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R Levi

Publications and source records attributed to R Levi.

At least 73 records · Page 4Linked to original sources
PubMed1997

Bradykinin B2-receptor activation augments norepinephrine exocytosis from cardiac sympathetic nerve endings. Mediation by autocrine/paracrine mechanisms.

We determined whether local bradykinin production modulates cardiac adrenergic activity. Depolarization of guinea pig heart sympathetic nerve endings (synaptosomes) with 1 to 100 mmol/L K+ caused the release of endogenous norepinephrine (10% to 50% above basal level). This release was exocytotic, because it depended on extracellular Ca2+, was inhibited by the N-type Ca(2+)-channel blocker omega-conotoxin and the protein kinase C inhibitor Ro31-8220, and was potentiated by the neuronal uptake-1 inhibitor desipramine. Typical of adrenergic terminals, norepinephrine exocytosis was enhanced by activation of prejunctional angiotensin AT1-receptors and attenuated by adrenergic alpha 2-receptors, adenosine A1-receptors, and histamine H3-receptors. Exogenous bradykinin enhanced norepinephrine exocytosis by 7% to 35% (EC50, 17 nmol/L), without inhibiting uptake 1. B2-receptor, but not B1-receptor, blockade antagonized this effect. The kininase II/angiotensin-converting enzyme inhibitor enalaprilat and the addition of kininogen or kallikrein enhanced norepinephrine exocytosis by approximately equal to 6% to 40% (EC50, 20 nmol/L) and approximately equal to 25% to 60%, respectively. This potentiation was prevented by serine protease inhibitors and was antagonized by B2-receptor blockade. Therefore, norepinephrine exocytosis is augmented when bradykinin synthesis is increased or when its breakdown is inhibited. This is the first report of a local kallikrein-kinin system in adrenergic nerve endings capable of generating enough bradykinin to activate B2-receptors in an autocrine/paracrine fashion and thus enhance norepinephrine exocytosis. This amplification process may operate in disease states, such as myocardial ischemia, associated with severalfold increases in local kinin concentrations.

Animals↗
PubMed1997

Sexuality in women with traumatic spinal cord injury.

BACKGROUND: Sexuality in spinal cord injured women has largely been neglected. One reason may be the male dominance amongst traumatically spinal cord injured individuals. The purpose of this study is to elucidate sexual issues in women with spinal cord injuries. METHODS: Survey of near-total prevalence population in the greater Stockholm area. Structured interview, based on a standardized questionnaire. Self-rating scales for evaluation of the importance of sexual activity before and after injury and for defining and rating the medical problem most significantly interfering with sexual activity. Marital status and/or partnership pre- and post-injury and information on sexual matters provided after injury were evaluated in detail. Out of a total 65 women, 62 participated in the study. RESULT: Women with complete and incomplete cervical lesions rated the importance of sexual activity significantly lower after, as compared to before, spinal cord injury. No significant differences were found in women with lower-level lesions. Urinary leakage, spasticity and positioning problems were the medical problems most significantly interfering with partner-related sexual activity. Only six women had received information on sexual matters before discharge from hospital. None of the partners had received such information. CONCLUSION: The women's neurological status affect their ability to adapt sexually after injury. Medical problems commonly interfere with sexuality and should be identified and treated. No adverse impact of spinal cord injury on marital status could be confirmed. Sexual counseling has yet to become an integral part of rehabilitation.

Female↗
PubMed1997

Activation of histamine H3 receptors inhibits carrier-mediated norepinephrine release in a human model of protracted myocardial ischemia.

