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M Koike

Publications and source records attributed to M Koike.

At least 145 records · Page 8Linked to original sources
PubMed1998

Efficient conditional transgene expression in hepatitis C virus cDNA transgenic mice mediated by the Cre/loxP system.

Conditional gene expression has greatly facilitated the examination of the functions of particular gene products. Using the Cre/loxP system, we developed efficient conditional transgene activation of hepatitis C virus (HCV) cDNA (nucleotides 294-3435) in transgenic mice. Efficient recombination was observed in transgenic mouse liver upon intravenous administration of adenovirus that expresses Cre DNA recombinase. After transgene activation, most hepatocytes were stained with anti-core polyclonal antibody, and 21-, 37-, and 64-kDa proteins were detected by Western blot analysis in liver lysates using anti-core, E1, and E2 monoclonal antibodies, respectively. Serum core protein was detected in transgenic mice 7 days after transgene activation with concurrent increases in serum alanine aminotransferase levels. Subsequently, an anti-core antibody response was detected 14 days after infection. Furthermore, a CD4 and CD8 positive cell depletion assay normalized both the serum alanine aminotransferase increases and pathological changes in the liver. These results suggest that HCV proteins are not directly cytopathic and that the host immune response plays a pivotal role in HCV infection. Thus, this HCV cDNA transgenic mouse provides a powerful tool with which to investigate the immune responses and pathogenesis of HCV infection.

Adenoviridae↗
PubMed1998

JAK2 and JAK1 constitutively associate with an interleukin-5 (IL-5) receptor alpha and betac subunit, respectively, and are activated upon IL-5 stimulation.

The human interleukin-5 receptor (hIL-5R) consists of a unique alpha subunit (hIL-5Ralpha) and a common beta subunit (betac) that activate two Janus kinases (JAK1 and JAK2) and a signal transducer and activator of transcription (STAT5). The precise stoichiometry of the hIL-5R subunits and the role of JAK kinases used in IL-5 signaling were investigated. We analyzed the interaction between hIL-5Ralpha and betac by immunoprecipitation using anti-hIL-5Ralpha and anti-betac monoclonal antibodies. The binding of JAK1 and JAK2 to each hIL-5R subunit was also evaluated in the hIL-5-responsive cell line, TF-h5Ralpha. It was observed that IL-5 stimulation induced the recruitment of betac to hIL-5Ralpha, although in the absence of IL-5 the subunits remain independent. In the absence of IL-5, JAK2 and JAK1 were associated with hIL-5Ralpha and betac, respectively. IL-5 stimulation resulted in tyrosine phosphorylation of JAK2, JAK1, betac, and STAT5. Moreover, IL-5-induced dimerization of IL-5R subunits caused JAK2 activation and betac phosphorylation even in the absence of JAK1 activation. Furthermore, tyrosine phosphorylation of JAK1 was dependent on the activation of JAK2. Detailed study of the C-terminal truncated cytoplasmic domain of hIL-5Ralpha revealed that the cytoplasmic stretch at position 346-387, containing the proline-rich region, is necessary for JAK2 binding. These observations suggest that activation of hIL-5Ralpha-associated JAK2 is indispensable for the IL-5 signaling event.

Humans↗
PubMed1998

Immunoreactivity of porcine heart dihydrolipoamide acetyl- and succinyl-transferases (PDC-E2, OGDC-E2) with primary biliary cirrhosis sera: characterization of the autoantigenic region and effects of enzymatic delipoylation and relipoylation.

