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Biomedical subjects

K Nishimura

Publications and source records attributed to K Nishimura.

At least 109 records · Page 6Linked to original sources
PubMed1999

The effect of high-dose inhaled beclomethasone dipropionate in patients with stable COPD.

BACKGROUND: The benefits of inhaled corticosteroids in the management of COPD are less apparent than they are in asthma therapy, and the potential for adverse systemic effects of high-dose inhaled corticosteroids has been recognized recently. It is therefore essential to know the maximal obtainable benefits in order to assess the risk/benefit ratio of this treatment. PURPOSE: The aim of this study was to investigate the maximal obtainable benefits of high-dose inhaled corticosteroids, 3 mg/d of beclomethasone dipropionate (BDP), when used in combination with adequate doses of regular bronchodilators in patients with stable COPD. STUDY DESIGN: Thirty patients with stable COPD completed a randomized, double-blind, placebo-controlled cross-over trial with either 3 mg/d of BDP or with a matching placebo using a metered-dose inhaler with a spacer device for 4 weeks during each treatment period. All of the patients continued to inhale both 400 microg of salbutamol qid and 80 microg of ipratropium bromide qid. RESULTS: The mean prebronchodilator FEV1 was 0.97+/-0.35 L during the placebo period and 1.08+/-0.38 L during the BDP period (p < 0.001). While on BDP, five patients demonstrated a response in their FEV1 of more than 8.5% of the predicted value, which was above the range that covered 95% of the distribution of the placebo response. The mean absolute improvement in the FEV1 in these 5 objective responders was 0.34+/-0.10 L, compared to 0.06+/-0.09 L in the 25 objective nonresponders. Symptom scores for wheezing and dyspnea were significantly better with BDP than with placebo. Hoarseness and sore throat were associated more with BDP treatment. CONCLUSION: Although a considerable minority of patients benefited substantially from this treatment, the overall outcome does not seem to justify the widespread use of this treatment in the light of increasing recognition of the potential adverse systemic effects of high-dose inhaled corticosteroids.

Administration, Inhalation↗
PubMed1999

A comparison of the level of dyspnea vs disease severity in indicating the health-related quality of life of patients with COPD.

STUDY OBJECTIVES: To compare categorizations of the level of dyspnea with the staging of disease severity as defined by the FEV(1) in representing how the health-related quality of life (HRQOL) is distributed in patients with COPD. DESIGN: Cross-sectional study. SETTING: Outpatient clinic at the respiratory department of a university hospital. PATIENTS: A total of 194 consecutive male patients with stable, mild-to-severe COPD. MEASUREMENTS: The score distributions for the components of the St. George's respiratory questionnaire (SGRQ) were used as disease-specific HRQOL measures, and the scores from the Medical Outcomes Study Short Form 36-item questionnaire (SF-36) were used as generic HRQOL measures. These scores were stratified according to the level of dyspnea, as defined by the Medical Research Council (MRC) dyspnea scale, and the stage of disease severity, as defined by the American Thoracic Society (ATS). Differences in the HRQOL scores among the subgroups were compared by an analysis of variance (ANOVA). Multiple pairwise comparisons were made with Fisher's least significant difference (LSD) method, with the overall alpha-level set at 0.05. RESULTS: In those groups classified according to the level of dyspnea, significant differences were observed for the scores on the SGRQ and SF-36 (ANOVA, p < 0.05). The scores for activity and impact, and the total scores of the SGRQ and all scales, except for bodily pain and general health on the SF-36, were significantly worse for patients with severe dyspnea (MRC scale grades, 3, 4, and 5, respectively) than for those with moderate dyspnea (MRC grade level, 2; Fisher's LSD method, p < 0.05). Significant differences were recognized among the different stages of disease severity with respect to the scores from all scales of the SF-36, except for bodily pain, and all scores from the SGRQ (ANOVA, p < 0.05). However, differences in the scores on the SGRQ and SF-36 between patients with ATS stage II disease (FEV(1), 35 to 49% predicted) and stage III disease (FEV(1), < 35% predicted) were not statistically significant. CONCLUSIONS: Using the SGRQ and SF-36, the HRQOL of patients with COPD was more clearly separated by the level of dyspnea than by the ATS disease staging. In addition to the ATS disease staging, categorizations based on the level of dyspnea may be useful to clinicians in terms of the HRQOL of COPD patients.

Aged↗
PubMed1999

Differential induction of androgen receptor transactivation by different androgen receptor coactivators in human prostate cancer DU145 cells.