During protracted myocardial ischemia, ATP depletion promotes Na+ accumulation in sympathetic terminals and prevents vesicular storage of norepinephrine (NE). This forces the reversal of the neuronal uptake1 transporter, and NE is massively released (carrier-mediated release). We had shown that histamine H3 receptors (H3Rs) modulate ischemic NE release in animals. We have now used a human model of protracted myocardial ischemia to investigate whether H3Rs may control carrier-mediated NE release. Surgical specimens of human atrium were incubated in anoxic conditions. NE release increased approximately 7-fold within 70 min of anoxia. This release was carrier mediated because it was Ca++ independent and inhibited by the uptake1 inhibitor desipramine. Furthermore, the Na+/H+ exchanger (NHE) inhibitors ethyl-isopropyl-amiloride and HOE 642, and the Na+ channel blocker tetrodotoxin inhibited NE release, whereas the Na+ channel activator aconitine potentiated it. The selective H3R agonist imetit decreased NE release, an effect that was blocked by each of the H3R antagonists thioperamide and clobenpropit. Notably, imetit acted synergistically with ethyl-isopropyl-amiloride, HOE 642 and tetrodotoxin to reduce anoxic NE release. Thus, activation of H3R appears to result in an inhibition of both NHE- and voltage-dependent Na+ channels. Most importantly, endogenous histamine was released from the anoxic human heart, and thioperamide and clobenpropit each alone increased NE release, indicating that H3R become activated in myocardial ischemia. Our findings indicate that H3Rs are likely to mitigate sympathetic overactivity in the ischemic human heart and suggest new therapeutic strategies to alleviate dysfunctions associated with myocardial ischemia.

Aged↗
PubMed1997

Nurse in profile.

Explore the source record for details and available documents.

Career Choice↗
PubMed1996

Synthetic recombinant influenza vaccine induces efficient long-term immunity and cross-strain protection.

Synthetic vaccines utilize specific antigenic epitopes in order to elicit a protective immune response. In this work we examined the immunogenicity of chimeric proteins expressing influenza epitopes and their ability, as single products or in various combinations, to protect mice from viral challenge. Oligonucleotides coding for three epitopes (HA91-108, NP55-69 and NP147-158) stimulating B cells, T helper cells and cytotoxic T lymphocytes (CTLs), respectively, were individually inserted into the flagellin gene of a Salmonella vaccine strain. Immunization of mice with the resultant hybrid flagella resulted in a specific humoral or cellular response. The protective efficacy of the chimeric flagella was evaluated by intranasal immunization of mice, without any adjuvant, and subsequent challenge with infectious virus. The construct containing the B-cell epitope by itself led to partial protection. However, the addition of the two T-cell epitopes augmented the protection in a significant manner. The protective immunity conferred by this combined vaccine, comprising the three epitopes, persisted for at least 7 months after the last boost, and was effective against several influenza A strains. Furthermore, this vaccine fully protected mice from a lethal challenge, and enhanced their recovery process. Our results indicate that stimulation of the different arms of the immune system is required for effective anti-influenza response, and demonstrate the applicability of such synthetic recombinant approach for preparing a broad spectrum influenza vaccine.

Amino Acid Sequence↗
PubMed1996

Increased levels of redox-active iron in follicular fluid: a possible cause of free radical-mediated infertility in beta-thalassemia major.

OBJECTIVE: Our purpose was to investigate the follicular fluid parameters associated with redox activity and the consequent production of the deleterious hydroxyl radical in beta-thalassemia major. STUDY DESIGN: The levels of ferritin, total iron, total copper, and redox-active iron were measured in follicular fluid aspirated from three follicles during three consecutive ovum pickups from a patient with beta-thalassemia major and were compared with the levels in nine follicles aspirates from nine healthy control patients. The redox activity in the follicular fluid samples was monitored by the extent of follicular fluid-mediated deoxyribonucleic acid degradation and salicylate hydroxylation. RESULTS: Total iron and ferritin concentrations were elevated in thalassemic follicular fluid samples compared with control samples (6.7 fold, and 53.3-fold, respectively), whereas the total copper concentration was similar. Thalassemic follicular fluid samples exhibited a marked increase of redox activity, indicating a higher potential of free radical production leading to deoxyribonucleic acid degradation. Likewise, free radical-induced conversion of salicylate to dihydroxybenzoic acid derivatives was enhanced in the thalassemic follicular fluid samples compared with controls (2,3-dihydroxybenzoic acid: 67.7 +/- 22 vs 20.3 +/- 12.9 ng/mg protein; 2,5-dihydroxybenzoic acid: 101.6 +/- 25.9 vs 4.42 +/- 2.7 ng/mg protein). CONCLUSIONS: The increased level of redox activity found in the follicular fluid from a patient with beta-thalassemia major focuses the attention on the small fraction of redox-active iron ions as mediators of free radical production, inducing tissue injury and possibly contributing to impairment of reproduction in these patients.

