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Biomedical subjects

H Yamaguchi

Publications and source records attributed to H Yamaguchi.

At least 685 records · Page 38Linked to original sources

[In vitro antifungal activity of omoconazole nitrate, a novel imidazone antimycotic drug, against clinical isolates from patients with cutaneous mycosis].

In vitro antifungal activities of omoconazole nitrate (OMZ), a novel antifungal imidazole antimycotic drug, are examined against clinical isolates obtained from patients with cutaneous mycosis and its activity was compared with that of bifonazole (BFZ). The clinical isolates tested were 70 of dermatophytes including Trichophyton rubrum (47 isolates), T. mentagrophytes (22 isolates), Microsporum gypseum (1 isolate), and 27 isolates of Candida albicans. MIC values of OMZ to dermatophytes distributed in a range of < or = 0.04 to 0.63 microgram/ml were similar to those of BFZ (< or = 0.04 to 1.25 micrograms/ml). MIC values of OMZ to C. albicans were in a range of 0.16 to 2.5 micrograms/ml indicating that OMZ had more potent activities than BFZ (1.25 to 5 micrograms/ml). These results showed that in vitro antifungal activities of OMZ against clinical isolates of dermatophytes and C. albicans were greater than or similar to those of BFZ.

Antifungal Agents↗

[Surgical pathology of infective endocarditis].

Underlying pathologic disorders of infected valves were analyzed in 36 consecutive patients with infective endocarditis (from April 1987 to May 1995) of 18 aortic, 11 mitral and 8 prosthetic valves. Among 29 cases of native valve endocarditis, 27 had known organic changes [aortic valve prolapse 8, bicuspid aortic valve 4, annuloaortic ectasia 1, mitral valve prolapse 9 (including 2 cases associated with hypertrophic cardiomyopathy), looping chordae 1, rheumatic heart disease 4]. However, the remaining two cases had unknown etiology. Histological examination of these two aortic valves revealed proliferation of small vessels and remnants of vascular smooth muscle cells, suggesting postinflammatory valve prolapse. Five cases with definite pathology had no clinical signs of infection. The preponderance of surgically resected valves with infective endocarditis in Japan is non-rheumatic in origin.

Adult↗

Long-term stability following surgical orthodontic treatment of mandibular prognathisms: investigation by means of lateral X-ray cephalogram.

The purpose of this study was to investigate the long-term stability of jaw relations and occlusion following surgical orthodontic treatment of mandibular prognathisms and skeletal openbites. Subjects consisted of fifteen adult patients. Ten patients underwent the sagittal split ramus osteotomy (SSRO) of the mandible and five patients underwent two jaw surgery (Le Fort I osteotomy of the maxilla and SSRO of the mandible). They were observed over five years after the end of active treatment, and lateral X-ray cephalograms were taken at each stage. In the SSRO group, pogonion was retrograded an average of 8.7mm due to the operation and it was further replaced 0.4mm backward after the end of active treatment. Although the vertical distance between nasion and menton decreased 2.9mm between the operative period, it increased 1.8mm after the end of active treatment. On the other hand, in the two jaw surgery group, point A was advanced 4.0mm forward and < SNA increased 3.1 degrees between the operative period. Pogonion was retrograded 11.4mm between the same period, but moved 0.7mm forward after the end of active treatment. A comparison of the osteosynthesis methods revealed that pogonion in the wiring group was retrograded 8.3mm backward between the operative period, but moved 2.1mm forward during the postsurgical orthodontic treatment. Pogonion in the rigid group was retrograded 12.6mm backward between the operative period, but moved 1.6mm forward during the postsurgical orthodontic treatment. However, both groups were stabilized completely after the end of active treatment. A comparison of the differences in the orthodontic treatment method revealed that < Ul-SN in the extraction group inclined 8.3 degrees lingually during presurgical orthodontic treatment, but it tipped 7.0 degrees labially during the postsurgical orthodontic treatment and inclined 3.4 degrees lingually after the end of active treatment. < Ul-SN in the non-extraction group inclined 5.5 degrees lingually during the presurgical orthodontic treatment, but it tipped 2.0 degrees labially during the postsurgical orthodontic treatment and inclined 1.9 degrees lingually after the end of active treatment.

Adult↗

Amyloid beta protein in rat soleus muscle in chloroquine-induced myopathy using end-specific antibodies for A beta 40 and A beta 42: immunohistochemical evidence for amyloid beta protein.

