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Biomedical subjects

K Kanai

Publications and source records attributed to K Kanai.

At least 127 records · Page 7Linked to original sources

Treatment of chronic hepatitis B with recombinant leukocyte interferon and cyanidanol.

Twelve male patients with chronic hepatitis B were treated by the combination of recombinant human alpha-interferon and cyanidanol. They received 3 million units of interferon twice a week and 2,250 mg of cyanidanol daily for 24 weeks. Four patients had sustained clinical improvement in which hepatitis B e antigen and DNA polymerase disappeared from sera and aminotransferase activities fell to normal levels. Elevated pretreatment aminotransferases were associated with the response to therapy. Also, decreased number of OKT4-positive cells prior to treatment were observed among responders. Side effects were minimal and all patients tolerated treatment on an outpatient basis. Twice weekly administration of recombinant leukocyte interferon with cyanidanol may be effective in treating chronic hepatitis when patients are appropriately selected.

Adult↗

Reflex increase in renal nerve activity during acutely altered portal venous pressure.

This study was designed to determine the reflex effects of renal nerve activity during acutely altered portal venous pressure in anesthetized dogs. Following inflation of a balloon in the main portal vein of animals with the neuraxis intact, mean blood pressure (MBP) fell significantly from 127 +/- 8 mm Hg to 101 +/- 7 mm Hg, while renal nerve activity (RNA) increased to 189 +/- 11%. This significant increase in RNA during inflation of the balloon was not entirely eliminated by either carotid sinus nerve (CSN) denervation (163 +/- 9% of the control level) or vagotomy (161 +/- 11% of the control level). The reflex increase in RNA observed with the combined denervation of the carotid sinus and vagal nerves (CSN + Va denervation) was 138 +/- 2% of the control level, and this level of RNA increase was significantly smaller compared to those in the other 3 groups (intact, CSN or Va denervated). Even when the portal venous pressure below caudal to the balloon was controlled at a pre-distension level by means of opening an artificial bypass constructed between the mesenteric vein and the femoral vein in the CSN + Va denervated group, the increased RNA response during inflation of the balloon remained. After hepatic denervation in the CSN + Va denervated group with the opening of the bypass, however, inflation of a balloon caused no significant changes in RNA, even when more profound hypotension existed during inflation of the balloon.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inhibitory effect of phenobarbital on peroxisome biogenesis in mouse hepatocytes.

Peroxisomes in hepatocytes from mice administered 35, 50, or 100 mg/kg of phenobarbital (PB) were analyzed by quantitative electron microscopy. In perivenular hepatocytes, the volume of peroxisomes per unit cytoplasmic volume decreased to 78 or 57% of that of control animals by administration of 50 or 100 mg/kg. Their average volume also decreased to 78 or 64% of that in control animals in animals injected with 35 or 50 mg/kg. Further, cytochemical catalase activity appeared decreased in peroxisomes of hepatocytes of this zone after administration of 50 or 100 mg/kg. These suggest an inhibitory action of PB administration of biogenesis of peroxisomes in perivenular hepatocytes. In periportal hepatocytes, however, the volume density, average volume, and cytochemical catalase activity of peroxisomes did not change by administration of any doses of PB. Thus, PB administration appears to produce no inhibitory effect on the peroxisome biogenesis in periportal hepatocytes. On the other hand, the number of peroxisomes per unit cytoplasmic volume increased in both periportal and perivenular hepatocytes in animals injected with 50 mg/kg, although it returned to the level of control animals by injection of 100 mg/kg. The inhibitory effect of PB on the peroxisome neogenesis in perivenular hepatocytes may be related to the marked smooth endoplasmic reticulum proliferation by administration of this drug.

Animals↗

Selective block of calcium current by lanthanum in single bullfrog atrial cells.

