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Biomedical subjects

D Talbot

Publications and source records attributed to D Talbot.

At least 127 records · Page 7Linked to original sources
PubMed1991

The 5'HS2 of the globin locus control region enhances transcription through the interaction of a multimeric complex binding at two functionally distinct NF-E2 binding sites.

The locus control region (LCR) of the human beta-globin locus consists of four hypersensitive regions (5'HS 1-4). One of these sites, 5'HS2, is active in both transient and stable transfection assays and transgenic mice. It has previously been shown that the jun/fos consensus binding sites in 5'HS2 are required for high levels of transcription. In this paper we show that it is the 5' of the two consensus sites that is required for this function with a contribution of the 3' site to the overall activity. The functional complex at both sites includes NF-E2. Its role in HS2 is to provide 'enhancer' activity but is not required for position independent activation. High levels of enhancement are achieved by interaction of the NF-E2 sites with three downstream elements. One of these sites binds the known factor GATA-1, whereas the other two interact with two novel DNA binding factors (H-BP and J-BP).

Base Sequence↗
PubMed1991

Effects of stress, social support, and self-esteem on depression in children with limb deficiencies.

Limb deficiencies in children are the result of trauma, disease, or congenital causes. The potentially negative impact on psychologic adjustment from the chronic strain of living with limb deficiencies appears to be mediated by perceived social support (interpersonal protective factor), microstressors and daily hassles (socioenvironmental risk factor), and self-esteem (intrapersonal protective factor). These risk and protective factors were simultaneously investigated as potential predictors of depressive symptomatology in 54 children with congenital or acquired limb deficiencies. Hierarchical multiple regression analyses were used to test the main effects and the interaction effects of the predictor variables on depressive symptomatology. None of the interaction terms were statistically significant. An overall simultaneous multiple regression analysis of the main effects model predicted 72% of the variance in depressive symptomatology, with perceived classmate social support emerging as the strongest predictor variable. The findings are discussed in terms of the risk and protective effects of mediating factors on the psychologic and social adaptation of chronically ill and handicapped children.

Adolescent↗
PubMed1990

The beta-globin dominant control region: hypersensitive site 2.

The Dominant Control Region (DCR) of the human beta-globin gene locus consists of four strong hypersensitive sites (HSS) upstream of the epsilon-globin gene. Addition of these sites confers copy number dependent expression on the human beta-globin gene in murine erythroleukaemia cells and transgenic mice, at levels comparable with the endogenous mouse globin genes. We have shown previously that a 1.9 kb fragment comprising HSS 2 accounts for 40-50% of the full effect of the DCR. In this paper we describe a deletional analysis of HSS 2. We show that a 225 bp fragment is sufficient to direct high levels of expression of the human beta-globin gene which is copy number dependent and integration site independent. This 225 bp fragment overlaps the major region that is hypersensitive 'in vivo'. DNase I footprinting shows the presence of four binding sites for the erythroid specific protein NF-E1; the three other footprinted regions display a remarkable redundancy of the sequence GGTGG and bind a number of proteins including Sp1 and the CACC box protein. The significance of these results for the regulation of globin gene expression is discussed.

Animals↗
PubMed1990

Detailed analysis of the site 3 region of the human beta-globin dominant control region.

Four DNase I hypersensitive sites characterize the human beta-globin Dominant Control Region (DCR) providing position independent, high levels of erythroid specific expression to linked homologous and heterologous genes when introduced into cultured cells or in transgenic mice. We have delineated the hypersensitive site located 10.5 kbp upstream of the epsilon-globin gene by short range DNase I sensitivity mapping to a 600 bp region. Using transgenic mice and MEL cells the functional part of this region was further mapped to a 300 bp central core, which provides position independent, high level expression. It contains a number of ubiquitous and erythroid specific protein binding sites, including the previously described factors NF-E1 (GF1) and NF-E2. The latter binds to a dimer of the consensus binding sequence for jun/fos. The presence of this sequence is required for the function of the element, but single or multimerized copies of this site failed to give position independent, high levels of expression in transgenic mice or MEL cells. We therefore conclude that a combination of factor binding sites is necessary to allow site 3 to function as a strong transcriptional activator, resulting in position independent expression of the beta-globin gene.

Animals↗
PubMed1990

Internal fixation of pubic symphysis diastasis with a tension banding technique.

We present the details of a method of internally fixing diastasis of the pubic symphysis with stout wires and a tension band which can be employed with speed and ease, through a minimal exposure or minimally extended laparotomy wound. The technique is suitable for those with little experience of internal fixation of the pelvis. Our initial cases are presented.

Adolescent↗
PubMed1990

High-dose cytosine arabinoside plus etoposide as initial treatment for acute myeloid leukaemia: a single centre study.

