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Biomedical subjects

T Nishimura

Publications and source records attributed to T Nishimura.

At least 1,405 records · Page 78Linked to original sources

Post-proline cleaving enzyme (prolyl endopeptidase) from bovine brain.

A post-proline cleaving enzyme [prolyl endopeptidase, EC 3.4.21.26] was purified about 3,700-fold from an extract of bovine brain by a series of column chromatographies on DEAE-Sephadex, hydroxyapatite and PCMB-T-Sepharose, and gel filtration on Sephadex G-200 using N-carbobenzoxy-Gly-Pro-beta-naphthylamide (Z-Gly-Pro-2-NNap), thyrotropin releasing hormone (TRH) and oxytocin as substrates. The purified enzyme appeared homogeneous as judged by disc gel and SDS gel electrophoreses. The enzyme was most active at pH 7.5 and 7.2 with Z-Gly-Pro-2-NNap and TRH, respectively, and hydrolyzed peptide bonds involving Pro-X (X=amino acid, peptide, ester and amide) bonds of synthetic substrates, oxytocin, vasopressin, neurotensin, substance P, tuftsin, bradykinin, and insulin B chain. However, the enzyme was inert toward collagen, gelatin, and casein. The enzyme was completely inactivated by diisopropylphosphorofluoridate (DFP), Z-Gly-Pro-chloromethyl ketone and p-chloromercuribenzoate (PCMB), while it was not inhibited by phenylmethane sulfonylfluoride (PMSF) or metal chelators. Determination of the amino acid composition revealed that the enzyme contained 25 half-cystines. Modification of three cysteine residues of the enzyme by PCMB led to complete inactivation. The isoelectric point of the enzyme was 4.8, and the molecular weight was estimated to be 76,000 by ultracentrifugal analysis and 75,000-74,000 by both gel filtration and sodium dodecyl sulfate (SDS) gel electrophoresis, suggesting that the enzyme is present as a monomer. These results indicate that the post-proline cleaving enzyme from bovine brain is very similar to those previously purified from lamb brain and kidney in its enzymatic properties, substrate specificity and physicochemical properties, in sharp contrast with the results obtained by Tate, who reported that the bovine brain prolyl endopeptidase was inert toward oxytocin, vasopressin and bradykinin.

Amino Acid Sequence↗

Metabolism of D-phenylalanine and its effects on concentrations of brain monoamines and amino acids in rats--a basic study on possibility of clinical use of D-phenylalanine as an antidepressant.

The effect of D-phenylalanine on the concentrations of brain catecholamines, serotonin, beta-phenylethylamine and amino acids was examined using rats injected intraperitoneally with 200 mg/kg of D-phenylalanine. The contents of these monoamines in the rat brain were not affected by the administration of D-phenylalanine. No spectacular change was observed in the concentrations of brain amino acids except phenylalanine, which increased about four times during 30-60 minutes after the injection. This increase was attributed to the administered D-phenylalanine. To confirm the finding that D-phenylalanine did not affect the content of beta-phenylethylamine, the metabolism of D-phenylalanine was examined using D-[14C]-phenylalanine. It was proven that D-phenylalanine did not convert to beta-phenylethylamine. On the basis of these findings the antidepressant effect of D-phenylalanine was critically discussed.

Amino Acids↗

Mechanism of action of habekacin, a novel amino acid-containing aminoglycoside antibiotic.

The molecular basis for activity of habekacin was studied by using Escherichia coli Q-13. Electron microscopic studies revealed that numerous blebs, derived from the outer membrane, were formed on cells treated with habekacin. Cytoplasmic contents leaked into the lumina of blebs, and the membrane of some enlarged blebs was disrupted. In a cell-free system, habekacin interfered with polypeptide synthesis, caused codon misreading, and inhibited translocation of N-acetylphenylalanyl-tRNA from the acceptor site to the donor site on ribosomes. [3H]habekacin bound to both 50S and 30S ribosomal subunits. The current experiments indicated that the mechanism of action of habekacin is similar to that of 2-deoxystreptamine-containing aminoglycoside antibiotics such as dibekacin, kanamycin, gentamicin, and related substances. The relationship of membrane damage to inhibition of ribosomal functions remains to be determined.

Aminoglycosides↗

Metabolic responses to a new beta-adrenoceptor agonist, ICI 118,587, in conscious rats.

