Biomedical subjects

M Shimada

Publications and source records attributed to M Shimada.

At least 289 records · Page 16Linked to original sources

PubMed1998

Enhanced expression of thrombospondin-1 and hypovascularity in human cholangiocarcinoma.

Cholangiocarcinoma (CCC) is relatively hypovascular, in contrast to hepatocellular carcinoma (HCC), which is often highly vascular. We investigated if the diminished vascularity of CCC is related to altered expression of thrombospondin-1 (TSP-1), an antiangiogenic factor, and/or vascular endothelial growth factor (VEGF), a potent angiogenic factor, comparing the relationships with those of high- and low-vascular HCC. We also investigated the relationship between the mutation of the p53 gene and TSP-1 expression or VEGF expression. Northern blot analysis and immunohistochemical staining were performed on surgically resected human CCC and HCC. The ratios of TSP-1 mRNA level in cancer cells versus adjacent noncancerous cells (T/N ratios) were significantly higher in CCC (n = 11) than in HCC with high vascularity (n = 15). In contrast, T/N ratios of VEGF mRNA level in CCC (n = 11) were comparable with those in HCC with low vascularity (n = 5). In CCC, the cancer cells and fibroblasts were positively stained with anti-TSP-1 antibody. We observed that T/N ratios of VEGF mRNA level, but not those of the TSP-1 mRNA level, were significantly correlated with vascularity in HCC. The relative increase in TSP-1 and the relative decrease in VEGF in tumors compared with normal tissue may underlie the limited angiogenesis of CCC. The p53 gene did not affect the expression of TSP-1 in CCC or VEGF in HCC.

Adult↗

PubMed1998

Perioperative change in albumin messenger RNA levels in patients with hepatocellular carcinoma.

A quantitative assay of albumin messenger RNA (mRNA) in blood samples was designed using the competitive reverse-transcription polymerase chain reaction, and the significance of measuring albumin mRNA levels in the blood of patients with hepatocellular carcinoma (HCC) in hepatic resection was evaluated. Albumin mRNA levels were measured in the following: (1) peripheral blood in 11 patients with HCC and 20 control subjects without liver disease, (2) blood in the portal and hepatic veins in five patients with HCC immediately after laparotomy, and (3) a perioperative series of peripheral blood in eight patients with HCC. Two patients with HCC whose albumin mRNA level in peripheral blood was markedly high were both at stage IVa. On the other hand, 20 control subjects showed negative or <5 x 10(3) transcripts/microgram RNA of albumin mRNA expression. Immediately after laparotomy, the albumin mRNA levels in the tumor-draining hepatic vein were greater than in the portal and non-tumor-draining hepatic veins in four of five patients with HCC. Albumin mRNA levels in peripheral blood showed a marked increase after mobilization and/or resection of the liver and, thereafter, gradually decreased at postoperative day 7 in all eight patients with HCC. A new method to measure the albumin mRNA levels in blood samples was developed, and high albumin mRNA levels in the peripheral blood of patients with advanced-stage HCC suggest the presence of HCC cells in the circulation. Increased levels in the tumor-draining hepatic vein could indicate the spontaneous release of tumor cells or nontumorous hepatocytes or an increased albumin transcription in activated blood mononuclear cells. An increase in the levels in peripheral blood during an operation is intermittent. Therefore, an increased albumin mRNA level in the tumor-draining vein suggests, but does not prove, that the increased albumin mRNA level reflects tumor cells entering the systemic circulation. This alone does not prove that the prognosis is worsened.

Aged↗

PubMed1998

Indication and efficacy of radiation therapy following radical surgery in patients with stage IB to IIB cervical cancer.

