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Biomedical subjects

E Gazit

Publications and source records attributed to E Gazit.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Association of a nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease.

Only about 30% of the cystic fibrosis chromosomes in the Israeli cystic fibrosis patient populations carry the major CF mutation (delta F508). Since different Jewish ethnic groups tended to live as closed isolates until recent times, high frequencies of specific mutations are expected among the remainder cystic fibrosis chromosomes of these ethnic groups. Genetic factors appear to influence the severity of the disease. It is therefore expected that different mutations will be associated with either severe or mild phenotype. Direct genomic sequencing of exons included in the two nucleotide-binding folds of the putative CFTR protein was performed on 119 Israeli cystic fibrosis patients from 97 families. One sequence alteration which is expected to create a termination at residue 1282 (W1282X) was found in 63 chromosomes. Of 95 chromosomes, 57 (60%) are of Ashkenazi origin. Together with the delta F508 (23% in this group), G542X, N1303K, and 1717-1G----A mutations, the identification of 92% of cystic fibrosis chromosomes of Ashkenazi origin becomes possible. Patients homozygous for the W1282X mutation (n = 16) and patients heterozygous for the delta F508 and W1282X mutations (n = 22) had similarly severe disease, reflected by pancreatic insufficiency, high incidence of meconium ileus (37% and 27%, respectively), early age at diagnosis, poor nutritional status, and variable pulmonary function. In conclusion, the W1282X mutation is the most common cystic fibrosis mutation in the Ashkenazi Jewish patient population in Israel. This nonsense mutation is associated with presentation of severe disease.

Cystic Fibrosis↗
PubMed1991

Engraftment and development of human T and B cells in mice after bone marrow transplantation.

A model for human lymphocyte ontogeny has been developed in a normal mouse. Human bone marrow, depleted of mature T and B lymphocytes, and bone marrow from mice with severe combined immunodeficiency were transplanted into lethally irradiated BALB/c mice. Human B and T cells were first detected 2 to 4 months after transplantation and persisted for at least 6 months. Most human thymocytes (30 to 50 percent of total thymocytes) were CD3+CD4+CD8+. Human immunoglobulin was detected in some chimeras, and a human antibody response to dinitrophenol could be generated after primary and secondary immunization.

Animals↗
PubMed1991

A variant of HLA-DR4 determines susceptibility to rheumatoid arthritis in a subset of Israeli Jews.

HLA-DR4 is associated with risk for developing rheumatoid arthritis (RA) in most populations. In Israeli Jews, in whom the Dw10 subtype of DR4 predominates, no association of RA with DR4 has been found. The inability to detect an association could be due to the high frequency of DR4-Dw10. We used DNA typing with amplification by the polymerase chain reaction and dot-blotting with allele-specific oligonucleotides to determine DR4 variants in 131 Jewish RA patients living in Israel and 134 controls. In both Ashkenazi Jews and non-Ashkenazi Jews, the rare variant Dw15 (previously identified in Japanese populations and in Japanese patients with RA) was found to be the main allele associated with the risk of developing RA (relative risk = 9.2, corrected P less than 0.001). However, this low-frequency allele could be responsible for susceptibility in only 11.5% of the patients. Susceptibility for rheumatoid factor-positive RA was associated with Dw4 and Dw15; the risk for rheumatoid factor-negative RA was associated only with Dw14. The distribution of the HLA-DQ alleles associated with DR4 showed that more than half of the RA patients with Dw15 also had HLA-DQw2. The frequencies of DQw7 and DQw8 were not different in RA patients compared with controls. The results suggest that, as in other populations, susceptibility for the development of RA in Israeli Jews is associated with DRB1 locus alleles of the DR4 group.

Alleles↗
PubMed1991

Anti-idiotypic IgM antibodies to anti-HLA class I antibodies in habitual abortion.

In order to investigate the role of the idiotypic network in miscarriages, sera from 28 habitually aborting women undergoing paternal leukocyte immunization were studied for the presence of HLA antibodies and related anti-idiotypes. Sixty-eight percent of sera from preimmunized patients which did not contain anti-lymphocyte antibodies inhibited the activity of antibodies to the HLA class I antigens expressed by the spouse. This inhibitory activity could be assigned to IgM antibodies, which cross-inhibit antibodies of similar specificity. This suggests that they are anti-idiotypes for the binding site of HLA antibodies. Immune sera of successfully treated patients exhibited both cytotoxic IgG anti-HLA antibodies and inhibitory IgM anti-idiotypic antibodies. A possible role for an intact idiotypic network in maintaining pregnancy is suggested.

Abortion, Habitual↗
PubMed1991

Macrodontia of maxillary central incisors: case reports.

Two cases of maxillary anterior macrodontia, resulting from fusion and gemination, were treated orthodontically. Problems of esthetics and overjet were solved in the first patient by sectioning and extraction of a fused mesiodens, and in the second patient by treating toward an Angle Class III buccal occlusion.

Child↗
PubMed1991

Rheumatoid arthritis in Israeli Jews: shared sequences in the third hypervariable region of DRB1 alleles are associated with susceptibility.

