Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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1. The ventilation and cardiac frequency during progressive exercise and the respiratory responses to breathing carbon dioxide have been measured in 33 female patients with mitral stenosis and in 31 control subjects. Compared with the control subjects, the patients' exercise ventilation and cardiac frequency were increased; the exercise tidal volume at standard minute volume, the vital capacity and the ventilatory response to carbon dioxide were reduced. The extent to which the standardized tidal volume was lower during exercise than during breathing carbon dioxide was correlated with the severity of the stenosis, as gauged by the increase in exercise cardiac frequency above the level predicted from anthropometric measurements. 2. Twenty patients were studied postoperatively. In the 12 who showed clinical improvement the exercise ventilation and cardiac frequency were reduced and the exercise tidal volume at a given minute ventilation was increased. The latter change occurred despite a reduction in vital capacity, which was probably a residual effect of thoractomy. There was no significant change in the response to breathing carbon dioxide. No material change in function was observed in the patients whose condition was not improved by the operation. 3. It is suggested that in mitral stenosis the tachypnoea which occurs during exercise, whilst mainly a mechanical consequence of the reduced vital capacity, is also partly due to pulmonary congestion stimulating intrapulmonary receptors.
Clin Sci Mol Med 1978 Jan
PMID:Ventilatory responses to exercise and to carbon dioxide in mitral stenosis before and after valvulotomy: causes of tachypnoea. 62 Apr 98

1. Using the mouth occlusion pressure technique, we have studied the control of breathing in seven hypercapnic and eight non-hypercapnic patients with chronic obstructive lung disease. 2. When breathing room air, pulmonary ventilation, mean inspiratory flow and P0.1 (mouth occlusion pressure developed 0.1 s after the onset of occluded inspiration at functional residual capacity) were not significantly different between the two groups of patients. Tidal volume, however, was significantly lower in the hypercapnic than in the non-hypercapnic patients, as a result of a significantly lower duration of inspiration. 3. The lower tidal volume in the hypercapnic patients leads to decreased alveolar ventilation, and appears to be the main cause of retention of carbon dioxide.
Clin Sci Mol Med 1978 Mar
PMID:Control of breathing in patients with chronic obstructive lung disease. 63 Aug 5

It has been recently demonstrated that some nitrosyl hemoglobin derivatives have different optical spectrum according to the nature of their quaternary structure (Cassoly, R. (1974) C. R. Seances Acad. Sci., Paris 278, 1417-1420; Salhany, J. M., Ogawa, S., and Shulman, R. G. (1974) Proc. Natl, Acad. Sci. U.S.A. 71, 3359-3362; Cassoly, R. (1975) J. Mol. Biol. 98, 581-595). This property has been used in order to detect the presence of asymmetrical hybrids alphaNObetaNOalpha'O2beta'O2 in a mixture of the two hemoglobins alpha2NObeta2NO and alpha2'O2beta2'O2. When one changes, by deoxygenation, the conformation of the hybrid, there is a characteristic modification in the optical spectrum of the nitrosyl subunits. Quantitative analysis of this phenomenon shows that asymmetrical alphaNObetaNOalphadeoxybetadeoxy and symmetrical alpha2NObeta2deoxy hybrids have distinct properties. The structure-linked optical transition is different in rate and amplitude; it is faster and larger for the asymmetrical molecule. Carbon monoxide binding kinetics performed in absence of phosphate have also indicated that the allosteric equilibrium is more displaced in favor of the T state for alphaNObetaNOalphadeoxybetadeoxy by comparison with the symmetrical deoxygenated intermediates.
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PMID:Use of nitric oxide as a probe for assessing the formation of asymmetrical hemoglobin hybrids. An attempted comparison between alphaNObetaNOalphadeoxybetadeoxy, alpha2NObeta2deoxy, and alpha2deoxybeta2NO hybrids. 64 91

