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Biomedical subjects

H Watanabe

Publications and source records attributed to H Watanabe.

At least 955 records · Page 53Linked to original sources

Central corticotropin-releasing factor and benzodiazepine receptor systems are involved in the social isolation stress-induced decrease in ethanol sleep in mice.

Social isolation stress has been demonstrated to decrease the hypnotic activity of ethanol in rodents. In this study, the role of central corticotropin-releasing factor (CRF) and GABA(A)/benzodiazepine (BZD) receptor systems in the social isolation stress-induced decrease in the hypnotic activity of ethanol in mice was investigated by examining the effect of alpha-helical CRF(9-41) (alpha hCRF) and flumazenil, antagonists of CRF and BZD receptors, respectively, on ethanol-induced sleep in group-housed and socially isolated mice. We also tested whether social isolation stress affects the ability of ethanol to enhance the GABA-induced 36Cl- influx into a synaptoneurosomal preparation of mouse forebrain. Social isolation stress significantly decreased both the ethanol (4 g/kg i.p.)-induced and pentobarbital (50 mg/kg i.p.)-induced sleeping times, while this stress had no effect on chloral hydrate (325 mg/kg i.p.)-induced sleep. The i.c.v. injection of alpha hCRF (6.5 nmol) and flumazenil (33 nmol) antagonized the social isolation stress-induced decrease in the ethanol sleep without affecting ethanol sleep in group-housed animals. Social isolation stress significantly attenuated the ability of GABA to stimulate 36Cl- influx but this stress had no effect on the ability of ethanol to enhance GABA-induced 36Cl- influx. These results suggest that the functional changes in central CRF and GABA(A)/BZD receptor systems are involved in the social isolation stress-induced decrease in the hypnotic activity of ethanol in mice.

Animals↗

rIFN-gamma-activated rat neutrophils induce tumor cell apoptosis by nitric oxide.

We have previously shown that 1) neutrophils activated with various cytokines, including rat recombinant interferon gamma (rIFN-gamma), inhibit tumor cell growth and that 2) nitric oxide (NO) is the effector molecule in tumor inhibition by rIFN-gamma-stimulated rat peritoneal exudate neutrophils. In this study, we examined the nature of tumor cell death induced by rat peritoneal neutrophils activated by rIFN-gamma in order to clarify the mechanism of apoptosis in neoplastic tumor cell death. DNA of 3 syngeneic rat tumor cell lines was significantly fragmented within 3 hr of incubation in the presence of rIFN-gamma-activated neutrophils, and this effect was dependent on both the concentration of rIFN-gamma and the number of neutrophils. This DNA fragmentation was inhibited by L-N-(I-iminoethyl)-ornithine (L-NIO), a NO synthase inhibitor, but not by superoxide dismutase (SOD). Tumor cells treated with the activated neutrophils were shown by electron microscopy to be apoptotic, exhibiting necrotic features with a longer incubation. On the other hand, cytolysis of tumor cells, as determined by a [3H]-uridine release assay, was first observed only at 24 hr of incubation with the rIFN- gamma-activated neutrophils. Taken together, our results suggest that tumor cell apoptosis by activated neutrophils is NO-dependent and that apoptotic tumor cells undergo necrosis as a secondary process. We suggest that tumor cell apoptosis induced by activated neutrophils plays an important role in regulation of neoplastic tumor cell growth and death in vivo.

Animals↗

[A case of depression manifesting incessant pacing and wandering following discontinuation of antipsychotic drugs due to neuroleptic malignant syndrome: a possible involvement of withdrawal akathisia].

A depressed 36-year-old woman manifesting a delusion of persecution was started on neuroleptics. In parallel with the increase of neuroleptics, she suffered from akathisia, such as wandering, and thereafter developed neuroleptic malignant syndrome. Thus, neuroleptics were discontinued. As a result, she manifested severer wandering, impairment of conversation, and unacceptable behavior (e.g. touching her stool) though neuroleptic malignant syndrome subsided. These symptoms improved following the administration of levomepromazine and amitriptyline. It seems difficult to regard these symptoms as just a prolongation of akathisia, since the level and frequency of akathisia increased. It also seems unlikely to regard these symptoms as those of agitated depression, since there were no complaints of irritability. On the other hand, it seems probable that "withdrawal akathisia" occurred following the discontinuation of neuroleptics and the reinstituted levomepromazine improved the withdrawal phenomena consisting of severer wandering, impairment of conversation, and unacceptable behavior.

Adult↗

A shift from negative to positive selection of autoreactive T cells by the reduced level of TCR signal in TCR-transgenic CD3 zeta-deficient mice.

