Biomedical subjects

H Ohtani

Publications and source records attributed to H Ohtani.

At least 199 records · Page 11Linked to original sources

PubMed1996

Increased expression of a brain/embryo-type myosin heavy chain isoform (MIIB2) in mesangial proliferative glomerulonephritis.

Proliferation of mesangial cells is frequently found in glomerulonephritis, such as IgA glomerulonephritis. Recent reports suggest that a brain/embryo-type myosin isoform (MIIB2) is involved in cell proliferation. We have studied the expression of MIIB2 in renal biopsy samples from patients with various renal diseases and in the renal tissues from the rat model of mesangial proliferative glomerulonephritis induced with anti-Thy 1.1 antibody. Immunohistochemical analysis of the biopsy samples using an anti-brain-type myosin heavy chain-specific monoclonal antibody (HBM1) indicated that 92% of the samples from patients with IgA glomerulonephritis contained a significant population of mesangial cells that reacted with the antibody. Most of the samples from patients with other types of proliferative glomerular diseases also contained HBM1-reactive mesangial cells, while none of the samples from patients with non-proliferative glomerular diseases contained a significant population of HBM1-reactive mesangial cells. The expression of a brain/embryo-type myosin heavy chain isoform (MIIB2) in the mesangial cells began at five days after injection of anti-Thy 1.1 antibody and peaked at the tenth day. On the other hand, the expression of the proliferating cell nuclear antigen in the mesangial cells was induced at two days after injection of anti-Thy 1.1 antibody and was maximal at the fourth day. These results indicate that the expression of the MIIB2 isoform by mesangial cells is accelerated in proliferative glomerulonephritis and suggest that the myosin isoform is involved in the phenotypic transformations of the glomerular tissues rather than in the cell proliferation.

Adolescent↗

PubMed1996

Mesodermal- vs. neuronal-specific expression of MafK is elicited by different promoters.

BACKGROUND: Small members of the Maf family of transcriptional regulatory proteins share similar basic-leucine zipper domains but have no intrinsic ability to activate transcription. One member of the family (MafK) has been shown to mediate both negative and positive regulation: in addition to forming a homodimer which represses transcription, MafK can also form a heterodimer with p45 (the large subunit of erythroid transcription factor NF-E2) to activate transcription. RESULTS: We examined the expression of mafK during murine development. mafK mRNA was first detected in 7.5 days post coitus (dpc) embryonic mesoderm and persisted in mesodermal derivatives (mesenchymal and haematopoietic cells) thereafter. However, around 13 dpc mafK was also strongly induced in neuronal cells and it is broadly expressed in neurones in postnatal mouse. The neuronal expression of mafK is directed by a distinct promoter located 6 kbp 3' to the mesoderm-specific promoter. mafK in neurones associates with a different partner molecule from p45. In transgenic mice, a regulatory domain in the immediate vicinity of the mesodermal promoter was found to direct mesenchymal, but not haematopoietic, expression of mafK. CONCLUSION: The cell type- and developmental stage-specific expression of MafK suggests that, in addition to its demonstrated role in erythroid transcriptional regulation, MafK also plays an important regulatory role in other mesodermally and neuroectodermally derived tissues during mouse embryonic development.

Animals↗

PubMed1996

Lymphedema due to chronic penile strangulation: a case report.

A 62-year-old man was admitted with swelling of the penis caused by long term use of a penis enlarging ring. For the previous 20 years, he had noticed small pruritic nodules on his penis. He had no micturitional or ejaculatory impairment. The penis had a diameter of 6 cm, a length of 10 cm, and was covered with thickened skin. The penis and the scrotal skin were covered with scattered, small, hemispheric nodules and papules ranging in size from 2 mm to 1 cm. Pathologic examination of the biopsied specimen from a nodule revealed enlargement of the lymphatic vessels of the dermis and fibrosis. This was compatible with lymphedema due to chronic strangulation by the ring. Scar resection and full thickness skin grafting was performed to prevent malignant changes in the lesions.

Chronic Disease↗

PubMed1996

Co-expression of TNF alpha and IL-1 beta in human acute pulmonary fibrotic diseases: an immunohistochemical analysis.

