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O Cohen

Publications and source records attributed to O Cohen.

At least 91 records · Page 5Linked to original sources
PubMed1995

The human thyrotropin-releasing hormone gene is regulated by thyroid hormone through two distinct classes of negative thyroid hormone response elements.

TRH is the principal positive regulator of TSH synthesis and secretion in man. T3 is able to control TRH synthesis through feedback inhibition at the transcriptional level, presumably by binding to its receptor which interacts with one or more negative thyroid hormone response elements (TREs) present within the human TRH promoter. In the present study we have identified the specific negative TREs within the TRH promoter and characterized their ability to interact with thyroid hormone receptors (TRs), and the retinoid X receptor (RXR). Our analysis demonstrates that ligand-independent and dependent regulation of the human TRH promoter is restricted to the TR beta 1 isoform. Deletional analysis of the TRH promoter identified two discrete regions that are responsible for mediating ligand-dependent negative regulation of the TRH promoter. Mutagenesis of potential TR binding half-sites within these regions identified three separate half-sites (site 4 from -55 to -60 base pairs (bp); site 5, +14 to +19 bp; and site 6, +37 to +42 bp) which act in combination to allow for negative regulation. Mutation and/or deletion of each of these sites leads to a loss of negative regulation of the TRH promoter by T3. Gel-mobility shift assays of site 4 and its surrounding nucleotides revealed that this region of the promoter is capable of binding TR monomers, homodimers, and TR-RXR heterodimers. Mutagenesis of site 4 leads to a loss of all binding to this region. The region encompassing sites 5 and 6 binds only TR monomer, and the addition of RXR to the binding reaction leads to a loss of specific monomeric binding. To assess the functional importance of site 4 and its surrounding nucleotides we cotransfected RXR isoforms along with TR beta with TRH promoter constructs containing either site 4 or its mutant. In the presence of wild type site 4 sequence, cotransfected RXR enhanced negative regulation of the TRH promoter. Mutation and or deletion of site 4 leads to a loss of this enhancement. These data demonstrate that two structurally different negative TREs cooperate to allow for negative regulation of the human TRH promoter and that negative regulation is TR isoform-specific and modulated by the RXR-signaling pathway through a novel negative TRE.

Animals↗
PubMed1995

[Human familial autosomal reciprocal translocations].

Reciprocal translocations are one of the most frequently observed structural chromosome abnormalities. They are defined by a segment exchange between two non-homologous chromosomes. A great number of different translocations exist since any chromosome can be involved in the translocation and the position of the breakpoint can vary. Though generally silent these translocations can be expressed in the form of reproduction failure or, more seriously, as offspring showing mental retardation/malformation syndromes. Since the risk of malformation varies from one translocation to the next, genetic counselling and prenatal diagnosis strategies should be adopted to suit the particular malformation risks of each individual translocation. This is currently not the case. Different prediction methods (for the most probable mode of unbalance at birth, the risk of unbalance at term) are presented. A computer system, called Reci-Conseil brings these different functionalities together to create a new aid for genetic counselling. The data base on which it is founded (approx 2000 families) offers interesting perspectives for genomic mapping of partial trisomies and monosomies.

Chromosome Mapping↗
PubMed1994

A novel C-terminal domain in the thyroid hormone receptor selectively mediates thyroid hormone inhibition.

Resistance to thyroid hormone (RTH) action is due to mutations in the beta-isoform of the thyroid hormone receptor (TR-beta). RTH patients display inappropriate central secretion of thyrotropin-releasing hormone (TRH) from the hypothalamus and thyrotropin (TSH) from the anterior pituitary in association with abnormal peripheral tissue responses to thyroid hormone. Whether TR-beta mutations cause a selective form of RTH, which only leads to abnormal pituitary TSH secretion (PRTH), is unclear. In a patient with PRTH, a novel mutation of a conserved arginine residue adjacent to the ninth heptad of TR-beta selectively disrupts TR homodimer formation. The mutant TR displays normal or enhanced function on stimulatory thyroid hormone response elements found in peripheral tissues, but has defective function on inhibitory thyroid hormone response elements found in the TRH and TSH subunit genes and explains the PRTH phenotype. This is the first report of a mutation in a member of the nuclear receptor superfamily that selectively abolishes hormone-dependent inhibition and localizes a novel C-terminal domain necessary for this property.

