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Biomedical subjects

A Yoshikawa

Publications and source records attributed to A Yoshikawa.

106 records · Page 6Linked to original sources

Hepatitis B immunoglobulin (HBIG) efficacy in the prevention of perinatal transmission of hepatitis B virus (HBV) infection.

Twelve out of 13 infants born from mothers having both HBsAg and HBeAg developed HBV carrier state within 4 months after birth. On the other hand, no babies from mothers having HBsAg and anti-HBe developed HBV carrier state. In order to prevent perinatal transmission of HBV, HBIG was administered into 14 babies born from mothers with positive HBeAg three or four times during 6 months after birth. During 12 months or more of observation period 5 out of 14 infants who received HBIG acquired active anti-HBs response after discontinuation of HBIG (passive-active immunization). However, 3 out of 14 infants unfortunately developed persistently positive HBsAg antigenemia at 12th, 14th and 14th month respectively after birth. Remaining 6 babies still have no virus markers, indicating not infected. These results indicates that HBIG administration was extremely effective for prevention of perinatal transmission of HBV. However, additional preventive measures with active immunization (HBV vaccine) seems to be necessary to prevent completely the perinatal transmission of HBV.

Carrier State↗

Evaluation of the antiviral effects of adenine arabinoside on chronic HBV infection.

Five male patients with HbsAg-positive liver disease were treated with ara-A at dosages ranging between 5 mg and 10 mg/kg/day for five days. Before treatment, all of them had detectable DNA polymerase activity and HbeAg in their sera. The five-day course of the drug resulted in a rapid fall in DNA polymerase activity in every patient, the effect being dose-dependent. The amount of circulating Dane particles also decreased simultaneously, or with a short time lag, with the fall of the enzyme activity. The following decrease in HBeAg concentration was observed in all patients, and it was also noteworthy that antiHBe response was found in two of the five. HBsAg titers were significantly diminished in two patients. In the present series of ara-A treatment, these effects were temporary in two patients, while, in the remaining three, they lasted for two to three months. Ara-A had no serious side effects at dosages of 10 mg/kg/day or less, and can thus be counted among the valuable therapeutic drugs against chronic HBV infection.

Adult↗

Increase in protein synthetic activity in chicken muscular dystrophy.

An increased level of protein synthesis was observed in an in vitro translation when the polyribosomes and postmicrosomal supernatant were prepared from dystrophic rather than normal muscle. This increment in protein synthetic activity was observed even in young dystrophic muscle in which no clinical and morphological abnormalities were detected. No specific increase in the rate of synthesis of any protein could be demonstrated in dystrophic muscle relative to normal muscle. Since a possible reason for the increment in protein synthetic activity was an increase in the activity of factor(s) in the postmicrosomal fraction, several of these were prepared from normal and dystrophic breast muscles and their activities were compared. Crude elongation factor (EF) from dystrophic muscle activated poly(U) directed polyphenylalanine synthesis more than the normal EF. This increase was shown to be due to higher levels of EF1 and EF2 in dystrophic than in normal muscle and not to a decrease in protease of RNase activity in the supernatant of dystrophic muscle relative to normal muscle. A comparison of the abilities of the postmicrosomal supernatants of normal and dystrophic muscle was made to support protein synthesis in vitro as a function of development age. The activity of aminoacyl-tRNA synthetase was also higher in the dystrophic supernatant than in the normal supernatant.

Amino Acyl-tRNA Synthetases↗

Reversible adrenergic alpha-receptor blocking action of 2,4'-dimethyl-3-piperidino-propiophenone (tolperisone).

The vascular action of 2,4'-dimethyl-3-piperidino-propiophenone hydrochloride (tolperisone hydrochloride), a centrally acting muscle relaxant, was investigated in pentobarbital anesthetized dogs. Tolperisone given intravenously produced a transient hypotension, tachycardia, and hyperventilation. The drug increased the femoral arterial flow, and decreased the superior mesenteric arterial flow following an initial transient increase. When injected directly into femoral and mesenteric arteries, tolperisone caused a rapid increase in both arterial flow (vasodilatation). However, femoral vessels were about 90 times as sensitive as mesenteric vessels to tolperisone. These results indicate that tolperisone shifts the blood volume from mesenteric (visceral) vessels to femoral (skeltal) ones. The femoral vasodilatation produced by i.a. tolperisone was not depressed by the pretreatment with i.a. propranolol, atropine or chlorphenylamine. Tolperisone decreased the contractile force in an isolated and cross-circulated papillary muscle. Tolperisone produced adrenaline reversal and antagonized the pressor response to noradrenaline. Moreover, femoral vasoconstriction caused by i.a. adrenaline was converted to vasodilatation and that caused by i.a. noradrenaline was depressed during an i.a. infusion of tolperisone. These results indicate that tolperisone blocks adrenergic alpha-receptors. The blocking action was rapid in onset, short-lived, and in addition, competitive.

Adrenergic alpha-Antagonists↗

Pharmacological action of FD-008, a new dopamine-beta-hydroxylase inhibitor. III. Effects on endogenous biogenic amine levels in rats.

