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Biomedical subjects

R Levi

Publications and source records attributed to R Levi.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1995

Intranasal immunization of mice against influenza with synthetic peptides anchored to proteosomes.

Synthetic vaccines that are based on peptides representing immunogenic epitopes require a carrier molecule as well as an adjuvant in order to be effective. The choice of carriers or adjuvants approved for use in humans is very limited, and a considerable effort is devoted to develop new and efficient delivery systems. One of these vehicles utilizes preparations of outer membranes of meningococci, that form hydrophobic interactions, denoted proteosomes. Immunogenic proteins and peptides can be anchored to these proteosomes vesicles, which may serve as both carrier and adjuvant functions. In the present study we examined the ability of proteosomes to present epitopes of influenza, to elicit specific anti-influenza responses and to protect mice against viral challenge after intranasal immunization. Three influenza peptides were used--one corresponding to amino acid residues 91-108 of the haemagglutinin surface glycoprotein of H3 subtype, which comprises a B-cell epitope, and two from the internal nucleoprotein--a T-helper cell (Th) epitope (residues 55-69) and a cytotoxic T-lymphocyte (CTL) epitope (147-158). Mice were immunized intranasally (i.n.) with preparations containing each of the above epitopes, or various combinations thereof. The results obtained with this system demonstrate that influenza epitopes represented by synthetic peptides anchored to a proteosome carrier elicit both humoral and cellular specific immune responses, that can lead to partial protection of the mice from viral challenge. The importance of immunizing with vaccines containing both B- and T-cell peptide epitopes was emphasized by the demonstration that such vaccines elicited longer lasting immunity and led to more effective protection against influenza viral challenge.

Administration, Intranasal↗
PubMed1995

The Stockholm Spinal Cord Injury Study: 2. Associations between clinical patient characteristics and post-acute medical problems.

The Stockholm Spinal Cord Injury Study (SSCIS) is an extensive evaluation of a sample of 353 subjects with traumatic SCI, constituting 93% of the known regional prevalence population with this diagnosis. In a previous analysis of this group, symptoms such as pain, incontinence, sexual dysfunction and neurological deterioration, as well as secondary complications, such as decubitus ulcers, urinary tract infections, spinal deformity and fractures, were found to be common. In the present report, we investigate associations between a few commonly used patient characteristics, ie gender, age at injury, duration of injury and extent of neurological compromise, and the occurrence of such problems, to assess differences in vulnerability in SCI subgroups. Results generally indicate an increased vulnerability in subjects with extensive neurological deficits, as well as a cumulation of complications with the increasing duration of injury. However, some exceptions are found, possibly indicating differences in temporal patterns of the occurrence of various complications, as well as certain gender-, age-, and lesion-associated variations in vulnerability. Symptoms directly related to the spinal cord lesion, eg neurogenic pain and neurological deterioration, seem to present rather soon post-injury. Males are more prone to experience excessive spasticity and sexual problems. Females experience more fractures and spinal deformity. Younger age at injury is associated with more spinal deformity but less severe pain problems. Higher age at injury is not found to be associated with more medical problems, with the exception of neurogenic pain, among post-acute, post-discharge survivors. The latter finding does not, however, preclude more such problems in the acute stage, since the present study neither addresses the pre-discharge period, nor includes information about mortality. Finally, the ASIA/IMSOP Impairment Scale Grade E-rated subjects were found to report problems to an extent that underlines the restricted sensorimotor sense in which this rating reflects recovery.

Adult↗
PubMed1995

The Stockholm Spinal Cord Injury Study. 3. Health-related issues of the Swedish annual level-of-living survey in SCI subjects and controls.

