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Biomedical subjects

S Ueda

Publications and source records attributed to S Ueda.

At least 127 records · Page 7Linked to original sources
PubMed1999

Increased plasma levels of adrenomedullin in patients with systemic inflammatory response syndrome.

We measured the plasma levels of adrenomedullin (AM), a novel vasodilating peptide, in 89 patients with various forms of systemic inflammatory response syndrome (SIRS) and 13 healthy volunteers serving as controls. Plasma levels of AM in SIRS (burns: 20.5 +/- 3. 2 fmol/ml [mean +/- SEM]; pancreatitis: 13.8 +/- 3.8 fmol/ml; trauma: 14.9 +/- 2.5 fmol/ml; traumatic shock: 41.1 +/- 7.8 fmol/ml; severe sepsis: 59.9 +/- 11.2 fmol/ml; septic shock: 193.5 +/- 30.1 fmol/ml) were significantly increased over those of controls (5.1 +/- 0.2 fmol/ml). The patients with traumatic shock or septic shock especially had higher levels of plasma AM than those with trauma or severe sepsis, respectively. These data showed that in patients with SIRS, plasma AM levels increased in proportion to the severity of illness. Subsequently, we measured the plasma levels of mediators such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, plasminogen activator inhibitor (PAI)-1, and thrombomodulin (TM) in patients with traumatic shock and septic shock. A significant correlation was observed between plasma AM and TNF-alpha levels in patients with septic shock, suggesting an important role for AM as well as of TNF-alpha in the pathophysiology of inflammation. Plasma AM and IL-8 levels correlated positively with Acute Physiology and Chronic Health Evaluation (APACHE) II score, peak multiple organ failure (MOF) score during the first month and prognosis in patients with septic shock, as did plasma IL-6 levels in patients with traumatic shock. The plasma AM level might serve as a useful marker for evaluating the severity of disease and as an early predictor of subsequent organ failure and outcome in septic shock.

APACHE↗
PubMed1999

Effect of pentobarbital anaesthesia on intestinal absorption and hepatic first-pass metabolism of oxacillin in rats, evaluated by portal-systemic concentration difference.

The effects of anaesthesia on intestinal drug absorption and hepatic first-pass metabolism in rats were investigated by observing the difference in the drug concentration between portal and systemic bloods. Oxacillin and pentobarbital were selected as a model drug and as an anaesthetic, respectively. Rats were divided into a conscious control group and an anaesthetized group. All rats were cannulated simultaneously in the portal vein and in the femoral artery, and oxacillin was orally administered after its intra-arterial injection (double dosing). For the anaesthetized group, pentobarbital was intrasubcutaneously administered twice, first before intra-arterial injection and again before oral administration of oxacillin. The arterial blood alone was sampled from the cannula in the femoral artery before oral administration, whereas the arterial and portal bloods were simultaneously sampled from both cannulated sites after oral administration. Oxacillin concentrations in plasma were assayed by HPLC. The anaesthesia increased the absolute bioavailability (F), the mean absorption time (MAT) and the hepatic recovery ratio (F(H)), but caused little change in the local absorption ratio into the portal system (Fa) and the total clearance (CL). The hepatic clearance (CL(H)) was significantly decreased, resulting in an apparent small change in CL-CL(H) which is considered to be renal clearance. By this method, it was shown directly that an increase in F due to pentobarbital anaesthesia was attributable to the significant increase in F(H). It is expected that the method is useful not only to evaluate the effect of anaesthesia on the first-pass effect, but also to assess the effect of co-administration of drugs on first-pass metabolism.

Anesthesia↗
PubMed1999

Glycyrrhizin inhibits TNF-induced, but not Fas-mediated, apoptosis in the human hepatoblastoma line HepG2.

