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Biomedical subjects

I Ohno

Publications and source records attributed to I Ohno.

At least 73 records · Page 4Linked to original sources
PubMed1995

[Effect of cyclosporin monotherapy on proteinuria in a patient with membranoproliferative glomerulonephritis].

A-34-year-old man with a 16-year history of proteinuria was successfully treated with cyclosporin A (CsA). He was diagnosed as having membranoproliferative glomerulonephritis (MPGN) by renal needle biopsy and was treated with dipyridamole. In July 1992, he was readmitted for the treatment of anasarka. Although conventional predonisolone was administered for 5 months after one cycle of methyl-predonisolone pulse therapy, his nephrotic state did not improve. Immediately after the cessation of this treatment, he was given CsA 3 mg/kg/day. A marked reduction in proteinuria and edema occurred during the use of CsA for 6 months, with a reduction in the fractional excretion of protein. The nephrotic condition of this patient was subsequently stable without massive proteinuria despite the discontinuation of CsA at least for several months. These findings suggest that CsA monotherapy may be useful in patients with MPGN and steroid-resistant nephrotic syndrome.

Adult↗
PubMed1994

TNF-alpha production by eosinophils in upper airways inflammation (nasal polyposis).

TNF-alpha is a cytokine with a wide spectrum of proinflammatory activities. Nasal polyps (NP), which occur in association with allergic rhinitis and asthma, are characterized by a marked infiltration of activated eosinophils, epithelial damage, and varying degrees of stromal fibrosis. By using Southern blot analysis after a reverse transcription-PCR, we detected a signal specific for TNF-alpha mRNA in five of seven NP samples, but not in control nasal mucosal samples. With in situ hybridization, we detected cells expressing mRNA specific for TNF-alpha in eight of thirteen NP samples, but not in four control samples. Counterstaining with chromotrope 2R demonstrated that virtually all cells expressing TNF-alpha message were eosinophils. The ratio of eosinophils expressing TNF-alpha to the total number of eosinophils varied greatly among tissues; as an average, we observed 24% TNF-alpha-positive eosinophils. Using a mAb against human TNF-alpha, we demonstrated TNF-alpha localization in 12 NP tissues (48.8 +/- 16.5 positive cells/mm2) but not in three control samples. Morphologically, cells localizing TNF-alpha were both mononucleated and polynucleated with only a small number of eosinophils, as determined by aniline blue counterstaining. Studies of purified blood eosinophils from a patient with hypereosinophilic syndrome and from four healthy donors indicated that TNF-alpha is produced, but rapidly secreted, so that TNF-alpha mRNA-positive cells contain little detectable protein. Furthermore, cells that retain detectable TNF-alpha may not contain sufficient TNF-alpha mRNA to be detected by using the probe developed for our studies. Together, these findings identify a novel mechanism by which eosinophils may contribute to mucosal inflammation and provide an approach to future investigation.

Eosinophilia↗
PubMed1994

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↗
PubMed1994

Diminished heat shock protein 70 mRNA induction in aged rat hearts after ischemia.

Vulnerability of aged hearts to ischemia may be due to defects in protective mechanisms provided by heat shock proteins (HSPs). To determine whether there is a defect in the induction of HSPs by ischemia in old hearts, HSP72 and HSP73 (inducible and constitutive HSP70, respectively) mRNA induction was examined in young (2-mo-old; n = 36) and old (18-mo-old; n = 32) rat hearts. Transient (10- or 20-min) ischemia was applied by tightening a snare placed around left coronary arterial branches 3 days before examination to avoid the effect of operation on induction. HSP72 mRNA was induced markedly in young hearts after 10-min ischemia, peaked at 2 h, but was induced only slightly in old hearts. HSP73 mRNA was also induced in young hearts, peaked at 4 h, but was not induced in old hearts. The mRNAs were markedly induced in old hearts as well after 20-min ischemia, which was accompanied by the induction of HSP72 protein. Thus the age-related modulation of HSP72 and HSP73 mRNAs suggests a defective sensing mechanism for ischemia in old hearts.

Aging↗
PubMed1994

Quinine inhibits production of tumor necrosis factor-alpha from human alveolar macrophages.

Although tumor necrosis factor-alpha (TNF-alpha) produced by alveolar macrophages plays a key role in acute and chronic inflammatory states of the lung, the regulation of TNF-alpha synthesis remains to be elucidated. Recently, a K channel blocker, quinine, has been reported to inhibit cell proliferation and protein synthesis in lymphocytes, implicating physiologic roles for K channels in lymphocytes. The effect of quinine on protein synthesis in human alveolar macrophages, however, has not been determined, although alveolar macrophages have been reported to have two types of K channels. Therefore, we investigated the effect of quinine on TNF-alpha production from human alveolar macrophages. The production of TNF-alpha was induced by lipopolysaccharide (LPS) stimulation. We obtained the following results. First, LPS induced time-dependent activation of both types of K channels. Second, quinine inhibited TNF-alpha release in a dose-dependent fashion at concentrations of 50 to 200 microM, concentrations capable of blocking both types of K channels, with no appreciable reduction of phagocytosis of latex beads. Third, the compound remarkably inhibited the expression of TNF-alpha mRNA without any appreciable effect on the expression of beta-actin mRNA. These results indicate that both types of K channels are activated by stimulation with LPS and that quinine, at concentrations required to inhibit K channels, specifically blocks TNF-alpha production of human alveolar macrophages at the level of gene transcription.

Adult↗
PubMed1994

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↗
PubMed1994

[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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

Eosinophils in chronically inflamed human upper airway tissues express transforming growth factor beta 1 gene (TGF beta 1).

Transforming growth factor beta (TGF beta) is a multifunctional protein which has been suggested to play a central role in the pathogenesis of chronic inflammation and fibrosis. Nasal polyposis is a condition affecting the upper airways characterized by the presence of chronic inflammation and varying degrees of fibrosis. To examine the potential role of TGF beta in the pathogenesis of this condition, we investigated gene expression and cytokine production in nasal polyp tissues as well as in the normal nasal mucosa. By Northern blot analysis using a porcine TGF beta 1 cDNA probe, we detected TGF beta 1-specific mRNA in nasal polyp tissues, as well as in the tissue from a patient with allergic rhinitis, but not in the normal nasal mucosa. By the combination of tissue section staining with chromotrope 2R with in situ hybridization using the same TGF beta 1 probe, we found that approximately 50% of the eosinophils infiltrating the polyp tissue express the TGF beta 1 gene. In addition, immunohistochemical localization of TGF beta 1 was detected associated with extracellular matrix as well as in cells in the stroma. These results suggest that in nasal polyposis where eosinophils are the most prevalent inflammatory cell, TGF beta 1 synthesized by these cells may contribute to the structural abnormalities such as stromal fibrosis and basement membrane thickening which characterize this disease.

Chronic Disease↗
PubMed1992

Renal artery thrombosis in a patient with membranous glomerulonephritis.

A 64-year-old man with renal artery thrombosis (RAT) associated with nephrotic syndrome (NS) is reported. Although this patient was diagnosed as NS due to membranous glomerulonephritis (MGN) and treated with prednisolone, RAT occurred as a result of unknown mechanisms and caused mild renal dysfunction. Creatinine clearance has been about 70 ml/min for 9 years since the onset of RAT. The renal scintigraphic image has not changed since the onset. NS responded to prednisolone therapy initially and at the time of the relapse. Recent data have shown proteinuria levels of less than 0.2 g/day.

Glomerulonephritis, Membranous↗