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Biomedical subjects

S G Gordon

Publications and source records attributed to S G Gordon.

At least 19 recordsLinked to original sources
PubMed2005

Transarterial coil embolization for canine patent ductus arteriosus occlusion.

Left to right shunting patent ductus arteriosus (PDA) is the most common canine congenital heart defect. If not occluded PDA is associated with high morbidity and mortality. Historically, surgical ligation has been the standard method of correction. Although highly successful, surgical ligation is associated with some operative morbidity and mortality. More recently, minimally invasive transcatheter techniques have been employed for PDA occlusion. Transarterial PDA coil embolization is a safe, cost effective, less invasive alternative offered by many specialty centers for PDA occlusion. This procedure involves catheterization of the femoral artery under general anesthesia. An angiogram is then performed to delineate PDA morphology and facilitate coil selection. Coils are commercially available and composed of surgical stainless steel with prothrombotic poly-Dacron fibers. Coils are advanced through a catheter into the PDA under fluoroscopic guidance until satisfactory angiographic occlusion is documented. Patients are then recovered and released the following day. This procedure requires substantial technical expertise and specialized equipment.

Animals↗
PubMed2001

Update on tumor cell procoagulant factors.

Tumor cells produce tissue factor, cancer procoagulant, plasminogen activators and other factors that interact with the coagulation system, the fibrinolytic system and vascular or blood cells such that they can upset the normal homeostasis and balance between activation and inhibition of the coagulation and fibrinolytic systems. These activities play a role in tumor cell growth and metastasis, vascular wall function, and hemostasis. Proteases and their inhibitors are intimately involved in all aspects of the hemostatic, cell proliferation and cellular signalling systems. This review provides a brief examination of recent observations in this complex interaction of cellular and hemostatic factors.

Blood Coagulation↗
PubMed1998

Cancer procoagulant and tissue factor are differently modulated by all-trans-retinoic acid in acute promyelocytic leukemia cells.

All-trans-retinoic acid (ATRA) downregulates the expression of two cellular procoagulants, tissue factor (TF) and cancer procoagulant (CP), in human promyelocytic leukemia cells. To evaluate whether or not changes of the procoagulant activities (PCAs) may share mechanisms with the ATRA-induced cyto-differentiation process, we have characterized the effect of ATRA on the TF and CP expression by NB4 cells, an ATRA maturation-inducible cell line, and two NB4-derived cell lines resistant to ATRA-induced maturation, the NB4. 306 and NB4.007/6 cells. Next, we evaluated the effect on the PCAs of the NB4 parental cells of three synthetic retinoid analogues, ie: AM580 (selective for the retinoic acid receptor [RAR] alpha), capable to induce the granulocytic differentiation of NB4 cells; and CD2019 (selective for RARbeta) and CD437 (selective for RARgamma), both lacking this capability. Cells were treated with either ATRA or the analogues (10(-6) to 10(-8) mol/L) for 96 hours. The effect on cell differentiation was evaluated by morphologic changes, cell proliferation, nitro blue tetrazolium reduction assay, and flow cytometry analysis of the CD33 and CD11b surface-antigen expression. PCA was first measured in 20 mmol/L Veronal Buffer cell extracts by the one-stage clotting assay of normal and FVII-deficient plasmas. Further TF and CP have been characterized and quantified in cell-sample preparations by chromogenic and immunological assays. In the first series of experiments, ATRA downregulates both TF and CP in NB4 parental cells, as expected. However, in the differentiation-resistant cell lines, it induced a significant loss of TF but had little or no effect on CP. In a second series of experiments, in the NB4 parental cells, the RARalpha agonist (AM580) induced cell maturation and reduced 91% CP expression, whereas CD437 and CD2019 had no cyto-differentiating effects and did not affect CP levels. On the other hand, in the same cells the TF expression was reduced by ATRA and AM580, but also by the RARbeta agonist CD2019, which did not induce cell maturation. These data indicate that in NB4 cells, ATRA modulation of CP occurs in parallel with signs of cell differentiation, while the regulation of TF appears to be at least in part independent from these processes, and involves both alpha and beta nuclear retinoid receptors.

Antineoplastic Agents↗
PubMed1998

Removing barriers and improving choices: a case study in reproductive health services and managed care.

Managed care contains inherent structural features that can create obstacles to time-sensitive, confidential reproductive health services. Such structural impediments often exacerbate the sociocultural barriers that have historically affected low-income women--the population that has been targeted for mandatory enrollment in Medicaid managed care plans in many states. This article recommends public policy strategies to overcome and prevent multiple barriers that were identified in a New York-based study in 1995, which focused on access to reproductive health services in managed care settings. This article also includes updated evidence supporting the study's findings and its relevance to other states.

