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Biomedical subjects

E Gazit

Publications and source records attributed to E Gazit.

At least 73 records · Page 4Linked to original sources
PubMed1994

Mutations of the hexosaminidase A gene in Ashkenazi and non-Ashkenazi Jews.

Tay-Sachs disease (TSD) is caused by mutations in the gene encoding the alpha-subunit of beta-hexosaminidase A (HexA). This disease is more prevalent in certain ethnic groups such as Jews of Ashkenazi origin. Three mutations are most commonly found among the latter population: a 4-nucleotide insertion in exon 11, a transversion at the splice site in intron 12, and the adult onset mutation in exon 7. The frequency and distribution of these mutations among Ashkenazi and non-Ashkenazi Jews were examined: 96% of the Ashkenazi carriers bore one of these mutations, while in only 30% of the non-Ashkenazi Jewish carriers were the mutations identified. The percentage distribution of the exon 11:intron 12:exon 7 and unidentified mutant allele(s) was 82:10:4:4 among 152 Ashkenazi carriers, and 16:12:2:70 among non-Ashkenazi Jewish carriers. When the non-Ashkenazi Jewish population was divided into two groups according to the geographical distance from Eastern Europe, it was obvious that the ancestral origin of the subjects bearing the exon 11 allele was predominantly from countries bordering Eastern and Central Europe, such as Turkey, Bulgaria, and Georgia. In carriers from other geographical areas of North Africa and the Middle East, this allele was about fivefold less frequent. The result is compatible with the assumption that this gene, of which the tested individuals were unaware, originates from interethnic marriage in neighboring populations. However, regardless of the ancestral origin, the intron 12 allele was quite evenly distributed throughout the Jewish population.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1994

The effect of pain from orthodontic arch wire adjustment on masseter muscle electromyographic activity.

Pain has been shown to have an effect on muscle activity even when it does not originate in the muscle itself or in the related joint. The effect of pain from arch wire adjustment on jaw muscle activity is unclear. This study systematically evaluated the effects of orthodontic arch wire adjustment pain on masseter electromyographic (EMG) activity and on the swallowing threshold. The EMG recordings were made on 22 subjects (ages 11 to 15) under three conditions: chewing five peanuts (10 seconds), watching TV chewing gum (15 minutes), and watching TV with no gum (15 minutes). An arch wire adjustment or placebo adjustment was then made. Subjects returned after 48 hours, and the EMG measurements were made under the same conditions. After 3 weeks, subjects received arch wire or placebo treatment in a crossover design with identical recording procedures. The EMG levels while chewing peanuts decreased in 18 of 22 subjects after treatment, compared with 9 of 22 subjects after the placebo. While watching TV with gum, the EMG levels of 20 of 22 subjects decreased after treatment, compared with 9 of 22 subjects after the placebo. The number of chewing strokes before swallowing increased significantly after treatment compared with after placebo. The results suggest that orthodontic pain on teeth tend to reduce muscle activity during function.

Adolescent↗
PubMed1994

The preferential expression of the anti-DNA associated 8.12 idiotype in lupus is not genetically controlled.

Anti-DNA antibodies are autoantibodies unique to systemic lupus erythematosus. Studies of their structure have demonstrated cross reactive idiotypes present in genetically unrelated individuals. Despite much research, it is still not clear what triggers their production and what governs the presence of particular idiotypic determinants in their structure. To study the role of genetic and environmental factors in the expression of idiotype, we analyzed sera of SLE patients, their family members and nonautoimmune individuals vaccinated with pneumococcal polysaccharide, for the presence of the 8.12 idiotype, which is present on lambda light chains of anti-DNA antibodies. Elevated titers of the 8.12 idiotype was found in the serum of 57% of SLE patients. Elevated titers were present in only 9% of family members, and always associated with the presence of high levels of IgG anti-DNA antibodies. Following vaccination with pneumococcal polysaccharide, 8.12 reactive anti-pneumococcal antibodies were produced by 7 of 10 non-autoimmune individuals and 8.12 reactive anti-DNA antibodies by one. These results suggest that 8.12 reactive antibodies are antigen driven and bind structurally related antigens, but there is no evidence that expression of this idiotype is genetically controlled.

