Biomedical subjects

Y Ohta

Publications and source records attributed to Y Ohta.

At least 253 records · Page 14Linked to original sources

PubMed1998

Myocardial CD36 expression and fatty acid accumulation in patients with type I and II CD36 deficiency.

Long-chain fatty acids (LCFA) are one of the major cardiac energy substrates, so understanding LCFA metabolism may help in elucidating the mechanisms of various heart diseases. CD36 is a multifunctional membrane glycoprotein that acts not only as a receptor for thrombospondin, collagen and oxidized low density lipoprotein but also as a receptor for LCFA. We investigated the relationship between CD36 expression in myocardial capillary endothelial cells and myocardial LCFA uptake in patients with CD36 deficiency. We analyzed CD36 expression in blood cells from 250 patients with heart diseases by means of a flow cytometer. In 218 patients, myocardial LCFA scintigraphy was performed with 123I-beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP). In 5 patients, myocardial capillary endothelial cells were examined immunohistochemically for CD36 expression. Eleven patients (4%) showed signs of type I CD36 deficiency (neither platelets nor monocytes expressed CD36). Twenty patients (8%) had type II CD36 deficiency (monocytes expressed CD36 but platelets did not). In all 11 patients with type I CD36 deficiency, no BMIPP accumulation was observed in the heart, but in 13 patients with type II CD36 deficiency, BMIPP accumulation in the heart was focally reduced, but there were no patients without BMIPP accumulation in the heart. Although the myocardial capillary endothelial cells from two CD36-positive patients expressed CD36, those from two patients with type I CD36 deficiency did not. In a patient with type II CD36 deficiency, some capillary endothelial cells displayed patchy CD36 expression. CD36 deficiency was documented in 31 (12%) patients with heart diseases. Because CD36 was not expressed in the myocardial capillary endothelial cells in patients with type I CD36 deficiency, type I CD36 deficiency is closely related to lack of myocardial LCFA accumulation and metabolism in the myocardium.

Adult↗

PubMed1998

Protection of islet allografts transplanted together with Fas ligand expressing testicular allografts.

Fas ligand (FasL) is highly expressed in testicular tissues and thought to be responsible for protection from allograft rejection by inducing apoptosis of anti-graft activated T cells. FasL-expressing islets have been shown to induce a granulocyte-mediated inflammatory reaction. We investigated whether a graft can be protected from alloimmune responses by manipulating the Fas/FasL-system. We transplanted allogeneic islets under the kidney capsule of streptozotocin-induced diabetic mice together with testicular tissue. Significant prolongation of survival of C3H islet allograft was observed in C57BL/6 (B6) recipients transplanted with C3H testicular tissue, but not in those transplanted with C3H-gld testicular tissue expressing non-functional FasL. No significant prolongation was observed in B6-lpr recipients expressing non-functional Fas. Immunohistochemical staining of C3H testicular tissue in the composite graft showed a high expression of FasL, but not that of the C3H-gld testicular tissue. In situ terminal deoxynucleotidyl transferase-mediated dUDP-biotin catalysed DNA nick-end labelling (TUNEL) staining of a composite graft of C3H islet and testicular tissue in B6 recipients demonstrated extensive apoptosis of infiltrating mononuclear cells around the graft. The protective effect of C3H testicular tissue was abrogated when anti-FasL monoclonal antibody was administered i.p. postoperatively. Our results suggest that FasL-positive testicular allografts protect composite islet allografts and indicate that manipulation of Fas/FasL mediated apoptosis is a suitable strategy for controlling rejection of islet allografts.

Animals↗

PubMed1998

Overexpression of mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase does not correct glucose-stimulated insulin secretion from diabetic GK rat pancreatic islets.

