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Biomedical subjects

M Ueno

Publications and source records attributed to M Ueno.

At least 127 records · Page 7Linked to original sources
PubMed2000

Secretion of thioredoxin enhances cellular resistance to cis-diamminedichloroplatinum (II).

Thioredoxin (TRX) is a redox-active protein induced by a variety of stress and secreted from cells. Collecting evidence revealed that extracellular TRX shows cytokine- and chemokine-like activities. In the present study, we studied the role of secreted TRX on cellular resistance to cis-diamminedichloroplatinum (II) (CDDP). The CDDP-resistant variants of HeLa cells not only have enhanced expression of intracellular TRX, but also show increased secretion of TRX into the culture medium, compared to the parental cells. The CDDP-resistant cells also exhibit an enhanced L-cystine uptake capability, which results in a significant increase in the intracellular sulfhydryl content, including glutathione (GSH). Exogenous administration of recombinant TRX (rTRX) increases cellular resistance to CDDP and augments the L-cystine uptake in the parental HeLa cells. Moreover, depletion of L-cystine from the culture medium or combined treatment with L-cystine uptake inhibitors increases cellular sensitivity to CDDP in the CDDP-resistant cells. These findings suggest that secreted TRX may play an important role in the acquisition of cellular CDDP resistance through enhancement of the L-cystine uptake activity, and that the L-cystine transport system, as well as the TRX system, may be a novel therapeutic target in CDDP-resistant cancer cells.

Biological Transport, Active↗
PubMed2000

A high fructose diet affects the early steps of insulin action in muscle and liver of rats.

A high fructose diet induces insulin resistance in rats, although the exact molecular mechanism involved is unknown. In this study, we used immunoprecipitation and immunoblotting to examine the levels and phosphorylation status of the insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), as well as the association of the IRS-1 with phosphatidylinositol 3-kinase (PI 3-kinase), and phosphotyrosine phosphatase (SHP2) in the liver and muscle of rats fed a control or high fructose diet for 28 d. There were no differences in IR and the IRS-1 protein levels in the liver and muscle of rats fed the control and high fructose diets. However, tyrosine-phosphorylation of the insulin receptor after insulin stimulation was reduced to 71 +/- 2% (P < 0.05) of control in the liver of the fructose-fed rats. In samples previously immunoprecipitated with anti-IRS-1 antibody and blotted with antiphosphotyrosine antibody, the insulin-stimulated IRS-1 phosphorylation levels in the liver and muscle of the fructose-fed group were only 70 +/- 6% (P < 0.05) and 76 +/- 5% (P < 0.05) of those of control rats, respectively. The insulin-stimulated IRS-1 association with PI 3-kinase was reduced to 84 +/- 3% (P < 0.05) in the liver and to 84 +/- 4% (P < 0.05) in the muscle of the fructose-fed group compared with control rats. Insulin-stimulated IRS-1 association with SHP2 was reduced to 79 +/- 5% (P < 0.05) in liver of the fructose-fed rats. These data suggest that changes in the early steps of insulin signal transduction may have an important role in the insulin resistance observed in these rats.

Animals↗
PubMed2000

Endothelin-A-receptor antagonist and oral prostacyclin analog are comparably effective in ameliorating pulmonary hypertension and right ventricular hypertrophy in rats.

Pulmonary hypertension (PH) has a poor prognosis and is a drug-resistant disease. Recently, it has been reported that continuous intravenous prostacyclin (PGI2) administration is effective for PH. In this study, we compared the effects of chronic treatment with an endothelin-A- (ETA) receptor antagonist with an oral PGI2 analog on PH in rats. We administered the ETA-receptor antagonist TA-0201 or beraprost sodium (BPS), which is an orally active PGI2 analog, to monocrotaline- (MCT) induced PH rats. Each drug was given orally for 19 days. The rats were divided into the following four groups: (1) normal rats with vehicle (control); (2) PH rats with vehicle treatment (PH + vehicle); (3) PH rats with TA-0201 treatment (0.5 mg/kg/day) (PH + TA-0201); (4) PH rats with BPS treatment (100 microg/kg/day) (PH + BPS). Nineteen days after MCT injection, Pp/Ps [the ratio of right ventricular (RV) systolic pressure to systemic systolic blood pressure) and the ratio of the RV weight to the body weight (RV/BW), indicators of PH and RV hypertrophy. were markedly higher in the PH + vehicle group than in the control (healthy) group. The increase in Pp/Ps and RV/BW was significantly depressed in the PH + TA-0201 group and PH + BPS group to a similar extent. The expression of beta-myosin heavy chain (MHC) mRNA, a molecular marker for cardiac hypertrophy, in the RV was greatly increased in the PH + vehicle group and this increase was inhibited in the PH + TA-0201 group and PH + BPS group to a similar effect. In conclusion, treatment with an ETA-receptor antagonist or an oral PGI2 analog is comparably effective in the prevention of progression of PH and RV hypertrophy.

