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Biomedical subjects

N Yoshida

Publications and source records attributed to N Yoshida.

At least 181 records · Page 10Linked to original sources
PubMed1999

Gentamicin blocks both fast and slow effects of olivocochlear activation in anesthetized guinea pigs.

The medial olivocochlear (MOC) efferent system, which innervates cochlear outer hair cells, suppresses cochlear responses. MOC-mediated suppression includes both slow and fast components, with time courses differing by three orders of magnitude. Pharmacological studies in anesthetized guinea pigs suggest that both slow and fast effects on cochlear responses require an initial acetylcholine activation of alpha-9 nicotinic receptors on outer hair cells and that slow effects require additional intracellular events downstream from those mediating fast effects. Gentamicin, an aminoglycoside antibiotic, has been reported to block fast effects of sound-evoked OC activation following intramuscular injection in unanesthetized guinea pigs, without changing slow effects. In the present study, we show that electrically evoked fast and slow effects in the anesthetized guinea pig are both blocked by either intramuscular or intracochlear gentamicin, with similar time courses and/or dose-response curves. We suggest that sound-evoked slow effects in unanesthetized animals are fundamentally different from electrically evoked slow effects in anesthetized animals, and that the former may arise from effects of the lateral OC system.

Acoustic Stimulation↗
PubMed1999

Adrenomedullin inhibits ovalbumin-induced bronchoconstriction and airway microvascular leakage in guinea-pigs.

Human adrenomedullin is a potent vasodilator with bronchodilation properties. The effects of adrenomedullin on antigen-induced bronchoconstriction and airway microvascular leakage in guinea-pigs was investigated. The portion of the adrenomedullin molecule possessing these pulmonary active profiles was also examined, using two truncated adrenomedullin molecules: adrenomedullin (1-25) and adrenomedullin (22-52). Four weeks after sensitization with ovalbumin (0.1 mg x k(-1)), the guinea-pigs were anaesthetized and mechanically ventilated. Respiratory resistance, dynamic compliance and arterial blood pressure were monitored. Airway microvascular leakage was evaluated by extravasation of 20 mg x kg(-1) Evans blue into airway interstitial tissue. In order to enhance the pulmonary effects of adrenomedullin, the active production of endogenous nitric oxide was inhibited by coadministration of a nitric oxide synthase inhibitor, L-N(G)-nitroarginine methethyl ester (10 mg x kg(-1)). Intravenous pretreatment with adrenomedullin (10, 30 and 100 microg x mL(-1)) dose-dependently inhibited ovalbumin-induced bronchoconstriction and airway microvascular leakage in all airway segments. Inhaled adrenomedullin (100 microg.mL(-1), 1 min) also significantly inhibited pulmonary changes induced by ovalbumin inhalation (3 mg x mL (-1) , 3 min). These pulmonary profiles of adrenomedullin were enhanced by inhibiting the active production of endogenous nitric oxide. In conclusion, adrenomedullin has inhibitory effects on antigen-induced microvascular leakage and bronchoconstriction in guinea-pigs. These beneficial effects strongly related to its unique ring structure and N-terminal segment, making it a potential anti-asthma.

Adrenomedullin↗
PubMed1999

[Pharmacological effects of the gastroprokinetic agent mosapride citrate].

Mosapride citrate (mosapride) is a novel gastroprokinetic agent that enhances the gastrointestinal motility by stimulating the 5-hydroxytryptamine4 (5-HT4) receptor. Mosapride dose-dependently enhanced the gastric emptying of a liquid or solid meal in rats with a potency equal to that of cisapride and more potent than that of metoclopramide. In rats, mosapride improved the gastric emptying delayed by gastroduodenal surgical intervention. In the conscious dogs with force transducers implanted chronically, mosapride stimulated antral and duodenal motility with a potency equal to those of cisapride. In isolated guinea-pig ileal longitudinal muscle preparations, mosapride enhanced the electrically stimulated contractions, and the enhancing effect of mosapride was antagonized by a high dose of tropisetron, a 5-HT4-receptor antagonist. In addition, mosapride inhibited [3H]-GR-113808 binding to 5-HT4 receptor sites of guinea-pig ileum and striatum. Mosapride had no affinity for dopamine D2 receptor, whereas metoclopramide and cisapride had a high affinity for dopamine D2 receptor. In isolated guinea-pig papillary muscles, mosapride did not prolong the duration of action potentials, whereas cisapride concentration-relatedly prolonged it. In conclusion, mosapride is a selective and potent 5-HT4 receptor agonist and improves gastrointestinal symptoms in patients with non-ulcer dyspepsia without causing the extrapyraminal syndrome associated with dopamine-D2-receptor blockage and adverse cardiovascular effects such as torsadoes de points.