Recently identified androgen receptor (AR) coactivators were used in this study to determine whether the specificity of sex hormones and antiandrogens could be modulated at the coactivator level. We found that ARA70 is the best coactivator to confer the androgenic activity on 17beta-estradiol. Only ARA70 and ARA55 could increase significantly the androgenic activity of hydroxyflutamide, a widely used antiand rogen for the treatment of prostate cancer. None of the AR coactivators we tested could significantly confer androgenic activity on progesterone and glucocorticoid at their physiological concentrations (1-10nM). We also found that ARA70, ARA55, and ARA54, but not steroid receptor coactivator-1 (SRC-1) and Rb, could significantly enhance the delta5-androstenediol-mediated AR transactivation. Furthermore, in comparing the relative specificity of these coactivators to AR in DU145 cells, our results suggested that ARA70 has a relatively higher specificity and that SRC-1 can enhance almost equally well many other steroid receptors. Finally, our data demonstrated that AR itself and some select AR coactivators such as ARA70 or ARA54 could, respectively, interact with CBP and p300/CBP-associated factors that have histone acetyl-transferase activity for assisting chromatin remodeling. Together, our data suggest that the specificity of sex hormones and antiandrogens can be modulated by some selective AR coactivators. These findings may not only help us to better understand the specificity of the sex hormones and antiandrogens, but also facilitate the development of better antiandrogens to fight the androgen-related diseases, such as prostate cancer.

Androgen Antagonists↗
PubMed1999

[The Research Encouragement Award. Effects of sex hormones on sexual difference of experimental paracoccidioidomycosis].

Paracoccidioidomycosis is a deep mycosis in Latin America. The causative agent is Paracoccidioides brasiliensis, a thermal dimorphic fungus. The incidence of the disease is much higher in men than in women. Although one explanation is the inhibitive effect of estradiol on fungal growth, its effect on the yeast form growth of P. brasiliensis is still unclear. There is limited information on progesterone and testosterone, which shows weak or no effects. On the other hand, numerous studies on sexual differences between male and female animals have been made with experimental paracoccidioidomycosis. The conclusions however, remain unclear. The present study shows the effects of estradiol (17 beta-estradiol), progesterone and testosterone on the yeast form growth of P. brasiliensis, and the sexual difference of the susceptibility in adult BALB/c mice at the initial stages of infection with view of their estrous cycles and body weight. The inhibitive effects of estradiol, progesterone and testosterone on the yeast form growth of P. brasiliensis were examined using a brain heart infusion broth with different doses of these hormones. The inhibition by estradiol was dose-dependent within the range of physiological concentrations. While the inhibitive effect of progesterone and testosterone was very weak. The phenomenon that estradiol inhibited the yeast form growth of P. brasiliensis may be one important reason for the sexual differences of paracoccidioidomycosis. The initial stages of the yeast form cells of P. brasiliensis infection were evaluated by three inoculation routes: intravenous, intraperitoneal and intratracheal. The mice were divided into 6 groups, including male and female at proestrus, estrus, metestrus- I, metestrus- II and diestrus. Four hours after inoculation, blood samples, peritoneal lavage and pulmonary homogenates were collected and their colony forming units were examined on brain heart infusion agar plates with 1 % of dextrose and 50 mg per liter of chloramphenicol. In all inoculation routes, the clearance of the yeast cells was influenced by the estrous cycles. In particular, female mice at estrus, thought to have high blood estradiol levels, showed a marked clearance of the yeast cells from the blood, peritoneal cavity and lung. All female groups inoculated by any of the three different routes, showed much higher clearance than the male groups. These results suggest that non-specific host resistance to the yeast form cells of P. brasiliensis in females was much higher than in males. There are two explanations for the tendency of higher occurrence of paracoccidioidomycosis in men. One is the inhibitive effect of estradiol on the growth of P. brasiliensis and the other is the superior tendency of non-specific host resistance in females than in males. These two factors seem to have synergistic actions in the sexual difference of paracoccidioidomycosis.

Animals↗
PubMed1999

Epidemiological survey of the imported mycoses in Japan.

