J Shani

Hebrew University of Jerusalem, Yerushalayim, Jerusalem District, Israel

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Publications (161)300.96 Total impact

  • International journal of dermatology 06/2008; 36(7):481 - 492. DOI:10.1046/j.1365-4362.1997.00286.x · 1.23 Impact Factor
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    ABSTRACT: Bathing in the Dead Sea is an established treatment for psoriasis. Penetration of Dead Sea minerals into psoriatic skin is an effective factor in this treatment, but applying it clinically requires frequent bathing in the Dead Sea or in its bath-salt solution. We tested an ethyl-cellulose-based transparent varnish with a sustained-release property, for its penetrability of such minerals. Minerals tested were MgBr2, and KBr, known for their relevance in psoriatic proliferation. They were applied for up to three weeks. We could demonstrate that two weekly applications of the salt-containing varnish on healthy rabbit skin are enough to obtain elevated levels of magnesium and potassium in their plasma. We propose the application of Dead Sea minerals containing varnish as a clinical treatment for psoriasis.
    Journal of the European Academy of Dermatology and Venereology 07/2006; 4(3):267 - 272. DOI:10.1111/j.1468-3083.1995.tb00349.x · 3.11 Impact Factor
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    ABSTRACT: The pathogenesis of morbidity and mortality associated with intervention of the biliary system in patients with obstructive jaundice is unknown. Mechanical jaundice initiates the development of morphological changes in hepatocytes with concomitant disturbances in metabolism. These are followed by changes in enzyme activity in hepatocytes and peripheral blood. Wistar rats were divided into three groups: group 1, sham-operated controls; group 2, rats with permanent jaundice; and group 3, rats with temporary mechanical jaundice. The animals were examined at 2 weeks (groups A), 4 weeks (groups B) and 6 weeks (groups C) after surgery. We explored the impact of induced mechanical jaundice on the activity of selected urea cycle enzymes (arginase [E.C.] and ornithine transcarbamoylase (OTC) [E.C.]). Mechanical jaundice was found to induce changes in hepatocytic metabolism, which in turn led to disturbances in the urea cycle and the process of transamination. After relief of the mechanical jaundice (recanalization of the common bile duct), the urea cycle activity in the liver was greatly increased despite the normalization of the basic biochemical indices. The results of the experiment confirmed the hypothesis that long-term mechanical jaundice causes lasting disturbances in hepatocytic metabolism. We conclude that the rate of nitrogen metabolism is higher after recanalization of the bile duct.
    Journal of Surgical Research 07/2005; 126(1):19-26. DOI:10.1016/j.jss.2005.01.026 · 2.12 Impact Factor
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    ABSTRACT: Levels of the 19 proteinous amino acids and total free amino acids were assayed by gas-liquid chromatography in cytosols of rat atrial and ventricular muscle cardiomyocytes. The tissues were assayed after the rats had been exposed to the cardioactive drugs digoxin, caffeine, and isoproterenol, each having different mechanisms of action. We demonstrated that, in the atrial and ventricular cardiac muscle cytosol of control (untreated) rats, arginine, glutamine, and cysteine existed in their highest levels: 35.1% and 17.6%; 14.8% and 51.6%; 9.9% and 0.25% of the total free amino acids, respectively. The levels of the other amino acids in the atrial and ventricular cardiac muscle cytosols ranged between 0.1% and 10.0% of the total free amino acids. Digoxin, caffeine, and isoproterenol significantly reduced the total amount of cytosolic free amino acids in the atrial heart muscle cytosol to 7.6%, 9.0%, and 9.2% of the control value (100%), and in the ventricular heart muscle cytosol to 31.1%, 43.2%, and 28.3% of the control. The three drugs tested changed the cytosols' levels of arginine, cysteine, tryptophane, asparagine, and tyrosine in atrial and ventricular heart muscle cytosol, as compared to the control groups (calculated as a percent of the total free amino acids in the experimental groups). The role of proteinous amino acids in the function of the heart muscle and in the mechanism of action of these drugs on the mammalian heart is discussed.
