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Biomedical subjects

M Imamura

Publications and source records attributed to M Imamura.

At least 253 records · Page 14Linked to original sources

Prognostic value of p27(Kip1) and CyclinD1 expression in esophageal cancer.

It has recently been reported that the reduced expression of p27(Kip1) is a negative prognostic marker in several carcinomas. In this study, we examined the expression of p27(Kip1) in esophageal squamous cell carcinomas in order to understand its prognostic role. We also examined the expression of cyclinD1, which is believed to be correlated with the prognosis. Of the 128 cases, 64 cases (50.0%) showed low grade p27(Kip1) immunostaining and 64 cases (50.0%) high grade immunostaining; there was no significant difference in survival (p = 0.0915) between the two groups. On the other hand, 51 of the 156 cases (32.7%) were classified as the high cyclinD1 group, and 105 of the 156 cases (67.3%) as the low group, thus representing prognostic significance with regard to survival (p = 0.0161). Multivariate analysis indicated that gender, lymph node metastasis and positive cyclinD1 were independent prognostic factors. Our results revealed that cyclinD1 was a significant prognostic predictor of esophageal squamous cell carcinomas, whereas p27(Kip1) was not a significant prognostic factor.

Aged↗

Acanthosis nigricans with severe obesity, insulin resistance and hypothyroidism: improvement by diet control.

We report on a 27-year-old man with acanthosis nigricans (AN) associated with severe obesity, insulin resistance and hypothyroidism. A very low-calorie diet treatment decreased his weight and then ameliorated the insulin-resistant state. These effects were followed by remarkable improvement of the AN prior to the correction of the hypothyroidism. This confirms that AN may be mainly attributed to insulin resistance rather than hypothyroidism per se.

Acanthosis Nigricans↗

Correlation of tensile strength with bursting pressure in the evaluation of intestinal anastomosis.

BACKGROUND: Although bursting pressure and tensile strength have long been measured to evaluate anastomotic techniques, it has yet to be clarified whether or not they are correlated, what implications they have, and which should be used as a gold standard. MATERIAL AND METHODS: Using an experimental model to estimate pressure and tension in the same colonic anastomosis, the following variables were measured in 48 rats between days 0 and 14: bursting pressure (BP); minimal tensile strength (MITS) necessary to break a part of the anastomosis, and maximal tensile strength (MATS) needed to disrupt the whole anastomosis. Also, circulatory wall tension (CWT) was derived from BP and the anastomotic circumference (AC), and longitudinal wall tension (LWT) from MITS and AC. These variables were compared using correlation and regression analysis. RESULTS: During the lag phase (days < or = 4) there was poor correlation between pressure-related and tension-related variables whereas highly significant correlations were noted in the subsequent fibroplastic phase (day > or = 5). It was shown by regression lines that positive MITS and MATS were expected when BP was zero. CONCLUSION: Contrary to the previous assumption, no correlation was found between BP and tensile strength in the critical postoperative period. Based on our present and previous studies, measurement of MITS is recommended to evaluate the healing of colonic anastomosis.

Anastomosis, Surgical↗

Rationale of the so-called extended resection for pancreatic invasive ductal carcinoma.

It has generally been recognized that for adenocarcinoma of the pancreas, surgical resection provides the only chance for cure. In this study, we have analyzed the long-term survival of 141 patients with invasive ductal adenocarcinoma of the pancreas who received macroscopically curative resection. Multivariate analysis demonstrated that comprehensive stage of the tumor, curability of the resection, and adjuvant radiation therapy were independent prognostic factors. Pancreatectomy in this study was done with an extensive retroperitoneal clearance of para-aortic lymph node and nerve tissues, so-called extended resection. Survival curves of these patients revealed that the R0 resection is essentially necessary for long-term survival. Survival curve without microscopic lymph node metastasis was significantly better than that with node metastasis; however, 3 patients with node metastasis have been alive for more than 3 years. The survival curve of the patients who received adjuvant radiation therapy was better than of those who underwent surgery alone, and postoperative regional chemotherapy with continuous 5-FU infusion decreased hepatic metastases within 6 months. The results suggest that local recurrence of pancreatic cancer might possibly be controlled by extended resection and adjuvant irradiation, and early development of hepatic metastases might be controlled with regional chemotherapy.

