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Biomedical subjects

H Nishimura

Publications and source records attributed to H Nishimura.

At least 235 records · Page 13Linked to original sources
PubMed1992

[Phase II study of 254-S (cis-diammine glycolato platinum) for gynecological cancer].

A phase II study of 254-S was conducted in 134 patients with gynecological malignancies by the gynecology section of the 254-S cooperative study group. The drug was administered at least twice at a dose of 100 mg/m2 by intravenous infusion at 4 week intervals. Forty-two of the 102 evaluable patients responded, including 8 CRs and 34 PRs, with a response rate of 41.2%. The response rate was 37.7% for ovarian cancer and 46.3% for cervical cancer. The response rate of 46.3% for cervical cancer was the highest reported for any single anticancer agent available in Japan. The major side effect was hematotoxicity, in particular thrombocytopenia and leukopenia, while nephrotoxicity was rarely observed. These results suggest that 254-S is an active cisplatin analogue with reduced nephrotoxicity and is a very promising anticancer agent for the treatment of ovarian and cervical cancer.

Adult↗
PubMed1992

[Relationship between tumor markers and clinical symptoms in ovarian cancer].

To assess their usefulness in the prediction of tumor recurrence, we retrospectively examined the accuracy of preoperative diagnosis of ovarian cancer based on tumor markers on 279 patients with benign and malignant ovarian tumors treated at our department. Of the tumor markers examined, CA125 had the highest diagnostic accuracy, suggesting that it is the most useful marker in the diagnosis of ovarian cancer. TPA and IAP were found to be relatively useful, the tumor markers recently identified, CA72-4 had a high true positive rate. We examined the factors affecting the cut-off value for CA125 in healthy volunteers and determined the corrected cut-off value. Using this value, we assessed the usefulness of CA125 in distinguishing between benign and malignant tumors and in predicting tumor recurrence. Factors found to affect the serum CA125 level included pregnancy, menstrual cycle, dysmenorrhea, menopause, and blood type. Using our equation for women over 40 years of age, we obtained a specific cut-off level of 16 U/ml for postmenopausal women, which was found to more accurately distinguish between ovarian tumors in this age group than did the conventional cut-off level of 35 U/ml, which has been used for all age groups. Furthermore, the specific cut-off level predicted tumor recurrence about 2 months earlier than did the conventional cut-off value. In tumor recurrence, CA125 had risen gradually but was within the normal range. Tumor recurrence was observed in all patients who had shown continuous three-stage elevation of CA125 within the normal range.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

[A phase II clinical study of cis-diammine glycolato platinum, 254-S, for cervical cancer of the uterus].

A phase II clinical study of 254-S, a new anticancer platinum complex, for cervical cancer was conducted by the 254-S Cervical Cancer Study Group consisting of 10 institutions. 254-S was administered at 80 mg/m2 by intravenous drip infusion and this administration was repeated at least 2 times at 4-week intervals, in principle. Forty of 45 patients registered, were eligible and 38 were evaluable for tumor response (complete cases). Complete response (CR) and partial response (PR) were obtained in 4 (10.5%) and 9 patients (23.7%), respectively, for a 34.2% response rate. Against squamous cell carcinoma, a 38.2% response rate (4 CR and 9 PR in 34 patients) was obtained. The response rate obtained in patients with no prior chemotherapy was 40.0% (2 CR and 8 PR in 25 patients), while that in patients with prior chemotherapy was 23.1% (2 CR and 1 PR in 13 patients). Major toxic effects observed were hematotoxicity, including thrombocytopenia (35.1%), leukopenia (73.0%), anemia (75.7%), gastrointestinal toxicity such as nausea and vomiting (83.8%) and anorexia (83.8%). Nephrotoxicity observed was in the form of an elevation of serum creatinine with an incidence of 2.7% and a decrease in creatinine clearance with an incidence of 21.7%. In comparison with the results obtained in the phase II clinical study for gynecological cancers in which 254-S was administered at 100 mg/m2, the response rate obtained in this study was slightly lower but thrombocytopenia and leukopenia observed were less frequent and milder. Based on these results, it was concluded that 254-S is a very useful anticancer agent for the treatment of cervical cancer.

Adenocarcinoma↗
PubMed1992

[A case of unknown origin cancer of the mediastinal lymph node].