Effect of a new dopamine beta-hydroxylase inhibitor, 5-(4'-chlorobutyl)-picolinic acid (FD-008) on endogenous amine levels in various tissue of normotensive and spontaneously hypertensive rats were determined in comparison with its mother compound, fusaric acid, and disulfiram. FD-008 decreased norepinephrine (NE) levels in the brain and heart with a slight increase of dopamine (DA) level in the brain. NE lowering activity of FD-008 was stronger than that of fusaric acid. Disulfiram was less active and the activity was one-tenth of FD-008. FD-008 lowered NE level even when DA was increased by pretreatment with L-DOPA or iproniazid but did not cause a further significant reduction of NE when catecholamines were practically depleted by pretreatment with reserpine.

Adrenal Glands↗

Electron microscopic studies of Dane particles in hepatocytes with special reference to intracellular development of Dane particles and their relation with HBeAg in serum.

Electron microscopic observations in 30 cases of HBsAg positive liver disease and 12 asymptomatic carriers of HBsAg suggested the following mechanism of intracellular development of Dane particles: core particles migrated from the nucleus into the cytoplasm through the nuclear pores. Intracytoplasmic core particles protruded into the cisternae of endoplasmic reticulum by budding the outer coat of Dane particles being derived from the membrane of endoplasmic reticulum. Release of Dane particles into the blood stream by reversed pinocytosis was suggested by the finding of submembranous localization of endoplasmic reticulum containing these particles. No budding from the cell surface of the hepatocytes was encountered. Dane particles in the hepatocytes were detected in 14 of 15 cases positive for serum HBeAg while no particles were seen in 27 HBeAg negative cases, thus suggesting that serum HBeAg reflected ongoing replication of hepatitis B virus in the hepatocytes.

Endoplasmic Reticulum↗

Increase in the amount of elongation factor 2 in chicken muscular dystrophy.

The amount of elongation factor 2 (EF2) in the cytoplasm and ribosome of breast muscle cell from normal and dystrophic strains of chicken was measured. Concentration in the cytoplasm of 20-day-old embryonic dystrophic muscle was higher than that in normal muscle, but no difference in content was found in muscles of 15-day-old embryos. The amount of EF2 bound to ribosomes was identical in normal and dystrophic muscles during all stages of development. Peptide mapping patterns of partial proteolytic fragments of EF2 from normal and dystrophic chicken breast muscles were similar. The increase in cytoplasmic protein synthetic activity of dystrophic breast muscles reported previously seems to be due to the corresponding increase in the number of EF2 molecules rather than to their modification in dystrophic muscle.

Animals↗

Chromosome III of Saccharomyces cerevisiae: an ordered clone bank, a detailed restriction map and analysis of transcripts suggest the presence of 160 genes.

Using lambda phage vector EMBL4, we isolated 344 clones containing segments of chromosome III of Saccharomyces cerevisiae, analysed their physical structure with eight restriction enzymes and sorted the data in contiguous groups with computer programmes. Furthermore, we performed Southern hybridizations between the sorted contiguous clone groups and interrelated them into larger groups. In this way, we constructed an ordered clone bank that covers almost the whole of chromosome III with a single gap of several kilobases in length. The consensus physical map thus obtained totals 334.6 kb, which is in good agreement with the size of this chromosome estimated by pulsed-field gel electrophoresis. Southern hybridization analysis with the DNA probes containing telomere-specific sequences showed that the bank contained a telomere at a position corresponding to the right arm terminus of chromosome III. Also, five Ty elements were found to be present. To estimate the number of genes on this chromosome and to analyse their levels of expression, we performed a series of Northern hybridization experiments using total poly(A)+ RNA from vegetatively growing cells and appropriate restriction enzyme fragments from the bank. Thus, we identified a total of 156 transcripts on chromosome III, indicating, on an average, one gene in every 2 kb on this chromosome. The transcripts were visually categorized into five groups according to their apparent levels of expression. It was found that the genes located near both termini are expressed only at low levels and that highly expressed genes are rather scattered over the chromosome.

Blotting, Northern↗

Clinical study of recombinant hepatitis B vaccine.

The efficacy and safety of a recombinant yeast-derived hepatitis B vaccine were evaluated in 209 subjects after three administrations at 0, 4 and 20 weeks. Subjects were divided into four groups given 5 micrograms vaccine subcutaneously, 10 micrograms subcutaneously, 10 micrograms intramuscularly and 20 micrograms subcutaneously to define the effective dose and to compare the effect of administration. Seroconversion of the antibody to hepatitis B surface antigen after the third vaccination reached 96.6% in the group given 5 micrograms vaccine subcutaneously and 100% in the other groups. The final geometric mean antibody titres were 700 IU/l in subjects given 5 micrograms subcutaneously, 2004 IU/l in those given 10 micrograms subcutaneously, 4674 IU/l in those given 10 micrograms intramuscularly and 3342 IU/l in those given 20 micrograms subcutaneously. In the groups given 10 micrograms, the early seroconversion rate of the antibody to hepatitis B surface antigen and the geometric mean antibody titres after the third vaccination were significantly higher in subjects administered intramuscularly than subcutaneously (P less than 0.05). No major adverse effects were observed and minor reactions were the same as, or less than, those reported for the plasma-derived vaccine. Before and after administration, no significant fluctuation in the yeast antibody titre was observed. These results demonstrate the efficacy and safety of the yeast-derived vaccine, and show that 10 micrograms was the effective dose.

Antibody Formation↗