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Biomedical subjects

E Alvarez

Publications and source records attributed to E Alvarez.

At least 217 records · Page 12Linked to original sources

Glucokinase-deficient mutant of Penicillium chrysogenum is derepressed in glucose catabolite regulation of both beta-galactosidase and penicillin biosynthesis.

One glucokinase-deficient mutant (glk1) of Penicillium chrysogenum AS-P-78 was isolated after germ tube-emitting spores were mutated with nitrosoguanidine and selected for growth on lactose-containing medium in the presence of inhibitory concentrations of D-2-deoxyglucose (3 mM). Penicillin biosynthesis was greatly reduced (55%) in D-glucose-grown cultures of the parental strain, but this sugar had no repressive effect on the rate of penicillin biosynthesis in the mutant glk1. This mutant was deficient in ATP-dependent glucokinase and showed a greatly reduced uptake of D-glucose. The parental strain P. chrysogenum AS-P-78 showed in vitro ATP-dependent phosphorylating activities of D-glucose, D-2-deoxyglucose, and D-galactose. The glk1 mutant was deficient in the in vitro phosphorylation of D-glucose and D-2-deoxyglucose but retained a normal D-galactose-phosphorylating activity. D-Glucose repressed both beta-galactosidase and isopenicillin-N-synthase but not acyl coenzyme A:6-aminopenicillanic acid acyltransferase in the parental strain. The glucokinase-deficient mutant was simultaneously derepressed in carbon catabolite regulation of beta-galactosidase and isopenicillin-N-synthase, suggesting that a common regulatory mechanism is involved in carbon catabolite regulation of both sugar utilization and penicillin biosynthesis.

Carbon↗

Comparative evaluation of oculokinetic perimetry and conventional perimetry in glaucoma.

Oculokinetic perimetry is a new method of visual field assessment in which the patient moves the eye around a central static target to look sequentially at an array of numbers. When fixation on a number is accompanied by disappearance of the central target, that number is deleted from a recording chart. Inversion of the recording chart gives a plot of the central visual field. In this study we have shown that in 64 eyes of 37 patients, with unequivocal field loss attending a glaucoma clinic, the test is efficient and reliable when compared with conventional static (Dicon 3000) and kinetic (Tübingen Oculus) field tests. The results were identical in 88% of eyes tested and approximately comparable in another 6%. Quantitative equivalent targets for the different methods are described. Oculokinetic perimetry was carried out by a previously untrained person, and it is suggested that this new method merits further study as a screening device for glaucoma in the community.

Adult↗

[Intensive lymphoid hyperplasia of the peripancreatic ganglia and extrahepatic cholestasis in Sjögren's syndrome. Report of an unusual case].

The diagnostic triad of Sjögren's syndrome is keratoconjunctivitis sicca, xerostomia with o without salivary gland enlargement and the presence of a connective tissue disease usually rheumatoid arthritis). Is postulated an altered immune response of lymphocytes to ductal antigens glands and the result is an chronic inflammatory process with eventual fibrosis and hyposecretion of the affected glands. Lymphoproliferation is characteristic of the Sjögren's syndrome, the lungs, kidneys and salivary glands are the most affected: in this paper is presented the disease complex and not described of Sjögren's syndrome and intensive lymphoid hyperplasia of peripancreatic lymph nodes without chronic pancreatitis but with obstructive jaundice for involvement of the distal common bile duct. The percutaneous transhepatic cholangiography was suggestive of pancreatic disease and the surgery and the pathology certified the final diagnosis. A choledocho-enteric anastomosis was performed to remedy the extrahepatic cholestasis.

Cholangiography↗

In vitro and in vivo antiaggregant effects of magnesium halogenates.

The in vitro antiplatelet aggregating activity of magnesium and magnesium associated with soluble citroflavonoids (hesperidin and eriodictin, 1:1) is well-established. The degree of inhibition of in vitro platelet aggregation activity produced by different concentrations of magnesium halogenates was determined. ADP (4 microM) was used to induce aggregation following Cardinal and Flowers' (1) technique. Antithrombotic activity was studied in vivo. The difference in duration of ADP-induced respiratory dysfunction was compared between animals fed 25 mg/kg magnesium halogenates for 10 days before testing and controls. An increase in circulating platelets was observed in rats treated with magnesium halogenates.

Adenosine Diphosphate↗

Characterization of glucagon receptors in Golgi fractions of fetal rat liver.

The present study was designed to determine if Golgi fractions from fetal rat liver contain glucagon receptors and to characterize the properties of such receptors. Purification patterns of liver plasma membranes and Golgi fractions from fetal and adult rats were similar, as verified by morphological and biochemical approaches. Glucagon binding was greater in plasma membranes of adult than fetal rats, while in Golgi fractions glucagon binding was similar in both groups. The modifications in in glucagon binding reflect changes in glucagon receptors. Glucagon association and glucagon receptor inactivation by liver membranes were similar in the two groups of animals, while glucagon degradation was lower in fetal than in adult rats.

Animals↗

Direct evidence that insulin does not down-regulate its own receptors in circulating monocytes of human newborns.

To determine the effect of insulin on its own receptor concentrations in circulating monocytes of normal human adults and full-term newborns, these cells were chronically exposed (2-18 h) to 10(-9) to 10(-7) mol/l insulin at 37 degrees C in vitro. The reduced 125I-insulin binding observed in monocytes from adult individuals was dependent on the concentration of unlabelled insulin and on the duration of exposure, while in the monocytes obtained from umbilical cord blood, insulin did not induce any reduction of insulin binding. The modifications observed in insulin binding were accounted for by changes in receptor concentrations rather than by any change in receptor affinity for the hormone. These findings show that insulin does not down-regulate its own receptors in monocytes of human newborns.

