Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 469 records · Page 26Linked to original sources

PubMed1995

Impaired release of cholecystokinin (CCK) from synaptosomes in old rats.

Cholecystokinin (CCK) is an abundant neurotransmitter peptide in the brain. CCK release from synaptosomes obtained from the cerebral cortex, the level of CCK mRNA and the tissue concentration of CCK were examined in young and old rats. CCK release stimulated by KCl was attenuated in old rats but that stimulated by calcium ionophore was comparable in animals at both ages. The CCK mRNA level in the cerebral cortex was decreased significantly in old rats despite the significant increase in CCK content. These results suggested that aging impaired CCK release, resulting in tissue accumulation and a decrease in the synthesis of CCK (the level of CCK mRNA).

Age Factors↗

PubMed1995

Clinical efficacy of fluvastatin in the long-term treatment of familial hypercholesterolemia.

The long-term clinical efficacy of fluvastatin was assessed in 24 patients with familial hypercholesterolemia over a total treatment period of 104 weeks. Patients received an initial fluvastatin dose of 20 mg/day for 8 weeks, which was increased to 30 mg/day for a further 16 weeks. From week 24, if serum total cholesterol remained > or = 230 mg/dL, the fluvastatin dose could be increased to 40 or 60 mg/day, as necessary. By the end of treatment, 4 patients were receiving 30 mg/day fluvastatin, 1 patient was receiving 40 mg/day, and 19 patients were receiving 60 mg/day. Serum total cholesterol and low density lipoprotein cholesterol (LDL-C) levels showed a significant decrease from baseline at week 104 (total cholesterol, -26.8 +/- 2.4%; LDL-C, -33.1 +/- 3.3%; p < 0.001). The reductions in total cholesterol and LDL-C were dose-related. Statistically significant (p < 0.05) increases in serum high density lipoprotein cholesterol (HDL-C) were observed at week 24 (12.1 +/- 5.0%) and at week 76 (11.0 +/- 3.3%), although the effect was variable. Nevertherless, at the end of treatment the LDL-C: HDL-C ratio showed a 35% reduction from baseline. Changes in triglyceride levels failed to achieve statistical significance, with a reduction from baseline of -13.9 +/- 7.3% at week 104. Changes in apolipoprotein A-I were variable, with statistically significant (p < 0.01) increases observed at week 24 (7.6 +/- 2.3%) and week 76 (8.4 +/- 2.7%). By contrast, a significant reduction from baseline in apolipoprotein B was achieved by week 12 (-15.0 +/- 2.3%; p < 0.001) and was maintained throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Seven megabase yeast artificial chromosome contig at region 11p15: identification of a yeast artificial chromosome spanning the breakpoint of a chromosomal translocation found in a case of Beckwith-Wiedemann syndrome.

Genetic alterations of chromosome region 11p15 have been detected in neoplastic diseases as well as in cancer-predisposing syndromes. The cloning of the entire chromosomal region will be important for the identification and characterization of critical tumor suppressor genes. We have developed a yeast artificial chromosome contig that covers up to 7 Mb of this chromosome band. The most centromeric marker included in the contig is D11S932 and the most telomeric is D11S470. We have developed 18 new STS markers, which have been located in the contig in relation to 16 known markers. One of the yeast artificial chromosome clones was found to span the chromosome 11 breakpoint of the translocation t(11;18), associated with a case of Beckwith-Wiedemann syndrome. Cloning the regions in proximity to this translocation might reveal the presence of a gene altered in association with the development of Beckwith-Wiedemann syndrome.

Base Sequence↗

PubMed1995

A phase II trial of oral tegafur and uracil plus cisplatin in patients with inoperable nonsmall cell lung cancer.

