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M Coles

Publications and source records attributed to M Coles.

At least 37 records · Page 2Linked to original sources
PubMed1998

The developmental fate of T cells is critically influenced by TCRgammadelta expression.

Differentiation of gammadelta and alphabeta T cells from a common precursor cell depends on productive rearrangement and expression of TCRgammadelta or TCRbeta genes, but whether it is an instructive or a stochastic mechanism that is responsible for this process is unclear. We report that expression of the productively rearranged TCRgamma transgene competitively inhibits alphabeta thymocyte development under conditions where TCRbeta gene rearrangement is limiting. The status of TCRdelta gene rearrangements in the remaining alphabeta-lineage cells indicates that the effect is mediated by the intact gammadelta receptor. Paradoxically, in TCRbeta-/- mice, gammadelta receptor expression can also drive differentiation of some alphabeta-lineage cells. To resolve this paradox, we provide evidence for a minor population of gammadelta-dependent alphabeta-lineage cells in normal mice. The results indicate that the T cell lineage commitment process is either error-prone or stochastic.

Animals↗
PubMed1998

Hierarchical interactions of control elements determine CD8alpha gene expression in subsets of thymocytes and peripheral T cells.

CD4 and CD8 are crucial for the development and function of T cells. An intergenic deoxyribonuclease I hypersensitive site region (cluster CIII) directs expression in mature CD8 T cells only. Here, we show that two further independent regions from the CD8 gene locus in conjunction with cluster CIII restore transgene expression in appropriate immature thymocytes. Deletion of two of the intergenic cluster CIII DNaseI-HSS in homozygous mutant mice affects expression of CD8alphaalpha homodimers on intraepithelial T cells (IEL), particularly on the gammadeltaTCR+ subset. Surprisingly, none of the thymocyte or peripheral alphabetaTCR T cell subsets are affected by this mutation, indicating hierarchical activation of these elements within the different T cell subsets.

Alleles↗
PubMed1997

The Bridgeport Hospital experience with autologous transfusion in orthopedic surgery.

The transfusion records of 341 orthopedic patients who donated blood preoperatively in the years 1992 and 1993 were audited to review the transfusion practices associated with the surgical procedures. The study sample underwent 182 total knee (TKA), 123 total hip (THA) arthroplasties, and 33 laminectomies with fusion (LAM) and 3 without. Data used were age, gender, predonation hemoglobin concentration (Hbd), initial (Hbi) and final (Hbf) hemoglobin concentration, surgical procedure, surgical blood order (SBO), and estimated blood loss (EBL). We analyzed for means and associations and differences between covariates. The means of EBL (mL), transfused units, donated units, Hbi, (g/dL), Hbd, and Hbf (g/dL) for the most common procedures were: TKA--272, 1.1, 2.1, 10.4, 13.9, and 10.1; THA--951, 2.3, 2.4, 9.4, 13.8, and 9.9; and LAM--589, 1.5, 2.2, 12.0, 14.6, and 11.2. Phlebotomies for procedures with minimal blood loss, as for total knee arthroplasties, result in wastage. Autodonation under such circumstances takes patients to an unnecessary low hemoglobin concentration prior to either retransfusing the blood taken or discarding part of it. The number of preoperative autologous units donated can be reduced if predonation hemoglobin concentration is > 15 g/dL and expected blood loss is not > 2 g.

Blood Loss, Surgical↗
PubMed1994

The solution structure of a monocyclic analogue of endothelin [1,15 Aba]-ET-1, determined by 1H NMR spectroscopy.

