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Timothy H Rainer

Publications and source records attributed to Timothy H Rainer.

41 records · Page 3Linked to original sources

L-selectin in health and disease.

This article reviews recent advances in the knowledge of the role of L-selectin, an adhesion molecule that is expressed on the surface of circulating leucocytes, in animal and human physiology and pathophysiology. After a brief discussion on nomenclature and structure, it progresses through the evidence for expression and regulation of L-selectin, cell collection and purification, physiological function and roles. The special role of knock out mice and monoclonal antibodies in determining a role for L-selectin in inflammatory states is described before proceeding to discuss the importance of L-selectin ligands and shed L-selectin. A second section describes a role for L-selectin in pathophysiological states in animals and man, with special reference to trauma, systemic inflammatory syndromes and sepsis. The review concludes with a summary of the potential role of anti-inflammatory medication and L-selectin blockers in the management of inflammation.

Animals↗

Effect of stress hormones on the expression of fibrinogen-binding receptors in platelets.

Acute coagulopathy is a common clinical complication after trauma, and contributes to posttraumatic multiple organ failure. The phenomenon may be due to the effect of stress hormones on platelet adhesion molecule expression after trauma. Catecholamine levels correlate with injury severity scores and changes of L-selectin expression on leucocytes, whilst adrenaline (ADR) (epinephrine) alone also activates platelets. This study thus investigates the effects of ADR and noradrenaline (NOR) (norepinephrine) on platelets, at doses similar to those found in the plasma of normal and trauma subjects. Blood was taken from 19 healthy subjects and placed in tubes containing sodium citrate. Anti-platelet-bound fibrinogen monoclonal antibody was used to identify the activated platelets while anti-CD41 was used to identify platelets with and without activation. Five increasing concentrations of ADR and NOR (1, 3, 5, 10, 30 nmol/l) as well as one negative control (0.9% normal saline) and one positive control (10 micromol/l adenosine diphosphate/ADP) were prepared for the stimulation. A whole blood protocol was used in order to minimize any activation artefacts, which might be created by centrifugation. The percentage of platelets expressing fibrinogen receptors increased significantly with ADR and NOR even at the lowest dose (1 nmol/l) and continued to increase in a dose-dependent manner. Although the effect of ADR was greater than NOR in stimulating platelets to express fibrinogen receptors, the average number of fibrinogen receptors on each platelet was constant. ADR and NOR activated platelets to express fibrinogen receptors at doses that are similar to those found in the plasma of trauma patients.

Adult↗

Presence of filterable and nonfilterable mRNA in the plasma of cancer patients and healthy individuals.

BACKGROUND: As RNA is labile, we investigated whether circulating RNA in human plasma may be present in a particle-associated form. METHODS: Blood was collected from 27 healthy individuals and 16 hepatocellular carcinoma (HCC) patients. The plasma from each individual was processed by two means: filtration through filters with different pore sizes (from 5 microm to 0.22 microm) and ultracentrifugation. We assessed plasma RNA content by a real-time quantitative reverse transcription-PCR assay for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcripts and plasma DNA by a real-time quantitative PCR assay for the beta-globin gene. RESULTS: The plasma GAPDH mRNA concentrations in the healthy individuals were significantly different in every pair of these filter sizes (P <0.05 for each pair). Overall, the plasma GAPDH mRNA concentration was higher by a median of 15-fold (interquartile range, 10- to 24-fold) in the paired unfiltered sample than in the sample filtered through a 0.22 microm filter. In contrast, no significant difference was seen in beta-globin DNA concentrations among different pore-size-filtered plasma samples (P = 0.455). Similarly, a significant difference was observed for RNA, but not DNA, between unfiltered plasma and ultracentrifuged plasma (P <0.05). No significant difference in GAPDH mRNA concentrations was seen between the 0.22-microm-filtered plasma samples and the ultracentrifuged plasma samples (P >0.05). In HCC patients, filtration with a 0.22 microm filter produced a median 9.3-fold (interquartile range, 6.9- to 311-fold) reduction in GAPDH mRNA concentration in plasma. Plasma GAPDH mRNA concentrations in HCC patients were significantly higher than those in healthy individuals, both with or without filtration (P <0.0 5 for filtered plasma samples; P <0.005 for unfiltered plasma samples). CONCLUSIONS: A substantial proportion of plasma mRNA species is particle-associated. In HCC patients, both circulating particle- and non-particle-associated plasma RNA are increased.

Carcinoma, Hepatocellular↗