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Biomedical subjects

T Iwase

Publications and source records attributed to T Iwase.

At least 145 records · Page 8Linked to original sources

Overexpression of ERK, an EPH family receptor protein tyrosine kinase, in various human tumors.

The ERK gene has been isolated as a genomic DNA encoding a part of the receptor protein-tyrosine kinase which belongs to the EPH subfamily. We previously identified a partial complementary DNA (cDNA) encompassing the catalytic domain of ERK from the expression library of human gastric cancer with an antiphosphotyrosine antibody. Using this cDNA as a probe, the cDNAs encoding mature ERK protein were isolated. The putative mature ERK protein, a total of 967 deduced amino acid residues, showed high homology with chicken Cek5 (92.5%) and mouse Nuk (99.1%). Chromosomal in situ hybridization revealed that human ERK cDNA is localized to chromosome 1p34-35. In Northern blot analysis of normal human tissues, the ERK gene was ubiquitously expressed mainly in cells of epithelial origin but not in the brain. Studies on RNAs from 76 human tumor tissues and cell lines showed that ERK is expressed at higher levels in various tumors of epithelial origin than in corresponding normal tissues, most frequently in gastric cancers (12 of 16, 75.0%). Overexpression of ERK was also detected in one osteosarcoma cell line. These findings suggest that ERK plays some significant role in carcinogenesis in the stomach and other tissues.

Amino Acid Sequence↗

[Results of surgical treatment of aortic dissections].

From January 1989 to September 1993, 59 consecutive patients (35 males and 24 females, mean age 59.6 years old) underwent surgical repair of aortic dissection on the cardiovascular surgical unit at Takeda Hospital. The type of aortic dissection were classified according to Stanford University criteria. Twenty-two patients had acute type A (Ac-A), 10 had chronic type A (Ch-A), 4 had acute type B (Ac-B), and 23 had chronic type B (Ch-B) dissection. Seventeen dissections (29%) in the entire group of 59 cases had ruptured (including cardiac tamponade, pleural effusion and hemoptysis etc.). Ischemia of lower extremity occurred in 7 patients and ischemia of visceral organs in 3 patients. Type A dissection were approached via a median sternotomy and cardiopulmonary bypass with systemic hypothermia. Type B dissections were approached through a left postrolateral thoracotomy. Left heart bypass (left atrial-femoral in 8 cases) and partial cardiopulmonary bypass (femoral-femoral in 12 cases) generally were utilized. Resection of intimal tear and replacement of aorta with vascular grafts (including aortic arch in 19 cases) were performed in most patients and primary closure of the intimal tear was performed in 9 cases using GRF. The over-all operative mortality rate was 36% (8/22) for Ac-A, 20% (2/10) for Ch-A, 25% (1/4) for Ac-B, 22% (5/23) for Ch-B. Main causes of operative death was perioperative brain damage. It is necessary to improve the operative mortality for Ac-A dissections (especially in replacement of aortic arch and arch vessels). Further researches are needed regarding optimal methods of the cerebral protection during reconstruction of aortic arch.

Adult↗

Benign schwannoma of the esophagus: report of two cases with immunohistochemical and ultrastructural studies.

Two cases of benign schwannoma of the esophagus are presented. The tumors were found in the thoracic esophagus of women of 56 and 64 years of age, respectively, who had complained of dysphagia and back pain. Tumorectomies were performed and the tumors were found to be located within the esophageal wall arising from the muscularis propria. The tumors were examined immunohistochemically and ultrastructurally. These tumors were identical in gross, histological and electron microscopic features. Grossly, the tumors showed yellowish-white cut surfaces without hemorrhage or necrosis. Microscopically, they were composed of spindle-shaped cells showing moderate variation in size and shape, and nuclear palisading. Lymphoid aggregates with germinal centers surrounded the tumors. Immunohistochemically, strong reactions for S-100 protein and neuron-specific enolase were observed in the cytoplasm of spindle cells, whereas reactions for muscle actin and desmin were negative. These findings, together with electron microscopic observations, supported the Schwann cell origin of these tumors.

