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M Shapira

Publications and source records attributed to M Shapira.

At least 37 records · Page 2Linked to original sources
PubMed1998

Independence of, and interactions between, cannabinoid and opioid signal transduction pathways in N18TG2 cells.

N18TG2 neuroblastoma cells co-express delta-opioid and CB1-cannabinoid receptors. Both receptors are negatively coupled to adenylyl cyclase through pertussis toxin-sensitive GTP-binding proteins. In the present study, we confirmed the independent activity of opioid and cannabinoid agonists, and investigated chronic interactions between the two signal transduction pathways in these cells. Opioid and cannabinoid agonists stimulated [35S]guanosine-5'-O-(3-thiotriphosphate) binding to N18TG2 membranes. When the opioid agonist etorphine and the cannabinoid agonist desacetyllevonantradol (DALN) were applied together, the stimulation was similar to the arithmetic sum of the two separate effects. This additivity existed even after partial ablation of the G-proteins reservoir with a low concentration of pertussis toxin, indicating that opioid and cannabinoid receptors activate different pools of G-proteins in N18TG2 cells. Chronic treatment of the cells with either opioid or cannabinoid agonists induced desensitization to the respective drug. In addition, asymmetric cross-desensitization was found: while long-term exposure to DALN induced homologous desensitization, and did not reduce the effect of etorphine, long-term exposure to etorphine attenuated the cannabinoid activation of G-proteins. Chronic exposure to either DALN or etorphine not only induced desensitization, but also elevated the basal activity of G-proteins in the exposed cells. The combination of the two drugs did not yield an additive activation, suggesting that chronic exposure of N18TG2 cultures to cannabinoid and opioid agonists modified a common responding element within the cells. This work presents the N18TG2 neuroblastoma as a suitable experimental model to study the molecular mechanism(s) underlying chronic interactions between opioid and cannabinoid drugs.

Adenylate Cyclase Toxin↗
PubMed1998

Ulcerative colitis in the Kinneret sub district, Israel 1965-1994: incidence and prevalence in different subgroups.

Ulcerative colitis (UC) is prevalent among Jews around the world, as well as in Israel. We evaluated the incidence rates of the disease in one of the northern districts of Israel (Kinneret) by religion and by type of settlement. The population in this district is composed of Jews who have immigrated to Israel in the last century from various countries all over the world, and from Arabs. The study population included all residents of Kinneret district diagnosed with UC between 1965 and 1994. The mean annual incidence rate of UC in the 30 years covered in this survey (1965-1994) proved to be 3.5/100,000. A trend of increase in the incidence rate was observed until 1989. It was most prominent among the Jewish rural settlements. Since 1989, the rates have been declining. Prevalence rates were 87/100,000 among the Jewish population, and 27/100,000 among the Arab population. Both prevalence and incidence rates were 2.5 times higher among Jews than among Arabs. We include that (1) UC morbidity had been increasing until 1989 and has been decreasing moderately ever since; (2) the lowest morbidity was found in the Arab population; and (3) the highest morbidity was found among the Jewish rural population.

Adolescent↗
PubMed1997

Inherited inverted duplication of X chromosome in a male: report of a patient and review of the literature.

Nineteen cases of duplication of segments of the long arm of chromosome X have been published in 13 males and in 6 females. We report an additional case of a male with growth and mental retardation, growth hormone deficiency, compensated primary hypothyroidism, distinctive anomalies of the face, hypoplastic genitalia, and hypotonia in whom inverted duplication of a segment in the long arm of X chromosome was diagnosed, 46,Y, dup (X)(q21.2q13.3), and mosaicism was demonstrated in his mother's X chromosome. The rearranged segment was diagnosed utilizing high resolution G-band technique and FISH studies, using chromosome X total chromosome probe and DNA XIST probe. This appears to be the first report of a patient with duplication of Xq and hypothyroidism.

Child, Preschool↗
PubMed1997

Long-term regulation of opioid receptors in neuroblastoma and lymphoma cell lines.

Long-term regulation of opioid binding was studied in the human neuroblastoma NMB and in the murine lymphoma R1.1 and R1.EGO cell lines. Binding was down-regulated following prolonged exposure to opioid agonists and up-regulated following exposure to antagonist. Down-regulation was inhibited by the metabolic blocker sodium-azide and by the protein kinase H-7. Up-regulation was blocked by the protein and mRNA synthesis blockers cycloheximide, alpha-amanitin and actinomycin D. A significant difference was found between the response of neuronal and immune cells to ethanol exposure: while opioid binding in neuroblastoma culture underwent a pronounced (75%) up-regulation, no effect of ethanol on opioid receptors in lymphoma cultures was detected. The described cell lines present an excellent experimental model to study long-term regulation of opioid receptors in the nervous and immune systems and to elucidate the biological effects of chronic use of opiates and alcohol.