To determine the transaminase-lowering action of glycyrrhizin (GL) immunologically, the effect of GL on tumor necrosis factor (TNF)-alpha- and Fas-mediated apoptosis was assessed using a human hepatoblastoma line, HepG2 cells. The HepG2 cells were resistant to TNF-alpha and anti-Fas antibody, but were rendered susceptible to TNF-alpha and anti-Fas antibody in the presence of actinomycin D (Act D), an inhibitor of RNA synthesis. The cytotoxicity induced by TNF-alpha/Act D or anti-Fas/Act D was accompanied by DNA fragmentation, indicating apoptotic death of HepG2 cells. GL partially prevented the apoptosis of HepG2 cells induced by TNF-alpha/Act D in a GL-dose dependent fashion. However, this protective effect of GL was not observed in the cytotoxicity of HepG2 caused by anti-Fas/Act D. Although the protection mechanism of GL, observed in a limited fashion against TNF-alpha-mediated apoptosis, is unclear, the present results provide an immunological explanation for the transaminase-lowering action of GL in the GL treatment of chronic liver diseases involving apoptotic hepatocyte death in their pathogenesis.

Anti-Infective Agents↗
PubMed1999

Analysis of a catalytic acidic pair in the active center of cellulase from Aspergillus aculeatus.

Four acidic amino acid residues, Asp97, Asp101, Glu118, and Glu202, were located in the cleft from the X-ray crystallographic analysis of FI-CMCase, endo-1,4-beta-glucanase (EC: 3.2.1.4) of Aspergillus aculeatus No. F-50. To identify the catalytic residues of the FI-CMCase, these residues were mutated to Glu or Ser from Asp97 and Asp101, and to Asp or Ser from Glu118 and Glu202 by site-directed mutagenesis, and totally 8 single mutant enzymes expressed in Escherichia coli were prepared: D97E, D97S, D101E, D101S, E118D, E118S, E202D, and E202S. Mutant enzymes E118S and E202S were not shown to have any detectable activity. Kinetic parameters of other mutant enzymes were measured after purification. The Km of mutant enzymes were not much different from that of wild type FI-CMCase, while the Vmax of mutant enzymes D97E, D97S, D101E, D101S, E118D, and D202E were much decreased to 1/50, 1/20, 1/4000, 1/2000, 1/800, and 1/1600 of the wild type FI-CMCase, respectively. From these results we concluded that Glu118 and Glu202 were most probable candidates for a catalytic pair of acidic amino acids in FI-CMCase.

Amino Acid Sequence↗
PubMed1999

Effects of mental task on heart rate variability during graded head-up tilt.

In this study, we used spectral analysis of heart rate variability (HRV) to estimate the changes in autonomic control in response to disparate stimuli produced by mental task and graded head-up tilting. The low frequency (LF) component of HRV provided a quantitative index of the sympathetic and parasympathetic (vagal) activities controlling the heart rate (HR), while the high frequency (HF) component of HRV provided an index of the vagal tone. We studied 17 healthy male subjects (21-25 yr of age) who were placed on a tilt-table and the graded tilt-protocol involved tilted sine angles 0.0, 0.2, 0.4, 0.6, 0.8, and 1.0. These tilt-protocols were repeated with or without the mental task, which consisted of auditory distinctive reaction-time tasks. The basal autonomic mode against the graded head-up tilt was characterized by reciprocal changes in sympathetic and vagal tones. There were significant increases of HR corresponding to the mental task with lower tilt-angle, albeit the changes with higher tilt angles were not significant. Furthermore, there were increases and decreases of the LF component induced by the mental task at lower and higher tilt-angles, respectively. These results revealed that the different responses of HR and LF component against the same tasks could be derived from the alterations of autonomic mode during gradual changes in autonomic control.

Adult↗
PubMed1999

Coronary artery stenosis evaluated by combined carotid and coronary angiography in patients undergoing carotid endarterectomy.

