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Biomedical subjects

D Segal

Publications and source records attributed to D Segal.

At least 37 records · Page 2Linked to original sources
PubMed2000

A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction.

TRAF proteins are major mediators for the cell activation, cell survival, and antiapoptotic functions of the TNF receptor superfamily. They can be recruited to activated TNF receptors either by direct interactions with the receptors or indirectly via the adaptor protein TRADD. We now report the structure of the TRADD-TRAF2 complex, which is highly distinct from receptor-TRAF2 interactions. This interaction is significantly stronger and we show by an in vivo signaling assay that TRAF2 signaling is more readily initiated by TRADD than by direct receptor-TRAF2 interactions. TRADD is specific for TRAF1 and TRAF2, which ensures the recruitment of clAPs for the direct inhibition of caspase activation in the signaling complex. The stronger affinity and unique specificity of the TRADD-TRAF2 interaction are crucial for the suppression of apoptosis and provide a mechanistic basis for the perturbation of TRAF recruitment in sensitizing cell death induction.

Amino Acid Sequence↗
PubMed2000

HIV-1 RNA load in needles/syringes from shooting galleries in Miami: a preliminary laboratory report.

We quantified HIV-1 RNA load in rinses from needles/syringes (N/S) obtained at shooting galleries in Miami and also analyzed the rinses for antibodies for viral proteins. In rinses from 36 N/S that contained visible blood, 14 (39%) had detectable amounts of HIV-1 RNA. Numbers of copies of HIV-1 RNA ranged from the detection limit (400 copies/ml) to 268,000 copies/ml. We also detected antibodies to HIV-1 polypeptides in 34/36 (94%) of rinses from visibly contaminated N/S using Western blots specific for the HIV-1 proteins. No antibodies were detected in laboratory rinses from six visibly clean needles. The presence of HIV-1 RNA in N/S is an important indication of the risk created by N/S sharing as well as by shared paraphernalia and wash waters by injecting drug users.

Blotting, Western↗
PubMed2000

Recombinant human single-chain MHC-peptide complexes made from E. coli By in vitro refolding: functional single-chain MHC-peptide complexes and tetramers with tumor associated antigens.

Soluble recombinant MHC-peptide complexes are valuable tools for molecular characterization of immune responses as well as for other functional and structural studies. In this study, soluble recombinant single-chain human MHC (scMHC)-peptide complexes were generated by in vitro refolding of inclusion bodies from bacterially expressed engineered HLA-A2 in the presence of tumor-associated or viral peptides. The scMHC molecule was composed of beta2-microglobulin connected to the first three domains of the HLA-A2 heavy chain through a 15-amino acid flexible linker. Highly purified scMHC-peptide complexes were obtained in high yield using several peptides derived from the melanoma antigens gp100 and MART-1 or a viral peptide derived from HTLV-1. The scMHC complexes were characterized in detail and were found to be correctly folded and able to specifically bind HLA-A2-restricted peptides. We also generated scMHC-peptide tetramers, which were biologically functional; they induced a peptide-specific CTL clone to be activated and secrete IFN-gamma, and were able to stain specifically CTL lines. Such recombinant soluble scMHC-peptide complexes and tetramers should prove of great value for characterization of immune responses involving CTL, for visualization of antigen-specific immune responses, for in vitro primary CTL induction, and for peptide binding assays and structural studies.

Antigens, Neoplasm↗
PubMed2000

The impact of early amniotomy on mode of delivery and pregnancy outcome.

OBJECTIVE: To evaluate the effect of early amniotomy in term gestation on the mode of delivery and pregnancy outcome in comparison with premature rupture of membranes (PROM) and oxytocin induction. STUDY DESIGN: The study population consisted of 60 consecutive parturients induced by early amniotomy. The two comparison groups were 147 women admitted with term PROM and 65 patients induced by oxytocin. All study participants were evaluated prospectively and had unfavorable cervical scores. RESULTS: The duration of the first stage of labor was significantly longer in the PROM group (987.8 +/- 572.3 min) as compared with the early amniotomy group (615.0 +/- 389.6 min) and the oxytocin induction group (650.9 +/- 349.5 min, P<0.001). Higher rates of CS were found in the study group (26.7%) as compared to the controls (11.6% in the PROM and 16.9% in the oxytocin groups, p=0.012). Neonatal outcome was similar in all groups. A stratified analysis comparing the risk of CS while controlling for a previous one did not show a significant difference between the early amniotomy and the oxytocin administration groups. CONCLUSIONS: Early amniotomy is associated with a higher rate of CS. While controlling for a previous CS, both ways of induction were comparable. In order to decrease the CS rates, induction should probably start with cervical ripening techniques in order to improve the Bishop scores.