Animals↗
PubMed1999

Calcitonin induces 25-hydroxyvitamin D3 1alpha-hydroxylase mRNA expression via protein kinase C pathway in LLC-PK1 cells.

The biosynthesis of 1alpha, 25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 is catalyzed by 25-hydroxyvitamin D3 1alpha-hydroxylase (CYP27B1) in renal proximal tubules. It was recently demonstrated that LLC-PK1 cells express CYP27B1 mRNA, which is regulated by intracellular cAMP but not vitamin D3. To clarify the effect of calcitonin on vitamin D3 metabolism in vitro, LLC-PK1 cells were incubated with hormonal factors, and expression of CYP27B1 mRNA was measured by quantitative reverse transcription-PCR. Calcitonin at 100 nmol/L significantly increased CYP27B1 mRNA expression by 24 h (271 +/- 21% of control). Incubation with calcitonin over a range of 1 micromol/L to 1 pmol/L resulted in a concentration-dependent increase in CYP27B1 mRNA levels. It is known that the calcitonin receptor has dual intracellular signaling pathways, via protein kinases A and C. Both 500 micromol/L 8-bromo-cAMP, a protein kinase A activator, and 100 nmol/L phorbol 12-myristate 13-acetate, a protein kinase C activator, increased CYP27B1 mRNA levels at 24 h (207 +/- 54 and 246 +/- 58% of control, respectively). However, calcitonin-induced CYP27B1 mRNA expression was only inhibited by the protein kinase C inhibitors staurosporine and calphostin C. The protein kinase A inhibitors Rp-cAMPS at 10 and 100 micromol/L and H-89 at 10 micromol/L had no effect on the action of calcitonin, in spite of cAMP-activation by calcitonin. The present data suggest that calcitonin upregulates CYP27B1 mRNA expression via the protein kinase C pathway in LLC-PK1 cells.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1999

Cloning of porcine 25-hydroxyvitamin D3 1alpha-hydroxylase and its regulation by cAMP in LLC-PK1 cells.

The 25-hydroxyvitamin D3 1alpha-hydroxylase, also referred to as CYP27B1, is a mitochondrial cytochrome P450 enzyme that catalyzes the biosynthesis of 1alpha, 25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) from 25-hydroxyvitamin D3 in renal proximal tubular cells. Recently, human, mouse, and rat CYP27B1 cDNA have been cloned, however the gene regulation has not been fully elucidated. In the present study, porcine CYP27B cDNA was cloned, and the effects of cAMP and vitamin D3 on the regulation of CYP27B1 mRNA expression in LLC-PK1 cells were examined. PCR cloning revealed that porcine CYP27B1 cDNA consisted of 2316 bp, encoding a protein of 504 amino acids. The deduced amino acid sequence showed over 80% identity to the human, mouse, and rat enzyme. LLC-PK1 cells were incubated with humoral factors, and expression of CYP27B1 mRNA was measured by a quantitative reverse transcription-PCR. At the completion of 3-, 6-, 12-, and 24-h incubations, 500 micromol/L 8-bromo-cAMP had significantly increased CYP27B1 mRNA expression (260 to 340%). The adenylate cyclase activator forskolin at 50 micromol/L also had a stimulatory effect at 6 h (190%). Moreover, the protein kinase A inhibitor H-89 reduced the cAMP effect. On the other hand, 1alpha,25(OH)2D3 had no effect on CYP27B1 mRNA expression at 10 and 100 nmol/L, whereas expression of 25-hydroxyvitamin D3 24-hydroxylase (CYP24) mRNA was markedly increased by 1alpha,25(OH)2D3. These findings suggest that LLC-PK1 cells express CYP27B1 mRNA, and that cAMP is an upregulating factor of the CYP27B1 gene in vitro.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1999

Pancreatic phospholipase A2 induces bacterial translocation in rats.

