Gene/Protein Disease Symptom Drug Enzyme Compound
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 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conventional methods of organ culture have proved unsatisfactory for mammalian lung because of the rapid collapse of the tissue and the loss of its normal structure. In an effort to circumvent this problem and to provide a means for visualizing the cellular relationships throughout the culture period, respiratory organs consisting of trachea and lungs of fetal or hysterectomy-derived 1- to 4-week-old pigs were embedded in warm 3% Noble agar in phosphate buffer silicone solution and cooled to firmness. By use of a described cutting device, the respective organs were sliced into thin, 0.5- to 1.0-mm tracheal ring or lung explants. These organ sections then were cultured by exposure to alternate gaseous and liquid-medium phases by rotation (12 rev per hr) in sealed Leighton tubes fitted in a described rotator. In short-,erm culture experiments, explants were best maintained in a culture-support medium containing Eagle's minimal essential medium, 20% fetal bovine serum, 0.5% lactalbumin hydrolysate, and other supplements in a pH range of 6.5 to 8.2, and a NaCl concentration of 0.1 M or less. By bright-field and scanning-electron microscopy, tracheal ring and lung explant cultures incubated for 2 months showed intact, uniform and active ciliated epithelial surfaces which compared favorably with those of fresh preparations. The lung cultures showed alveoli that remained expanded, and the cellular integrity of the tissues remained normal in appearance. This new method provides respiratory organs as continuous records with exceptional cellular clarity and readily available for histological processing. The organ cultures lend themselves well to pathogenesis studies in which subtle cellualr changes or a sequence of changes induced in pulmonary tissues are difficult to observe in the host.
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PMID:Preparation and long-term cultivation of porcine tracheal and lung organ cultures by alternate exposure to gaseous and liquid medium phases. 2 5

The dose of 0.5 mg/kg i.v. of compound 48/80 was lethal in 97.2% of the injected rats. Observations before death and at autopsy were in accordance with the basic effect of compound 48/80 in rats i.e. the sustained release of mast cell mediators, whose action on the cardiovascular system leads to circulatory collapse. The administration of drugs with various pharmacological effects before the intravenous challenge with compound 48/80 allowed us to conclude that the following effects are not sufficient to prevent the lethal shock: inhibition of prostaglandin biosynthesis; H2-histamine antagonism; cholinergic, alpha- or beta-adrenergic blockade; beta-adrenergic stimulation; CNS-effects of antidepressants, hypnotics, sedatives, neuroleptics or narcotic analgesics; ganglion blockade; glucocorticoid or cromoglycate-like activity. Dose-dependent protection from the lethal reaction was obtained with compounds known to exert a single or several actions of the following types: oxatomide-like inhibition of mast cell mediator release; h1-histamine antagonism; serotonin antagonism. Quantitatively, however, when measured in in vitro systems these effects are poorly related to the protection from lethal compound 48/80 challenge. The new test offers the advantage of a simple, comprehensive measure of the potency of a compound to prevent mast cell-mediated shock.
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PMID:Protection of rats from compound 48/80-induced lethality. A simple test for inhibitors of mast cell-mediated shock. 3 Apr 20

Tetrahedral intermediates in the reaction of elastase with specific di- and tripeptide p-nitroanilide substrates have been detected, accumulated, and stabilized at high pH by using subzero temperatures and fluid aqueous/organic cryosolvents. The tetrahedral adducts are characterized by spectra with lambda max of 359 +/- 2 nm, compared with thata of 380 nm for p-nitroaniline and 315-320 nm for the substrates. The maximal concentration of intermediate that could be accumulated varied with the different substrates from 40 to 100% of the active enzyme present. The pH dependence of the reactions indicated that formation of the tetrahedral intermediates was rate-limiting at low pH (pK* = 7.0 at -39 degrees C) and that collapse to the acylenzymes was rate-determining at high pH. When corrected for the effect of temperature and cosolvent, the rate of intermediate formation was in good agreement with that measured at 25 degrees C in aqueous solution by stopped-flow techniques.
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PMID:Detection and accumulation of tetrahedral intermediates in elastase catalysis. 3 9