Administration, Oral↗
PubMed2000

Endothelin-1 and right-sided heart failure in rats: effects of an endothelin receptor antagonist on the failing right ventricle.

The development of pulmonary hypertension (PH) causes right-sided heart failure. We investigated whether chronic treatment with the endothelin-A- (ETA) receptor antagonist BMS-193884 in rats with monocrotaline- (MCT) induced PH improves right-sided heart failure. Administration of BMS-193884 (100mg/kg) was commenced on the day before treatment with MCT. At 19 days, hemodynamics were measured under anesthesia and hearts were removed. The right ventricular systolic pressure (RVSP), an indicator for pulmonary hypertension, was remarkably elevated in the PH group compared with the normal control group. BMS-193884 effectively prevented this elevation. The central venous pressure, an indicator for right-sided heart failure, was markedly increased in the PH group. This increase was reduced to the normal level by BMS-193884. In the failing right ventricle of the PH group, the expression of atrial natriuretic peptide (ANP) mRNA, which is a molecular marker for the failing heart, was markedly increased. BMS-193884 greatly prevented this increase. The present study suggests that ET-1 contributes to the right-sided heart failure caused by PH and that an ETA-receptor antagonist is a beneficial drug which improves both hemodynamics and cardiac gene expression in the failing right ventricle.

Animals↗
PubMed2000

Tyrosine kinase inhibitors reduce bcl-2 expression and induce apoptosis in androgen-dependent cells.

The signal transduction pathway showing how androgen withdrawal induces apoptosis in androgen-dependent cells has not been clearly understood. In these studies, we focused on the behavior of tyrosine kinases in androgen-dependent cells and investigated its correlation with apoptosis and bcl-2 expression. We used SC2G, an androgen-dependent mouse mammary carcinoma cell line, which had been cloned from Shionogi Carcinoma 115 (SC115). When SC2G cells were cultured with herbimycin A (HMA), a potent tyrosine kinase inhibitor, the number of viable cells decreased significantly after 24 h. Terminal deoxyribonucleotidyltransferase-mediated dUTP-biotin nick end labeling and flow cytometric analysis of annexin V staining showed that HMA induced apoptosis of SC2G cells. The level of bcl-2 mRNA in SC2G cells was suppressed by HMA in a dose-dependent manner on RT-PCR. Preincubation with caspase inhibitors protected HMA-induced apoptosis of SC2G cells. When a human bcl-2 gene was transfected in SC2G cells and overexpressed, SC2G cells seemed to acquire tolerance for HMA. These data indicate that HMA-sensitive tyrosine kinase(s) can regulate apoptosis and inhibit bcl-2 expression in SC2G mouse androgen-dependent cells. Tyrosine kinase(s) seemed to be a member of signal transduction between androgen receptor activation and bcl-2 expression.

Animals↗
PubMed2000

Induction of polyploidization by jaspamide in HL-60 cells.

Jaspamide, a natural peptide isolated from the marine sponge Hemiastrella minor, was used in the study of polyploidy in HL-60 cells. Jaspamide at 5 x 10(-8) M concentration exhibited antiproliferative activity and an increased CD4 and CD14 surface expression. After 2 days of cultivation, 56.3% of the exposed cells became multinuclear compared with 2.4% in controls. Moreover, the size and the number of nuclei of the cells increased in a time-dependent manner. An increased number of metaphase chromosomes was observed by microscopical enumeration after colcemid treatment for 60 min. The analysis of the DNA content of these cells, measured by propidium iodide staining, revealed a significant increase in the cells percentage with increased DNA content. Taken together, these findings indicate that the jaspamide treatment induces polyploidization in the HL-60 cell line.

Antineoplastic Agents↗
PubMed2000

A high-fructose diet induces changes in pp185 phosphorylation in muscle and liver of rats.

