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Biomedical subjects

K Nishimura

Publications and source records attributed to K Nishimura.

At least 19 recordsLinked to original sources
PubMed1992

Accumulation of protoporphyrin IX in light-sensitive mutants of Escherichia coli.

The accumulation of protoporphyrin IX (Proto IX) in light-sensitive mutants of Escherichia coli was detected by spectrofluorimetry. Fluorescence emission and excitation spectra were recorded from extracts of bacterial cells. Proto IX clearly accumulated in cells with mutations in the visA (hemH) gene but not in the wild-type strain CA274 or in visA mutants that had been rendered light-resistant by introduction of the wild-type visA+ gene. Accumulation of Proto IX was also not observed in cells with a mutation in the visB gene. These results confirm the hypothesis that the sensitivity of the visA mutants to light is caused by the abnormal accumulation of Proto IX, a substrate of ferrochelatase, as the result of a genetic defect in the gene for ferrochelatase.

Escherichia coli↗
PubMed1992

A YIGSR-containing novel mutein without the detrimental effect of human TNF-alpha of enhancing experimental pulmonary metastasis.

The injection of B16F10 melanoma cells with recombinant human tumor necrosis factor alpha (TNF-alpha) into the tail vein of C57BL/6 mice resulted in 2- to 25-fold more metastatic foci in the lungs than the injection of tumor cells alone. Clearly, TNF-alpha significantly enhanced experimental tumor metastasis. Furthermore, it enhanced the metastasis of Lewis lung carcinoma cells. In contrast, a mutein of TNF-alpha, designated as F4236, having the cell-adhesive sequence (Tyr-Ile-Gly-Ser-Arg) at the N-terminus of the TNF molecule did not enhance metastasis, but rather exhibited similar antitumor activity to wild-type TNF-alpha in fibrosarcoma-bearing mice.

Amino Acid Sequence↗
PubMed1992

Studies on the relationship between the estrous cycle of BALB/c mice and their resistance to Paracoccidioides brasiliensis infection.

A relationship between the estrous cycle and non-specific host resistance to Paracoccidiodes brasiliensis yeast cells was examined by using both sexes of adult BALB/c mice. They were divided into 6 groups, including a male group and females at proestrus, estrus, metestrus-I, metestrus-II and diestrus. The mice received yeast cells through three different inoculation routes; intravenous, intraperitoneal and intratracheal. In all of the inoculation routes, the clearance of the yeast cells was influenced by the estrous cycle. The female mice at estrus, which might have high blood estrogen levels, showed a marked clearance of the yeast cells from the blood, peritoneal cavity and lungs. These results suggested that non-specific host resistance to the yeast cells was enhanced by estrogen. All female groups inoculated by the three routes showed higher clearance of the yeast cells than the male group.

Animals↗
PubMed1992

p53 point mutations in primary human gastric carcinomas.

p53 point mutations in primary gastric carcinomas were analyzed by performing cDNA deoxynucleotide sequencing of the gene. Out of 16, 9 (56.3%) primary gastric carcinoma cases, including early cancer, showed one or more p53 point mutations in their open-reading frame, and 4 out of 9 cases had a p53 point mutation within highly conserved domains. The characteristics of the p53 mutation spectrum observed in primary tumors were (a) frequent mutation at an A:T pair (50%, 7 out of 14 mutations), (b) high transversion incidence (29%, 4 out of 14 mutations), (c) no transition at CpG, and (d) no G:C to T:A transversion. Our results suggest that p53 mutation is a common event in gastric carcinoma occurring from the early stage of progression with its specific mutation spectrum.

Adult↗
PubMed1992

Predictive indicators for the therapeutic effect of OK-432 in patients with chronic active type B hepatitis.

Twenty-two patients with chronic type B hepatitis were treated with OK-432. Immunological parameters were serially measured to find predictive indicators for the seroconversion from hepatitis B envelope antigen (HBe Ag) to anti-HBe. In patients who achieved the disappearance of HBe Ag associated with or without the appearance of anti-HBe, the numbers of CD8+DR+ and CD4+DR+T cells in peripheral blood increased gradually during OK-432 therapy and then reduced subsequently to the seroconversion from HBe Ag positive to anti-HBe positive. Increases of DR-positive T cells in numbers were significantly correlated with increased amounts of IFN-gamma produced in response to in vitro OK-432 stimulation. In vitro OK-432-stimulated IFN-gamma production and the increase of CD8+DR+T cells in number in peripheral blood could be proposed as predictive indicators for the disappearance of HBe Ag.