Antibodies, Antinuclear↗
PubMed1993

Structural characterization, membrane interaction, and specific assembly within phospholipid membranes of hydrophobic segments from Bacillus thuringiensis var. israelensis cytolytic toxin.

The Bacillus thuringiensis var. israelensis (Bti) cytolytic toxin is hypothesized to exert its toxic activity via pore formation in the cell membrane as a result of the aggregation of several monomers. To gain insight into the toxin's mode of action, 2 putative hydrophobic 22 amino acid peptides were synthesized and characterized spectroscopically and functionally. One peptide corresponded to the putative amphiphilic alpha-helical region (amino acids 110-131, termed helix-2), and the other to amino acids 50-71 (termed helix-1) [Ward, E. S., Ellar, D. J., & Chilcott, C. N. (1988) J. Mol. Biol. 202, 527-535] of the toxin. Circular dichroism spectroscopy revealed that both segments adopt high alpha-helical content in a hydrophobic environment, in agreement with previous models. To monitor peptide-lipid and peptide-peptide interactions, the peptides were labeled selectively with either 7-nitro-2,1,3-benzoxadiazol-4-yl (NBD) (to serve as donor) or tetramethylrhodamine (to serve as an acceptor), at their N-terminal amino acids. Both segments bind strongly to small unilamellar vesicles, composed of zwitterionic phospholipids, with surface partition coefficients on the order of 10(4) M-1. The shape of the binding isotherms indicates that helix-2 forms large aggregates within phospholipid membranes. Resonance energy transfer experiments demonstrated that the segments self-associate and interact with each other, but do not associate with unrelated membrane-bound peptides. Functional characterization demonstrated that helix-2 permeates phospholipid SUV with a potency similar to that of naturally occurring pore-forming peptides. Thus, the results support a role for helices-1 and -2 in the assembly and in the pore formation by Bti toxin.

Amino Acid Sequence↗
PubMed1993

Structural and functional characterization of the alpha 5 segment of Bacillus thuringiensis delta-endotoxin.

One of the most conserved sequences in various delta-endotoxins is the 30 amino acid long block I. Block I of cryIIIA delta-endotoxin contains a 23 amino acid amphiphilic alpha-helix termed alpha 5. The potential involvement of this alpha 5 helix in the toxic mechanism of delta-endotoxin was examined. For this purpose, a peptide corresponding to the alpha 5 segment and its proline incorporated analogue (P-alpha 5) were synthesized and characterized. The alpha-helical content of the peptides, assessed in methanol by circular dichroism (CD), was 58% and 24% for alpha 5 and P-alpha 5, respectively. To monitor the interaction of alpha 5 peptides with phospholipid membranes, they were selectively labeled at their N-terminal amino acids with the fluorescent probes 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) or carboxyfluorescein. Fluorometric studies allowed the calculation of membrane surface partition constants, which were about 10(4) M-1 for both alpha 5 and P-alpha 5, and revealed that their N-terminals are located within the lipid bilayers. The shape of the binding isotherms indicated that alpha 5 aggregated in both zwitterionic and acidic vesicles. Functional characterization of the alpha 5 peptides was determined by assessing their ability to dissipate a diffusion potential from sonicated small unilamellar vesicles (SUV) composed of zwitterionic or acidic phospholipids and to lyse human erythrocytes. alpha 5 was much more active than P-alpha 5 in both assays. Moreover, membrane-bound alpha 5 was more protected from enzymatic proteolysis than P-alpha 5.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

[Screening for carriers of cystic fibrosis mutations in Ashkenazi volunteers].

309 DNA samples obtained from healthy volunteers were tested for the cystic fibrosis mutations DF508 and W1282X. 14 carriers were identified, 7 of each mutation. Since the 2 mutations account for only 80% of CF mutations, the actual number of carriers is 1 in 18. In spite of the fact that this is only a pilot study, the results suggest that screening for CF carriers is feasible and that it identifies unambiguously those who carry the CF genes. When testing for CF carriers becomes available for the general public, it will undoubtedly contribute in reducing significantly the incidence of children born with the disease.

Cystic Fibrosis↗
PubMed1993

Anti-DNA antibodies secreted by peripheral B cells of lupus patients have both normal and lupus-specific features.

