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Biomedical subjects

N Levy

Publications and source records attributed to N Levy.

At least 73 records · Page 4Linked to original sources
PubMed1996

The distribution of Ag-NORs proteins and ribosomal RNA genes in human spermatogonia: an original procedure associating silver-staining, fish and confocal microscopy.

It is generally accepted that Ag-NORs proteins are associated with nucleolar components engaged in rRNA synthesis. Since conflicting results have been reported concerning the intranucleolar sites of active ribosomal genes, the relationships between the silver-stained areas and the distribution of rDNA were analyzed in human spermatogonia using confocal microscopy of fluorescent in situ hybridized preparations previously stained with silver. The fluorescent signal strictly corresponded to the silver-stained area, identified at the ultrastructural level as the fibrillar center and the surrounding dense fibrillar component. A quantitative evaluation of nucleolar activity solely based on silver-staining may be misleading, taking into account that only Ag-positive proteins located in the dense fibrillar component can be associated with transcriptional activity, while those stored in the fibrillar center are associated with non-transcribed rRNA genes.

DNA, Ribosomal↗
PubMed1995

Seasonal fluctuations in acute gastrointestinal bleeding.

We investigated the seasonal variability of upper gastrointestinal bleeding retrospectively during 1988-92 in Haifa, Israel, a city with a subtropical climate. Four hundred and thirty three patients were included in the study: duodenal ulcer, 202; hemorrhagic gastritis 108; gastric ulcer 101; duodenal ulcer and hemorrhagic gastritis 12; and duodenal ulcer and gastric ulcer, 10. The highest incidence of bleeding was observed during winter (31.7%) and spring (28.3%), progressively diminishing throughout summer (18.5%) and fall (21.5%) (p < 0.0001). Both females and males showed this significant seasonal variation (p < 0.025 and p < 0.005, respectively). As a group, patients over 57 years of age had the highest incidence of bleeding during winter and spring (p < 0.005). Interestingly, the ingestion of NSAID had no influence in the increased seasonal bleeding. Duodenal ulcer (p < 0.01) and hemorrhagic gastritis (p < 0.05) showed a significant seasonal variation while gastric ulcer did not. Although there are several reports in the literature concerning seasonal fluctuations in duodenal and gastric ulcers, no such studies have hitherto been published on hemorrhagic gastritis.

Adolescent↗
PubMed1995

Clinical similarity and biological diversity in the response to alprazolam in patients with panic disorder and generalized anxiety disorder.

Thirty-six patients with panic disorder (PD) and 35 patients with generalized anxiety disorder (GAD) participated in an open alprazolam treatment phase that preceded controlled withdrawal from alprazolam. Clinical ratings, blood pressure and heart rate were obtained along with plasma measurements of cortisol, ACTH, growth hormone and catecholamines. A similar clinical response profile was evident in both groups with rapid onset of improvement within the first week. The two diagnostic groups differed in their biological response to alprazolam. PD patients had a significant reduction in blood pressure, plasma cortisol and a trend toward significant reduction in plasma epinephrine, which were not seen in the GAD patients. GAD patients showed a significant reduction in plasma norepinephrine. These findings provide further evidence that PD and GAD are biologically distinct syndromes.

Adrenocorticotropic Hormone↗
PubMed1995

Identification of several alpha-globin gene variations in a small Laotian family.

The present study concerns the identification of four alpha-globin gene deficiencies, one alpha 1-globin gene mutation, and one beta-globin gene mutation in a Laotian couple and their newborn baby. The parents were Hb E heterozygotes and the baby was an Hb E homozygote. The father carried the 4.2-kb deletion on one chromosome and a TAA-->CAA mutation at the terminating codon of the alpha 2-gene (Hb Constant Spring or CS) on the other chromosome. Moreover, the remaining alpha 1-globin gene on the chromosome with the 4.2-kb deletion was mutated at codon 74 (GAC-->CAC; Asp-->His; Hb Q-Thailand). The mother had the 3.7-kb deletion on one chromosome and a TAA-->TAT mutation at the terminating codon of the alpha 2-globin gene (Hb Paksé) of the second chromosome. The baby was a compound heterozygote for the two termination codon mutations and, at birth, had a high level of Hb Bart's (16.6%) reflecting a mild form of Hb H disease.

