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Biomedical subjects

M Lahav

Publications and source records attributed to M Lahav.

At least 109 records · Page 6Linked to original sources
PubMed1984

Effect of prolonged fasting on heme metabolism in the rat.

It is known that fasting may provoke an acute attack in patients with latent hepatic porphyrias. We examined the influence of fasting on some aspects of heme synthesis in rats. Urinary excretion of both uroporphyrin and coproporphyrin, as well as fecal elimination of protoporphyrin and coproporphyrin, were increased on fasting. These biochemical aberrations resemble those found in subjects with latent porphyria variegata, suggesting that fasting rats may constitute an experimental model for latent variegate porphyria. The administration of phenobarbitone had a pronounced, synergistic effect on the urinary excretion of porphyrins. The activity of delta-aminolevulinic acid synthase (ALAS) and the concentration of cellular heme were determined in homogenates and subcellular fractions of the livers of fasting rats. A marked increase in the concentration of heme in the homogenate, the nuclei and the postmicrosomal supernatant fractions was observed. ALAS activity in the homogenate and the supernatant fraction increased while that in the mitochondria decreased. The possible relationship of these results to the human disease is discussed.

5-Aminolevulinate Synthetase↗
PubMed1983

2-Mercapto-1-(beta-4-pyridethyl) benzimidazole inhibition of basal and aldosterone-stimulated sodium transport but prolongation of the transient theophylline-induced stimulation in the toad bladder.

2-Mercapto-1-(beta-4-pyridethyl) benzimidazole (MPB) was originally introduced as a reversible inhibitor of RNA synthesis, but subsequent findings made this suggestion doubtful. We examined the effect of MPB on active sodium transport, measured as short-circuit current (scc), across the isolated urinary bladder of the toad (Bufo marinus). The drug caused a rapid, dose-dependent inhibition of baseline scc; 25 micrograms/ml MPB reduced it by 70%. Sensitivity to MPB was the same in the presence and absence of metabolizable substrate. The transport stimulation by aldosterone (7 X 10(-8)M) was abolished entirely when MPB was introduced 30 min before the hormone. In bladders incubated with MPB with or without aldosterone, removal of both agents resulted in a rise in scc, which was more rapid in the aldosterone-pretreated hemibladders; a significant difference was observed after 30 min. This suggests that MPB inhibited transport at a site distal to messenger RNA accumulation. The effect of 3 hr of pretreatment with MPB on the response of the bladders to antidiuretic hormone (ADH, 20 mU) and cyclic AMP (cAMP, 10 mM) was then examined. The absolute increment in scc due to these agents was the same as in the absence of MPB, though the baseline was much reduced by the drug. After challenging MPB-pretreated bladders with theophylline (22.5 mM), sodium transport rose continuously for 90 min, in contrast to the small, short-lived rise in the absence of MPB. It is proposed that, in the toad bladder, MPB may: (1) inhibit cAMP-dependent protein kinase, as found by us in other tissues; and (2) counteract the accumulation of a transport inhibitor, possibly calcium or cyclic GMP, in tissues treated with endogenous or exogenous cAMP.

Aldosterone↗
PubMed1983

Erythrocyte uroporphyrinogen synthase activity as a possible diagnostic aid in the diagnosis of lymphoproliferative diseases.

Patients with active lymphoproliferative diseases were shown to have high activity of erythrocyte uroporphyrinogen synthetase (URO-S), the enzyme which converts porphobilinogen to uroporphyrinogen. In a few patients examined the lymphocyte URO-S was markedly increased. No correlation was found between the high URO-S activity and the degree of anemia, reticulocytosis, or the presence of hemolysis. Patients with epithelial malignancies and with some common viral diseases had normal erythrocyte URO-S values. Three patients with nonalcoholic cirrhosis also had high erythrocyte URO-S activities. The determination of erythrocyte and lymphocyte URO-S activity may be of aid in the diagnosis of lymphoproliferative diseases. It may also indicate whether remission has been achieved and whether treatment should be continued or reinstituted. These preliminary observations justify the investigation of a larger patient and control material.

Adult↗
PubMed1983

Evidence for a therapeutic effect of dl-propranolol in benign and malignant insulinoma: report of three cases.