OBJECTIVE: To determine the role of radiation therapy following radical surgery in patients with cervical cancer. METHOD: A total of 104 patients with International Federation of Gynecology and Obstetrics stage IB to IIB cervical cancer who underwent radical hysterectomy and pelvic lymph node dissection at Tottori University Hospital between 1988 and 1994 were entered in this study. The criteria for postoperative radiotherapy included positive lymph node involvement, compromised surgical margin, parametrial extension, or deep stromal invasion of cervix with less than 3 mm of distance from serosa. Postoperative radiotherapy consisted of 10-20 Gy whole pelvis and an additional parametrial dose with a midline block to deliver a total of 44-50 Gy to the pelvic side wall. RESULTS: Sixty-two patients (59.6%) who met the criteria received postoperative radiotherapy. Lymph node metastasis was most frequent in stage IIB followed by stage IIA and then stage IB (36.7, 22.2, and 10.7%, respectively). Parametrial extension was observed 8.7% of patients with stage IB and 27.7% of those with stage IIA. The estimated 5-year survival rate for patients undergoing surgery alone was 97.6% and that for patients receiving postoperative radiotherapy was 82.7% (P = 0.038). Multivariate analysis showed that lymph node metastasis and parametrial extension were major prognostic factor, but the survival rate did not relate to depth of stromal invasion. CONCLUSION: Postoperative radiotherapy may improve the survival of patients with cervical cancer exhibiting lymph node metastasis or parametrial extension.

Adult↗

PubMed1998

Toxicity profile of benzo[a]pyrene in the male LacZ transgenic mouse (MutaMouse) following oral administration for 5 consecutive days.

The toxicity profile of benzo[a]pyrene (BP) was examined in the MutaMouse. The transgenic mouse integrated with lambda gt10 lacZ vectors is used worldwide as an experimental animal in in vivo mutagenesis testing systems. There are few toxicity studies including carcinogenicity in the MutaMouse, and so far only a few carcinogenicity studies of BP accompanied with hematological and plasma biochemical examinations have been conducted even in generic mice. Accordingly, male mice were orally administered BP at doses of 75 and 125 mg/kg/day for 5 consecutive days, and complete autopsy was conducted together with pathological, hematological, and plasma biochemical examinations and measurement of organ weights 41 weeks after the last treatment. Squamous cell papilloma and hyperplasia in the forestomach were induced at incidences of 25 and 50%, respectively and were induced 26 weeks after the final treatment without any significant alterations in t he hematological and plasma biochemical parameters in mice of the 125 mg/kg/day BP-treated satellite group. Fourty-one weeks after the final treatments, 75 and 125 mg/kg/day BP induced squamous cell carcinoma, papilloma, and hyperplasia in the forestomach at incidences of 18 and 18%, 36 and 45%, and 91 and 91%, respectively, and anemia possibly due to continuous hemorrhage from tumors in the forestomach. BP (125 mg/kg/day) also produced malignant lymphoma with an incidence of 18%, accompanied by a marked increase in leukocyte count and decrease in erythrocyte count and by a remarkable decrease in body weights 26 and 39 weeks after the last treatment. Moreover, administration of 75 and 125 mg/kg/day BP induced bronchiolar-alveolar hyperplasia in the lung at incidences of 18 and 9%, respectively. Slight increases were also observed in the weight of the liver and in the levels of urea nitrogen, creatinine, and potassium ion in the plasma biochemical examinations, although no significant pathological alterations were found in the liver and kidney. This study provides new information about BP toxicity including carcinogenicity in the MutaMouse developed for in vivo mutational analysis.

Administration, Oral↗

PubMed1998

Expression and localization of cysteine dioxygenase mRNA in the liver, lung, and kidney of the rat.

The expressions of cysteine dioxygenase (CDO) gene in the liver, lung, skeletal muscle, and kidney were studied by in situ hybridization with a cDNA probe from rat liver CDO under normal conditions. Significant expression of the CDO gene was detected in the liver, lung, and kidney, but not skeletal muscle. In the liver, the signal was confined to the cytoplasm of the hepatocytes. Furthermore, the signal was stronger in the periportal than that in the perivenous areas. In the lung, an intensive signal was found in the bronchiolar epithelium. As to the kidney, an intensive signal was observed in the distal convoluted tubules, while no signal was found in the proximal convultions.

Animals↗

PubMed1998

The application of radio-opaque markers prior to ileostomy in an infant with chronic intestinal pseudo-obstruction: report of a case.

