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Biomedical subjects

H Sakai

Publications and source records attributed to H Sakai.

At least 1,063 records · Page 59Linked to original sources

The effects of malotilate on hepatic drug metabolizing systems in different strains of rats.

1. In Sprague-Dawley (SD) rats treated for 7 days with malotilate (MAL:250 mg/kg, p.o.), cytochrome P-450 and b5 contents, aminopyrine N-demethylase and heme oxygenase activities were significantly increased. In Wistar rats, cytochrome b5 content and heme oxygenase and delta-aminolevulinic acid synthetase activities were found to be significantly increased. 2. Among the antipyrine metabolites excreted in urine during the 24 hr after antipyrine (100 mg/kg, i.p.) administration, norantipyrine increased significantly in Sprague-Dawley rats, while a significant increase of 4-hydroxyantipyrine was observed in Wistar rats. 3. The serum dimethadione/trimethadione ratio was only found to be significantly increased in Sprague-Dawley rats. 4. These results indicate that malotilate may have inducible effects on hepatic drug metabolizing enzymes, and that it affects the various cytochrome P-450 isozymes from different strains of rat in different ways.

Alkaline Phosphatase↗

DNA damage caused by ascorbate in the presence of Cu2+ induces mutations.

The DNA damage induced by ascorbate in the presence of Cu2+ was analyzed by sequencing, and the mutagenic consequences of damages to plasmid pUC18 lacZ' were assayed in a forward repairing system in E. coli JM109 in vivo. Ascorbate induced two classes of DNA damage in the presence of Cu2+, one being non-base-specific direct strand cleavage, and the other being sequence-specific base modification labile to alkali treatment. Radicals generated from ascorbate hydroperoxide were involved in DNA damaging reactions. Ascorbate and Cu2+ caused mutations in pUC18 lacZ' gene. The mutation frequency by this method was about 10(-4) at 18% survivors when measured as a loss of alpha-complementation. All the mutations found were single-base substitutions that occurred in the structural part of the lacZ' gene. They were predominantly G:C----A:T transitions.

Ascorbic Acid↗

Molecular weights of IgA-circulating immune complexes (CIC) in patients with IgA nephropathy: application of HPLC and solid-phase anti-C3 Facb EIA.

The detection of molecular weights of IgA-circulating immune complexes (CIC) in sera is described. Measurement of IgA-, IgG- and IgM-CIC in sera was also performed. Serum samples were obtained from nine patients with IgA nephropathy, nine patients with chronic proliferative glomerulonephritis without IgA deposits (PGN) and 19 healthy adults. Serum samples of these patients were subjected to high performance liquid chromatography (HPLC) and then divided into 50 fractions. Measurement of IgA-, IgG- and IgM-CIC in such fractions was performed using solid-phase anti-C3 Facb EIA. The levels of IgA-CIC in sera from patients with IgA nephropathy were significantly higher than those from patients with PGN or healthy adults. The peak values of molecular weights of IgA-CIC in sera from patients with IgA nephropathy ranged from 2.6 X 10(5) to 3.0 X 10(5) daltons (mean +/- SD; 2.9 +/- 2.0). It was suggested that the increase of IgA-CIC in sera from patients with IgA nephropathy may be mainly due to dimers and/or polymers.

Adult↗

Immunofluorescent studies on IgA nephropathy: type IV collagen and glomerular basement membrane component detected by Goodpasture's syndrome serum and laminin.

A study of immunofluorescence of unfractionated Type IV collagen, non-collagenous (NC-1) domain of Type IV collagen, basement membrane (GBM) component detected by Goodpasture's syndrome patient's serum and laminin (LN) in the glomeruli from 10 patients with IgA nephropathy was described. Type IV collagen, non-collagenous (NC-1) domain of Type IV collagen, GBM component or LN was observed linearly in the glomerular capillary walls in all patients with IgA nephropathy examined. The deposition of IgA, IgM or C3 was marked in the glomerular capillary walls in patients in the moderate or advanced stage of IgA nephropathy. However, the staining of Type IV collagen, GBM component or LN in such walls was not altered by the depositions of IgA, IgM and C3. In particular, a wrinkled pattern of NC-1 domain of Type IV or GBM component was detected in the glomerular capillary walls of totally sclerotic glomeruli in some patients with IgA nephropathy. It appears that the deposits of IgA and/or C3 did not influence the major components of glomerular capillary walls in patients with IgA nephropathy. It is concluded that the initiating factors of the collapse and/or sclerosis of glomerular capillary walls might be due to various factors other than the deposition of glomerular IgA-dominant immune-complexes in patients with IgA nephropathy.

Anti-Glomerular Basement Membrane Disease↗

Polyclonal IgA in IgA nephropathy.

Polyclonality of IgA production in IgA nephropathy (IgAN) was studied to elucidate the immunological aberrations in patients with this disease. The amounts of IgG, IgA and IgM and their kappa/lambda ratios in sera and supernatants of lymphocyte cultures were determined by the enzyme-linked immunosorbent assay. This method was sensitive enough to detect as little as 10% of monoclonal IgA in total IgA. The amount of IgA in IgAN was significantly increased in sera and supernatants without pokeweed-mitogen (PWM), but not changed in supernatants with PWM. There were no significant changes in the production of other immunoglobulins between IgAN and controls both in vivo and in vitro with and without addition of PWM. As far as the kappa/lambda ratios of immunoglobulins were concerned, no significant deviations were observed between IgAN and controls in any samples. These results indicated that increased IgA in patients with IgAN was polyclonal, supporting the concept of the heterogeneity of this disorder.