Adult↗
PubMed1995

Pilot radioimmunotherapy trial with 131I-labeled murine monoclonal antibody CC49 and deoxyspergualin in metastatic colon carcinoma.

An antimouse immune response is invariable following administration of murine monoclonal antibody (mAb), precluding effective multidose therapy. In advanced colorectal cancer patients, we carried out a pilot study with multiple doses of 131I-labeled CC49 administered with deoxyspergualin (DSG), an immunomodulator, to determine its effect on immune response. Cumulative toxicity and efficacy were also evaluated. Six patients with tumor-associated glycoprotein 72-expressing colorectal cancer were treated i.v. with 15 mCi/m2 131I-labeled to 20 mg mAb CC49 biweekly, along with concurrent DSG 200 mg/m2 daily for 5 days, for a maximum of four courses. None had received prior murine mAbs. All patients had targeting of radioactivity to known tumor sites following initial infusion. Four of six patients received all four courses of therapy, three without any acute side effects. In these patients, there was no change in serum clearance with variable tumor targeting following repeat infusions. Two patients had </= grade II anaphylactoid reactions, which were treated without sequelae. One of these had faster serum clearance of radioactivity following repeat infusions of 131I-labeled CC49. Human antimouse antibody titers in all patients were significantly less compared to concurrent times in patients receiving CC49 without DSG (P < 0.05). There was no correlation between the human antimouse antibody titer and serum clearance or tumor targeting of 131I-labeled CC49. There were no clinical responses. We concluded that multiple doses of murine antibody 131I-labeled CC49 can be safely administered with no change in serum or whole-body kinetics in 50% of patients treated biweekly. DSG may reduce the human immune response to the murine mAb.

Aged↗
PubMed1994

Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas: a prospective Southwest Oncology Group trial.

The growth fraction of tumors from patients with non-Hodgkin's lymphomas (NHL) has been shown to correlate with survival in retrospective studies. The growth fraction can be evaluated using immunohistochemical techniques employing the Ki-67 monoclonal antibody (MoAb) that marks a nuclear protein present in cycling cells. The purpose of this study was to evaluate the clinical utility of the Ki-67 MoAb for predicting survival. Using a prospective trial design in a multi-institutional cooperative trials group, the proliferative index, clinical outcome, and statistical correlations were independently assessed for previously untreated patients with advanced stages of intermediate- and high-grade histologies of NHL treated on Southwest Oncology Group study (SWOG 8516, Intergroup 0067). The proportion of Ki-67-positive cells was determined on snap-frozen thin tissue sections. A proliferative index of 80% or greater, as determined from prior retrospective studies, identified a group of patients (18%) who had a poor outcome. Overall survival was significantly reduced in these patients with a high Ki-67-associated proliferative index compared with those with a low proliferative index (P = .001). One-year survival estimates were 82% (low proliferative index) versus 18% (high proliferative index). A multivariate regression analysis incorporating commonly used clinical prognostic features confirmed the independent effect of proliferation on survival (relative risk estimate 5.9; 95% confidence interval, 2.2, 16.1). The Ki-67 MoAb identifies a group of patients with rapidly fatal NHL for whom currently available chemotherapy is inadequate.

Adult↗
PubMed1994

The genetics of retinoblastoma.

Retinoblastoma is a malignant tumor of the eye that affects about one in 20,000 young children and occurs as hereditary and non-hereditary (sporadic) forms. It results from successive loss or inactivation of the two alleles of the Rb1 gene, located in 13q14. A chromosomal deletion in 13q14 is revealed by cytogenetic investigation in about 5% of affected patients. Molecular studies have confirmed that inactivation of both alleles of the Rb1 gene, even by point mutation, is required for tumorigenesis, leading to the concept of antioncogenes or tumor suppressor genes. The protein (p110RB) produced by the Rb1 gene is involved in cell cycle regulation. Absence or abnormal forms of the protein may result in deregulation of the cell cycle and subsequent cell proliferation. Association of p110RB with viral oncoproteins may be a step in tumorigenesis. Differences in penetrance and expressivity among families, could be explained by balanced insertional translocation and by defects of the Rb1 gene, which codes for a shortened Rb protein with partial oncosuppressor function. Techniques allowing analysis of Rb1 mutations can be successfully used to predict or exclude the development of retinoblastoma in newborn infants.

