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Biomedical subjects

A Philip

Publications and source records attributed to A Philip.

At least 37 records · Page 2Linked to original sources
PubMed1995

The blood saving potential of vortex versus roller pump with and without aprotinin.

To evaluate the potential of centrifugal blood pumps for saving blood, 120 patients scheduled for elective coronary artery bypass grafting were entered into a prospective randomized trial. A standard roller pump (group I) was compared with a centrifugal blood pump (group II) and roller pump plus aprotinin (group III). There was no significant difference between groups I and II with respect to free haemoglobin, lactic dehydrogenase, serum bilirubin, platelet surface glycoprotein IIb-IIIa and granule membrane protein 140, chest-tube drainage, use of blood products, length of stay in intensive care, time on ventilator and postoperative mortality. Aprotinin reduced chest-tube drainage and use of blood products significantly. Three cases of graft occlusions were noted in group III. Centrifugal blood pumps offer no advantage in routine heart surgery over conventional roller pumps. Aprotinin reduces blood loss, but does not influence GP IIb-IIIa and GMP 140 expression on blood platelets.

Blood Component Transfusion↗
PubMed1994

Binding of transforming growth factor-beta (TGF-beta) to pregnancy zone protein (PZP). Comparison to the TGF-beta-alpha 2-macroglobulin interaction.

Pregnancy zone protein (PZP) is quantitatively the most important pregnancy-associated plasma protein and it has strong similarity to alpha 2-macroglobulin. Since alpha 2-macroglobulin is a binding protein for transforming growth factors-beta (TGF-beta), it was of interest to test whether the related protein, PZP, also binds to these growth-regulatory proteins. Using affinity-labelling methods, we demonstrate that PZP binds both TGF-beta 1 and TGF-beta 2 and that the binding characteristics are similar to those of the TGF-beta-alpha 2-macroglobulin interaction. TGF-beta 2 and TGF-beta 1 bind to PZP in a predominantly noncovalent manner in vitro. TGF-beta 1 and TGF-beta 2 bind to both the dimeric and tetrameric forms of PZP. Our studies also indicate that PZP binds TGF-beta 2 with higher affinity than TGF-beta 1. Finally, we demonstrate that PZP inhibits the binding of TGF-beta 1 and TGF-beta 2 to their cell surface receptors. The increased level of PZP during pregnancy may affect the action of TGF-beta by regulating the distribution, clearance and/or general availability of TGF-beta. The preferential binding of TGF-beta 2 over TGF-beta 1 by PZP implies that PZP may differentially regulate the action of TGF-beta 1 and TGF-beta 2.

Autoradiography↗
PubMed1993

Cellular localization and regional distribution of an angiotensin II-forming chymase in the heart.

The human heart is a target organ for the octapeptide hormone, angiotensin II (Ang II). Recent studies suggest that the human heart contains a dual pathway of Ang II formation in which the major Ang II-forming enzymes are angiotensin I-converting enzyme (ACE) and chymase. Human heart chymase has recently been purified and its cDNA and gene cloned. This cardiac serine proteinase is the most efficient and specific Ang II-forming enzyme described. To obtain insights into the cardiac sites of chymase-dependent Ang II formation, we examined the cellular localization and regional distribution of chymase in the human heart. Electron microscope immunocytochemistry using an anti-human chymase antibody showed the presence of chymase-like immunoreactivity in the cardiac interstitium and in cytosolic granules of mast cells, endothelial cells, and some mesenchymal interstitial cells. In the cardiac interstitium, chymase-like immunoreactivity is associated with the extracellular matrix. In situ hybridization studies further indicated that chymase mRNA is expressed in endothelial cells and in interstitial cells, including mast cells. Tissue chymase levels were determined by activity assays and by Western blot analyses. Chymase levels were approximately twofold higher in ventricles than in atria. There were no significant differences in chymase levels in ventricular tissues obtained from non-failing donor hearts, failing ischemic hearts, or hearts from patients with ischemic cardiomyopathy. These findings suggest that a major site of chymase-dependent Ang II formation in the heart is the interstitium and that cardiac mast cells, mesenchymal interstitial cells, and endothelial cells are the cellular sites of synthesis and storage of chymase. In the human heart, because ACE levels are highest in the atria and chymase levels are highest in ventricles, it is likely that the relative contribution of ACE and chymase to cardiac Ang II formation varies with the cardiac chamber. Such differences may lead to differential suppression of cardiac Ang II levels during chronic ACE inhibitor therapy in patients with congestive heart failure.

