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Biomedical subjects

N Nishimura

Publications and source records attributed to N Nishimura.

At least 91 records · Page 5Linked to original sources
PubMed1998

Human parvovirus B19-associated thrombocytopenic purpura.

We report two patients who presented with thrombocytopenic purpura (TP) associated with primary human parvovirus B19 (B19) infection. One patient also had transient liver dysfunction. In both cases, B19-DNA was detected in serum and bone marrow by polymerase chain reaction. Six months after the illness in patient 1 and 8 months after the illness in patient 2, B19-DNA disappeared from the serum. Serum immunoglobulin (Ig)G antibody to B19 remained positive in both cases, but B19 IgM antibody became negative 3 months after the onset in case 1 and 4 months after the onset in case 2. The mechanism of TP by B19 infection is unknown.

Adolescent↗
PubMed1998

Effects of Sho-saiko-to on the pharmacokinetics and pharmacodynamics of tolbutamide in rats.

Although Sho-saiko-to (Xiao Chai Hu Tang), a major Chinese traditional medicine, is frequently prescribed with other synthetic or biotechnological drugs for the treatment of various chronic diseases, there is a dearth of information about interactions between sho-saiko-to and co-administered drugs. This paper reports the effects of Sho-saiko-to on the pharmacokinetics and glucose responses of a sulphonylurea hypoglycaemic agent, tolbutamide, after their oral administration in rats. After oral administration of tolbutamide (50 mg kg(-1)) with or without Sho-saiko-to extract powder (300 mg kg(-1)) to male Sprague-Dawley rats cannulated in the jugular vein, plasma tolbutamide and glucose levels were periodically measured. Co-administration of Sho-saiko-to tended to elevate the plasma tolbutamide concentration in the absorption phase. A two-compartment lag-time model was found to describe the plasma tolbutamide concentration-time data. The maximum concentration of tolbutamide was significantly increased and time to reach the maximum concentration was reduced to about 70% by co-administration with Sho-saiko-to. There was no significant change in area under the curve or in the elimination half-life of tolbutamide. The extent of the lowering effect of tolbutamide on plasma glucose levels was increased up to 0.75 h and decreased after 5 h after co-administration of Sho-saiko-to. In conclusion, these studies suggest that sho-saiko-to slightly hastens the gastrointestinal absorption of tolbutamide. Furthermore, it is considered that elevation of the gastrointestinal absorption rate by Sho-saiko-to might potentiate the hypoglycaemic effect of this sulphonylurea in the early period after oral administration.

Administration, Oral↗
PubMed1998

Ultraviolet A radiation (320-400 nm) protects hairless mice from immunosuppression induced by ultraviolet B radiation (280-320 nm) or cis-urocanic acid.

T cell-mediated immune function, here measured as the contact hypersensitivity reaction, is readily suppressed by moderate exposure of mice to ultraviolet B (UVB) or solar-simulated radiation (SSUV), or by topical application of cis-urocanic acid. The effect of ultraviolet A (UVA) radiation on immune function has been unclear. Here we have demonstrated that when UVA radiation from a fluorescent tube source was rigorously filtered to remove contaminating UVB radiation, it was immunologically innocuous at physiologically relevant doses. Furthermore, we have found that mice exposed to UVA radiation, either immediately after, or up to 24 h before, immunosuppressive treatment with either UVB radiation, SSUV or cis-urocanic acid, became refractory to the immunosuppression and retained more normal contact hypersensitivity. A greater UVA exposure reversed the immunosuppression more effectively. The results suggest that there are immunologically significant interactions between UV wavebands, and that UVA exposure may induce a relatively long-lived immunoprotective photoproduct, as yet unidentified, that can inhibit the activity of epidermal cis-urocanic acid and thus provide protection from photoimmunosuppression.

Animals↗
PubMed1998

[Effects of KB-R7943, a novel Na+/Ca2+ exchange inhibitor, on myocardial ischemia/reperfusion injury].