Rheumatoid arthritis (RA) is known to be associated with class II HLA antigens in most populations, but recent studies in Israeli Jewish patients showed no significant differences in either DR4 or DR1 between patients and controls. In a previous DR4 subset study we found DR4-Dw15 to be associated with susceptibility (RR = 9.2) but this allele occurred in only 12% of the patients. We analyzed all DRB1 genes, using the polymerase chain reaction (PCR) and hybridization with allele specific oligonucleotides, in 49 Jewish patients with RA and 40 normal Jewish controls. Six DRB1 alleles that are similar to the prototype DR4-Dw4 (DRB1*0401) appeared to contribute to the risk for developing RA. In addition to DR4-Dw15 (DRB1*0405) 2 other alleles having substitutions in codons 71 only (DR1-Dw1/DRB1*0101, DR4-Dw14.2/DRB1*0408) or in codons 70 and 71 (DRw10/DRB1*1001) gave highly significant relative risks. Together, this group, with valine in position 85, and glycine in codon 86, gave a relative risk of 11.0 (p = 0.0002). Two other alleles with the same sequence in the third hypervariable region (amino acids 67-74) but with valine in codon 86 (DR4-Dw14.1/DRB1*0404) or alanine in 85 and valine in 86 (DR1-Dw20, DRB1*0102) gave a combined risk of 3.6 (p = 0.049). Altogether these 7 alleles with similar sequences in the third hypervariable region accounted for 55.6% of the patients, with an overall relative risk of 8.6 (p = 0.00002). Our results in this population indicate that shared epitopes in the third hypervariable region of DRB1 alleles also play a role in susceptibility to RA.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1990

[DNA fingerprinting in paternity testing].

Laboratory tests used in cases of disputed paternity identify genetically determined gene products inherited in a dominant Mendelian fashion. Red blood cell groups, isoenzymes, serum proteins and the HLA system are the most commonly used systems in these tests. The application of DNA technology increases the scope of paternity tests and provides the court with extremely precise laboratory-based conclusions which approach near certainty.

DNA↗
PubMed1990

Selection of patients with habitual abortion for paternal leucocyte immunization.

After potentiation of the immune response in habitual aborters 75-85% of subsequent pregnancies are claimed to result in healthy term infants. However, all publications to date have either been based on the authors concept of the immune processes involved or an attempt to demonstrate the efficacy of treatment either empirically or by matched trials. As immunization is coming into wider clinical use, it is necessary to determine which patients will benefit from this form of treatment. This paper presents our experience with paternal leucocyte immunization over the period 1985-1988. 207 patients were classified on a clinical basis and by immunological testing. 143 patients have been immunised, 129 pregnancies have occurred in 108 patients. The vast majority of our patients have recurrent missed abortions. Only six women habitually aborted live fetuses. Two had subsequent live births. Secondary aborters seem to do well in subsequent pregnancies, whether immunized or not. The patient most likely to benefit from immunization is the Primary missed aborter who does not possess antipaternal antibody (APCA), but is induced to produce APCA by immunization. Using these criteria, 75% success rates are observed in the subsequent pregnancy. This success rate is irrespective of HLA antigen sharing or in-vitro mixed lymphocyte reactivity.

Abortion, Habitual↗
PubMed1990

Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene.

Additional mutations in the cystic fibrosis (CF) gene were identified in the regions corresponding to the two putative nucleotide (ATP)-binding folds (NBFs) of the predicted polypeptide. The patient cohort included 46 Canadian CF families with well-characterized DNA marker haplotypes spanning the disease locus and several other families from Israel. Eleven mutations were found in the first NBF, 2 were found in the second NBF, but none was found in the R-domain. Seven of the mutations were of the missense type affecting some of the highly conserved amino acid residues in the first NBF; 3 were nonsense mutations; 2 would probably affect mRNA splicing; 2 corresponded to small deletions, including another 3-base-pair deletion different from the major mutation (delta F508), which could account for 70% of the CF chromosomes in the population. Nine of these mutations accounted for 12 of the 31 non-delta F508 CF chromosomes in the Canadian families. The highly heterogeneous nature of the remaining CF mutations provides important insights into the structure and function of the protein, but it also suggests that DNA-based genetic screening for CF carrier status will not be straightforward.

Adenosine Triphosphate↗
PubMed1990

Immunization by paternal leukocytes for prevention of primary habitual abortion: results of a matched controlled trial.

Habitual abortion is a difficult clinical problem, as no cause can be found for abortion in over 50% of patients. At the habitual abortion clinic of the Sheba Medical Center, immunological activity is tested and patients who are considered suitable are offered immunopotentiation with paternal leukocytes. Patients are only treated if they have no other cause for habitual abortion, no lupus anticoagulant and no antipaternal complement-dependent antibodies (APCA). Immunization is thought to potentiate the maternal immune response to paternal antigens encountered on the trophoblast. The production of APCA antibody indicates that an immune response has occurred. Of the 156 patients so far immunized, 109 have developed these antibodies. To date, 79 of these 156 patients have become pregnant. Sixty-seven patients (with 3-12 miscarriages each) belong to the antibody-positive group. Sixty-four of the 89 subsequent pregnancies have been carried past their previous dates of abortion. Forty-seven live births have occurred. By contrast, 12 patients have been pregnant in the antibody-negative group, of the 16 subsequent pregnancies only 6 were successful. A control group is available for comparison. This consists of patients suitable for immunization, but not immunized. Of these patients, only 11 of 30 pregnancies have been carried to term.

Abortion, Habitual↗
PubMed1990

Craniographic examination of the condylar angle and the maxillary incisal palatal angle in Bedouin skulls.

Craniographic registrations were used to examine 25 Bedouin skulls. The skulls were divided into three groups according to the anatomy and position of the maxillary incisor. Correlations between condylar guidance angle, maxillary incisal palatal angle, attrition, and flaring were investigated. No correlation was found between the condylar and maxillary incisal palatal angles. In the presence of severe attrition and/or flaring, the maxillary incisal palatal angle was reduced and mild reduction was also found in the condylar guidance angle. A strong correlation was found between the level of attrition and flaring.

Cephalometry↗