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Biomedical subjects

K Koike

Publications and source records attributed to K Koike.

At least 937 records · Page 52Linked to original sources

IgM anti-HBc in anti-HBe positive chronic type B hepatitis with acute exacerbations.

IgM anti-HBc was measured by radioimmunoassay in serially collected serum samples during 20 acute exacerbations which developed in 14 patients with anti-HBe positive chronic type B hepatitis. IgM anti-HBc became positive in 12 of the 14 (86%) patients and in 18 of the 20 (90%) exacerbations, and elevation of IgM anti-HBc which was believed to be significant was also observed in the remaining two patients. In most of the patients who also had determinations of serum hepatitis B virus DNA, the hepatitis B virus DNA became positive. These results suggest that ALT elevation in anti-HBe positive chronic type B hepatitis is associated with active replication of hepatitis B virus. It is considered to be useful to measure IgM anti-HBc for the purpose of identifying the causes of ALT elevation in anti-HBe positive chronic type B hepatitis.

Adult↗

RNA transcripts of hepatitis B virus in hepatocellular carcinoma.

The states of hepatitis B virus DNA, RNA transcripts and antigens (HBsAg and HBcAg) were studied in the liver with hepatocellular carcinoma by blot hybridization and immunohistological methods. We used whole hepatitis B virus DNA and gene specific probes (S, C and X genes) for hybridization. Integrated viral DNA was found in all five tumors, but episomal DNA was not detected in the neoplastic tissue. In the nonneoplastic cirrhotic liver, episomal DNA was found in four cases and integrated viral DNA in four cases. A large amount of hepatitis B virus-specific RNA transcripts was demonstrated in nonneoplastic liver of all five cases. Two major transcripts, 2.4 and 3.4 kb in length, were identified. The former hybridized with the S gene probe and the latter with the C gene probe, suggesting that they were messenger RNAs for HBsAg and HBcAg, respectively. In contrast to nonneoplastic liver, RNA transcripts were found in the neoplastic portion in only two cases, small in quantity; they primarily hybridized with S and X, but not with C genes. Novel species of 4.0 and 3.9 kb transcripts were found in the neoplastic and the nonneoplastic portions, respectively, in one case. They may represent fusion transcripts of integrated viral DNA and cellular flanking sequences.

Adult↗

Use of the internal jugular vein approach in balloon dilatation angioplasty of pulmonary artery stenosis in children.

Generally, the approach used for balloon dilatation angioplasty for pulmonary artery stenosis in children is from the femoral vein. However, sometimes an alternative approach must be used because of femoral vein occlusion or some other reason. As reports have been limited about the results achieved using the internal jugular vein approach in pediatric interventional catheterization, we report on the internal jugular vein approach in balloon dilatation angioplasty of the pulmonary artery for pediatric patients and discuss the advantages of this approach. From 1991 through 1993 15 balloon dilatation angioplasties of the pulmonary artery using the internal jugular vein approach were performed in 14 pediatric patients, ranging in age from 4 months to 13 years. Based on this experience, we have evaluated this method from several viewpoints including the technique and possible complications. All procedures were performed without complications in all patients; and by inserting a 7 sheath it was even possible to perform balloon dilatation in a 4-month-old infant. A sheath as large as 9F could be inserted in other patients, and the double balloon method was used in seven patients. The Seldinger method was also available when the balloon catheter was too large to use with a sheath. For pediatric interventional cardiac catheterization, it was found that the internal jugular vein approach is relatively safe and reliable. Furthermore, catheterization of the pulmonary artery was easier with the internal jugular vein approach than with the femoral vein approach.

Adolescent↗

Stent implantation for native coarctation of the aorta: lessons learned from a case involving a 17-year-old patient.

Recent studies have shown that stenting for coarctation of the aorta (CoA) may be an effective treatment modality for this disease. We report a case of stent repair of CoA in a 17-year-old patient. An incompletely expanded stent caused by a balloon rupture had been implanted in the femoral artery. Subsequent implantation for CoA was successfully achieved using a high-profile balloon catheter. Stent implantation may be an effective modality for CoA repair and may prove useful as an initial procedure for adolescents and adults with CoA. However, one must consider that incomplete expansion of a stent associated with dilatation balloon rupture can cause serious complications. The current case raises important issues that require further discussion to improve the results of this procedure.