Insulin stimulates the tyrosine kinase activity of its receptor resulting in the tyrosine phosphorylation of pp185, which contains insulin receptor substrates IRS-1 and IRS-2. These early steps in insulin action are essential for the metabolic effects of insulin. Feeding animals a high-fructose diet results in insulin resistance. However, the exact molecular mechanism underlying this effect is unknown. In the present study, we determined the levels and phosphorylation status of the insulin receptor and pp185 (IRS-(1/2)) in liver and muscle of rats submitted to a high-fructose diet evaluated by immunoblotting with specific antibodies. Feeding fructose (28 days) induced a discrete insulin resistance, as demonstrated by the insulin tolerance test. Plasma glucose and serum insulin and cholesterol levels of the two groups of rats, fructose-fed and control, were similar, whereas plasma triacylglycerol concentration was significantly increased in the rats submitted to the fructose diet (P<0.05). There were no changes in insulin receptor concentration in the liver or muscle of either group. However, insulin-stimulated receptor autophosphorylation was reduced to 72 +/- 4% (P<0.05) in the liver of high-fructose rats. The IRS-1 protein levels were similar in both liver and muscle of the two groups of rats. In contrast, there was a significant decrease in insulin-induced pp185 (IRS-(1/2)) phosphorylation, to 83 +/- 5% (P<0.05) in liver and to 77 +/- 4% (P<0.05) in muscle of the high-fructose rats. These data suggest that changes in the early steps of insulin signal transduction may have an important role in the insulin resistance induced by high-fructose feeding.

Animals↗
PubMed2000

Treatment of membranoproliferative glomerulonephritis associated with hepatitis C virus infection. Niigata Research Group of Glomerulonephritis and Nephrotic Syndrome.

OBJECTIVE: Interferon has been used as a new therapeutic agent for glomerulonephritis since a manifest relationship between membranoproliferative glomerulonephritis (MPGN) and hepatitis C virus (HCV) infection was documented. However, several side effects and rebound phenomenon have been significant problems. We retrospectively evaluated the therapeutic effect and safety of the standard treatment with steroids and/or immunosuppressive agents for MPGN patients with an HCV infection. METHODS: Remission and renal survival rates as well as clinical and histological data were compared between MPGN groups with or without an HCV infection. In addition, the hepatic function was followed-up after the treatment. PATIENTS: The subjects were 42 biopsy proven MPGN patients. Seven were positive for an HCV infection. Secondary causes of MPGN excluding an HCV infection were omitted. Most patients were treated with steroids and/or immunosuppressive agents. RESULTS: The mean age of the MPGN patients with an HCV infection was significantly higher than that of those without an HCV infection. The renal function and the interstitial change of the former group were significantly worse than those of the latter. Nevertheless, remission and renal survival rates were not significantly different between the two groups. None in the HCV positive MPGN group showed an impairment of hepatic function during the clinical course. However, 2 subjects died from severe pneumonia during the treatment. CONCLUSION: The standard treatment with steroids and/or immunosuppressive agents did not reveal a statistical difference in the therapeutic efficacy between MPGN patients with or without an HCV infection. However, some in the former group showed a poor prognosis.

Adult↗
PubMed2000

Enzyme/prodrug gene therapy for human colon cancer cells using adenovirus-mediated transfer of the Escherichia coli cytosine deaminase gene driven by a CAG promoter associated with 5-fluorocytosine administration.

Escherichia coli cytosine deaminase (CD), which is a prokaryotic enzyme, converts nontoxic prodrug 5-fluorocytosine (5-FC) into the toxic chemotherapeutic agent 5-fluorouracil (5-FU). To investigate an enzyme/prodrug gene therapy for colorectal cancer, using adenoviral gene transfer of the E. coli CD gene associated with administration of 5-FC, we constructed replication-defective adenovirus vectors expressing the E. coli CD gene or lacZ gene driven by a CAG promoter (composed of a cytomegalovirus immediate early enhancer and a chicken beta-actin promotor). The present study demonstrated that an adenoviral gene transfer system using a CAG promoter induced sufficient gene expression of CD to confer the cytotoxicity of 5-FC to HT29 human colon cancer cells by converting it into 5-FU even at an moi of one. Furthermore, experimental gene therapy using intratumoral injection of the CD-expressing adenovirus with systemical administration of 5'-FC successfully suppressed the growth of established HT29 subcutaneous tumors in nude mice. These results suggest that enzyme/prodrug gene therapy using the adenoviral gene transfer of the E. coli CD gene with concomitant administration of 5-FC may be an effective strategy in the local control of colorectal cancer.

Adenoviridae↗
PubMed2000

[Perioperative risk factors in valve surgery concomitant with coronary artery bypass grafting].

