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Biomedical subjects

N Shimada

Publications and source records attributed to N Shimada.

At least 181 records · Page 10Linked to original sources
PubMed1993

Estradiol up-regulates the stimulatory GTP-binding protein expression in the MCF-7 human mammary carcinoma cell line.

The effect of estradiol treatment of the human mammary carcinoma cell MCF-7 on the adenylyl cyclase system was examined. Treatment with 10 nM estradiol for 72 h increased the basal level of cAMP, and isoproterenol-, PGE2- or calcitonin-stimulated cAMP production. Estradiol also increased the response to cholera toxin but did not alter the response to forskolin. No significant change in growth rate was observed during the 72 h of estradiol treatment. In MCF-7 cell membranes the responsiveness to isoproterenol, PGE2, or cholera toxin was also enhanced by estradiol treatment. The cholera toxin-catalyzed ADP-ribosylation of Gs alpha in MCF-7 cell membranes was significantly increased by 72 h of treatment with estradiol. Consistent with this observation, the level of Gs alpha immunoreactivity was increased in the estradiol-treated cell membranes. On the other hand, pertussis toxin did not change the responsiveness to isoproterenol, PGE2 or calcitonin in either control or estradiol-treated cells. In addition, ADP-ribosylation with pertussis toxin also did not reveal any change in Gi. These results clearly indicate that Gs expression is under the control of estradiol, and that this effect may contribute to the increased sensitivity of hormone-stimulated adenylyl cyclase activities in MCF-7 cells.

Adenylate Cyclase Toxin↗
PubMed1993

A second form (beta isoform) of nucleoside diphosphate kinase from rat. Isolation and characterization of complementary and genomic DNA and expression.

Complementary and genomic clones for a second form (the beta isoform) of rat nucleoside diphosphate kinase were isolated. Structural studies revealed that nucleotide and deduced amino acid sequences of the beta isoform were quite similar to those of the alpha isoform (identities were 82 and 89%, respectively), which were delineated in our previous study (Kimura, N., Shimada, N., Nomura, K., and Watanabe, K. (1990) J. Biol. Chem. 265, 15744-15749). The gene encoding the beta isoform, covering 10 kilobases and comprising five exons, was located in tandem in the immediate vicinity (at a 3-kilobase distance) of the 5' upstream of the alpha isoform gene which was recently reported from this laboratory (Ishikawa, N., Shimada, N., Munakata, Y., Watanabe, K., and Kimura, N. (1992) J. Biol. Chem. 267, 14366-14372), suggesting their generation by gene duplication. The exon-intron junctions were exactly conserved between the two genes. Southern blot analyses showed that unidentified fragments cross-reacted with the beta isoform cDNA probe besides those containing the genuine gene, and at least two of them were identified as possible processed pseudogenes. Northern and dot blot hybridization studies demonstrated that the alpha isoform was more expressed than the beta isoform in rat tissues examined except brain, from which the isoform designation was derived. These results suggest independent expression and specific roles of these isoforms in the cell. Comparative studies between rat and human isoforms indicate that the isoforms could have differentiated before the two species evolutionally diverged.

Amino Acid Sequence↗
PubMed1993

Characterization of specific cytochrome P450 enzymes responsible for the metabolism of diazepam in hepatic microsomes of adult male rats.

The role of several P450 enzymes in the metabolism of diazepam (DZ) has been investigated. Hepatic microsomes of adult male rats were pretreated with antisera raised against the P450s CYP3A2, 2B1, 2C6, 2C11, 2D1 and 2E1, and their influence on the subsequent metabolism of DZ was determined by simultaneously measuring the changes in the relative rates of formation of its metabolites. Several forms of P450 were found to be positively involved in DZ metabolism. Antisera of the "male-specific" P450 enzyme CYP2C11 partially inhibited both DZ N-demethylase and C3 hydroxylase activities (60%) which resulted in decreased formations of N-desmethyl-DZ (NDZ) and 3-hydroxy-DZ (3HDZ), respectively. In a reconstitution experiment with the purified enzyme, CYP2C11 predominantly catalysed the formation of NDZ from DZ. Antisera of a further male-specific P450 CYP3A2 strongly inhibited (95%) the C3 hydroxylase of DZ and thus 3HDZ formation. A corresponding reconstitution experiment with this same P450 enzyme gave 3HDZ as principal product. CYP2D1 antisera inhibited the aromatic hydroxylation of DZ (98%) and subsequent formation of 4'-hydroxy-DZ (4'HDZ). This enzyme was also observed to inhibit DZ N-demethylase activity (60%). A reconstitution experiment with pure CYP2D1 catalysed the formation of both 4'HDZ and NDZ.

