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M Ninomiya

Publications and source records attributed to M Ninomiya.

At least 55 records · Page 3Linked to original sources
PubMed1999

A controlled trial of combined therapy for newly diagnosed severe childhood IgA nephropathy. The Japanese Pediatric IgA Nephropathy Treatment Study Group.

The most appropriate treatment for patients with IgA nephropathy is controversial. Treatment with prednisolone, azathioprine, heparin-warfarin, and dipyridamole early in the course of disease may prevent immunologic renal injury in children with severe IgA nephropathy. To determine whether similar results can be obtained with a combination of just heparin-warfarin and dipyridamole, the effects of such treatment were compared to those of treatment with prednisolone, azathioprine, heparin-warfarin, and dipyridamole in 78 children with newly diagnosed IgA nephropathy showing diffuse mesangial proliferation. The patients were randomly assigned to receive either prednisolone, azathioprine, heparin-warfarin, and dipyridamole for 2 yr (group 1) or heparin-warfarin and dipyridamole for 2 yr (group 2). All of the 40 patients in group 1 and 34 of the 38 patients in group 2 completed the trial. The mean urinary protein excretion fell in group 1 patients (P < 0.0001), but remained unchanged in group 2 patients. The mean serum IgA concentration was reduced in group 1 patients (P = 0.0002), but was unchanged in group 2 patients. BP and creatinine clearance were normal at the end of the trial in all but one group 2 patient, who developed chronic renal insufficiency. The percentage of glomeruli showing sclerosis was unchanged in group 1 patients, but increased in group 2 patients (P = 0.006). The intensity of mesangial IgA deposits decreased in group 1 patients (P = 0.02), but remained unchanged in group 2 patients. In conclusion, the present study shows that treatment of children with severe IgA nephropathy with prednisolone, azathioprine, heparin-warfarin, and dipyridamole for 2 yr early in the course of disease reduces immunologic renal injury and prevents increase of sclerosed glomeruli.

Adolescent↗
PubMed1999

[The relationship between the histopathological atypia and expression of beta-catenin in colonic neoplasms resected by endoscopy; comparison with that of p53 protein].

Previous studies have reported predominantly nuclear localization of beta-catenin as a role for colorectal carcinogenesis. In this study, we examined the immunohistochemical expression of beta-catenin and p53 protein in 90 colonic neoplasms {33 carcinomas in adenoma (CIA), 28 high grade adenomas and 29 low grade adenomas}, resected by colonic endoscopy. Out of 33 CIAs. 28 (84.8%) cases showed predominantly nuclear localization of beta-catenin, and that was significantly higher than those of both high grade (46.4%) and low grade (13.8%) adenomas. The positiveness of p53 expression in CIAs was 51.5% (17/33), while 17.9% in high grade and 3.4% in low grade adenomas. However, there was no correlation between both protein expressions (p = 0.3472, chi 2 test). The results suggests that nuclear localization and accumulation of beta-catenin is earlier event than that of p53 mutation in adenoma-carcinoma sequence, and is useful as a marker in histopathological diagnosis for malignant conversion as well as p53.

Adenoma↗
PubMed1998

Sequence of the cDNA of a human dihydrodiol dehydrogenase isoform (AKR1C2) and tissue distribution of its mRNA.

