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Biomedical subjects

N Levy

Publications and source records attributed to N Levy.

At least 55 records · Page 3Linked to original sources
PubMed1998

Serotonin transporter (5-HTT) gene polymorphisms are not associated with susceptibility to mood disorders.

In a population-based association study, we tested the hypothesis that allelic variants of the human serotonin transporter (5-HTT) gene confer susceptibility to mood disorders. Both a biallelic repeat polymorphism in the 5' promotor region that differentially modulates gene expression and a second intron variable-number-tandem-repeat (VNTR) marker were genotyped in 294 controls and 115 patients with mood disorders. Subjects were of West European descent and included 36 patients with major depressive disorder (MDD) and 79 patients with bipolar I disorder (BD). No significant differences in genotype or allele frequencies were found at either locus between controls and combined patients, nor between controls and MDD or BD patients separately. Thus, our data do not support the association between depressive disorder and a nine-repeat allelic variant of the 5-HTT VNTR marker recently reported by Ogilvie et al. (Lancet 347:731-733, 1996). More importantly, no association between alleles conveying functional differences in 5-HTT gene expression and MDD or BD could be found. Taken together, our data suggest that the 5-HTT gene is not commonly involved in the susceptibility to mood disorders.

Alleles↗
PubMed1998

Memory maintenance via neuronal regulation.

Since their conception half a century ago, Hebbian cell assemblies have become a basic term in the neurosciences, and the idea that learning takes place through synaptic modifications has been accepted as a fundamental paradigm. As synapses undergo continuous metabolic turnover, adopting the stance that memories are engraved in the synaptic matrix raises a fundamental problem: How can memories be maintained for very long time periods? We present a novel solution to this long-standing question, based on biological evidence of neuronal regulation mechanisms that act to maintain neuronal activity. Our mechanism is developed within the framework of a neural model of associative memory. It is operative in conjunction with random activation of the memory system and is able to counterbalance degradation of synaptic weights and normalize the basins of attraction of all memories. Over long time periods, when the variance of the degradation process becomes important, the memory system stabilizes if its synapses are appropriately bounded. Thus, the remnant memory system is obtained by a dynamic process of synaptic selection and growth driven by neuronal regulatory mechanisms. Our model is a specific realization of dynamic stabilization of neural circuitry, which is often assumed to take place during sleep.

Animals↗
PubMed1998

Ambience in the endoscopy room has little effect on patients.

With hopes of alleviating discomfort and improving the tolerance of patients undergoing endoscopy, we have assessed the influence of various background conditions in the endoscopy room. Two hundred twenty-one candidates for upper endoscopy were randomly allocated to four groups, each with one of the following conditions in the endoscopy room: background music and conversation related to the patient's complaints (n=50); background music and conversation unrelated to the patient (n=53); background music only, with the staff maintaining silence (n=49); and complete silence (n=47). Before endoscopy patients answered a 26-item questionnaire that included an evaluation of their degree of anxiety before the examination. Conscious sedation was induced by using 3 mg midazolam. After complete recovery from sedation, patients answered another set of questions. Patients in all four groups felt quite comfortable with the atmosphere in which gastroscopy was performed. Neither music, conversation, nor silence had a great effect on patients as far as improving tolerance or diminishing anxiety. Therefore, endoscopists and nurses may have a free hand in choosing the prevailing conditions during the examination. This conclusion may be valid for both patients and the staff involved in other invasive procedures performed under light sedation.

Anxiety↗
PubMed1998

Neuronal regulation versus synaptic unlearning in memory maintenance mechanisms.

