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Biomedical subjects

K Nishimura

Publications and source records attributed to K Nishimura.

At least 271 records · Page 15Linked to original sources

New PCR primer pairs specific for Cryptococcus neoformans serotype A or B prepared on the basis of random amplified polymorphic DNA fingerprint pattern analyses.

Thirty-three strains of Cryptococcus neoformans were isolated from clinical specimens, including specimens from AIDS patients in Brazil, and were classified into two serotypes; we detected 31 and 2 strains of serotypes A and B, respectively. Random amplified polymorphic DNA (RAPD) fingerprint pattern analyses of these strains of serotypes A and B showed that the patterns were similar for strains of each serotype when three 10-mer primers were used as the RAPD primers. Comparative studies of the fingerprint patterns of the study isolates with those of the reference strains also showed that the RAPD patterns for strains of each serotype were related and that most of the fingerprint bands existed commonly for all strains of each serotype tested. The common RAPD bands (an approximately 700-bp band for serotype A and an approximately 450-bp band for serotype B) were extracted and the DNA sequences were determined. Using this information, we prepared two and one PCR primer pairs which were expected to be specific for C. neoformans serotypes A and B, respectively. Use of each PCR primer combination thus prepared for serotype A or B was 100% successful in identifying the respective C. neoformans serotypes, including the 33 clinical isolates tested in the present study. Among these combinations, one for serotype A was found to amplify DNA from C. neoformans serotype B as well as serotype A. Serotype B-specific PCR primer pairs amplified DNA from not only serotype B strains but also from serotype C strains. The usefulness of other serotype-specific PCR primers for clinical C. neoformans isolates is discussed.

AIDS-Related Opportunistic Infections↗

Comparison of low attenuation areas on computed tomographic scans between inner and outer segments of the lung in patients with chronic obstructive pulmonary disease: incidence and contribution to lung function.

BACKGROUND: The low attenuation areas on computed tomographic (CT) scans have been reported to represent emphysematous changes of the lung. However, the regional distribution of emphysema between the inner and outer segments of the lung has not been adequately studied. In this study the regional distribution of low attenuation areas has been compared by quantitative CT analysis and the contribution of the regional distribution to pulmonary function tests evaluated in patients with chronic obstructive pulmonary disease (COPD). METHODS: Chest CT images and the results of pulmonary function tests were obtained from 73 patients with COPD. The lung images were divided into inner and outer segments in the upper (cranial), middle, and lower (caudal) sections. The percentage ratio of low attenuation area to corresponding lung area (LAA%) was then calculated. The LAA% of each segment was also compared with the results of pulmonary function tests. RESULTS: The mean (SD) LAA% of the inner segment was 39.1 (18.5) compared with 28.1 (13.2) for the outer segment (p<0.0001). Linear and multiple regression analyses revealed that airflow limitation is closely correlated with the inner segment LAA% of the lower lung. In contrast, the carbon monoxide transfer factor is closely correlated with the inner segment LAA% of the upper lung. CONCLUSION: Low attenuation areas on CT scans are more often found in the inner segment of the lung than in the outer segment, and the contribution of the inner segment to pulmonary function tests may be greater than the outer segment.

Aged↗

Comparison of the bronchodilator effects of salbutamol delivered via a metered-dose inhaler with spacer, a dry-powder inhaler, and a jet nebulizer in patients with chronic obstructive pulmonary disease.

The aim of this study was to compare the bronchodilator effects of salbutamol delivered via three different devices: a dry-powder inhaler (DPI), a metered-dose inhaler (MDI) with a large-volume spacer and a jet nebulizer (NEB) in patients with stable chronic obstructive pulmonary disease (COPD). Ten male patients with stable COPD [age: 67.2 +/- 3.8 years, forced expiratory volume in 1 s (FEV1): 1.56 +/- 0.32 liters] were studied in a randomized, double-blind and crossover manner. Each patient received 200 or 1, 000 microg salbutamol via an MDI with an InspirEaseTM spacer, a RotahalerTM, or a DeVilbiss 646(TM) nebulizer (NEB), or matching placebo on 7 separate days. Spirometry was performed before and 15, 30, 60, 90, 120, and 240 min after inhalation. With the 200- microg dose, only DPI produced a small but greater response in maximum FEV1 and in area under the time-response curve (AUC-FEV1) compared with placebo. With the 1,000- microg dose, DPI and MDI produced equally greater improvements in both maximum FEV1 and AUC-FEV1 than NEB. An equal bronchodilating effect can be obtained using either DPI or MDI with a spacer device, whereas the NEB was less effective when the same dose was administered.