The authors surveyed the present situation for imported (introduced) mycoses from papers published in Japan as of the end of October, 1998. There were 16 cases of coccidioidomycosis, 22 of histoplasmosis, 13 of paracoccidioidomycosis and one of penicilliosis marneffei. In coccidioidomycosis the ages ranged from 17 to 55, for 14 males and two females. There were eight cases of primary pulmonary coccidioidomycosis and the remaining eight were of the disseminated type, of which two were fatal. For histoplasmosis, the ages ranged from 17 to 74 of which five cases were female and 17 male. They consisted of 13 pulmonary histoplasmosis, seven disseminated type and two cutaneous type. All cases of the disseminated type died. All of the patients with paracoccidioidomycosis were infected in Latin American countries. They consisted of 12 males and one female, and the ages ranged from 34 to 68. The clinical types were dominated by mucocutaneous-lymphangitic paracoccidioidomycoses (10 cases). A single case of penicilliosis marneffei (38 years old, male) was reported very recently. The case was complicated by AIDS and became critical. Blastomycosis has not yet been reported. This survey indicates that the number of the imported mycoses in Japan is increasing. It is necessary for the responsible authorities to take counter measures to cope with this situation.

Adolescent↗
PubMed1999

[Analysis of the cases in which Schizophyllum commune was isolated].

Infections caused by Schizophyllum commune have recently been on the increase. We analyzed cases in which this fungus was isolated from clinical samples from 1991 to 1995. Regular morphological methods were first employed in the identification of S. commune, and when necessary, mating was made with a known S. commune isolate. IgG antibodies against S. commune in the patients' serum were determined by the ELISA method. Profiles of the cases were analyzed and the English-language medical literature was reviewed. S. commune was isolated from 12 patients. Eighty three percent of the patients were female, most of which presented with allergy-related pulmonary diseases, i. e. allergic bronchopulmonary mycosis or mucoid impaction of bronchi. IgG antibodies were detectable in nine of eleven patients examined (82%). Fifty eight percent of the isolates were monokaryotic, and therefore, unidentifiable by regular morphological methods. In contrast, analysis of the English literature disclosed that sinusitis is the most common form of infection, and that hyphal invasion into the tissue was seen in 50% of reported cases. Our study shows that S. commune should be regarded as a pathogenic fungus, and is infecting humans much more frequently than previously assumed. Further investigation is warranted.

Adolescent↗
PubMed1999

Ploidy of serotype AD strains of Cryptococcus neoformans.

Twenty-four serotype AD strains of Cryptococcus neoformans were tested for ploidy and mating type. These included 13 natural isolates (1 from a patient, 1 from peach juice, 11 from pigeon droppings), 2 single clones from one of these natural isolates, 7 F1 progeny from a self-fertile strain and 2 F1 progeny of a cross between a strain from a patient (serotype A, alfa-mating type: MATalfa) and a tester strain (serotype D, a-mating type: MATa). Six strains (2 of natural isolates, 1 of single clone and 3 of F1 progeny) were MATalfa, 1 of F1 progeny was MATa, 4 (1 of natural isolate, 1 of single clone and 2 of F1 progeny) were a-alfa-mating type (MATa-alfa) and 13 (10 of natural isolates and 3 of F1 progeny) were untypable. Most strains, regardless of mating type, were diploid.

Cryptococcus neoformans↗
PubMed1999

AS-924, a novel bifunctional prodrug of ceftizoxime.

To improve the oral absorption of ceftizoxime (CZX), 7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]- 3-cephem-4- carboxylic acid, we synthesized and evaluated a novel series of bifunctional prodrugs, in which L-alanine was introduced into the aminothiazole-oxime moiety at the C-7 position of the various lipophilic esters of CZX. Among these prodrugs, pivaloyloxymethyl 7beta-[(Z)-2-(2-(S)-alanylaminothiazol-4-yl)-2-methoxyiminoa cetamido]-3-cephem-4-carboxylate hydrochloride (ceftizoxime alapivoxil, AS-924) was well absorbed after oral administration in experimental animals and showed potent therapeutic effects in mice infected with gram-positive and gram-negative bacteria.

Animals↗
PubMed1999

[A case of retroperitoneal teratoma in an adult resembling adrenal tumors].

A retroperitoneal teratoma arising from the vicinity of the upper pole of the right kidney in a 61-year-old woman is described. Computed tomographic (CT) scan showed well marginated fat density mass with calcification. Magnetic resonance imaging (MRI) on T1 weighted image and T2 weighted image showed a high-intensity mass above the upper pole of the right kidney. Needle biopsy under computed tomography was performed, but no specimen was obtained. The preoperative diagnosis was retroperitoneal teratoma or right adrenal myelolipoma. The tumor was resected and the histological diagnosis was benign retroperitoneal cystic teratoma.

Adrenal Gland Neoplasms↗
PubMed1999

Fungistatic and fungicidal activities of murine polymorphonuclear leucocytes against yeast cells of Paracoccidioides brasiliensis.