Adolescent↗

Spontaneous pregnancy after a pregnancy induced by treatment in hyperprolactinemic women.

The relationship between spontaneous pregnancy of hyperprolactinemic patients after a first pregnancy induced by treatment and their serum prolactin levels was examined. Of the 100 patients with hyperprolactinemia studied, 74 became pregnant after treatment; namely, 20 transsphenoidal adenomoidectomy for pituitary prolactinoma (group 1), 26 on treatment with bromocriptine for pituitary prolactinoma (group 2), and 28 on treatment with bromocriptine for hyperprolactinemia without prolactinoma (group 3). After delivery in the first pregnancy, the rates of menstrual restoration and subsequent spontaneous pregnancy in group 1 (72.2% and 75.0%) were significantly (p less than 0.05) higher than those in group 2 (32.0% and 25%) and group 3 (13.6% and 18.2%). The serum levels of prolactin after the first pregnancy and weaning were significantly (p less than 0.05) lower in patients with subsequent spontaneous pregnancy than in patients without spontaneous pregnancy in each group, and the levels in patients with spontaneous pregnancy were significantly (p less than 0.05) lower in group 1 (15.2 +/- 8.8 ng/ml) than in group 2 (46.6 +/- 2.9 ng/ml). These data suggest that the transsphenoidal adenomoidectomy for pituitary prolactinoma may be better than bromocriptine treatment for recovery of reproductive function.

Adult↗

Effects of thyrotropin-releasing hormone and phorbol ester on dopamine release from dispersed rat tuberoinfundibular dopaminergic neurons.

We have investigated the intracellular mechanisms underlying thyrotropin-releasing hormone (TRH)-mediated [3H]dopamine ([3H]DA) release from dispersed rat tuberoinfundibular dopaminergic (TIDA) neurons. The specific binding of [3H]Me-TRH to these cells is characterized by a single, high-affinity binding site (Kd = 1.2 nM) with a Bmax value of 178 fmol/mg protein. Thyrotropin-releasing hormone markedly increased [3H]DA release and intracellular free calcium concentration ([Ca2+]i) in TIDA neurons, and its effect was abolished by treatment with EGTA (5 mM) or chlordiazepoxide, a specific TRH receptor antagonist (10 microM). Furthermore, to examine the involvement of protein kinase C on [3H]DA release, we investigated the effect of phorbol myristate acetate (PMA), which is known to activate protein kinase C directly. Phorbol myristate acetate induced a significant increase in [3H]DA release in a concentration-dependent manner. Treatment with TRH (1 microM) plus PMA (100 nM) resulted in an additive increase in [3H]DA release. Thyrotropin-releasing hormone (1 microM) still increased [3H]DA release even after preincubation with PMA (500 nM) for 24 h, but PMA (100 nM) did not under the same conditions. These results suggest that TRH may induce DA release in dispersed rat TIDA cells by increasing calcium influx and activating the protein kinase C system.

Animals↗

Analysis of synergism between stem cell factor and granulocyte-macrophage colony-stimulating factor on human megakaryoblastic cells: an increase in tyrosine phosphorylation of 145 kDa subunit of c-kit in two-factor combination.

In normal hematopoiesis, stem cell factor (SCF) stimulates survival, proliferation and differentiation of hematopoietic progenitors. Although SCF acts synergistically with a variety of cytokines, the mechanism of growth factor-cooperation remains to be determined. To analyze the synergism between SCF and granulocyte-macrophage colony-stimulating factor (GM-CSF), we established a new megakaryoblastic cell line, HML-2, by culture in the presence of both SCF and GM-CSF. While SCF alone or GM-CSF alone supported modest cell growth, SCF and GM-CSF together induced substantial growth of this cell line. SCF alone tyrosine-phosphorylated several bands including the 145 kDa subunit of c-kit. GM-CSF alone did not cause the tyrosine phosphorylation of the 145 kDa subunit, but markedly up-regulated the expression of the 145 kDa subunit of c-kit. The combination of SCF and GM-CSF resulted in a synergistic increase in tyrosine phosphorylation of the 145 kDa subunit of c-kit. Several proliferation inhibitors which removed the two-factor interaction on the growth of the HML-2 cells down-regulated the 145 kDa subunit of c-kit. Thus, a synergistic increase in tyrosine phosphorylation of the 145 kDa subunit of c-kit may be one possible mechanism underlying the cooperation of SCF and GM-CSF on the HML-2 cell growth.