To clarify the involvement of TNF alpha and IL-1 beta in the initiation of fibrotic lung diseases, their localization was examined by immunohistochemistry. Fibrotic lung diseases observed were classified into acute and old pulmonary fibrotic changes. The acute fibrotic changes included adult respiratory distress syndrome, acute interstitial pneumonia and idiopathic pulmonary fibrosis with acute exacerbation. Acute pulmonary fibrotic changes histopathologically corresponded to a mixture of the exudative and proliferative phases of diffuse alveolar damage. Both TNF alpha and IL-1 beta were positive in the alveolar macrophages and proliferating type II pneumocytes in acute fibrotic changes. In contrast, positive cells for TNF alpha and IL-1 beta were sparse in the areas of old fibrotic change and in the normal tissue. These findings suggest that TNF alpha and IL-1 beta play an important role in the initiation of pulmonary fibrotic responses and in the architectural remodeling, irrespective of the etiology of fibrotic lung diseases.

Acute Disease↗

PubMed1996

Malignant fibrous histiocytoma of the esophagus.

A 78-year-old man presented with an esophageal polyp that was confirmed by immunohistochemistry and electron microscopy to be malignant fibrous histiocytoma. The tumor was comprised of a proliferation of spindle-shaped cells admixed with bizarre giant cells. These tumor cells were immunoreactive for smooth muscle actin, vimentin, alpha-1-anti-chymotrypsin and CD68. Electron microscopic examination revealed the myofibroblastic and histiocytic features of the tumor cells. No elements of epithelial or myogenic differentiation were found in the tumor. Malignant fibrous histiocytoma of the esophagus is extremely rare, with 10 cases being documented so far in the literature. The differential diagnosis of pleomorphic tumors of the esophagus is discussed.

Aged↗

PubMed1996

Spontaneous rupture of non-aneurysmal ascending aorta.

Two autopsy cases with pericardial tamponade and spontaneous rupture of non-aneurysmal ascending aorta are described. In case 1, no apparent predisposing factor was clinically noticed in a 74 year old male patient, but postmortem examination revealed laceration of the ascending aorta associated with aortic valvular deformity and slight dilatation of the ascending aorta. In case 2, a 61 year old man, a mild to moderate grade of aortic regurgitation was noticed clinically 5 months before death. Postmortem examination revealed a slight dilatation of the aortic annulus and post-valvular portion of the ascending aorta. These two cases emphasize the clinical significance of aortic valvular disease with subsequent disordered blood flow, even when asymptomatic, as a potential causative factor for spontaneous rupture of the ascending aorta.

Aged↗

PubMed1996

Toxicodynamic analysis of cardiac effects induced by four cholinesterase inhibitors in rats.

The cardiac effect of edrophonium (2-20 mumol kg-1), pyridostigmine (0.5-5 mumol kg-1), neostigmine (0.05-0.5 mumol kg-1) and ambenonium (0.02-0.3 mumol kg-1) was investigated after intravenous administration to rats. For pyridostigmine and neostigmine, the heart rate decreased in a dose-dependent manner, and then gradually recovered to the basal level at about 10 min. Rapid decrease of heart rate was observed after edrophonium and ambenonium administration, and rapid recovery to the basal level within 1 min. For ambenonium, a dose-dependent tachycardiac response was observed. The time-course of heart rate change was analysed by the effect-compartment model. Significant correlation was observed between bradycardiac EC50 values obtained by effect-compartment model analysis and inhibitory constant (Ki) to acetylcholinesterase in-vitro, suggesting that the bradycardiac response was induced by inhibition of this enzyme and following elevation of acetylcholine concentration in the synaptic elect. On the other hand, the tachycardiac EC50 values of edrophonium and ambenonium based on the effect-compartment model analysis were similar to dissociation constants (Kd) of these drugs to muscarinic receptors in-vitro, suggesting that the tachycardiac activity of these drugs may be associated with antagonistic activity to postsynaptic muscarinic receptors. We conclude that, clinically, edrophonium and ambenonium are safer drugs than pyridostigmine and neostigmine, at least as regards muscarinic side-effects, including bradycardia.

Animals↗

PubMed1996

Pharmacokinetic-pharmacodynamic analysis of the electrocardiographic effects of terfenadine and quinidine in rats.

