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Biomedical subjects

M Nomoto

Publications and source records attributed to M Nomoto.

At least 91 records · Page 5Linked to original sources
PubMed1997

Metallothionein expression and concentrations of copper and zinc are associated with tumor differentiation in hepatocellular carcinoma.

Metallothionein is the carrier protein of heavy metal ions, such as copper (Cu) and zinc (Zn). In this study, the relationships among immunohistochemical expression of metallothionein, concentrations of Cu and Zn, histological differentiation and proliferative activity of hepatocellular carcinoma were investigated in 51 cases. The concentrations of Cu and Zn in both tumor and non-tumor tissues were determined using electron probe microanalysis. Immunohistochemical expression of metallothionein in tumor tissues decreased with the degree of differentiation, whereas the number of hepatocytes positive for Ki-67 increased. Furthermore, the concentrations of Cu and Zn in tumor tissues decreased with the degree of histological differentiation in human hepatocellular carcinoma.

Biomarkers, Tumor↗
PubMed1997

Changes in nitric oxide synthase activity during exposure to hydrogen peroxide in cultured endothelial cells.

This study clarified the changes in maximum nitric oxide synthase (NOS) activity in cultured bovine aortic endothelial cells during exposure to hydrogen peroxide (H2O2). NOS activity was determined by measuring the conversion of [3H]arginine to [3H]citrulline. Ionomycin, a Ca2+ ionophore, was used to stimulate NOS activity. Addition of ionomycin (10(-5) M) increased the level of L-citrulline formation, and the ionomycin-induced increase in L-citrulline formation was stimulated by H2O2 pretreatment (15-90 min). Longer exposure to H2O2 (> or = 180 min) markedly inhibited the ionomycin-induced L-citrulline formation. The stimulation of ionomycin-induced L-citrulline formation by H2O2 was completely inhibited by N(G)-nitro-L-arginine (L-NNA) or N(G)-methyl-L-arginine (L-NMA), both blockers of NOS. Cell death which was determined by lactate dehydrogenase (LDH) release was induced from 120 min after the addition of H2O2. These findings suggest that the maximum L-citrulline formation from L-arginine, coupled with NOS activity, was increased by H2O2 treatment before cell death. The stimulation of NOS activity may be implicated in H2O2-induced endothelial cell death.

Animals↗
PubMed1996

Effect of anticomplement agent K76 COOH on hamster-to-rat and guinea pig-to-rat heart xenotransplantation.

In normal rats, the xenobiotic K76 inhibited the C5 and probably the C2 and C3 steps of complement and effectively depressed classical complement pathway activity, alternative complement pathway activity, and the C3 complement component during and well beyond the drug's 3-hr half-life. It was tested alone and with intramuscular tacrolimus (TAC) and/or intragastric cyclophosphamide (CP) in rat recipients of heterotopic hearts from guinea pig (discordant) and hamster (concordant) donors. Single prevascularization doses of 100 and 200 mg/kg increased the median survival time of guinea pig hearts from 0.17 hr in untreated controls to 1.7 hr and 10.2 hr, respectively; with repeated injections of the 200-mg dose every 9-12 hr, graft survival time was increased to 18.1 hr. Pretreatment of guinea pig heart recipients for 10 days with TAC and CP, with or without perioperative splenectomy or infusion of donor bone marrow, further increased median graft survival time to 24 hr. Among the guinea pig recipients, the majority of treated animals died with a beating heart from respiratory failure that was ascribed to anaphylatoxins. Hamster heart survival also was increased with monotherapy using 200 mg/kg b.i.d. i.v. K76 (limited by protocol to 6 days), but only from 3 to 4 days. Survival was prolonged to 7 days with the addition of K76 of intragastric CP at 5 mg/kg per day begun 1 day before operation (to a limit of 9 days); it was prolonged to 4.5 days with the addition of intramuscular TAC at 2 mg/kg per day beginning on the day of transplantation and continued indefinitely. In contrast to the limited efficacy of the single drugs, or any two drugs in combination, the three drugs together (K76, CP, and TAC) in the same dose schedules increased median graft survival time to 61 days. Antihamster antibodies rapidly increased during the first 5 days after transplantation, and plateaued at an abnormal level in animals with long graft survival times without immediate humoral rejection. However, rejection could not be reliably prevented, and was present even in most of the xenografts recovered from most of the animals dying (usually from infection) with a beating heart. Thus, although effective complement inhibition with K76 was achieved in both guinea pig- and hamster-to-rat heart transplant models, the results suggest that effective interruption of the complement cascade will have a limited role, if any, in the induction of xenograft acceptance.