The relationship between coronary artery stenosis and the postoperative outcome was investigated in patients who underwent carotid endarterectomy (CEA). The benefit of combined carotid and coronary angiography was also evaluated. Combined carotid and coronary angiography was performed in 72 patients treated with CEA (mean age 64.0 years). Fourteen patients with a history of ischemic heart disease (IHD) had a higher Gensini score for coronary artery stenosis than patients with no history of IHD (37.9 +/- 36.8 vs. 7.9 +/- 12.5, p < 0.0001). However, 39.7% of patients with no history of IHD had a Gensini score exceeding 6. Patients with diabetes mellitus had a significantly higher Gensini score than nondiabetic patients. Eleven patients (15.3%) underwent percutaneous transluminal coronary angioplasty and three (4.2%) underwent coronary artery bypass grafting during the CEA perioperative period. None of the patients who underwent combined angiography showed signs of IHD during or after CEA (mean follow-up period 30 months). Combined angiography was not performed in 189 previous patients. Of these, two died of acute myocardial infarction in the postoperative period, 11 manifested nonfatal IHD, and 18 succumbed to IHD (mean follow-up period 8 years). Although patients with a history of IHD manifested more severe coronary artery stenosis than patients without such a history, the possibility of coronary artery stenosis must be considered in patients with no history of IHD, especially those with diabetes mellitus. Combined carotid and coronary angiography and careful management of coronary artery stenosis can be expected to decrease the mortality and morbidity in patients treated with CEA.

Adult↗
PubMed1999

[An autopsy case of elderly idiopathic enlargement of the right atrium].

We report an autopsy case of an 88-year-old man with idiopathic enlargement of the right atrium which is considered to be the oldest case reported. The patient was given a diagnosis of atrial fibrillation at the age of 75 years, when he developed congestive heart failure. Bradycardia associated with partial atrial standstill was detected and, the patient underwent implantation of a pacemaker at age 77. An echocardiogram revealed marked enlargement of the right atrium and moderate enlargement of the left atrium. Thus, idiopathic enlargement of the right atrium was diagnosed. He had recurrent congestive heart failure before admission to our hospital because of malnutrition and anemia. Although he was treated with high calorie intravenous infusion and blood transfusion, he died of pneumonia and heart failure. Postmortem examination revealed that the heart weighed 430 g, and there was marked dilatation of the right atrium which had an extremely thin wall. The annular circumference of the tricuspid valve was markedly dilated, 170 mm, resulting in tricuspid regurgitation. The left atrium was moderately dilated and the right and left ventricles were slightly dilated. Histologically, the free wall of the right atrium was totally replaced by fibrous tissue and atrioventricular valves did not reveal any rheumatic changes. These pathological findings were compatible with idiopathic enlargement of the right atrium. There has been no previous case report of idiopathic enlargement of the right atrium in a patient aged 80 years of age or over.

Aged↗
PubMed1999

Effect of mutations at the residues R25, D27, P69, and N70 of B95a-MCP on receptor activities for the measles viruses Nagahata wild-type strain and CAM vaccine strain.

Human membrane cofactor protein (MCP, CD46) is a regulator of complement activation and also serves as a receptor for measles virus (MV). We recently isolated an MCP homolog from B95a, an Epstein-Barr virus-transformed marmoset B-lymphoblastoid cell line, which is 76% identical to human-MCP. B95a-MCP acts as an MV receptor for CAM, a vaccine strain of MV, but not for Nagahata, wild-type MV strain. The four residues in human-MCP (Asp27, Lys29, Arg69, and Asp70) are reportedly MV binding sites, and these are changed in B95a-MCP (Glu27, Asp29, Pro69, and Asn70). In the present study, we constructed B95a-MCP mutants by replacing the four residues with those in human-MCP, and tested whether the Chinese hamster ovary (CHO) transfectants expressing B95a-MCP mutants become susceptible to the Nagahata strain. The CHO transfectants expressing B95a-MCP mutants formed syncytium with the CAM strain but not with the Nagahata strain. The binding of the hemagglutinin (H) of MV with B95a-MCP mutants was observed with the CAM strain but not with the Nagahata strain. These results suggest that the failure of B95a-MCP as the MV receptor for the Nagahata strain is not due simply to the natural mutations at these four residues. The critical residues for MV binding in an MCP molecule seem to differ depending upon the structure of the MV H protein.

Amino Acid Sequence↗
PubMed1999

[Sarcomatoid carcinoma of the urinary bladder in a hemodialysis patient: a case report].