Previous immunohistochemical studies from this laboratory demonstrated that monoclonal antibodies raised against various regions of amyloid precursor protein (APP) (i.e., N-terminus, amyloid beta protein (A beta), and C-terminus) strongly labeled vacuoles in chloroquine-induced myopathy-affected muscle in rats. In this study, we used antibodies end specific for the A beta 40 and A beta 42 species, and a monoclonal antibody to A beta 1-9 which reacts with APP and A beta. Most vacuoles clearly reacted with anti-A beta 1-9, while about half reacted with anti-A beta 42, and only a few reacted with anti-A beta 40. These results demonstrate that vacuoles in chloroquine-induced myopathy-affected muscle contain cleaved A beta, and that distribution of the two major A beta species is similar to what is observed in A beta deposition in Alzheimer's disease (AD)-affected brain. This provides further evidence that chloroquine-induced myopathy in rats provides a suitable model to understand APP processing into A beta, and the role of APP in terms of the pathogenesis of AD.

Amyloid beta-Peptides↗

Thermostable peroxidase activity with a recombinant antibody L chain-porphyrin Fe(III) complex.

In order to engineer a new type of catalytic antibody, we attempt to use a monoclonal antibody L chain as a host protein for a porphyrin. TCPP (meso-tetrakis(4-carboxyphenyl)porphyine) was chemically synthesized and Balb/c mice were immunized using TCPP as a hapten. Two hybridoma cells (03-1, 13-1), that produce monoclonal antibody against TCPP, were obtained. Genes for both H and L chains of monoclonal antibodies were cloned, sequenced and overexpressed using E. coli as a host. ELISA and fluorescence quenching method show that the independent antibody L chains from both Mab03-1 and Mab13-1 have specific interaction with TCPP. Furthermore, the recombinant antibody L chain from Mab13-1 exhibits much higher peroxidase activity than TCPP Fe(III) alone. The enzyme activity was detectable with pyrogallol and ABTS (2,2-azinobis-3-ethylbenzthiazolin-6-sulfonic acid) but not with catechol. This new catalytic antibody was extremely thermostable. Optimum temperature of the peroxidase reaction by the complex of 13-1L chain and TCPP Fe(III) was 90 degrees C, while that the TCPP Fe(III) alone was 60 degrees C.

Amino Acid Sequence↗

A hotspot of spontaneous and UV-induced illegitimate recombination during formation of lambda bio transducing phage.

To study the mechanism of spontaneous and UV-induced illegitimate recombination, we examined the formation of the lambda bio specialized transducing phage in Escherichia coli. Because most lambda bio transducing phages have double defects in the red and gam genes and have the capacity to form a plaque on an E. coli P2 lysogen (Spi- phenotype), we selected lambda bio transducing phage by their Spi- phenotype, rather than using the bio marker. We determined sequences of recombination junctions of lambda bio transducing phages isolated with or without UV irradiation and deduced sequences of parental recombination sites. The recombination sites were widely distributed on E. coli bio and lambda DNAs, except for a hotspot which accounts for 57% of UV-induced lambda bio transducing phages and 77% of spontaneously induced lambda bio transducing phages. The hotspot sites on E. coli and lambda DNAs shared a short homology of 9 bp. In addition, we detected direct repeat sequences of 8 bp within and near both the bio and lambda hotspots. A recA mutation did not affect the frequency of the recombination at the hotspot, indicating that this recombination is not a variant of recA-dependent homologous recombination. We discuss a model in which the short homology as well as the direct repeats play essential roles in illegitimate recombination at the hotspot.

Bacteriophage lambda↗

Amyloid beta peptide induces cytoplasmic accumulation of amyloid protein precursor via tau protein kinase I/glycogen synthase kinase-3 beta in rat hippocampal neurons.

Exogenous application of synthetic amyloid beta protein (A beta) is known to induce neurotoxic effects in rat hippocampal culture. We report here that A beta (25-35) induces accumulation of amyloid precursor protein (APP) derivatives in the cytoplasm of neurons. At the same time, the level of the secreted form of APP released into the culture medium decreases. Tau protein kinase I/glycogen synthase kinase-3 beta (TPK I/GSK-3 beta) antisense oligonucleotide blocked APP accumulation and prevented neuronal death. These results provide evidence that APP accumulation after A beta treatment is regulated by TPK I/GSK-3 beta. A beta neurotoxicity is probably mediated via phosphorylation of tau by TPK I/GSK-3 beta, resulting in an impairment of axonal transport, and cytoplasmic accumulation of APP.

Amyloid beta-Peptides↗

Two novel rat guanylin molecules, guanylin-94 and guanylin-16, do not increase cyclic GMP production in T84 cells.

