Biomedical subjects

A Watanabe

Publications and source records attributed to A Watanabe.

At least 361 records · Page 20Linked to original sources

PubMed1997

Effect of TYB-2285 on passive cutaneous anaphylaxis in rats.

1. TYB-2285 (1-30 mg/kg p.o.) inhibited ovalbumin (OA)- and dinitrophenyl-Ascaris (DNPAs)-induced passive cutaneous anaphylaxis (PCA) in a dose-dependent manner. 2. The ED50 of TYB-2285 and ketotifen fumarate on OA-induced PCA were 0.5 and 3.9 mg/kg, respectively. The ED50 of TYP-2285 and amlexanox on DNP-As-induced PCA were 3.5 and 0.9 mg/ kg, respectively. 3. TYB-2285 (3-30 mg/kg p.o.) inhibited histamine consumption at the PCA site. 4. Unlike cyproheptadine or amlexanox, TYB-2285 (30 mg/kg p.o.) did not inhibit histamine-, serotonin-, ascites-, 48/80-, or A23187-induced capillary permeability. It inhibited dextran-induced capillary permeability slightly. 5. These results demonstrate that TYB-2285 inhibits PCA by inhibiting histamine release, although it does not inhibit capillary permeability.

Animals↗

PubMed1997

Effect of TYB-2285 on lung anaphylaxis in actively sensitized rats.

1. We examined the effect of TYB-2285 on the acute phase and the late phase of lung anaphylaxis in rats. 2. TYB-2285 (3-30 mg/kg PO) inhibited antigen-induced bronchoconstriction and TxB2 production during the acute phase of lung anaphylaxis in a dose-dependent manner. 3. Ketotifen fumarate (30 mg/kg p.o.) inhibited bronchoconstriction and TxB2 production less potently than TYB-2285. 4. TYB-2285 (30 mg/kg p.o.) inhibited the accumulation of neutrophils during the late phase of lung anaphylaxis significantly without a significant change in total cells. 5. Hydrocortisone acetate (100 mg/kg p.o.) inhibited the accumulation of total cells as potent as neutrophils.

Anaphylaxis↗

PubMed1997

Effects of TYB-2285 on the accumulation of eosinophils in the airway induced by antigen exposure in actively sensitized brown Norway rats.

1. The effect of TYB-2285 on the antigen-induced accumulation of eosinophils into the airway was investigated in two models (inhalant sensitization and noninhalant sensitization) using Brown Norway (BN) rats. 2. In the method of inhalant sensitization, BN rats were sensitized by weekly exposure to ovalbumin (OA). The accumulation of eosinophils was inhibited by the oral administration of TYB-2285 for the first 2 days of each sensitization in a dose-dependent manner. 3. With noninhalant sensitization, BN rats were sensitized by i.m. injection of OA and i.p. injection of killed Bordetella pertussis. The accumulation of eosinophils was inhibited by TYB-2285 in a dose-dependent manner, when TYB-2285 is given p.o. 5 mm before and 5 hr after the antigen exposure. Moreover, this accumulation of eosinophils was inhibited by a single administration of TYB-2285 5 hr after the antigen exposure, presumably when the mast cell degranulation was already finished. 4. In the method with noninhalant sensitization, the accumulation of eosinophils was not inhibited by mast cell stabilizers such as ketotifen, tranilast, or DSCG. 5. The present study demonstrates that TYB-2285, unlike other mast cell stabilizers, inhibits the antigen-induced accumulation of eosinophils into the airway. It also suggests that this drug might be effective in asthmatic patients.

Animals↗

PubMed1997

The effects of TYB-2285 and its metabolites on lymphocyte responses in vitro.

1. We examined the effects of TYB-2285 and its metabolites (TC-286 and TC-326) on antigen-induced lymphocyte proliferation, allogeneic mixed lymphocyte reaction (MLR) and mitogen-induced lymphocyte proliferation. 2. Splenic lymphocytes from C57BL/6 strain mice sensitized with human serum albumin were cultured with the antigen in the presence of TYB-2285 or its metabolites (10(-7)-10(-4) M). The lymphocyte proliferation enhanced by antigen was inhibited by TYB-2285 and its metabolites in a dose-dependent manner. 3. Splenic lymphocytes collected from C57BL/6 and Balb/C strain mice were cocultured in the presence of TYB-2285 and its metabolites (10(-7)-10(-4) M). Allogeneic MLR was inhibited by TYB-2285 and its metabolites in a dose-dependent manner. 4. Splenic lymphocytes from C47BL/6 strain mice were cultured with concanavalin A (Con A) in the presence of TYB-2285 and its metabolites (10(-7)-10(-4) M). TYB-2285 and its metabolites did not affect Con A-induced lymphocyte proliferation. Cyclosporin A showed an inhibitory effect on Con A-induced lymphocyte proliferation that was as strong as the inhibitory effect on antigen-induced lymphocyte proliferation and allogeneic MLR at a lower concentration.

