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Biomedical subjects

Y Hashimoto

Publications and source records attributed to Y Hashimoto.

At least 145 records · Page 8Linked to original sources

[Effects of ambroxol HCl on the guinea pig tracheal mucous secretion and the rat pulmonary surfactant secretion].

The effects of orally administered ambroxol HCl (ambroxol) on guinea pig tracheal mucous secretion and rat pulmonary surfactant secretion were investigated histologically and biochemically. Ambroxol significantly increased the number of active goblet cells in guinea pig tracheal epithelium and total mucopolysaccharide level. Moreover, ambroxol significantly increased the neutral mucopolysaccharide level and PAS-positive substance in the guinea pig tracheal submucosal glands. Ambroxol did not show a significant effect on the content of the total phosphatidylcholine in rat lung lavage fluid, while ambroxol significantly increased the ratio of disaturated phosphatidylcholine to total phosphatidylcholine. From these results, it is suggested that ambroxol increases both the tracheal mucous secretion, especially the neutral mucopolysaccharide, and pulmonary surfactant secretion and these effects reflect part of the expectorant mechanism of the drug.

Ambroxol

[Studies on angiotensin I converting enzyme (ACE) inhibitory effect of imidapril. (I). Inhibition of various tissue ACEs in vitro].

Imidapril is a newly synthesized non-sulfhydryl-containing angiotensin I converting enzyme (ACE) inhibitor. The present study describes the inhibitory effects of imidapril and its active metabolite 6366A on ACEs from various tissues and compares its effects to those of captopril, enalapril and enalaprilat in vitro. 6366A inhibited swine renal and human serum ACEs with an inhibition constant (Ki) of 0.067 nM and 0.04 nM, respectively. These values were 3 to 18 times more potent than those of the other inhibitors. The kinetic study showed that 6366A exerted competitive type inhibition. The ACE inhibition (IC50 values) of 6366A, enalaprilat and the structurally related compounds (6366DM and 6366PY) were compared in homogenates of lung, aorta, heart, brain and kidney from spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs). The inhibitory effects of 6366A on all tissue ACEs from SHRs and WKYs were the most potent among these compounds. And the inhibitory potencies of these compounds were correlated with their chemical structure. The present results suggest that 6366A may show a strong inhibitory effect on ACEs from several tissues and species due to its chemical characteristics.

Angiotensin-Converting Enzyme Inhibitors

Cloning and sequence analysis of cDNA encoding Rhizopus niveus lipase.

Complementary DNA encoding Rhizopus niveus lipase (RNL) was isolated from the R. niveus IF04759 cDNA library using a synthetic oligonucleotide corresponding to the amino acid sequence of the enzyme. A clone, which had an insert of 1.0 kilobase pairs, was found to contain the coding region of the enzyme. The lipase gene was expressed in Escherichia coli as a lacZ fusion protein. The mature RNL consisted of 297 amino acid residues with a molecular mass of 32 kDa. The RNL sequence showed significant overall homology to Rhizomucor miehei lipase and the putative active site residues were strictly conserved.

Amino Acid Sequence

Are there M cells in the cecal tonsil of chickens?

A unique morphological cell type, "microfold or membranous (M) cell-like cell", was detected electron-microscopically in the cecal tonsil epithelium of the chicken. M cell-like cells possessed a few short microvilli of irregular arrangement and a large number of lymphocytes and macrophages wedged into their basal surfaces. Triticum vulgaris was found to bind to M cell-like cells. With horseradish peroxidase (HRP) treatment, M cell-like cells showed an active HRP uptake just as did the neighbouring usual absorptive epithelial cells. No uptake of colloidal carbon particles from the intestinal lumen was recognized in any part of the intestinal epithelium. These results suggest that M cell-like cells of the chicken possess some M cell-characteristic morphological and histochemical features, but that their active uptake of foreign materials is not so developed as in mammalian M cells.

Animals

Thyroxine-binding globulin variant (TBG-Kumamoto): identification of a point mutation and genotype analysis of its family.

Thyroxine-binding globulin (TBG) is the major thyroid hormone transport protein. Several inherited TBG variants resulting in partial or complete TBG deficiencies have been shown to be caused by either one or two nucleotide substitutions, or one nucleotide deletion in the coding regions of the TBG gene. In this report, a Japanese female patient (proband) with hyperthyroid state, whose lower TBG levels did not return to normal under the euthyroid state after treatment was examined. Genomic DNA samples from the proband with thyroxine-binding globulin deficiency (termed TBG-Kumamoto) and her family were subjected to the polymerase chain reaction, and the generated DNA fragments were sequenced. A single nucleotide substitution in the codon for the amino acid 363 of native TBG molecule (CCT to CTT) was found, resulting in the replacement of proline by leucine. It was revealed that the proband was a heterozygote and her father was a hemizygote. The mutation was confirmed by the allele-specific amplification of genomic DNAs from the proband and her father using oligonucleotide primers of normal or mutant residues at the 3' position in the polymerase chain reaction. These results indicate that the abnormality of TBG-Kumamoto is the consequence of this mutation. Genetically, this point mutation observed in TBG-Kumamoto might be classified as a new type of TBG deficiency.

