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Biomedical subjects

K Wada

Publications and source records attributed to K Wada.

At least 271 records · Page 15Linked to original sources
PubMed1998

[Development of a new gastric ulcer model and the evaluation of drug effects].

A new gastric ulcer model was developed by the ischemia-reperfusion procedure in rats. The ischemia-reperfusion was produced by clamping the celiac artery and subsequent removal of the clamp. Until 36 hr after the ischemia, erosive lesions were observed in the gastric glands. However, 48 and 72 hr after the ischemia, gastric ulcers involving damage of muscularis mucosae were observed. Seven days after the ischemia, the injured areas were covered with regenerated mucosa. This model may be useful for investigating the mechanisms of pathogenesis of gastric ulcer and to evaluate efficacy of drugs.

Animals↗
PubMed1998

Novel bioactive oxazolomycin isomers produced by Streptomyces albus JA3453.

Two novel oxazolomycin isomers, oxazolomycins B (2) and C (3), were isolated from the fermentation broth of an oxazolomycin-producing strain, Streptomyces albus JA3453. Both compounds are geometrical isomers of oxazolomycin (1), the configurations of their triene moieties being (4'E, 6'E, 8'E) (2) and (4'Z, 6'E, 8'E) (3) while that of oxazolomycin (1) is (4'Z, 6'Z, 8'E). Compounds 2 and 3 exhibited potent inhibitory activity against crown gall formation with the same MIC (0.8 microgram/disk) as oxazolomycin. Compounds 2 and 3 showed no antibacterial activity against Agrobacterium tumefaciens, in contrast to oxazolomycin which has specific anti-A. tumefaciens activity.

Anti-Bacterial Agents↗
PubMed1998

Reflecting adult drinking culture: prevalence of alcohol use and drinking situations among Japanese junior high school students in Japan.

OBJECTIVE: To estimate the prevalence of Japanese adolescents' alcohol use in Japan and the situations surrounding their drinking. METHOD: A general population self-administered questionnaire survey was conducted with a sample of 5,240 Japanese junior high school students obtained from 12 representative schools of the Chiba Prefecture in Japan. RESULTS: Almost 80% of the boys and 75% of the girls reported having consumed an alcoholic beverage on at least one occasion. Consumption occurred most frequently on a ceremonial occasion (52.4%), followed by drinking with family (39.0%), with peers (20.6%), after a bath (9.7%) and at ritual parties among friends (9.3%). In this sample, a greater percentage of students in a higher grade reported a drinking occasion after a bath, at parties among friends, or with peers. However, this trend was not observed for drinking on ceremonial occasions or with family in the evening. A gender difference was observed for the prevalence of drinking after a bath. A majority of students agreed with the statement that minors' use of alcohol was "acceptable depending on the situation." This was in sharp contrast with their perception of cigarette smoking and solvent use (16.3% and 3.8%, respectively, endorsing the same statement). CONCLUSIONS: By sometime in their first year of junior high school (when most students are age 12 years), more than 75% of Japanese adolescents have tried alcohol. Prevalence rates and trends across grades are different depending on the occasions of drinking. The findings on situational drinking among adolescents of this age group appear to reflect that assimilation into Japanese drinking culture takes place early on in family or traditional settings.

Adolescent↗
PubMed1998

Successful application of three-dimensional transcranial power Doppler imaging in two stroke patients.

We applied a new technique of three-dimensional (3-D) transcranial power Doppler imaging to demonstrate the middle cerebral artery (MCA) in the 2 stroke patients. In the first patient, the 3-D power Doppler study clearly showed the horizontal portion, bifurcation, proximal portion of the upper and lower trunks, and the major branches of the lower trunk of the MCA. In the second patient, the 3-D power Doppler clearly revealed the proximal bifurcation of the left MCA. The 3-D transcranial power Doppler seems to be useful in making clear 3-D images of the MCA.

Cerebral Angiography↗
PubMed1998

Role of nitric oxide in traumatic brain injury in the rat.