The effect of a new beta-adrenoceptor agonist, ICI 118,587, on the blood levels of cyclic AMP, glucose, lactate, and FFA was studied in conscious rats. ICI 118,587 (200 micrograms/100 g s.c.) increased the cyclic AMP level in the normal and reserpine-pretreated rat, and increased the FFA level in the reserpine-pretreated rat. Adrenaline (10 micrograms/100 g s.c.) increased the levels of cyclic AMP, glucose, and lactate in the normal rat, and increased the FFA level in the reserpine-pretreated rat. The increases in these metabolites induced by this particular dose of adrenaline were inhibited by ICI 118,587. In the normal or reserpine-pretreated rat, ICI 118,587 acts as a beta-agonist on metabolism, and is capable of antagonizing the metabolic effects of adrenaline.

Adrenergic beta-Agonists↗

Influence of diethylmaleate on the formation of bis(methylmercuric)selenide and methylmercury distribution in rats.

This study was undertaken to examine a possible role of bis(methylmercuric) selenide(BMS) in selenite-induced redistribution of methylmercury in rats. Pretreatment of diethylmaleate(DEM), which depletes tissue reduced glutathione(GSH), completely suppressed the significant increase of BMS produced by selenite injection in the blood of methylmercury-treated rats. Its inhibitory effect was also observed in the kidney and brain. Under the same conditions, the characteristic accumulation in the brain and testis of total mercury induced by selenite was markedly inhibited by DEM pretreatment. Total mercury in these tissues was not altered by DEM alone and BMS in the blood existed in the erythrocytes, but not in the plasma. Thus, it seems likely that the suppressed formation of BMS in the erythrocytes mainly leads to the decreased accumulation of total mercury in the brain and testis.

Animals↗

A diastolic mid-echo in torn chordae tendineae of the mitral valve.

Echocardiographic studies were performed on 3 patients with torn chordae tendineae of the mitral valve proven by open heart surgery or during autopsy. Mitral regurgitation was noted after episodes of bacterial endocarditis in 3 patients; one had had rheumatic valvular disease before the episode. Conventional M-mode echocardiograms showed coarse diastolic fluttering of the mitral valve, multiple mitral valve echoes in systole, and diastolic mid-echoes between both anterior and posterior leaflets. The last pattern was found in all 3 patients. There was only one patient with an unusual systolic echo in the left atrium. Two-dimensional echocardiograms from 2 patients revealed an abnormal echo in the left ventricle in diastole which moved into the left atrium in systole, slightly beyond the closure line of the mitral valve. This moving abnormal echo observed in two-dimensional echograms presumably originated from torn chordae tendineae and was consistent with the diastolic mid-echo noted in M-mode echograms. Thus, the diastolic mid-echo of the mitral valve by M-mode echocardiography is an important finding in the diagnosis of torn chordae tendineae of the mitral valve, and two-dimensional echocardiography can identify the movement of torn chorda itself.

Adult↗

Meiosis-inhibiting effects in vivo of antiserum to progesterone on follicular ova in immature rats treated with gonadotropins.

Effects of the neutralization of endogenous progesterone with rabbit antiserum to progesterone (anti-progesterone) on germinal vesicle breakdown of ova in follicles of small (less than 125 micrometers), intermediate (125-250 micrometers) and large (greater than 250 micrometers) diameter were examined by a quantitative histological technique. Immature rats were treated with 5 IU pregnant mare's serum gonadotropin (PMS) then with 10 IU human chorionic gonadotropin (hCG). Administration of anti-progesterone together with hCG 6 h later significantly decreased the incidence of germinal vesicle breakdown of ova in the large follicles, but not in the intermediate ones. This treatment did not affect the proportion of intermediate to large follicles in the population. Replacement with progesterone 1 h after the simultaneous injection of hCG and anti-progesterone partly reversed the reduced incidence of meiosis. An injection of rabbit antiserum to estrone, in addition to the replacement with progesterone 1 h after the simultaneous injections of hCG and anti-progesterone, restored the incidence of meiosis to a value comparable to the values found for control rats treated sequentially with PMS and hCG. We concluded that the hCG-induced preovulatory rise in progesterone has a limited but definite stimulatory effect on the resumption of meiosis in the ova of large follicles and that it mediates the meiosis-inducing action of hCG.

Animals↗

Endoscopic control of gastrointestinal hemorrhage by local injection of absolute ethanol: a basic assessment of the procedure.