Adult

A Ca(2+)-independent protein kinase C, nPKC eta: its structure, distribution and possible function.

Protein kinase C consists of a protein family which can be classified into two major groups: Ca(2+)-dependent conventional protein kinase C and Ca(2+)-independent novel protein kinase C (nPKC). Among eight known members of protein kinase C family, we found that nPKC eta (eta) isolated from cDNA library of mouse skin, is most abundant in epithelial tissues including skin and epithelia of digestive and respiratory tracts. These data suggest potential role of this isoform in growth, differentiation and carcinogenesis of epithelial tissues.

Animals

Basic approach to application of liposomes for cancer chemotherapy.

The method for augmentation of systemic in vivo anticancer effect of liposomes (Lip) containing adriamycin (ADM) and endocytosis activity of cancer cells to liposomal preparations have been studied. Encapsulation of ADM in liposomes increases its maximal tolerated dose and pretreatment of animals bearing tumor with tumor necrosis factor alpha (TNF) resulted in effective targeting of ADM-Lip to tumor, leading to its augmented therapeutic effect, but only when TNF and ADM-Lip were administered with an appropriate interval. All human tumor cell lines tested showed endocytosis activity to liposomes but the activity was differed among different tumor cell lines.

Animals

Diminished acetylcholine-induced vasodilation in renal microvessels of cyclosporine-treated rats.

The mechanisms mediating cyclosporin A (CsA)-induced nephrotoxicity have not been established, but damage to endothelial cells by CsA has been proposed as an important factor. In the study presented here, whether endothelial cell function is impaired in the renal vasculature of CsA-treated rats is investigated. The vasodilatory effects of acetylcholine (ACH) on norepinephrine (NE)-induced microvascular constriction in isolated perfused hydronephrotic rat kidneys pretreated with CsA were therefore examined. Hydronephrosis was established to permit direct visualization of renal microvessels. Nephrotoxicity was induced by s.c. injection of CsA (60 mg/kg/day for 5 days). NE (0.3 microM)-induced afferent arteriolar (AA) constriction was exaggerated in CsA rats as compared with that in vehicle (olive oil)-treated control rats. (reduction in diameter of -34 +/- 3 (SE) versus -26 +/- 2%; P less than 0.05). Similarly, efferent arteriolar (EA) constriction by NE in CsA rats exceeded that of controls (-34 +/- 2 versus -22 +/- 3%; P less than 0.01). The vasodilatory responses evoked by ACH were blunted in CsA rats. The AA response to ACH in CsA rats was significantly decreased (P less than 0.005) at ACH concentrations from 1 nM to 1 microM. Similarly, ACH (1 nM to 100 nM) induced less EA vasodilation in CsA rats (P less than 0.025). In control and CsA rats, the addition of nitro-L-arginine abolished AA and EA vasodilation induced by ACH, suggesting that the sustained vasodilatory responses of AA and EA to ACH are mainly dependent on nitric oxide synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

Endothelial cell destruction by polymorphonuclear leukocytes incubated with sera from patients with systemic lupus erythematosus (SLE).

When normal polymorphonuclear leukocytes (PMN) were incubated with sera from patients with active systemic lupus erythematosus (SLE), a significantly increased cytotoxicity against human cultured vascular endothelial cells (EC), compared with normal control sera, was demonstrated by the standard 51Cr release method. The degree of this cytotoxicity was correlated with the immune complex level in each serum. The cytotoxicity did not correlate with the presence of anti-EC antibody. An absorption study with C1q-Sepharose 4B further suggested that the immune complexes are the factor which induce cytotoxicity. A gel fractionation study, however, indicated the heterogenity of the cytotoxic activity, and suggested the possible contribution of other substances including anti-EC, at least in some of the patients. This type of cytotoxicity may initiate the inflammatory process including vascular damage of the disease.

Adult

Comparative study of renin expression in the coagulating glands of C57BL/6 and Balb/c mice.