BACKGROUND: The combination of uracil and tegafur in a 4:1 molar concentration (UFT) has a greater antitumor activity than 5-fluorouracil (5-FU) and tegafur. Because the combination of 5-FU and cisplatin has been proven to have a synergistic antitumor effect in many experimental and clinical studies, a Phase II study was conducted using the combination of UFT and cisplatin in patients with inoperable nonsmall cell lung cancer. METHODS: Thirty-one patients with measurable disease were entered into the study; all were evaluable for toxicity and response. Their median age was 61 years (range, 36-75 years). There were 13 patients with Stage III and 17 with Stage IV disease. Twenty-two (71%) patients had received no prior treatment. UFT (400 mg/m2) was administered orally on days 1 through 21 and cisplatin (80 mg/m2) was injected intravenously on day 8. This treatment was repeated every 4 weeks. RESULTS: The median number of treatment cycles was two (range, 1-4 cycles). There were 11 partial responses (35%; 95% confidence interval, 19%-52%). The median response time was 6 months (range, 3-13 months). The median survival time was 11 months (range, 4-27+ months) for Stage III and 8 months (range, 2-22 months) for Stage IV. This chemotherapy regimen was well tolerated. The hematologic toxicities, such as leukopenia and thrombocytopenia of grades 3 and 4, occurred in only 2 of 31 (6%) patients. Nonhematologic toxicities of grades 3 or 4 were not observed. CONCLUSIONS: Oral UFT plus cisplatin administration demonstrated an activity comparable with that of other combinations based on cisplatin and an extremely low incidence of side effects. These observations suggest that this chemotherapy regimen is worthy of further investigation in a multi-institutional trial to determine the antitumor effect and the quality of life of patients.

Administration, Oral↗

PubMed1995

A novel dodecadepsipeptide, cereulide, is an emetic toxin of Bacillus cereus.

A vacuole-formation substance, cereulide of Bacillus cereus, is an emetic toxin in animals. Both oral administration and intraperitoneal injection of cereulide caused dose-dependent emesis in Suncus murinus, a new animal model of emesis. Vagotomy or a 5-HT3 receptor antagonist completely abolished this emetic effect. Therefore, cereulide causes emesis through the 5-HT3 receptor and stimulation of the vagus afferent. We also found that our purified cereulide caused swelling of mitochondria of HEp-2 cells.

Animals↗

PubMed1995

Identification and synthetic pathway of sialyl-Lewisx-containing neolacto-series gangliosides in lens tissues. 1. Characterization of gangliosides in human senile cataractous lens.

Human lens accumulates gangliosides in association with aging and senile cataract progression. In this study we purified and characterized five major gangliosides in human cataractous lenses. Structural analyses and immunological studies revealed the presence of ganglio-series gangliosides, GM3, GM2, GM1 and GD1a, and a sialyl-Lewisx-containing neolacto-series ganglioside, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1ceramide (IV3NeuAcIII3FucnLc4). Slow-moving gangliosides, although minor components, were also found to have sialyl-Lewisx-related structures, based on anti-Lewisx antiserum binding to their asialo forms. However, sialyl-paragloboside, a possible precursor of the sialyl-Lewisx ganglioside, was not identified.

Aged↗

PubMed1995

Detection of myc translocations in lymphoma cells by fluorescence in situ hybridization with yeast artificial chromosomes.

Translocations involving chromosome 8 at band q24 and one of the Ig loci on chromosomes 14q32, 22q11, and 2p11 are the hallmark of Burkitt's lymphoma (BL). It has been previously observed that the exact localization of the breakpoints at chromosome 8q24 can vary significantly from patient to patient, scattering over a distance of more than 300 kb upstream of c-myc and about 300 kb downstream of c-myc. To generate probes for fluorescence in situ hybridization (FISH) that detect most c-myc translocations, we screened a yeast artificial chromosome (YAC) library from normal human lymphocytes by colony hybridization, using three markers surrounding the c-myc gene as probes. We obtained 10 YAC clones ranging in size between 500 and 200 kb. Two nonchimeric clones were used for FISH on several BL cell lines and patient samples with different breakpoints at 8q24. Our results show that the YAC clones detected translocations scattered along approximately 200 kb in both metaphase chromosomes and interphase nuclei. The sensitivity, rapidity, and feasibility in nondividing cells render FISH an important diagnostic tool. Furthermore, the use of large DNA fragments such as YACs greatly simplifies the detection of translocations with widely scattered breakpoints such as these seen in BL.

