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Biomedical subjects

H Oka

Publications and source records attributed to H Oka.

At least 451 records · Page 25Linked to original sources

Studies on the effect of glucagon on human pancreatic secretion by analysis of endoscopically obtained pure pancreatic juice.

The effect of glucagon on human exocrine pancreatic secretion was evaluated in ten patients by analysis of pure pancreatic juice. Pancreatic juice was obtained by endoscopic cannulation of the pancreatic duct at 2-min intervals during constant intravenous infusion of secretin (1 U per kg of body weight per hr) plus caerulein (0.04 micrograms per kg of body weight per hr). Since steady secretion was established 20 minutes after the start of juice collection, a further five 2-min fractions were collected as controls, then constant intravenous infusion of glucagon (15 micrograms per kg of body weight per hr) was commenced. Pancreatic juice was collected for a further 20 minutes. The control fractions and post-glucagon fractions were compared in each patient using Student's test. Glucagon depressed secretin-caerulein-stimulated pancreatic secretions. More uniform reductions were observed in the concentration and output of protein and enzymes. Individual variations were observed in the secretory volume and bicarbonate concentration and output. Amylase and lipase were depressed in a parallel fashion in seven patients and in the remaining three, amylase was more depressed than lipase. The post-glucagon reduction in pancreatic secretion was not proportional to the rise in plasma glucagon and blood glucose.

Adenocarcinoma↗

Human prolyl hydroxylase. Purification, radioimmunoassay and clinical studies in liver diseases.

Prolyl hydroxylase was purified from human placentae, specific antiserum against it was prepared, and a new radioimmunoassay system employing 125I-labelled enzyme preparation was established. The molecular weight of the placental enzyme was shown to be 320,000 by gel filtration. SDS-polyacrylamide gel electrophoresis showed two bands of unequal intensity having molecular weights of 60,000 and 130,000. Their amino acid compositions were identical to each other, suggesting the polypeptide with a molecular weight of 130,000 might be a dimer of the polypeptide with a molecular weight of 60,000. The new radioimmunoassay established had a sensitivity of the order of 10 ng/ml, indicating it was more sensitive than previous radioimmunoassay employing 3H-labelling method. Clinical studies on patients with liver diseases disclosed that the concentrations of serum immunoreactive prolyl hydroxylase were elevated both in cases of hepatocellular damage and in cases of cholestasis. In cases of hepatocellular damage the enzyme behaved like cytoplasmic enzymes such as glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and lactic dehydrogenase, but in cases of cholestasis it resembled biliary enzymes such as alkaline phosphatase and gamma-glutamyl transpeptidase. This result might be associated with the peculiar location of the enzyme within the cell, in the membrane of rough endoplasmic reticulum.

Amino Acids↗

Benefit of transcatheter arterial embolization for ruptured hepatocellular carcinoma complicating liver cirrhosis.

In 6 patients with spontaneous rupture of hepatocellular carcinoma complicating liver cirrhosis, but with no occlusion of the main portal trunk, transcatheter arterial embolization was performed within 7 days of the rupture. All 6 patients were thought to be inoperable because of shock state or severe hepatic dysfunction. In all 6 patients, the progressive decrease in the hematocrit ceased soon after the embolization. Five patients survived for 31-168 days after the embolization; 1 patient who developed septicemia died 10 days later. We conclude that transcatheter arterial embolization is beneficial as a procedure of first choice for ruptured hepatocellular carcinoma when the portal blood flow is maintained.

Adult↗

Organization of afferent connections to the lateral and interpositus cerebellar nuclei from the brainstem relay nuclei: a horseradish peroxidase study in the cat.

Afferent projections to the lateral (dentate) and interpositus cerebellar nuclei from the brainstem relay nuclei were studied in cats using the horseradish peroxidase (HRP) method. In the first series of experiments, HRP was injected into the brachium pontis. Mossy fiber terminals were anterogradely labeled, predominantly in the lateral (hemispherical) part, moderately in the intermediate part, and slightly in the vermal part of the cerebellum. Besides these terminals in the cerebellar cortex, axon terminals labeled anterogradely were also found in the cerebellar nuclei. The labeled terminals appeared almost exclusively in the lateral nucleus and rarely in the interpositus nucleus. Cells labeled retrogradely were found both in the pontine nuclei and the tegmental reticular nucleus, but not in other brainstem nuclei. In the second series of experiments, HRP was injected into the lateral and interpositus nuclei, and retrograde labeling was examined in the brainstem relay nuclei. After HRP injection into the lateral nucleus, the number of labeled cells was significantly large in the pontine nuclei, but fairly small in the reticular or vestibular nuclei. The number of labeled cells was generally large in the inferior olive, mainly in the principal olive. After HRP injection into the interpositus nucleus, the number of labeled cells was moderate in the reticular or vestibular nuclei, but small in the pontine nuclei. The number of labeled cells in the inferior olive was also large, being distributed mainly in the accessory olives. These results indicate that the pontine nuclei and the principal olive provide major afferent inputs to the lateral nucleus, whereas the reticular nuclei, the vestibular nuclei and the accessory olives are the major afferent sources to the interpositus nucleus.