Human liver contains three isoforms (DD1, DD2 and DD4) of dihydrodiol dehydrogenase with 20alpha- or 3alpha-hydroxysteroid dehydrogenase activity; the dehydrogenases belong to the aldo-oxo reductase (AKR) superfamily. cDNA species encoding DD1 and DD4 have been identified. However, four cDNA species with more than 99% sequence identity have been cloned and are compatible with a partial amino acid sequence of DD2. In this study we have isolated a cDNA clone encoding DD2, which was confirmed by comparison of the properties of the recombinant and hepatic enzymes. This cDNA showed differences of one, two, four and five nucleotides from the previously reported four cDNA species for a dehydrogenase of human colon carcinoma HT29 cells, human prostatic 3alpha-hydroxysteroid dehydrogenase, a human liver 3alpha-hydroxysteroid dehydrogenase-like protein and chlordecone reductase-like protein respectively. Expression of mRNA species for the five similar cDNA species in 20 liver samples and 10 other different tissue samples was examined by reverse transcriptase-mediated PCR with specific primers followed by diagnostic restriction with endonucleases. All the tissues expressed only one mRNA species corresponding to the newly identified cDNA for DD2: mRNA transcripts corresponding to the other cDNA species were not detected. We suggest that the new cDNA is derived from the principal gene for DD2, which has been named AKR1C2 by a new nomenclature for the AKR superfamily. It is possible that some of the other cDNA species previously reported are rare allelic variants of this gene.

Base Sequence↗
PubMed1998

[Assessment of saphenous vein graft wall characteristics with intravascular ultrasound imaging].

The wall characteristics of saphenous vein grafts (SVGs) after coronary artery bypass grafting (CABG) were assessed with intravascular ultrasound (IVUS) imaging. Twenty-seven SVGs in 25 patients who had undergone CABG were studied with IVUS in vivo. Ten SVGs excised from 6 patients who had undergone reoperation were studied with IVUS in vitro. The results were compared with the histopathologic findings. IVUS images of four SVGs studied within 1 month after CABG showed a thin and single-layer structure, which was almost identical to the IVUS features of a normal, fresh SVG. In five SVGs studied between 3 months and 1 year after CABG, the wall thickness was increased, and there were hypoechoic areas. In sixteen SVGs studied more than 2 years after CABG, two patterns were noted on IVUS imaging. One pattern was a triple-layer structure of alternating hyperechoic, hypoechoic, and hyperechoic bands seen in the angiographically normal sections of the SVGs. The second pattern was a heterogeneous, echogenic monolayer found in the angiographically irregular and diseased sections of the SVGs. Comparison of the in vitro IVUS images with the histopathology of the SVGs showed a strong correlation between the triple-layer structure and fibrointimal proliferation, and between the heterogeneous monolayer and atherosclerosis. In conclusion, IVUS is useful for assessing SVGs and for long-term qualitative monitoring of vein graft disease after CABG.

Coronary Artery Bypass↗
PubMed1998

Identification of a principal mRNA species for human 3alpha-hydroxysteroid dehydrogenase isoform (AKR1C3) that exhibits high prostaglandin D2 11-ketoreductase activity.

Human 3alpha-hydroxysteroid dehydrogenase exists in four isoforms, which belong to the aldo-keto reductase (AKR) superfamily and are named AKR1C1-AKR1C4. The properties of AKR1C3 have not been fully characterized compared to the other isoforms. In addition, a cDNA that shows more than 99% homology with AKR1C3 cDNA has been cloned from human myeloblasts. We have here expressed and purified a recombinant enzyme (designated as DBDH) from this cDNA. DBDH oxidized xenobiotic alicyclic alcohols and 3alpha- or 17beta-hydroxy-5beta-androstanes, and catalyzed the reversible conversion between prostaglandin D2 and 9alpha,11beta-prostaglandin F2 more efficiently than that of 3alpha- or 17beta-hydroxysteroids:the respective Km values were 0.6 and 6.8 microM, and kcat/Km values were about 1,000 min-1.mM-1. Anti-inflammatory drugs highly inhibited the enzyme. The recombinant AKR1C3 prepared by site-directed mutagenesis of DBDH also showed the same properties as the wild-type DBDH. Analyses of expression of mRNAs for DBDH and AKR1C3 by reverse transcription-PCR indicated that only one mRNA species for DBDH is expressed in 33 human specimens of liver, kidney, lung, brain, heart, spleen, adrenal gland, small intestine, placenta, prostate, and testis. These results suggest that AKR1C3 acts as prostaglandin D2 11-ketoreductase, and that its principal gene in the human has a coding region represented by DBDH cDNA.

