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Biomedical subjects

M Kodama

Publications and source records attributed to M Kodama.

At least 91 records · Page 5Linked to original sources

Occult breast cancer presenting axillary nodal metastasis: a case report.

We report a case of a 42-year-old female with occult breast cancer presenting axillary nodal metastasis. She complained of a swelling of the right axillary lymph node, but no breast mass was palpable. Biopsy of the lymph node was performed and histological examination showed a metastatic ductal carcinoma with papillotubular formation. Estrogen receptor of the lymph node was positive. No pathological findings were obtained by mammography and ultrasonography and systemic examinations revealed no extramammary primary lesion. All these data suggested an occult carcinoma of the breast and modified radical mastectomy was performed. Pathological findings of the removed specimen failed to find the primary breast cancer lesion. The patient has been treated with hormonal therapy and she is well without evidence of disease 5 years after surgery.

Adult↗

Cloning and characterization of a cyclic peptide synthetase gene from Alternaria alternata apple pathotype whose product is involved in AM-toxin synthesis and pathogenicity.

Afternaria afternata apple pathotype causes Alternaria blotch of susceptible apple cultivars through the production of a cyclic peptide host-specific toxin, AM-toxin. PCR (polymerase chain reaction), with primers designed to conserved domains of peptide synthetase genes, amplified several products from A. alternata apple pathotype that showed high similarity to other fungal peptide synthetases and were specific to the apple pathotype. Screening of a Lambda Zap genomic library with these PCR-generated probes identified overlapping clones containing a complete cyclic peptide synthetase gene of 13.1 kb in length with no introns. Disruption of this gene, designated AM-toxin synthetase (AMT), by transformation of wild-type A. afternata apple pathotype with disruption vectors resulted in toxin-minus mutants, which were also unable to cause disease symptoms on susceptible apple cultivars. AM-toxin synthetase is therefore a primary determinant of virulence and specificity in the A. alternata apple pathotype/apple interaction.

Alternaria↗

Bacterial translocation and tumor necrosis factor-alpha gene expression in experimental hemorrhagic shock.

OBJECTIVE: To investigate whether bacterial translocation is the causative mechanism underlying cytokine production during hemorrhagic shock. DESIGN: Prospective, randomized, unblinded animal study. SETTING: Surgical research laboratories of Shiga University of Medical Science. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: The rats were randomly divided into three groups. Each animal was anesthetized with pentobarbital, given a continuous infusion of 0.9% saline, and monitored for blood pressure. The normoxic and sham shock groups breathed room air, whereas the hyperoxic shock group was administered 100% oxygen. Except in the sham shock group, blood was withdrawn to induce a hemorrhagic shock state, then the shed blood was reinfused. Sixty minutes after the induction of hemorrhagic shock, arterial blood cultures were performed in all three groups. The animals were then killed, and their mesenteric lymph nodes (MLNs) were harvested for bacterial culture. The terminal ileum, liver, spleen, kidney, lung, and MLNs were also collected for histologic study by in situ hybridization. MEASUREMENTS AND MAIN RESULTS: In the bacteriologic study, the prevalence of bacterial translocation was 0% (0/11) in the hyperoxic shock group, 55% (6/11) in the normoxic shock group, and 0% (0/9) in the sham shock group. In the in situ hybridization study, tumor necrosis factor-alpha gene expression was detected only in the ileal tissue, MLNs, and spleens of the normoxic shock group. Blood cultures were sterile in all three groups. CONCLUSIONS: Bacterial translocation occurred in MLNs within 1 hr of hemorrhage. Hemorrhagic shock causes tumor necrosis factor-alpha gene expression as well as bacterial translocation in MLNs, but not in the liver, in this model. Bacterial translocation was prevented by hyperoxia early in the course of hemorrhagic shock. Hyperoxia also prevented tumor necrosis factor-alpha gene expression along the bacterial invasion route.

Animals↗

Carvedilol enhances atrial and brain natriuretic peptide mRNA expression and release in rat heart.