We report the case of a 6-month-old boy who developed chronic intestinal pseudo-obstruction soon after birth. A rectal biopsy demonstrated immaturity of the neuronal cells in the enteral ganglion. His clinical course was stressful, with remission and exacerbation despite conservative treatment with daily bowel irrigation, prokinetic agents, and parenteral nutrition. Since the infant developed serious enterocolitis associated with the increased severity of his bowel obstruction, and no substantial gain in body weight was observed, a loop-ileostomy was performed based on X-ray findings with radio-opaque markers, which were employed to evaluate the whole gut transit time. The radio-opaque markers proved extremely useful for determining which loop of the ileum should be utilized for the ileostomy.

Barium Sulfate↗

PubMed1998

Manual reduction with the index finger for infantile intussusception. A modification of Hutchinson's maneuver.

Manual reduction with the index finger (modified Hutchinson's maneuver) enabling simple and safe manual reduction of infantile intussusception is described. The procedure was used in four patients, two boys and two girls, ranging in age from 2 to 15 months, as greater than normal compression was necessary and/or serosal splitting occurred during conventional reduction. The technique is as follows: in addition to the proximal bowel compression with Hutchinson's maneuver, the surgeon inserts his index finger into the intussusceptum via its neck. The finger enables the surgeon to sound a wider space between the intussusceptum and intussuscipiens, which is most likely to be responsive to bowel compression. Although the intussusceptions in the four patients were categorized as ileo-ileo-colic (three cases) and ileo-ileal (one case) types, this manual reduction technique was successful in all cases, no bowel rupture occurred, and hospitalization was no longer than with the conventional procedure. We conclude that this modified Hutchinson's maneuver may contribute to successful surgical reduction of infantile intussusception.

Female↗

PubMed1998

Diffusely infiltrative squamous cell carcinoma of the esophagus.

This study was designed to clarify the clinical and pathologic features of diffusely infiltrative squamous cell carcinoma of the esophagus. Diffusely infiltrative squamous cell carcinomas were classified grossly into two types, namely, scirrhous carcinoma and nonscirrhous carcinoma. There were seven patients with the former type and three with the latter type. Scirrhous-type carcinoma was associated with a prominently thickened esophageal wall with strictures, whereas nonscirrhous-type carcinoma demonstrated thickening of the esophageal wall without strictures. Microscopically, all patients had lymph node metastases and lymphatic invasion. Blood vessel invasion was found in seven patients and extranodal invasion was found in seven. The prognosis of patients with both types of carcinoma was extremely poor. Only two patients who underwent curative surgery as well as chemoradiotherapy survived for more than 1 year. Therefore, further morphological studies on the early stages of diffusely infiltrating esophageal carcinoma should be performed. New treatment strategies such as intensive preoperative chemoradiotherapy based on sensitivity tests in individual patients will be required for treating the advanced stages of this disease.

Aged↗

PubMed1998

Gilbert syndrome caused by a homozygous missense mutation (Tyr486Asp) of bilirubin UDP-glucuronosyltransferase gene.

We report a case of Gilbert syndrome caused by a homozygous missense mutation (Tyr486Asp) of the bilirubin UDP-glucuronosyltransferase gene. Homozygous missense mutations of the gene have previously been recognized as responsible for Crigler-Najjar syndrome type II. We conclude that Gilbert syndrome in some patients results from homozygous missense mutations of the UDP-glucuronosyltransferase gene.

Child↗

PubMed1998

Peripheral type benzodiazepine receptor in T lymphocyte rich preparation.

