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Biomedical subjects

S Howes

Publications and source records attributed to S Howes.

9 recordsLinked to original sources

Isolated P-selectin glycoprotein ligand-1 dynamic adhesion to P- and E-selectin.

Leukocyte adhesion to vascular endothelium under flow involves an adhesion cascade consisting of multiple receptor pairs that may function in an overlapping fashion. P-selectin glycoprotein ligand-1 (PSGL-1) and L-selectin have been implicated in neutrophil adhesion to P- and E-selectin under flow conditions. To study, in isolation, the interaction of PSGL-1 with P- and E-selectin under flow, we developed an in vitro model in which various recombinant regions of extracellular PSGL-1 were coupled to 10-microm-diameter microspheres. In a parallel plate chamber with well defined flow conditions, live time video microscopy analyses revealed that microspheres coated with PSGL-1 attached and rolled on 4-h tumor necrosis factor-alpha-activated endothelial cell monolayers, which express high levels of E-selectin, and CHO monolayers stably expressing E- or P-selectin. Further studies using CHO-E and -P monolayers demonstrate that the first 19 amino acids of PSGL-1 are sufficient for attachment and rolling on both E- and P-selectin and suggest that a sialyl Lewis x-containing glycan at Threonine-16 is critical for this sequence of amino acids to mediate attachment to E- and P-selectin. The data also demonstrate that a sulfated, anionic polypeptide segment within the amino terminus of PSGL-1 is necessary for PSGL-1-mediated attachment to P- but not to E-selectin. In addition, the results suggest that PSGL-1 has more than one binding site for E-selectin: one site located within the first 19 amino acids of PSGL-1 and one or more sites located between amino acids 19 through 148.

Animals

The effect of castanospermine on the synthesis of synaptic glycoproteins by rat brain slices.

Slices were prepared from rat forebrains and the incorporation of [3H]mannose and [35S]methionine into proteins and glycoproteins determined. The incorporation of methionine continued to increase for up to 8 hours whereas mannose incorporation was maximal between 2 and 4 hours and declined thereafter. Glycopeptides prepared by pronase digestion of [3H]mannose-labeled glycoproteins were digested with endoglucosaminidase H (endo H) and analysed by gel filtration. The major endo H-sensitive oligosaccharide eluted in a position similar to standard Man8GlcNAc. In the presence of castanospermine, which inhibits glucosidase I, the first enzymatic step in the processing of N-linked oligosaccharides, a new endo H-sensitive glycan similar in size to standard Glc3Man9GlcNAc2 accumulated. Synaptic membranes (SMs) were isolated from slices which had been incubated with either [3H]mannose or [35S]methionine in the presence and absence of castanospermine. In the presence of inhibitor the relative incorporation of [3H]mannose into high-mannose glycans of synaptic glycoproteins was increased. The incorporation of newly synthesized, [35S] methionine-labeled, Con A-binding glycoproteins into SMs was not affected by the addition of inhibitor. Many of the glycoproteins synthesized in the presence of castanospermine exhibited a decreased electrophoretic mobility indicative of the presence of altered oligosaccharide chains. The results indicate that changes in oligosaccharide composition produced by castanospermine had little effect on the subsequent transport and incorporation of glycoproteins into synaptic membranes.

Alkaloids

Influence of angiotensin II on the concentration of arterial plasma electrolytes in anaesthetized sheep.

Angiotensin II and I significantly raised potassium and lowered sodium and chloride ion concentrations in arterial plasma, with peak changes occurring in the first 2 min of a 6-min infusion period. The octapeptide increased the arterial K+ level in a dose-dependent manner, but the response showed tachyphylaxis when multiple infusions of 6-min duration were administered after a recovery interval of only 5 min. Raising the arterial blood pressure by 20-33 mmHg with adrenaline and noradrenaline failed to account for the increase in arterial plasma K+ concentration produced by the two peptides. These findings, in particular the rise in K+ concentration, are discussed in relation to possible mechanisms by which angiotensin II affects arteriolar tone.

Angiotensin I

Substance misuse and psychiatric comorbidity: an overview of the OPCS National Psychiatric Morbidity Survey.

There have been a number of national surveys of psychiatric morbidity which have included questions on drugs, alcohol and tobacco. These surveys have helped delineate the overlap between substance use and dependence and other psychological morbidity. There is a strong association reported between high substance consumption and other measures of psychological problems. This article provides an overview of a national household survey, a survey of institutional residents with psychiatric disorders and a national survey of a homeless population. All three surveys used comprehensive and complex sampling strategies and lay interviewers to conduct structured diagnostic interviews. The household survey included over 10,000 households, the institutional survey interviewed 755 individuals and the homeless survey of hostels, night-shelters, day centres and private-sector leased accommodation interviewed 1,061 individuals. This overview looks at patterns of nicotine, alcohol and other drug use in the different samples and examines interactions with other psychiatric morbidity. The survey reports that substance-related disorders are some of the commonest disorders in the community, with 5% of the household sample alcohol dependent, 7% alcohol dependent in the institutional sample and over 21% in the homeless sample recorded as alcohol dependent. Tobacco, alcohol and other drug use and dependence were dramatically higher in the homeless sample than in either of the other two samples. Substance use was significantly associated with higher rates of psychological morbidity as measured by the Clinical Interview Schedule Revised. Future service planning needs to take account of the striking disparity of prevalence of psychiatric disorders in different subsections of the population.

Alcohol Drinking

The effect of an educational program on transfusion practices in a regional blood program.

With the increased complexity of blood component therapy, it is important to be able to modify physician behavior with reliable educational programs. A standardized educational program on the use of red blood cells and whole blood was tested in 22 hospitals in a regional blood program using medical audit and computer monitoring to evaluate effectiveness. Most hospitals were eager to take advantage of the education program but were unwilling to use the audit-education cycle. At the same time, computer monitoring of indivisual hospital ordering and transfusion practices demonstrated an increased utilization of red blood cells in 64 per cent of hospitals with an overall improvement of 8 per cent. The improved use of red blood cells was appreciated within the month of the program and then sustained for six to twelve months at the new level.

Blood Transfusion