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Biomedical subjects

T Kitamura

Publications and source records attributed to T Kitamura.

At least 55 records · Page 3Linked to original sources

Hepatocyte growth factor inhibits intercellular communication via gap junctions in rat hepatocytes.

We demonstrated that HGF reduces gap junctional intercellular communication of rat hepatocyte doublets and increases cell spreading. Intercellular communication via gap junctions was markedly reduced in hepatocyte doublets with HGF (20 ng/ml) 3-12 hr after inoculation. Immunocytochemistry revealed spotty localization of connexin 32 on the plasma membrane of 3-hr cultured control hepatocyte doublets, whereas HGF-treated doublets showed significantly less connexin 32 staining. Genistein maintained intercellular communication in the presence of HGF, indicating that HGF reduces intercellular communication by down regulation of connexin 32 through the c-met/HGF receptor-tyrosine-kinase-mediated pathway. Furthermore, TGF-beta 1 maintained intercellular communication in the presence of HGF. Regulation of intercellular communication in hepatocytes by HGF and TGF-beta 1 might play an important role during liver regeneration.

Analysis of Variance

Induction of endometrial adenocarcinomas by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine to aged Donryu rats showing spontaneously persistent estrus.

Induction of endometrial adenocarcinomas by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) to aged rats was examined. Donryu rats showing spontaneously persistent estrus were given a single intra-uterine administration of ENNG (20 mg/kg) at 10 months (44 weeks) of age. At the termination of the experiment (week 34 after the ENNG-treatment), 22% and 13% incidences of endometrial adenocarcinomas were observed in the experimental and control groups, respectively, the difference being without significance. No variation was found in the endocrine environment between experimental and non carcinogen-treated control animals throughout the experimental period. These results show that ENNG-treatment alone is not sufficient in aged rats for high induction of endometrial carcinomas. Comparison of the data with those from our previous studies, in which ENNG was given at a young age (10 weeks of age), indicates that young rats may be more sensitive than their old counterparts.

Adenocarcinoma

Interleukin 2 and erythropoietin activate STAT5/MGF via distinct pathways.

Signal transducers and activators of transcription (STAT) proteins play an important role in cytokine signal transduction in conjunction with Janus kinases (JAKs). MGF/STAT5 is known as prolactin regulated STAT. Here we demonstrate that interleukin 2 (IL-2) as well as erythropoietin (EPO) stimulate STAT5 and induce tyrosine phosphorylation of STAT5. These IL-2- and EPO-induced STATs have an identical DNA binding specificity and immunoreactivity. We also show that IL-4 induces a DNA binding factor which possesses similar, but distinct, DNA binding specificity from that of STAT5 and is immunologically different from STAT5. Analysis of two EPO receptor (EPOR) transfected CTLL-2 cell lines discloses that IL-2 activates JAK1 and JAK3 as well as STAT5, while EPO stimulates STAT5 and JAK2 in EPO-responsive CTLL-2 cells (ERT/E2). On the contrary, EPO activates neither JAK2 nor STAT5 in other cell lines that failed to respond to EPO (ERT cells). EPOR and JAK2 associate with each other regardless of EPO presence in ERT/E2 cells, however, such an interaction is not present in ERT cells. Thus, EPOR and JAK2 association seems to be important for EPO responsiveness in CTLL-2 cells.

Animals

Late rectal complication following high dose rate intracavitary brachytherapy in cancer of the cervix.

