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Biomedical subjects

G Cohen

Publications and source records attributed to G Cohen.

At least 235 records · Page 13Linked to original sources
PubMed1990

Fate of highly expressed proteins destined to peroxisomes in Saccharomyces cerevisiae.

Import of proteins into organelles usually requires a cis-acting targeting signal. Analysis of various hybrid proteins, consisting of mouse DHFR and parts of catalase A from Saccharomyces cerevisiae, revealed that fusion proteins containing the N-terminal 126 amino acids, or less, of catalase A remain in the cytosol whereas fusion proteins containing 140, or more, N-terminal amino acids of catalase A form large aggregates inside the cell. These protein bodies, which lack a surrounding membrane, copurified with peroxisomes on cell fractionation. The peroxisomal targeting signal of catalase A does not reside at the C-terminus or at the N-terminus.

Amino Acid Sequence↗
PubMed1990

Effects of CBDP and MEPQ on the toxicity and distribution of [3H]-soman in mice.

Soman poisoning presents a problem in terms of its detailed pathophysiology and its detoxification mechanism(s). The present study was designed to evaluate the role of carboxylesterases (CaE) and cholinesterase (ChE) in the distribution and detoxification of soman in vivo. Mice were injected (i.v.) with 0.06-1.0 LD50 of [3H]-soman, 60 min following pretreatment with either 2-O-cresyl-4H-1:2:3 benzodioxa-phosphorine-2-oxide (CBDP), which blocks CaE or 7-(methylethoxyphosphinyloxy)-1-methyl quinolinium iodide (MEPQ), which selectively inhibits intravascular ChE. One hour after [3']-soman administration animals were sacrificed and whole body autoradiography was performed. High concentrations of [3H]-soman were found in lung and kidney in control mice, and low concentrations were found in central nervous system. Pretreatment with CBDP caused a 93% decrease in radioactive labelling in the lung, and a minor decrease in overall labelling, whereas pretreatment with MEPQ did not change the distribution pattern of [3H]-soman. It is concluded that lung is a major target organ for soman detoxification and that it exerts this effect by means of enzymatic reaction with soman through the abundant amounts of CaE which are present in the lung. Intravascular ChE has little (if any) effect on the distribution and detoxification of soman in vivo.

Animals↗
PubMed1990

Microbial isopenicillin N synthase genes: structure, function, diversity and evolution.

Clinically and economically, penicillins and cephalosporins are the most important class of the beta-lactam antibiotics. They are produced by a wide variety of microorganisms including numerous species of Streptomyces, some unicellular bacteria and several filamentous fungi. A key step common to their biosynthetic pathways is the conversion of a linear, cysteine-containing tripeptide to a bicyclic beta-lactam antibiotic by isopenicillin N synthase. Recent successes in the cloning and expression of isopenicillin N synthase genes now permit production of a plentiful supply of this enzyme, which may be used for structural and mechanistic studies, or for biotechnological applications in the creation of novel beta-lactam compounds from peptide analogues. New ideas concerning the evolution and prevalence of the penicillin and cephalosporin biosynthetic genes have emerged from studies of isopenicillin N synthase genes.

Amino Acid Sequence↗
PubMed1990

Iron toxicosis.

Explore the source record for details and available documents.

Animals↗
PubMed1990

Evolution of isopenicillin N synthase genes may have involved horizontal gene transfer.

The isopenicillin N synthase genes from three fungal species, three Gram-positive species, and one Gram-negative bacterial species share an unusually high sequence similarity. A phylogenetic analysis was carried out to determine which type of evolutionary scenario best accounts for this similarity. The most plausible scenario is one in which a horizontal gene-transfer event, from the prokaryotes to the eukaryotes, occurred at a time close to the divergence between the Gram-positive and the Gram-negative bacteria.

Amino Acid Sequence↗
PubMed1990

Ventricular abnormalities in affective disorder: clinical and demographic correlates.

Ventricle-brain ratio was measured by CT scan in 24 bipolar patients, 27 unipolar patients with major depression, 108 schizophrenic patients, and 75 normal control subjects. The male bipolar patients had significantly larger ventricles, but the depressive patients did not. The findings suggest the possibility that ventricular enlargement in bipolar patients is independent of age, as it appears to be in schizophrenia, whereas in depressed patients it may be related to the aging process. Ventricular enlargement in bipolar patients was not related to relevant clinical correlates, such as response to treatment, history of substance abuse, history of ECT, or cognitive impairment.

Adult↗
PubMed1990

Vasodilator activity of endothelin-1 and endothelin-3: rapid development of cross-tachyphylaxis and dependence on the rate of endothelin administration.

