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Biomedical subjects

M Lahav

Publications and source records attributed to M Lahav.

At least 73 records · Page 4Linked to original sources

The heme biosynthetic pathway in lymphocytes of patients with malignant lymphoproliferative disorders.

The metabolism of heme is impaired in lymphocytes of patients with malignant lymphoproliferative disorders (MLPO). Two of the enzymes of the heme biosynthetic pathway, delta-aminolevulinic acid dehydrase (ALAD) (EC 4.2.1.24) and ferrochelatase (FC) (EC 4.99.1.1) are markedly reduced. The activity of porphobilinogen deaminase (PBGD) (EC 4.3.1.8) is increased. The rate-limiting enzyme of heme biosynthesis in the liver, aminolevulinate synthase (ALAS) (EC 2.3.1.37) remains unchanged although the concentration of total heme in the lymphocytes is markedly reduced. This might reflect a lack of negative feedback inhibition by heme on ALAS activity in this system.

5-Aminolevulinate Synthetase↗

Effects of prostaglandin F2 alpha and a gonadotropin-releasing hormone agonist on inositol phospholipid metabolism in isolated rat corpora lutea of various ages.

The sensitivity of rat corpora lutea to luteolytic agents increases with luteal age. We examined the effect of prostaglandin F2 alpha (PGF2 alpha) and [D-Ala6,Des-Gly10]GnRH ethylamide (GnRHa) on inositol phospholipid metabolism in day 2 and day 7 corpora lutea from PMSG-treated rats. Isolated corpora lutea were incubated with 32PO4 or [3H]inositol and were treated with LH, PGF2 alpha, or GnRHa. Phospholipids were purified by TLC, and the water-soluble products of phospholipase-C activity (inositol phosphates) were isolated by ion exchange chromatography. In day 2 corpora lutea, PGF2 alpha, (10 microM) and GnRHa (100 ng/ml) significantly increased 32PO4 incorporation into phosphatidic acid (PA) and phosphatidylinositol (PI), but not into other fractions. LH provoked slight increases in PA. Results were similar with 30 min of prelabeling or simultaneous addition of 32PO4 and stimulants. In other experiments, PGF2 alpha and GnRHa provoked rapid increases (1-5 min) in the accumulation of inositol mono-, bis-, and trisphosphates. LH did not significantly increase inositol phosphate accumulation, but stimulated cAMP accumulation in 2-day-old corpora lutea. Inositol phospholipid metabolism was increased in day 7 corpora lutea compared to that in day 2 corpora lutea. This increase was associated with increased incorporation of 32PO4 into PA and PI and increased accumulation of [3H]inositol phosphates. In day 7 corpora lutea, which are very sensitive to the luteolytic effect of PGF2 alpha, the PG-induced increase in PA labeling was small and inconsistent, whereas PI labeling was unaffected in 30-min incubations. GnRHa was without effect in such corpora lutea. LH, PGF2 alpha, or GnRHa did not increase inositol phosphate accumulation in 7-day-old corpora lutea. These studies demonstrate that the transformation of young (day 2) to mature (day 7) corpora lutea is associated with an increase in luteal inositol phospholipid metabolism. The results also show that PGF2 alpha and GnRHa stimulate phospholipase-C activity in young corpora lutea, but are ineffective in mature corpora lutea, and suggest that an increase in inositol phospholipid metabolism by itself is not sufficient to explain the acute luteolytic action of PGF2 alpha and GnRH in vitro. However, phospholipase-C-derived second messengers may be involved in the action of hormones that control luteal function.

Animals↗

IgA, IgG, IgM, and IgE levels in normal, healthy, non-atopic Israeli children.

IgA, IgG, IgM, and IgE levels in healthy, non-atopic, Israeli-born children aged 20 days to 16 years were analyzed and showed similar age-related values and dynamics as those of white populations found in other countries. No significant effect of sex of the individual or ethnic origin of the parents was found on the IgE values at different ages. This may indicate that total IgE levels are strongly influenced by environmental factors. Establishing tolerance limits at 97.5, 95, 75, 25 and 5th percentiles and the geometric mean provides the practitioner with more complete reference values. The use of multivariate control charts with tolerance limits from normal IgA, IgG, IgM, and IgE levels is described and is offered as an additional tool for the diagnosis of an allergic individual.

Adolescent↗

Pigmentary retinal degeneration and Coats' disease: a case study.

We report a 22-year-old Hispanic man with familial congenital nystagmus, iris transillumination, and pigmentary retinal anomalies with subretinal fatty exudates similar to those seen in Coats' disease. Direct treatment of the telangiectatic vessels with cryotherapy caused a subretinal hemorrhage. We therefore recommend surrounding the area of abnormal vessels (posterior to vessels and between vessels and ora serrata) with cryotherapy to reverse the formation of the vascular anomalies.

Adult↗

The heme biosynthetic pathway in the regenerating rat liver. The relation between enzymes of heme synthesis and growth.

