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Biomedical subjects

E Gazit

Publications and source records attributed to E Gazit.

At least 37 records · Page 2Linked to original sources

Generalized joint laxity and its relation with oral habits and temporomandibular disorders in adolescent girls.

A group of 248 girls, aged 15-16 years, were randomly selected and examined both clinically and by questionnaire with regard to the signs and symptoms of temporomandibular disorders (TMD), generalized joint laxity (GJL), range of mandibular opening, temporomandibular joint (TMJ) hypermobility and presence of oral parafunctions. The prevalence of GJL was 43% and that of TMJ hypermobility (TMJH) was 27.3%. A significant, albeit weak, correlation was found between the two. In the presence of joint click, both active and passive opening were significantly larger. When either muscle or joint sensitivity to palpation was present, the difference between the active and passive range of mouth opening increased significantly. The presence of reported clicks was negatively associated with GJL. This association was not valid in the presence of parafunction. Some of the signs and symptoms of TMD affected the range of mouth opening. In the presence of joint clicks, the mean active and passive mandibular opening were significantly larger. In the presence of joint and muscle sensitivity to palpation, the difference between passive and active mouth opening was larger. This was possibly because of the effect of pain on the full active range of opening, which was invalid in the registration of the passive mandibular opening. GJL, when present, did not seem to jeopardize the health of the stomatognathic system as expressed in the signs and symptoms of TMD. There was a negative association between GJL and the presence of reported joint clicks and catch. When a parafunction was present in addition to GJL, this association was invalid but not reversed, as has been previously reported.

Adolescent↗

Hereditary juvenile-onset craniocervical predominant generalized dystonia with parkinsonism.

OBJECTIVE: To report a unique hereditary, juvenile onset, craniocervical predominant, generalized dystonia and parkinsonism affecting four members of one family. FAMILY DESCRIPTION: A father and three of his four daughters presented to us over the past 30 years with a similar picture of generalized dystonia, starting in the craniocervical region in the second or third decade of life. They later developed moderate parkinsonism, mainly manifesting bradykinesia, rigidity and abnormal postural reflexes. Biochemical and genetic tests excluded Wilson's disease, Huntington's disease and Oppenheim's dystonia. CONCLUSION: This is a new type of familial dystonia-parkinsonism where the craniocervical dystonic symptoms are most prominent in the early stages while parkinsonism becomes the predominant problem later in life. A search for the genetic mutation in this family is underway.

Adolescent↗

Topical application of capsaicin for the treatment of localized pain in the temporomandibular joint area.

AIMS: To determine the effectiveness of topical capsaicin cream application on localized pain in the temporomandibular joint (TMJ) area. METHODS: A randomized, double-blind, placebo-controlled study was conducted on 30 patients suffering from unilateral pain in the TMJ area. Patients were randomly divided into experimental and placebo groups; they were instructed to apply 0.025% capsaicin cream or its vehicle to the painful TMJ area 4 times daily for 4 weeks. Subjective parameters of present pain, most severe pain, effect of pain on daily activities, and pain relief were assessed each week on a visual analog scale. Muscle and joint sensitivity to palpation on the painful and contralateral joints and maximal mouth opening (assisted/passive and non-assisted/active) were examined weekly by the same experienced examiner. RESULTS: Capsaicin cream produced no statistically significant influence on measured variables when compared to placebo. Both experimental and placebo groups showed statistically significant improvement in most variables during the experiment. CONCLUSION: The factor of time had a major effect in the non-specific improvement of the parameters assessed. The placebo effect played an important role in the treatment of patients with pain in the TMJ area.

Activities of Daily Living↗

Shared HLA antigens in couples with 5 or more, compared to 3 or 4 consecutive recurrent miscarriages.

OBJECTIVE: Couples with consecutive recurrent miscarriages (CRM) are not generally believed to share more HLA antigens with their spouses than expected by chance. This paper attempted to determine the situation in patients with five or more miscarriages. METHODS: The number of shared HLA class I and class II antigens, HLA phenotype, and the ability to mount an antibody response in a large cohort of 425 couples with CRM was assessed, according to whether the patient had three or four, or five or more miscarriages. RESULTS: There was no significant difference in the frequency of shared HLA antigens in women with five or more miscarriages when compared to three or more miscarriages or control patients. No specific HLA antigen or phenotype was associated with CRM in male or female partners of either group. The number of shared antigens did not influence ability to develop anti paternal antibodies (APA). Moreover, HLA antigen sharing had no influence on the subsequent pregnancy after paternal leucocyte immunization. CONCLUSION: Class I and Class II HLA antigens are not diagnostic for immunologically mediated abortion, do not predict the ability to mount an antibody response, or the outcome of a subsequent pregnancy.