Adenocarcinoma↗

Hyperenterostatinemia in premenopausal obese women.

Enterostatins [Val-Pro-Asp-Pro-Arg (VPDPR), Val-Pro-Gly-Pro-Arg (VPGPR), and Ala-Pro-Gly-Pro-Arg (APGPR)] are pentapeptides derived from the NH2-terminus of procolipase after tryptic cleavage and belong to the family of gut-brain peptides. Although enterostatin-like immunoreactivities exist in blood, brain, and gut, and exogenous enterostatins decrease fat appetite and insulin secretion in rats, the roles of these peptides in human obesity remain to be examined. To determine whether VPDPR and APGPR secretion is altered in obesity, serum VPDPR and APGPR levels were measured in 38 overnight-fasted subjects (body mass index, 17.9-54.7 kg/m2) before and after a meal. The mean fasting VPDPR in the serum of lean subjects was significantly lower than that in obese subjects [lean = 603 +/- 86 nmol/L (n = 17); obese, 1516 +/- 227 nmol/L (n = 21); P = 0.0023]. In addition, the rise in serum APGPR after a meal (postmeal/fasting ratio) was significantly higher in lean than in obese subjects [lean, 1.71 +/- 0.24 (n = 17); obese, 1.05 +/- 0.14 (n = 21); P = 0.0332]. The results of these studies show hyperenterostatinemia in obesity and a diminution in enterostatin secretion after satiety.

Adult↗

Expression and regulation of type II iodothyronine deiodinase in cultured human skeletal muscle cells.

T4, which is a major secretory product of the thyroid gland, needs to be converted to T3 by iodothyronine deiodinase to exert its biological activity. After the molecular cloning of human type II iodothyronine deiodinase (DII) complementary DNA, DII expression was unexpectedly detected in human skeletal muscle tissue. In the present study, we have identified DII activity and DII messenger ribonucleic acid (mRNA) in cultured human skeletal muscle cells and studied the mechanisms involved in the regulation of DII expression in those cells. All of the characteristics of the deiodinating activity in cultured human skeletal muscle cells were compatible with those of DII. Northern analysis has demonstrated that DII mRNA, approximately 7.5 kb in size, was expressed in cultured human skeletal muscle cells. DII mRNA and DII activity were rapidly increased by (Bu)2cAMP, forskolin, or beta-adrenergic agonists and were negatively regulated by thyroid hormones in cultured human skeletal muscle cells. Although interleukin-1beta and interleukin-6 did not decrease DII expression in cultured human skeletal muscle cells, tumor necrosis factor-alpha decreased DII expression in those cells in a dose-dependent manner. These data have demonstrated, for the first time, that DII activity and DII mRNA are present in cultured human skeletal muscle cells, and that the DII expression is stimulated by beta-adrenergic mechanisms through a cAMP-mediated pathway and is negatively regulated by thyroid hormones and tumor necrosis factor-alpha.

Adrenergic beta-Agonists↗

Plectin is a linker of intermediate filaments to Z-discs in skeletal muscle fibers.

Plectin is a versatile linker protein which is associated with various types of cytoskeletal components and/or filaments including intermediate filaments, and its deficiency causes the disruption of myofibrils, or muscular dystrophy. To better understand the functional role of plectin in skeletal muscle fibers, we have examined the topological and structural relationships of plectin to intermediate filaments and Z-discs in rat diaphragm muscles by confocal and immunoelectron microscopy. Immunofluorescence analysis revealed that plectin was colocalized with desmin at the periphery of Z-discs. This plectin localization around Z-discs was constantly maintained irrespective of the contracted or extended state of the muscle fibers, suggesting either direct or indirect association of plectin with Z-discs. Immunogold labeling in skinned muscle fibers clearly demonstrated that plectin-labeled fine threads linked desmin intermediate filaments to Z-discs and connected intermediate filaments to each other. These results indicate that through plectin threads desmin intermediate filaments form lateral linkages among adjacent Z-discs, preventing individual myofibrils from disruptive contraction and ensuring effective force generation.

