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Biomedical subjects

K Koike

Publications and source records attributed to K Koike.

At least 595 records · Page 33Linked to original sources

Serum titers of pre-S(2) antigen in patients with acute and chronic type B hepatitis: relation to serum aminotransferase activity and other hepatitis B virus markers.

The peptide which is encoded by the pre-S(2) region of hepatitis B virus DNA, the pre-S(2) antigen, was determined quantitatively by an enzyme immunoassay system employing monoclonal antibodies. The prevalence and titer of pre-S(2)Ag were 91.9% (91/99) and 10,356 +/- 19,053 units (mean +/- S.D., arbitrary units) for hepatitis B e antigen (HBeAg)-positive patients with acute and chronic HBV infection and 86.0% (74/86) and 952 +/- 1,565 units for HBeAg-negative subjects. In four patients with acute hepatitis B, pre-S(2)Ag titers changed in parallel with HBV DNA levels, and the disappearance of pre-S(2)Ag from serum was associated with a rapid fall of ALT levels into the normal range, whereas the fluctuation of pre-S(2)Ag titer correlated with persistence of ALT elevations. In all of the 19 episodes of acute exacerbation of hepatitis which occurred in nine patients with chronic active hepatitis B, a significant elevation of pre-S(2)Ag titer was observed, closely overlapping an increase or appearance of HBV DNA, and its peak preceded peaks of ALT by 1 to 11 weeks (mean +/- S.D. = 4.26 +/- 2.57 weeks). These observations suggest that quantitative measurement of pre-S(2)Ag would be useful for estimation of the magnitude of HBV replication and would help predict the prognosis of acute hepatitis B and of acute exacerbation in chronic hepatitis B.

Acute Disease↗

A simple rapid method for prolactin assay by reversed passive hemagglutination: evaluation of its clinical application.

Measurement of the serum prolactin (PRL) level is essential in diagnosis and treatment of infertile women. At present, the serum PRL level is generally measured routinely by a radioimmunoassay (RIA) technique, but this assay requires a qualified technician and special equipment. Here we report a semi-quantitative method for PRL assay (MS-8701 kit) by reversed passive hemagglutination (R-PHA) using monoclonal PRL antibody. This assay with the MS-8701 kit is specific, and its sensitivity is 1 ng/ml. The serum PRL levels determined with the MS-8701 kit were significantly correlated with those determined by RIA (correlation coefficient 0.932). Furthermore, the effect of bromocriptine on the serum PRL level in patients with prolactinoma, and the change in the serum PRL level after metoclopramide loading could be determined using this kit. These results suggest that the MS-8701 kit should be useful in an out-patient clinic to screen for hyperprolactinemia, to check the effect of bromocriptine, and to follow up patients after operation for prolactinoma.

Amenorrhea↗

Decrease in neonatal suckled milk volume in diabetic women.

To clarify the influence of diseases with hormonal disturbance on puerperal lactation, we studied the amounts of milk obtained by suckling and manual extraction during the first 6 days after delivery and the rate of breast-feeding in 40 patients with diabetes mellitus, 40 with hyperthyroidism, 28 with hypothyroidism and 57 with ovulatory disturbance, and in 40 healthy women. The mean body weight of the patients with diabetes mellitus was 7 kg more than those in other groups, and delivery occurred one gestational week earlier than in other groups. The amounts of suckled milk produced by patients with diabetes mellitus and hypothyroidism were significantly (p less than 0.05) less than those in other groups; there was no significant difference in milk productions in the other groups. One month after delivery, 35.5% of the babies in the diabetic group were receiving complete breast-feeding, which was significantly (p less than 0.05) lower than the percentages (52-55%) in the other groups. These data suggest that neonatal suckled milk volume in diabetic women is decreased, and that hypothyroidism may influence the initiation of lactation even when the patients are euthyroid due to treatment.

Adult↗

Effect of histamine on two different affinity sites in beta-adrenoceptors.

1. To study the effect of histamine on two different affinity sites in beta-adrenoceptors, we tested specific binding of [3H]befunolol to microsomal fractions from the guinea pig taenia caecum in the presence and absence of histamine (10(-5) M). 2. The Scatchard plot of data in the absence of histamine was recognized as two straight lines suggesting the existence of two different affinity sites: high and low. However, a curvilinear plot with upward concavity was observed in the presence of histamine (10(-5) M). 3. These results suggest the possibility that histamine alters the binding sites of beta-adrenoceptors into several classes of sites with lower affinity. 4. Further, an antagonism between isoprenaline and BFE-55, which interacts only with the high affinity site, was tested on the atria (beta 1-adrenoceptor predominant) and tracheae (beta 2-adrenoceptor predominant) of the guinea pig. The pA2-values in the atria were almost equal to those in the trachea, suggesting that both beta 1- and beta 2-adrenoceptors contained two different affinity sites.

Adrenergic beta-Agonists↗

Effect of tetrahydroisoquinoline (TIQ), one of endogenous substances inducing parkinsonism, on isolated rat vas deferens.

