Search PubMedSearch

Biomedical subjects

A Nomura

Publications and source records attributed to A Nomura.

At least 19 recordsLinked to original sources

ET-1 released histamine from guinea pig pulmonary but not peritoneal mast cells.

Endothelin(ET)-1 triggered histamine release of mast cells from pulmonary tissue but not from the peritoneal cavity of guinea pigs. The observed difference in response to ET-1 was attributable to a quantitative difference in ET-1 binding sites between both cells. The concentrations of ET-1 required for half maximal release of histamine and half maximal binding of [125I]ET-1 were approximately 0.05 and 0.08 nM, respectively. The release of histamine by ET-1 was a Ca(2+)-dependent but not a cytotoxic process. These observations, taken together, suggest that ET-1 induces histamine release from mast cells in a receptor-dependent fashion.

Animals

Regulation of endothelin-1 synthesis in cultured guinea pig airway epithelial cells by various cytokines.

To study regulatory mechanisms influencing the synthesis and release of ET-1, a potent bronchoconstrictor, epithelial cells from guinea pig tracheas were cultured to test various cytokines for the synthesis of ET-1 and its precursor, big ET-1. Cytokines tested were divided into 4 groups, based on their potential modes of action. IL-8, TNF alpha and TGF beta transiently increased the synthesis of ET-1, while EGF, PDGF and GM/CSF promoted proliferation of ET-1 synthesizing cells. IL-1 enhanced the synthesis of ET-1 precursor without mitogenesis, whereas IL-2, IL-6 and IGF-1 induced both the synthesis of big ET-1 and mitogenesis. These observations suggest that cytokines involved in damage, inflammation and repair of the airway epithelial layer regulate the synthesis and release of ET-1 by multiple mechanisms, thereby influencing airway muscle tone.

Animals

A variety of catalases and bromoperoxidases in genus Pseudomonas and their characterization.

A survey of bromoperoxidase in some Pseudomonas strains revealed that they contain different types of bromoperoxidase, catalase-bromoperoxidase and catalase. Although all Pseudomonas strains exhibited catalase activity, the enzyme isolated from P. pyrrolnitrica was named catalase-bromoperoxidase, because it catalyzed not only a catalase reaction, but also the bromination of monochlorodimedone. Except heme-type catalase-bromoperoxidase, this strain contained four isoenzymes of general nonheme bromoperoxidase, and their molecular weights were about 73,000. On the other hand, P. putida and P. aeruginosa had the usual heme-type catalase, but they differed in molecular weight and pI value. Both strains also had a nonheme bromoperoxidase which catalyzed the bromination of monochlorodimedone and aniline, and the molecular weight of each enzyme was 68,000 for P. putida and 86,000 for P. aeruginosa. Considering the results reported by Van Pée et al. [1] and Weisner et al. [2], regarding the haloperoxidases of Pseudomonas, the genus was revealed to contain a wide variety of bromoperoxidase and catalase.

Catalase

ET-1 induced bronchoconstriction in the early phase but not late phase of anesthetized dogs is inhibited by indomethacin and ICI 198615.

Intratracheally injected or aerosolized ET-1 induced quick and long-lasting bronchoconstriction of anesthetized mongrel dogs, thus increasing respiratory resistance(Rrs) with concomitantly decreasing dynamic compliance(Cdyn). As collateral resistance(Rcs) was measured postexposure to aerosolized ET-1 using wedged bronchoscope technique, ET-1 increased Rcs in a dose and time dependent manner. The increase attained maximal in 2 min and then, gradually declined. When the dogs were pretreated with the intravenous injection of 0.1 micrograms/kg ICI 198615, an inhibitor of lipoxygenase, the constrictive response was slowed down. Essentially similar results were also observed with the intravenous injection of 5 mg/kg indomethacin. Our observations suggest that the early phase of the ET-1 induced bronchoconstriction is mediated by eicosanoid metabolites.

Anesthesia, Intravenous

Prospective study of clinical gallbladder disease and its association with obesity, physical activity, and other factors.

The association of anthropometric measurements, serum tests, and life-style factors with the risk of clinical gallbladder disease was investigated in a prospective study of 7831 American men of Japanese ancestry in Hawaii. After 152,831 person-years of observation, 471 incident cases of gallbladder disease were diagnosed by histology or radiology. There was an increase in risk of gallbladder disease with a progressive increase in body mass index, height, pack-years of cigarette smoking, and diastolic blood pressure. There was a decrease in risk with an increase in physical activity, after controlling for the effect of other variables. There was also an inverse association with total caloric intake that could be related to dietary restriction in obese subjects or to the limitations of the 24-hr diet history. Serum cholesterol levels and the intake of total fat were not related to clinical gallbladder disease in this cohort.

Age Factors

Enantioselective pharmacokinetics of homochlorcyclizine. II: Disposition and metabolism of (+)-, (-)- and racemic homochlorcyclizine after oral administration to man.

