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Biomedical subjects

K Koike

Publications and source records attributed to K Koike.

At least 433 records · Page 24Linked to original sources
PubMed1993

Cytotoxic T lymphocyte activity to hepatitis B virus DNA-transfected HepG2 cells in patients with chronic hepatitis B.

Cytotoxic T lymphocyte (CTL) activity for hepatitis B virus (HBV) DNA-transfected HepG2 cells (designated HB3-5), which secrete HBsAg, HBeAg and HBV particles, was investigated in 31 patients with chronic HBV infection (18 chronic hepatitis and 13 asymptomatic carriers). 51Cr-labeled HB3-5 with A2 as a major HLA class I antigen served as target cells and T cells from peripheral blood mononuclear cells as effector cells. The CTL activity was measured by a 51Cr release assay. Patients were divided into two groups, the A2 group bearing HLA-A2 and the non-A2 group not bearing HLA-A2. Chronic hepatitis patients in the A2 group showed increased HBV Ag-specific cytotoxicity compared with that seen in the non-A2 group (5.2 +/- 3.1% vs. 0.9 +/- 1.4%; means +/- SD, P < 0.01). In the A2 group with chronic hepatitis, the cytotoxicity was greater in anti-HBe positive patients than in HBeAg positive patients (8.6 +/- 1.9% vs. 3.4 +/- 2.0%, P < 0.01), and asymptomatic carriers showed less cytotoxicity (0.35 +/- 0.31%, P < 0.001) compared with chronic hepatitis patients. In the non-A2 group, HBV Ag-specific CTL activity was negligible in most patients and thus no differences were found among all patient groups. The HBV Ag-specific cytotoxicity was inhibited by antibodies to CD3, HLA class I and hepatitis B nucleocapsid antigens. Removal of CD8+ cells also resulted in marked decrease in the cytotoxicity. These findings indicate that HBV Ag-specific cytotoxicity reflects liver cell damage and HBeAg/anti-HBe status. Furthermore, our assay system appears to be useful to assess CTL response in patients with chronic HBV infection.

Adult↗
PubMed1993

Serology of acute exacerbation in chronic hepatitis B virus infection.

BACKGROUND: Liver injury in many patients with chronic hepatitis B is sporadic and is often characterized by acute exacerbations alternating with relatively normal liver function. The aim of this study was to perform detailed serological and biochemical analysis during periods of active liver disease to better understand the mechanisms responsible for the cyclic nature of liver injury. METHODS: A series of serum samples from 19 hepatitis B e antigen (HBeAg)-positive patients were analyzed for alterations in serum hepatitis B virus (HBV) DNA, HBeAg, anti-HBe production, and HBeAg-specific immune complex formation before, during, and after spontaneous acute exacerbations of liver injury. RESULTS: This analysis revealed significant correlations between increasing levels of serum HBV DNA, HBeAg, HBeAg-specific immune complexes, and liver injury. These results suggest that increases in viral replication and accumulation of viral proteins in the serum and intracellularly and the subsequent immune response play an important role in initiating acute exacerbations of liver injury in chronic hepatitis B infection. CONCLUSIONS: We propose that production of the secreted and cellular forms of the nucleoprotein reaches a threshold level and elicits specific immune responses, which mediate liver injury.

Antibodies, Monoclonal↗
PubMed1993

Hypercalcemia associated with all-trans-retinoic acid in the treatment of acute promyelocytic leukemia.

Recent reports have described clinical benefits of all-trans-retinoic acid (ATRA) therapy for acute promyelocytic leukemia (APL). This paper describes severe hypercalcemia (serum calcium: 18.7 mg/dl) in association with ATRA treatment in a 14 year old girl with APL. Serum parathyroid hormone (PTH) concentrations were normal (0.21 ng/ml), which precludes the possibility of primary hyperparathyroidism or ectopic PTH secretion as a cause of the hypercalcemia. As for the factors which can accelerate mineral resorption, there were no apparent increases in the levels of PTH-related protein (PTH-rP), prostaglandins and vitamin D metabolites. In our in vitro experiment, ATRA did not stimulate the leukemic cells to produce PTH-rP. We speculate that ATRA, like PTH, may increase osteoclastic activity and induce hypercalcemia.

