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Biomedical subjects

H Shimura

Publications and source records attributed to H Shimura.

At least 37 records · Page 2Linked to original sources

Modulation of cholesterol metabolism affects tumor growth in hamsters.

To investigate the effects of cholesterol and cholesterol-lowering agents on cholesterol metabolism and tumor growth, 0.5% cholesterol, 2% cholestyramine, or 0.01% simvastatin was fed to hamsters with transplanted Simian virus40 transformed tumor cells. Tumor weight, tissue cholesterol and DNA concentrations, and HMG-CoA reductase activities were determined. Cholesterol or cholestyramine feeding did not affect the tumor growth, however, the tumor weight and DNA concentration were decreased and tumor HMG-CoA reductase activity was increased in the simvastatin group. In conclusion, simvastatin may inhibit the DNA synthesis and growth of the Simian virus40 transformed tumor cells possibly through the inhibition of cholesterol and isoprenoids synthesis in the hamster.

Animals

[Thoracoscopic repair of diaphragmatic eventration sustained at knife injury: a case report].

A 46-year-old male taxi driver was stabbed onto the left chest while on duty. On arrival soon after, he was hemodynamically stable. Computed tomography showed omental prolapse into the left thorax through the diaphragm. On the 11th day, he underwent thoracoscopy revealing omental prolapse via a 3-cm rent in the left diaphragm, which was reduced manually. The diaphragmatic orifice was lifted and debrided with suturing using a stapling cutter. The post-operative course was uneventful. Finger palpation through the orifice enabled safe suturing of the left diaphragm facing the omentum, the colon, and the stomach, all of which may suffer iatrogenic injury.

Endoscopy

HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor.

We prepared a specific antagonist for hepatocyte growth factor (HGF) and designated it HGF/NK4. HGF/NK4 is composed of N-terminal 447 amino acids of the alpha-chain of HGF, thus contains the N-terminal hairpin domain and subsequent four kringle domains. HGF/NK4 competitively inhibited the specific binding of HGF to the receptor. Importantly, HGF/NK4 neither stimulated DNA synthesis of primary cultured rat hepatocytes (mitogenesis) nor induced cell scattering (motogenesis) and branching tubulogenesis (morphogenesis) of MDCK renal epithelial cells, however, HGF/NK4 almost completely inhibited the mitogenic, motogenic, and morphogenic activities of HGF. HGF/NK4 also suppressed tyrosine phosphorylation of the c-Met/HGF receptor induced by HGF. Apparently this is the first documentation of a specific antagonist which abrogates the mitogenic, motogenic, and morphogenic activities of HGF.

Animals

Allopurinol reduced hepatic ischemia-reperfusion injury exacerbated by inhalation of high-concentration oxygen in rats.

Exposure to high-concentration oxygen (O2) increases lipid peroxidation of the cellular membrane, leading to tissue injury which may involve hepatic ischemia-reperfusion (I/R) injury. We examined the effects of inhaling high-concentration O2 on hepatic I/R injury with allopurinol, which is a xanthine oxidase inhibitor. Partial hepatic ischemia was performed in rats with or without allopurinol under 21 or 100% O2 inhalation. Levels of lipid peroxide, serum liver enzymes, and hepatocellular oxidative stress in the 100% O2 group were significantly higher than in the 21% O2. Administration of allopurinol significantly inhibited those changes in the 100% O2 group. Severe degeneration of mitochondria were noted in the 100% O2 group, but appeared to be reduced by allopurinol. Results suggest that inhalation of high-concentration O2 during liver surgery may increase lipid peroxidation and exacerbate hepatic I/R injury, but those changes may be prevented by allopurinol.

Alanine Transaminase

Iodide uptake and experimental 131I therapy in transplanted undifferentiated thyroid cancer cells expressing the Na+/I- symporter gene.

131I therapy is a widely accepted treatment for differentiated thyroid cancers which can accumulate iodide. We evaluated the efficiency of 131I therapy against tumors which are transfected with the Na+/I- symporter (NIS) gene. We transfected the rat NIS cDNA expression vector into malignantly transformed rat thyroid cells (FRTL-Tc) which do not concentrate iodide. The resultant cell line (Tc-rNIS) accumulated 125I 60-fold in vitro. The FRTL-Tc cells formed solid tumors after injection of cells into subcutaneous tissues of Fischer 344 rats. Tumors formed with Tc-rNIS cells accumulated up to 27.3% of total 125I administered, and concentrated 125I 11 to 27-fold in the tumors. Extracorporeal measurement of radioactivity in the tumors revealed that 125I accumulation peaked at 90 min, and decreased to half levels 6 h after the injections. To investigate the effect of 131I administration on the tumor growth, we injected Na131I 2 and 3 weeks after the transplantation of the cells. The Na131I did not change the tumor volume significantly in either the FRTL-Tc or the Tc-rNIS-induced tumors. The short (6 h) effective half life of 131I in the tumors diminished the radiation dose to the tumor cells. However, this approach may prove beneficial in the treatment of radiosensitive cancers, and could be employed diagnostically.

