administration, but not by that of D/L-p. Changes in renal morphology induced by Cd involving marked degeneration and necrosis of tubules as shown by light microscopy, were unaffected by treatment with D/L-p or NMC. We thus demonstrated the efficacy of D/L-p of NMC in treating the nephropathy induced by Cd in hamsters. The mechanism of therapeutic effect is not known.

Acetylglucosaminidase↗

The influence of aging on renal response to cadmium in Syrian hamsters.

To determine the renal effects of cadmium (Cd) in older animals, we administered subcutaneously a single dose of cadmium, 3.0 mg/kg/BW, to Syrian hamsters aged 16 wk ("young") and 60 wk ("old"). Marked morphologic changes in the kidney and renal dysfunction were observed, especially in the older animals. The concentration of MDA in the renal cortex was significantly increased only in young hamsters treated with cadmium. Concentrations of glutathione (GSH) in the renal cortex were increased in the old hamsters on d 6. Increased levels of renal MDA after cadmium treatment may induce the production of GSH in the kidney thus preventing renal damage. Aging can increase the susceptibility to the renal effects of cadmium.

Acetylglucosaminidase↗

Mizoribine reduces urinary protein excretion in rats given puromycin aminonucleoside.

Mizoribine (MZR), a purine nucleoside antibiotic, is an effective immunosuppressive agent that prevents rejection reactions after kidney transplantation in humans. The present study was performed to examine the effect of MZR on nephrosis produced in rats given puromycin aminonucleoside (PAN). Urinary protein excretion in rats injected with PAN and MZR (PAN + MZR rats) was shown to be reduced significantly in comparison with rats given only PAN (PAN rats). Although mild hypoproteinemia persisted during the experimental period in PAN + MZR rats, no loss of body weight or state of malnutrition was observed. The reduction of serum IgG and C3 was reversed by administration of MZR. Polyethyleinamine (PEI) staining of renal sections showed increased numbers of anionic sites in PAN + MZR rats in comparison with PAN rats, suggesting that MZR improved the permselectivity of the glomerular basement membrane (GBM). Moreover, the production of thromboxane B2 (TxB2) was significantly inhibited in PAN + MZR rats compared with PAN rats. No serious adverse effects of MZR were observed after a large dose of the agent. It is possible that restoration of the charge barrier of the GBM damaged by PAN, or reduction of TxB2 production by the glomeruli may underlie the reduction of protein excretion induced by administration of MZR.

Animals↗

Significance of serum lipase in patients undergoing hemodialysis.

Serum levels of lipase (Lp) during the end of the dialysis showed a significant increase after the administration of heparin in hemodialysis patients. However, serum Lp levels were not increased after the administration of the anti-coagulant nafamostat mesylate in hemodialysis patients. Serum levels of Lp were significantly correlated with serum levels of lipoprotein lipase (LPL), hepatic triglyceride lipase (H-TGL) and nonesterified fatty acid (NEFA) 20 min after the administration of heparin during maintenance hemodialysis. Lp activity did not appear with the NEFA ligand for determining the NEFA activity. Inhibitors of LPL and H-TGL reduced the measured Lp activity in vitro. The main mechanism of elevated measured serum Lp activity in hemodialysis patients was determined to be cross-reactivity with LPL or H-TGL. Furthermore, measurement of Lp may be a method for determining optimal coagulation time in patients with hemodialysis.

Adult↗

Effect of triethylenepentaminehexaacetic acid on the renal damage in cadmium-treated Syrian hamsters.

Cadmium (Cd)-induced nephropathy was treated by triethylenepentaminehexaacetic acid (TTHA) in male Syrian hamsters. Hamsters injected three times a week with 3 mg/kg body wt CdCl2 showed proteinuria, urinary N-acetyl-beta-D-inglucosaminidase (NAG), and fractional excretion of sodium (FENa) when compared to saline-injected control. Cd-treated hamsters injected ip with TTHA 10 mg/kg body wt five times a week showed reduction of renal damage, including reductions in urinary protein (from 6.7 +/- 2.2 to 4.3 +/- 0.5 mg/d) and NAG (0.17 +/- 0.06 to 0.04 +/- 0.02 U/d). Urinary excretion of Cd was significantly increased (from 87 +/- 51.3 to 3052 +/- 1485 mg/L) by TTHA administration. Cd concentration in renal cortical tissue was slightly reduced (26.4 +/- 3.0 to 21.8 +/- 2.7 mg/g. protein). Excretion of malondialdehyde (MDA) was increased only in Cd-injected hamsters (to 2.1 +/- 1.6 nM/L), and elevated MDA in renal cortical tissue was not reduced by the administration of TTHA (1041 +/- 105 vs 1104 +/- 358 nM/g protein). Glutathione (GSH) concentration in the renal cortex was significantly elevated after Cd administration and further increased after TTHA administration (5.5 +/- 2.1 to 9.8 +/- 2.0 micrograms/50 mg protein). There were no marked effects on creatinine clearance (Ccr) and hematocrit. Moreover, renal morphological changes were improved significantly by treatment with TTHA. We demonstrated the efficacy of TTHA in the treatment of Cd-induced nephropathy in hamsters. Although the precise mechanism of the TTHA effects on Cd-induced nephropathy has not been elucidated, it might involve GSH reducing the elevated MDA concentration in renal tissue.

