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Biomedical subjects

E Gazit

Publications and source records attributed to E Gazit.

At least 55 records · Page 3Linked to original sources
PubMed1997

Antiperinuclear factor--clinical, serological and genetic correlates in Israeli patients with rheumatoid arthritis.

The possible association between the presence of antiperinuclear factor (APF) and clinical and genetic parameters was investigated in 54 Israeli patients with rheumatoid arthritis (RA). Rheumatoid factor (RF) was detected in the sera of 43 patients (80%) and APF was positive in 33 (61%). No significant statistical differences were found in the presence of HLA-DR4 and/or DR1 between APF-positive and -negative patients. Furthermore, neither the Ritchie articular index nor the patient's functional class correlated with the presence of APF. The results of our study suggested that although Israeli patients have a different genetic background, the presence and behaviour of APF is similar to that of other Caucasian populations.

Adult↗
PubMed1997

The coronoid process as a cause of mandibular hypomobility--case reports.

In an attempt to draw the clinician's attention to the coronoid process site while evaluating the aetiology of the restriction of mandibular opening, four cases are illustrated. These cases represent a diversity of causes hampering the free rotational movement of the coronoid process in space during jaw function. Case 1 is an example of unilateral hyperplastic coronoid process and osteochondroma; case 2 shows unusually shaped short and divergent coronoid processes combined with a bucally displaced maxillary third molar on one side; cases 3 and 4 represent an anatomical variation of an extremely narrow vestibular space due to the close proximity of the medial aspect of the coronoid process to the distal molar. It is suggested that each clinical examination include the width of the buccal vestibular space while performing mandibular movements.

Adult↗
PubMed1997

Allogenic leukocyte immunization after five or more miscarriages. Recurrent Miscarriage Immunotherapy Trialists Group.

Rather than investigate whether paternal leukocyte immunization improves the live birth rate in women with three or more abortions, we analysed the results of patients expected to have a poor outcome in a subsequent pregnancy if untreated, i.e. women with five or more abortions and no anti-paternal complement-dependent antibody (APCA) at initial testing. The analysis included the results of patients treated by us over the last 8 years and the results of randomized and non-randomized trials reported by the Recurrent Miscarriage Immunotherapy Trialists Group. Patients with a previous live birth were classified into two groups: secondary aborters if there was an initial live birth followed by miscarriages, or tertiary aborters if there were miscarriages followed by a live birth and at least three subsequent miscarriages. The results were evaluated separately for primary, secondary and tertiary aborters who demonstrated APCA activity as a result of immunization. The 107 primary aborters had double the live birth rate if immunized, with an overall benefit of 31%. The 45 tertiary aborters had an almost 3-fold increase in the live birth rate, with an absolute benefit of 50%. The number of patients needed to treat to achieve one extra live birth was three to four primary aborters or two tertiary aborters. Immunization had little beneficial effect in secondary aborters but was effective in preventing abortion in primary or tertiary aborters with five or more abortions.

Abortion, Habitual↗
PubMed1997

Lymphocytotoxic antibodies in Israeli patients with rheumatoid arthritis.

The presence, antigenic specificity, and clinical role of lymphocytotoxic antibodies (LCAs) were studied in 72 Israeli patients with rheumatoid arthritis (RA). Using the microlymphocytotoxicity assay on a cell panel of 47 donors, LCAs were found in 55% of the 72 RA sera, each displaying a distinct pattern of anti-lymphocytic reactivity, mostly against B lymphocytes. Human lymphocytic antigens (HLA) analysis of donors' lymphocytes suggested that activity of LCA-positive RA sera is HLA directed in 60% of cytotoxic sera. The anti-HLA antibodies found were not autoreactive and were not restricted to a particular class I or class II antigen. Relating the presence of LCAs to selective clinical features revealed that LCAs are inversely associated with the presence of an erosive disease (P <0.01) and with the patients' HLA-DQw1 (P <0.01). These findings suggest that LCAs in Israeli patients with RA are very common, multispecific and may have a protective role not mediated through interaction with self-HLA antigens.

Antilymphocyte Serum↗
PubMed1996

Structure and orientation of the mammalian antibacterial peptide cecropin P1 within phospholipid membranes.

