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Biomedical subjects

K Nishimura

Publications and source records attributed to K Nishimura.

At least 199 records · Page 11Linked to original sources
PubMed2000

Impairment of airway mucociliary transport in patients with sinobronchial syndrome: role of nitric oxide.

Nitric oxide (NO) produced within the respiratory tract can stimulate ciliary motility of airway epithelial cells and hence mucociliary transport. In this study, to determine the role of NO in mucociliary dysfunction in sinobronchial syndrome (SBS), we measured NO concentrations in the exhaled air by chemiluminescence analyzer and nasal clearance time (NCT) by saccharin test. Exhaled NO concentrations in patients with SBS were 39% of those in healthy nonsmokers and 55% of those in healthy smokers. The patients also showed prolonged NCT compared with healthy subjects, and there was a significant negative correlation between exhaled NO concentrations and NCT. Furthermore, concentrations of chloride (Cl) in the sputum supernatant were higher in SBS patients than in healthy subjects, and there was a significant negative correlation between sputum Cl concentrations and exhaled NO concentrations. These results suggest that airway mucociliary clearance is impaired in patients with SBS and that this impairment might result from the reduced production of NO and the impaired availability of the molecule in the mucociliary apparatus.

Adult↗
PubMed2000

Clinical course and prognosis of patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a basically benign disease, but the prognosis is so poor that the mortality rate is similar to some malignant diseases. Depending on the disease severity, the 5-year mortality rate of patients with COPD varies from 40 to 70%. The three major causes of death have been identified as COPD itself, lung cancer, and cardiovascular disease. The following factors have been reported to be related to survival: FEV1 (especially the maximal attainable lung function), age, gender, PaO2, PaCO2, body weight, and comorbidity. There have been several large-scale randomized clinical trials to examine the prophylactic effects of inhaled anti-cholinergics and inhaled corticosteroids on the annual decline in FEV1. However, unfortunately, in all of the published studies, these drugs had no effect on the annual decline in FEV1.

Cause of Death↗
PubMed2000

Crystallization and preliminary X-ray analysis of endopolygalacturonase SE1 from Trichosporon penicillatum.

Endopolygalacturonase SE1 from Trichosporon penicillatum has been crystallized by the hanging-drop method of vapour diffusion using ammonium sulfate as a precipitant. The crystals belong to the hexagonal space group P6(1) or P6(5), with unit-cell parameters a = b = 135.0, c = 70.7 A, gamma = 120 degrees. The calculated V(M) based on one molecule per asymmetric unit is 3.09 A(3) Da(-1). A native data set from a crystal has been collected to 2.0 A resolution on a Cu Kalpha rotating-anode X-ray source.

Crystallography, X-Ray↗
PubMed2000

Preferential activity of wild-type and mutant tumor necrosis factor-alpha against tumor-derived endothelial-like cells.

Tumor-derived endothelial-like cells (tEC) were prepared by culturing human umbilical vein endothelial cells (HUVEC) in the presence of HT1080 human fibrosarcoma-conditioned medium. tEC showed higher permeability and less cell-adhesion activity than normal HUVEC (nEC). Tumor necrosis factor-alpha (TNF) is known to have tumor-vasculature disrupting activity. tEC showed higher cytotoxicity to recombinant human TNF (rhTNF) than nEC, and was not observed using HUVEC cultured with WI38 human diploid cell-conditioned medium as a medium-control. These results demonstrate that tEC acquire physiological properties of tumor-associated vasculature, and may be a useful model system for the study of the mechanisms of TNF antitumor action. The TNF-mutant RGD-V29 (code No. F4614), which has an inserted 4Arg-Gly-Asp sequence and an 29Arg-->Val replacement, was found to induce greater preferential destruction of tEC compared to rhTNF. When the preferential activities were evaluated in terms of 30% cytotoxicity (IC30) ratio (nEC/tEC), the ratio was 460 for RGD-V29 compared to 4.2 for rhTNF. RGD-V29 also exhibited cell-adhesive function and bound preferentially to the p55 TNF-receptor. Both these properties of RGD-V29 contributed to the tEC selective cytotoxicity, indicating that the RGD ligands and selective p55 receptor binding on the cells, although uncharacterized, are involved in tEC targeting. Therefore, the TNF mutant RGD-V29 may show greater selectivity toward tumor vasculature than wild-type TNF.

Binding, Competitive↗
PubMed2000

Effect of hepatocyte growth factor on sperm motility.