    Receptors and Channels 02/2004; 10(2):91-7. DOI:10.1080/10606820490464352
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    ABSTRACT: Tissue levels of nineteen amino acids and total free amino acids, were assayed by gas-liquid chromatography in cytosols of rat atrial and ventricular muscle cardiomyocytes. The tissues were assayed after the rats had been administered IP with the three cardioactive drugs, exerting a significant effect on their heart action: propranolol, pentylenetetrazol and reserpine. It was demonstrated that while in the atrial and ventricular cardiac muscle cytosols of control rats, arginine, glutamine and cysteine were detected in high levels (35.1% and 17.6%; 14.8% and 51.6%; 9.9% and 0.25% of the total free amino acids, respectively), all three drugs significantly reduced the total amounts of cytosolic free amino acids in both atrial and ventricular heart muscles. All three drugs (with reserpine in particular) modified the levels of arginine, cysteine, phenylalanine, tryptophan, isoleucine and tyrosine. The role of these amino acids in the heart muscle cytosol, and their involvement in the mechanism of action of these three cardioactive drugs, is discussed.
    Receptors and Channels 02/2004; 10(2):83-90. DOI:10.1080/10606820490464343
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    ABSTRACT: To date experimental in vivo pheochromocytoma (PC) models have not been available. A major in vitro PC model consists of PC12 cells that respond to nerve growth factor (NGF) by differentiation, mediated by the trkA receptor. We report the establishment of PC12 tumor models expressing low and high levels of trkA receptor in CD1 nude mice. The tumors are characterized by their responsiveness to NGF, karyotype, presence of enolase, and chromaffin granules, as well as dopamine release. These novel PC models facilitate research on the role of the trkA receptor in cancer and the development of trkA-selective anti-cancer agents.
    Cancer Letters 10/2003; 200(2):177-85. DOI:10.1016/S0304-3835(03)00414-2 · 5.02 Impact Factor
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    ABSTRACT: Snake venoms are a very abundant source of nerve growth factors (NGF). NGFs of Elapidae showing 65% sequence homology with mouse or human NGF, while the Viperidae NGF shows N-glycosylation (Asn-21) typical of these mammalian NGFs. Snake NGF-induced neurite outgrowth (neurotropic activity) was measured in the past by using PC12 cell or dorsal root ganglion bioassays. The present study was aimed at comparing, by dose-response experiments, the neurotropic activity of cobra and vipera versus mammalian NGFs, by using a novel bioassay involving PC12 cells genetically engineered to overexpress NGF-trkA receptors of human origin. These cells respond to NGF by differentiation (morphologically expressed as neurite outgrowth) by a process mediated by NGF-trkA receptors. This process was evaluated by two different criteria: (1) elongation of neurites (E), and (2) Percentage of responsive cells (PRC) determined by digital acquisition of data and computer analysis. We found that snake venom NGFs were less potent than mouse NGF, and that cobra NGF was more potent than vipera NGF. These data indicate the following order of NGF activity towards recombinant human trkA receptors: recombinant human NGF>mouse NGF>cobra NGF>vipera NGF. The neurotropic efficacy of these NGFs was found to be similar, reaching 80-90% of maximal activity obtained with all NGF forms. Interestingly, cobra (but not vipera) NGF demonstrated prolonged neurotropic activity compared with mouse NGF. The results of the present study indicate that cobra and vipera venom NGFs represent natural agonists of human trkA-receptor of a lower potency, but of similar efficacy, compared with mammalian NGFs. These compounds are important pharmacological tools to characterize the trkA receptor structure-function relationship, and to develop novel neurotropic drugs.
    Toxicon 10/2003; 42(5):481-90. DOI:10.1016/S0041-0101(03)00225-3 · 2.58 Impact Factor
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    ABSTRACT: Luminol-amplified chemiluminescence was generated by alveolar macrophages, harvested from the bronchoalveolar lavages of 16 patients with different radiological stages of non-invasive (asymptomatic) sarcoidosis. None of the patients received any steroid therapy during this study. The mean duration of the disease in these patients was 8 months, with a duration time range of 6-14 months. Six patients were in radiological stage 1, five in radiological stage 2 and five in radiological stage 3. Alveolar macrophages from bronchoalveolar lavages of eight healthy non-smoking volunteers were used as controls. All alveolar macrophages were stimulated by phorbol myristate acetate. A significant decrease was recorded in the intensity of chemiluminescence generated by the phorbol-ester-stimulated alveolar macrophages obtained from patients with sarcoidosis of radiological stages 1 and 2, as compared to the cells collected from healthy individuals (controls). No decrease was recorded in the chemiluminescence generated by stimulated alveolar macrophages collected from patients with radiological stage 3, or from unstimulated alveolar macrophages of any patient. These results provide us with an indicative tool, which might enable us to differentiate, on a functional basis, between the activities of alveolar macrophages in non-active sarcoidosis.