Albumins↗

PubMed1997

Outside-in signaling from integrin alpha IIb beta 3 into platelets in the absence of agonist-induced signaling.

Platelet agonists generate intracellular signals which lead to activation of the platelet membrane glycoprotein IIb-IIIa (integrin alpha IIb beta 3). The resulting occupancy of alpha IIb beta 3 by ligands also generates signals into the cell (outside-in signaling). We reported previously that unlike platelet agonists, the F(ab')2 fragments of an anti-alpha IIb beta 3 monoclonal antibody, PMA4, induced fibrinogen binding to alpha IIb beta 3 without causing intracellular activation. In this study, in order to determine whether outside-in signaling occurs in the absence of agonist-induced intracellular signals, we used PMA4 F(ab')2 as an inducer of fibrinogen binding to alpha IIb beta 3. PMA4 F(ab')2-induced fibrinogen binding and subsequent platelet aggregation triggered tyrosine phosphorylation of several proteins including pp72syk but not pp125FAK. No Ca2+ influx or mobilization, thromboxane B2 synthesis, phosphorylation of pleckstrin or the myosin light chain, cytoplasmic alkalinization, or platelet shape changes, were detected. These findings suggest that, in the absence of agonist-induced signaling, alpha IIb beta 3 occupied by soluble fibrinogen generates only a limited outside-in signal.

Antibodies, Monoclonal↗

PubMed1997

Treatment of acute myeloid leukemia and myelodysplastic syndrome with orally administered cytarabine ocfosfate and granulocyte colony-stimulating factor.

Cytarabine ocfosfate (SPAC) was administered orally to 19 patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). SPAC was administered at doses of 200-300 mg/day for more than 14 days with granulocyte colony-stimulating factor (G-CSF). Four of the 12 patients with AML and 1 of the 7 patients with MDS achieved complete remission (CR) after one cycle of SPAC treatment. Especially, 3 of the 6 patients with newly diagnosed AML achieved CR. Major side effects of SPAC were myelosuppression and tolerable gastrointestinal disorders. The treatment with SPAC is a therapeutic option in elderly patients or patients with organ failure.

Administration, Oral↗

PubMed1997

Cell-cycle-regulated transcription of A- and B-type plant cyclin genes in synchronous cultures.

Synchronously dividing cell cultures of Catharanthus roseus were used to isolate cDNAs for two mitotic cyclins, named CYS and CYM. The deduced protein sequence of CYS is similar to that of A-type cyclins, and CYM belongs to the group of B-type cyclins. In a fashion similar to the pattern of expression seen for A-type and B-type cyclins in mammalian cells, CYS is expressed before CYM in C. roseus cells during the cell cycle. CYS mRNA accumulated at the onset of S phase and disappeared early in the G2 phase, whereas CYM mRNA was detected in the G2 and M phases of the cell cycle. Tobacco homologs of the two genes showed similar cell-cycle dependent expression patterns in synchronous cultures of tobacco BY2 cells. In both systems, CYS was expressed much earlier in the cell cycle than most other plant A-type cyclins, and hence CYS along with the soybean cyc1GM can be classified into a distinct subclass. The activities of CYM and CYS promoters during the cell cycle were analyzed in stably transformed tobacco BY2 cells. Cyclin promoter sequences of 0.5 kb could confer the typical cell-cycle-dependent expression to the beta-glucuronidase (GUS) reporter gene: the CYS promoter directed S-phase-specific expression, whereas the CYM promoter drove M-phase-specific expression. These results indicate the important role of transcriptional regulation in the oscillations of cyclin mRNA levels during the cell cycle.

Cell Cycle↗

PubMed1997

Establishment of in vitro spermatogenesis from spermatocytes in the medaka, Oryzias latipes.

Spermatocytes of the teleost, Oryzias latipes, at meiotic prophase were cultured without contact with somatic cells. They began to divide, progressing through the meiotic divisions and differentiating into round spermatids within 48 h. The chromosome number in both the primary and secondary spermatocytes at metaphase was n = 24. In spermatids, a single flagellum was formed and the release of residual bodies was observed in vitro. The size and shape of the flagellum were the same as those seen in vivo. The expression of protamine mRNA was detected in round spermatids. This result suggests that gene expression, as well as morphological change, is regulated by the progression of spermatogenesis in cell culture. Furthermore, when the eggs of O. latipes were inseminated with germ cells cultured for 10 days, normal embryos developed and hatched out. These results suggest that the spermatocytes of O. latipes develop into fertile sperm in cell culture.