PROBLEM: Hepatocyte growth factor (HGF) exists abundantly in seminal plasma and its receptor, c-met, is expressed on spermatozoa. Considering its motogenic activity, we speculated that HGF might affect the movement ability of spermatozoa. METHODS: Recombinant HGF was added to washed spermatozoa and their movements were analyzed using a computer-assisted sperm analyzer. The concentration of HGF in the seminal plasma of infertile patients (n = 83) was measured by ELISA, and the data were compared with their hormonal profile and semen parameters. RESULTS: The HGF physiological concentration (1 ng/mL) maintained the motility of sperm after a long incubation, though the difference was not statistically significant. Recombinant HGF did not affect the linearity or frequency of movement, which suggested that it does not evoke the hyperactivation of spermatozoa. The concentration of HGF in seminal plasma did not correlate with any clinical parameter of the patients. CONCLUSIONS: These findings contradict the theory that HGF controls the movement of sperm. The main role of this axis in the male reproductive system might be maturation in the epididymis.

Hepatocyte Growth Factor↗
PubMed2000

Identification and phylogenetic relationship of the most common pathogenic Candida species inferred from mitochondrial cytochrome b gene sequences.

We sequenced a 396-bp region of the mitochondrial cytochrome b gene of the most common clinically important Candida species: Candida albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, and C. lusitaniae. The recently described species of Candida, C. dubliniensis, associated with mucosal candidiasis in human immunodeficiency virus-infected individuals, was also included. Two to five strains of each species were examined. Some species represented intraspecies variation, which was not more than 1.8% (DNA). However, interspecies variations were more than 10 and 7%, respectively, for DNA and amino acid sequences. Multiple alignments of nucleotide and deduced amino acid sequences revealed species-specific nucleotides and amino acids. Nucleotide- and amino acid-based phylogenetic trees were constructed and are discussed. Using the database, it is possible to identify presumptive Candida species within a working day.

Amino Acid Sequence↗
PubMed2000

Mitochondrial cytochrome b gene analysis of Aspergillus fumigatus and related species.

Nucleotide sequences of 426 bp from the mitochondrial (mt) cytochrome b genes of six anamorph species and two species of Neosartorya teleomophs of Aspergillus section Fumigati were determined. These sequences were used to build nucleotide- and amino acid-based trees for phylogenetic analysis. Thirteen strains of A. fumigatus including 10 clinical isolates of A. fumigatus, 1 type culture of A. fumigatus var. fumigatus, 1 type culture of A. fumigatus var. ellipticus, and 1 strain of A. fumigatus var. albus, had the same nucleotide sequences. One strain of A. fumisynnematus, two strains labeled A. neoellipticus, two strains of A. viridinutans, and one strain of A. duricaulis had distinct nucleotide and amino acid sequences. Two strains of A. brevipes were divided into two types. One produced a 1,500-bp fragment that included an intron. The nucleotide sequences of its two exons were similar to those of the A. fumigatus, and the derived amino acid sequence was the same as that for A. fumigatus. The other produced a 426-bp fragment and had the same nucleotide and amino acid sequences as A. unilateralis. Neosartorya fischeri var. fischeri and N. stramenia had nucleotide sequences that differed from that of A. fumigatus. These species possessed their own characteristic nucleotide sequences that differed from each other. In comparisons of homologous sequences from four other pathogenic species of Aspergillus, regions specific to section Fumigati were found. The mt cytochrome b gene analysis was valuable for the identification, classification, and phylogenetic analysis of isolates of section Fumigati.

Amino Acid Sequence↗
PubMed2000

Bacillus Calmette-Guérin perfusion therapy for the treatment of transitional cell carcinoma in situ of the upper urinary tract.

OBJECTIVES: The aim of this study is to evaluate the efficacy and safety of intrarenal bacillus Calmette-Guérin (BCG) instillation as a treatment for transitional cell carcinoma in situ (CIS) of the upper urinary tract. METHODS: Diagnostic criteria of upper urinary tract CIS were (1) positive urinary cytology, (2) negative multiple random biopsy of the bladder and prostatic urethra, (3) negative radiographic findings in the upper urinary tract and (4) two serial positive cytologies in selective ipsilateral urine sampling from the pyeloureteral system. Eleven patients diagnosed as having upper urinary tract CIS were enrolled in this study. Thus, 11 renal units were treated with BCG instillation. After placing a 6-french Double-J stent, BCG (80 mg) in 40 ml saline was instilled into the bladder weekly, 6 times in total as one course. RESULTS: At the end of one course, 9 cases showed negative urinary cytology. Among these 9 cases, 2 showed recurrence in the upper urinary tract after 4 months and 8 months of disease-free interval, respectively. These 2 cases have received an additional course of BCG instillation, but the urinary cytology did not normalize. Mean recurrence-free time was 19.6 months. Of the other 7 cases who responded to the first course of instillation, 6 cases were alive with no evidence of the disease. The remaining patient died of rectal cancer with no evidence of transitional cell carcinoma (TCC). Of the 2 cases who showed positive urinary cytology even after the first course, 1 underwent nephroureterectomy. The other case was diagnosed as having malignant lymphoma 3 months after the end of this instillation therapy, and he died of malignant lymphoma. As side effects, 8 cases (72.7%) showed bladder irritability, and 4 presented fever higher than 38 degrees C. However, no patient needed antitubercular treatment. CONCLUSION: As for the short-term response, BCG instillation for the treatment of upper urinary tract CIS is considered to be effective and safe. Longer follow-up and further experience with this treatment are required.