Adult↗
PubMed1996

The Stockholm spinal cord injury study: 4. Psychosocial and financial issues of the Swedish annual level-of-living survey in SCI subjects and controls.

In a series of articles from the Stockholm Spinal Cord Injury Study (SSCIS), the health status of a near-total regional SCI population comprising 353 subjects has been investigated. The present study describes the psycho-social and financial consequences of SCI in this group. It is based on a level-of-living survey that has been used annually on 8000-14,000 Swedes since 1974. The health-focused version of this survey was used for data collection in the subset of 326 subjects in the SSCIS that were residents of the Greater Stockholm area. The normative material consisted of 1978 interviews of residents of the same area, provided by the Swedish Bureau of Statistics. The results show that SCI subjects, although provided with basic material commodities up to par with the general population, have less financial reserves and more frequently express worry about their finances. Less than half of the subjects are gainfully employed, when part-time jobs are also included. Social activities are more restricted, and more centered on the core social network. Several items in the survey point to a preoccupation with personal rather than public matters. We feel that these factors, at least to some degree, are consequential to separation from the workplace, with resulting disadvantageous financial and social effects. Intensified vocational rehabilitation efforts might thus be justified from both an economic and a psycho-social point of view.

Adolescent↗
PubMed1996

Frequency-spatial transformation: a proposal for parsimonious intra-cortical communication.

This work examines a neural network model of a cortical module, where neurons are organized on a 2-dimensional sheet and are connected with higher probability to their spatial neighbors. Motivated by recent findings that cortical neurons have a resonant peak in their impedance magnitude function, we present a frequency-spatial transformation scheme that is schematically described as follows: An external input signal, applied to a small input subset of the neurons, spreads along the network. Due to a stochastic component in the dynamics of the neurons, the frequency of the spreading signal decreases as it propagates through the network. Depending on the input signal frequency, different neural assemblies will hence fire at their specific resonance frequency. We show analytically that the resulting frequency-spatial transformation is well-formed; an injective, fixed, mapping is obtained. Extensive numerical simulations demonstrate that a homogeneous, well-formed transformation may also be obtained in neural networks with cortical-like "Mexican-hat" connectivity. We hypothesize that a frequency-spatial transformation may serve as a basis for parsimonious cortical communication.

Cell Communication↗
PubMed1996

Is intertwin birth weight discordance predictable?

OBJECTIVE: To compare the efficacies of intertwin difference in abdominal circumferences (ACs) and estimated fetal weight (EFWs) to predict birth weight discordance in twin gestations. METHODS: Ninety pairs of twins with sonographic measurements of AC and femur length, performed within 2 weeks before delivery, were included in the study. The EFW was calculated (Hadlock's formula). We used Bayes' theorem and the Mantel-Haenszel chi 2 test to calculate and compare the rates of false-positive and false-negative prediction of the cutoff values of 15, 20, and 25% intertwin birth weight discordance by the intertwin EFW difference and an intertwin AC difference of > or = 18 mm. RESULTS: There were no significant difference between the two methods to predict birth weight discordance at 15-25% discordance (p = 0.254, OR = 0.33, 95% CI = 1.45-0.24) and at > 25% discordance (p = 0.112, OR 0.18, 95% CI = 0.03-1.34). CONCLUSIONS: Both the intertwin AC difference (> or = 18 mm) and intertwin EFW difference have similar negative predictive values and the same efficacy to exclude discordant growth. Because of the relatively low positive predictive values, birth weight discordance cannot be accurately predicted by either method.