Amino Acid Sequence↗
PubMed1994

Progressive de novo DNA methylation at the bcr-abl locus in the course of chronic myelogenous leukemia.

De novo methylation of CpG islands is a rare event in mammalian cells. It has been observed in the course of developmental processes, such as X chromosome inactivation and genomic imprinting. The methylation of DNA, an important factor in the epigenetic control of gene expression, may also be involved in tumorigenesis. After the t(9;22) chromosomal translocation and generation of the Philadelphia chromosome, the initiating event in chronic myelogenous leukemia (CML), most of the abl coding sequence is fused to the 5' region of the bcr gene. Expression of the hybrid bcr-abl gene is, therefore, regulated by the bcr promoter. In most cases of CML, one of the two abl promoters (Pa) is nested within the bcr-abl transcriptional unit and should be able to transcribe the type Ia 6-kb normal abl mRNA from the Philadelphia chromosome. However, we have found that the 6-kb transcript is present only in CML cell lines containing a normal abl allele and that the apparent inactivation of the nested Pa promoter is associated with allele-specific methylation. Furthermore, we have noticed that the Pa promoter is contained within a CpG island and undergoes progressive de novo methylation in the course of the disease. This is attested to by the fact that DNA samples from CML patients that are methylation-free at the time of diagnosis invariably become methylated in advanced CML. Since tumor progression in CML cannot always be inferred from the clinical presentation, assessment of de novo CpG methylation may prove to be of critical value in management of the disease. It could herald blastic transformation at a stage when bone marrow transplantation, the only potentially curative therapeutic procedure in CML, is still effective.

Animals↗
PubMed1994

[Convulsive disorder in celiac disease].

Several recent reports have described convulsions in patients with celiac disease, and in some, folic acid deficiency and brain calcifications. A 40-year-old woman with celiac disease, hypocalcemia and generalized tonic-clonic seizures is reported. Hypocalcemia was corrected and convulsions disappeared, but the EEG showed persistent occipital epileptiform activity. Patients with celiac disease and hypocalcemia due to malabsorption are particularly at increased risk for convulsions. Therefore, even a mild degree of hypocalcemia in these patients should be corrected as soon as possible.

Adult↗
PubMed1994

Integrating a shared patient-psychotherapist crisis into one's professional identity: Israeli psychotherapists look back at the Gulf War.

One year after the Gulf war, psychotherapists' recollections of their professional functioning and personal reactions during the war were investigated in an attempt to understand better how these events had been integrated into their professional identity. The war had been an extremely stressful time that had brought a real threat of mass destruction. Memories were investigated along three independent variables: time, proximity to directly affected areas, and professional experience. Results indicate that psychotherapists remember themselves as having been more available to their work and having been less affected than what they reported during the war. The difficulty for psychotherapists in integrating their limitations into their professional identity is discussed.

Adaptation, Psychological↗
PubMed1994

Viability thresholds for partial trisomies and monosomies. A study of 1,159 viable unbalanced reciprocal translocations.

From a data base of 1,590 independent families with autosomal reciprocal translocations, 1,159 viable unbalances were studied and the lengths of their trisomy/monosomy segments measured according to the method proposed by Daniel. About 5% of cases were found not to comply with Daniel viability criteria. The thresholds of viability vary with the mode of unbalance and with the sex of the carrier. Thus, new viability criteria are proposed as a guide for genetic counseling and prenatal diagnosis.

Chromosome Aberrations↗
PubMed1994

Prevalence of mutations in the insulin receptor gene in subjects with features of the type A syndrome of insulin resistance.