Animals↗
PubMed1993

Relationship between content of hepatic glutathione S-transferases and the kinetics of indocyanine green elimination in various liver diseases.

The glutathione (GSH) S-transferases are believed to have dual functions as hepatic detoxifying enzymes and intrahepatic binding proteins. Little is known about their alterations in human liver diseases. Therefore, we have studied the relationship between the enzyme activity and rose bengal (RB) binding in hepatic cytosol and plasma indocyanine green (ICG) kinetics in patients with various liver diseases. The enzyme activity was measured in samples of hepatic cytosol obtained from 52 patients. In addition, the content of cationic and neutral transferases was estimated in 17 biopsy samples by densitometry of Coomassie blue stained sodium dodecyl sulphate polyacrylamide gel electrophoretograms. RB binding studies also were performed on cytosol samples. ICG kinetic parameters were determined using the two-compartment open model in 17 patients who were given the dye (0.5 mg kg-1) intravenously. Correlations between the enzyme activity and liver function tests, content of the enzyme, RB binding and ICG kinetic parameters were evaluated. The following results were obtained. (1) The enzyme activities were high in alcoholic liver disease, fatty liver and Gilbert's syndrome, and low in cirrhosis. (2) The enzyme activities were positively correlated with serum cholinesterase activity, serum albumin level and hepaplastin test, and negatively correlated with ICG retention rate at 15 min. (3) The enzyme activity, its content and RB binding affinity of the cytosol were positively correlated with each other. (4) The enzyme activity was positively correlated with hepatic ICG distribution volume. These results are consistent with the role of the GSH S-transferases as ligandins in intracellular storage of dyes.

Adenoma, Bile Duct↗
PubMed1993

Ischemia-induced accumulation of extracellular amino acids in cerebral cortex, white matter, and cerebrospinal fluid.

In a global model of brain ischemia, accumulation of amino acids was studied in the extracellular space of the auditory cortex and the internal capsule using microdialysis, and in CSF of halothane anesthetized cats. In both brain regions, blood flow determined by hydrogen clearance decreased below 10 ml/100 g/min after extracranial multiple-vessel occlusion, and extracellular potassium activity (Ke) measured in the dialysate increased significantly. A delayed rise in Ke was observed in CSF. In contrast, ischemic amino acid accumulation differed markedly between the two brain regions investigated. In cortex, transmitter amino acids glutamate, aspartate, and gamma-aminobutyric acid (GABA) rose almost immediately after onset of ischemia, and increased 30-, 25-, and 250-fold, respectively, after 2 h of ischemia. The nontransmitter amino acids taurine, alanine, and serine increased 10-, seven-, and fourfold, respectively, whereas glutamine and essential amino acids (valine, phenylalanine, isoleucine, and leucine) increased only 1.5-fold. In the internal capsule, increases in amino acids, if any, were delayed and much smaller than in cortex. The largest alteration was a fivefold elevation of GABA. In CSF, changes in amino acids were small and comparable to those in the internal capsule. Our results demonstrate that ischemia-induced extracellular amino acid accumulation is a well localized phenomenon restricted to gray matter structures that possess release and reuptake systems for these substances. We assume that amino acids diffuse slowly into adjacent while matter structures, and into CSF.

Amino Acids↗
PubMed1993

[Effects of buprenorphine on gastrointestinal interdigestive myo-electric complex in dogs].

The effect of buprenorphine on the interdigestive myoelectric complex (IMC) was studied by gastrointestinal electromyogram in 3 mature mongrel dogs. The electromyograms were used to study the IMC cycle and total elapsed time (TET). Buprenorphine had very strong hyperkinetic action on the gastrointestinal tract at doses of 1 and 2 micrograms/kg which revealed phasic contraction, but since this action disappeared when atropine was administered. The phasic contraction originated in the upper jejunum just under the ligament of Treitz and then showed a migration pattern of J-->D and J-->I in 11 out of 23 cases (47.8%), D-->J-->I in nine cases (39.1%), J-->D-->J-->I in one case and no response in two cases. TET (min) showed a mean value of 90.3 +/- 11.2 (n = 23), which was not significantly different from the controls (106.1 +/- 14.3) (n = 24), but tended to be longer (0.1 > p > 0.05). After administration of buprenorphine at a dose of 20 micrograms/kg, phasic contraction migrated to ileum, which was disappeared an interval of 6-7 hours until next IMC. At low doses of buprenorphine were administered after a meal, the postprandial pattern was restored and converted to fasted pattern only one IMC cycle. Buprenorphine is partial agonist for the mu receptor. Ahmad et al. (1989) reported that alpha 2 adrenergic receptor and opiate receptors (mainly mu) were presented in submucosal plexus. In concludes that alpha 2 adrenergic activity and other humoral factors seems to take an important role for the initiation of phasic contraction and to control maintenance of IMC cycle.