The pharmacokinetics of a single oral dose of 20 mg (+)-, (-)- and racemic homochlorcyclizine (HCZ) have been studied in humans. The formation of the quarternary ammonium-linked glucuronide was an important metabolic pathway, and the metabolic process was enantioselective as a result of differing urinary excretion rates of (+)-, (-)- and racemic glucuronide. There were significant differences between (+)-, (-)- and racemic HCZ in AUC (0-14 h) and plasma protein binding, but all HCZ enantiomers were slowly absorbed and eliminated (elimination half-lives about 11 h). The results shows help to establish a more efficient dosage regimen for HCZ therapy.

Administration, Oral

Determinants of sex hormone levels in men as useful indices in hormone-related disorders.

Because the determinants of serum sex hormone levels in men have been infrequently studied, we investigated the relation of several personal characteristics to serum levels of testosterone (T), dihydrotestosterone (DHT), estrone (E1), estradiol (E2) and sex hormone-binding globulin (SHBG) among 98 Japanese American men in Hawaii, aged 52-74. The SHBG levels and T/(E1 + E2) ratios decreased progressively with increasing body mass index. The SHBG levels were also inversely associated with hematocrit levels. Serum androgen and estrogen levels did not correlate with smoking, alcohol intake, serum cholesterol, serum uric acid and blood pressure. Some of the associations observed in the present study may be implicated in the etiology of hormone-related neoplasms in men.

Aged

Endothelins constrict guinea pig tracheas by multiple mechanisms.

When tracheal rings isolated from guinea pigs were treated with endothelins (ETs), a dose-dependent constriction was observed and measured isometrically. ET potencies were ET-1 = ET-2 greater than ET-3. Dose-response curves of epithelium-denuded tracheas were shifted to the left by approximately one order of magnitude. Lung tissue contained saturable binding sites to 125I-labeled ET-1. These binding sites were replaced by ET-1 = ET-2 greater than ET-3. Because the airway tissue contained primarily ET-1 as measured by immunoassay after high-performance liquid chromatography separation, we investigated the mechanism of ET-1-induced tracheal constriction. Tracheal constriction induced by ET-1 required Ca++ in the medium. Because suppression of the contractile response by nicardipine and diltiazem was small, Ca++ entry appeared to be gated primarily through Ca++ channels rather than via voltage-dependent ones. FPL55712, SC47014A, indomethacin and OKY046 suppressed the dose-response curves, suggesting that lipid mediators are formed in response to ET-1. Diphenhydramine also altered dose-response curves, suggesting that histamine release from mast cells was partially responsible for the constriction. Pretreatment of tracheas with compound 48/80 resulted in suppression of the contractile responses. Furthermore, the combination of indomethacin, FPL55712 and diphenhydramine gave essentially identical effects. Our observations suggest that ET-1 provokes the contractile response of guinea pig tracheas not only by direct actions on smooth muscle but also by indirect actions through production of chemical mediators in mast cells and other inflammatory cells.

Animals

Purification and localization of p10, a novel protein that increases in nymphal regenerating legs of Periplaneta americana (American cockroach).

Content of a protein with a molecular mass of 10 kDa (p10) was found to increase significantly in regenerating legs of the American cockroach (Periplaneta americana). This protein was purified to homogeneity from a homogenate of regenerating legs. Partial amino acid sequencing indicated that p10 is a novel protein. Immunoblotting showed that its content in regenerating legs was 30 times that in normal legs, and decreased significantly when leg regeneration was complete. An immunofluorescence study revealed that p10 localizes exclusively on the external side of newly formed epidermis of regenerating legs.

Amino Acid Sequence

[Effect of enkephalinase inhibitor on endothelin-1 induced bronchoconstriction in guinea pigs].

Endothelin-1 (ET-1) is one of the most potent bronchoconstrictors in the guinea pig. The mechanism of its metabolism is still unclear. Phosphoramidon is known to be an enkephalinase inhibitor. We studied the effect of phosphoramidon on bronchoconstriction induced by ET-1. In the first in vitro study, a tracheal preparation was mounted in oxygenated Krebs-Ringer solution. The response was monitored by isometric transducer. Dose-response curves to ET-1 with or without phosphoramidon were obtained. Phosphoramidon potentiated ET-1 induced bronchoconstriction significantly. Next, the specific airway conductance (sGaw) was measured in conscious guinea pigs exposed to an aerosol of phosphoramidon or saline, followed by ET-1 aerosol inhalation. The ET-1 dose was increased by successively doubling the concentration. sGaw, after inhalation of phosphoramidon, was significantly reduced when exposed to ET-1. Phosphoramidon also potentiated ET-1 induced bronchoconstriction in vivo. Next, lung parenchymal tissues were prepared and placed in oxygenated Krebs-Ringer solution with or without phosphoramidon. ET-1 was added and incubated, and samples were injected into a high performance liquid chromatography column. Phosphoramidon inhibited an analysis of ET-1. These data suggest that enkephalinase plays a role in the break down of ET-1 in the airway of the guinea pig. Under the condition of decreased enkephalinase, ET-1 would potentiate bronchoconstriction.