The structure of [1,15 Aba]-ET-1 has been determined in aqueous acetonitrile solution (10% acetonitrile, 1.5% acetic acid). [1,15 Aba]-ET-1 is an analogue of endothelin (ET-1) in which the disulfide bridge linking residues 1 and 15 has been removed by replacement of the cysteine residues with the mimicking group alpha-aminobutyric acid (Aba). The structure has been determined by 1H NMR spectroscopy and simulated annealing calculations based on NOE constraints, 3JHN-H alpha scalar coupling constants, and amide-proton-exchange rates. Distance information was extracted from 2D NOESY spectra using full-relaxation matrix techniques (utilizing the program DISCON). The structure can be described in terms of three defined segments: a type I beta-turn over residues 5-8, a helix over residues 9-16, and a structured C-terminus over residues 17-21. The data indicate that some conformational averaging occurs throughout the peptide, particularly for residues 1-4 in the N-terminus, where no preferred conformation is present. The structure is compared with those previously reported for native ET-1. In general, removal of the disulfide bridge does not cause a major structural change in the helical and turn regions of the sequence, but increased structural disorder is noted at the N-terminus. The implications of the monocyclic analogue's conformation for the pharmacological activity and the ETA/ETB selectivity of the endothelin family of peptides and analogues are described. The N-terminus is proposed to be a key structural region for differentiation of binding activity at the ETA and ETB receptor sites.

Amino Acid Sequence↗
PubMed1994

THE POSITION-DEPENDENT NATURE OF POSTURAL RESISTANCE REFLEXES IN THE LOCUST

The resistance reflexes of tibial extensor and flexor muscles, of all six legs in the locust, show changes in gain at different femur­tibia angles (FTA). In all muscles the gain is high for small angles (near full flexion) and low for large angles (near full extension, approximately 160 °). An exception occurs in the mesothoracic flexor muscle, which shows two modes: one as above and another in which maximum gain occurs at 100­120 ° FTA. The position-dependent character is evident at each stage of the reflex pathway: motor neurone, non-spiking interneurone and femoral chordotonal organ (the afferent source of the reflex). We conclude that position-dependency originates from a decrease in the number of phasic femoral chordotonal organ neurones sensitive to joint movement as larger FTAs are approached. Position-dependency is only roughly correlated with the postural FTAs most commonly observed in the meso- and metathoracic legs of unrestrained resting locusts; no such correlation was evident for prothoracic legs. We propose that the major role of position-dependency is to allow resistance reflexes efficiently to counter torque introduced onto the femur­tibia joint by perturbations in the horizontal plane when the insect rests on a horizontal substratum and in the vertical plane when it rests on a vertical substratum.

Journal Article↗
PubMed1993

A conformational study by 1H NMR of a cyclic pentapeptide antagonist of endothelin.

The selective endothelin antagonist cyclo(D-Glu-L-Ala-D-allo-Ile-L-Leu-D-Trp, BE18257B) has been synthesized via solid-phase methods and its solution conformation determined by NMR spectroscopy and simulated annealing calculations based on NOE constraints. Additional information used in the structure determination included coupling constants and chemical-shift measurements as a function of temperature. The chemical shifts of two of the NH protons (D-Glu and D-Ile) exhibit low sensitivity to changes in temperature, indicating their involvement in hydrogen-bonded interactions. The main features of interest in the solution conformation include the presence of both a type-II beta-turn and an inverse gamma-turn, with central hydrogen bonds between HN of D-Glu1 and the C = O of D-allo-Ile3 and between HN of D-allo-Ile3 and the C = O of D-Glu1. The correlation of this solution conformation to the peptide's biological activity is discussed. The data are also compared with recently derived structures for BQ123, cyclo(D-Asp-L-Pro-D-Val-L-Leu-D-Trp), another highly potent endothelin antagonist. The backbone conformations of the two cyclic peptides are found to be similar. Comparisons with literature structure-activity data suggest that these peptides may mimic structural features of the C-terminal tail of the endothelins.

Amino Acid Sequence↗
PubMed1993

Positive selection of V beta 8+ CD4-8- thymocytes by class I molecules expressed by hematopoietic cells.

