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Biomedical subjects

K Nishimura

Publications and source records attributed to K Nishimura.

At least 325 records · Page 18Linked to original sources

Presence of DNase gamma-like endonuclease in nuclei of neuronal differentiated PC12 cells.

DNase gamma, which cleaves chromosomal DNA into nucleosomal units (DNA ladder formation), has been suggested to be the critical component of apoptotic machinery. Using rat pheochromocytoma PC12 cells, which are differentiated to sympathetic neurons by nerve growth factor (NGF), we investigated whether DNase gamma-like enzyme is present in neuronal cells and is involved in neuronal cell death. The nuclear auto-digestion assay for DNase catalyzing internucleosomal DNA cleavage revealed that nuclei from neuronal differentiated PC12 cells contain acidic and neutral endonucleases, while nuclei from undifferentiated PC12 cells have only acidic endonuclease. The DNA ladder formation observed in isolated nuclei from neuronal differentiated PC12 cells at neutral pH requires both Ca(2+) and Mg(2+), and is sensitive to Zn(2+). The molecular mass of the neutral endonuclease present in neuronal differentiated PC12 cell nuclei is 32000 as determined by activity gel analysis (zymography). The properties of the neuronal endonuclease present in neuronal differentiated PC12 cell nuclei were similar to those of purified DNase gamma from rat thymocytes and splenocytes. Interestingly, in neuronal differentiated PC12 cells, internucleosomal DNA fragmentation is observed following NGF deprivation, whereas undifferentiated PC12 cells fail to exhibit DNA ladder formation during cell death by serum starvation. These results suggest that the DNase gamma-like endonuclease present in neuronal differentiated PC12 cell nuclei is involved in internucleosomal DNA fragmentation during apoptosis, induced by NGF deprivation.

Journal Article↗

Intradural extra-arachnoid schwannoma of the upper cervical spine.

A very rare case of intradural extra-arachnoid schwannoma involving the upper cervical spine is described. The tumour most likely originated from the extra-subarachnoid angle region, with its unusual pattern of expansion within the spinal canal resulting from such characteristics of the upper cervical region as a relatively wide spinal canal, an extensive ventral subarachnoid space, and membranous ventromedian and lateral anchoring structures which influenced the direction of tumour enlargement.

Cervical Vertebrae↗

Sphingosylphosphorylcholine stimulates proliferation and upregulates cell surface-associated plasminogen activator activity in cultured human keratinocytes.

Of the various sphingolipid metabolites, including sphingosine, sphingosylphosphorylcholine (SPC), dimethylsphingosine, sphingosine-1-phosphate, N-acetylsphingosine, and skin-specific ceramides, only SPC accelerated cutaneous wound healing in full-thickness excision wounds in genetically healing-impaired diabetic (db/db) mice. A histologic examination revealed that SPC promoted not only granulation tissue formation, but also the re-epithelization of epidermal keratinocytes. As the direct effects of SPC on keratinocytes are completely unknown, we investigated the effects of SPC on normal cultured human keratinocytes. SPC concentration-dependently enhanced DNA synthesis in keratinocytes, with an increase in intracellular calcium concentrations due to the release of calcium ions from intracellular stores. SPC upregulated cell surface plasminogen activity, and at the same time increased the cell surface expression of urokinase-type plasminogen activator (uPA) and urokinase-type plasminogen activator-receptor (uPA-R) in keratinocytes. Furthermore, SPC promoted the in vitro wound repair of cultured keratinocytes, which was partially blocked by an anti-uPA monoclonal antibody. Our results suggest that one of the mechanisms responsible for the SPC-mediated promotion of cutaneous wound healing seems to be an enhancement of re-epithelization caused by the direct stimulation of the proliferation of keratinocytes, and an activation of the uPA/uPA-R system, which enhances the migration of keratinocytes.

Animals↗

Platelet adhesion, contact phase coagulation activation, and C5a generation of polyethylene glycol acid-grafted high flux cellulosic membrane with varieties of grafting amounts.