In establishing a method of electrocardiographic (ECG) measurement for investigating drug-induced ECG changes, we examined the ECG effects and pharmacokinetics of terfenadine (TFN) and quinidine (QND) in rats. The time profiles of the plasma concentration and ECG parameters, such as the QT interval determined from limb lead II (QT-II) and the precordial chest lead (QT-V), heart rate and PR interval, were examined during constant intravenous infusion of TFN (5 or 15 mg/kg/h) or QND sulfate dihydrate (10 or 30 mg/kg/h). Both agents provided significant and concentration-dependent QT prolongation. The plasma concentrations (C10), where 10 ms of QT prolongation was observed, were 1.03 microM for TFN and 5.12 microM for QND, respectively. The calculated plasma unbound concentration of C10 (C10-f) was 10.3 nM for TFN and 3.82 microM for QND, which coincides with previously reported in vitro values of IC50 for potassium channels. The drug-induced QT prolongation was quantitatively reproduced in rats within the clinical concentration range. The usefulness of our methodology for the evaluation of arrhythmogenic hazards of the drugs was also demonstrated.

Animals↗

PubMed1996

Lack of potentiation with felbinac patch on the convulsive toxicity of enoxacin in rats.

We investigated the possible potentiation of the convulsive toxicity of enoxacin (ENX) by the concomitant topical application of a felbinac (FLB) patch in rats. A felbinac patch (Seltouch; 0.5%, 3 cm x 4 cm) was attached on the back of rats where their hair has been removed. ENX was infused from the left jugular vein at 8 h after the application of FLB patch under an unanesthetized and unstrained condition. Blood, CSF and brain samples were collected at the occurrence of convulsion, and ENX concentrations of each part were determined. As a result, no significant potentiation by FLB patch was found in the onset time of convulsion or in the ENX concentration of each part. Moreover, based on the assumption that there are no inter-species differences in ENX concentration in the brain at the occurrence of a convulsion (Cbr), the predicted plasma ENX concentration required to elicit convulsions in humans, which was estimated from the Cbr and Kp value of ENX in the brain of rats, was 20 times higher than the therapeutic plasma level.

Administration, Cutaneous↗

PubMed1996

Late onset bone marrow transplant nephropathy.

We report a patient who exhibited proteinuria and renal failure 93 months after receiving an allogeneic bone marrow transplantation (BMT) from his HLA-identical brother. A renal biopsy specimen revealed segmental sclerosis, mesangiolysis, subendothelial lucency in the glomeruli, fibrosis and small round cell infiltration in the interstitium, and hyaline droplets in the intimal spaces of arterioles and small arteries. These histological findings were consistent with late onset BMT nephropathy. This nephropathy may represent a more serious problem in the near future in Japan, since the number of BMT performed has been increasing with the establishment of a bone marrow bank.

Adult↗

PubMed1996

Clinicopathological analysis and therapy in hepatitis C virus-associated nephropathy.

We analyzed the clinicopathological features and therapy in 19 patients with kidney disease accompanied by hepatitis C viral infection, including 12 patients with mesangial proliferative glomerulonephritis (including eight with IgA nephropathy), six with membranoproliferative glomerulonephritis (MPGN), and one with membranous nephropathy. Persistent hematuria and/ or proteinuria (10 patients) was the most common finding, followed by nephrotic syndrome (8 patients). Cryoglobulinemia was detected in six of 19 patients examined (four of six patients with MPGN). Analysis of hepatitis C virus (HCV)-RNA genotype in 13 patients revealed that nine of them had type II genotype. All four patients with MPGN, who had serum positive for HCV-RNA, had type II genotype. Five patients were treated with interferon-alpha (IFN-alpha) without a demonstrable effect on renal impairment, whereas five of 11 patients treated with steroids showed improvement of the renal impairment. During the course of steroid therapy, the serum titer of HCV-RNA decreased in 5 of 7 patients. These observations suggest that HCV infection may be associated with several forms of glomerulonephritis. Type II HCV-RNA may have a strong association with MPGN in Japan. Steroid therapy is not contraindicated in patients with HCV-associated nephropathy if they are resistant to IFN-alpha treatment.

Adolescent↗

PubMed1996

New method for assaying free and total cholesterol in cultured cells by high-pressure liquid chromatography.

