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Biomedical subjects

G C Hart

Publications and source records attributed to G C Hart.

9 recordsLinked to original sources
PubMed1991

Regulation of the Xenopus laevis transcription factor IIIA gene during oogenesis and early embryogenesis: negative elements repress the O-TFIIIA promoter in embryonic cells.

Expression of the Xenopus laevis transcription factor IIIA (TFIIIA) gene is developmentally regulated. In this study we have used defined nucleotide mutations to map cis-elements involved in transcriptional regulation of the promoter for oocyte-TFIIIA (O-TFIIIA) in stage II-IV oocytes, stage VI oocytes, and tail bud embryos. During oogenesis O-TFIIIA mRNA levels decline 5- to 10-fold, and during early embryogenesis O-TFIIIA mRNA levels decline approximately 10(6)-fold per cell. In stage II-IV oocytes we find evidence for at least three distinct positive-acting cis-elements that contribute to the efficient expression of O-TFIIIA. These elements are located between -1800 to -425, -280 to -235, and -235 to -220. The most distal cis-element(s) appears to be developmentally regulated during oogenesis, since deletion of nucleotide sequences from -1800 to -425 does not reduce O-TFIIIA expression in stage VI oocytes. However, the two cis-elements located between -280 to -235 and -235 to -220 are required for the efficient expression of O-TFIIIA in stage VI oocytes. In tail bud embryos we find evidence for several developmentally regulated positive and negative cis-elements involved in O-TFIIIA expression. The positive-acting cis-elements are located between -159 to -110 and -110 to -58. The negative-acting cis-elements are found at positions -425 to -350 and -200 to -159. In addition to the developmentally regulated elements controlling O-TFIIIA gene expression in tail bud embryos, the positive-acting cis-elements active during oogenesis (located between -280 to -235 and -235 to -220) are also active during early embryogenesis. Thus, transcription from the O-TFIIIA promoter appears to be regulated by a combination of constitutive positive factors and developmentally regulated positive and negative factors during oogenesis and early embryogenesis.

Animals↗
PubMed1990

Activities of 3'-azido-3'-deoxythymidine nucleotide dimers in primary lymphocytes infected with human immunodeficiency virus type 1.

The relative antiviral potencies of five nucleotide heterodimers of 3'-azido-3'-deoxythymidine (AZT), 3'-azido-3'-deoxythymidilyl-(5',5')-2'-3'-dideoxy-5'-adenylic acid (AZT-P-ddA), 3'-azido-3'-deoxythymidilyl-(5',5')-2',3'-dideoxy-5'-inosinic acid (AZT-P-ddI), and the corresponding 2-cyanoethyl congeners AZT-P(CyE)-ddA and AZT-P(CyE)-ddI, were determined in primary human peripheral blood mononuclear cells infected with human immunodeficiency virus type 1. The homodimer 3'-azido-3'-deoxythymidilyl-(5',5')-3'-azido-3'-deoxythymidilic acid (AZT-P-AZT) was also included for comparison. The potencies of the compounds were AZT-P-ddA greater than or equal to AZT-P-ddI greater than AZT-P(CyE)-ddA greater than or equal to AZT-P(CyE)-ddI greater than or equal to AZT greater than AZT-P-AZT. Whereas AZT-P-ddA and AZT-P-ddI had in vitro therapeutic indices greater than that of AZT, the homodimer of AZT had a low therapeutic index. AZT-P-ddI exhibited the lowest toxicity in peripheral blood mononuclear, Vero, or CEM cells. Combination studies between AZT and 2',3'-dideoxyinosine (ddI) at nontoxic concentrations indicated a synergistic interaction at a drug ratio of 1:100. At higher ratios (1:500 and 1:1,000), the interactions were synergistic only at concentrations that produced up to 75% virus inhibition. At higher levels of antiviral effects, this combination was antagonistic, as determined by the multiple drug effect analysis method. AZT-P-ddI was about 10-fold less toxic than AZT to human granulocyte-macrophage progenitor cells. However, no significant difference was apparent when the compounds were evaluated against cells of the erythroid lineage. The greater antiviral activity and lower toxicity of this compound could not be attributed to the extracellular decomposition of the dimer in media at physiological temperature and pH. However, in acidic solutions, AZT-P-ddI decomposed in a pH-dependent manner. Advanced preclinical studies with this heterodimer of two clinically effective antiretroviral agents should be considered.

Cell Survival↗
PubMed1989

Dynamic radionuclide imaging with 99mTc-sucralfate in the detection of oesophageal ulceration.

Standard oesophageal scintigraphic techniques using 99mTc-colloids rarely identify oesophageal mucosal damage. Sucralfate can be labelled with 99mTc for the detection of oesophageal mucosal ulceration. This method uses two separate supine swallows of 10 MBq 99mTc-colloid in 10 ml, followed by a single supine swallow of 30 MBq 99mTc-sucralfate. The data are processed to give time-activity curves, mean transit times and condensed dynamic images. When oesophageal ulceration is detected, the time-activity curves using sucralfate show residual activity in the oesophagus after the transit time indicated by the colloid swallow. The condensed dynamic image shows a persistence of activity at the level of the ulceration. Erect sucralfate images taken immediately after the dynamic sequence show no oesophageal localisation. The results from a study of 62 patients have shown excellent correlation between the dynamic 99mTc-sucralfate images and endoscopy findings. Sequential sucralfate studies for healing also correlate well. The use of labelled sucralfate to detect oesophageal ulceration could modify the indications for endoscopy in gastrooesophageal reflux disease.

Adolescent↗
PubMed1988

Improved sensitivity in bone scintigraphy using quantitative spinal profile analysis.

Full-length skeletal scintiscans were acquired onto a data processor in a series of 256 X 256 matrices. A series of interactive computer programs enables the operator to select profiles down the spine and to standardize them by interpolation to a standard length and by normalization to a given count level. The counts within any section of a profile can then be calculated and the profile examined for any significant deviation from a reference 'normal' curve. In a study of 68 patients, 66% of the spinal profiles were judged abnormal, compared with 26% of scans assessed by visual inspection alone. Of 14 patients with positive profiles and negative or equivocal visually assessed scans, 11 had developed metastases within 14 months of the scan. All five patients with positive profile and raised alkaline phosphatase have died of metastatic disease. The technique appears to increase the sensitivity of bone scintigraphy.

Bone Neoplasms↗
PubMed1987

The random walk function in the analysis of time-activity curves from dynamic radionuclide studies.

The random walk function is a mathematical function derived from studies of the mass transport and flow of diffusible materials through tubes. Approximations to the function were first used some time ago in the field of cardiac tracer dilution curves, but in the absence of rapid and reproducible curve fitting the method never became commonplace. The current study uses the latest curve-fitting techniques and shows how the method may be used with precision in the analysis of time-activity curves from dynamic oesophageal and blood flow studies. The physiological basis of the method is given and parameters obtained which relate to both the rate of flow and the local dispersion of the bolus.

Esophagus↗
PubMed1986

Moiré interference in gamma camera quality assurance images.

Moiré interference effects have been noted in gamma camera images for some time. Recent work has shown that the effects are still prevalent with the current generation of cameras, though apparently dependent upon collimator design. All previous work has been related to bar phantom images only. This paper also demonstrates a variety of moiré effects using the Anger "pie" phantom. Some of the principles underlying moiré interference as they apply to gamma cameras are given and possible uses of the effects are discussed, as well as the limitations they impose upon the use of certain test objects in routine quality assurance testing.

Interferometry↗