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M Shimada

Publications and source records attributed to M Shimada.

At least 73 records · Page 4Linked to original sources
PubMed2001

Correlation of three-dimensional gradient echo dynamic MR imaging with CT during hepatic arteriography in patients with hypervascular hepatocellular carcinomas: preliminary clinical experience.

The purpose of this study is to elucidate the usefulness of dynamic MR study of the whole liver using 3DFISP with double dose gadolinium (Gd) enhancement in detecting enhancing lesions in 20 patients. Twenty patients with hepatocellular carcinoma (HCC) underwent 3DFISP dynamic study with double dose Gd. The demonstration of enhancing hypervascular lesions regardless of etiology was evaluated on a segment-by-segment basis with receiver operating characteristic (ROC) analysis, using findings on CT during hepatic arteriography as a gold standard. Diagnostic accuracy of 3DFISP in the detection of HCC was also evaluated. As to the demonstration of enhancing lesions, the Az value of the ROC curve was 88%. The detection rate of HCC with 3DFISP was 98%. 57% of enhancing pseudolesions were not detected on 3DFISP. We concluded that Dynamic MR study of the whole liver using 3DFISP with double dose Gd enhancement is a useful method to demonstrate hypervascular HCC.

Aged↗
PubMed2001

Depressive symptoms and associated factors in a cognitively normal elderly population: the Tajiri Project.

BACKGROUND AND OBJECTIVE: Since depression is one of the main problems of elderly subjects, it is important to examine the prevalence of this condition and to identify associated factors. METHODS: A total of 1525 cognitively normal subjects aged 65 years and over in the town of Tajiri, a typical agricultural town in Japan, were analysed. Their MMSE (mini-mental state examination) scores were 24 or over. Depressive state was assessed by Zung's SDS (self-rating depression scale) with a comprehensive interview to examine ADL, demographics and symptoms associated with illness, etc. The prevalence of depression was calculated. To determine the factors associated with depression, the t-test and the Chi-square test were used. To examine the relative strength of each factor, logistic regression analysis was performed. RESULTS: The ratio of the depressive subjects was 6.4%, lower than those of previous reports, probably due to the effect of excluding dementia subjects. The ratio for older females aged 80 years and over was 14.3%, which was significantly higher than that of the males. Among socio-demographic factors, sex, age, number of children and perception of economic status, were significantly related. For health status and ADL, such factors as perception of health and medical history of heart disease and rheumatism were related. For familial and social status, factors such as daily activity and several conversation abilities were related. The logistic regression analysis indicated that perception of health and daily activity were associated. CONCLUSIONS: In this study, we isolated some factors related to depression in a cognitively normal population. Knowledge of such factors is important for appropriate mental care of aged subjects.

Activities of Daily Living↗
PubMed2001

Neuronal apoptosis mediated by IL-1 beta expression in viral encephalitis caused by a neuroadapted strain of the mumps virus (Kilham Strain) in hamsters.

The neuroadapted Kilham strain of the mumps virus produces lethal encephalitis in newborn hamsters after intracerebral inoculation. The pathogenesis of this encephalitis is not fully understood, but recently, apoptosis and associated cytokine production have been recognized to be major pathologic mechanisms by which viruses cause injury to neuronal host cells. To analyze the main factors producing brain injury in this viral encephalitis, the following questions were investigated: (1) does the virus induce neuronal apoptosis and (2) does expression of cytokines regulate the induction of neuronal apoptosis? Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) was used as a marker of neuronal apoptosis and TUNEL-positive neurons were widespread in the infected cerebral cortex. DNA fragmentation yielding DNA ladders characteristic of apoptosis was also observed in infected hamster brain tissue. Apoptotic cells in infected brains were observed after the appearance of inflammatory changes. Overexpression of IL-1 beta, but not TNF-alpha or Fas-L, was clearly detected in infected brains, as determined by Western blot and RT-PCR. Immunohistochemistry revealed a striking correlation between IL-1 beta expression and neuronal apoptosis. Injection of recombinant IL-1 beta into normal hamster brain resulted in neuronal apoptosis in cerebral cortex. On the other hand, neutralizing IL-1 beta antibodies decreased the number of cells undergoing apoptosis in infected hamster brains and subsequent death. We conclude that the fatal encephalitis induced by the Kilham strain of the mumps virus is mediated by immunopathological processes and that overexpression of IL-1 beta, which mediates the induction of neuronal apoptosis, may play a major role in these processes.