Analysis of the primary structure of the lipoyl domain of the dihydrolipoamide acetyltransferase (PDC-E2) component of the porcine pyruvate dehydrogenase complex (PDC) reveals a high degree of homology with M2 antigen and human PDC-E2. The porcine PDC-E2 and the dihydrolipoamide succinyltransferase (OGDC-E2) component of the porcine 2-oxoglutarate dehydrogenase complex (OGDC) were identified as mitochondrial autoantigen with sera from patients with primary biliary cirrhosis (PBC). Immunodominant regions (autoepitopes) on the porcine-PDC-E2 component have been mapped to two regions around Lys-46 (outer lipoyl domain) and Lys-173 (inner lipoyl domain), which contained covalently bound lipoic acid prosthetic group. When these lipoyl domains were cleaved at Asp-45 or Asp-172 with endoproteinase Asp-N, the autoantigenicities of the two domains completely disappeared; this suggested the requirement of Asp-45 or Asp-172 residues for the immunoreaction with PBC sera. In addition, a single 14-amino acid epitope peptide histidine-substituted at Asp-172 did not exhibit competitive inhibition of autoantigen binding. Fragmentation of lipoyl domain of the porcine PDC-E2 by limited proteolysis and BrCN-cleavage after alkylation resulted in rapid loss of autoantigenicity. Enzymatic delipoylation and relipoylation of the complexed and free PDC-E2 and OGDC-E2 components did not influence immunoreactivity with PBC sera.

Amino Acid Sequence↗
PubMed1998

Immunohistochemical expression of thymidine phosphorylase in human endometrial cancer.

OBJECTIVE: To investigate correlations between the expression of thymidine phosphorylase (TP) by endometrial cancer cells and the density of microvessels within the tumor, the clinicopathologic features, and the prognosis. METHODS: We examined tumor specimens obtained from 46 patients with endometrial cancer (9 FIGO stage IA, 16 stage IB, 8 stage IC, 1 stage IIA, 6 stage IIB, and 6 stage IIIC). The cellular expression of TP and the intratumoral density of microvessels were determined by immunohistochemistry using monoclonal antibodies to TP and factor VIII-related antigen, respectively. We investigated the relationship between the cellular expression of TP and the following factors: clinicopathologic features (menopausal status, histologic type, tumor size, histologic grade, myometrial invasion, cervical invasion, and metastasis), the microvessel count, and the disease-free survival period. RESULTS: Of the 46 tumors, 19 (41%) were TP-positive. The microvessel count was significantly higher in TP-positive tumors than in TP-negative tumors (P = 0.01, Mann-Whitney U test). There was no significant correlation between TP expression and clinicopathologic features, and there was no significant difference in the disease-free survival period between patients with TP-positive tumors and patients with TP-negative tumors. CONCLUSION: TP expression was not correlated with clinicopathologic features or prognosis, but was associated with an increased density of microvessels in endometrial cancer. These findings suggest that TP may play an important role in angiogenesis and may be involved in the tumorigenesis of endometrial cancer.

Adult↗
PubMed1998

Characteristics of pancreatic carcinoma in the elderly.

CONCLUSION: Lymphogenous as well as hematogenous metastases were significantly less frequent in the elderly group of patients, although local invasion was comparable. Survival was comparable between both groups although palliative therapy alone was significantly more frequent in the elderly. BACKGROUND: The relative and absolute numbers of elderly patients continue to increase, as does the incidence of pancreatic carcinoma. To determine the optimal therapy for elderly patients with pancreatic carcinoma, we examined their clinicopathological features. METHODS: The clinical and histopathological features of pancreatic carcinoma in patients 70 yr of age or older (n = 89) were compared with those in patients aged 69 yr or less (n = 184). RESULTS: A total of 273 patients showed histologically tubular adenocarcinomas and their major variants. The male:female ratio peaked at 1:0.3 in patients under 49 yr old but gradually decreased to 1:1.2 in those aged over 80 yr. There were no significant differences between the two groups in the resectability, prognosis, location, or histology of the tumor. Hematogenous and lymphogenous metastases were detected at autopsy in 68 and 61% of patients old than 70, and in 82 and 80% of the younger group.

Adenocarcinoma↗
PubMed1998

Neuroendocrine differentiation in thymic epithelial tumors with special reference to thymic carcinoma and atypical thymoma.