Two patients suffering from benign and one patient suffering from malignant insulinoma experienced frequent incapacitating hypoglycemic attacks which did not respond to treatment with streptozotocin, diazoxide and/or diphenylhydantoin. Dl-propranolol, in dosages ranging from 30-240 mg/day, successfully abolished the symptoms of hypoglycemia, prevented recurrent hypoglycemic attacks, and normalized blood glucose levels concomitant with a reduction in pulse rate to 60/min. The main mechanism of the drug's effect seems to be the suppression of insulin release. However, other mechanisms may be involved such as increased peripheral insulin resistance. No side effects of treatment with dl-propranolol were noted. In patients suffering from insulinoma who are refractory to other forms of treatment, and for those who need symptomatic relief before surgery, dl-propranolol may play an important therapeutic role.

Adenoma, Islet Cell↗
PubMed1983

The role of calcium ion in luteal function in the rat.

The regulatory role of calcium ion was investigated in isolated 10-day-old corpora lutea incubated in vitro. The corpora lutea were induced in immature rats by a single injection of PMSG (15 i.u.) on day 30. We examined the effect of various incubation conditions on the increase (about 7-fold) in cyclic AMP (cAMP) concentration by LH (5 micrograms/ml) and its reversal by PGF2 alpha (10 microM). In calcium-free medium (+0.5 mM EGTA) the stimulation by LH was only slightly impaired, and PGF2 alpha was fully effective in suppressing it. Similarly, both LH and PGF2 alpha acted normally in the presence of 100 microM verapamil, a blocker of calcium uptake. Trifluoperazine (TFP, 3-300 microM) a potent inactivator of calmodulin, did not interfere with the action of PGF2 alpha. The effect of LH was increased by TFP (30 and 300 microM); this was probably due to inhibition of calmodulin-dependent phosphodiesterase, since the increase of the response to LH by IBMX (0.5 mM) plus TFP (30 microM) was similar to that by IBMX alone. Finally, the uptake of radioactive calcium was not increased by PGF2 alpha in the absence or presence of LH. These results do not support the suggestion that calcium ion mediates the hormonal regulation of cAMP in the rat corpus luteum.

Animals↗
PubMed1983

Adherence properties of enterotoxigenic Escherichia coli (ETEC) isolated in the Tel-Aviv area.

We tested the expression of adherence properties of Enterotoxigenic Escherichia coli (ETEC) strains isolated in the Tel-Aviv area by examining their hemagglutination (HA) patterns, and their adherence in vitro to Human Kidney (Huk) cells in tissue culture. Hemagglutination patterns of 75 ETEC and 63 non-ETEC strains isolated from stool samples were examined. The strains were tested for mannose-sensitive hemagglutination (MSHA) capacity of guinea pig erythrocytes, and for mannose-resistant hemagglutination (MRHA) capacity of human and bovine erythrocytes. The distribution of HA patterns among groups of non-ETEC and ETEC predominating strains was compared. (The latter contained strains which were isolated from 21 stool samples as at least two identical isolates.) The ratio of strains containing at least one of MS and MR hemagglutinins was found to be significantly higher in the group of ETEC-predominating strains than in non-ETEC. Eleven of 21 ETEC- predominating strains showed MRHA, and in ten of them Colonization Factor Antigens, CFA/I or CFA/II were identified by HA inhibition and agglutination using specific antisera. The influence of the bacterial culture conditions on expression of MSHA and MRHA and on adherence capacity of the bacteria to HuK cell culture was tested. Results show that ETEC strains exhibited a wide range of phenotypic manifestations of type and strength of adhesions. The variations depend not only on strain but also on culture condition and the type of target cells used in the experiments. In some strains a correlation was observed in the expression of adhesions using various experimental models; in others this correlation was not found. These findings suggest that, although CFAs were relatively common among ETEC-predominating strains isolated in the Tel-Aviv area, other adhesions could be involved in the pathogenic process.

Adhesins, Escherichia coli↗
PubMed1983

Absorption of retinal and subretinal hemorrhages.

