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Biomedical subjects

T Koga

Publications and source records attributed to T Koga.

At least 307 records · Page 17Linked to original sources
PubMed1995

[Comparison of CAF plus MPA with CAF plus TAM for advanced or recurrent breast cancer--Kyushu CAFT Study Group of Advanced or Recurrent Breast Cancer].

A multi-center randomized comparison study of CAF + TAM therapy (Arm A) and CAF + MPA therapy (Arm B) in advanced or recurrent breast cancer was conducted at 37 institutions in Kyushu. Out of 119 registered cases, 114 were eligible and 76 were evaluable. The response rate was 42% (15/36) in Arm A and 58% (23/40) in Arm B. In the comparison of side effects, nausea/vomiting and anorexia were significantly less and moon face and body weight gain were significantly more in Arm B. Leucocytopenia was significantly inhibited in Arm B compared with Arm A, which indicated the myeloprotective effect of MPA. These results indicated that CAF + MPA therapy (Arm B) may be more advantageous than CAF + TAM therapy (Arm A) in advanced or recurrent breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

D-myo-inositol 1,4,5-trisphosphate binding domain of phospholipase C-delta 1.

D-myo-Inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) binding domain of phospholipase C-delta 1 (PLC-delta 1) was determined by examining binding activity of the synthetic peptide corresponding to residues 30-43 of PLC-delta 1. The peptide coupled with carrier proteins such as keyhole limpet hemocyanin or bovine serum albumin bound Ins(1,4,5)P3, whereas a scrambled peptide with the same amino acids did not do so. Polyclonal antibody against the peptide was examined to determine whether it would cause inhibition of the Ins(1,4,5)P3 binding to PLC-delta 1. Fab fragment of antibody to the peptide did inhibit binding to PLC-delta 1, in a dose-dependent manner. Thus it seems likely that the region of residues 30-43 of PLC-delta 1 is responsible for the binding of Ins(1,4,5)P3.

Amino Acid Sequence↗
PubMed1994

Bulbospinal augmenting inspiratory neurons may participate in contractions of the diaphragm during vomiting in decerebrate dogs.

Contradictory results have been reported regarding the participation of bulbospinal inspiratory (BSI) neurons in vomiting contractions of the diaphragm in dogs and cats maintained at low and high end-tidal CO2 levels, respectively. To resolve this discrepancy, effects of CO2 levels on vomiting activities were observed in 159 BSI-neurons of paralyzed decerebrate dogs. About half of the BSI-neurons exhibited a vigorous burst with each fictive retch regardless of the CO2 level and 28 of 51 BSI-neurons produced a burst during the early phase of expulsion. These BSI-neurons were not concentrated in any particular area. While these results do not resolve the above contradiction, they do suggest that some BSI-neurons participate in the vomiting contraction of the diaphragm.

Abdominal Muscles↗
PubMed1994

Identification and characterization of PilS, an essential regulator of pilin expression in Pseudomonas aeruginosa.

Expression of the pilin gene, pilA, of Pseudomonas aeruginosa requires the alternative sigma factor, sigma 54, and also two other transcriptional regulators encoded by the pilS and pilR genes. These two linked genes, which have been identified by transposon insertion mutagenesis, share significant amino acid sequence homology with members of the two-component family of regulators. The transcriptional regulator, PilR, has been described previously. PilS, a 37,285 Dalton protein, shares significant homology with the protein kinase sensors of the two-component regulatory family. PilS, however, has no hydrophobic domains which might be membrane-spanning alpha-helices, suggesting that PilS is a cytoplasmic protein. Characterization of the pilS gene revealed that when overexpressed in Escherichia coli by the bacteriophage T7 promoter it specifies a protein of approximately 40,000 daltons, corresponding to the molecular weight of PilS predicted from the deduced amino acid sequence. Deletion analysis of the pilS promoter fused to a promoterless lacZ gene further showed that a significant region upstream of pilS is essential for expression of pilS and pilR, suggesting a need for transcriptional activation. The pilA promoter can be activated in E. coli but only when PilR and sigma 54 are present. This work suggests that the PilS activation signal is received in the bacterial cytoplasm, and that the mechanism of PilS/PilR-mediated signal transduction resulting in activation of the pilin gene promoter is likely to be similar to that of other two-component systems.

Amino Acid Sequence↗
PubMed1994

Purification and characterization of 240-kDa cGMP-dependent protein kinase substrate of vascular smooth muscle. Close resemblance to inositol 1,4,5-trisphosphate receptor.

