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Biomedical subjects

N Shimada

Publications and source records attributed to N Shimada.

At least 199 records · Page 11Linked to original sources
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

Isolation and characterization of bovine haptoglobin from acute phase sera.

A macromolecular hemoglobin-binding protein, which was not detectable in normal bovine sera but appeared during acute phase inflammation, was purified, characterized, and designated as bovine haptoglobin (Hp). The purified protein had a molecular mass of 1,000-2,000 kDa, and was composed of two kinds of peptides, a 20-kDa peptide (alpha chain) and a 35-kDa glycopeptide (beta chain) linked by disulfide bonds. Amino acid composition and N-terminal sequence analyses revealed that both peptides were homologous to each counterpart of human Hp. Studies using some reducing reagents proved that highly polymerized Hp in serum was composed of 2-20 polymerized forms of alpha 2 beta 2 tetramer. Hp could bind one molecule of hemoglobin/alpha 2 beta 2 unit. Hp with smaller sizes obtained from native Hp by partial reduction with cysteine showed almost the same Hb-binding capacity.

Acute-Phase Reaction↗
PubMed1991

Mechanism of inhibition of human cytomegalovirus replication by oxetanocin G.

Oxetanocin G(9-(2-deoxy-2-hydroxymethyl-beta-D-erythro-oxetanosyl)guanine, OXT-G) is a potent and selective agent against human cytomegalovirus (HCMV). In this study we synthesized the triphosphate form of OXT-G, OXT-GTP, and examined its effect on the activities of HCMV DNA polymerase, herpes simplex type 2 (HSV-2) DNA polymerase and human DNA polymerase alpha. OXT-GTP was found to inhibit all these polymerases in a competitive manner with respect to dGTP. The Km for dGTP and the Ki for OXT-GTP of HCMV DNA polymerase were 0.86 and 0.53 mu M, respectively, while the corresponding values of DNA polymerase alpha were 2.2 and 3.6 mu M, respectively. HPLC analysis using [3H]OXT-G also revealed that OXT-G was converted to its triphosphate form 7- to 8-fold more efficiently in HCMV-infected cells than in uninfected cells. The results suggest that both the preferential phosphorylation of OXT-G in HCMV-infected cells and the preferential inhibition of HCMV DNA polymerase by OXT-GTP may contribute towards the selective activity of OXT-G against HCMV replication.

Antiviral Agents↗
PubMed1991

Changes in left ventricular output from fetal to early neonatal life.

Using pulsed Doppler and two-dimensionally directed M-mode echocardiographic techniques, we measured left ventricular (LV) output, stroke volume, heart rate, LV end-diastolic dimension (LVEDD), LV end-systolic dimension, and LV percent fractional shortening (%FS) in 34 normal term infants 12 to 24 hours before parturition and thereafter serially 1, 24, and 96 hours after birth. Stroke volume was calculated as the product of the aortic flow velocity integral and aortic valve area. There was a twofold increase in LV output 1 hour after birth (fetal 170 +/- 46 ml/min/kg vs 1 hour 327 +/- 66 ml/min/kg; p less than 0.01) which was associated with significant increases in stroke volume, %FS, and LVEDD (stroke volume 1.21 +/- 0.33 ml/kg vs 2.25 +/- 0.37 ml/kg; %FS 34.3% +/- 5.8% vs 37.7% +/- 5.4%; LVEDD 15.4 +/- 1.1 mm vs 17.7 +/- 1.4 mm). Heart rate did not change 1 hour after birth. During the subsequent hours after birth, LV output decreased significantly to a value of 245 +/- 56 ml/min/kg (p less than 0.01) at 24 hours, which did not change 96 hours after birth. There were significant declines in stroke volume, LVEDD, and heart rate 24 hours after birth (stroke volume 2.02 +/- 0.42 ml/kg; LVEDD 17.0 +/- 1.1 mm; heart rate 121 +/- 11 beats/min). The %FS remained unchanged within the first 96 hours of age. These results indicate that the major regulator of LV output immediately after birth is stroke volume and not heart rate. The increase in stroke volume is related to an increase in LV size and LV myocardial contractility. Our data provide a useful basis for the interpretation of abnormal LV function in the early neonatal period.

Cardiac Output↗
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

[Determination of the management level for a body mass index using multivariate analysis].