In previous articles on the Stockholm Spinal Cord Injury Study (SSCIS), we have reported the frequent occurrence of medical problems in a near-total regional SCI population comprising 353 subject. This present study further investigates health-related issues in this SCI population, by 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 those 326 subjects in the SSCIS who were residents of the Greater Stockholm area. Subjects of the SSCIS living on the island of Gotland were excluded because they represented a sociodemographically different (rural) population. The normative material consisted of 1978 interviews of residents of the Greater Stockholm area, provided by the Swedish Bureau of Statistics. Results show a higher utilisation of health care resources among SCI subjects, shown by higher rates of long-term sick leave and sick pension, and more treatment as inpatients, emergency room attendees, and outpatients. Pain, bladder problems, and psychological symptoms are more commonly reported by SCI subjects. Medications such as antibiotics, analgesics, sedatives, hypnotics and laxatives are used more frequently in the SCI group. In contrast, no statistically significant differences were found as regards reported prevalence of diseases other than SCI, including diabetes, hypertension and cardiac disease. The results thus verify the impression from our previous studies of a clearly increased morbidity among these SCI subjects. The increased morbidity seems to be accounted for by the SCI itself, or conditions directly caused by it.

Adolescent↗
PubMed1995

The Stockholm spinal cord injury study: 1. Medical problems in a regional SCI population.

Out of a regional traumatic spinal cord injury population consisting of 379 individuals, 353 (93.1%) participated in the present study. Subjects were individually interviewed using semi-structured protocols. In addition, previous medical records were available for over 96% of subjects, and were used in all these cases to minimise recall bias. Cause of injury, prevalence of present medical symptoms and occurrence of medical complications in the post-acute, post-discharge phase were recorded. Neurological classification was verified by physical examination according to ASIA/IMSOP standards. Many subjects had experienced complications since discharge from initial hospitalisation, especially urinary tract infections, decubitus ulcers, urolithiasis, and neurological deterioration. Prevalence of medical symptoms was also high. More than 41% of subjects with spastic paralysis reported excessive spasticity to be associated with additional functional impairment and/or pain. Almost two-thirds of subjects reported significant pain, with a predominance of neurogenic-type pain. Bladder and bowel dysfunction were each rated by nearly 41% of subjects as a moderate to severe life problem. As expected, sexual dysfunction was also commonly reported. Prevalence of reported symptoms by general systems review was high, particularly fatigue, constipation, ankle oedema, joint and muscle problems, and disturbed sleep. However, lack of adequate normative data precludes comparison with the general population. The frequent occurrence of reported medical problems and complications support advocacy of comprehensive, life-long care for SCI patients. The commonly reported problems of neurogenic pain and neurological deterioration, in particular, require more attention, as these symptoms are not seldom ominous, either by virtue of their impact on quality of life, or because of underlying pathology.

Adolescent↗
PubMed1995

New aspects of the role of histamine in cardiovascular function: identification, characterization, and potential pathophysiological importance of H3 receptors.

As a result of intensive research during several decades, the distribution, function, and pathophysiological role of cardiovascular H1 and H2 receptors are well known, whereas reports on the occurrence and function of H3 receptors in blood vessels and the heart have not become available before the last 7 years (i.e., 4 years after the first description of these receptors in the central nervous system in 1983). The development of selective and potent H3 receptor agonists and antagonists was a prerequisite for convenient investigations of cardiovascular H3 receptors, which like H1 and H2 receptors are G-protein coupled but unlike them have not yet been cloned. Both in blood vessels and the heart, H3 receptors are located on noradrenergic nerve endings and upon stimulation mediate an inhibition of noradrenaline release. Whereas it remains to be clarified under which conditions the vascular H3 receptors may be stimulated by endogenous histamine, those in the heart become activated in the early phases of myocardial ischemia characterized by an increased histamine spillover. The H3 receptors in the central nervous system also appear to be of importance for the control of vascular function. Inhibitory presynaptic H3 receptors occur on trigeminal sensory C fibres supplying blood vessels in the dura mater. Release of neuropeptides from these fibres induces a neurogenic inflammation, which has been suggested to be involved in the pathogenesis of migraine. An interaction, involving presynaptic H3 receptors, between sensory C fibres and mast cells in close apposition to these fibres plays a role in the control of histamine synthesis in the dura mater.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