The 240-kDa, cGMP-dependent protein kinase substrate protein obtained from porcine aortic smooth muscle, whose phosphorylation was closely associated with stimulation of plasma membrane Ca(2+)-pump ATPase (Yoshida, Y., Sun, H.-T., Cai, J.-Q., and Imai, S. (1991) J. Biol. Chem. 266, 19819-19825), was purified to near homogeneity by three successive chromatographic runs with calmodulin-, concanavalin A-, and heparin-Sepharose columns from microsomes solubilized with Triton X-100. The purified protein was found to bind inositol 1,4,5-trisphosphate (InsP3) in a specific, heparin-inhibitable manner with a Kd of 2.0 nM and Bmax of 450 pmol/mg protein (the binding of inositol 1,3,4,5-tetrakisphosphate was much weaker). In sedimentation experiments on a linear sucrose density gradient the InsP3 binding activity was always with the 240-kDa protein. Protein kinase G phosphorylated the InsP3 receptor purified from the rat cerebellum as well as the 240-kDa protein. Sialic acid content of the protein measured with Limulus polyphemus agglutinin was not significantly different from that of the cerebellar InsP3 receptor. Thus, 240-kDa protein closely resembles InsP3 receptor and may be a type of InsP3 receptor. The only difference was the behavior on SDS-polyacrylamide gel electrophoresis. The 240-kDa protein presented itself as two polypeptides with similar but slightly differing M(r) values, both of which were phosphorylated by protein kinase G.

Amino Acid Sequence↗
PubMed1994

GM1 reduces infarct volume after focal cerebral ischemia.

The efficacy of monosialoganglioside GM1 treatment was evaluated in a model of experimental stroke. Cerebral ischemia was induced by permanent occlusion of left middle cerebral artery. GM1 was administered intravenously soon after the occlusion of the artery and then intramuscularly daily for 7 days. Results indicate that GM1 can reduce the extent of infarct volume and neurochemical deficits associated with the ischemic event. The protection was more evident in the cortex than in the caudate-putamen. These observations confirm and extend the evidence of the GM1 efficacy in experimental models of stroke and further support the usefulness of gangliosides in the treatment of these pathologies.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Synthesis of a phosphatidyl derivative of vitamin E and its antioxidant activity in phospholipid bilayers.

A novel phospholipid containing a chromanol structure at its polar head group was synthesized from egg yolk phosphatidylcholine and 2,5,7,8-tetramethyl-6-hydroxy-2-(hydroxyethyl)chroman by transphosphatidylation catalyzed by phospholipase D from Streptomyces lydicus. The structure of the product synthesized was shown by spectral analysis to be 1,2-diacyl-sn-glycero-3-phospho-2'-hydroxyethyl- 2',5',7',8'-tetramethyl-6'-hydroxychroman. The phosphatidylchromanol (PCh) showed antioxidant activity against radical chain oxidation of methyl linoleate in solution in a manner similar to that of d-alpha-tocopherol (alpha-Toc) and 2,2,5,7,8-pentamethyl-6-chromanol. However, PCh was less effective as a chain-breaking antioxidant than was alpha-Toc when unilamellar egg yolk phosphatidylcholine liposomes were exposed to either a water-soluble or a lipid-soluble radical initiator. It is likely that the phospholipid nature of PCh affects the location and the mobility of the chromanol moiety in the membrane bilayer resulting in a decrease in antioxidant activity. On the other hand, the antioxidant activity of PCh was little different from that of alpha-Toc in unilamellar liposomes when exposed to a lipid-soluble radical initiator in the presence of ascorbic acid. It appears that PCh in phospholipid bilayers can be regenerated by ascorbic acid in aqueous phase as can be alpha-Toc. The new phospholipid, phosphatidylchromanol, should prove useful as a chain-breaking antioxidant in phospholipid membranes.

Antioxidants↗
PubMed1994

Phorbol ester-induced inhibition of GABA uptake by synaptosomes and by Xenopus oocytes expressing GABA transporter (GAT1).

We examined the effect of 12-O-tetradecanoylphorbol 13-acetate (TPA) on the sodium-dependent uptake of gamma-aminobutyric acid (GABA) by the synaptosomal fraction from rat cerebral cortex. Activation of protein kinase C (PKC) by 100 nM TPA inhibited the Na(+)-dependent uptake of GABA by 38.1%, whereas 4 alpha-phorbol-12,13-didecanoate (4 alpha-PDD), an inactive phorbol ester, did not alter the uptake. The inhibition was blocked by preincubation with 100 nM staurosporine, a potent inhibitor of PKC. The Eadie-Hofstee plots revealed the presence of a high affinity uptake system. The treatment with TPA increased the Km value from 6.76 microM to 18.5 microM with a trend toward a slight decrease of Vmax. In the presence of beta-alanine, TPA inhibited the GABA uptake by increasing the Km value from 8.65 microM to 15.0 microM without affecting Vmax. The molecular basis of the inhibitory effect of TPA was further examined using Xenopus oocytes expressing GAT1, a beta-alanine-insensitive and nipecotate-sensitive neuronal GABA transporter, resulting in a similar effect of TPA. The value of Km, but not Vmax, was increased by the treatment with 100 nM TPA. These results suggest that PKC may modulate the GABA uptake into presynaptic terminals through the inhibition of GAT1 activity.