Esophageal Neoplasms↗

Chronic dynamic exercise improves a functional abnormality of the G stimulatory protein in cardiomyopathic BIO 53.58 Syrian hamsters.

BACKGROUND: The effects of chronic exercise training on myocardial contractility and beta-adrenergic signal transduction in hearts with left ventricular dysfunction have not been determined. METHODS AND RESULTS: Fourteen-week-old cardiomyopathic BIO 53.58 and normal F1B Syrian hamsters underwent 10 weeks of treadmill training and were compared with 24-week-old BIO 53.58 and F1B untrained controls. Left ventricular isovolumic maximum positive dP/dt and peak developed pressure were significantly lower in BIO 53.58 than in F1B controls. Exercise training improved left ventricular contractile indices in BIO 53.58 but not F1B hamsters. The left ventricular beta-adrenergic receptor number (Bmax) was similar in BIO 53.58 and F1B controls. Basal adenylate cyclase activity (ACA) and ACAs stimulated by isoproterenol, 5'-guanylylimidodiphosphate (GppNHp), sodium fluoride, and forskolin were significantly lower in BIO 53.58 than in F1B controls. The functional activity of stimulatory guanine nucleotide-binding protein (Gs), as determined by reconstitution with S49 lymphoma cyc- cell membranes, was significantly lower in BIO 53.58 controls. After 10 weeks of exercise training, Bmax and basal and isoproterenol-stimulated ACAs were unchanged in either BIO 53.58 or F1B hamsters compared with controls. However, in F1B hamsters, training decreased ACAs stimulated by GppNHp, sodium fluoride, and forskolin, with a reduced functional activity of Gs. In contrast, these ACAs increased significantly in association with an enhanced Gs activity in cardiomyopathic BIO 53.58 hamsters after training. CONCLUSIONS: Chronic exercise training does not change receptor-mediated beta-adrenergic responsiveness in either F1B or BIO 53.58 hamsters. However, exercise training reduces Gs activity in normal F1B hamsters and improves the functional abnormality of Gs in cardiomyopathic BIO 53.58 hamsters. This improvement may potentially contribute to augmented left ventricular contractility in BIO 53.58 after training.

Adenylyl Cyclases↗

In vitro study of teratogenic effects of caffeine on cultured rat embryos and embryonic cells.

The teratogenic potential of caffeine was examined in vitro by a whole embryo culture system (WECS) and an embryonic cell culture system (micromas teratogen assay: MTA) in the rat. In the WECS, hyperemia of the tail, and a reduction of the placental size was induced by caffeine at concentrations higher than 50 micrograms/ml; hypoplasia of the forelimb bud was induced at concentrations higher than 100 micrograms/ml; hematoma in the yolk sac and dysmorphogenesis of the fore- and hind-limb buds, prosencephalon and tail were induced by 200 micrograms/ml caffeine. In the MTA, even with 200 micrograms/ml caffeine, the toxicological parameters obtained by proliferation and differentiation assays of the midbrain and limb bud cells were almost the same as in the control. In conclusion, caffeine induced various morphological anomalies, but did not affect proliferation or differentiation of cells in these experimental systems.

Abnormalities, Drug-Induced↗

Cytochrome P-450 lA1 genotype in lung cancer patients and controls in Rio de Janeiro, Brazil.

Mspl restriction fragment length polymorphism in cytochrome P-450 IA1 (CypIA1) gene, which has been associated with lung cancer susceptibility in Japanese, was studied in persons from Rio de Janeiro, in the framework of a hospital-based, age, race (black or nonblack), and gender-matched case-control study (n = 222; 110 cases and 112 controls). Contrary to the hypothesis, there was no difference in the frequency of the C genotype (Mspl site-present homozygous), even after racial breakdown. There were no significant differences between cases and controls when categorized according to tobacco consumption. The lifetime quantity of tobacco smoked was not different among lung cancer patients with three different genotypes (A, Mspl site-absent, homozygous; B, heterozygote; and C). The background frequency of the Mspl polymorphism C genotype is a little less than 10%, similar to that of the Japanese healthy population. The CyplA1 Mspl polymorphism itself does not seem to be related to susceptibility to bronchial carcinogenesis in this area.

