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Biomedical subjects

Y Ben-David

Publications and source records attributed to Y Ben-David.

At least 55 records · Page 3Linked to original sources

Welfare support for Israeli Negev Bedouin elderly men: adaptation during spatioecological transformation.

We interviewed 120 Bedouin men to elicit their views about the traditional Bedouin support system for the elderly (a collective family fund) and the more recent welfare support allowances that all Israeli elders are entitled to. Desire to maintain or return to the traditional system varied with the respondent's place on a continuum of seminomadism to rural sedentarization to semiurbanization. Differences were also found between the real Bedouin and the fellahim Bedouin respondents.

Aged↗

Temporal order and functional analysis of mutations within the Fli-1 and p53 genes during the erythroleukemias induced by F-MuLV.

The erythroleukemias induced by Friend murine leukemia virus (F-MuLV) result from the accumulation of a number of genetic changes, including activation of the Fli-1 proto-oncogene and inactivation of the p53 tumor suppressor gene. We have determined the temporal order of mutation of the genes involved in this multistage malignancy, by serial in vivo transplantation of F-MuLV induced primary erythroleukemias into syngenic Balb/c mice. These primary tumors are capable of growing when transplanted into syngenic mice, but die after several days of in vitro culture. From the transplanted tumors grown in syngenic mice, erythropoietin-dependent cell lines were established in culture that are clonally related to cells in the primary tumors. We show that retroviral insertional activation of the Fli-1 ets family member is the first detectable genetic event in F-MuLV induced primary erythroleukemias. Mutations in the p53 gene were observed in the Epo-dependent cell lines but not in the transplanted erythroleukemias used to establish these cell lines in culture. These data suggest that activation of Fli-1 plays an important role in the early stages of F-MuLV-induced leukemia, perhaps by altering the self-renewal probabilities of erythroid progenitor cells and that p53 mutations immortalize these cells, enabling them to grow in vitro in the presence of Epo.

Animals↗

The Fli-1 proto-oncogene, involved in erythroleukemia and Ewing's sarcoma, encodes a transcriptional activator with DNA-binding specificities distinct from other Ets family members.

The late stages of the erythroleukemias induced by either the replication-defective Friend spleen focus-forming virus (SFFV) or the Friend murine leukemia virus (F-MuLV) are associated with the insertional activation of one of two members (Spi-1 or Fli-1) of the Ets protooncogene family of transcriptional factors. Fli-1 is not rearranged or activated in the erythroleukemias induced by SFFV, and similarly Spi-1 is not rearranged or activated in the leukemic cell clones induced by F-MuLV. This strict specificity of integration sites suggests that Fli-1 and Spi-1 may be functionally distinct and transactivate different downstream genes during the progression of multistage Friend erythroleukemia. In this study, we show that the Fli-1 protein, like other Ets proteins, has DNA-binding activity and can act as a sequence-specific transcriptional activator. We also show that the Fli-1 and Spi-1 proteins are functionally distinct in that they recognize and transactivate through distinct DNA binding sites. Furthermore, we have identified an octanucleotide core sequence that is required in vitro for optimal binding of Fli-1 to the Drosophila E74 target and the promoter sequence of the human GPIIB gene.

Animals↗

[Psychological aspects of cochlear implantation].

Psychological aspects of cochlear implantation were studied in 20 adults and children. Patients were interviewed before admission and were given tests and questionnaires to answer with regard to overall wellbeing, intellectual functioning, hopes and beliefs, expectations with regard to the implant and the support they were getting (last 2 also for a family member). Those who passed the screening were referred for surgery, and those who didn't were referred for therapy. 6 months after implantation the patient and the family member were again interviewed and answered questionnaires with regard to adjustment to the implant and the patient's satisfaction with it. In those who benefitted from the implant there were no psychopathological features, there was good cognitive functioning, a moderate level of concentration and attention span and a great degree of flexibility in personality traits. Crucial to better adjustment was quality of family support. Following cochlear implantation there was considerable improvement in life style.

Adaptation, Psychological↗

A mammalian dual specificity protein kinase, Nek1, is related to the NIMA cell cycle regulator and highly expressed in meiotic germ cells.

Screening of mouse cDNA expression libraries with antibodies to phosphotyrosine resulted in repeated isolation of cDNAs that encode a novel mammalian protein kinase of 774 amino acids, termed Nek1. Nek1 contains an N-terminal protein kinase domain which is most similar (42% identity) to the catalytic domain of NIMA, a protein kinase which controls initiation of mitosis in Aspergillus nidulans. In addition, both Nek1 and NIMA have a long, basic C-terminal extension, and are therefore similar in overall structure. Despite its identification with anti-phosphotyrosine antibodies, Nek1 contains sequence motifs characteristic of protein serine/threonine kinases. The Nek1 kinase domain, when expressed in bacteria, phosphorylated exogenous substrates primarily on serine/threonine, but also on tyrosine, indicating that Nek1 is a dual specificity kinase with the capacity to phosphorylate all three hydroxyamino acids. Like NIMA, Nek1 preferentially phosphorylated beta-casein in vitro. In situ RNA analysis of nek1 expression in mouse gonads revealed a high level of expression in both male and female germ cells, with a distribution consistent with a role in meiosis. These results suggest that Nek1 is a mammalian relative of the fungal NIMA cell cycle regulator.