The comparative localisation of renin in the genital organs, especially in the coagulating glands of male mice of the strains C57BL/6 and Balb/c, was investigated using immunocytochemical, immunoelectron microscopical and Northern blot techniques. Dot-like reactions for renin, of varying diameters, were detected immunocytochemically in the epithelial cells of coagulating glands of C57BL/6 mice, but not in those of Balb/c mice. In both strains, many electron dense granules differing in content and morphology were observed in the epithelial cells of the coagulating glands. Crystalline materials were sometimes contained in these granules. Colloidal gold particles indicating the presence of renin were detected in the electron dense granules of C57BL/6 mice, in which they showed a heterogeneous distribution and were especially located on the crystalline structure. No positive reaction was detected in these crystalline structures in Balb/c mice. Renin mRNA was detected in the coagulating glands of both C57BL/6 and Balb/c mice by Northern blot analysis. However, the expression in C57BL/6 coagulating glands was stronger than that in Balb/c. These findings suggest that renin is synthesised and released in the coagulating glands.

Animals

[Effects of epithelium removal and cooling on tracheal contraction in guinea pigs].

We investigated the effects of epithelium removal and cooling (32 degrees C, 27 degrees C, 22 degrees C) on isolated tracheal smooth muscle contraction induced by bethanechol (BCh), acetylcholine (ACh), histamine (Hist), and KCl in guinea pigs. The pD2 values (-logED50) increased in the epithelium damaged group compared with the intact group when ACh was administered at 37 degrees C, 32 degrees C, 27 degrees C and 22 degrees C, with histamine at all four temperature conditions, and with KCl at 37 degrees C, 32 degrees C and 27 degrees C. In both groups, the pD2 values for BCh, ACh, and KCl tended to decrease as temperature was lowered, and significant decrease in pD2 was observed at 27 degrees C. In contrast, the pD2 value for histamine tended to increase as temperature was lowered in every group. Concerning these agents, we conclude that epithelium removal and cooling exert neither significant nor consistent effect on tracheal epithelial function.

Acetylcholine

Lobenzarit disodium (CCA) inhibits the proliferation of human endothelial cells and the activity of DNA polymerase alpha.

N-(2)-Carboxyphenyl-4-chloroanthranilic acid disodium [Lobenzarit disodium (CCA)] is widely used for the treatment of patients with RA in Japan; however, the pharmacological mechanism of the compound is still unclear. In this report, the effect of CCA on the proliferation and DNA synthesis of endothelial cells was examined. CCA inhibited DNA synthesis in endothelial cells at a rather lower concentration than that in fibroblasts and HeLa cells. The DNA polymerase alpha activity was inhibited by CCA at a lower concentration than E. coli DNA polymerase I and avian myeloblastosis virus reverse transcriptase. Thus, CCA is a potent inhibitor of DNA polymerase alpha and this inhibitory effect could cause the inhibition of endothelial cell proliferation, which may be related to the therapeutic and pharmacological mechanisms of CCA.

Anti-Inflammatory Agents, Non-Steroidal

[Chlamydia trachomatis infection with symptoms and signs of the central nervous system damage--a case report].

A 32-year-old woman developed myalgia, fever, consciousness disturbance, mental disorder, pyramidal tract signs and meningeal irritation signs at about 2 months after a normal labor. Laboratory examination showed hypopituitarism (decreased ACTH, TSH), renal dysfunction and hypercalcemia. A variety of antibiotics, acyclovir and gamma-globulin failed to improve her symptoms. A diagnosis of Chlamydia trachomatis infection was considered from the elevated antibody titers. In this case, minocycline was very effective. Rarely Chlamydia trachomatis infection involved general organs, including the central nervous system. It was interesting that she had endocrine disorders. We must take a look for Chlamydia trachomatis infection because this infection infrequently involves general organs, including the central nervous system and minocycline is very effective for this infection.

Adult

[Use of omeprazole for premedication].

Omeprazole, a proton pump inhibitor was used for premedication for general anesthesia, and its effects on gastric secretion and serum gastrin level were investigated in 60 patients. The patients were divided into the following 4 groups and each group received one of the following medications; (I) a tablet of omeprazole 20 mg before sleep at the night before the surgery, (II) a tablet 2 hours before the induction of anesthesia, (III) one on the night before and another tablet 2 hours before the induction, or (0) no tablet. In the patients who received any dose of the drug, the volume of gastric juice at the beginning of the surgery was significantly less than that in those who received no drug (P less than 0.05). Gastric pH showed a tendency to increase depending on the dose of omeprazole (0 less than I less than II less than III), but it was not significant. No significant change in serum gastrin level was observed in this study. A 20 mg omeprazole tablet may not be adequate as the premedication for general anesthesia.

Administration, Oral