Animals↗
PubMed1996

Herbal medicine 'Sho-saiko-to' induces tumour necrosis factor-alpha and granulocyte colony-stimulating factor in vitro in peripheral blood mononuclear cells of patients with hepatocellular carcinoma.

'Sho-saiko-to' (TJ-9) is a Japanese herbal medicine that is commonly administered to patients with chronic viral liver disease in order to improve their overall physical condition and to prevent the development of liver cancer, The present in vitro study demonstrated that, by adding TJ-9 to cell cultures, there were dose-dependent increases in production levels of tumour necrosis factor-alpha (TNF-alpha) and granulocyte colony-stimulating factor (G-CSF) in peripheral mononuclear cells of patients with hepatocellular carcinoma accompanied by liver cirrhosis. Increases in the production of TNF-alpha and G-CSF in control cell cultures exposed to different herbal medicines were low, and this indicates the specificity of the response increases in production of these cytokines to TJ-9. TNF-alpha and G-CSF are known to play important roles in the biological defence mechanism. Administration of TJ-9 may, therefore, be beneficial for patients afflicted with intractable liver diseases because it could mildly induce these cytokines.

Carcinoma, Hepatocellular↗
PubMed1996

Expression of mucin antigens and Lewis X-related antigens in carcinomas and dysplasia of the pharynx and larynx.

Recent studies have identified that mucin antigens and Lewis X (Lex)-related antigens behave like oncodevelopmental tumor-associated antigens in several human adenocarcinomas. However, the expression of these antigens in pharyngeal and laryngeal squamous cell carcinomas (SCC) and in the precursor lesion is not fully elucidated yet. In the present study, the expression of mucin core protein antigens associated with the MUC1 gene product (DF3 antigen, mammary-type apomucin) and the MUC2 gene product (intestinal-MRP antigen, intestinal-type apomucin) mucin carbohydrate antigens that are associated with the earliest steps in mucin glycosylation (Tn, sialyl-Tn and T), and Lex-related antigens (Lex, Ley and sialyl Lex-i) in biopsy or resected specimens from 26 normal squamous epithelia (NSE), 49 dysplastic squamous epithelia (DSE) and 51 SCC were examined. The DF3 antigen was not expressed in NSE (0%), whereas it was expressed in 20 DSE (41%) and in 31 SCC (61%). The intestinal-MRP antigen showed no expression in NSE, DSE or SCC. The Tn antigen showed no expression in NSE, but showed low expression rates in DSE (14%) and in SCC (16%). The sialyl-Tn and T antigens were expressed in NSE, as well as in DSE and SCC. The T antigen expression increased with progression from NSE to DSE to SCC, while the sialyl-Tn antigen did not show such a tendency. Any of the three Lex-related antigens showed no characteristic expression in DSE and SCC. In the eight antigens examined, only DF3 antigen was an effective marker for DSE and SCC in the pharyngeal and laryngeal region. Cytoplasmic expression of DF3 and sialyl-Tn antigens were more frequently seen in SCC than in DSE, and might be useful to differentiate SCC from DSE.

Antigens, Neoplasm↗
PubMed1996

Characteristic upregulation of dopamine D1-receptor in rat striatum after 6-hydroxydopamine treatment.

We measured the number of D1-receptors (Bmax) in the striatum whose dopaminergic terminals were destroyed to various degrees by 6-hydroxydopamine (6-OHDA) to clarify the relationship between the degree of denervation and the change in Bmax for D1-receptor. Rats were sacrificed 28 days after 6-OHDA treatment, and [3H]SCH23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine) binding capacity and monoamine content were measured in striatal homogenate. Bmax was significantly upregulated when dopamine content was reduced to less than 5% of that in the vehicle-treated striatum. In contrast, it was significantly decreased when dopamine content was 5-25% of that in the vehicle-treated striatum. The D1-receptors showed either upregulation or downregulation depending on the degree of denervation.

Animals↗
PubMed1996

Severe cryoglobulinemia in a patient with asymptomatic hepatitis C virus infection.

A patient with severe type II cryoglobulinemia after ten years of asymptomatic hepatitis C virus (HCV) infection is reported. Laboratory data showed hypergammaglobulinemia with polyclonal IgG and monoclonal IgM, blood hyperviscosity, high level of cryocrit (60%), HCV viremia, and normal levels of serum transaminases. Due to cold exposure, acrocyanosis and cardiac ischemic attack occurred; he recovered after being artificially warmed. Administration of prednisolone and natural interferon-alpha for three months resulted in significant decreases in the levels of serum IgM and cryocrit.