3-Hydroxysteroid Dehydrogenases↗
PubMed1997

P/Q-type Ca2+ channel blocker omega-agatoxin IVA protects against brain injury after focal ischemia in rats.

Recently, P/Q-type Ca2+ channels have been shown to be involved in neurotransmission in the central nervous system in mammals. We evaluated the effects of the P/Q-type Ca2+ channel blocker omega-agatoxin IVA (omega-Aga-IVA) on brain edema formation and infarct size determined after 24 h of reperfusion following 1 h of middle cerebral artery (MCA) occlusion in rats. Intracerebroventricular (i.c.v.) treatment with omega-Aga-IVA significantly attenuated the postischemic increase of brain water content. omega-Aga-IVA also significantly reduced the size of the infarct area determined by triphenyltetrazolium chloride staining after 24 h of reperfusion. omega-Aga-IVA (30 pmol, i.c.v.), which exhibited a neuroprotective effect, had no significant effect on the magnitude of intra- and postischemic brain temperature when compared with vehicle-treated rats. This indicates that the postischemic neuroprotective effect of omega-Aga-IVA is produced by a direct and not an indirect effect via hypothermia. These results suggest that P/Q-type Ca2+ channels may be involved in the development of focal ischemic brain injury and that blockers of these channels may be therapeutically useful against ischemic injury.

Animals↗
PubMed1997

Four-channeled aortic dissection and rupture.

A four-channeled aortic dissection is quite rare, which is a highly life-threatening situation predisposing to aortic rupture. We report a successful management of a four-channeled aortic dissection and an aortic rupture in a 59-year-old woman with Marfan's syndrome 11 years after an initial Bentall procedure for DeBakey type I dissection. The total arch and the descending thoracic aorta were replaced under deep hypothermia and circulatory arrest.

Adult↗
PubMed1997

[Preventive concomitant aortic root replacement for annuloaortic ectasia in a patient with Marfan syndrome undergoing mitral valve replacement for mitral regurgitation].

A 28-year-old woman presented with Marfan syndrome combined with severe mitral regurgitation and annuloaortic ectasia. The ascending aorta was dilated to 48 mm in diameter without aortic regurgitation. Considering the increased operative risk due to complication with aortic dissection, simultaneous replacement of the mitral valve and aortic root were performed. Her postoperative course was uneventful. Several options of the surgical treatment for Marfan syndrome are discussed.

Adult↗
PubMed1997

[A prospective controlled study of sairei-to in childhood IgA nephropathy with focal/minimal mesangial proliferation. Japanese Pediatric IgA Nephropathy Treatment Study Group].

To determine the effect of the Chinese herbal medicine, Sairei-to (TJ-114) in children with newly diagnosed IgA nephropathy showing focal/minimal mesangial proliferation, we undertook a prospective controlled study. One hundred and one patients were randomly assigned to receive Sairei-to for 2 years (group 1) or no drug for 2 years (group 2). Forty-six of the 50 patients in group 1 and 48 of the 51 patients in group 2 completed their trial. At entry, the two groups of patients did not differ in the clinical, laboratory and pathologic findings. At the end of the trial, urinary protein excretion and hematuria were significantly reduced in group 1, but were unchanged in group 2. Twenty-one group 1 patients (46%) had normal urine, but only 5 group 2 patients (10%) had normal urine at the end of the trial (p < 0.001). Blood pressure and creatinine clearance were normal at the end of the trial in all but one group 2 patient, who developed chronic renal failure. The present study demonstrates that 2-year Sairei-to treatment early in the course of disease is effective in children with IgA nephropathy showing focal/minimal mesangial proliferation.

Adolescent↗
PubMed1996

Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group.