1. Ten studies were performed on nine patients with haematological disorders but with normal lungs, who required intermittent blood transfusions. The transfer factor for carbon monoxide and uptake of carbon monoxide per unit lung volume (KCO) were measured with the single breath technique before and at various intervals after transfusion. 2. The mean haemoglobin concentration increased from 7.7 to 11.1 g/dl. 3. The TLCO increased according to a formula based on the Roughton & Forster (1957) diffusion equations. TLCO (standardized) = TLCO (observed). (10.2 + Hb)/1.7 Hb, where haemoglobin (Hb) is expressed as g/dl. 4. The correlation between measured and predicted values was slightly better if changes in alveolar volume were taken into account, by using the KCO value.
Clin Sci Mol Med 1978 Jun
PMID:Effect of blood transfusion on the carbon monoxide transfer factor of the lung in man. 65 32

1. The respiratory response to inhaled 3% and 6% CO2 was measured in 10 normal subjects after a 3 h acclimatization period to 3% CO2 in an environmental chamber. Control studies were carried out after a 3 h period of breathing air in the chamber. 2. At the end of the acclimatization period studies were carried out during 20 min periods breathing 3% CO2, 6% CO2 and air. 3. At 2-min intervals during the studies measurements were made of tidal volume (Vt), breathing frequency (fR), minute ventilation (Ve), viscous pulmonary rate of work (Wp) and total viscous rate of work across the lungs and apparatus (Wt). Blood gas tensions were measured at the end of this period. 4. After acclimatization to 3% CO2 there was a significant shift in the response curves Ve/Pa,CO2 and Wt/Pa,CO2 such that subjects showed higher Pa,CO2 values for given values of Ve or Wt. There was no significant change in the slope of the response curves. 5. No correlation was found between the slope of the response curve after the control period breathing air and the degree of shift of the response curve. 6. There was no difference in respiratory pattern or in pulmonary resistance. 7. Similar results were found in two subjects studied after 24 h acclimatization to 3% CO2 but one subject also showed a significant change in the slope of the Ve/Pa,CO2 curve.
Clin Sci Mol Med 1978 Sep
PMID:The respiratory response to inhaled carbon dioxide in man after 3 hours exposure to 3% carbon dioxide. 69 7

Determinations of carbon monoxide binding curves for hemoglobin from Brevoortia tyrannus under equilibrium and photostationary conditions show that in the light, the curve is shifted to the right and altered in shape. The Bohr effect is much less in the light. The kinetics of the transition between equilibrium and photostationary states has been examined. All of the results are satisfactorily described using the two-state model of Monod, J. Wyman, J., and Changeux, J.P. (1965) J. Mol. Biol. 12, 88-118 with the assumption that light produces an additive increase in the rate of dissociation of ligand from the R and T states.
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PMID:Carbon monoxide binding to a fish hemoglobin under photostationary conditions. 70 Dec 55

1. To study the validity of a CO2-rebreathing method at rest and during graded exercise, cardiac output was measured simultaneously on 59 occasions in 16 subjects with normal pulmonary function with the CO2-rebreathing method and the direct Fick method for oxygen. The correlation coefficient between the results of both methods was significantly higher during exercise than at rest. 2. No systematic difference was shown between (a-v)CO2 content difference determined on whole blood and end-tidal gas, which justified the exclusion of a correction factor for blood to alveolar gas PCO2 gradients. 3. In the calculation of cardiac output by the direct Fick method for CO2 and by CO2 rebreathing, a standard CO2 dissociation curve was preferred to a synthetic CO2 dissociation curve, constructed by allowance for changes in haemoglobin concentration, pH and oxygen saturation. The latter curve tended to increase values for cardiac output and induced a large dispersion around the line of identity, when compared with simultaneous cardiac output estimates by the direct Fick method for oxygen.
Clin Sci Mol Med 1978 Nov
PMID:Comparison of cardiac output determined by a carbon dioxide-rebreathing and direct Fick method at rest and during exercise. 71 98