Diprenorphine↗
PubMed1997

Differential regulation of chloroplast gene expression in Chlamydomonas reinhardtii during photoacclimation: light stress transiently suppresses synthesis of the Rubisco LSU protein while enhancing synthesis of the PS II D1 protein.

Transfer of Chlamydomonas reinhardtii cells grown photoautotrophically in low light to higher light intensities has a dramatic transient effect on the differential expression of the two major chloroplast encoded photosynthetic proteins. Synthesis of the D1 protein of Photosystem II increases more than 10-fold during the first six hours in high light (HL), whereas synthesis of the large subunit (LSU) of Rubisco drops dramatically within 15 min and only gradually resumes at about 6 h. Synthesis of the chloroplast-encoded ATP synthase beta subunit, the nuclear-encoded Rubisco small subunit and the nuclear-encoded beta-tubulin is not noticeably affected. Up regulation of psbA mRNA translation accounts for a substantial fraction of the increased D1 synthesis, since accumulation of psbA mRNA increases 4.2- and 6.3-fold less than D1 synthesis at 6 and 18 h in HL. Down-regulation of LSU synthesis is not correlated with a reduction in the steady-state level of the rbcL transcript. Primer extension mapping of the 5' ends of the rbcL mRNAs reveals transcripts with start points located at -93 and -168 relative to the first translated ATG. Transfer of low light (LL)-grown cells to HL temporarily decreases the ratio of the -93 to -168 transcripts, but this ratio normalizes after 6 h in HL, coincident with the recovery in the synthesis of LSU. These several distinct effects of temporary light stress were correlated with a rapid, sustained increase in the reduction state of QA, a transient decline in photosynthetic efficiency, a less rapid drop in total chlorophyll content and a delay in cell division.

Adaptation, Physiological↗
PubMed1996

[Optic nerve sheath enlargement and reversal of optic nerve head in pseudotumor cerebri].

Using standard cerebral computerized tomography (CT), we diagnosed pseudotumor cerebri (PTC) and correlated the CT findings with CSF pressure and severity of visual impairment. 13 patients with a clinical diagnosis of PTC were compared with 20 age-matched controls with headache, but without papilledema or other neurologic signs. Cerebral CT consisted of axial sections of the posterior fossa, including the orbits. In all subjects the diameter of the optic nerve sheath, reversal of the optic nerve head, presence of empty sella, and size of the ventricles, cisterns and sulci were evaluated. There were no differences in basal cisterns and ventricles between those with PTC and control subjects. Empty sella was found in 6 of 13 PTC patients, compared with 1 of the 20 controls. Optic nerve sheath diameter in controls ranged from 3.5-5.0 mm (average 4.2 +/- 0.54 mm) but from 4.5-9.0 mm (average 6.8 +/- 1.54 mm) in those with PTC. Reversal of the optic nerve head was seen in 4 cases of PTC but in none of the controls. In PTC patients with opening CSF pressure greater than 270 mm water, the diameter of the optic nerve was wider than 7.5 mm. Thus, in most cases of PTC, bilateral enlarged optic nerves can be measured by standard cerebral CT and intracranial space-occupying lesions can be excluded as well. Moreover, reversal of optic nerve head, and empty sella can frequently be seen on CT in those with PTC.

Adolescent↗
PubMed1996

Cloning from Leishmania major of a developmentally regulated gene, c-lpk2, for the catalytic subunit of the cAMP-dependent protein kinase.

Protein kinases are important in the regulation of cellular processes including growth and differentiation. Using the polymerase chain reaction with oligonucleotide primers derived from conserved regions of cAMP-dependent protein kinases (PKAs), three different DNA fragments were amplified from leishmanial genomic DNA. One fragment was used to isolate a stage specific gene, c-lpk2, from a Leishmania major genomic library. This gene shows high homology to other eukaryotic PKAs, and the open reading frame encodes a 332 amino acid protein with a predicted molecular mass of 38.2 kDa. When aligned with other PKAs the leishmanial enzyme has a unique eight amino acid extension at the carboxy terminus. The c-lpk2 gene is present as a single copy in L. major, L. donovani and L. amazonensis. The 5'-flanking region contains a polypyrimidine rich tract upstream from the predicted ATG start codon. The gene is highly expressed in promastigotes and barely detectable in amastigotes of L. major. Temperature increase was shown to rapidly down-regulate c-lpk2 expression. Transfer of L. amazonensis promastigotes to 35 degrees C resulted in the rapid disappearance of c-lpk2 mRNA (> 70% in 1 h), while at 26 degrees C the mRNA was more stable. The strict temperature dependence of mRNA degradation rate suggests that PKA expression is regulated post-transcriptionally.