Recently, a novel culture medium for detecting live yeast cells of Paracoccidioides brasiliensis was developed by Kurita et al. Using this culture medium, murine peritoneal polymorphonuclear leucocytes (PMN) were examined for fungistatic and fungicidal activities against P. brasiliensis yeast cells. The magnitude of the antifungal effect of PMN varied depending upon the fungal isolates used. PMN exhibited a killing effect on P. brasiliensis isolate Bt-4 in 2 h of coculture. In contrast, the other three fungal isolates employed were resistant to killing by PMN. However, PMN considerably suppressed the growth of isolates Tatu and Recife in a long-term assay (approximately 72 h). The growth of isolate Bt-9 was also suppressed by PMN during the first 24 h, but was found to be considerably promoted at 72 h of coculture. Interferon-gamma (IFN-gamma), but not tumour-necrosis factor-alpha, significantly augmented the antifungal activity of PMN. IFN-gamma-treated PMN exhibited a killing effect on isolates Tatu, Recife and Bt-9 after 24 h of coculture, and showed an enhanced killing effect on isolate Bt-4. Contact between PMN and fungal cells was required for PMN to exert the antifungal effect. Our results suggest that PMN, whether activated with cytokines or not, might play a critical role in host resistance in early infection with this fungus by buying time for development of more effective immunologic responses.

Animals↗
PubMed1999

[Long-term immunological study on postoperative adjuvant treatment with interferon-gamma in patients with renal cell carcinoma who underwent nephrectomy].

Previously, we reported the short-term immunological effects of postoperative adjuvant interferon-gamma (IFN-gamma) administration to renal cell carcinoma patients as determined by three-color flow cytometry. We now report the results of a long-term study on a larger number of subjects. Thirty-three patients with renal cell carcinoma received a prophylactic intramuscular injection of IFN-gamma (300 x 10(4) units per week) after nephrectomy. We evaluated immunological changes by measuring peripheral blood lymphocyte subsets including activated cytotoxic T lymphocytes (ACTL), cytotoxic T lymphocytes (CTL), activated suppressor T lymphocytes (ASTL), helper T lymphocytes (HTL), activated suppressor-inducer T lymphocytes (AITL), and suppressor-inducer T lymphocytes (SITL). We also estimated the natural killer (NK) activity by a cytolytic test. All 33 patients were examined for at least 12 months after the start of IFN-gamma injection, and 18 patients were examined for 30 months including the 6-month period following discontinuation of IFN-gamma injection. We found significant enhancement of the ACTL subset from the second week to the sixth month after the start of IFN-gamma injection. On the other hand, we found a significant decrease in the percentage of the HTL and SITL subsets for a long time after the start of injection. NK activity significantly increased throughout the period of administration, and it continued to increase for six months after discontinuation of IFN-gamma injection.

Adult↗
PubMed1999

Panipenem, a carbapenem antibiotic, enhances the glucuronidation of intravenously administered valproic acid in rats.

Previously, a significant decrease in the trough plasma-concentration of valproic acid (VPA) owing to the concomitant administration of panipenem (PAPM)/betamipron, a carbapenem antibiotic, in epileptic patients was reported. To determine the site and mechanism of the drug interaction between VPA and PAPM, we performed in vivo and in vitro experiments using rats. A 30 mg/kg bolus dose of VPA was given i.v. to normal Sprague-Dawley rats, nephrectomized rats, and hepatectomized rats, with and without prior treatment of PAPM. PAPM treatment resulted in a significant reduction of biological half-life and a significant increase of total body clearance in normal rats. The effects of PAPM on the disposition kinetics of VPA were also observed in nephrectomized rats, whereas hepatectomy abolished the interaction completely. Thus, the site of interaction was identified as the liver. At steady state, PAPM treatment significantly increased total body clearance, the biliary excretion rate of VPA glucuronide, and the apparent metabolic clearance of VPA by glucuronidation, but did not affect the biliary excretion clearance of VPA glucuronide. Initial uptake velocity of VPA into rat hepatocytes proportionally increased as a function of VPA concentration added and was not affected by PAPM. The plasma-unbound fraction of VPA in vitro was not altered by PAPM. These data demonstrate that PAPM does not affect the uptake of VPA into the liver, the plasma-unbound fraction, and the excretion process of VPA glucuronide. Consequently, PAPM appears to enhance the rate of metabolism of VPA to VPA glucuronide in the liver.

Animals↗
PubMed1999

[Open heart surgery without the use of homologous blood in infants and young children: effectiveness of the intraoperative autologous blood donation from arterial monitoring line].