Alkaloids↗
PubMed1994

Ultraviolet-B irradiation alters cytokine production by immune lymphocytes in herpes simplex virus-infected mice.

Previous studies from our laboratories have shown that UV-B irradiation at the site of an intradermal infection of herpes simplex virus (HSV) resulted in a higher incidence of zosteriform lesions and suppressed cellular immune responses to HSV in mice. In order to determine whether the production of T-cell-derived cytokine (IFN-gamma, IL-2 and IL-4) by immune cells from irradiated mice is also suppressed, we examined the production of cytokines by lymph node cells and spleen cells taken from UV-B irradiated, HSV type 1 (HSV-1)-infected mice. UV-B irradiation (120 mJ/cm2) prior to HSV-1 infection was found to markedly suppress IFN-gamma production compared to that of the non-irradiated control. IL-4 production was enhanced compared to IL-2 in the UV-B irradiated mice. These results suggest that alteration(s) in the cytokine production profile may therefore be involved in the development of severe skin lesions caused by HSV infection in UV-B irradiated mice.

Animals↗
PubMed1994

Membrane-associated interleukin-1 promotes osteoclast-like cell formation in vitro.

The effect of paraformaldehyde-fixed murine macrophage P388D1 cells on osteoclast-like cell formation was investigated in mouse marrow cultures. When mouse marrow cells were cocultured for 8 days with paraformaldehyde-fixed P388D1 cells stimulated with lipopolysaccaride (LPS), many tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells were formed. Non-stimulated, and paraformaldehyde-fixed P388D1 cells did not induce the formation of TRACP-positive multinucleated cells. Salmon calcitonin and indomethacin strongly inhibited the paraformaldehyde-fixed, LPS-stimulated P388D1 cells-induced TRACP-positive multinucleated cell formation. Monospecific anti-mouse recombinant IL-1 alpha serum inhibited TRACP-positive multinucleated cell formation in the presence of paraformaldehyde-fixed P388D1 cells stimulated with LPS. These results suggest that membrane-associated IL-1 on macrophages is responsible for the resorptive effect of paraformaldehyde-fixed P388D1 cells stimulated with LPS.

3T3 Cells↗
PubMed1994

D-myo-inositol 1,4,5-trisphosphate-binding proteins in rat brain membranes.

Rat brain membrane fractions obtained using Triton X-100 were applied to a D-myo-inositol 1,4,5-trisphosphate [D-Ins(1,4,5)P3] immobilized column, followed by gel filtration and anion-exchange chromatography. Two proteins with molecular masses of 130 and 85 kDa, as assessed by SDS-polyacrylamide gel electrophoresis, were purified to apparent homogeneity as D-[3H]Ins(1,4,5)P3-binding proteins with no D-Ins(1,4,5)P3-metabolizing activity. Partial amino acid sequence determinations of these proteins revealed that the 130 kDa protein appears to be a new D-Ins(1,4,5)P3-binding protein and the 85 kDa protein is a delta 1-isozyme of phospholipase C. We have previously purified 130 and 85 kDa proteins as D-[3H]Ins(1,4,5)P3-binding proteins, from rat brain cytosol fraction. Antibodies against the 130 kDa protein from the cytosol cross-reacted with the membrane 130 kDa protein purified in this study, suggesting that the membrane 130 kDa protein is likely to be the same as the protein from the cytosol fraction. The inhibition of D-[3H]Ins(1,4,5)P3 binding by D-isomers of inositol phosphates available clarified that the 130 kDa protein has a similar affinity for D-Ins(1,4,5,6)P4 to that for D-Ins(1,4,5)P3, while the 85 kDa protein is specific to D-Ins(1,4,5)P3.

Amino Acid Sequence↗
PubMed1994

Isolation and characterization of three porin-like proteins from Vibrio vulnificus: effect of different growth media on their production.

The effect of the culture media on the composition of the outer membrane protein of Vibrio vulnificus strain 393 from human blood was examined. Only one major outer membrane protein, with an apparent molecular weight of 37,000 (37K protein) and 34,000 (34K protein), was formed in the cells grown in 3% NaCl-BHI broth and chemically defined medium, respectively. The production of one major outer membrane protein was also observed in other isolates from humans and asari clam when they were grown in 3% NaCl-BHI broth. On the other hand, three major outer membrane proteins, with apparent molecular weights of 48,000 (48K protein), 37,000 (37K protein), and 34,000 (34K protein), were produced in the cells grown in 3% NaCl-nutrient broth. Three proteins, 48K, 37K, and 34K from strain 393, were purified and the amino acid compositions were determined. Although there was a little difference in the composition of amino acid among three proteins, the amino acid compositions of the three porin-like proteins showed characteristic properties of the porins of Escherichia coli and Salmonella typhimurium. Immunoblot analysis of the outer membrane proteins from four vibrios, E. coli, and S. typhimurium using monospecific antisera against these three porin-like proteins showed that only the antiserum against 37K protein cross-reacted with the outer membrane proteins from all the strains tested.

Amino Acids↗