Between January 1990 and December 1999, 20 patients underwent the valve surgery concomitant with coronary artery bypass grafting. There were 16 males and 4 females, their mean age was 66.5 years. Of the 20 patients, aortic stenosis was noted in 7, aortic regurgitation in 3, mitral stenosis in one, and mitral regurgitation in 9 patients. The cause of mitral regurgitation was considered to be an ischemic change in six patients, including ruptured papillary muscle due to myocardial infarction in two patients. On the contrary, LMT lesion was recognized in 5, LAD lesion in 17, LCX in 16, and RCA in 12 patients. Seven patients had preoperative myocardial infarction, three patients were required preoperative IABP support. AVR was performed in 10, MVR in 5, and MAP in 5 patients. The number of bypass was 1.9 +/- 0.85. Four patients died of LOS and MOF. The remaining 16 patients have been doing well. The significant difference between the survived and the not survived patients was recognized in the factor of emergency, preoperative IABP, papillary muscle rupture due to myocardial infarction, history of PTCA, LAD lesion, and the time of CPB. The factors regarding coronary artery had the influence on the outcome of a patients of valve surgery concomitant with CABG. Therefore, an appropriate myocardial protection and perioperative management for ischemia were mandatory.

Adult↗
PubMed2000

[Neuromonitoring of acute internal carotid artery occlusion].

We experienced a patient with acute thrombosis of the unilateral internal carotid artery. We monitored the brain tissue temperature and intracranial pressure not only in both hemispheres simultaneously but also continuously throughout the process of brain death. The patient was a 73-year-old male who presented to our emergency room with right hemiparesis and aphasia. On admission to our department, no specific pathological findings were identified by brain CT. However a following investigation with left carotid arteriogram demonstrated a complete occlusion of the left internal carotid artery. Probes to monitor intraparenchymal temperature (Tip) and intracranial pressure(ICP) were inserted surgically into the bilateral hemispheres, and these two parameters were monitored continuously until the patient's death. Initially, Tip in the infarcted hemisphere was lower than that in the intact hemisphere, and the left hemisphere's ICP was significantly higher than that of the right one. When the ICP in the left hemisphere exceeded 40 mmHg, bilateral ICPs became equal. Brain herniation was confirmed when the ICP became progressively elevated thereafter. Subsequently the bilateral Tips became equal and lower than the bladder temperature following the brain herniation. In this case, we successfully monitored two parameters while the patient was in the process of brain death; i.e., brain ischemia, complete loss of brain circulation and subsequent decrease in the brain tissue temperature.

Acute Disease↗
PubMed2000

[Clinical significance of 24-hour intraesophageal pH monitoring in GERD patients].

24-hour intraesophageal pH monitoring(24-pH-M) is a method of choice to measure the esophageal acid exposure, and evaluate a patient's lifestyle who has reflux symptoms. The 24-pH-M is indicated to the cases who have at least one of the following signs/symptoms; endoscopy negative GERD(gastroesophageal reflux disease), atypical clinical course for reflux disease, atypical symptoms of GERD, and those who are subjected to have surgical treatment. In the 24-pH-M, not only the duration of gastroesophageal reflux(GER), but also reflux and symptom association should be evaluated. The 24-pH-M is useful to investigate the diagnosis and treatment of GERD including reflux esophagitis.

Esophagus↗
PubMed2000

[Clinical significance of ambulatory intraesophageal bilirubin monitoring in diagnosis of gastroesophageal reflux].

To evaluate the usefulness of ambulatory intraesophageal bilirubin monitoring in the diagnosis of GER, 38 patients with reflux symptoms and 7 controls were studied, using Bilitec 2000. The % time of bilirubin and acid reflux was less than 5% in all of the controls. In 3 patients of NUD, % time of acid reflux was less than 5%, but that of bilirubin was more than 8% in 2 patients. Acid reflux was found only in 1 of 4 patients who had a history of subtotal gastrectomy, but abnormal bilirubin reflux was found in all of 4 patients. In the other 31 patients, a significant difference was found in the % time of bilirubin reflux by the severity of reflux esophagitis, whereas this difference was not found in that of acid reflux. Intraesophageal bilirubin monitoring is useful in the diagnosis of GER and is essential in patients with hypochlorhydria or minimal reflux.

Adult↗
PubMed2000

[A case of renovascular hypertension with normalized blood pressure despite interval progression of stenosis of the bilateral renal arteries].

We report here a unique case of renovascular hypertension(RVH) showing spontaneously normalized blood pressure(BP) after progression of a stenosis of the renal arteries for 16 years. The patient was a 41-year-old man. At the age of 25, he developed drug-resistant hypertension with hypokalemia, hyperreninemia and severe stenosis of the right renal artery, and was diagnosed with RVH. He soon discontinued medication without medical advice. At age 40, he developed pons infarction and his aortography showed progression of the stenosis to the bilateral renal arteries. However, his BP along with the levels of plasma potassium and renin activity were normalized and his renal function was preserved. Renal scintigraphy revealed a significant size difference between the bilateral kidneys. We assume that the hypotrophic changes in the ischemic kidneys counterbalanced the reduction in renal blood flow.

Adult↗