PURPOSE: To examine the incidence of radiation-induced late rectal complications using a rectal reference point in patients with cancer of the uterine cervix. METHODS AND MATERIALS: The subjects were 253 patients with cancer of the cervix who underwent high dose rate intracavitary brachytherapy (HDR-ICR). The rectal point (RP) was defined according to the criteria recommended in the ICRU Report 38. The time-dose factor (TDF) and the biologically effective dose (BED) were calculated as components of the cumulative reference rectal dose using the rectal reference point dose in intracavitary brachytherapy combined with the external whole pelvis dose. RESULTS: Statistical comparison of factors affecting the incidence of late rectal complication was conducted using data for 161 patients. The incidence of late rectal complications in the 161 patients was 9 patients (5.6%) for grade 1, 51 patients (31.7%) for grade 2, 11 patients (6.8%) for grade 3, and 13 patients (8.1%) for grade 4. The TDF and BED values were significantly correlated with the incidence of late rectal complication, and also showed strong correlation (r = 0.976) with each other. Grade 4 rectal complication was not observed in any patients with TDF below 130 or BED below 147. The calculated incidence of complications ranged from 5 to 10% at TDF values from 104 to 124 and at BED values from 119 to 146. CONCLUSION: These data regarding the incidence of rectal complication may be useful in reducing the incidence of late rectal complications arising after HDR-ICR treatment of cervical uterine cancer by adjusting the dose per fraction and number of fractions of HDR-ICR in individual patients and by improving the technique of inserting the intracavitary radiation apparatus.

Female

Human IL-3 receptor signaling: rapid induction of phosphatidylcholine hydrolysis is independent of protein kinase C but dependent on tyrosine phosphorylation in transfected NIH 3T3 cells.

Although tyrosine kinases are clearly activated after ligand engagement of the human IL-3R in both hematopoietic and nonhematopoietic cytoplasmic environments, a role for phospholipid hydrolysis and protein kinase C in IL-3R signal transduction is emerging. We have used NIH 3T3 cells transiently transfected with human IL-3R alpha- and beta-subunits to study phosphatidylcholine hydrolysis in response to human IL-3. We have found that NIH 3T3 cells expressing the complete human IL-3R respond to human IL-3 with a rapid and sustained increase in sn-1'2'-diacylglycerol. Accompanying this was a rapid increase in intracellular levels of phosphorylcholine. The protein kinase C inhibitor H-7, however, was not effective in inhibiting phosphatidylcholine hydrolysis in response to human IL-3 in NIH 3T3 cells expressing the human receptor. Thus the human IL-3R induces a rapid protein-kinase-C-independent hydrolysis induced by the murine receptor. Simultaneous with the increase in phosphatidylcholine hydrolysis induced by the murine receptor. Simultaneous with the increase in diacylglycerol levels was an increase in membrane-bound protein kinase C enzyme activity. Immunoblotting with isoform-specific Abs against protein kinase C showed that, whereas the zeta-isoform is constitutively membrane bound, the alpha-isoform of protein kinase C is translocated to the membrane in response to IL-3. Activation of phosphatidylcholine hydrolysis and protein kinase C activation required both alpha- and beta-receptor subunits. To determine the relationship of tyrosine phosphorylation to the activation of phosphatidylcholine hydrolysis and protein kinase C translocation, we used the specific and structurally unrelated tyrosine kinase inhibitors genistein and herbimycin. Both inhibitors effectively blocked human IL-3-induced tyrosine phosphorylation. In addition, both inhibitors blocked phosphatidylcholine hydrolysis and protein kinase C translocation. These data, combined with our previous report showing that c-jun induction by IL-3 is dependent on protein kinase C, suggest that, in hematopoietic and nonhematopoietic cells expressing the human IL-3R, phosphatidylcholine hydrolysis and protein kinase C are downstream effectors of tyrosine phosphorylation in the IL-3 signal transduction cascade resulting in immediate early response gene induction.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Endoscopic ultrasonography in diagnosis and staging of pancreatic cancer.

The accuracy of endoscopic ultrasonography (EUS) for diagnosis of pancreatic cancers was evaluated in consecutive 232 patients with possible pancreatic cancer, and that for assessment of their locoregional spread was evaluated in 28 patients with pancreatic cancer subjected to pancreatectomy, in comparison with the accuracies of transabdominal ultrasonography (US) and computed tomography (CT). EUS was found to be significantly more accurate than US or CT and was especially useful for detecting small pancreatic cancers of less than 2 cm in diameter. With EUS, pancreatic cancers could be detected as a hypoechoic mass with a relatively unclear margin and irregular internal echoes. EUS was also more sensitive than CT and US for detecting venous and gastric invasions: it was more useful for detecting direct invasion of pancreatic cancers when the tumors were less than 3 cm in diameter. These findings indicate that EUS is an accurate method for diagnosis of pancreatic cancer and assessment of their locoregional spread and is particularly useful for detecting small tumors.