Glucose-stimulated insulin secretion is impaired in GK (Goto-Kakizaki) rats, perhaps because of abnormalities in glucose metabolism in pancreatic islet beta cells. The glycerol phosphate shuttle plays a major role in glucose metabolism by reoxidizing cytosolic NADH generated by glycolysis. In the pancreatic islets of GK rats, the activity of mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase (mGPDH), the key enzyme of the glycerol phosphate shuttle, is decreased and this abnormality may be responsible, at least in part, for impaired glucose-stimulated insulin secretion. To investigate this possibility, we overexpressed mGPDH in islets isolated from GK rats via recombinant adenovirus-mediated gene transduction, and examined glucose-stimulated insulin secretion. In islets isolated from diabetic GK rats at 8 to 10 weeks of age, glucose-stimulated insulin secretion was severely impaired, and mGPDH activity was decreased to 79 % of that in non-diabetic Wistar rats. When mGPDH was overexpressed in islets from GK rats, enzyme activity and protein content increased 2- and 6-fold, respectively. Basal (3 mmol/l glucose) and glucose-stimulated (20 mmol/l) insulin secretion from the Adex1CAlacZ-infected GK rat islets were, respectively, 4.4 +/- 0.7 and 8.1 +/- 0.7 ng. x islet(-1) x 30 min(-1), and those from mGPDH-overexpressed GK rat islets 4.7 +/- 0.3 and 9.1 +/- 0.8 ng x islet(-1) x 30 min(-1), in contrast to those from the AdexlCAlacZ-infected non-diabetic Wistar rat islets (4.7 +/- 1.6 and 47.6 +/- 11.9 ng x islet(-1) x 30 min(-1)). Thus, glucose-stimulated insulin secretion is severely impaired in GK rats even in the stage when mGPDH activity is modestly decreased, and at this stage, overexpression of mGPDH cannot restore glucose-stimulated insulin secretion. We conclude that decreased mGPDH activity in GK rat islets is not the defect primarily responsible for impaired glucose-stimulated insulin secretion.

Adenoviridae↗

PubMed1998

Diagnostic value of atypical lymphocytes in cerebrospinal fluid from adults with enteroviral meningitis.

We have noted two morphologically distinct types of atypical lymphocytes (AL) in the cerebrospinal fluid (CSF) of adult patients with meningitis: one, which we designate type-I AL, with multilobulated nuclei resembling those of the abnormal cells in adult T-cell leukaemia (ATL); and another, type-II AL, characterized by large lymphocytes with basophilic cytoplasm and nuclei containing coarse chromatin. Type-I AL were detected in 25 of 39 patients (64%) with enteroviral and in 11 of 109 (11%) with aseptic meningitis presumed to be caused by other viruses, but not in meningitis resulting from Cryptococcus neofirmans (n = 14), Mycobacterium tuberculosis (n = 19) or acute bacterial infection (n = 49). Type-I AL were not seen in herpes zoster (n = 15) aseptic meningeal reactions (n = 15), or in leptomeningeal carcinomatosis (n = 14). Type-II AL were often present in meningitis of various aetiologies and in aseptic meningeal reactions, but not in leptomeningeal carcinomatosis. The presence of type-I AL in the CSF was found to be indicative of enteroviral meningitis with the highest predictive value (69%), while type-II AL had a lower diagnostic positive predictive value in meningitis of the five aetiologies above. Type-I AL immunostained for CD4, while type-II AL were stained for CD8. The presence of type-I AL in CSF strongly suggests enteroviral meningitis, which warrants careful follow-up without antifungal, antituberculous or antibacterial agents. However, type-I AL, which are likely to be virally transformed lymphocytes, must be distinguished from ATL cells, which frequently involve the meninges.

Adolescent↗

PubMed1998

Signet-ring cell carcinoma of the ileum: report of a case and review of the Japanese literature.

We report herein the extremely unusual case of a 71-year-old woman with signet-ring cell carcinoma of the ileum. She originally presented with a 6-month history of intermittent nausea and abdominal distention, but initial examinations, including gastrointestinal fiberscopy, ultrasonography, and computed tomography (CT) scan, failed to reveal any cause of her symptoms. A barium-enema study performed 11 months after her initial visit demonstrated a narrow portion of the terminal ileum. An ileocecal resection was subsequently performed, and an epigastric subcutaneous tumor was simultaneously excised. The specimen contained a tumor with a stenotic lumen resembling a "lead pipe", an ulcerative portion, and mucosa with a granular appearance adjoining its proximal site. Many small aphthous lesions with IIa + IIc appearance were seen in the apparently normal mucosa. Histopathological examination confirmed a diagnosis of signet-ring cell carcinoma. The small aphthous lesions seemed to be metastases spread via the lymphatic vessels. Our review of the medical literature revealed three cases of signet-ring cell carcinoma of the jejunum; however, this is the first reported case of signet-ring cell carcinoma of the ileum.