Animals

Regulation of thyrotropin receptor gene expression in 3T3-L1 adipose cells is distinct from its regulation in FRTL-5 thyroid cells.

We previously have demonstrated that rat adipose tissue expresses TSH receptor (TSHR) messenger RNAs (mRNAs) at levels approaching those detected in the thyroid. Furthermore, we recently reported that TSHR mRNA is detected in fibroblast-like 3T3-L1 cells after their hormone-induced differentiation into adipocytes. TSH induces cAMP formation and lipolysis in differentiated 3T3-L1 cells. We now show that, in Northern blot analyses, TSH-induced down-regulation of TSHR mRNA levels, which can be duplicated by forskolin and dibutylyl cAMP, i.e. which is cAMP-mediated. We also have demonstrated that a beta-adrenergic stimulant, which stimulates cAMP formation in adipocytes, induces a down-regulation of TSHR mRNA levels in 3T3-L1 adipocytes. Nuclear run-on assays show that the ability of TSH/cAMP to decrease TSHR mRNA levels in 3T3-L1 cells reflects transcriptional regulation. This report also demonstrates that TSHR gene expression in 3T3-L1 adipocytes is regulated in a manner distinct from that observed in thyroid cells. Thus, in fully differentiated 3T3-L1 adipocytes, TSH-induced down-regulation of TSHR mRNA levels is evident within 1 h and is near maximum within 4 h after addition of TSH. A transient increase of TSHR gene expression, which has been demonstrated in FRTL-5 thyroid cells, was not observed in 3T3-L1 adipocytes. The down-regulation of TSHR gene expression induced by TSH/cAMP in 3T3-L1 cells is cycloheximide-insensitive, suggesting that continuous protein synthesis is not required for this process. In contrast, the down-regulation of TSHR gene expression observed in FRTL-5 cells is sensitive to cycloheximide. In both FRTL-5 thyroid cells and 3T3-L1 adipocytes, insulin or serum increased TSHR mRNA levels. Although insulin or serum was required for the TSH-induced down-regulation of TSHR mRNA levels in FRTL-5 thyroid cells, neither insulin nor serum was required for TSHR down-regulation in 3T3-L1 adipocytes. These findings demonstrate that TSH/cAMP regulates TSHR mRNA levels in adipocytes via a regulatory system distinct from that used in FRTL-5 cells. This report further demonstrates that adipose cells do not express thyroid transcription factor-1, which interacts with the TSHR promoter region in FRTL-5 cells, and that 3T3-L1 nuclear extracts exhibit a different binding activity to the cAMP-response element-like element in the TSHR promoter region compared with extracts from FRTL-5 cells.

3T3 Cells

Total excision of mesenteric cysts by laparoscopic surgery: report of two cases.

Mesenteric cysts are relatively rare tumors, and most patients present nonspecific abdominal symptoms until developing larger cysts. We report two cases of mesenteric cysts that were totally excised during laparoscopic surgery. The cysts of both patients were located in the mesenterium of the cecum or ascending colon. Under laparoscopy, the cyst was punctured to collect the cystic fluid for cytology and then completely removed without bowel resection. Histological examination revealed cystic lymphangiomas with endothelial cell lining. The postoperative course was uneventful. Laparoscopic treatment of benign abdominal cysts is an alternative safe and less invasive operation.

Aged

Xanthogranulomatous cholecystitis versus gallbladder cancer: clinical differentiating factors.

Xanthogranulomatous cholecystitis (XC) is occasionally difficult to differentiate from gallbladder cancer and mandates efforts to avoid extensive operations. We studied the clinical factors to differentiate XC from cancer. Subjects were a consecutive series of 10 patients with XC and 10 with carcinoma, all of whom radiologically showed thickened gallbladder walls. As opposed to cancer, XC was typified by invisible gallbladders on cholangiography (1), the presence of cholelithiasis (P = 0.01) (2), and, intraoperatively, an aspirate of pus or nothing (P < 0.01) (3). To diagnose XC against gallbladder cancer, (1) and (2) in combination and (3) demonstrated an accuracy of 82.4% and 85.0 per cent, respectively. Clinically, XC can be distinguished from gallbladder cancer by cholangiography, calculous findings, and a gallbladder aspirate of pus or nothing.

Aged

A case of Meckel's diverticulum complicated by stenosis of the colon.