Adolescent↗
PubMed1997

Cancer procoagulant: a factor X activator, tumor marker and growth factor from malignant tissue.

Hemostatic abnormalities associated with malignant disease led to the search for and discovery of a proteolytic enzyme that activated factor X in the blood coagulation cascade. It was named cancer procoagulant (CP). CP is a cysteine proteinase that is found in malignant and fetal (human amnion-chorion) tissue; it has not been found in normally differentiated tissue. It is a calcium-dependent, Mn2+ stimulated enzyme that has enhanced activity and inhibition in a reduced environment. This review presents a complete compilation and discussion of the known chemical and enzymatic characteristics of CP as well as many purification and assay procedures. Several unique properties of these procedures are described. Some problems and controversies are highlighted in each of the sections. An immunoassay for CP as a tumor marker and some of its potential applications in the diagnosis and monitoring of cancer are reviewed. Some therapeutic implications of CP are noted in light of the observation that antibodies to CP block the metastatic seeding of lung colonies in vivo and diminish the viability of tumor cells in vitro. Finally, comments about the relationship between tissue factor and CP in the malignant cells are provided.

Animals↗
PubMed1996

Enhanced isolated lung function after ischemia with anti-intercellular adhesion molecule antibody.

The binding of leukocytes to intercellular adhesion molecules expressed on endothelial surfaces during ischemia and subsequent reperfusion initiates leukocyte-mediated reperfusion injury. Interruption of this leukocyte-endothelium interaction may therefore prevent reperfusion injury. In an isolated, ventilated, blood-perfused rabbit lung preparation, we studied the effect of a monoclonal anti-intercellular adhesion molecule antibody on lung function during reperfusion. Lungs were harvested with 50 ml/kg cold Euro-Collins flush and 30 micrograms prostaglandin E1 before storage for 18 hours at 4 degrees C. Experimental groups received low-dose (100 micrograms) or high-dose (200 micrograms) anti-intercellular adhesion molecule antibody added to the pulmonary flush at harvest and to the initial reperfusate. Eighteen-hour control preparations were preserved for 18 hours and received saline solution vehicle. Immediate control preparations were harvested and immediately reperfused. The oxygen tension in the recirculated pulmonary venous effluent was measured after 30 minutes of reperfusion. Histologic specimens were graded by blinded observers for degree of leukocyte infiltration (0, normal, to 4, severe infiltration). The mean oxygen tensions (+/-standard error of the mean) were 138.29 +/- 6.23, 58.86 +/- 9.14, 86.87 +/- 11.32, and 139.33 +/- 16.15 mm Hg in immediate control preparations, 18-hour control preparations, low-dose antibody group, and high-dose antibody group, respectively (p = 0.0001). The leukocyte grades (mean +/- standard error of the mean) were 1.5 +/- 0.723, 3.0 +/- 0.955, 1.9 +/- 0.899, and 1.2 +/- 0.834, respectively (p = 0.0002). We conclude that anti-intercellular adhesion molecule antibody added to the pulmonary flush and initial reperfusate results in a dose-dependent enhancement of the reperfused lung's ability to oxygenate blood, possibly as a result of decreased leukocyte sequestration.

Animals↗
PubMed1994

Application of cancer procoagulant as an early detection tumor marker.

BACKGROUND: In spite of many advances in the analytical reagents (antibodies), analytical systems, and the clinical application of tumor markers, the present markers do not detect early stage cancer. Preliminary data with an antigen specific to tumor tissue, cancer procoagulant (CP), suggest its possible role in the detection of early stage cancer. This study was aimed at determining the clinical use of CP as an early stage tumor marker. METHODS: An improved enzyme-linked immunosorbent assay (ELISA) was developed to measure CP concentration in serum. A panel of 817 blinded serum samples were examined from three groups of people: 573 cancer, 106 benign, and 139 normal. RESULTS: The sensitivity of all samples analyzed from cancer patients was 80%. The CP ELISA was able to detect ovarian, colon, and kidney cancer at a sensitivity greater than 85%; breast, prostate and small cell lung cancer was detected at a sensitivity of 80-85%. Particularly interesting was the observation that early stage cancers, regardless of site, were detected effectively. In some groups, the CP assay correctly identified 100% of the patients with stage I and II cancer. The assay was able to identify correctly noncancer patient sera at a specificity of 83% for those with benign disease and 82% for the normal individuals. CONCLUSIONS: The CP assay has potential as an aid in diagnosing early stage malignancies and thereby may significantly improve the survival rate of cancer patients.