Open heart surgery without the use of homologous blood transfusion was attempted in 81 pediatric patients weighing 5.5-14.9 kg. Autologous blood was donated from arterial monitoring line after induction of anesthesia. This donated blood, actual volume of 9.2 +/- 1.7 ml/kg, was reinfused following the cessation of extracorporeal circulation. Hemodilution resulting from autologous blood donation was well tolerated by all patients. Sixty-eight patients (84%) were operated on successfully without the need for homologous blood. These data suggest that autologous blood donation from arterial monitoring line is a safe and effective method to avoid homologous blood transfusion especially in infants and young children undergoing open heart surgery.

Blood Pressure↗
PubMed1999

[A case of pheochromocytoma detected by hypertensive crisis immediately after drip infusion urography].

We report a rare case of a 60-year-old man with a pheochromocytoma detected by a hypertensive crisis immediately after drip infusion urography. The patient initially consulted our hospital complaining of dysuria. He underwent a drip infusion urography and experienced a hypertensive crisis. The next day he was diagnosed with paralytic ileus. An endocrinological examination, abdominal computed tomography and 123I-metaiodobenzyl-guanidine scintigraphy revealed a pheochromocytoma. The tumor mass was removed, and immediately his blood pressure became normal and the paralytic ileus improved; however, temporary postoperative hypoglycemia was seen. Frequent monitoring of his blood glucose and the administration of an appropriate solution of dextrose, both during and after the operation, were recommended.

Adrenal Gland Neoplasms↗
PubMed1999

[Detection size dependence of field factor for narrow beam].

An absorbed dose in the narrow beam is calculated based on the depth dose distribution and a field factor. The field factor has to be measured with especially high accuracy because it is highly variable. The field factor was calculated when detection size was changed, by using Monte Carlo simulation, which had no energy dependency or geometrical error. Then the relation between field factor and detection size in the narrow beam was investigated. An absorbed dose in peak depth and reference depth according to detection size was calculated for each field size. Detection size dependency was recognized in the case of measuring a field factor, because the absorbed dose tended to decrease as detection size increased. The absorbed dose in the narrow beam has to be calculated within a change of +/- 2%. The change in peak depth according to detection size was eliminated, and then the relation between an absorbed dose at the ideal detection size of 0 mm phi by extrapolation and detection size which has a deference of 2% from it, were acquired. In addition, the maximum usable detection size was estimated in the case of measuring the field factor.

Models, Theoretical↗
PubMed1999

[Spontaneous rupture of a renal angiomyolipoma in pregnancy: a case report].

A 32-year-old woman in the 36th week of pregnancy was admitted to obstetrics with a complaint of left flank pain. Magnetic resonance imaging demonstrated a left perinephric hematoma before the cesarean section. Spontaneous rupture of renal angiomyolipoma was suspected by computed tomographic scan and renal angiography after the cesarean section. We attempted partial nephrectomy, but performed nephrectomy because of perinephric adhesion. This is the 11th case of spontaneous rupture of renal angiomyolipoma during pregnancy in the Japanese literature.

Adult↗
PubMed1999

Species differences in the transport activity for organic anions across the bile canalicular membrane.

Species differences in the transport activity mediated by canalicular multispecific organic anion transporter (cMOAT) were examined using temocaprilat, an angiotensin-converting enzyme inhibitor whose biliary excretion is mediated predominantly by cMOAT, and 2,4-dinitrophenyl-S-glutathione, a typical substrate for cMOAT, in a series of in vivo and in vitro experiments. Temocaprilat was infused to examine the biliary excretion rate at steady-state. The in vivo transport clearance values across the bile canalicular membrane, defined as the biliary excretion rate divided by the hepatic unbound concentrations, were 9.8, 39.2, 9.2, 1.1, and 0.8 ml/min/kg for mouse, rat, guinea pig, rabbit, and dog, respectively. The K(m) and V(max) values for ATP-dependent uptake of 2, 4-dinitrophenyl-S-glutathione into canalicular membrane vesicles were 15.0, 29.6, 16.1, 55.8, and 30.0 microM and 0.38, 1.90, 0.15, 0. 47, and 0.23 nmol/min/mg protein, yielding the in vitro transport clearance across the bile canalicular membrane (V(max)/K(m)) of 25.5, 64.2, 9.4, 8.4, and 7.7 for mouse, rat, guinea pig, rabbit, and dog, respectively. A close in vivo and in vitro correlation was observed among animal species for the transport clearance across the bile canalicular membrane. These results suggest that the uptake experiments with canalicular membrane vesicles can be used to quantitatively predict in vivo excretion across the bile canalicular membrane.

Animals↗