Cecropins are positively charged antibacterial peptides that act by permeating the membrane of susceptible bacteria. To gain insight into the mechanism of membrane permeation, the secondary structure and the orientation within phospholipid membranes of the mammalian cecropin P1 (CecP) was studied using attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy and molecular dynamics simulations. The shape and frequency of the amide I and II absorption peaks of CecP within acidic PE/PG multibilayers (phosphatidylethanolamine/phosphatidylglycerol) in a 7:3 (w/w) ratio (a phospholipid composition similar to that of many bacterial membranes), indicated that the peptide is predominantly alpha-helical. Polarized ATR-FTIR spectroscopy was used to determine the orientation of the peptide relative to the bilayer normal of phospholipid multibilayers. The ATR dichroic ratio of the amide I band of CecP peptide reconstituted into oriented PE/PG phospholipid membranes indicated that the peptide is preferentially oriented nearly parallel to the surface of the lipid membranes. A similar secondary structure and orientation were found when zwitterionic phosphatidylcholine phospholipids were used. The incorporation of CecP did not significantly change the order parameters of the acyl chains of the multibilayer, further suggesting that CecP does not penetrate the hydrocarbon core of the membranes. Molecular dynamics simulations were used to gain insight into possible effects of transmembrane potential on the orientation of CecP relative to the membrane. The simulations appear to confirm that CecP adopts an orientation parallel to the membrane surface and does not insert into the bilayer in response to a cis positive transmembrane voltage difference. Taken together, the results further support a "carpet-like" mechanism, rather than the formation of transmembrane pores, as the mode of action of CecP. According to this model, formation of a layer of peptide monomers on the membrane surface destablizes the phospholipid packing of the membrane leading to its eventual disintegration.

Amino Acid Sequence↗
PubMed1996

[Huntington's disease: molecular basis and detection of carriers].

Huntington's disease (HD) results from extensive damage to the nerve cells of the brain cortex and basal ganglia. The gene associated with these changes was mapped in 1983 to the short arm of chromosome 4, at 4p16.3. A decade later it was cloned and the mutation was identified as an increase in the number of CAG repeats in the coding sequence. In the normal gene there are up to 34 repeats but in HD there are more than 36. This is termed dynamic mutation and is found in several other diseases, most of which manifest neurological symptoms. We summarize our studies of 10 families with HD, and 20 individuals with no known history of the disease. Our studies suggest that Jewish patients with HD exhibit the same dynamic gene mutation found in non-Jews. The number of repeats, both in diseased patients and normal controls, is similar to that found in non-Jews. Paternal inheritance was associated with increased severity of symptoms and earlier clinical manifestation, similar to what has been reported. Our experience testing for Huntington gene mutations indicates that this is a relatively simple, reliable and accurate test which can be used in the diagnosis of the disease, in identifying carriers, and for prenatal diagnosis.

Genetic Carrier Screening↗
PubMed1996

HLA DR and DQ polymorphism in Ashkenazi and non-Ashkenazi Jews: comparison with other Mediterraneans.

HLA-DR and DQ alleles have been detected by DNA typing in Ashkenazi and non-Ashkenazi Jews from Israel. Allele frequencies, characteristic DR/DQ linkage disequilibria, population distances and their corresponding dendrogram by using the Neighbor-Joining method were used to study relatedness between Jewish and other Mediterranean and non Mediterranean populations. Closest relatedness is observed between Ashkenazi and non-Ashkenazi Jews, and, in decreasing order, also with Algerians, Spaniards (including Spanish-Basques), French and Italians. Also, particular characteristic Central European alleles are observed in Ashkenazi Jews and Mediterranean/African alleles in non-Ashkenazi Jews. This is consistent with historical data, Jews being an ancient Mediterranean population, who have had a certain degree of admixture with their 2000-3000 years old neighbors in spite of cultural and religious traditions which have preserved identity outside Israel.

Algeria↗
PubMed1996

Intravenous immunoglobulin in women with five or more abortions.