Animals↗
PubMed2001

The role of neoadjuvant radiochemotherapy using low-dose fraction cisplatin and 5-fluorouracil in patients with carcinoma of the esophagus.

OBJECTIVE: We clarified the role of neoadjuvant radiochemotherapy in patients with carcinoma of the esophagus and compared it to neoadjuvant chemotherapy. METHODS: We retrospectively examined 40 patients diagnosed with advanced thoracic esophageal carcinoma who underwent neoadjuvant therapy followed by esophagectomy between 1993 and 1999. We divided them into 2 groups: radiochemotherapy (17) and chemotherapy (23). Radiochemotherapy patients underwent 40 Gy radiation and low-dose fraction cisplatin (7 mg/body/day, 5 days a week x 4 weeks) and 5-fluorouracil (350 mg/body/day x 28 days). Chemotherapy patients received high-dose fraction cisplatin/5-fluorouracil involving 2 courses of cisplatin (70 mg/m2/day on day 1) and 5-fluorouracil (700 mg/m2/day on days 1-5). RESULTS: Complete pathological response was 17.6% in the radiochemotherapy group and 0% in the chemotherapy group respectively. No hospital mortality occurred in the radiochemotherapy group, and 1 of the 23 chemotherapy patients died in the hospital due to postoperative complications. The incidence of residual tumors was significantly higher in the chemotherapy group (34.8%) than in the radiochemotherapy group (0%). Actuarial survival in the radiochemotherapy group at 1 year was 80.2% and at 3 years 53.5%. Actuarial survival in the chemotherapy group at 1 year was 56.5% and at 3 years 30.4%. CONCLUSIONS: Histological effectiveness was greater in patients treated with preoperative radiochemotherapy than those treated with preoperative chemotherapy. The combination of radiation and low-dose fraction CDDP/5-FU thus is first choice in neoadjuvant radiochemotherapy for the advanced esophageal carcinoma.

Aged↗
PubMed2001

Characteristics of multicentric hepatocellular carcinomas: comparison with intrahepatic metastasis.

Characteristics of multicentric hepatocellular carcinomas (HCCs) remain obscure. We therefore aimed to clarify them and compare them with HCC with intrahepatic metastases. A series of 118 patients who had definite hepatitis C viral status and multinodular HCC were divided into two groups: a multicentric occurrence (MO) group (n = 38), with multicentric HCCs; and an intrahepatic metastasis (IM) group (n = 80), with HCC having intrahepatic metastases. Clinicopathologic variables, including the patient's survival and disease-free survival rates, were compared between the MO and IM groups. Univariate analysis revealed the presence of esophageal varices, the presence of hepatitis C virus infection, a platelet count of less than 10 x 10(4)/microliter, hepaplastin test, gamma-globulin, the histologically active hepatitis, tumor size, des-gamma-carboxy prothrombin > 0.1 AU/ml, positive portal vein invasion, and histologic grade as discriminating factors. The MO score to differentiate multicentric HCCs from intrahepatic metastatic HCCs was determined using the following four independent factors selected by a stepwise regression analysis: the presence of hepatitis C virus infection, a platelet count of less than 10 x 10(4)/microliter, tumor size, and histologic grade. The sensitivity and specificity of the MO scores using those factors were 84% and 70%, respectively, when the cutoff value was 0.4. The disease-free survival rate in the MO group was similar to that in the IM group, whereas the survival rate in the MO group was significantly better than that in the IM group. The multivariate analysis revealed the multicentric occurrence of HCC as one of the independent prognostic factors. Clinicopathologic factors differentiating multicentric HCCs from intrahepatic metastatic HCCs were the presence of hepatitis C virus infection, a platelet count of less than 10 x 10(4)/microliter, small tumor size, and low histologic grade.