In a single centre, 52 newly diagnosed patients with acute myeloid leukemia (AML) under the age of 56 years received induction chemotherapy commencing with high-dose cytosine arabinoside (Ara-C) and etoposide (Protocol BF11), followed by Ara-C, 6 thioguanine (6TG). A total of 67% of patients entered remission using these drugs. An anthracycline was added for those patients not in remission. The overall remission rate (CR) was 86.5% (45/52), with a minimum follow-up of 90 days. Patients are hospitalised for relatively short periods, and consequently require less blood product and antibiotic support. Patients in continuing first remission following induction with Ara-C and etoposide are similar in number to those in continuing first remission who initially received an anthracycline. This would imply that the efficiency of Ara-C and etoposide in inducing long-term disease-term survival is comparable with anthracycline-containing regimens. We conclude that high-dose Ara-C and etoposide used in the first induction cycle for treating AML have good antileukaemic effect with acceptable toxicity.

Adolescent↗
PubMed1990

Phase II trial of UFT in advanced colorectal and gastric cancer.

A phase II trial of continuous oral therapy with UFT, a combination of uracil and the 5-fluorouracil analogue 1-(2-tetrahydrofuryl)-5-fluorouracil (Futraful, Ftorafur), was conducted in 40 patients with advanced colorectal cancer and 18 patients with advanced gastric cancer. Six partial responses were seen in the 36 evaluable patients with colorectal cancer (response rate 16.6%; 95% confidence limits 6.4-32.8%), and one partial response was seen in the 16 evaluable patients with gastric cancer (response rate 6%; 95% confidence limits 0.27-30.2%). The overall toxicity of the treatment was low, and all patients were treated as outpatients. The results suggest that oral UFT has comparable activity to standard regimes of 5-fluorouracil, and because of the convenience of oral administration is a useful therapy in the management of patients with advanced colorectal cancer.

Adult↗
PubMed1990

Renal allograft rejection. Possible involvement of antibody-dependent cell-mediated cytotoxicity.

We have demonstrated that serum from appropriately sensitized patients can contain IgG antibodies that bind to cultured renal epithelial cells. The presence of such antibodies on the surface of renal cells enables otherwise nonlytic PBMC to lyse these renal cells by an antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. Experiments involving cell-sorting and specific complement-mediated lysis showed that the ADCC effector cells were of the CD3 -ve, C16 +ve phenotype characteristic of NK cells. In this report it is argued that an ADCC mechanism may be of importance in mediating chronic renal cell damage in the absence of acute allograft rejection.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

Teicoplanin compared to flucloxacillin for antibiotic treatment of neutropenic patients.

Ninety-eight neutropenic patients were randomized to receive piperacillin and gentamicin in combination with either teicoplanin or flucloxacillin. Sixty-seven of these patients, most of whom had myeloma, were given this combination as prophylaxis 5 d after high dose chemotherapy, 35 receiving flucloxacillin and 32 receiving teicoplanin. Of 31 patients with leukaemia who were febrile and neutropenic following induction chemotherapy or bone marrow transplantation, 18 received flucloxacillin and 13 received teicoplanin. For those given flucloxacillin, the mean number of days to change of antibiotics was 7.8 in the prophylaxis group and 5.1 in the treatment group. In the teicoplanin arm, the mean number of days to change antibiotics was 6.8 in the prophylaxis group and 6.1 in the treatment group. Two patients in the flucloxacillin arm developed drug rashes. Four patients developed rigors after teicoplanin administration and one asthmatic became wheezy. One patient had a progressive rise in creatinine, but overall the patients having teicoplanin did not have any appreciable increase of renal toxicity compared to the flucloxacillin arm. Blood cultures were positive prior to commencement in the treatment group in nine patients, and during treatment in six patients. Organisms grown were Gram-positive in 14 patients. Teicoplanin appears to be as effective as flucloxacillin when each is used in combination with piperacillin and gentamicin in the treatment of neutropenic patients, with similar rates of toxicity.

Anti-Bacterial Agents↗
PubMed1989

A dominant control region from the human beta-globin locus conferring integration site-independent gene expression.

The regulatory elements that determine the expression pattern of a number of eukaryotic genes expressed specifically in certain tissues have been defined and studied in detail. In general, however, the expression conferred by these elements on genes reintroduced into the genomes of cell lines and transgenic animals has turned out to be at a low level relative to that of endogenous genes, and influenced by the chromosomal site of insertion of the exogenous construct. We have previously shown that if regions flanking the human beta-globin locus are introduced into the mouse genome along with the human beta-globin gene, a level of expression comparable to that of endogenous genes can be achieved that is also independent of integration site. We have now defined a dominant control region with these properties consisting of 6.5 kilobases of DNA encompassing erythroid cell-specific DNase I hypersensitive sites. The identification of such dominant control regions could have important applications in somatic gene therapy.

Animals↗
PubMed1989

Paget's disease.

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Anus Neoplasms↗