Adolescent↗
PubMed1993

Augmented expression of a type IV collagen-binding protein in a highly metastatic murine fibrosarcoma clone.

The adhesive properties of highly and weakly metastatic murine sarcoma (Meth A) clones were investigated. A highly metastatic clone, MH-02, preferentially adhered to type IV collagen-coated plastic dishes and to bovine pulmonary arterial endothelial cell-coated plastic dishes as compared to a weakly metastatic clone, ML-01. Pretreatment of MH-02 and ML-01 cells with antisera against MH-02 cells resulted in almost equivalent adhesiveness to type IV collagen. Preincubation of 125I-radiolabeled tumor cells with the antisera against MH-02 significantly reduced the arrest of MH-02 cells in the lung, but ML-01 cells were not affected. The number of pulmonary metastatic nodules of MH-02 cells was reduced to the same level as that of ML-01 cells by preincubation of the tumor cells with the antisera in an experimental metastasis experiment. These results indicated that the high metastatic ability of MH-02 can be attributed to its preferential adhesiveness to type IV collagen. The type IV collagen-binding proteins of MH-02 and ML-01 were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography. Among several proteins which bound to type IV collagen, expression of a protein with a molecular weight of 29 kD was significantly greater in MH-02 than in ML-01. These results suggest that the greater adhesion of highly metastatic MH-02 cells to type IV collagen is due to enhanced expression of the type IV collagen-binding 29 kD protein.

Animals↗
PubMed1993

Alterations of integrin expression in human lung cancer.

Integrins are cell-surface receptors which are involved in cell-matrix and/or cell-cell adhesion. They have been suggested to play a role in tumor invasion and metastasis. We examined the expression of various integrin subunits in normal and cancer cells of the lung using 33 human lung cancer cell lines as well as 6 lung cancer samples from which tumor cell lines could be established. This study clearly demonstrated that changes in the expression of certain integrins occur frequently in lung cancer, especially in small cell lung cancer. Loss of the alpha 1 subunit of the beta 1 integrin family appears to be the most prominent change, although loss of other integrin subunits such as alpha 2 or emergence of some integrin subunits such as alpha v can also be observed. These results suggest that changes in integrin expression may contribute to the invasive and/or metastatic behavior of lung cancer.

Carcinoma, Small Cell↗
PubMed1993

Stem cell factor enhances the growth of primitive erythroid progenitors to a greater extent than interleukin-3 in patients with aplastic anaemia.

We examined the combined effects of stem cell factor (SCF), or interleukin-3 (IL-3) with erythropoietin on the development of haemopoietic progenitors in 19 patients with aplastic anaemia (AA) and eight normal controls by using an in vitro clonal assay. SCF significantly enhanced the growth of total erythroid colonies (erythroid bursts, mixed colonies) in 11 patients and all normal controls, whereas IL-3 did so in only three patients. The number of SCF- or IL-3-dependent erythroid colonies was substantially lower in AA patients than in the controls. Comparison of the capacity of SCF and IL-3 to increase total erythroid colony growth indicated that half of the AA patients responded more strongly to SCF than the normal controls, while few patients responded in such a manner to IL-3. These findings suggest that SCF in vivo will have a more dramatic effect than IL-3 in improving anaemia in patients with AA.

Adolescent↗
PubMed1993

A transcription initiation site for the hepatitis B virus X gene is directed by the promoter-binding protein.

