Rapidly reducible and slowly reducible complexes of heme a.
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Biomedical subjects
Publications and source records attributed to S Horie.
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The effect of neuroactive progesterone metabolites, 5alpha- and 5beta-pregnan-3alpha-ol-20-one, and their stereoisomers at the 3 C site, 5alpha- and 5beta-pregnan-3beta-ol-20-one, on gastric acid secretion was investigated in urethane-anesthetized rats. Both 5alpha- and 5beta-pregnan-3alpha-ol-20-one dose-dependently (0.3-3 mg x kg(-1), i.v.) stimulated gastric acid secretion with an early onset of action. Their potency and efficacy were almost the equivalent of one another. In contrast, their stereoisomers did not have a significant effect even at 10 mg x kg(-1) (i.v.). The 5beta-pregnan-3alpha-ol-20-one (3 mg x kg(-1), i.v.)-stimulated gastric acid secretion was remarkably inhibited by bilateral vagotomy or pretreatment with atropine (1 mg x kg(-1), i.v.). An antagonist of the GABA(A) receptor, picrotoxin, at 3 and 6 mg x kg(-1) (i.v.), significantly inhibited the 5beta-pregnan-3alpha-ol-20-one (3 mg x kg(-1), i.v.)-stimulated gastric acid secretion. These results indicate that naturally occurring neuroactive steroids, 5alpha- and 5beta-pregnan-3alpha-ol-20-one, stimulate gastric acid secretion in a stereoselective and dose-dependent manner in urethane-anesthetized rats. It is likely that the action of these neuroactive steroids is of central origin and that interaction with GABA(A) receptors and stimulation of vagal pathway are involved in its mechanism of action.
We previously reported that endogenous nitric oxide (NO) is involved in the peripheral control of gastric acid secretion induced by some secretagogues, and that endogenous NO is involved in the acid secretion process via histamine release from histamine-containing cells. However, the stimulus-secretion coupling in the cells remains to be clarified. In the present study, we investigated the effect of dibutyryl cyclic GMP on gastric acid secretion in mouse isolated stomach and on histamine release in gastric mucosal cells, in comparison with those of dibutyryl cyclic AMP. Dibutyryl cyclic GMP (300 microM) produced a slight but significant increase of gastric acid secretion, which was completely inhibited by the histamine-H2 receptor antagonist famotidine. In contrast, dibutyryl cyclic GMP (1 mM) markedly inhibited histamine-induced acid secretion. Dibutyryl cyclic AMP (100 microM) produced a sustained increase of gastric acid secretion. The pretreatment with famotidine partially inhibited dibutyryl cyclic AMP-induced gastric acid secretion. Dibutyryl cyclic GMP and dibutyryl cyclic AMP significantly increased the histamine release from gastric mucosal cells. These results suggest that both intracellular cyclic GMP and cyclic AMP act as second messengers for histamine release in the histamine-containing cells, probably ECL cells. On the other hand, in gastric parietal cells, cyclic AMP has a stimulatory effect on gastric acid secretion, whereas cyclic GMP has an inhibitory effect.
To investigate the effect of SG-210, a potent inhibitor selective to aldose reductase (ARI), on the impaired polyol pathway, we examined biochemically and histologically the potencies of this compound in streptozotocin-induced diabetic or galactosemic rats. The study with diabetic rats showed that SG-210 (1-10 mg x kg(-1)) dose-dependently inhibited sorbitol accumulations in erythrocytes, sciatic nerves, lens, and retina with ED50 values of 1.4, 1.3, 3.5, and 4.6 mg x kg(-1), respectively. Zenarestat, currently under clinical trials both in Japan and the United States, was about two or over five times less potent than SG-210 in suppressing sorbitol contents of erythrocytes or other tissues, respectively. Epalrestat, commercially available, was much less potent in reducing the contents with ED50 values of more than 30 mg x kg(-1) in all of the cells and the tissues examined. An extensive study using galactosemic rats indicated that SG-210 (3-30 mg x kg(-1)) inhibited galactitol accumulations in lens and retina as well as in erythrocytes, preventing the progression of histological abnormalities in lens accompanied by the reduction in galactitol contents. Epalrestat (3-30 mg x kg(-1)) failed to show any significant effects. Pharmacokinetic studies suggested that SG-210 has a high bioavailability and possesses a long half-life in rats (ca. 10 h). Taken together with its excellent pharmacokinetic profiles, the potent suppressive effects of SG-210 observed in this study may be available as a new treatment of diabetic complications.