1. The effect of feeding with a diet containing 0.2% (w/w) hexachlorobenzene on hepatic and urinary porphyrins and hepatic cytochrome P-450 was studied at various time intervals in female Wistar rats. 2. Hexachlorobenzene administration for 45 days resulted in the development of porphyria in rats, which biochemically closely resembles symptomatic porphyria in humans, with elevation of urinary uroporphyrin excretion, hepatic uroporphyrin content, and hepatic cytochrome P-450 content, in addition to appearance of porphyrins of the isocoproporphyrin (P1) series in the faeces. 3. Spectral studies of the induced hepatic cytochrone P-450 at 45 days with carbon monoxide and ethyl isocyanide as ligands indicated the presence of a greater admixture of a haemoprotein distinct from cytochrome P-450. 4. Study in vitro of the kinetics of two reactions, namely aminopyrine N-demethylation and 3,4-benzpyrene hydroxylation, catalysed by the hepatic microsomal cytochrom P-450-dependent enzyme system, suggested that hexachlorobenzene induced a form of cytochrome P-450-dependent enzyme system, suggested that hexachlorobenzene induced a form of cytochrome P-450 with different catalytic properties from those of forms induced by either phenobarbital or 3-methylcholanthrene.
Clin Sci Mol Med 1978 Nov
PMID:The nature of hepatic cytochrone P-450 induced in hexachlorobenzene-fed rats. 71 99

1. The effect on respiration of a single dose of propranolol has been studied in normal subjects. 2. The degree of beta-adrenoreceptor blockade was assessed in terms of the impaired heart-rate response to progressive exercise and the plasma propranolol concentration. 3. No effect of propranolol was demonstrated on either the ventilatory response to rebreathing CO2 in hyperoxia, or the response to progressive isocapnic hypoxia. Simple indices of maximal expiratory flow (FEV 1.0% and PEFR) were also unchanged. 4. The absence of any effect of propranolol on the chemical control of breathing in man is discussed in relation to the conflicting literature.
Clin Sci Mol Med 1978 Nov
PMID:Propranolol and the ventilatory response to hypoxia and hypercapnia in normal man. 72 3

Transplantable rat liver tumors 5123 t.c., 7288 ct.c., 5123 t.c.(H) and the Novikoff hepatoma have active mixed function oxidase systems capable of metabolizing a variety of drug and polycyclic hydrocarbon substrates. The tumor drug metabolism systems are at best 20% as active as rat liver. The tumor drug metabolism activities are induced by pretreatment with phenobarbital or beta-naphthoflavone and can be inhibited with specific inhibitors such as carbon monoxide or 7,8-benzoflavone. Tumor drug metabolism systems appear to consist of cytochrome P-450 and cytochrome P-450 reductase. The properties of the two protein components from tumors are highly similar to the corresponding components of the liver drug metabolism system. Cytochrome P-450 reductase has been at least partially purified from the Novikoff hepatoma and hepatoma 5123 t.c.(H). The kinetic and physical properties of the tumor reductases are similar to those of the liver reductase except that the Km of hepatoma 5123 t.c.(H) reductase, but not of the Novikoff hepatoma reductase for NADPH, is elevated an order of magnitude over the Km of the liver reductase. The mechanism for the interaction of electron donor and electron acceptor with liver or tumor reductases seems to be a sequential reaction mechanism. Experiments on the NADP-inhibition of the interaction of NADPH and cytochrome c with liver reductase indicate that NADP is competitive with NADPH and noncompetitive with cytochrome c. This result is consistent with the postulate of a sequential reaction for NADPH-cytochrome P-450 reductases of liver and tumors. These data support the conclusions that an active drug metabolism system is present in liver tumors and that the tumor systems are constituted like the liver system.
Mol Cell Biochem 1978 Dec 22
PMID:The drug metabolism systems of liver and liver tumors: a comparison of activities and characteristics. 74 99


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