To clarify the role of the natriuretic peptide (NP) system in the myocardial protective effects of carvedilol, a beta-blocking agent, we investigated the effects of carvedilol on the NP system in the rat heart. After oral administration of carvedilol (low-dose group: 2 mg/kg/day, group C2; high-dose group: 20 mg/kg/day, group C20) for 1 week, plasma rat atrial NP (r-ANP), atrial mRNA levels of ANP, left ventricular mRNA of brain NP (BNP), NP receptor-A and NP receptor-C (NPR-C) (as a clearance receptor) were measured. Values were compared with those in vehicle-treatment rats (group V). The concentration of r-ANP was significantly higher in group C2 (135 +/- 9 pg/ml) and group C20 (161 +/- 11 pg/ml) than group V (75 +/- 6 pg/ml; both p < 0.01). ANP and BNP mRNA levels were significantly increased and NPR-C was significantly down regulated in group C2 (151 +/- 7, 120 +/- 8 and 78 +/- 7%, respectively, vs. group V) and group C20 (164 +/- 8. 133 +/- 7 and 72 +/- 8%, respectively, vs. group V) compared with group V (all p < 0.01). These results suggest that not only a high dose, but a low dose of carvedilol has the effect of increasing plasma ANP and BNP levels. This effect was closely related to the upregulation of ANP and BNP mRNA expression, and the down regulation of NPR-C mRNA expression in the heart. These mechanisms seem to account for a sizable portion of the protective effect of carvedilol for heart diseases.

Adrenergic beta-Antagonists↗

Acute effects of endothelin-1 and TAK-044 (ET(A) and ET(B) receptor antagonist) in rats with dilated cardiomyopathy.

The hemodynamic effects of endothelin (ET)-1 and TAK-044 (ET(A) and ET(B) receptor antagonist) were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Six weeks after immunization, survived Lewis rats (30/43 = 70%) were randomly allocated into five groups to be given 0, 0.3, 3, 30 and 60 mg/kg/day (groups F0, F0.3, F3, F30 and F60; each group, n = 4) of TAK-044 using an osmotic pump subcutaneously. Age-matched normal Lewis rats (n = 26) were also randomly divided into four groups to be given 0, 0.3, 3 and 30 mg/kg/day (groups N0, N0.3, N3 and N30; each group, n = 4). ET-1 concentrations in plasma and myocardium were measured, and immunohistochemical detection of ET-1 in the left ventricle from the remaining rats (groups F and N) was performed. After administration of TAK-044 for 7 days, 2, 4, 11, 21 and 42 ng/min ET-1 every 20 min was infused using a pump, and the change in mean arterial pressure of each group during the infusion was examined. The plasma and myocardial ET-1 concentrations were significantly higher in group F than group N (12.3 +/- 1.5 vs. 5.4 +/- 0.2 pg/ml and 426 +/- 31 vs. 98 +/- 6 pg/g tissue; both p < 0.01). Strong positive signals for ET-1 were found to be widely distributed in the left ventricular myocardium of both groups of rats. Although the ET-1-induced increase in the mean arterial pressure was abolished in group N30, the maximal dose of ET-1 produced a 34% increase in the mean arterial pressure in group F30. Even in group F60, ET-1-induced hypertension was blocked incompletely. These results indicate that the heart may be a major ET-1-producing organ, and a higher dose of ET-1 antagonist is needed to block the effect of ET-1 in rats with dilated cardiomyopathy.

Animals↗

Therapeutic effect of basic fibroblast growth factor on experimental pancreatitis in rat.