    Luminescence 03/2003; 18(2):103-6. DOI:10.1002/bio.711 · 1.68 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate how ethanol pretreatment and storage temperatures of brain striatum affect levels of biogenic amines in this tissue. Adult Wistar male rats were injected with 25% ethanol (5.0 g/kg i.p.) while the control rats were administered i.p. with the same volume of saline. Two hours later the rats were decapitated, their brains removed, and the striatum separated. Each striatum was divided into three parts: one part was immediately frozen on dry ice and kept at -70 degrees C; a second fragment was kept in a household refrigerator (+4 degrees C); and the third fragment was kept at +22 degrees C. Twenty-four hours later, levels of DA, DOPAC, HVA, 3-MT, 5-HT, and 5-HIAA in the striatum were assayed by HPLC/ED. Immediately after decapitation; ethanol levels were assayed in the serum of ethanol-pretreated and saline-pretreated rats using gas chromatography. Our results indicate that levels of striatal DA, DOPAC, and HVA in saline-pretreated rats decreased significantly when the storage temperature of the striatum was raised from -70 degrees C, through +4 degrees C, to +22 degrees C, while levels of striatal 5-HT and 5-HIAA remained constant within the temperature range tested and levels of 3-MT fluctuated. In ethanol-pretreated rats, striatal levels of DOPAC, HVA, and 5-HIAA were increased in all three storage temperatures, while levels of DA, 5-HT, and 3-MT were decreased in those temperatures. Those decreases were most profound in striatal samples kept at +22 degrees C. We conclude that concern about possible interactions between drugs and biogenic amines should be exercised.
    Receptors and Channels 02/2003; 9(5):339-42.
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    ABSTRACT: Levels of 19 proteinous amino acids and of total free amino acids were assayed by gas-liquid chromatography in cytosols of rat atrial and ventricular heart muscle cardiomyocytes. These amino acids were assayed after the rats had been exposed to either exercise (swimming) or hypoxia (hypobaric pressure of 686 hectoPascals). Out of the total free amino acids levels of arginine, glutamine and cysteine in atrial and ventricular cardiac muscle cytosols of control rats were the highest of all amino acids assayed. The control levels of all other amino acids assayed in atrial or ventricular cardiac muscles ranged from 0.1% to 10.6% of the total free amino acids in the control rats. Physical stress (exercise and hypoxia) significantly reduced the total amount of cytosolic free amino acids in both heart muscles. While hypoxia decreased the levels of arginine in both heart muscles, exercise abolished the level of cysteine in the atrial heart muscle. Decrease in arginine levels, and elimination of cysteine from the heart's atrial muscle after physical stress, may be attributed to its utilization of nitric oxide and to its synthesis of atriopeptin and/or endothelin during stress. No change was recorded in either experimental group in the level of glutamine in heart muscle cytosol. Exercise and hypoxia affect, in different modes, the levels of all other amino acids assayed, except for tryptophan, tyrosine, and histidine, which are precursors of endogenous neurotransmitters. The impact of proteinous amino acids on some bodily functions is discussed.
    Receptors and Channels 02/2003; 9(5):301-7.
