[Case of Reye's syndrome with multiple organ failure induced by diclofenac sodium].
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
H Matsuo
Publications and source records attributed to H Matsuo.
Plasma levels of adrenomedullin in primary and secondary pulmonary hypertension in patients <20 years of age.
To elucidate the pathophysiologic significance of adrenomedullin in pulmonary hypertension, we measured plasma adrenomedullin-like immunoreactivity (AM-LI) concentrations in blood samples obtained from various sites during cardiac catheterization by using radioimmunoassay in patients with pulmonary hypertension in comparison with patients without pulmonary hypertension. In patients with pulmonary hypertension, plasma AM-LI concentrations were significantly elevated and there was a significant uptake of AM-LI in pulmonary circulation, indicating the involvement of adrenomedullin in the cardiovascular regulation of pulmonary circulation in pulmonary hypertension.
Adolescent↗
Human alveolar macrophages synthesize endothelins by thrombin.
Alveolar macrophages (AM) play pivotal roles in the defense mechanism and the regulation of inflammatory processes in the airways. Macrophages express receptors for thrombin on their surfaces, and thrombin induces the chemotaxis and the proliferation of macrophages. Thrombin acts on vascular endothelial cells to synthesize endothelin (ET)-1. AM have been known to express prepro ET-1 mRNA. Thus, we hypothesized that thrombin stimulates AM so as to synthesize ET. Surgically resected human lungs were irrigated by saline to remove intravascular blood, then saline was instilled into the bronchus, and the fluids were recovered. AM were separated by Percoll density centrifugation (density, 1.060 g/ml). AM were resuspended in culture medium without FCS in the presence or absence of thrombin. ET was synthesized by thrombin in a concentration-dependent manner, and the amounts of ET synthesized by thrombin (10 U/ml) were equivalent to those by LPS (10 microg/ml). Dexamethasone (10(-6)-10(-10) M), IL-4 (100 U/ml), and TGF-beta (10 ng/ml) significantly suppressed the ET synthesis by thrombin (p < 0.05). In contrast, 1,25-dihydroxyvitamin D3 (10(-8)-10(-10) M) enhanced the ET synthesis up to approximately 300%. The analysis using high pressure liquid chromatography revealed that AM-derived ET consists of ET-1, ET-2, and ET-3. Major constituents were ET-2 and ET-1, and the ratio of ET-2/ET-1 was 1.7 +/- 0.4 (mean +/- SE). These results indicate that thrombin is a potent agonist for AM to synthesize ET.
Cells, Cultured↗
Negative inotropic effect of adrenomedullin in isolated adult rabbit cardiac ventricular myocytes.
BACKGROUND: Adrenomedullin (AM) is a potent vasodilator peptide. AM-induced vasodilatation is mediated by an increase of NO as well as cAMP. Both AM and binding sites for this peptide have been found in cardiac tissue, indicating the possible existence of an autocrine or paracrine system of AM in the heart. METHODS AND RESULTS: Myocytes were isolated by use of retrograde coronary perfusion with physiological solution containing collagenase and hyaluronidase from adult rabbit ventricles. Contraction of cardiac myocytes was traced with a video motion detector, and [Ca2+]i was measured with indo 1 at 37 degrees C. The Ica was measured with a whole-cell patch clamp at 23 degrees C. AM and calcitonin gene-related peptide (CGRP), another member of the same peptide family, showed a concentration-dependent negative inotropic effect (10(-7) mol/L AM: contraction amplitude, 64 +/- 7% of control; [Ca2+]i, 52 +/- 5% of control; n = 10; 10(-6) mol/L CGRP: contraction amplitude, 64 +/- 25%; [Ca2+]i, 70 +/- 3%; n = 5; mean +/- SD). Ica was decreased to 60 +/- 39% by superfusion with AM after the cessation of NG-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor. Pretreatment with L-NMMA (10 mumol/L) abolished the negative inotropic effect of AM, whereas switching from AM+L-NMMA to AM+L-arginine (1 mmol/L) restored it. Superfusion with 8-bromo-cGMP also showed a negative inotropic effect. AM significantly increased the intracellular content of cGMP, a second messenger of NO, but not that of cAMP. AM (10 nmol/L) blunted the effect of 1 mumol/L forskolin. CONCLUSIONS: AM has a negative inotropic effect and decreased both [Ca2+]i and Ica, with these effects being at least party mediated via the L-arginine-NO pathway in adult rabbit ventricular myocytes.