To determine the neuroendocrine (NE) features of thymic epithelial tumor, immunohistochemistry and electron microscopy studies were performed on eight NE tumors (thymic carcinoids) and 26 non-NE tumors (nine thymic carcinomas, five atypical thymomas, and 12 thymomas other than lymphocytic thymoma). Immunohistochemical studies were performed with antibodies against general markers for NE cells (synaptophysin, alpha subunit of a guanine nucleotide-binding protein, Go, and small-cell lung carcinoma cluster 1 antigen), and a broad panel of antibodies for hormonal substances. Thymic carcinoid showed synchronous diffuse immunoreactivity for the three NE markers and contained cells that were positive for a variety of hormonal products: human chorionic gonadotropin (hCG) alpha-subunit (eight of eight), hCG beta-subunit (three of eight), adrenocorticotropic hormone (ACTH) (three of eight), calcitonin (two of eight), calcitonin gene-related peptide (two of eight), and serotonin (one of eight). Conversely, although positivity for NE markers was neither synchronous nor diffuse in non-NE tumors, seven of nine thymic carcinomas, three of five atypical thymomas (focal or dispersed distribution), and none of the five thymomas were positive for at least two of these NE markers. A small number of neoplastic cells were positive for hCGalpha-subunit or ACTH in three thymic carcinomas and one atypical thymoma. Ultrastructurally, dense core granules (DCG) were much more frequent in thymic carcinoid, but several DCG-like granules were identified in 12 of 13 non-NE tumors with or without immunoexpression of NE markers. The presence of focal or dispersed NE cells in thymic carcinoma and atypical thymoma may reflect multidirectional differentiation within the tumor, which, like cytological atypia, epithelial CD5 expression, and lack of immature T cell infiltration, may be another feature of this group at thymic tumors.

Adenocarcinoma↗
PubMed1998

The ATM gene and susceptibility to childhood T-cell acute lymphoblastic leukaemia.

Ataxia-telangiectasia (A-T) is a multisystem recessive disease characterized by cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency and increased risk of cancer. The ATM gene, responsible for A-T, was recently cloned at human chromosome band 11q22-23, a region of frequent alterations in childhood acute lymphoblastic leukaemia (ALL). Children with A-T frequently develop T-ALL. We investigated 18 T-ALL samples for ATM mutations and loss of heterozygosity (LOH) at the ATM locus. No mutations of ATM were found within the coding region in the 18 T-ALL samples, and LOH at the ATM locus was detected in three. The ATM gene appears to be an infrequently altered tumour suppressor gene in childhood T-ALL.

Ataxia Telangiectasia Mutated Proteins↗
PubMed1998

Effect of high concentrations of bile acids on cultured hepatocytes.

High concentrations of bile acids have been reported as injurious to hepatocytes. We report the influence of various combinations of bile acids on the liver-specific function of cultured rat hepatocytes. Using 4 bile acids (glycocholate [GC], taurocholate [TC], glycohenodeoxycholate [GCDC], and taurochenodeoxycholate [TCDC]), we obtained 6 bile-acid mixtures, each containing equal amounts of 2 bile acids (total bile acids [TBA], 2 mM). Changes in gluconeogenesis, ureagenesis, DNA contents, medium alanine aminotransferase, and morphologies were compared among the paired bile acid compositions by measuring the C/CDC ratio ([GC + TC]/[GCDC + TCDC]) of each. In terms of their relative impairments of ureagenesis from greatest to least, the acids were GCDC, TCDC, and GC, which was almost the same as TC. When the C/CDC ratio was 0, the values of all parameters measured deteriorated. When the C/CDC ratio was 1 in the presence of 1 mM GCDC, only the rate of ureagenesis was diminished. When the C/CDC ratio was infinite, no hepatocellular injury was observed. GCDC and TCDC, together or separately, showed significant hepatocellular injury when the TBA concentration was 2 mM.

