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Biomedical subjects

A Levy

Publications and source records attributed to A Levy.

At least 163 records · Page 9Linked to original sources

Morphological alterations in the hippocampus following hypobaric hypoxia.

1. The morphological consequences of hypobaric hypoxia, exposure to reduced pressure atmospheres, were examined in the hippocampus of male Fischer 344 rats. Severe chronic hypoxia can produce permanent neuronal damage with hippocampal structures being especially vulnerable. 2. Hippocampal morphology was studied using histological observations after a 4 day exposure to sea level, 3500 m, or 6400 m. Two groups tested at 6400 m were sacrificed at different intervals following exposure, 72 and 144 h, to examine the effect of post-exposure time on neuronal damage. 3. Histological damage was observed in rats' brains following exposure to altitude, with cell degeneration and death increasing as altitude increased. In addition, it was found that the longer the time following exposure before sacrifice, the more noticeable the damage, suggesting delayed neurotoxicity. Increases in the number of damaged cells following altitude were significant for the CA3 region of one 6400 m group; however, other differences did not reach statistical significance. Rats exposed to altitude for 4 days ate less and lost significantly more weight than did animals at sea level. 4. It appears that 4 days of exposure to altitudes less than or equal to 6400 m does produce changes in the CA3 subfield, but the damage is different than that seen with other models of non-transient ischemia.

Altitude Sickness↗

Effects of extracellular nucleotides in the pituitary: adenosine triphosphate receptor-mediated intracellular responses in gonadotrope-derived alpha T3-1 cells.

We have recently identified gonadotropes as target cells for ATP action via ATP receptors of the P2U subtype. The present studies have used gonadotrope-derived alpha T3-1 cells to examine the possible signaling mechanisms subserving ATP action in gonadotropes. Addition of ATP produced a biphasic intracellular Ca2+ (Ca2+i) response: a transient spike followed by a small plateau. Removal of extracellular Ca2+ or depolarization with KCl abolished the plateau but had no effect on the spike. The plateau was also blocked by cadmium or nifedipine but not nickel. Pretreatment with GnRH or thapsigargin but not ryanodine inhibited the subsequent Ca2+i response to ATP. Pertussis toxin had no effect on ATP-induced Ca2+i response, whereas the phospholipase C inhibitor U73122 reduced the response. These observations suggest that the Ca2+i response is mediated by a pertussis toxin-insensitive and phospholipase C-coupled G-protein and reflects Ca2+ release from the GnRH- and thapsigargin-sensitive Ca2+ pool followed by Ca2+ influx through high voltage-gated Ca2+ channels. Activation of these ATP receptors had no apparent effects on the cAMP and cGMP signaling systems. Treatment with ATP-gamma S caused the translocation of protein kinase C (PKC) epsilon but not PKC zeta and PKC alpha to the particulate fraction. These data not only characterize the ATP receptor-mediated intracellular signaling in alpha T3-1 cells and render further evidence for a mediator role for nucleotides in gonadotrope function but also provide the first direct demonstration of PKC translocation by ATP receptors.

Biological Transport↗

Molecular cloning and functional characterization of a rat pituitary G protein-coupled adenosine triphosphate (ATP) receptor.

There is increasing evidence that pituitary ATP receptors may play a novel role in modulating pituitary function. This work reports the isolation and expression of a pituitary ATP receptor gene clone from a rat pituitary complementary DNA library. The isolated clone (rpP2U) has a 1125-bp coding sequence flanked by 483 bp of 5' - and 422 bp of 3'-untranslated sequences. The deduced 374-amino acid product shows structural features common to other G protein-coupled receptors, and when stably transfected into a glioma cell line lacking endogenous ATP receptors, is functionally characterized as a P2U purinoceptor. Specifically, the ATP-induced intracellular Ca2+ mobilization in the transfected cells was inhibited by suramin, 2-methylthio-ATP had a modest stimulatory effect on intracellular Ca2+ mobilization, and beta, gamma-methylene ATP and alpha, beta-methylene ATP had no effect. The cloned receptor exhibited the agonist potency and efficacy profile of ATP approximately equal to uridine triphosphate > ADP approximately equal to uridine diphosphate > GTP. Such characteristics very closely mimic the pharmacologically defined P2U purinoceptor of primary rat gonadotropes and mixed sheep pituitary cells, and Southern blot analysis further indicates that there is only one allele in rat genome for the P2U purinoceptor. These findings suggest that the P2U purinoceptor is the predominant G protein-linked ATP receptor found in the pituitary.

Adenosine Triphosphate↗

Differential regulation of the growth hormone receptor gene: effects of dexamethasone and estradiol.