The effects of KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate) on major ion transporters were studied in canine cardiac sarcolemmal and sarcoplasmic reticular vesicles. KB-R7943 inhibited the Na+/Ca2+ exchange more potently than the Na+/H+ exchange, the Na+/K(+)-ATPase and the Ca2(+)-ATPase. The effects of KB-R7943 on ischemia/reperfusion-induced injury were studied in isolated rat perfused hearts in comparison with those of diltiazem and lidocaine. In normal hearts, diltiazem (10 microM) and lidocaine (100 microM) markedly reduced contractile function, but KB-R7943 (1, 10 microM) had no such effect. In the hearts subjected to 25-min ischemia and 30-min reperfusion, KB-R7943 concentration-dependently and significantly improved post-ischemic recovery of left ventricular developed pressure, left ventricular dP/dtmax and left ventricular end-diastolic pressure by pre-ischemic treatment (5 min) or post-ischemic treatment (10 min). Diltiazem and lidocaine showed similar improvement of recovery by pre-ischemic treatment, but they had no effect by post-ischemic treatment. Furthermore, the effect of KB-R7943 on arrhythmia was studied in anesthetized rats subjected to 5-min cardiac ischmeia and 10-min reperfusion. KB-R7943 (1, 10 mg/kg, i.v.) dose-dependently reduced the incidence and the duration of ventricular fibrillation. These results indicate that KB-R7943, a selective Na+/Ca2+ exchange inhibitor, has beneficial effects against myocardial ischemia/reperfusion injury and suggest that activation of the Na+/Ca2+ exchange mainly occurs immediately after reperfusion in the pathophysiological process of myocardial ischemia/reperfusion injury.

Animals↗
PubMed1998

Carbamazepine-induced sinus node dysfunction and atrioventricular block in elderly women.

We report on four elderly women in whom carbamazepine was suspected of inducing sinus node dysfunction (3 patients) and atrioventricular block (1 patient). Patients were treated with carbamazepine, 200 to 600 mg a day, for trigeminal neuralgia (n = 3) or epilepsy (n = 1). After 1 to 16 months of carbamazepine therapy, these patients were admitted to our emergency room because of bradyarrhythmia. Their conduction disturbances on electrocardiographic monitoring disappeared immediately after the cessation of carbamazepine intake. Provocation tests were performed on three patients. Because of renal insufficiency, one patient could not undergo the provocation test. Her carbamazepine clearance was markedly decreased. Carbamazepine induced sinus arrest in two patients within 48 hours after intake, but did not induce atrioventricular block in the remaining patient. In two patients, computer simulation of carbamazepine pharmacokinetics was performed and disclosed a clear-cut relationship between the plasma concentration of carbamazepine and the frequency of sinus arrest. During the test, the maximum plasma carbamazepine concentration in these two patients did not exceed the therapeutic range. However, it did exceed the range in the one with a negative test. Our results suggest that careful monitoring of ECG and plasma drug concentration is required with carbamazepine therapy, especially in elderly women.

Aged↗
PubMed1998

Functional outcome of double-stapled and transanal ileal pouch-anal anastomosis after proctocolectomy.

Improvement of functional outcome after proctocolectomy for ulcerative colitis and familial adenomatous polyposis was compared between transanal ileal pouch-anal anastomosis (T-IAA group, n = 29) and double-stapled ileal pouch-anal anastomosis (DS-IAA group, n = 8). Clinical functions were evaluated using a functional scoring system, and physiologic functions by anorectal manometry after one year postoperatively. Although in the T-IAA group 4 of the 29 patients (13.8%) displayed partial incontinence (< 9 points), all of 8 patients in the DS-IAA group showed good results referring to continence (> 10 points). The maximum resting pressure was 44.3 +/- 5.2 cmH2O in the T-IAA group vs. 56.6 +/- 5.8 cmH2O in the DS-IAA group, and postoperatively the maximum squeezing pressure was 96.8 +/- 9.2 cmH2O in the T-IAA group vs. 106.3 +/- 8.1 cmH2O in the DS-IAA group. There was a significant difference of maximum resting pressure and no significant difference of maximum squeezing pressure between the two groups. The length of the high pressure zone in the anal canal was significantly shorter in patients of the T-IAA group (2.1 +/- 0.8 cm) than in those of the DS-IAA group (3.5 +/- 1.1 cm) (p < 0.05). The DS-IAA is associated with excellent objective physiologic and subjective functional results. This reflects the sacrifice of the internal anal sphincter 1.5 cm cephalad necessary to effect this anastomosis at a mean of 1.4 cm from the dentate line.

Adolescent↗
PubMed1998

A plaque hybridization assay for quantifying and cloning infectious human immunodeficiency virus type 1 virions.

A biological method was developed for quantifying and cloning of infectious virions of human immunodeficiency virus type 1 (HIV-1). Virus preparations were mixed with permissive cells for binding, and the cells were cast in an agarose gel. After incubation for 9 days viral particles released from infected cells propagating from each initially infected cell were transferred on nylon membrane and subjected to hybridization using a radioactive HIV-1 DNA probe. Infectious centers of HIV-1 were detected as hybridization spots on autoradiographs regardless of cytopathic effects or syncytium formation. Three different CD4+ cell lines (MT-4, MOLT-4 and U937) and peripheral blood mononuclear cells from healthy donors were used as recipient cells. Infectious virions were recovered from a portion of agarose gel corresponding to each hybridization spot. This assay is suitable for quantifying infectious HIV-1 virions with different cell tropisms and for investigating the relationship between the phenotype and genotype of HIV-1 at a clonal level.