OBJECT: Although nitric oxide (NO) has been shown to play an important role in the pathophysiological process of cerebral ischemia, its contribution to the pathogenesis of traumatic brain injury (TBI) remains to be clarified. The authors investigated alterations in constitutive nitric oxide synthase (NOS) activity after TBI and the histopathological response to pharmacological manipulations of NO. METHODS: Male Sprague-Dawley rats underwent moderate (1.7-2.2 atm) parasagittal fluid-percussion brain injury. Constitutive NOS activity significantly increased within the ipsilateral parietal cerebral cortex, which is the site of histopathological vulnerability, 5 minutes after TBI occurred (234.5+/-60.2% of contralateral value [mean+/-standard error of the mean ¿SEM¿], p < 0.05), returned to control values by 30 minutes (114.1+/-17.4%), and was reduced at 1 day after TBI (50.5+/-13.1%, p < 0.01). The reduction in constitutive NOS activity remained for up to 7 days after TBI (31.8+/-6.0% at 3 days, p < 0.05; 20.1+/-12.7% at 7 days, p < 0.01). Pretreatment with 3-bromo-7-nitroindazole (7-NI) (25 mg/kg), a relatively specific inhibitor of neuronal NOS, significantly decreased contusion volume (1.27+/-0.17 mm3 [mean+/-SEM], p < 0.05) compared with that of control (2.52+/-0.35 mm3). However, posttreatment with 7-NI or pre- or posttreatment with nitro-L-arginine-methyl ester (L-NAME) (15 mg/kg), a nonspecific inhibitor of NOS, did not affect the contusion volume compared with that of control animals (1.87+/-0.46 mm3, 2.13+/-0.43 mm3, and 2.18+/-0.53 mm3, respectively). Posttreatment with L-arginine (1.1+/-0.3 mm3, p < 0.05), but not 3-morpholino-sydnonimine (SIN-1) (2.48+/-0.37 mm3), significantly reduced the contusion volume compared with that of control animals. CONCLUSIONS: These data indicate that constitutive NOS activity is affected after moderate parasagittal fluid percussion brain injury in a time-dependent manner. Inhibition of activated neuronal NOS and/or enhanced endothelial NOS activation may represent a potential therapeutic strategy for the treatment of TBI.

Animals↗
PubMed1998

Gastric epithelial cells secrete a PDGF-like peptide, a potent mitogen for human gastric fibroblasts.

To investigate whether gastric epithelial cells secrete growth factors involved in stromal cell growth, we examined the effects of conditioned media obtained from gastric cancer cells on murine BALB/c 3T3 cells and primary cultured human gastric fibroblasts. Conditioned media from MKN-1 gastric cancer cells were applied to a heparin-affinity column. The fraction eluted from the column at 0.4 M NaCl stimulated DNA synthesis and phosphorylation of PDGF alpha-receptors on tyrosine in BALB/c 3T3 cells. The fraction-induced stimulation of DNA synthesis in gastric fibroblasts was more marked than in BALB/c 3T3 cells. However, the fraction failed to stimulate DNA synthesis in CHO-ER cells overexpressing EGF receptors and phosphorylation of PDGF beta-receptors on tyrosine in BALB/c 3T3 cells. Immunoblot analysis of the media confirmed that PDGF-AA-like peptides are released from gastric cancer cells, immortalized gastric epithelial cells, and primary cultured gastric epithelial cells. Anti-PDGF neutralizing antibodies produced only a partial inhibition of 0.4 M NaCl fraction-induced enhanced DNA synthesis. Thus, in addition to PDGF-AA peptide, other bioactive substance(s) are probably released from MKN-1 gastric cancer cells. Our results suggest that gastric epithelial cells secrete PDGF-AA-like peptides responsible for stromal cell growth through paracrine mechanisms.

3T3 Cells↗
PubMed1998

Novel phosphodiesterase 4 inhibitor T-440 reverses and prevents human bronchial contraction induced by allergen.