Animals↗

Detection of extrapancreatic nerve plexus invasion of pancreatic adenocarcinoma. Cytokeratin 19 staining and K-ras mutation.

BACKGROUND: Neural invasion is known to be one of the aggressive characteristics of pancreatic adenocarcinoma. However, there have been no systematic studies on intraoperative examination of neural invasion of pancreatic carcinomas after wide dissection of the retroperitoneum, particularly at the surgical margin. METHODS: We performed intraoperative immunostaining on the frozen sections of several excised plexus specimens, using peroxidase-labeled anti-cytokeratin 19 antibody in 17 cases of resectable pancreatic carcinoma. Postoperatively, we also tried to detect occult micrometastasis by direct sequencing of the K-ras gene in the same samples. RESULTS: Intraoperative staining for cytokeratin 19 was positive in 4 of 17 (23.5%) cases. Patients with margin-positive neural invasion had significantly worse prognosis than patients who were margin negative (P < 0.05). One patient had micrometastasis in the nerve plexus, revealed by K-ras mutation, whereas neither cytokeratin 19 staining nor postoperative pathological investigation detected involvement of the analyzed portion. In the four patients margin-positive for cytokeratin 19 staining, the diagnosis of neural invasion by cytokeratin 19 staining was in agreement with the K-ras gene analysis. CONCLUSION: Intraoperative staining for cytokeratin 19 is useful for detecting pancreatic cancer involvement of the neural plexus margin. The results can be also utilized as a prognostic indicator during the follow-up period.

Adenocarcinoma↗

Endocrine tumor of the pancreas--an evaluation of eighteen patients who underwent resection followed by long-term survival.

Tumors arising from the pancreatic endocrine (islet) cells represent a heterogeneous group of lesions. Some tumors present with well characterized syndromes, while others appear to be nonfunctioning. Eighteen patients with pancreatic endocrine tumors who received surgical treatment at Kurume University Hospital during a 24-year period were reviewed. There were 10 patients with nonfunctioning tumors including 3 patients with benign tumors, and 8 patients with insulinomas. No patients had multiple endocrine neoplasms. Location of the pancreatic tumor was determined preoperatively in 83.3% of the patients. Immunohistochemical analysis of the resected specimens showed multi immunoreactivity to gut hormones among benign lesions and one malignant lesion, whereas malignant lesions showed no or mono immunoreactivity except in one case. In this series, there were no characteristic immunohistochemical findings in the tumors. Both patients with malignant and benign lesions have good prognoses if the main tumors and metastatic lesions are removed.

Adult↗

A so-called carcinosarcoma of the gallbladder in a patient with multiple anomalies--a case report.

The patient was a 65-year-old woman with a chief complaint of right upper quadrant pain. Under the diagnosis of gallbladder tumor, preduodenal portal vein and absence of the pancreatic tail, cholecystectomy was performed. Intraoperative findings resulted in a diagnosis of gallbladder tumor, absence of the pancreatic tail, presence of preduodenal portal vein, and malrotation of the intestine. Histological examination of the resected specimens showed a so-called carcinosarcoma. Carcinosarcoma of the gallbladder is a rare tumor of the hepatobiliary region. The present case differs from previously reported cases in its presentation with multiple anomalies including the presence of preduodenal portal vein. Many cases of preduodenal portal vein in an association with duodenal stenosis in children have been reported, but reports of cases of preduodenal portal vein in adult patients are rarely seen in the literature.

Adult↗

A case of lymphoepithelial cyst of the pancreas.

