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Biomedical subjects

H Okazaki

Publications and source records attributed to H Okazaki.

At least 235 records · Page 13Linked to original sources

Lactivicin, a naturally occurring non-beta-lactam antibiotic having beta-lactam-like action: biological activities and mode of action.

Lactivicin is moderately active against a wide range of Gram-negative bacteria and highly active against Gram-positive bacteria. It shows various biological activities commonly observed with beta-lactam antibiotics, such as higher activity against beta-lactam hypersensitive mutants than against their parents, sensitivity to beta-lactamases, inhibitory activity against beta-lactamases and ability to induce beta-lactamase activity. The primary lethal target of lactivicin in Escherichia coli is highly likely to be penicillin-binding protein (PBP) 1; lactivicin strongly lysed E. coli cells with induction of spheroplasts at its MIC, and showed high affinity for PBPs 1A and 1B. At concentrations above x 5 MIC, however, lactivicin dominantly exhibited secondary antibacterial action possibly owing to inhibition of crucial SH proteins engaged in the fundamental membrane functions. In contrast, against Bacillus subtilis, lactivicin showed the typical beta-lactam action under a wide range of concentrations. It showed high affinity for PBPs 1, 2 and 4, the possible lethal targets of beta-lactam antibiotics in this organism. In conclusion, lactivicin is the first non-beta-lactam antibiotic showing beta-lactam action through binding to PBPs.

Anti-Bacterial Agents↗

[Percutaneous transluminal angioplasty in patients with prior coronary artery bypass grafting].

Seventeen patients with stenosis of bypass grafts or native coronary arteries (NCA) following coronary artery bypass underwent percutaneous transluminal angioplasty (PTCA). Stenoses were located in the saphenous vein graft (SVG) in 11 cases (involving 16 lesions), in the internal mammary artery graft (IMAG) in 2 cases (2 lesions), and in the NCA in 9 cases (13 lesions). All patients had disabling angina pectoris or a post-operative stenosis of more than 50%. PTCA was successful in 75% of all the SVG stenotic lesions, 50% of the IMAG lesions and in 67% of the NCA lesions. There were no complications associated with PTCA. After successful PTCA, restenosis developed in 23% of the SVG cases, 0% of the IMAG cases and in 38% of the NCA cases. Though relief of chest pain was found in 10 patients (59%), PTCA of the NCA was not so effective as PTCA of the bypass grafts.

Angioplasty, Balloon↗

Stabilization of hexokinases I and II of ELD cells by binding to mitochondria.

Significance of the binding of hexokinase to mitochondria was examined with respect to stabilization of the enzyme by the binding. Stability during the incubation of the mitochondria-bound forms of hexokinases I and II, both prepared from Ehrlich-Lettre ascites hyperdiploid tumor cells (ELD cells), were compared with that of the corresponding free forms. During the incubation at pH 7.4 and 37 degrees C up to 60 min, hexokinase activities decreased gradually, and the decrease in the activity of the free form was much more marked than that of the bound form for both hexokinases. Hexokinase II was much less stable than I, and the activity of the free form of the former was almost lost by the incubation for 15 min. But, more than a half of the original activity of hexokinase II was retained even after 60 min of the incubation when the enzyme was bound to mitochondria. Addition of 50 mM glucose increased the stability of hexokinase II, but the stabilizing effect was less marked for hexokinase I. On the other hand, addition of 28 mg/ml of bovine serum albumin markedly stabilized hexokinase I to almost the same extent as was observed with mitochondria. On the contrary, the serum albumin had little stabilizing effect on hexokinase II. These findings indicate that the binding to mitochondria stabilizes the hexokinases of ELD cells, though the stability is different by nature between hexokinases I and II.

Animals↗

[Factors influencing the prognosis of carcinoma of the pancreas--an analysis of 155 cases].

At the National Cancer Center Hospital, the survival rates of 155 patients with pancreatic cancer, during the period from 1980 to 1987, have been retrospectively analysed. The size of tumor, type of histology, liver metastases, peritoneal metastases, and type of therapy affected the survival rates significantly. Survival rates at one year were 64% among the curative resections, 29% among non-curative resections, 30% for radiotherapy and chemotherapy and 10% for patients with only chemotherapy. We have concluded from the above that the combination of radiotherapy and chemotherapy enabled a longer survival in patients with a non-resectable pancreatic cancer.

Adenocarcinoma↗

[Clinical and pharmacokinetic evaluation of cefodizime in children].