The importance of pancreatic enzymes, particularly phospholipase A2 (PLA2), for bacterial translocation, which is considered to be one of the aggravating causes of acute pancreatitis, was investigated. Male rats were administered an intraperitoneal or intravenous injection of normal saline, PLA2, or amylase. Four days later, the mesenteric lymph nodes (MLNs) and portal blood of the animals were cultured. None of the animals had a positive portal blood culture. The MLNs contained enteric bacteria in 78% of the animals given 50 mg/kg of PLA2 intraperitoneally. 5 mg/kg of PLA2 intraperitoneally, 50 mg/kg of amylase intraperitoneally, or 50 mg/kg of PLA2 intravenously showed positive cultures in 25%, 20%, and 11%, respectively. None of the animals given intraperitoneal or intravenous normal saline had positive cultures of their MLNs. Intraperitoneal injection of 25 mg/kg of nafamostat mesilate just before intraperitoneal PLA2 (50 mg/kg) resulted in a reduction of positive MLNs from 70% to 30%. The cecal myeroperoxidase (MPO) activity of animals administered 50 mg/kg of PLA2 intraperitoneally was significantly higher compared with animals administered saline intraperitoneally. These results indicate that intraperitoneal leakage of PLA2 plays an important role in bacterial translocation during acute pancreatitis and that administration of a protease inhibitor may be effective against the bacterial translocation.

Acute Disease↗
PubMed1999

Suppression of growth and dissemination in human pre-B leukemia cells by tumor necrosis factor-alpha in scid mice.

Tumor necrosis factor (TNF) has been shown to inhibit the growth of ALL cells. Since the systemic administration of TNF for malignancy results in poor response and severe toxicity, future efforts should concentrate on local treatment. Here we examined the suppressive effect of TNF alpha on leukemic cells engrafted in scid mice. NALM6 cells derived from pre-B ALL were injected in scid mice subcutaneously with or without Matrigel. In mice with Matrigel, subcutaneous tumors rapidly increased with time, whereas none of the mice without Matrigel showed any obvious signs of disease or apparent tumors. High levels of leukemic infiltration were observed in peripheral organs in mice with Matrigel by flow cytometry and PCR for human beta-actin mRNA expression, while mice without Matrigel showed low or undetectable infiltration in these organs. Human TNF alpha was also coinjected subcutaneously with NALM6 cells and Matrigel into scid mice. Mice with 10 ng of TNF alpha showed small subcutaneous tumors at 8 weeks, which slowly increased. They were found to have a small number of leukemic cells in peripheral organs by flow cytometry. By PCR, all organs with the exception of lung and brain showed low or undetectable expression of beta-actin. However, a large dose of TNF alpha (100 ng) had no suppressive effect on tumor growth and leukemic infiltration in mouse organs. Similar results were obtained in colony formation of leukemic cells in vitro. To examine the mechanism of the suppressive effect of TNF alpha, the expression of TNF receptors in tumor cells was analyzed by flow cytometry. Parental NALM6 expressed both TNF alpha receptors I (TNFR60) and II (TNFR80), but these expressions were suppressed in tumor cells from mice with Matrigel. Only TNFR80 expression was induced in tumor cells of mice with 10 ng of TNF alpha. The induction of Fas expression was also detected, whereas neither DNA fragmentation nor apoptotic change in histology was observed in tumor cells of mice with TNF alpha. These results suggest that the suppressive effect of TNF alpha on the growth of leukemic cells in scid mice is mediated through the activation of TNFR80 without apoptotic signal.

Animals↗
PubMed1999

[Two cases of bladder tumor producing granulocyte colony stimulating factor].