Patients with intra- and subretinal hemorrhages who recovered useful vision from an initially poor visual acuity are described. Three patients with intraretinal hemorrhages all cleared without adverse visual sequelae within four to eight weeks; three patients with subretinal or subpigmental hemorrhages cleared with minimal loss of visual acuity, within three to six months. It seems that the amount of damage done to the retina by an intraretinal or subretinal hemorrhage is related to its size and the ability of ocular tissue to clear the blood. Small amount of hemorrhage in or under the retina is capable of clearing with minimal damage. Subretinal hemorrhage seem to be associated more often with damage to the retina for few possible reasons: (a) direct iron toxicity on the photoreceptors; (b) iron toxicity or mechanical damage to the RPE; (c) cellular migration and proliferation in the subretinal space; (d) proliferation of fibrovascular membrane which may further damage the external retina.

Adult↗
PubMed1982

The influence of propranolol on the concentration of heme and on the activity of delta aminolevulinate synthase in monolayers of chick embryo liver cells.

The addition of propranolol to monolayers of chick embryo liver cells caused a rapid increase in cellular heme, followed by an equally rapid decrease. Subsequently the concentration of heme rose at a relatively slower rate. About 10 hr after addition of propranolol to the medium a plateau level was reached at +/- 35% above control values. Changes in the activity of delta-aminolevulinate synthase (ALAS) were negatively correlated with those of cellular heme. Cycloheximide prevented the above phenomenon. ALAS activity was not clearly correlated with the rapid, partial inhibition of protein synthesis, caused by propranolol. These observations are related to the beneficial influence of administration of hemin or of propranolol to patients with acute attacks of hepatic porphyria.

5-Aminolevulinate Synthetase↗
PubMed1982

Toxicity of intravitreous miconazole.

Miconazole nitrate is a broad-spectrum antimycotic agent with low systemic and ocular toxicity. Since this drug does not adequately penetrate the vitreous cavity by topical, subconjunctival, or intravenous routes, we determined whether it can be given intravitreously for fungal endophthalmitis. Retinal and lens toxicity studies were carried out in 40 rabbits and three owl monkeys. Results showed that both miconazole and its vehicle produced toxic damage to the retina and crystalline lens in concentrations of 100 micrograms or greater. Concentrations of 10 to 80 micrograms caused mild to moderate retinal necrosis in some rabbit eyes. In monkey eyes, these concentrations did not cause significant histopathologic or electroretinographic changes. We believe that clinical use of this drug in doses not to exceed 40 micrograms may be justified in desperate cases of fungal endophthalmitis.

Animals↗
PubMed1982

Effect of leukocyte hydrolases on bacteria XVI. Activation by leukocyte factors and cationic substances of autolytic enzymes in Staphylococcus aureus: modulation by anionic polyelectrolytes in relation to survival of bacteria in inflammatory exudates.

The mechanisms involved in the activation of autolytic enzymes in Staphylococcus aureus, by leukocyte extracts, cationic proteins, phospholipase A2, amines, and membrane-damaging agents was studied in a resting cell system as well as by growing staphylococci. The bacteria were labeled with [14C]N-acetylglucosamine and were subjected to a variety of agents either in 0.1 M acetate buffer, pH 5.0, or in phosphate buffer, pH 7.4. While intact log-phase cultures were found to undergo partial autolysis at pH 5.0 and almost complete lysis at pH 7.4, both heat-killed bacteria and bacterial cell walls were completely resistant to autolysis in buffers. Autolysis at pH 5.0 can be further activated by leukocyte extracts, nuclear histone, crystalline ribonuclease, egg-white and human lysozyme, phospholipase A2, as well as by spermine, spermidine, and polymyxins B and E. The addition of viable log-phase bacteria to radiolabeled heat-killed staphylococci or to radiolabeled cell walls which had been cleaned off autolytic enzymes resulted in degradation of the radiolabeled targets. The data suggest that the various inducers of autolysin activation caused leakage of autolytic enzymes from the intact bacteria which attacked the depolymerized the bacterial cell walls. Anionic polyelectrolytes like heparin, dextran sulfate, suramine, polyglutamic acid, and liquid (polyanethole sulfonic acid) markedly inhibited both spontaneous and induced lysis. Staphylococci which had grown in the presence of anionic polyelectrolytes became highly resistant to lysis triggered by any of the inducers of autolysis. Since inflammatory exudates are known to be rich in anionic polyelectrolytes, it is suggested that the prolonged survival of intact bacterial cells in such a milieu may be due to the inactivation of autolytic enzymes. It is also postulated that the degradation of certain bacterial species following phagocytosis or extracellular degradation may not be the result of the action of hydrolytic enzymes but rather the result of activation by leukocyte factors of autolytic enzymes which lead to bacteriolysis.