Abortion, Habitual↗

The Doc toxin and Phd antidote proteins of the bacteriophage P1 plasmid addiction system form a heterotrimeric complex.

The toxin (Doc) and antidote (Phd) proteins of the plasmid addiction system of bacteriophage P1 were purified as a complex. Cocrystals of the complex contained a 2:1 molar ratio of Phd:Doc as assayed by dye binding following SDS-polyacrylamide gel electrophoresis and as determined by amino acid analysis. Gel filtration and analytical ultracentrifugation revealed that the two addiction proteins interact in solution to form a P2D trimer composed of one Doc and two Phd molecules. These results support a model in which Phd inhibits the toxic activity of Doc by direct binding. Circular dichroism experiments showed that changes in secondary structure accompany formation of the heterotrimeric complex, raising the possibility that Phd may act by an allosteric mechanism. Studies of Phd and Doc molecules labeled with fluorescent energy donor and acceptor groups gave an equilibrium dissociation constant of about 0.8 microM(2) and a very short, sub second half-life of complex dissociation. As a consequence, low concentrations of free Doc toxin are likely to be present both transiently and in the steady state in cells containing the Phd antidote, making mechanisms of single-hit Doc toxicity improbable.

Bacteriophage P1↗

Stability and DNA binding of the phd protein of the phage P1 plasmid addiction system.

The plasmid addiction module of bacteriophage P1 encodes two proteins, Doc, a toxin that is stable to proteolytic degradation, and Phd, the toxin's antidote that is proteolytically unstable. Phd has been shown to autoregulate its expression by specific DNA binding. Here, we investigate the secondary structure and thermal stability of Phd, the effect of operator DNA binding on the structure and stability of Phd, and the stoichiometry, affinity, and cooperativity of Phd binding to operator subsites and intact operator DNA. Phd folds as a monomer at low temperatures or in the presence of osmolytes but exists predominantly in an unfolded conformation at 37 degreesC. The native state of Phd is stabilized by operator binding. Two Phd monomers bind to each operator subsite, and four monomers bind to the intact operator. The subsite binding reaction shows a second-order dependence on protein concentration and monomer-bound DNA species are unpopulated, suggesting that two Phd molecules bind cooperatively to each operator subsite. In intact operator binding experiments, both dimer-bound and tetramer-bound DNA species are populated, and binding occurs at protein concentrations similar to those required for subsite binding, suggesting that there is no significant dimer-dimer cooperativity.

Bacteriophage P1↗

The prognostic value of anti-paternal antibodies and leukocyte immunizations on the proportion of live births in couples with consecutive recurrent miscarriages.

Anti-paternal antibodies directed towards paternal leukocytes have been used to predict the prognosis for the subsequent pregnancy in women with consecutive recurrent miscarriages (CRM) and also to determine if the patient has become immune after paternal leukocyte immunization. The predictive value is controversial, as these antibodies are not essential for pregnancy to develop, and only occur in a minority of parous women. This study tried to determine the predictive value of these antibodies when assessed separately for women with five or more abortions and compared to women with three or four abortions. The patients were assessed separately so that the higher live birth rate in the latter group would not obscure meaningful results in the former group with a poor prognosis. Antibody production, whether spontaneous, or induced by immunization, raised the live birth rate in primary and tertiary aborters with three, four, five or more abortions. Anti-paternal antibodies increased the proportion of live births from 18.5 to 53. 7% (P </= 0.01) and from 44.4 to 67.5% (P </= 0.001) in primary aborters with >/= 5 CRM and 3-4 CRM respectively. Both immunization with paternal leukocytes per se and the ability to express anti-paternal antibodies were associated with an increased proportion of live births in the next pregnancy. Multivariate analysis showed that that the odds ratio for a live birth was approximately four times greater in women who were immunized and produced anti-paternal antibodies than in control patients. The lack of anti-paternal antibodies at initial testing could serve as a marker for the benefit of immunization with paternal leukocytes; the subsequent presence as a prognostic marker for the subsequent pregnancy.