Adolescent↗
PubMed1992

A cocaine analog and a GBR analog label the same protein in rat striatal membranes.

Because some evidence suggests that cocaine and GBR12935 bind to different sites, we utilized photoaffinity probes from both classes of compounds to see if they label the same protein. [125I]RTI-82 a cocaine analog, and [125I]DEEP, a GBR analog, labeled protein(s) showing the same molecular weight, a similar pharmacological profile and a similar sensitivity to neuraminidase.

Animals↗
PubMed1991

Potent substituted-3 beta-phenyltropane analogs of cocaine have cocaine-like discriminative stimulus effects.

Two novel phenyltropane analogs of cocaine, 3 beta-(4-chlorophenyl) tropane-2 beta-carboxylic acid methyl ester (RTI-COC-31) and 3 beta-(4-methylphenyl) tropane-2 beta-carboxylic acid methyl ester (RTI-COC-32), were evaluated for cocaine-like discriminative stimulus effects in rats. Two groups of rats were trained to discriminate 10 mg/kg cocaine from saline using a standard 2-lever discrimination procedure with correct-lever responding reinforced under a fixed-ratio 20 schedule of food reinforcement. One group of rats was used to evaluate RTI-COC-31 and the unsubstituted-3 beta-phenyltropane reference compound WIN 35,065-2 in substitution tests. Another group of rats was used to evaluate RTI-COC-32. For purposes of comparison, a cocaine dose-effect curve was also determined in each group. Both RTI-COC-31 and RTI-COC-32, as well as WIN 35,065-2, substituted completely for cocaine. RTI-COC-31 was 26.8-fold and RTI-COC-32 was 6-fold more potent than cocaine for producing cocaine-lever responding. The potent cocaine-like effects of the RTI analogs in vivo correspond with their high affinities for a cocaine recognition site on the dopamine transporter, providing further evidence that this site may mediate behavioral effects of cocaine relevant to its abuse.

Animals↗
PubMed1991

Interaction of transforming growth factor-beta 1 with alpha 2-macroglobulin. Role in transforming growth factor-beta 1 clearance.

It has been widely assumed that the interaction of transforming growth factor-beta 1 (TGF-beta 1) with its serum-binding protein, alpha 2-macroglobulin (alpha 2M), mediates the rapid clearance of TGF-beta 1 from the circulation. To test this, we have analyzed the effect of TGF-beta 1 binding on the conformational state of alpha 2M. Our results demonstrate that the binding of TGF-beta 1 to alpha 2M does not lead to the conformational change in the alpha 2M molecule that is required for the clearance of the alpha 2M.TGF-beta 1 complex via the alpha 2M receptor. Furthermore, endogenous TGF-beta 1 is associated with the conformationally unaltered slow clearance form of alpha 2M. Clearance studies in mice show that the half-life of 125I-TGF-beta 1 in the circulation (1.6 +/- 0.71 min) is not affected by blocking the alpha 2M receptor with excess conformationally altered alpha 2M. These results suggest that TGF-beta 1 is rapidly cleared from the circulation after injection by a pathway not involving alpha 2M.

Animals↗
PubMed1991

Isothiocyanate derivatives of cocaine: irreversible inhibition of ligand binding at the dopamine transporter.