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    ABSTRACT: Pregnant rats consumed 50 ppm cadmium (as CdCl2) in their drinking water, with or without 10% v/v of added ethanol, for the 21 days of their pregnancies. Levels of the following biogenic amines were assayed by HPLC/ED in the hippocampus and in the frontal cortex of their 2-month-old adult offspring: dopamine, DOPAC, HVA, 5-HT, 5-HIAA and noradrenaline. Also, levels of cadmium in the brain, liver, kidneys and bone of 6-week-old offspring were assayed by atomic absorption spectrometry. In the hippocampus, an increase in noradrenaline levels was recorded in the cadmium- and the ethanol-pretreated groups, compared with their controls. Concomitant prenatal exposure of the rats to cadmium and ethanol prevented this increase, and kept the noradrenaline at its control level. No changes in dopamine or DOPAC levels were observed in any of the groups studied. Hippocampal 5-HT was increased in both groups that consumed cadmium prenatally. A decrease in levels of DOPAC was observed in the cortex of all rats pretreated with cadmium or ethanol. Concomitant consumption of cadmium and ethanol brought the levels of DOPAC to their control values. Elevated tissue levels of cadmium were recorded in organs of 6-week-old offspring that had consumed this metal prenatally. Also, concomitant prenatal consumption of both cadmium and ethanol by the rats brought the cadmium levels in the brains of their 6-week-old offspring to the control levels. We conclude that if rats consume during their pregnancies cadmium and/or ethanol in their drinking water, levels of some of their central neurotransmitters are affected. We also conclude and re-affirm that ethanol modulates the deposition of cadmium in rats that had consumed this metal during their pregnancies.
    Pharmacology Reviews and Communications 10/2002; 12(4):229-239. DOI:10.1080/10604450214705
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    ABSTRACT: Pregnant rats consumed 50 ppm cadmium as CdCl2, with or without ethanol (10% v/v) in their drinking water, for the entire 21 days of their pregnancies. Control rats drank filtered tap water without these additives. Levels of dopamine, DOPAC, HVA, 3-MT, 5-HT, 5-HIAA, and noradrenaline were determined in the striatum of the rats' adult offspring, by HPLC/EC. In addition, turnover (rate of synthesis) of dopamine and 5-hydroxytryptophan from their precursors was determined in the striatum. Also, DOPAC release in the striatum of the adult offspring was recorded by in vivo voltametry. This study demonstrates that whereas consumption of cadmium or ethanol increased dopamine levels in the striatum (embryotoxic effect), concomitant consumption of cadmium plus ethanol dropped dopamine levels to their control levels. As for dopamine turnover, cadmium, but not ethanol, decreases dopamine turnover and DOPAC release in the striatum of adult offspring rats, while concomitant consumption of cadmium plus ethanol prevented those changes. We conclude that when offspring of rats are exposed during their intrauteral development to cadmium and/or to ethanol, via their mothers, when adults, they experience modulation of their central dopaminergic neurotransmitter system.
    Pharmacology Reviews and Communications 10/2002; 12(4):249-259. DOI:10.1080/10604450214703
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    ABSTRACT: Levels of the amino acids tryptophan, phenylalanine and tyrosine, and total free amino acids, were assayed by gas-liquid chromatography in cytosols of rat atrial and ventricular muscle cardiomyocytes. The tissues were assayed after the rats had been exposed to either exercise (swimming), hypoxia, or one of six cardioactive drugs. The drugs, all known to exert a significant effect on the heart muscle, were propranolol, digoxin, pentylenetetrazol, reserpine, isoproterenol and caffeine. Physical stress and the test drugs significantly reduced the total amount of cytosolic free amino acids in both heart muscles. In the atrial muscle, exercise and pentylenetetrazol increased, while isoproterenol and propranolol decreased, the ratio of tryptophan to the total free amino acids. In the ventricular muscle, caffeine and pentylenetetrazol increased, while isoproterenol, propranolol, and digoxin decreased, that ratio. Only reserpine increased the ratio of phenylalanine to the total free amino acids in the ventricular muscle. Digoxin completely abolished the level of tyrosine in the atrial muscle. Hypoxia, isoproterenol, caffeine, propranolol, and pentylenetetrazol increased the ratio of tyrosine to the total free amino acids in the atrial muscle, while in the ventricular muscle the ratio of tyrosine to the total free amino acids increased after hypoxia and decreased after digoxin pretreatment.
