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Biomedical subjects

K Murakami

Publications and source records attributed to K Murakami.

At least 973 records · Page 54Linked to original sources

[An analysis of regional ventilation in pulmonary sarcoidosis by inspired 133Xe washout test].

Xenon-133 ventilation study were used to measure regional ventilation in seven patients with pulmonary sarcoidosis and in four normal subjects. For the purpose of analyzing the washout curves on the whole lungs, two ventilation indexes were calculated, which were TA/H and T1/2. TA/H is that the area under the curve divided by the difference in mean count rate during equilibrium and at 120 s after washout started. T1/2 value represents the time required to 50% of the mean count rate during equilibrium. The average time of TA/H on the whole lung was 13.5 +/- 1.1 s in normal subjects (n = 4), 13.0 +/- 4.3 s in stage I (bilateral hilar lymphadenopathy without lung involvement on chest X-ray) sarcoidosis (n = 3), 21.3 +/- 1.8 s in stages I, II (lung involvement) sarcoidosis (n = 4). The average time of T1/2 on the whole lung was 43.7 +/- 4.7 s in normal subjects, 42.3 +/- 16.0 s in stagel sarcoidosis, 72.5 +/- 28.6 s stages II, III sarcoidosis. The ventilation indexes on the regional lungs showed almost a similar tendency to that on the whole lung. The ventilation indexes in patients with stage II, III sarcoidosis were significantly longer than in normal subjects and in patients with stage I sarcoidosis. It was suggested that 133Xe washout test might detect regional ventilation abnormalities which were not recognized on chest X-ray in pulmonary sarcoidosis.

Aged↗

Antibacterial and pharmacokinetic properties of M14659, a new injectable semisynthetic cephalosporin.

In vitro and in vivo antibacterial activities and pharmacokinetics of M14659 were investigated. In vitro activity of M14659 was superior to that of ceftazidime against Staphylococcus aureus. Against Gram-negative bacteria except Pseudomonas aeruginosa, its activity was almost equal to that of ceftazidime. M14659 was more active against P. aeruginosa including multi-drug resistant strains than cefsulodin, cefoperazone or ceftazidime. Affinities of M14659 for penicillin-binding proteins (PBPs) of Escherichia coli and P. aeruginosa were 2 to 14 times higher for PBP-1A and PBP-1B than found for ceftazidime, and almost the same for PBP-3. In vivo activity of M14659 against S. aureus was superior to that of cefamandole, cefotaxime or ceftazidime. Against Gram-negative bacteria including P. aeruginosa, M14659 was 2 to 220 times more active than cefotaxime or ceftazidime. Plasma half-life of M14659 in mice was about 3 times longer than that of ceftazidime. M14659 administered intravenously to mice was mainly excreted in urine without metabolism, and its recovery rate was almost equal to that of ceftazidime.

Animals↗

[Preoperative treatment of lymph node metastases of gastric cancer by local injection of 5-FU adsorbed on activated carbon--clinical study of 5-FU concentration in resected lymph nodes].

The concentration of 5-fluorouracil (5-FU) in blood and lymph node of 55 patients with gastric cancer who were endoscopically injected 250 mg of 5-FU alone or adsorbed on activated carbon into the gastric wall or 300 mg of 5-FU dry syrup orally before operation, were measured chronologically. The concentration of 5-FU in blood were similar in all cases but higher in lymph node in the group given adsorbed preparation than other cases. In the cases given adsorbed preparation, the lymph node concentration was remained high 7 days after injection, and in 37% cases more than the minimum inhibitory concentration of 5-FU remained. Therefore, for the purpose to elicit anticancer effect on micrometastasis in lymph nodes in the patients with gastric cancer, endoscopically preoperative injection of 5-FU adsorbed on activated carbon seemed to be useful.

Adsorption↗

[Clinical significance of serum levels of SCC antigen in patients with esophageal squamous cell carcinoma].

