PubMed Health⌕ Search

Biomedical subjects

D L Beckman

Publications and source records attributed to D L Beckman.

At least 19 recordsLinked to original sources
PubMed1992

DNA gyrase activities from Rhodobacter capsulatus: analysis of target(s) of coumarins and cloning of the gyrB locus.

Bacterial DNA gyrase is composed of two subunits, gyrase A and B, and is responsible for negatively supercoiling DNA in an ATP-dependent manner. The coumarin antibiotics novobiocin and coumermycin are known inhibitors of bacterial DNA gyrase in vivo and in vitro. We have cloned, mapped, and partially sequenced Rhodobacter capsulatus gyrB which encodes the gyrase B subunit that is presumably involved in binding to coumarins. DNA gyrase activities from crude extracts of R. capsulatus were detected and it was shown that the R. capsulatus activity is (1) inhibited by novobiocin and coumermycin, (2) ATP-dependent and, (3) present in highly aerated and anaerobically grown cells. We previously observed that when R. capsulatus coumermycin-resistant strains are continuously recultured on media containing coumermycin they sometimes acquired mutations in hel genes (i.e., cytochromes c biogenesis mutations). We discuss the possibility that coumarins may inhibit cytochromes c biogenesis as a second target in R. capsulatus via hel (i.e., a putative ATP-dependent heme exporter).

Adenosine Triphosphate↗
PubMed1992

Bacterial cytochromes c biogenesis.

We report the primary sequence analyses of two loci, hel and ccl, whose gene products are required specifically for the biogenesis of c-type cytochromes in the Gram-negative photosynthetic bacterium Rhodobacter capsulatus. Genetic and molecular analyses show that the hel locus contains at least four genes, helA, helB, helC, and orf52, and the ccl locus contains two genes, ccl1 and ccl2, that are essential for cytochromes c biogenesis. HelA is homologous to a class of proteins called ABC transporters and helA, helB, and helC are proposed to encode an export complex. Cytochrome c2-alkaline phosphatase gene fusions were used to show that apocytochrome c2 synthesis and secretion are not affected by the hel and ccl defects. Ccl1 and Ccl2 possess typical signal sequences to direct them to the periplasm. The periplasmic orientation of Ccl1 was confirmed using a Ccl1-alkaline phosphatase gene fusion. The Ccl1-alkaline phosphatase gene fusion analysis also demonstrated that Ccl1 does not require hel genes for its synthesis and secretion. Ccl1 is homologous to proteins encoded by chloroplast and mitochondrial genes, suggesting analogous functions in these organelles. Taken together, these results support the hypothesis that the hel-encoded proteins are required for the export of heme to the periplasm where it is subsequently ligated to the c-type apocytochromes.

Alkaline Phosphatase↗
PubMed1991

A bacterial homolog to HPRT.

The deduced 182 amino acid sequence of an open reading frame in the photosynthetic bacterium Rhodobacter capsulatus shows significant similarity to the hypoxanthine-guanine phosphoribosyltransferases of other organisms. This similarity includes conserved amino acid residues involved in Lesch-Nyhan syndrome.

Amino Acid Sequence↗
PubMed1991

A bacterial homolog to the mitochondrial enoyl-CoA hydratase.

A 257-amino acid (aa) open reading frame in the photosynthetic bacterium, Rhodobacter capsulatus, shows significant homology to the mitochondrial enoyl-CoA hydratase (290 aa). This similarity in size and sequence suggests that R. capsulatus oxidizes fatty acids using specific components, more like the mitochondrial system than the multifunctional component system of Escherichia coli.

Amino Acid Sequence↗
PubMed1987

Neurogenic pulmonary edema in a pulmonary normotensive model.