Adrenomedullin↗
C-type natriuretic protein inhibits intimal thickening after vascular injury.
Explore the source record for details and available documents.
Animals↗
Isolation and characterization of cDNA encoding mouse RNA polymerase II subunit RPB14.
By means of the yeast two-hybrid system using the 40-kDa subunit of mouse RNA polymerase I, mRPA40, as the bait, we isolated a mouse cDNA which encoded a protein with significant homology in amino acid sequence to the 12.5-kDa subunit of Saccharomyces cerevisiae RNA polymerase II, B12.5 (RPB11). Specific antibody raised against the recombinant protein that was derived from the cDNA reacted with a 14-kDa polypeptide in highly purified mammalian RNA polymerase II and did not react with any subunit of RNA polymerase I or III. Moreover, the antibody co-immunoprecipitated the largest subunit of mouse RNA polymerase II. These results provide biochemical evidence that the cDNA isolated, named mRPB14, encodes a specific subunit of RNA polymerase II, and indicate that the subunit organization of the enzyme is conserved between yeast and mouse. A possible role of the alpha-motif [Dequard-Chablat, M., Riva, M., Carles, C. and Sentenac, A., J. Biol. Chem. 266 (1991) 15300-15307] in the protein-protein interaction between mRPA40 and mRPB14 is also discussed.
Amino Acid Sequence↗
Aortic arch operation using selective cerebral perfusion for nondissecting thoracic aneurysm.
BACKGROUND: Risks of increasing mortality and disability in aortic arch operations using the selective cerebral perfusion method for nondissecting aneurysm have not yet been determined. A multicenter, retrospective study was employed. METHODS: The subjects were 143 patients who were admitted to one of the nine cardiovascular centers between January 1988 and December 1993, including 15 with ruptured aneurysm. A graft replacement of the transverse aortic arch or distal arch was performed in 80 patients, extensive aortic reconstruction comprising simultaneous replacement of the ascending or descending thoracic aorta (or both) in 46, and patch repair of involved arch in 17. The mean postoperative follow-up period was 19 months. RESULTS: Hospital mortality was 36/143 patients (25.2%). Univariate analysis revealed that age of 70 years or more, ruptured aneurysm, and renal dysfunction affected hospital mortality. Neurologic deficits were noted in 15 patients (10.5%). Reoperation was performed in 13 patients for residual distal aneurysm or false aneurysm. Late death occurred in 10 patients and were due to vascular complications in 6. Multivariate analysis confirmed that aneurysmal rupture and renal dysfunction were independent predictors for vascular death including hospital mortality. CONCLUSIONS: The present study confirmed that age, aneurysmal rupture, and renal dysfunction were significant predictors for mortality and disability in the aortic arch operation using selective cerebral perfusion for nondissecting thoracic aneurysm.
Aged↗
Operation for nondissecting aneurysm in the descending thoracic aorta.
