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Biomedical subjects

N Matsumura

Publications and source records attributed to N Matsumura.

At least 19 recordsLinked to original sources

Regulation of Chk2 gene expression in lymphoid malignancies: involvement of epigenetic mechanisms in Hodgkin's lymphoma cell lines.

The tumor suppressor Chk2 kinase plays crucial roles in regulating cell-cycle checkpoints and apoptosis following DNA damage. We investigated the expression levels of the genes encoding Chk2 and several cell-cycle regulators in nine cell lines from lymphoid malignancies, including three Hodgkin's lymphoma (HL) lines. We found that all HL cell lines exhibited a drastic reduction in Chk2 expression without any apparent mutation of the Chk2 gene. However, expression of Chk2 in HL cells was restored following treatment with the histone deacetylase inhibitors trichostatin A (TsA) and sodium butyrate (SB), or with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5Aza-dC). Chromatin-immunoprecipitation (Chip) assays revealed that treatment of HL cells with TsA, SB or 5Aza-dC resulted in increased levels of acetylated histones H3 and H4, and decreased levels of dimethylated H3 lysine 9 at the Chk2 promoter. These results indicate that expression of the Chk2 gene is downregulated in HL cells via epigenetic mechanisms.

Acetylation↗

Impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas: a single-institution retrospective study.

Neuronavigation has become an effective therapeutic modality and is used routinely for intra-axial tumor removal. This retrospective study was conducted to evaluate the clinical impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas. Between 1990 and 2002, 76 adult patients with pathologically confirmed malignant astrocytomas underwent craniotomy and removal of the tumors at the Toyama Medical and Pharmaceutical University Hospital. Of these 76 patients, 42 were treated using neuronavigation with conventional microneurosurgery and the other 34 were treated with conventional microneurosurgery alone. Postoperative early MRI with contrast enhancement was done, and gross total resection was defined as the complete absence of residual tumor. Survival time was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from the Cox proportional hazards model. In univariate analysis, age (< 65), grade 3, preoperative KPS (>/= 80), use of neuronavigation, and gross total resection were significantly associated with longer survival. However, when the data were submitted to multivariate analysis, grade 3, preoperative KPS (>/= 80), and gross total resection were independent prognostic factors. The median survival periods of patients receiving gross total resection (vs. partial resection) and neuronavigation (vs. no neuronavigation) were 16 (vs. 9) months and 16 (vs. 10) months, respectively. The percentage of a gross total resection was significantly higher in the neuronavigation group compared to that in the no-navigation group (64.3 % vs. 38.2 %, p < 0.05). Neurological deterioration occurred in 4 of 42 (9.5 %) and in 6 of 34 (17.6 %) patients after surgery with neuronavigation and surgery without neuronavigation, respectively, although this difference was not statistically significant. Our results showed that neuronavigation increases the radicality in the resection of malignant astrocytomas and is objectively useful for improving survival time.

Adolescent↗

Livaditis' circular myotomy does not decrease anastomotic leak rates and induces deleterious changes in anastomotic healing.

Considering that Livaditis' myotomy is still accepted as a good method for lengthening the esophagus to allow primary repair of long-gap esophageal atresia, the aim of this experimental study was to verify if this procedure decreases the incidence of leaks in anastomoses performed under severe tension. In addition, it was verified whether the myotomy promotes any morphological or biochemical change in the healing esophageal anastomosis. Sixty small dogs were submitted to a cervicotomy and resection of an esophageal segment (8.0 - 10.0 cm) resulting in an anastomosis under severe tension. The animals were divided into two groups (control group: only anastomosis; experimental group: anastomosis plus circular myotomy in the proximal esophageal segment). The animals were sacrificed on the 14th postoperative day, submitted to autopsy, and were evaluated as to the presence of leaks. Twelve scars of each group were collected for histological, histomorphometric (evaluation of scar thickness), electrophoretic and immunoblotting studies of collagen (total collagen and types of collagen determinations). Leak rates were the same in both groups. Histologic examination showed that the scar at the anastomosis was formed by fibrous tissue, without mucosa or muscular tissue. In the myotomy animals, a decreased number of newly formed small vessels was noted in comparison to control animals, and morphometric analysis showed that in the myotomy animals the anastomotic scar was thinner than in the control animals. Biochemical analysis of scars demonstrated that myotomy promoted a decrease in the soluble collagen content in comparison with the control animals and no alteration in the content of insoluble collagen. The electrophoretic separation of the types of collagen and characterization by immunoblotting demonstrated the presence of collagen types I, III, and V, and the quantification by densitometry of the bands showed a reduction in collagen type V (present in the blood vessels) in the myotomy animals in comparison to controls. This result is in accordance with the histological observation of a decrease in newly formed blood vessels. Circular myotomy does not decrease the possibility of anastomotic leaks, in addition to promoting deleterious changes in anastomotic healing.