Adenocarcinoma↗
PubMed1994

Effect of divalent ions on the activity of cancer procoagulant.

The effect of calcium (Ca2+), magnesium (Mg2+), manganese (Mn2+), iron (Fe2+), and zinc (Zn2+) on the factor X-activating activity of cancer procoagulant (CP) was studied. Activity of CP was evaluated with a three-stage chromogenic assay (liquid-phase assay, "native" CP) and with an immunocapture enzyme (ICE) assay (solid-phase assay, immobilized CP). In the liquid-phase assay, CP activity was Ca(2+)-dependent, and Mg2+ (5 mM) or Mn2+ (0.01-0.1 mM) could substitute for Ca2+. There was no additive effect of Mg2+ and Ca2+ on the activity of CP. Activity of CP in the liquid-phase assay, in the presence of 7 mM Ca2+, was enhanced by 0.1 mM Mn2+ to about 240% of the activity observed when only Ca2+ was present in the reaction. Zn2+ and Fe2+ did not activate CP in the absence of Ca2+; they inhibited CP activity in a concentration-dependent mode when administered in the presence of Ca2+. The activity of CP evaluated by the solid-phase assay (ICE assay) was neither Ca(2+)-dependent nor was it susceptible to potentiation by Mn2+ administered after CP was bound to IgM. CP exposed to 5 mM Mn2+ before binding to IgM expressed about 85% higher activity than without the presence of Mn2+. When CP was first preincubated with divalent ion and then immunocaptured, the signal generated in the enzyme-linked immunoadsorbent assay by Mn(2+)-containing CP was significantly different (30% greater) than signals generated by CP without Mn2+ or containing different ion. These data suggest that: (1) there is a significant conformational change of the CP molecule that takes place after capturing CP by the monoclonal IgM antibody on the solid surface; (2) the divalent ions are not directly involved in enzyme-substrate interactions in the CP moiety; and (3) the interaction of Mn2+ with CP seems to be different from that of the other divalent ions.

Amnion↗
PubMed1994

Cancer procoagulant.

Cancer procoagulant is a unique cysteine proteinase. The enzyme has been purified by several procedures and many of its characteristics and enzymatic properties have been determined. Several sensitive and reproducible assays are now available. Many proteinase inhibitors have been evaluated for their effect on CP; most low molecular weight inhibitors work well in a reduced environment. In the foreseeable future, protein and gene sequence information, expression vectors, molecular probes, and highly specific antibodies and inhibitors should provide the research tools to delineate a functional understanding of CP at the molecular and cellular level.

Animals↗
PubMed1994

Reduced expression of glutathione S-transferase Yb2 during progression of chemically induced hepatocellular carcinomas in Fischer 344 rats.

We followed the expression of several glutathione S-transferase subunits in altered foci, liver neoplasms and metastases produced in male Fischer 344 rats by a modified Solt-Farber protocol, to determine whether components of the resistant phenotype are lost during neoplastic progression. At 6 mo after initiation, altered foci and persistent nodules displayed increased immunohistochemical expression of glutathione S-transferase subunits Yf (pi-class), Ya (alpha-class) and Yb1 (mu-class) in comparison with normal or surrounding liver tissue. However, although most altered foci exhibited little change in glutathione S-transferase Yb2 (mu-class) subunit expression, 5% of Yf-positive foci and nodules were partially or completely deficient in Yb2 expression. At 12 and 18 mo after initiation, most grossly visible hepatocellular tumors retained induced expression of glutathione S-transferase subunits Yf, Ya and Yb1, but 63% of the carcinomas, 88% of the primary metastatic carcinomas and 94% of the pulmonary metastases were deficient in Yb2 expression. These differences in glutathione S-transferase subunit expression were confirmed by quantitative analysis by reverse-phase HPLC of S-hexylglutathione affinity-purified glutathione S-transferases from advanced tumors. Cytosolic glutathione S-transferase activity for trans-4-phenyl-3-buten-2-one in advanced tumors ranged from 42% to 66% of the activity in matched surrounding liver, whereas glutathione S-transferase activities for 1-chloro-2,4-dinitrobenzene were increased by 140% to 161%. These studies demonstrate that progression of hepatocellular carcinomas in the resistant hepatocyte model of carcinogenesis in which several glutathione S-transferase subunits are induced is associated with the loss of a major constitutive mu-class hepatic glutathione S-transferase. Although the mechanism and role of the reduction or loss of glutathione S-transferase Yb2 during malignant progression are unknown, we propose that loss of glutathione S-transferase Yb2 in some preneoplastic populations of hepatocytes might be conducive to further DNA damage by presently unknown environmental or endogenous compounds that are normally detoxified preferentially by glutathione S-transferase isoenzymes containing this subunit.