Adjuvants, Immunologic↗
PubMed2000

Airflow limitation in Japanese smokers: significance of serum neutrophil elastase/alpha(1)-proteinase inhibitor ratio and FEV(1) (%pred) adjusted by pack-years.

BACKGROUND: In spite of the known role of cigarette smoking in the development of airflow limitation (AL), fewer than 20% of smokers actually develop chronic obstructive pulmonary disease (COPD). OBJECTIVES: We examined how smoking histories and indices in blood are related to the degree of AL in asymptomatic smokers in order to determine whether they can predict the development of AL. METHODS: Spirometry and peripheral blood tests were examined in 433 Japanese asymptomatic current smokers at the initial examination. Forced expiratory volume in 1 s (FEV(1)) was measured periodically for 2 or more years (2-13 years) in 66 of the subjects. RESULTS: AL defined as an FEV(1)/vital capacity of less than 0.7, was found in 11.3% (49 of 433) of the smokers. Pack-years of smoking, serum amounts of alpha(1)-proteinase inhibitor, and serum procollagen III peptide activities were correlated with the degree of AL. Fifteen percent (10 of 66) of subjects underwent rapid declines in FEV(1) that were found to be related not with smoking amounts or initial FEV(1), but with low FEV(1) (%pred) adjusted by pack-years and an elevated serum neutrophil elastase/alpha(1)-proteinase inhibitor ratio. These results suggest that smokers with a low FEV(1) out of proportion to pack-years are susceptible smokers at a high risk of developing COPD, and further, that increased proteinase burden relative to antiproteinase activity may contribute to the development of COPD. CONCLUSIONS: We conclude that the serum neutrophil elastase/alpha(1)-proteinase inhibitor ratio and FEV(1) (%pred) adjusted by pack-years can be reliable predictors of the development of COPD.

Adult↗
PubMed2000

Distorted trachea in patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVES: We evaluated the size and configuration of the trachea in patients with chronic obstructive pulmonary disease (COPD; n = 35) on high-resolution computed tomography (HRCT) images and compared them with those of healthy volunteers (n = 24). METHODS: Using a newly developed computed method for analyzing the digital data of HRCT, the size and configuration of the trachea were automatically evaluated. RESULTS: The size of the trachea of the COPD subjects was the same as that of the control subjects; however, the configuration was more distorted in the COPD patients. There was no difference in the tracheal index (TI), which is the ratio of the coronal to the sagittal length, between these two groups; however, the ratio of the short to the long radius (SR/LR) was significantly smaller in the COPD group than in the control group. There was a significant correlation between SR/LR and airflow limitation as assessed by pulmonary function tests in the COPD group. CONCLUSIONS: The SR/LR is a better index of tracheal deformity than the classical TI. This deformity is not a consequence secondary to hyperinflation or emphysematous change of the lung, because the low attenuation area of the lung was not correlated with SR/LR.

Aged↗
PubMed2000

Squamous cell carcinoma of the prostate without evidence of recurrence 5 years after operation.

A 54-year-old man underwent radical cystoprostatectomy after prostatic needle biopsy which revealed squamous cell carcinoma of the prostate. However, the positive surgical margin of the pubis suggested residual disease. He received chemotherapy with methotrexate, peplomycin and cisplatin (MPD regimen). He is at present still alive without evidence of recurrence 5 years after the operation. This suggests that MPD chemotherapy is effective for squamous cell carcinoma of the prostate.

Carcinoma, Squamous Cell↗
PubMed2000

The effects of oxitropium bromide on exercise performance in patients with stable chronic obstructive pulmonary disease. A comparison of three different exercise tests.