Grafting of polyethylene glycol chains onto cellulosic membrane can be expected to reduce the interaction between blood (plasma protein and cells) and the membrane surface. Alkylether carboxylic acid (PEG acid) grafted high flux cellulosic membranes for hemodialysis, in which the polyethylene glycol chain bears an alkyl group at one side and a carboxyl group at the other side, have been developed and evaluated. PEG acid-grafted high flux cellulosic membranes with various grafting amounts have been compared with respect to platelet adhesion, the contact phase of blood coagulation, and complement activation in vitro. A new method of quantitating platelet adhesion on hollow-fiber membrane surfaces has been developed, which is based on the determination of lactate dehydrogenase (LDH) activity after lysis of the adhered platelets. PEG acid-grafted high flux cellulosic membranes showed reduced platelet adhesion and complement activation effects in grafting amounts of 200 ppm or higher without detecting adverse effects up to grafting amounts of 850 ppm. The platelet adhesion of a PEG acid-grafted cellulosic membrane depends on both the flux and grafting amounts of the membrane. It is concluded that the grafting of PEG acid onto a cellulosic membrane improves its biocompatibility as evaluated in terms of platelet adhesion, complement activation, and thrombogenicity.

Animals↗

Effects of inhaled oxygen concentration on fat metabolism during propofol infusion in rabbits.

We have investigated the effect of inhaled oxygen tension on lipid metabolism during propofol infusion. Propofol is supplied as a lipid emulsion containing 10% soybean oil, which is rich in triglycerides (TG). Infused TG are metabolized via three pathways in the liver cell; Krebs cycle, ketogenesis and release as very low density lipoproteins (VLDL) into the blood. For this reason, we measured TG and the products of the three pathways; carbon dioxide, ketone bodies and VLDL. Thirty-two rabbits were anaesthetized under four different conditions: propofol under hyperoxia, normoxia, hypoxia and isoflurane anaesthesia under hyperoxia. Our results indicated that hyperoxia produced more ketone bodies, normoxia more PaCO2 and hypoxia more free fatty acids (FFA) and TG compared with the other propofol infusion groups. We conclude that hyperoxia during propofol infusion facilitated fat metabolism through ketogenesis, while normoxia did so via the Krebs cycle. Also, hypoxia suppressed utilization of TG and VLDL production in the liver.

Anesthetics, Intravenous↗

Growth, pigmentation, and expression of the puf and puc operons in a light-responding-repressor (SPB)-disrupted Rhodobacter sphaeroides.

We previously cloned a trans-repressor, SPB, for the puf operon of Rhodobacter sphaeroides (Shimada et al. 1996) and revealed that SPB was a putative genetic counterpart to HvrA in Rhodobacter capsulatus, a trans-activator for the puf and puh operons (Mizoguchi et al. 1997). In this study we constructed a spb-disrupted R. sphaeroides, strain L-7, to elucidate the function of SPB. This disruption of the spb gene increased the photosynthetic growth rate and the cellular levels of photopigments under low-intensity light conditions. The disruption also derepressed the expression of the puf and puc operons under high-intensity light conditions. In strain L-7, however, strong illumination still reduced the cellular levels of photopigments as it did in the wild strain, suggesting that SPB did not directly affect the formation of photopigments. These results support our previous suggestion that SPB functions as a high-light repressor for puf operon in R. sphaeroides in striking contrast to HvrA, which is a low-light activator for puf and puh operons in R. capsulatus, even though SPB and HvrA are highly homologous. Disruption of spb gene had no effect on the oxygen-mediated regulation of the pigmentation or the expression of puf and puc operons.

Bacterial Proteins↗

Comparison of different computed tomography scanning methods for quantifying emphysema.

Computed tomography (CT) is used to detect emphysematous changes in the lungs of living patients. It is therefore important to develop a standard method for the radiographic quantification of emphysematous lesions using CT. The authors determine the best CT scanning methods for assessing the degree of pulmonary emphysema. Computed tomography scanning was performed in 85 consecutive patients with stable chronic obstructive pulmonary disease. Scans were obtained using 2-mm or 5-mm collimation, at full inspiration or full expiration, and with standard or high spatial-resolution reconstruction images (eight images each). Emphysema was then assessed by visual scoring using a five-point scale for each lung. Emphysema was scored as significantly less severe using standard reconstruction images. There were no significant differences in CT-scored emphysema on scans obtained with 2-mm and 5-mm collimation. Emphysema was scored as significantly less severe on expiratory scans. The postbronchodilator forced expiratory volume in one second value correlated better with emphysema scored on expiratory scans. Computed tomography-scored emphysema obtained by all methods correlated well with the diffusion capacity and total lung capacity, regardless of the method used. Using a visual scoring system with a five-point scale, narrow collimation is probably not necessary for the quantification of emphysema, although a high spatial-resolution reconstruction appears to be of value. Scans obtained in exhalation appear to underemphasize the severity of emphysema.

Aged↗

Health-related quality of life in patients with chronic obstructive pulmonary disease.