Mutations of the insulin receptor gene are a cause of the type A syndrome of extreme insulin resistance. This study assessed the prevalence of such mutations in women with clinical features of the type A syndrome including ovarian hyperandrogenism, moderate-to-severe degrees of insulin resistance, and acanthosis nigricans. We studied 22 unrelated women with insulin resistance (fasting insulin > 300 pM [50 microU/ml] and/or peak during an oral glucose tolerance test (OGTT) > 1,800 pM [300 microU/ml]), acanthosis nigricans, and the polycystic ovary syndrome (hyperandrogenemia, oligoamenorrhea, and hirsutism). Two insulin-resistant probands with congenital generalized lipodystrophy and one male proband with severe insulin resistance also were included in the study. Southern blotting experiments were performed to exclude gross gene deletions, insertions, or rearrangements. Exons 2-22 of the insulin receptor gene were polymerase chain reaction (PCR) amplified from genomic DNA and screened for nucleotide variation using single-strand conformation polymorphism (SSCP). No nucleotide variation between study subjects was detected in exons 4-6, 10-12, 15, 16, 18, 19, or 21. Sequencing of amplified DNA revealed that SSCP variants in exons 2, 3, 8, 9, and 17 corresponded to known silent polymorphisms within the coding region. Variants in exons 2, 9, 13, and 14 were caused by novel silent polymorphisms; variants in exons 7 and 22 were caused by nucleotide substitutions in flanking introns. One proband was found to have a heterozygous point mutation in exon 20 (CGG-->CAG, Arg1174-->Gln) that involves the intracellular receptor beta-subunit.(ABSTRACT TRUNCATED AT 250 WORDS)

Acanthosis Nigricans↗
PubMed1994

Serum prolactin-binding protein (PRL-BP) of human and rat are identified as IgG.

Heterogeneity of circulating prolactin in various species including rat and man is well known. We have recently shown that PRL was able to bind to a protein of high molecular weight in plasma obtained from estradiol treated ovariectomized females rats. This study was undertaken to look for a possible PRL-binding in woman serum and to identify the PRL-BP in both rat and human sera. Pooled sera from normal women taking oral contraception and from women on the 3rd trimester of pregnancy were purified on affinity chromatography column, prepared with sepharose 4B-CNBr coupled to oPRL (ovine PRL). Elution resulted in a protein of 160 kD mol wt when subjected to SDS PAGE in non reducing conditions. Under reducing conditions 2 forms of 50 and 27 kD were found. The 160 kD and the 50 kD forms were able to bind to hPRL. The 3 forms (160, 50 and 27 kD) were recognized by monoclonal antibodies against PRL receptors. Both the 50 and 27 kD forms obtained from rat and human sera were sequenced and revealed to be the heavy and light chain of IgG1. This result was confirmed by specific immunoprecipitation of the PRL-BP by antibodies against human and rat IgG. This study showed, that autoantibodies to PRL were present in rat and human sera, even in physiological conditions such as pregnancy.

Amino Acid Sequence↗
PubMed1993

Human reciprocal translocations: is the unbalanced mode at birth predictable?

Two methods of prediction for the risk of unbalance at birth were tested on a large data base of reciprocal translocation (1376 families): the pachytene diagram predictive method (PDP method) and the discriminant method (D method). These method succeeded in correctly predicting the segregation mode in 66% of the data for the PDP method and in 80% of the data for the D method. The quality of chromosome material (in particular R bands) must be taken into account for more accurate prediction. Some difficulties still exist in predicting the 3:1 tertiary segregation mode, which can frequently be incorrectly classified as the adjacent 1 mode.

Humans↗
PubMed1993

Logistic regression model to estimate the risk of unbalanced offspring in reciprocal translocations.

The aim of this study was to estimate the risk of viable unbalanced offspring for a parental carrier of reciprocal translocation. On a large computerized database of reciprocal translocations we used logistic regression to model this risk. The status of the progeny is the outcome variable. Explanatory covariates are cytogenetic characteristics of the translocation, age and sex of the parental carrier, and potential viability of the gametes. The results obtained by the logistic model demonstrate the important role of certain variables such as the sex of the parental carrier and the R band length of the translocated segments. Within the group of lower risk (risk of viable unbalanced offspring less than 5%), 97% of the individuals are correctly classified with this model. For this group, the choice prenatal diagnosis can be best discussed by considering both the risk for viable unbalanced offspring and the risk of induced abortion following prenatal diagnosis.