GH receptor (GHR) expression differs during development between central and peripheral tissues. Peripheral GHR expression is known to be sensitive to gonadal and adrenal steroids, but little is known about their effects on GHR in the central nervous system. We have now studied the effects of estradiol (E2) or dexamethasone on GHR expression in rat arcuate nucleus (ARC) and hippocampus, using quantitative in situ hybridization. Dexamethasone, which strongly down-regulates hepatic GHR expression, had no effect on central GHR transcript abundance, whereas E2 treatment, which stimulates hepatic GHR expression, significantly reduced ARC GHR messenger RNA (mRNA) levels. E2 also increased somatostatin (SS) expression significantly in both ARC and periventricular nuclei but did not reduce ARC GH-releasing hormone (GHRH) mRNA levels. Ovariectomy stimulated GHR and GHRH mRNA levels in the ARC, whereas it lowered ARC SS expression. E2 replacement in ovariectomized animals restored GHRH and SS mRNA levels to control values. Hippocampal GHR mRNA transcripts showed the same response to these endocrine manipulations as seen in the ARC. The induction of hepatic GHR expression by E2 is known to involve the transcription of an alternate 5' untranslated first exon, GHR1. This was readily detectable in the liver using a specific GHR1 probe but could not be detected in any CNS area. Our results show that GHR expression in the CNS is sensitive to regulation by peripheral steroids but that CNS and hepatic expression of GHR is differentially regulated by the same treatments.

Animals↗

Burkitt's lymphoma-leukemia in patients treated for Hodgkin's disease.

We reviewed all reported cases of Burkitt's lymphoma and/or Burkitt's leukemia (BLL) occurring following therapy for Hodgkin's disease. In addition to the case described in this report, a total of 19 patients have been previously reported. The male/female ratio was 3.75. Treatment for Hodgkin's disease included chemotherapy combined with radiation therapy in 15 patients, chemotherapy in 3 patients, and radiation therapy alone in 1 patient. Median interval between Hodgkin's disease and the diagnosis of BLL was 97 months. Patient characteristics are similar to those with de novo BLL. Bone marrow, abdomen, central nervous system, as well as extranodal organs were commonly involved. Typical cytogenetic translocations seen in patients with primary BLL were found in 6 patients, but 5 of these patients had additional cytogenetic abnormalities. Only 2 patients achieved complete remission after chemotherapy. The mechanism for the development of BLL after treatment for Hodgkin's disease is unknown. Although the majority of cases have been seen in patients treated with combined-modality therapy, the role of previous therapy in causing this complication cannot be assessed in this study.

Adult↗

Distinct expression levels of cytokines and soluble cytokine receptors in seminal plasma of fertile and infertile men.

OBJECTIVE: To compare the levels of interleukin (IL) 1 beta, IL-6, tumor necrosis factor (TNF) alpha, and soluble TNF (sTNF) receptors types I and II, and IL-1 receptor antagonist in seminal plasma of fertile and infertile men. DESIGN: Prospective and comparative study. SETTING: Andrology clinic of a university hospital. PATIENTS: Four groups of normogonadotropic men: group 1, donors with proven fertility (controls, n = 15); group 2, azoospermic men (n = 12); group 3, infertile men with oligoteratoasthenospermia (n = 20); and 11 men with oligoteratoasthenospermia and genital infection (n = 11). INTERVENTIONS: None. MAIN OUTCOME MEASURE: Measurement of cytokines and cytokine-soluble receptors in the semen by specific commercial kits. RESULTS: The levels of IL-1 beta, TNF-alpha, and IL-6 were similar in seminal plasma of controls and infertile men. The mean level of sTNF-I receptor in the seminal plasma of group 4 was 2.4 +/- 0.2 ng/mL, which was significantly lower than observed in seminal plasma of group 1 (3.88 +/- 0.5 ng/mL), the group 3 (4.1 +/- 0.4 ng/mL), or group 2 (3.03 +/- 0.35 ng/mL). The soluble receptor of TNF-II could not be detected in any group. Interleukin 1ra was 120 +/- 10 pg/mL in seminal plasma of group 1, but increased levels were detected in group 2 (420 +/- 180 pg/mL), group 3 (480 +/- 90 pg/mL), and even higher (760 +/- 120 ng/mL) in group 4 patients. CONCLUSIONS: During genital infection cytokines and various soluble receptors of immunoregulatory cytokines are expressed distinctly in seminal plasma. These factors also may be involved in the regulation of sperm cell functions and thus may affect male fertility. Our results may indicate local production of these factors in the secondary sex glands, independently of spermatogenesis.

Cytokines↗

Lessons denied: a history of therapeutic response to combat stress reaction during Israel's War of Independence (1948), the Sinai Campaign (1956) and the Six Day War (1967)

The current article examines the history of therapeutic response in the Israel Defense Forces toward combat stress reaction during two decades, and in the course of three wars: the 1948 War of Independence, the 1956 Sinai Campaign, and the 1967 Six Day War. Three independent sources were used: recorded debriefing materials; interviews conducted with therapists, commanders and military historians; and professional literature on the wars in Hebrew and other languages. The collected material is described and issues of attitudes, treatment approaches and preparedness are discussed.