Cefodizime (CDZM, THR-221), a new cephem antibiotic, was investigated for its clinical efficacy and pharmacokinetics in children. The results obtained are summarized as follows. 1. Antimicrobial activities Antimicrobial activities of CDZM against clinically isolated organisms were determined. MICs of CDZM against 1 strain each of Streptococcus pneumoniae, Escherichia coli and Klebsiella pneumoniae were 0.05 micrograms/ml to 0.10 micrograms/ml. Especially, MIC against all 6 strains of Haemophilus influenzae was less than or equal to 0.024 micrograms/ml. This MIC value was lower than those of other antibiotics such as cefotaxime, cefotiam, cefazolin, piperacillin. 2. Pharmacokinetics CDZM was given to 1 case at a dose of 20 mg/kg by a 60-minute intravenous drip infusion. The peak value of serum concentration of CDZM was 207.80 micrograms/ml at the end of the infusion. The half-life was 2.15 hours. The mean urinary excretion rate was 68.5% in the first 4 hours, 79.2% in 6 hours and 76.5% in 8 hours after the 30-minute drip infusion. 3. Clinical efficacy CDZM was given to a total of 27 patients, 13 with pneumonia, 1 with bronchitis, 2 with acute pharyngitis, 1 with purulent tonsillitis, 5 with urinary tract infection, 1 each with retrograde cholangitis, acute enteritis, pericementitis, phlegmon and inguinal lymphadenitis. Overall clinical efficacies were excellent in 5 cases, good in 17 and the efficacy rate was 81%. Bacteriological effects were investigated in 13 cases and the eradication rate was 85%. No adverse reactions were observed in any case. As abnormal laboratory findings, elevated GOT, GPT, A1-P, LAP and gamma-GTP, were noted in 1 out of the 28 cases examined.

Adolescent↗

[Complement activation during cardiopulmonary bypass: mechanism and prevention].

The mechanism of complement activation during cardiopulmonary bypass was studied for the prevention. In ten patients undergoing open-heart procedures, the serum levels of complement fractions (C3, C4, and C3 activator) were measured by a single radial immune diffusion method. In four of ten patients, the plasma levels of C3a, C4a, and C5a fractions were studied by the radioimmunoassay 2 antibodies method. The serum levels of C3, C4, and C3 activator decreased after cardiopulmonary bypass. The plasma levels of C3a, C4a, and C5a increased after bypass. The lower level of C3 activator shows that C3 activator was not excessively produced during cardiopulmonary bypass. Therefore it can be thought that much C4b2a from classical pathway as well as C3a over-production localizing extra-corporeal circuits and little inhibitors on alternative pathway resulted in increased complement activation. The prevention should be done from these etiologies.

Adult↗

[Ischemia-induced neurotrophic activity detected in the peri-infarcted brain tissue].

In the experimental ischemia induced by occlusion of the rat middle cerebral artery, axons of both cortical and thalamic neurons were affected. However, cortical neurons survived thereafter and thalamic neurons died because of retrograde degeneration. The fate in these two groups of neurons was remarkably different and may be related to neurotrophic activity induced by ischemia. To detect ischemia-induced neurotrophic activity, fetal cortical neuron was cultured and neurotrophic activity was detected by applying tissue extract to the culture system. Fetal neurons obtained from 17 days rat embryo were cultured for 24 hours at 3.75 x 10(4) cells per 15 mm well in modified Eagle's minimum essential (MEM) supplemented by 10% fetal bovine serum (FBS), then for next 3 to 7 days with Dulbecco's modified Eagle's medium/Ham's nutrient mixture F-12 (DME/F-12) supplemented with insulin 5 mg/l, transferrin 10 mg/l, progesterone 6.3 micrograms/l, Na2SeO3 5.2 micrograms/l. The tissue extract was obtained from the rat subjected to ischemia and homogenized with DME/F-12. The homogenate was centrifuged at 100,000 g for 90 minutes and the supernatant was obtained. Application of peri-ischemic cortical extract improved neurons' survival by 50% as compared to extract of the contralateral side. However, the thalamic extract of the ischemic side had no neurotrophic activity as compared to the contralateral side. The activity was detected in the extract obtained at 8 days after ischemia but not detected in the extract obtained at 4 days after ischemia. The neurotrophic activity was disappeared by heating the extract at 90 degrees C for 10 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Interactions between cations in modifying the binding of hexokinases I and II to mitochondria.