We encountered an unusual case with a sole cancer focus at the mediastinal lymph node. The patient was a 44-year-old man who visited our department with a chief complaint of chest pain. Subsequent chest X-ray and CT revealed an enlargement of a mediastinal lymph node. The excised lymph node measured 6.8 x 5.5 x 4.0 cm and weighed 51 g. It showed metastasis of poorly differentiated adenocarcinoma. In spite of a thorough systemic examination, no primary foci were detected. Lymph node tumors of the mediastinum or hilar region with unknown primary foci are extremely rare (there have been only 2 reported cases of lesions found at the hilar lymph node with unknown primary focus). There have been no reports on cancerous foci limited to the mediastinal lymph nodes. The patient has been under chemotherapy and radiotherapy during the past 3 years following surgery. He shows no signs of recurrence. It is a very unusual case. A possible classification of T0N2M0 has been considered.

Adenocarcinoma↗
PubMed1991

Phosphorylation state of the GLUT4 isoform of the glucose transporter in subfractions of the rat adipose cell: effects of insulin, adenosine, and isoproterenol.

The acute effects of insulin, adenosine, and isoproterenol on the activity, subcellular distribution, and phosphorylation state of the GLUT4 glucose transporter isoform were investigated in rat adipocytes under conditions carefully controlled to monitor changes in cAMP-dependent protein kinase (A-kinase) activity. In contrast to GLUT1, which has not been shown to be phosphorylated even when cells are exposed to any of the above agents, GLUT4 was partially phosphorylated (0.1-0.2 mol/mol) when the activity of the A-kinase was suppressed, and remained unchanged in response to insulin. Isoproterenol elicited a 64% inhibition of insulin-stimulated glucose transport activity in the absence, but not the presence, of adenosine receptor agonists. However, in either the presence or the absence of agonists, A-kinase was activated as assessed by examining the phosphorylation of the major adipocyte A-kinase substrate, perilipin. Similarly, under either condition, phosphorylation of GLUT4 was enhanced 1.4-fold in the intracellular membranes, but no significant change was observed in the plasma membrane. In the absence of adenosine receptor agonists, isoproterenol exerted a small (14%) but significant inhibition of the insulin-induced translocation of GLUT4 but had no effect on the translocation of GLUT1. Thus, changes in the phosphorylation state and/or subcellular distribution of GLUT4 cannot account for the inhibition of insulin-stimulated glucose activity induced by isoproterenol.

Adenosine↗
PubMed1991

Staurosporine, a protein kinase inhibitor, attenuates basal forebrain-lesion-induced amnesia and cholinergic neuronal deficit.

We have investigated whether administration of staurosporine, which has been reported to induce differentiation in the human neuroblastoma cell in vitro, attenuates amnesia induced by basal forebrain lesion in rats. Multiple dosage of staurosporine at the doses of 0.05 and 0.1 mg/kg (i.p.) attenuated the impaired performance of the water maze task. Moreover, staurosporine (0.1 mg/kg) reversed the decrease of choline acetyltransferase activity in the fronto-parietal cortex. These results suggest that staurosporine attenuates amnesia through reversal of deficits in cholinergic neurons induced by basal forebrain lesion, and that neurotrophic factor-like substances may open the way for novel therapeutic approaches to Alzheimer's disease.

Alkaloids↗
PubMed1991

Contribution of the gene linked to the T cell receptor beta chain gene complex of NZW mice to the autoimmunity of (NZB x NZW)F1 mice.

We have investigated the contribution to the autoimmune disease of (NZB x NZW)F1 (NZB/W) mice made by the T cell receptor beta (TcR beta) chain gene complex, or genes linked to it, that are derived from the NZW strain. For this we developed the NZW.TcR beta NZB strain, a NZW congenic line carrying the TcR beta of NZB type, and produced NZB x NZW.TcR beta NZB (NZB/W.TcR beta NZB)F1 mice. We compared the amounts of anti-DNA and anti-histone antibodies and also the severity of lupus nephritis in these mice with those in the original NZB/W F1 mice. We obtained evidence for significantly lower serum levels of autoantibodies to double-stranded and single-stranded DNA and histone, and a later onset and a lower incidence of proteinuria in the NZB/W.TcR beta NZB F1 mice than in the original NZB/W F1 mice. These findings clearly indicate that the gene(s) within or closely linked to the TcR beta chain gene complex on chromosome 6 of the NZW strain acts to intensify the feature of systemic lupus erythematosus in the NZB/W F1 strain. The significant relationship of this finding to the strict dependency of NZB/W F1 disease on the H-2d/H-2z heterozygosity is discussed.

Animals↗
PubMed1991

Immunohistochemical localization of metallothionein in the eye of rats.