    Pharmacology Reviews and Communications 07/2002; 12(3):151-162. DOI:10.1080/10604450213834
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    ABSTRACT: Nerve growth factor (NGF) is a neurotrophin required for differentiation, development, and survival of the sympathetic nervous system, with many of its biological effects being mediated via trkA receptors. There is a need for a standard quantitative bioassay for NGF, to be used in basic research and in pharmaceutical studies. The objective of the present research was to develop a selective, quantitative, and reliable bioassay for NGF, using a morphological criterion: neurite cell outgrowth. In addition, we aimed to apply the aforementioned bioassay to measure NGF administered to mice. Pheochromocytoma PC12 cell variants including wild-type cultures, and a trkA-overexpressing stable transfectant PC12-6.24-I, PC12nnr5, and PC12EN lacking trkA receptors, were used. Dose-response curves were generated with NGF beta-subunit (2.5S) purified from mouse submaxillary glands. Our results demonstrated that the bioassay was sensitive to 0.3-20 ng/mL, and selective, as neurite outgrowth was not seen by any other growth factor other than NGF. In addition, variant clones PC12nnr5 and PC12EN, lacking trkA receptors, did not respond to NGF. The bioassay detected NGF in serum of mice injected with NGF. This novel developed bioassay can serve as a model system for various neuroscience purposes.
    Journal of Molecular Neuroscience 07/2002; 18(3):251-64. DOI:10.1385/JMN:18:3:251 · 2.76 Impact Factor
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    ABSTRACT: Studies with cell cultures indicate that extremely low-frequency magnetic fields may exert distinct biological effects on cellular systems. In the present study, selected biological effects of such magnetic fields are investigated in mammalian J774.2 macrophages in culture. J774.2 murine macrophages were exposed to extremely low-frequency magnetic field (ELF-MF) (25 Hz), and stimulated by lipopolysaccharide (LPS) and/or interferon-γ (IFN-γ). The generation of nitrite (NO2−), prostaglandin-E2 (PGE2), tumor necrosis factor-alpha (TNF-α), chemiluminescence, and proteins were measured. While 1.5 mT and 25 Hz frequency did not affect the viability of the cells, higher flux density (2.4 mT) impaired it significantly. A 24-h exposure of the cells to such frequencies increased their chemiluminescence count rate and TNF-α levels, but not their PGE2, NO2−, or protein concentrations. These results demonstrate that exposure of J774.2 cells to extremely low-frequency magnetic field, at certain flux densities, decreases cell viability and may have biological significance in the antitumoricidal effect of such magnetic fields.
    Electromagnetic Biology and Medicine 05/2002; 21(2):141-153. DOI:10.1081/JBC-120006786 · 0.77 Impact Factor
  • Pharmacology Reviews and Communications 04/2002; 12(2):77-77. DOI:10.1080/10604450213051
  • Pharmacology Reviews and Communications 04/2002; 12(2):101-108. DOI:10.1080/10604450213048
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    ABSTRACT: The effect of manganese intoxication on modulation of reactivity of central dopaminergic, serotoninergic and muscarinic receptors, was studied in Wistar rats and in their adult offspring. Pregnant Wistar rats were allowed to drink water containing either 1,000 or 10,000 ppm manganese during their entire pregnancies, and receptor reactivity of their male offspring was evaluated when they were two months old. 7-OH-DPAT (a D3 agonist), SKF-38393 (a D1 agonist), apomorphine (a D1/D2 agonist), mCPP (a 5-HT2C agonist) and pilocarpine (a muscarinic agonist) were used as agonists of the dopaminergic, serotoninergic and muscarinic receptors, while yawning, oral movements, locomotion, exploratory activity and stereotype behavior were the end parameters for the activation of these receptors. Also, D1 and D2 receptor antagonists (SCH-23390 and haloperidol, respectively) were used for evaluating the effect of manganese intoxication on drug-induced cataleptogenicity in rats. Irritability and reaction to pain stimulus on a hot plate were also examined. In addition, 3H-glucose uptake in discrete parts of the brain, and in some peripheral tissues, was examined in two-month old rat offspring. In conclusion, our results indicate that manganese change the reactivity of the central dopaminergic and muscarinic receptors, but not of the serotoninergic ones. Prenatal exposure to manganese in drinking water did not affect glucose uptake in brain fractions or in peripheral tissues of offspring born to manganese-consuming pregnant rats.
