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Biomedical subjects

M R Cunningham

Publications and source records attributed to M R Cunningham.

At least 19 recordsLinked to original sources
PubMed1998

Cytotoxic effects of basic FGF and heparin binding EGF conjugated with cytotoxin saporin on vascular cell cultures.

Vascular smooth muscle cell (SMC) proliferation is an integral component of intimal lesion formation. In this study we compared the mitogenic effects of basic fibroblast growth factor (bFGF) and heparin binding epidermal growth factor (HBEGF) and the cytotoxic effects of bFGF and HBEGF conjugated with plant cytotoxin saporin (SAP) on vascular cell cultures. Human vascular SMCs and endothelial cells were cultured and FGF receptor-1 (FGFR-1) and EGF receptor (EGFR) expression were detected by immunohistochemical staining. Cells were grown in 24-well plates. Variable amounts of testing drugs (bFGF, HBEGF, SAP, bFGF-SAP, or HBEGF-SAP) were added to quadruplicate wells after 24 h. Cells without drugs were used as control. The total number of cells was counted at 72 h using a hemocytometer. The cultured human vascular SMCs and endothelial cells expressed both FGFR-1 and EGFR with predominant perinuclear localization. bFGF and HBEGF demonstrated equally potent mitogenic effects on SMC proliferation. SAP alone showed a limited cytotoxic effect on both SMCs and endothelial cells. bFGF had a more potent effect on endothelial cell proliferation than HBEGF. bFGF-SAP was equally cytotoxic for both SMCs and endothelial cells, while HBEGF-SAP had a more selectively cytotoxic effect on SMCs than on endothelial cells. These data suggest that the mitogenic effects of bFGF and HBEGF and the cytotoxic effects of bFGF-SAP and HBEGF-SAP may both be mediated by their corresponding growth factor receptors. Because of its selective cytotoxic effect on SMCs, HBEGF-SAP may become a more attractive agent for controlling intimal lesion formation.

Aorta↗
PubMed1996

Identification of the motor vehicle accident victim who abuses alcohol: an opportunity to reduce trauma.

OBJECTIVE: We hypothesized that a poor driving history and alcohol abuse, evident in a large number of people injured in automobile accidents, contribute to repeated injury, and that treatment for alcohol abuse may reduce vehicular trauma. METHOD: Patients (N = 150) admitted to the emergency surgical service because of injury sustained in a motor vehicle accident (MVA) were tested for their blood alcohol concentrations, and they responded to a questionnaire concerning their prior driving and medical histories. RESULTS: Contrary to the assumption that motor vehicle injuries are isolated episodes, 68% of MVA patients had experienced a prior accident, and 43% had been injured in an MVA before the present event. Prior MVAs were associated with having been previously arrested for driving while intoxicated (DWI), with illegal drug use and with prior hospitalization. Of the MVA patients, 37% were intoxicated (blood alcohol concentration [BAC] > or = 100 mg/dl). Elevated BAC was associated with having been stopped for drinking, having a restricted license, having a DWI arrest, using illegal drugs and having a previous admission to a hospital. Prior MVAs, prior DWIs, elevated BAC and male gender formed the Louisville Alcohol Abuse Predictor Checklist and were independent predictors of alcohol abuse diagnosis, based on the patient's self-report of problems with alcohol. Forty-two percent of MVA patients were diagnosed as alcohol abusers. The alcohol abuser had a significantly higher rate of recurrent MVAs, DWIs and injuries than did nonabusers. CONCLUSIONS: Surgical service may present an opportunity for assessment of alcohol abuse among MVA victims, and treatment for alcoholism might reduce vehicular trauma.

Accidents, Traffic↗
PubMed1996

Steroid therapy of chronic hepatitis: characteristics associated with response in anti-hepatitis C virus-positive and -negative patients.