Animals↗
PubMed1993

Changes in the amounts of cytochromes P450 in rat hepatic microsomes produced by cyclosporin A.

1. The effect of cyclosporin A, an immunosuppressive drug, on the levels of individual cytochromes P450 of rat liver was studied by immunoblotting with specific antibodies. Changes in the metabolic activities of the microsomal enzymes were similarly studied. 2. Total P450 was decreased by treatment with cyclosporin A for 17 days. NADPH-P450 reductase activity was also decreased by treatment with cyclosporin A for 10 days and decreased further after 17 days. 3. Cytochromes 2B2 and 2C6 concentrations were decreased by treatment with cyclosporin A for 17 and 10 days, respectively. Administration of cyclosporin A for 17 days also decreased the levels of the male specific cytochromes 2C11 and 3A2, and consequently decreased testosterone 2 alpha-, 16 alpha-, 2 beta- and 6 beta-hydroxylation activities. Shorter periods (7 and 10 days) of cyclosporin A treatment decreased the level of cytochrome 3A2, which metabolizes cyclosporin A. In contrast, the level of cytochrome 2C13 was unchanged.

Animals↗
PubMed1993

[Autonomic dysfunction in sensory ataxic neuropathy with Sjögren's syndrome].

Sjögren's syndrome (SjS) is occasionally associated with chronic progressive sensory neuropathy, and its major pathology is suggested to be dorsal root ganglionitis with the T-lymphocyte invasion. Autonomic dysfunction is frequently accompanied by SjS-associated sensory neuropathy but its underlying pathology is uncertain. We reported four patients with SjS-associated sensory ataxic neuropathy who satisfied the diagnostic criteria of Sjögren's syndrome and also showed a wide variety of autonomic disturbances. The sensory involvement was initially those of multiple mononeuritis in the distal extremities, but in the advanced stage it involved the area distributed along the spinal segmental dermatomes particularly in the trunk. Complete anhidrosis with discrete segmental distribution, as well as absence of response to cholinergic agents, was observed in three cases. Surface skin temperature recorded by a thermoviewer also showed a segmental involvement along the spinal dermatomes in two cases. Adie's pupils were present in two cases. These features suggested that the segmental involvement of the postganglionic sympathetic ganglion cells could be present in the underlying pathological condition. As for the other autonomic dysfunction, two cases showed severe postural hypotension and three cases had an abnormal heart rate variation (R-R interval). Our cases indicated that SjS-associated sensory ataxic neuropathy also manifest variable autonomic disturbances and suggested that similar pathological process to that involving the dorsal root ganglia would be present in the pathology of sympathetic and ciliary ganglion cells.

Aged↗
PubMed1993

[Uveitis in human T-lymphotropic virus type I (HTLV-I) carriers--2. An analysis of clinical features].

The clinical features of human T-lymphotropic virus type (HTLV-I) uveitis, an idiopathic uveitis in HTLV-I seropositive patients, were analyzed in a hospital located in an area where HTLV-I was endemic (Miyakonojo, Miyazaki). A total of 61 patients (25 males and 31 females) with HTLV-I uveitis were the subjects of the analysis. Intermediate uveitis with moderate to severe vitreous opacities accompanied by mild iritis and retinal vasculitis was the most characteristic feature, and was observed in the majority of the patients (66% of all or 84% in young adult patients between 20 and 49 years of age). The uveitis affected one eye in 57% and both eyes in 43% of the patients, with subacute onset of floaters and foggy vision. The uveitis responded well to therapy with topical or systemic corticosteroids, but recurred in many cases. A significant number of patients (15% of all and 25% of female patients) had a previous history of Graves' disease with hyperthyroidism.

Adult↗
PubMed1993

[Significance of short-term blood pressure variation in health management].