Cryoglobulinemia↗
PubMed1996

[Recent progress in development of psychotropic drugs (3)--Antiparkinsonian agents applied in the treatment of Parkinson's disease or are under investigation for patients or model animals].

Tremor, akinesia, rigidity and postual instability are key signs of Parkinson's disease. The most important one is akinesia, which includes decreased spontaneous locomotor activity, slowness of movement, awkwardness and freezing. On the other hand, an electrical focal lesion in the brain, neurotoxin to dopaminergic neurons such as 6-hydroxydopamine (6-OHDA) or I-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), cholinomimetic tremorogenic agents such as oxotremorine or tremorine, monoamine depleting agents such as reserpine or tetrabenazine, or dopamine receptor antagonists such as haloperidol are applied to render animal parkinsonism. The estimation of locomotor activity can be done accurately in animal models. Tremor can be studied using the animals treated by cerebral focal lesion, neurotoxins or cholinomimetics. Skillfulness is hard to estimate in animals, however, it can be done in primates. Freezing appeared in patients with levodopa treatment over a long period. This is a specific motor sign in Parkinson's disease, and cannot be observed in animals. Supplementing dopamine by levodopa administration, retarding the metabolism of levodopa or dopamine by dopa decarboxylase inhibitor (DCI), monoamine oxidase inhibitor type B (MAO-B) inhibitor or catechol-O-methyltransferase (COMT) inhibitor, dopamine receptor agonists, anticholinergic agents, dopamine release enhancer/ uptake inhibitor, N-methyl-D-aspartate (NMDA) receptor antagonists, adenosine receptor antagonists, neurotrophic factors, GM1-ganglioside and nicotinic receptor agonists have been applied in the treatment of Parkinson's disease or are under investigation for patients. Agents to facilitate nerve growth or to inhibit the degeneration of nerves will be developed in the future.

Animals↗
PubMed1996

Glutamine metabolism of intestine grafts: influence of mucosal injury by prolonged preservation and transplantation.

The demand for glutamine increased only in the preserved intestine in the early postoperative period (3 days after transplantation). Glutamine demand of the preserved grafts returned to control and immediate levels 7 and 14 days after transplantation. Three days after intestinal transplantation, when the intestinal mucosa was actively regenerating, the demand for glutamine was markedly enhanced. The enhanced demand for glutamine was met by increased output of glutamine by the liver and skeletal muscle. Glutamine uptake by the intestinal graft was enhanced by a brief infusion of glutamine. Thus, we believe exogenous glutamine supplementation may be beneficial for the recovery of intestinal grafts with severe mucosal injury.

Animals↗
PubMed1996

Effect of nipradilol, a beta-adrenergic blocker with vasodilating activity, on oxotremorine-induced tremor in mice.

The effect of nipradilol, a nonselective beta-adrenergic receptor blocker with nitroglycerin-like vasodilating activity, on oxotremorine-induced tremor was studied in mice. General tremor in mice was elicited by 0.5 mg/kg oxotremorine. The tremor was quantified using a capacitance transducer, then analyzed by a signal processor. The strength of the tremor was expressed in "points". The point values of the tremor (mean +/- SE) in control mice for 5 mg/kg (+/-)-propranolol, 2.5 mg/kg arotinolol, 0.5 mg/kg nipradilol, 1.0 mg/kg nipradilol and 2.5 mg/kg nipradilol were 87 +/- 16, 42 +/- 6, 38 +/- 6, 99 +/- 28, 28 +/- 6 and 31 +/- 7, respectively. The strength of the tremor was reduced by all beta-blockers. Although 1.0 mg/kg nipradilol significantly reduced the tremor, further inhibition of the tremor was not obtained with dosages up to 2.5 mg/kg of the drug. In conclusion, nipradilol was effective for suppressing oxotremorine-induced tremor, as were other beta-blockers.

Adrenergic beta-Agonists↗
PubMed1995

Analysis of cis-acting regions upstream of the rat Na+/K(+)-ATPase alpha 1 subunit gene by in vivo footprinting.

By means of in vivo footprinting, we examined the putative cis-acting DNA elements located between -50 and -122 of rat Na+/K(+)-ATPase alpha 1 subunit gene ATP1A1. Proximal and distal GC box sequences and a consensus sequence for the active transcription factor (ATF) were protected for all the tissues examined (kidney, brain and liver). Putative cooperation between two binding factors on the ATF site and the proximal GC box was observed. The overall in vivo footprinting profiles of the three tissues did not exhibit any marked differences that could account for the variation in the extent of tissue-specific transcription. The alpha 1 regulatory element (ARE) found by Suzuki-Yagawa et al. does not appear to be an element responsible for tissue-specific regulation of the gene.

Animals↗