PROBLEM: Treatment for recurrent miscarriage has usually been given to all women with three or more abortions of unknown cause. As these patients have a 50-60% subsequent live birth rate, no treatment has been shown to unequivocally improve the live birth rate. Immunoglobulin is the latest treatment to be applied. In order to determine if immunoglobulin improves the live birth rate, we analyzed the results of patients expected to have a poor outcome in the subsequent pregnancy if left untreated, i.e., women with five or more abortions, who have aborted after paternal leucocyte immunization or who continue to abort despite possessing anti-paternal complement dependent antibody (APCA). METHODS: A preliminary trial was carried out using immunoglobulin (Sandoglobulin, Sandoz, Switzerland). It was infused at a dose of 400 mg/Kg body weight, in the follicular phase of a cycle in which pregnancy was planned. A booster dose was administered as soon as pregnancy was diagnosed. RESULTS: Twelve patients were treated, ten conceived. Five have had subsequent live births. Two infants were premature but their size was appropriate for gestational age. The other three infants delivered at term. CONCLUSIONS: This is still too small a group from which to draw definite conclusions about the efficacy of immunoglobulin to prevent abortion. However, five live births in ten patients is an encouraging result, especially when the expected poor obstetric outcome is considered. Hence the efficacy of immunoglobulin should be evaluated further in high risk patients.

Abortion, Habitual↗
PubMed1995

Interaction of the mammalian antibacterial peptide cecropin P1 with phospholipid vesicles.

Cecropins are positively charged antibacterial polypeptides that were originally isolated from insects. Later on a mammalian homologue, cecropin P1 (CecP), was isolated from pig intestines. While insect cecropins are highly potent against both Gram-negative and Gram-positive bacteria, CecP is as active as insect cecropins against Gram-negative but has reduced activity against Gram-positive bacteria. To gain insight into the mechanism of action of CecP and the molecular basis of its antibacterial specificity, the peptide and its proline incorporated analogue (at the conserved position found in insect cecropins), P22-CecP, were synthesized and labeled on their N-terminal amino-acids with fluorescent probes, without significantly affecting their antibacterial activities. Fluorescence studies indicated that the N-terminal of CecP is located on the surface of phospholipid membranes. Binding experiments revealed that CecP binds acidic phosphatidylserine/phosphatidylcholine (PS/PC) vesicles better than zwitterionic PC vesicles, which correlates with its ability to permeate the former better than the latter. The shape of the binding isotherms suggest that CecP, like insect cecropin, binds phospholipids in a simple, noncooperative manner. However, resonance energy transfer (RET) measurements revealed that, unlike insect cecropins, CecP does not aggregate in the membrane even at relatively high peptide to lipid ratios. The stoichiometry of CecP binding to vesicles suggests that amount of CecP sufficient to form a monolayer causes vesicle permeation. In spite of the incorporation of the conserved proline in P22-CecP, the analogue has reduced antibacterial activity, which correlates with its reduced alpha-helical structure and its lower partitioning and membrane permeating activity with phospholipid vesicles. Taken together, our results support a mechanism in which CecP disrupts the structure of the bacterial membrane by (i) binding of peptide monomers to the acidic surface of the bacterial membrane and (ii) disintegrating the bacterial membrane by disrupting the lipid packing in the bilayers. These results, combined with data reported for other antibacterial polypeptides, suggest that the organization of peptide monomers within phospholipid membranes contributes to Gram-positive/Gram-negative antibacterial specificity.

Amino Acid Sequence↗
PubMed1995

[Multidisciplinary approach to counseling in Huntington's disease].

The recent cloning of the Huntington's disease gene now allows definitive presymptomatic and even prenatal testing. This achievement has posed a considerable challenge for the genetic counselor. We present the multidisciplinary approach implemented in our center, and experience in our first 13 diagnoses. Individuals at risk undergo neuropsychiatric evaluation, genetic counseling, molecular studies, post-counselling follow-up and support according to the protocols suggested by the International Huntington's Disease Association. Molecular studies of cytosine-arginine-guanine repeats showed that 4 individuals and 1 at-risk fetus were unaffected and 6 at-risk individuals, including the mother of the fetus, had inherited the disease mutation. The diagnosis was excluded in 2 individuals clinically suspected of Huntington's disease. All but 1 of those investigated had accepted, and adapted to the new reality. The exception was a carrier who asked to discontinue the contact a week after being informed of the results.

Clinical Protocols↗
PubMed1995

The assembly and organization of the alpha 5 and alpha 7 helices from the pore-forming domain of Bacillus thuringiensis delta-endotoxin. Relevance to a functional model.