Carcinoma, Hepatocellular↗
PubMed2001

Techniques available for the management of massive sacrococcygeal teratomas.

An infant born in the 34th week of gestation weighing 5,355 g with a massive sacrococcygeal (SC) tumor was delivered by elective cesarean section. An ultrasonographic examination showed solid and cystic components in the tumor. Resection was successfully undertaken with insertion of a Nélaton catheter into the rectum to avoid unnecessary impairment of the viscera. The tumor weighed 2,380 g, measured 25 x 14 x 11 cm, and was clinicopathologically diagnosed to be a SC teratoma. This experience and other publications show that several considerations including control of hemorrhage and coagulopathies, visceral protection, and avoidance of wound infection are necessary to facilitate the surgical management of massive SC tumors. Several suggestions are made concerning the pre- and intraoperative management of this rare tumor.

Female↗
PubMed2001

Repeat hepatectomy is the most useful treatment for recurrent hepatocellular carcinoma.

Hepatic resection has been regarded as a curative treatment for primary hepatocellular carcinoma (HCC), but a high incidence of postoperative recurrence is general. Thus it is important to predict the patterns of recurrence and select the appropriate treatment for recurrence for a better long-term prognosis of patients with HCC. Clinicopathological studies on 80 patients with intrahepatic recurrence after curative hepatectomy suggested that nodular-type recurrence with up to three nodules is mainly due to metachronous multicentric hepatocarcinogenesis rather than intrahepatic metastases. We reviewed 300 patients with recurrent HCC, and repeat hepatectomy was done in 78 cases (26.0%). The 3- and 5-year survival rates after repeat hepatectomy were 82.8% and 47.5%, respectively, showing better prognosis than those for other treatments. Repeat hepatectomy is the preferred treatment offering a hope of long-term survival for patients with recurrent HCC as long as liver function is sufficient; thus early detection of recurrence should be ensured.

Adult↗
PubMed2001

The role of macroscopic classification in nodular-type hepatocellular carcinoma.

BACKGROUND: Little has been reported on the role of macroscopic classification of hepatocellular carcinoma (HCC). We hypothesized that macroscopic classification of HCC might have a strong correlation with long-term prognosis after hepatectomy. METHODS: Four hundred and four patients with a macroscopically nodular type of HCC who underwent a hepatectomy were studied. The patients were divided into three groups: single nodular (SN) group (n = 312); single nodular with extranodular growth (SNEG) group (n = 52); and confluent multinodular (CMN) group (n = 40). Clinicopathological variables were compared among the three groups. The patient survival rate was also compared among the three groups. Finally, a multivariate analysis was performed to clarify the independent significant variables of the long-term prognosis. To confirm the consistency of the results in small-size HCC, the same analyses were made using patients whose tumor size was equal to or less than 3 cm in diameter. RESULTS: The alpha-fetoprotein value, tumor size, and rate of absolute noncurative operation in the SNEG group were higher than in other groups. The positive rate of both portal vein invasion of cancer cells and intrahepatic metastasis in the SN group was lower than those in other groups. The rate of poorly differentiated histology in the SN group was lower than in the other groups. Patient survival in the SNEG group was worst among the three groups. However, patient survival showed no significant difference between the SN and CMN groups. The multivariate analysis showed that the presence of intrahepatic metastasis, the macroscopic classification of SNEG type, and absolute noncurative operation were independent poor prognostic indicators. The results for patients with small HCCs measuring equal to or less than 3 cm in diameter were quite similar to the results for the other patients. CONCLUSIONS: Among the three subtypes of macroscopically nodular type of HCCs, the SNEG type showed higher rates of portal vein invasion of cancer cells, intrahepatic metastasis, and poorly differentiated histology. The patient survival rate in the SNEG type was worst, and the SNEG type was an independent poor prognostic indicator. The macroscopic classification of HCC, especially the SNEG type, helps predict the long-term outcome after hepatectomy.

Carcinoma, Hepatocellular↗
PubMed2001

The role of overexpression and gene amplification of cyclin D1 in intrahepatic cholangiocarcinoma.

BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma (ICC) is a primary liver malignant tumor with an extremely poor prognosis, but less attention has been directed to factors related to molecular carcinogenesis, including cell cycle proteins. We examined the expression and gene amplification of cyclin D1, the cell cycle regulating protein. Our objective was to evaluate correlations with clinicopathological factors in ICC. METHODS: Cyclin D1 overexpression and cellular proliferative activity (Ki-67 labeling index) were investigated immunohistochemically, and 20 cases were further investigated for cyclin D1 gene amplification, using differential PCR. We examined the correlation between the expression and gene amplification of cyclin D1 and clinicopathological factors, including overall survival in patients with ICC. RESULTS: Immunohistochemical analysis revealed an overexpression of cyclin D1 protein in 28 of 66 subjects with ICCs (42%). The cyclin D1 overexpression was associated with poor histological differentiation (P = 0.04), high cellular proliferative activity (P < 0.01), and a poor prognosis (P = 0.02) by univariate analysis, although it is not an independent prognostic factor by multivariate analysis. Cyclin D1 gene amplification was confirmed in five of the 20 patients. Of those five cases of ICC, all had poor histological differentiation, and four of the five ICCs (80%) showed evidence of cyclin D1 immunoreactivity. CONCLUSIONS: Overexpression and gene amplification of cyclin D1 are frequent and contribute to dedifferentiation and cellular proliferative activity of ICCs, and overexpression also indicates a poor prognosis for patients with ICC.

Adult↗
PubMed2001

Decreased expression of an ATP-binding cassette transporter, MRP2, in human livers with hepatitis C virus infection.

BACKGROUND/AIMS: To understand hepatic injury during the process of hepatitis viral infection, determination of liver-specific functions at molecular levels is critical. Because the transport of endogenous/exogenous toxic substances is an intrinsically important hepatic function, we examined whether expression of the ATP-binding cassette (ABC) transporter gene was affected in patients with hepatitis viral infection. METHODS: To determine which ABC transporter was expressed differently in patients with hepatic viral infection, we assayed the expression of MDR1, MDR3, MRP1, MRP2, and MRP3 in non-cancerous regions in the liver of 42 patients with hepatic tumors using both quantitative RT-PCR and immunological staining analysis, and compared the hepatic expression levels between patients with hepatitis viral infection and non-infected controls. RESULTS: Of the five ABC transporter genes studied, the mRNAs of MRP2 and MRP3 were highly expressed in the human liver. There was a significant reduction in MRP2 expression to 29% in the virus-infected liver. Treatment of hepatic cells with inflammatory cytokines resulted in decreased mRNA levels of MRP2 and decreased MRP2 promoter activity. CONCLUSIONS: The down-regulation of MRP2 might induce a failure in the transport of various genotoxic substances in the liver with hepatitis virus infection.

Adult↗
PubMed2001

Altered expression of beta-catenin without genetic mutation in intrahepatic cholangiocarcinoma.

beta-catenin which has a role in E-cadherin mediated cell-to-cell adhesion, and is also involved in Wnt signaling pathways as a downstream signaling molecule accumulating in the cytoplasm and nucleus constitutively activates Tcf/LEF-associated transcription of oncogenic genes. We examined the expression pattern and the genetic alteration of beta-catenin to determine the role of beta-catenin in cancer formation and/or progression in intrahepatic cholangiocarcinoma (ICC). beta-catenin expression was immunohistochemically examined in 71 surgically resected ICC samples, and correlation between the expression pattern and clinicopathologic factors was investigated. Mutation analysis of beta-catenin exon 3, which included the responsible element for Wnt signaling was done in 55 samples, using PCR-SSCP and direct sequence methods. Immunohistochemical analysis revealed the reduced membranous expression of beta-catenin in 58 (82%) ICCs and aberrant nuclear expression in 11 (15%) ICCs. The membranous expression was preserved in 62% of the papillary adenocarcinomas, and was frequently reduced in tumors with a poorer histological differentiation (84%), with a significant difference (P =.01). Genetic analysis showed that none of the 55 ICCs examined carried mutations in beta-catenin exon 3. The present study indicates that reduced membranous expression of beta-catenin is associated with non-papillary ICCs which have a more malignant behavior, and that nuclear translocation of beta-catenin results in oncogenic events. Mutations in beta-catenin exon 3 do not appear to be responsible for nuclear translocation of beta-catenin in ICCs.