The following is a case report bladder of sarcomatoid carcinoma in a Japanese 65-year old female patient treated with hemodialysis. She developed chronic renal failure due to chronic glomerulonephritis. Fifteen months after the beginning of the hemodialysis, continuous gross hematuria was noticed, and cystoscopy revealed a broad-based bladder tumor spreading from the right lateral wall to the posterior wall. The histopathologic diagnosis of the TUR-Bt specimens was sarcoma. Radical cystectomy was performed under the diagnosis clinical stage III, T3bN0M0. The post-operative histopathologic diagnosis of the tumor was sarcomatoid carcinoma, composed of nests of transitional cell carcinoma (G 3) and predominant areas of spindle cell sarcomatoid transformation. Sarcomatoid carcinoma of the bladder in a hemodialysis patient is extremely rare, and to date this may be only the second case in Japanese medical literature.

Aged↗
PubMed1999

Endothelial dysfunction by acute hyperhomocyst(e)inaemia: restoration by folic acid.

Recent evidence demonstrates that hyperhomocyst(e)inaemia is a novel risk factor for cardiovascular diseases. In patients with chronic hyperhomocyst(e)inaemia, endothelial function is impaired. However, whether hyperhomocyst(e)inaemia per se is a cause or an epiphenomenon of endothelial dysfunction remains unknown. In this study, we examined the effects of methionine-induced acute hyperhomocyst(e)inaemia on human endothelial function. In healthy volunteers we administered methionine (0.1 g/kg body weight, per os), a substrate of homocyst(e)ine, with or without folic acid (20 mg, per os) and examined flow-mediated vasodilatation of the brachial artery by high-resolution ultrasonography as a non-invasive measure of endothelial function. We also measured plasma levels of homocyst(e)ine before and 3, 8 and 24 h after methionine loading. Methionine administration increased plasma levels of homocyst(e)ine by four times the basal level at 8 h (P<0.0001, ANOVA). The plasma levels returned to baseline at 24 h. Flow-mediated vasodilatation was significantly decreased to half of the baseline value at 8 h and returned to baseline at 24 h (P<0.0001, ANOVA), whereas endothelium-independent vasodilatation by glyceryl trinitrate was not affected by the methionine loading. Co-administration of folic acid did not attenuate methionine-induced hyperhomocyst(e)inaemia but completely prevented endothelial dysfunction. Our results suggest that in humans a methionine-rich diet may acutely impair endothelial function, which can be prevented by folic acid supplementation.

Acute Disease↗
PubMed1999

[Thoraco-abdominal impalement injury with diaphragmatic injury: a case report].

A 60-year-old man was admitted to our hospital because of impalement injury due to traffic accident. Chest X-ray on admission revealed normal lung field. CT scans of the chest and abdomen revealed slight pneumothorax and intra-abdominal organ protruding from abdominal cavity. An emergency operation was performed. Diaphragmatic injury was not detected during the abdominal procedure. On exploring the back wound, we found a laceration of 8 cm in diameter in the diaphragm and repaired it. Impalement injuries which have aspects of both blunt and penetrating trauma are uncommon. Accordingly, wound exploration and debridement of fistulous tract are necessary. In the case of thoraco-abdominal injuries by impalement, one should bear in mind the existence of diaphragmatic injury even with normal diaphragmatic shadow on chest X-ray.

Abdominal Injuries↗
PubMed1999

[Usefulness and safety of intravenous thrombolytic therapy for elderly patients with acute myocardial infarction: relationship with cardiac rupture].