In the present study our aim was to determine whether or not neurogenic pulmonary edema would develop from a brief pulse of intracranial pressure (ICP) in the absence of any obvious pulmonary hypertension. There were three groups of cats: sham-operated controls, ICP only, and ICP plus variable occlusion of the pulmonary artery. Partial occlusion of the pulmonary artery was carried out by placing a ligature around the pulmonary trunk and mechanically constricting the artery to maintain pulmonary arterial pressure (PAP) and left atrial pressure (LAP) at pre-ICP levels. In sham-operated animals the extravascular lung water/blood free dry weight ratio (EVLW/BFDW) was 3.26 +/- 0.07 and broncho-alveolar lavage (BAL) protein, 6.49 +/- 0.62 mg/g lung. ICP-only caused a rise in PAP, left atrial pressure, and EVLW/BFDW to 3.67 +/- 0.08 (P less than 0.05). ICP with partial occlusion of the pulmonary artery prevented any rise in PAP or LAP while EVLW/BFDW rose to 3.67 +/- 0.10 (P less than 0.05) and BAL protein was 8.37 +/- 1.27 mg/g lung. Our results show that EVLW/BFDW can increase with neurogenic pulmonary edema in cats in the absence of an obvious increase in pulmonary arterial or left atrial pressure.

Animals↗
PubMed1986

Cardiopulmonary response to an induced pulse in intracranial pressure.

Increased intracranial pressure may result in the Cushing response. We applied a short pulse of pressure to the cranial cavity of anesthetized cats which were intubated, curarized, ventilated, and the cranium exposed to an 80- to 100-msec pulse of pressure at 5.3 atm. The following significant increases developed: Intracranial pressure rose from 7.4 +/- 1.5 to 150.6 +/- 19.4 mm Hg, systolic arterial peak pressure from 130.7 +/- 8.1 to 299.0 +/- 11.4, pulmonary peak pressure from 18.9 +/- 1.9 to 42.9 +/- 4.9. Alveolar lavage protein in controls was 6.7 +/- 0.4 mg/g lung compared to 11.9 +/- 2.0 in the experimental group. Extravascular lung water/dry weight ratios increased from 3.36 +/- 0.04 in controls to 3.51 +/- 0.09 but varied inversely with pulmonary systolic peak pressure (r = 0.59). These results showed that a pulse of pressure applied to the cranium of cats produced lung edema which was inversely related to pulmonary artery pressures.

Animals↗
PubMed1984

Stellate ganglion stimulation with alpha and beta adrenergic blockade: effect on lung lipids and compliance in cats.

Stellate ganglion stimulation (SGS) can alter lung lipids and reduce static lung compliance, although the mechanisms remain unclear. Phentolamine and propranolol were administered to anesthetized cats prior to stimulation in order to investigate SGS effects on lung lipids and compliance mediated via alpha and beta adrenergic pathways. Analysis of lung lavage revealed that SGS alone decreased cholesterol and the cholesterol/DSPC ratio which might be expected to decrease lung compliance. Alpha and beta blockade alone resulted in no changes from control in cholesterol or DSPC. Alpha blockade plus SGS yielded increased rather than decreased cholesterol and DSPC, while beta blockade prevented any change. A reduction in both static and dynamic lung compliance caused by SGS also was blocked by both alpha and beta blockade. Thus both the alpha and beta blockade prevented the SGS-induced decreases in cholesterol, cholesterol/DSPC ratio, and lung compliance. Furthermore, alpha blockade plus SGS resulted in increased TPL as well as cholesterol and DSPC. The data are consistent with the view that DSPC and cholesterol are released into the subphase by beta adrenergic mechanisms, and that their relative amounts may influence surface properties.

Adrenergic alpha-Antagonists↗
PubMed1983

Beta adrenergic receptors and glucagon in seizures from exposure to oxygen at high pressure (OHP).