Blood pressure is known to vary under the influence of many factors. Although this variation can also occur in the short term, the significance of short-term blood pressure variation remains to be explained. The purpose of this study was to study the significance of short-term blood pressure variation in health management. Blood pressure was measured on 505 railway employees using an automatic blood pressure recorder based on an oscillometric method. "Continual blood pressure measurement" in which 5 blood pressure measurements were made at one-minute intervals was used. The following conclusions were obtained. 1. Blood pressure gradually fell during the 5 measurements made at one-minute intervals. There was a significant variation between the 1st and 2nd measured blood pressures, but there was no significant variation between the 4th and 5th measured blood pressures in most cases. These results suggest that 4 measurements made at one-minute intervals are needed to obtain stable blood pressure. 2. According to analysis of covariance, both sex and age had an influence on short-term blood pressure variation, but the body mass index (BMI) did not. 3. According to cluster analysis using 8 blood pressure variations, all subjects were classified into 4 clusters. These clusters showed significant relationship to age for males and BMI for females.

Adult↗
PubMed1992

Isolation and characterization of a gene encoding rat nucleoside diphosphate kinase.

Two overlapping genomic clones for a rat nucleoside diphosphate kinase (NDP kinase) have been isolated and characterized. Complete sequencing of the genomic segment including the whole coding region for the enzyme revealed that the gene consists of four exons spanning 5.5 kilobase pairs. Primer extension analyses and ribonuclease protection assays indicated that the transcription may start from multiple sites with the major initiation site at 3 base pairs upstream from the translation initiation site, Met-1. Neither CAAT-box nor TATA-box could be assigned for each transcription initiation site, whereas five putative Sp1-binding sites (GC-boxes) were present in the 5'-flanking region. These features of the NDP kinase gene represent those of housekeeping genes. In genomic Southern blotting using a full-length rat NDP kinase cDNA as a probe, many positively hybridized fragments were detected. In support of this, five possible processed pseudogenes were identified in different DNA segments although many other NDP kinase-related genomic fragments remained to be characterized. These results demonstrate that the NDP kinase gene may consist of a multiple gene family.

Amino Acid Sequence↗
PubMed1992

Activation of nucleoside diphosphate kinase by mastoparan, a peptide isolated from wasp venom.

We have previously reported that GDP-bound alpha beta gamma-trimeric GTP-binding (G) proteins can be converted into the active GTP-bound form with nucleoside diphosphate (NDP) kinase and ATP, although its exact activation mechanism still remains to be resolved. In the present study, we investigated whether NDP kinase activity was modified by mastoparan, a wasp venom peptide that is known to activate G proteins as an agonist-receptor complex. The activity of NDP kinase measured by the formation of GTP from ATP and GDP was markedly stimulated, when the kinase was incubated with mastoparan. The concentration of mastoparan required for the activation was much lower than that observed for the peptide-induced activation of G proteins under similar assay conditions. There was also an increase in the phosphorylated intermediate of NDP kinase as well as the catalytic activity upon its incubation with mastoparan. These results suggest that mastoparan not only activates G proteins directly via guanine nucleotide exchange reaction but also stimulates NDP kinase activity.

Animals↗
PubMed1992

Flow thresholds for extracellular purine catabolite elevation in cat focal ischemia.

Ischemic glutamate excitotoxicity may be counteracted by adenosine which appears extracellularly during ischemia as an intermediate purine catabolite and has the potential to modulate glutamate release and its receptor action. The present study was conducted to evaluate the flow threshold for purine catabolite accumulation in relation to that for glutamate elevation in focal ischemia which was induced by middle cerebral artery (MCA) occlusion in halothane anesthetized cats. Assemblies of platinum electrodes and microdialysis probes were inserted into the somatosensory (SF, n = 13) and the auditory (A, n = 9) cortices to assess local cerebral blood flow (CBF) using hydrogen clearance and purine catabolite (adenosine, inosine and hypoxanthine) as well as glutamate concentrations in the dialysate using high-performance liquid chromatography (HPLC). In both investigated areas, purine catabolites were elevated if CBF fell below 25 ml/100 g/min, while glutamate increased at a flow threshold below 20 ml/100 g/min. Maximum elevations of adenosine, inosine and hypoxanthine were 76-, 29- and 11-fold, respectively, that of glutamate was 24-fold. In the range between 20 and 25 ml/100 g/min, significant increases of adenosine (5-15-fold) were measured, while glutamate did not markedly increase. The elevation of adenosine was transient whereas that of inosine, hypoxanthine and glutamate persisted over an ischemic period of 3 h. The higher flow threshold for adenosine may reflect an inherent but time limited protective mechanism against glutamate excitotoxicity.