Adult↗
PubMed2000

courtless, the Drosophila UBC7 homolog, is involved in male courtship behavior and spermatogenesis.

The courtless (col) mutation disrupts early steps of courtship behavior in Drosophila males, as well as the development of their sperm. Most of the homozygous col/col males (78%) do not court at all. Only 5% perform the entire ritual and copulate, yet these matings produce no progeny. The col gene maps to polytene chromosome band 47D. It encodes two proteins that differ in their carboxy termini and are the Drosophila homologs of the yeast ubiquitin-conjugating enzyme UBC7. The col mutation is caused by an insertion of a P element into the 3' UTR of the gene, which probably disrupts translational regulatory elements. As a consequence, the homozygous mutants exhibit a six- to sevenfold increase in the level of the COL protein. The col product is essential, and deletions that remove the col gene are lethal. During embryonic development col is expressed primarily in the CNS. Our results implicate the ubiquitin-mediated system in the development and function of the nervous system and in meiosis during spermatogenesis.

Alleles↗
PubMed2000

Effect of microwave oven induced mild hyperthermia on bone viability and strength.

Extracorporeal hyperthermia treatment of bone followed by reimplantation may be an option for treating bone tumors. However, intensive heat treatment, such as autoclaving, causes a decline of mechanical and biologic functions of bone tissue. In the current study, a microwave oven was used for minimal hyperthermic treatment, and it was found that complete eradication of all viable cells in rat bone could be achieved with minimal reduction in mechanical function. When the cells were evaluated histologically by special lactate dehydrogenase activity staining, complete bone cell death occurred after 60 seconds of heating in an empty Petri dish and after 30 seconds when heated in a Petri dish containing normal saline. Mechanical stiffness and strength of the bones, tested in three-point bending, showed no decrease after this heating. Microwave oven induced hyperthermia eradication of viable cells without significant damage to the mechanical properties may have clinical relevance in limb salvage tumor surgery.

Animals↗
PubMed1999

The COP9 signalosome is essential for development of Drosophila melanogaster.

The COP9 signalosome (originally described as the COP9 complex) is an essential multi-subunit repressor of light-regulated development in plants [1] [2]. It has also been identified in mammals, though its role remains obscure [3] [4] [5]. This complex is similar to the regulatory lid of the proteasome and eIF3 [5] [9] [10] [11] [12] and several of its subunits are known to be involved in kinase signaling pathways [4] [6] [7] [8]. No proteins homologous to COP9 signalosome components were identified in the Saccharomyces cerevisiae genome, suggesting that the COP9 signalosome is specific for multi-cellular differentiation [13]. In order to reveal the developmental function of the COP9 signalosome in animals, we have isolated Drosophila melanogaster genes encoding eight subunits of the COP9 signalosome, and have shown by co-immunoprecipitation and gel-filtration analysis that these proteins are components of the Drosophila COP9 signalosome. Yeast two-hybrid assays indicated that several of these proteins interact, some through the PCI domain. Disruption of one of the subunits by either a P-element insertion or deletion of the gene caused lethality at the late larval or pupal stages. This lethality is probably a result of numerous pleiotropic effects. Our results indicate that the COP9 signalosome is conserved in invertebrates and that it has an essential role in animal development.

Animals↗
PubMed1999

Regulation of apoptosis in myeloid cells by interferon consensus sequence-binding protein.

Mice with a null mutation of the gene encoding interferon consensus sequence-binding protein (ICSBP) develop a disease with marked expansion of granulocytes and macrophages that frequently progresses to a fatal blast crisis, thus resembling human chronic myelogenous leukemia (CML). One important feature of CML is decreased responsiveness of myeloid cells to apoptotic stimuli. Here we show that myeloid cells from mice deficient in ICSBP exhibit reduced spontaneous apoptosis and a significant decrease in sensitivity to apoptosis induced by DNA damage. In contrast, apoptosis in thymocytes from ICSBP-deficient mice is unaffected. We also show that overexpression of ICSBP in the human U937 monocytic cell line enhances the rate of spontaneous apoptosis and the sensitivity to apoptosis induced by etoposide, lipopolysaccharide plus ATP, or rapamycin. Programmed cell death induced by etoposide was specifically blocked by peptides inhibitory for the caspase-1 or caspase-3 subfamilies of caspases. Studies of proapoptotic genes showed that cells overexpressing ICSBP have enhanced expression of caspase-3 precursor protein. In addition, analyses of antiapoptotic genes showed that overexpression of ICSBP results in decreased expression of Bcl-X(L). These data suggest that ICSBP modulates survival of myeloid cells by regulating expression of apoptosis-related genes.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Do axial dynamic fixators really produce axial dynamization?