Previous studies have shown that sympathetic factors and blood glucose are of importance in the development of seizures and lung damage from OHP. In the present study we examined the influence of beta sympathetic agonists and blocking agents and glucagon on OHP toxicity. Rats were exposed to 6 ATA OHP and examined for time-to-seizure and lung damage. Pretreatment with propranolol increased the time-to-seizure by 70% and practolol by 50% without altering gross lung appearance or lung wet wt/dry wt. Propranolol and practolol also prevented brain glycogen depletion prior to seizure which otherwise occurred in subconvulsive exposure to OHP. Isoproterenol and glucagon pretreatment had no effect on time-to-seizure but isoproterenol did increase lung injury. Both practolol and propranolol block the beta-receptor influence on adenyl cyclase-stimulated second messenger production, while both isoproterenol and glucagon activate adenyl cyclase to produce second messenger. Our results may suggest a possible role for second messenger in mediating some of the acute toxic effects of OHP on the CNS.

Animals↗
PubMed1979

Lung compliance and cholesterol during stellate ganglion stimulation.

The relationships between lung compliance, surface tension, and cholesterol during stimulation of the sympathetic nervous system were studied in 28 cats. Cats were anesthetized with ketamine hydrocholoride, injected with one of five sympathetic blocking agents or inhibitors and injected with isoprotenol. The left stellate ganglion was then stimulated electrically for 5 min. We found that stimulation decreased lung compliance and increased the surface tension and the cholesterol concentration in the lung wash fluid. Alpha blockers (phentolamine and phenoxybenzamine) and catecholamine inhibitors (reserpine and guanethidine) prevented these changes, but the beta blocker practolol did not. In additional experiments airway resistance, functional residual capacity and lung weights did not change during stellate stimulation. The results from the present study suggest that stellate ganglion stimulation resulted in decreased lung compliance with an increased surface tension and cholesterol in lung wash fluid.

Animals↗
PubMed1978

Rat lung hyper-reactivity to stress.

Rats have been used frequently as a model for determining the pulmonary response to various stressful situations. It has been shown in the literature that rat lungs are remarkably sensitive to factors which result in the development of gross pulmonary injury, such as stress from exposure to hyperbaric oxygen. Similarly, a high degree of pulmonary reactivity was found in rats after administration of various CNS, convulsants and also exposure to mechanical vibration. The present study was confined to a determination of the gross pulmonary response of rats exposed to mechanical CNS traumatization compared to that of 10 other laboratory species. The frequency and severity of pulmonary injury from CNS traumatization, as indicated by lung weight/body weight ratios and gross appearance, was very striking in the traumatized rats, but we found little or no change in cats, dogs, rabbits and guinea pigs, in Rhesus, squirrel, vervet, and cynomolgus monkeys or in baboons and chimpanzees. Previous studies showed that the gross pulmonary injury from this mechanical head injury in rats, as well as from hyperbaric oxygen exposure, vibration, and CNS convulsants, was ameliorated by the prior administration of various sympathetic blocking agents. The results from the present comparative study tend to suggest that rat lungs are hyper-reactive to this stress.

Animals↗
PubMed1978

Protection against high-pressure oxygen seizures by amino-oxyacetic acid.

A variety of autonomic blocking agents, general anesthetics, and anticonvulsants have been shown to offer protection from seizures caused by hyperbaric oxygen. Amino-oxyacetic acid (AOAA) has been shown to offer rats only minimal protection from such seizures. This study investigated whether AOAA protected cats and mice from hyperbaric-oxygen-induced seizures. Cats and mice were exposed to 100% oxygen at 5 ATA until seizures occurred or for a period of up to 60 min. Approximately half of the animals were pretreated with AOAA either 30 or 240 min before oxygen exposure. Results showed that the interval between exposure and grand mal seizures increased significantly in cats pretreated 30 or 240 min before exposure with 17 to 25 mg/kg AOAA; the number of cats remaining seizure-free for 60 min also increased markedly. However, mice received little protection even at doses up to 40 mg/kg. At higher doses the AOAA itself caused seizures even in the absence of hyperbaric oxygen.

Acetates↗
PubMed1976

Aspiration pneumonitis and pulmonary phospholipids.