Health-related quality of life is usually impaired in patients with moderate to severe chronic obstructive pulmonary disease. The Sickness Impact Profile, the Medical Outcome Study "short form" 36, and the Nottingham Health Profile have all been used as generic measures of health-related quality of life. Although the discriminative properties of three disease-specific instruments, the Chronic Respiratory Disease Questionnaire, the St. George's Respiratory Questionnaire, and the Breathing Problems Questionnaire, are similar, the responsiveness of the Chronic Respiratory Disease Questionnaire and the St. George's Respiratory Questionnaire has been the most clearly demonstrated. The characteristics of each instrument should be considered in the selection of specific health-related quality of life questionnaires for clinical research.

Female↗

Colorimetric MTT assessment of antifungal activity of D0870 against fluconazole-resistant Candida albicans.

The in vitro antifungal activity of D0870 against eight isolates of fluconazole-resistant Candida albicans was compared with that of itraconazole, ketoconazole and miconazole. The colorimetric MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide] assay was used to assess the antifungal activities. The 50% minimum inhibitory concentration (MIC50) of D0870 was below 0.031 microgram ml-1 for seven isolates and 0.25 microgram ml-1 for one isolate. The activity of D0870 was superior to that of the other azoles. Ketoconazole was the most effective azole next to D0870. Therefore, the new bis-triazole, D0870, is expected to be promising for the therapy of fluconazole-resistant candidosis. The present data also confirmed that the MTT assay may be useful for evaluation of resistance and detection of resistant C. albicans.

Antifungal Agents↗

Imidazole-induced morphological abnormalities of mitochondria of Candida albicans.

The mitochondrial morphology of live Candida albicans samples treated with several imidazoles (miconazole, econazole and clotrimazole) was observed with a fluorescent carbocyanine probe, 3,3'-dihexyloxacarbocyanine [diO-C6-(3)], under a fluorescence microscope. Nearly all non-treated C. albicans cells carried only long tubular mitochondria. Treatment with antimycotics at half the minimum inhibitory concentrations (MIC100) rapidly induced mitochondrial cleavage or fragmentation, which was followed by recovery to the normal tubular morphology within 1 h. Exposing the yeast to drugs at concentrations higher than the MICs resulted in the development of swollen mitochondria or amorphous bodies. These phenomena were concentration dependent. The fluorescence images were also compared with ultrastructural images obtained by transmission electron microscopy.

Antifungal Agents↗

Child rearing in Japan: current trends and problems.

Loyalty to one's extended family, a well-known Japanese tradition, has broken down following World War II. Child rearing in Japan, therefore, has been changing gradually and clearly. Traditionally, child rearing was taught to young mothers by the grandmothers. However, recently young couples are no longer living with their parents. Therefore, there are no advisers nor consultants available at home for their child rearing. Commercialism has certainly invaded the field of child rearing, including too many guidebooks and even baby-sitting companies. Children's lives have become much more competitive, busy and unnatural in comparison with those of 20-30 years ago. This might be one cause of the increased incidence of bullying, school phobia and psychological disorders in children.

Child↗

Antitumor effect of irinotecan hydrochloride (CPT-11) on human renal tumors heterotransplanted in nude mice.

BACKGROUND: There has been a paucity of antitumor drugs that are active against renal tumors. Irinotecan hydrochloride (CPT-11), a DNA topoisomerase type 1 inhibitor, has demonstrated antitumor activity against human tumors, however, no antitumor effect of CPT-11 on renal tumors has been reported. The antitumor effect of CPT-11 was investigated on 2 human renal tumors (OUR-10 and OUR-20) heterotransplanted into nude mice. METHODS: Tumor-bearing nude mice were given daily intraperitoneal injections of multiple anticancer drugs suspended in 0.2 mL of phosphate-buffered saline (PBS) 3 times at 3-day intervals. Control mice were injected with 0.2 mL of PBS. The antitumor effects were evaluated by calculating the T/C ratio (treated tumors/controls) of the tumor volume. RESULTS: Among the 10 anticancer drugs tested, 50 mg/kg of CPT-11 showed an active antitumor effect on OUR-20 (T/C ratio 34). However, all drugs tested on OUR-10 failed to show antitumor activity. CONCLUSION: Since CPT-11 was effective in 1 of 2 renal tumors examined without severe toxicity, this drug could be a candidate for chemotherapy of renal cell carcinoma.

Animals↗

Regulation of invasive potential of human prostate cancer cell lines by hepatocyte growth factor.