Cell Line, Transformed↗
PubMed1998

Egg maturation in neotropical malaria vectors: one blood meal is usually enough.

The requirement of more than one blood meal to complete a gonotrophic cycle is reported here to be infrequent among field-collected Anopheles (Nyssorhynchus), including Anopheles darlingi, South America's most important malaria vector. The overall frequencies of host-seeking females that did not develop eggs after one blood feeding were low for Anopheles darlingi (6.6%), Anopheles rondoni (5.0%), and Anopheles triannulatus (2.2%); the majority of wild-caught females that did not develop eggs after one blood meal were nulliparous. Laboratory-reared Anopheles albimanus and Anopheles albitarsis, other species of the same subgenus, were grown on enriched and impoverished larval diets to yield a range of adult sizes and to examine relationships between egg maturation, body size, and blood meal intake. 10.7% of nulliparous An. albimanus and 22.9% of An. albitarsis failed to mature eggs after sugar and one blood meal, and shorter wings and smaller blood meals predisposed females to require multiple blood feeds for egg maturation. Unmated An. albitarsis were significantly more likely than mated females not to develop eggs. Multiple blood meals within a single gonotrophic cycle appear to be less important in the life histories of neotropical Nyssorhynchus species compared to afrotropical malaria vectors.

Animals↗
PubMed1997

The lysine cluster in the collagen-like domain of the scavenger receptor provides for its ligand binding and ligand specificity.

Scavenger receptors bind modified low-density lipoproteins (LDL) on a collagen-like domain which possesses a lysine cluster at the carboxy end. We previously constructed a receptor model peptide containing the lysine cluster. In the present study, we evaluated the ligand specificity of the receptor model peptide. It selectively bound modified-LDLs, and not LDL. The binding of acetylated-LDL (Ac-LDL) was inhibited by dextran sulfate, fucoidan, and sulfatides in a manner similar to that of the natural receptor. Both polyguanylic and polyinosinic acids inhibit the Ac-LDL binding whereas polycytidylic acid did not. These results indicate that the lysine cluster in the collagen-like domain has important roles in both ligand binding and ligand specificity.

Amino Acid Sequence↗
PubMed1997

A di-acidic signal required for selective export from the endoplasmic reticulum.

Transport of membrane proteins between intracellular compartments requires specific sequences in the protein cytoplasmic domain to direct packaging into vesicle shuttles. A sequence that mediates export from the endoplasmic reticulum (ER) has proved elusive. A di-acidic signal (Asp-X-Glu, where X represents any amino acid) on the cytoplasmic tail of vesicular stomatitis virus glycoprotein (VSV-G) and other cargo molecules was required for efficient recruitment to vesicles mediating export from the ER in baby hamster kidney cells. The existence of such a signal provides evidence that export from the ER occurs through a selective mechanism.

Acid Phosphatase↗
PubMed1997

Effects of estrogenic hormones on early development of Xenopus laevis.

Many chemicals released into the environment have estrogenic activity and can disrupt animal development and the function of endocrine systems. In order to study the effects of estrogens on aquatic animals, we examined the effects of certain estrogens on early development in Xenopus laevis. X. laevis embryos were kept in water containing 10(-10), 10(-9), 10(-7), 10(-6), and 10(-5) M 17 beta-estradiol (E2); 17 alpha-estradiol; diethylstilbestrol (DES); 10(-5) M progesterone (P); or dihydrotestosterone (DHT) beginning at developmental stage 3. Survival rates of the embryos developed in water containing 10(-10)-10(-6) M E2 or DES, all concentrations of 17 alpha-estradiol, and 10(-5) M P or DHT, which were over 70% after stage 48, whereas the rates of the embryos treated with 10(-5) M E2 and DES decreased remarkably after stage 27 and all embryos were dead by stages 42 and 32, respectively. Embryos treated with 10(-5) M E2 showed malformations of the head and abdomen and suppressed organogenesis, including crooked vertebrae at stage 38; the head was smaller and the abdomen was larger than in the controls. Similar effects were observed in embryos developed in 10(-5) M DES but not in 10(-5) M 17 alpha-estradiol, P, or DHT. After 10(-5) M E2 treatment, abnormalities were induced only when the treatment was started before stage 39. However, on day 30 after fertilization, the stage of the embryos treated with 10(-6) M E2 was more progressed than that of the controls. Estrogen receptor (ER 4) mRNA was examined in eggs, embryos, and adult female liver by reverse-transcription polymerase chain reaction. ER4 mRNA was expressed in adult liver, unfertilized and fertilized eggs, and embryos, but ER3 mRNA was not expressed. ER4 mRNA in 10(-6) and 10(-5) M E2-treated embryos showed different expression patterns, which may result from the diverse developmental effects of E2. The present results demonstrate that 10(-5) M E2 and DES induced embryo death and malformations and that ER may be involved in the induction of various developmental defects in X. laevis embryos.