Guanylin, a 15-amino acid peptide homologue of bacterial heat-stable enterotoxins, is an endogenous activator of guanylate cyclase C (GC-C). We isolated two novel guanylin molecules from rat intestinal mucosa. They contained guanylin-15 at their C-termini and were identified as guanylin-94 and guanylin-16 by amino acid sequencing and mass spectrometry. Guanylin-94 and guanylin-16 in total account for 85% of guanylin molecules in both the small and large intestine, guanylin-15 being a minor component. Rat guanylin-94 and guanylin-16 did not increase cyclic GMP production in T84 cells. Identification of the post-translational processing products of guanylin should provide a better understanding of the biosynthesis of the peptide.

1-Methyl-3-isobutylxanthine↗

Structures of metal sites of oxidized bovine heart cytochrome c oxidase at 2.8 A.

The high resolution three-dimensional x-ray structure of the metal sites of bovine heart cytochrome c oxidase is reported. Cytochrome c oxidase is the largest membrane protein yet crystallized and analyzed at atomic resolution. Electron density distribution of the oxidized bovine cytochrome c oxidase at 2.8 A resolution indicates a dinuclear copper center with an unexpected structure similar to a [2Fe-2S]-type iron-sulfur center. Previously predicted zinc and magnesium sites have been located, the former bound by a nuclear encoded subunit on the matrix side of the membrane, and the latter situated between heme a3 and CuA, at the interface of subunits I and II. The O2 binding site contains heme a3 iron and copper atoms (CuB) with an interatomic distance of 4.5 A; there is no detectable bridging ligand between iron and copper atoms in spite of a strong antiferromagnetic coupling between them. A hydrogen bond is present between a hydroxyl group of the hydroxyfarnesylethyl side chain of heme a3 and an OH of a tyrosine. The tyrosine phenol plane is immediately adjacent and perpendicular to an imidazole group bonded to CuB, suggesting a possible role in intramolecular electron transfer or conformational control, the latter of which could induce the redox-coupled proton pumping. A phenyl group located halfway between a pyrrole plane of the heme a3 and an imidazole plane liganded to the other heme (heme a) could also influence electron transfer or conformational control.

Animals↗

Potent inhibitors of acyl-CoA:cholesterol acyltransferase. Structure-activity relationships of novel N-(4-oxochroman-8-yl)amides.

Novel N-(4-oxochroman-8-yl)amide derivatives 1 were synthesized and tested for their ability to inhibit rabbit small intestinal ACAT (acyl-CoA:cholesterol acyltransferase) in vitro and to lower serum total cholesterol in cholesterol-fed rats in vivo. Among the synthesized compounds, N-(7-alkoxy-4-oxochroman-8-yl)amide derivatives showed potent ACAT inhibitory activity both in vitro and in vivo. The structure-activity relationships of these N-(4-oxochroman-8-yl)amides and related compounds are discussed on the basis of these two assays. The carbonyl group at position 4 of the 4-chromanone was essential for potent ACAT inhibitory activity. N-(Chromon-8-yl) derivatives were less potent than N-(4-oxochroman-8-yl) derivatives. An alkoxy group at position 7 of the 4-chromanone moiety was important for potent ACAT inhibitory activity. In the N-(7-alkoxy-4-oxochroman-8-yl)amide derivatives, another necessary factor to elicit the potent ACAT inhibitory activity was lipophilicity of the molecules. The highly lipophilic acid amides N-(7-methoxy-4-oxochroman-8-yl)-2,2-dimethyldodecanamide (35) and 4-[[6-(4-chlorophenoxy)hexyl]oxy]-N-(7-methoxy-4-oxochroman-8- yl)benzamide (63) showed potent activity. Introduction of a highly lipophilic alkoxy group at position 7 of the 4-chromanone moiety instead of methoxy group also resulted in potent activity. In this case, highest inhibitory activity was obtained by N-[7-(decyloxy)-4-oxochroman-8-yl]-2,2-dimethylpropanamid e (65). The most potent compound, N-(7-methoxy-4-oxochroman-8-yl)-2,2-dimethyldodecanamide (35, TEI-6522), showed significant ACAT inhibitory activity (rabbit small intestine IC50 = 13 nM, rabbit liver IC50 = 16 nM), foam cell formation inhibitory activity (rat peritoneal macrophage IC50 = 160 nM), and extremely potent serum cholesterol-lowering activity in cholesterol-fed rats (61% at a dose of 0.1 mg/kg/day po).

Animals↗

Effects of simvastatin on plasma lipoprotein subfractions, cholesterol esterification rate, and cholesteryl ester transfer protein in type II hyperlipoproteinemia.