Administration, Inhalation↗

Clinical study of brain metastasis of renal cell carcinoma.

OBJECTIVES: To evaluate the natural history and the efficacy of treatments for renal cell carcinoma (RCC) with brain metastasis, we reviewed 18 patients with this disease. METHODS: Out of 325 cases with RCC treated at Osaka University Hospital from 1957 to 1993, 18 (5.5%, male:female ratio 16:2) cases developed brain metastases. Median follow-up was 44 months after the initial treatment of the primary lesion. Twelve patients had surgical resection of brain metastases (surgical group), and 7 of them received adjuvant radiotherapy. Six patients with poor performance status were treated with supportive therapy alone (nonsurgical group). RESULTS: Of 18 RCC patients with brain metastasis, 16 were male and 2 female. All brain metastases except for 1 case were symptomatic. Median interval between the initial treatment of the primary lesion and the diagnosis of brain metastasis was 19 months. The most frequent metastatic site prior to brain was the lung, which was detected in 7 cases (38.9%). Median survival of the entire group, measured from the onset of brain metastasis, was 9.5 months. One-year survival rate after the diagnosis of brain metastasis was 43.2% (64.8% in surgical group, 0% in nonsurgical group), 3-year 18.5% and 5-year 0%. Among 109 metastatic RCC, 14 patients were treated by lymphokine-activated killer (LAK) therapy. Out of 14 metastatic RCC patients treated by LAK therapy, 3 (21.4%) developed brain metastases. On the other hand, out of 95 metastatic RCC patients without LAK therapy, 15 (15.8%) had brain metastases. There was no significant difference in the rate of brain metastases between these two groups. CONCLUSION: There was a trend for prognosis of the surgical group to be better compared to that of the nonsurgical group, although it is not statistically significant. The optimum treatment for brain metastasis of RCC remains undefined, but our data suggested surgical resection in selected patients might contribute to prolonged survival of patients with brain metastasis. LAK therapy was not necessarily the risk factor of the brain metastasis.

Adult↗

A novel, short, and simple questionnaire to measure health-related quality of life in patients with chronic obstructive pulmonary disease.

A novel, short, and simple questionnaire, the Airways Questionnaire 20 (AQ20), has been developed to measure and quantify disturbances in the health-related quality of life (HRQoL) of patients with asthma or chronic obstructive pulmonary disease (COPD). The AQ20 has 20 items with yes/no responses, and should take 2 min to complete and score. The purpose of this study was to assess the discriminative properties and responsiveness of the AQ20 in patients with COPD. First, in a cross- sectional study, 165 patients with mild-to-severe COPD (mean age, 69 +/- 7 yr; FEV1, 40 +/- 16% of predicted) completed the AQ20, the St. George's Respiratory Questionnaire (SGRQ), the Chronic Respiratory Disease Questionnaire (CRQ), pulmonary function tests, a progressive cycle ergometer exercise test, and an assessment of their dyspnea and anxiety. The score distribution of the AQ20 was skewed toward the mild end of the scale, whereas the SGRQ and CRQ showed a normal distribution. The AQ20 showed a moderately strong correlation with the maximal oxygen uptake and the assessment of dyspnea (Spearman's correlation coefficients [rs] = -0.49, -0.60, respectively), but a weak correlation with the FEV1 (rs = -0.18). Moderate to strong correlations were also recognized between the AQ20 and SGRQ and CRQ (rs = -0.80, -0.72, respectively). Multiple regression analysis revealed that dyspnea and anxiety accounted for 43% of the variance in the AQ20, almost the same as in the SGRQ and CRQ. Second, longitudinal changes over time in the FEV1, AQ20, SGRQ, and CRQ were examined in 86 patients with newly detected COPD (mean age, 69 +/- 8 yr; FEV1, 45 +/- 19% of predicted). All three measures showed significant improvements in their scores over a 3-mo period after initiating medical intervention. The change in the AQ20 showed a moderate to strong correlation with each dimension of the SGRQ and CRQ (rs = 0.56, -0.52, respectively), but no significant correlation was noted with the FEV1. In conclusion, the AQ20 may have discriminative properties and responsiveness that are similar to more complex questionnaires such as the SGRQ and CRQ. Because it is short and can be quickly answered and scored, the AQ20 may be useful in studies with limited time for HRQoL assessments.

