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Biomedical subjects

W Lloyd

Publications and source records attributed to W Lloyd.

18 recordsLinked to original sources

A study of aspirin and clopidogrel in idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) is characterised by in situ thrombosis and increased thromboxane (Tx) A2 synthesis; however, there are no studies of antiplatelet therapy in IPAH. The aim of the current study was to determine the biochemical effects of aspirin (ASA) and clopidogrel on platelet function and eicosanoid metabolism in patients with IPAH. A randomised, double-blind, placebo-controlled crossover study of ASA 81 mg once daily and clopidogrel 75 mg once daily was performed. Plasma P-selectin levels and aggregometry were measured after exposure to adenosine diphosphate, arachidonic acid and collagen. Serum levels of TxB2 and urinary metabolites of TxA2 and prostaglandin I2 (Tx-M and PGI-M, respectively) were assessed. A total of 19 IPAH patients were enrolled, of whom nine were being treated with continuous intravenous epoprostenol. ASA and clopidogrel significantly reduced platelet aggregation to arachidonic acid and adenosine diphosphate, respectively. ASA significantly decreased serum TxB2, urinary Tx-M levels and the Tx-M/PGI-M ratio, whereas clopidogrel had no effect on eicosanoid levels. Neither drug significantly lowered plasma P-selectin levels. Epoprostenol use did not affect the results. In conclusion, aspirin and clopidogrel inhibited platelet aggregation, and aspirin reduced thromboxane metabolite production without affecting prostaglandin I2 metabolite synthesis. Further clinical trials of aspirin in patients with idiopathic pulmonary arterial hypertension should be performed.

Adult↗

TraT: a powerful carrier molecule for the stimulation of immune responses to protein and peptide antigens.

A number of integral membrane proteins (Imps) isolated from Escherichia coli have been examined for their ability to generate serum antibody responses in the absence of adjuvant. These proteins were found to stimulate high titers of serum antibody when injected into rabbits or mice in saline. The antibody titers elicited were not significantly increased by the addition of a powerful adjuvant such as IFA. Covalent conjugation of BSA, of the DNP group, and of a peptide Ag from Plasmodium falciparum to these protein carriers resulted in a significant enhancement of the immune response to the conjugated material in comparison with the response elicited when the immunogen was injected without adjuvant or was not conjugated to Imps. The antibody response to these conjugates could not be significantly increased by the addition of IFA. Thus, the Imps of E. coli represent powerful carrier molecules which, when injected into mice and rabbits, are not only capable of generating high titers of antibody to themselves, but also to molecules conjugated to them. Immunization with immunogens coupled to these proteins results in the production of high titers of antibody without the need for oil-based adjuvants, thereby avoiding the unwanted side effects of such adjuvants.

Adjuvants, Immunologic↗

Actions of growth factors on plasma calcium. Epidermal growth factor and human transforming growth factor-alpha cause elevation of plasma calcium in mice.

Specific humoral substances produced and secreted by human tumors that cause hypercalcemia have not been identified. Certain growth factors (such as epidermal growth factor, platelet-derived growth factor, and transforming growth factors-alpha and -beta) have been shown to stimulate the resorption of bone in organ culture by both prostaglandin-dependent and prostaglandin-independent pathways. In this report we demonstrate that epidermal growth factor and recombinant human transforming growth factor-alpha induce a significant rise in plasma calcium concentration when administered repeatedly to intact mice for periods ranging from 24 h to 16 d. The elevation of plasma calcium is not dependent on dietary calcium and is not invariably accompanied by an increase in systemic levels of the prostaglandin E2 metabolite 13,14-dihydro-15-keto-prostaglandin E2. The in vivo calcium-mobilizing activity of epidermal growth factor and transforming growth factor-alpha indicate that these or related growth factors need be considered as potential mediators of tumor-induced hypercalcemia.

Animals↗

Immune complexes, complement, and anti-DNA in exacerbations of systemic lupus erythematosus (SLE).

The usefulness of serological parameters in assessing clinical exacerbations of SLE was examined. Patients with active renal disease tend to have lower levels of CH50 and C3 and highest levels of immune complexes detected by C1qBA than those patients with extrarenal manifestations only. Patients with a combination of both active extrarenal and renal disease are more likely to demonstrate the lowest levels of CH50, C4, and C3. However, immune complex levels are not higher than levels detected in patients with only active nephritis. A normal C3 level argues against active nephritis. Low complement levels without appreciably elevated levels of C1qBA suggest that significant renal disease is unlikely. The serial measurements that best reflect evolving clinical activity and which may serve as markers of impending exacerbation are, in decreasing order of usefulness: C4, CH50, C1qBA, C4, C3 and ADA. However, a combination of CH50, C4, C3 and C1qBA appeared to be the most useful. Given various serologic changes, guidelines for following patients are offered.

Antibody-Dependent Cell Cytotoxicity↗

Effects of a bone resorptive factor from human cancer ascites fluid on rat bone cell calcium and cyclic AMP.

The effects of a bone resorptive protein isolated from human cancer ascites fluid on bone cell calcium and cyclic AMP were studied with fetal rat cells. The osteoclast-activating factor increased bone cell calcium uptake at 37 degrees C and 4 degrees C with no direct effects on calcium efflux. Concentrations of the resorptive factor that increased in vitro bone resorption and cell calcium uptake had no effect on cyclic AMP. The effects of the protein on calcium uptake were not specific for bone cells, and large increases were also observed in isolated fetal rat skin cells. These studies suggest that increases in the permeability of the cell membrane to calcium are involved in the mechanism of action of the ascites fluid resorptive protein.

Animals↗