Adult↗

PubMed1995

Frog cytochrome P-450 (11 beta,aldo), a single enzyme involved in the final steps of glucocorticoid and mineralocorticoid biosynthesis.

A cDNA for cytochrome P-450(11 beta,aldo) was cloned from a library of bullfrog interrenal tissue (tissue corresponding to the mammalian adrenal gland). The 1919-bp cDNA encoded a protein of 517 amino acids. Its amino acid sequence was highly similar to the sequences of bovine P-450(11 beta) and rat P-450(11 beta,aldo) when P-450(11 beta) family enzymes reported to date were examined. The enzyme expressed in COS7 cells had the 11 beta-hydroxylation, 18-hydroxylation activities and aldosterone synthetic activity. Northern-blot and immunoblot analyses suggested that a single P-450(11 beta) enzyme was expressed in bullfrog interrenal tissue. These results suggest that a single enzyme catalyzes the final steps of glucocorticoid and mineralocorticoid biosynthesis in bullfrog interrenal tissue as in bovine adrenal gland. A phylogenetic tree of CYP11B genes suggests that the frog enzyme diverged at an earlier evolutionary time from other vertebrate enzymes. Immunohistochemical and in situ hybridization studies indicated that steroidogenic cells existed in the outer region of interrenal tissue more densely than in the inner region, whereas some medullary cells made clusters like islets. Most of the cells were diffusely distributed in the tissue.

Amino Acid Sequence↗

PubMed1995

Antihyperglycemic effects of M16209, a novel aldose reductase inhibitor, in normal and diabetic rats.

The effect of a single oral administration of M16209 (1-(3-bromobenzo[b]furan-2-yl-sulfonyl)hydantoin), a novel aldose reductase inhibitor, on serum glucose was investigated. In normal rats, M16209 (100 mg/kg) had a weak hypoglycemic effect but markedly stimulated the disappearance of serum glucose in intravenous glucose tolerance tests. In diabetic rats, M16209 (100 mg/kg) significantly suppressed the hyperglycemia of streptozotocin-induced, mildly diabetic rats and stimulated serum glucose disappearance in neonatally streptozotocin-induced, non-insulin-dependent diabetes mellitus (NIDDM) rats in glucose tolerance tests. Additionally, M16209 augmented insulin secretion in glucose-loaded, normal and NIDDM rats and restored the reduced serum insulin in streptozotocin-induced, mildly diabetic rats. M16209, however, showed no hypoglycemic effect in severely diabetic rats. In contrast, gliclazide, a sulfonylurea, showed a much more potent hypoglycemic effect in normal rats than in mildly diabetic rats. These results suggest that M16209 suppresses hypoglycemia through augmentation of glucose-stimulated insulin secretion. The antihyperglycemic activity of M16209, combined with its potent aldose reductase inhibiting activity, is expected to be beneficial in the treatment of diabetic complications.

Aldehyde Reductase↗

PubMed1995

Effects of M16209 on insulin secretion in isolated, perfused pancreases of normal and diabetic rats.

We investigated the stimulatory effect of M16209 (1-(3-bromobenzo[b]furan-2-yl-sulfonyl)hydantoin), a novel aldose reductase inhibitor, on insulin secretion using isolated, perfused pancreases of rats. In the pancreases from normal rats, M16209 (100 microM) greatly augmented glucose-stimulated insulin secretion, but showed no effect on unstimulated insulin secretion at 2.8 mM glucose. In contrast, gliclazide (10 microM), a sulfonylurea, strongly enhanced both glucose-stimulated and unstimulated insulin secretion. Sorbinil and epalrestat, potent aldose reductase inhibitors, had no stimulatory effect on insulin secretion. M16209 (100 microM) improved appreciably the decreased insulin response to 22.2 mM glucose and enhanced slightly unstimulated insulin secretion in the pancreases of rats with neonatally streptozotocin-induced, non-insulin-dependent diabetes mellitus (NIDDM). Gliclazide (10 microM), however, failed to affect the pancreases of NIDDM rats. Furthermore, M16209 showed no appreciable effect on ATP-sensitive K(+)-channels in pancreatic beta-cells. These results suggest that M16209, unlike sulfonylureas, selectively enhances glucose-stimulated insulin secretion in both normal and NIDDM rats through a direct action on the pancreas. The site of action remains unknown, but the inhibition of aldose reductase or the ATP-sensitive K+ channels is unlikely to be involved.