    Pharmacology Reviews and Communications 01/2002; 12(1):9-24. DOI:10.1080/10604450213044
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    ABSTRACT: Effect of prenatal oral administration of manganese on the level, turnover and release of biogenic amines in the brain, was studied in adult offsprings of rats. Pregnant Wistar rats were allowed to drink water without or with manganese 10,000 ppm, during their entire pregnancies. Levels of biogenic amines and their metabolites (DA, DOPAC, HVA, 3-MT, 5-HT, 5-HIAA and NA) were assayed in the striatum, frontal cortex and hippocampus of adult male offsprings, by HPLC/ED. In addition, the effect of amphetamine and haloperidol on release of the above amines was evaluated in the striatum of freely-moving rats, by brain microdialysis. Also, DOPAC release was measured in the striatum by in vivo voltametry, after amphetamine administration. Manganese levels were assayed in the brain, liver, kidneys and bone of the mothers, and in their one-day-old offsprings. Our results indicate that prenatal exposure of manganese does not alter the levels of biogenic amines in the rats' brains, and does not affect the release of biogenic amines in the striatum, after administration of amphetamine and haloperidol. Release of striatal DOPAC decreased in amphetamine-treated rats, prenatally exposed to manganese. Also, prenatal manganese decreased DA and 5-HT turnover in the striatum of adult offspring rats. In conclusion, increased manganese levels were noticed in the brain and liver of rat mothers exposed to manganese during their pregnancies, but its levels in their one-day-old offsprings was about 20 times lower as compared to the tissues of the mothers, and no differences between control and prenatally manganese-exposed rats were noticed, suggesting an extensive excretion of this pollutant from the body.
    Pharmacology Reviews and Communications 01/2002; 12(1):61-75. DOI:10.1080/10604450213046
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    ABSTRACT: This study evaluates the homogeneity of alveolitis by estimating lymphocyte subsets in bronchoalveolar lavage, and by high-resolution computed tomography (HRCT). This may help in determining the usefulness of HRCT as a guiding method in selecting the lung region most suitable for bronchoalveolar lavage. Simultaneous double lavage, from upper and lower lung segments, was performed in 28 patients with sarcoidosis who were evaluated previously using HRCT. Twenty-eight patients with sarcoidosis and 11 healthy volunteers participated in this study. Twelve of the patients showed a homogenous distribution, and 16 showed a nonhomogenous distribution of changes observed by HRCT. HRCT was performed in all patients at maximum inspiration. Most and least affected segments were determined. Bronchoalveolar lavage was then performed in both sites. Lymphocyte subpopulations (CD3, CD19, NK, CD4, CED8, HLA-DR (human lymphocytes antigen-D-region), and CD25) were estimated by flow cytometry. In the extensively involved lung sites of the patients with nonhomogenous involvement of the disease, there are substantially more lymphocytes and higher CD4 to CD8 ratios compared with the less involved sites. When all results were pooled together, the mean percentage of lymphocytes in the upper lobe was substantially higher than that in the lower lobe. It is concluded that although HRCT is useful for selecting the most reliable lung region for bronchoalveolar lavage, alveolitis is not fully homogenous and its intensity is greater in lung sites with more extensive involvement of sarcoidosis, as determined by HRCT.
    09/2001; 8(4):260-266. DOI:10.1097/00128594-200110000-00005

Publication Stats

2k Citations
300.96 Total Impact Points


  • 1970–2008
    • Hebrew University of Jerusalem
      • • Department of Pharmacology
      • • School of Pharmacy
      • • Faculty of Medicine
      Yerushalayim, Jerusalem District, Israel
  • 2004
    • Medical University of Silesia in Katowice
      • Department of Histology and Embryology
      Katowice, Silesian Voivodeship, Poland
  • 1998
    • Ben-Gurion University of the Negev
      • Department of Nuclear Engineering
      Beersheba, Southern District, Israel
  • 1996–1998
    • Polish Academy of Sciences
      • Institute of Pharmacology
      Warszawa, Masovian Voivodeship, Poland
  • 1990
    • University of California, Los Angeles
      Los Ángeles, California, United States
  • 1989
    • Hadassah Medical Center
      • Department of Pharmacology
      Yerushalayim, Jerusalem District, Israel
  • 1976–1989
    • University of Southern California
      • • School of Pharmacy
      • • Department of Medicine
      Los Angeles, CA, United States
  • 1982
    • University of Wisconsin–Madison
      Madison, Wisconsin, United States
  • 1981
    • Technion - Israel Institute of Technology
      H̱efa, Haifa, Israel