The pore-forming domain of Bacillus thuringiensis insecticidal CryIIIA delta-endotoxin contains two helices, alpha 5 and alpha 7, that are highly conserved within all different Cry delta-endotoxins. To gain information on the mode of action of delta-endotoxins, we have used a spectrofluorimetric approach and characterized the structure, the organization state, and the ability to self-assemble and to co-assemble within lipid membranes of alpha 5 and alpha 7. Circular dichroism (CD) spectroscopy revealed that alpha 7 adopts a predominantly alpha-helical structure in methanol, similar to what has been found for alpha 5, and consistent with its structure in the intact molecule. The hydrophobic moment of alpha 7 is higher than that calculated for alpha 5; however, alpha 7 has a lesser ability to permeate phospholipids as compared to alpha 5. Binding experiments with 7-nitrobenz-2-oxa-1,3-diazole-4-yl (NBD)-labeled peptide demonstrated that alpha 7 binds to phospholipid vesicles with a partition coefficient in the order of 10(4) M-1 similar to alpha 5, but with reduced kinetics and in a noncooperative manner, as opposed to the fast kinetics and cooperativity found with alpha 5. Resonance energy transfer measurements between fluorescently labeled pairs of donor (NBD)/acceptor (rhodamine) peptides revealed that, in their membrane-bound state, alpha 5 self-associates but alpha 7 does not, and that alpha 5 coassembles with alpha 7 but not with an unrelated membrane bound alpha-helical peptide. Furthermore, resonance energy transfer experiments, using alpha 5 segments, specifically labeled in either the N- or C-terminal sides, suggest a parallel organization of alpha 5 monomers within the membranes. Taken together the results are consistent with an umbrella model suggested for the pore forming activity of delta-endotoxin (Li, J., Caroll, J., and Ellar, D. J. (1991) Nature 353, 815-821), where alpha 5 has transmembrane localization and may be part of the pore lining segment(s) while alpha 7 may serve as a binding sensor that initiates the binding of the pore domain to the membrane.

4-Chloro-7-nitrobenzofurazan↗
PubMed1995

Variation of skin surface temperature over the masseter muscles in patients with myofascial pain following occlusal splint treatment.

The skin surface temperature (SST) over the masseter muscles was measured in 19 patients suffering from myofascial pain (MP) and 20 controls who had no history of any craniomandibular disorder. Seven measurements with intervals of 2 weeks were carried out. MP patients received an occlusal stabilization appliance during their second visit as their only treatment. Clinical symptoms, including muscle sensitivity to palpation, jaw movement and general feeling were evaluated at each visit and compared to baseline. The results indicated that SST in the control group remained almost unchanged throughout the study. In the MP group, the mean temperature decreased during the study after initial treatment. Accordingly, there was a probability of 88.5% that the occlusal appliance treatment in the MP group would cause a decrease of SST over the masseter muscle. A significant relationship between clinical improvement and a decrease of SST was found in the MP group. Temperature recordings with certain limitations could be an objective assessory tool in diagnosis and follow-up of patients with myofascial pain.

Adolescent↗
PubMed1995

HLA-B5 in the diagnosis of Behcet's disease.

Behçet's disease, a multisystem disease is, by its nature, difficult to diagnose. The first manifestation of the disease may precede the appearance of other symptoms and signs essential for diagnosis by many years. In patients of Mediterranean origin, the early manifestations of the disease, may be confused with those of familial Mediterranean fever (FMF). Determination of HLA-B5 may, however, contribute to the diagnosis in children with partial manifestations of Beh,cet syndrome.

Adolescent↗
PubMed1994

The alpha-5 segment of Bacillus thuringiensis delta-endotoxin: in vitro activity, ion channel formation and molecular modelling.