It is evident that obesity has adverse effects on health and longevity. The body mass index (BMI) is a simple measurement highly correlated with other estimates of fatness and is useful in determining the extent of obesity, but the management level of the BMI for Japanese remains to be evaluated. The purpose of this study is to determine the management level of the BMI for Japanese adjusted for individual life style factors such as smoking and drinking. Among 1,854 male workers in a financial company, those who had periodical health examinations, 1,445 workers (aged 40-58) were chosen. Excluded were those who were below 150 cm or above 180 cm in height or those who had stopped smoking or drinking. Stepwise logistic regression of the findings of 10 medical test items was performed, using age, the BMI, smoking habits, and drinking habits as independent variables. The following conclusions were obtained. 1. The BMI was chosen as independent variable in all medical test items except glutamic oxaloacetic transaminase. In contrast, age and drinking habits were chosen in 6 medical test items, and smoking habits were chosen in 3 medical test items. 2. When the BMI exceeded 24 (kg/m2), significantly higher odds ratios were observed in the following medical test items: total cholesterol, triglyceride, fasting blood glucose and uric acid. Thus, this level of the BMI should be used as the management level in the Japanese male. Taking life styles into consideration, the management level of the BMI seemed to be slightly lower than the ordinary level used in Japan. In order to conduct effective health counseling, this level should be used in health care.

Adult↗
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↗
PubMed1991

[Ulcerative colitis and pregnancy].

The relationship between ulcerative colitis (UC) and pregnancy was studied in 83 cases (124 deliveries). The results were as follows: 1) In women with UC, there was no significant difference in fertility compared with the general population. 2) The existence of UC and treatment of UC during pregnant period had no significant adverse effects for the course of pregnancy. 3) In the 17 out of 36 pregnancies with inactive UC at the onset of pregnancy suffered relapses. Relapse rate in same patients in the pregnant period was significant higher than that in the non-pregnant period. 4) First attack of UC developing in 12 cases during pregnancies or the puerperium, the onset being commonly in the first trimester. UC developing during pregnancy was especially severe in other patients. We concluded that the relapse rate of UC is high during pregnant period, however, the course of pregnancy is not affected with UC.

Colitis, Ulcerative↗
PubMed1991

CPITN assessments in institutionalised elderly people in Kitakyushu, Japan.

A CPITN survey was conducted on 1958 institutionalised elderly people aged 59 years and older at 29 of the 30 public and private institutions in the city of Kitakyushu, Japan. About 60 per cent of the sample was edentulous, and the prevalence of periodontal conditions was high. The percentages of dentate subjects with healthy gingivae, bleeding on probing, calculus, shallow pockets, and deep pockets were 3, 4, 32, 52, and 9 per cent respectively. Half the sextants in the dentate subjects were scored as excluded (less than two teeth), indicating that many teeth were missing. Only very few sextants were healthy. These findings indicate the importance of preventive programmes for periodontal diseases in the younger generations, because (a) dental care for the elderly population becomes more difficult with increasing age and (b) periodontal care, if it is available at all, is provided too late for most people.

Aged↗
PubMed1990

Conversion of GDP into GTP by nucleoside diphosphate kinase on the GTP-binding proteins.

A direct interaction of alpha beta gamma trimeric GTP binding proteins (G proteins; G0 and Gs) with nucleoside diphosphate kinase (NDP kinase) was investigated with homogeneously purified proteins. There was a progressive release of 32Pi from [gamma-32P]ATP when GDP-bound G0 was incubated together with NDP kinase. The Pi release induced by the interaction of G0 with NDP kinase was not accompanied by the dissociation of GDP bound to the alpha-subunit of G0. This was a sharp contrast to G protein-catalyzed GTP hydrolysis observed with GTP as the substrate; the dissociation of bound GDP was essentially required for the following binding of the substrate, GTP, to be hydrolyzed. A kinetic analysis displayed different properties for the substrate of NDP kinase between free GDP and G protein-bound GDP. NDP kinase-dependent phosphorylation of GDP on G0 was indeed demonstrated with adenosine 5'-(3-O-thio)triphosphate as the phosphate donor; there was a formation of guanosine 5'-(3-O-thio)triphosphate-bound G0 from the ATP analogue. Moreover, purified Gs was readily ADP-ribosylated by cholera toxin in the presence of NDP kinase, ATP, and an ADP-ribosylation factor, also suggesting that the nucleotide form on Gs was certainly GTP. These results indicate that NDP kinase can transfer the gamma-phosphate of ATP directly to GDP bound to G proteins and that this phosphorylation results in the activation of the signal-coupling proteins. A possible role of the new activation mechanism of G proteins is discussed in comparison with the previously characterized GDP-GTP exchange pathway by the agonist-receptor complex.