Enzymes of heme synthesis, porphyrins and heme content of regenerating rat livers were examined. During the first three days of regeneration the weights of livers of one-third and two-third hepatectomized rats increased 1.5-fold and 2.7-fold and the activity of porphobilinogen deaminase increased 2-fold and 4-fold and was inversely correlated with ferrochelatase activity. delta-Aminolevulinic acid synthase and delta-aminolevulinic acid dehydratase activities were reduced. Concomitantly an increase in the concentration of porphyrins and a decrease in that of heme were observed. The changes in the biosynthetic pathway of heme during rapid growth of the liver are discussed.

Ammonia-Lyases↗

Increased porphobilinogen deaminase activity in patients with malignant lymphoproliferative diseases. A helpful diagnostic test.

Patients with malignant lymphoproliferative diseases, ie, chronic lymphocytic leukemia and lymphoma, were found to have higher porphobilinogen deaminase (PBGD) activity in their peripheral lymphocytes than normal control subjects, patients with other malignant neoplasms, and patients with various infectious diseases. The specificity and sensitivity of the test were 99% and 87%, respectively. The sensitivity of the test was 100% in patients with chronic lymphocytic leukemia and 82% in patients with lymphoma. The diagnostic value of PBGD determinations was shown in a prospective study of a group of patients evaluated because of fever of unknown origin, anemia, or other constitutional symptoms with or without lymphadenopathy or a mediastinal mass. The positive and negative predictive values in these patients were 91% and 100%, respectively. Nearly all patients who were in remission had normal enzyme activity. Lymphocyte PBGD determinations also may be of value in determining when to terminate or reinitiate drug treatment.

Adult↗

Lymphocyte urosynthase in non-Hodgkin's lymphoma. An indicator of disease extensiveness.

The activity of lymphocyte uroporphyrinogen synthase (URO-S) was examined in 51 non-Hodgkin's lymphoma (NHL) patients at various follow-up periods. Mean +/- SD activity (pmol porphyrin/mg protein/hr) at diagnosis (n = 24), on relapse (n = 14) and during active disease (n = 14) were 31.7 +/- 19.8, 31.7 +/- 27.2 and 29.4 +/- 18.5, respectively. These values were significantly higher than the enzyme activity during remission (14.1 +/- 4.0), which was in the normal range (14.5 +/- 3.8). Abnormally high activity was found in 65.4% of determinations at diagnosis, on relapse and during active disease, compared to 5.5% during remission (P less than 0.001). Significant association of abnormal URO-S activity was found with advanced clinical stage (P less than 0.01), spleen enlargement (P = 0.048), involvement of bone marrow (P = 0.02), as well as lymphoma cell spread to peripheral blood (P = 0.03). Highly significant correlation (r = 0.65, P less than 0.001) was found between URO-S activity and serum lactic dehydrogenase (LDH) levels. Excessively high levels of URO-S activity were found only in patients with lymphoma cells in peripheral blood. No association was found with histopathologic classification and liver size. The authors conclude that URO-S activity is a biochemical indicator for patients in all stages of NHL and seems to be a specific marker for the extensiveness of the disease.

Adolescent↗

Adrenergic receptor hyperactivity--a cause for pseudopheochromocytoma?

Two patients with classical signs and symptoms of pheochromocytoma, are described. In these two patients the 24-hr urinary excretion of dopamine, norepinephrine, epinephrine and their metabolites were normal or low, both in basal states or after attacks (spontaneous or provoked). However, the 24-hr urinary excretion of cyclic AMP was exceedingly high in one patient (13000 nmol/gm creatinine), and elevated in the second (5920 nmol/gm creatinine). Both patients were benefited by treatment with a combination of alpha and beta adrenergic blocking drugs. The first patient, after stopping treatment, developed hypertensive crisis and died. Post-mortem examination did not detect a pheochromocytoma or any other abnormality which could explain the excessively elevated cyclic AMP. In the second patient, extensive X-ray and CT examinations were negative for pheochromocytoma. A hypothesis is developed linking the symptoms and biochemical findings of both patients to an abnormality of the adrenergic receptor.

Adrenal Gland Neoplasms↗

New clinical classification for iris neovascularization.

A new classification scheme for neovascularization of the iris (NVI) is presented. This system designates the location of the new vessels by a letter and the number of quadrants involved by a numeral. The presence of elevated intraocular pressure (IOP) is denoted by a "+" sign. It was found to be a reliable method in the evaluation of the clinical course and results of treatment in patients with NVI.

Aged↗

Suppression of penicillin-induced bacteriolysis of staphylococci by some anticoagulants.

Heparinoids and related negatively-charged substances caused suppression of the penicillin-induced bacteriolysis of staphylococci and a higher viability rate. Furthermore, the penicillin-induced release of cell wall material was reduced by these substances. The main reason for this suppression of bacteriolysis was an inhibition of the activity of cell wall autolytic enzymes while the penicillin-specific perturbations of wall morphogenesis were not affected.

Anticoagulants↗

Atopic babies with wheezy bronchitis. Follow-up study relating prognosis to sequential IgE values, type of early infant feeding, exposure to parental smoking and incidence of lower respiratory tract infections.