Isothiocyanate derivatives of (-)-cocaine were prepared and tested for inhibitory potency at the cocaine receptor in rat striatal membranes. Coincubation with m-isothiocyanatobenzoylecgonine methyl ester (m-ISOCOC), p-isothiocyanatobenzoylecgonine methyl ester (p-ISOCOC), and 3 beta-(4-isothiocyanatophenyl)tropane-2-carboxylic acid methyl ester (ISOWIN) resulted in inhibition of [3H]WIN 35,428 binding, but the compounds were about 10-fold weaker than (-)-cocaine. However, p-ISOCOC was approximately 3-fold more potent than metaphit, an isothiocyanate derivative of phencyclidine. p-ISOCOC was equipotent at the serotonin transporter but was much less potent at the norepinephrine transporter and was inactive at the D2 dopamine receptor at 1000 microM concentration. The IC50 value for m-ISOCOC and p-ISOCOC varied with tissue concentration, suggesting irreversible inhibition of binding. Preincubation with m-ISOCOC and p-ISOCOC resulted in inhibition of [3H]WIN 35,428 binding that could not be removed by washing of the membranes; in contrast, preincubation with (-)-cocaine caused inhibition that was readily removed by washing. Preincubation with 1 microM concentrations of p-ISOCOC resulted in a large reduction in Bmax of the high affinity binding site for [3H]WIN 35,428. Preincubation with 100 microM p-ISOCOC eliminated the high affinity site and apparently reduced the affinity at the low affinity site. Coincubation of 10 microM p-ISOCOC with 100 microM cocaine prevented the total loss of [3H]WIN 35,428 binding. The uptake of [3H]dopamine was inhibited by p-ISOCOC with an IC50 comparable to that of cocaine. Additionally, preincubation of rat striatal synaptosomes with 10 microM p-ISOCOC reduced the Vmax of [3H]dopamine uptake after washing. These data suggest that m-ISOCOC and p-ISOCOC are useful irreversible acylators of (-)-cocaine binding sites at the dopamine transporter.

Animals↗
PubMed1990

New, potent cocaine analogs: ligand binding and transport studies in rat striatum.

Two potent cocaine analogs have been developed that have the highest known affinities for the cocaine binding site in rat striatum. Both 3 beta-(4-chlorophenyl)- (RTI-COC-31) and 3 beta-(4-methylphenyl)-tropane-2-carboxylic acid methyl ester (RTI-COC-32) compete for [3H]WIN 35,428 and [3H]mazindol binding with a IC50 that is 100 times more potent than that of (-) cocaine. Additionally, these compounds inhibit [3H]dopamine uptake with a similar, high potency. These results may lead to the development of high affinity probes for the cocaine binding site.

Animals↗
PubMed1990

Multicenter clinical evaluation of the Du Pont Herpchek HSV ELISA, a new rapid diagnostic test for the direct detection of herpes simplex virus.

A new 4h rapid enzyme-immunoassay for direct detection of herpes simplex virus (HSV) antigen (Du Pont Herpchek) was evaluated with 743 clinical samples collected at obstetrics and gynecology (OB/GYN), sexually transmitted diseases (STD), and ophthalmology clinics. The sensitivity and specificity of Herpchek was 98.0% and 98.4% respectively compared to virus isolation in cell culture. Confirmatory blocking ELISA tests, clinical history and follow up indicate that the true specificity of the test is 100%.

Adult↗
PubMed1990

S-[2-[(2'-carbamoylethyl)amino]ethyl] phosphorothioate and related compounds as potential antiradiation agents.

A reinvestigation of the radiation protection activity of S-[2-[(2'-carbamylethyl)amino]ethyl] lithium hydrogen phosphorothioate (4a) revealed that this compound possessed good (70% protection at a dose of 600 mg/kg) activity. The thione and imino bioisosteres of 4, S-[2-(2'-thiocarbamylethylamino)ethyl] lithium hydrogen phosphorothioate (13a) and S-[2-(2'-amidinoethylamino)ethyl] phosphorothioic acid (18b) showed 100% protection at doses of 300 and 150 mg/kg, respectively. The N-methyl (4b) and tert-butyl (4c) analogues of amide 4a, the N-methyl (13b) analogue of the thioamide 13a, the N-methyl (18a) analogue of amidine (18b), and the cyclic amidine S-[2-[[2'-(4,5-dihydroimidozoyl)ethyl]amino]ethyl] lithium hydrogen phosphorothioate (21) all showed 80% protection at the highest dose tested.

Amifostine↗
PubMed1990

Atrioventricular plane displacement in severe congestive heart failure following dilated cardiomyopathy or myocardial infarction.