Blotting, Western↗

Simple method for efficient production of hepatitis B virus core antigen in Escherichia coli.

To obtain good antigenicity and high purity of the hepatitis B virus core antigen (HBcAg) in large quantities without using the fused protein technique employed in recombinant DNA technology, a protein molecule with the same primary sequence as that of wild-type HBcAg (subtype adr) was directly expressed in Escherichia coli JM109 (DE3) using pGd1 expression vector. Purification of the expressed HBcAg yielded high-quality protein by means of simple purification steps, such as sonication, ammonium sulphate precipitation and heat treatment, before final purification by conventional ultra-centrifugation. The HBcAg preparation thus obtained contains small round particles similar in appearance to the HBcAg particles from the HBV-infected human liver tissue.

Escherichia coli↗

Multicolor flow-cytometric, morphologic, and clonogenic analysis of marrow CD10-positive cells in children with leukemia in remission or nonmalignant diseases.

PURPOSE: To characterize nonleukemic CD10-positive cells in the marrows of children with leukemia in remission or benign conditions. PATIENTS AND METHODS: Seventeen children with acute leukemia in complete remission, 12 with solid tumors, and 17 with benign blood diseases were included in this study. Bone marrow cells were analyzed by multicolor flow-cytometry and polymerase chain reaction (PCR) to detect immunoglobulin gene rearrangement. The CD10-positive cells were purely sorted and examined by light microscopy and single cell hemopoietic progenitor assay. RESULTS: In patients with acute leukemia, CD10-positive cells were present in higher proportion after completion of therapy than during chemotherapy. They were also higher in the patients of preschool age than in the older age group with benign blood diseases and solid tumors. These CD10-positive cells were morphologically compatible with immature lymphocytes but some blast-like cells also occurred in this population. Most CD10-positive cells coexpressed CD19 and HLA-DR, although only 10 to 30% coexpressed CD20 and CD34. Although some CD10-positive cells expressed CD34, they did not make any colonies. PCR analysis did not show monoclonal bands in CD10-positive bone marrow cells in any patients in remission. CONCLUSION: Marrow CD10-positive cells possess immature B-lymphocyte phenotype and are present in higher proportion in the marrows of children with acute leukemia in continuous complete remission after completion of therapy and children of preschool age than school-age children with benign diseases or solid tumors without marrow involvement. The clonality of these cells was excluded by PCR, which is a distinct point from CD10-positive ALL blasts.

Bone Marrow Cells↗

Phenotypic analysis of peripheral T cell lymphoma among the Japanese.

From 1980 to 1990, 174 peripheral T cell lymphomas were studied morphologically and immunophenotypically with a panel of monoclonal antibodies which were reactive with T cell differentiation antigens in cryostat sections and/or cell suspensions. Histologically, 57% of the lymphomas were categorized into low-grade tumors according to the updated Kiel classification, while 41% were high-grade tumors. By immunologic studies, 50% of the lymphomas were of helper/inducer (CD4) phenotype, 6% were of cytotoxic/suppressor (CD8) phenotype, 3% expressed both CD4 and CD8, 3% lacked both CD4 and CD8, and 36% were phenotypically undetermined because of an admixture of a fairly even number of CD4 and CD8-positive cells. The phenotypically undetermined cases were more frequently noted in the low-grade groups than in the high-grade group, and the latter often showed a loss of pan-T antigens, although there was no definite correlation between the histologic category and the immunophenotype. CD25, which is strongly manifested in anti-HTLV-1 antibody-positive cases, was negative or only weakly expressed in anti-HTLV-1 antibody-negative cases. Anaplastic large cell lymphomas (LC-Ana) strongly expressed CD30, which was also detectable in only large blast-like cells in the low-grade tumors. Seventy-one per cent of the lymphomas expressed Ia antigens. In this series, the clinical data were available on 154 patients. For individual markers, the expression of CD30 and HLA-DR were associated with a longer actuarial survival (P < 0.01 and P < 0.05 by the generalized Wilcoxon test). The absence of CD25 or the presence of CD3 on tumor cells correlated with a relatively favorable prognosis, but not significantly. The detection of CD4 and CD8 had relatively little prognostic value. In the cases excluding LC-Ana, a significant difference was also recognized between the groups with and without CD25, CD30 and HLA-DR (P < 0.05 by the generalized Wilcoxon test). These results suggest that the immunophenotypic analysis of peripheral T cell lymphoma provided its use as an adjunct to a histopathologic diagnosis and was related to prognostic prediction.