The purpose of the present study was to compare the characteristics of three different exercise tests in evaluating the effects of oxitropium bromide on exercise performance. Thirty-eight males with stable chronic obstructive pulmonary disease (COPD) (FEV(1) = 40.8 +/- 16.5% predicted; mean +/- SD) completed randomized, double-blind, placebo-controlled, crossover studies for each exercise test. The exercise tests were performed 60 min after the inhalation of either oxitropium bromide 400 microg or placebo. The patients performed 6-min walking tests (6MWT) on Days 1 and 2, progressive cycle ergometry (PCE) on Days 3 and 4, and cycle endurance tests at 80% of the maximal workload of PCE on Days 5 and 6. Spirometry was conducted before and at 45 and 90 min after the inhalation. Oxitropium bromide significantly increased FEV(1) as compared with placebo. Oxitropium bromide increased the endurance time significantly, by 19% (p < 0.001), and caused a small but significant increase in the 6-min walking distance by 1% (p < 0.05), but induced no significant increase in maximal oxygen consumption (V O(2)max) in PCE. The responses in these three exercise tests were different, and we conclude that the endurance test was the most sensitive in detecting the effects of inhaled anticholinergic agents on exercise performance in patients with stable COPD. An endurance procedure may be performed to detect clinical changes in evaluating the effects of oxitropium bromide on exercise performance.

Administration, Inhalation↗
PubMed2000

Computed tomographic measurements of airway dimensions and emphysema in smokers. Correlation with lung function.

Chronic obstructive pulmonary disease (COPD) is characterized by the presence of airflow obstruction caused by emphysema or airway narrowing, or both. Low attenuation areas (LAA) on computed tomography (CT) have been shown to represent macroscopic or microscopic emphysema, or both. However CT has not been used to quantify the airway abnormalities in smokers with or without airflow obstruction. In this study, we used CT to evaluate both emphysema and airway wall thickening in 114 smokers. The CT measurements revealed that a decreased FEV(1) (%predicted) is associated with an increase of airway wall area and an increase of emphysema. Although both airway wall thickening and emphysema (LAA) correlated with measurements of lung function, stepwise multiple regression analysis showed that the combination of airway and emphysema measurements improved the estimate of pulmonary function test abnormalities. We conclude that both CT measurements of airway dimensions and emphysema are useful and complementary in the evaluation of the lung of smokers.

Adult↗
PubMed2000

Airway wall thickness in asthma assessed by computed tomography. Relation to clinical indices.

Postmortem studies have shown that airway wall thickening is present in asthmatic patients and may play a pathophysiologic role. We investigated the presence and characteristics of airway wall thickening in patients with asthma, using helical computed tomography. Eighty-one asthmatic patients and 28 healthy control subjects were studied cross-sectionally. Airway wall thickness was assessed by a validated method on the basis of wall area (WA), WA corrected by body surface area (WA/BSA), and WA%, defined as (WA/total area) x 100 at the apical bronchus of the right upper lobe. Airway luminal area (Ai) and Ai/BSA were also examined. Asthma duration and severity, pulmonary function, and serum eosinophil cationic protein levels were evaluated. Intraobserver and interobserver reproducibility of WA, WA%, and Ai measurements were good. As compared with control, WA, WA/BSA, and WA% were significantly increased in patients with mild (n = 13), moderate (39), and severe persistent (22) asthma but not in patients with intermittent asthma (7). Comparison of the four asthmatic subgroups demonstrated thicker airways in more severe disease, but no difference in Ai or Ai/BSA. When all asthmatic patients were analyzed together, WA and WA/BSA correlated with the duration, although weakly, and severity of asthma. WA and WA/BSA negatively correlated with FEV(1) (percentage of predicted), FEV(1)/FVC (%), and FEF(25-75%) (percentage of predicted), whereas WA% negatively correlated with only FEV(1). We conclude that airway wall thickening occurs in patients with asthma and is not limited to those with severe disease. The degree of airway wall thickening may relate to the duration and severity of disease and the degree of airflow obstruction.

Adult↗
PubMed2000

Effects of sulfhydryl compounds on interleukin-1-induced vascular endothelial growth factor production in human synovial stromal cells.

We investigated the effects of various sulfhydryl compounds on interleukin-1 (IL-1)-induced vascular endothelial growth factor (VEGF) production in human synovial stromal cells (HSSC). HSSC stimulated by IL-1beta (100 ng/ml) produced VEGF and interleukin-6 (IL-6) in vitro. Monosulfhydryl compounds, N-acetylcysteine, D-penicillamine, tiopronin and the bucillamine-like disulfhydryl compound, compound A scarcely affected VEGF or IL-6 production at concentrations of 10(-5) and 10(-4) M. However, the disulfhydryl compound, bucillamine inhibited VEGF production but not IL-6 production at concentrations of 10(-5) and 10(-4) M. These results suggest that bucillamine may be a selective inhibitor of IL-1-induced VEGF production in HSSC, and that inhibition of VEGF production may require not only SH groups but also a specific chemical structure.

Acetylcysteine↗