Autoantibodies present in sera of patients with systemic lupus erythematosus (SLE) are found in low titer in sera of healthy individuals. Hence, it is possible that B cell populations in SLE patients and in normal individuals are homologous and in the absence of regulatory forces would secrete similar antibodies. We therefore studied antibody secretion of Epstein-Barr virus-transformed B cells of 20 SLE patients and 20 healthy subjects. Normal and lupus antibody repertoires did not differ significantly with respect to antigenic specificities, isotype, avidity, and titer. However, anti-DNA antibodies bearing the anti-DNA-associated idiotype 8.12 were found only in SLE. These findings suggest that the B cell repertoire of SLE and normal individuals is more similar than the serum antibody profile. However, part of the anti-DNA response in SLE probably reflects affinity (antigen driven) maturation as it differs in idiotype profile from anti-DNA response of normal individuals.

Antibodies, Antinuclear↗
PubMed1993

Evidence for linkage of the gene causing familial Mediterranean fever to chromosome 17q in non-Ashkenazi Jewish families: second locus or type I error?

Familial Mediterranean fever (FMF) is an autosomal recessive disorder of unknown pathogenesis, characterized by recurrent, self-limited attacks of fever with synovitis, peritonitis, or pleurisy. Using DNAs from affected Israeli families, we have recently mapped the gene causing FMF (designated MEF) to the short arm of chromosome 16, with two-point lod scores in excess of 20. In this report we consider the possibility of a second FMF susceptibility locus. Before discovering linkage to markers on chromosome 16, we had found suggestive evidence for linkage to chromosome 17q, with the following maximal two-point lod scores: D17S74 (pCMM86), Z = 2.47, (theta = 0.20); D17S40 (pLEW101), Z = 2.15 (theta = 0.15); D17S35 (CRI-pP3-1), Z = 1.78 (theta = 0.15); D17S46 (pLEW108), Z = 1.69 (theta = 0.18), D17S254, Z = 2.30 (theta = 0.20). Moreover, multipoint linkage analysis using D17S74 and D17S40 as fixed loci gave Z = 3.27 approximately 10 centimorgans (cM) telomeric to D17S40. Data with the chromosome 17 markers alone in our families suggested locus heterogeneity. Nevertheless, our families were not separable into complementary subsets showing linkage either to chromosome 16 or to chromosome 17. We also examined the possibility that the positive lod scores for chromosome 17 might reflect a secondary, modifying locus. By several measures of disease severity, families with positive lod scores for chromosome 17 loci had no worse disease than those with negative lod scores for these loci. We conclude that chromosome 17 does not encode a major FMF susceptibility gene for some of the families, nor does it encode a disease-modifying gene. Rather, it would appear that linkage to chromosome 17 is a "false positive" (type I) error. These results reemphasize the fact that a lod score of 3.0 corresponds to a posterior probability of linkage of 95%, with an attendant 1 in 20 chance of observing a false positive.

Blotting, Southern↗
PubMed1993

Differential suppression activity induced by paternal leukocyte immunization in habitual abortion.

In order to investigate the possible role of suppressor cells in paternal leukocyte immunization to prevent recurrent miscarriages, peripheral blood lymphocytes from habitually aborting women before and after immunization were assessed. Immunization-induced suppressor activity as shown by (1) rise in CD8-positive cells and a decline in the CD4/CD8 ratio, (2) failure of cyclosporine A to inhibit the proliferation of phytohemagglutinin- and alloantigen-stimulated cells and (3) unresponsiveness to the immunizing spouses' antigen. These findings resembled those in normal pregnant women. Hence, paternal leukocyte immunization may induce specific and nonspecific T cell suppression which may induce the immune tolerance necessary to maintain pregnancy.

Abortion, Habitual↗
PubMed1992

Membrane interactions of the sodium channel S4 segment and its fluorescently-labeled analogues.