Aged↗

PubMed1998

Hepatitis C virus infection and mutations of mannose-binding lectin gene MBL.

We assessed the genetic polymorphism of mannose-binding lectin (MBL) in 93 patients with chronic hepatitis C (45 responders and 48 nonresponders to interferon) and 218 healthy controls. Mutant allele was identified only at codon 54 (Gly-->Asp), leading to three genotypes (54 m/m, 54 W/m, and 54 W/W). Frequency of 54 m/m was significantly lower in interferon-responders (2.2%), compared to those in nonresponders (14.6%) and controls (10.6%): p < 0.05. Our results suggest that homozygous carriage of the variant allele of codon 54 of MBL may predict poor response to interferon in chronic hepatitis C patients.

Adult↗

PubMed1998

Hepatitis B virus genomic sequence in the circulation of hepatocellular carcinoma patients: comparative analysis of 40 full-length isolates.

We determined full-length nucleotide sequence of hepatitis B virus (HBV) genome in sera from 40 Japanese patients with HBsAg-positive hepatocellular carcinoma (HCC), in order to obtain information on HCC-specific characteristics, if any, of the HBV genome. Direct sequencing of the long distance PCR products starting from 50 microliters of serum samples revealed that 95% of our isolates were of genotype C, and that mutations and deletions/insertions were very common. With respect to envelope protein genes, deletions and missense mutations were frequent in preS2, and the determinant a domain of HBsAg was rich in "antibody-escape" mutations. Within the precore/core region, the most remarkable mutation was the replacement of proline of wild type by other amino acids at codon 130 of the core gene, which was found in 58% of our isolates, while precore-stop mutation was found in 45%. Most interestingly, however, about 90% of our isolates had mutations at nt positions 1762 (A-to-T) and 1764 (G-to-A) within the core promoter, which had been implicated in "e-suppressive" phenotype of HBV genome. G-to-A at nt 1613 and C-to-T at nt 1653 within enhancer II and T-to-C/A at nt 1753 within core promoter were also evident: 38%, 53%, and 40%, respectively. It was interesting that some of the characteristics observed in our isolates form HCC patients had been previously implicated in fulminant hepatitis and/or acute exacerbation of chronic hepatitis.

Adult↗

PubMed1998

Simple and large-scale production of N-acetylneuraminic acid from N-acetyl-D-glucosamine and pyruvate using N-acyl-D-glucosamine 2-epimerase and N-acetylneuraminate lyase.

N-Acetylneuraminate lyase and N-acyl-D-glucosamine 2-epimerase had been cloned and overexpressed in Escherichia coli. Simultaneous use of these two enzymes and feeding of appropriate amounts of pyruvate to the reaction mixture made possible the high conversion of N-acetylneuraminic acid (Neu5Ac) from N-acetyl-D-glucosamine (GlcNAc) with a 77% conversion rate on a molar basis. As a result, 29 kg of Neu5Ac was obtained from 27 kg of GlcNAc. The product was recovered by direct crystallization, and verified as identical to authentic Neu5Ac.

Acetylglucosamine↗

PubMed1998

Remnants of chylomicron and very low density lipoprotein impair endothelium-dependent vasorelaxation.