Animals↗

PubMed1997

Clinical efficacy of lactulose in cirrhotic patients with and without subclinical hepatic encephalopathy.

Seventy-five cirrhotic patients with hyperammonemia in the past or at the time of the study were randomly divided into two groups (treated with lactulose or nontreated) in 14 hospitals in Japan. Thirty-six cirrhotic patients were diagnosed as having subclinical hepatic encephalopathy (SHE), and 39 were diagnosed as non-SHE. SHE was diagnosed when the results of all three of the quantitative psychometric tests used (number connection test, and symbol digit and block design tests of the Wechsler adult intelligence scale [revised]) were abnormal as compared with age-matched normal values. The mean number of abnormal psychometric test results and the prevalence of SHE were used for a quantitative evaluation of the efficacy of the lactulose treatment. Twenty-two of the SHE patients were treated with lactulose (45 mL/d) for 8 weeks, and the other 14 SHE patients did not receive lactulose. In the SHE patients administered lactulose, the results of the quantitative psychometric evaluation were significantly improved at 4 and 8 weeks after the beginning of the lactulose administration. The SHE had disappeared in 10 (50%) of the 20 treated patients at week 8, but it persisted in 11 (85%) of the untreated 13 patients. We concluded that lactulose treatment in cirrhotic patients with SHE is effective with respect to psychometric tests.

Administration, Oral↗

PubMed1997

Abnormality in fatty acid composition of gastric mucosal phospholipids in patients with liver cirrhosis and its correction with a polyunsaturated fatty acid-enriched soft oil capsule.

The abnormal composition of the fatty acids in gastric mucosal phospholipids was examined in 11 patients with non-alcoholic liver cirrhosis accompanied by gastritis and in 10 healthy subjects without liver disease and gastritis. The cases positive for serum anti-Helicobacter pylori immunoglobulin G antibody were excluded. The arachidonic acid (AA, C20:4n-6) contents of the two main components of phospholipid, the phosphatidylcholine (PC) and phosphatidylethanolamine (PE) fractions, in gastric biopsy specimens were significantly lower in the cirrhosis group, although PC and PE contents in gastric biopsy specimens were not altered. In the cirrhosis group, AA contents of the PC fractions in gastric biopsy specimens were significantly correlated with AA contents of plasma PC fractions and serum albumin levels. Soft oil capsules containing polyunsaturated fatty acid (PUFA) such as AA, eicosapentanoic acid (EPA, C20:5n-3) and docosahexanoic acid (DHA, C20:6n-3) were administered after each meal daily for 4 weeks to six cirrhotic patients and four control subjects, who were randomly selected from the patients and control subjects. After administration of PUFA-enriched oil capsules, gastric mucosal AA contents of PC and PE fractions were significantly improved almost to the control levels. In three cirrhotic patients with severe or mild gastritis whose gastric mucosal lesions were endoscopically shown to have responded to PUFA-enriched oil capsules, AA contents of plasma PC and PE fractions before administration were much lower than in the remaining three cirrhotics that did not respond to the PUFA-enriched oil capsules, but significantly improved to the control levels after administration of oil capsules. The results demonstrate that administration of PUFA-enriched soft oil capsules increased AA contents of the phospholipids in gastric mucosa and thus improved gastric mucosal lesions endoscopically in cirrhotic patients with gastritis.

Adult↗

PubMed1997

High-dose dexamethasone therapy for a 14-month-old boy with refractory idiopathic thrombocytopenic purpura.

A 14-month-old boy with refractory idiopathic thrombocytopenic purpura (ITP), who was successfully treated with pulsed high-dose oral dexamethasone therapy is reported. The platelet count increased after six scheduled courses of treatment (10 mg/day x 4 days, six courses). Twenty-four months later, the platelet count remained over 10.0 x 10(4)/microL. No obvious side effects were observed during or after the therapy. This treatment could be taken into consideration not only for adults but also for young children with refractory ITP. It is effective, safe, easy to administer, patient comfort is taken into consideration, and hospitalization duration and costs are minimized.

Anti-Inflammatory Agents↗

PubMed1997

Clonal accumulation of V beta 5.1-positive cells in the liver of a patient with autoimmune cholangiopathy.

