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Biomedical subjects

J Sherlock

Publications and source records attributed to J Sherlock.

30 records · Page 2Linked to original sources
PubMed1994

Rapid molecular method for prenatal detection of Down's syndrome.

We have evaluated a rapid method that allows prenatal detection of Down's syndrome in less than 24 hours. DNA from uncultured amniotic fluid, fetal blood, and tissue samples was amplified with the small tandem repeat (STR) marker D21S11. Quantitative analysis of fluorescent STR products with evaluation of their sizes provided clear evidence for trisomy 21. Whilst most normal samples showed two amplification peaks of equal size, Down's syndrome samples were characterised by either three STR peaks or two peaks with a ratio of 2:1. Co-amplification with a non-polymorphic sequence allowed analysis of samples that were homozygous for the 21-derived STRs.

Amniotic Fluid↗
PubMed1993

Signaling events initiated by transforming growth factor-beta 1 that require Gi alpha 1.

Transforming growth factor-beta 1 (TGF-beta 1) initiates a series of signaling events leading to diverse cell type-specific effects on proliferation and morphology. The multiple effects of TGF-beta 1 are not due to selective expression of receptor subtypes, but rather probably reflect cell-specific expression of downstream components of the particular signaling system. To address this possibility and to identify specific signaling pathways activated by TGF-beta 1, we attempted to restore cell responsiveness to the cytokine by introducing various intracellular signal transducers in NIH-3T3 fibroblasts, a cell line that is minimally responsive to TGF-beta 1. In NIH-3T3 fibroblasts stably transfected with Gi alpha 1 cDNA, TGF-beta 1 induced a reversible morphological transformation that was identical to the effect of this cytokine in indicator cells such as AKR-2B fibroblasts. Gi alpha 1 transfectants also exhibited mitogenic hyperresponsiveness to TGF-beta 1. TGF-beta 1 does not elicit these responses in control nontransfected fibroblasts or cells transfected with the guanine nucleotide-binding protein Go alpha 1. The response to TGF-beta 1 in Gi alpha 1 transfectants is blocked by pertussis toxin and is lost in Gi alpha 1 transfectants that have spontaneously reverted and no longer express Gi alpha 1. These data indicate that the expression of the guanine nucleotide-binding protein Gi alpha 1, normally absent in these cells, confers cell sensitivity to TGF-beta 1.

3T3 Cells↗
PubMed1984

Determinants of oxygenation during hemodialysis and related procedures. A report of data acquired under varying conditions and a review of the literature.

A decrease in arterial oxygen tension during hemodialysis has been attributed to a number of factors. In order to more completely define these factors, we studied respiratory gas exchange, arterial blood gases and pH, and dialyzer flux of CO2 during pure ultrafiltration, three types of acetate dialysis, and sorbent regenerated bicarbonate dialysis in which the dialysate concentration of bicarbonate varies. Changes due to position and extracorporeal circulation of a 300-ml volume of blood (sham dialysis) were studied for any effect contributing to the hypoxemia noted with circulation through the membrane and variation in dialysate. Alveolar oxygen tension (PAO2) is calculated by the equation PAO2 = PIO2-PaCO2 (FIO2 + 1-FIO2/RE). RE is the ratio of CO2 excretion by the lung (VCO2) to oxygen consumption (VO2). RE equals RQ (metabolic quotient) when no extrapulmonary CO2 losses occur. Normals in a lounge chair had no change in RE and PAO2. RE decreased to 0.75 during sham dialysis and PAO2 decreased. During pure ultrafiltration RE decreased due to a decrease in VO2 and VCO2 with proportionately greater decrease in VCO2. PAO2 decreased accordingly. Acetate dialysis produced an increase in oxygen consumption without a proportional increase in CO2 excretion and both RQ and RE decreased. When PAO2 decreased during any of these procedures, arterial oxygen tension (PaO2) decreased without a change in A-aO2 gradient. No changes in PaCO2 were noted. RQ did not change during bicarbonate dialysis. At high bicarbonate dialysate concentrations, however, PaCO2 increased and PAO2 decreased. The major reason for hypoxemia during acetate dialysis is a decrease in alveolar oxygen tension due to changes in metabolism and a decrease in pulmonary CO2 excretion when CO2 is lost from the dialyzer. The increasing pH may contribute to the metabolic change during acetate dialysis and the hypoventilation during bicarbonate dialysis. There is little evidence to support an effect of pulmonary capillary obstruction or changes in oxyhemoglobin association on the decrease in arterial oxygen tension observed.

Acetates↗
PubMed1984

Elevation of mercury in human blood from controlled chronic ingestion of methylmercury in fish.

The relationship between the intake of methylmercury in fish and mercury in blood has been investigated in man. The intakes of methylmercury were carefully controlled and lay in the range 40-230 micrograms/day, the Provisional Tolerable Weekly Intake is equivalent to about 30 micrograms/day. The results indicate that a daily intake of 1 microgram methylmercury would, at equilibrium, produce a blood mercury concentration of 0.8 micrograms/kg. There is a good close-to-linear correlation between methylmercury intake and blood mercury concentrations within the wide range of intakes employed.

Adult↗
PubMed1982

Assessment of lead intakes and dose-response for a population in Ayr exposed to a plumbosolvent water supply.

1 Dietary lead intakes, blood lead concentrations and water lead concentrations were measured and their relationships investigated for 31 adults and 11 infants living in dwellings in Ayr with lead plumbing. 2 For adults, some lead intakes were found to be higher than the provisional tolerable weekly intake for lead, and for infants most of the intakes were high. 3 A cube root relationship fitted the data on blood lead versus water lead better than a linear relationship. Similarly, blood lead varied with the cube root of weekly dietary lead intake. 4 These cube root equations provided a means of estimating the impact on blood lead concentrations of exposure to lead from food and water. If cube root relationships correctly describe the association between these parameters, then the curve fitted to the results for adults indicates that the contribution to the blood lead concentrations from sources other than the diet and water was relatively small.

Adult↗
PubMedDate not supplied

First trimester prenatal diagnosis using transcervical cells: an evaluation.

Human trophoblastic cells can be retrieved by minimally invasive procedures from the endocervical canal between between 6 and 15 weeks gestation. The incidence with which fetal cells can be detected in transcervical cell (TCC) samples varies according to the method of collection and the molecular techniques employed for their identification. Fluorescence in-situ hybridization (FISH) and polymerase chain reaction (PCR) assays have been successfully used to detect aneuploidies and Y-derived DNA sequences in TCC samples obtained from male fetuses. Chromosome specific polymorphic DNA sequences (small tandem repeats) have also been employed to identify, by quantitative fluorescent PCR, fetal cells in TCC samples. Furthermore, Rh(D) sequences have been amplified in samples retrieved from Rh(D) negative mothers. Preliminary results also suggest that prenatal diagnoses of thalassaemia and sickle cell anaemia can be performed on clumps of cells isolated from TCC samples. Overall systematic studies allow optimism about the possibility of using TCC samples for the prenatal diagnosis of selected inherited disorders.

Cervix Uteri↗