We developed a simple, sensitive and accurate method for assaying cellular free and total cholesterol by monitoring 4-cholesten-3-one, a conversion product of the cholesterol oxidase-catalyzed oxidation of the free cholesterol that has a strong chromophoric alpha, beta-unsaturated ketone at 240 nm, using a high-pressure liquid chromatographic system. This method measured picomole quantities of free and total cholesterol and precisely determined their concentrations in cells (10(4) range) in culture using 7 beta-hydroxycholesterol as an internal standard.

Biomarkers↗

PubMed1996

[Nucleotide sequences at intron 6 and exon 7 junction of fibroblast growth factor receptor 2 and rapid mutational analysis in Apert syndrome].

Apert syndrome, acrocephalosyndactyly Type I, is an autosomal dominant craniosynostosis comprising acrocephaly, facial dysmorphism and severe syndactyly of the hands and feet. Missense mutations at codons 252 and 253 at 5'-end on exon 7 of fibroblast growth factor receptor (FGFR) 2 have been identified in a large number of patients with Apert syndrome. In this study, nucleotide sequences on the intron 6 were determined by vector ligation-PCR and direct sequencing. Five DNA samples from sporadic Apert syndrome were examined by non-RI SSCP and direct sequencing using a primer pair of intron 6 and exon 7. All cases of the syndrome showed abnormal banding pattern in the SSCP and missense mutations from Ser to Trp at codon 252 of the FGFR2 gene. The non-RI SSCP and direct sequencing of the FGFR2 exon 7 from genomic DNAs may be a useful and rapid molecular means for clinical diagnosis of Apert syndrome.

Acrocephalosyndactylia↗

PubMed1996

[Frequent missense mutations of fibroblast growth factor receptor (FGFR) gene families in craniofacial syndromes in Japanese patients].

Craniofacial syndromes, including Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome, Apert syndrome and achondroplasia, have been indicated that syndromes were associated with mutations of fibroblast growth factor receptor (FGFR) gene families. In this report, seven Japanese patients with craniofacial syndromes, three Crouzon syndromes and four achondroplasias, were analyzed on FGFR2 and FGFR3 genes by non RI-SSCP (single strand conformation polymorphisms) and direct sequencing. Missense mutations of the FGFR3 exon 10, at codon 380 in two sporadic cases and codon 375 in two familial cases, were detected in all cases of achondroplasia. Mutations of the FGFR2 were noted in Crouzon and Apert syndromes. One of three Crouzon syndromes has a missense mutation at codon 342 on exon 9. Highly frequent mutations were clustered within some localized regions of the FGFR genes in craniofacial syndromes. Alterations in these receptors due to missense mutations would thus appear closely involved in pathogenesis of craniofacial syndrome. The non RI-SSCP and direct sequencing of the FGFR genes, shown in this report, may be an appropriate approach for diagnosis of these syndromes with extensive clinical application.

Base Sequence↗

PubMed1996

Immunophenotypic characterization of Epstein-Barr virus-associated gastric carcinoma: massive infiltration by proliferating CD8+ T-lymphocytes.

A subset of gastric carcinoma carries Epstein-Barr virus (EBV). The immunophenotypic features of EBV-associated (EBV+) gastric carcinoma, which we have analyzed using 25 EBV+ cases, remain unclear. Frozen tissue samples were stained with antibodies to various immune cell markers. To evaluate the proliferative activity of CD8+ cells, we performed CD8/Ki-67 double staining on paraffin-embedded sections. The results were compared with those in EBV-negative (EBV-) gastric carcinomas. All EBV+ and EBV- gastric carcinoma cells expressed major histocompatibility complex class I, whereas major histocompatibility complex class II expression in tumor cells was more prominent in EBV+ cases. Intercellular adhesion molecule-1 and Fas/APO-1 expression was largely restricted to EBV+ cases. The lymphocytes that infiltrated EBV+ tumor nests were predominantly CD8+ T cells, many of which expressed perforin. Immunoelectron microscopy confirmed a close cell to cell contact between these CD8+ cells and carcinoma cells. CD8+ cells were CD11a+ and CD11b- by flow cytometry performed in one case. The labeling index of Ki-67, the proliferation-associated antigen, in CD8+ cells was 4 times higher in EBV+ cases than in EBV- cases. Our data suggest that these CD8+ cells, which bear a cytotoxic phenotype, are actively proliferating in close contact with EBV+ tumor cells and that the specificity of the CD8+ cells may be directed to EBV and/or cellular antigens expressed by the tumor. This is consistent with a generally favorable prognosis of EBV+ gastric carcinoma. Because the observed T-cell infiltration is insufficient to eradicate the tumor cells, certain immunosuppressive factors were speculated to allow the essentially immunogenic carcinoma cells to establish a macroscopic lesion.

