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Biomedical subjects

R M Simpson

Publications and source records attributed to R M Simpson.

54 records · Page 3Linked to original sources
PubMed1982

Platelet inhibitory effects of CRP preparations are due to a co-isolating low molecular weight factor.

We previously reported that C-reactive protein (CRP), an acute phase reactant, inhibits platelet activation through an effect upon a factor(s) critical to ADP-mediated secondary wave platelet aggregation but independent of a direct effect upon platelet contractile elements. However, a role for an accessory factor in this inhibitory effect became of concern because of an inconsistency in the effects of CRP preparations upon the platelet: inhibition was lost upon storage and CRP preparations differed, on a weight basis, in inhibitory capacity and sensitivity to the presence of the CRP ligand C-polysaccharide (CPS(. The studies presented herein were thus intended to assess whether an accessory factor was involved in the inhibition of platelet activation observed with CRP. We report that the activity of the inhibitory CRP preparations resulted from association with a low molecular weight factor (LMF) with an apparent nominal molecular weight of 8300-12,500 and an A280:A260 ratio of approximately 0.4. Purified CRP did not inhibit platelet responsiveness but CRP with associated LMF (CRP-LMF) did. Moreover, the inhibitory capacity of CRP-LMF but not LMF was substantially reversed in the presence of CPS. These studies indicate that the platelet inhibitory properties of CRP preparations result from and are contingent upon the presence of a co-isolating low molecular weight factor.

C-Reactive Protein↗
PubMed1982

Activation of platelets by modified C-reactive protein.

The functional similarities between C-reactive protein (CRP) and immunoglobulin raised the possibility that modified CRP might resemble immunoglobulin in its activating effects upon the human platelet. Thermally-aggregated CRP (H-CRP), but not unmodified CRP, induced reactions of aggregation and secretion from isolated platelets; maximum responses occurred with less than 50 microgram/ml H-CRP and were similar to responses mediated by thermally-aggregated human IgG (AHGG). Platelet activation induced by H-CRP was sensitive to the presence of EDTA and dibucaine, required metabolic energy and was inhibited by increased levels of cAMP. Like AHGG, H-CRP acted synergistically with other platelet stimulators, although on a weight basis H-CRP appeared approximately ten- to twenty-fold more effective than AHGG. Complexes formed between CRP and certain of its polycationic ligands (PLL and protamine) shared platelet activating properties with H-CRP, whereas complexes of CRP and CPS did not. These data point to the ability of appropriately modified CRP to stimulate or enhance platelet responsiveness, and taken together with those reactivities described previously between modified CRP and certain lymphocytes, phagocytes, and the complement system, support the concept that CRP can initiate biological activities similar to those mediated by immunoglobulin.

C-Reactive Protein↗
PubMed1982

Generation of thromboxane A2 and aorta-contracting activity from platelets stimulated with modified C-reactive protein.

The classical acute phase reactant, C-reactive protein (CRP), appears in markedly elevated concentration in the sera of individuals undergoing reactions of acute inflammation and tissue degradation. We previously demonstrated that like IgG, appropriately purified CRP could be thermally modified (H-CRP) such that it enhanced platelet activation in plasma and initiated platelet responses in isolated systems. We now report that this direct platelet activation by modified CRP results in the secretion of both platelet dense body and alpha-granule constituents, and is sensitive to non-steroidal anti-inflammatory drugs as well as the adenosine diphosphate (ADP)-removing enzyme system creatine phosphate/creatine phosphokinase. Thin-layer chromatographic (TLC) analysis of prostanoate endproducts following platelet activation with H-CRP revealed the formation of thromboxane B2 (the hydrated endproduct of thromboxane A2), an important endogenous platelet activator and contractor of vascular tissue; bioassay on rabbit aorta strips of supernatants obtained from platelets undergoing challenge with H-CRP supported the TLC analysis. Complexes formed between CRP and one major ligand, the polycation, were found to share certain platelet activating properties with H-CRP, as does latex-aggregated CRP. These data imply a potential agonist role for this acute phase reactant in platelet physiology and suggest that the interaction of modified forms of CRP with the platelet at sites of vascular damage could have pathological significance.

Adenosine Diphosphate↗
PubMed1982

Comparison of the enzymatic sensitivities of the platelet receptor for human C-reactive protein and its functional relationship to the platelet IgG Fc receptor.

Thermally modified human C-reactive protein (H-CRP) and IgG (AHGG) each activate isolated human platelets to reactions of aggregation and secretion. As these molecules exhibit many functional similarities, we questioned whether they might also share a receptor on the platelet membrane. Neither plasmin nor phospholipase C altered the platelet response to H-CRP or AHGG, although these reagents enhanced the platelet expression to acid soluble collagen (ASC). Conversely, chymotrypsin treatment of platelets resulted in an elevated response to each H-CRP and AHGG, but not to ASC. These data suggest that the H-CRP and AHGG platelet receptors share characteristics which contrast with those of the receptor for collagen. However, monomeric IgG, which can bind with the platelet and inhibit the response to AHGG, exerted no effect on the platelet response to H-CRP. Further, a functional receptor for thermally modified human or rabbit CRP was detected on rabbit platelets in the absence of a demonstrable Fc receptor for aggregated IgG. These data indicate that the platelet receptors for the modified forms of CRP and IgG are distinct.

Animals↗
PubMed1978

Sensitive and specific gas-liquid chromatographic-spectrophotometric screening procedure for trace levels of five sulfonamides in liver, kidney, and muscle tissue.