Alanine Transaminase↗
PubMed1998

Esophageal strictures in children with recessive dystrophic epidermolysis bullosa: experience of balloon dilatation in nine cases.

BACKGROUND: Recessive dystrophic epidermolysis bullosa is a rare disorder characterized by extreme vulnerability of the squamous epithelium and mucous membranes. Minor trauma such as is caused by swallowing solid food is followed by blistering and scarring. Stricture formation at the pharyngoesophageal junction (C6 or C7) is the severest complication of this disease. METHODS: We evaluate the effectiveness of Microvasive Rigiflex balloon dilatation and extensive nutritional support as a primary treatment for this condition. Nine of 21 recessive dystrophic epidermolysis bullosa patients developed esophageal strictures at the level of the pharyngo-esophageal junction (C6). We treated them with intensive nutritional therapy followed by balloon dilatation, which produces longitudinal pressure and provides prompt relief from esophageal stricture. Eleven balloon dilatations have been performed in 9 patients. RESULTS: All patients had poor physical development and were severely malnourished; extensive nutritional support was required before treatment could begin. Balloon dilatation was performed once in seven patients and twice in two patients. No recurrent stricture formation was observed after balloon dilatation. CONCLUSION: Intensive nutritional support followed by balloon dilatation is the first choice of treatment for esophageal strictures complicating recessive epidermolysis bullosa. By following this regime, invasive surgery can be avoided.

Adolescent↗
PubMed1998

Establishment and characterization of a human Epstein-Barr virus-associated gastric carcinoma in SCID mice.

A transplantable human Epstein-Barr virus-associated gastric carcinoma (EBVaGC), designated KT, was propagated in severe combined immunodeficiency (SCID) mice for 12 passages. Mucin and cytokeratin expression and the Alu sequence in tumor DNA confirmed that the KT tumor was derived from human epithelial tissue. The identity of clonal EBV in the original and KT tumors was demonstrated by terminal repeat analysis of EBV DNA. The pattern of latency gene expression of EBV was the same in both tumors. EBER1 was presented similarly in tumor cell nuclei by in situ hybridization. Reverse transcription-PCR analysis also demonstrated Q-promoter-driven EBNA1 expression but not BZLF1, EBNA2, or LMP1 expression. Thus, the transplantable human EBVaGC KT retains the original EBV with the same latency gene expression and can serve as a model for this unique type of gastric carcinoma.

Adenocarcinoma↗
PubMed1998

Apoptosis is a major mode of cell death caused by ischaemia and ischaemia/reperfusion injury to the rat intestinal epithelium.

BACKGROUND AND AIMS: Injuries caused by ischaemia and ischaemia/reperfusion in the small intestine have been widely accepted as resulting in necrosis. The aim of this study was to ascertain whether apoptosis also occurs. METHODS: Intestinal epithelium from rats subjected to ischaemia (15-90 minutes) and ischaemia/reperfusion (15 minutes ischaemia followed by 15-75 minutes of reperfusion) was studied using histological, immunohistochemical, and molecular biological methods as well as FACS. RESULTS: Mucosal injury was induced by both ischaemia and ischaemia/reperfusion. Detachment of epithelial cells from the villous stroma was an early morphological change indicating mucosal injury. More than 80% of the detached cells exhibited characteristic morphological features of apoptosis (condensation of chromatin and nuclear fragmentation). The remainder demonstrated necrotic features. The apoptotic cells eventually underwent spontaneous degeneration with membrane rupture, a process morphologically identical to necrosis. DNA fragmentation was also confirmed by immunohistochemical methods and agarose gel electrophoresis. CONCLUSION: Apoptosis is a major mode of cell death in the destruction of rat small intestinal epithelial cells induced by ischaemia and ischaemia/reperfusion injury. Disruption of epithelial cell-matrix interactions ("anoikis") may play an important part in induction of apoptosis in detached enterocytes.

Animals↗
PubMed1998

The presence of nitric oxide synthase in the mammary glands of lactating rats.