Interactions between cations in modifying the binding of hexokinases I and II to mitochondria was examined with reference to the intracellular condition. Mitochondria-binding of either of hexokinases I and II, both prepared from mouse ascites ELD cells, was markedly increased by Mg2+ as has been known well. However, even in the absence of Mg2+, marked binding was attained by 100 mM K+ alone especially for hexokinase I, which seemed generally more ready to bind to mitochondria. On the other hand, the effect of Mg2+ to increase the binding was reduced by the addition of K+, and the decreasing effect of K+ was much more marked for hexokinase II than I. These results indicate that, in addition to Mg2+, monovalent cations as represented by K+, also have marked effect on the binding, and the effect is different for each hexokinases I and II, which may be responsible for the difference in the intracellular distribution between these hexokinases.

Animals↗

Primary structure of two mRNAs encoding putative salmon alpha-subunits of pituitary glycoprotein hormone.

1. By random sequence analyses, we isolated from the cDNA library of salmon pituitary glands two clones, the deduced amino acid sequences corresponding to the C-terminal region of which are almost the same as those of the alpha subunits of mammalian glycoprotein hormones. 2. Comparison of the nucleotide sequences and deduced amino acid sequences from these two clones with those of mammalian species revealed that the two newly-isolated cDNAs corresponded to mRNAs encoding the putative salmon pre-alpha subunit of glycoprotein hormones. 3. Homology in the nucleotide sequences of these two clones suggested that corresponding mRNAs may be encoded by separate genes which probably evolved from a common ancestral gene.

Amino Acid Sequence↗

Absence of a gamma-melanocyte-stimulating hormone sequence in proopiomelanocortin mRNA of chum salmon Oncorhynchus keta.

1. Complete nucleotide sequence of one of the salmon proopiomelanocortin mRNAs (POMC mRNAs) was determined. 2. The region corresponding to gamma-melanocyte-stimulating hormone (gamma-MSH) was lacking in salmon POMC mRNA, although overall organization of the multi-hormone structure was exactly the same as that of mammalian POMC mRNAs. 3. The possible evolutional history of POMC mRNA in mammalian species may be revealed from the finding of this characteristic that salmon POMC mRNA lacks the region corresponding to gamma-MSH.

Amino Acid Sequence↗

[3H]neurotensin(8-13) binds in human brain to the same sites as does [3H]neurotensin but with higher affinity.

The binding of [3H]neurotensin(8-13) to membranes from human frontal cortex at 0 degree C was time dependent, specific, saturable, and reversible. Saturation isotherms provided an equilibrium dissociation constant (KD) of 0.52 nM, and the maximal number of binding sites (Bmax) was 3.5 pmol/g original wet weight of tissue. Scatchard analysis yielded a straight line, and the Hill coefficient was equal to 1, a result indicating that [3H]neurotensin(8-13) bound to single, noncoopertive sites. The KD values of several analogs of neurotensin determined in competition with [3H]neurotensin(8-13) were similar to those previously determined in competition with [3H]neurotensin. The regional distribution of binding sites for [3H]neurotensin(8-13) was also similar to that for [3H]neurotensin. These results suggest that [3H]neurotensin(8-13) binds to the same sites as [3H]neurotensin and that [3H]neurotensin(8-13) has a higher affinity than [3H]neurotensin for these sites in human brain.

Aged↗

Central pontine myelinolysis and its imitators: MR findings.

The clinical, radiologic, and neuropathologic findings in 13 patients with central pontine myelinolysis were reviewed. Antemortem computed tomography (CT) had been performed in nine, and ante- or postmortem magnetic resonance (MR) imaging in 11. Chronic alcoholism or rapid correction of hyponatremia was present in over 75% of cases. One CT scan was positive, but only on retrospective review. In all but one patient, MR imaging eventually revealed an abnormality within the pons; in two patients the initial study was normal. The lesions varied in shape, with peripheral involvement in two patients and extrapontine involvement in four. The abnormality was smaller at 6-month follow-up in one patient and unchanged at 1 year in another. One patient never had a demonstrable pontine lesion but did have symmetric basal ganglia abnormalities, which were consistent with extrapontine myelinolysis. MR imaging disclosed similar central pontine alterations resulting from infarct, metastasis, glioma, multiple sclerosis, encephalitis, and radiation or chemotherapy; thus, such changes are not unique.

Adult↗