Amino Acid Sequence↗
PubMed1996

Presence of family member during upper endoscopy. What do patients and escorts think?

We evaluated what effect an escort present during upper endoscopy had on the attitude and anxiety level of patients and on the escorts. The study consisted of 206 patients (ages 15-85, 47% male) and their escorts. Both patients and escorts were interviewed before the procedure. Escorts were then randomly divided into two groups-on-the-spot escorts, who present throughout the procedure, as opposed to waiting-room escorts. Both groups were reinterviewed following the procedure. Before the procedure, 80% of the patients understood the nature of endoscopy. Thirteen percent believed the procedure to be dangerous, and only 33% were totally worry-free. Fifty percent preferred to be escorted during the procedure, while 17% refused. Following the procedure, 89% of the patients who were escorted in the endoscopy room expressed satisfaction. Fifty-two percent of the patients found the procedure to be mild, with a higher proportion among escorted patients. Among the escorts, 63% felt that their close presence had lessened their own fears and anxiety regarding the procedure, and 72% believed their presence to have been supportive to the patient. Having an escort present throughout endoscopy appears to be a promising approach.

Adolescent↗
PubMed1994

Transgenic engineering of neuromuscular junctions in Xenopus laevis embryos transiently overexpressing key cholinergic proteins.

To examine the role of key cholinergic proteins in the formation of neuromuscular junctions (NMJs), we expressed DNAs encoding the mouse muscle nicotinic acetylcholine receptor (nAChR) or human brain and muscle acetylcholinesterase (hAChE) in developing Xenopus laevis embryos. Acetylthiocholine hydrolysis and alpha-bungarotoxin binding in homogenates of transgenic embryos revealed transient overexpression of the respective proteins for at least 4 days postfertilization. Moreover, hAChE injection induced an approximately 2-fold increase in endogenous Xenopus nAChR. Electron microscopy coupled with cytochemical staining for AChE activity revealed that AChE-stained areas, which reached 0.17 microns2 in NMJs of control embryos raised at 21 degrees C, increased up to 0.53 and 0.60 microns2 in nAChR and hAChE transgenics, respectively. These increases coincided with the appearance of a class of large NMJs with average postsynaptic lengths up to 1.8-fold greater than controls. As much as 57% and 34% of the NMJs in animals transgenic for nAChR and hAChE, respectively, displayed AChE activity in nerve terminals in addition to muscle labeling, as compared with 10% nerve-labeled NMJs in control animals. Moreover, area, but not length values, were > 2-fold larger in hAChE-expressing NMJs labeled in their nerve terminals than in those labeled in muscle alone, reflecting a hAChE-induced increase in synaptic cleft width. These findings indicate that modulation of cholinergic neurotransmission in NMJs modifies the features of nerve-muscle connections.

Acetylcholinesterase↗
PubMed1994

A regulatory role for the 5' and 3' untranslated regions in differential expression of hsp83 in Leishmania.

Exposure of Leishmania promastigotes to temperatures typical of mammals result in a stress response, which is accompanied by an increase in the steady state level of heat shock transcripts and their translation. Accumulation of the heat shock protein (hsp83) mRNA occurs due to differential decay rates at the altered temperatures, while transcription is unaffected. A similar pattern of post-transcriptional regulation was observed for a transfected chloramphenicol acetyltransferase (CAT) gene, which was flanked at both ends by intergenic regions (IR) of hsp83. Shortening the 5' untranslated region (UTR) by 100 nts produced an active CAT enzyme, but abolished the temperature-dependent regulation of the CAT-hsp83 mRNA turn-over. The 3' UTR is also involved in the temperature-dependent degradation of hsp83 mRNA, since exchange of the hsp83 3' UTR with a parallel fragment from a non-heat shock gene abolished the differential turn-over of CAT mRNA. Thus, the regulated decay of hsp83 mRNA is controlled by sequence or conformational elements present in both upstream and downstream UTRs. Like the endogenous hsp83, translation of CAT mRNA which contained hsp83 UTRs was higher at 35 degrees C. This was observed only with transcripts in which stability increased at elevated temperatures. Modifications which abolished the temperature dependence of CAT mRNA decay, eliminated its elevated translation at the higher temperatures. The correlation suggests a mechanistic link between the translational machinery and mRNA stability.

Animals↗
PubMed1994

Deletion of the short arm of chromosome 10 (10p13): report of a patient and review.