Bacteriolysis↗
PubMed1982

Bacteria and zymosan opsonized with histone, dextran sulfate, and polyanetholesulfonate trigger intense chemiluminescence in human blood leukocytes and platelets and in mouse macrophages: modulation by metabolic inhibitors in relation to leukocyte-bacteria interactions in inflammatory sites.

Human blood leukocytes and platelets and mouse peritoneal macrophages emit very rapid and very intense Luminol-dependent chemiluminescence (CL) signals when treated with streptococci, staphylococci, or with zymosan, which have been preopsonized with arginine-rich histone, dextran sulfate or polyanetholesulfonate (liquoid). Liquoid alone at 10-30 micrograms/2 X 10(5) leukocytes also triggers intense CL responses in the absence of a carrier. Strong CL can also be triggered, and at the same levels, when the various polyelectrolytes are simply mixed with the bacteria or zymosan and added to the leukocyte suspensions. The CL responses induced by the polyelectrolyte-bacteria complexes greatly exceed those triggered in leukocytes by antibody-complement-coated particles. Liquoid also shows a unique property of markedly augmenting CL signals which have already been induced by other ligand-coated bacteria or zymosan particles. Streptococci and staphylococci were found to be much superior to zymosan, Gram-positive bacilli, or E. coli as carriers for the various polyelectrolytes in the CL reaction. Neither protamine sulfate, lysozyme, myeloperoxidase, crystalline ribonuclease (all cationic in nature), chondroitin sulfate, heparin, nor alginate sulfate acted as ligands for triggering CL, when used to opsonize bacteria or zymosan. The induction of CL in blood leukocytes by the various ligand-coated bacteria is markedly inhibited by azide, KCN catalase, aminotriazole, and EDTA, agents known to inhibit the production of oxygen radicals following stimulation of leukocytes by opsonized bacteria. Two children diagnosed for chronic granulomatous diseases (CGD) of childhood and an apparently healthy sister of one of the male patients completely failed to respond with CL either to the polyelectrolyte-bacteria complexes, liquoid or antibody-coated bacteria and zymosan. It is proposed that liquoid be employed for the rapid screening of defects in certain oxygen-dependent metabolic processes in both PMNs and macrophages. It is also suggested that polyelectrolytes like the ones described in this study may markedly enhance the bactericidal properties of leukocytes and macrophages towards both extracellular and intracellular microorganisms and may perhaps also augment the tumoricidal effects of activated macrophages.

Adult↗
PubMed1982

Cell wall degradation of Staphylococcus aureus by lysozyme.

In contrast to former findings lysozyme was able to attack the cell walls of Staphylococcus aureus under acid conditions. However, experiments with 14C-labelled cell walls and ribonuclease indicated that, under these conditions, lysozyme acted less as an muralytic enzyme but more as an activator of pre-existing autolytic wall enzymes. Electron microscopic studies showed that under these acid conditions the cell walls were degraded by a new mechanism (i.e. "attack from the inside"). This attack on the cell wall started asymmetrically within the region of the cross wall and induced the formation of periodically arranged lytic sites between the cytoplasmic membrane and the cell wall proper. Subsequently, a gap between the cell wall and the cytoplasmic membrane resulted and large cell wall segments became detached and suspended in the medium. The sequence of lytic events corresponded to processes known to take place during wall regeneration and wall formation. In the final stage of lysozyme action at pH 5 no cell debris but "stabilized protoplasts" were to be seen without detectable alterations of the primary shape of the cells. At the same time long extended ribbon-like structures appeared outside the bacteria. The origin as well as the chemical nature of this material is discussed. Furthermore, immunological implications are considered.

Cell Wall↗