Basic fibroblast growth factor (bFGF) is one of the mitogens that facilitate endothelial proliferation and angiogenesis. This study was designed to examine the therapeutic effect of bFGF on experimental pancreatitis in rat. Edematous pancreatitis was induced by intraperitoneal injections of cerulein (50 microg/kg) at hourly intervals. BFGF (70 nmol/kg) was administered intraperitoneally after induction of pancreatitis. DNA synthesis of isolated pancreatic acinar cells of normal rats was determined as the uptake of 5-bromo-2'-deoxyuridine (BrdU) into the cells. Immunohistochemical staining of DNA synthesis in acinar cells during cerulein-induced pancreatitis was also examined with BrdU labeling in vivo technique. Cerulein administration increased serum amylase, lipase level, and wet weight of pancreatic tissue. Treatment with bFGF markedly ameliorated all these parameters. In primary culture system of isolated pancreatic acinar cells of normal rats, bFGF caused a dose-dependent increase in BrdU incorporation into DNA, showing an EC50 value of 0.8 nmol/L and a maximum response of 2.5-fold increase at a concentration of 400 nmol/L. bFGF treatment (70 nmol/kg) markedly increased BrdU labeling in the nucleus of acinar cells of the pancreatitis rats group in immunohistochemical examination when compared with control without bFGF treatment. Treatment with bFGF may represent a promising therapeutic concept for patients with acute pancreatitis.

Animals↗

Interleukin-8 as a predictor of the severity of bacteremia and infectious disease.

The relationship between cytokines and sepsis has been studied frequently in the intensive care unit (ICU). However, the determination of cytokines in patients as they enter the emergency department (ED) would be more meaningful in predicting the outcome of infection. This study investigated plasma interleukin-8 in the ED as the predictor of bacteremia and sepsis. One hundred patients admitted through the ED with signs of systemic inflammatory response syndrome were studied. Plasma IL-8, IL-6, and tumor necrosis factor (TNF) were assayed by enzyme-linked immunosorbent assay. Patient's data were evaluated using the APACHE II scoring system as predictive factors of morbidity and mortality. Plasma IL-8 (149 pg/mL) detected bacteremia with a positive predictive value of 90.9% and a specificity of 98.7%. Results indicated that the odds ratios (ORs) of bacteremia were 24.78 (P < 0.01, CI = 2.27-270.8), 5.42 (P < 0.05, CI = 1.37-21.4), and 6.05 (P < 0.05, CI = 1.36-26.8) for IL-8, IL-6, and APACHE II, respectively. Occurrence of bacteremia was highly correlated with increases in plasma IL-8 (P < 0.01). IL-8 (OR = 8.25, CI = 1.03-65.9) and APACHE II scores (OR = 12.6, CI = 2.24-70.4) were found to be significantly better predictive factors of mortality (P < 0.01) than IL-6 (OR = 3.60, CI = 0.57-22.7), TNF (OR = 0.24, CI = 0.01-11.0) and age (OR = 1.02, CI = 0.98-1.06). During bacteremia, IL-8 also correlated well with patient use of a ventilator (P < 0.01, OR = 2.43, CI = 2.41-311.19), use of vasopressors (P < 0.05, OR = 2.67, CI = 1.79-370.78), length of stay in the hospital (P < 0.01, OR = 3.14, CI = 1.87-988.31), and stay in the ICU (P < 0.01, OR = 2.51, CI = 2.98-449.80). Measuring IL-8 on patients in the ED with apparent bacterial infections appears to be a reliable predictor of bacteremia and the severity of disease.

APACHE↗

Detection of peptidoglycan in human plasma using the silkworm larvae plasma test.

Silkworm larvae plasma (SLP) reagent, which is prepared from the body fluid of the silkworm, reacts with peptidoglycan (PG), a fragment of both the Gram-positive and Gram-negative bacterial cell wall, as well as with beta-glucan, a component of fungi. We developed a quantitative method for the detection of PG in human plasma from cases with bacterial infection using the SLP reagent. Tested in this way, the SLP method showed 86.2% sensitivity, 90.6% specificity, 89.3% positive predictive value, and 88.5% efficiency. The SLP method provides a valuable tool for the diagnosis of systemic infection using patients' blood.

Animals↗

New method for the detection of bacterial translocation using intestinal permeability with polyethylene glycol 4000.