In pentobarbital anesthetized cats, i.v. bolus injections of endothelin-1 (ET-1, 1 microgram) and ET-3 (3 micrograms) produced a rapidly appearing but short-lasting fall in aortic blood pressure followed in the case of ET-1 only by a small pressor response. When these peptides were administered repeatedly after 10- to 12-min intervals, there was a gradual attenuation of the hypotension that by the fourth injection was replaced by a monophasic pressor response. The i.v. infusion of ET-1 (0.3 microgram/min) or ET-3 (0.9 microgram/min) for 20 min produced sole systemic vasoconstriction. The decrease in blood pressure produced by an i.v. bolus injection of ET-1 and ET-3 was no longer observed 5 min after the end of the ET-1 or ET-3 infusion. In contrast, the hypotensive activity of bradykinin was not modified after the depressor responses to ET-1 and ET-3 had disappeared. Thus, the failure of i.v. bolus injections of ET-1 and ET-3 to lower blood pressure under these experimental conditions cannot be attributed to the development of tachyphylaxis to endogenous endothelium-derived relaxant factor, which is known to mediate the effects of bradykinin. These results suggest that ET-1 and ET-3 share a single vascular receptor for vasodilation, which becomes refractory upon repeated or maintained exposure to these peptides. Alternatively, this refractoriness may be due to depletion of an intracellular mediator(s) that is jointly used by the membrane binding sites of ET-1 and ET-3. Moreover, the present data suggest that the vasodilator activity of ETs depends on the rate of the peptide administration.

Animals↗
PubMed1990

A modified rebreathing method to study the ventilatory response of the newborn to carbon dioxide.

Measurement of the ventilatory response of the newborn to carbon dioxide using the rebreathing method usually involves raising the concentration of oxygen in the inspired gas in order to prevent hypoxaemia developing during the test. Described here is a modified rebreathing method which avoids the need to use hyperoxic gas mixtures. Subjects rebreathed 5-7% carbon dioxide in air for 1.5-3 min; hypoxaemia was prevented by the addition of oxygen to the rebreathing circuit at the rate of approximately 7 ml/min per kg body weight. Arterial oxygen saturation (measured by a pulse oximeter) was maintained at approximately 95% throughout the tests. The technique was successfully used to study the ventilatory responses of eight full-term and 4 pre-term babies during behaviorally defined rapid-eye movement and quiet sleep. The reproducibility of the ventilatory response measured by this method was evaluated by repeated testing of each subject. This revealed considerable variability in the magnitude of the response from test to test. Some of the factors which might contribute to this variability are discussed.

Carbon Dioxide↗
PubMed1989

Genetic analysis of the lytic replicon of bacteriophage P1. I. Isolation and partial characterization.

Despite the extensive genetic analysis of bacteriophage P1, the region of the viral genome that is responsible for its lytic (vegetative) replication has not been identified. In this paper we describe the identification of various fragments of P1 DNA that can replicate an otherwise replication-defective lambda vector when they are cloned into that vector. The fragments share a 2800 base-pair segment of the P1 genome that is located adjacent to the immI region of the phage. Replication mediated by the cloned P1 fragments is abolished by the product of the P1 c1 gene, the repressor of phage lytic functions. Since these properties resemble those of the P1 lytic replicon, we suggest that the 2800 base-pair segment identified here contains that replicon.

Base Composition↗
PubMed1989

Genetic analysis of the lytic replicon of bacteriophage P1. II. Organization of replicon elements.

The region of bacteriophage P1 DNA containing a lytic (vegetative) replicon has been identified by cloning P1 fragments into a phage lambda vector. We present the sequence of that replicon. Using a novel fusion vector containing two P1 loxP recombination sites, we have developed a transformation assay for replicon function and have used that assay to identify some of the components of the P1 lytic replicon. Among those components is a transcription promoter, P53, whose activity is essential for replicon function. When that promoter is inactivated by the binding of P1 repressor to an operator site, Op53, whose sequence overlaps the promoter, replicon function is blocked. The P53 promoter can be replaced for replicon function by other promoters and, when the lacZ promoter was used, the extent of replication was shown to be proportional to promoter activity. Two open reading frames are located downstream from P53. The promoter-proximal reading frame is 266 amino acid residues long and is not essential for replicon function. In fact, expression of that open reading frame either interferes with plasmid establishment after transformation or is lethal to cells. The promoter-distal reading frame, designated the repL open reading frame, is either 269 or 281 amino acid residues long and is essential for replicon function. Insertion of a Tn5 transposon into the 266 amino acid residue open reading frame inactivates the cloned lytic replicon probably by interfering with the transcription of the repL open reading frame from P53. In P1, this Tn5 insertion mutation completely blocks lytic replication, indicating that the replicon identified here is either the only P1 lytic replicon or, if not, is at least necessary for the function of any other lytic replicon. A four base insertion in the repL open reading frame has largely the same inhibitory effect on phage lytic replication as the Tn5 insertion.

Base Sequence↗
PubMed1989

Deprenyl suppresses the oxidant stress associated with increased dopamine turnover.

Tissue glutathione disulfide (GSSG) was studied as an index of changes in redox state in the striatum. When increased turnover of dopamine was provoked in mice by injection of haloperidol (1 mg/kg), the concentration of GSSG in the striatum tripled. Deprenyl (2.5 mg/kg) suppressed the rise in GSSG by 71.9%. These results indicate that deprenyl suppresses an oxidant stress associated with increased dopamine turnover.

Animals↗
PubMed1989

Prenatal relationship of surfactant lipid and protein constituents in infants with respiratory distress syndrome: a preliminary communication.