Anastomosis, Surgical↗

Helicobacter pylori infection and the development of gastric cancer.

BACKGROUND: Although many studies have found an association between Helicobacter pylori infection and the development of gastric cancer, many aspects of this relation remain uncertain. METHODS: We prospectively studied 1526 Japanese patients who had duodenal ulcers, gastric ulcers, gastric hyperplasia, or nonulcer dyspepsia at the time of enrollment; 1246 had H. pylori infection and 280 did not. The mean follow-up was 7.8 years (range, 1.0 to 10.6). Patients underwent endoscopy with biopsy at enrollment and then between one and three years after enrollment. H. pylori infection was assessed by histologic examination, serologic testing, and rapid urease tests and was defined by a positive result on any of these tests. RESULTS: Gastric cancers developed in 36 (2.9 percent) of the infected and none of the uninfected patients. There were 23 intestinal-type and 13 diffuse-type cancers. Among the patients with H. pylori infection, those with severe gastric atrophy, corpus-predominant gastritis, and intestinal metaplasia were at significantly higher risk for gastric cancer. We detected gastric cancers in 21 (4.7 percent) of the 445 patients with nonulcer dyspepsia, 10 (3.4 percent) of the 297 with gastric ulcers, 5 (2.2 percent) of the 229 with gastric hyperplastic polyps, and none of the 275 with duodenal ulcers. CONCLUSIONS: Gastric cancer develops in persons infected with H. pylori but not in uninfected persons. Those with histologic findings of severe gastric atrophy, corpus-predominant gastritis, or intestinal metaplasia are at increased risk. Persons with H. pylori infection and nonulcer dyspepsia, gastric ulcers, or gastric hyperplastic polyps are also at risk, but those with duodenal ulcers are not.

Adult↗

Glufosinate ammonium induces convulsion through N-methyl-D-aspartate receptors in mice.

Glufosinate ammonium, a broad-spectrum herbicide, causes convulsion in rodents and humans. Because of the structural similarities between glufosinate and glutamate, the convulsion induced by glufosinate ammonium may be ascribed to glutamate receptor activation. Three N-methyl-D-asparate (NMDA) receptor antagonists, dizocilpine, LY235959, and Compound 40, and an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor antagonist, NBQX, were coadministrated with glufosinate ammonium (80 mg/kg, intraperitoneally) in mice. Statistical analyses showed that the NMDA receptor antagonists markedly inhibited the convulsions, while the AMPA/kainate receptor antagonist had no effect on the convulsion. These results suggest that the convulsion caused by glufosinate ammonium is mediated through NMDA receptors.

Aminobutyrates↗

Intramedullary spinal teratoma with spina bifida.

Spinal intramedullary teratoma is a rare tumor. We report a case of intramedullary teratoma of the conus medullaris with spina bifida. A 5-year-old boy was admitted to our hospital for removal of a lumbosacral tumor sited in an intramedullary location at the conus medullaris, which was totally resected with neuroendoscopic assistance. The pathological diagnosis was mature teratoma consisting of three germ cell layers. The pathogenesis of spinal intramedullary teratoma is discussed with special reference to spina bifida.

Adolescent↗

Severe congenital cytomegalovirus infection with fetal hydrops in a cytomegalovirus-seropositive healthy woman.

We report the case of a woman whose two consecutive pregnancies resulted in intrauterine fetal death due to severe congenital cytomegalovirus infection. In both pregnancies, congenital cytomegalovirus infection was prenatally diagnosed on the basis of detection of cytomegalovirus DNA and specific IgM in cord blood. This case suggests that severe congenital cytomegalovirus infection can occur even in seropositive healthy women.

Adult↗

Side-to-side arterial anastomosis model in the rat internal and external carotid arteries.

Microvascular anastomosis has become a general and essential technique in the field of vascular reconstructive surgery. Side-to-side microvascular anastomosis is rarely performed by microsurgeons. Laboratory training models are essential for the development and refinement of microsurgical techniques. A new experimental model of a side-to-side "arterial" anastomosis in the rat internal and external carotid arteries is presented, in which 100 percent patency was accomplished immediately, and was maintained 7 days after anastomosis. This model can provide an experimental and training tool for side-to-side anastomosis of small arteries.

Anastomosis, Surgical↗

Study on free radicals and pancreatic fibrosis--pancreatic fibrosis induced by repeated injections of superoxide dismutase inhibitor.