We investigated the effects of simvastatin on plasma levels of lipoprotein subfractions, cholesterol esterification rates and activities of cholesteryl ester transfer protein in 28 patients with type II hyperlipoproteinemia (i.e., nonfamilial hyperlipoproteinemia type IIa and type IIb, and heterozygous familial hypercholesterolemia (FH)). Plasma levels of VLDL-cholesterol (C) and VLDL-triglyceride (TG) were significantly reduced overall by 12.9 +/- 58.0% (mean +/- S.D.; P < 0.05) and 4.2 +/- 54.2% (P < 0.05) respectively, but not in FH. Plasma levels of IDL-C and IDLT-G were decreased overall by 23.2 +/- 47.5% (P < 0.001) and 12.3 +/- 49.7% (P < 0.05), respectively, again mainly due to decreases seen in nonfamilial type II hyperlipoproteinemia. Plasma levels of LDL1 (1.019 < d < 1.045)-C and LDL1-TG were significantly reduced by 33.1 +/- 12.9% (P < 0.001) and 23.3 +/- 24.7% (P < 0.001), respectively. Plasma levels of LDL2 (1.045 < d < 1.063)-C were significantly reduced by 22.9 +/- 18.1% (P < 0.001) overall but not in FH. Gradient PAGE showed no consistent changes in the distribution of LDL particles. Thus, plasma levels of all apo B-containing lipoprotein subfractions were reduced by simvastatin, but its effects varied among the three subgroups. Cholesterol esterification rates were suppressed by 9.3 +/- 19.7% (P < 0.01) and activities of cholesteryl ester transfer protein were reduced by 30.6 +/- 21.5% (P < 0.001). Changes in CETP activity and in plasma levels of cholesterol in lipoprotein subfractions were not correlated. Thus, the changes in distribution of lipoprotein subfractions were not due mainly to CETP suppression.

Adult↗

Etiology of gastric remnant cancer with special reference to the effects of denervation of the gastric mucosa.

BACKGROUND: Gastric mucosal blood flow, secretion of mucin, and renewal of the gastric mucosal cells are considered to be defensive factors against gastric mucosal injuries. These factors are regulated by the nervous system and neuropeptides. Gastrectomy may affect this regulation and induce gastric mucosal changes, such as atrophic gastritis and carcinoma. The effects of denervation of the gastric mucosa on tumorigenesis of the remnant stomach were investigated. METHODS: Using male Wistar rats, four groups of Billroth I (B-I)gastrectomy, Billroth II (B-II) gastrectomy, and those with denervation were conducted. Subdiaphragmatic truncal vagotomy was performed in the denervated group. Thirty weeks after the operations, histologic examination and periodic acid-Schiff--Alcian blue (PAS-AB) staining of the gastric mucosa, analysis of cell kinetics of the gastric mucosa by immunohistochemistry of proliferating cell nuclear antigen, and measurement of intragastric pH, intragastric bile acid concentration, and serum gastrin levels were performed. No carcinogenic agents were given. RESULTS: The B-I group showed no remarkable gastric mucosal changes, but B-I with denervation showed a significant increase in the development of tumor (67%) and carcinoma (42%). In the B-II groups, the denervation induced a significant increase in tumorigenesis, from 22% to 58%. Analysis of cell kinetics revealed a significant increase of labeling index in those groups that developed tumors. PAS-AB staining showed a decrease of PAS positive mucin but an increase of acidic mucin-producing cells in the denervated groups, suggesting an increase in the number of immature cells that are more susceptible to atrophic gastritis and carcinoma. There was no close relationship between tumorigenesis and intragastric pH, intragastric bile acid concentration, or serum gastrin levels. CONCLUSIONS: After gastrectomy, not only duodenogastric reflux, but also the denervation of the gastric mucosa play an important role in the etiology of gastric remnant cancer.

Animals↗

Vocal cord paralysis in patients with thoracic esophageal carcinoma.

Of 478 consecutive patients with intrathoracic esophageal carcinoma, 5% had vocal cord paralysis. In two thirds of the patients with vocal cord paralysis, the paralysis was caused by a metastatic lymph node located along the recurrent laryngeal nerve. These findings indicate that the possibility exists for radical surgery by esophagectomy and resection of the metastatic lymph node infiltrating the recurrent laryngeal nerve, even in patients with vocal cord paralysis. However, in only two patients was radical surgery accomplished. None of the 24 patients with paralysis survived without disease for more than 1 year. Thus, in patients with vocal cord paralysis, the need for combined therapy should be emphasized.

Adenocarcinoma↗