Amino Acid Sequence↗

Retroviral insertions downstream of the heterogeneous nuclear ribonucleoprotein A1 gene in erythroleukemia cells: evidence that A1 is not essential for cell growth.

A large number of novel cellular proto-oncogenes have been identified and cloned by analysis of common integration sites in retrovirally induced malignancies. In the multistage erythroleukemias induced by the various strains of Friend leukemia virus, the analysis of proviral-integration events has led to the identification of two genes, Fli-1 and Spi-1, both novel members of the ets oncogene family of transcription factors. In this report, we describe the identification of another integration site, designated Fli-2 (Friend leukemia virus integration-2), in an erythroleukemia cell line induced by Friend murine leukemia virus (F-MuLV). Rearrangements at the Fli-2 locus were found in two erythroleukemia cell lines independently induced by F-MuLV and one leukemic cell line derived from the spleen of a mouse infected with the polycythemia strain of Friend leukemia virus. The deduced amino acid sequence of a cDNA corresponding to a transcript originating from genomic DNA adjacent to Fli-2 is identical to that of the human heterogeneous nuclear ribonucleoprotein A1 gene, a member of the gene family of RNA-binding proteins involved in RNA splicing. In one erythroleukemia cell line, A1 expression was undetectable as a result of F-MuLV integration in one allele and loss of the other allele. These results suggest that perturbations in RNA splicing mechanisms may contribute to malignant transformation and provide direct evidence that the A1 protein is not required for cell growth.

Amino Acid Sequence↗

Multiple cDNAs encoding the esk kinase predict transmembrane and intracellular enzyme isoforms.

A novel protein kinase, the Esk kinase, has been isolated from an embryonal carcinoma (EC) cell line by using an expression cloning strategy. Sequence analysis of two independent cDNA clones (2.97 and 2.85 kb) suggested the presence of two Esk isoforms in EC cells. The esk-1 cDNA sequence predicted an 857-amino-acid protein kinase with a putative membrane-spanning domain, while the esk-2 cDNA predicted an 831-amino-acid kinase which lacked this domain. In adult mouse cells, esk mRNA levels were highest in tissues possessing a high proliferation rate or a sizeable stem cell compartment, suggesting that the Esk kinase may play some role in the control of cell proliferation or differentiation. As anticipated from the screening procedure, bacterial expression of the Esk kinase reacted with antiphosphotyrosine antibodies on immunoblots. Furthermore, in in vitro kinase assays, the Esk kinase was shown to phosphorylate both itself and the exogenous substrate myelin basic protein on serine, threonine, and tyrosine residues, confirming that the Esk kinase is a novel member of the serine/threonine/tyrosine family of protein kinases.

Amino Acid Sequence↗

[Tuberculosis of the middle ear].

Tuberculosis is rare in Israel, especially that of the middle ear. Its rarity leads to both underdiagnosis and misdiagnosis. Since tuberculosis is treatable, diagnosis is of the utmost importance. The recent wave of immigration from countries in which tuberculosis is endemic may confront us with more cases of tuberculosis of this type.

Ear Diseases↗

Diamond-Blackfan anemia: heterogenous response of hematopoietic progenitor cells in vitro to the protein product of the steel locus.

Diamond-Blackfan anemia is a congenital disorder of erythropoiesis in humans, characterized by a macrocytic anemia often associated with physical anomalies. Mutations at either the W or Steel loci in the mouse also leads to a severe macrocytic anemia, as well as other developmental abnormalities. The W locus encodes the proto-oncogene c-kit, a member of the receptor tyrosine kinase family, while the Steel locus encodes a potent hematopoietic growth factor that is the ligand for c-kit. Growth of clonogenic marrow erythroid progenitor cells in vitro in the presence of the recombinant hematopoietic growth factors interleukin-3 (IL-3) and Steel was used to characterize this disease at the cellular level. Three patterns of in vitro marrow response to both recombinant IL-3 or Steel were observed among 10 Diamond-Blackfan patients: those that responded quantitatively and qualitatively almost as well as cells from normal marrow, those that responded at an intermediate level, and those that did not respond at all. These results provide evidence for cellular heterogeneity underlying the pathogenesis of this disorder and therefore raise the possibility that there may be more than one underlying molecular basis for the disease. No gross abnormalities in the structure of either the c-kit or Steel loci were observed in these patients. The normal response in culture of the progenitor cells from at least some patients to Steel with or without IL-3 raises the possibility of using this novel growth factor as a therapeutic agent in Diamond-Blackfan anemia.