Antigens, CD↗

PubMed1996

[Variations of serum amyloid A protein and interleukin-6 in patients with low concentration of serum C-reactive protein].

Both C-reactive protein (CRP) and Serum amyloid A protein(SAA) are determined as an indicator of inflammation and tissue damage. But serum CRP in the range less than 10 micrograms/dl was not correlated with SAA. We determined CRP, SAA and interleukin-6(IL-6) in sera of patients who had received corticosteroid therapy. CRP decreased extremely after administration of more than 50 mg/day corticosteroid. However, SAA and IL-6 levels changed independently from CRP levels. In the patients under long-term corticosteroid therapy, CRP decreased rapidly to the level below the reference range and remained low, while SAA decreased but to the level in the reference range, and IL-6 levels was unchanged. When they were complicated with infectious disease during the corticosteroid therapy, CRP increased to or above the reference level but not so markedly, however, SAA increased markedly and exceeded the upper reference range three or four days earlier than the day of CRP increase. It is suggested that serial SAA monitoring will be reliable for the early diagnosis of infection if the patients is taking corticosteroid therapy.

Adolescent↗

PubMed1996

[Analysis of mutations and heteroplasmy at mitochondrial DNA 11778 using non-RI single strand conformation polymorphisms in Leber's hereditary optic neuropathy].

Leber's hereditary optic neuropathy(LHON) is a maternally inherited mitochondrial disease of an acute or subacute bilateral loss of central vision. G to A substitutions at nucleotide position 11778 in mitochondrial DNA(mt DNA) have been identified in approximately 40% to 90% of patients. In this study, regions containing mt DNA 11778 mutations were analyzed by polymerase chain reaction(PCR), non-RI single strand conformation polymorphisms(SSCP) and direct sequencing. In 26 visually affected patients, mt DNA 11778 mutations were detected in 9 patients (36.4%). In one pedigree of a LHON patient(L-6), four unaffected family members had heteroplasmy of the 11778 mutation using non-RI SSCP. Ratios of the heteroplasmy between wild type and mutant mt DNAs can be detected in non-RI SSCP and accurately quantified by video densitometric analyzer. Two types of novel polymorphisms, 11696 G to A and 11719 A to G, in the mt DNA region were also found in this non-RI SSCP analysis. Non-RI SSCP is an efficient and accurate method for diagnosis of mt DNA 11778 mutations and quantifying heteroplasmy in patients with LHON and pedigrees.

Base Sequence↗

PubMed1996

Tubulointerstitial nephritis with renal tubular acidosis and asymptomatic primary biliary cirrhosis accompanied by antibody to a 52-kDa mitochondrial protein alone.

We report a patient presenting with a mixed type of renal tubular acidosis, who demonstrated anti-mitochondrial antibodies on immunofluorescent study. However, study of anti-M2 antibody (enzyme immunoassay) was negative. Renal biopsy revealed lymphocyte infiltration in the interstitium compatible with chronic tubulointerstitial nephritis. Liver biopsy demonstrated a mild degree of primary biliary cirrhosis (PBC) but biochemical liver function tests were normal, resulting in a diagnosis of asymptomatic PBC. Using affinity chromatography conjugated with the patient's IgG, we purified a 52-kDa protein from a porcine renal mitochondrial fraction. This protein was identified as a component of a mitochondrial multienzyme complex such as dihydrolipoamide acyltransferase of the branched-chain alpha-keto acid dehydrogenase complex (BCKD), based on the molecular mass analysis and partial amino acid sequence of the purified protein. This is the first report of the detection of antibody to 52-kDa mitochondrial protein alone in a patient who showed predominantly tubulointerstitial damage in the kidney rather than liver damage.

Acidosis, Renal Tubular↗