H(+)/site, charge/site, and ATP/site ratios have been determined at coupling sites I, II, and III. Three e(-) donors have been used for coupling site III: ferrocyanide, ascorbate + tetramethyl-p-phenylenediamine (TMPD), and succinate + TMPD. The H(+)/site ratios are 4.0 with ferrocyanide and 6.0 with succinate + TMPD (at pH <7.0); the charge/site ratios are 6.0 with ferrocyanide and with succinate + TMPD (at pH <7.0) and 4.0 with ascorbate + TMPD; the ATP/site ratio is 1.34 with ascorbate + ferrocyanide. These ratios have been obtained in the presence of amounts of antimycin A that provide full inhibition of site II. For coupling sites I and II, ferricyanide has been used as e(-) acceptor and succinate or NAD-linked substrates as e(-) donors. The H(+)/site ratios are 4.0 at sites I and II; the charge/site ratios are 4.0 at site I and 2.0 at site II; the ATP/site ratios are 1.0 at site I and 0.5 at site II. Two major factors affect the stoichiometries: (i) dimension of [unk](H) and (ii) supply of H(+) from the matrix. There is a correlation between collapse of [unk](H) and increase of H(+)/site and charge/site ratios. This indicates that approximation of the phenomenologic stoichiometry of the H(+) pump is obtained when flow ratios are measured at level flow. That charge/site and ATP/site ratios increase when ferrocyanide is e(-) donor and decrease when ferricyanide is e(-) acceptor is attributed to the localization of the redox couple. This leads to separation of 1 charge/e(-) when ferrocyanide is e(-) donor and to consumption of 1 charge/e(-) when ferricyanide is e(-) acceptor. To account for an extrusion of H(+) in excess of that predicted by the loop model, it is proposed that each coupling site contains a channel acting as a H(+) pump.
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PMID:H+/site, charge/site, and ATP/site ratios in mitochondrial electron transport. 3 12

1. Electron paramagnetic resonance spectra at 8-60 K of NADH-reduced membrane particles prepared from Paracoccus denitrificans grown anaerobically with nitrate as terminal electron acceptor show the presence of iron-sulfur centers 1-4 in the NADH-ubiquinone segment of the respiratory chain. In addition resonance lines at g = 2.058, g = 1.953 and g = 1.88 are detectable in the spectra of succinate-reduced membranes at 15 K, which are attributed to the iron-sulfur-containing nitrate reductase. 2. Sulphate-limited growth under anaerobic conditions does not affect the iron-sulfur pattern of NADH dehydrogenase or nitrate reductase. Furthermore respiratory chain-linked electron transport and its inhibition by rotenone are not influenced. These results contrast those observed for sulphate-limited growth of P. denitrificans under aerobic conditions [Eur. J. Biochem. (1977) 81, 267-275]. 3. Proton translocation studies of whole cells indicate that nitrite increases the proton conductance of the cytoplasmic membrane, resulting in a collapse of the proton gradient across the membrane. Nitrite accumulates under anaerobic growth conditions with nitrate as terminal electron acceptor; the extent of accumulation depends on the specific growth conditions. Thus the low efficiencies of respiratory chain-linked energy conservation observed during nitrate respiration [Arch. Microbiol. (1977) 112, 17-23] can be explained by the uncoupling action of nitrite.
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PMID:Anaerobic respiration and energy conservation in Paracoccus denitrificans. Functioning of iron-sulfur centers and the uncoupling effect of nitrite. 3 82

Liver mitochondria treated with N-ethylmaleimide can accumulate Ca2+ but cannot retain it. Ca2+ loss following uptake occurs in parallel with a proton uptake and collapse of the membrane potential. Respiration is not activated during Ca2+ release and cannot be stimulated by uncoupler. After Ca2+ release and accompanying phenomena are nearly complete, the mitochondria undergo a large amplitude swelling. Nupercaine inhibits the premature release of Ca2+, proton uptake, decline in membrane potential, inhibition of uncoupler-stimulated respiration, and large amplitude swelling. Ruthenium red also prevents these effects. Neither Sr2+ or Mn2+ will substitute for Ca2+ to induce these effects in N-ethylmaleimide-treated mitochondria. The effects of N-ethylmaleimide plus Ca2+ on mitochondria are not accompanied by a significant alteration in the content or composition of phospholipids but are accompanied by small increases in the mitochondrial content of free fatty acids. Free fatty acids accumulate more rapidly in response to limited Ca2+ loading in the absence of N-ethylmaleimide than they do in its presence. In the absence of N-ethylmaleimide, polyunsaturated fatty acids and saturated plus monounsaturated fatty acids accumulate at nearly equal rates. In the presence of N-ethylmaleimide, polyunsaturated fatty acids accumulate more rapidly than saturated plus monounsaturated fatty acids. Any condition or agent tested which inhibited swelling and the other effects produced by Ca2+ plus N-ethylmaleimide also prevented the more rapid accumulation of polyunsaturated, compared to saturated plus monounsaturated, fatty acids. In the light of a positional analysis of phospholipid acyl moieties, these data suggest that 1-acyllysophospholipids accumulate in swelling mitochondria but not in response to noraml Ca2+ loading or when swelling is blocked by other agents. The free fatty acid accumulation, per se, is not responsible for swelling, but levels of exogenous palmitic acid as low as 1 nmol/mg of protein dramatically alter the dependence of swelling velocity on Ca2+ concentration, producing a shift from a sigmoidal- to a hyperbolic-like relationship. This same alteration is brought about by aging the mitochondrial preparation at 0 degrees C. Either pyruvate or DL-carnitine prevents the effect of exogenous palmitate and restores the Aa2+ swelling dependence of aged N-ethylmaleimide-treated mitochondria to that of fresh N-ethylmaleimide-treated mitochondria. Intramitochondrial acylcoenzyme A or acylcarnitine, or both, therefore, to be the modulator of Ca2+ sensitivity rather than free fatty acid. The findings are discussed in terms of the role of intramitochondrial phospholipase and other phospholipid metabolizing enzymes in the mechanisms of N-ethylmaleimide plus Ca2+ effects on mitochondria.
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PMID:Intramitochondrial phospholipase activity and the effects of Ca2+ plus N-ethylmaleimide on mitochondrial function. 4 Sep 83

