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Biomedical subjects

T Cohen

Publications and source records attributed to T Cohen.

At least 19 recordsLinked to original sources
PubMed1992

Application of the Health Belief Model in a study on parents' intentions to utilize prenatal diagnosis of cleft lip and/or palate.

Parents of children with cleft lip and/or palate (42 women and 35 men) participated in a study on intentions to use prenatal diagnosis of cleft by ultrasound in subsequent pregnancies. Based on the Health Belief Model (HBM) [Rosenstock, 1974], parents' cognitions on 4 factors were measured by questionnaires: "susceptibility" and "severity perceptions," "benefits" and "barriers" evaluations. Most parents perceived the defect as severe. Over-estimation of recurrence risks was predominant even among parents who had received genetic counseling. Results showed that most parents intend to utilize prenatal diagnosis but do not intend to abort an affected fetus. Subjects' reported reasons represented 3 thematic categories: cognitive (the need to know), emotional, and behavioral. Parents' intentions to diagnose and to terminate were related to the factors predicted by the HBM model. Regression analyses indicated that 38% of the variance in intentions to diagnose and 56% of the variance in intentions to terminate could be explained by the studied variables. The best predictor of both intentions was the perceived benefits of the diagnosis. Implications of these findings for genetic counseling are discussed.

Abortion, Therapeutic↗
PubMed1992

High frequency of congenital adrenal hyperplasia (classic 11 beta-hydroxylase deficiency) among Jews from Morocco.

Steroid 11 beta-hydroxylase deficiency is relatively frequent in Israel among North African Jews. Over a 39-year period, 38 affected individuals from 25 families were diagnosed. Nineteen families came from Morocco, and in another 2, one parent came from Morocco (80% of all parents). Demographic studies showed that most of their grandparents were born in the region of the Atlas Mountains. In Israel, the overall incidence of the disorder is estimated between 1 in 30,000 to 1 in 40,000 births, but in offspring of Moroccan Jews the ratio is 1 in 5,000 to 1 in 7,000, with an allele frequency of 1 in 70 to 1 in 84 and a carrier frequency of 1 in 35 to 1 in 42. The clinical expression is characterized by a wide range of variability in the signs of androgen and mineralocorticoid excess. Virilization in the female ranged from enlarged clitoris in the mildest forms, to markedly hypertrophied clitoris with penile urethra and fused labial-scrotal folds in the most severe forms. Hypertension causing vascular accidents and death was observed in both severe and mildly virilized patients, whereas masculinized females were sometimes normotensive. Based on historical evidence, the origin of the ancestors, and the onomastic analysis of the families surnames, we propose that the mutation of 11 beta-hydroxylase deficiency in Jews from Morocco may have originated in either the ancient Jewish settlers or the native Berber tribes who lived in the region of the Atlas Mountains in the southern region of Morocco before the destruction of the Second Temple by the Romans, in the year 70 C.E.

Adrenal Hyperplasia, Congenital↗
PubMed1992

Digestion of Bacillus thuringiensis var. israelensis spores by larvae of Aedes aegypti.

The larvicidal activity of Bacillus thuringiensis var. israelensis against mosquitoes and the blackfly is included in parasporal crystalline bodies which are produced during sporulation. Following ingestion, the crystals are solubilized in the larval midgut and induce death within a short time; the spores germinate in the dead larvae and complete a growth cycle. The fate of the spores in surviving live larvae was elucidated by using a nonlarvicidal B. thuringiensis var. israelensis mutant. When introduced as the only food source, spores of this mutant support development to the adult stage of newly hatched Aedes aegypti larvae at a rate directly related to spore concentration. The conclusion that spores of B. thuringiensis var. israelensis are digested in the larval gut was substantiated by following the incorporation of [35S]methionine-labeled spores into larval tissues.

Aedes↗
PubMed1992

High levels of biologically active vascular endothelial growth factor (VEGF) are produced by the baculovirus expression system.

