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Biomedical subjects

H Ogino

Publications and source records attributed to H Ogino.

At least 163 records · Page 9Linked to original sources

cdc2-like kinase is associated with the retinoblastoma protein.

The growth-suppressive activity of the retinoblastoma (RB) protein is suggested to be regulated by phosphorylation. In studies on the kinase that phosphorylates the RB proteins, we have previously found that RB proteins can be phosphorylated by purified cdc2 kinase. In this study, we noted that RB proteins immunoprecipitated from human cell lysates are weakly phosphorylated in the absence of purified cdc2 kinase. Immunoblot analysis showed the presence of p34cdc2 in the immunoprecipitates with anti-RB monoclonal antibody. In addition, the coprecipitated kinase was found to have the same substrate specificity as cdc2 kinase. The associated kinase activity was particularly high in cells arrested in G1/S and S phase by aphidicolin. Furthermore, RB proteins were shown to be phosphorylated in nuclear extracts by some endogenous cdc2-like kinase(s). These results suggest that cdc2-like kinase is the main kinase for phosphorylation of RB proteins in vivo.

Amino Acid Sequence↗

Arterial ketone body ratio during and after cardiopulmonary bypass.

This study is the first to investigate the alteration in hepatic function during and after cardiopulmonary bypass in 30 patients by measuring the arterial ketone body ratio, an index of mitochondrial redox potential (oxidized nicotinamide-adenine dinucleotide/reduced nicotinamide-adenine dinucleotide). Although the preoperative arterial ketone body ratio was within normal limits (1.24 +/- 0.63), it decreased markedly 5 minutes after the start of cardiopulmonary bypass to 0.35 +/- 0.12 and remained at this low level throughout bypass. After bypass it continued to rise in a time-dependent fashion, returning to its preoperative level by the morning of the second postoperative day in normal convalescent patients. However, the ratio recovered more slowly in patients who required prolonged circulatory or respiratory support than in other patients. Thus we suggest that cardiopulmonary bypass had deleterious effects on the hepatic mitochondrial redox potential, which may contribute to homeostatic derangements and metabolic abnormalities.

Aged↗

Rates of reactions catalysed by a dimeric enzyme. Effects of the reaction scheme and the kinetic parameters on co-operativity.

For the reaction S in equilibrium P catalysed by a dimeric enzyme, the reaction schemes are considered on the basis of the KNF model. For each of the ten possible schemes, the rate equation is derived on the basis of the combined steady-state and rapid-equilibrium assumptions. The curves of the plots of initial velocity v versus the substrate concentration [S] and the Hill coefficients h calculated from the rate equations depend strongly on the reaction scheme and the parameter X1. This parameter is defined by log (KS2/KS1) and is a measure of the relative affinities of the first and second protomers for the substrate. When X1 less than 0, v-[S] curves for some schemes exhibit negative co-operativity (h less than 1.0) and v-[S] curves for other schemes are similar to that of the Michaelis-Menten scheme, indicating that, even if there is interaction between the distinct protomers, sigmoidal rate behaviour is not necessarily observed. When X1 greater than 0, all the reaction schemes except one, which shows substrate-inhibition kinetic behaviour, exhibit sigmoidal kinetic behaviour (h greater than 1.0), and at the limit of X1 much greater than 0 the Hill coefficients attain the maximum possible value of 2.0. Furthermore, we have found that, even if X1 = 0, the v-[S] curve for almost all the schemes considered in the present work does not necessarily agree with that for the Michaelis-Menten scheme. This means that the deviation of the v-[S] curve from a hyperbola can be observed even if there is no interaction between the distinct protomers.

Binding Sites↗

Stable expression of human tissue-type plasminogen activator regulated by beta-actin promoter in three human cell lines: HeLa, WI-38 VA13 and KMS-5.