The prenatal relationships between surfactant disaturated phosphatidylcholine (DSPC) and surfactant-associated proteins of preterm infants with respiratory distress syndrome (RDS) have not been well documented. In the present study we measured the concentration of DSPC, surfactant glycoproteins (GP), and surfactant proteolipids (PLP) in amniotic fluids obtained within 6 hours prior to delivery of 16 newborn infants with gestational ages between 27 and 32 weeks. In control infants of 27-32 weeks gestation without RDS, the values of DSPC, GP, and PLP per milliliter of amniotic fluid were 20 +/- 2.9 micrograms, 684 +/- 115.3 ng and 289 +/- 62.5 ng, respectively. These values were significantly higher, threefold for PLP, fourfold for DSPC, and fivefold for GP, than amniotic fluid levels in infants with RDS. The findings support the concept that immaturity of surfactant in RDS involves both phospholipids and surfactant-associated proteins. Measurements of surfactant lipid-protein complex appear to enhance the reliability for identifying prenatally, infants at risk of developing hyaline membrane disease. More extensive studies are warranted to assess the usefulness of these assays for clinical application.

Amniotic Fluid↗
PubMed1989

In vivo formation of hydroxyl radicals following intragastric administration of ferrous salt in rats.

Accidental poisoning by oral iron preparations is a serious problem in young children. We investigated the formation of hydroxyl radicals (.OH) in rats after intragastric instillation of ferrous sulfate. .OH was detected via its reaction with intragastrically administered 2-keto-4-methylthiobutyrate to generate ethylene gas. Ascorbic acid is typically present in oral iron preparations in order to facilitate absorption by maintaining iron in the reduced state. However, ascorbate possesses two properties that can affect .OH, recycling of oxidized iron to the ferrous state augments .OH production, while ascorbate in high concentration scavenges .OH. In experiments conducted in vitro, both actions were evident, depending upon the concentration of ascorbate. In parallel experiments conducted in vivo, the scavenging action of ascorbate was more prominent. Experiments in vitro with .OH-scavengers (dimethylsulfoxide, ethanol) and with the enzyme, catalase, confirmed both the presence of .OH and its dependence upon generated hydrogen peroxide during the oxidation of ferrous salt by molecular oxygen. Hydroxyl radicals (and/or reactive higher oxidation states of iron) may play a role in tissue damage after accidental overdose of oral iron.

Administration, Oral↗
PubMed1989

Age differences in source forgetting: effects on reality monitoring and on eyewitness testimony.

Age differences in memory for the source of memories were investigated using two different experimental paradigms. Experiment 1 used a reality monitoring paradigm. A series of actions were either performed, imagined, or watched, and subjects were later tested for their ability to recognize the actions and identify their origins. Elderly subjects made more false positive responses than did young subjects, and they made more source confusion errors, attributing actions to the wrong sources. Both new and imagined actions were most often misclassified as watched. Experiment 2 used an eyewitness testimony paradigm. After watching a film, subjects read a written version of the story. A recognition test showed that elderly subjects were more often misled by false information in the story than were the younger subjects, and were more confident that their erroneous responses were correct. The findings suggest that a decline in memory for sources may diminish the accuracy of elderly witnesses.

Adult↗
PubMed1989

Dopamine turnover and glutathione oxidation: implications for Parkinson disease.

Parkinson disease is characterized by a major loss (approximately 80% or more) of dopaminergic nigrostriatal neurons and by an increased turnover of neurotransmitter by surviving neurons of the nigrostriatal tract. In theory, increased turnover of dopamine should be associated with an oxidative stress derived from increased production of hydrogen peroxide. The peroxide is formed during the oxidative deamination of dopamine by monoamine oxidase. In experiments with mice, increased presynaptic turnover of dopamine was evoked by injection of reserpine, which interferes with the storage of dopamine in synaptic vesicles. Loss of dopamine and formation of deaminated metabolites were accompanied by a significant rise (87.8%) in the level of oxidized glutathione in brain. This change was observed in the striatum, which is richly innervated by dopamine terminals, but not in the frontal cortex, which receives a much sparser innervation by catecholamine nerve terminals. The rise in oxidized glutathione was seen even though dopamine terminals constitute only 1% or less of the mass of the striatum. Clorgyline, an inhibitor of monoamine oxidase type A, blocked the formation of oxidized glutathione. These observations confirm that a selective increase in neurotransmitter turnover within nigrostriatal nerve terminals can evoke a change in cellular redox status. We suggest that an oxidative stress may play a role in the natural history of Parkinson disease.

Animals↗
PubMed1989

Acute leukemia presenting as a unilateral exudative retinal detachment.

The leukemias commonly involve the eyes and adnexae. It is unusual, however, for leukemia to present with visual complaints. Furthermore, there are only rare case reports of leukemic patients presenting with bilateral exudative retinal detachments. We report a unique case of a boy who presented with visual loss due to a unilateral exudative retinal detachment. A systemic evaluation discovered acute lymphocytic leukemia (ALL). There was rapid settling of the exudative detachment and improvement in vision while the patient received chemotherapy and radiotherapy for the ALL.

Biopsy↗