BACKGROUND: Little is known about the risks of mortality and morbidity after descending thoracic aortic aneurysm repair using left heart bypass and temporary arterioarterial bypass. METHODS: A multicenter, retrospective study was performed on 120 patients who were admitted to one of nine cardiovascular centers between January 1988 and December 1993 and underwent operation for nondissecting thoracic aortic aneurysm. The present series included 10 patients with ruptured aneurysm. Graft replacement was performed in 95 patients, patch repair in 22, and suture of the ruptured aorta in 3. Venoarterial bypass was used in 45 patients, left heart bypass in 56, and temporary arterioarterial bypass in 19 as circulatory support. The mean postoperative follow-up period was 30 +/- 21 months. RESULTS: Hospital mortality occurred in 7 patients (5.8%). Univariate analysis revealed that only aneurysmal rupture was related to hospital mortality. Brain or cord injury was observed in 4. Of nine deaths that occurred after discharge, five were related to aneurysm and two were due to vascular event. No significant difference was noticed in probability of survival according to the circulatory supporting method. Only aneurysmal rupture affected probability of survival. Multivariate analysis revealed that aneurysmal rupture was the only independent predictor for vascular death including hospital mortality. CONCLUSIONS: The present study confirms that aneurysmal rupture is a significant predictor for mortality and morbidity in aortic operations for nondissecting descending thoracic aneurysm, and that a similarly good outcome would be expected when using left heart bypass, temporary arterioarterial bypass, or venoarterial bypass.
Aged↗
Structure of translation factor eIF4E bound to m7GDP and interaction with 4E-binding protein.
eIF4E, the mRNA cap binding protein, is a master switch that controls eukaryotic translation. To be active, it must bind eIF4G and form the eIF4F complex, which also contains eIF4A. Translation is downregulated by association of eIF4E with 4E-BP, which occupies the eIF4G binding site. Signalling events acting on 4E-BP cause it to dissociate from eIF4E, and eIF4E is then free to bind eIF4G to form the active eIF4F complex. We have solved the structure of the yeast eIF4E/m7Gpp complex in a CHAPS micelle. We determined the position of the second nucleotide in a complex with m7GpppA, and identified the 4E-BP binding site. eIF4E has a curved eight-stranded antiparallel beta-sheet, decorated with three helices on the convex face and three smaller helices inserted in connecting loops. The m7G of the cap is intercalated into a stack of tryptophans in the concave face. The 4E-BP binding site is located in a region encompassing one edge of the beta-sheet, the adjacent helix a2 and several regions of non-regular secondary structure. It is adjacent to, but does not overlap the cap-binding site.
Amino Acid Sequence↗
Vasodilator effects of adrenomedullin on small pulmonary arteries and veins in anaesthetized cats.
1. This study was conducted to determine adrenomedullin (AM) action sites in the pulmonary vascular bed and the relation between its vasodilator effects and vascular tone. Moreover, an examination was made into whether calcitonin gene-related peptide (CGRP) receptors mediate pulmonary vasodilatations induced by AM. To this end, we directly measured internal diameter (i.d.) changes in small pulmonary arteries and veins (100-1100 microns i.d.) by use of an X-ray television system on the in vivo cat lung. 2. Under control (resting vascular tone) conditions, AM injections into the left main pulmonary artery caused dose-related i.d. increases in both small arteries and veins. The mean i.d. increase of the 100-1100 microns arteries (4 +/- 1, 11 +/- 2, and 17 +/- 2% with 0.01, 0.1, and 1 nmol kg-1 AM, respectively) was significantly larger than that for the veins (1 +/- 1, 5 +/- 2, and 7 +/- 2% with 0.01, 0.1 and 1 nmol kg-1 AM, respectively) whatever the injected dose of AM. 3. When unilobar hypoxia (5% O2) had decreased the i.d. of the 100-1100 microns arteries and veins by 16 +/- 3 and 6 +/- 3%, respectively, AM (0.1 nmol kg-1) was able to induce significantly larger i.d. increases in the arteries (28 +/- 3%) and veins (11 +/- 3%) than those under control conditions. 4. The AM-induced i.d. response pattern in the serially connected pulmonary arteries was quite different from that induced by CGRP; AM caused a greater increase in smaller vessels (100-500 microns) than in larger vessels (500-1100 microns). In the case of CGRP, a greater increase was observed in the larger vessels. 5. CGRP8-37 (100 nmol kg-1, i.v., followed by a continuous infusion of 0.2 nmol kg-1 min-1) had no significant effect on the i.d. increase induced by AM (0.1 nmol kg-1) in any serial segments of the arteries and veins. 6. The results indicate that, in the cat, AM induces greater vasodilatation in small pulmonary arteries and lesser vasodilatation in small veins, the maximum dilatation being in the more peripheral arterial segment (100-500 microns). The vasodilator effect of AM was enhanced when vascular tone was elevated. The data suggest that the AM-induced pulmonary vasodilatation is not mediated by CGRP receptors but by its own specific receptor.