Endoscopy, Digestive System

Porto-hepatic venous shunt via portal vein aneurysm with splenomegaly.

A 59-year-old woman presented with consciousness disturbance with flapping tremor. Laboratory examinations revealed normal liver functions, and imaging studies, ultrasonography, magnetic resonance imaging, and angiography, showed portal vein aneurysm communicating from the portal vein to the hepatic vein, splenomegaly, and splenic artery aneurysm. These examinations confirmed porto-systemic shunt leading to hepatic encephalopathy. Porto-hepatic venous shunt via portal vein aneurysm is extremely rare, and there are few reports that it causes encephalopathy; therefore, little is known about the entity and this association. The literature in English is reviewed and the etiology, clinical features, and prognosis discussed.

Aneurysm

Liver with hypoechoic nodular pattern as a risk factor for hepatocellular carcinoma.

BACKGROUND/AIMS: Ultrasonography should be used for screening of hepatocellular carcinoma, but there are few reports on the relationship between liver ultrasonographic findings and the development of hepatocellular carcinoma (HCC). Using prospective follow-up studies, we examined the role of liver with a hypoechoic nodular pattern as a high-risk factor in HCC. METHODS: The study was performed by follow-up on 593 patients with chronic liver disease recorded at our hospital. The ultrasonographic pattern of the liver parenchyma was classified either as a small or large hypoechoic nodular pattern or as a nonnodular pattern. Patients were followed up from the time of initial ultrasonographic examination (1985-1987) until January 1, 1991. RESULTS: During the follow-up period (average, 4.2 years, range, 0.3-6.0 years), 62 patients were found to have HCC (12%). Patients whose livers showed small or large hypoechoic nodular pattern had a significantly higher risk of HCC than did patients whose livers showed a nonnodular pattern (rate ratios were 14.0 and 20.0, respectively, adjusted for age, sex, hepatitis virus markers, ICG R15, alpha-fetoprotein concentration, and ultrasonographic pattern of the liver). CONCLUSIONS: Liver showing a hypoechoic nodular pattern is a major risk factor in HCC.

Adult

In vivo effect of GroESL on the folding of glutamate racemase of Escherichia coli.

The overexpression of the murI (glr) gene, which encodes the glutamate racemase of Escherichia coli, resulted in the formation of inclusion bodies of the enzyme, and little activity was found in the soluble fraction of the transformant cells. The coexpression of the groESL gene with murI caused an in vivo solubilization of glutamate racemase in an active form. We isolated the active enzyme and purified it effectively.

Amino Acid Isomerases

Increased prevalence of HTLV-I infection in patients with hepatocellular carcinoma associated with hepatitis C virus.

The progression from chronic hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) has been reported. We evaluated whether co-infection with the human T-lymphotropic virus type I (HTLV-I) might be associated with this transition in a cross-sectional analysis of 127 patients with HCV-chronic hepatitis (mean age = 51.7) and 43 patients with HCV-associated HCC (mean age = 62.4); the seroprevalence of anti-HTLV-I was 9.5% and 30.2%, respectively. For subjects 50 years or older, the seroprevalence of anti-HTLV-I in HCC patients was 13/41 (31.7%) which was significantly higher than that in chronic hepatitis patients (6/82, 7.3%) (P = 0.001). The relative risk (RR) of association was 12.8 (P = 0.0004) among the males, however, no association was evident among the females, RR = 1.3 (P = 0.80). The increased prevalence of HTLV-I positivity among the HCC cases could not be attributed to a higher rate of prior transfusion. These data suggest that co-infection with HTLV-I may contribute to the development of HCC among patients with HCV-induced chronic liver diseases in a highly HTLV-I-endemic area.