Bayes Theorem↗
PubMed1996

Activation of histamine H3-receptors inhibits carrier-mediated norepinephrine release during protracted myocardial ischemia. Comparison with adenosine A1-receptors and alpha2-adrenoceptors.

We previously showed that prejunctional histamine H3-receptors downregulate norepinephrine exocytosis, which is markedly enhanced in early myocardial ischemia. In the present study, we investigated whether H3-receptors modulate nonexocytotic norepinephrine release during protracted myocardial ischemia. In this setting, decreased pH(i) in sympathetic nerve endings sequentially leads to a compensatory activation of the Na+-H+ antiporter (NHE), accumulation of intracellular Na+, reversal of the neuronal uptake of norepinephrine, and thus carrier-mediated release of norepinephrine. Accordingly, norepinephrine overflow from isolated guinea pig hearts undergoing 20-minute global ischemia and 45-minute reperfusion was attenuated approximately 80% by desipramine (10 nmol/L) and 70% by 5-(N-ethyl-N-isopropyl)-amiloride (EIPA, 10 micromol/L), inhibitors of norepinephrine uptake and NHE, respectively. The H3-receptor agonist imetit (0.1 micromol/L) decreased carrier-mediated norepinephrine release by approximately 50%. This effect was blocked by the H3-receptor antagonist thioperamide (0.3 micromol/L), indicating that H-receptor activation inhibits carrier-mediated norepinephrine release. At lower concentrations, imetit (10 nmol/L) or EIPA (3 micromol/L) did not inhibit carrier-mediated norepinephrine release. However, a 25% inhibition occurred with imetit (10 nmol/L) and EIPA (3 micromol/L) combined. This synergism suggests an association between H-receptors and NHE. Conceivably, activation of H-receptors may lead to inhibition of NHE. In fact, alpha2-adrenoceptor activation, which is known to stimulate NHE, enhanced norepinephrine release, whereas alpha2-adrenoceptor blockade attenuated it. Furthermore, activation of adenosine A1-receptors markedly attenuated norepinephrine release, whereas their inhibition potentiated it. Because norepinephrine directly correlated with the severity of reperfusion arrhythmia and imetit reduced the incidence of ventricular fibrillation by 50%, our findings with H-receptor agonists may further the development of novel pharmacological means to reduce reperfusion arrhythmias in the clinical setting.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1996

Histamine H3-receptor-mediated inhibition of calcitonin gene-related peptide release from cardiac C fibers. A regulatory negative-feedback loop.

Antidromic stimulation of cardiac sensory C fibers releases calcitonin gene-related peptide (CGRP), which increases heart rate, contractility, and coronary flow. C-fiber endings are closely associated with mast cells, and CGRP may release mast-cell histamine. Because prejunctional histamine H3-receptors inhibit transmitter release from autonomic nerves, we tested the hypothesis that H3-receptors modulate CGRP release in the heart. CGRP released by bradykinin in the electrically paced guinea pig left atrium and by capsaicin in the spontaneously beating isolated heart caused marked positive inotropic and chronotropic effects, respectively. Capsaicin significantly enhanced the overflow of CGRP (fivefold) and histamine (twofold) into the coronary effluent. All of these effects were prevented by prior chemical destruction of C fibers in vivo. The H3-receptor agonist imetit attenuated the inotropic response to bradykinin by 50%. Imetit also decreased the capsaicin-induced tachycardia and the increase in CGRP overflow by 50%. Imetit, however, did not modify the response to exogenous CGRP. The effects of imetit were blocked by the H3-receptor antagonist thioperamide. Notably, thioperamide by itself potentiated the capsaicin-evoked increases in heart rate and CGRP overflow (by 25% and 50%, respectively). Thus, our findings identify a negative-feedback loop, whereby CGRP releases histamine from cardiac mast cells and histamine in turn inhibits CGRP releases by activating H3-receptors on C-fiber terminals. Because CGRP release is augmented in pathophysiological conditions, such as septic shock, heart failure, and acute myocardial infarction, modulation of CGRP release may be clinically relevant.