BACKGROUND: In patients with hepatocellular carcinoma (hepatoma), the rate of recurrent and second primary hepatomas is high despite surgical resection and percutaneous ethanol-injection therapy. We developed an acyclic retinoid, polyprenoic acid, that inhibits hepatocarcinogenesis in the laboratory and induces differentiation and apoptosis in cell lines derived from human hepatoma. In a randomized, controlled study, we tested whether the compound reduced the incidence of recurrent and second primary hepatomas after curative treatment. METHODS: We prospectively studied 89 patients who were free of disease after surgical resection of a primary hepatoma or the percutaneous injection of ethanol. We randomly assigned the patients to receive either polyprenoic acid (600 mg daily) or placebo for 12 months. We studied the remnant liver by ultrasonography every three months after randomization. The primary end point of the study was the appearance of a histologically confirmed recurrent or new hepatoma. RESULTS: Treatment with polyprenoic acid significantly reduced the incidence of recurrent or new hepatomas. After a median follow-up of 38 months, 12 patients in the polyprenoic acid group (27 percent) had recurrent or new hepatomas as compared with 22 patients in the placebo group (49 percent, P = 0.04). The most striking difference was in the groups that had second primary hepatomas--7 in the group receiving polyprenoic acid as compared with 20 in the placebo group (P = 0.04 by the log-rank test). Cox proportional-hazards analysis demonstrated that as an independent factor, polyprenoic acid reduced the occurrence of second primary hepatomas (adjusted relative risk, 0.31; 95 percent confidence interval, 0.12 to 0.78). CONCLUSIONS: Oral polyprenoic acid prevents second primary hepatomas after surgical resection of the original tumor or the percutaneous injection of ethanol.

Aged↗
PubMed1996

Role of platelet-activating factor and thromboxane A2 in radical production during ischemia and reperfusion of the rat brain.

Oxygen radicals produced by activated neutrophils have been involved in brain injury during ischemia-reperfusion. Platelet-activating factor (PAF) is a candidate as one of the mediators of neutrophil activation during cerebral ischemia-reperfusion. Recent evidence indicates that PAF-induced neutrophil activation is mediated by thromboxane A2 (TXA2). To study the role of PAF and TXA2 in radical production during cerebral ischemia-reperfusion, we evaluated the effects of a PAF antagonist, Y-24180, and a TXA2 antagonist, S-1452, on radical formation in rats with 1 h middle cerebral artery (MCA) occlusion. In the present study, we employed a new electron spin resonance (ESR) method coupled with brain microdialysis. The method uses the endogenous ascorbyl radical (AR) concentration as a marker of oxygen radicals and requires no spin-trapping agents. In the vehicle controls, extracellular AR from the ischemic brain cortex decreased during MCA occlusion. Following reperfusion, AR significantly increased at 30 mm and 1 h, returned to near the basal levels at 2 h, and increased again at 24 h after reperfusion. In the rats treated with S-1452 or Y-24180, AR decreased during MCA occlusion to the same extent as in the vehicle control. However, pretreatment with Y-24180 or S-1452 significantly attenuated the increase in extracellular AR after reperfusion, while it exerted no effect on the changes in extracellular ascorbate or tissue pO2 throughout the experimental period. In conclusion, PAF and TXA2 might contribute to cerebral ischemia-reperfusion injury by increasing the generation of oxygen radicals.

Animals↗
PubMed1996

Recurrent exercise-induced acute renal failure in renal hypouricemia.

We describe a male patient with four episodes of acute renal failure after strenuous exercise occurring between the age of 14 and 25 years. He was found to have low serum uric acid (0.4 mg dl-1 after recovery) and high fractional excretion of uric acid. A benzbromarone/pyrazinamide test suggested that renal hypouricemia was due to defective proximal tubular reabsorption of uric acid at a presecretory site. A renal biopsy revealed acute tubular necrosis, a renal computer tomography scan showed patchy contrast enhancement and a treadmill exercise test induced an immediate fall in creatinine clearance. These findings suggest that the cause of acute renal failure was renal vasoconstriction rather than obstruction by uric acid crystals.

Acute Kidney Injury↗
PubMed1996

Efficient oligonucleotide delivery using the HVJ-liposome method in the central nervous system.