Adolescent↗
PubMed1992

Phase differences between chest and mouth flows in patients suffering from pulmonary disease.

The phase difference (PD) between mouth flow and chest flow during rest breathing was measured in pulmonary diseased patients using a body box and the results were compared with normal subjects. Whereas the PD increased in patients with chronic pulmonary obstructive disease (COPD) compared to normal subjects, PD was found to be normal in patients with interstitial pulmonary fibrosis (IPF) (Normal: 2.94 +/- 1.25, COPD: 11.32 +/- 4.17*, IPF: 2.62 +/- 1.67 degrees; *P < 0.01). PD correlated well with FEV1.0/VC%, PFR, RV/TLC, VTG and Ra (r: -0.759, -0.672, -0.788, 0.666, 0.606). From an in-depth analysis of the results, we suggest that the factors which increase PD in COPD patients include hyperinflation of the lung, increases in airway resistance and increases in the parallel inhomogeneity of airway resistance accompanied by an unevenness of alveolar pressures. PD was thought to be clinically useful for the evaluation of the pathological stages of COPD because it reflects the overall clinical manifestations in COPD patients.

Adult↗
PubMed1992

A basis for resistance of Blastomyces dermatitidis killing by human neutrophils: inefficient generation of myeloperoxidase system products.

The mechanism by which the yeast form of Blastomyces dermatitidis resists killing by human peripheral blood polymorphonuclear neutrophils (PMN) was investigated. The metabolic products of the oxidative burst generated during the interaction of PMN and B. dermatitidis or Candida albicans were detected by lucigenin- or luminol-enhanced chemiluminescence (CL). Interaction of PMN and C. albicans resulted in luminol-enhanced CL 100-fold greater than that generated by PMN and B. dermatitidis. This correlated with killing of C. albicans and resistance of B. dermatitidis. Since B. dermatitidis and PMN interactions resulted in significant lucigenin-enhanced CL, deficient luminol CL was not due to a lack of products from the NADPH oxidase system. Killed B. dermatitidis cells at 37 degrees C were more efficient than live cells in stimulating PMN for luminol-enhanced CL; however, only fragmented B. dermatitidis cells elicited luminol-enhanced CL equivalent to that of C. albicans. Since lysates of PMN were active in a cell-free hydrogen peroxide-peroxidase-halide system, resistance of B. dermatitidis to PMN was not due to a defect in PMN peroxidase. Taken together, these findings indicate that resistance of B. dermatitidis to killing by PMN results from inefficient generation of products from the peroxidase-dependent PMN microbicidal system.

Acridines↗
PubMed1992

Composition of free long-chain (sphingoid) bases in stratum corneum of normal and pathologic human skin conditions.

The composition of molecular species of free long-chain bases (FLCB) isolated from stratum corneum of various human skin conditions was analyzed by the high-performance liquid chromatographic and fast atom bombardment mass spectrometric methods. FLCB with carbon length ranging from 16 to 20 comprised about 0.3% of total lipids in stratum corneum of normal and pathologic skin conditions. Major FLCB included sphinganines and sphingenines with 18 to 20 carbons and some phytosphingosines such as t17:1, t18:1, t18:0, t20:1, and t20:0. Compared with stratum corneum of normal lower legs, molar percentages of FLCB having 18 carbons and those with 20 carbons were slightly higher and lower, respectively, in normal plantar epidermis, showing site-related differences in normal skin. Psoriatic scales and hyperkeratotic stratum corneum from clavus and plantar keratoderma contained increased levels of FLCB with 18 carbons and decreased levels of FLCB with 20 carbons. These findings may reflect abnormal keratinization in hyperkeratotic skin conditions.

Adolescent↗
PubMed1992

[Studies on the effect of combination of amphotericin B and flucytosine on Candida albicans by flow cytometry].

The antifungal effects of amphotericin B (AMPH) and flucytosine (5-FC) on three strains of Candida albicans were studied by flow cytometry (FCM). When the IFM4954 and IFM4949 were treated with AMPH or 5-FC alone, cytograms of cell distribution changed at the concentration of 1/2 MIC, respectively. Next, the effect of combination of AMPH and 5-FC were examined. Cytogram of cell distribution of IFM4954 and IFM4949 changed under the combination of 1/4 MIC of AMPH and 1/4 MIC of 5-FC, namely a synergic effect was observed. In conclusion, FCM is a useful apparatus for analysis of the effect of antifungal agents.