Animals↗

Effect of pentoxifylline on CdCl2-induced nephrotoxicity in the rat.

We developed a rat model of cadmium (Cd)-induced nephrotoxicity and tried to prevent renal damage by treating the animals with pentoxifylline (PTX). Sprague-Dawley (SD) rats given CdCl2 3.0 mg/kg sc, daily for 2 wk showed evidences of renal proximal tubular damage, including significant increases in urine volume, urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and fractional excretion of sodium (FENa), and a decrease in the percentage of tubular reabsorption of phosphate (%TRP). PTX significantly improved the urinary excretion of NAG and %TRP. Urine volume was increased threefold in the CdCl2-treated rats and fivefold in the Cd + PTX-treated rats, respectively, as compared with saline-treated control. Total protein, AAP, and creatinine clearance, showed no change after PTX administration. Concentration of Cd in the renal cortex was three times higher than that in the renal medulla, but there were no differences in concentration between the Cd-treated rats and the Cd + PTX-treated rats. Our animal model was useful in studying the renal tubular damage produced by cadmium. PTX appears useful for improving the nephrotoxicity of Cd.

Acetylglucosaminidase↗

Characteristics of anemia in patients with nephrotic syndrome.

Primary nephrotic syndrome can, although infrequently, cause severe anemia. However, the mechanisms of the anemia remain unknown. We investigated the mechanism of anemia in nephrotic syndrome by measuring parameters of nephrotic syndrome and anemia in 44 nephrotic patients (male: female; 21:23, average age; 43.6 +/- 20.3 years). Nephrotic patients had significantly lower hematocrits than did healthy controls (43.3 +/- 3.7 vs. 46.8 +/- 3.4% in males, 37.4 +/- 3.5 vs. 40.8 +/- 2.8% in females). Serum erythropoietin (Epo) concentrations were correlated inversely with hemoglobin (Hb), hematocrit (Hct), and red blood cell corpuscle (RBC) counts. Furthermore, serum Epo correlated with the serum iron concentration, but not with the other parameters, such as reticulocytes, serum protein and proteinuria. However, the maximum Epo concentration was less than 100 mU/ml in spite of severe anemia, and this was thought to be inappropriate. On the contrary, urine Epo was not detected by the same method of serum Epo determination in spite of aggressive dialysis with distilled water. When four patients with severe anemia were subcutaneously administered recombinant Epo 6,000 unit two times a week, they showed marked improvement in Hb/Hct/RBC. The precise mechanism of anemia in NS was not elucidated by this investigation, but further study should clarify the causes of the inappropriately low concentration of serum Epo in patients with primary nephrotic syndrome.

Adult↗

[Pregnancy and delivery in patients with lupus nephritis].

To investigate some of the problems associated with pregnancy and delivery in lupus nephritis, 13 pregnancies in 7 patients with inactive lupus nephritis and 5 pregnancies in one patient with primary antiphospholipid syndrome (PAPS) were compared with 36 pregnancies in 22 patients with primary nephrotic syndrome (NS). Furthermore, a follow-up survey during 0-8 years was made with 12 babies born to mothers with lupus nephritis. Some pregnancies during lupus nephritis were accompanied by disease exacerbation and worsening of renal function. There was a higher incidence of babies born with a low birth weight, and the incidences of fetal loss or premature birth and toxemia were higher in lupus nephritis than in NS. The number of babies with a low birth weight was significantly higher in patients with pregnancy-induced hypertension or skin lesion due to lupus erythematosus. The presence of antibodies against SSA/RO in the mother was associated with the occurrence of congenital heart block. Birth weight of babies born to mothers with lupus nephritis was low, but there were no statistical differences in the growth of babies after 6 months of age compared with babies born to normal women.

Adult↗

Effect of Sairei-to on gentamicin nephrotoxicity in rats.

The effect of Sairei-to, an oriental traditional medicine, against gentamicin nephrotoxicity was examined in gentamicin nephrotoxicity rat models. Gentamicin nephrotoxicity was induced by s.c. injection of gentamicin (100 mg/kg/day, for 3 days) in male Sprague-Dawley rats. Renal functions of two rat groups were compared, one eating rat chow containing 2.5% Sairei-to, the other eating normal rat chow. Sairei-to administration reduced the increase of urinary N-acetyl-beta-D-glucosaminidase (NAG) and protein excretion, and decreased creatinine clearance induced by gentamicin. Gentamicin increased renal cortical malondialdehyde (MDA) concentration in normal diet group but not in the Sairei-to diet group. The renal cortical gentamicin concentration was not different between the two groups. In conclusion, Sairei-to shows reno-protective action against gentamicin nephrotoxicity, possibly through its anti-oxidant action.

