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L M Thomas

Publications and source records attributed to L M Thomas.

At least 37 records · Page 2Linked to original sources

BW755C or staurosporine inhibits collagen-stimulated phosphoinositide phosphorylation in platelets.

Stimulation of platelets by collagen results in increased formation of the polyphosphoinositides, phosphatidylinositol phosphate (PtdInsP) and phosphatidylinositol bisphosphate (PtdInsP2) through stimulation of phosphoinositide kinase activities. We investigated a possible regulatory role of endogenous thromboxane formation and protein kinase C (PKC) activation in the induction of phosphoinositide phosphorylation following collagen stimulation, as well as following stimulation by the thromboxane mimetic, U-46619. Human platelets were prelabeled with [3H]inositol and stimulated with collagen (2 micrograms/mL) or U-46619 (1 microM), in the absence or presence of either the cyclo-oxygenase/lipoxygenase inhibitor, BW755C, or staurosporine, a putative inhibitor or PKC. Collagen stimulation resulted in a time-dependent increase in [3H]inositol-labeled PtdInsP and PtdInsP2 which was completely inhibited in the presence of BW755C. Addition of U-46619 to BW755C-treated, collagen-stimulated platelets restored the increased polyphosphoinositide formation. Stimulation of platelets with U-46619 alone also resulted in increased formation of [3H]PtdInsP and [3H]PtdInsP2, but this was not affected by the presence of BW755C. These results suggest that the collagen-induced activation of phosphoinositide kinases was dependent upon thromboxane formation, but that U-46619-induced phosphoinositide formation was rather independent of further thromboxane production. Pretreatment of platelets with staurosporine, prior to agonist addition, completely blocked the collagen-stimulated rise in radiolabeled PtdInsP and the U-46619-induced PtdInsP and PtdInsP2 generations, suggesting that protein kinase, possibly PKC, may play a role in the activation of phosphoinositide kinases by these agonists.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Inhibition of phosphatidic acid production and lysophospholipid formation in collagen-stimulated human platelets by staurosporine, a protein kinase inhibitor.

To investigate a possible regulatory role of protein kinase C (PKC) on collagen-induced phospholipase activity, human platelets were prelabelled with either [3H] arachidonic acid or [14C]stearic acid and stimulated with collagen (2 micrograms/ml) in the presence or absence of the protein kinase inhibitor, staurosporine (1 microM). The collagen-induced release of [3H]arachidonic acid and formation of [14C]stearoyl-labelled lysophospholipids was inhibited by prior incubation with staurosporine, as was the formation of 3H-labelled thromboxane B2, thereby suggesting inhibition of the collagen-induced phospholipase A2 activity. The degradation of phosphatidylinositol (PI) and elevation of phosphatidic acid (PA) in platelets prelabelled with either radiotracer were also completely blocked by staurosporine pretreatment, indicating a suppression of collagen-stimulated phospholipase C activity. Suppressed phospholipase C activity may have been due to diminished thromboxane A2 formation since treatment with the dual cyclo-oxygenase/lipoxygenase inhibitor, BW755C, also resulted in an inhibition of the collagen-stimulated loss of 14C-labelled PI and rise in PA by 75-80%. Our results suggest that protein kinase, possible PKC, may be involved in the regulation of these phospholipases in collagen-stimulated human platelets.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Financial modeling: creating a plan for the future.

In response to decreasing utilization and increasing competition, hospitals are looking for new business opportunities to strengthen their present financial position. But they need a method to evaluate potential new ventures. Using a financial forecasting model, Metropolitan Medical Center was able to effectively evaluate new business opportunities. And by incorporating assumptions specific to an institution into the model, any institution can use this model as a guide for developing an analytical tool for making future business decisions.

Accounts Payable and Receivable↗

The formation of lysophosphatidylinositol phosphate in human platelet microsomes.