Two cases of bladder tumor producing granulocyte colony-stimulating factor (G-CSF) are reported. The first case was in a 79-year-old female patient. A large bladder tumor was diagnosed as right-sided hydronephrosis. The tumor consisted mostly of squamous cell carcinoma with a few transitional cells. Total cystectomy could not be performed because of direct invasion by the tumor into the pelvis. The patient died without aggressive treatment about 7 months after admission. Her leukocyte count consistently increased up to 76,200/mm3. The serum G-CSF levels were not analyzed. However, immunohistochemical examination revealed a high concentration of G-CSF in the tumor specimen. The other case was in an 80-year-old male patient. The patient, who had refused total cystectomy for bladder tumor (transitional cell carcinoma, grade 2, T2N0M0) 2 years earlier, underwent ureterocutaneostomy for obstructive renal insufficiency. Total cystectomy was not performed at this admission because of tumor invasion into the rectum and his advanced age. Radiotherapy was administered. However, he developed ileus caused by direct tumor invasion into the ileum. He died about 10 months after the urinary diversion. Leukocytosis, which improved transiently following radiotherapy, became more severe. The maximum leukocyte count was 49,500/mm3 just before death. The serum G-CSF levels during and after radiotherapy were 54 pg/ml and < 30 pg/ml, respectively. Immunohistochemical examination revealed the presence of G-CSF in the tumor. These findings suggest the production of G-CSF by the bladder tumor.

Aged↗
PubMed1999

[Primary lung cancer (adenocarcinoma) associated with cardiac sarcoidosis].

A 56-year-old woman who had been given oral prednisolone for iridocyclitis by an ophthalmologist received a diagnosis of pulmonary sarcoidosis on the basis of transbronchial lung biopsy findings, and began receiving therapy at our hospital on an outpatient basis. Chest X-ray films disclosed hilar lymphadenopathy in both lungs. In addition, Holter electrocardiograms detected ventricular premature beat (Lown 4B) and echocardiograms detected reduced left ventricular wall motion with dilatation of the left ventricular chamber. Cardiac sarcoidosis developed in the patient. She was admitted to our hospital because of shortness of breath on exertion. Chest X-ray films on admission disclosed a large nodular heterogeneous mass in the right upper lobe. Histologically, transbronchial lung biopsy specimens of the mass disclosed an adenocarcinoma. Although lung cancer and sarcoidosis are common, their coexistence in the same patient is not. Furthermore, the coexistence of lung cancer with cardiac sarcoidosis, as in this case, is very rare.

Adenocarcinoma↗
PubMed1999

A novel splice acceptor site mutation which produces multiple splicing abnormalities resulting in protein S deficiency type I.

In an attempt to explore the molecular mechanisms for protein S deficiency, a patient with such a deficiency was examined at the DNA, RNA and protein levels. Nucleotide analyses revealed that the proband, the mother and the grandmother had a G-->C substitution in the invariant AG dinucleotide at the splicing acceptor site of intron A/exon 2. This patient was heterozygous for this substitution and the mutant allele was inherited from the proband's mother and grandmother. Reverse transcription-polymerase chain reaction analysis demonstrated several kinds of splicing abnormalities such as exon skipping and cryptic splicing, in addition to correct splicing. Semiquantitation of mRNA for the protein S gene revealed that the amount of the proband's mRNA was reduced to 60% of normal. Thus, this mutation impaired the normal processing of mRNA for the protein S gene, resulting in the subject's severe protein S deficiency.

Adolescent↗
PubMed1999

[Two cases of Kimura's disease associated with bronchial asthma].

We encountered two rare cases of Kimura's disease associated with bronchial asthma presenting eosinophilia and hyperimmunoglobulinemia E. Patient 1 was a 26-year-old man who had been admitted to our hospital with recurrent increase in left parotid mass in May 1997. He had previously undergone surgery for local excision at another hospital in September 1987; the excised specimens were re-evaluated and the diagnosis of Kimura's disease was confirmed. Because the patient was suffering from an acute asthma attack on admission, prednisolone (PSL) 30 mg/day was administered orally. PSL reduced the parotid mass and improved control of the asthma. Patient 2 was an 18 year-old man who had been given a diagnosis of Kimura's disease on the basis of histologic findings from a biopsy specimen of a subcutaneous tumor in the left cheek in 1988. Following the diagnosis, the patient was treated with methotrexate for the first several months, and then with loxioprofen for 9 years, but the size of the mass remained unchanged. Bronchial asthma developed in this patient in 1995 and had been treated with theophylline. However, because this therapy caused a deterioration of asthma control, the patient was admitted to our hospital in October 1997 for the treatment of bronchial asthma. Inhaled corticosteroids (beclometasone 0.8 mg/day) in addition to theophylline alleviated the patient's asthma symptoms and yielded improved lung function. Because few cases of Kimura's disease associated with bronchial asthma have been reported, patients with eosinophilia and hyperimmunoglobulinemia E were not necessarily considered at high risk for the onset of bronchial asthma.