The levels of squamous cell carcinoma-related antigen (SCC) in sera of 71 patients with esophageal squamous cell carcinoma, 7 patients with benign esophageal diseases, 11 gastric cancer patients and 15 normal volunteers were studied in order to evaluate its clinical significance as a tumor marker. In the patients with esophageal carcinoma, immunosuppressive acidic protein (IAP) and carcinoembryonic antigen (CEA) were also measured simultaneously. In the normal volunteers, patients with benign esophageal diseases and gastric cancer patients, the SCC levels were negative except for only one patient. However, in patients with carcinoma of the esophagus 37 out of 71 were positive, the positivity rate being 52.1%. Comparison among SCC, IAP and CEA showed that the positivity rates for SCC and IAP increased with progression of the disease. In contrast, CEA levels did not correspond to clinical stage except in several patients with non-resectable and recurrent disease. With regard to the changes in serum levels of SCC, IAP and CEA before and after surgery and radio-chemotherapy. SCC was the most sensitive marker of the three, and responded well to the effects of therapy. SCC was thus considered to be a useful marker for monitoring esophageal cancer patients.

Aged↗

[Preoperative treatment of lymph node metastasis in cases of gastric cancer by local injection of anticancer drugs--preliminary report].

For the purpose of producing an anticancer effect on the micrometastasis of the lymph nodes and free cancer cells in the lymphatic ducts in a gastric cancer, activated charcoal was endoscopically injected into the gastric wall preoperatively in 49 cases to adsorb anticancer drugs. The correlation between the histological degree of black staining of the dissected lymph nodes and the clinicopathological factors was studied. Among 2,426 dissected lymph nodes, the degree of black staining was found to amount to 49.9%. Among 201 metastatic lymph nodes, the degree of black staining was 24.9%. Thus, the possibility of an anticancer effect was realized in 25% of the metastatic lymph nodes. From a study of the clinicopathological findings, the degree of black staining was low in cases of advanced cancer. In a histological study, the degree of black staining was found to be higher in the undifferentiated types than in the differentiated types, suggesting that there is a difference in the function of the lymph-reticulo-endothelial system according to the histological type.

Antineoplastic Agents↗

Protein kinase C inhibitors eliminate hippocampal long-term potentiation.

Recent findings suggest that protein kinase C (PKC) regulates the persistence of long-term potentiation (LTP). To test the hypothesis that PKC inhibition would decrease persistence of potentiation we applied PKC inhibitors (mellitin, polymyxin B, H-7) by micropressure ejection to the intact hippocampus either before or after LTP induction. When inhibitor was given 15 min before LTP, initial potentiation was unaffected, yet responses decayed to baseline levels by 60 min after the onset of potentiation. PKC inhibitor treatment 10 min after LTP onset induced decay of responses to pre-LTP baseline levels within 50 min of ejection. Inhibitor applied 60 min after LTP onset induced substantial decay but not to baseline levels. Potentiation was unaffected by inhibitor treatment 4 h after the induction of LTP. Measurement of PKC subcellular distribution revealed that inhibitor significantly reduced the proportion of PKC associated with the membrane. These findings represent the first demonstration that PKC inhibitors prevent persistence of potentiation. They also suggest that PKC regulates the persistence of synaptic enhancement beginning after its onset, and that PKC's role decreases with time after the induction of enhancement.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Regulation of protein kinase C activity by cooperative interaction of Zn2+ and Ca2+.

cis-Fatty acids such as oleic acid or linoleic acid have been previously shown to induce full activation of protein kinase C in the absence of Ca2+ and phospholipids (Murakami, K., and Routtenberg, A. (1985) FEBS Lett. 192, 189-193; Murakami, K., Chan, S.Y., and Routtenberg, A. (1986) J. Biol. Chem. 261, 15424-15429). In this study, we have investigated the effects of various metal ions on protein kinase C activity without the interference of Ca2+ since cis-fatty acid requires no Ca2+ for protein kinase C activation. Here we report a specific interaction of Zn2+ with protein kinase C in either a positive or negative cooperative fashion in concert with Ca2+. At low concentrations (approximately 5 microM) of Ca2+, Zn2+ enhances protein kinase C activity induced by both oleic acid and phosphatidylserine/diolein. In contrast, Zn2+ inhibits the activity at higher concentrations (over 50 microM) of Ca2+. In the absence of Ca2+, Zn2+ shows no effect on protein kinase C activity. Our results suggest that Zn2+ does not recognize or interact with protein kinase C in the absence of Ca2+, that protein kinase C possesses high and low affinity Ca2+-binding sites, and that at least one Zn2+-binding site exists which is distinct from Ca2+-binding sites.