A small subset of T cells of mature phenotype express the alpha/beta T cell receptor, but not CD4 and CD8 coreceptors (alpha/beta double-negative [DN] cells). The repertoire of V beta usage of alpha/beta DN cells is strongly biased towards V beta 8 expression, suggesting that the formation of the population is subject to selection. We now report that deficiency of class I expression leads to a strongly depressed frequency of V beta 8+ DN cells, but has little effect on V beta 8- DN cells. Studies of hematopoietic chimeras between class I+ and class I- mice demonstrated that expression of class I molecules by hematopoietic cells is necessary and sufficient for selection of most V beta 8 DN cells. The lack of a role for class I expression by thymic epithelial cells suggests that the mechanism of selection of these cells by class I differs significantly from the mechanism of selection of conventional T cells. Models to explain the selection of these cells as well as their possible function in vivo are discussed.

Animals↗
PubMed1993

1,25-Dihydroxy vitamin D3 and 12-O-tetradecanoyl phorbol-13-acetate synergistically induce monocytic cell differentiation: FOS and RB expression.

1,25-dihydroxy vitamin D3 and 12-O-tetradecanoyl phorbol-13-acetate (TPA) interact synergistically to induce monocytic differentiation of U937 histiocytic lymphoma cells. Addition of TPA causes an otherwise ineffective dose of 1,25-dihydroxy vitamin D3 to induce differentiation. The induced differentiation depends on the simultaneous (vs. sequential) presence of both agents. The kinetics of induced differentiation are consistent with a G1 specific cellular response to initiate the metabolic cascade culminating in cell differentiation. The induced differentiation occurs with down-regulation of c-fos protein and an accompanying up-regulation of RB protein expression, consistent with a possible need for up-regulated RB expression to maintain a given differentiated phenotype and suppress transcriptional activators that might typically be associated with proliferation.

Antigens, Differentiation, Myelomonocytic↗
PubMed1993

Surgical management of advanced squamous cell skin cancers.

Squamous cell cancer of the skin usually follows prolonged exposure to known carcinogens including ultraviolet light, ionizing radiation, chronic infection or irritation, chemicals, and immunologic suppression. The majority of squamous cell skin cancers metastasize infrequently and can be cured with aggressive wide local excision. However, on occasion they can be quite aggressive locally, with or without associated distant metastasis, and may require a radical surgical approach. We report a series of four male patients covering the spectrum of this disease with the following distribution: lower pole of the right ear, right posterior thigh below gluteal fold with positive inguinal nodes, lateral aspect of the foot with bone involvement, and as an incidental finding in a pilonidal cyst. We conclude that one should not hesitate to proceed with aggressive surgical resection as it may provide the only chance for cure. Finally, one should always look for lymph node metastasis, particularly with large (> 5 cm) lesions adjacent to a regional lymph node drainage basin.

Aged↗
PubMed1990

An outbreak of Salmonella saint-paul infection associated with beansprouts.

In March 1988, there was an outbreak of infection by a strain of Salmonella saint-paul with a distinctive antigenic marker. A total of 143 reports were received between 1 March and 7 June. Preliminary investigations suggested that raw beansprouts were a possible source of infection and a case-control study confirmed the association. S. saint-paul of the epidemic type was isolated from samples of beansprouts on retail sale in different cities in the United Kingdom and from mung bean seeds on the premises of the producer who was most strongly associated with cases. In addition, Salmonella virchow PT34 was isolated from samples of raw beansprouts and was subsequently associated with seven cases of infection. Four other serotypes of salmonella were also isolated from beansprouts. On 8 April the public were advised to boil beansprouts for 15 seconds before consumption, and the premises of the one producer associated with many cases were closed. As a result of these actions there was a significant decrease in the number of infections with S. saint-paul.

Adolescent↗
PubMed1989

An unusual case of dermatofibrosarcoma protuberans.

A dermatofibrosarcoma protuberans involving the thumb of a nondominant hand is reported and represents the first case reported in this location. Dermatofibrosarcoma protuberans is a soft tissue neoplasm. It is a slow growing, locally aggressive fibrous tumor that occurs with equal frequency on the chest, abdomen, back, and proximal aspect of the extremities. Only two cases involving the hand are reported in the literature.

Adult↗