A peptide with a sequence corresponding to the highly conserved alpha-5 segment of the Cry delta-endotoxin family (amino acids 193-215 of Bacillus thuringiensis CryIIIA [Gazit and Shai (1993) Biochemistry 32, 3429-3436]), was investigated with respect to its interaction with insect membranes, cytotoxicity in vitro towards Spodoptera frugiperda (Sf-9) cells, and its propensity to form ion channels in planar lipid membranes (PLMs). Selectively labelled analogues of alpha-5 at either the N-terminal amino acid or the epsilon-amine of its lysine, were used to monitor the interaction of the peptides with insect membranes. The fluorescent emission spectra of the 7-nitrobenz-2-oxa-1,3-diazole-4-yl (NBD)-labelled alpha-5 peptides displayed a blue shift upon binding to insect (Spodoptera littoralis) mid-gut membranes, reflecting the relocation of the fluorescent probes to an environment of increased apolarity, i.e. within the lipidic constituent of the membrane. Moreover, midgut membrane-bound NBD-labelled alpha-5 peptides were protected from enzymic proteolysis. Functional characterization of alpha-5 has revealed that it is cytotoxic to Sf-9 insect cells, and that it forms ion channels in PLMs with conductances ranging from 30 to 1000 pS. A proline-substituted analogue of alpha-5 is less cytolytic and slightly more exposed to enzymic digestion. Molecular modelling utilizing simulated annealing via molecular dynamics suggests that a transbilayer pore may be formed by alpha-5 monomers that assemble to form a left-handed coiled coil of approximately parallel helices. These findings further support a role for alpha-5 in the toxic mechanism of delta-endotoxins, and assign alpha-5 as one of the transmembrane helices which form the toxic pore. The suggested role is consistent with the recent finding that cleavage of CryIVB delta-endotoxin in a loop between alpha-5 and alpha-6 is highly important for its larvicidal activity [Angsuthanasombat, Crickmore and Ellar (1993) FEMS Microbiol. Lett. 111, 255-262].

4-Chloro-7-nitrobenzofurazan↗
PubMed1994

Congenital bilateral absence of vas deferens in the absence of cystic fibrosis.

The high frequency of mutations in the cystic fibrosis gene in patients with congenital bilateral absence of vas deferens (CBAVD) has raised the question whether all of them have a genital form of cystic fibrosis. We investigated 47 CBAVD patients by ultrasonography, 10 (21%) had renal malformations and 37 (79%) did not. In the former group, no cystic fibrosis mutations were found and sweat chloride concentrations were normal. In the latter group, 18 patients (49%) carried at least one cystic fibrosis mutation and sweat chloride was high in 17 of 26 tested (65%). Our findings suggest that CBAVD patients with renal malformations do not necessarily have cystic fibrosis.

Cystic Fibrosis↗
PubMed1994

Mode of action of the antibacterial cecropin B2: a spectrofluorometric study.

Cecropin B2 (CecB) is a 35 amino acid residue, antibacterial peptide that was isolated from the hemolymph and cuticular matrix of the silkworm, Bombyx mori. Synthetic peptides with sequences corresponding to CecB and its truncated analogue, [3-->35]CecB, were synthesized and selectively labeled at their N-terminal amino acids with either 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) or rhodamine fluorescent probes. Utilization of these probes facilitated study of the interaction of cecropin with model phospholipid membranes at a high lipid/peptide molar ratio (approximately 3000:1), permitting investigation of the initial steps involved in this process. The surface partition coefficient of CecB, derived from binding isotherms of the NBD-labeled peptide, was 10-fold higher with acidic phospholipids than with zwitterionic ones, which correlates with the high efficiency of CecB and its analogues in permeating acidic phospholipid vesicles. Furthermore, a direct correlation was found between the antibacterial activity of CecB or its truncated analogues and the ability of their Rho-labeled analogues to interact with bacteria and human red blood cells. We propose that CecB binds phospholipid membranes preferentially as monomers lying on the surface, rather than cooperatively as bundles that form transmembranal pores via a "barrel stave" mechanism. This is based on the following: (i) the linearity of CecB's binding isotherms; (ii) the low energy transfer between membrane-embedded donor and acceptor-labeled CecB, even in the presence of a transmembrane potential; (iii) the surface localization of CecB's N-terminus; (iv) the need for more than 100 peptide molecules per phospholipid vesicle to induce initial ion leakage; and (v) the fact that CecB is a highly positively charged amphipathic alpha-helix, and therefore it is not expected to transverse the membrane as a monomer. We speculate that the non-cooperative binding of the peptides on the outer surface of the bacteria (i.e., no aggregation of CecB monomers) may help them to diffuse efficiently into the inner membrane, which is thought to be the target of antibacterial peptides.

Amino Acid Sequence↗