Humans↗

Decreased plasma serotonin in melancholic patients: a study with clomipramine.

Eighteen unmedicated patients suffering from major depressive disorder with melancholia (DSM-III) were examined for abnormalities in peripheral serotonin (5-HT) and related metabolites. Serotonin in platelet-free plasma and in platelets from melancholics was significantly reduced to 30% and 60% of their respective control values. Plasma 5-hydroxyindoleacetic acid was also found to be reduced, but not significantly. Other plasma compounds related to 5-HT (indoleacetic acid, total tryptophan, and free tryptophan) were found to be unchanged in these patients. Of all variables, only platelet 5-HT was affected while patients were on clomipramine (CIM) treatment. After 2 weeks on CIM (100-150 mg/day, orally), platelet 5-HT was reduced to 8% of pretreatment values, but plasma 5-HT did not change and continued to be reduced upon clinical recovery. The existence of a distinct pool of plasma 5-HT that is clearly independent of the platelet pool is indicated by the differences observed in plasma and platelet 5-HT during CIM treatment, as well as by previous data from this laboratory. The very marked decrease in plasma 5-HT levels may be in accord with the central nervous system changes reported in depression and suggests the possibility of using plasma 5-HT as a peripheral indicator of abnormal serotonin function in melancholia.

Aged↗

Lack of insulin effect on its own receptors in fetal rat hepatocytes.

To determine the effect of insulin on its receptor concentrations in hepatocytes of fetal and adult rats, these cells were preincubated in the presence or absence of insulin. The reduced [125I]-insulin binding observed in adult hepatocytes was dependent on the concentration of insulin and on the duration of exposure, while in fetal hepatocytes insulin did not induce any reduction in insulin binding. In contrast, glucagon receptors were unaffected by preincubation with insulin. The modifications observed in insulin binding were accounted for by changes in receptor concentrations rather than any change in receptor affinity for the hormone. Studies on the kinetic properties of the insulin receptors of fetuses and adult rats revealed that association and dissociation rates were undistinguishable. These results indicate an absence of insulin receptor down-regulation in the fetus, which could favour anabolic processes during intrauterine life.

Aging↗

Myoclonic movements as a side-effect of treatment with therapeutic doses of clomipramine.

Myoclonic movements have been observed in depressed patients receiving therapeutic doses of clomipramine. Such movements, which appear in states of deep muscular relaxation such as sleep, do not appear to have any repercussion in the outcome of the depression and are reversible following withdrawal of the drug. In this study the plasma levels of clomipramine and desmethylclomipramine were determined and their possible relationship with myoclonus studied. No statistically significant relationships were found.

Adult↗

Enhanced binding of [3H] (-) adrenaline to platelets of depressed patients with melancholia: effect of long-term clomipramine treatment.

The specific binding of the full agonist [3H] (-) adrenaline to platelet membranes was measured in 14 drug-free depressed patients with melancholia. There was an increased number of binding sites (Bmax) with the same apparent affinity (KD) for the radioligand, indicating that platelet alpha 2-adrenoceptor density in the high affinity state was increased in depressed patients. Long-term administration of clomipramine was associated with decreases in platelet alpha 2-adrenoceptor densities which correlated with the duration of treatment. The results support the hypothesis that in endogenous depression there is a dysfunction of the alpha 2-adrenoceptor and that antidepressant treatment might involve a time-dependent desensitization process of this receptor.

Adult↗

A simple clinical method of assessing patients with optic nerve hypoplasia. The disc-macula distance to disc diameter ratio (DM/DD).

The diagnosis of optic nerve hypoplasia may be difficult when the optic disc is only slightly reduced in size, or when central visual acuity is normal, or only minimally decreased. In these cases, measurement of the DM/DD ratio can provide a valuable tool in establishing the diagnosis. By means of fundus photographs the ratio of the distance between the centre of the optic disc and the fovea centralis, to the diameter of the optic disc (the DM/DD ratio) is measured. We have calculated the DM/DD ratio in 19 eyes of 11 patients with optic nerve hypoplasia and found it to be significantly higher than the ratios obtained for 58 eyes of 48 normal subjects, 22 eyes of 11 patients with primary open angle glaucoma and 25 eyes of 16 patients with optic atrophy. The DM/DD ratio is easily estimated and is recommended as a simple means of establishing the diagnosis of optic nerve hypoplasia.

Adolescent↗

Purification to homogeneity and characterization of acyl coenzyme A:6-aminopenicillanic acid acyltransferase of Penicillium chrysogenum.

The acyl coenzyme A (CoA):6-aminopenicillanic acid (6-APA) acyltransferase of Penicillium chrysogenum AS-P-78 was purified to homogeneity, as concluded by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing. The enzyme is a monomer with a molecular weight of 30,000 +/- 1,000 and a pI of about 5.5. The optimal pH and temperature were 8.0 and 25 degrees C, respectively. This enzyme converts 6-APA into penicillin by using phenylacetyl CoA or phenoxyacetyl CoA as acyl donors. The pure enzyme showed a high specificity and affinity for 6-APA and did not accept benzylpenicillin, 7-aminocephalosporanic acid, cephalosporin C, or isocephalosporin C as substrates. The enzyme converted isopenicillin N into penicillin G, although with a lower efficiency than when 6-APA was used as the substrate. It did not show penicillin G acylase activity. The acyl CoA:6-APA acyltransferase required dithiothreitol or other thiol-containing compounds, and it was protected by thiol-containing reagents against thermal inactivation. The acyltransferase was inhibited by several divalent and trivalent cations and by p-chloromercuribenzoate and N-ethylmaleimide. The activity was absent in four different mutants that were blocked in penicillin biosynthesis.

Acyltransferases↗