Animals↗
PubMed1996

Producing directed behaviour: muscle activity patterns of the cockroach escape response

The cockroach responds to wind from the front left by making an escape turn to the right, and vice versa. So far, no interneurones in the escape system are known that respond only to wind from the left or only to wind from the right. In this study, we used electromyographic recordings to determine whether motor neurones respond in this direction-selective manner during escape behaviour. In the mesothoracic coxal-femoral joint, whose movement direction is diagnostic for escape direction, the fast motor neurones of one muscle respond selectively to one wind direction, and those of the antagonistic muscle respond selectively to wind from the other direction, resulting in an appropriate turning response. This rules out an alternative hypothesis, a co-activation mechanism of specifying turn direction. These results suggest that it would be fruitful to search among the interneurones of the escape system for additional cells and circuit properties that could give rise to this sharp directional discrimination.

Journal Article↗
PubMed1995

Nitric oxide-stimulated guanine nucleotide exchange on p21ras.

The protooncogene p21ras, a monomeric G protein family member, plays a critical role in converting extracellular signals into intracellular biochemical events. Here, we report that nitric oxide (NO) activates p21ras in human T cells as evidenced by an increase in GTP-bound p21ras. In vitro studies using pure recombinant p21ras demonstrate that the activation is direct and reversible. Circular dichroism analysis reveals that NO induces a profound conformational change in p21ras in association with GDP/GTP exchange. The mechanism of activation is due to S-nitrosylation of a critical cysteine residue which stimulates guanine nucleotide exchange. Furthermore, we demonstrate that p21ras is essential for NO-induced downstream signaling, such as NF-kappa B activation, and that endogenous NO can activate p21ras in the same cell. These studies identify p21ras as a target of the same cell. These studies identify p21ras as a target of NO in T cells and suggest that NO activates p21ras by an action which mimics that of guanine nucleotide exchange factors.

Antibodies↗
PubMed1995

The intrauterine ponderal index in relation to birth weight discordance in twin gestations.

OBJECTIVE: To establish the relationship between the fetal ponderal index and birth weight discordance in twins. METHOD: The fetal ponderal index (estimated fetal weight divided by femur length3) was calculated in 86 pairs of twins delivered within 2 weeks of the last sonography and analyzed in relation to birth weight discordance. RESULTS: A weak but significant correlation between fetal ponderal index and birth weight (r = 0.26, P < 0.0007) but no correlation with gestational age (r = 0.035, P = 0.65) were found. Members of concordant pairs (< 15% birth weight difference) had a significantly higher fetal ponderal index compared with members of mildly (15-25%) discordant pairs (P < 0.02), but not as compared with members of severely discordant (> 25%) pairs. CONCLUSION: The characteristics of the fetal ponderal index in twins are similar to those in singletons. Fetal size seems to be diminished in severe but not in mild discordants. However, in its present form, the fetal ponderal index is a poor predictor of discordant growth and therefore should be employed cautiously in twin gestations.

Birth Weight↗
PubMed1995

Microculture virus titration--a simple colourimetric assay for influenza virus titration.

Influenza antigens can be detected by several well established methods. However, when it is important to determine the titre of infective virions, a bioassay should be employed. The standard and the most widely used tests for influenza infectivity are titration carried out in embryonated hen eggs, or the plaque assay employing tissue culture techniques. A simple colourimetric assay for influenza virus detection and titration is described. Samples of allantoic fluid or mice lung homogenates were used to infect MDCK cultures in microplate wells. After an incubation period, the tetrazolium (MTT) colourimetric assay was used to determine cell viability, and when compared to untreated culture control enabled the detection and titration of several influenza strains. When samples were assayed simultaneously in embryonated eggs and by the MCVT method, good correlation in determined titres was obtained. The availability of an additional method for influenza titration allows more flexibility in the choice of titration method according to the specific needs of the study. Furthermore, this method lends itself to full automatization. Similar procedures should also be applicable to titration of other cytopathic viruses.

Animals↗