We report a relatively rare case of lymphoepithelial cyst of the pancreas. The patient, a 43-year-old man with no subjective symptoms, was found to have a pancreatic tumor during a physical examination. Based on the ultrasonographic and abdominal computed tomographic findings, a pancreatic cystic tumor was diagnosed. Endoscopic retrograde pancreatography showed a normal duct system. Enucleation was easily performed. Macroscopically, the cyst resembled an atheroma. Histopathologic examination disclosed lymphoepithelial cyst of the pancreas.

Adult↗

Possible role of granulocyte colony-stimulating factor in increased serum soluble interleukin-2 receptor-alpha levels after allogeneic bone marrow transplantation.

Serum soluble interleukin-2 receptor - alpha (sIL-2R) levels markedly increased at the engraftment period in patients who underwent allogeneic bone marrow transplantation (BMT). Since serum G-CSF levels increased during G-CSF administration and decreased after the cessation, increased sIL-2R levels appeared to be induced by G-CSF administration. There was no increase in sIL-2R levels in a patient given macrophage colony-stimulating factor (M-CSF). The sIL-2R levels at the engraftment period and the onset of acute graft-versus-host disease (GVHD) were higher in patients who developed acute GVHD during G-CSF administration than in those who developed acute GVHD after G-CSF cessation. This finding suggests that G-CSF administration may possibly augment acute GVHD. However, it appears to be unlikely, because in the entire population, 18 of 35 patients had acute GVHD while only 6 of 17 patients had acute GVHD during G-CSF administration. Further analysis is still needed in order to draw definite conclusions. Preconditioning regimens did not appear to affect the sIL-2R levels, when the variable frequencies of methotrexate (MTX) administration were compared.

Adolescent↗

Damage to DNA purified from the radioresistant prokaryote, Deinococcus radiodurans, by acid heating.

Using a highly radioresistant bacterium, Deinococcus radiodurans, the mechanism of degradation of the purified DNA molecules by heating was examined under acidic conditions. Setting the treatment temperature at 55ûC with a duration of 0 to 20 min and adjusting the pH of the cell suspension to 3, 5 or 7, cell viabilities after the treatment were compared. The survival rate decreased in proportion to the reduction of pH. DNA purified from D. radiodurans was then damaged by irradiation with gamma-rays at 0.22 kGy or 1 kGy. It was considered that the radioresistance of D. radiodurans was due to its high repair capability, rather than any specificity of DNA structure. Purified D. radiodurans DNA was resistant to heating up to 90ûC at neutral pH. However, marked DNA damage occurred when it was heated at pH values below 5.0. Then, DNA labeled with [3H]adenine was examined. Treatment at lower pH and higher temperature resulted in release of more adenine base, i.e., the purine ring, from the DNA molecules. Therefore, we assumed that the decrease in survival of D. radiodurans in vivo and damage to its DNA in vitro by acid heating were due to the release of adenine and guanine from the DNA, i.e., depurination.

Acids↗

Clinicopathologic significance of protein induced vitamin K absence or antagonist II and alpha-fetoprotein in hepatocellular carcinoma.

Protein induced vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) have been considered useful serum markers of hepatocellular carcinoma (HCC). In this study, we examined the clinicopathologic significance of these tumour markers in patients with HCCs by measuring their serum levels and performing immunohistochemistry. We studied 349 Japanese patients with HCCs. Their serum PIVKA-II and AFP levels were determined by enzyme immunoassay before treatment. We examined the correlations between serum PIVKA-II and AFP levels and tumour size, presence of satellite nodules, histologic HCC grade, and concomitant liver diseases and subjected tumour tissues to immunohistochemical staining to detect PIVKA-II and AFP expression. The serum PIVKA-II levels of patients with poorly differentiated HCCs were significantly higher than those of patients with well and moderately differentiated HCCs (p<0.05) and they were higher in HCC patients with than without satellite nodules. The serum AFP levels were influenced significantly by concomitant liver diseases, but not by the other factors. Immunohistochemical staining revealed the PIVKA-II expression levels of poorly differentiated HCCs were higher than those of well and moderately differentiated HCCs (p<0.05). Some HCC cells were PIVKA-II-positive, others were AFP-positive, and some expressed both. The serum PIVKA-II concentration was a better indicator of HCC than AFP, as it was not influenced by concomitant liver diseases. The presence of PIVKA-II in serum correlated with the presence of satellite nodules and the histologic HCC grade, a result concordant with the immunohistochemical findings.