Meckel's diverticulum is a common anomaly of the GI tract that is known to cause small intestinal obstruction. A 17-yr-old male who had no history of previous surgery was admitted with intermittent abdominal pain. A barium enema showed extraintestinal compression of the ascending colon, suggesting the existence of a congenital band. Laparoscopy revealed that the ascending colon was lifted up and compressed by the intestinal end of a Meckel's diverticulum with a fibrous band connecting to the umbilicus. The portion of the ileum including the Meckel's diverticulum was resected. This is the first case of stenosis of the colon caused by a Meckel's diverticulum.

Adolescent

Telomerase activity in pancreatic juice differentiates ductal carcinoma from adenoma and pancreatitis.

Telomerase activity was measured in pancreatic juice obtained by endoscopic retrograde pancreatography from 34 patients (12 with ductal carcinoma, 12 with pancreatic adenoma, and 10 with pancreatitis). The activity in pancreatic juice was expressed as the number of cells of a human pancreatic cancer cell line, MIA PaCa-2, that exhibit an activity equal to that expressed in 1 microg of protein from pancreatic juice. A telomerase ladder was detected in the pancreatic juice obtained from a majority of the patients with ductal adenocarcinoma. The median value of relative telomerase activity in the carcinoma samples was 9.38 (25th percentile, 3.14; 75th percentile, 95.8), a value significantly higher than that derived from patients with either pancreatitis or pancreatic adenoma (P < 0.0001). When a threshold value of relative telomerase activity of 3.00 was used, 75% (9 of 12) of the samples obtained from patients with ductal carcinoma were positive. We conclude that telomerase activity in pancreatic juice differentiates adenocarcinoma from adenoma and pancreatitis and may serve as a useful diagnostic tool.

Adenocarcinoma

Telomerase elevation in pancreatic ductal carcinoma compared to nonmalignant pathological states.

Telomerase activity was measured in surgically resected tissues of 20 human pancreatic ductal carcinomas, 12 adenomas, 5 pancreatitis tissues, 14 normal pancreatic ducts, and 13 normal pancreatic tissues (primarily made up of acinar cells) using a PCR-based telomerase assay. Relative telomerase activity was expressed as the equivalent telomerase intensity of the number of cells of a human pancreatic cancer cell line, MIA PaCa-2, per microgram of protein in the tissue samples. The median value (25th percentile, 75th percentile) of relative telomerase activity in pancreatic carcinomas was 13.2 (3.58, 244), which was significantly higher relative to normal tissues, normal ducts, pancreatitis tissues, and adenomas (P < 0.0001). When the cutoff value of relative telomerase activity was set at 1.00 and 3.00, the positivity rates of telomerase activity in pancreatic ductal carcinomas were 100 and 80%, respectively. Some of the adenoma samples displayed a weak telomerase ladder. However, when semiquantitatively analyzed, the relative telomerase activity of all adenoma tissues was less than 1.00 equivalent cells per microgram protein of the tissues, which was equivalent to the values encountered in normal ducts. Thus, our results indicate that reactivation of telomerase may occur at a late stage of pancreatic ductal carcinogenesis. Therefore, telomerase may be a specific marker for distinguishing pancreatic cancer from pancreatitis and adenomas.

Adenocarcinoma

Functional expression of thyrotropin receptor in differentiated 3T3-L1 cells: a possible model cell line of extrathyroidal expression of thyrotropin receptor.

Thyrotropin receptor (TSHR) in extrathyroidal tissue, especially fat tissue, is supposed to have important roles in the development of extrathyroidal manifestations of Graves' disease. However, the molecular mechanism of TSHR expression is not known. Expression of TSHR mRNA and TSH-dependent cAMP production were observed in differentiated but not in undifferentiated 3T3-L1 cells. Maximal expression was obtained when the cells were differentiated in the presence of insulin, dexamethasone, and isobutylmethylxanthine (IBMX). Dexamethasone and IBMX were indispensable for the first three days. On the other hand, after day 4, insulin was indispensable for the expression of TSHR. 3T3-L1 cell is the first non-thyroidal cell line reported that expresses TSHR and whose expression can be induced. 3T3-L1 cell can be a good model to investigate the mechanism of expression of TSHR and extrathyroidal manifestations of Graves' disease.

1-Methyl-3-isobutylxanthine

In vitro analysis of peritoneal adhesions in peritonitis.