Recent studies have demonstrated the transacting function of the X gene product of hepatitis B virus. However, little information is available on the regulation of X gene expression. In this report, we first investigate a cellular factor regulating X gene transcription by DNA transfection, using the human hepatoma cell line HuH-7, which is permissive for HBV replication as well as X mRNA transcription. A sequence-specific cellular factor was found to bind to the promoter region upstream of the first ATG (nucleotide [nt] 1248) of the X open reading frame. DNase I footprinting analysis showed the binding sequence of this factor to be situated between nt 1097 and 1119, where an 8-bp palindrome structure resides. S1 nuclease analysis of X gene transcripts demonstrated the binding site to be adjacent to two major start sites (nt 1117 and 1125) of X mRNA. Second, we demonstrate that introduction of a mutation into the binding site gives rise to a loss of the binding with a concomitant shift of the transcription start site of X mRNA beyond the 8-bp palindrome structure, causing it to become more heterogeneous. Thus, the promoter-binding protein appears to be involved in directing the transcription initiation site of the X gene toward the downstream region of the X promoter when X protein is produced from X mRNA.

Base Sequence↗
PubMed1993

Aging changes in the alignment of chromosomes after human chorionic gonadotropin stimulation may be a possible cause of decreased fertility in mice.

The relation between the alignment of chromosomes in the aged oocyte and its capacities of fertilization and development of oocytes was examined. More embryos in the condition of insemination at 12 and 16 h after human chorionic gonadotropin (hCG) however grew into two and more cell stages than those in the insemination of 20, 24 and 28 h. Some embryos in the group of insemination at 12, 16 and 20 h after hCG injection had grown into the blastocyst stage. The embryos inseminated 24 h after hCG and later had shown no further development. Twelve hours after hCG injection, 67% of oocytes have chromosomes on a straight line (A), and 29% have chromosomes scattered in one group (B). Three percent of oocytes have them separated toward both spindle ends (C) and 2% of oocytes have no chromosomes (D). At 16 h after hCG, the alignments of chromosomes are almost the same as that of 12 h after hCG injection. At 20 h after hCG, the most common alignment of chromosomes was scattered in a small group. The alignment of chromosomes of most oocytes was splitting at 24 and 28 h after hCG injection. Thus the oocytes with the chromosome alignment of A or B can be fertilized and developed into the blastocyst stage. The alignment of A and B lasts only about 8 h after ovulation, and the time was extremely restricted for oocytes to develop normally.

Animals↗
PubMed1993

Plasma fibrinogen and its correlates in Japanese and US population samples.

In a preliminary 1987 study, we reported that the plasma fibrinogen level was significantly higher in Caucasian American men than Japanese men. To confirm this finding, we used data from 1,020 Japanese men and women in a 1989-1991 Akita, Japan, population study and from > 15,000 men and women from the 1986-1989 Atherosclerosis Risk in Communities (ARIC) Study. To examine further the correlates of plasma fibrinogen level, subsamples of nonsmoking Akita Japanese (n = 150) and Minneapolis Caucasians (n = 150) were also studied separately in 1990. Compared with the Japanese in the Akita study, Caucasians and African Americans in ARIC had a 23-40 mg/dL higher age-adjusted fibrinogen level for men and a 25-67 mg/dL higher level for women. In the subsample, the mean plasma fibrinogen value was 288 mg/dL in Caucasian men and 248 mg/dL in Japanese men (test for difference: p < 0.001). Women showed a similar racial difference: 300 mg/dL in Caucasians and 257 mg/dL in Japanese (p < 0.001). There were weak but positive correlations of plasma fibrinogen with age and body mass index and weak inverse correlations with alcohol intake, high density lipoprotein cholesterol, and triglycerides in most of the sex-race groups. For women, plasma fibrinogen was positively associated with menopause and inversely associated with the use of hormone replacement therapy. Total fish intake was inversely associated with plasma fibrinogen in all sex-race groups, and the association was statistically significant for Caucasian men.(ABSTRACT TRUNCATED AT 250 WORDS)

Asian People↗
PubMed1993

The serology of chronic hepatitis B infection revisited.