T cell selection is thought to be determined through the interaction between TCR and Ag/MHC. However, the contribution of the level of TCR signal to thymic selection remains unclear. To address this issue, we analyzed T cell selection of male Ag (HY)-specific TCR transgenic (HYTg) mice crossed with CD3 zeta-deficient (zeta KO) mice (HYTg/zeta KO), which have impaired signaling through TCR. In male HYTg/zeta KO mice, the number of thymocytes was comparable to that in normal mice, and almost all the peripheral T cells were HY specific, although these positively selected cells were anergic to male Ag. From these observations, the decrease in TCR signaling by CD3 zeta deficiency resulted in both the avoidance of negative selection and the acquisition of positive selection of autoreactive T cells in male HYTg/zeta KO mice. There was a shift of T cell selection from positive to no selection of HY-specific T cells in female HYTg/zeta KO mice also. Collectively, these findings suggest that the level of TCR signal directly regulates T cell selection; furthermore, the findings have integrated the models of T cell selection into a concept based on the quantity of TCR signal.

Animals↗

Flumazenil reverses the decrease in the hypnotic activity of pentobarbital by social isolation stress: are endogenous benzodiazepine receptor ligands involved?

Long-term social isolation stress has been shown to cause a decrease in pentobarbital (PB)-induced sleeping time in mice. In the present study, to clarify whether the GABAA/benzodiazepine (BZD) receptor system is involved in the decrease in the hypnotic activity of PB by social isolation stress, we examined the effects of BZD receptor ligands on the PB-induced sleep in group-housed and socially isolated mice. Moreover, we also tested whether social isolation stress affects the ability of GABA to stimulate 36Cl- uptake or the modulatory effect of diazepam and PB and GABA-induced stimulation of 36Cl- uptake into synaptoneurosomes prepared from mouse brain. Social isolation stress significantly decreased the PB-induced sleeping time in mice. The BZD receptor diazepam (0.1-0.8 mg/kg, i.p.) dose-dependently prolonged PB sleep in group-housed and isolated mice, but the effect was weaker in isolated mice. In contrast, FG7142 (5-10 mg/kg, i.p.), a BZD receptor inverse agonist, shortened the sleep in group-housed but not in isolated mice. Flumazenil (16.5-33 nmol, i.c.v.), a selective BZD receptor antagonist, caused PB sleep in isolated mice to return to the level of group-housed mice, at the dose that antagonized the effects of diazepam and FG7142 on PB sleep in group-housed mice. However, this antagonist alone produced no effect on PB sleep in group-housed mice. Social isolation stress decreased the ability of GABA (0.6-200 microM) to stimulate 36Cl- uptake into synaptoneurosomes but this stress had no effect on PB- and diazepam-induced enhancement of GABA-stimulated 36Cl- uptake. These results suggest that endogenous substance(s) with an inverse BZD receptor agonist-like property and the changes in the ability of GABA to stimulate chloride ion channels are involved in the decrease in the hypnotic activity of pentobarbital following social isolation stress.

Animals↗

Cationic liposomes enhanced firefly bioluminescent assay of adenosine 5'-triphosphate disodium salt.

Cationic liposomes containing stearylamine enhanced the intensity of maximum light emission from the firefly luciferin-luciferase reaction with ATP in the range of 1.0 pM up to 5.5 nM. In contrast, the bioluminescent intensities in the presence of anionic and zwitterionic liposomes were about the same as those in water alone. The detection limit for ATP in the presence of cationic liposomes was 1.0 pM in aqueous ATP standard solutions. The sensitivity for ATP was improved by a factor of five times compared to that in water alone. The method was applied to the determination of ATP in Escherichia coli extracts. The sensitivity threshold was presumed to be 340 cells ml-1.

Adenosine Triphosphate↗

Simple technique for pancreatogastrostomy and the histological findings of pancreatogastric anastomosis.

The leakage of pancreatic juice is the most serious complication after pancreatoduodenectomy. In an attempt to lessen the incidence of this complication, we have developed a simple technique for the anastomosis of pancreatogastrostomy. Since March 14, 1995, we have already performed surgical procedures on 8 cases of pancreatogastrostomy using this technique and as yet have never experienced fatal complications. We report the autopsy findings of pancreatogastric anastomosis histologically. The specimen taken from the anastomosis reveals good mucosal continuity. This result suggests the importance of reliable sutures between the pancreatic parenchyma and the full thickness of the gastric wall for the anastomosis of pancreatogastrostomy.

Adenocarcinoma↗

Thoracic esophageal carcinoma above the carina: a more formidable adversary?