Adult↗

[Our experience with breast conservation].

In the Cancer Institute Hospital, two kinds of breast conservation have been adopted. Q + Ax is applied for cancers at the upper--outer quadrant and LUART is applied for those at other quadrants. The method, clinical matters, pathological findings and results are discussed together with the LUART of the national BCT group study funded by the Japanese Ministry of Welfare.

Adult↗

Identification of protein-tyrosine kinase genes preferentially expressed in embryo stomach and gastric cancer.

For identification of the protein-tyrosine kinases that are expressed in embryo stomach and gastric cancer, a 16-day rat embryo stomach and two human gastric cancer cDNA expression libraries were screened with an anti-phosphotyrosine antibody. Eight cDNAs encoding protein-tyrosine kinase were isolated, and Northern blot analysis revealed that five out of eight clones were highly expressed in rat embryo stomach, but not in adult rat stomach. From nucleotide sequence analysis, these five cDNAs were identified as elk, erk, esk, TTK and fyn, respectively. We report here that the expression levels of two families of receptor type tyrosine kinase genes, elk/erk and esk/TTK are developmentally regulated in rat stomach and highly expressed in human gastric cancer tissues. These findings suggest that elk/erk and esk/TTK genes play important roles in embryonic development and carcinogenesis of the stomach.

Adenocarcinoma↗

Over-expression of HOX-8, the human homologue of the mouse Hox-8 homeobox gene, in human tumors.

A human ovarian yolk sac tumor cDNA library was screened for homeobox genes with an oligonucleotide probe under low stringent condition. Three homeobox genes were isolated, two of which were identified as HHO.c1 and HB24. The third was highly homologous with the mouse Hox-8 gene and was designated as HOX-8. Studies on RNAs from 25 human tumor tissues and cell lines showed that the profile of HOX-8 expression was different from those of HHO.c1 and HB24. The expression of HOX-8 was not detected in hematopoietic tumor cells, in which HHO.c1 and HB24 were highly expressed. HOX-8 was expressed at higher levels in a variety of tumors of epithelial origin than in their corresponding normal tissues more frequently than HHO.c1 and HB24. All three homeobox genes were highly expressed in a yolk sac tumor, an immature tumor of gonadal origin. These results suggest that HOX-8 plays a more important role in human tumors of epithelial origin than those of hematopoietic origin.

Animals↗

A mucous histochemical and immunohistochemical study of precancerous and neoplastic lesions in the human pancreas.

A total of 44 cases of pancreatic lesions, including hyperplasia (six) cases, adenoma (mucinous cystadenomas [eight] and intraductal papillary adenoma [eight]), noninvasive intraductal papillary tumors (five), and invasive ductal carcinomas (17) were investigated possibly to establish a diagnostic marker. We examined the type of mucin secreted and immunoreactivities of antibodies to ras-p21 and c-erB-2 oncogene products. A significant decrease in the amount of mucin was found in invasive lesions, and this was associated with a shift toward production of neutral mucins and especially sialomucins. Hyperplasia and adenoma, in contrast, demonstrated a predominance of neutral mucin. The sulfated mucins found in normal epithelium were only very weakly stained in any of the tumor types. Thirty-three percent of non-invasive intraductal papillary tumors and 88% of invasive ductal adenocarcinomas demonstrated strong binding of the ras-p21 antibody. In contrast no obvious differences in expression of c-erbB-2 were evident between the groups. In conclusion, a combined mucin histochemical/immunohistochemical approach may facilitate accurate diagnosis.

Biomarkers, Tumor↗

Decreased dimethylnitrosamine-induced O6- and N7-methyldeoxyguanosine levels correlate with development and progression of lesions in rat hepatocarcinogenesis.