Animals↗
PubMed1994

A structured literature review for risk assessment: EMF and human health risk.

The volume of publications on any given topic makes it difficult to select an appropriate subset of publications for review by an expert panel. This paper proposes a method for selecting a subset using a protocol that attempts to order publications based upon good research methods. The protocol was followed by graduate students with no expert knowledge of the area they were reviewing. They reduced 11730 articles on the topic of EMF and Health risk to 68 articles that were reviewed by an expert panel. The interrater reliability was 96% and 94% of the relevant articles were captured by this process.

Animals↗
PubMed1994

New immunocapture enzyme (ICE) assay for quantification of cancer procoagulant activity: studies of inhibitors.

A new, sensitive and specific immunocapture enzyme (ICE) assay for quantitation of the enzymatic activity of cancer procoagulant (CP) has been developed. The assay had good reproducibility (inter- and intra-assay CV were 6.4% and 5.7% respectively) and was linear for concentrations of CP from 0.5 microgram/ml to 10 micrograms/ml (r2 = 0.995). Using this assay the inhibition of CP by iodoacetamide, mercuric chloride, E-64, leupeptin and antipain was demonstrated. There was no significant effect of cystatin and natural plasma proteinase inhibitors alpha 1-antitrypsin, alpha 1-antichymotrypsin, alpha 2-macroglobulin and antithrombin-III/heparin, on the activity of the CP.

Biomarkers, Tumor↗
PubMed1994

Cancer procoagulant in the human promyelocytic cell line NB4 and its modulation by all-trans-retinoic acid.

Acute promyelocytic leukemia (APL) cells express different types of procoagulant activity (PCA), including tissue factor (TF), and cancer procoagulant (CP). The aim of this study was to investigate whether the NB4 cell line, the first ever isolated human APL line, with the typical t(15;17) chromosomal balance translocation, possess CP as well as the cells freshly isolated from APL patients. Secondly, since the NB4 line is maturation inducible by all-trans-retinoic acid (ATRA), we wanted to verify whether CP, if present, was affected by ATRA treatment. The NB4 cells were able to shorten the recalcification assay of normal human plasma (total PCA). To distinguish CP in the assay for clotting activity, two criteria were used, the independence from factor VII to trigger blood coagulation and the sensitivity to cysteine proteinase inhibitors. Forty-seven per cent of total PCA of cell extracts was found to be FVII-independent PCA. A similar proportion of FVII-independent activity (42%) was detected in the cell serum-free supernatants. The activity was significantly decreased by cysteine proteinase inhibitors, including HgCl2, lodoacetic acid and Z-Ala-AlaCHN2. Additionally CP was directly identified and quantified by an immunocapture enzyme assay. The mean +/- SD concentration of CP detected by this assay in the NB4 cells, before any treatment, was 1.89 +/- 0.5 microgram/mg protein. Treatment of NB4 cells with 10(-6) M ATRA for 5 days significantly decreased the expression of CP, which became virtually undetectable by the clotting assay, and was 64% less than the untreated control by the immunocapture enzyme assay. This study provides the first evidence that the human promyelocytic cell line NB4 possess CP. The expression of this procoagulant is modulated by ATRA.

Blood Coagulation Factors↗
PubMed1993

Three-stage chromogenic assay for the analysis of activation properties of factor X by cancer procoagulant.

The cysteine proteinase, cancer procoagulant (CP; EC 3.4.22.26) was isolated from human amnion-chorion and purified by precipitation with polyethylene glycol and either ion exchange or immunoaffinity chromatography. A new, sensitive, three-stage chromogenic assay was developed for determination of CP factor X-activating activity. Using this assay some properties including dose-response, effect of calcium, phospholipid and pH on the activation of factor X by CP was determined. There was an excellent linear correlation (r2 = 0.99) between concentration and the enzymatic activity of CP. The activation of factor X by purified CP was calcium dependent with an optimum calcium concentration of 7 mM. CP was not phospholipid dependent. There was a rather broad pH optimum between pH 6.9 and 7.25 for the activation of factor X by CP.

Blood Coagulation Tests↗