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Biomedical subjects

G Gill

Publications and source records attributed to G Gill.

At least 73 records · Page 4Linked to original sources
PubMed1994

Transcriptional initiation. Taking the initiative.

Recent results suggest that there may be several ways to assemble active transcription complexes containing RNA polymerase II, and highlight the potential importance of core promoter elements in gene regulation.

Animals↗
PubMed1994

The cAMP-regulated transcription factor CREB interacts with a component of the TFIID complex.

cAMP regulates the expression of a number of genes through the protein kinase A-mediated phosphorylation of CREB at Ser-133. The effects of Ser-133 phosphorylation appear to be primarily transmitted through a modulatory kinase-inducible domain in CREB that functions cooperatively with a 120-amino acid glutamine-rich region (Q2) to stimulate transcription. Indeed, the kinase-inducible domain activity alone is not sufficient to sustain a transcriptional response as illustrated by the CREM family of repressors, which contain the kinase-inducible domain but lack the Q2 region. Here we demonstrate that Q2 functions as a potent constitutive activator in vitro. The transcription factor TFIID fraction supports transcriptional activation by Q2, although the "TATA" binding protein alone does not, suggesting that other components of the TFIID complex mediate the response to CREB Q2. In fact, Q2 associates with the TATA binding protein-associated factor dTAFII110. As the transcriptionally inactive CREM alpha and beta proteins lack sequences in Q2 that are necessary for binding dTAFII110, our results suggest that these proteins may repress transcription because they are unable to interact with the basal transcription complex.

Cyclic AMP↗
PubMed1994

A glutamine-rich hydrophobic patch in transcription factor Sp1 contacts the dTAFII110 component of the Drosophila TFIID complex and mediates transcriptional activation.

Activation of transcription by the promoter-specific factor Sp1 requires coactivators that are tightly associated with the TATA-box-binding protein (TBP) in the TFIID complex. Recent work has shown that the two glutamine-rich activation domains of Sp1, A and B, can interact with at least one component of this complex, the TBP-associated factor dTAFII110. Here we report the mapping of a region of Sp1 with alternating glutamine and hydrophobic residues which is required for the interaction with dTAFII110 and is important for mediating transcriptional activation. Substitution of bulky hydrophobic residues within this region decreased both interaction with dTAFII110 and transcriptional activation in Drosophila cells. In contrast, mutation of glutamine residues in this region had no effect. Thus, the strength of the Sp1-TAF interaction correlates with the potency of Sp1 as a transcriptional activator, indicating that this activator-TAF interaction is an important part of the mechanism of transcriptional activation. Sequence comparison of three activation domains shown to bind dTAFII110 suggests that different activators that utilize dTAFII110 as a coactivator may share common sequence features that we have determined to be important for the Sp1-dTAFII110 interaction.

Amino Acid Sequence↗
PubMed1994

A small cell bronchogenic carcinoma associated with tumoral hypophosphataemia and inappropriate antidiuresis.

A patient is described with small cell carcinoma of the lung, associated with profound hypophosphataemia and hyponatraemia. Increased phosphate excretion and inappropriately high urine osmolality were observed. The abnormalities are consistent with tumoral hypophosphataemia and inappropriate antidiuresis. These tumour-related metabolic abnormalities have only been described once before with this malignancy.

Aged↗
PubMed1993

Molecular cloning and functional analysis of Drosophila TAF110 reveal properties expected of coactivators.

The general transcription factor TFIID is a multiprotein complex containing the TATA-binding protein and several associated factors (TAFs), some of which may function as coactivators that are essential for activated, but not basal, transcription. Here we describe the isolation and characterization of the first gene encoding a TAF protein. The deduced amino acid sequence of TAF110 revealed the presence of several glutamine- and serine/threonine-rich regions reminiscent of the protein-protein interaction domains of the regulatory transcription factor Sp1 that are involved in transcription activation and multimerization. In both Drosophila cells and yeast, TAF110 specifically interacts with the glutamine-rich activation domains of Sp1. Moreover, purified Sp1 selectively binds recombinant TAF110 in vitro. These findings taken together suggest that TAF110 may function as a coactivator by serving as a site of protein-protein contact between activators like Sp1 and the TFIID complex.

Amino Acid Sequence↗
PubMed1993

The importance of bleomycin in combination chemotherapy for good-prognosis germ cell carcinoma. Australasian Germ Cell Trial Group.

PURPOSE: In an effort to maintain the excellent long-term results achieved with combination chemotherapy for good-prognosis germ cell carcinoma, but to reduce the toxicities encountered, a randomized trial was conducted comparing cisplatin and vinblastine with or without bleomycin. PATIENTS AND METHODS: Two hundred eighteen assessable patients with a good prognosis were randomized to receive induction chemotherapy with cisplatin 100 mg/m2 intravenously (IV) day 1 and vinblastine 6 mg/m2 IV days 1 and 2 every 3 weeks (PV) with or without bleomycin 30 mg intramuscularly (IM) weekly (PVB) for a maximum of 12 weeks. Once maximum response was achieved, patients with a complete remission (CR) received two courses of consolidation chemotherapy, while those with residual abnormalities and normal tumor markers underwent surgical resection whenever possible. RESULTS: Toxicities encountered in this study were clearly greater for those patients who received bleomycin, with significantly more leukopenia, thrombocytopenia, anemia, alopecia, and renal and pulmonary toxicities. The proportion of patients who achieved CR and had no evidence of disease (resection of all viable malignancy) was 89% for PV and 94% for PVB (P = .29). After a minimum of 4 years of follow-up, relapses have occurred in 7% of patients who received PV and 5% who received PVB. A total of five patients on each therapy arm were successfully treated with further salvage chemotherapy and surgery. Thus, deaths from progressive malignancy have occurred in 15% of patients on PV and 5% on PVB (P = .02), a rate that was partly offset by the higher proportion of toxic deaths with PVB (P = .06). CONCLUSION: Despite the toxicities encountered with bleomycin in cisplatin-based combination chemotherapy for these patients, complete deletion of this drug compromises therapeutic efficacy.

Adolescent↗
PubMed1993

Transient global amnesia after cerebral angiography with iohexol.

Transient global amnesia is an unusual neurologic phenomenon that occasionally occurs after angiography, usually of the cerebral vessels. It represents a benign event, and normal function is ultimately restored, but the amnesia may be frightening for both the patient and the physician until its nature is recognized. The authors describe two cases of transient global amnesia occurring after cerebral angiography with iohexol, outline the criteria for the diagnosis and discuss the proposed mechanism of the phenomenon.

Adult↗
PubMed1992

Selection of dental procedures for antibiotic prophylaxis against infective endocarditis.

A dental source of infection remains the most common identifiable risk factor in infective endocarditis and this may be particularly important in patients at 'high risk'. We therefore performed a questionnaire survey of dental practitioners to assess acceptance of The British Society of Antimicrobial Chemotherapy (BSAC) recommendations, especially with regards to selection of dental procedures for antibiotic prophylaxis. The results showed that the dental practitioners surveyed treated the 'high risk' patient group differently by extending the range of dental procedures covered by antibiotics but the BSAC only recommend that they be treated differently by hospital treatment and/or parenteral antibiotics. This must be an area of concern and deserves further attention, especially with regards to the need for wider publicity and the range of dental procedures that should be covered in the 'high risk' group where morbidity and mortality from infective endocarditis are higher.

Anti-Bacterial Agents↗