BACKGROUND: Currently, there is no method of accurately diagnosing bacterial translocation (BT) in humans. BT may be related to changes in intestinal permeability. In this study, we examined the correlation between intestinal permeability using polyethylene glycol (PEG) 4000 and BT. MATERIALS AND METHODS: Under general anesthesia, laparotomy was done in rats, and PEG4000 was administered to the small intestine. We prepared models of invasive stimulation in which lipopolysaccharide (LPS) was intravenously administered, and a hemorrhagic shock model in which blood pressure was decreased to 30 mm Hg. Blood PEG4000 levels were measured. We also measured blood PEG levels in a model in which oxygen was administered to treat hemorrhagic shock. In all models, the presence or absence of BT development was evaluated. RESULTS: In groups given LPS, mean blood PEG levels were significant higher than in the group treated with saline solution. In the hemorrhagic shock group, the mean PEG level was increased but was slightly inhibited by oxygen administration. In the LPS and hemorrhagic shock groups, the incidene of BT was significantly greater than in the control group. In the hemorrhagic shock group, the incidence of BT was 0% after oxygen administration. There was a correlation between the incidence of BT and changes in the intestinal permeability of PEG4000 (R(2) = 0.824). CONCLUSIONS: LPS stimulation enhanced intestinal permeability in a dose-dependent manner. An increase in intestinal permeability was correlated with the incidence of BT. Blood PEG4000 levels correlated positively with the grade of invasion and the incidence of BT.

Animals↗

Levels of serum interleukin-10 reflect disease activity in patients with cardiac sarcoidosis.

Cardiac involvement is the major determinant of morbidity and mortality in patients with sarcoidosis, but clinical evaluation of the disease activity is occasionally difficult in cardiac sarcoidosis. The present study examined whether serum levels of interleukin-10 (IL-10) could reflect the disease activity of patients with cardiac sarcoidosis. Serum IL-10 levels were measured using an enzyme-linked immunosorbent assay, and compared with clinical manifestation, levels of angiotensin-converting enzyme (ACE), levels of lysozyme and accumulation of gallium-67 citrate. Sera were collected from 8 patients with cardiac sarcoidosis (CS group), 22 patients with miscellaneous heart diseases except for sarcoidosis (MHD group), and 8 healthy control subjects (HC group). Serum IL-10 levels of the CS group were significantly higher than those of the 2 control groups. Before steroid therapy, the levels of IL-10 in the CS group showed a significantly positive correlation with levels of ACE (r=0.868, p<0.05) and lysozyme (r=0.890, p<0.05). In 5 patients who were analyzed before and after steroid therapy, the levels of IL-10 tended to correlate with a decrease of an abnormal accumulation in gallium-67 citrate. Serum IL-10 levels may play a role in evaluation of the disease activity in patients with cardiac sarcoidosis.

Adult↗

Molecular structure of rDNA repeat unit in Magnaporthe grisea.

The 8-kb repeat unit of M. grisea rRNA-encoding DNA (rDNA) was cloned as three subclones, pM50, pM21, and pM86. Nucleotide sequencing of these subclones uncovered the structure of an rDNA repeat unit similar to those of other ascomycetes. The intergenic spacer (IGS) of the rDNA cistron contained a repetitive (R) region, which was rich in two kinds of short tandemly repeated elements.

Base Sequence↗

Anti-CD2 monoclonal antibodies prevent the induction of experimental autoimmune myocarditis.

We investigated the effect of a monoclonal antibody against CD2 molecules (OX34) in preventing the induction of experimental autoimmune myocarditis (EAM) induced by immunizing Lewis rats with cardiac myosin. Administration of OX34 before immunization, on Days -6, -4, -2 and 0, completely prevented EAM. On the other hand, treatment with OX34 just before the appearance of myocardial lesions, on Days 9, 11, 13 and 15, had only a partial effect in preventing the disease. Flow cytometric analysis of lymph node cells showed that CD3+ T cells were immediately depleted with the administration of OX34 but had largely recovered on Day 21. Lymph node cells in OX34-treated rats had no proliferative responses to cardiac myosin-rod, but the proliferation was restored when recombinant IL-2 was added. Ultimate production of the anti-myosin antibody was not inhibited by the treatment with OX34. These results suggest that the prevention of EAM by administering the anti-CD2 monoclonal antibody OX34 resulted from T cell depletion during the induction phase, and might in addition result from T cell anergy of Th1, but not Th2 cells.