Adrenomedullin↗
Increased plasma concentrations of adrenomedullin correlate with relaxation of vascular tone in patients with septic shock.
OBJECTIVE: To investigate plasma concentrations of adrenomedullin in patients with septic shock and the potential association of these concentrations with relaxation of vascular tone. DESIGN: Prospective, case series. SETTING: Department of Emergency and Critical Care Medicine, Nara Medical University. PATIENTS: Twelve patients who fulfilled the clinical criteria for severe sepsis or septic shock (as defined by the Members of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee) and 13 healthy volunteers. INTERVENTIONS: Arterial blood samples were obtained via a 20-gauge cannula inserted into each patient's radial artery. MEASUREMENTS AND MAIN RESULTS: After extraction and purification, plasma adrenomedullin was measured by radioimmunoassay. Systemic vascular resistance index, pulmonary vascular resistance, cardiac index, and stroke volume index were determined with a thermodilution catheter. The mean plasma concentration of adrenomedullin was markedly higher in patients than in controls (226.1 +/- 66.4 [SEM] vs. 5.05 +/- 0.21 fmol/mL, p < .01). Moreover, these concentrations correlated significantly with cardiac index, stroke volume index, and heart rate values, and correlated significantly with decreases in diastolic blood pressure, systemic vascular resistance index, and pulmonary vascular resistance index values. CONCLUSIONS: Enhanced production of adrenomedullin in patients with septic shock may contribute to reduced vascular tone, hypotension, or both. More data are needed to clarify the role of adrenomedullin in the regulation of vascular tone in this patient population.
Adrenomedullin↗
Effects of short-term administration of sublingual nifedipine on coronary arterial wall elastic properties: evaluation by intravascular ultrasound.
Intravascular ultrasound is suited to measure coronary cross-sectional anatomy. Therefore the regional coronary wall elasticity was evaluated by examining the response to nifedipine. In 20 patients, coronary ostial pressure (P) and intravascular ultrasound images were simultaneously recorded before and after sublingual administration of 10 mg nifedipine. We identified the perimeter of the vessel wall, with normal or atherosclerotic plaque, on ultrasound image. At the atherosclerotic site, we measured segmental perimeter (S) for each normal or plaque segment. The ratio of the individual segment length (delta S/delta P) and cyclic variation of cross-sectional area (delta A/delta P) per mm Hg increase in P were calculated. Nifedipine decreased pressure (133/79-120/73 mm Hg) and increased heart rate (79-82 beats/min). After nifedipine, delta A/delta P increased from 8.5 +/- 10.2 x 10(-3) to 16.5 +/- 14.4 x 10(-3) mm2/mm Hg at 20 normal sites (p = 0.005) but was unchanged at 17 atherosclerotic sites (6.6 +/- 7.0 x 10(-3) to 6.7 +/- 7.1 x 10(-3) mm2/mm Hg). Nifedipine increased delta S/delta P in normal segments (4.5 +/- 8.7 x 10(-3) to 9.9 +/- 10.9 x 10(-3) mm/mm Hg; p = 0.02) but produced no change in segments with calcified or soft plaque (-1.1 +/- 0.3 x 10(-3) to 1.4 +/- 1.6 x 10(-3) mm/mm Hg and 5.0 +/- 3.6 x 10(-3) to 6.1 +/- 4.8 x 10(-3) mm/mm Hg, respectively). This study demonstrated that nifedipine increases regional coronary arterial elasticity at normal segments but not at that containing mildly atherosclerotic segment, and likely that the arterial wall function indicated by the response to nifedipine was impaired at an early stage of atherosclerosis.