A single suction microelectrode voltage-clamp technique was used to study the actions of lanthanum ions (La3+) on ionic currents in single cells isolated from bullfrog right atrium. La3+, added as LaCl3, blocked the "slow" inward Ca2+ current (ICa) in a dose-dependent fashion; 10(-5) M produced complete inhibition. This effect was best fitted by a dose-response curve that was calculated assuming 1:1 binding of La3+ to a site having a dissociation constant of 7.5 x 10(-7) M. La3+ block was reversed (to 90% of control ICa) following washout and, in the presence of 10(-5) M La3+, was antagonized by raising the Ca2+ concentration from 2.5 to 7.5 mM (ICa recovered to 56% of the control). However, the latter effect took approximately 1 h to develop. Concentrations of La3+ that reduced ICa by 12-67%, 0.1-1.5 x 10(-6) M, had no measurable effect upon the voltage dependence of steady state ICa inactivation, which suggest that at these concentrations there are no significant surface-charge effects of La3+ on this gating mechanism. Three additional findings indicate that doses of La3+ that blocked ICa failed to produce nonspecific effects: (a) 10(-5) M La3+ had no measurable effect on the time-independent inwardly rectifying current, IK1; (b) the same concentration had no effect on the kinetics, amplitude, or voltage dependence of a time- and voltage-dependent K+ current, IK; and (c) 10(-4) M La3+ did not alter the size of the tetrodotoxin-sensitive inward Na+ current, INa, or the voltage dependence of its steady state inactivation. Higher concentrations (0.5-1.0 mM) reduced both IK1 and IK, and shifted the steady state activation curve for IK toward more positive potentials, presumably by reducing the external surface potential. Our results suggest that at a concentration of less than or equal to 10(-5) M, La3+ inhibits ICa selectively by direct blockade of Ca channels rather than by altering the external surface potential. At higher concentrations, La3+ exhibits nonspecific effects, including neutralization of negative external surface charge and inhibition of other time- and voltage-dependent ionic currents.

Action Potentials↗

Role of central nervous system in renal nerve activity during prolonged hemorrhagic shock in dogs.

The contribution of sympathetic efferent outflow through the central nervous system (CNS) during prolonged hemorrhagic hypotension of 50 mmHg was examined in anesthetized dogs. Mean blood pressure, heart rate, and renal nerve activity (RNA) were recorded simultaneously after arterial bleeding for 2 h. In animals with an intact neuraxis, hemorrhage to approximately 50 mmHg increased RNA to 180 +/- 12% of control level at 5 min after bleeding, but returned close to control level after 10 min. A secondary increase in RNA followed, with its maximum (280 +/- 12%) at 30 min after bleeding. Then RNA gradually decreased so that at end of experiment (120 min after bleeding) RNA was 10 +/- 9% of control. The initial increase in RNA was abolished by denervation of afferents from carotid sinus and cardiopulmonary regions, but secondary RNA response during hemorrhagic hypotension was similar to that in the intact group and occurred when the head region of animals was exposed to a hypotension of 50 mmHg, and perfusion to peripheral regions of the body was maintained near normal range. However, when perfusion to the head was maintained at a steady level and peripheral regions were exposed to hypotension of 50 mmHg, RNA response did not change significantly. These results provide evidence that prolonged hemorrhagic hypotension, which induces severe brain ischemia, causes biphasic sympathetic outflow via the CNS. The increase in sympathetic activity was followed by decrease with time. This decrease may contribute to the pathogenesis of vasomotor paralysis occurring at the irreversible stage of hemorrhagic shock.

Animals↗

Glucagon receptors in endothelial and Kupffer cells of mouse liver.

To determine whether hepatic sinusoidal cells contain glucagon receptors and, if so, to study the significance of the receptors in the cells, binding of [125I]-glucagon to nonparenchymal cells (mainly endothelial cells and Kupffer cells) isolated from mouse liver was examined by quantitative autoradiography and biochemical methods. Furthermore, the pathway of intracellular transport of colloidal gold-labeled glucagon (AuG) was examined in vivo. Autoradiographic and biochemical results demonstrated many glucagon receptors in both endothelial cells and Kupffer cells, and more receptors being present in endothelial cells than in Kupffer cells. In vivo, endothelial cells internalized AuG particles into coated vesicles via coated pits and transported the particles to endosomes, lysosomes, and abluminal plasma membrane. Therefore, receptor-mediated transcytosis of AuG occurs in endothelial cells. The number of particles present on the abluminal plasma membrane was constant if the amount of injected AuG increased. Therefore, the magnitude of receptor-mediated transcytosis of AuG appears to be regulated by endothelial cells. Kupffer cells internalized the ligand into cytoplasmic tubular structures via plasma membrane invaginations and transported the ligand exclusively to endosomes and lysosomes, suggesting that the ligand is degraded by Kupffer cells.

Animals↗

Pseudomonas pseudomallei and melioidosis, with special reference to the status in Thailand.