We describe a 43-year-old woman with clinical features compatible with autoimmune cholangiopathy recently reported by Ben Ari et al. She was negative for anti-mitochondrial antibody, positive for high titer anti-nuclear antibody with homogeneous pattern, high levels of serum immunoglobulin G and nearly normal levels of serum immunoglobulin M for more than five years. In the early stages of the disease, the elevations of serum transaminase, alkaline phosphatase and gamma-glutamyl transpeptidase were well controlled by the administration of ursodeoxycholic acid. After five years of follow-up, she showed the second exacerbation of liver function tests, which then rapidly improved by prednisone administration. To analyze the antigen diversity recognized by T-cells in the liver, T-cell receptor repertoire was examined by immuno-histochemistry. The liver biopsy obtained in the early stage showed clonal accumulation of V beta 5.1-positive cells in portal areas, which was found in patients neither with primary biliary cirrhosis nor autoimmune hepatitis. In conclusion, these data suggest that T-cell response in autoimmune cholangiopathy is different from those two autoimmune liver diseases, which may imply a distinct entity of the disease.

Adult↗

PubMed1997

[Usefulness of 7 day therapy with cefluprenam in the management of respiratory tract infections].

Efficacy and safety of a newer injectable cephalosporin, cefluprenam (CFLP) on cases with bacterial pneumonia and chronic respiratory tract infections were evaluated at a dose of 1g (potency), d.i.d for 7 days. 1. Of 130 cases in total, 116 cases were enrolled for the clinical efficacy evaluation. The efficacy rate (excellent and good responses) was 94.8% (110/116). The efficacy rate was 93.8% (60/64) for cases with bacterial pneumonia, and 96.2% (50/52) for cases with chronic respiratory tract infections. The recurrence was noted in 1.2% (1/82). The bacteriological response rate was 100.0% (32/32) for gram positive cocci, 93.8% (15/16) for gram negative rods and 97.9% (47/48) in total. 2. Adverse drug reactions were noted in 3.9% (5/129), consisting of 2 cases with skin rash, 1 case with drug fever, 1 case with skin rash and skin itching and 1 case with drug fever and headache. The abnormal laboratory changes were noted in 23.6% (30/127), mainly containing the elevation in GPT and GOT, and eosinophylia. The safety rate (no problem evaluation) was 74.8% (95/127). 3. The usefulness rate (very useful and useful evaluations) was 93.1% (108/116). As suggested by the evaluation on the secondary endpoint in the phase III comparative studies with both bacterial pneumonia and chronic respiratory tract infections, it was confirmed that the 7 day therapy of CFLP was promising for treatment of moderate bacterial pneumonia and chronic respiratory tract infections, because the high clinical efficacy was obtained and also the incidence of allergic reactions with CFLP was almost the same as that of ceftazidime (CAZ) evaluated highly safe. Based on these results, it was concluded that CFLP was useful in the management of moderate respiratory tract infections and also the recommended therapeutic period with CFLP was within 7 days.

Adult↗

PubMed1997

Bacterial pneumonia causes augmented expression of the secretory leukoprotease inhibitor gene in the murine lung.

The cDNA of murine secretory leukoprotease inhibitor (SLPI) was cloned from a mouse lung cDNA library. The amino acid sequence deduced from the cDNA showed 58 and 51% homology with those of human and porcine SLPI, respectively. A two-domain structure with similar amino acid sequences, four intradomain disulfide bonds, and high proline content, which are characteristics common to human and porcine SLPI, was also found in the mouse protein. The amino acid residues for the signal sequence and active site are also conserved in mouse SLPI. RNase protection assay showed the expression of the SLPI gene in liver, intestine, spleen, and epididymis, suggesting the distribution of SLPI in tissues other than lung and seminal vesicles. In the lung infected with Streptococcus pneumoniae strain FP1284, 10 h after inoculation of bacteria the number of SLPI mRNA transcripts was three times higher than baseline. The increased level of expression remained constant for at least 48 h. This result clearly contrasts to that obtained for spleen, in which the SLPI mRNA transcript level was mostly unchanged during the course of pneumonia. These facts suggested the local regulation of the SLPI gene expression in vivo in response to inflammatory stimuli at the site of inflammation.

Amino Acid Sequence↗

PubMed1997

Adoptively transferred late allergic airway responses are associated with Th2-type cytokines in the rat.