Afferent Pathways↗

Purified hydrophobic proteins, chargerins, are essential for energy transduction in oxidative phosphorylation.

Studies on anisotropic inhibitors, a unique type of inhibitor of energy transduction in oxidative phosphorylation, suggested that redox reactions generate two kinds of negative charges on the outer surface of mitochondrial inner membranes, on redox complexes and on F0, and that the inhibitors inhibit energy transduction by binding to these negative charges. Recent experiments on photoaffinity labeling of mitochondria with monoazide ethidium, which is an anisotropic inhibitor, showed that the inhibitor specifically binds to a hydrophobic protein of the membranes. In the present work the mitochondrial components labeled with monoazide ethidium were further purified and two kinds of hydrophobic proteins (apparent molecular masses, 8 and 13 kDa) were found to be specifically labeled with the inhibitor. These proteins were named chargerin I and II, respectively. Redox reactions greatly increased the molar ratio of ethidium bound to chargerin I and II in mitochondria, reflecting a conformational change of the chargerins coupled with the redox reactions. It was also shown that antibody against chargerin II specifically inhibited ATP synthesis in mitoplasts (inner membranes plus matrix) prepared from rat liver mitochondria. Thus, the present findings show that chargerins have an essential role in energy transduction in oxidative phosphorylation in rat liver mitochondria, in good accord with the conformational coupling model of the H+ pumps and ATP synthesis.

Affinity Labels↗

Partial purification of the apolipoprotein E receptor of rat liver membrane.

The liver has two distinct lipoprotein receptors; one is the apolipoprotein (apo) B, E receptor and the other the apo-E receptor. In this study, the protein to which apo-E HDLc (cholesterol-induced high density lipoprotein containing apo-E as the predominant protein species) bound specifically was partially purified from the rat liver membrane by ion exchange chromatography and preparative gel electrophoresis. The molecular weight of the protein was estimated to be about 36K daltons and the protein bound to 125I-apo-E HDLc in a specific and saturable manner, suggesting that the protein is the apo-E receptor.

Animals↗

Changes in quantity of fibronectin from human skin fibroblasts with cellular aging.

Using an enzyme-linked immunosorbent assay, we investigated the amount of cell surface fibronectin and the amount released to the culture medium in human skin fibroblasts during successive cultivation. Cell surface fibronectin did not show a remarkable change in quantity through early and midpassage, but it decreased markedly in late passage. Released fibronectin per cell also did not show a remarkable change through early and midpassage. In late passage, however, it exhibited a marked increase.

Cell Membrane↗

Collagen prolyl hydroxylase inhibitor and reduced collagen formation in cotton pellet-induced granuloma and skin wound healing in rats.

P-1894B an inhibitor of collagen prolyl hydroxylase was applied topically to cotton pellet-induced granuloma and to skin lesions in rats. The total hydroxyproline content of the granulomata was significantly reduced by this agent. It also reduced the hydroxyproline content in the tissues surrounding skin lesions during the healing process, with delayed diminution in lesion size. These results suggest that collagen prolyl hydroxylase inhibitor P-1894B may be a suitable agent for topical treatment of hypertrophic scar tissue or keloid.

Animals↗

Post-natal development of pyramidal tract neurones in kittens.

The post-natal development of pyramidal tract neurones (p.t.n.s) was investigated in twenty-one barbiturate-anaesthetized kittens from birth to 28 days of age using a combination of electrophysiological and anatomical techniques. P.t.n. responses were recorded intracellularly as well as extracellularly with glass micropipettes filled with horseradish peroxidase (HRP) on stimulation of the medullary pyramid and cerebellar nuclei. Latency histograms of antidromic responses of p.t.n.s were compared at various ages. In the neonate, p.t.n.s were divided into two groups which were presumed to be analogous with fast and slow p.t.n.s in adult animals. During the first post-natal week, latency shortening was not conspicuous, but by the end of the second post-natal week, the faster group showed a marked decrease of latencies (up to around 10 ms at 14 days of age), while those of the slower group did not change so much. The slower group increased their conduction velocity during the third post-natal week (latencies up to around 18 ms). At the end of the fourth post-natal week, the distribution of antidromic latencies was in a narrower range, but the values were still longer than those reported in adult animals. Intracellular HRP staining revealed that apical dendrites of p.t.n.s spread fully to the pial surface even at birth. The somata of these neurones were characteristically covered with somatic appendages and development of the basal dendritic tree was immature in 0-1-day-old kittens. Basal dendrites developed nearly completely by 7 days, but somata were still covered with appendages. During the fourth post-natal week, these appendages disappeared almost completely. The sizes of the dendritic field, especially of apical dendrites, became larger in parallel with the development of cortical layers. From the morphological point of view, differentiation of fast and slow p.t.n.s was not clear until 28 days of age except in somatic volumes, which were already different in the first post-natal week. At the end of the fourth post-natal week, p.t.n.s with short antidromic latencies had a tendency to bear spines more sparsely over the secondary and tertiary dendritic surface in comparison with p.t.n.s with longer latencies. Intracortical axonal trajectories developed fairly well in the immature cerebral cortex, and the general pattern of ramification changed little during the first month after birth.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Pharmacological comparison of captopril and MK-422 by a new method for measuring activity of angiotensin converting enzyme (ACE).