1. The effect of tetrahydroisoquinoline (TIQ) was examined on isolated rat vas deferens. 2. TIQ shifted the concentration-response curve for norepinephrine towards lower concentrations: the pD2-value of norepinephrine in the presence of TIQ was significantly greater than in its absence. 3. Tyramine-induced contraction in the presence of TIQ decreased by a significant 35% more than in the absence of TIQ. 4. These results indicate that the pharmacological effect of TIQ is due to the inhibition of the neuronal uptake of catecholamines.

Animals↗

Dose difference in beta-adrenergic blockers with intrinsic sympathomimetic action to block beta-adrenoceptors and induce sympathomimetic action.

1. Isoprenaline, a beta-adrenergic full agonist, and carteolol, befunolol and BFE-55, beta-adrenergic blockers with an intrinsic sympathomimetic action, induced dose-related increases in heart rate when administered intravenously (i.v.). 2. The beta-partial agonists administered i.v. shifted a dose-heart rate increased response curve of isoprenaline, suggesting a competitive antagonism. 3. In carteolol, doses to block beta-adrenoceptors were found to be 400-1000 times lower than that to induce agonistic action. In BFE-55, doses to block beta-adrenoceptors were equal to that to induce sympathomimetic action. The difference between doses of the befunolol to produce both actions was intermediate. 4. These results suggest that there may be a difference between doses blocking beta-adrenoceptors and inducing sympathomimetic action in some beta-adrenergic partial agonists and, therefore, that there may exist beta-partial agonists which do not induce sympathomimetic action in doses blocking beta-adrenoceptors.

Adrenergic beta-Agonists↗

Some pharmacological properties of a new antitumor drug, CPT-11, in isolated muscle preparations.

1. Pharmacological properties of a new antitumor drug, CPT-11, were studied in some muscle preparations. 2. CPT-11 induced contraction of guinea-pig ileal and tracheal preparations, which was blocked by atropine (10(-6) M). 3. CPT-11 potentiated the contractile responses of guinea-pig ileum to acetylcholine, nicotine, serotonin and BaCl2. 4. The chronic and inotropic effects induced by isoprenaline were depressed by CPT-11. 5. These results suggest that CPT-11 has an acetylcholine action.

Animals↗

Effect of aging on presynaptic alpha 2-adrenoceptor mechanisms in guinea pig ileum.

1. Presynaptic alpha 2-adrenoceptor mechanisms in electrically stimulated longitudinal muscles of ilea isolated from 3, 10, 20 and 47 week-old guinea pigs were studied by analysis of the concentration-response curves of noradrenaline, a full agonist, and clonidine, a partial agonist, and the Scatchard plot of specific binding of [3H]-p-aminoclonidine to synaptosomal fractions from the longitudinal muscle of guinea pig ileum. 2. The pD2 value of noradrenaline and the maximum contraction induced by clonidine increased with age from 3 to 20 weeks and there after decreased to 47 weeks, while the pA2 value of yohimbine against noradrenaline did not alter with age. 3. The capacity of the maximum binding sites of [3H]-p-aminoclonidine increased with increasing age (3-20 weeks), while the dissociation constant (Kd) of [3H]-p-aminoclonidine did not change during the same period. 4. The changes in the presynaptic alpha 2-adrenoceptor mechanisms with age are considered to be due to the change in the total concentration of presynaptic of alpha 2-adrenoceptors.

Aging↗

Transgenic mouse model for human gastric carcinoma.

To understand the pathogenesis that may be induced by human adenovirus type 12 (Ad12), we have generated transgenic mice carrying the Ad12 early region 1 under control of the mouse mammary tumor virus long terminal repeat. Eleven of 11 male founder mice, but only 2 of 12 females, died between 3 to 4 mo of age. Death was associated with presence of tumors at or near the squamocolumnar junction of the stomach. Microscopically, these multifocal tumors appeared to arise from hyperplastic epithelium and showed features consistent with adenocarcinoma or adenosquamous carcinoma. High levels of expression of both the Ad12 E1A and E1B genes were seen in the tumor-bearing stomach. Various levels of expression were also detected in other tissues, although the stomach was the only organ with detectable pathology. These observations suggest an organ-specific action of the Ad12 early region 1 gene products. This transgenic mouse model provides an experimental system for studying the development of human carcinomas at sites of transition from squamous to columnar epithelium.

Adenovirus Early Proteins↗

In vitro expansion of the murine pluripotent hemopoietic stem cell population in response to interleukin 3 and interleukin 6. Application to bone marrow transplantation.