The usefulness and safety of intravenous thrombolytic therapy were investigated in 298 patients older than 65 years (145 males, 153 females, mean age 78 years) with acute myocardial infarction from 1984 to 1993. These patients were divided into 2 groups of 88 patients younger than 74 years (Group A) and 210 patients older than 75 years (Group B). Seventy patients received thrombolytic therapy with urokinase (UK) or tissue-plasminogen activator [t-PA (UK96 X 10(4)U: 57 patients, t-PA 30-40 X 10(4)U/kg: 12, UK + t-PA: 1)] within 6 hours after the onset of acute myocardial infarction (Group TL). Two hundred twenty-eight patients received conventional therapy (Group C). There were no differences in the frequencies of the site of myocardial infarction, Killip class, admission within 6 hours after the onset of acute myocardial infarction or thrombolytic therapy between the 2 age groups. In-hospital mortality was significantly higher in Group B than in Group A (43% vs 24%, p < 0.01). In Groups A and B, in-hospital mortality was 20% lower in Group TL compared with Group C (20% vs 25% in Group A, 36% vs 45% in Group B). In Group B, the mortality from pump failure including shock and congestive heart failure was half in Group TL compared with Group C (13% vs 30%). Cardiac rupture was found in 11 patients of Group TL and 7 patients of Group C. Therefore, the mortality from cardiac rupture was fivefold higher in Group TL compared with Group C (8% vs. 1.6% in Group A, 20% vs 3.6% in Group B). Of 11 patients with cardiac rupture in Group TL, 8 patients suffered rupture in the early phase within 12 hours after the onset of acute myocardial infarction and the tear was present near the center of infarcted area in all 7 autopsy cases. The case of recanalization of the infarct-related coronary artery in Group TL revealed moderate to massive hemorrhagic infarction at autopsy. This indicates that the mechanisms involved in cardiac rupture are different in thrombolytic therapy and conventional therapy. Intravenous thrombolytic therapy is effective for the reduction of mortality from pump failure in elderly patients with acute myocardial infarction older than 75 years. However, it must be evaluated as one of the risk factors of cardiac rupture in elderly patients.

Age Factors↗
PubMed1999

[Cytopathology of the breast--benign and malignant neoplastic conditions].

Breast cancer is one of the most common malignancies in women and the incidence has been increasing. Cytology plays a very important role not only in the diagnosis of breast lesions, but also in keeping the benign-to-malignant biopsy ratio low, so that unnecessary surgery is not performed. A fundamental feature of a benign aspirate is the presence of a dual population of ductal epithelial cells (variable within limits, but cohesive and orderly) and myoepithelial cells (naked, bipolar nuclei). Several cytologic features must be assessed to make the diagnosis of malignancy, including high cellularity, cell dissociation, large nuclear and cell size, cell pleomorphism, intracytoplasmic lumens (containing mucin), irregular nuclear margin, coarse chromatinic pattern, prominent nucleoli, and the presence of abnormal mitoses. Other criteria of lesser importance include necrosis, absence of myoepithelial cells and intranuclear inclusions. However, breast carcinomas do not always show every feature of malignancy. The well-differentiated or low-grade carcinomas are often difficult to differentiate from benign cells. It may be helpful to consider the clinical and radiological findings. We reported here, typical neoplastic lesions of the breast by correlating cytological with histopathological features.

Biopsy↗
PubMed1999

Evaluation of phosphoinositide turnover on ischemic human brain with 1-[1-11C]-butyryl-2-palmitoyl-rac-glycerol using PET.

UNLABELLED: It is important to evaluate cerebral function from neural signal transduction in ischemic brain in judging morbid state and prognosis. We synthesized 1-[1-(11)C]-butyryl-2-palmitoyl-rac-glycerol (DAG) for the purpose of imaging the second messenger on PET and applied it to clinical cases of cerebral infarction. METHODS: Five patients, who had ischemic stroke, were examined with PET. [15O]-CO2 and [15O]-O2 inhalation methods were applied to cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2). For the measurement of phosphoinositide turnover after intravenous injection of DAG, dynamic PET data were collected continuously for 46 min. Arterial blood samples were taken to evaluate changes in the serum concentration of DAG. To quantify the metabolic activity of inositol phospholipid, the incorporation constant k*(DAG) was calculated on the basis of the kinetics of DAG. RESULTS: The plasma concentration of DAG increased rapidly and peaked 30 s after injection of DAG solution. In the normal cortex, DAG concentration increased gradually and reached a plateau between 15 and 20 min after injection. In the ischemic core (infarction), DAG concentration increased slowly, and its peak concentration was lower than that in normal tissue. In comparison with blood flow and metabolic parameters, k*(DAG) showed the best correlation with CMRO2, suggesting a reflection of neuronal activity. Locally, CBF and CMRO2 gradually decreased from the normal area toward the ischemic center (infarction), whereas k*(DAG) and OEF significantly decreased only in the ischemic center. CONCLUSION: The k*(DAG) of ischemic brain, including that caused by infarction, significantly correlated with CMRO2, suggesting that metabolic activity of inositol phospholipid reflects neural viability. Maintained metabolic activity of inositol phospholipid in the region around the ischemic core indicated preservation of the signal transduction system through the metabotropic receptor.