The exact mechanisms of the development of pancreatic fibrosis are still unknown. To clarify the relationship between pancreatic fibrosis and free radicals, the effect of the administration of a superoxide dismutase (SOD) inhibitor, diethyldithiocarbamate (DDC), on pancreatic fibrosis in rats was studied. A single intraperitoneal injection of 500 mg/kg of DDC significantly reduced SOD activity and significantly increased lipid peroxidation products in the pancreas, showing no histologic changes of inflammation or necrosis. Repeated administration of 500 mg/kg DDC, twice a week, caused inter- and intralobular fibrosis with atrophy of acinar cells in the pancreas for at least 2 weeks without fibrosis of the liver and kidney. Administration of allopurinol showed preventive effects against DDC-induced pancreatic fibrosis. In conclusion, repeated administration of DDC, which caused pancreatic fibrosis, is a new experimental model of pancreatic fibrosis from the viewpoint of oxidative stress.

Allopurinol↗

Right sylvian fissure subarachnoid hemorrhage has electrocardiographic consequences.

BACKGROUND AND PURPOSE: Abnormal ECG changes are frequently observed in patients with subarachnoid hemorrhage (SAH). Recently, evidence has been obtained that right insular cortex mediates sympathetic cardiovascular effects. We therefore assessed the laterality and location of SAH dominance in inducing cardiovascular changes as measured by ECG, blood pressure, and heart rate. METHODS: After exclusion of 11 SAH patients who died within 1 month after onset, we studied 118 consecutive patients. Data were obtained from records of blood pressure and pulse on admission. Abnormal ECG changes were determined from ECGs on admission and almost 1 month later. From brain CT scans performed immediately after admission, the amount of SAH in each of the 8 cisterns and fissures was measured semiquantitatively. RESULTS: Twenty-six patients had abnormal changes on admission ECG, while 92 patients did not. Systolic blood pressure, diastolic blood pressure, and the amounts of blood in the left ambient cistern, left suprasellar cistern, quadrigeminal cistern, right ambient cistern, right suprasellar cistern, right sylvian fissure, and the set of all cisterns were significantly greater in the group with ECG change than in the group without ECG change. Multivariate logistic regression analysis with stepwise method indicated that systolic blood pressure >160 mm Hg (P=0.0006) and the amounts of SAH in the quadrigeminal cistern (P=0.022) and right sylvian fissure (P=0.0019) were independently associated with abnormal ECG change. CONCLUSIONS: Cardiac consequences are possible in patients with massive right sylvian fissure SAH or when systolic blood pressure is >160 mm Hg.

Autonomic Nervous System Diseases↗

Asymptomatic pyuria in diabetic women.

The aim of the present study was to determine the prevalence of and the host factors for asymptomatic pyuria (ASP) in women with type 2 diabetes. The study included 179 type 2 diabetic women and consecutive 455 non-diabetic women attending as out-patients in 1996. Patients with symptoms of a urinary tract infection were excluded. ASP was defined as the presence of more than 10 leukocytes/high-power field in a random urine sample. Diabetic women more often had ASP than non-diabetic women (27.9 vs. 15.8%, P<0.001). The prevalence of ASP was significantly increased in patients with a duration of diabetes exceeding 15 years (0 approximately 4 years; 20.3%, 5 approximately 9 years; 24.3%, 10 approximately 14 years; 23.8%, and > or =15 years; 46.3%). No differences were evident in HbA(1C) between diabetic patients without ASP and those with ASP. Diabetic women with ASP more often had diabetic retinopathy, neuropathy, nephropathy, cerebrovascular disease, ischemic heart disease, and hyperlipidemia than those without ASP. However, no statistically significant differences were evident in the prevalence of hypertension, constipation, or dementia. As the degree of neuropathy increases, it is accompanied by an increasing prevalence of ASP (none, 21.4%; blunt tendon reflexes, 24.5%; symptomatic, 50.0%; and gangrene, 66.6%). The prevalence of ASP was significantly increased in the patients with proliferative diabetic retinopathy (none, 23.2%; background, 29.4%; pre-proliferative, 18.2%; and proliferative, 50.0%). As the degree of nephropathy increases, it is accompanied by an increasing prevalence of ASP (none, 20.0%; microalbuminuria, 31.9%; macroalbuminuria, 37.0%; and renal failure, 60.0%). Thus, the prevalence of ASP is increased in women with diabetes and increased with longer duration of diabetes but was not affected by glucose control. The incidence of ASP increases significantly as diabetic microangiopathy becomes severer.

Aged↗

[A four-year prospective study on the influence of serum elevated lipoprotein (a) concentration on ischemic heart disease and cerebral infarction in elderly patients with type 2 diabetes].

