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Biomedical subjects

A Sutton

Publications and source records attributed to A Sutton.

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

Scleroderma fibroblasts promote migration of mononuclear leucocytes across endothelial cell monolayers.

Perivascular infiltrates of inflammatory cells are a hallmark of lesional skin in scleroderma. We have explored the potential for scleroderma fibroblasts to modulate mononuclear leucocyte migration across endothelial cell monolayers in tissue culture, and to regulate expression of endothelial cell adhesion molecules. Fibroblasts were grown from skin biopsies of eight patients with active diffuse cutaneous scleroderma and from four healthy controls. Co-culture and conditioned medium transfer experiments examined the effect of soluble fibroblast products on mononuclear leucocyte (U937) cell migration across endothelial cell (1E-7) monolayers grown on tissue culture inserts. Co-culture of scleroderma, but not control fibroblasts, promoted transendothelial migration of U937 cells. Scleroderma fibroblast-conditioned medium had qualitatively similar effects and equivalent results were obtained using Jurkat-6 (T lymphocyte) cells, and with peripheral blood mononuclear cells from a patient with diffuse cutaneous scleroderma. Promotion of leucocyte migration does not appear to result from increased endothelial adhesion molecule expression, since fibroblast-conditioned medium did not up-regulate endothelial cell expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) or E-selectin. Moreover, leucocyte migration across cytokine-activated endothelial cell layers in co-culture with fibroblasts was less than across resting cells, although the selective effect of scleroderma fibroblast co-culture persisted. Recombinant monocyte chemoattractant protein-1 (MCP-1) or IL-8 increased passage of mononuclear leucocytes across endothelial cell monolayers, whilst anti-MCP-1, but not anti-IL-8 antibodies, significantly reduced the effect of fibroblast conditioned medium. These data suggest that systemic sclerosis (SSc) fibroblasts promote leucocyte migration across endothelial cell monolayers in tissue culture via an MCP-1-dependent mechanism. These findings may be relevant to the perivascular mononuclear leucocyte infiltrates characteristic of early SSc lesions.

Cell Line, Transformed↗
PubMed1997

The Cak1p protein kinase is required at G1/S and G2/M in the budding yeast cell cycle.

The CAK1 gene encodes the major CDK-activating kinase (CAK) in budding yeast and is required for activation of Cdc28p for cell cycle progression from G2 to M phase. Here we describe the isolation of a mutant allele of CAK1 in a synthetic lethal screen with the Sit4 protein phosphatase. Analysis of several different cak1 mutants shows that although the G2 to M transition appears most sensitive to loss of Cak1p function, Cak1p is also required for activation of Cdc28p for progression from G1 into S phase. Further characterization of these mutants suggests that, unlike the CAK identified from higher eukaryotes, Cak1p of budding yeast may not play a role in general transcription. Finally, although Cak1 protein levels and in vitro protein kinase activity do not fluctuate during the cell cycle, at least a fraction of Cak1p associates with higher molecular weight proteins, which may be important for its in vivo function.

CDC28 Protein Kinase, S cerevisiae↗
PubMed1997

A comparison of the effects of tramadol and morphine on gastric emptying in man.

In a previous study using an electrical bioimpedance technique and the paracetamol absorption test, we demonstrated that 0.09 mg.kg-1 of morphine delayed gastric emptying in healthy human volunteers. The aim of this study was to investigate whether analgesic doses of tramadol would cause a delay in gastric emptying similar to conventional opioids. Using the same volunteers and techniques as in our previous study, placebo or tramadol (1 mg.kg-1) was given in a randomised, double-blinded, cross-over placebo-controlled study. Gastric emptying was measured concurrently by a noninvasive epigastric bioimpedance technique and by the paracetamol absorption test. After the ingestion of 500 ml of deionised water plus paracetamol 1.5 g, the mean (SEM) time taken for gastric volume to decrease to 50% (t0.5) was recorded. No difference in gastric emptying rates (t0.5) between placebo, 7.7 (1 min), and tramadol, 9.5 (2 min), was noted. In our previous study, morphine prolonged t0.5 to 21 (3) min (p < 0.03). The maximum concentration and area under the curve of serum paracetamol concentrations following morphine were significantly different from placebo (p < 0.05) and tramadol (p < 0.05). We conclude that tramadol at a dose of 1 mg.kg-1 does not delay gastric emptying in humans.

Absorption↗
PubMed1997

Authority, autonomy, responsibility and authorisation: with specific reference to adolescent mental health practice.