Aldehyde Reductase↗

PubMed1995

Tenascin-C induction by the diffusible factor epidermal growth factor in stromal-epithelial interactions.

Tenascin-C, a six-armed extracellular matrix glycoprotein, is expressed in a temporally and spatially restricted pattern during carcinogenesis and invasion or metastasis of carcinoma cells in association with stromal-epithelial interactions. The human epidermoid carcinoma-derived cell lines, A431 and HEp-2, which do not express tenascin-C by themselves in vitro, do express tenascin-C after transplantation into nude mice, and transforming growth factor beta 1 (TGF-beta 1) induces them to express tenascin-C in vitro. Epidermal growth factor (EGF) induced tenascin-C in these cells more effectively (about 3.5-fold greater) than did TGF-beta 1. Hepatocyte growth factor (HGF) and platelet-derived growth factor (PDGF) had little effect on the induction of tenascin-C. EGF also induced other extracellular matrix components, fibronectin and laminin. Tenascin-C was also induced when the carcinoma cells were co-cultured with embryonic fibroblasts from mice which were homozygous for a null mutation in the tenascin-C gene, or when the conditioned medium from these cells was added. The induction of tenascin-C in the co-culture was reduced by treating the cells with antibodies against EGF or its receptor. The addition of EGF caused both cell types to disrupt their cytoskeleton and focal contacts as evidenced by the loss of stress fibers and vinculin plaques. EGF did neither induce tenascin-C nor affect the morphology in tenascin-C-nonproducing A549 carcinoma cells, which did not produce tenascin-C after transplantation. Thus, EGF induces tenascin-C in tenascin-C-nonproducing human carcinoma cells through EGF receptors. Furthermore, in stromalepithelial interactions, the diffusible factor EGF participates in the induction of human tenascin-C in these cells through EGF receptors.

Animals↗

PubMed1995

Use of a guanidine extract of demineralized bone in the treatment of osteochondral defects of articular cartilage.

In order to evaluate the ability of a guanidine extract of demineralized bone to repair osteochondral defects in articular cartilage, plugs made of this extract were implanted into defects in rabbit knees. The repair tissue was examined macroscopically, histologically, and immunohistochemically at 4, 8, 12, and 30 weeks. Controls (defects that were left empty) showed no cartilage formation. Four weeks after implantation of a guanidine extract plug, histological examination showed a nonhomogeneous metachromatically stained region extending from the surface of the repair tissue down to cancellous bone. This region also was labeled by an anti-type-II collagen antibody, indicating that cartilage-like tissue had been induced. At 8 weeks, the newly formed cartilage in the subchondral and cancellous bone had been partially replaced by bone. At 12 weeks, the thickness of the newly formed cartilage layer had decreased, and most of the newly formed cartilage in the subchondral and cancellous bone had been replaced by bone. In addition, a tidemark was observed. At 30 weeks, the repair tissue was a mixture of cartilage and fibrocartilage, and there was severe degeneration of the cartilage surrounding the repaired defects. These findings indicate that osteochondral defects of articular cartilage can be partially repaired by the implantation of a guanidine extract and that the newly formed cartilage-like tissue is not permanent.

Animals↗

PubMed1995

Endoscopic injection sclerotherapy for esophageal varices associated with concomitant portal venous thrombus of hepatocellular carcinoma.