Free and conjugated sulfonamides are extracted from edible animal tissue with acetone. Carbohydrate is precipitated and removed, and the acetone is evaporated. The residue is transferred to a separatory funnel with ethyl ether and 1N HCl. The acid layer is drawn off and a portion of the 1N HCl is screened, using the Bratton-Marshall reaction. If this portion is positive, the remaining portion is buffered to pH 6.5 and extracted with methylene chloride. The residue is methylated with diazomethane and then acylated with pentafluoropropionic anhydride. The resulting derivatives are detected by gas-liquid chromatography, using electron capture (63Ni) detection and a column packed with 3% OV-17 on Gas-Chrom Q. This method has been validated by recovering sulfathiazole, sulfachloropyrazine, sulfamethazine, sulfadimethoxine, and sulfabromomethazine from liver, kidney, and muscle at levels of 0.1, 0.5, and 1.0 ppm. The 5 sulfonamides were recovered in excess of 60%, with an average mean recovery of 81.5% at the 0.1 ppm level, 79.1% at the 0.5 ppm level, and 76.0% at the 1.0 ppm level.

Animals↗
PubMed1977

Prevention of infection in nurseries for the newborn.

Prevention of infection in nurseries involves consideration of the design of hospitals, wards and equipment, the study of nursing and domestic procedures, the monitoring of environmental flora and the planning of antiseptic and antibiotic policies. These subjects cannot be considered in isolation from each other and are most suitably managed by a Control of Infection Committee. Ultimately the safety of infants in nurseries rests upon the degree to which each individual involved in their care pays attention to the agreed policies of general and personal hygiene.

Bacterial Infections↗
PubMed1977

Effects of C-reactive protein on platelet function. III. The role of cAMP, contractile elements, and prostaglandin metabolism in CRP-induced inhibition of platelet aggregation and secretion.

It was previously demonstrated that C-reactive protein (CRP) inhibits platelet aggregation and release reactions, activation of platelet factor 3, and platelet-dependent clot retraction. Multiple considerations including selective inhibition of secondary wave aggregation suggested that CRP exerted its inhibitory effects by interfering with the release of endogenous ADP. In the present investigation, CRP was found by direct assay to inhibit the release of endogenous ADP and/or serotonin concomitant with inhibition of platelet aggregation stimulated by ADP, epinephrine, thrombin, and AHGG. CRP did not induce an increase in the basal level of platelet cAMP, suggesting independence of a direct effect upon this mediator system. Furthermore, CRP did not inhibit the aggregation and secretion induced by the antibiotic ionophore A23187, suggesting the absence of a direct effect upon the activation of platelet contractile elements. By contrast, CRP did inhibit both thrombin-induced release of malondialdehyde, a prostaglandin endoperoxide nonprostanoate endproduct, and platelet aggregation induced by the prostaglandin endoperoxide precursor arachidonic acid. These data, therefore, raise the possibility that CRP inhibits platelet reactivities by interfering with an aspect of porstaglandin metabolism, and that this occurs subsequent to the hydrolytic accumulation of arachidonic acid and prior to the movement of calcium from the platelet dense tubules. These studies support the concept that CRP serves to modulate platelet reactivities during acute inflammatory reactions.

Adenosine Diphosphate↗
PubMedDate not supplied

Thoracoscopy as a nonpharmacotherapeutic research modification for limiting postoperative chest pain.

Diminished tissue injury and shortened clinical recovery are benefits of using an endoscopic approach for patients needing operative procedure. In the course of developing an experimental model requiring procurement of topographically precise lung biopsy specimens, we sought to apply thoracoscopy as a research alternative to thoracotomy. In addition, we investigated the influence of thoracoscopy on postprocedure recovery practices using rabbits divided into four treatment groups. Rabbit groups 1 and 2 underwent thoracoscopy and lung biopsy while maintained by one-lung anesthesia. Additionally, group 2 had ketoprofen and bupivacaine HCl analgesics injected for treatment during postprocedure recovery. These two groups were compared to control rabbits in groups 3 and 4, which underwent inhalant anesthesia without thoracoscopy. Control group 3 also received the injection analgesic combination. During recovery, rabbit behavior was systematically assessed for evidence of pain. No behavior considered indicative of pain needing intervention was observed regardless of treatment group. Limited changes in plasma corticosterone, catecholamines, and prostaglandin E2 levels measured during recovery were difficult to associate with any treatment. Unexpectedly, significantly different mean corticosterone and catecholamines levels were detected in rabbits given the injection analgesic combination in the absence of thoracoscopic procedure, as compared to other treatment groups. The results highlight the importance of awareness that analgesic drug administration has the potential to alter homeostasis and affect interpretation of some study findings by its own guise. Correlation of the mean pain study results with plasma biochemical data supports preferential use of thoracoscopy as a refinement for limiting postprocedural pain in research models.

Anesthesia, Inhalation↗
PubMedDate not supplied

Quantitative gas chromatographic-mass spectrometric assay of five sulfonamide residues in animal tissue.

A gas chromatographic-mass spectrometric procedure using isotopically labeled internal standards and the technique of selective-ion monitoring was used to assay sulfamethazine, sulfadimethoxine, sulfabromethazine, sulfathiazole, and sulfaquinoxaline in liver and muscle tissue of swine, poultry, and cattle. The data presented clearly demonstrate the applicability of this procedure for confirmation of sulfonamide residues in animal tissue.

Animals↗