The formation of lysophosphatidylinositol phosphate (lysoPIP) from lysophosphatidylinositol (lysoPI) via kinase activity was studied in microsomal preparations from human platelets. For this purpose, [3H]lysoPI or [3H]phosphatidylinositol ([3H]PI) was prepared and incubated in the presence or absence of ATP, MgCl2 and Triton X-100, and the appearances of radioactivity in [3H]lysoPIP and [3H]phosphatidylinositol phosphate ([3H]PIP), respectively, were monitored using thin layer chromatography. Both lysoPI and PI phosphorylations were completely dependent upon the presence of ATP and MgCl2 in the incubation medium; Triton X-100 addition stimulated both reactions, with the stimulation of PI conversion being considerably greater than that for lysoPI can be converted to lysoPIP by phosphorylation in human platelet microsomes. The potential significance of this enzymatic reaction in stimulated cells is discussed in relation to the generation of inositol-1,4,5-trisphosphate, an important intracellular second messenger.

Blood Platelets↗

Temporalis muscle-galea flap in craniofacial reconstruction.

With the advent of increasing technological and surgical sophistication in craniofacial surgery, reconstructive efforts are challenged to provide a reliable means of compartmentalization. When dural integrity is compromised in the face of nasopharyngeal or paranasal communication, the risk of ascending infection and potential life-threatening meningitis mandate cranial and facial compartments, separated by sufficient and healthy soft tissues. This paper describes a method of providing pedicled soft tissue coverage and support for the contents of the anterior cranial fossa using a temporalis muscle-galea rotation flap. The vascularized myofascial tissues, capable of carrying skin and bone grafts, are well suited to cover and protect large areas of the skull base. Several cases are described to show the advantages and disadvantages of the technique.

Adult↗

Structure and function of candidate vaccine antigens in Plasmodium falciparum.

Analysis of Plasmodium falciparum antigens expressed in Escherichia coli has identified several different proteins as potential vaccine components. Fragments of one of these antigens, the ring-infected erythrocyte surface antigen (RESA) have been used to protect Aotus monkeys against overwhelming infection with P. falciparum. In this vaccine, trial protection correlated with antibody responses to two of three repetitive sequences in RESA. RESA is released from merozoites and becomes associated with the erythrocyte membrane at the time of merozoite invasion. The 3' repeat structure of RESA encodes a polyacidic sequence that has homology with the N-terminal sequence (cytoplasmic domain) of band 3, the erythrocyte anion transporter. These homologous sequences both include a recognition sequence for a protein tyrosine kinase. It is postulated that RESA disrupts the normal intermolecular interactions of the cytoplasmic domain of band 3 and that phosphorylation of RESA by an erythrocyte membrane kinase in some way regulates this function of RESA.

Amino Acid Sequence↗

High-performance liquid chromatographic method for the analysis of a candidate 8-aminoquinoline antileishmanial drug using oxidative electrochemical detection.

An analytical method was developed for the quantitation of a candidate antileishmanial drug, 6-methoxy-8-(6-diethylaminohexylamino)-4-methylquinoline, dihydrochloride, in canine plasma. The assay utilized internal standard technique with a structural similar 8-aminoquinoline, 6-methoxy-8-(7-diethylaminoheptylamino)-4-methylquinoline, dihydrochloride, as the internal standard. The method employs a liquid-solid extraction procedure with prepackaged silica gel columns upon which the drug and internal standard are adsorbed, then selectively washed and eluted. Reversed-phase chromatography was then employed to analyze the extracted sample by means of oxidative electrochemical detection at +0.75 V. Good accuracy and precision were obtained over the range of concentration tested (10-1500 ng/ml plasma). Analyses of plasma samples from human volunteers given the drug demonstrate the method is also suitable for analysis of human plasma samples. The entire procedure is relatively simple and requires only 1 ml of plasma.

Aminoquinolines↗

Inflammation of the neck.

In the evaluation of a large series of infectious processes in the cervical region, certain diagnostic sonographic patterns have been established, which prove very helpful in differentiating the various stages and the extension of inflammatory processes. The advantages of sonographic imaging are demonstrated.

Abscess↗