A method is described for the direct measurement of changes in luminal diameter at all levels of the airway. Using this method it was found that (i) abrupt bronchiolar collapse occurred in the preterminal and terminal bronchioles once the luminal diameter was reduced to a critical level: (ii) decreased temperatures resulted in airway narrowing which was reversed by increasing the temperature to above 25 degrees C; as a rule, airway narrowing followed a cranial to caudal direction, and higher concentration of a drug being required to close the peripheral airways; (iii) bronchodilators except Carbuterol had no effect on resting bronchial tone or on acetylcholine-induced constriction in the absence of alpha-adrenoceptor blockade; (iv) at 35 degrees C rhythmic waves (frequency 6--20/min) were observed; these waves travelled from the periphery in a cranial direction.
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PMID:Direct determination of luminal diameter changes in intrapulmonary airways. 4 29

The study of twenty patients with poisoning by central nervous system depressant drugs is reported. The authors emphasized clinical aspects, complications and mainly the lung function impairment. Barbiturates were the most common drugs, at least in 60% of the cases, used alone or in combination with sedatives and tranquilizers. In 55% of patients the amount of the drug ingested could not be measured. In 60% of the cases we didn't know the period of time between drug ingestion by the patients and their admission to the hospital. On admisson all patients were in coma. The coma was of varying degrees and the deeper the coma the worse was lung function and complications were more frequent. Whenever a cardiovascular collapse was present there was also a high mortality rate. The authors emphasized the importance of a follow-up of these patients in intensive care units, mainly with cardiovascular and ventilatory support.
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PMID:[Acute respiratory insufficiency associated with the ingestion of central nervous system depressants]. 4 18

A study of elderly patients (fourteen men, sixteen women) who were admitted to hospital with acute illness and extreme self-neglect revealed common features which might be called Diogenes syndrome. All had dirty, untidy homes and a filthy personal appearance about which they showed no shame. Hoarding of rubbish (syllogomania) was sometimes seen. All except two lived alone, but poverty and poor housing standards were not a serious problem. All were known to the social-services departments and a third had persistently refused offers of help. An acute presentation with falls or collapse was common, and several physical diagnoses could be made. Multiple deficiency states were found--including iron, folate, vitamin B12, vitamin C, calcium and vitamin D, serum proteins and albumin, water, and potassium. The mortality, especially for women, was high (46%); most of the survivors responded well and were discharged. Half showed no evidence of psychiatric disorder and possessed higher than average intelligence. Many had led successful professional and business lives, with good family backgrounds and upbringing. Personality characteristics showed them to tend to be aloff, suspicious, emotionally labile, aggressive, group-dependent, and reality-distorting individuals. It is suggested that this syndrome may be a reaction late in life to stress in a certain type of personality.
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PMID:Diogenes syndrome. A clinical study of gross neglect in old age. 4 14

We wish to determine what cellular and functional alterations are associated with the development of glomeruloscierosis when rats with one kidney are fed an excess of salt or protein. Rats with one kidney are more likely to develop pronteinuria and glomerulosclerosis than control animals. Blood pressure recordings indicate that proteinuria and glomerulosclerosis occur before hypertension is evident. Fluorescent antibody studies disclose that albumin accumulates in the epithelial cells of glomeruli and tubules. Ultrastructural examination shows that vacuolozation of epithelial cells and basement membrane thickening precede the sclerotic collapse of capillary loops. Increased concentrations of sodium or urea that are found in urines of these rats favor the point of view that an elevation of solute load when combined with a reduction of renal mass will on some unknown manner accelerate the deterioration of glomeruli.
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PMID:Protein overload nephropathy in rats with unilateral nephrectomy. A correlative light immunogluorescence and electron microscopical analysis. 4 49


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