Vascular endothelial growth factor (VEGF) is a recently discovered mitogen for endothelial cells in vitro, and a potent angiogenesis promoting factor in vivo. VEGF is secreted from producing cells as a homodimer, binds to specific receptors on the cell surface of endothelial cells, and is produced in four forms as a result of alternative splicing. We have expressed the cDNA encoding the 165 amino-acid long isoform of VEGF in insect cells using the baculovirus based expression vector. We show that infected insect cells secrete large amounts of VEGF. Antibodies directed against a synthetic peptide prepared from human VEGF identify the secreted factor. The baculovirus derived VEGF expressed in insect cells (inVEGF) binds directly to the VEGF receptors inVEGF competes with pure mammalian cells derived [125I]-VEGF for binding to the VEGF receptors that are present on the cell surface of endothelial cells. Furthermore, inVEGF is biologically active and induces the proliferation of human umbilical vein derived endothelial cells.

Animals↗
PubMed1992

Screening for five mutations detects 97% of cystic fibrosis (CF) chromosomes and predicts a carrier frequency of 1:29 in the Jewish Ashkenazi population.

To determine the distribution and frequency of cystic fibrosis (CF) mutations in the Israeli population, we have screened 96 patients for 11 relatively common mutations. Five mutations--delta F508, G542X, W1282X, N1303K, and 3849 + 10kb C-->T--were found to account for 97% of the CF alleles in the Ashkenazi Jews. In contrast, of the 11 mutations tested, only delta F508 was detected in Jewish patients of Sephardic or Oriental origin, accounting for 43% of the CF alleles. Four mutations--delta F508, G542X, W1282X, and N1303K--accounted for 55% of the CF alleles in Arab patients. In a pilot screening study, a random sample of 424 Ashkenazi individuals was analyzed for three mutations--delta F508, W1282X, and G542X. Thirteen individuals were detected as heterozygotes (six for delta F508 and seven for W1282X), predicting a heterozygote frequency of 1:29. This is similar to the frequency of carriers in the Caucasian population of northern European ancestry. On the basis of these data, the Ashkenazi population is considered to be a candidate for CF heterozygote screening.

Base Sequence↗
PubMed1991

Estimated number of loci for autosomal recessive severe nerve deafness within the Israeli Jewish population, with implications for genetic counseling.

Deafness occurs in about 1 per thousand live births, and at least 50% of congenital deafness is hereditary. The aim of this study was to examine the number of loci for recessively inherited severe nerve deafness of early onset within the Israeli population and to compare the results to those obtained in other populations. The Jewish population in Israel originates from many countries and may be divided into Sephardi, Eastern and Ashkenazi Jews, and the matings will be intraethnic or interethnic. Data were obtained on 133 deaf couples who lived in the Tel Aviv area, through the files of the Helen Keller Center. Causes of deafness in the spouses were studied and data on their children were obtained. Among 111 couples who had recessive or possibly recessive deafness and had at least 1 child, there were 12 with only deaf children and 5 with both deaf and hearing children. The number of loci for recessive deafness in the whole group was estimated at 8-9. Intraethnic and interethnic matings gave an estimate of 6.7 and 22.0 loci, respectively, which indicates that within populations fewer loci exist with recessive mutations for deafness than between populations. It could be shown that the sharing of loci between spouses decreased with increasing geographical distance of their origin. The results provide data for genetic counseling in Israel for deaf couples who have no children or have one hearing or one deaf child.

Chromosome Mapping↗
PubMed1991

Structural organization of the pigment cell-specific gene located at the brown locus in mouse. Its promoter activity and alternatively spliced transcript.