Adolescent

Gene expressions of protein tyrosine phosphatases in regenerating rat liver and rat ascites hepatoma cells.

mRNA levels for ten protein tyrosine phosphatases (PTPs), PTP-S, PTPH1, PTP-1, GLEPP1, LRP, PTP1D, PTPG1, PTP gamma, PTP delta, and LAR, were determined during regeneration of rat liver, and mRNA levels for 5 PTPs, PTP-S, PTP-1, PTP gamma, PTP delta, and LRP, were determined in three lines of rat ascites hepatoma cells. In regenerating rat liver, the expression patterns of PTP genes after partial hepatectomy could be classified into four groups. In group 1 (PTP-S and PTPH1), the mRNA levels increased rapidly, reached a maximum 7 h after partial hepatectomy, remained at a plateau for 1-2 days and then decreased gradually. In group 2 (PTP-1, GLEPP1, and LRP), the mRNA levels showed two peaks on days 1 and 5, and then decreased gradually. In group 3 (PTP1D and PTPG1), the mRNA levels increased rapidly, reached a maximum at 7 h, remained high for several days, and then did not decrease but rather increased after day 7. In group 4 (PTP gamma, PTP delta, and LAR), the mRNA levels remained constant for the first 5 days and increased over the control levels after day 7. In rat ascites hepatomas, gene expression of non-receptor-like PTPs (PTP-S and PTP-1) showed various neoplastic alterations, whereas mRNAs of receptor-like PTPs (PTP gamma, PTP delta, and LRP) were lost or drastically decreased.

Amino Acid Sequence

Integrity of myosin light chain kinase is essential for Ito cell contraction.

Hepatic sinusoidal Ito cells (fat storing cells) are believed to play a regulatory role on hepatic sinusoidal blood flow through their contraction. The detailed mechanism of contraction of Ito cells, however, is still unknown. The present study was undertaken to clarify the effect of new myosin light chain kinase inhibitor, wortmannin, on Ito cell contraction. Ito cells prepared from rat liver were cultured for 4 days before the study. The contraction of Ito cells, which was monitored and analysed by time-lapse video tape recording, was triggered by addition of endothelin-1. Wortmannin pretreatment for 1 h inhibited endothelin-induced Ito cell contraction dose-dependently. Therefore, the integrity of the actomyosin system is essential for Ito cell contraction and normal sinusoidal blood flow.

Androstadienes

Increased incidental detection and reduced mortality in renal cancer--recent retrospective analysis at eight institutions.

A retrospective survey of renal cell carcinoma between 1975 and 1993 at eight collaborating institutions was conducted with special reference to the incidental detection and mortality of renal cancer. The analysis demonstrated a recent dramatic increase in the frequency of incidental renal cancer, which now comprises two-thirds of all renal cancers, and a simultaneous recession in non-incidental or suspected renal cancer. Incidental renal cancer has remained unchanged during the last decade as far as patient demographics, occasion and method of detection, and the degree of tumor extension are concerned. On the other hand, the annual number of deaths from renal cancer has significantly decreased, and kidney-sparing surgery has been more frequently performed. These results indicate that incidental renal cancers are now in the majority, and earlier detection may contribute to improving the mortality and morbidity from the disease as a whole.

Aged

Accuracy of prostatic volume calculation in transrectal ultrasonography.