Adolescent↗

[Clinical application of microfibrillar collagen hemostat (Avitene) in neurosurgical field].

Microfibrillar collagen hemostat (Avitene) is a new absorbable hemostatic agent, of which mechanisms are adhesion to the bleeding site and platelet aggregation. Histopathological examinations revealed that Avitene was biocompatible with cerebral cortex in an animal experiments. Our previous studies indicated that Avitene is very effective and safe to use as a topical hemostatic agent during craniotomy in an experimental animal. Avitene was used as a topical hemostatic agent during craniotomy in 36 patients with intracranial organic lesions. Its effectiveness of hemostasis was revealed in 95%. This agent was especially useful to prevent oozing during craniotomy. Side effect of this agent was not reported in this study. Therefore, Avitene is very effective and safe to use as a topical hemostatic agent in the neurosurgical field.

Brain↗

Tyrosine phosphorylation by the epidermal growth factor receptor kinase induces functional alterations in microtubule-associated protein 2.

We have examined the effect of tyrosine phosphorylation of microtubule-associated protein 2 (MAP2) by the epidermal growth factor (EGF) receptor kinase on its functions. Incubation of MAP2 with the EGF receptor in the presence of ATP resulted in a great decrease in the ability of MAP2 to promote tubulin polymerization. Under a variety of conditions, the decrease in the ability correlated with the extent of phosphorylation of MAP2. Furthermore, another function of MAP2, the actin filament cross-linking activity, was also inactivated by the incubation of MAP2 with the EGF receptor and ATP. The loss of this activity also correlated well with the extent of phosphorylation. These data indicate that tyrosine phosphorylation of MAP2 by the EGF receptor kinase inactivates both the tubulin polymerizing activity and actin filament cross-linking activity of MAP2. Thus, this study has clearly shown that tyrosine phosphorylation could modify the function of a cytoskeletal protein.

Actins↗

Protein kinase C and cAMP-dependent protein kinase induce opposite effects on actin polymerizability.

Protein kinase C phosphorylated muscle and non-muscle monomeric actin more efficiently than filamentous actin in vitro. By sedimentation assay, the ratio of phosphorylated to unphosphorylated actin was much higher in sedimentable actin than in the non-sedimentable form, suggesting that phosphorylated actin was more readily incorporated into F-actin than unphosphorylated actin. In contrast, actin phosphorylated by cAMP-dependent protein kinase was found to have weaker polymerizability than the unphosphorylated form. The phosphopeptide mapping pattern of actin phosphorylated by protein kinase C was different from that of actin phosphorylated by cAMP-dependent protein kinase. Thus, both the protein kinases phosphorylate actin differently and induce opposite effects on actin polymerizability.

Actins↗

Human monoclonal cryoimmunoglobulins. II. Comparative studies on the carbohydrate contents and compositions of cryoglobulins and myeloma proteins.

The carbohydrate contents and compositions of cryoglobulins and myeloma proteins were comparatively investigated by gas-liquid chromatographic and colorimetric analyses. Human monoclonal cryoglobulins, Jir (IgG3 kappa), Wat (IgG3 lambda), Fji (IgM kappa), and human myeloma proteins, Har (IgGl kappa) and Kob (IgA kappa) were used for the present experiments. The results obtained were that the carbohydrate contents of Jir and Wat were 2.7 and 4.4% in weight basis; the N-acetyl glucosamine of Wat was almost two times higher than that of Jir and no sialic acid was found in both of these proteins; the total carbohydrate content of Fji was 7.7% and the sialic acid content was 19.3% of the total carbohydrate moiety; the myeloma proteins, Har and Kob, contained 5.3 and 10.4% carbohydrate, respectively, and sialic acid was detectable in these proteins. These results indicate that the carbohydrate contents are variable in each of the proteins, but the relative compositions of monosaccharides in individual samples are nearly the same, except for Kob containing O-glycosidic carbohydrate linkages. In addition, the results showing that sialic acid was detectable in Fji, but not in Jir nor Wat, suggested that the lack of terminal carbohydrate residue was not a common structural feature of cryoglobulins, and was not responsible for the temperature-dependent precipitability of these unusual proteins.

Amino Acids↗

A novel 60-kDa smooth muscle protein that binds filamin-actin filament complex.

From the low salt-extracted debris of bovine stomach smooth muscle, a protein having a molecular mass of 60 kDa in SDS-PAGE was newly isolated. Co-sedimentation assay with actin filaments and several actin binding proteins such as filamin, alpha-actinin, caldesmon and fodrin showed that this protein co-sediments with actin only in the presence of filamin. Falling ball viscometric assay showed that this protein increases the viscosity of actin-filamin solution in a dose-dependent manner. Immunoblotting analysis showed specific localization of this protein in smooth and striated muscles.

Actins↗

Protein kinase C phosphorylates tau and induces its functional alterations.

We found that tau, one of the major microtubule-associated proteins, is a good substrate for protein kinase C. The phosphorylation occurred mainly on serine residues and the sites phosphorylated by protein kinase C were largely different from those phosphorylated by cAMP-dependent protein kinase as analyzed by phosphopeptide mapping. The protein kinase C-mediated phosphorylation of tau reduced its abilities to promote tubulin polymerization and to cross-link actin filaments. The reduction in its abilities was in proportion to the number of phosphates incorporated into tau.

Actins↗