Peritoneal adhesions due to peritonitis make surgery more difficult and may cause complications. Clarifying the formation mechanism of peritoneal adhesions could help identify methods useful for their prevention. We cultured mesothelial monolayers on plates and microcarriers to simulate the parietal and visceral peritoneum, respectively. We then investigated the effects of lipopolysacchride (LPS) and tumor necrosis factor (TNF) on the homologous adhesion of these mesothelial monolayers. There was no adhesion of mesothelial monolayers in the control medium. When monolayers were cultured with endotoxin (LPS), approximately 90% of the microcarriers adhered to the mesothelial microplate. Adhesions occurred at LPS concentrations of 10 ng/ml and increased linearly in a dose-dependent manner. Kinetic studies revealed that the mesothelial adhesion appeared at 12 hr, and that 90% of the microcarriers were adherent after 24 hr. Open intercellular spaces were observed after a 24-hr treatment with LPS. Scanning electron microscopy revealed that the mesothelial cells adhered to the naked glass. LPS also caused increased permeability of the mesothelial monolayer. TNF did not cause any significant adhesion. Through our experiments we were able to develop an in vitro model of peritoneal adhesion using peritoneal mesothelial cell culture. Endotoxin caused an increase in homologous adhesion of peritoneal mesothelial monolayers, which may correspond to the initial stage of peritoneal adhesion formation in peritonitis.

Dose-Response Relationship, Drug

Semi-quantitative analysis of telomerase in pancreatic ductal adenocarcinoma.

Using a polymerase chain reaction-based amplification assay, we measured telomerase activity in surgically resected pancreatic ductal carcinomas (n = 16 cases) and normal ducts (n = 6), comparing findings with the telomerase activity of a human pancreatic cancer cell line, MIA PaCa-2, as a standard, i.e., relative telomerase activity was determined. Telomerase activity was expressed as the equivalent telomerase intensity of the number of cells of MIA PaCa-2 per microgram protein of tissue samples. The median value for telomerase activity in normal pancreatic ducts was 0.13 and the 25th and 75th percentile were 0.01 and 0.76. The median value for telomerase activity in pancreatic ductal adenocarcinoma was 34.7 (25th percentile, 4.98; and 75th percentile, 296), significantly higher than that of normal ducts (P < 0.001). When the cut-off value was set at 1.0 and 3.0, the telomerase positivity rate of pancreatic ductal adenocarcinomas was 100% and 81.3%, respectively. Telomerase may be specific marker for pancreatic ductal carcinomas.

Biomarkers, Tumor

Acquisition of invasive phenotype in gallbladder cancer cells via mutual interaction of stromal fibroblasts and cancer cells as mediated by hepatocyte growth factor.

Growth and motility of carcinoma cells are regulated through their interactions with host stromal cells, i.e., tumor-stromal interactions. Hepatocyte growth factor (HGF), a ligand for c-Met tyrosine kinase, is a stromal-derived regulator of growth, motility, and morphogenesis. HGF stimulated proliferation and motility of GB-d1 gallbladder carcinoma cells from a patient with gallbladder cancer. HGF induced in vitro invasion of GB-d1 cells into a collagen gel matrix, and this potent, invasive effect was not seen with epidermal growth factor, transforming growth factor-beta 1, basic fibroblast growth factor, or platelet-derived growth factor. Although GB-d1 did not produce HGF, the cells did produce a factor which enhances HGF production in human skin fibroblasts, and this factor proved to be interleukin-1 beta (IL-1 beta). When GB-d1 cells were co-cultured with fibroblasts such that a collagen gel matrix was layered between the GB-d1 cells and fibroblasts, GB-d1 cells invaded the gel, but invasion of the cells in the co-culture system was inhibited by antibodies against HGF and partially inhibited by antibodies against IL-1 beta. Thus, GB-d1 cell-derived IL-1 beta stimulates HGF production in stromal fibroblasts and HGF up-regulated in the fibroblasts induces invasion of GB-d1 cells. The looped interaction of carcinoma cells and stromal fibroblasts mediated by HGF and a HGF-inducer such as IL-1 beta may be one mechanism which would explain the acquisition of malignant phenotype through tumor-stromal interactions.

Cell Communication

Experimental correspondence between spore dosimetry and spectral photometry of solar ultraviolet radiation.

The biologically effective dose of solar UV radiation was estimated from the inactivation of UV-sensitive Bacillus subtilis spores. Two types of independent measurements were carried out concurrently at the Aerological Observatory in Tsukuba: one was the direct measurement of colony-forming survival that provided the inactivation dose per minute (ID/min) and the other was the measurement of the spectral irradiance by a Brewer spectrophotometer. To obtain the effective spectrum, the irradiance for each 1 nm wavelenght interval from 290 to 400 nm was multiplied with the efficiency for inactivation derived from the inactivation action spectrum of identically prepared spore samples. Integration of the effective spectrum provided the estimate for ID/min. The observed values of ID/min were closely concordant with the calculated values for the data obtained in four afternoons in 1993. The average ratio (+/- SD) between them was 1.24 (+/- 0.16) for 14 data points showing high inactivation rates (> 0.05 ID/min). Considering difficulties in the absolute dosimetry of UV radiation, the concordance was satisfactory and improved credibility of the two types of monitoring systems of biologically effective dose of solar UV radiation.

Bacillus subtilis