Peptic aspiration pneumonitis (Mendelson's syndrome) results when gastric acid is aspirated into the lung, as may occur during anesthesia. In the present study, 0.1 N HCl was insufflated via the endotracheal tube into pentobarbital-anesthetized dogs in an amount sufficient to cause severe pulmonary damage. At death, the thorax was opened, the lungs grossly examined, and either weighed and desiccated for determination of wet/dry lung weight ratios, rinsed with saline for removal of alveolar surface phospholipids, or homogenized for whole lung phospholipid determination. Gross appearance and wet/dry lung weight ratios indicated severe pulmonary edema. The surface tension values of the lung wash were elevated over control values. Lysophophatidyl-choline (LPC) showed a striking increase over control values. Because LPC is a potent hemolytic agent which builds up in the lung following this pulmonary insult, and because increased hemorrhaging gradually develops following experimental acid insufflation, it is concluded that LPC is most probably causally related to the hemorrhagic pneumonia of Mendelson's syndrome.

Animals↗
PubMed1975

Pulmonary surface tension and head injury.

Previous studies have shown that exposure of monkeys to lethal experimental head injury by means of a captive-bolt mechanism results in a decreased lung compliance and a high minimum surface tension. Such changes which occurred in the absence of any increase in lung weight/body weight ratios were ameliorated by the prior administration of various sympathetic blocking agents. Exposure of monkeys and cats to stimulation of the pulmonary sympathetics via the stellate ganglion also resulted in similar compliance and surface tension changes without any increase in lung weight. The present experiments were carried out in order to determine the effect of lethal mechanical head injury in the cat on the surface tension of the alveolar lining layer and reasons for any possible changes. Previous reports have shown that the addition of very small amounts of cholesterol to lung wash fluid raised the minimum surface tension to abnormal levels. The results from the present study show that a sudden lethal blow to the occiput in cats results in an abnormally high minimum surface tension (over 20 dynes/cm) in the lung wash fluid and a nearly 200% increase in cholesterol content. There was little or no change in lung wet weight/dry weight ratios or gross lung appearance following this head injury. Thus the results from the present study strongly suggests that the previously reported decreased lung compliance and high minimum surface tension following a blow to the head may be due in part at least to the presence of increased intra-alveolar cholesterol.

Animals↗
PubMed1975

Neurogenic influence on pulmonary surface tension and cholesterol in cats.

Previous work showed that stress involving the sympathetic nervous system via mechanical head injury and hyperbaric oxygen results in a decreased lung compliance and altered alveolar surfactants. Similar changes were associated with sympathetic nerve stimulation via the stellate ganglion. In view of reports that the minimum surface tension attained by lung wash fluid is increased by very small amounts of cholesterol content of the alveoli. The results show a nearly 200% increase in intra-alveolar cholesterol as well as high minimum surface tensions following sympathetic nerve stimulation. Such changes developed in the absence of any increase in lung wet wt/dry wt ratios. The results from the present study suggest that the previously reported decreased lung compliance and increased minimum surface tension associated with sympathetic stimulation may be due at least in part to contamination of the alveolar surfactants with large amounts of cholesterol.

Animals↗
PubMed1975

Hyperbaric oxygen and pulmonary surface tension.

Previous work has shown that short-term exposure of cats to oxygen at high pressure (OHP), to the extent of overt convulsive seizures, has little or no effect on the lung appearance or lung weight but does alter the alveolar surfactants. More prolonged exposure results in hemorrhagic edema of the cat lung similar to that observed in rats after only short-term exposure. Previous work showed that sympathetic stimulation via the stellate ganglion and mechanical CNS injury results in altered surfactants attributed to increased intra-alveolar cholesterol. In the present study, cats exposed to OHP until the animals convulsed intermittently for 3 min (approximately 1 hour, 6 ATA) similarly showed altered surfactants with a high minimum surface tension and a 150% increase in intra-alveolar cholesterol. These changes also occurred in the absence of any gross lung injury. The results from the present study suggest that an important causal mechanism involved in the development of gross lung injury associated with prolonged OHP exposure is an initial increase in minimum surface tension due to increased intra-alveolar cholesterol.

Animals↗