Aged↗
PubMed2001

Preclinical and therapeutic utility of HVJ liposomes as a gene transfer vector for hepatocellular carcinoma using herpes simplex virus thymidine kinase.

Although gene therapy has been suggested to be a novel strategy to treat hepatocellular carcinoma (HCC), no study showing the clinical feasibility of vectors to treat HCC has been reported. In this preclinical study, we show evidence indicating that hemagglutinating virus of Japan (HVJ) liposomes are a feasible vector to treat HCC in a clinical setting using ganciclovir (GCV) and herpes simplex virus thymidine kinase (HSV-tk), which is driven by the cytomegalovirus immediate early enhancer/promoter (plasmid pcDNA3/HSV-tk). In in vitro experiments, almost complete tumor cell regression was achieved with the optimal GCV concentration (100 microg/mL) and more than 1/3 regression was seen even with a 20% transduction ratio using HuH7 HCC cells stably transformed by HSV-tk. HVJ liposomes showed a 19.7% (mean) transduction rate of the lacZ gene in a relatively large mass of more than 300 mm3 in vivo, which is a clinically detectable size, implanted into SCID mice. Moreover, a single HSV-tk injection of HVJ liposomes followed by GCV treatment inhibited tumor growth at least within a week, and repeat administration was more effective. Furthermore, subcutaneous injection of an HVJ liposomes vehicle induced no apparent inflammatory response in C3H/HeN mice, whereas lacZ gene transfection resulted in inflammatory pathology, suggesting a lower immunogenicity of the HVJ envelope protein than those of bacteria-derived plasmid DNA or the beta-galactosidase gene product. From these findings, we conclude that HVJ liposomes are a clinically safe and effective gene transfer vector to treat HCC.

Animals↗
PubMed2001

Value of lymph node dissection during resection of intrahepatic cholangiocarcinoma.

BACKGROUND: Hepatectomy with extensive lymph node dissection is the standard operation for intrahepatic cholangiocarcinoma (IHCC). However, lymph node dissection may not always be effective at reducing tumour recurrence. METHODS: Forty-nine patients with IHCC who underwent hepatectomy were investigated to determine patterns of tumour recurrence and to estimate the value of lymph node dissection during resection. RESULTS: At hepatectomy most metastatic lymph nodes were identified at least to the level of group 2 lymph nodes. Among 23 patients who developed recurrence, 17 had liver metastases and the other six had recurrence at other sites, mainly in the peritoneum. Poorly differentiated histology was related to the development of liver metastases. No patient with the intraductal growth type of IHCC had tumour recurrence. Lymph node dissection did not appear to improve patient survival. Histological findings of lymph node metastases and intrahepatic metastases were independent indicators of poor prognosis. CONCLUSION: Lymph node metastases were seldom limited to the regional lymph nodes; most tumour recurrence occurred in the liver. Lymph node dissection did not appear to improve patient survival. Lymph node dissection alone is not likely to improve the prognosis without further control of liver metastases.

Bile Duct Neoplasms↗
PubMed2001

Cooperation of interleukin-17 and interferon-gamma on chemokine secretion in human fetal intestinal epithelial cells.