Our objective was to show the presence of nitric oxide synthase (NOS) in the mammary glands of lactating rats and to determine the role that nitric oxide plays in lactation of humans. We used the nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase reaction and immunostaining on fresh frozen breast tissue obtained from lactating Wistar rats (13-18 wk old, 320-380 g, 3-4 d after parturition, first pregnancy). The breast tissues positive for NADPH diaphorase staining were the mammary gland, muscle, sebaceous gland, epidermis, and endothelium of the lactiferous ducts and blood vessels. These findings corresponded to tissues that were NOS-immunoreactive. The NOS detected in the mammary glands was the constitutive NOS. The finding of positive anti-NOS immunoreactivity and of positive NADPH diaphorase activity in the cells of the rat mammary glands leads us to conclude that nitric oxide is synthesized in mammary glands of rats. The high nitric oxide activity in the human breast was previously reported by measuring the total concentration of nitrite plus nitrate, biopterin, and neopterin in human milk. These results suggest that nitric oxide plays a role in the secretion of human breast milk.

Animals↗
PubMed1998

Pseudotumor cerebri in a patient with acute promyelocytic leukemia during treatment with all-trans retinoic acid.

We report a rare case of pseudotumor cerebri associated with all-trans retinoic acid (ATRA) treatment of acute promyelocytic leukemia (APL). An 18-year-old male was admitted to our hospital complaining of palpitations and shortness of breath; he was found to have APL. The administration of ATRA and chemotherapy was started. After 23 days, he complained of nausea, headache and double vision. Computed tomography and magnetic resonance imaging of the head showed no intracranial abnormalities. Bilateral papilledema, a symptom of increased intracranial pressure, was noted. A diagnosis of pseudotumor cerebri was made. Symptoms were improved by administration of glycerin and the discontinuation of ATRA. After 29 days, a complete remission was achieved.

Adolescent↗
PubMed1998

Novel vitamin D3 analog (CB1093) when combined with paclitaxel and cisplatin inhibit growth of MCF-7 human breast cancer cells in vivo.

Vitamin D3 compounds paclitaxel (Taxol) and cisplatin (CDDP, cis-diamminodichloroplatinum) inhibit growth of a variety of malignant cells. We examined the ability of a novel 20-epi-vitamin D3 analog (code name, CB1093), Taxol and CDDP either alone or in combination to inhibit the growth of a human mammary cancer (MCF-7) growing in BNX triple immunodeficient mice. Tumors in control animals demonstrated infiltrating poorly differentiated adenocarcinomas. At the doses chosen, the antitumor effect of Taxol alone was greater than that of either CB1093 or CDDP alone; and additive effects were observed when either CB 1093 + Taxol or CB 1093 + CDDP + Taxol were administered together. The combination of CB 1093 + Taxol + CDDP was most potent, inhibiting tumor weights by nearly 83% compared to control tumors and producing extensive necrosis of the remaining tumor mass. No additive effect occurred by combining either CB1093 + CDDP or Taxol + CDDP compared to Taxol alone. For all cohorts, their complete hematopoietic blood counts, serum electrolyte analyses including serum calciums as well as their liver and renal functions were within the normal range. Extensive histological analyses of the liver, spleen, kidneys, bone marrow, skin and subcutaneous fat pads from these mice showed no abnormalities. In summary, combined therapy with CB1093 (a potent vitamin D3 analog), Taxol and CDDP, which have non-cross reactive toxicities, holds promise in the treatment of patients with breast cancer.

Animals↗
PubMed1998

[Clinical usefulness of ultrasound (US) database and reporting system].

Our US database and reporting system is a relational database designed for US image-management and navigation through volumes of US images, ACR code, text and diagnostic reports. This program, running on a network of Unix servers and Macintosh clients, supports jukebox 5 inch optical disks for data storage. With simple keywords for ACR code, we can make a cross-reference and categorize US images of teaching files.

Data Display↗