Administration, Sublingual↗
Hilar and mediastinal invasion of bronchogenic carcinoma: evaluation by thin-section electron-beam computed tomography.
The diagnostic accuracy of thin-section incremental dynamic computed tomography (IDCT) using an electron-beam scanner in evaluating hilar or mediastinal invasion of bronchogenic carcinoma was assessed. Thirty-seven patients with proven bronchogenic carcinoma, contiguous with hilar or mediastinal structures, underwent IDCT. The area of contact was scanned using 19 contiguous 3-mm thick sections during injection of contrast material. The degree of contact between mass and pulmonary artery or vein and their distortion were recorded. Irregular thickening of the bronchial wall, soft tissue within the lumen, or distortion were used to determine airway involvement. Sixty-nine sites were assessed retrospectively and compared with pathology reports. The accuracy, sensitivity, and specificity in evaluating invasion of the pulmonary artery were 75.0%, 77.8%, and 71.4%, respectively. Limited reliability also was found for invasion of the main bronchus and "secondary" carina, with accuracies of 66.7% and 70.5%, sensitivities of 75.0% and 70.0%, and specificities of 57.1% and 71.4%, respectively. Thin-section IDCT with electron beam scanner is not accurate in the detection of hilar or mediastinal invasion by bronchogenic carcinoma.
Adult↗
Effect of exercise on plasma adrenomedullin and natriuretic peptide levels in myocardial infarction.
1. We investigated the effect of exercise on plasma adrenomedullin, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations and studied the relationship between these peptides and haemodynamic parameters in nine patients with old myocardial infarction (MI) and in eight normal subjects. 2. The exercise protocol consisted of two fixed work loads (40 and 80 W) for 4 min each and venous blood samples were taken at rest, during each exercise stage and after exercise while monitoring the mean arterial pressure (MAP) and heart rate (HR). In MI, pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), left ventricular end-diastolic pressure (LVEDP) and cardiac output (CO) were measured throughout exercise. 3. Adrenomedullin levels did not significantly increase with exercise. Adrenomedullin levels correlated with PAP and PCWP at rest (P < 0.05). Atrial natriuretic peptide levels correlated with PAP, PCWP and LVEDP throughout exercise (P < 0.05) but, on multiple regression analysis, PCWP correlated only with ANP (P < 0.01). Brain natriuretic peptide levels correlated with LVEDP throughout exercise (P < 0.01) and its increment correlated closely with basal BNP levels at rest (P < 0.01). 4. These results suggest that adrenomedullin does not respond to the acute haemodynamic changes of exercise, whereas ANP responds to it and PCWP is the major stimulus factor. Brain natriuretic peptide responds to exercise in proportion to the basal synthesis of BNP in patients with left ventricular dysfunction and LVEDP may play a role in increasing BNP during exercise.
Adrenomedullin↗
Treatment of experimental allergic encephalomyelitis by selective removal of CD4+ T cells.
Experimental allergic encephalomyelitis (EAE) is a major animal model of human multiple sclerosis (MS). The pathogenesis of both MS and EAE directly involves CD4+ helper T cells. To remove CD4+ T cells selectively from the circulation, we designed a new column in which anti-CD4 monoclonal antibody was immobilized on the activated substance. Most of the CD4+ T cells, including pathogenic T cells, were selectively adsorbed from whole blood with a direct perfusion through the column in vitro, resulting in depletion of the antigen-specific T cell responses. A preliminary trial of ex vivo treatment with the column in EAE rats lowered the percentages of CD4+ populations but failed to alter the course of the disease, suggesting repeated treatment would be necessary to suppress the development of the disease. We conclude that this new column is potentially useful, and repeated treatment would be beneficial in MS and other CD4+ T cell dependent autoimmune diseases.