Animals↗

Comparison of the inhibitory effects of nicorandil, nitroglycerin and isosorbide dinitrate on vascular smooth muscle of rabbit aorta.

The inhibitory effects of nicorandil, nitroglycerin and isosorbide dinitrate on the contractions induced by 10(-6) M norepinephrine or by 65.4 mM K+ were compared in the vascular smooth muscle of rabbit aorta. These compounds relatively selectively inhibited the contraction induced by norepinephrine. Norepinephrine induced a sustained contraction in the aorta depolarized with high K+ and treated with 10(-6) M verapamil, and this contraction was also inhibited by these compounds. The increase in Ca2+ influx induced by norepinephrine, but not by high K+, was inhibited by the three compounds. The norepinephrine-induced transient contraction, which is due to release of stored Ca2+, was inhibited by these compounds. The inhibitory effects of nicorandil and nitroglycerin on this contraction were attenuated by high-K+ depolarization. Methylene blue (10(-5) M) antagonized and M&B 22948 (10(-5) M) potentiated the inhibitory effects of these compounds. These results suggest that nicorandil, nitroglycerin and isosorbide dinitrate have a similar mechanism of action. These compounds inhibit the norepinephrine-induced sustained contraction possibly by inhibiting the Ca2+ influx through receptor-linked Ca2+ channels, and inhibit the transient contraction by membrane hyperpolarization and also by direct inhibition of Ca2+ release although other mechanism of action may also be involved.

Animals↗

Ovarian renin gene expression is regulated by follicle-stimulating hormone.

The regulation of renin and renin messenger RNA (mRNA) in the rat ovary was examined to test the hypothesis that the expression of renin gene and the secretion of renin in the ovary is the estrogen-mediated process that responds to follicle-stimulating hormone (FSH). In the ovary of the immature 25-day female rats, the concentration of renin mRNA was comparatively low, but 36 h after injection of FSH, the renin mRNA content showed a three-fold increase compared to the basal level. This increase was consistent with the stimulation of the total renin concentration in the ovary. On the other hand, the total renin concentration in the rat uterus gradually decreased, suggesting that the enhancement of the contents of renin and renin mRNA by FSH is an ovary-specific phenomenon. In hypophysectomized rats, the total renin concentration in the rat ovary was stimulated by the estrogen as well as FSH. These findings suggest that the production of ovarian renin is regulated by the pituitary hormone, particularly FSH.

Animals↗

Degradation of proteins with blocked amino groups by cytoplasmic proteases.

The effect of blocking amino groups on the susceptibility of BSA and calmodulin to high molecular weight protease (HMP) and calpain, the two major cytosolic proteases, was studied. Both proteases hydrolyzed methylated vs. unmodified BSA more slowly. Methylation of BSA resulted in the accumulation of proteolytic intermediates, especially of larger sizes. However, similar fragments were generated from unmodified BSA indicating that rates of hydrolysis rather that sites of proteolytic cleavage were altered. Calmodulin from Dictyostelium discoideum was hydrolyzed rapidly by HMP whereas brain and muscle calmodulins which have a epsilon-N-trimethyl residue on the single surface lysine were relatively stable.

Animals↗

Estimation and characterization of glycosylated carbonic anhydrase I in erythrocytes from patients with diabetes mellitus.

Glycosylated form of carbonic anhydrase isozyme I was found in human erythrocytes. The percent of glycosylated enzyme of the total erythrocyte carbonic anhydrase I of patients with diabetes mellitus was significantly higher than that from normal controls. Characterization of the glycosylated carbonic anhydrase I was studied using an enzyme purified from diabetic patients. The glycosylated enzyme showed a slightly acidic isoelectric point in comparison with that of a nonglycosylated enzyme. The specific activity of the glycosylated enzyme was approximately 40% of that of the normal enzyme, and the immunological activity decreased to 52% of that of the normal enzyme. Estimation of carbohydrates which may form a ketoamine linkage with the enzyme was studied using [3H]-labelled glycosylated enzyme synthesized by incubation of the enzyme with [3H]-D-glucose in vitro, and it was found that one mol of glucose binds to one mol of enzyme. Exposure of red cells to a higher concentration of glucose in diabetics brought about glycosylation of carbonic anhydrase, which is associated with its low activity enzymatically and immunologically.

Adult↗