Adenosine Triphosphate↗
PubMed1990

Isolation and characterization of a cDNA clone encoding rat nucleoside diphosphate kinase.

A cDNA clone for cytosolic nucleoside diphosphate (NDP) kinase was isolated from a cDNA library of rat skeletal muscle using synthetic oligonucleotides as probes. The clone constitutes a 621-base pair cDNA sequence including the 456-base pair coding region and 137-base pair 3'-untranslated one with polyadenylation site. The complete primary structure of NDP kinase was deduced from the coding sequence. An NH2-terminal amino acid sequence analysis suggested that the translated enzyme protein suffered proteolytic cleavage followed by modification at the alpha-NH2 group of the newly produced NH2-terminal amino acid residue. Taking this into account, it was tentatively concluded that the mature NDP kinase consists of 147 amino acid residues with a molecular weight of 16,724. Northern blot hybridization analysis showed that NDP kinase mRNA could be detected in total RNA fractions of brain, spleen, heart, lung, liver, kidney, testis as well as skeletal muscle, and that there was no difference in the size of mRNAs from these tissues. Tissue distribution of the mRNA nearly paralleled those of protein moiety and activity of the enzyme.

Amino Acid Sequence↗
PubMed1990

Evidence for complex formation between GTP binding protein(Gs) and membrane-associated nucleoside diphosphate kinase.

When the Gs in rat liver membranes was prelabeled with [32P]NAD and cholera toxin, solubilized with octylglucoside, and then analyzed by sucrose density gradient centrifugation, it was fractionated into two peaks with approximate molecular sizes of 12-13S and 3-4S. Pretreatment without or with GDP beta S of the labeled membranes resulted in a larger peak in the high molecular weight region, whereas pretreatment with glucagon plus GTP gamma S caused almost equal peaks in both regions. The affinity-purified anti-nucleoside diphosphate (NDP) kinase antibodies only precipitated the Gs in high molecular weight region. Under the same condition, small but significant NDP kinase activity was associated with the high molecular weight Gs region although a large portion of the enzyme activity was recovered in fractions where it alone should appear (6.2S). Both Lubrol-PX and digitonin solubilized the Gs in forms insensitive to immunoprecipitation by anti-NDP kinase antibodies although the latter detergent was able to solubilize the Gs in a high molecular weight form, that is, a ternary glucagon-receptor-G protein complex. These results demonstrate that Gs and membrane-associated NDP kinase may exist in part in a complexed form in membranes. Physiological relevance of the complex formation in membrane signal transduction is discussed.

Adenosine Diphosphate Ribose↗
PubMed1990

Pregnancy after laser therapy for the treatment of uterine cervical neoplasia.

Three hundred and twenty-four patients with cervical intraepithelial neoplasia (33 mild dysplasia, 109 moderate dysplasia, 118 severe dysplasia, 64 carcinoma in situ) underwent laser vaporization with the CO 2 laser. Eighty-two patients with CIN (mild dysplasia 7, moderate dysplasia 10, severe dysplasia 16, carcinoma in situ 46) and microinvasive cancer (3) underwent laser excisional conization with the YAG laser. Their first cure rates showed 93.5% and 98.8%, respectively, for the follow-up period 6 months to 7 years. During the same period, 36 pregnancies in 34 patients occurred. Of these patients, 14 underwent dilatation and curettage, 6 terminated by spontaneous abortion in the first trimester and 1 in the second trimester (previous MacDonald's suture), and 1 had fetal death at 13 weeks of gestational age. There were 13 deliveries, 2 by cesarean section (either postenucleation of uterine myoma or premature rupture of the membranes and fetal distress), 3 by vacuum extraction, 1 by breech delivery, and 7 by normal vaginal delivery. One patient is currently in her 22nd week of pregnancy. Our laser therapies are good conservative methods for the treatment of CIN because of favorable cure rates and no effect on succeeding pregnancy and delivery.

Adult↗