To clarify the influence of elevated serum lipoprotein (a) (Lp(a)) concentration on ischemic heart disease (IHD) and the perforating artery occlusion type of cerebral infarction (CI) in elderly patients with type 2 diabetes, we measured the serum levels of Lp(a) of type 2 diabetic patients (n = 158, 81 men and 77 women). The group was followed up prospectively for 4 years and the incidence of IHD or CI was monitored. The diagnosis of CI was confirmed by computed tomography and that of IHD, which includes myocardial infarction and angina pectoris, was diagnosed by electrocardiogram and blood chemistry examination, Lp(a) concentrations of 20 mg/dl or more were identified as elevated Lp(a) levels and Lp(a) concentrations of less than 20 mg/dl were identified as normal Lp(a) levels. A Kaplan-Meier survival analysis (log-rank test) assessed the time to event rate stratified by an Lp(a) cutoff point of 20 mg/dl. The predictive value for CI or IHD events was assessed by multiple logistic regression analysis. The probability of IHD events was significantly higher in the elevated Lp(a) group than in the normal Lp(a) group without a history of IHD but was similar in the two groups for those patients with a history of IHD. There was no significant difference between the elevated Lp(a) group and the normal Lp(a) group with regard to CI events in patients without a history of CI and with a history of CI. On multiple logistic regression analysis, Lp(a), hyperlipidemia and a history of IHD were significant predictors of IHD and hypertension, hyperlipidemia and a history of CI were significant predictors of CI. These results show that elevated serum Lp(a) concentrations is an independent risk factor for IHD, but not for the perforating artery occlusion type of CI in type 2 elderly diabetic patients.

Aged↗

[A case of collecting duct carcinoma (Bellini duct carcinoma) producing carcinoembryonic antigen].

We report a case of collecting duct carcinoma (Bellini duct carcinoma) producing carcinoembryonic antigen (CEA). A 61-year-old man visited our hospital because of a left renal mass detected by ultrasonography in an other hospital. Computed tomography showed a low density tumor measuring about 3 cm in the left kidney. Angiography demonstrated a hypovascular tumor. The serum level of CEA was increased to 20 ng/ml. (normal < 7 ng/ml). Left radical nephrectomy was performed. Histological examination revealed collecting duct carcinoma with papillary growth (T1aN1M0). Cancer cells showed a positive immunohistochemical staining for CEA. Under a diagnosis of CEA-producing collecting duct carcinoma of the left kidney, the patient underwent systemic chemotherapy (M-VAC). The serum level of CEA decreased to the normal level after the nephrectomy, but six months postoperatively, metastatic bone tumor at the left pelvic bone was revealed on the plain film and at the same time, the CEA level was increased again.

Antineoplastic Combined Chemotherapy Protocols↗

One-Pot synthesis of N-heterocyclic compounds from cyclopropenethione derivatives

The one-pot reaction of 2-tert-butylthio-3-phenylcyclopropenethione (1a) and its 3-(2-thienyl) derivative (1b) with lithium pyrrolidinide at -70 degrees C, followed by methylation with methyl iodide, gives 6-methylthio-5-phenyl-2,3-dihydro-1H-pyrrolizine (2a) and its 5-(2-thienyl) derivative (2b), respectively. The reaction of 2-tert-butylthio-3-(pyrrolidin-1-yl)cyclopropenethione (1c) with phenyllithium gives also 2a in a high yield under similar conditions, and the reactions of 1a with N-lithium salts of 3-pyrroline, hexamethyleneimine, indoline, and carbazole, piperidine-potassium tert-butoxide mixture, and phenyllithium give 6-methylthio-5-phenyl-3H-pyrrolizine (3), 2-methylthio-3-phenyl-6,7, 8,9-tetrahydro-5H-pyrrolo[1,2-a]azepine (5), 6-tert-butylthio-5-methylthio-4-phenyl-1,2-dihydro-6H-pyrrolo[3,2, 1-ij]quinoline (6), 4-tert-butylthio-5-methylthio-6-phenyl-4H-pyrido[3,2,1-jk]carbazole (7), 2-methylthio-3-phenyl-5,6,7,8-tetrahydroindolizine (4), and 1-tert-butylthio-2-methylthio-3-phenylindene (9), respectively. The structures of 2a and 3 were determined by X-ray analyses of their tricarbonylchromium complexes.

Journal Article↗

Purification and characterization of an extracellular alkaline serine protease from Aspergillus terreus (IJIRA 6.2).