In order to elucidate possible physiological roles of metallothionein (MT), we have studied immunohistological localization of MT in the eye of the rat, using an avidin-biotin peroxidase complex method. As a result, strong MT immunostaining was observed in the epithelium of the lens and cornea. In the retina, considerably strong MT immunostaining was observed in the pigment cell layer while the nerve fiber layer and inner plexiform layer showed weak MT staining. Glial cells in the optic nerve were found to have marked MT staining. The present result is consistent with the hypothesis that MT may be involved not only in activation of zinc enzymes and cell proliferation through supply of zinc ions, but also in a protective mechanism in the blood-retina barrier.

Animals↗
PubMed1991

Humoral factor mediates acetylcholine-induced endothelium-dependent relaxation of chicken aorta.

A superfusion cascade system was used to determine whether endothelium-dependent vasorelaxation induced by acetylcholine (ACh) is mediated by a humoral factor(s) in the domestic fowl. An abdominal aorta (5 cm in length) with intact endothelium, excised from the donor bird, was mounted in an organ bath and perfused with avian Ringer solution. The vasorelaxing activity of the effluent was determined by an endothelium-denuded aortic ring (bioassay ring) equilibrated and precontracted with phenylephrine (PHE) (10(-6) M). The effluent (containing PHE) from the donor aorta with intact endothelium did not significantly change the PHE-induced tension of the bioassay rings. ACh (10(-6) M), when added to the perfusion medium that runs through the control polyethylene tubing, produced further contraction of the PHE-precontracted endothelium-denuded bioassay rings, whereas ACh caused relaxation of the rings when added to the perfusate that passes through the endothelium-intact donor aorta. The ACh-induced relaxation of the bioassay ring was slightly potentiated by superoxide dismutase (100 U/ml). Hemoglobin (10(-5) M) increased the basal tension of the bioassay rings and completely inhibited the ACh-induced relaxation of the rings. These results suggest that ACh-induced relaxation of fowl aorta is, at least partially, mediated by a humoral factor(s) that resembles endothelium-derived relaxing factor demonstrated in mammals.

Acetylcholine↗
PubMed1991

Fuzzy realization in clinical test database system.

To be able to obtain useful information from medical data easily and quickly in daily use for the hospital staff, it is necessary to construct a proper database system using methodologies suitable for the nature of medical data. From this viewpoint we have developed the clinical test relational database system at Hiroshima University Hospital, which provides the functions of easy on-line retrieval and statistical analysis. Fuzzy query processing based on the fuzzy set theory is adopted in the system. This enables us to use natural linguistic representation and makes it easy to introduce medical knowledge representation. Fuzzy set approaches turn out to be superior in clinical evaluation of laboratory data to the ordinary clear-cut definition of normalcy.

Artificial Intelligence↗
PubMed1991

Nine phenethyl alcohol glycosides from Stachys sieboldii.

Three new phenethyl alcohol glycosides together with six known compounds have been isolated from the leaves of Stachys sieboldii. On the basis of chemical and spectral analyses, the structures of three new compounds named stachysosides A, B and C have been established as 2-(3,4-dihydroxyphenyl)ethyl O-alpha-L-arabinopyranosyl-(1----2)-alpha-L-rhamnopyranosyl- (1----3)-4-O-E-caffeoyl-beta-D-glucopyranoside, 2-(3,4-dihydroxyphenyl)ethyl O-alpha-L-arabinopyranosyl-(1----2)-alpha-L-rhamnopyranosyl- (1----3)-4-O-E-feruloyl-beta-D-glucopyranoside and 2-(3-hydroxy-4-methoxyphenyl)ethyl O-alpha-L-arabinopyranosyl-(1----2)-alpha-L-rhamnopyranosyl- (1----3)-4-O-E- feruloyl-beta-D-glucopyranoside, respectively.

Carbohydrate Sequence↗
PubMed1991

CD5+ B cells in autoimmune disease and lymphoid malignancy.

