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Biomedical subjects

E Joseph

Publications and source records attributed to E Joseph.

At least 37 records · Page 2Linked to original sources

An acute phase response does not elevate rat heart metallothionein levels, nor inhibit adriamycin toxicity.

An acute phase response, a group of adaptations to some types of stress, blocks injury in rodents due to hepatotoxins and agents generating arthritis-like inflammation. In contrast, this study found no protection against adriamycin-induced acute cardiotoxicity in rats. The acute phase response was initiated by turpentine-stimulated leg inflammation. Injury was assessed by survival, macroscopic signs of injury, and heart lipid peroxidation. Acute phase response produced the expected rises in the stress-responsive proteins: serum ceruloplasmin and liver metallothionein. However, cardiac metallothionein was unaffected. These results suggest that an acute phase response will not necessarily protect tissues where levels of stress-induced proteins are not raised.

Acute-Phase Reaction↗

Predictors of blinding or serious eye injury in blunt trauma.

Multivariate analysis was used to identify factors predicting injury and visual outcome in 94 blunt trauma patients evaluated for eye injuries among 6700 admissions to a level I trauma center over a 29-month period. Patients with penetrating eye injuries were excluded from this review. Eye injury was detected in 93% or 87 of the patients evaluated. Seven percent of eye injuries resulted in blindness, 22% were serious (visual acuity between 20/40 and 20/200 or eye injury requiring surgery), and 71% were temporary (final visual acuity of 20/40 or better). The presence of an afferent pupillary defect or a nonreactive pupil was the most important factor in predicting the severity of eye injury (p = 0.0023), followed by facial fractures (p = 0.0084), and no eye opening or eye opening to pain within the Glasgow Coma Scale (p = 0.02). Eye injury is an infrequent complication of blunt trauma. Appropriate consultation for evaluation of this problem can be obtained based on findings from the initial history and screening physical examination.

Adolescent↗

Keratoplasty for complicated leucomas.

Fifty cases of complicated leucomata in which keratoplasty was done during the last two years, are analysed. Although complicated cases yield not so good optical result, the results are much improved by proper pre-operative, operative and post-operative management.

Corneal Diseases↗

Role of 2-ketobutyrate as an alarmone in E. coli K12: inhibition of adenylate cyclase activity mediated by the phosphoenolpyruvate: glycose phosphotransferase transport system.

2-ketobutyrate and its analogues were found to inhibit strongly and transiently the rate of beta-galactosidase synthesis in Escherichia coli K12. This effect was ascribed to a strong and transient inhibition of the adenylate cyclase activity. By using pts mutants, we showed, in agreement with our previous results (Daniel et al. 1983), that the likely target of 2-ketobutyrate and its analogues is the phosphoenolpyruvate: glycose phosphotransferase transport system (PTS). Furthermore, evidence for such a cascade effect caused by 2-ketobutyrate and its analogues allowed us to corroborate our previous proposal (Daniel et al. 1983) that 2-ketobutyrate, a precursor of isoleucine, acts as an E. coli alarmone monitoring the passage from anaerobic to aerobic growth conditions.

Adenylyl Cyclase Inhibitors↗

Two functional domains in adenylate cyclase of Escherichia coli.

To study the regulation of Escherichia coli adenylate cyclase, plasmids that carry part of the cya gene, as well as plasmids containing hybrid genes having part of cya fused to part of lacZ, were constructed. This allowed us to propose that the enzyme is made of at least two well-defined domains. The NH2 terminus carries the ATP leads to cAMP catalytic activity, whereas the COOH-terminal end corresponds to a regulatory polypeptide domain.

Adenylyl Cyclases↗

Effect of cholestasis produced by bile duct ligation on hepatic heme and hemoprotein metabolism in rats.