Biomarkers↗

Beta-adrenoceptors in the detrusor of guinea pig bladder.

In the present study, we tried to determine which beta-adrenoceptor subtypes are involved in the inhibitory regulation of bladder motility in the guinea pig by using in vitro functional analysis. Isoprenaline, norepinephrine and epinephrine decreased spontaneous contractile activity of the bladder concentration-dependently, the rank order of their potency being isoprenaline (pD2 = 7.38)>norepinephrine (6.71)>epinephrine (6.31). Dobutamine was also effective in inhibiting the spontaneous contraction (5.81). However, CGP-12177, BRL37344, salbutamol, and clenbuterol were not effective at the concentration of 30 microM. The concentration response curves of catecholamines (isoprenaline, norepinephrine and epinephrine) were rightward shifted by the presence of atenolol. Schild regression analyses carried out for atenolol against isoprenaline, norepinephrine and epinephrine gave pA2 values of 6.93, 6.78 and 6.69, respectively. The concentration-response curve for isoprenaline was unaffected by 10 microM butoxamine. In the presence of 1 microM propranolol, bupranolol produced shifts of the concentration-response curve for isoprenaline, and the apparent pA2 value for bupranolol against isoprenaline was 5.50. These results suggest that the inhibition of spontaneous contraction of the guinea pig bladder by beta-adrenoceptor agonists is mediated mainly via beta1-adrenoceptor and the effect of isoprenaline is mediated partly via atypical beta-adrenoceptor subtype.

Adrenergic beta-Agonists↗

Alpha1-adrenoceptors in the guinea pig thoracic aorta.

In the present study, we tried to determine which alpha1-adrenoceptor subtypes are involved in the guinea pig thoracic aorta by using in vitro functional analysis. In first, we tried to estimate the pA2 values of some key alpha1-adrenoceptor antagonists (prazosin, 5-methylurapidil, WB4101, BMY7378 and tamsulosin) against responses to norepinephrine in the thoracic aorta of guinea pigs. The concentration-response curves of norepinephrine were rightward shifted by the presence of prazosin, 5 methylurapidil, WB4101, BMY7378 and tamsulosin. The pA2 values for these antagonists against norepinephrine were 7.83, 7.78, 8.20, 5.73 and 9.57, respectively. In second, we tried to compare the estimated pA2 values obtained in the present study with reported pKi and pA2 values for cloned and native alpha1-adrenoceptor subtypes. In rabbit mesenteric artery, trigone, urethra, prostate and human lower urinary tract which were proposed to contain the putative alpha1L-adenoceptor, we obtained the good correlation for the pA2 values reported in these tissues with pA2 values estimated in guinea pig thoracic aorta. Moreover, regression lines were close to the line of identity. These results suggest that the alpha1-adenoceptors mediating contraction of guinea pig thoracic aorta are similar pharmacologically to the putative alpha1L-adenoceptor subtype in rabbit mesenteric artery, trigone, urethra, prostate and human lower urinary tract. As a final point, guinea pig thoracic aorta may be able to use as a tool to develop the new alpha1-adrenoceptor antagonist which is therapeutically advantageous in the treatment of urinary tract obstruction (e. g., in benign prostatic hyperplasia).

Adrenergic alpha-1 Receptor Antagonists↗

Myelodysplastic syndrome during recombinant human growth hormone supplementation after treatment for neuroblastoma.