Animals

The association of blood pressure with cancer incidence in a prospective study.

A cohort of 8,006 Japanese-American men living in Hawaii was examined from 1965 to 1968 and followed for about 20 years. The study identified 1,155 incident cases of histologically confirmed cancer and 648 deaths due to cancer. There was no association between systolic or diastolic blood pressure and total cancer incidence or deaths due to cancer. The relative risk was 1.03 for cancer incidence and 1.00 for cancer mortality for subjects with a systolic pressure of 160 mmHg or greater. Adjustment was made for age, smoking, alcohol, and measures related to obesity. When cancers of specified sites were studied, blood pressure was positively associated with the incidence of kidney cancer (17 cases). After adjustment for the significant effect of taking antihypertensive medication, the effect of blood pressure became nonsignificant. Among seven other cancer sites, there were no statistically significant associations with blood pressure after adjustment for confounding factors.

Antihypertensive Agents

Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii.

BACKGROUND: Helicobacter pylori are gram-negative spiral bacteria that are associated with chronic gastritis, a known precursor of gastric carcinoma. Persons at high risk for gastric carcinoma have been shown to have a high prevalence of H. pylori infection. METHODS: We studied the relation of H. pylori infection and gastric carcinoma in a cohort of Japanese American men living in Hawaii. The 5908 men were enrolled and examined from 1967 to 1970. By 1989, 109 cases of pathologically confirmed gastric carcinoma had been identified. The store serum of each patient with gastric carcinoma and of each matched control subject were tested for the presence of serum IgG antibody to H. pylori. RESULTS: Ninety-four percent of the men with gastric carcinoma and 76 percent of the matched control subjects had a positive test for H. pylori antibodies, for an odds ratio of 6.0 (95 percent confidence interval, 2.1 to 17.3). As the level of antibody to H. pylori increased, there was a progressive increase in the risk of gastric carcinoma (P for trend = 0.0009). The association was strong even for men in whom the diagnosis was made 10 or more years after the serum sample was obtained (odds ratio, 10.5; 95 percent confidence interval, 2.5 to 44.8). CONCLUSIONS: Infection with H. pylori is strongly associated with an increased risk of gastric carcinoma. However, most persons infected with H. pylori will never have gastric carcinoma. Therefore, other factors that increase the risk of gastric carcinoma among persons infected with H. pylori need to be identified.

Antibodies, Bacterial

Endotoxin stimulates endothelin release from cultured epithelial cells of guinea-pig trachea.

We examined the release of endothelin from cultured epithelial cells of guinea-pig trachea in response to treatment with endotoxin, using a sandwich-enzyme immunoassay. Cultured epithelial cells released endothelin in a time-dependent fashion (3, 6, 12, 24 h), and endotoxin (4-40 micrograms/ml) significantly increased endothelin release. Endotoxin (4-10 micrograms/ml) showed no cytotoxicity against epithelial cells. These results suggest that guinea-pig airway epithelial cells are capable of producing endothelin and this peptide may be related to the pathophysiological effects of endotoxin.

Animals

A study on the inactivation of wheat carboxypeptidase. Implication of the transient active monomer and the half-site reactivity.

The mechanism of inactivation of carboxypeptidase from wheat at high pH was studied kinetically and spectrophotometrically. Inactivation of wheat carboxypeptidase is characterized by initial, transient high activity, soon followed by loss of activity, accompanied by an increase in both fluorescence intensity and anisotropy and a decrease in circular dichroism. A scheme was proposed in which the enzyme undergoes dissociation into monomers, the total activity of which becomes twice that of the normal dimer on a mass basis, and soon further denatures and aggregates. Treatment of the enzyme with a bifunctional reagent partly prevented denaturation of the monomer and hence increased the peptide synthetic activity.

Carboxypeptidases

Initiation of DNA replication cycle in fertilized eggs of the starfish, Asterina pectinifera.

Starfish oocytes or eggs were inseminated at various times between first prometaphase and pronuclear stage, and were subsequently labeled with the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU) in order to detect the onset of DNA synthesis phase (S phase) during the first cell cycle using a monoclonal antibody against BrdU. The interval between fertilization and the first S phase was found to be constant (30-45 min, depending on batches) in eggs fertilized after formation of the first polar body. Eggs fertilized before first polar body formation, however, always entered the S phase 10-20 min after the second polar body formation. On the basis of these observations we conclude that (i) the chain of events triggered by fertilization, collectively called "postactivation process" for the first S phase, goes on in parallel with the process of maturation and (ii) only the final step of the postactivation process is arrested until the termination of meiosis. In eggs that had been fertilized before the first polar body formation, the female and male pronuclei exhibited uniformly distributed chromatin soon after the second polar body formation. In eggs that had been fertilized after the second polar body formation, however, the chromatin of the pronuclei remained fibrillar even during the S phase. Thus full decondensation of chromatin appears to depend on a certain advance in the postactivation process.

Animals