The serology of chronic hepatitis B infection has been established through the use of commercial immunoassays to measure the structural antigens of the hepatitis B virus and their respective antibodies in serum. However, the commercial assays have not been designed to detect serum antibodies in the presence of an excess of circulating antigens. A series of serum samples from 200 HBeAg-positive, chronically infected hepatitis B patients with varying degrees of liver disease were analyzed using novel immunoassays designed to detect antibodies in the presence of circulating viral antigens. All patients, regardless of their liver disease, were seronegative for antibodies specific for the envelope antigens or the secreted nucleoprotein antigen (HBeAg) when the commercial assays were used. In contrast, virtually all chronically infected patients with liver disease and approximately 50% of patients without liver disease demonstrated anti-HBe and anti-envelope antibodies when sera were tested in the more sensitive immunoassays. Furthermore, asymptomatic patients could be serologically distinguished from symptomatic patients based on antibody fine specificity, titer, and IgG subclass. This study revealed that the majority of chronically infected hepatitis B patients produce a variety of antibodies for many years, and are not immunologically unresponsive, as suggested by the current assays.

Antibody Formation↗
PubMed1993

Intraventricular administration of histidyl-proline-diketopiperazine [Cyclo(His-Pro)] suppresses prolactin secretion and synthesis: a possible role of Cyclo(His-Pro) as dopamine uptake blocker in rat hypothalamus.

Histidyl-proline-diketopiperazine [Cyclo (His-Pro) (CHP)] was discovered to be one of the metabolites of TRH. To understand the specific role of CHP in rat hypothalamic dopamine neurons, we examined the in vivo effects of intraventricular (icv) infusion of CHP on the release and synthesis of PRL in the rat pituitary and the 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine ratio in the rat hypothalamus. We also examined the in vitro effects of CHP on the release of [3H]dopamine from dispersed tuberoinfundibular dopamine neurons, [3H]dopamine reuptake in hypothalamic membrane fractions, and PRL release from rat pituitary cultured cells. Female rats were treated by icv infusion of 1 microM CHP daily for 1, 3, and 7 days, using Alzet osmotic pumps. After 1 day of treatment, the serum PRL concentration was significantly decreased. Northern blot analysis of the total RNA isolated from the pituitary glands of control animals using 32P-labeled PRL cDNA as a probe indicated the presence of PRL gene transcript, 1.0 kilobase in size, and its amount was decreased by CHP treatment. CHP did not affect [3H]dopamine release from dispersed tuberoinfundibular dopaminergic neurons at any concentration up to 1 microM. CHP did not inhibit PRL release from cultured pituitary cells at low concentrations (1-100 nM), but it stimulated PRL release at high concentrations (1 and 10 microM). We also examined the concentrations of dopamine and DOPAC in the rat hypothalamus when CHP was administered icv for 1 or 7 days. There was a significant decrease in the DOPAC/dopamine ratio after CHP treatment for 1 day. Furthermore, CHP caused dose-dependent inhibition of [3H]dopamine uptake by the rat hypothalamus similar to other dopamine uptake blockers, such as benztropine and GBR12909. These data suggest that icv administration of CHP might decrease both PRL secretion and accumulation of PRL gene transcripts in the pituitary by decreasing the DOPAC/dopamine ratio and inhibiting dopamine reuptake in the rat hypothalamus.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Pituitary folliculo-stellate-like cell line (TtT/GF) responds to novel hypophysiotropic peptide (pituitary adenylate cyclase-activating peptide), showing increased adenosine 3',5'-monophosphate and interleukin-6 secretion and cell proliferation.