Some types of mood disorders and drugs are suggested to affect peripheral type benzodiazepine receptors (PBR), but their mechanisms are unclear. The isolation of pure lymphocytes is requisite for the investigation of the function of PBR on lymphocytes, since platelets and monocytes also have many PBR. The objective of this study was to establish a method of binding assay for PBR using pure T lymphocytes. Mononuclear cells and T lymphocytes were prepared by using a density gradient material and magnetic beads, respectively. The cells were analyzed using flow cytometry and a counting chamber. Binding studies were performed using T lymphocytes from 10 normal volunteers. The T lymphocytes were incubated with [3H]PK11195, harvested on glass fiber filters, and counted with a plate scintillation counter. The binding data were analyzed by the Scatchard method. With the magnetic bead technique, pure T cells were selected that contained only 1.5% monocytes and platelet/cell ratio of 1.4. The Scatchard plot of the data indicated that only one type of specific binding site was involved in the binding. The dissociation constant (Kd) was 3.8+/-1.3nM (mean+/-SD), and the Bmax was 379+/-124 fmol//10(6) cells (mean+/-SD). The density gradient- magnetic beads technique can be used as an appropriate method of preparation of T cells for PBR binding assay.

Binding Sites↗

PubMed1998

Alteration of telomerase activity associated with development and extension of epithelial ovarian cancer.

OBJECTIVE: To assess telomerase activity associated with the development and extension of epithelial ovarian cancer and to investigate the relationship between p53 gene status and telomerase activity. METHODS: A total of 53 samples (41 epithelial ovarian cancers, five borderline epithelial tumors, four benign adenomas, and three surface epithelia) were examined for telomerase activity by the polymerase chain reaction (PCR) -based telomeric repeat amplification protocol assay. Mutations in the p53 gene were determined by PCR-single strand conformation polymorphism analysis. RESULTS: Telomerase activity was detected in 33 of 41 epithelial ovarian cancers and in three of five borderline malignancies but was not detectable in either benign tumors or normal surface epithelium. The mean (+/-standard deviation [SD]) intensity of telomerase activity in cancers was significantly higher than that in borderline malignancies (10.6+/-8.2 versus 3.6 4+/-1.3). The positivity of telomerase activity did not correlate with any clinical findings, but the intensity (+/-SD) of telomerase activity was significantly higher in tumors with lymph node involvement (12.2+/-8.3 versus 3.8+/-1.1). Mutations of the p53 gene were observed in 44% of ovarian cancers; p53 gene status did not relate to telomerase activity. Multivariate analysis showed that the intensity of telomerase activity was not an independent factor for prognosis of patients with ovarian cancer. CONCLUSION: Telomerase activity may be associated with development and extension of epithelial ovarian cancer.

Adenocarcinoma, Mucinous↗

PubMed1998

Possible role for phosphatidylinositol 3-kinase in regulating meiotic maturation of bovine oocytes in vitro.

In this study 2 phosphatidylinositol 3-kinase (PI 3-kinase)-specific inhibitors, wortmannin and 2-[4-Morpholinyl]-8-phenyl-4H-1-benzopyran-4-one (LY294002), were used to investigate whether PI 3-kinase is involved in the signal transduction that leads to bovine oocyte maturation. Bovine follicular oocytes were cultured in vitro for 24 h in a basic medium consisting of tissue culture medium-199 supplemented with LH, FSH, fetal cow serum, Na-pyruvate and gentamicin. The oocytes were then examined for the stage of meiotic progression and degree of cumulus expansion. In Experiment 1, in cumulus-oocyte complexes (COCs), wortmannin, at any level tested (10(-8) M, 10(-7) M or 10(-6) M), had no effect on resumption of meiosis as judged by germinal vesicle breakdown and progression to prometaphase I or metaphase I. However, wortmannin significantly (P < 0.01) decreased the proportion of oocytes developing to metaphase II in a dose-dependent manner. In Experiment 2, when denuded oocytes were cultured with wortmannin at 0, 10(-7) M and 10(-6) M concentrations, the same pattern of response for COCs was observed, with no effect on meiotic resumption and a significant (P < 0.01) decrease in the proportion of oocytes reaching metaphase II. In Experiment 3, half of the recovered COCs were denuded and both denuded and intact COCs were cultured in the presence of 0, 2.5 x 10(-5) M, 5.0 x 10(-5) M and 7.5 x 10(-5) M LY 294002 before being examined for meiotic progression. Whereas LY294002, at any examined level, had no effect on the percentage of oocytes developing to metaphase I, it significantly (P < 0.01) decreased the proportion of metaphase II oocytes when used at 5.0 x 10(-5) or 7.5 x 10(-5) M for both intact COCs and denuded oocytes. In Experiment 4, no significant difference in the degree of cumulus expansion was scored after the COCs were cultured in the presence of wortmannin or LY294002 or in the absence of either treatment. These results provide indirect evidence for a role of PI 3-kinase in the bovine oocyte itself in regulating meiotic progression beyond metaphase I.