Chromosomes, Human, Pair 13↗
PubMed1993

Tay-Sachs disease--carrier screening, prenatal diagnosis, and the molecular era. An international perspective, 1970 to 1993. The International TSD Data Collection Network.

OBJECTIVES: To provide an update of the international experience with carrier screening and prenatal diagnosis for Tay-Sachs disease (TSD), to assess the impact of these efforts, and to review the recent developments in DNA technology with application to TSD carrier detection and screening. DESIGN: Through the International TSD Testing, Quality Control, and Data Collection Center, all testing centers in the world were surveyed annually to assess overall experience with carrier testing and prenatal diagnosis. Quality control and laboratory surveillance of testing centers were performed through an annual assessment, using samples provided by the center. SETTING: Tay-Sachs disease testing centers around the world. PARTICIPANTS: Nearly 1 million young adults from both Jewish and non-Jewish populations. INTERVENTION: Gene product screening (enzyme testing) and DNA-based mutation analysis (in some populations). MAIN OUTCOME MEASURE: Impact of screening program on disease incidence. RESULTS: Data from all centers in the international TSD network on experience with TSD carrier testing and prenatal diagnosis since 1974 indicated that more than 36,000 heterozygotes were identified and 1056 couples found to be at risk for TSD in their offspring. A total of 2416 pregnancies at increased risk for TSD were monitored by amniocentesis or chorionic villus sampling. A dramatic decrease in the incidence of TSD in the Jewish populations was demonstrated. With both serum and leukocyte proficiency testing, there have been only 16 instances (of 845 cumulative laboratory evaluations) of one or more errors reported by a laboratory since 1983 resulting in nonaccreditation. CONCLUSIONS: This analysis represents a prototypic effort in coordinating adult education, carrier testing, and genetic counseling directed toward prospective prevention of a uniformly fatal childhood disease and demonstrates that such an effort can dramatically affect disease incidence.

Clinical Enzyme Tests↗
PubMed1993

Oncogenic activity of the c-Myc protein requires dimerization with Max.

c-Myc (Myc) and Max proteins dimerize and bind DNA through basic-helix-loop-helix-leucine zipper motifs (b-HLH-LZ). Using a genetic approach, we demonstrate that binding to Max is essential for Myc transforming activity and that Myc homodimers are inactive. Mutants of Myc and Max that bind efficiently to each other but not to their wild-type partners were generated by either exchanging the HLH-LZ domains or reciprocally modifying LZ dimerization specificities. While transformation defective on their own, complementary mutants restore Myc transforming activity when coexpressed in cells. The HLH-LZ exchange mutants also have dominant negative activity on wild-type Myc function. In addition, wild-type max antagonizes myc function in a dose-dependent manner, presumably through competition of Max-Max and Myc-Max dimers for common target DNA sites. Therefore, Max can function as both suppressor and activator of Myc. A general model for the role of Myc and Max in growth control is discussed.

Amino Acid Sequence↗
PubMed1993

Sequence-specific DNA binding by p53: identification of target sites and lack of binding to p53 - MDM2 complexes.

An immune selection procedure was employed in order to isolate p53 binding sites from mouse genomic DNA. Two DNA clones capable of tight specific interaction with wild type p53 were subjected to further characterization. In both cases, the p53 binding regions displayed a high degree of sequence homology with the consensus binding site defined for human genomic DNA. One of the clones was found to be derived from the LTR of a retrovirus-like element (a member of the GLN family). The region encompassing the GLN LTR p53 binding site could confer p53 responsiveness upon a heterologous promoter. Furthermore, the expression of the endogenous, chromosomally integrated GLN elements was significantly induced upon activation of wild type p53 in cells harboring a temperature sensitive p53 mutant. Finally, it was demonstrated that p53 - MDM2 complexes fail to bind tightly to such a p53 binding site. This may contribute to the inhibition by MDM2 of p53-mediated transcriptional activation.

Animals↗
PubMed1993

Bowel habits in Israel. A cohort study.