Acetylglucosaminidase↗

A case of pheochromocytoma of the urinary bladder in a long-term hemodialysis patient.

The development is reported of a pheochromocytoma of the urinary bladder in a 33-year-old patient with systemic lupus erythematosus who had undergone long-term hemodialysis. A hypertensive episode followed by defecation was demonstrated by the monitoring of blood pressure with a portable automated sphygmomanometer without elevation of plasma catecholamines. The tumor was surgically removed and normalization of the patient's blood pressure followed. Thus, monitoring of blood pressure for 24 h proved useful for the diagnosis of pheochromocytoma and, in particular, of paroxysmal hypertension.

Adult↗

Lactic dehydrogenase anomaly in a patient with chronic renal failure.

A 67-year-old man with chronic renal failure (CRF) was defined to have lactic dehydrogenase (LDH)-immunoglobulin A (IgA) complex, the so-called "LDH anomaly", in his serum and pleural effusion. He was found to have a pleural effusion on the right side during maintenance dialysis at a satellite hospital. A LDH-IgA complex was detected in the serum and pleural effusion by the method of current electrophoresis. The immunoglobulin class was found to be IgA (K) by counter immunoelectrophoresis. LDH anomaly is extremely rare in patients with CRF; the clinical significance of this substance in serum and pleural effusion remains unclarified.

Aged↗

Pravastatin administration to hyperlipidemia in patients with nephrotic syndrome.

We treated hyperlipidemia in patients with nephrotic syndrome (NS) using pravastatin for more than one year. There were 7 cases consisting of 3 with minimal change nephrotic syndrome (MCNS), 1 with focal glomerulosclerosis (FGS), 1 with proliferative glomerulonephritis (PGN), 2 with membranous glomerulonephritis (MGN) and 1 of unknown origin. Three cases consisted of frequent relapsers, and 4 were steroid-resistant. Six randomly selected age- and sex-matched nephrotic patients were used as controls. The daily excretion of proteinuria was not decreased after pravastatin treatment, but, the serum albumin rose from 3.1 +/- 1.1 to 3.4 +/- 1.0 mg/dl. The serum total cholesterol level was significantly reduced from 401 +/- 174 mg/dl to 331 +/- 103 mg/dl in spite of an absence of marked change in the control group. However, there were no significant changes in the triglyceride and lipoprotein levels. The atherogenic index was 7.1 +/- 3.7 before and 2.8 +/- 1.7 after pravastatin treatment, respectively. Improvement of renal function defined by delta decrement of renal function per year (0.08 +/- 0.06 vs. 0.12 +/- 0.26) was observed after the discontinuation of pravastatin administration in 3 out of 4 intractable cases. We conclude that pravastatin has a potent effect in reducing the serum level of total cholesterol, but not triglyceride in NS. Furthermore, pravastatin can induce renal dysfunction especially in patients with intractable nephrotic syndrome.

Adult↗

Characteristics of cadmium-induced nephrotoxicity in Syrian hamsters.

Male Syrian hamsters were used to evaluate cadmium (Cd)-induced nephrotoxicity. Furthermore, they were treated with polyaspartic acid (PAA) in an attempt to prevent renal damage due to Cd. To induce renal proximal tubular damage, the hamsters were administered a single subcutaneous injection of cadmium chloride (CdCl2) at the dose of 3 mg/kg body weight. Within 24 hours, they exhibited significant proteinuria and an increased urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG). Renal histological changes consisted of degenerative changes in renal tubule cells, irregularly shaped nuclei with marginated chromatin and rounded mitochondria. The administration of PAA did not improve creatinine clearance or urinary protein excretion. The concentration of Cd in the renal tissue showed a gradual increase on day 3 following cadmium exposure. Cadmium nephrotoxicity appears to be more severe in Syrian hamsters than in rats or mice. Thus, this animal model appears to be excellent for studying Cd-induced nephrotoxicity.

Animals↗

Disseminated intravascular coagulation syndrome in anorexia nervosa.

A 15 year old boy with anorexia nervosa developed disseminated intravascular coagulation syndrome (DIC). Because of severe cachexia he had been admitted to the Shimane Prefectural Central Hospital. During his hospitalization he developed generalized massive ecchymosis. Laboratory data revealed not only DIC but also multiple organ complications. The patient was treated intravenously with FOY (gabexate mesilate, a protease inhibitor), heparin, a transfusion of fresh frozen plasma, antithrombin III concentrates and platelets. Intravenous hyperalimentation was also administered. The laboratory data, the general condition and the emotional state of the patient improved remarkably. We emphasize the importance of keeping in mind coagulopathy as a complication in anorexia nervosa.

Adolescent↗