Abortion, Habitual↗

Human leukocyte antigen typing, response to neuroleptics, and clozapine-induced agranulocytosis in jewish Israeli schizophrenic patients.

The atypical antipsychotic agent clozapine is known to be effective in schizophrenic patients refractory to other medications; however, it induces agranulocytosis in approximately 1-2%. In Jews, this complication is associated with the haplotype HLA B38,DR4,DQ3. The aim of the present study was to determine which human leukocyte antigen (HLA) antigens are involved in clozapine-induced agranulocytosis. We performed HLA typing in 88 Jewish Israeli schizophrenic patients and in 127 ethnically matched healthy individuals. Thirty-eight patients responsive to standard antipsychotic medications were treated with haloperidol, and 50 refractory patients received clozapine. A trend was noted for elevated rates of HLA B38 among control individuals and clozapine-treated patients of Ashkenazi origin compared to individuals of non-Ashkenazi origin, but the findings failed to reach statistical significance. No association was found between HLA class I antigens and the response to haloperidol or clozapine. Neutropenia developed in two clozapine-treated patients and agranulocytosis in one. Two of these three patients were of Ashkenazi origin, and both demonstrated the HLA B38 phenotype. Although the findings did not reach a statistical significance because of the small number of patients, they may support an association between clozapine-induced neutropenia/agranulocytosis and Ashkenazi origin and the HLA B38 phenotype. The rate of agranulocytosis in our sample (2%) is similar to the usual cumulative risk of agranulocytosis but in contrast to its high frequency among Jewish American patients. One possible explanation for this difference is the high rate of Ashkenazi patients in the American sample and the preponderance of non-Ashkenazi patients in our population.

Adolescent↗

The structure and organization within the membrane of the helices composing the pore-forming domain of Bacillus thuringiensis delta-endotoxin are consistent with an "umbrella-like" structure of the pore.

The aim of this study was to elucidate the mechanism of membrane insertion and the structural organization of pores formed by Bacillus thuringiensis delta-endotoxin. We determined the relative affinities for membranes of peptides corresponding to the seven helices that compose the toxin pore-forming domain, their modes of membrane interaction, their structures within membranes, and their orientations relative to the membrane normal. In addition, we used resonance energy transfer measurements of all possible combinatorial pairs of membrane-bound helices to map the network of interactions between helices in their membrane-bound state. The interaction of the helices with the bilayer membrane was also probed by a Monte Carlo simulation protocol to determine lowest-energy orientations. Our results are consistent with a situation in which helices alpha4 and alpha5 insert into the membrane as a helical hairpin in an antiparallel manner, while the other helices lie on the membrane surface like the ribs of an umbrella (the "umbrella model"). Our results also support the suggestion that alpha7 may serve as a binding sensor to initiate the structural rearrangement of the pore-forming domain.

Amino Acid Sequence↗

Serum lipase levels pre and post Lundh meal: evaluation of exocrine pancreatic status in cystic fibrosis.

Determination of pancreatic function is essential in cystic fibrosis. The most-reliable method is by measuring pancreatic enzymes in the duodenum following intravenous or oral stimulation. However, this is invasive, time consuming, and expensive. Indirect tests are non-invasive but lack accuracy. This study examines a simple test which combines pancreatic stimulation by Lundh meal and sequential serum lipase measurements. The test was performed on three groups: group A, 36 cystic fibrosis patients carrying two mutations associated with severe disease and pancreatic insufficiency (delta F508, W1282X, G542X, N1303K, S549R); group B, 8 compound heterozygote cystic fibrosis patients carrying one mutation causing mild disease with pancreatic sufficiency (3849 + 10 kb C-->T); group C, 17 healthy individuals. Basal lipase levels were 2-16.5, 16.4-73, and 8.5-27.8 U/l in groups A, B, and C, respectively, with some overlapping between groups. There were three patterns of lipase activity (1) consistently low levels (group A) suggested a severely affected insufficient pancreas; (2) normal basal levels followed by a linear rise peaking 30 min after the meal (found in 16 of 17 healthy individuals and 3 patients of group B) reflecting an unaffected sufficient pancreas; (3) elevated lipase levels not influenced by the meal (5 patients of group B). This reflects an ongoing destructive process in the pancreas which will eventually result in conversion from pancreatic sufficiency to pancreatic insufficiency. Hence serum lipase activity prior to and 30 min after Lundh meal is a good indicator of pancreatic status allowing categorization of cystic fibrosis patients as pancreatic insufficient, pancreatic sufficient, or pancreatic sufficient with late conversion to insufficiency.