Aged↗

Thiol depletion induces apoptosis in cultured lung fibroblasts.

Thiol antioxidants are implicated in the protection of cells from oxidative injury. We studied the role of thiols in the regulation of apoptosis in cultured lung fibroblasts. Thiol depletion by culturing fibroblasts in cystine-free medium or with thiol-depleting agents induced oxidant accumulation and cell death by apoptosis. The cell death was prevented by the antioxidants ascorbic acid (AA) and catalase. Thiol depletion also induced leukotriene (LT) C4, LTD4, and LTE4 production and selective phosphorylation of p38-mitogen-activated protein kinase (MAPK) and its nuclear substrate ATF2. LT production and p38-MAPK phosphorylation were required for induction of apoptosis because thiol depletion-induced apoptosis was completely blocked by the 5-lipoxygenase inhibitor AA861, the LT antagonists FPL55712 and ONO1078, and the p38-MAPK inhibitor SB203580. LT production was inhibited by AA and p38-MAPK phosphorylation was inhibited by AA, AA861, and FPL55712. In an in vitro scratch wound model, repopulating fibroblasts at the wound margin, but not quiescent cells at the intact site, selectively underwent thiol depletion- induced apoptosis that was completely blocked by AA861, FPL55712, and SB203580. Thus, thiol depletion induces apoptosis through an ordered pathway involving oxidant accumulation, LT production, and p38-MAPK activation. Apoptosis of wound fibroblasts may be responsible for impaired wound healing in various organs, including the lung.

Apoptosis↗

AS-924, a novel orally active bifunctional prodrug of ceftizoxime. Synthesis and relationship between physicochemical properties and oral absorption.

Ceftizoxime (CZX), a parenteral cephalosporin, has potent and broad antibacterial activity. To improve its oral absorption, we synthesized a series of monofunctional and bifunctional prodrugs of CZX. In rabbits, urinary recovery after oral administration of CZX was improved by esterification of the carboxyl group at the C-4 position with various lipophilic moieties (monofunctional prodrugs), and was further increased by introduction of a hydrophilic L-alanine to the amino group on the thiazole ring at the C-7 position (bifunctional prodrugs). Least-squares analysis showed good parabolic correlations between log P and urinary recovery for monofunctional and bifunctional prodrugs, respectively. AS-924, a bifunctional prodrug with a pivaloyloxymethyl and L-alanyl moiety had the best balance of lipophilicity and water-solubility for oral absorption among the prodrugs synthesized.

Administration, Oral↗

[Effect of plasma-treatment on suppression of drug adsorption to the surface of plastic infusion bag].

Plastics has been widely used at the hospitals and dominates the field of the manufacture of infusion bag sets and packaging materials as a disposable product. Recently, it has been reported, however, that expected drug effects could not be obtained owing mainly to the drug adsorption to the surface of plastic bags observed when several injection drugs such as nitroglycerin, isosorbide dinitrate, diazepam, and insulin were injected mixedly into a certain plastic intravenous bags. And there is a possibility of the occurrence of chemical reactions between the added drugs and the surface of plastic bags. We also can not deny the possibility of the dissolution of softener from the plastic bags. On the other hand, we have been working on the nature of plasma treatment of polymer surfaces by irradiation of low temperature plasma and its pharmaceutical application studies. In this study, we obtained the data concerning the effect of plasma treatment on the reduction of adsorption of insulin to the surface of ethylene-vinylacetate (EVA) bag.

Adsorption↗

Structure-activity relationships of RGD mimetics as fibrinogen-receptor antagonists.

The activities of a series of RGD mimetics, which contained a variety of cationic structures, for the inhibition of platelet aggregation and fibrinogen-receptor binding were measured. The stability of the coulombic ion-pairing complex of the model compounds with the acetate anion as a model for the receptor was calculated in terms of the ionic interaction energy. The results suggest that stability is one of the significant factors which govern the inhibitory potency of fibrinogen-receptor binding. The distance between cationic and anionic groups might also affect the potency. A compound which contained an amidinophenyl structure as the cationic moiety showed exceptionally high inhibitory activity, suggesting that some other factors, in addition to coulombic interaction and the distance, affect the potency.

Blood Platelets↗

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↗

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↗

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↗

[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↗

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↗

[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↗

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↗

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↗