Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. In forty non-smoking healthy subjects and seventy-two patients with left heart diseases measurements were made of the volume expired in the first second of a forced expiration (FEV1) and the total volume expired in a forced expiration (FVC) before and after inhalation of salbutamol. Before and after salbutamol the healthy subjects and patients also inhaled maximally an inspirate, the first part of which contained 133Xe and, during controlled expiration, the radioactivity of the expirate was measured and plotted against its volume. the resulting curves were divided into phases of different slope by eye, the point at which phase 3 changed to phase 4 being nominated the closing volume. 2. In forty non-smoking healthy subjects inhalation of salbutamol was followed by significant increase in FEV1 but FVC and closing volume did not change. 3. Change in posture from seated erect to supine in thirty of these healthy subjects was accompanied by significant reduction in FEV1 and FVC and as closing volume was not significantly different in the two positions the ratio closing volume/vital capacity was increased with recumbency. 4. In seventy-two patients with left heart diseases without a history of cough or wheeze, FEV1, FVC, closing volume and the ratio closing volume/vital capacity were significantly different from values in the healthy subjects. There was no significant difference between non-smokers and ex-smokers amongst the patients. 5. Significant increase in FEV1, FVC and reduction in closing volume and the ratio closing volume/vital capacity followed inhalation of salbutamol in patients with heart diseases but the values remained significantly different from those recorded in the healthy subjects. 6. In twenty patients with heart diseases, FEV1 and FVC were reduced by change in posture from seated erect to supine but the ratio closing volume/vital capacity and the regression with age of this ratio were not significantly changed by change in position. 7. In patients with heart diseases the ratio closing volume/vital capacity was significantly correlated with severity of breathlessness and length of symptom-history but not with left ventricular end-diastolic or pulmonary vein wedge pressures.
Clin Sci Mol Med 1975 Sep
PMID:Airway function in healthy subjects and patients with left heart disease. 117 38

1. The effect of breathing an anaesthetic aerosol of 5% bupivacaine hydrochloride has been assessed in dog and man. 2. In the dog, the cough reflex was abolished and the Hering-Breuer inflation reflex severely impaired or abolished; breathing became slower and deeper; no pathological changes were found in the lungs of these dogs. 3. In man, no untoward effects resulted from a 10 min period of aerosol inhalation; there were no systematic effects on airway resistance or lung volumes and the cough reflex in response to either tactile or chemical (citric acid aerosol) stimulation was invariably abolished. The Hering-Breuer inflation reflex was impaired, but this was not associated with any change in resting ventilation. The Ve/CO2 response was enhanced after aerosol anaesthesia; subjects felt an exaggerated dyspnoea. The aerosol anaesthesia abolished the afferent pathway of a reflexly elicited bronchoconstriction in one subject. There was no effect on the ability to hold the breath, or on the quality of the associated sensation. 4. Control aerosols of sodium chloride solution or phosphate buffer produced no effects. Control experiments with intravenous infusions of bupivacaine proved that none of the effects could have been produced by systemic effects of the absorbed anaesthetic. 5. Plasma concentrations of bupivacaine in man did not exceed a recognized toxic level. The experiments demonstrate a safe reversible anaesthesia of the airways in man lasting for a period of 10-20 min.
Clin Sci Mol Med 1976 Jun
PMID:The effect of anaesthesia of the airway in dog and man: a study of respiratory reflexes, sensations and lung mechanics. 127 53

The National Biotherapy Study Group (NBSG) conducted a broad phase II trial using interleukin-2 (IL-2) by continuous infusion and alpha interferon (IFN) subcutaneously in 267 patients with a variety of advanced cancers, including 29 with breast cancer, 89 with renal cancer, and 69 with melanoma. IL-2 [18 million international units (MIU)/m2] was given by continuous infusion for 108 hours with 3 mu/m2 subcutaneous IFN every other day during the IL-2 infusion. The patients were treated for 1 week followed by a 2-week rest. After two cycles of treatment, patients were evaluated for response. Of the 237 patients evaluable for response, 20 (8%) had a complete or partial response and 128 (54%) were stable. Therefore, 62% of the evaluable patients were nonprogressive during the first 90 days of IL-2/IFN therapy. The objective response rate was 11% in melanoma, 7% in renal cancer, 14% in breast cancer, and 3% in patients with a variety of malignancies for an overall response rate of 7% in these patients with advanced cancer. The patients were treated on a general medical ward and tolerated treatment well with fatigue and fever being nearly universal. Dyspnea, pruritus, chills, and elevated creatinines were frequent but less common. This combination biotherapy regimen has minimal activity in a variety of advanced cancers and must be compared with the best existing chemotherapy for each cancer type in randomized, prospective trials.
Mol Biother 1992 Mar
PMID:Combination biotherapy utilizing interleukin-2 and alpha interferon in patients with advanced cancer: a National Biotherapy Study Group Trial. 162 72