BACKGROUND: Prognosis with esophageal carcinoma above the carina is generally thought to be the worst without any conclusive demonstration. METHODS: Clinicopathologic features of 101 patients with thoracic esophageal carcinoma above the carina (AC group) were compared with those of 665 patients with a tumor below this level (BC group). RESULTS: The number of T4 tumor was significantly larger in the AC group (P < 0.001). Survival curve for all patients in the AC group was significantly worse than the BC group (P < 0.001). Survival in patients who underwent any treatment other than esophagectomy was equally bad in the two groups. However, survival in patients undergoing esophagectomy was similar in the two groups (P = 0.64), with the cumulative 5-year survival rates of 44.5% and 43.1%, respectively. Even in patients with metastatic disease in the lymph nodes, the cumulative 5-year survival rates after radical esophagectomy were similar. CONCLUSIONS: The prognosis of patients in the AC group is generally worse than the BC group because of the close anatomical relationship with the tracheobronchial tree. However, radical esophagectomy is recommended for patients at stages less advanced than T4.

Adenocarcinoma↗

Synchronous primary tumors of the extrahepatic bile duct and gallbladder.

BACKGROUND AND OBJECTIVES: This study aims to clarify clinicopathologic characteristics of synchronous primaries of the extrahepatic bile duct and gallbladder. Understanding multiplicity and its histologic confirmation is an important step for successful surgical management. METHODS: Of the 190 cases of resection of biliary tract neoplasms in this study, 10 had two separate tumors in the extrahepatic bile duct and gallbladder, which were investigated by the microscopic mapping technique for tumor extent using serial stepwise sectioning of specimens. RESULTS: Clinical diagnosis was made successfully in only two cases. Detailed histologic examination revealed seven cases with synchronous primaries and three cases with metastatic tumors. Several microscopic parameters had additional diagnostic value. The presence of synchronous primaries is not necessarily associated with a poor prognosis, since we had four long-term survivors. CONCLUSIONS: Diagnosis of synchronous extrahepatic biliary neoplasms is rarely made preoperatively. However, aggressive resection and careful microscopic examination are essential for the successful management and diagnosis of these special cases.

Aged↗

Second primary carcinoma in the residual cervical esophagus after thoracic esophagectomy: report of five cases.

BACKGROUND AND OBJECTIVES: Development of second primary carcinomas after thoracic esophagectomy has become of much concern, because recently the prognosis of thoracic esophageal carcinoma after esophagectomy with extended lymph node dissection has been improving. We report our experience of diagnosing and treatment second primary carcinomas arising in the remaining esophagus after thoracic esophagectomy. METHODS: Among 253 patients who underwent esophagectomy for thoracic esophageal carcinoma more than 2 years previously, second primary esophageal carcinomas developed in five (2.0%), and these five patients were examined. RESULTS: All second primary carcinomas were found by endoscopy, and were diagnosed as superficial carcinoma (Tis or T1) of the residual cervical esophagus. One patient underwent laser irradiation, another endoscopic mucosal resection, two had surgical mucosectomy, and one segmental resection of the esophagus. After the second treatment, three patients were disease free for 37-38 months, one died of recurrent disease of the first carcinoma 36 months later, and one died of distant metastases of the second carcinoma 8 months later. There have been no local recurrences after treatments for the second primaries. CONCLUSIONS: A variety of low-trauma treatments were employed for the second carcinomas because they were found at an early stage. Endoscopic follow-up is proposed to detect second lesions at an early stage.

Carcinoma, Squamous Cell↗

Low level c-myc gene amplification in gastric cancer detected by dual color fluorescence in situ hybridization analysis.

BACKGROUND AND OBJECTIVES: By using the dual color fluorescence in situ hybridization analysis, the amplification of c-myc gene can be detected in the tumor tissue samples obtained from patients with gastric cancer, and the relationship between the molecular cytogenetic change and the clinical stage or histological type may be clarified. METHOD: The tumor tissue samples were obtained from 21 patients with gastric cancer. Simultaneous detection of signals from the chromosome 8 centromere and c-myc gene in each cell after hybridization with appropriate probes was carried out on 50-200 tumor cells in each case. RESULTS: Chromosome 8 polysomy was found in 10 patients. The average centromere 8 copy number was significantly higher in differentiated (2.7) than in undifferentiated (2.3) types of gastric cancer. However, there was no significant difference in occurrence of polysomy 8 between early and advanced cancer. The relative gain (1.1-1.9) of c-myc copy number was found in all 21 cases. There was no significant difference in the fraction of cells with c-myc gene amplification between early (pT1) and advanced (pT2-4) carcinomas. CONCLUSION: We conclude that the present dual color fluorescence in situ hybridization of gastric cancer may be useful in the evaluation of low level c-myc gene amplification, which is difficult to detect by Southern blotting, and may be applicable to the diagnosis of early gastric cancer.

Adult↗

Immuno-scanning electron microscope characterization of large tubules in human deciduous dentin.