Animals↗

Rupture of a giant saccular aneurysm of coronary arteriovenous fistulas.

A 58-year-old Japanese woman was admitted to our hospital because of chest pain. A continuous murmur was detected at the left parasternal area. Electrocardiogram showed ST elevation in leads V2, V3 and V4. Chest computed tomography and echocardiography demonstrated pericardial effusion and a large mass which was adjacent to the pulmonary artery. An abnormal blood flow was detected in the mass by Doppler echocardiography. Coronary angiography confirmed that the mass was a giant aneurysm of coronary arteriovenous fistula arising from both the left and right coronary arteries. This patient had no symptoms until rupture of the fistula. Rupture of a coronary arteriovenous fistula is very rare but can be a cause of chest pain and pericardial effusion.

Aneurysm, Ruptured↗

Carotid intima-media thickness in Japanese type 2 diabetic subjects: predictors of progression and relationship with incident coronary heart disease.

OBJECTIVE: To examine carotid intima-media thickness (IMT), predictors of its progression, and its relationship with incident coronary heart disease (CHD) in type 2 diabetic Japanese patients. RESEARCH DESIGN AND METHODS: Carotid IMT of 287 subjects with type 2 diabetes (mean age 61.6 years) without CHD or cerebrovascular disease was examined at baseline and after a mean follow-up of 3.1 years. RESULTS: The annual progression of IMT (means +/- SEM) was 0.04+/-0.004 mm/year. Stepwise multivariate analysis demonstrated that independent risk factors for progress of IMT were the initial IMT (P<0.001), the average HbA1c level (P<0.001), and age (P = 0.001). Both the initial IMT (odds ratio [OR] 4.9, 95% CI 1.7-14.1) and a low average HDL cholesterol (OR 0.2, 0.1-0.8) were identified as predictors of incident nonfatal CHD (angina pectoris or nonfatal myocardial infarction; 3-year incidence 10.1%) after adjusting for age, sex, average HbA1c, and other risk factors. CONCLUSIONS: The predictors of the progression of carotid IMT in Japanese type 2 diabetic subjects were its baseline thickness and the average HbA1c during the follow-up. Baseline carotid IMT and low HDL cholesterol predicted the incidence of nonfatal CHD.

Asian People↗

Effects of gliclazide on low-density lipoprotein oxidizability and atherosclerosis in cholesterol-fed rabbits.

We studied the effects of a widely-used sulfonylurea, gliclazide, on the oxidizability of low density lipoprotein (LDL) and the development of experimental atherosclerosis in cholesterol-fed rabbits. Daily oral administration of gliclazide (20 mg/kg/day) tended to inhibit the aortic atherosclerosis induced by feeding a 1% cholesterol diet for 10 weeks, although it did not affect diet-induced hyperlipidemia. The administration of gliclazide tended to inhibit the increase of serum thiobarbituric acid-reacting substances (TBARS) by cholesterol feeding and to increase the lag time of the conjugated-diene formation of LDL subjected to in vitro oxidation by copper ion, although without significance. The present study suggests that gliclazide may have antioxidative properties in vivo, and have further beneficial effects for the treatment of diabetes mellitus by inhibiting the oxidation of LDL.

Animals↗

Induction of apoptosis in human esophageal cancer cells by sequential transfer of the wild-type p53 and E2F-1 genes: involvement of p53 accumulation via ARF-mediated MDM2 down-regulation.