The synergistic action of interleukin 6 with interleukin 3 on the proliferation of a murine hemopoietic stem cell population in a short-term liquid culture system was examined by radioprotective assay. The numbers of colony-forming units in spleen (CFU-S), together with granulocyte/macrophage colony-forming units and viable nucleated cells, were found to increase markedly in culture in the presence of both IL-3 and IL-6, compared with the presence of IL-3 or IL-6 alone. The peak CFU-S value in response to the combination of IL-3 and IL-6 was obtained 6 days after culture initiation, exceeding 5-fold of the input value. Consistent with these data, marrow cells cultured with both IL-3 and IL-6 for 6 days were shown to have a much higher capability of rescuing lethally irradiated mice than did controls. The results may portend the potential clinical use of the combination of IL-3 and IL-6, in particular, in bone marrow transplantation.

Animals↗

The X gene of hepatitis B virus induced growth stimulation and tumorigenic transformation of mouse NIH3T3 cells.

To examine the transforming potential of the X gene product of hepatitis B virus (HBV), the X-gene-containing region (referred to as the HBx region) was introduced into mouse NIH3T3 cells. Each transformed cell line expressed X-coding mRNA at a different level. A positive correlation was found between the level of X-coding mRNA and the saturation density of the cells. The HBx-transformed cell lines exhibited X protein production and tumor formation in nude mice. The function of HBV in oncogenesis may involve the continuous expression of the X-gene-coded product in the HBV DNA-integrated cells.

Animals↗

Childhood transient erythroblastopenia complicated by thrombocytopenia and neutropenia.

We report on 4 children with transient erythroblastopenia complicated by thrombocytopenia and/or neutropenia. Bone marrow examination revealed severe erythroid hypoplasia with normal granulopoiesis and thrombopoiesis. Human parvovirus B19 infection was confirmed serologically in 2 children. An in vitro study using autologous bone marrow cells after recovery demonstrated IgG-mediated inhibition of erythropoiesis in 4 children. Additionally, antibodies directed against platelets and neutrophils were detected. These findings suggest that the IgG-mediated mechanism may be pathogenetic for the transient pancytopenia of these children.

Agranulocytosis↗

Molecular cloning of cDNAs for alpha and beta subunits of human pyruvate dehydrogenase.

The cDNAs encoding human PDH alpha and PDH beta were isolated from a HeLa cell cDNA library in the lambda gt11 expression vector by immunoscreening, followed by colony hybridization from a human foreskin fibroblast cDNA library. Nucleotide sequence analyses of the positive plasmid clones (pHPDA and pHPDB) revealed an insert of 1.36 kilobases (kb) for PDH alpha and one of 1.69 kb for PDH beta, respectively, allowing us to predict the complete amino acid sequences of the precursor and mature proteins of these two subunits. The amino acid sequences of the amino-terminal regions of the two subunits of human PDH were highly homologous with those of mature porcine PDH. The amino acid sequences of phosphorylation sites determined in PDH alpha of the bovine and porcine enzymes were also conserved in the human PDH alpha. Blot analysis of HeLa cell poly(A)+ RNA and the transcriptional product of the two cDNAs showed a single mRNA of 1.8 kb for PDH alpha and one of 1.7 kb for PDH beta. The precursor proteins of PDH alpha and PDH beta were detected by immunoprecipitation from an 35S-labeled, cell-free translation system. Our sequence of PDH alpha cDNA was compared with those of two other origins. The differences among these three PDH alpha cDNAs have been discussed.

Amino Acid Sequence↗

Identification of a promoter region for 3.6-kilobase mRNA of hepatitis B virus and specific cellular binding protein.

The promoter region for transcription of the 3.6-kilobase mRNA of hepatitis B virus was identified by the chloramphenicol acetyltransferase assay by using HuH-7 hepatoma cells and was found to function directly in virus production by way of the transient expression system of HBV. The 5'-upstream sequence from nucleotides 1573 to 1657 (the transcription start site) was indispensable for promoter function, while the AT-rich sequence (from nucleotides 1581 to 1604) containing a directly repeated sequence TGTT connecting the same flanking sequence PyAAAGAC (where Py is a pyrimidine) at both sides was an essential element within this promoter region. A specific cellular factor which interacted with the essential element was detected in the HuH-7 cell extract. A similar binding factor was also observed in HepG2 and huH2-2 hepatoma cells. This factor may thus be responsible for regulating 3.6-kilobase mRNA, pregenome RNA transcription, or both.

Base Sequence↗

Interferon inhibits hepatitis B virus replication in a stable expression system of transfected viral DNA.

The effect of interferon (IFN) on hepatitis B virus (HBV) replication was investigated in a stable expression system, using HepG2 cells transfected with recombinant HBV DNA. IFN was found to cause a marked reduction in the levels of both minus and plus strands of HBV DNA from core particles in the cytoplasm. Neither HBV DNA from virus particles nor the HBV surface antigen in the culture medium primarily underwent change in quantity by treatment with IFN, as was also found for HBV mRNAs and the HBV core antigen/HBV e antigen in the cytoplasm. IFN exerted no influence on HBV DNA synthesis by endogenous DNA polymerase in the core particle fraction. From these findings, it would appear that IFN inhibits HBV replication by blocking some step in the pregenome RNA-primed assembly of core particles.

Antigens, Viral↗