An extracellular alkaline serine protease has been purified from Aspergillus terreus (IJIRA 6.2). The purification procedure involved chromatography on DEAE-Sephadex A25, phosphocellulose, hydroxyapatite, casein-Sepharose, gel filtration on Sephacryl-S-300 and by glycerol density gradient centrifugation. The enzyme was further purified to apparent homogeneity through a combination of electrophoresis in polyacrylamide gel containing 0.1% sodium dodecyl sulfate (SDS) with or without protease substrate (gelatin) and subsequent regeneration of its activity in situ by removal of SDS. The active enzyme was visualized in a zymogram or on the basis of protease activity exhibited on an X-ray film. The protein in the unstained segment of the gel was electroeluted. The eluted protein with protease activity exhibited a molecular mass of 37,000-daltons on electrophoresis in SDS-polyacrylamide gel. A sedimentation coefficient of 3.2S was obtained by glycerol density gradient contrifugation. Maximum activity of protease was observed at pH 8.5 and at 37 degrees C. Purified protease was active between pH 5.5 and 9.5 and was found to be stable up to 60 degrees C. With Na-caseinate, the K(m) of the purified protease was found to be 0.055 mM. Antipain, phenylmethane sulfonyl fluoride, and chymostatin served as non-competitive inhibitors. Substrate specificity was determined by using a synthetic chromogenic peptide containing N-P-Tosyl-Gly-Pro-Arg-p-nitroanilide. Results showed that the protease cleaved the peptide on the -COOH end of arginine residue.

Aspergillus↗

Determination of intracellular and extracellular beta-lactamase activities of Pseudomonas aeruginosa after exposure to beta-lactams in vitro and in vivo.

Beta-lactamase production in Pseudomonas aeruginosa was determined in in-vitro models and in rat pouch infection models after exposure to ceftazidime, imipenem, and piperacillin. Exposure of 28 P. aeruginosa strains to 1/4 minimum inhibitory concentration (MIC) of ceftazidime, imipenem, and piperacillin for 24 h enhanced intracellular beta-lactamase activities in 14, 22, and 6 strains, respectively, of the 28 clinical strains tested, and enhanced extracellular beta-lactamase activities which were not detected without exposure to antibiotics, in 7, 23, and 1 of the 28 strains, respectively. Extracellular beta-lactamase activity from P. aeruginosa S-1278, producing an inducible beta-lactamase, scarcely increased after exposure to ceftazidime and piperacillin 24 h after incubation, while the activity increased after exposure to imipenem over the range of 1/8 to 8 MIC. In the rat granuloma pouch models infected with P. aeruginosa S-1278, ceftazidime and piperacillin, after single administration (20 mg/kg) and serial administration (20 mg/kg per day x 3 days), did not enhance extracellular beta-lactamase activities. However, the activities were enhanced with single and serial administrations of imipenem, and levels over 10 mU/ml were detected until the third day. The beta-lactamase activity, similar to the activity found in rat pouches after serial administration of imipenem, inactivated various cephalosporins. In conclusion, extracellular beta-lactamase activity was detected both in vitro and in vivo after exposure to a good inducer, and extracellular beta-lactamase remained at infection site at levels that could inactivate cephalosporins.

Animals↗

High prevalence of herpes simplex virus type 2 in acute retinal necrosis syndrome associated with herpes simplex virus in Japan.

PURPOSE: To determine the type of herpes simplex virus in acute retinal necrosis syndrome associated with herpes simplex virus. METHODS: Herpes simplex virus type 1, herpes simplex virus type 2, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus were examined by polymerase chain reaction in intraocular specimens from 16 patients with acute retinal necrosis syndrome. Anti-herpes simplex virus type 1 and anti-herpes simplex virus type 2 type-specific antibodies in serum from the patients were detected by enzyme immunoassay. RESULTS: Of 16 patients with acute retinal necrosis syndrome, seven were polymerase chain reaction positive for herpes simplex virus type 2 and nine were positive for varicella-zoster virus. Anti-herpes simplex virus type 2 antibody was positive and anti-herpes simplex virus type 1 antibody was negative in the sera of the seven patients with herpes simplex virus type 2 DNA-positive acute retinal necrosis syndrome. In contrast, anti-herpes simplex virus type 2 antibody was absent in all nine varicella-zoster virus DNA-positive acute retinal necrosis syndrome patients. CONCLUSION: Herpes simplex virus type 2 has been demonstrated to be the major causative agent in acute retinal necrosis syndrome associated with herpes simplex virus by molecular biological and serological methods. Negative preexisting anti-herpes simplex virus type 1 antibody may play an important role in acute retinal necrosis syndrome associated with herpes simplex virus type 2.

Adolescent↗