Abdomen↗
PubMed1997

p21 (WAF1/Cip1/Sdi1/Pic1) mRNA is expressed in neuroblastoma cell lines but not in Ewing's sarcoma and primitive neuroectodermal tumor cell lines.

The p21 protein inhibits the activity of cyclin-Cdk complexes and suppresses cell cycle progression. Wild type p53 can induce p21, but mutated p53 cannot. Previous studies have demonstrated that mutation of p53 is absent in neuroblastoma (NB). These reports prompted us to examine whether p53 induced p21 in NB. We examined the expression of p21 and p53 mRNA in eight NB, two Ewing's sarcoma (ES) and two primitive neuroectodermal tumor (PNET) cell lines by Northern blot analysis, and sequenced p53 cDNA of these cells. Although p53 mRNA was detected in all analyzed cell lines by Northern blot analysis, p21 mRNA was detected in six NB but not in two NB, two ES and two PNET cell lines. We detected the point mutation of p53 at codon 273 (CGT to TGT) in one NB and two ES cell lines. The non-transforming substitution at codon 72 (CCC to CGC) was detected in all analyzed cell lines. One PNET cell line had a large deletion of p53 cDNA. These results showed that p21 mRNA was usually expressed in NB but not in ES and PNET. This may suggest that the down stream of the p53 signal transduction pathway in NB is different from that of the closely related tumors of ES and PNET.

Blotting, Northern↗
PubMed1997

Synthesis and structure-activity relationships of thienylcyanoguanidine derivatives as potassium channel openers.

In our series of studies on potassium channel openers, several thienylcyanoguanidine derivatives were synthesized and evaluated for smooth muscle relaxation activity in vitro. Among the newly synthesized compounds, N-cyano-N'-(5-cyano-3-thienyl)-N"-tert-pentylguanidine (4b) and N-(5-bromo-3-thienyl)-N'-cyano-N"-tert-pentylguanidine (4f) exhibited excellent activity which was proved to be based on potassium channel-opening action. Bioisosterism between benzene and thiophene ring was observed in the arylcyanoguanidines. After intravenous administration to dogs, 4b lowered the blood pressure more strongly than pinacidil.

Animals↗
PubMed1997

[Intraperitoneal single-dose toxicity studies of active metabolite, optical isomers, hydrolysis products and bi-product of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a novel drug for urinary frequency and incontinence, in mice].

NS-21, (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, is a new drug for the treatment of urinary frequency and incontinence. To evaluate acute toxicities of its related compounds including the optical isomers of NS-21 ((S)NS-21 and (R)NS-21), the active metabolite of NS-21 ((R/S)RCC-36), the optical isomers of (R/S)RCC-36 ((S)RCC-36 and (R)RCC-36), the hydrolysis products of NS-21 (RCC-32 and RCC-38) and the bi-product of NS-21 (RCC-66), single-dose intraperitoneal toxicity studies were conducted in ddY mice. The LD50 values of these compounds in male and female mice were as follows: 199 and 184 mg/kg for (S)NS-21, 261 and 240 mg/kg for (R)NS-21, 74 and 100-150 mg/kg for (R/S)RCC-36, 93 mg/kg for (S)RCC-36 in both sexes, 83 and 104 mg/kg for (R)RCC-36, higher than 510 mg/kg for RCC-32 in both sexes, 340-510 mg/kg for RCC-38 in both sexes, and 1000-2000 mg/kg for RCC-66 in both sexes, respectively. The clinical signs included decreased spontaneous locomotor activity, prone or lateral position, ataxic gait, clonic convulsion, hypopnea, hypothermia, pale skin, mydriasis, abdominal distention and unkempt fur for (S)NS-21, (R)NS-21, (R/S)RCC-36, (S)RCC-36 and (R)RCC-36, decreased spontaneous locomotor activity, prone position, ataxic gait, clonic convulsion, tail elevation and hypopnea for RCC-32 and RCC-38, and decreased spontaneous locomotor activity and unkempt fur for RCC-66. Body weight was decreased or its gain was suppressed for every compound examined. Pathological examination of the dead mice showed atrophy of the thymus and spleen, intestinal distention with the retention of dark red contents, white spots or white materials in the abdominal fatty tissue for (S)NS-21, (R)NS-21, (R/S)RCC-36, (S)RCC-36, (R)RCC-36 and RCC-66, but no treatment related change for RCC-32 and RCC-38. Adhesion between the abdominal organs was observed in survivors treated with (S)NS-21, (R)NS-21, (S)RCC-36, (R)RCC-36, RCC-32 and RCC-66.