Interleukin (IL)-17 is a newly identified T cell-derived cytokine that can regulate the functions of a variety of cell types. In this study, we investigated the effects of IL-17 and interferon (IFN)-gamma on chemokine secretion in human fetal intestinal epithelial cells. IL-8 and monocyte chemoattractant protein (MCP)-1 secretion by the human fetal intestinal epithelial cell line, intestine-407, was evaluated by ELISA and Northern blot. The expression of IL-17 receptor (R) was analysed by a binding assay using [(125)I]-labelled IL-17. The activation of nuclear factor-kappa B (NF-kappa B), NF-IL6 and AP-1 was assessed by an electrophoretic gel mobility shift assay (EMSA). IL-17 induced a dose-dependent increase in IL-8 and MCP-1 secretion. The inducing effects of IL-17 on IL-8 and MCP-1 mRNA abundance reached a maximum as early as 3 h, and then gradually decreased. IL-17 and IFN-gamma synergistically increased IL-8 and MCP-1 secretion and mRNA abundance. IFN-gamma induced a weak increase in IL-17 R mRNA abundance, and incubation with IFN-gamma for 24 h enhanced [(125)I]-labelled IL-17-binding by 2.4-fold. IL-17 rapidly induced the phosphorylation and degradation of I kappa B alpha molecules, and the combination of IL-17 and IFN-gamma induced a marked increase in NF-kappa B DNA-binding activity as early as 1.5 h after the stimulation. Furthermore, this combination induced an increase in NF-IL-6 and AP-1 DNA-binding activity. In conclusion, it becomes clear that IL-17 is an inducer of IL-8 and MCP-1 secretion by human fetal intestinal epithelial cells. The combination of IL-17 with IFN-gamma synergistically enhanced chemokine secretion. These effects of IL-17 and IFN-gamma might play an important role in the inflammatory responses in the intestinal mucosa.

Cell Line↗
PubMed2001

Genetics of larval urea and ammonia tolerance and cross-tolerance in Drosophila melanogaster.

Five laboratory populations of Drosophila melanogaster previously selected for over 60 generations for larval resistance to ammonium chloride (NH4Cl), and five populations selected for over 60 generations for larval resistance to urea, were investigated to determine the genetic mechanisms through which such tolerance had evolved. To examine the genetics of tolerance to urea and ammonia, egg-to-adult survivorship and developmental time were measured at two different NH4Cl levels and two different urea levels for each selection regime relative to the control lines, and among reciprocal crosses between each selection regime and the control lines. To examine tolerance to novel nitrogenous compounds (cross-tolerance), egg-to-adult survivorship and developmental time were measured at two different NH4Cl levels and two different urea levels for reciprocal crosses between the selection lines. Dominance is a major genetic factor in egg-to-adult survivorship in the presence of either urea or ammonia, while cross-tolerance to novel nitrogenous compounds also shows dominance as a major genetic mechanism controlling egg-to-adult survivorship. Dominance and X-linkage appear to be factors affecting developmental time in the presence of either urea or ammonia, although we could not exclude cytoplasmic inheritance as influencing our results. Cross-tolerance to novel nitrogenous compounds shows dominance and X-linkage as the main genetic factors controlling developmental time. We develop a simple hypothesis, in accordance with the results, that there may be two X-linked loci: one controlling urea tolerance and one controlling ammonia tolerance, and one autosomal locus exerting a pleiotropic control of tolerance. However, many other possibilities exist.

Ammonium Chloride↗
PubMed2001

Involvement of Rel/NF-kappaB in regulation of ascidian notochord formation.

The Rel/NF-kappaB family is known to be involved in a wide variety of biological processes, including morphogenesis. In the present study, two protochordate cDNA clones encoding Rel/NF-kappaB proteins, named As-rel1 and As-rel2, were isolated from a fertilized egg cDNA library of the ascidian Halocynthia roretzi. The As-rel1 protein is a typical Rel/NF-kappaB family member, containing a Rel homology domain, a nuclear localization sequence and a C-terminal putative transcription activation domain, while the As-rel2 protein is a novel Rel/NF-kappaB family member that lacks a nuclear localization sequence and the C-terminal domain. Northern blot analyses showed that both transcripts were maternally expressed and that their expression changed during development of H. roretzi embryos. Although injection of the As-rel2 mRNA into H. roretzi fertilized eggs had little effect on embryonic development, injection of the As-rel1 mRNA interfered greatly with notochord formation, resulting in a shortened tail with a reduced number of notochord cells. In contrast, embryos co-injected with As-rel1 and As-rel2 mRNA developed normally, indicating that the As-rel2 protein rescued the defect in notochord formation induced by the injection of As-rel1 mRNA alone. These results strongly suggest that the As-rel1 protein functions as a suppressor in ascidian notochord formation, while the As-rel2 protein has an antagonistic effect on the action of the As-rel1 protein.

Amino Acid Sequence↗