Standards for professional training and practice are defined by accrediting organisations or statutory bodies. These describe the arena in which the practitioner may speak with authority. The sphere of authorised practice is further delineated by the external resources available. Within this explicit framework, unconscious mental processes can affect the professional response in potentially adverse ways. This is particularly important in mental health practice. Professionals must be prepared to examine their own responses on this basis in order to enhance their knowledge of the patient and minimise the possibilities of the patient becoming the victim of the professional's own psychopathology. The maintenance of such a position in an institution or organisation requires a similar process within its structure in order to provide the necessary setting and define the limits of good practice. In this paper, the field of adolescent mental health is specifically examined.

Adolescent↗
PubMed1996

The Cdk-activating kinase (CAK) from budding yeast.

Activation of the cyclin-dependent kinases to promote cell cycle progression requires their association with cyclins as well as phosphorylation of a threonine (residue 161 in human p34cdc2). This phosphorylation is carried out by CAK, the Cdk-activating kinase. We have purified and cloned CAK from S. cerevisiae. Unlike CAKs from other organisms, Cak1p is active as a monomer, has full activity when expressed in E. coli, and is not a component of the basal transcription factor, TFIIH. A temperature-sensitive mutation in CAK1 confers a G2 delay accompanied by low Cdc28p protein kinase activity and shows genetic interactions with altered expression of the gene for the major mitotic cyclin, CLB2. Our data raise the intriguing possibility that p40MO15-cyclin H-MAT1, identified as the predominant CAK in vertebrate cell extracts, may not function as a physiological CAK.

Amino Acid Sequence↗
PubMed1996

Evidence of sensitivity to structural contrasts in the literature on children's language comprehension.

This paper reviews the developmental literature on grammatical knowledge in language comprehension in the preschool years from the perspective of sensitivity to structural contrasts. This concept differs from mastery of individual grammatical structures. Structural sensitivity focuses on increments of partial grammatical knowledge that can be observed in distinctive response patterns to contrasting grammatical structures. Direct evidence of sensitivity to structural contrasts is found in comprehension studies that measured differential responding. Indirect evidence of sensitivity can also be discovered by detailed examination of the data presented in several additional studies. The evidence suggests that there may be a developmental sequence of increasing sensitivity with age to finer distinctions and to more detailed aspects of grammatical structure. The notion of sensitivity to structural contrasts has implications for future research.

Age Factors↗
PubMed1995

Protracted post-traumatic confusional state treated with physostigmine.

A case study is presented of confusion in a head-injured man, lasting for more than 2 years, when intermittent treatment with physostigmine resulted in progressive improvement in both confusion and usable cognitive functions. Aetiological mechanisms and implications for treatment plans are discussed.

Awareness↗
PubMed1992

SIT4 protein phosphatase is required for the normal accumulation of SWI4, CLN1, CLN2, and HCS26 RNAs during late G1.

In Saccharomyces cerevisiae, the RNA levels of the G1 cyclins CLN1, CLN2, and HCS26 increase dramatically during the late G1 phase of the cell cycle. The SIT4 gene, which encodes a serine/threonine protein phosphatase, is required for the normal accumulation of CLN1, CLN2, and HCS26 RNAs during late G1. This requirement for SIT4 in normal G1 cyclin RNA accumulation is at least partly via SWI4. Strains containing mutations in SIT4 are sensitive to the loss of either CLN2 or CLN3 function. At the nonpermissive temperature, temperature-sensitive sit4 strains are blocked for both bud emergence and DNA synthesis. Heterologous expression of CLN2 in the absence of SIT4 function results in DNA synthesis, but most of the cells are still blocked for bud emergence. Therefore, SIT4 is required for at least two late G1 or G1/S functions: the normal accumulation of G1 cyclin RNAs (which is required for DNA synthesis) and some additional function that is required for bud emergence or cell cycle progression through late G1 or G1/S.

Cyclins↗
PubMed1991

Characterization of SIS1, a Saccharomyces cerevisiae homologue of bacterial dnaJ proteins.

The Saccharomyces cerevisiae SIS1 gene was identified as a high copy number suppressor of the slow growth phenotype of strains containing mutations in the SIT4 gene, which encodes a predicted serine/threonine protein phosphatase. The SIS1 protein is similar to bacterial dnaJ proteins in the amino-terminal third and carboxyl-terminal third of the proteins. In contrast, the middle third of SIS1 is not similar to dnaJ proteins. This region of SIS1 contains a glycine/methionine-rich region which, along with more amino-terminal sequences, is required for SIS1 to associate with a protein of apparent molecular mass of 40 kD. The SIS1 gene is essential. Strains limited for the SIS1 protein accumulate cells that appear blocked for migration of the nucleus from the mother cell into the daughter cell. In addition, many of the cells become very large and contain a large vacuole. The SIS1 protein is localized throughout the cell but is more concentrated at the nucleus. About one-fourth of the SIS1 protein is released from a nuclear fraction upon treatment with RNase. We also show that overexpression of YDJ1, another yeast protein with similarity to bacterial dnaJ proteins, can not substitute for SIS1.