Several studies have shown that folliculo-stellate cells (FS cells) in the anterior pituitary gland exhibit paracrine functions. Recently, we established a pituitary FS-like cell line, TtT/GF, which was derived from an isologously transplantable pituitary thyrotropic tumor line induced by radiothyroidectomy. In studies to examine the function of FS cells, we found that two forms of a novel hypophysiotropic peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), were potent activators of TtT/GF cells. Both the 27- and 38-amino acid forms of PACAP (PACAP-27 and PACAP-38) and vasoactive intestinal peptide (VIP) increased the levels of cAMP in TtT/GF cells in a similar dose-dependent manner. PACAP-27 and PACAP-38 specifically stimulated the proliferation of TtT/GF cells dose dependently, whereas VIP was ineffective. The minimal effective concentration of the PACAPs inducing cell proliferation was between 10(-8)-10(-7) M. However, PACAP-27 was much less potent than PACAP-38 in stimulating cell proliferation and DNA synthesis. PACAP-38, PACAP-27, and VIP all stimulated the release of interleukin-6 (IL-6) from TtT/GF cells. PACAP 38 (10(-8) M) stimulated IL-6 production effectively within 1 h of incubation, and the level attained at 8 h of cultivation (620 pg/ml) was nearly 10-fold that in the absence of PACAP-38 (60 pg/ml). PACAP-38 and VIP stimulated IL-6 secretion significantly at 10(-10)-10(-9) M in a bell-shaped manner; the maximum values were 10(-7) and 10(-8) M, respectively. On the other hand, IL-6 secretion stimulated by PACAP-27 became saturated at 10(-8) M, and the maximum value (320 pg/ml) was about 25% of that stimulated by PACAP-38 (1280 pg/ml). These findings obtained using TtT/GF cells as a model of FS cells suggest that PACAP acts as a hypophysiotropic factor, which targets FS cells and stimulates their proliferation, adenylate cyclase activation, and IL-6 secretion.

Animals↗
PubMed1993

[Drug-receptor interactions in single smooth muscle cells].

Smooth muscle tissues were contracted by excitation of each muscle cell. Single cells prepared from guinea pig taenia caecum and trachea were contracted by extracellular application of acetylcholine and/or carbachol, whose concentrations were the same as those in the tissues. The concentration-response curve was shifted in a parallel fashion by competitive antagonists. The pA2-values of the antagonists were in good agreement with those estimated using the intact tissue. The apparent dissociation constants of cholinergic drugs estimated from inhibition of the specific binding of [3H]QNB (quinuclidinyl benzilate) to the single cells by the cholinergic drugs were also in agreement with the values in other membrane preparations. Similar findings were obtained in the single cells, microsomal fractions and isolated tissues from the guinea pig tracheal smooth muscles. In rabbit aortic single cells, the existence of two pharmacologically distinct alpha 1-adrenoceptor subtypes, alpha 1A and alpha 1B, in vascular smooth muscle cells was supported. Furthermore, the amount of prostaglandin F2 alpha released from guinea pig tracheal single cells was increased through activation by alpha 2-adrenoceptor agonists. The amount of prostaglandin F2 alpha released by norepinephrine decreased with age, while the total amount of alpha 2-adrenoceptors and the dissociation constants of the alpha 2-adrenergic drugs from the receptor did not change. The relaxation induced by beta-adrenoceptors did not alter with age. The total amount of beta-adrenoceptor and the dissociation constants of beta-adrenergic drugs from their receptor did not alter with age. An excellent relationship between the potency of isoprenaline and the maximum binding of [3H]dihydroalprenolol estimated in the single cells from 6- to 40-week-old guinea pigs was found, suggesting that the increase in the potency of isoprenaline is due to the increase in the maximum binding. The value in the single cells from 100-week-old guinea pigs deviated significantly from the regression line. This result suggests that the decrease in potency in the single cells from 100-week-old animals is due to a change in post beta-receptor processes in responsiveness. The smooth muscle single cells are useful for the study of drug-receptor interactions. Furthermore, post-receptor processes in responsiveness were discussed.

Acetylcholine↗
PubMed1993

NC-1300, a proton-pump inhibitor, requires gastric acid to exert cytoprotection in rat gastric mucosa.