Late allergic airway responses can be transferred by CD4+ T cells in the rat. To investigate the role of T-cell cytokines in these responses, we examined the expression of mRNA for Th2 (interleukin [IL]-4 and IL-5) and Th1 (IL-2 and interferon gamma [INF-gamma])-type cytokines in Brown Norway rats that were administered either antigen-primed W3/25(CD4)+ or OX8(CD8)+ T cells. Donors were actively sensitized by subcutaneous injection of ovalbumin (OVA) in the neck and T cells were obtained from the cervical lymph nodes by immunomagnetic cell sorting for administration to unsensitized rats. Control rats received bovine serum albumin (BSA)-primed CD4+ and CD8+ T cells. Two days later, recipient rats were challenged with aerosolized OVA, and bronchoalveolar lavage (BAL) was performed 8 h after challenge. BAL cells expressing mRNA for IL-2, IL-4, IL-5, and INF-gamma were analyzed using the technique of in situ hybridization. Recipients of OVA-primed CD4+ T cells had an increase in the fraction of BAL cells expressing mRNA for IL-4 and IL-5 compared with BSA-primed CD4+ or OVA-primed CD8+ cells (P < 0.001). Recipients of CD8+ T cells had an increase in INF-gamma mRNA expression after OVA challenge compared with recipients of BSA-primed-CD8+ or OVA-primed CD4+ T cells (P < 0.001). In conclusion, T-cell-dependent allergen-induced late responses are associated with the expression of mRNA for IL-4 and IL-5, indicating Th2 cell activation. Furthermore, the increased expression of INF-gamma in allergen challenge recipients of antigen-primed CD8+ T cells suggests that CD8+ T cells may be important in modulating allergic responses.

Adoptive Transfer↗

PubMed1997

Synthesis biological evaluation of alkyl, alkoxy, alkylthio, or amino-substituted 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones.

2,3-Dihydro-1,5-benzothiazepin-4(5H)-ones substituted with an alkyl, alkoxy, alkylthio, hydroxy, or amino group on the fused benzene ring of the 1,5-benzothiazepine skeleton were synthesized and their vasodilating, antihypertensive, and platelet aggregation-inhibitory activities were investigated. (-)-cis-3-Acetoxy-5-[2-(di-methylamino) ethyl]-2,3-dihydro-8-methyl-2-(4-methylphenyl)-1,5-benzothiazepin- 4(5H)-one ((-)-13e) was selected for further studies as a potent inhibitor of platelet aggregation.

Alkylation↗

PubMed1997

Novel benzoxazole 2,4-thiazolidinediones as potent hypoglycemic agents. Synthesis and structure-activity relationships.

A new series of benzoxazole 2,4-thiazolidinediones was synthesized and evaluated for hypoglycemic activity in genetically obese and diabetic yellow KK mice. 2-Arylmethyl- and 2-(heteroarylmethyl)benzoxazole derivatives showed far more potent activity than known 2,4-thiazolidinedione derivatives such as ciglitazone, troglitazone and pioglitazone. A facile synthesis of benzoxazole 2,4-thiazolidinediones was also established using aminophenol 2,4-thiazolidinedione (11) as a key intermediate. Details of synthesis and structure-activity relationships for this series are described.

Animals↗

PubMed1997

Synthesis and characterization of radioiodinated (S)-5-iodonicotine: a new ligand for potential imaging of brain nicotinic cholinergic receptors by single photon emission computed tomography.

(S)-5-Iodonicotine (4a), an (S)-nicotine analog iodinated at the 5-position of the pyridine ring, was synthesized and evaluated as a potential radiopharmaceutical for investigating brain nicotine receptors by single photon emission computerized tomography (SPECT). [125I]-(S)-Iodonicotine ([125I]-4a) was synthesized by the iododestannylation reaction under no-carrier-added conditions and purified by high-performance liquid chromatography (HPLC). The binding affinity of 4a for brain nicotine receptors was measured in terms of displacement of [3H]cytisine from binding sites in rat cortical membranes. The binding data revealed that the affinity of 4a was the same as that of (S)-nicotine and 80-fold higher than that of the (R)-enantiomer (4b). Biodistribution studies in mice disclosed that the brain uptake of [125I]-4a was rapid and profound. Regional cerebral distribution studies in rats by autoradiography disclosed that the accumulation of [125I]-4a was dense in the thalamus, intermediate in the cortex and striatum, and less marked in the cerebellum. Furthermore, the administration of (S)-nicotine reduced the uptake of [125I]-4a in the thalamus and resulted in a nearly identical level of radioactivity in the cerebellum. [125I]-(R)-5-Iodonicotine ([125I]-4b) showed more rapid washout from the brain and a less extensive regional cerebral distribution than the (S)-enantiomer ([125I]-4a). Thus, 4a bound to brain nicotine receptor in vivo, and therefore iodine-123-labeled 4a may be a potential radioligand for use in vivo cerebral nicotinic receptor studies by SPECT.

Animals↗