Amphotericin B↗
PubMed1992

Isolation and characterization of a light-sensitive mutant of Escherichia coli K-12 with a mutation in a gene that is required for the biosynthesis of ubiquinone.

Cells with a novel mutation that is lethal when the cells are exposed to visible light were isolated from Escherichia coli K-12. The mutation was mapped at 63 min on the linkage map of the E. coli chromosome, and the gene, designated visB, was cloned and sequenced. From its map position and the evidence that the gene product VisB exhibits homology with flavin monooxygenase of Pseudomonas fluorescens, the visB gene was deduced to be identical to the ubiH gene, which is a gene required for the biosynthesis of ubiquinone and is thought to be similar to the gene for flavin monooxygenase. The photosensitive phenotype appears to be due to the accumulation of the substrate for the reaction catalyzed by the visB (ubiH) gene product because other mutations that block earlier steps in the biosynthesis of ubiquinone can reverse the photosensitivity. The accumulated intermediates may produce active species of oxygen in the mutant bacteria upon illumination by visible light, and these active oxygen species may cause the death of the cells by a mechanism similar to that associated with mutations in visA (hemH).

Amino Acid Sequence↗
PubMed1992

Usual interstitial pneumonia: histologic correlation with high-resolution CT.

The authors reviewed 46 cases of idiopathic pulmonary fibrosis with usual interstitial pneumonia (UIP), correlating findings on high-resolution computed tomographic (HRCT) scans with findings in specimens obtained at open lung biopsy and autopsy. The following HRCT findings were observed: (a) an accumulation of small cystic spaces with thick walls, (b) air bronchiolograms within areas of intense lung attenuation, (c) rugged pleural surfaces, (d) irregularly thickened pulmonary vessels, (e) bronchial wall thickening, and (f) slightly increased lung attenuation. Macroscopic honeycombing correlating with small cystic spaces was demonstrated at HRCT and pathologic examination. Air bronchiolograms in the areas of intense lung attenuation (ie, microscopic honeycombing) corresponded to dilated bronchioles (greater than 1 mm in diameter) with fibrosis. Irregularly thickened vessels and bronchial walls and irregular pleural surfaces were the result of fibrosis in the periphery of the secondary pulmonary lobules. Areas of slightly increased lung attenuation seen on the HRCT scans correlated with patchy alveolar septal fibrosis or inflammation. The authors conclude that microscopic honeycombing and a perilobular distribution in UIP may be clearly identified with HRCT.

Adult↗
PubMed1992

Diffuse panbronchiolitis: correlation of high-resolution CT and pathologic findings.

Diffuse panbronchiolitis (DPB) is characterized by chronic airflow limitation and airway inflammation with bronchiolar lesions. Chest radiographs of patients with DPB usually show small nodular shadows throughout both lungs. The authors investigated the nature and pathogenesis of the radiologic features of DPB by correlating high-resolution computed tomographic (HRCT) findings with histopathologic features. The HRCT images of nine patients with DPB were compared with the observations made with inflated lung specimens. The HRCT findings of DPB included centrilobularly distributed, small rounded areas of attenuation; branched linear areas of attenuation, contiguous with the small rounded areas; dilated airways with thick walls, also common outside secondary pulmonary lobules; and decreased lung attenuation in peripheral areas due to air trapping caused by bronchiolar narrowing in the subpleural zones. The authors believe that HRCT best demonstrates this characteristic location of small rounded areas of attenuation associated with dilated airways.

Adult↗
PubMed1992

Importance of hydrolysis of amino acid moiety in water-soluble prodrugs of disodium cromoglycate for increased oral bioavailability.

The relationship between physicochemical properties and oral absorption was investigated in prodrugs for the oral delivery of disodium cromoglycate (DSCG). To improve the lipophilicity of DSCG, various lipophilic moieties were introduced into the twin carboxyl groups. However, this did not lead to improved oral absorption in rabbits because of loss of water solubility, in spite of improved lipophilicity. Water-soluble prodrugs, in which an amino acid was introduced into a hydroxy group by ester linkage in addition to ethyl residues at twin carboxyl groups of DSCG, were synthesized and examined for oral absorption in rabbits and rats. The oral absorption of these prodrugs was affected by the species of amino acids introduced as a water-soluble moiety. Therefore, we examined the relation between the oral absorption of water-soluble prodrugs and the hydrolysis rate of the amino acid moiety. A good linear correlation was obtained between the oral absorption and the hydrolysis rate constant catalyzed by digestive enzymes, trypsin or alpha-chymotrypsin. It was thus concluded that the amino acid moiety of water-soluble prodrugs must be rapidly hydrolyzed to a permeable lipophilic prodrug still possessing the ethyl moiety at twin carboxyl groups in the small intestinal tract for good oral absorption.