Adenosine Triphosphate↗
PubMed1992

Inhibitory effects of triphosphate derivatives of oxetanocin G and related compounds on eukaryotic and viral DNA polymerases and human immunodeficiency virus reverse transcriptase.

In order to clarify the biological activities of (-)-oxetanocin G, and (-)-oxetanocin A and its carbocyclic analogue, (-)-carboxetanocin G, the inhibitory effects of triphosphate derivatives of these compounds (OXT-GTP, OXT-ATP, and C-OXT-GTP) on eukaryotic and viral DNA polymerases were examined. DNA polymerase alpha purified from calf thymus was weakly inhibited by OXT-GTP and OXT-ATP but strongly by C-OXT-GTP, the Ki value being 0.22 microM. On the other hand, rat DNA polymerase beta was not affected by these analogues. DNA polymerase gamma purified from bovine testes was very weakly inhibited by OXT-GTP and OXT-ATP, but not by C-OXT-GTP. DNA polymerase from herpes simplex virus type-II (HSV-II) was strongly inhibited by all three analogues, the Ki values ranging from 0.5 to 1.0 microM. Human immunodeficiency virus-encoded reverse transcriptase (HIV RT) was also strongly inhibited by these three analogues, the Ki value of C-OXT-GTP being slightly smaller than that of OXT-GTP or OXT-ATP. Analysis of products synthesized on singly primed M13 single-stranded DNA by DNA polymerase alpha, HSV-II DNA polymerase or HIV RT in the presence of the analogues revealed that OXT-GTP and C-OXT-GTP were incorporated into DNA and caused chain termination mainly at sites one or two nucleotides beyond the cytosine bases on the template.

Adenine↗
PubMed1992

Oral health conditions and denture treatment needs in institutionalized elderly people in Japan.

Oral health conditions, including dental conditions, temporomandibular joint (TMJ) conditions, denture status, and oral hygiene status, were assessed on 1908 institutionalized elderly people 65 yr of age and older at 29 of the 30 existing institutions in the city of Kitakyushu, Japan. The percentage of edentulous people was 27% in the 65-74-yr-old group, and increased with age to 56% in the 85 yr and older group. In dentate persons, the mean number of remaining teeth and DF teeth were 13.4 and 8.6, 9.5 and 6.8, and 8.4 and 6.5 in the groups aged 65-74 yr old, 75-84 yr old, and 85 yr and older, respectively. 81% of all the persons examined had no unusual symptoms in their TMJ. A clicking sound was the most frequent symptom (17%). Hygiene of both their teeth and dentures was very poor. Of all the subjects, 36% needed new full and/or partial denture(s), and 41% needed only repair. When the institutionalized elderly people were compared according to their general health condition, no clear differences were observed in percentage of edentulousness, mean number of remaining teeth and DF teeth, and TMJ conditions. However, a higher level of both untreated teeth and denture treatment needs, and poorer oral hygiene, was found in elderly people having poor general health than was observed in those with better health.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[Quantitative evaluation of stress using the Type A behavior pattern].

The problem of quantitative assessment of individual stress remains to be solved. The purpose of this study was to attempt to quantify the evaluation of stress using the Type A behavior pattern. A total of 1,101 factory workers, 602 male workers (aged 20-59) completed questionnaires regarding subjective symptoms, Type A behaviors, shift work, age, and lifestyles such as drinking habits and smoking habits. Using the results of our previous study, 3 component scores were calculated from the responses to 11 questions pertaining to the Type A behavior pattern. Stepwise logistic regression analysis of complaints of 8 stress-related subjective symptoms was performed, using shift work, age, drinking habits, and smoking habits as categorical independent variables, and 3 component scores as interval-scaled independent variables. The following conclusions were obtained. 1. The first component score, which represented overall irritability, was chosen as an independent variable for complaints of "hunger pains" and "tendency to have diarrhea." The first component score had a positive association with complaints of these stress-related subjective symptoms, and the association with "hunger pains" was statistically significant with P less than 0.05, though the association with "tendency to have diarrhea" was not significant. 2. The second component score, which represented relaxation, was chosen for complaints of "heartburn or gastric reflux" and "abnormal thirst." The second component score had a negative association with complaints of these stress-related subjective symptoms, and both associations were statistically significant with P less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