A high-level and stable expression system of human tissue-type plasminogen activator (t-PA) was accomplished in human cells by selecting a promoter and a host cell line. First, we have constructed two types of t-PA expression plasmids containing 3 kb of the human beta-actin promoter region or 0.3 kb of SV40 early promoter region and these plasmids were transfected into HeLa cells, respectively, and the resulting transfectants were found to secrete various amounts of t-PA derived from the plasmids to the culture media. Southern blot analysis revealed that the beta-actin promoter was more efficient than the SV40 early promoter with regard to the expression level per single copy of the t-PA gene in the transfected HeLa cells. Next, the t-PA expression plasmid containing the beta-actin promoter was also transfected into WI-38 VA13 cells, a human fibroblastic cell line, and KMS-5 cells, a human lymphoid cell line, in order to compare the expression ability of the promoter among these three cell lines. Some of the transfectants from both cell lines were also found to produce t-PA. It was also found that the expression levels in HeLa and WI-38 VA13 seemed to be more efficient than that in KMS-5.

Actins↗

Carcinogenicity examination of Agaricus bisporus, edible mushroom, in rats.

Carcinogenicity of Agaricus bisporus, the edible mushroom, was studied in rats. Female Charles River Sprague - Dawley rats (CD rats) were given a diet containing a 30% dry powder of A. bisporus for 500 days until the termination of the experiment. A control group was given a basal diet without A. bisporus. The rats in the experimental group had mammary tumor, thymoma, adrenal adenoma and pituitary adenoma. However, there was no significant difference in the incidence of these tumors between the experimental group and control group. No carcinogenic activity of A. bisporus was observed in this experiment.

Animals↗

Abortion in Japanese cows caused by Chlamydia psittaci.

An outbreak of abortion in cows occurring in Niigata Prefecture was shown to be caused by Chlamydia psittaci. Elementary bodies characteristic of Chlamydia were found in the liver of aborted fetuses and C. psittaci antigen was demonstrated by indirect immunofluorescence. Chlamydia was isolated from the liver of aborted fetuses by the yolk sac inoculation of developing chick embryos and by the intraperitoneal inoculation of guinea pigs. Abortion occurred mostly in middle or late pregnancy. Aborted fetuses showed subcutaneous edema and gelatinous infiltration, enlarged liver and spleen, and dark red pleural and ascitic fluid. Focal necrosis was shown in the liver, spleen and lymph nodes. Serological findings and isolation of Chlamydia from fecal specimens indicated a wide dissemination of C. psittaci among cows in the area.

Abortion, Veterinary↗

Thrombosis-inducing activity in plasma of patients with acute respiratory tract infection disappears after treatment.

Thrombosis-inducing activity (TIA) was identified in plasma from 16 of 27 patients (59%) with acute respiratory tract infections. On the other hand, it was present in only 9 of 79 subjects (11%) with chronic lung diseases and 4 of 49 healthy volunteers (8%). In the patients with acute respiratory tract infections, there were significant elevations in plasma fibrinogen, C-reactive protein and erythrocyte sedimentation rate in the TIA-positive group compared with the negative group. Plasma TIA disappeared in all of the 8 patients who were retested for TIA 2-5 weeks after they became disease free. Pneumonia was induced in rabbits by transbronchial injection of viable Escherichia coli. TIA was not present in plasma from normal rabbits, but it appeared in plasma collected 3 days after injection. It then disappeared after 1-2 weeks of treatment with antibiotics. TIA may serve as a marker for inflammatory responses and be a factor responsible for elevated blood coagulation activity in patients with acute infectious diseases.

Acute Disease↗

Plasma thrombosis-inducing activity in 120 patients with primary lung cancer.

One hundred and twenty patients with primary lung cancer were examined for the presence of thrombosis-inducing activity (TIA) in their plasma. TIA was identified in plasma from 16 of 38 patients with stage 3 (42%) and 31 of 65 patients with stage 4 (48%) disease. On the other hand, only 1 of 17 patients with stages 1 and 2 (6%) showed TIA in their plasma. Cell type did not seem to correlate with the presence of plasma TIA, since TIA was identified in plasma from patients with all cell types. Survival of 32 patients with inoperable non-small cell lung cancer, all stage 4, was studied. The mean survival time was 7.2 months in the TIA-positive group and 10.3 months in the TIA-negative group. This difference was statistically significant.