Cholestasis produced by bile duct ligation has been associated with decreased concentrations of hepatic microsomal cytochrome P450 and decreased hepatic microsomal oxidative drug metabolism. Bile duct ligation producing cholestasis results in a marked increase in hepatic microsomal heme oxygenase activity, with corresponding decreases in hepatic microsomal cytochrome P450 concentration, reduced form of nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity, and hepatic delta-aminolevulinic acid synthetase activity. As sham-operated rats also demonstrate a less prolonged decrease in cytochrome P450 concentration and reduced form of nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity, the metabolic effects of surgery and anesthesia must also be involved in these alterations in microsomal oxidative drug metabolism. The relative rate of hepatic cytochrome P450 synthesis and of degradation are both decreased after bile duct ligation. These data suggest that decreased hepatic microsomal cytochrome P450 concentrations in cholestasis are partly the result of decreased cytochrome P450 synthesis. Increased levels of heme oxygenase activity are not related to increased cytochrome P450 turnover, but may instead reflect enlargement and increased catabolism of a free heme pool resulting from decreased hemoprotein (cytochrome P450) synthesis.

5-Aminolevulinate Synthetase↗

Multiple regulation of the activity of adenylate cyclase in Escherichia coli.

We have studied the correlation between the activities of adenylate cyclase (ATP pyrophosphatelyase-(cyclizing); EC 4.6.1.1) and in vivo rates of synthesis and intracellular concentrations of adenosine 3',5' cyclic monophosphate (cAMP) under various growth conditions in wild-type Escherichia coli and in mutants lacking or overproducing the cAMP receptor protein (CAP). We showed that when wild-type bacteria are grown in the presence of a variety of carbon sources the intracellular concentrations of cAMP are inversely related to the adenylate cyclase activities determined in permeabilized cells, suggesting that the carbon source-dependent modulation of cAMP levels is not directly related to the regulation of adenylate cyclase activity. In mutants lacking functional CAP (crp) the in vivo rates of cAMP synthesis are several hundred-fold higher than in the wild-type parent without a parallel increase of adenylate cyclase activities. In a strain carrying multiple copies of the crp gene and overproducing CAP the activity of adenylate cyclase is severely inhibited, although the in vivo rate of cAMP synthesis is similar to the parental strain. We interpret these results as indicating that CAP controls mainly the activity rather than the synthesis of adenylate cyclase.

Adenylyl Cyclases↗

crpX mutants of Escherichia coli K12: specific regulatory effects of altered cyclic AMP receptor proteins.

We attempted to correlate structural modifications of the adenosine 3',5' cyclic monophosphate (cAMP) receptor protein (CAP), to changes in some of its in vivo regulatory functions such as (i) stimulation of the lactose operon expression and (ii) control of adenylate cyclase activity. A radioimmunological procedure was used to study the structure of CAP synthesized by three mutants (crpX) grown under various conditions, in the presence or absence of endogenous or exogenous cAMP. In one mutant CAP appears to be sensitive to thermal inactivation. In another mutant CAP is particularly sensitive to degradation in the absence of cAMP; this degradation is enhanced by high temperature and during stationary phase of growth, and prevented by the addition of glucose. Functional alterations of CAP were not found to follow structural changes strictly. In the crpX mutants and in strains carrying the crp+ or other crp allele, the stimulation of the lactose operon expression and the modulation of the in vivo rates of cAMP synthesis appear to vary in parallel, favoring an indirect mechanism of regulation of adenylate cyclase by CAP.

Adenylyl Cyclases↗

Transcription-translation coupling and polarity: a possible role of cyclic AMP.

Using specific mutants exhibiting altered translational rates we found that when the rate of protein synthesis is reduced the polarity of the lactose and galactose operons is increased. This polarity is in part relieved by cyclic AMP. On the basis of in vitro hybridization experiments were propose that the cyclic AMP-CAP complex and the ribosomes display similar functions, namely destabilization of the RNA-DNA hybrid formed during transcription.

Bacteria↗

Regulation of galactose operon expression: glucose effects and role of cyclic adenosine 3',5'-monophosphate.

We studied the following two aspects of the glucose effect on galactose operon expression in Escherichia coli K-12: catabolite repression and inducer exclusion. Using both inducible and constitutive strains and measuring the rate of promoter-proximal enzyme synthesis, we found that the galactose operon did not seem to exhibit catabolite repression. The only glucose effect on galactose operon expression which we observed was inducer exclusion, as shown by the existence of diauxic growth in the presence of glucose and galactose. This diauxie was not relieved by cyclic adenosine 3',5'-monophosphate. Cyclic adenosine 3',5'-monophosphate did not seem to be an antagonist of any glucose effect on galactose operon expression; its only effect was to stimulate promoter-distal gene expression.

Cyclic AMP↗