We interviewed 1,900 healthy subjects who belonged to one of the three following ethnic groups: (a) Ashkenazi Jews, (b) Sephardi and Oriental Jews, and (c) Arabs (including Druses)--about their bowel habits, laxative use, and beliefs about bowel action. Using stepwise logistic regression, we found that the following variables were significantly and independently related to bowel frequency: (a) sex--male > female (p = 0.0001); (b) age--young > old (p = 0.0001); (c) physical activity--high > little (p = 0.001); (d) body habitus--lean > obese (p = 0.02); (e) marital status--married > single (0 = 0.009); and (f) ethnic group--Arab > Jewish (p = 0.004). Regular use of laxatives was found in 18.4% of women and 10.8% of men (p < 0.0001). This habit was more common among Ashkenazi Jews (17%) than among Sephardi and Oriental Jews (10.7%) and Arabs (4.8%). Laxative intake was higher among the elderly (p = 0.0001) and the obese (p = 0.0004). Concerning the "ideal" bowel frequency, 12.4% of the Ashkenazis, 22.7% of the Sephardis and Oriental Jews, and 26.1% of the Arabs preferred to have at least 9 movements per week. Strikingly, 51.8% of all interviewed believed that constipation was "harmful to health;" women were more concerned than men (56.3% versus 47.5%). Subjects with a high level of education were significantly more concerned about constipation.

Adolescent↗
PubMed1993

Complementation by wild-type p53 of interleukin-6 effects on M1 cells: induction of cell cycle exit and cooperativity with c-myc suppression.

Stable transfection of M1 myeloid leukemia cells with a temperature-sensitive mutant of p53 results in two phenomena that are manifested exclusively at the permissive temperature. On one hand, activation of wild-type p53 by the temperature shift induced an apoptotic type of cell death which could be inhibited by interleukin-6 (IL-6) (E. Yonish-Rouach, D. Resnitzky, J. Lotem, L. Sachs, A. Kimchi, and M. Oren, Nature 352:345-347, 1991). On the other hand, as reported in this work, activated p53 complemented the antiproliferative effects of IL-6 in M1 cells. A shift to the permissive temperature concomitant with or early after IL-6 treatment imposed a novel pattern of cell cycle arrest in which about 95% of the cells were retained within a G0-like quiescent state. This phase was characterized by 2N DNA content and low RNA and protein content. On the molecular level, activation of wild-type p53 transrepressed the c-myc gene but not the cyclin A, D1, or D2 gene, which are all independently suppressed by IL-6 in M1 cells. To further analyze whether c-myc inhibition mediates or complements p53 effects, the p53-transfected M1 cells were infected with a retroviral vector expressing deregulated c-myc, refractory to p53 or IL-6 action. It was found that the process of cell death was not interrupted at all in these M1 c-myc-p53 double transfectants, suggesting that the transrepression of c-myc is not a major obligatory event mediating p53-induced cell death. In addition, some of the antiproliferative effects of activated p53, manifested in the presence of IL-6, could still be transmitted in the background of constitutive c-myc. Yet the context of deregulated c-myc interfered with the final accumulation of cells within a G0-like phase, suggesting complementary interactions between the outcome of p53 activation and of c-myc suppression in the control of cell cycle arrest.

Cell Cycle↗
PubMed1993

Further investigation of the HEXA gene intron 9 donor splice site mutation frequently found in non-Jewish Tay-Sachs disease patients from the British Isles.

In a previous study we found that a Tay-Sachs disease (TSD) causing mutation in the intron 9 donor splice site of the HEXA gene occurs at high frequency in non-Jewish patients and carriers from the British Isles. It was found more frequently in subjects of Irish, Scottish, and Welsh origin compared with English origin (63% and 31% respectively). We have now tested, in a blind study, 26 American TSD carriers and 28 non-carriers who have British ancestry for the intron 9 splice site mutation. Six of the carriers and none of the controls were positive for the mutation. All six had Irish ancestry, compared with nine of the 20 other (intron 9 mutation negative) TSD carriers (p < 0.05). These results confirm the previously found high frequency of the intron 9 mutation in non-Jewish TSD families of British Isles, particularly Irish, origin, and reinforce the need to screen such families for this mutation.

England↗