The use of dynamic external fixators for the treatment of long bone fracture is widespread and well accepted. It is claimed that dynamization, i.e. small micromovements of compression/distraction at the fracture site, can be produced by allowing sliding of an inner rod within an outer housing. However, as the forces on the fixator are not direct but transferred from the bone via bone pins, there is a bending moment on the fixator. This produces "self-locking" and effectively prevents axial movements. We have studied the effect of this moment on the binding properties of the Orthofix system. The amount of movement at a simulated fracture site allowed before this locking occurs was measured and its implications discussed. It would appear that true axial dynamization does not take place using this system.

External Fixators↗
PubMed1999

The unreamed tibial nail in the treatment of distal metaphyseal fractures.

In recent years biological surgical solutions have been recommended in cases of distal tibial fractures, with the aim of reducing damage to soft tissues and to bone vascular supply. Between the years 1991-1995, 52 patients suffering from fractures of the distal tibial metaphysis were treated in our department with an unreamed tibial nail (UTN). Fractures were categorized in accordance with the AO Classification. 32 fractures had no articular involvement (43A1, 43A2, 43A3) and 20 included intra-articular extension (43C1, 43C2). 32 fractures had significant metaphyseal comminution (43A2, 43A3, 43C2). 12 were open fractures. All the fractures were treated by means of UTN using distal locking. In 13 patients an additional percutaneous interfragmentary fixation was also applied. 22 patients underwent an additional operation in order to facilitate bone union (dynamization, bone grafting and/or fibulectomy). In 50 of the 52 patients the fracture united with a very good range of knee and ankle motion. In 2 patients non-union with breakage of the UTN occurred and in two open fractures post-operative infections were observed. Our experience with the treatment of fractures of the distal tibia, including intra-articular fractures with no comminution, points at an excellent functional outcome with a low incidence of complications.

Adult↗
PubMed1999

Combined injuries to the lower limbs.

Several patterns of severe lower limb injuries are presented. They all indicate high energy trauma and affect the immediate care of the patient. The improvement of evacuation systems and resuscitating methods in intensive care create many reconstruction challenges for the orthopaedic surgeon. Awareness of the different combinations which are presented can serve as a tool that may be helpful in these demanding injuries. Guidelines for management of combined injuries are essential to improve the outcome of these life-threatening situations.

Femoral Fractures↗
PubMed1999

Does the station of the fetal head during epidural analgesia affect labor and delivery?

OBJECTIVE: To assess whether the station of the fetal head when lumbar epidural analgesia is administered influences the duration or the mode of delivery in low-risk laboring women. METHODS: We prospectively evaluated 131 consecutive cases of low-risk parturients at term who requested intrapartum epidural analgesia. Obstetric outcome of 65 parturients who underwent epidural analgesia when the fetal head was low in the birth canal was compared to 66 patients whose fetal head station was above the ischial spine. RESULTS: Both groups were similar in their obstetric characteristics. Cervical dilatation when performing the epidural analgesia was similar in both groups. The duration of labor and mode of delivery, as well as percentage of malpositions, were not significantly different in the two groups. CONCLUSIONS: The station of the fetal head while initiating epidural analgesia does not influence the duration of labor or the mode of delivery. Therefore, there is no justification to delay epidural analgesia in labor until the presenting fetal part is engaged.

Adult↗
PubMed1999

Neurofibromatosis in pregnancy. Maternal and perinatal outcome.