Evidence is accumulating that CD5+ B cells belong to a developmental lineage distinct from that of conventional B cells and mainly participate in natural immunity. They have attracted attention because of their involvement in autoimmunity and lymphoid malignancy in both mice and humans. Patients with rheumatoid arthritis and Sjögren's syndrome were found to show a striking increase in the number of CD5+ B cells. B cell-chronic lymphocytic leukemia cells frequently express CD5. However, there are arguments against the role for CD5+ B cells in autoimmune disease, particularly in murine and human systemic lupus erythematosus (SLE). Whereas most IgM anti-DNA antibodies are produced by CD5+ B cells, high-affinity, pathogenic IgG antibodies are produced mainly by CD5- B cells. Either of two possibilities can explain the failure of CD5 expression of B cells responsible for producing IgG anti-DNA antibodies: either the cells are conventional B cells or the cells are CD5+ B cells that lack CD5 expression. In studies using SLE-prone NZB x NZW F1 mice and their H-2-congenic progeny, we discussed herein the possibility that CD5+ B lineage cells are also responsible for the pathogenic IgG autoantibody production by phenotypic switching from CD5+ to CD5-, probably under a particular genetic background. A line of H-2-congenic NZB x NZW F1 progeny failed to produce IgG anti-DNA antibodies, but in turn, showed a marked clonal proliferation of CD5+ B cells. Thus, it appears that genetically determined signals for either proliferation or differentiation would lead CD5+ B cells to cause distinct disease, i.e., autoimmune disease or lymphoid malignancy. Further studies using H-2-congenic New Zealand mice may provide insights into the correlation between autoimmunity and related lymphoid malignancy.

Animals↗
PubMed1991

TNF susceptibility-related gene expression.

A series of BWL hybridoma lines has been generated by cell fusion of a TNF-resistant BW5147 cell line and a highly TNF-sensitive WR19L cell line, and has exhibited a wide variety of TNF susceptibility. A cDNA library, BWL47rp10, from a TNF-susceptible hybridoma line BWL47 has been screened by hybridization with a 32P-labeled subtraction cDNA probe from WR19L cells. Thirty-nine candidates for TNF susceptibility were cloned, and 20 clones larger than 1.0 kb have been examined so far. A cDNA clone, 10-2, hybridized to mRNA of 1.8 kb. It was expressed higher in highly TNF-sensitive cells, especially in BWL47, BWL40, and BWL57 cells. Thus, at least, the expression of the mRNA identified with cDNA 10-2 correlated well with TNF susceptibility in BWL cells, although its functional identity remains to be determined.

Animals↗
PubMed1991

Regulation of glucose transporter synthesis in cultured human skin fibroblasts.

The present study was designed to see the effects of glucose on glucose transporter expression and glucose transport activity using cultured human skin fibroblasts. When the cells were incubated with various concentrations of glucose (11.1-44.4 mM), no differences were found in the HepG2 glucose transporter mRNA, protein levels and basal and insulin-stimulated 2-deoxyglucose uptake. Glucose deprivation, however, resulted in approximately 4-fold increases in the mRNA and 3-fold increases in the protein and the basal 2-deoxyglucose uptake. Chronic exposure to insulin increased the glucose transporter protein levels to similar degrees in the cells incubated with 11.1, 22.2 and 44.4 mM glucose accompanied by increases in the glucose transport activity. Effects of insulin on the glucose transporter mRNA and protein levels, however, were not evident in the glucose-deprived cells. It is concluded that glucose transport activity correlates closely with HepG2 glucose transporter expression in cultured human fibroblasts and that glucose (11.1-44.4 mM) does not affect the glucose transporter expression and glucose transport activity.

Blotting, Western↗
PubMed1991

Community-acquired influenza C virus infection in children.

To clarify the epidemiologic and clinical features of community-acquired influenza C infection in children, we took specimens throughout the year from a larger number of patients with acute respiratory illnesses in a pediatric clinic in Yamagata, Japan. During a 2-year survey, 20 strains of influenza C virus were isolated from 13,426 specimens. These isolates were recovered throughout the year. The ages of patients with influenza C virus isolates ranged from 2 months to 11 years and peaked at the age of 1 year. The clinical diagnosis of patients with influenza C virus infection included bronchitis in one child and pneumonia in four. Community-acquired influenza C infection in children can cause a variety of respiratory illnesses that cannot be clinically differentiated from those caused by other viruses.

Child↗
PubMed1991

Regional variation in oral mucosal drug absorption: permeability and degree of keratinization in hamster oral cavity.

The regional permeability of oral mucosa to salicylic acid was investigated in vivo in hamsters along with histological variations, especially the degree of keratinization. Histological sections from six regions, i.e., sublingual mucosa, buccal mucosa, dorsum of tongue, ventral surface of tongue, labial mucosa, and cheek pouch mucosa, were prepared to assess the degree of keratinization. The area under the plasma concentration-time curve of salicylic acid following the administration of salicylic acid to the oral mucosa with a film dosage form and the thickness of stratum corneum of each site were in inverse proportion to each other, suggesting that the stratum corneum layer represents the principle barrier to drug absorption.

Absorption↗