Hebbian learning, the paradigm of memory formation, needs further mechanisms to guarantee creation and maintenance of a viable memory system. One such proposed mechanism is Hebbian unlearning, a process hypothesized to occur during sleep. It can remove spurious states and eliminate global correlations in the memory system. However, the problem of spurious states is unimportant in the biologically interesting case of memories that are sparsely coded on excitatory neurons. Moreover, if some memories are anomalously strong and have to be weakened to guarantee proper functioning of the network, we show that it is advantageous to do that by neuronal regulation (NR) rather than synaptic unlearning. Neuronal regulation can account for dynamical maintenance of memory systems that undergo continuous synaptic turnover. This neuronal-based mechanism, regulating all excitatory synapses according to neuronal average activity, has recently gained strong experimental support. NR achieves synaptic maintenance over short time scales by preserving the average neuronal input field. On longer time scales it acts to maintain memories by letting the stronger synapses grow to their upper bounds. In ageing, these bounds are increased to allow stronger values of remaining synapses to overcome the loss of synapses that have perished.

Adult↗
PubMed1997

Putative odour receptors localize in cilia of olfactory receptor cells in rat and mouse: a freeze-substitution ultrastructural study.

Two different polyclonal antibodies were raised to synthetic peptides corresponding to distinct putative odour receptors of rat and mouse. Both antibodies selectively labelled olfactory cilia as seen with cryofixation and immunogold ultrastructural procedures. Regions of the olfactory organ where label was detected were consistent with those found at LM levels. Immunopositive cells were rare; only up to about 0.4% of these receptor cells were labelled. Despite chemical, species, and topographic differences both antibodies behaved identically in their ultrastructural labelling patterns. For both antibodies, labelling was very specific for olfactory cilia; both bound amply to the thick proximal and the thinner and long distal parts of the cilia. Dendritic knobs showed little labelling if any. Dendritic receptor cell structures below the knobs, supporting cell structures, and respiratory cilia did not immunolabel. There were no obvious differences in morphology between labelled and unlabelled receptor cells and their cilia. Labelling could be followed up to a distance of about 15 microns from the knobs along the distal parts of the cilia. When labelled cells were observed, this signal was detectable in two, sometimes three, sections taken through these cells while being consistently absent in neighbouring cells. This pattern argues strongly for the specificity of the labelling. In conclusion, very few receptor cells labelled with the antibodies to putative odour receptors. Additionally the olfactory cilia, the cellular regions that first encounter odour molecules and that are thought to transduce the odorous signal, displayed the most intense labelling with both antibodies. Consequently, the results showed these cilia as having many copies of the putative receptors. Finally, similar patterns of subcellular labelling were displayed in two different species, despite the use of different antibodies. Thus, this study provides compelling evidence that the heptahelical putative odour receptors localize in the olfactory cilia.

Amino Acid Sequence↗
PubMed1997

Putative odour receptors localize in cilia of olfactory receptor cells in rat and mouse: a freeze-substitution ultrastructural study.

Two different polyclonal antibodies were raised to synthetic peptides corresponding to distinct putative odour receptors of rat and mouse. Both antibodies selectively labelled olfactory cilia as seen with cryofixation and immunogold ultrastructural procedures. Regions of the olfactory organ where label was detected were consistent with those found at LM levels. Immunopositive cells were rare; only up to about 0.4% of these receptor cells were labelled. Despite chemical, species, and topographic differences both antibodies behaved identically in their ultrastructural labelling patterns. For both antibodies, labelling was very specific for olfactory cilia; both bound amply to the thick proximal and the thinner and long distal parts of the cilia. Dendritic knobs showed little labelling if any. Dendritic receptor cell structures below the knobs, supporting cell structures, and respiratory cilia did not immunolabel. There were no obvious differences in morphology between labelled and unlabelled receptor cells and their cilia. Labelling could be followed up to a distance of about 15 microns from the knobs along the distal parts of the cilia. When labelled cells were observed, this signal was detectable in two, sometimes three, sections taken through these cells while being consistently absent in neighbouring cells. This pattern argues strongly for the specificity of the labelling. In conclusion, very few receptor cells labelled with the antibodies to putative odour receptors. Additionally the olfactory cilia, the cellular regions that first encounter odour molecules and that are thought to transduce the odorous signal, displayed the most intense labelling with both antibodies. Consequently, the results showed these cilia as having many copies of the putative receptors. Finally, similar patterns of subcellular labelling were displayed in two different species, despite the use of different antibodies. Thus, this study provides compelling evidence that the heptahelical putative odour receptors localize in the olfactory cilia.