OBJECTIVE: The aim of this study was to assess the maternal and perinatal outcome in pregnant patients with neurofibromatosis (NF). STUDY DESIGN: During the period between January 1994 and December 1996 eight women with NF were delivered at the Soroka University Medical Center. Maternal age, parity, gravidy and ethnic origin were matched with a control group that included 65 healthy parturients out of a total of 31,642 deliveries that occurred in our institution during this period. Maternal outcome and perinatal complications were compared between the two groups. RESULTS: The prevalence of NF during the study period was 1:2434 deliveries. The mean gestational age at delivery was significantly lower in the study group as compared to the control group, 36.8+/-3.3 vs. 39.2+/-1.5 weeks, respectively (P=0.029). The rate of intrauterine growth restriction was significantly higher in the study group, (46.2% vs. 8.95%, respectively, P=0.0005), as well as stillbirth rate (23% vs. 1.5%, respectively, P=0.011) and cesarean section rate (38.5% vs. 7.7%, respectively, P=0.01). CONCLUSION: Patients with NF have an increased risk of perinatal complications. Thus, close antenatal observation at high risk tertiary centers is required.

Adult↗
PubMed1999

Early amniotomy -- high risk factor for cesarean section.

OBJECTIVE: To evaluate the effect of early amniotomy on mode of delivery and pregnancy outcome in comparison to a group of patients admitted with premature rupture of membranes at term. STUDY DESIGN: The study population consists of all women (n=338) whose labor was induced by amniotomy, between the years 1988 to 1995. The comparison group were all women (n=1865) who were admitted with premature rupture of membranes during the same period. RESULTS: Cesarean section was significantly higher in the amniotomy group than in the comparison group (162 (47.9%) vs. 348 (18.7%), P<0.001). This significant difference was noted only for those who did not had a previous cesarean section (106 (42.4%) vs. 224 (13.8%), P<0.001). Non progressive labor during the first stage was threefold higher in the amniotomy group than in the control group (30.8% vs. 10.9%, P<0.001). Abnormal fetal heart rate patterns were detected during labor in 52 patients (15.4%) of amniotomy group, as compared to 141 cases (7.6%) in the control group (P<0.001). To assess the independent contribution of early amniotomy to having cesarean section in the present delivery, a multiple logistic model was used. Early amniotomy (odds ratio [OR] 3.07, 95% confidence interval [CI] 2.36-4.01), as well as a previous cesarean section (OR 5.04, 95% CI 3.90-6.52) and high parity (OR 1.07, 95% CI 1.03-1.26) were all found as independent risk factors for cesarean section. CONCLUSIONS: Early amniotomy appears to be associated with an increased risk for cesarean section.

Adult↗
PubMed1999

Maternal serum concentrations of CA-125 in second trimester pregnancy complicated by congenital fetal anomalies.

OBJECTIVE: The purpose of the study was to determine the value of maternal serum CA-125 concentrations in pregnancies complicated by fetal anomalies with or without hydramnios. STUDY DESIGN: The study population (n=40) consisted of the following four groups of patients: (1) 10 women with abnormal maternal serum alpha fetal protein (MSAFP) in whom no fetal anomalies were observed; (2) 10 women in whom fetal anomalies were diagnosed in addition to abnormal MSAFP; (3) 10 women with fetal anomalies accompanied by hydramnios and abnormal MSAF, and (4) 10 women had normal MSAFP and were diagnosed with hydramnios without fetal anomaly. The control group consisted of 10 patients who were matched for gestational age with normal MSAFP and normal ultrasonographic examination. In all 50 cases MSAFP and maternal serum CA-125 levels were assessed. CA-125 was measured using OC 125 monoclonal antibody (IMX CA-125, Abott Lab. IL) and a value of >20 U/ml was defined as abnormal. RESULTS: Maternal serum CA-125 levels were significantly higher in the study group than in the control group, 19.8+/-15.9 U/ml and 9.9+/-4.0 U/ml (P=0.015). The difference was even greater when patients with malformed fetuses and hydramnios were compared to those with fetal anomalies and normal amount of amniotic fluid, 32.4+/-12.7 U/ml and 7.2+/-2.1 U/ml, respectively (P=0.0005). The maternal serum CA-125 levels in patients with hydramnios but without fetal anomalies were significantly lower when compared with those of the malformed fetuses and hydramnios, 9.8+/-2.3 U/ml and 32.4+/-12.7 U/ml, respectively (P=0.002). CONCLUSION: Maternal serum CA-125 is lacking in value for screening fetal structural anomalies as a significant increase in maternal serum CA-125 levels was found only in patients with fetal anomalies accompanied by hydramnios.

Amniotic Fluid↗