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Biomedical subjects

N Shimada

Publications and source records attributed to N Shimada.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Preclinical and clinical study of FK506 in uveitis.

Efficacy of a new immunosuppressive agent, FK506, in refractory uveitis was studied in 8 patients: 5 with Behcet's disease and 3 with idiopathic retinal vasculitis. The agent was given by oral administration every 12 hours. The previous therapy with systemic corticosteroids or immunosuppressive agents including cyclosporine failed to subside uveitis in these cases. During the observation period of 21.6 +/- 7.8 weeks (mean +/- SD) under FK506 at doses with 0.05, 0.1, 0.15 or 0.2 mg/kg/day, the visual acuity was increased in 44% of treated eyes, unchanged in 44% and decreased in 12%. The inflammatory activity in the ocular fundus was improved in 69% and unchanged in 6% of treated eyes. The effects of FK506 on uveitis by the criteria of improvement of visual acuity and uveitis activity was dose-dependent: 0.05 and 0.1 mg/kg/day were ineffective but 0.15 and 0.2 mg/kg/day were effective in most cases. One patient with Behcet's disease converted from cyclosporine developed moderate renal impairment in 4 weeks under FK506 and the therapy was discontinued in 8 weeks, though the uveitis activity as well as visual acuity was markedly improved. Other 7 cases had no side effect of FK506. Although the number of cases was small and observation period was short, the present clinical data indicate that FK506 is effective to treat refractory uveitis.

Administration, Oral↗
PubMed1992

44-Homooligomycins A and B, new antitumor antibiotics from Streptomyces bottropensis. Producing organism, fermentation, isolation, structure elucidation and biological properties.

Oligomycin antibiotics, 44-homooligomycin A (NK86-0279 II) and B (NK86-0279 I) are newly discovered antitumor antibiotics with the substitution of ethyl for methyl at carbon 26. They were isolated from the culture broth of Streptomyces bottropensis NK86-0279. The structure of these two compounds was deduced by spectroscopic and X-ray crystallographic analyses. These antibiotics showed potent antitumor activities against various tumor cells in vitro, and were active against Colon 26 carcinoma in vivo. Although they showed no activity at 1,000 micrograms/ml against Gram-positive and Gram-negative bacteria and yeast, they have antifungal activity.

Antibiotics, Antineoplastic↗
PubMed1991

Periodontal condition of pregnant women assessed by CPITN.

The periodontal conditions of 2424 pregnant and 1565 non-pregnant women were assessed according to the community periodontal index of treatment needs (CPITN). The aim of this survey was to obtain information which is necessary for the planning of preventive programs of periodontal disease for pregnant women. 95% of the pregnant women and 96% of the non-pregnant women had some signs of periodontal disease. The % of pregnant women having 4 or 5 mm pockets was significantly higher than that of non-pregnant women, increased with the month of pregnancy, reached a maximum of 31% in the 8-month group, but decreased to the control level in the 9-month group. These changes were interpreted to suggest that the increase of pocket depth during pregnancy was caused by gingival enlargement rather than by periodontal destruction. The results show that pregnant women had a healthier periodontal condition when compared with non-pregnant women, i.e., the number of sextants with healthy periodontal tissues was higher, the % of people having deep pockets (6 mm or deeper) was lower, and the need for prophylaxis was lower in pregnant than in non-pregnant women. These findings suggest that a special program of periodontal disease prevention for pregnant women is not necessary.

Adolescent↗
PubMed1991

Purine catabolites in cerebral interstitial fluid during progression of and recovery from ischemia.

The concentrations of purine catabolites in the cerebral interstitial fluid during progression of and recovery from ischemia were studied using brain microdialysis and high-performance liquid chromatography. Sealed 0.5-mm hollow dialysis fibers were stereotactically implanted into either the cerebral cortex or hippocampus of ketamine anesthetized gerbils and perfused with artificial cerebrospinal fluid at 2 microliters/min. Cerebral ischemia was induced by occlusion of the bilateral common carotid arteries. The reflectance spectra of oxy- and deoxyhemoglobin at the brain surface were monitored over the scalp to assess ischemia and confirm recirculation. Ischemia caused a rapid, 4.8-fold increase in the extracellular concentration of adenosine. The progressive increase in the concentration of adenosine, inosine, and hypoxanthine soon after recirculation is particularly interesting. The subsequent decrease in purine compound concentration was rapid for adenosine but more gradual for inosine and hypoxanthine. Calculated K values for adenosine deaminase and purine nucleoside phosphorylase were 0.045/min and 0.016/min, respectively. However, no xanthine, uric acid, or purine nucleotides were found in the perfusate. These observations indicated the presence of purine catabolites in the cerebral interstitial space as well as consecutive degradation and recycling involving the interconversion of purine compounds by biochemical metabolic pathways.

Animals↗