Since the first description by Elliot et al. [1970, Am J Dis Child 119:72-73] of a probable partial deletion of chromosome 10p, 17 other cases have been reported. The phenotypic expression is variable, but the craniofacial malformations constitute a more consistent finding. The 10p deletion syndrome has been associated with the DiGeorge anomaly in several patients. We report on an additional case of 10p deletion syndrome and review the literature.

Child, Preschool↗
PubMed1994

Functional analysis of cis-acting DNA elements required for expression of the SL RNA gene in the parasitic protozoan Leishmania amazonensis.

DNA sequences, that control expression of the spliced leader (SL) RNA gene in the parasitic protozoan Leishmania amazonensis, were mapped by block substitution mutagenesis. In the absence of a functional in vitro system for transcription, no promoter elements have yet been identified in this organism. We therefore developed an alternative in vivo approach, in which the SL RNA gene was tagged and then subjected to a series of linker scanning mutations. Each tagged and mutated SL RNA construct was introduced into parasite cells via the pX transfection vector, and was examined for expression of the tagged SL RNA followed by characterization of its transcriptional start site. The replacement of a critical DNA element was expected to prevent expression of the tagged SL RNA. We found that the putative SL RNA promoter is complex and includes two elements: one is located upstream to the coding region, between positions -30 to -70; and the other is located between -10 to +10, and includes transcribed sequences. In addition to the functional relationship between the SL RNA and vertebrate U snRNAs, we found structural similarities in their regulatory elements, which may possibly indicate a common evolutionary ancestry for these molecules.

Animals↗
PubMed1994

Crohn's disease in the Kinneret sub-district, Israel, 1960-1990. Incidence and prevalence in different ethnic subgroups.

Crohn's disease has been predominant in Jewish patients in some countries (USA, UK, Sweden). The purposes of this study were: to continue to map the morbidity in Israel and the trends of the rate over time. The mean annual incidence rate in the Kinneret sub-district among Jews was 1.96/100,000 during 1960-1990 and 2.98/100,000 in the last decade. The prevalence rate in 1990 among Jews was 45.9/100,000 and was twofold among European-American-born compared to other ethnic groups. No cases were found among Arabs, although they make up about 25% of the area's population. The conclusions are: (1) morbidity rate of Crohn's disease increased over time, and (2) in the last decade incidence rates among Jews of Asian-African origin are similar to, or even higher than those of European-American origin.

Adult↗
PubMed1994

Expression of heat shock protein 83 in Leishmania is regulated post-transcriptionally.

Mechanisms for regulation of heat shock protein (hsp) 83 expression were examined in Leishmania amazonesis. Transcripts of hsp83 accumulated upon temperature elevation; however, in contrast to non-protozoan eukaryotes (i.e. Drosophila, yeast, avian or human cells), no transcriptional activation was observed. The increase in the hsp83 mRNA level evolved from temperature induced variations in mRNA turn-over: the hsp83 transcript was rapidly degraded at normal temperatures, whereas heat shock led to its stabilization. The quick decay of the mRNA at lower temperatures was dependent on active protein synthesis. A similar pattern of regulation was observed for the transfected chloramphenicol acetyltransferase (CAT) gene, which was flanked by sequences from the hsp83 intergenic region (IR), and cloned into the pX transfection vector (pX-ICI). CAT mRNA was abundant at normal temperatures and further accumulated upon temperature elevation. The altered turn-over rates of CAT mRNA at the different temperatures were observed only in the presence of flanking hsp83 IR sequences. The increase in temperature also affected translational regulation of hsps, and synthesis of hsp83 was more efficient at 35 degrees C than at 26 degrees C. However, the effect of translation was transient, and the steady state level of the protein was hardly altered.

Animals↗
PubMed1994

The role of pH and temperature in the development of Leishmania parasites.

Protozoans of the genus Leishmania are obligate intracellular parasites that cycle between the midgut of sandflies and the phagolysosomes of mammalian macrophages and therefore are exposed to extreme environmental changes. Recent evidence obtained from in vitro experiments indicate that such environmental changes trigger a developmental program in the parasites. Thus, following heat shock, promastigotes from certain Leishmania species differentiate to amastigotes. Promastigotes also respond to acidification of their environment by changing the expression of a number of genes. However, the combination of both low pH and high temperature induces the transformation of the promastigote to the amastigote in all Leishmania species examined to date. This review discusses the role of pH and heat shock in gene regulation and its contribution to the differentiation processes in Leishmania spp. Cycling between cold-blooded insect vectors and the warm-blooded mammalian host is not unique to Leishmania spp., but typical to most parasitic protozoa. It is therefore likely that the mechanism of stress-induced differentiation is shared by other mammalian parasites.

Animals↗