Adolescent↗

HLA-B38 and clozapine-induced agranulocytosis in Israeli Jewish schizophrenic patients.

To further substantiate reports of an association between the major histocompatibility complex subtypes and clozapine-induced agranulocytosis, HLA typing was performed in 61 Jewish Israeli schizophrenic patients, in 11 of whom agranulocytosis developed following clozapine treatment and in 50 (controls) of whom it did not. Of the 11 agranulocytosis patients, seven (63%) were of Ashkenazi origin and four (37%) of Sephardi origin. There was no difference in ethnic origin between the arganulocytosis and non-agranulocytosis groups (chi 2 = 2.4, d.f. = 1, P = 0.11), although the agranulocytosis patients had a higher frequency of the HLA B38 antigen (8/11 or 72% vs. 6/50 or 12%; chi 2 = 18.7, d.f. = 1, P < 0.001). These results suggest that major histocompatibility complex gene products could be involved in clozapine-mediated haematological complications.

Adult↗

The effect of three different recording materials on the reproducibility of condylar guidance registrations in three semi-adjustable articulators.

Sagittal condylar guide settings of three semi-adjustable articulators: WhipMix, Hanau 158 and Denar Mark II were compared using registrations of base plate wax, copper wax and self-curing acrylic resin in two subjects. Four-way ANOVA showed differences between instruments (P < 0.0001), materials (P < 00001), registrations (P < 0.0001), and no difference between operators. Mean differences between materials were 3 degrees and 6 degrees within the range of registration and articulator variability. Denar Mark II gave the highest values, Hanau 158 the lowest with pantronic values generally lower than articulator settings. Neither acrylic nor copper wax were superior to base plate wax. This and previous studies show low reproducibility and variability between instruments, occlusal records and registration material.

Acrylic Resins↗

Bacillus thuringiensis cytolytic toxin associates specifically with its synthetic helices A and C in the membrane bound state. Implications for the assembly of oligomeric transmembrane pores.

The CytA toxin exerts its activity by the formation of pores within target cell membranes. However, the exact mechanism of pore formation and the structural elements that are involved in the toxic activity are yet to be determined. Recently, the structure of the highly similar CytB toxin was solved (Li et al., 1996), and a beta-barrel was suggested as a possible structure of the pores. Due to the similarity between the toxins, the existence and positioning of alpha-helices and beta-sheets in CytA were predicted from the alignment of the sequences. Here peptides corresponding to beta5, beta6, and beta7 strands, to a conserved nonhelical region of the CytA toxin (P149-170), to helices B and D, and to an analogue of helix A were synthesized, fluorescently labeled, and characterized. We found that, unlike helices A and C (Gazit and Shai, 1993), neither the beta-strand peptides nor helix B could interact with lipid membranes, whereas P149-170 and helix D bind the membrane weakly. Membrane permeation experiments suggested that CytA toxin exerts its activity by aggregation of several monomers. To learn about the structural elements that may mediate CytA oligomerization, the ability of the synthetic peptides to interact with membrane-bound CytA was studied. Helices A and C, but not the beta-strands, helix D, or a control peptide, caused a large increase in the fluorescence of membrane-bound fluorescein-labeled CytA, whereas helix B had only a slight effect. Moreover, the addition of rearranged helix A, a peptide with the same composition as helix A, but with only two pairs of amino acids rearranged, did not affect the fluorescence. The addition of unlabeled CytA also caused an increase in the fluorescence intensity, further demonstrating the interaction between CytA monomers within the membrane. Taken together, our results provide further support for the suggestion that the CytA toxin self-assembles within membrane and that helices A and C are major structural elements involved in the membrane interaction and intermolecular assembly of the toxin.

Amino Acid Sequence↗