A 37-year-old man suffered from photosensitivity and urinary casts with serological findings of positive anti-DNA antibody, LE cells and false positive VD reaction in September of 1979. He developed general fatigue, dyspnea and diplopia with ptosis of bilateral eyelids in November of 1979, which were improved by the anti-cholinesterase drugs. In January of 1980, he had an attack of unconsciousness and his chest X-ray film showed several tumorous shadows in the anterior mediastinum and middle and lower lung fields. Treating him with chemotherapy of VEMP, the pulmonary shadows disappeared. However, he developed severe muscle weakness with an elevated CPK (430 mU/ml) and a myogenic EMG pattern along with an increased anti-acetylcholine receptor antibody (243 n Mol/l), dysphagia and eyelid-ptosis. He died in September of 1985 and his autopsy disclosed a malignant thymoma of mixed type in the anterior mediastinum and an atrophy and fibrosis with infiltration of inflammatory cells in the striated muscles.
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PMID:[An autopsy case of a patient with myasthenia gravis who showed various symptoms of collagen diseases and complicated with malignant thymoma]. 281 7

Digitalis, diuretics and vasodilators are considered the standard therapy for patients with congestive heart failure, for which treatment is tailored according to the severity of the syndrome and the patient profile. Apart from the clinical seriousness, heart failure is always characterized by an energy depletion status, as indicated by low intramyocardial ATP and coenzyme Q10 levels. We investigated safety and clinical efficacy of Coenzyme Q10 (CoQ10) adjunctive treatment in congestive heart failure which had been diagnosed at least 6 months previously and treated with standard therapy. A total of 2664 patients in NYHA classes II and III were enrolled in this open noncomparative 3-month postmarketing study in 173 Italian centers. The daily dosage of CoQ10 was 50-150 mg orally, with the majority of patients (78%) receiving 100 mg/day. Clinical and laboratory parameters were evaluated at the entry into the study and on day 90; the assessment of clinical signs and symptoms was made using from two-to seven-point scales. The results show a low incidence of side effects: 38 adverse effects were reported in 36 patients (1.5%) of which 22 events were considered as correlated to the test treatment. After three months of test treatment the proportions of patients with improvement in clinical signs and symptoms were as follows: cyanosis 78.1%, oedema 78.6%, pulmonary rales 77.8%, enlargement of liver area 49.3%, jugular reflux 71.81%, dyspnoea 52.7%, palpitations 75.4%, sweating 79.8%, subjective arrhytmia 63.4%, insomnia 662.8%, vertigo 73.1% and nocturia 53.6%. Moreover we observed a contemporary improvement of at least three symptoms in 54% of patients; this could be interpreted as an index of improved quality of life.
Mol Aspects Med 1994
PMID:Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. 775 41

A simple, noninvasive, bias-flow ventilated wholebody plethysmographic technique and noninvasive pulmonary analyzer (Buxco dyspnea monitor) were used to quantitate allergic dyspnea in chronically sensitized freely moving guinea pigs. In this study, the effect of azelastine on aeroallergen-induced dyspnea in allergic guinea pigs was investigated. Aeroallergen challenge produced severe dyspnea which was characterized by a 390% increase in the amplitude of pseudo flow signal, a 93% increase in box pressure (delta P) and a 68% decline in relaxation time; these changes signify a tremendous increase in the effort of breathing. The oral administration of azelastine (1 mg/kg) two hours before aeroallergen provocation significantly inhibited allergic dyspnea in this acute allergic asthma model. This technique permits quantitative measurement of the severity of the airway allergic responses in freely moving guinea pigs.
Res Commun Mol Pathol Pharmacol 1994 Aug
PMID:Azelastine inhibits acute allergic dyspnea in a conscious guinea pig asthma model. 799 65

Chronic heart failure is a well-recognized syndrome in which left ventricular impairment produces a constellation of secondary changes in other organ symptoms leading to symptoms such as muscular fatigue and dyspnoea and objective limitation to exercise tolerance. With modern drug therapy of diuretics and ACE inhibitors, the majority of patients have minimal if any signs of congestion, and yet severe symptomatic limitation remains. This limitation bears little relationship to conventional measures of either left ventricular function or the haemodynamic profile of the patient. The symptoms limiting exercise are predominantly fatigue or dyspnoea, and yet the classical pathophysiological explanations for their genesis now seem inadequate. Recent investigations, as demonstrated, in part, by the research presented in this symposium, attest to the importance of abnormalities in peripheral blood flow and in skeletal muscle in producing both objective limitation to exercise and in explaining the generation of the exercise-limiting symptoms of the syndrome of stable optimally treated chronic heart failure. In addition it is now evident that these muscle changes may in addition have pathophysiological significance for the maintenance of sympatho-excitation during exercise and potentially therefore in the progression of left ventricular remodelling and in the susceptibility to ventricular arrhythmias. This paper presents some of the background evidence which leads to the hypothesis that a feedback loop links changes in skeletal muscle to abnormal reflex cardiopulmonary control which may both limit exercise and be harmful in the progression of the syndrome.
J Mol Cell Cardiol 1996 Nov
PMID:The "muscle hypothesis" of chronic heart failure. 893 79