Animals↗
PubMed1997

Vasodepressor effects of exercise are accompanied by reduced circulating ouabainlike immunoreactivity and normalization of nitric oxide synthesis.

Our object was to evaluate the effects of regular mild exercise on blood pressure and on circulating level of ouabainlike factors (OLF) and of nitrate anion, an endproduct of nitric oxide (NO) in humans. We measured plasma ouabainlike immunoreactivity (OLI) and nitrate ions (NO3.) before and after mild exercise for 3 months' duration in 16 patients with essential hypertension, diabetes mellitus, obesity, or hyperlipidemia. Plasma OLI was measured using an amplified ELISA system with anti-ouabain antibody and biotinyl-tyramide. Serum NO3. was measured with high-performance liquid chromatography (HPLC) with an anion-exchange column. With the reverse phase HPLC system with an octa decylsilyl silicagel column, the elution volume of plasma OLI of a healthy volunteer matched that of authentic ouabain in a gradient elution system of acetonitrile/H2O. Plasma OLI levels decreased significantly by about 34% after mild exercise, and NO3. levels tended to be within the reference interval in normal volunteers. Body weight, diastolic and systolic blood pressure, serum triglyceride and acetylcholine esterase (a marker of the fatty liver) were significantly decreased (p < 0.01) after 3 months of regular mild exercise. The plasma OLI level was significantly correlated with plasma NO3., there was a trend toward a correlation with diastolic blood pressure (p = 0.06) before and after regular exercise. Regular mild exercise led to a decrease in plasma levels of OLI, and acetylcholine esterase activity and blood pressure in adult patients. Results suggest that changes in OLF production contribute to the blood pressure regulation seen in patients who exercise regularly.

Adult↗
PubMed1997

Enhanced renal toxicity by inorganic mercury in metallothionein-null mice.

To elucidate a protective role of metallothionein (MT) in the manifestation of inorganic mercury toxicity, we studied the susceptibility of MT-null mice to the renal toxicity of mercuric chloride. Because the MT-null (J) mice are a genetic background of 129/Sv strain, the 129/Sv mice were used as wild-type controls. Nine-week-old male MT-null (J) and 129/Sv mice were given subcutaneous injections of mercuric chloride at doses of 10 to 40 micromol/kg. The basal MT level in the kidney of MT-null (J) mice was undetectable (<0.2 microg/g of tissue) and approximately 2.5 microg/g of tissue in 129/Sv mice. The sensitivity to the renal toxicity of mercuric chloride was markedly enhanced in the MT-null (J) mice compared with the 129/Sv mice. The renal mercury level was similar for the MT-null (J) and 129/Sv mice at 4 hr after the injection of mercuric chloride (20 micromol/kg) but became significantly lower in MT-null (J) mice than in 129/Sv mice at 24 and 72 hr. Based on the present results, we conclude that MT is an important protective factor against the renal toxicity caused by inorganic mercury and that it may play a major role in the retention of mercury in the kidney.

Animals↗
PubMed1997

Clinical studies of second revision in total hip replacement.

Eleven patients (12 hips) underwent the second revision of total hip replacement. The mean age at the second revision was 61 years (range: 31 to 79); 2 patients were men and 9 women. Loosening of components was the most common reason for the revision surgery. Supplemental ring or wire-mesh reinforcement was used for the revision of the acetabular that had poor bone stock. On the acetabular side, an allograft was used in 4 hips; on the femoral side, a long stem was used in 11 hips. The mean operative time was 298 minutes (range: 195 to 525), and the mean bleeding volume was 2278 ml (range: 810 to 4800) which was about twofold more than that of the primary operation. The mean length of follow up after the second revision was approximately 5 years. In the clinical results, the mean total Japan Orthopaedic Association score was 56 points before the second revision and it was 70 points during the follow-up period. Pain score was especially improved after the second revision. On final roentgenographic examination there was noted a clear zone in three acetabular components and five femoral components. As yet, we have not experienced any case requiring a third revision.

Adult↗