The authors recently reported the development of a new method for measuring angiotensin converting enzyme (ACE) by means of a highly sensitive angiotensin II RIA technique. We have carried out a comparative study of the pharmacological properties of captopril and MK-422, two ACE inhibitors recently developed as new antihypertensive agents. In this study, in vivo and in vitro animal experiments were performed using the Göttingen Mini-pig (Mini-pig G) animal model of the human disease. In the in vivo experimental system, each drug was administered by intravenous injection at a dose of 1 mg/kg, and a slight difference was found in the time-course of the per cent inhibition of ACE in the blood. In the in vitro system (cultured aortic endothelial cells), the ACE inhibitory activities of the two drugs were compared in terms of the 50%-inhibition point on the dose response curve, and it was found that MK-422 was about 100 times more potent than captopril. These results indicate that our newly-developed experimental system can be useful in the establishment of the clinical dose of vasoactive drugs that act on the renin-angiotensin system.

Animals↗

An improved method for measuring angiotensin I converting enzyme activity using a highly sensitive angiotensin II radioimmunoassay.

A highly sensitive assay for angiotensin I converting enzyme has been developed by using angiotensin I as a substrate. Angiotensin II generated in the reaction mixture was measured by a newly developed specific radioimmunoassay. To protect against angiotensin II destruction, bestatin, an inhibitor of renin, was also used to inhibit plasma renin activity. The reaction was stopped by adding EDTA and MK-521, inhibitors of angiotensin I converting enzyme. The specificity of the antiserum used for the angiotensin II radioimmunoassay was very high. The cross reactivity with angiotensin I was less than 0.5% and none of the proteolytic enzyme inhibitors crossreacted in the assay. The inhibitory effect of pepstatin on plasma renin activity was very high (more than 80%) under the standard assay conditions employed. Serum angiotensinase activity was completely inhibited by the addition of bestatin. An excellent correlation was obtained between this new method and the spectrophotometric method using a synthetic substrate, Hip-His-Leu. The generation of as little as 12 pM of Angiotensin II can be detected. Such low concentration have not been measurable with the usual spectrophotometric method. This new method will facilitate clinical and experimental studies on this unique enzyme, since very low levels of activity can be determined by this highly sensitive radioimmunoassay for angiotensin II.

Angiotensin I↗

Structural study of a new antitumor antibiotic, kazusamycin.

The structure of a new antitumor antibiotic, kazusamycin produced by Streptomyces sp. No. 81-484, was determined on the basis of its spectral and chemical properties. Kazusamycin has a structure characteristic of an unsaturated, branched-chain fatty acid with a terminal delta-lactone ring.

Antibiotics, Antineoplastic↗

Hypomethylation of c-myc and epidermal growth factor receptor genes in human hepatocellular carcinoma and fetal liver.

The methylation state of cellular oncogenes (c-oncs) and epidermal growth factor (EGF) receptor gene from human liver tissues was examined by means of restriction endonuclease analysis. c-myc and EGF receptor gene from hepatocellular carcinoma and fetal liver were substantially hypomethylated in comparison with those genes from normal liver, while the extents of methylation of c-mos and c-Ki-ras genes were the same among these tissues. It can be speculated that the specific hypomethylation of c-myc and EGF receptor genes may be associated with the development of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

[Effect of PSK on prostaglandin metabolism (I)].

The effect of PSK (Krestin) on the metabolism of prostaglandins was investigated. The effect of PSK on the thromboxane A2 (TXA2) level, which stimulates tumor proliferation and platelet aggregation, was examined using platelets. PSK suppressed platelet aggregation and the production of malondialdehyde (MDA) and TXB2 which is a stable metabolite of TXA2. The effect of PSK on the production of prostacyclin (PGI2), which is an anti-tumor PG, was then examined using rat arterial rings. It was found that PGI2 production was stimulated by PSK. The in vivo inhibition of platelet activation by PSK was then examined using two thrombosis models in which platelet aggregation was mainly involved. PSK exerted its anti-platelet effect by regulation of PG production. It was concluded that not only an immune regulating effect but also PG regulation are involved in the pharmacological action of PSK.

Animals↗