Animals↗
Administration of aminoglycosides to hemodialysis patients immediately before dialysis: a new dosing modality.
We describe a new modality for administering aminoglycosides to hemodialysis (HD) patients, namely, a modification of the once-daily regimen which consists of administering the aminoglycosides over 60 min by drip infusion just before each HD session, with a preplanned peak concentration being reached at the beginning of the session and then with a rapidly decreasing concentration being achieved by the start of HD. The area under the concentration-time curve (AUC), i.e., the accumulation of the drug in the body, is thus minimized by this modality. Arbekacin (ABK) was given at a dose of 2 mg/kg of body weight to 10 HD patients infected with methicillin-resistant Staphylococcus aureus (MRSA) for 2 weeks (six sessions in total), resulting in the complete disappearance of MRSA in 5 patients. A high rate of elimination of ABK was attained for each patient while the patient was on HD (range, 0.20 to 0.42 h-1; mean 0.28 +/- 0.08 h-1) by using high-performance dialyzers provided with membranes made of either polymethylmethacrylate, cellulose triacetate (CTA), or ethylene vinyl alcohol. The best results were obtained with the CTA membrane, as revealed by the overall mass transfer coefficient (Ko). The AUC in the simulation model for the variation in the serum ABK concentration in this modality was calculated to be 40% of that of the conventional post-HD dosing modality, suggesting that a much higher dose could be administered to HD patients who receive HD thrice weekly (4 h per session), giving, e.g., 4 mg/kg initially and before the HD sessions, when there is an interval of 68 h from HD session to HD session, and giving 2 mg/kg before the other sessions.
Aged↗
Plasma concentrations of adrenomedullin correlate with the extent of pulmonary hypertension in patients with mitral stenosis.
OBJECTIVE: To examine the pathophysiological significance of adrenomedullin in the pulmonary circulation by investigating the relation between plasma concentrations of adrenomedullin and central haemodynamics in patients with mitral stenosis. METHODS: Plasma concentrations of adrenomedullin in blood samples obtained from the femoral vein, pulmonary artery, left atrium, and aorta were measured by a newly developed specific radio-immunoassay in 23 consecutive patients with mitral stenosis (16 females and seven males, aged 53 (10) years (mean (SD)) who were undergoing percutaneous mitral commissurotomy. RESULTS: Patients with mitral stenosis had higher concentrations of adrenomedullin than age matched normal controls (3.9 (0.3) v 2.5 (0.3) pmol/l, p < 0.001). There was a reduction in adrenomedullin concentrations between the pulmonary artery and the left atrium (3.8 (0.2) v 3.2 (0.4) pmol/l, p < 0.001). The venous concentrations of adrenomedullin correlated with mean pulmonary artery pressure (r = 0.65, p < 0.001), total pulmonary vascular resistance (r = 0.83, p < 0.0001), and pulmonary vascular resistance (r = 0.65, p < 0.001). Plasma concentrations of adrenomedullin did not change immediately after percutaneous mitral commissurotomy; however, they decreased significantly one week later. CONCLUSIONS: Plasma concentrations of adrenomedullin are increased in patients with mitral stenosis. This may help to attenuate the increased pulmonary arterial resistance in secondary pulmonary hypertension due to mitral stenosis.
Adrenomedullin↗
Management of eyelid sebaceous carcinomas.
We retrospectively studied 14 patients confirmed histopathologically to have eyelid sebaceous carcinoma during 1986-1994. We removed all tumors totally with frozen section controls and performed reconstruction either by primary apposition or transposition flaps. We observed recurrence in 5 patients (35.7%) in whom a surgical margin of either 1 or 3 mm was taken but none in those with a 5-mm surgical margin. At least 5 mm of normal tissue around the tumor should be removed considering the metastatic potential of these tumors.
Adenocarcinoma, Sebaceous↗