The pigment cell-specific gene, located at the brown (b) locus in mouse, has been cloned and characterized. Its gene product is required for the formation of black melanin rather than brown, although its exact function remains to be elucidated. We thus tentatively named it b-locus protein in this report. The b-locus protein gene is about 18 kilobase pairs long and organized into 8 exons and 7 introns. Functional analysis of its promoter region suggests that the nucleotide residues -38/154 is sufficient to direct the pigment cell-specific transcription in melanoma whole cell extracts. On the other hand, we were unable to detect its transcripts in HeLa whole cell extracts. Sequence comparison with the promoter region of the tyrosinase gene, another pigment cell-specific gene, reveals that two elements of the b-locus protein gene (-33/-24 and 18/28) are also conserved in the tyrosinase gene at equivalent positions, suggesting that these two elements may be involved in their pigment cell-specific transcription. Furthermore, we have cloned a cDNA, pMT3, coding for an isoform of b-locus protein from a cDNA library of mouse B16 melanoma cells. Sequence analysis of pMT3 reveals a deletion of 103 base pairs, which corresponds to the 5'-end of the exon 8 of the b-locus protein gene, indicating that pMT3 represents a mRNA species generated by alternative splicing. Since this deletion changes the reading frame and eliminates the transmembrane domain of b-locus protein, the pMT3-type mRNA may code for a soluble isoform. Such an isoform, consisting of 553 amino acids, differs only in its carboxyl terminus and is larger than b-locus protein by 16 amino acids. Using transient expression assays, we confirmed that such an isoform is able to react with anti-b-locus protein monoclonal antibody, TMH-1, suggesting that a b-locus protein isoform may have some function in pigmentation.

Amino Acid Sequence↗
PubMed1991

[Prenatal diagnosis of thalassemia: identification of mutations in conjunction with gene amplification in vitro].

Prenatal diagnosis of thalassemia and sickle cell anemia using DNA analysis has been performed in Israel since 1982. Until recently the tests involved analysis of polymorphic markers linked to the beta-globulin gene (RFLP). This method is not suitable for many of the families at risk. The recently developed technique of gene amplification in vitro (PCR) facilitates direct identification of the genetic lesions (mutations) using minimal amounts of DNA. The diagnosis is rapid, reliable and unambiguous and can be made early in pregnancy. Our experience in prenatal diagnosis during the past year is reported. Of 14 diagnoses, 13 were made by direct identification of mutations following PCR.

Female↗
PubMed1991

Evolution of a genetic disease in an ethnic isolate: beta-thalassemia in the Jews of Kurdistan.

beta-Thalassemia is a hereditary disease caused by any of 90 different point mutations in the beta-globin gene. Specific populations generally carry a small number of mutations, the most common of which are those that are widely distributed regionally. The present study constitutes an extensive molecular characterization of this disease in a small, highly inbred ethnic group with a high incidence of beta-thalassemia--the Jews of Kurdistan. An unusual mutational diversity was observed. In 42 sibships 13 different mutations were identified, of which 3 are newly discovered: a C----A transversion at -88 to the cap site, a frameshift in codon 36/37, and an A----G transition in the polyadenylylation signal. Four of the mutations are unique to Kurdish Jews and have not been discovered in any other population. A fifth was found outside Kurdish Jews only in an Iranian from Khuzistan, a region bordering Kurdistan. Two-thirds of the mutant chromosomes carry the mutations unique to Kurdish Jews. We traced the origin of the mutations to specific geographic regions within Kurdistan. This information, supported by haplotype analysis, suggests that thalassemia in central Kurdistan (northern Iraq) has evolved primarily from multiple mutational events. In Turkish Kurdistan, the primary mechanism is genetic admixture with the local population. In Iranian Kurdistan, a founder effect appears to be partly responsible. We conclude that several evolutionary mechanisms contributed to the evolution of beta-thalassemia in this small ethnic isolate.

Base Sequence↗
PubMed1991

Recurrent tetraamelia and pulmonary hypoplasia with multiple malformations in sibs.