Remnants of chylomicron and very low density lipoprotein (VLDL) have been implicated as potentially atherogenic. Since endothelial dysfunction is an early event in atherosclerosis, we examined effects of the remnants on endothelium-dependent vasorelaxation. The remnant lipoproteins were isolated from postprandial plasma in hyperlipidemic subjects using the immunoaffinity gel mixture of anti apo A-1 and anti apo B-100 monoclonal antibodies and ultracentrifugation. Rabbit aortic strips suspended in the organ chambers were incubated for 2 h with the preparations of lipoproteins and lipids. After incubation, the strips were tested with vasodilators after precontraction with phenylephrine (1 microM). The remnant lipoproteins (750-1500 microg triglyceride/ml) but not VLDL fraction (up to 1500 microg triglyceride/ml) impaired vasorelaxation in responses to acetylcholine, substance P and A23187. Carbamylated or methylated remnant lipoproteins, chemically modified remnant lipoproteins, had comparable impairment of the vasorelaxation as unmodified remnant lipoproteins. Incubation with lipid extracts from the remnant lipoproteins also exerted an inhibitory effect on the vasorelaxation. Relaxation to sodium nitroprusside was fully preserved in all aortas exposed to the lipoprotein preparations. Thus, the remnant lipoproteins impair endothelium-dependent arterial relaxation at the concentrations observed in the plasma in patients with coronary artery disease (500-2000 microg triglyceride of remnant lipoprotein/ml). The impairment may be in apoprotein receptor-independent manner, and the lipids in the remnants seem to contribute to the inhibitory effect. The endothelial dysfunction caused by the remnant lipoproteins may play a role in the high prevalence of atherosclerotic coronary artery disease in postprandial hyperlipidemic patients.

Acetylcholine↗

PubMed1998

Association of mannose-binding lectin gene haplotype LXPA and LYPB with interferon-resistant hepatitis C virus infection in Japanese patients.

BACKGROUND/AIMS: Mannose-binding lectin, a key factor of the innate immune system, has genetic polymorphism, and individuals who carry certain genotypes of mannose-binding lectin are known to be more prone to severe or prolonged infectious diseases. We aimed to find any relevance of mannose-binding lectin polymorphism to hepatitis C virus infection. METHODS: We determined the mannose-binding lectin genotypes by sequence specific priming-polymerase chain reaction in 159 hepatitis C virus-infected chronic hepatitis patients and 218 healthy controls in Japan by looking at 4 polymorphic loci: 2 (H/L and X/Y) within the promoter region and 2 (P/Q and A/B) within exon-1 of the mannose-binding lectin gene. RESULTS: A group of mannose-binding lectin genotypes designated "XB-type" (containing LXPA or LYPB haplotype at least heterozygously) was less frequently found in interferon-responsive patients (38.5%) than in interferon-resistant patients (60.7%, p=0.008) and controls (57.3%, p=0.014). Individuals with the "XB-type" had lower serum concentrations of mannose-binding lectin, compared to those with "YA-type", which is defined by homozygous carriage of both Y and A alleles: 0.63+/-0.61 vs 2.06+/-1.17 mg/l, p<0.001. CONCLUSIONS: Our results suggest that the mannose-binding lectin-related innate immune system plays an important role in elimination of hepatitis C virus during interferon therapy. Determining mannose-binding lectin genotypes may help in selecting the hepatitis C virus-infected patients to be treated with interferon.

Antiviral Agents↗

PubMed1998

Extent of mediastinal node metastasis in clinical stage I non-small-cell lung cancer: the role of systematic nodal dissection.

OBJECTIVE: To determine the extent of lymph node metastasis in clinical stage I non-small-cell lung cancer (NSCLC). METHODS: We performed a retrospective review of 524 patients with clinical stage I NSCLC who underwent lobectomy with systematic nodal dissection. RESULTS: The nodal status was N0 in 409 patients (78%), N1 in 44 (8%), N2 in 67 (13%), and N3 in four (0.8%). Thirty-six patients had single-level mediastinal nodal metastases and 35 had multi-level metastases. The incidence of N2/3 disease in patients with adenocarcinoma/squamous cell carcinoma/other histologic types according to tumor size was 0/0/0%, respectively, in tumors < or = 10 mm in diameter, 12/0/0% in tumors 11-20 mm in diameter, 14/4/23% in tumors 21-30 mm in diameter, and 26/14/20% in tumors >30 mm in diameter. Nodal metastases to the upper mediastinum from middle or lower lobe lesions were frequently observed in 51 N2 adenocarcinomas, whereas those to the lower mediastinum from upper lobe lesions were rare. Of 10 N2 squamous cell carcinomas, seven had regional and three had non-regional nodal metastases. The 5-year survival rate was 68, 43, and 30% in N0, N1, and N2, respectively (P<0.01, N0 versus N1, N0 and N2). CONCLUSIONS: Systematic mediastinal nodal dissection should be routinely performed for clinical stage I lung cancer to ensure the correct nodal status, but it might be dispensable in the patients with peripheral squamous cell carcinoma < or = 20 mm in diameter, with central squamous cell carcinoma < or = 30 mm, and with adenocarcinoma < or = 10 mm. When systematic nodal dissection cannot be performed, the incidence and extent of nodal metastases should be taken account with respect to histologic type, size, and location of the tumor.