Transcriptional factor E2F-1 as well as tumor suppressor p53 have been shown to cause apoptosis independently in some types of human cancer cells when overexpressed. Here we report that sequential transfer of the wild-type p53 and E2F-1 genes efficiently induces apoptosis in human esophageal cancer cells and that E2F-1 overexpression directly, activates expression of p14 (ARF), which inhibits MDM2-mediated p53 degradation, resulting in the stabilization of p53. Infection of human esophageal cancer cell lines T.Tn and TE8 with adenovirus vector-expressing E2F-1 (Ad-E2F-1) enhanced mRNA and protein expression of ARF and decreased MDM2 protein expression. Transfection of ARF plasmid decreased MDM2 protein expression, which in turn increased p53 protein expression. Infection of T.Tn and TE8 cells first with adenovirus-expressing wild-type p53 (Ad-p53) and then with Ad-E2F-1 resulted in rapid induction of apoptosis; in contrast, simultaneous infection with Ad-E2F-1 and Ad-p53 had no significant antitumor effect. As shown by Western blot analysis, infection with suboptimal concentrations of Ad-E2F-1 induced the accumulation of exogenous p53 transduced by suboptimal concentrations of Ad-p53. Moreover, Ad-E2F-1-mediated ARF expression inhibited the up-regulation of MDM2 by overexpressed p53 in TE8 cells. Thus, overexpression of ectopic E2F-1 protein may stabilize endogenous as well as ectopic p53 protein via the E2F-1/ARF/MDM2/p53 regulatory pathway and, in this way, render cells more sensitive to apoptosis, an outcome that has important implications for the treatment of human esophageal cancers.

Adenoviridae↗

The prevention of bile duct injury during laparoscopic cholecystectomy from the point of view of anatomic variation.

The aim of this study was to evaluate ways to prevent bile duct injury during laparoscopic cholecystectomy in patients with anomalous biliary tract anatomy. The biliary tract was studied using cholangiograms of 511 patients who had gallbladder disease and was dissected in 92 cadaveric specimens. The authors classified confluent forms of the cystic duct and the bile duct into five different types, including four anomalous types. Sixteen instances (3.13%) of anatomic variation of the biliary tract were found among the patients, and four cases (4.35%) were found in the cadavers. Among the 511 patients, there were 495 cases of type C anatomy, three cases of type A, seven cases of type R, six cases of type P, and zero cases of type L; among the 92 cadaveric specimens, there were 88 cases of type C anatomy, one case of type R, two cases of type P, and one case of type L. For anatomic types A, P, and R, there is a high probability of risk of cutting the wrong duct. Therefore, it is important to clarify the anatomy of the biliary tract by preoperative examination and to carefully dissect the cystic duct close to the neck of the gallbladder during laparoscopic cholecystectomy. Anatomic variation of the biliary tract is common and can create a rare pitfall during laparoscopic cholecystectomy.

Adolescent↗

Effect of Na(+) concentration on the subgel phases of negatively charged phosphatidylglycerol.

The effect of Na(+) concentration on the subgel phase of dimyristoylphosphatidylglycerol (DMPG) was investigated by differential scanning calorimetry (DSC) and negative stain electron microscopy, and the results were compared with dipalmitoylphosphatidylglycerol (DPPG). The conversion mode of DMPG vesicle to the subgel phase by annealing at 5 degrees C was grouped into two types depending on whether Na(+) concentration is above or below 200-250 mM. For [Na(+)]>200-250 mM, the subgel phase of a crystalline superstructure of bilayers wrapped in a cylinder was attained during a 24-h period of annealing and transformed directly to the liquid crystal phase on heating. For [Na(+)]<200-250 mM, two subgel phases which transform to the gel phase on heating were observed after annealing up to 24 h. Both subgel phases showed belt-like structures composed of loosely and closely stacked lamellae, respectively, and their fractions were found to depend on Na(+) concentration. With a further annealing up to 30 days, only the closely stacked subgel phase converted subsequently into the cylindrical superstructure of a more ordered phase. Similar two subgel phases were detected for DPPG at [Na(+)]< or =100 mM. The difference in the relative enthalpy between the gel and subgel phases was investigated from the van der Waals interaction energy between the hydrocarbon chains.

Journal Article↗