To investigate the hemostatic mechanism of local ethanol injection, ethanol was injected into the gastric mucosa of five adult mongrel dogs and one guinea pig and histologic changes at acute and healing stages were followed. Following a local injection of absolute ethanol, the blood flow in small vessels at the site of injection became instantaneously arrested. Histopathologically, thrombosis of blood vessels in the mucosa and submucosa with edema, predominantly submucosal, was found 10 min after the ethanol injection. There was little or no inflammatory cell infiltration in the injected region. By 4 days after the injection, the base of the formed ulcer became stabilized with a uniform white coating, which, microscopically, was mainly composed of a thick layer of necrotized mucosal tissue. Ethanol showed fixative activity when applied to tissues at concentrations of greater than or equal to 20% although an ethanol concentration of at least 70% was required to accomplish adequate tissue fixation. With 95% or lower concentrations of ethanol, dehydration of tissue was insufficient, and hemostasis due to local vasoconstriction was less conspicuous than with absolute alcohol. Nevertheless, a fixative effect with consequent degeneration and necrosis of cells and secondary thrombosis was evident even at these ethanol concentrations. In patients treated with this hemostatic procedure, exposed blood vessels in the gastric ulcer became necrotized and corroded by fixation with injected absolute ethanol and disappeared from the base of the ulcer within 24 hr as seen in the animals.

Adult↗

Endoscopic hemostasis of gastrointestinal hemorrhage by local application of absolute ethanol: a clinical study.

The procedure of endoscopic hemostasis with topical injection of absolute ethanol has been developed and applied since 1975 for the control of postoperative hemorrhage associated with diathermic polypectomy. Since June 1979, upper gastrointestinal hemorrhages other than varices have also been subjected to this procedure. This method is based on the principle of dehydration and fixation of the tissue with absolute ethanol. In this procedure, the bleeding vasculatures are dehydrated and fixed with consequent vasoconstriction and necrosis of the vascular wall including its endothelial lining, thereby thrombogenesis and hemostasis are facilitated. The troubled blood vessels fixed in vivo are disintegrated and disappeared. Rebleeding from the ulcer has been extremely rare with this method since the necrotized tissue seldom defoliates but often constitutes a part of the white coating and protects the base of ulcer. Treatment by this method has been successful in all 23 cases of upper gastrointestinal hemorrhage associated with endoscopic diathermy, and none has developed rebleeding. The hemostasis has also been successful in 51 cases (72 hemorrhagic lesions) with fresh blood clots adhering to the lesion, exposed blood vessels in the lesion or an actively bleeding lesion out of 126 cases referred for emergency endoscopic examination because of upper gastrointestinal hemorrhage during the 3-year period from June 1979 to May 1982. After hemostasis, however, 3 patients received an elective operation and one patient was also operated due to perforation of the gastric wall. Rebleeding occurred in 3 cases more than a week after the hemostasis; one of these was the above-described operated case of perforation. The rebleeding occurred in stress ulcers following surgery for femoral fracture. The other two were at the terminal stage of malignancy and complicated with DIC respectively. Of the patients treated by this method, 8 died by causes other than gastrointestinal hemorrhage. All the rest of 39 cases attained cure of ulcer by the non-surgical treatment alone.

Adult↗

Combination therapy of gastric atypical epithelium and elevated type early gastric cancer with high frequency current and laser.

A total of 11 lesions, consisting of elevated type early gastric cancer and atypical epithelium of more than 2 cm in diameter which were found in 9 cases, were jumbo biopsied using high-frequency current and the specimens obtained were examined histologically. Based on the results, the final diagnosis was established in terms of the benign or malignant nature of the lesions, some modifications were made in the irradiation method in accordance with the depth of invasion of the gastric cancer, and the adequacy of the irradiation therapy was examined. Then, the remaining tumor was irradiated with laser. This combination therapy of high frequency current and laser can make up for the drawback associated with laser therapy which does not permit collection of specimens for pathohistological study.

Adenocarcinoma↗

Co-operation of progesterone and prostaglandins in ovulation induced by human chorionic gonadotrophin in immature rats primed with pregnant mare serum gonadotrophin.