To study the roles of phosphodiesterase (PDE) 4 in the human airways, we examined the effect of the novel PDE4 inhibitor T-440 in the isolated human bronchus. T-440 inhibited PDE4 extracted from human bronchial smooth muscle. IC50 values for the effect of T-440, rolipram (a PDE4 inhibitor) and theophylline on PDE4 activity of the bronchial tissues were 0.08 microM, 2 microM and > 100 microM, respectively. T-440 (10(-6) M to 10(-5) M) and aminophylline (3.3 x 10(-5) M) significantly reversed the 10(-5) M histamine-induced contraction, the efficacy of 10(-6) M T-440 being almost the same as that of 3.3 x 10(-5) M aminophylline. T-440 (10(-6) M to 10(-5) M) and aminophylline (3.3 x 10(-5) M) significantly reversed the 10(-4) M ACh-induced contraction. But their reversal effects on the ACh-induced contraction were weaker than those on the histamine-induced contraction. T-440 (10(-5) M) significantly reversed the contraction induced by allergen in passively sensitized bronchi. The efficacy of the reversal effect of T-440 (10(-5) M) was significantly higher than that of aminophylline (10(-5) M). T-440 and aminophylline significantly relaxed the basal tension, but pretreatment with T-440 or aminophylline did not significantly prevent histamine- or ACh-induced contraction. In contrast, both T-440 (10(-5) M) and aminophylline (3.3 x 10(-5) M) prevented the contraction induced by allergen, which suggests that PDE4 inhibitor inhibits the release of chemical mediators probably from bronchial mast cells in the allergic response. T-440 (10(-6) M to 10(-5) M) caused the accumulation of cAMP at the concentration that relaxed histamine-induced contraction. Thus selective PDE4 inhibitor is a candidate for the treatment of asthma.

Acetylcholine↗
PubMed1998

[DNA and RNA contents of megakaryocytes using acridine orange staining].

We developed a new microfluorometric method to measure the DNA and RNA contents of individual megakaryocytes using acridine orange (AO) staining in human bone marrow smears. Some bone marrow smears were fixed with ethanol and treated with pretreatment solution and then stained with an AO staining solution. The DNA content was assayed by measuring the green fluorescence and the RNA content was assayed by measuring the red fluorescence under B excitation with microfluorometer using peripheral lymphocytes as the control. The ploidy peak was shown to be 16N in all of 5 normal controls, but it was 8N in the patient with refractory anemia with excess of blasts in transformation (RAEB-T). There was not difference in the RNA content/DNA content ratios (RI) between each ploidy in the normal controls. The RI of the patient with RAEB-T was lower than that of the normal controls. The measurement of the DNA-RNA contents may be useful as a new megakaryocytic parameter.

Acridine Orange↗
PubMed1998

Effect of theophylline withdrawal on airway inflammation in asthma.

Theophylline has been used as a bronchodilator in acute and chronic asthma management, although there is accumulating evidence that it may have anti-inflammatory effects. We have investigated the effect of theophylline withdrawal for 6 weeks in asthmatic subjects whose peak expiratory flow (PEF) readings were more than 80% of the predicted value and its variability was less than 20% (Green Zone) by treatment with both a moderate dose of inhaled corticosteroids (BDP), 400-800 microg/day) and low dose theophylline (400 mg/day) for more than 3 months. In 38 asthmatic subjects, changes in clinical symptoms, respiratory function and airway inflammation detected with hypertonic saline induced sputum, and airway reactivity to histamine were investigated. One half of the patients were randomly withdrawn from theophylline, while the other half continued to take the same dose of theophylline for a period of 6 weeks. Mean steady state plasma theophylline concentrations when receiving treatment with theophylline were 8.08 microg/mL in the theophylline withdrawal group and 7.64 microg/mL in the control theophylline group, respectively. Although a significant increase in asthma symptoms emerged in the theophylline group, there were no significant changes in the theophylline administration group. In the theophylline withdrawal group, there were small but significant falls in PEF in the morning, FEV1 and V50 at the end of the study period. Analysis of induced sputum showed that there was also a significant increase in the percentage of total and activated (EG2+) eosinophils only in those patients who withdrew from theophylline. These results indicate that chronic treatment with low dose theophylline exerts an anti-inflammatory effect and that the additional use of theophylline with inhaled corticosteroids provides an effective treatment for moderate asthma. Taken together, we conclude that theophylline has long-term beneficial effects on the chronic asthma management.