Administration, Oral↗
PubMed1992

Characteristics of 1,3-bis-(2-ethoxycarbonylchromon-5-yloxy)-2-((S)- lysyloxy)propane dihydrochloride (N-556), a prodrug for the oral delivery of disodium cromoglycate, in absorption and excretion in rats and rabbits.

The absorption and excretion of 1,3-bis-(2-ethoxycarbonylchromon-5-yloxy)-2- ((S)-lysyloxy)propane dihydrochloride (N-556), which is a prodrug for the oral delivery of disodium cromoglycate (DSCG), were studied in rats and rabbits. In both animal species, the plasma concentration of DSCG after oral administration of N-556 peaked within 1.0 h, and thereafter declined with a half-life of about 1.2 h in rats and rabbits. The area under the plasma DSCG level versus time curve (AUC) increased in proportion to the dose of N-556 in both animals. The bioavailability of N-556 as calculated from AUC was about 6% in rats and 40% in rabbits, whereas that of DSCG was only 0.1% in rats and 2.5% in rabbits. About 2% and 15% of the dose were respectively excreted as DSCG in the urine and bile after the oral administration of N-556 in rats. The ratio of biliary excretion to urinary excretion (B/U) after the oral administration of N-556 was about twice that after the intravenous injection of DSCG. In rabbits, the urinary and biliary excretions of DSCG after oral administration of N-556 were about 25% and 5%, respectively. The B/U ratio after the oral administration of N-556 in rabbits was similar to that after intravenous administration of DSCG. The difference in the systemic bioavailability of N-556 between rats and rabbits thus appears to be due to a first-pass effect, in addition to a difference in the absorption rate.

Absorption↗
PubMed1992

Bronchiolitis obliterans organizing pneumonia. Clinical features and differential diagnosis.

The clinical features of 34 Japanese patients with bronchiolitis obliterans organizing pneumonia (BOOP) are discussed. Thirty-two patients (94 percent) had symptoms of cough, fever, or dyspnea. On chest roentgenograms, bilateral patchy infiltrates were seen most frequently in 23 patients (68 percent), followed by small linear opacities in five (15 percent), both patchy infiltrates and reticulonodular opacities in four (12 percent), and reticulonodular opacities in two (6 percent). The bronchoalveolar lavage fluid (BALF) cell findings obtained from 26 patients revealed an increase in the percentage of lymphocytes in 20 patients (77 percent), neutrophils in 15 (58 percent), and eosinophils in 16 (62 percent), and a decrease in the CD4+/CD8+ ratio in 14 of 23 patients (61 percent). Corticosteroids were administered to 25 patients. Except for one patient who died, the prognosis was good in all patients. Further, in patients without corticosteroid therapy, the prognosis was good.

Adrenal Cortex Hormones↗
PubMed1992

Response to oral corticosteroid in patients with chronic obstructive pulmonary disease.

We studied the effect of 30 mg of prednisolone on 29 Japanese patients with chronic obstructive pulmonary disease (COPD). The mean value of the baseline forced expiratory volume in one second (FEV1; mean +/- SEM) was 1.14 +/- 0.12 l (46.9 +/- 3.9% pred) and the FEV1 following the steroid trial was 1.30 +/- 0.12 l (53.7 +/- 4.3% pred). Post-trial FEV1--baseline FEV1/predicted FEV1 was 6.8 +/- 1.9%. Five patients (17%) had more than a 15% increase in FEV1 as a percentage of predicted FEV1. Post-trial FEV1/baseline FEV1 was 117.3 +/- 4.3%, and 12 patients (41%) had more than a 20% increase in FEV1 after the trial. Acute bronchodilator response to beta-agonist correlated positively with the response to corticosteroid. Baseline spirometries, blood eosinophil counts, serum IgE levels, sputum eosinophil counts, family history of asthma, and history of paroxysmal dyspnea did not vary across responders and non-responders. Patients with severe COPD should be treated to achieve the best possible pulmonary functions indicated by a steroid trial within the limit of acceptable levels of adverse effects.

Aged↗