A term amelic female infant was born to an apparently nonconsanguineous Arab Moslem couple. This was followed by the birth of 4 normal children. Afterwards, in 2 subsequent pregnancies, 2 amelic fetuses were diagnosed by transabdominal ultrasonography in the 18th and 12th week of gestation. Pregnancies were terminated and on autopsy both amelic fetuses had severe lung hypoplasia and aplasia of the peripheral pulmonary vessels. The first fetus also had apparently low-set ears and micrognathia, whereas the last had hydrocephaly and left cleft lip beside the lung hypoplasia and aberrant pulmonary artery. This appears to be a new autosomal recessive malformation syndrome.

Abnormalities, Multiple↗
PubMed1991

The ATC (ataxia-telangiectasia complementation group C) locus localizes to 11q22-q23.

The multisystem autosomal recessive disease ataxia-telangiectasia (A-T) is determined by several genes, as evidenced by the existence of four complementation groups in this disorder. Using linkage analysis, the ATA (A-T complementation group A) gene was previously localized to chromosome 11, region q22-q23. Analysis of the segregation of RFLP markers from this region in a Jewish-Moroccan family assigned to group C indicates that the ATC (A-T complementation group C) gene localizes to chromosome 11q22-q23 as well.

Ataxia Telangiectasia↗
PubMed1991

Organization and dynamics of pyrene and pyrene lipids in intact lipid bilayers. Photo-induced charge transfer processes.

The dynamics of fluorescence quenching and the organization of a series of pyrene derivatives anchored in various depths in bilayers of phosphatidylcholine small unilamellar vesicles was studied and compared with their behavior in homogeneous solvent systems. The studies include characterization of the environmental polarity of the pyrene fluorophore based on its vibronic peaks, as well as the interaction with three collisional quenchers: the two membrane-soluble quenchers, diethylaniline and bromobenzene, and the water soluble quencher potassium iodide. The system of diethylaniline-pyrene derivatives in the membrane of phosphatidylcholine vesicles was characterized in detail. The diethylaniline partition coefficient between the lipid bilayers and the buffer is approximately 5,800. Up to a diethylaniline/phospholipid mole ratio of 1:3 the perturbation to membrane structure is minimal so that all photophysical studies were performed below this mole ratio. The quenching reaction, in all cases, was shown to take place in the lipid bilayer interior and the relative quenching efficiencies of the various probe molecules was used to provide information on the distribution of both fluorescent probes and quencher molecules in the lipid bilayer. The quenching efficiency by diethylaniline in the lipid bilayer was found to be essentially independent on the length of the methylene chain of the pyrene moiety. These findings suggest that the quenching process, being a diffusion controlled reaction, is determined by the mobility of the diethylaniline quencher (with an effective diffusion coefficient D approximately 10(-7) cm2 s-1) which appears to be homogeneously distributed throughout the lipid bilayer. The pulsed laser photolysis products of the charge-transfer quenching reaction were examined. No exciplex (excited-complex) formation was observed and the yield of the separated radical ions was shown to be tenfold smaller than in homogenous polar solutions. The decay of the radical ions is considerably faster than the corresponding process in homogenous solutions. Relatively high intersystem crossing yields are observed. The results are explained on the basis of the intrinsic properties of a lipid bilayer, primarily, its rigid spatial organization. It is suggested that such properties favor ion-pair formation over exciplex generation. They also enhance primary geminate recombination of initially formed (solvent-shared) ion pairs. Triplet states are generated via secondary geminate recombination of ion pairs in the membrane interior. The results bear on the general mechanism of electron transfer processes in biomembranes.

Calorimetry, Differential Scanning↗
PubMed1990

Syndrome of brittle cornea, blue sclera, and joint hyperextensibility.