Combat Disorders↗

Lessons relearned--when denial becomes impossible: therapeutic response to combat stress reaction during the Yom Kippur War (1973), the Lebanon War (1982) and the Intifada.

This article presents the attitudes toward CSR during and after the 1973 Yom Kippur War, the 1982 Lebanon War and the Intifada. It analyzes the transition from denial to recognition which evolved following the Yom Kippur War. Several explanations are suggested and discussed, including structural, political and psychoanalytic perspectives.

Combat Disorders↗

Forensic implications of the difficulties of defining delusions.

Delusions are evasive to define: (1) Within the process of defining, one uses part of the final conclusion, which should derive from the basic definition (in other words, Circular reasoning); (2) Many, if not most, of so-called normal persons, hold delusion-like ideas; (3) Delusion becomes, usually, more understandable and less bizarre when investigated; (4) Delusions are not unique by remaining resistible to reason; (5) For every delusional content, as bizarre and remote as it may be, there is at least one cultural niche, in which the same content is considered legitimate and reasonable, (if no important and dignified). The forensic implications of these difficulties (to define delusions), will be discussed and elaborated.

Culture↗

[Consequences of misdiagnosis and labeling in psychiatry].

Differences in diagnostic approaches between psychiatry and other medical specialties were examined and problems resulting from misdiagnosis are presented. The labelling and stigma resulting from misdiagnosis have severe implications and there is inherent difficulty in correcting misdiagnoses of major psychiatric disorders. We present a 38-year-old man who underwent numerous psychiatric and psychological examinations in order to change a previous misdiagnosis. The difficulties examiners had in accepting the possibility of misdiagnosis, and its severe consequences, are described.

Adult↗

Possible involvement of atrial natriuretic peptides in olfaction.

Atrial natriuretic peptides (ANP) are a family of humoral compounds released from the heart atria and involved in water and salt homeostasis. ANP immunoreactivity and ANP-binding sites were also found in several areas of the central nervous system including the olfactory bulb. In the present study, the possible involvement of ANP in olfaction was tested by measuring the content and distribution of IR-ANP and ANP-binding sites in rat olfactory bulb in control and rats. The results implicate ANP in the processes leading to olfactory perception.

Animals↗

Evidence for a role of pituitary ATP receptors in the regulation of pituitary function.

Despite a rapidly increasing acceptance for a role of ATP as an extracellular mediator in several biological systems, the present report shows that ATP may mediate physiological responses in pituitary cells. We have now been able to demonstrate a specific action of ATP receptors to mediate the release of luteinizing hormone from gonadotropes and have coupled them with further studies that clearly show that ATP can be exocytotically released from cultured rat pituitary cells. Both ATP and UTP (100 microM) caused a > 14-fold increase in the rate of luteinizing hormone release from superfused cells. Adenosine 5'-[alpha, beta-methylene]triphosphate and 5'-[beta,gamma-methylene triphosphate were ineffective, and 2-methylthio-ATP had only a modest stimulatory effect. Homologous and heterologous desensitization occurred with UTP and ATP, and these did not have additive effects. Thus, nucleotides can be effective stimulators of luteinizing hormone release through a single class of ATP receptor (P2U subtype). The calcium ionophore A23187 provoked release of a substantial amount of ATP from pituitary cells in a concentration- and Ca(2+)-dependent manner, which was desensitized by pretreatment with A23187. This implies a possible paracrine and/or autocrine mechanism by which nucleotides may exert their effects on pituitary cells. In conclusion, we have provided strong evidence for a novel role of extracellular nucleotides as mediators in pituitary--in particular, in gonadotrope--function.

Adenosine Triphosphate↗

Nimodipine counteracts corticosterone-induced habituation impairments.

Corticosterone or placebo sustained-release pellets (4 pellets of 200 mg each, released over 90 days) were implanted subcutaneously in young Fischer-344 rats, fed with either regular food or with food containing 860 ppm of nimodipine. Following 2 weeks of treatment, the habituation of the rats to a new environment was studied. On the first test day, placebo-implanted rats explored the new environment and exhibited a characteristic habituation. On the second test day, 48 hr later, low activity was measured in the already familiar environment. This habituation was absent in corticosterone-implanted rats fed with regular food. However, corticosterone-implanted rats fed with food containing nimodipine behaved during the second test similarly to the placebo-implanted group. The data indicated that the behavioral deficit, induced in Fischer-344 rats by the high corticosterone levels, was reversed by the nimodipine treatment. Thus, nimodipine may be useful in counteracting certain prolonged stress-related cognitive impairments.

Animals↗