ABSTRACT
A psychrotrophic bacterium, strain Mct-9, which produced an N-acetylglucosamine-6-phosphate deacetylase, was isolated from a deep-seawater sample in the Mariana Trough. The Mct-9 strain was identified as Alteromonas sp. The native enzyme had a molecular mass of 164,000 Da, and was predicted to be composed of four identical subunits with molecular masses of 41,000 Da. The purified enzyme hydrolyzed N-acetylglucosamine (GlcNAc), GlcNAc-6-phosphate, and GlcNAc-6-sulfate. Considering the low K(m) and high k(cat)/K(m) for GlcNAc-6-phosphate, it probably acts as a GlcNAc-6-phosphate deacetylase in vivo. The enzyme was functional in the temperature range of 5 degrees to 70 degrees C and displayed optimal activity at 55 degrees C. The optimal temperature was higher than that of the deacetylase from the mesophilic bacterium Vibrio cholerae non-O1. The characteristics of the GlcNAc-6-phosphate deacetylase from Alteromonas sp. are unique among psychrotrophs and psychrophiles, whose intracellular enzymes are mostly thermolabile.
ABSTRACT
Signal transducers and activators of transcription 6 (STAT6) is essential for interleukin 4-mediated responses, including class switching to IgE and induction of type 2 T helper cells. To investigate the role of STAT6 in allergic asthma in vivo, we developed a murine model of allergen-induced airway inflammation. Repeated exposure of actively immunized C57BL/6 mice to ovalbumin (OVA) aerosol increased the level of serum IgE, the number of eosinophils in bronchoalveolar lavage (BAL) fluid, and airway reactivity. Histological analysis revealed peribronchial inflammation with pulmonary eosinophilia in OVA-treated mice. In STAT6-deficient (STAT6-/-) C57BL/6 mice treated in the same fashion, there were no eosinophilia in BAL and significantly less peribronchial inflammation than in wild-type mice. Moreover STAT6-/- mice had much less airway reactivity than wild-type mice. These findings suggest that STAT6 plays a crucial role in the pathogenesis of allergen-induced airway inflammation.
Subject(s)
Bronchial Hyperreactivity/immunology , Eosinophils/immunology , Inflammation/immunology , Signal Transduction/physiology , Trans-Activators/deficiency , Animals , Disease Models, Animal , Hypersensitivity/immunology , Immunoglobulin E/blood , Immunoglobulin M/blood , Lung/cytology , Lung/immunology , Mice , Mice, Inbred Strains , Mice, Knockout , Ovalbumin/immunology , STAT6 Transcription FactorABSTRACT
A teratogenicity study was carried out in Crj: CD (SD) rats orally administered ranitidine hydrochloride, a histamine H2-receptor antagonist, at dose levels of 50, 200 and 800 mg/kg/day as base weight for a period of 11 days from day 7 to day 17 of gestation. Two-thirds of the pregnant females in each group were sacrificed on day 20 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and the postnatal development of the offspring was observed. The incidences of external, internal, and skeletal anomalies were not significantly increased in the fetuses of any treated group. Ranitidine treatment caused no effects on parturition, lactation, postnatal growth and reproductive ability of the male and female offspring.
Subject(s)
Anti-Ulcer Agents/toxicity , Furans/toxicity , Histamine H2 Antagonists/toxicity , Teratogens , Administration, Oral , Animals , Animals, Newborn/growth & development , Anti-Ulcer Agents/administration & dosage , Female , Fetal Heart/drug effects , Fetus/drug effects , Furans/administration & dosage , Gestational Age , Histamine H2 Antagonists/administration & dosage , Male , Maternal-Fetal Exchange , Pregnancy , Pregnancy, Animal/drug effects , Ranitidine , Rats , Rats, Inbred Strains , Reproduction/drug effectsABSTRACT
A perinatal and postnatal study was carried out in the Crj:CD (SD) rats orally administered ranitidine hydrochloride, a histamine H2-receptor antagonist, at dose levels of 50, 200, and 800 mg/kg/day as base for a period of time from day 17 of gestation to day 21 after delivery. All pregnant rats were allowed to litter naturally, and the postnatal development of the offsprings was observed. In the 800 mg/kg group, the delivery rate was significantly decreased and offspring mortality during the lactation period showed a tendency to increase as compared with control, but the difference was not significant. No significant differences between the control group and the treated groups were found in postnatal growth and differentiation, behavior and reproductive ability of male and female offsprings.
Subject(s)
Animals, Newborn/growth & development , Anti-Ulcer Agents/toxicity , Furans/toxicity , Histamine H2 Antagonists/toxicity , Postpartum Period , Pregnancy, Animal/drug effects , Administration, Oral , Animals , Anti-Ulcer Agents/administration & dosage , Female , Fetus/drug effects , Furans/administration & dosage , Histamine H2 Antagonists/administration & dosage , Humans , Male , Maternal-Fetal Exchange , Pregnancy , Ranitidine , Rats , Rats, Inbred Strains , Reproduction/drug effectsABSTRACT
A fertility study was carried out in Crj: CD (SD) rats orally administered ranitidine hydrochloride, a histamine H2-receptor antagonist, at dose levels of 50, 200 and 800 mg/kg/day in base weight. Male rats were treated from 60 days before mating until the completion of mating. Female rats were administered ranitidine hydrochloride from 14 days prior to mating up to day 7 of gestation. All pregnant females were sacrificed on day 20 of gestation and all fetuses were examined for abnormalities. Temporary salivation was noted in rats of both sexes given 800 mg/kg/day of ranitidine and in the male rat group given 200 mg/kg/day. No abnormal signs were seen in mating or fertility in the rats treated with ranitidine. No external, internal and skeletal anomalies attributable to ranitidine hydrochloride were observed in the fetuses. It was concluded that ranitidine hydrochloride has no harmful effect on mating, fertilization, implantation, or embryonic development.