Aged↗

Bradykinin promotes ischemic norepinephrine release in guinea pig and human hearts.

We previously reported that bradykinin (BK; 1-1000 nM) facilitates norepinephrine (NE) release from cardiac sympathetic nerves. Because BK production increases in myocardial ischemia, endogenous BK could foster NE release and associated arrhythmias. We tested this hypothesis in guinea pig and human myocardial ischemia models. BK administration (100 nM) markedly enhanced exocytotic and carrier-mediated NE overflow from guinea pig hearts subjected to 10- and 20-min ischemia/reperfusion, respectively. Ventricular fibrillation invariably occurred after 20-min global ischemia; BK prolonged its duration 3-fold. The BK B2 receptor antagonist HOE140 (30 nM) blocked the effects of BK, whereas the B1 receptor antagonist des-Arg9-Leu8-BK (1 microM; i.e., 2.5 x pA2) did not. When serine proteinase inhibitors (500 KIU/ml aprotinin and 100 microg/ml soybean trypsin inhibitor) were used to prevent the formation of endogenous BK, NE overflow and reperfusion arrhythmias were diminished. In contrast, when kininase I and II inhibitors (DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid and enalaprilat, each 1 microM) were used to prevent the degradation of endogenous BK, NE overflow and reperfusion arrhythmias were enhanced. B2 receptor blockade abolished these effects but was ineffective if kininases were not inhibited. B2 receptor stimulation, by either exogenous or endogenous BK, also markedly enhanced carrier-mediated NE release in the human myocardial ischemia model; conversely, inhibition of BK biosynthesis diminished ischemic NE release. Because atherosclerotic heart disease impairs endothelial BK production, in myocardial ischemia BK could accumulate at sympathetic nerve endings, thus augmenting exocytotic and carrier-mediated NE release and favoring coronary vasoconstriction and arrhythmias.

Angiotensin-Converting Enzyme Inhibitors↗

The role of accessory cells in allogeneic peripheral blood stem cell transplantation.

Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (G-PBMC) have been used increasingly to reconstitute hematopoiesis after myeloablative therapy in allogeneic transplantation. Compared with conventional bone marrow, faster engraftment is consistently observed with G-PBMC, with differences more pronounced in platelet than in neutrophil recovery. G-PBMC contain not only severalfold more CD34+ cells than bone marrow but also, on average, 50-fold more monocytes, which may stimulate stromal cell function and facilitate engraftment. Although G-PBMC also contain 10-fold more T cells, the incidence and severity of acute graft-vs.-host disease (GVHD) is no higher than that observed in allogeneic bone marrow transplantation. Hypothetically, these clinical observations can be explained by the direct effect of G-CSF on T cell function as demonstrated by polarization of T cells expressing the T helper type 2 (Th 2) cytokine interleukin (IL)-4 in the murine model. Alternatively, G-PBMC may contain cells that actively suppress donor T cell responsiveness. Recent reports indicate that the large number of CD14+ monocytes in G-PBMC can suppress donor T cell proliferation in vitro. This effect may be attributable to both the increased ratio of CD14+:CD3+ cells in G-PBMC and the evidence that CD14+ cells in G-PBMC have decreased expression of both B7.2 and HLA-DR. There is some indication that natural killer (NK) cell number and function may be augmented in G-PBMC, which could have a favorable impact on the graft-vs.-leukemia (GVL) effect. Therefore, both the CD34+ and accessory cell content of G-PBMC may be important in early engraftment by controlling acute GVHD and facilitating GVL.

Antigen-Presenting Cells↗