Serial injections of a mixture of prostaglandin (PG) E2 and F2 alpha 0, 2, 4, and 6 h after simultaneous injection of human chorionic gonadotrophin (hCG) and indomethacin incompletely restored the ovulation that would have been blocked by indomethacin in immature rats treated with pregnant mare serum gonadotrophin followed by hCG. Serial injections of another mixture of PGE2 and PGF2 alpha 6, 8, 10 and 12 h after simultaneous injection of hCG and indomethacin similarly reversed, in part, the inhibitory effects of indomethacin on hCG-induced ovulation. In contrast, serial injections of the mixtures of PGE2 and PGF2 alpha 0, 2, 4, 6, 8, 10 and 12 h after simultaneous injection of hCG and indomethacin completely restored the indomethacin-blocked ovulation, suggesting that the prostaglandins mediate the action of hCG on ovulation both in the earlier and later stages of the preovulatory process. Six hours after simultaneous injection of hCG and indomethacin serial injections of a mixture of PGE2 and PGF2 alpha reproduced the acute and temporary increase in concentrations of progesterone and testosterone in plasma which would have been abolished by indomethacin. Progesterone given concurrently with hCG and indomethacin partially antagonized the inhibitory action of indomethacin on ovulation. Serial injections of a mixture of PGE2 and PGF2 alpha 6, 8, 10 and 12 h after concurrent administration of progesterone with hCG and indomethacin completely restored the indomethacin-blocked ovulation, suggesting that progesterone can substitute the action of prostaglandins injected serially in the first half of the preovulatory process. It was concluded that the co-operation of progesterone in the earlier stage and of prostaglandins in the later stage of the preovulatory interval is required to mediate the action of hCG on ovulation.

Animals↗

[The antibacterial activity of new cephem antibiotics against clinical isolates. A comparison of the antibacterial activity of cefotaxime with 6 other antibiotics].

During the period from May through July 1981, a comparative study was carried out on the antibacterial activities of cefotaxime (CTX) and ceftizoxime (CZX), cefoperazone (CPZ), latamoxef (LMOX), cefotiam (CTM), cefmetazole (CMZ) and cefazolin (CEZ). CTX and these other cephem antibiotics were tested against fresh clinical isolates which had been obtained from clinical materials by the laboratories of 14 participating medical institutions. 1. The clinical isolates were obtained from various clinical materials in the following decreasing order: urine, sputum and pus/discharge; 85.7% of the isolates came from these materials. 2. Concerning the sources of each species of clinical isolates, it was found that P. aeruginosa was isolated from the greatest number -9- of different clinical materials. This was followed by E. coli and E. cloacae, each isolated from 8 different clinical materials, and C. freundii and E. aerogenes, each found in 7 different clinical materials. 3. In relation to S. pyogenes, S. agalactiae and S. pneumoniae, CTX showed the best antibacterial activity; the second most potent antibiotic was CZX. CMZ and LMOX were found to show relatively high MIC values for those species. Against S. aureus, CEZ showed the best antibacterial activity, but 3 resistant strains had MICs of greater than 100 micrograms/ml. 4. With regard to Gram-negative bacteria, CTX and CZX showed the best antibacterial activities for all of the species, except for P. aeruginosa. These were followed, in order, by LMOX and CPZ. Compared with these 4 antibiotics, CTM, CMZ and CEZ were found to have inferior antibacterial activities against these bacteria. In relation to P. aeruginosa, the peak of the MIC distribution for CPZ was 6.25 micrograms/ml, and this was the best antibacterial activity detected with the various antibiotics tested. This was followed by CTX (25 micrograms/ml) LMOX (25 micrograms/ml) and CZX (50 micrograms/ml). CTM had an MIC of 100 micrograms/ml for 1 strain, and MICs of greater than 100 micrograms/ml for all of the other strains of P. aeruginosa, indicating them to be resistant to this antibiotic. All of the strains were resistant to CMZ and CEZ, showing MICs of greater than 100 micrograms/ml. 5. For each of the tested antibiotics, no correlation was found between the MIC and the serogroup for either P. aeruginosa or S. marcescens.

Bacteria↗

[Clinical studies of cefotiam in otorhinolaryngologic infections].

Cefotiam (CTM) was intravenously given to 12 patients with infectious diseases in the field of otorhinolaryngology including 10 cases with chronic suppurative otitis media. Daily doses of CTM were 1 to 4 g. Clinical responses were excellent in 3 patients, good in 5, fair in 1 and poor in 3. The rate of overall clinical effectiveness was 67%. Staphylococcus species were most frequently isolated from the patients and all of them were eradicated by the CTM treatment. No side effects and no abnormal laboratory findings relating to the drug administration were observed.

Adolescent↗