Melioidosis is a long-known disease since 1912, but only quite recently we have obtained the knowledges about its actual clinical and epidemiological features. The disease is so unique in having a wide spectrum of disease course and clinical manifestation. The causative agent, P. pseudomallei, is free-living bacterium in the natural environments (soil and surface water) of tropical and subtropical areas. Just like legionnaires' disease, melioidosis is a good example of infectious disease in which pneumonia is produced by inhalation of contaminated soil dusts or water droplets. The infection becomes dormant for years, but with a chance of recrudescence under a variety of insults to the host resistance. The disease, may it be acute or chronic, will be symptomatically confused with malaria, typhoid fever, leptospirosis, septicemia caused by other gram-negative bacteria, tuberculosis and mycotic infections. Isolation of the causative agent from clinical specimens is the only reliable method for diagnosis. Because of the increasing clinical awareness and the development of diagnostic methods, the reported cases of melioidosis have numbered almost one thousand in Thailand during the past 20 years. This country has now the most ample clinical experiences on melioidosis. We have reviewed the history of melioidosis research from bacteriological, immunological, clinical and epidemiological viewpoints, especially including the recent reports in Thailand.

Humans↗

An experimental model of chemotherapy on dormant tuberculous infection, with particular reference to rifampicin.

Mice were infected intravenously with a streptomycin (SM)-dependent strain of tubercle bacilli which had been starved of the antibiotic. The inoculum persisted in the spleen for a fairly long period, especially keeping almost the initial level of viable counts in the first few weeks. Isoniazid (INH) administration exerted little effect on such fate of the infection at a bactericidal dose to the same strain multiplying under the supply of SM. Rifampicin (RFP) was, however, highly effective in either case. Similar results were obtained in the corresponding in vitro experiments. The data suggest that this animal model is a convenient system for screening drugs effective on the dormant tuberculous infection.

Animals↗

Synthesis of 7'-(3-hydroxypropyl)fortimicin A and 6'-epifortimicin A.

1,10-Di-0-acetyl-2,3,4,6,7,8,9-heptadeoxy-2,6-bis(2, 4-dinitrophenylamino)-L-lyxo-decopyranose (7) and -D-ribo-decopyranose (8) have been prepared from methyl 2-acetamido-2,3,4,6-tetradeoxy-6-nitro-alpha-D-erythro-hexopyranoside via a nitro aldol reaction with 4-[(tetrahydropyranyl)oxy]butanal in the presence of cesium fluoride, and their configurations at C-6 have been established by conversion of the precursor of 8, namely, methyl 2,6-diacetamido-10-O-acetyl-2,3,4,6,7,8,9-heptadeoxy-alpha-D - ribo-decopyranoside, into the known methyl 2,6-diacetamido-2,3,4,6,7,8,9,10-octadeoxy-alpha-D-ribo-d ecopyranoside. The title fortimicin A derivatives, 7'-(3-hydroxypropyl)fortimicin A and 6'-epifortimicin A, have been synthesized by condensation of compound 7 and 8, respectively, with 2,5-di-O-benzoyl-1,4-bis[N-(methoxycarbonyl)]fortamine B, followed by deprotection and introduction of a glycyl group. Their antimicrobial activities have been found to be weak compared to that of fortimicin A.

Aminoglycosides↗

Significance of increase in glucose 6-phosphatase activity in brown adipose cells of cold-exposed and starved mice.

Cytochemical and biochemical glucose 6-phosphatase (G6Pase) activity was examined in brown adipose tissues of normal, cold-exposed, or starved mice. In addition, G6Pase activity in white adipose tissue and hexokinase activity in brown and white adipose tissues were biochemically measured. In normal animals, the reaction product for G6Pase activity was localized in the endoplasmic reticulum and nuclear envelope of brown adipose cells. The amount of the reaction product increased in cold-exposed or starved animals. Biochemical G6Pase activity (259.7 +/- 48.5 ng Pi/min/mg protein) in brown adipose tissues of normal animals was higher when the value was compared with values of other organs. Biochemical G6Pase and hexokinase activities increased rapidly in brown adipose tissues of cold-exposed animals, and a close relation was found between activities of the two enzymes. In brown adipose tissues of animals starved for 3 days, biochemical G6Pase activity increased, but hexokinase activity did not change. In white adipose tissues of normal, cold-exposed, or starved animals, G6Pase activity was very low, although the enzyme activity increased slightly in animals starved for 3 days. The results show that the high G6Pase activity in brown adipose cells probably relates to thermogenesis in cold-exposed animals and may be concerned with glucose release into the blood in starved animals.

Adipose Tissue, Brown↗