Echocardiographic recording of the atrioventricular (AV) plane displacement during the cardiac cycle was used to assess left ventricular (LV) global function in patients with congestive heart failure (CHF). The study population consisted of 70 patients with chronic CHF (NYHA functional groups III and IV) following dilated cardiomyopathy (DCM) or myocardial infarction (MI), and 35 age-matched healthy subjects. The AV plane displacement was recorded from the apical 4- and 2-chamber views at four LV sites located about 90 degrees apart and representing the septal, anterior, lateral and posterior parts of the LV wall. A mean value was calculated from the above sites (AV-mean). Patients with CHF showed a significant generalized reduction of AV plane displacement compared to healthy subjects (5.6 mm vs. 14.5 mm, P less than 0.001). Thirty CHF patients also underwent radionuclide angiography in order to determine the ejection fraction (EF). The correlation between AV-mean and EF was good (r = 0.82, P less than 0.001). The selection of an AV-mean of less than 7 mm to define a severely depressed LV function (EF less than 30%) gave a sensitivity of 92% and a specificity of 67%. It is concluded that the AV plane displacement can be used to estimate LV systolic function in patients with CHF.

Cardiomyopathy, Dilated↗
PubMed1990

Evaluation of isolator system and large-volume centrifugation method for culturing body fluids.

The Isolator system was compared with the large-volume centrifugation method for processing and recovering organisms from body fluids other than blood, cerebrospinal fluid, and urine. A total of 155 body fluid samples were processed for the recovery of clinically significant organisms. Of the 55 positive cultures, Isolator detected 94% and the large-volume centrifugation method detected 64%. The time necessary to indicate positivity was not significantly different in the two methods; however, in five cases, the Isolator system yielded clinically significant organisms 24 h sooner than the conventional method. The Isolator system was found to be a more sensitive alternative than the conventional large-volume centrifugation method.

Bacteria↗
PubMed1989

Identification of 20 alpha-hydroxy-5 alpha-pregnan-3-one and 20 beta-hydroxy-5 alpha-pregnan-3-one in human pregnancy urine.

20 beta-Hydroxy-5 alpha-pregnan-3-one and 20 alpha-hydroxy-5 alpha-pregnan-3-one were isolated and identified from a pool of urine collected from women in the third trimester of pregnancy. Following isolation by Sephadex LH-20 and HPLC, the identity of each compound was established by comparison of GC-MS data for the methyloxime-trimethylsilyl ethers with those for authentic standards.

Chromatography, High Pressure Liquid↗
PubMed1989

Low polarity ligands of sex hormone-binding globulin in pregnancy. Part I--Characterization.

Certain previously unidentified substances of low polarity binding to the sex hormone binding globulin (SHBG) in pregnancy were investigated. This material consisted of four major peaks (designated 1a, 1b, 2 and 3) as defined in maternal serum on Sephadex LH-20 chromatography. They were characterized with respect to changes in their concentration at various gestational ages and at premature and term labour in maternal serum, cord serum, placenta and maternal urine. Levels were much higher in placenta than in serum, suggesting that all four peaks were of placental origin. In the serum of mothers not in labour, while there was a significant increase in the mean serum concentration of peak (1a + 1b) and peak 3 for 12-24 weeks to 30-38 weeks gestation, there was no significant difference in the mean level of peak 2. However, there was a significant decrease in the serum levels of peak 2, but not peaks (1a + 1b) and 3, from 30-38 weeks gestation to 39-41 weeks gestation (P less than or equal to 0.05). In the serum of mothers in premature labour (30-38 weeks gestation), the levels of peak 2 but not those of peak (1a + 1b) and 3, were decreased (P less than or equal to 0.01) compared to those not in labour. These findings are consistent with the identification of peak 1a as 5 alpha-dihydroprogesterone, peak 1b as progesterone and peak 3 as 2-methoxyestrone as described in part 2. The decrease in the levels of peak 2 (for which the identification remains unconfirmed) in association with premature and impending term spontaneous labour suggest that it may be involved in the maintenance of pregnancy.

Chromatography↗