Aged↗
PubMed1998

The development of autoimmune inflammatory arthropathy in mice transgenic for the human T cell leukemia virus type-1 env-pX region is not dependent on H-2 haplotypes and modified by the expression levels of Fas antigen.

Previously, we reported that human T cell leukemia virus type-1 env-pX region-introduced transgenic (pX-Tg) mice develop an inflammatory polyarthropathy. Although autoimmune pathogenesis was suggested, the detailed mechanisms remain to be elucidated. In this report, we examined effects of the MHC and fas genes on the development of the disease. When pX-Tg mice were backcrossed with different inbred strains, the incidence of arthritis differed among strains; 64% and 72% in BALB/cAn (H-2d), 25% and 46% in C3H/HeN (H-2k), and 0% and 2% in C57BL/6J (H-2b) background at 3 and 6 months of age, respectively. Rheumatoid factor levels in the serum correlated with the susceptibility to the disease, whereas IL-1beta and MHC gene expression were similarly elevated in all of these strains, suggesting involvement of immune regulatory genes in this strain difference. However, introduction of the H-2d locus into C57BL/6J pX-Tg mice did not increase the incidence of arthritis, and substitution of the BALB/cAn H-2 locus with the H-2b did not decrease it. The results indicate that the H-2 locus is not the major determinant of the disease. Then, since previous study indicated a defect in Fas-mediated apoptosis of transgenic T cells, the effects of fas gene modification on the disease were examined. The incidence increased when these pX-Tg mice were crossed with lpr/lpr mice, while it decreased when crossed with fas-transgenic mice. These observations suggest that aberration of Fas-mediated apoptosis of peripheral lymphocytes, rather than negative selection in the thymus, is involved in the development of autoimmune arthropathy in pX-Tg mice.

Animals↗
PubMed1998

Redox regulation of caspase-3(-like) protease activity: regulatory roles of thioredoxin and cytochrome c.

Oxidative stress induces a variety of cellular responses, including apoptosis, and caspase family proteases are known to be involved in apoptosis. Caspase-3(-like) protease activity was examined in Jurkat T cells to investigate the mechanism of apoptosis induced by a thioloxidant, diamide. Caspase-3 was activated when cells were cultured with 200 microM diamide that induced apoptosis, whereas no caspase-3 activation was detected with 500 microM diamide that induced necrosis. When apoptosis was induced in cells with exposure to 200 microM diamide, the intracellular thioredoxin (TRX) levels were maintained and the intracellular generation of reactive oxygen intermediates was marginal. The cytosolic fractions of cytochrome c were increased earlier than the activation of caspase-3. In contrast, when cells were exposed to 500 microM diamide, intracellular reactive oxygen intermediate generation was increased and processing of caspase-3 was not detected despite cytochrome c release, resulting in necrosis. Caspase-3 activity in cell lysate precultured with anti-Fas Ab was suppressed dose dependently by diamide and restored by thiol-reducing agents, DTT or TRX. When cells were precultured with 5 mM of buthionine sulfoximine, an inhibitor of glutathione synthesis, intracellular TRX levels were maintained, and as low as 20 microM diamide could induce apoptosis associated with the increase of cytosolic cytochrome c and the activation of caspase-3. These results indicate that the activation of caspase-3 in diamide-induced apoptosis is mediated, at least partly, by cytochrome c release from mitochondria, and the cellular reducing environment maintained by TRX, as well as glutathione, is required for caspase-3 activity to induce apoptosis.

Antibodies, Monoclonal↗