Adult↗

In vitro and in vivo antibacterial activities of ME1220 and ME1221, novel cephalosporins.

The antibacterial activities and serum pharmacokinetic properties of ME1220 and ME1221, new aminothiazolylalkoxyiminoacetylcephalosporins having an N-alkylpyridiniumthiomethyl side chain at C-3, were compared with those of cefpirome and ceftazidime. ME1220 and ME1221 exhibited broad antibacterial activity against Gram-positive and Gram-negative bacteria. The in vitro and in vivo activities of ME1220 were similar to cefpirome, while ME1221 was superior to ceftazidime against almost all test organisms except pseudomonas. On intravenous injection in rats, ME1220 and ME1221 were excreted mainly in the urine. ME1221 was excreted moderately in the bile and showed higher serum concentration and AUC than those of ME1220.

Animals↗

Hepatocellular and biliary expression of HLA antigens in primary biliary cirrhosis before and after ursodeoxycholic acid therapy.

Recently, there have been reports that ursodeoxycholic acid (UDCA) therapy has a beneficial effect on liver function in patients with primary biliary cirrhosis. However, information regarding the effects of UDCA therapy on hepatic histology remains insufficient. Aberrant expression of HLA antigens on hepatocytes is regarded important in the progression of hepatocellular damages mediated by cytotoxic T-cells in primary biliary cirrhosis. In this study, we examined immunohistochemically hepatocellular expression of HLA antigens on hepatocytes before and after UDCA therapy in four patients with asymptomatic primary biliary cirrhosis. Piecemeal necrosis, intralobular focal necrosis, and portal inflammation, as well as infiltration of activated T-lymphocytes and expression of HLA class I antigens on hepatocytes, disappeared, or diminished in parallel after the therapy. In two of four patients, expression of HLA-DR on some periportal hepatocytes before the therapy also disappeared after the therapy. These observations imply that UDCA therapy decreases the hepatocellular expression of HLA antigens and thereby reduces or abolishes T-cell-mediated hepatocellular necrosis in primary biliary cirrhosis.

Adult↗

Synthetic sialyl glycolipids (sialo-cholesterol and sialo-diglyceride) induce granulocytic differentiation of human myelogenous leukemia cell line HL-60.

When HL-60 cells were cultivated with synthetic sialyl glycolipids, sialo-cholesterol and sialo-diglyceride, the cells were found to be differentiated into mature granulocytes on morphological and functional criteria. The differentiation of cells was accompanied by inhibition of cell proliferation. The differentiation-inducing activity of sialo-cholesterol was greater than that of sialo-diglyceride on a molar basis, and the alpha-anomer of each compound was more potent than the beta-anomer, suggesting that the stereospecific structure of the compounds is important for the differentiation-inducing activity.

Cell Transformation, Neoplastic↗

Gastric lesions in rats fed salted food materials commonly eaten by Japanese.

A high intake of salted food is thought to be related to the high incidence of stomach cancer in Japan. In the present study, female F344 rats were divided into four groups. They were fed a nutritionally deficient purified diet (Group 1) and standard purified diet (Group 3) for 113 weeks and the same diets supplemented with salted cuttlefish guts, broiled, salted, dried sardines, pickled radish, and soy sauce (Groups 2 and 4). The incidence of papillomas and ulcers of the forestomach was highest in Group 4, which was given the standard diet supplemented with the salty food materials (p less than 0.05). These results suggest the importance of salted food as a suspicious causal factor in human stomach cancer in Japan.

Animals↗

Synthesis and biological activity of (cyclopentenopyridinium) thiomethylcephalosporins.