Amino Acid Sequence↗
PubMed1997

Effect of ranitidine on the urea breath test: a controlled trial.

Because Helicobacter pylori is an acid-sensitive organism, an elevation of the gastric pH by H2 inhibitors might improve the intragastric conditions for the development of this organism. We tested this hypothesis in a prospective and controlled trial including 43 patients positive for H. pylori using the rapid urease test. Twenty-six patients received 150 mg ranitidine twice daily and 17 patients received no treatment. The 14C-urea breath test was performed in both groups at the beginning of the study and 2 weeks later. Radioactive 14C in exhaled carbon dioxide was significantly increased (p = 0.045) in the patients treated with ranitidine, compared with the patients in the control group. Administration of this drug to patients infected with H. pylori is associated with an increase in the bacterial load after 2 weeks of treatment. This phenomenon might be attributed to increased bacterial growth due to the H2 blocker.

Anti-Ulcer Agents↗
PubMed1996

Tyrosine kinase inhibitors and cycloheximide inhibit Li+ protection of cerebellar granule neurons switched to non-depolarizing medium.

Recently, it has been shown that Li+ robustly enhances the survival of cerebellar granule neurons acutely switched to non-depolarizing medium after maturing in vitro, a condition which elicits massive apoptotic death in this cell type. Tyrosine protein phosphorylation is known to underlie the activity of a number of trophic factors. This prompted us to investigate whether specific tyrosine kinase inhibitors could modulate the Li+ protection of cultured granule neurons switched to non-depolarizing medium. Genistein and herbimycin A dose dependently abolished the Li+ effect. Furthermore, this effect was substantially prevented by the translational inhibitor cycloheximide, suggesting that it requires de novo protein synthesis. Overall, these results suggest that Li+ protection of cerebellar granule neurons switched to non-depolarizing medium involves tyrosine kinases and transcriptional activation.

Apoptosis↗
PubMed1996

Neuronal-based synaptic compensation: a computational study in Alzheimer's disease.

In the framework of an associative memory model, we study the interplay between synaptic deletion and compensation, and memory deterioration, a clinical hallmark of Alzheimer's disease. Our study is motivated by experimental evidence that there are regulatory mechanisms that take part in the homeostasis of neuronal activity and act on the neuronal level. We show that following synaptic deletion, synaptic compensation can be carried out efficiently by a local, dynamic mechanism, where each neuron maintains the profile of its incoming post-synaptic current. Our results open up the possibility that the primary factor in the pathogenesis of cognitive deficiencies in Alzheimer's disease (AD) is the failure of local neuronal regulatory mechanisms. Allowing for neuronal death, we observe two pathological routes in AD, leading to different correlations between the levels of structural damage and functional decline.

Alzheimer Disease↗
PubMed1996

The alpha / beta and alpha 2 / alpha 1-globin mRNA ratios in different forms of alpha-thalassemia.

The present study provides information about the alpha / beta and alpha 2 / alpha 1-mRNA ratios in reticulocytes of normal adults and individuals with different alpha-globin gene deficiencies; it found its origin in analytical data of blood samples from a Laotian couple and their newborn baby. The father carried the 4.2 kb deletion on one chromosome and a TAA --> CAA mutation at the terminating codon of the alpha 2 gene (Hb Constant Spring or CS) on the other chromosome. The mother had the 3.7 kb deletion on one chromosome and a TA A --> TAT mutation at the terminating codon of the alpha 2-globin gene (Hb Paksé) of the second chromosome. The baby was a compound heterozygote for the two termination codon mutations. The mRNA data for this family were compared to those for persons with several well-defined alpha-globin gene deficiencies. The results confirm the importance of the alpha 2 alpha 1-mRNA for the synthesis of alpha chains in alpha-thalassemia-2 homozygotes (-alpha/-alpha) and in patients with Hb H disease due to the deletion of three alpha-globin genes (-alpha/--). Furthermore, the MRNA production of the alpha 1-globin gene on the chromosome with the alpha CS mutation (alpha CS alpha) is only one-half of that by the alpha 2 alpha 1-globin gene of a chromosome with a 3.7 or 4.2 kb deletion, explaining the greater severity of, and higher Hb H level in Hb H patients with the alpha CS alpha condition (alpha CS alpha/--) as compared to those with the three gene deletion (-alpha/--). The methodology could be useful as a preliminary screening for the presence of point mutations leading to the functional loss of a single alpha-globin gene, provided common deletional alleles have been excluded.