We examined the efficiency and intracellular fate of oligodeoxy-nucleotides (ODN) in the central nervous system (CNS) after delivery with a hemagglutinating virus of Japan (HVJ)-liposome vector in vivo and in vitro. In primary cultured granular cells of the rat cerebellum, application of fluorescein isothiocyanate (FITC)-labeled ODN complexed with HVJ-liposomes in vitro resulted in strong fluorescence localized in nuclei that persisted for > or = 2 wk, in contrast to 3 days with ODN alone. In vivo ODN transfer was attempted by different approaches: infusions into the paraventricular nuclei of the hypothalamus and the lateral cerebroventricle. Injection of FITC-labeled ODN into the hypothalamus by the HVJ-liposome method produced a higher concentration and more persistent fluorescence than did injection of ODN alone. Administration of ODN into the lateral cerebroventricle with HVJ-liposomes yielded more conspicuous and prolonged fluorescence in the periventricular layer, predominantly in cell nuclei. Furthermore, the distribution of fluorescent cells was broader with the HVJ-liposome method. These results indicate that the HVJ-liposome method prolongs the half-life of ODN and concentrates them in cell nuclei. Thus it is an efficient method for ODN transfer and holds promise as a gene delivery method in the CNS.

Animals↗
PubMed1996

Left ventricular function following conventional mitral valve replacement in patients with chronic mitral regurgitation.

Conventional mitral valve replacement (MVR) for patients with chronic mitral regurgitation (MR) is usually associated with decrease in left ventricular (LV) ejection fraction (EF). This study investigated the effect of preoperative LV size on LV performance and examined loading conditions before and after conventional MVR. Echocardiographic study was performed on 13 and 9 patients with LV end-systolic dimension of less than 26 mm/m2 (group A) or greater than 26 mm/m2 (group B), respectively. Postoperatively, the LV end-diastolic dimension and EF decreased significantly in both groups. There was a decrease in end-systolic wall stress after MVR. Preoperative LV forward flow estimated by the normalized aortic peak velocity increased significantly in both groups after surgery. The decrease in EF after MVR is not the result of increased systolic loading, and LV performance may not decrease after conventional MVR. Preoperative echocardiographic evaluation can provide important prognostic information in patients with MR undergoing MVR.

Adolescent↗
PubMed1996

[Assessment of left ventricular contractility during intravenous induction of anesthesia by echocardiographic automated border detection].

A recently developed echocardiographic imaging system provides real-time automated border detection (ABD), which enables the measurement of cyclic changes in cavity area, and thus the calculation of changes in intracavity volumes. Eight patients (ASA 1-2) for non-cardiac surgery received thiopental (6 mg.kg-1) and succinylcholine (1 mg.kg-1) intravenously, and the trachea was intubated. The transthoracic echocardiography (TTE) was performed before induction. after induction, and after orotracheal intubation. Left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) were measured with ABD in apical four-chamber view. Mean arterial pressure (MAP) was measured simultaneously. MAP/ESV and MAP/SV were calculated as parameters of left ventricular contractility and left ventricular afterload, respectively. EF decreased significantly (P < 0.05) after induction (50.3 +/- 8.6%) compared with the value before induction (57.9 +/- 8.7%), and decreased further after intubation (41.7 +/- 10.6%). MAP/ESV also decreased significantly (P < 0.05) after induction (2.75 +/- 1.12 mmHg.ml-1) compared with the pre-induction value (3.81 +/- 1.73 mmHg.ml-1), and then returned to the pre-induction level after intubation (3.25 +/- 1.22 mmHg.ml-1). MAP/ SV showed no significant change during induction, and increased significantly (P < 0.05) after intubation (4.60 +/- 1.66 mmHg.ml-1) compared with pre-induction value (2.60 +/- 0.46 mmHg.ml-1). These findings suggest that the significant reduction in EF after induction of anesthesia was due to depression of cardiac contractility by thiopental, and that the further decrease after intubation was due to increase in afterload caused by the stimuli during intubation.

Adolescent↗