Adolescent↗

A mammalian protein kinase with potential for serine/threonine and tyrosine phosphorylation is related to cell cycle regulators.

In a screen of mouse erythroleukemia cDNA expression libraries with anti-phosphotyrosine antibodies, designed to isolate tyrosine kinase coding sequences, we identified several cDNAs encoding proteins identical or very similar to known protein-tyrosine kinases. However, two frequently isolated cDNAs, clk and nek, encode proteins which are most closely related to protein kinases involved in regulating progression through the cell cycle, and contain motifs generally considered diagnostic of protein-serine/threonine kinases. The clk gene product contains a C-terminal cdc2-like kinase domain, most similar to the FUS3 catalytic domain. The Clk protein, expressed in bacteria, becomes efficiently phosphorylated in vitro on tyrosine as well as serine/threonine, and phosphorylates the exogenous substrate poly(glu, tyr) on tyrosine. Direct biochemical evidence indicates that both protein-tyrosine and protein-serine/threonine kinase activities are intrinsic to the Clk catalytic domain. These results suggest the existence of a novel class of protein kinases, with an unusual substrate specificity, which may be involved in cell cycle control.

Amino Acid Sequence↗

Erythroleukemia induction by Friend murine leukemia virus: insertional activation of a new member of the ets gene family, Fli-1, closely linked to c-ets-1.

The retroviral integration site Fli-1 is rearranged in 75% of the erythroleukemia cell clones induced by Friend murine leukemia virus (F-MuLV), whereas Spi-1/PU.1, a member of the ets family of DNA-binding proteins, is rearranged in 95% of the erythroleukemias induced by Friend spleen focus-forming virus (SFFV). To determine the transcriptional domain defined by Fli-1, we have isolated a cDNA clone that is highly expressed only in erythroleukemia cell lines with Fli-1 rearrangements. The protein sequence of this cDNA is very similar to Erg2, another member of the ets gene family. The hydrophilic carboxy-terminal end of the Fli-1 cDNA shares significant sequence similarity to the DNA-binding ETS domain found in all members of the ets family. PFGE analysis localized Fli-1 within 240 kb of the ets-1 proto-oncogene on mouse chromosome 9 and human chromosome 11q23, suggesting that ets-1 and Fli-1 arose from a common ancestral gene by gene duplication. The involvement of the murine Fli-1, Spi-1, and avian v-ets genes in erythroleukemia induction suggests that activation of ets gene family members plays an important role in the progression of these multistage malignancies.

Amino Acid Sequence↗

Transient osteoporosis of the hip during pregnancy. A case report.

Transient hip osteoporosis is a benign, process mainly affecting men. A 31-year-old woman in the 31st week of pregnancy was diagnosed as having the disorder. Impairment of venous flow associated with pregnancy might have been the cause of the osteoporosis and superficial thrombophlebitis.

Adult↗

Idiopathic subjective tinnitus treated by biofeedback, acupuncture and drug therapy.

The effect of three treatment modalities of idiopathic-subjective tinnitus (IST): acupuncture (AP), biofeedback (BF) and Cinnarizine (Cin), was investigated in 58 randomly selected subjects. The findings show that at the end of treatment, 50% of the patients in the biofeedback group reported some amelioration in the level of the tinnitus, while 30% of the acupuncture group and only 10% of the group receiving Cinnarizine reported an amelioration of the tinnitus. Treatment by biofeedback caused a significant easing in the degree of discomfort caused by the tinnitus to patients during rest. Within the limitations of the sample study, our results indicate that the biofeedback method is more effective in comparison with acupuncture and Cinnarizine in the treatment of those suffering from tinnitus.

Acupuncture Therapy↗

Gradual cervical dilation for termination of early second-trimester pregnancy with a double balloon device.

Thirty-two women with pregnancies of 12-15 weeks underwent cervical dilation before abortion using a double balloon device. In all cases, satisfactory dilation was achieved and evacuation accomplished. The slow dilation process, resulting from the continuous indirect dilator effect of the balloons, was not associated with patient inconvenience in most cases. Larger dilation was achieved by adding a continuous instillation of extraovular prostaglandin E2 solution through the device. The double balloon device is a convenient and safe cervical dilator and may be a suitable method for cervical dilation before abortion.

Abortion, Induced↗

The efficacy of oral steroids in the treatment of persistent otitis media with effusion.

One hundred thirty-six children with otitis media with effusion of at least 2 months' duration were investigated in a strict, double-blind, randomized prospective study to evaluate the efficacy of oral steroids in the treatment of this disease. The results of our study showed a significant complete and partial recovery from otitis media with effusion in the group treated by a combination of antibiotics (amoxicillin) and oral steroids (prednisone), compared with an amoxicillin-treated group and a placebo-treated group. We believe that this treatment mostly benefits children aged 4 to 10 years without oversized adenoids. The findings of our study imply that a combined course of antibiotics and oral steroids deserves its place as a routine conservative trial before surgery.

Administration, Oral↗