Clinical course and sequential IgE values were recorded in a 4-year prospective study of 80 atopic wheezing babies at ages from 6 months to 4-5 years. At final assessment, 68% of the children had been symptom-free for at least 1 year whilst 32% still suffered from wheezing attacks. Total IgE levels from the first visit until final assessment were greater than 2 SD above normal for age in 63% of all children, but no significant correlation could be found between sequential IgE levels and the clinical picture or course of the disease. In all cases IgE levels rose steadily with increasing age, independently of whether wheezing disappeared or persisted. The most significant rise in IgE values occurred between 1 and 2 years of age, and IgE levels at 4 years could be predicted by the value at the age of 2 years (r = 0.97). In the group of children that lost their wheezing tendency there was: a significantly greater number of infants that were breast-fed during at least the first 3 months of life (P less than 0.01), a lower incidence of exposure to parental smoking (P less than 0.01), and a lesser incidence of lower respiratory tract infections (P less than 0.01). Though there was no correlation between increase of IgE levels and type of feeding or exposure to cigarette smoke, statistical data confirms that bottle feeding and parental smoking lead to persistence of wheezing in atopic children.

Asthma↗

Calmodulin inhibitors and 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate do not prevent the inhibitory effect of prostaglandin F2 alpha on cyclic AMP production in isolated rat corpora lutea.

In the rat corpus luteum, prostaglandin F2 alpha (PGF2 alpha) rapidly inhibits LH-induced cyclic AMP (cAMP) production when given in vivo or to isolated corpora lutea, but not to broken-cell preparations. The suggestion that increased cytosolic calcium concentration mediates PGF2 alpha action was investigated in corpora lutea of pseudopregnancy induced in immature rats by administration of pregnant mare serum gonadotrophin (15 i.u.). Isolated 10-day-old corpora lutea were incubated for 90 min with LH (5 micrograms/ml), PGF2 alpha (10 mumol/l) and other additions, and cAMP concentration in the tissue was estimated. The putative inhibitor of intracellular calcium release or action, 8-(n,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8; 30 or 150 mumol/l), did not abolish the effect of PGF2 alpha. Similarly ineffective was the combination of TMB-8 (150 mumol/l) and calcium-depleted medium (free ionized calcium concentration, 30 nmol/l). Calmodulin inhibitors of three different chemical structures were then tested. The phenothiazine trifluoperazine, at 300 as well as 30 mumol/l, did not interfere with the inhibitory effect of PGF2 alpha on cAMP, while suppressing (at 300 mumol/l) progesterone secretion in LH-treated tissue. Furthermore, inhibition by PGF2 alpha was not impaired by pimozide, a diphenylbutylpiperidine (25 and 50 mumol/l) nor by N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide (W-7; 15 and 45 mumol/l). In the presence of LH alone, W-7 (45 mumol/l) inhibited and TMB-8 (30 mumol/l augmented cAMP accumulation, indicating that the luteal tissue was effectively exposed to these compounds. Thus, drugs known to inhibit calcium- and calmodulin-dependent processes in a variety of tissues did not abolish the inhibitory action of PGF2 alpha on luteal cAMP production.

Animals↗

Simplified diagnostic coding sheet for computerized data storage and analysis in ophthalmology.

A review of currently-available diagnostic coding systems revealed that most are either too abbreviated or too detailed. We have compiled a simplified diagnostic coding sheet based on the International Coding and Diagnosis (ICD-9), which is both complete and easy to use in a general practice. The information is transferred to a computer, which uses the relevant (ICD-9) diagnoses as database and can be retrieved later for display of patients' problems or analysis of clinical data.

Diagnosis, Computer-Assisted↗

Inhibition by vanadate of cyclic AMP production in rat corpora lutea incubated in vitro.

Vanadate, a normal constituent of cells, has been reported to affect a variety of enzymes involved in phosphate transfer; the findings regarding adenylate cycle vary with the tissue and experimental system. In the corpus luteum, cyclic AMP (cAMP) stimulates steroidogenesis; and prostaglandin F2 alpha, which induces luteal regression, inhibits luteinizing hormone (LH)-induced cAMP accumulation. We examined the influence of orthovanadate on cAMP concentration in isolated corpora lutea from pseudopregnant rats. With 2 mM vanadate, basal cAMP level was unaffected, but LH-induced cAMP accumulation was inhibited by 45-68%. Lower doses of vanadate (0.2-1 mM) were almost as effective. When added simultaneously with LH, vanadate was inhibitory within 25 min, but no inhibition occurred when vanadate was added for 30 min to tissue pretreated with LH for 60 min. The decrease in cAMP accumulation was observed also when corpora lutea were exposed to vanadate in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.5 mM), indicating that vanadate inhibits cAMP synthesis. Vanadate may increase cytosolic calcium by inhibiting ion pumps in cell membranes. Thus, we examined the effect of vanadate in corpora lutea incubated in calcium-depleted medium and found that vanadate still inhibited cAMP formation. Vanadyl sulfate (0.4 and 2 mM) reduced the LH-induced cAMP accumulation as effectively as vanadate. Thus, the use of vanadate as a tool for exploring physiological regulators of luteal adenylate cyclase should be considered.

1-Methyl-3-isobutylxanthine↗