Substituted (cyclopentenopyridinium)thiomethyl groups were introduced as C-3 substituents of (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-oxyimino]acetami docephalosporins. Structure-activity relationships of this class of cephalosporins are discussed on the basis of their MIC. The selected compounds, 3a and 4a (ME1221), having an acidic substituent, showed excellent in vivo efficacy and low toxicity.

Animals↗

A new antipseudomonal cephalosporin CP6162 and its congeners.

The synthesis and biological activity of a series of 3-[2-(5-hydroxy-4-pyridon-2-yl)ethenyl]cephalosporin derivatives are described. They showed very potent activity against Gram-negative bacteria, especially Pseudomonas aeruginosa. (6R, 7R)-7-[(Z)-2-(2-Aminothiazol-4-yl)-2 -(1-carboxy-1-methyl)-ethoxyiminoacetamido]-3-[(Z)-2-(1,5-dihydrox y-4- pyridon-2-yl)ethenyl]ceph-3-em-4-carboxylic acid, CP6162 (8e), was selected for further evaluation as antipseudomonal chemotherapeutic agent.

Animals↗

New aminothiazolylglycylcephalosporins with a 1,5-dihydroxy-4-pyridone-2-carbonyl group. I. Synthesis and biological activity of cephalosporin derivatives leading to MT0703.

A series of new aminothiazolylglycylcephalosporins with a mono- or dihydroxypyridonecarbonyl group at the alpha-amino group of the C-7 substituent have been prepared and antibacterial activity of these compounds was investigated. Among them, the compounds having a 1,5-dihydroxy-4-pyridone-2-carbonyl group showed excellent anti-pseudomonal activity. In particular, (6R,7R)-7-[(RS)-2-(2-aminothiazol-4-yl)-2-(1,5-dihydroxy-4- pyridone-2-carboxamido)- acetamido]-3-[[1-(2-hydroxyethyl)pyridinium-4-yl]thiomethyl]ceph-3 -em- 4-carboxylate (MT0703, 7g) was found to be a well balanced compound with respect to antibacterial activity.

Animals↗

New aminothiazolylglycylcephalosporins with a 1,5-dihydroxy-4-pyridone-2-carbonyl group. II. Synthesis and antibacterial activity of MT0703 and its diastereomers.

A practical synthetic method for large scale production of MT0703, (6R,7R)-7-[(RS)-2-(2-aminothiazol-4-yl)-2-(1,5-dihydroxy-4-pyridon e-2- carboxamido)acetamido]-3-[[1-(2-hydroxyethyl)pyridinium-4- yl]thiomethyl]ceph-3-em-4-carboxylate, was established. Its two diastereomers on configuration of the aminothiazolylglycyl moiety were synthesized using chemico-enzymatic method. The S-isomer of MT0703 was found to be more active against Gram-positive and Gram-negative bacteria including beta-lactamase-producing strains than the R-isomer.

Animals↗

In vitro antimicrobial activity of a novel aminothiazolylglycylcephalosporin, MT0703S, compared with that of ceftazidime, cefoperazone and aztreonam.

The antibacterial activity of a novel aminothiazolylglycylcephalosporin, MT0703S, possessing a dihydroxypyridone moiety was compared in vitro with the activity of ceftazidime, cefoperazone, aztreonam and other beta-lactam antibiotics using seven bacterial species of a clinical origin. MT0703S showed the most potent activity against P. aeruginosa, including the ceftazidime-resistant strains, E. coli, K. pneumoniae and C. freundii. MT0703S was comparable to aztreonam but more active than ceftazidime and cefoperazone in its activity against K. oxytoca and E. cloacae, and comparable to ceftazidime against S. aureus and S. marcescens. MT0703S was more active than cefoperazone against S. marcescens but less active against S. aureus. The stability of MT0703S against various beta-lactamases appeared to be intermediate between the stability of ceftazidime and that of cefoperazone. The antimicrobial activity of MT0703S increased in a low-iron environment and decreased in a high ferric ion concentration.

Aztreonam↗