Carcinoma, Non-Small-Cell Lung↗

PubMed1998

Inhibitory effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract on hepatic triglyceride accumulation with the progression of carbon tetrachloride-induced acute liver injury in rats.

The inhibitory effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15) on hepatic triglyceride (TG) accumulation with the progression of acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl4). TJ-15 at a dose of 100, 250 or 500 mg/kg body weight (BW) was orally administered to male Wistar rats aged 7 weeks, 6 h after the intraperitoneal injection of CCl4 (1.0 ml/kg BW) at which time apparent liver injury and hepatic TG accumulation occurred. TJ-15 significantly prevented not only the progression of liver injury but also inhibited hepatic TG accumulation with the progression of the injury in a dose-dependent manner when these effects were examined 24 h after CCl4 injection. In CCl4-untreated rats with oral administration of TJ-15 at a dose of 100, 250 or 500 mg/kg BW, liver and serum TG concentrations decreased depending on the dose of the herbal medicine. These results indicate that in rats intoxicated once with CCl4, orally administered TJ-15 can inhibit hepatic TG accumulation with the progression of acute liver injury by its decreasing action on serum and liver TG levels, leading to a prevention of the progression of the liver injury.

Administration, Oral↗

PubMed1998

Improved visualization of the left atrial appendage by transthoracic 2-dimensional tissue harmonic compared with fundamental echocardiographic imaging.

We compared fundamental and tissue harmonic transthoracic echocardiographic imaging for the delineation of the left atrial appendage (LAA) in 32 subjects. The LAA images recorded in the parasternal short-axis view were divided into 4 segments and 2 observers independently graded for each segment using a visual scoring system ranging from 0 to 3 (0 = no, 3 = clearly visible over the entire length of the segment). For the 128 segments, the averaged segment scores were significantly increased after switching to harmonic imaging (1.32 +/- 0.69 versus 1.60 +/- 0.81 for fundamental and tissue harmonic imaging, respectively; P <.0005 for observer 1, and 1.38 +/- 0.65 versus 1.61 +/- 0.82, respectively; P <.001 for observer 2). In a patient with LAA thrombus, the image contrast of the thrombus was improved in harmonic compared with fundamental imaging. These data suggest that tissue harmonic imaging significantly improves image quality of the LAA.

Adult↗

PubMed1998

In vitro and in vivo selectin-blocking activities of sulfated lipids and sulfated sialyl compounds.

There is accumulating evidence that sulfated lipids, sulfated oligosaccharides and other sulfated compounds are reactive with selectins in a manner that interferes with selectin interactions with their natural ligands. In the report we describe the ability of sulfated lipids (sulfatides and gangliosides) and multimeric forms of sulfated sialic acid to block binding of P- and E-selectin-Ig to neutrophils. The in vivo ability of these compounds to block lung injury in rats following i.v. infusion of purified cobra venom factor (CVF), which induces injury that is L- and P-selectin dependent, was also determined as well as effects on recruitment of neutrophils, as measured by lung myeloperoxidase. There was a significant correlation between the ability of sulfated lipids and sialyl compounds to interfere in vitro with P-selectin-Ig binding to neutrophils and to protect against P-selectin-dependent acute lung injury induced by CVF. The biological effects of these sulfated compounds were also associated with diminished accumulation of neutrophils. The protective effects of these compounds may be linked to their ability to interfere with P-selectin binding to counter-receptors on neutrophils.

Animals↗

PubMed1998

Immunoreactive endothelin levels in the vitreous fluid are decreased in diabetic patients with proliferative retinopathy.