Amino Acid Sequence↗
PubMed1991

The SIT4 protein phosphatase functions in late G1 for progression into S phase.

Saccharomyces cerevisiae strains containing temperature-sensitive mutations in the SIT4 protein phosphatase arrest in late G1 at the nonpermissive temperature. Order-of-function analysis shows that SIT4 is required in late G1 for progression into S phase. While the levels of SIT4 do not change in the cell cycle, SIT4 associates with two high-molecular-weight phosphoproteins in a cell-cycle-dependent fashion. In addition, we have identified a polymorphic gene, SSD1, that in some versions can suppress the lethality due to a deletion of SIT4 and can also partially suppress the phenotypic defects due to a null mutation in BCY1. The SSD1 protein is implicated in G1 control and has a region of similarity to the dis3 protein of Schizosaccharomyces pombe. We have also identified a gene, PPH2alpha, that in high copy number can partially suppress the growth defect of sit4 strains. The PPH2 alpha gene encodes a predicted protein that is 80% identical to the catalytic domain of mammalian type 2A protein phosphatases but also has an acidic amino-terminal extension not present in other phosphatases.

Amino Acid Sequence↗
PubMed1988

Rat brain NADPH-dependent diaphorase. A possible relationship to cytochrome P450 reductase.

An enzyme (NADPH-dependent diaphorase) present in rat brain microsomes has been solubilised and shown to utilise both nitrobluetetrazolium and cytochrome c as electron acceptors, when reduced by NADPH. The kinetics of the enzyme have been determined using cytochrome c (Km = 1.3 microM), NADPH (Km = 1.4 microM) and the Vmax (4.7 nmol/min/mg solubilised microsome protein). The subunit Mr is approximately 73,000 D and that of the native enzyme is 170,000-180,000 D, indicating that the enzyme is probably a dimer. Evidence is also provided to show that the enzyme is a flavoprotein, and that it has equimolar amounts of FAD and FMN with respect to the subunit concentration. It seems a possibility that the rat brain diaphorase enzyme may be cytochrome P450 reductase, EC 1.6.2.4.

Animals↗
PubMed1988

Combined enzymatic assay of phosphatidylglycerol and phosphatidylcholine in amniotic fluid.

We present here a combined, quantitative enzymatic procedure for determining amniotic fluid phosphatidylglycerol and phosphatidylcholine and relate these findings to the assessment of fetal lung maturity. Under the assay conditions described phospholipase C specifically hydrolyses phosphatidylglycerol (PG) and phosphatidylcholine (PC) but not sphingomyelin, precluding the need for removal of sphingomyelin prior to analysis. Solvent extraction of the phospholipids from the amniotic fluid is, however, employed to avoid spurious elevation of PG and PC results by endogenous glycerol and choline. Of 45 amniocentesis fluids examined, 28 yielded detectable PG concentrations (greater than 0.5 mumol/l) and all but three of these exhibited PC concentrations in excess of 10 mumol/l. One case of respiratory distress occurred in an infant of 29 wk gestation with severe intrauterine growth retardation. Of the remaining 17 fluids in which PG was undetected enzymatically (less than or equal to 0.5 mumol/l), 14 also contained PC concentrations less than or equal to 10 mumol/l and all six cases of true respiratory distress syndrome came from within this sub-group. Strong correlations between the PC concentration and the lecithin:sphingomyelin ratio, r = 0.85 (p less than 0.001) and the PC and PG concentrations, r = 0.96 (p less than 0.001) were also found.

Amniocentesis↗
PubMed1988

Capsular antibodies induce type-specific phagocytosis of capsulated Staphylococcus aureus by human polymorphonuclear leukocytes.

Capsular types 5 and 8, which account for about 70% of Staphylococcus aureus strains isolated from the blood of patients, resisted in vitro phagocytosis by human polymorphonuclear leukocytes (PMN). Antisera and monoclonal antibody to type 5 and 8 capsular polysaccharides (CPS) induced type-specific in vitro phagocytosis of capsulated organisms by PMN. Antibodies directed against the O-acetyl moiety of the type 8 CPS were more effective in inducing phagocytosis of type 8 organisms by PMN. Either type-specific antiserum or monoclonal antibody reactive with the native O-acetylated type 8 CPS was most effective in inducing in vitro phagocytosis of type 8 organisms by PMN. These results provide further evidence that CPS of S. aureus are associated with host immunity to this organism.

Antibodies, Bacterial↗