In 3 families 4 patients were affected with the syndrome of brittle cornea, blue sclera, and hyperextensible joints (brittle cornea syndrome). From the review of 17 affected patients described previously and our cases, it appears that this rare autosomal recessive syndrome has variable expressivity. Two different groups of patients may be distinguished: one includes 5 families, all of Tunisian Jewish origin. All patients in this group also have red hair. In the second group, 9 families are from various ethnic origins; affected patients in this group have a normal distribution of hair color. A possible explanation for the existence of these 2 different group of patients is that the locus of the gene responsible for the syndrome is closely linked to the locus for a gene responsible for hair color with linkage disequilibrium in Tunisian Jews (Sepharadim).

Corneal Diseases↗
PubMed1990

A study of seroprevalence of HIV-1 and HIV-2 in six provinces of People's Republic of Angola: clues to the spread of HIV infection.

A seroepidemiological study was carried out to determine the distribution of the human immunodeficiency viruses type 1 (HIV-1) and type 2 (HIV-2) in the People's Republic of Angola, where HIV-2 existence was previously unknown and HIV-1 seropositivity was only reported to be present in Luanda and Cabinda. A total of 1,695 serum samples were obtained from healthy persons (control group) and from a group of patients in the provinces of Zaire (13), Lunda-Norte (L.N.) (749), Luanda (556), Huambo (154), Kuando-Kubango (K.-K.) (49), and Namibe (119). All samples were tested for HIV-1 and HIV-2 antibodies by enzyme-linked immunosorbent assay and an indirect immunofluorescence assay using MOLT-T4 cells. Positive samples were confirmed by the Western-blot technique. Sera giving cross reactivity at the level of HIV-1 and HIV-2 large glycoproteins were further tested by radioimmunoprecipitation assay and by reactivity against a peptide corresponding to the dominant epitope of the transmembrane protein. The overall seroprevalance was 14.2%, with significantly higher values in the patient group [19.4% (HIV-1 = 8.8%; HIV-2 = 8.4%; HIV-1 + HIV-2 = 2.2%)] than the control group [9.3% (HIV-1 = 3.3%; HIV-2 = 5.3%; HIV-1 + HIV-2 = 0.7%)]. HIV-2 as well as HIV-1 infection is actually present in Angola in all studied provinces. Higher seroprevalence was seen in the provinces of Zaire, Lunda Norte, and Huambo. People displacements, mainly as a consequence of the war, certainly play an important role in spreading HIV infection from the northern frontier areas of the country to the central and southern regions.

Adolescent↗
PubMed1979

Relief of polarity in E. coli depleted of 30S ribosomal subunits.

Escherichia coli was depleted of ribosomes by a thermal shock at 47 degrees C which quantitatively destroyed the 30S ribosomal subunits. During recovery in minimal medium at 30 degrees C RNA is synthesized while protein synthesis resumes only after about 90 min. It is shown that lac mRNA is synthesized in the complete absence of ribosomal activity and hence RNA synthesis is not coupled to protein synthesis. Lac mRNA from a series of lac nonsense mutants was examined in both heated and untreated cells. It was found that the polar effect of nonsense mutation is relieved in the absence of ribosomes and that this relief is due to the synthesis of larger mRNA molecules. Since Rho remained active in thermally treated cells, premature termination at secondary signals within the lac operon must also depend on the presence of active ribosomes.

Escherichia coli↗
PubMed1979

Amelogenesis imperfecta among Israeli Jews and the description of a new type of local hypoplastic autosomal recessive amelogenesis imperfecta.

Amelogenesis imperfecta (AI) was detected in nine of 70,359 school children surveyed, a prevalence approximating 1:8,000. Of these cases, eight were the hypoplastic type and one the snow-capped hypomaturation type. Family studies demonstrated that hypoplastic AI was an autosomal dominant trait in two children and an autosomal recessive in six. Of three additional families referred to our clinic, two had autosomal recessive hypoplastic AI and one the hypocalcified type, inherited as an autosomal dominant trait. In four families, a new type of local hypoplastic autosomal recessive AI was observed, characterized by horizontal pitting and grooving more pronounced in the middle third of the crowns of most teeth in both dentitions.

Adolescent↗