Endothelin (ET) plays an important role in the pathogenesis of various cardiovascular lesions. To elucidate the pathophysiologic significance of ET in the development of diabetic retinopathy, we determined immunoreactive ET levels in the vitreous fluid collected during vitrectomy in seven patients with non-insulin dependent diabetes mellitus with proliferative diabetic retinopathy and in 10 nondiabetic subjects as controls. Immunoreactive vitreous ET levels in diabetic patients with proliferative retinopathy (7.5 +/- 3.4 pg/ml, mean +/- SD) were significantly lower than those in the nondiabetic subjects (55.0 +/- 38.1 pg/ml; p < 0.005). The decreased rather than increased immunoreactive ET levels may simply reflect severe endothelial injury to the retinal vessels caused by diabetic microangiopathy rather than an important role in diabetic retinopathy.

Blood Pressure↗

PubMed1998

Local cytokine expression in steroid-modified tinea faciei.

In tinea faciei, a dermatophyte infection of the face, early stage lesions show erythema with crust and/or vesicles, a condition often misdiagnosed as dermatitis. Steroid application retards the healing in some cases and may induce penetration of the dermatophyte hyphae into hair and hair follicles. In the present study, we examined local immunity mediated by cytokines derived from lesional T lymphocytes in late stage of this disease. Interferon-gamma (IFN-gamma) and macrophage migration inhibitory factor (MIF) were highly expressed, but neither interleukin-4 (IL-4) nor interleukin-5 (IL-5) could be detected by RT-PCR using cryosections. These data suggested that IFN-gamma and MIF may be important in the delayed-type hypersensitivity (DTH) response against the fungus in the hair follicle in late stages.

Adult↗

PubMed1998

The nature of psychiatric problems among disaster victims.

One-quarter of the residents (about 52,000) in the disaster area around the volcanic eruption area of Mt Unzen-Fugen have been forced to evacuate over a 3 year period. We conducted a psychological controlled study using the GHQ-30 for evacuees. As a result, the percentage of people with a high score over 8 points was 67% of evacuees, markedly higher than 10% of the control group. Some mental support activities, such as counseling by community nurses and crisis intervention/medication by psychiatrists and others, have been promoted. Subjects who received a psychiatric intervention had good outcome as a whole. The nature of psychiatric problems among disaster evacuees and the necessity of long-term support are discussed in this paper.

Adolescent↗

PubMed1998

A new internal ribosomal entry site 5' boundary is required for poliovirus translation initiation in a mouse system.

Four mutants of the virulent Mahoney strain of poliovirus were generated by introducing mutations in nucleotides (nt) 128 to 134 of the genome, a region that contains a part of the stem-loop II (SLII) structure located within the internal ribosomal entry site (IRES; nt 120 to 590) (K. Shiroki, T. Ishii, T. Aoki, Y. Ota, W.-X. Yang, T. Komatsu, Y. Ami, M. Arita, S. Abe, S. Hashizume, and A. Nomoto, J. Virol. 71:1-8, 1997). These mutants (SLII mutants) replicated well in human HeLa cells but not in mouse TgSVA cells that had been established from the kidney of a poliovirus-sensitive transgenic mouse. Their neurovirulence in mice was also greatly attenuated compared to that of the parental virus. The poor replication activity of the SLII mutants in TgSVA cells appeared to be attributable to reduced activity of the IRES. Two and three naturally occurring revertants that replicated well in TgSVA cells were isolated from mutants SLII-1 and SLII-5, respectively. The revertants recovered IRES activity in a cell-free translation system from TgSVA cells and returned to a neurovirulent phenotype like that of the Mahoney strain in mice. Two of the revertant sites that affected the phenotype were identified as being at nt 107 and within a region from nt 120 to 161. A mutation at nt 107, specifically a change from uridine to adenine, was observed in all the revertant genomes and exerted a significant effect on the revertant phenotype. Exhibition of the full revertant phenotype required mutations in both regions. These results suggested that nt 107 of poliovirus RNA is involved in structures required for the IRES activity in mouse cells.

Animals↗