Administration, Oral↗
PubMed1998

[Significance of serum surfactant protein-D (SP-D) level in patients with pulmonary tuberculosis].

Elevated levels of serum surfactant protein-D (SP-D) have been previously reported in patients with idiopathic pulmonary fibrosis (IPF) and pulmonary alveolar proteinosis. To determine whether the same change is seen in other pulmonary diseases, especially pulmonary tuberculosis (TB), we measured the serum SP-D levels in active pulmonary TB (smear and/or culture: positive), acute interstitial pneumonia (AIP), IPF, acute exacerbation of IPF, hypersensitivity pneumonitis (HP), pneumoconiosis, bronchiectasis, and bacterial pneumonia by an enzyme-linked immunosorbent assay using monoclonal antibodies to human lung SP-D, and compared them with those of healthy elderly subjects over 50 years of age. The SP-D level in the healthy elderly subjects was 57.6 +/- 38.4 ng/ml (mean +/- SD, n = 287). The levels in patients with active pulmonary TB (140.6 +/- 18.2 ng/ml, n = 49), AIP (1,021 ng/ml, n = 1), IPF (307.0 +/- 180.7 ng/ml, n = 42), acute exacerbation of IPF (817.7 +/- 283.6 ng/ml, n = 3), and HP (716.6 +/- 548.8 ng/ml, n = 4) were significantly higher than those in the healthy elderly controls (p < 0.05), whereas those of pneumoconiosis, bronchiectasis, and bacterial pneumonia, 121.9 +/- 92.8 ng/ml (n = 8), 93.9 +/- 72.9 ng/ml (n = 11), and 72.7 +/- 3.4 ng/ml (n = 4), respectively, showed no significant difference with the controls. In active pulmonary TB, the percentage of patients whose serum SP-D levels were over 134.6 ng/ml (mean + 2SD of healthy elderly controls) was 34.7%, and therefore we considered the serum SP-D level was not useful for the diagnosis of pulmonary TB. However, it was significantly higher in the patients with cavity formation than in those without (p < 0.05), and there was a significant positive correlation between the serum SP-D level and the number of tubercle bacilli in the sputum (r = 0.416, p = 0.00165), erythrocyte sedimentation rate at 1 hr (r = 0.489, p < 0.01), and CRP level (r = 0.383, p = 0.003). These findings suggest that the serum SP-D level is a useful indicator of the disease activity in pulmonary TB.

Aged↗
PubMed1998

[Hydromyelia associated with spinal lipoma].

We studied morphological changes of hydromyelia complicated with spinal lipoma of infants who were untethered. Since the MRI was introduced, early detection of spinal lipoma with lumbosacral skin abnormalities has become possible. We have experienced 44 surgical cases of spinal lipoma. Out of 36 such cases, 25 (69.4%) had hydromyelia, and hydromyelia of 9 patients was found to be of the terminal ventricle type. As many as 36% of spinal lipoma patients with hydromyelia concurrently had terminal-type hydromyelia, which was considered to fall under a specific category of congenital hydromyelia. At the stage of embryogenesis of the spinal cord, the caudal cell mass undergoes vacuolization, canalization and retrogressive differentiation, and during this process, the terminal ventricle with ependymallined cells becomes morbid. Though the morphological changes of hydromyelia after surgery as untethering were varied, hydromyelia of 9 patients became smaller after untethering, and hydromyelia of 8 expanded but attenuated afterwards, totaling 17 (68.0%). However, 5 had an expanding tendency and 3 did not show any morphological changes during the follow-up period (20.6-26.9 months) by MRI.