Adult↗
PubMed1996

Alpha interferon suppresses the cyclin D3 and cdc25A genes, leading to a reversible G0-like arrest.

Alpha interferon is a potent growth inhibitor of Daudi Burkitt's lymphoma cells. We show here that alpha-interferon signaling interacted simultaneously with several components of the basic cell cycle machinery, causing cells to enter into a state that had many features characteristic of the G0 state. Within a few hours after alpha-interferon treatment, cyclin D3 mRNA and protein levels dropped to undetectable levels and, in parallel, the activities of cyclin A- and cyclin E-associated kinases were significantly reduced. The latter resulted from the rapid alpha-interferon-mediated elimination of cdc25A, a phosphatase that is required for antagonism of negative tyrosine phosphorylation of cdk2 in cyclin-cdk complexes. This regulation represents a novel mechanism through which an external inhibitory cytokine interacts with the cell cycle machinery. At later time points after alpha-interferon treatment, the levels of the 55-kDa slowly migrating hyperphosphorylated form of cyclin E and of cyclin A were also reduced. The antiproliferative effects were reversible, and cultures from which alpha interferon was removed reentered S phase after a lag that typically corresponded to approximately two doubling times. During this lag period, the expression of cyclin D3 and cyclin A, as well as of the cdc25A phosphatase, continued to be switched off, in spite of the removal of alpha interferon from the cell surface. In contrast, c-myc, which represents another downstream target gene that is subjected to negative regulation by alpha interferon, was relieved from suppression much earlier, concomitant with the decay in early signaling of the cytokine. The delayed pattern of cyclin reexpression provides evidence that alpha-interferon signaling imposes a G0-like state on this system.

Burkitt Lymphoma↗
PubMed1996

Stage IE non-Hodgkin's lymphoma involving the dura: A clinicopathologic study of five cases.

OBJECTIVE AND DESIGN: Non-Hodgkin's lymphomas rarely present as a localized mass involving the dura. In this report we describe the clinical, histologic, and immunohistochemical features of five cases of stage IE non-Hodgkin's lymphoma involving the dura. PATIENTS: Four women and one man, 36 to 67 years of age (median 50.6 years). RESULTS: Myelography and magnetic resonance imaging scans revealed discrete expansile masses involving the dura of the cervical, thoracic, and lumbar regions of the spinal cord and the frontal lobe of the brain. Histologically, the tumors were classified in the Working Formulation as small lymphocytic (2), diffuse large cell (2), and large cell immunoblastic (1) (anaplastic large cell lymphoma). Four tumors were of B-cell lineage and the anaplastic large-cell lymphoma was of T-cell lineage. The two small lymphocytic neoplasms had immunoglobulin heavy-chain gene rearrangements as shown by either Southern blot hybridization or the polymerase chain reaction. Four patients underwent decompression laminectomy; three received spinal radiation; two received chemotherapy (one intrathecal, one systemic) for lymphocytosis of the cerebrospinal fluid. The dural mass overlying the frontal lobe was excised and focally irradiated. Clinical follow-up was available for all patients. Four patients were alive 12 to 40 months after diagnosis and showed no evidence of recurrent or disseminated disease. The patient with anaplastic large-cell lymphoma died 10 days after laminectomy, secondary to pulmonary thromboemboli. CONCLUSIONS: We conclude that non-Hodgkin's lymphomas of varied histologic types and of either B- or T-cell lineage may rarely present as a stage IE dural mass. These lesions appear to have a good initial response to treatment; however, longer clinical follow-up is necessary to assess the incidence of relapse and final outcome.

Adult↗