Adolescent↗
PubMed1998

Stat3 activation is responsible for IL-6-dependent T cell proliferation through preventing apoptosis: generation and characterization of T cell-specific Stat3-deficient mice.

Stat3, a member of STAT, is activated by a variety of cytokines such as IL-6 family of cytokines, granulocyte CSF, epidermal growth factor, and leptin. A recent study with mice genetically deficient in the Stat3 gene has revealed its important role in the early embryogenesis. To assess the function of Stat3 in adult tissues, we disrupted the Stat3 gene specifically in T cells by conditional gene targeting using Cre-loxP system. In Stat3-deficient T cells, IL-6-induced proliferation was severely impaired. IL-6 did not enhance cell cycle progression, but prevented apoptosis of normal T cells. In contrast, IL-6 did not prevent apoptosis of Stat3-deficient T cells. Antiapoptotic protein, Bcl-2, was normally up-regulated in response to IL-6 even in Stat3-deficient T cells. These results demonstrate that Stat3 activation is involved in IL-6-dependent T cell proliferation through prevention of apoptosis independently of Bcl-2.

Amino Acid Sequence↗
PubMed1998

Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3.

Fever, a hallmark of disease, is elicited by exogenous pyrogens, that is, cellular components, such as lipopolysaccharide (LPS), of infectious organisms, as well as by non-infectious inflammatory insults. Both stimulate the production of cytokines, such as interleukin (IL)-1beta, that act on the brain as endogenous pyrogens. Fever can be suppressed by aspirin-like anti-inflammatory drugs. As these drugs share the ability to inhibit prostaglandin biosynthesis, it is thought that a prostaglandin is important in fever generation. Prostaglandin E2 (PGE2) may be a neural mediator of fever, but this has been much debated. PGE2 acts by interacting with four subtypes of PGE receptor, the EP1, EP2, EP3 and EP4 receptors. Here we generate mice lacking each of these receptors by homologous recombination. Only mice lacking the EP3 receptor fail to show a febrile response to PGE2 and to either IL-1beta or LPS. Our results establish that PGE2 mediates fever generation in response to both exogenous and endogenous pyrogens by acting at the EP3 receptor.

Animals↗
PubMed1998

Predictors of sudden cardiac death in hypertrophic cardiomyopathy.

Patients with hypertrophic cardiomyopathy (HC) die suddenly. Proposed risk factors for sudden cardiac death (SCD) in HC are youth, a family history of SCD, syncope, and ventricular tachycardia. Hemodynamic variables have not convincingly proved to be risk factors for SCD. Therefore, this study was designed to examine predictors of SCD in a large number of patients with HC during long-term follow-up periods. The relation of studied variables (clinical, electrocardiographic, echocardiographic, hemodynamic, and exercise test findings) to SCD in 309 patients with HC who were initially diagnosed during 1971 through 1994 (mean follow-up 9.4 years) was examined by multivariate analysis. SCD occurred in 28 patients. Independent predictors of SCD were a smaller difference between peak and rest systolic blood pressure during exercise testing (p=0.006), and higher left ventricular outflow tract pressure gradient at rest (p=0.003). Exercise-related SCD occurred in 8 patients and exercise-unrelated SCD in 20 patients (mean age 28 vs 47 years, p <0.05). Thus, patients of exercise-related SCD were younger and had smaller increases in systolic blood pressure during exercise testing, whereas patients with exercise-unrelated SCD were older and had higher left ventricular outflow tract pressure gradient.

Adolescent↗
PubMed1998

A novel series of 6-methoxy-1H-benzotriazole-5-carboxamide derivatives with dual antiemetic and gastroprokinetic activities.

A novel series of 6-methoxy-1H-benzotriazole-5-carboxamide derivatives with a medium perhydroazacycle ring in the amine moiety were prepared, and their antiemetic and gastroprokinetic activities were evaluated. Among them, N-(1-ethylhexahydroazepin-3-yl)-, N-(1-ethyloctahydroazocin-3-yl)- and N-(1-ethyloctahydroazonin-3-yl)-6-methoxy-1H-benzotriazole-5-carbo xamides (24, 36, 37) showed a potent antiemetic activity (inhibition of apomorphine-induced emesis in dogs) along with gastroprokinetic activity (gastric emptying in rats).

Animals↗