Child↗
PubMed1997

Glutamate transporter GLAST is expressed in the radial glia-astrocyte lineage of developing mouse spinal cord.

The glutamate transporter GLAST is localized on the cell membrane of mature astrocytes and is also expressed in the ventricular zone of developing brains. To characterize and follow the GLAST-expressing cells during development, we examined the mouse spinal cord by in situ hybridization and immunohistochemistry. At embryonic day (E) 11 and E13, cells expressing GLAST mRNA were present only in the ventricular zone, where GLAST immunoreactivity was associated with most of the cell bodies of neuroepithelial cells. In addition, GLAST immunoreactivity was detected in radial processes running through the mantle and marginal zones. From this characteristic cytology, GLAST-expressing cells at early stages were judged to be radial glia cells. At E15, cells expressing GLAST mRNA first appeared in the mantle zone, and GLAST-immunopositive punctate or reticular protrusions were formed along the radial processes. From E18 to postnatal day (P) 7, GLAST mRNA or its immunoreactivity gradually decreased from the ventricular zone and disappeared from radial processes, whereas cells with GLAST mRNA spread all over the mantle zone and GLAST-immunopositive punctate/reticular protrusions predominated in the neuropils. At P7, GLAST-expressing cells were immunopositive for glial fibrillary acidic protein, an intermediate filament specific to astrocytes. Therefore, the glutamate transporter GLAST is expressed from radial glia through astrocytes during spinal cord development. Furthermore, the distinct changes in the cell position and morphology suggest that both the migration and transformation of radial glia cells begin in the spinal cord between E13 and E15, when the active stage of neuronal migration is over.

ATP-Binding Cassette Transporters↗
PubMed1997

Lipopolysaccharide-induced increase in plasma nitrotyrosine concentrations in rats.

Since the production of peroxynitrite may contribute to the pathophysiology of endotoxemia or sepsis, the quantities of the produced peroxynitrite were evaluated in rats after lipopolysaccharide (LPS) treatment by measuring plasma nitrotyrosine concentrations with a new method. The intraperitoneal administration of LPS caused a persistent increase in plasma nitrotyrosine concentrations, which reached a maximum with 6-fold level of the base line (105 pmol ml-1) at 24 h and gradually declined to 3-fold level of the base line at 7 days. However, plasma concentrations of nitrite and nitrate peaked at 18 h, returning to base line within 48 h. The effect of LPS on the increase in plasma concentration of nitrotyrosine was dose-dependent and consistent with that of nitrite and nitrate concentrations. On the other hand, intravenous injection of nitrotyrosine revealed a rapid clearance with a plasma half-life of 1.67 h. These results indicate that the elevation of plasma nitrotyrosine concentrations may persist for more than a week after LPS treatment, and that the determination of plasma nitrotyrosine concentrations may be useful to detect the previous peroxynitrite-dependent oxidative damages.

4-Chloro-7-nitrobenzofurazan↗
PubMed1997

Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity.

Mammalian bombesin-like peptides are widely distributed in the central nervous system as well as in the gastrointestinal tract, where they modulate smooth-muscle contraction, exocrine and endocrine processes, metabolism and behaviour. They bind to G-protein-coupled receptors on the cell surface to elicit their effects. Bombesin-like peptide receptors cloned so far include, gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor (NMB-R), and bombesin receptor subtype-3 (BRS-3). However, despite the molecular characterization of BRS-3, determination of its function has been difficult as a result of its low affinity for bombesin and its lack of an identified natural ligand. We have generated BRS-3-deficient mice in an attempt to determine the in vivo function of the receptor. Mice lacking functional BRS-3 developed a mild obesity, associated with hypertension and impairment of glucose metabolism. They also exhibited reduced metabolic rate, increased feeding efficiency and subsequent hyperphagia. Our data suggest that BRS-3 is required for the regulation of endocrine processes and metabolism responsible for energy balance and adiposity. BRS-3-deficient mice provide a useful new model for the investigation of human obesity and associated diseases.

Adipose Tissue, Brown↗