BACKGROUND: The growth and progression of prostate cancer depends on the stromal-epithelial interaction which is under paracrine control. Hepatocyte growth factor (HGF), produced by mesenchymal cells, is a multifunctional growth factor stimulating the movement and growth of epithelial cells including cancer cells. We therefore assessed the relationship between the invasive potential of prostate cancer and HGF in vitro. METHODS: Three human prostate cancer cell lines were used including PC-3 and DU145 (androgen-independent), and LNCaP (androgen-dependent). We studied the expression of the HGF receptor c-met proto-oncogene (c-met) by Western blot analysis, and also determined the effects of HGF on cell scattering, and the mechanisms of invasion and proliferation, by microscopic observation, the matrigel invasion chamber assay, and the MTT assay. RESULTS: c-met was detected in PC-3 and DU145 cells, but not in the LNCaP cells. There was increased cell motility in the scatter assay and an increased cell invasive potential in the matrigel invasion chamber assay by stimulation with HGF only with DU145 cells. CONCLUSION: HGF plays an important role in the invasion and metastasis of the DU145 cell line through a paracrine mechanism mediated by the c-metreceptor. In the PC-3 cell line, the lack of downstream signal transduction after the c-met receptor is suggested.

Biocompatible Materials↗

Familial occurrence of gastric carcinoid tumors associated with type A chronic atrophic gastritis.

We present here familial occurrence of two patients with gastric carcinoid. Both patients, a sister and older sister, had type A chronic atrophic gastritis with hypergastrinemia. This is the first case report of familial occurrence of gastric carcinoid associated with type A chronic atrophic gastritis in the world literature. The possible mechanism of familial occurrence in the patients is discussed.

Adult↗

Proton gradient-driven nickel uptake by vacuolar membrane vesicles of Saccharomyces cerevisiae.

A vacuolar H+-ATPase-negative mutant of Saccharomyces cerevisiae was highly sensitive to nickel ion. Accumulation of nickel ion in the cells of this mutant of less than 60% of the value for the parent strain arrested growth, suggesting a role for this ATPase in sequestering nickel ion into vacuoles. An artificially imposed pH gradient (interior acid) induced transient nickel ion uptake by vacuolar membrane vesicles, which was inhibited by collapse of the pH difference but not of the membrane potential. Nickel ion transport into vacuoles in a pH gradient-dependent manner is thus important for its detoxification in yeast.

Hydrogen-Ion Concentration↗

Effects of theophylline and ipratropium bromide on exercise performance in patients with stable chronic obstructive pulmonary disease.

BACKGROUND: The effects of theophylline or anticholinergic agents on exercise capacity in patients with chronic obstructive pulmonary disease (COPD) remain controversial. The aim of the present study was to compare the effect of an oral theophylline with an inhaled anticholinergic agent and to examine the effects of combined therapy on exercise performance using progressive cycle ergometry. METHODS: Twenty one men with stable COPD and a mean (SD) forced expiratory volume in one second (FEV1) of 1.00 (0.40) 1 were studied. Theophylline (600 or 800 mg daily), ipratropium bromide (160 micrograms), a combination of both drugs, and placebo were given in a randomised, double blind, four period crossover design study. Spirometric data, pulse rate, and blood pressure were assessed before and at 90 and 120 minutes after inhalation. Symptom limited progressive cycle ergometer exercise tests (20 watts/min) were performed 90 minutes after each inhalation, and dyspnoea was measured during exercise using the Borg scale. RESULTS: The mean (SD) serum theophylline concentration was 18.3 (6.3) micrograms/ml, and seven patients had side effects during treatment with theophylline. Theophylline and ipratropium bromide produced greater increases in FEV1, maximal oxygen consumption, maximal minute ventilation, and several dyspnoea ratios than placebo. There were no differences between theophylline and ipratropium bromide except in maximal heart rate. A combination of both drugs produced greater improvements in pulmonary function and exercise capacity than either drug alone. CONCLUSIONS: Both high dose theophylline and high dose ipratropium bromide improved exercise capacity in patients with stable COPD. Although data based on short term effects cannot be directly applied to long term therapy, theophylline added to an inhaled anticholinergic agent may have beneficial effects on exercise capacity in patients with COPD.

Aged↗

A case of small cell lung cancer metastasizing to prostatic cancer.

Although the fact that the presence of two or more malignancies in a single patient is not a rare occurrence, metastasis of cancer to cancer is rare. Generally the most frequent donor tumor is a lung cancer, and the most common recipient tumor is a renal cell carcinoma. A rare case of lung cancer with metastasis to prostatic cancer is described. To our knowledge, this report represents the first case of a small cell lung cancer metastasizing to a prostatic cancer.

Adenocarcinoma↗