BACKGROUND: This study was undertaken to elucidate the type and origin of collagen fibrils which construct the large tubules in deciduous coronal dentin by scanning electron microscope and anti-types I and III collagen antibody procedures. METHODS: The studies were performed on human deciduous teeth. The teeth were fixed in 4% paraformaldehyde solution and then fractured either mesio-distally parallel to the long axis of the tooth or transversely perpendicular to the long axis of the tooth crown. The specimens were three-dimensionally observed employing the scanning electron microscope to distinguish the content of large tubules. Polyclonal antibodies of anti-type I and anti-type III collagen with 20 nm colloidal gold, and secondary electron imaging and backscatter electron imaging of high-resolution field emission scanning electron microscopy were used to examine the types of collagen fibrils. RESULTS: The large tubules extended from the vicinity of the incisal edge of the dentino-enamel junction to the pulp cavity. Inside the large tubules, fibers in compact bundles run parallel to the longitudinal axis of the tubules. The fiber bundles consisted of collagen fibrils which were 50-150 nm in diameter with typical cross striation. Immuno-scanning electron microscopy showed type I collagen-labelling gold particles and type III collagen-labelling gold particles to be abundant on the fibrils. Types I and III collagen-labelling gold particles were present on the banded collagen fibrils regardless of their diameter. CONCLUSIONS: It was found that type III collagen is present together with type I collagen on the fibrils constructing the large tubules of the human deciduous dentin. This immunohistochemical study suggested that the fibrils constructing the large tubules were derived from the von Korff fibers, and types I and III collagens formed copolymers.

Child↗

Coronary artery perforation with subepicardial hematoma.

Coronary artery perforation is a relatively rare complication in coronary angioplasty. We report the case of a 71-year-old male, who was salvaged by emergency surgery, for cardiogenic shock due to subepicardial hematoma associated with balloon angioplasty. Such a case has not yet previously been reported.

Aged↗

Mouse liver T cells: their change with aging and in comparison with peripheral T cells.

Mouse liver contains both IL-2Rbeta- (or low positive) high T-cell receptor (TCR(hi)) cells and IL-2Rbeta+ intermediate TCR (TCR(int)) cells. TCR(int) cells consist of natural killer 1.1 (NK1)+ and NK1- subsets. NK1- TCR(int) cells increase constantly with age whereas TCR(hi) cells decrease. NK1+ TCR(int) cell proportions in the liver increase until middle age and decrease thereafter. Although NK1+ TCR(int) cells in other organs are few regardless of age, NK1- TCR(int) cells gradually appear in other lymphoid organs with aging. Skewed usage of Vbeta7 and Vbeta8 TCR was observed in NK1+ TCR(int) cells in the liver but the predominance was less obvious in NK1- TCR(int) and TCR(hi) cells in the liver and other organs. TCR V alpha14 messenger RNA (mRNA) was detected in NK1+ TCR(int) cells but not in the other two populations. In contrast, although NK1+ TCR(int) cells contain virtually no V alpha11+ T cells, NK1- TCR(int) cells contain a much higher proportion (approximately 12%) of V alpha11+ T cells, whereas approximately 4% of TCR(hi) cells are V alpha11+. NK activities of liver mononuclear cells (MNC) and splenocytes decrease with aging, although the former is always greater than the latter. NK activity of liver MNC is a function of NK cells, partly NK1+ TCR(int) cells but not NK1- TCR(int) cells or TCR(hi) cells. These results suggest that lymphocytes of liver and other organs at old age are no longer occupied solely by conventional thymus-derived T cells, and the increase of extrathymic IL-2Rbeta+ NK1- TCR(int) cells in liver and periphery could be closely related to immunological changes with aging.

Aging↗

Sclerosing pancreatitis showing rapidly progressive changes with recurrent mass formation.

CONCLUSION: Sclerosing pancreatitis might develop repeatedly or might rapidly extend to the whole pancreas with recurrent mass formation. BACKGROUND: Nothing is known concerning course or development of sclerosing pancreatitis. METHODS: A 63-yr-old male was followed up for 2.5 yr. RESULTS: The patient was admitted because of a tumor in the body and tail of the pancreas. Serum pancreatic enzymes were transiently elevated, but tumor markers were all negative. Imaging studies showed a tumor 7 cm in size. The main pancreatic duct was normal in the head and obstructed at the body on endoscopic retrograde pancreatography (ERCP). The K-ras oncogene mutation was positive in pure pancreatic juice. Distal pancreatectomy was performed because pancreatic cancer was highly suspected. Pathological findings showed that the tumor was a densely fibrotic mass without malignant cells. Inflammatory cell infiltration was observed in the stroma. One year later, another mass 3 cm in size was noted in the remnant pancreatic head. ERCP revealed diffuse irregular narrowing of the main pancreatic duct, its branches, and the common bile duct. Liver dysfunction improved and an elevation of serum pancreatic enzymes subsided without any specific treatment, and the mass diminished in size. The patterns of various imaging studies on the second tumor were the same as those of the previous resected mass. Corticosteroid was not administered.

Genes, ras↗