Androstadienes↗

PubMed1998

The restraint stress drives a shift in Th1/Th2 balance toward Th2-dominant immunity in mice.

When mice were physically restrained in 50-ml tubes for 24 h, a marked decrease of NK activity was demonstrated in parallel with the elevation of serum corticosterone levels. The release of mice from restraint stress resulted in the recovery of NK activity, with a decrease of serum corticosterone levels within 48 h. Using this stress model, we also investigated the influence of restraint stress on mouse Th1/Th2 balance. Consistent with the decrease of NK activity, IFN-gamma production of mouse spleen cells greatly reduced after suffering from restraint stress. In contrast, the IL-4 producing ability of spleen cells was not so much affected by restraint stress. These results initially indicated that stress may induce the skewing of the Th1/Th2 balance toward Th2-dominant immunity, which stimulates the occurrence of infectious diseases and allergic disorders.

Animals↗

PubMed1998

A newly developed adenovirus-mediated transfer of a wild-type p53 gene increases sensitivity to cis-diamminedichloroplatinum (II) in p53-deleted ovarian cancer cells.

A new recombinant adenovirus carrying a wild-type p53 gene (AxCAp53) was developed and the combination effect of p53 gene transfer and cis-diamminedichloroplatinum (II) (CDDP) was examined in an ovarian cancer cell line, SK-OV-3, with deletion of the p53 gene. AxCAp53 showed a high efficiency of gene transduction and increased sensitivity to CDDP in the SK-OV-3 cells. It was found that the sensitivity of the cells to CDDP correlated with the amount of infectious units of virus per cell of AxCAp53 which correlated with p53 protein expression. The results suggest that the combination of CDDP and AxCAp53 may be a potential strategy for the therapy of CDDP-resistant ovarian cancer.

Adenocarcinoma↗

PubMed1998

Role of adhesion molecule expression and soluble fractions in hepatic resection.

BACKGROUND: Little has so far been documented about the relationship between liver injury and adhesion molecules. The aim of this study is to clarify the role of adhesion molecules in hepatic resection by studying both the expression of such adhesion molecules and the measurement of their soluble fractions in the blood. STUDY DESIGN: To study adhesion molecule expression in the liver, liver biopsies were obtained before and after hepatectomy in 14 patients. Using frozen sections, immunochemical staining for intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was then performed. To study the soluble fractions of adhesion molecules in the hepatic venous blood, the serum soluble fractions of ICAM-1 and VCAM-1 from another 17 patients were measured using an enzyme-linked immunosorbent assay. The plasma levels of polymorphonuclear leukocyte (PMN) elastase were also measured using an enzyme immunoassay. Both the preoperative and postoperative values of the serum soluble fractions of ICAM-1, VCAM-1, and PMN elastase were then compared. The correlation between their values and the perioperative variables was also investigated. RESULTS: Either ICAM-1 or VCAM-1 was stained on the sinusoidal endothelial cells and Kupffer cells or circulating PMNs in the sinusoid. The positive rate of either ICAM-1 or VCAM-1 staining in livers with more than 40 minutes of total ischemic time (80%) was significantly higher than that in livers with less than 40 minutes of total ischemic time (0%; p < 0.05). The incidence of postoperative complications in the ICAM-1 positive staining group tended to be higher than that in the ICAM-1 negative group. Both soluble fractions of ICAM-1 and VCAM-1 in patients with cirrhotic liver disease were also significantly higher than those in patients with a normal liver. The soluble VCAM-1 level in patients with a chronic active hepatitic liver tended to be higher than that in those with a nonactive hepatitic liver. The preoperative level of soluble ICAM-1 correlated with that ofVCAM- 1, PMN elastase, albumin, aspartate aminotransferease (AST), and the indocyanine green dye retention test at 15 minutes (ICG R15), while the preoperative level of VCAM-1 correlated with albumin, the hepaplastin test, AST, and ICG R15. Both the serum soluble ICAM-1 and VCAM-1 levels after hepatectomy were significantly lower than those before hepatectomy. By contrast, the posthepatectomy level of PMN elastase was significantly higher than its prehepatectomy level. The difference between the postoperative and preoperative values of soluble ICAM-1 correlated with the postoperative AST level, postoperative alanine aminotransferase level, and total ischemic time. CONCLUSIONS: Adhesion molecules were expressed in the liver after hepatic resection, and such expression correlated with a total ischemic time during hepatectomy. In addition, judging from the soluble forms of such molecules, these adhesion molecules play an important role in hepatic resection.