Adolescent↗
PubMed1993

The effect of H-ras expression on tumorigenicity and immunogenicity of Balb/c 3T3 fibroblasts.

In an attempt to define immunological parameters affected by the H-ras oncogene, we have used Balb/c 3T3 cells transfected with either H-ras (98/6), H-ras+v-myc (98/4v) or plasmid only (98/1). We found that while control and oncogene-transfected Balb/c 3T3 cells exhibit similar low sensitivity to lysis by natural killer (NK) cells, H-ras+v-myc-transfected cells could immunize syngeneic Balb/c mice and induce cytotoxic T cells (CTL) with broad specificity, that lysed all types of Balb/c 3T3 cells tested. Immunization of Balb/c mice with 98/4v cells prevented homologous tumor formation and partially inhibited the formation of tumors derived from H-ras-transfected cells. 98/6 cells were not immunogenic in vivo and did not protect the animals from a challenge of 98/6 cells. The results suggested that CTLs but not NK effector cells were important for eliciting in vivo tumor rejection of H-ras+v-myc-transfected cells. In contrast, antigens eliciting the cytotoxic T-cell response, and possibly also the in vivo tumor cell rejection response, were expressed on all cell types tested but were immunogenic only on the surface of 98/4v cells. We further determined major histocompatibility complex (MHC) class-I molecule expression on the outer cell surface and found that H-2K was down-regulated in H-ras-transfected cells. The results support the observation that oncogenes can down-regulate specific MHC antigens, thereby preventing presentation of tumor antigens and allowing tumor escape from immune recognition.

3T3 Cells↗
PubMed1993

Thrombocytopenic purpura as a manifestation of acute hepatitis A.

Extrahepatic autoimmune manifestations are rare in patients with acute hepatitis A infection. We describe a 34-year-old man in whom severe autoimmune thrombocytopenic purpura developed as the manifestation of acute hepatitis A infection. Thrombocytopenic purpura is rarely described in association with hepatitis A, but to our knowledge has never been reported as a manifestation of acute hepatitis A.

Acute Disease↗
PubMed1993

Malignant external otitis in nondiabetic patients.

The purpose of this study is to point out that contrary to traditional belief, there is a small but significant group of nondiabetic patients with malignant external otitis. Thirty patients with a diagnosis of malignant external otitis were treated and followed up at the Department of Otolaryngology-Head and Neck Surgery, Beilinson Medical Center, between 1987 and 1991. Nine of these patients did not have clinical or laboratory evidence of diabetes. This study analyzes this group and concludes that the diagnosis of malignant external otitis should be considered by the treating physician in nondiabetic patients presenting with a Pseudomonas aeruginosa infection of the external ear canal. Severe pain and edematous closure of the canal, together with typical granulation tissue and failure to respond to medical treatment, are specific characteristics of this group.

Aged↗
PubMed1993

Skin surface pH in intertriginous areas in NIDDM patients. Possible correlation to candidal intertrigo.

OBJECTIVE: To compare skin surface pH and moisture in intertriginous areas in diabetic patients and healthy control subjects and to study the relationship between these parameters and candidal infection. RESEARCH DESIGN AND METHODS: We measured the skin surface pH and moisture in the axillary, inframammary, inguinal, and forearm skin with a pH meter with a flat-glass electrode and skin corneometer. The subjects were 50 NIDDM patients from the diabetic outpatient clinic at Beilinson Medical Center, Petah Tiqva, Israel, and 40 healthy control subjects from hospital personnel. The main outcome measures were skin surface pH, skin moisture, and skin culture for Candida. RESULTS: Skin pH in the inguinal and axillary regions was significantly higher in diabetic patients compared with healthy control subjects (P < 0.0001), whereas no difference was noted in the forearm. In the inframammary region, diabetic women had significantly higher pH than nondiabetic women (P < 0.01). No difference was noted in men in this region. Six patients (12%) had candidal infection in intertriginous areas. CONCLUSIONS: Our study indicates that in intertriginous regions, skin surface pH of diabetic patients is significantly higher than in normal control subjects and implies the significance of skin pH as a possible factor promoting host susceptibility to skin candidal infection.

Adult↗