At 6 months of age, the patient was diagnosed as having neuroblastoma stage IV and was given the chemotherapy, local irradiation, and operation. The treatment was completed in September 1989. In 1992, at 6 years of age, her height was -3 SD and growth hormone secretion was depressed. She had been supplemented with recombinant human growth hormone (rhGH). Because the white blood cell counts began to decrease gradually in 1993, the rhGH therapy was interrupted on January 19, 1994. The rhGH supplement was resumed after a 3-month interval because of the parent's desire. Pancytopenia soon became apparent. She was diagnosed as having myelodysplastic syndrome (MDS) as a refractory anemia with an excess of blasts in transformation with monosomy 7. The rhGH therapy was interrupted again, without any improvement of the MDS. In culture studies, neither rhGH nor insulin-like growth factor-1 stimulated proliferation of her bone marrow cells. These data suggested that the treatment with rhGH after the chemotherapy played some role in the promotion, but not acceleration, of the MDS.

Child, Preschool↗

Subcellular localization of hepatitis C virus structural proteins in the liver of transgenic mice.

Hepatitis C virus (HCV) core and envelope proteins are suggested to be responsible for the pathogenesis of hepatic and extrahepatic manifestations in chronic hepatitis C. Moreover, the core protein is implicated in the regulation of the transcription of cellular genes including c-myc, RB and p53. Determining the subcellular localization of the core and envelope proteins is therefore necessary to elucidate their behaviors, particularly in vivo ones, regarding the interaction with transcriptional regulatory proteins or gene elements. We defined the subcellular localization of HCV envelope and core proteins which were expressed in substantial levels in the liver of transgenic mice. Subcellular fractionation by ultra-centrifugation revealed that the envelope proteins were present principally in the microsomes of the liver, while a small amount of the protein was detected also in the nuclei. Immunohistochemistry confirmed the localization of envelope proteins in the nuclei. In contrast, the core protein was detected principally in the cytoplasmic fraction, where it was closely associated with lipids. A low level of the core protein was detected also in the nuclei and microsomal fraction. These results suggest possible interaction of the HCV structural proteins with some factors in hepatocytes thereby perturbing intracellular circumstances.

Animals↗

Expression of 11 beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor in primary lung carcinomas.

We examined the immunohistochemical distribution of 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) and mineralocorticoid receptor (MR) in 63 primary lung carcinomas. Immunoreactivity of 11 beta HSD2 and MR was detected in 37 cases and in 32 cases of 42 adenocarcinomas, respectively. There was a significant correlation between 11 beta HSD2 and MR immunoreactivity. In three adenosquamous carcinomas, both 11 beta HSD2 and MR were detected only in adenocarcinomatous components. Neither 15 squamous cell carcinomas, 2 small cell carcinomas nor 1 large cell carcinoma expressed 11 beta HSD2 or MR. In papillary and acinar adenocarcinomas, both 11 beta HSD2 and MR immunoreactivity was significantly correlated with the grade of histological differentiation. The patterns of 11 beta HSD2 and MR expression in 10 lymph-node metastases were similar to those determined in the primary lesions. These data suggest that the patterns of 11 beta HSD2 and MR expression may reflect cellular origin and differentiation status of primary lung adenocarcinomas and serve as a new useful marker of differentiation.

11-beta-Hydroxysteroid Dehydrogenases↗

Reversal of P-glycoprotein associated multidrug resistance by new isoprenoid derivatives.

To find a drug to overcome P-glycoprotein associated multidrug resistance, we synthesized 43 new isoprenoid derivatives. Ten compounds were effective in an in vitro assay with the human MDR-type resistant carcinoma KB/VJ-300 and MRP-type KB/VP-4 cell lines. One of the most effective compounds, N-5228 [trans-N,N'-bis(3,4-dimethoxybenzyl)-N-solanesyl-1,2-diaminocyclohexane, mol. wt 1100.481, was tested in P388/VCR-bearing mice. It showed a antitumor effect on MDR-type resistant tumor cells. Moreover, N-5228 potentiated the accumulation of [3H]vincristine in drug-resistant cells and blocked [3H]azidopine photoaffinity labeling of P-glycoprotein molecules in MDR-type resistant cell membranes. We think that N-5228 is promising as a lead compound in the screening of resistance reversing drugs for multidrug resistant cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