Formation and repair of O6-medG and N7-medG (O6- and N7-methyldeoxyguanosine) in glutathione S-transferase-P form (GST-P)-positive liver cell foci, nodules, primary hepatocellular carcinoma (HCC) and transplanted hepatocellular carcinoma (TRP) induced by N-ethyl-N-hydroxyethylnitrosamine (EHEN) were immunohistochemically assessed following a single exposure to dimethylnitrosamine (DMN). Male Fischer 344 rats received a 0.1% solution of EHEN as their drinking water for 4 weeks and were maintained on basal diet until week 40, when a single 50 mg/kg body weight dose of DMN was administered intraperitoneally. Nude rats (NIH rnu/rnu) bearing TRP were similarly treated. Sequential killing 6, 12, 24, 48 and 72 h thereafter revealed significantly decreased indices of cells binding antibodies to O6-medG and N7-medG adducts in GST-P-positive foci and nodules, and particularly HCC and TRP, as compared to background parenchyma values. Similarly, differences between foci/nodules and HCC/TRP were also significant, indicating that decrease in adduct formation is associated with further malignant conversion. The rate of DNA adduct repair in foci and nodules subsequent to the peak found at the 12 h time-point did not appear to be significantly different from that in the surrounding tissue at the dose of DMN studied. The results indicate decreased formation of DMN-associated DNA damage, in line with the known metabolic profile of carcinogen-induced focal liver lesions.

Animals↗

Ischemic preconditioning is associated with a delay in ischemia-induced reduction of beta-adrenergic signal transduction in rabbit hearts.

BACKGROUND: It has been reported that the A1-adenosine receptor mediates the cardioprotective effect of ischemic preconditioning. This receptor couples inhibitory guanine nucleotide-binding protein (Gi) and inhibits adenylate cyclase activity. However, the role of adenylate cyclase in preconditioning is unknown. METHODS AND RESULTS: We compared the effects of ischemia on the sarcolemmal beta-adrenergic receptor density (Bmax), the stimulatory guanine nucleotide-binding protein (Gs) activity as determined by reconstitution with S49 lymphoma cyc- membranes, and baseline and maximally stimulated adenylate cyclase activities (ACAs) in control and preconditioned rabbit hearts. The control population (n = 28) received 0, 10, 20, and 60 minutes of coronary occlusion (n = 6 to 8 per stage), and preconditioned rabbits (n = 24) received two cycles of alternating 5-minute occlusion and reperfusion before sustained ischemia (n = 6 per stage). In control hearts, occlusion induced rapid and progressive reductions in the Bmax, Gs, and ACAs after 10 to 60 minutes of ischemia. Preconditioning did not affect the reduction in Bmax, but it preserved reductions in Gs activity and ACAs after 10 to 20 but not 60 minutes of sustained ischemia. In another study, 18 rabbits were treated with pertussis toxin 48 hours before surgery to block Gi. During treatment, no significant difference was observed in the ischemia-induced reduction in ACAs in the ischemic region between control (n = 8) and preconditioned (n = 10) animals after 20 minutes of ischemia. CONCLUSIONS: Preconditioning delays ischemia-induced reductions in beta-adrenergic signal transduction. Inhibition of ACA is not the target effect of the A1-adenosine receptor-Gi pathway responsible for the cardioprotective role of preconditioning.

Adenylate Cyclase Toxin↗

Early expression of human J chain and mu chain gene in the fetal liver.

The expression of J chain and mu chain genes has been investigated during human fetal ontogeny by the polymerase chain reaction performed on liver sections. With this technique, we have been able to detect expression of J chain and mu chain in a single 6-10-microns-thick formalin-fixed paraffin-embedded section of fetal liver tissue. J chain expression reached a maximum at 16 weeks of gestation but was clearly detectable in the liver at the 6th week. Although not detectable at the 6th week, mu chain mRNA became readily detectable at 7 weeks of gestation. These results indicate that J chain expression precedes that of mu chain by at least one week. Therefore, our results imply that J chain is the first immunoglobulin-related polypeptide expressed during the embryogenesis and differentiation of B cells in the fetal liver.

Base Sequence↗

[Right ventricular function in patients with dilated cardiomyopathy: assessment using krypton-81 m blood pool scintigraphy].