Effect of gastric acid suppression on the cytoprotective effect of a single dose of NC-1300 given intragastrically was studied. NC-1300 given intragastrically prevented gastric mucosal damage caused by absolute ethanol in rats in a dose-related manner, while the drug given subcutaneously did not. Pretreatment with NC-1300 given subcutaneously to suppress acid secretion abolished the protective effect of NC-1300 given intragastrically, but not in the presence of 0.1 N HCl. Repeated intragastric administration of NC-1300 for 7 days failed to prevent the ethanol damage. These results suggest that NC-1300 requires gastric acid to exert a protective effect against ethanol in rat gastric mucosa.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1993

Stereoselective total synthesis of tri- and tetrahexoside wheat flour ceramide.

The wheat glycosphingolipids, O-(beta-D-mannopyranosyl-[(1-->4)-O-(beta-D-mannopyranosyl)]n-O-(beta-D -glucopyranosyl)-(1-->1)-(2S,3S,4R)-4-hydroxy-N-tetracosanoylsphingan ine (n = 1 and 2), were stereoselectively synthesized. Silver silicate promoted glycosylation when 4-O-acetyl-2,3,6-tri-O-benzyl-alpha-D-mannopyranosyl bromide was used for elongating the glycan chains, which were latter coupled with the ceramide derivative by the trichloroacetimidate method.

Carbohydrate Sequence↗
PubMed1993

Prolactin stimulates [3H]dopamine release from dispersed rat tubero-infundibular dopaminergic neurons and dopamine decreases gonadotropin-releasing hormone release induced by calcium ionophore.

In order to investigate the involvement of prolactin-dopamine and dopamine-gonadotropin interactions in the hypothalamo-pituitary axis of hyperprolactinemia, in vitro studies were performed using primary cultures of dispersed rat hypothalamic heterogeneous cells containing tubero-infundibular dopaminergic neurons or gonadotropin-releasing hormone (GnRH) neurons. We observed that prolactin caused dose-dependent stimulation of [3H]dopamine release after a 16-h incubation. Staurosporin (10 nmol/l), an inhibitor of protein kinase C, significantly reduced the [3H]dopamine release induced by prolactin (1 mg/l). Incubation of tubero-infundibular dopaminergic neurons with prolactin (1 mg/l) had no effect on intracellular cyclic adenosine monophosphate accumulation. Dopamine (1 mumol/l) significantly (p < 0.01) reduced the release of GnRH induced by 50 mumol/l calcium ionophore from dispersed hypothalamic cells from the preoptic area, while prolactin had no effect on GnRH release. These data support the hypothesis that the antigonadotropic effect of prolactin on the hypothalamus is mediated by an inhibitory effect of dopamine on GnRH release.

Animals↗
PubMed1993

Stimulation of pulmonary intravascular macrophages increases microvascular permeability in awake sheep.

The purpose of this study is to determine if stimulation of pulmonary intravascular macrophages (PIMs) increase microvascular permeability in sheep. We infused latex microbeads, 1 micron in diameter, for 1 hr continuously and analysed lung hemodynamic and lymph-dynamic changes. More than 70% of latex microbeads in the lung were assigned to PIMs, and caught in their phagosomes as determined by morphological examination. This implies that infused latex microbeads predominantly stimulate PIMs. Pulmonary arterial pressure increased during the infusion period, and returned to baseline after the infusion period. Lung lymph flow increased and remained high while the lymph to plasma protein ratio ultimately increased above baseline. This implies that infusion of latex microbeads increases pulmonary microvascular permeability. The increase in lung lymph protein clearance was blocked completely by pretreatment with indomethacin, but not with a thromboxane synthetase inhibitor (OKY-046). These data indicate that the increase in microvascular permeability is mediated by an arachidonic acid cyclooxygenase metabolites but not by thromboxane. We conclude that PIMs can act as an initiator to increase pulmonary microvascular permeability by releasing arachidonic acid cyclooxygenase metabolites through their stimulation with latex beads.

Animals↗