Between 1983 and 1994, we treated 51 patients with esophageal varices and portal trunk and main branch invasion of hepatocellular carcinoma, using endoscopic injection sclerotherapy. Variceal bleeding was controlled in 28 of 29 patients (96.6%), esophageal varices were completely eradicated in 28 (54.9%), and only 2 of 28 (7.1%) bled from small, dilated, venous vessels after eradication. The cumulative nonbleeding rate at 3 years was 87.5%. Death caused by hepatocellular carcinoma accounted for 89.4% of the patients, whereas the rate of bleeding from esophageal varices was 4.3%. Variables significantly associated with the duration of survival were Okuda's clinical stage, alpha-fetoprotein, eradication of esophageal varices by sclerotherapy, and treatment of hepatocellular carcinoma, as determined in a univariate analysis. Multivariate analysis showed that eradication of esophageal varices by sclerotherapy, Okuda's clinical stage, and age were independent factors which significantly influenced survival time. We propose that complete eradication of esophageal varices and close follow-up using endoscopy may lead to a reduction in bleeding from esophageal varices, and hence may reduce mortality rates related to this bleeding.

Carcinoma, Hepatocellular↗

PubMed1995

Tenascin-C induction in Whitlock-Witte culture: a relevant role of the thiol moiety in lymphoid-lineage differentiation.

The extracellular matrix (ECM) glycoprotein tenascin-C is expressed in a temporally and spatially restricted pattern during embryogenesis and carcinogenesis in association with stromal-epithelial interactions. First, we investigated the production of tenascin-C and other ECM glycoproteins in the established in vitro model system specific for the lymphoid-lineage hemopoiesis, i.e., the Whitlock-Witte (W-W) culture system. In murine primary long-term bone marrow cultures, tenascin-C was produced constitutively and was expressed significantly in higher amounts in this system than in the other established in vitro model system specific for the myeloid-lineage hemopoiesis, i.e., the Dexter culture system. 2-Mercaptoethanol (2-ME), a component of the W-W system, induced the secretion of tenascin-C and upregulated the expression of its mRNA. Furthermore, the reduced glutathione, which, like 2-ME, contains a thiol moiety, induced tenascin-C glycoprotein and its mRNA. By contrast, hydrocortisone (HC), a component of the Dexter system, inhibited the secretion of ECM glycoproteins. 2-ME and TGF-beta 1, the latter of which is known as an inducer of ECM glycoproteins, had an additive effect on the induction of tenascin-C when they were simultaneously added to the W-W system. The TGF-beta receptor binding analysis demonstrated that this induction by 2-ME was not mediated by the cell-surface TGF-beta receptors, suggesting that it was regulated independently of TGF-beta 1. Then, the role of thiol compounds in the lymphoid-lineage differentiation was examined. The omission of 2-ME from the W-W system completely eliminated its ability to support the lymphoid-lineage differentiation. Glutathione, which, unlike 2-ME, does not passively permeate through the plasma membrane, did not support the development of a lymphoid lineage. These results indicate that 2-ME, essential for the lymphoid-lineage differentiation in the W-W culture system, is a potent inducer of tenascin-C expression in vitro.

Animals↗

PubMed1995

A possible mechanism for the increase in serum luteinizing hormone levels in male rats by oxolinic acid.

Oxolinic acid (1-ethyl-1,4-dihydro-6,7-methylenedioxy-4-oxo-3- quinolinecarboxylic acid), an antimicrobial agent, raises the serum levels of luteinizing hormone (LH) and increases the incidence of testicular Leydig cell tumors in male rats. In the present study the mechanism by which serum LH levels are raised in male rats receiving oxolinic acid was investigated. Aged Wistar rats were fed a diet containing oxolinic acid at 0 or 3000 ppm for more than 4 weeks. There was no effect of oxolinic acid on either the maximal levels of serum LH after castration nor on the serum levels of LH stimulated with 1 microgram/rat of luteinizing hormone-releasing hormone (LHRH). The concentrations of testosterone in serum and testis were not changed by the treatment of oxolinic acid. In the in vitro organ culture, the testes of rats receiving oxolinic acid released testosterone in the same manner as the controls, in the presence or the absence of human chorionic gonadotropin (100 mIU/ml). The oxolinic acid-stimulated serum LH was not increased further by the daily administration of L-dopa (500 mg/kg/day, po, 7 days) and was blocked by the injection of a dopamine antagonist, haloperidol (2 mg/kg, ip). In a microdialysis study, oxolinic acid increased the extracellular concentration of dopamine in the preoptic area of hypothalamus. These findings suggest that a high dietary level of oxolinic acid elevates LH release from the anterior pituitary with an increase in LHRH, in part, by the excitatory input of a dopaminergic system in the preoptic area of rat hypothalamus.