The characteristics and pathogenesis of right ventricular dysfunction in 14 patients with dilated cardiomyopathy (DCM) were investigated by equilibrium right ventricular blood pool scintigraphy using ultrashort-lifetime 81mKr. Thirteen patients with severe left ventricular dysfunction due to old anterior myocardial infarction (OMI) and nine normal subjects were used as controls. The right ventricular end-diastolic pressure and volume index, mean pulmonary arterial pressure, and total pulmonary vascular resistance index were almost the same in the DCM and OMI patients. The right ventricular ejection fraction was 44.2 +/- 6.0% (mean +/- SD) in DCM patients and 47.1 +/- 7.9% in OMI patients, both significantly lower than those in the normal subjects (54.5 +/- 5.3%), but with no difference between the two case groups. The right ventricular peak filling rate was significantly reduced in both case groups as compared with the normal subjects (2.46 +/- 0.81 EDV/sec). The reduction was significantly greater (p < 0.05) in the DCM group (0.97 +/- 0.47 EDV/sec) than in the OMI group (1.61 +/- 0.46 EDV/sec). Cineangiography showed that the wall motion abnormality of the interventricular septum was remarkable in OMI patients, but was relatively mild in DCM patients. Lesions of the interventricular septum may be of major importance in right ventricular dysfunction in OMI, while extensive severe damage to the right ventricular free wall may be important in DCM. 81mKr blood pool scintigraphy is useful in the study of the right ventricular systolic and diastolic function. The diastolic parameters are more sensitive indicators for evaluation of right ventricular function in DCM than the systolic parameters.

Cardiomyopathy, Dilated↗

Small, polypoid-appearing carcinoid tumors of the rectum: clinicopathologic study of 16 cases and effectiveness of endoscopic treatment.

Fifteen cases of small-size rectal carcinoid tumors (RCTs) were discovered among a total of 21,522 healthy teachers who received proctosigmoidoscopy. Adding another case seen in the outpatients, a total of 16 RCTs were clinicopathologically studied. The average age of the patients was 48.8 yr, and the incidence was predominantly among males. Prior to endoscopy, digital examination of the rectum revealed a palpable firm nodule in 13 patients. On endoscopy, RCTs were generally round, yellow-discolored polyps with a size less than 13 mm in diameter, covered by a normal-appearing mucosa. An erythematous change or depression was seen in three tumors. Histologically, they showed pure insular, trabecular, or mixed structures, and tumor cells were confined to the mucosa and/or submucosa in all cases. Immunohistochemically, RCTs never failed to show focal or diffuse positivities for chromogranin A and/or neuron-specific enolase. Pancreatic polypeptide was immunostained in 14 tumors to a varying degree. The tumors having been safely treated by endoscopic polypectomy and/or surgical excision, all of the patients are alive and clinically free of disease during the average observation period of 79 months.

Carcinoid Tumor↗

Mode of photocatalytic bactericidal action of powdered semiconductor TiO2 on mutans streptococci.

Powdered semiconductor TiO2 has a photocatalytic bactericidal capacity on some kinds of bacteria, but its mechanism still remains unclear. The mode of its photocatalytic bactericidal action on the mutans group of streptococci was investigated. Powdered TiO2 had a bactericidal capacity on all serotypes of mutans streptococci. Streptococcus sobrinus AHT was mainly used for these experiments. The most effective concentration of TiO2 was about 1 mg ml-1 and, at this concentration, 10(5) colony-forming units of S. sobrinus AHT per millilitre were completely killed within 1 min. In order to search for the mechanism of this effect, a high bacterial cell density (10(9) colony-forming units ml-1) was used in the following studies. "Rapid" leakage of potassium ions from the bacteria occurred parallel to the decrease in cell viability. Protein and RNA were "slowly" released from bacterial cells for a reaction time up to 120 min. The pH of the reaction mixture decreased continuously to 4.5 after 120 min. Co-aggregation of S. sobrinus AHT and powdered TiO2 occurred at high bacterial densities (above 10(8) colony-forming units ml-1). Aggregates gradually decomposed with light irradiation. Transmission electron microscopy of S. sobrinus AHT after photocatalytic action for 60-120 min indicated complete destruction of bacterial cells. From these results, bacterial death appears to be caused by a significant disorder in cell membranes and finally the cell walls were decomposed.

Hydrogen-Ion Concentration↗