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Two microsatellite markers, D16S283 and D16S284, closely linked to the locus of autosomal polycystic kidney disease (PKD1), were amplified in a Japanese population sample by the polymerase chain reaction to investigate differences in allele frequencies between Japanese and Caucasian populations. Ten D16S283 alleles and four D16S284 alleles were discerned among 53 Japanese. The observed heterozygosities of D16S283 and D16S284 in this study were 76.8 and 9.1%, and the polymorphism-informative contents were 0.75 and 0.09, respectively. Several allele frequencies of D16S283 exhibited significant differences. The Y9 allele (19 CA repeats, 91 bp) was the most frequent in both populations but its frequency in Caucasians was higher. The second most frequent allele was different: Y6 (22 CA repeats, 97 bp) in Japanese and Y10 (18 CA repeats, 89 bp) in Caucasians. Y8 (20 CA repeats, 93 bp) and Y11 (17 CA repeats, 87 bp) alleles also showed different frequencies. For D16S284, no differences in allele frequencies were observed between the two populations. As we observed differences in allele frequencies for D16S283, an association study with this polymorphism should carefully control for the ethnic origin of subjects.
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There are few reports regarding the measurement of cytokines and surface analysis of eosinophils in Churg-Strauss syndrome (CSS). To examine the pathophysiology of CSS, concentrations of cytokines in serum and bronchoalveolar lavage fluid (BALF), and surface antigens on peripheral blood eosinophils were analyzed in five patients with CSS. Concentrations of cytokines (interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-3 (IL-3), interleukin-5 (IL-5) and granulocyte/macrophage colony stimulating factor (GM-CSF) were measured using ELISA. Surface antigens on eosinophils in peripheral blood were analyzed using flow cytometry. A concentration of interleukin-5 (IL-5) and TNF-alpha in serum was detected in five cases; however IL-1 beta, GM-CSF, and IL-3 were detected in 3 of 5, 2 of 5, and 1 of 5 patients, respectively. In BALF, TNF-alpha and IL-5 were detected in 2 of 3 and 1 of 3 patients, respectively; however, neither IL-1 beta, GM-CSF, nor IL-3 was detected in any. Newly expressed surface antigens such as CD25, CD4, and CD69 were observed on peripheral blood eosinophils in five cases. CD54 and HLA-DR were expressed in 4 of 5 and 3 of 5 patients, respectively. Eosinophils in peripheral blood are activated to various degrees, possibly depending on cytokine stimulation. This eosinophil activation may be related to the clinical stage of CSS.
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Cytologic examination of sputum samples from an elderly patient revealed the presence of two cell populations: squamous cell carcinoma cells and rhabdomyosarcoma cells. The abnormal squamous cells showed both keratinizing and nonkeratinizing forms while some of the rhabdomyosarcoma cells showed cross striations. Sputum cytology was thus able to suggest a diagnosis of pulmonary carcinosarcoma. Histologically, the tumor was composed mainly of sarcomatous tissue showing various kinds of cells: fusiform or fibrous cells, round anaplastic cells, spindled cells with typical cross striations and myoblastic cells. A partially myxomatous degeneration was present. In addition, squamous cell carcinoma proliferated along the bronchi and formed small invasive cell nests in the sarcomatous tissue. No transition between the two components was noted. Both cellular constituents had metastasized to an interlobar lymph node.