BACKGROUND: Estimation of the prostatic volume by transrectal ultrasonography is now widely used to evaluate the effect of conservative treatment and to improve the specificity of prostate specific antigen. Accurate measurement of prostatic volume is necessary for the calculation of prostate specific antigen density (PSA/prostatic volume ratio). METHODS: Three dimensional models of the prostatic contour were constructed from transrectal ultrasonotomograms taken at 5 mm intervals in 20 cases. Using these models, the accuracy of ellipsoid volume calculation and prolate ellipse volume calculation were examined. For prolate ellipse volume calculation, prostatic length was measured in two ways; length (Lv) vertical to the transverse section, and length (Lp) parallel to the prostatic urethra. RESULTS: Ellipsoid volume calculation showed errors of about 20%. Moreover, ellipsoid volume calculation fluctuated markedly (up to 50%) in accordance with the change of the scanning angle of the transverse section. The error of prolate ellipse volume calculation using Lp for length increased by an average of 25% as the angle moved away from the perpendicular. The prolate ellipse volume calculation using Lv for length was the most reliable method. The degree of error was least dependent on the angle between the plane and the axis. CONCLUSION: Although prolate ellipse volume calculation was more accurate than ellipsoid volume calculation, it is essential to have the three axes cross at right angles to obtain an accurate value by the prolate ellipse volume calculation.

Humans

Parent-to-child transmission is relatively common in the spread of the human polyomavirus JC virus.

JC polyomavirus (JCV), the causative agent of progressive multifocal leukoencephalopathy, is ubiquitous in the human population, infecting children asymptomatically and then persisting in renal tissue. In most adults, renal JCV replicates and the progeny are excreted in urine. We used this urinary JCV to elucidate the routes of JCV transmission. A 610-bp JCV DNA region (IG region) encompassing the 3'-terminal sequences of both T-antigen and VP1 (major capsid protein) genes was amplified by means of PCR from urine specimens collected from all members of seven families. JCV strains were then unequivocally identified by the nucleotide sequences of the amplified IG regions. We could identify 18 distinctive JCV strains from 27 individuals. Different JCV strains were detected from all unrelated persons. However, the same viral strain was detected from one (four families), two (one family), or three offspring (one family) as well as from the fathers (three families) or from the mothers (three families). In total, the JCV strains detected in half of the JCV-positive children were identified in their parents. Since most humans are infected during childhood, these findings indicated that JCV is transmitted frequently from parents to children. We roughly estimated that 50% of JCV transmission occurs by this route and that the other 50% occurs outside the family.

Adult

Symptoms of psychoses. A factor-analytic study.

BACKGROUND: The literature on the statistical analysis of symptoms of psychoses was limited to positive and negative symptoms in schizophrenia. The present study explored the relationship between positive and negative symptoms as well as affective symptoms in a wider category of psychotic disorders. METHOD: The symptoms of 584 psychiatric patients, consecutively admitted to any of the 95 mental hospitals in Japan, were studied. They manifested at least one of the following: (a) delusions, (b) hallucinations, (c) formal thought disorder, (d) catatonic symptoms, or (e) negative (defect) symptoms. RESULTS: Factor analysis yielded five factors interpretable as (a) manic symptoms, (b) depressive symptoms, (c) negative (defect) symptoms and formal thought disorders, (d) positive (psychotic) symptoms, and (e) catatonic symptoms. CONCLUSION: These results suggest that although major symptoms seen among psychotic patients can be categorised into positive, negative, manic, and depressive groups, corresponding to current knowledge of phenomenology, catatonic symptoms constitute a discrete syndrome, while formal thought disorders merge into the negative syndrome.

Adolescent

Isolation and characterization of a hantavirus from Rattus norvegicus in a residential area of Nagoya City, Japan.

The prevalence of antibodies to hantavirus among Rattus norvegicus in Nagoya city was examined during the period from 1986 to 1993. Eight sera of 675 were antibody positive in an indirect fluorescent antibody test. Antibody positive rats were found in 1988, 1990, 1991 and 1992 and the numbers of rats were 1, 1, 3 and 3, respectively. A hantavirus strain was isolated from a rat captured in 1990 at a residential area adjoining to a pier in Nagoya port. The virus strain, named NR-9, was identified antigenically as the Seoul type of hantavirus in a neutralization test. Suckling rats inoculated with NR-9 strain survived, while those with SR-11 strain succumbed. A difference between the virulence of strains, NR-9 and SR-11 was demonstrated.

Animals