Aged↗

PubMed1998

Elevation of plasma interleukin-6 level is involved in postoperative fever following major oral and maxillofacial surgery.

OBJECTIVE: The purpose of this study was to evaluate whether the changes in plasma cytokine levels including interleukin-6 (IL-6) interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) are involved in postoperative fever following oral and maxillofacial surgery. STUDY DESIGN: Ten patients undergoing elective oral and maxillofacial surgery were studied. We investigated the plasma cytokine levels by using an enzyme-linked immunosorbent assay and measured the core temperature and degree of postoperative shivering and peripheral vasoconstriction after surgery. The relationships between the changes in plasma cytokine levels and postoperative fever were statistically evaluated using Spearman's rank correlation coefficients. RESULTS: The elevation of plasma IL-6 level was significantly correlated with the increase in core temperature after surgery and with the degree of postoperative shivering and vasoconstriction, whereas the changes in plasma II-1 beta or TNF-alpha levels were not. CONCLUSIONS: Elevation of plasma IL-6 level is probably involved in postoperative fever following oral and maxillofacial surgery.

Aged↗

PubMed1998

Risk factors linked to postoperative morbidity in patients with hepatocellular carcinoma.

BACKGROUND: The aim of this study was to clarify the risk factors for morbidity as well as to establish an optimum surgical strategy for hepatocellular carcinoma (HCC). METHODS: The risk factors linked to postoperative complications were analysed in 388 patients over a 10-year period, according to the kind of operative procedure. RESULTS: Stepwise regression analysis revealed that the most important factors related to postoperative morbidity were: age, creatinine level and the histological grade of fibrosis for the bisegmentectomy; the presence of diabetes mellitus, blood urea nitrogen level, the indocyanine green dye retention rate at 15 min and blood loss for the segmentectomy; the presence of diabetes mellitus and blood loss for subsegmentectomy; the presence of diabetes mellitus, the aspartate aminotransferase level, and the total operating time for resection less than subsegmentectomy. CONCLUSION: The most important risk factors were not always related to liver function tests, but instead to other coexisting conditions such as diabetes mellitus and operation stress including operating time and blood loss. Therefore, any future treatment strategy of hepatic resection for HCC should make every effort both to evaluate coexisting conditions carefully and to reduce operative stress as far as possible.

Age Factors↗

PubMed1998

Hypertension in Leigh syndrome--a case report.

A female patient, who was diagnosed with Leigh syndrome at 15 months of age, developed fulminating severe hypertension and died at 8 years of age. Hypertension has not been reported as an important clinical symptom in Leigh syndrome. Laboratory findings indicated that it was not associated with endocrinopathic diseases such as pheochromocytoma and aldosteronism, or renal diseases. Brain MRI scan showed symmetrical lesions in the basal ganglia and medulla oblongata including the nucleus tractus solitarius. This nucleus is known to play an important role in maintaining blood pressure. Since the medulla oblongata is a vulnerable site, potential development of hypertension should be taken into consideration when managing Leigh syndrome.

3-Iodobenzylguanidine↗