A 24-amino acid peptide corresponding to the S4 segment of the sodium channel was synthesized. In order to perform fluorescence energy transfer measurements and to monitor the interaction of the peptide with lipid vesicles, the peptide was selectively labeled with fluorescence probes at either its N- or C-terminal amino acids. The fluorescent emission spectra of 7-nitrobenz-2-oxa-1,3-diazol-4- yl-(NBD-)labeled analogues displayed blue shifts upon binding to small unilamellar vesicles (SUV), reflecting the relocation of the fluorescent probe to an environment of increased apolarity. The results revealed that both the N- and C-terminus of the S4 segment are located within the lipid bilayer. Titration of solutions containing NBD-labeled peptides with SUV was used to generate binding isotherms, from which surface partition constants, in the range of 10(4) M-1, were derived. The shape of the binding isotherms as well as fluorescence energy transfer measurements suggest that aggregation of peptide monomers within the membrane readily occurs in acidic but not in zwitterionic vesicles. Furthermore, the results provide good correlation between the incidence of aggregation in PC/PS vesicles and the ability of the peptides to permeate the vesicle's membrane. However, a transmembrane diffusion potential had no detectable effect on the location of the peptide within the lipid bilayer or on its aggregation state.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Lupus anti-DNA antibodies bearing the 8.12 idiotype appear to be somatically mutated.

Anti-DNA antibodies in systemic lupus erythematosus (SLE) sera were analyzed using an antiidiotype designated 8.12 which recognizes a determinant on lambda light chains highly expressed in SLE sera. Eight of ten normal individuals had peripheral blood lymphocytes which produced high-titered 8.12-positive antibodies, following transformation with Epstein Barr virus, implying that the 8.12-reactive sequence originates in the germline gene (GLG). Of 58 SLE sera, 32 contained elevated titers of 8.12-reactive antibodies. Twenty-three of these sera had 8.12-reactive anti-DNA antibodies, suggesting a strong correlation between 8.12 idiotype and DNA binding. Moreover, 20 of 26 8.12-reactive IgG antibodies and only 4 of 10 8.12-reactive IgM antibodies bound DNA (P less than 0.05). These observations strengthen our previous findings in myeloma sera that DNA binding is associated with IgG isotype in the 8.12 idiotype system and suggest that the acquisition of anti-DNA reactivity in antibodies bearing the GLG idiotype 8.12 is achieved by somatic mutation, a feature of an antigen-driven response.

Antibodies, Antinuclear↗
PubMed1992

Ambiguous genitalia due to partial activity of cytochromes P450c17 and P450c21.

We describe a patient with male pseudohermaphrodism who has normal basal serum concentrations of cortisol and high basal levels of progesterone and 17 hydroxyprogesterone. Serum concentrations of androstendione, dehydroepiandrosterone sulfate and testosterone were low. On adequate human chorionic gonadotropin (HCG) stimulation, no rise in serum androstendione, dehydroepiandrosterone sulfate or testosterone concentrations was observed. After ACTH stimulation there was an excessive rise in progesterone and 17 hydroxyprogesterone with no rise in androstendione, dehydroepiandrosterone sulfate, testosterone, deoxycorticosterone or cortisol. These clinical and laboratory data suggest that the patient has a combined defect in both cytochromes P450c17 and P450c21. The genes coding for these cytochromes are on different chromosomes, 10 and 6, respectively. Unlike isolated 21 hydroxylase deficiency where all identical HLA siblings suffer from the disease, HLA typing of the patient's family revealed a healthy brother with identical HLA. This suggests that the gene coding for P450c21 on chromosome 6 is not affected and that the lesion might be on a common enzyme which donates an electron to both cytochromes, most probably a flavoprotein.

17-alpha-Hydroxyprogesterone↗
PubMed1992

A comparative study of three therapeutic modalities in a temporomandibular disorder (TMD) population.

A comparative study of three treatment modalities, pharmacologic, occlusal appliance, and their combined use, was conducted to test their therapeutic efficacy on 61 temporomandibular disorder (TMD) patients. Alprazolam (Xanax) was used for the pharmacologic treatment; the occlusal appliance therapy consisted of a flat maxillary stabilization splint. Of the 61 patients, 19 received Alprazolam, 30 received occlusal appliance therapy, and 12 received combined therapy. Subjects were examined at two-week intervals for two months. Only 42 patients attended all follow-up visits. Eight parameters were studied: severity of pain, periodicity of pain, self-evaluated stress, muscle sensitivity to palpation, joint sensitivity to palpation, joint noises, limitation of opening, and limitation of lateral movement. No significant difference was found between the treatment modalities for most of the parameters. All three proved to be effective. Alprazolam increased the restricted mandibular movement, was least effective on joint sensitivity to palpation, and had no effect on joint noises. The combined treatment approach not only failed to prove superior to the other treatments, but showed less improvement in some parameters, possibly due to the small sample.

Alprazolam↗