Animals↗

PubMed1995

Effect of erythropoiesis on splenic cadmium-metallothionein level following an injection of CdCl2 in mice.

The effects of erythropoiesis on cadmium-metallothionein (Cd-MT)2 levels in spleen, a major erythropoietic tissue, was examined following sc injection of 109CdCl2 into mice. As the concentration of Cd in plasma decreased following injection of 109CdCl2 into control mice, the levels in spleen and liver increased rapidly. After 48 hr, when the concentration of Cd in the erythrocyte (RBC) was at maximum, the level of Cd in the spleen, but not liver, had decreased. These variations of Cd concentration in spleen and RBC were more notable in mice made anemic by phenylhydrazine (PH). Zinc (Zn)-MT was detected in the PH-induced hemopoietic spleen. A subsequent injection of CdCl2 further induced Cd-MT in the spleen. The protein in spleen contained Cd and Zn but not Cu as in RBCs. Maximum levels of Cd-MT in spleen and RBCs of the PH-treated mice were about four times higher than those of control mice. The concentration of Cd-MT in the spleen of polyemia mice, induced by RBC transfusion, was 50% lower than that of control mice. When erythropoietin was injected into the polyemia mice prior to CdCl2, the concentration of Cd-MT in spleen increased about sixfold. These changes in Cd-MT levels in spleen were not observed in either liver or kidney. The effects of erythropoiesis on the concentration of Cd-MT in the spleen corresponded with effects seen in RBC. These results suggest that splenic Cd-MT can be the source of Cd-MT in mature RBC.

Anemia↗

PubMed1995

Three types of nuclear genes encoding chloroplast RNA-binding proteins (cp29, cp31 and cp33) are present in Arabidopsis thaliana: presence of cp31 in chloroplasts and its homologue in nuclei/cytoplasms.

Five chloroplast RNA-binding proteins with consensus sequence-type RNA-binding domains have been isolated from tobacco chloroplasts. Here we report three nuclear genes for similar chloroplast RNA-binding proteins (cp29, cp31 and cp33) from Arabidopsis thaliana. Each of the three genes consists of four exons and three introns and their exon/intron junctions were determined by sequencing respective cDNAs. In vitro import assays showed that all three proteins are located in chloroplasts. The three genes are singly-copy each and the transcription start sites were determined to be 80/82 bp (cp29) and 76/88 bp (cp31) upstream from the translational initiation codons. Northern blot analysis revealed that the three genes are transcribed both in leaves and roots, but the transcript level in leaves is higher than in roots. Phylogenetic analysis of chloroplast RNA-binding proteins so far identified shows that these proteins can be classified into three groups. Tobacco and Arabidopsis have these three types of proteins and structural features of each group are conserved between the two plants, suggesting that they are important for chloroplast functions. Interestingly, cp31 (238 amino acids) shares the identical amino acid sequence from the 30th to the last (238th) residues (including two RNA-binding domains) with the Arabidopsis nucleolin-like ribonucleoprotein, FMV3bp [11]. FMV3bp lacks a transit-peptide and must be located in the nucleus or the cytoplasm.

Amino Acid Sequence↗

PubMed1995

Laparoscopic hepatic resection for hepatocellular carcinoma.

Despite recent progress in diagnostics for hepatocellular carcinoma, the rate of resectability remains low, mainly because of the advancement of the underlying liver disease. We report a case of a 54-year-old man with a hepatocellular carcinoma and poor liver function that was treated successfully with a laparoscopic hepatic resection. Laparoscopic hepatic resection is considered to be feasible with the aid of an ultrasonic dissector and a microwave coagulator; however, close attention should be paid to the development of air embolism and hepatic vein injury.

Carcinoma, Hepatocellular↗