Respiratory muscle dysfunction has been demonstrated in several clinical situations including chronic respiratory disease, such as chronic obstructive pulmonary disease, as well as cardiac insufficiency. In the latter case, respiratory muscle dysfunction has been demonstrated in acute situation (cardiogenic shock) and in chronic cardiac insufficiency. In the former case, it has been shown in an animal model that respiratory muscle dysfunction could influence markedly the outcome of cardiogenic shock. In chronic cardiac insufficiency histologic, biochemical and contractile abnormalities of the respiratory muscles have been demonstrated in an animal model as well as in humans. These alterations may account, at least in part, for the sensation of dyspnea that these patients encountered. Finally, several pharmacological agents such as angiotensin-converting enzyme inhibitors have been shown to restore muscle abnormalities observed during chronic cardiac insufficiency.
J Mol Cell Cardiol 1996 Nov
PMID:Alteration in diaphragmatic function during cardiac insufficiency: potential pharmacology modulation. 893 83

Hypertrophic cardiomyopathy (HCM) is manifested by severe thickening of the left ventricle with significant diastolic dysfunction. Previous observations on the improvement in diastolic function and left ventricular wall thickness through the therapeutic administration of coenzyme Q10 (CoQ10) in patients with hypertensive heart disease prompted the investigation of its utility in HCM. Seven patients with HCM, six non-obstructive and one obstructive, were treated with an average of 200 mg/day of CoQ10 with mean treatment whole blood CoQ10 level of 2.9 micrograms/ml. Echocardiograms were obtained in all seven patients at baseline and again 3 or more months post-treatment. All patients noted improvement in symptoms of fatigue and dyspnea with no side effects noted. The mean interventricular septal thickness improved significantly from 1.51 +/- 0.17 cm to 1.14 +/- 0.13 cm, a 24% reduction (P < 0.002). The mean posterior wall thickness improved significantly from 1.37 +/- 0.13 cm to 1.01 +/- 0.15 cm, a 26% reduction (P < 0.005). Mitral valve inflow slope by pulsed wave Doppler (EF slope) showed a non-significant trend towards improvement, 1.55 +/- 0.49 m/sec2 to 2.58 +/- 1.18 m/sec2 (P < 0.08). The one patient with subaortic obstruction showed an improvement in resting pressure gradient after CoQ10 treatment (70 mmHg to 30 mmHg).
Mol Aspects Med 1997
PMID:Treatment of hypertrophic cardiomyopathy with coenzyme Q10. 926 16

Adriamycin, an effective anticancer chemotherapeutic agent, causes an insidious and delayed cardiotoxicity. Different subcellular abnormalities including calcium transport changes in the sarcolemma (SL) as well as downregulation of the adrenergic system have been shown to be associated with the development of this cardiomyopathy. Since both of these activities are influenced by phospholipid methylation, effects of adriamycin on the three catalytic sites of SL phosphatidylethanolamine N-methyltransferase were examined. Rats were administered with a cumulative dose of adriamycin (15 mg/kg) over 2 weeks and examined after 3 weeks. Vehicle injected animals served as controls. Dyspnea, high mortality rate, ascites and decrease in aortic and left ventricular systolic pressure, as well as increase in left ventricular end diastolic pressure were seen in the adriamycin group. Myocardial cell damage typical of adriamycin cardiomyopathy, i.e. sarcotubular swelling, vacuolization and myofibrillar drop-out, was also apparent. Total methyl group incorporation into SL phosphatidylethanolamine using radiolabeled S-adenosyl-L-methionine as the donor was significantly depressed in the 3 week group at catalytic sites II and III. Decreased production of methylated intermediates, phosphatidyl-N-monomethylethanolamine and phosphatidyl-N,N-dimethylethanolamine as well as phosphatidylcholine (PC) was seen. Depression of phosphatidylethanolamine N-methylation was also noticed when SL, isolated from untreated hearts, was exposed in vitro to different concentrations (10, 100 and 1000 microM) of adriamycin. Inhibition of phosphatidylethanolamine N-methylation appears to be mediated by adriamycin-induced increase in the oxidative stress and may contribute in the pathogenesis of subcellular changes associated with this cardiomyopathy.
Mol Cell Biochem 1997 Nov
PMID:Adriamycin depresses in vivo and in vitro phosphatidylethanolamine N-methylation in rat heart sarcolemma. 940 67


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