OBJECTIVES: The goals of this study were to examine responses to corticosteroid-containing therapy in non-B chronic hepatitis patients with different anti-hepatitis C virus (HCV), autoantibody, and biochemical test results and to determine what factors correlate with response. METHODS: Patients with a prior or current history of steroid therapy for putative autoimmune or chronic non-A, non-B hepatitis were assessed. Responses during the first 6 months of therapy were categorized as "complete" (normal aminotransferases for > or = 1 month), "partial" ( > 50% reduction), or "no response." RESULTS: Sufficient data available to permit evaluation in 32 patients. Complete responses were noted in 17, partial responses in 12, and no response in three subjects. By multivariate analysis, only absence of anti-HCV and presence of cirrhosis were independent predictors of response. Nonresponders were found to have lower scores in a proposed autoimmune hepatitis scoring system, but scores of complete and partial responders were not significantly different. Despite a lower likelihood of a complete response, 80% (12/15) of patients with multiantigen positive anti-HCV tests had either partial or complete initial responses to corticosteroid-containing therapy, and, in nine patients, aminotransferases fell to < 2 times the upper limit of normal. All 15 anti-HCV-negative patients, but only three of 15 anti-HCV-positive patients, entered complete responses that were sustained (aminotransferases < twofold abnormal) on regimens containing < 20 mg/day or prednisolone or prednisone. CONCLUSIONS: Although anti-HCV-positive patients frequently exhibit partial initial responses to immunosuppressive therapy, the absence of specific anti-HCV antibodies was better as a predictor of completeness of response than assessment of autoantibodies or degree of biochemical abnormalities.

Adrenal Cortex Hormones↗
PubMed1994

Self-presentation dynamics on overt integrity tests: experimental studies of the Reid Report.

Three experiments examined impression-management responses to the Reid Report Integrity Attitude Inventory. Subjects encouraged to score high on the honesty test attained higher scores than a control group, but no higher than a group of job applicants. Study 2 offered money for high scores, and provided information to use concerning the first, second, or both factors of the Reid Report. Subjects in the three information conditions scored higher than those in a control condition, but again were no higher than job applicants. In a third study, subjects were asked to respond to the Reid Report and to several other measures as if they seriously wanted a job. After the test, each subject was overpaid for the participation. Reid Report scores were significantly correlated with returning versus retaining the money. These results suggest that integrity tests possess predictive validity despite some impression-management response distortion. Relations with other personality measures also are presented.

Adult↗
PubMed1994

Chimeric 7E3 prevents carotid artery thrombosis in cynomolgus monkeys.

BACKGROUND AND PURPOSE: We compared the current antithrombotic strategy of antiplatelet therapy with aspirin, and anticoagulant therapy with heparin, with a specific genetically engineered chimeric antibody (c7E3 Fab) directed against the human glycoprotein IIb/IIIa receptor in an animal model of arterial thrombosis. METHODS: Anesthetized cynomolgus monkeys (Macaca fascicularis) were instrumented for monitoring of arterial blood pressure, heart rate, and carotid artery flow velocity. Animals were treated with saline (n = 6), aspirin (25 mg PO daily for 3 days; n = 6), heparin (100 U/kg i.v. plus infusion adjusted to maintain activated partial thromboplastin time at 2 to 3 times baseline; n = 6), aspirin plus heparin (as administered separately, n = 6), or c7E3 Fab (0.10 mg/kg i.v., n = 7; 0.15 mg/kg i.v., n = 6; 0.20 mg/kg i.v., n = 6; 0.25 mg/kg i.v., n = 6). Thrombus formation via anodal electrolytic stimulation (100 microA) to the intimal surface of the right carotid artery was initiated 15 minutes after drug administration and continued for 180 minutes. Electrolytic injury to the left carotid artery began 210 minutes after drug administration and continued for 180 minutes. Whole blood cell counts, glycoprotein IIb/IIIa receptor blockade, ex vivo platelet aggregation, template bleeding time, and activated partial thromboplastin time were assessed at various time points throughout the experimental protocol. RESULTS: Hemodynamic and hematologic parameters were comparable among groups at baseline. Treatment with c7E3 Fab inhibited ex vivo platelet aggregation, increased bleeding time, decreased thrombus weight, and increased time to occlusion in a dose-dependent manner in both vessels. Treatment with aspirin, heparin, or the combination of aspirin plus heparin was ineffective for the prevention of carotid artery thrombosis in this model. CONCLUSIONS: Inhibition of the platelet glycoprotein IIb/IIIa receptor with c7E3 Fab was found to be safe and effective for the prevention of primary thrombus formation, whereas treatment with either aspirin or heparin or the combination of the two agents failed to protect against occlusive thrombus formation in cynomolgus monkeys.

Abciximab↗
PubMed1990

Inhibition of mink lung epithelial cell proliferation by transforming growth factor-beta is coupled through a pertussis-toxin-sensitive substrate.

Transforming growth factor beta 1 (TGF beta 1) inhibits the proliferative response of mink lung epithelial cells (CCL64) to serum and to epidermal growth factor (EGF). This response to TGF beta 1 can be inhibited by prior exposure of the cells to nanogram concentrations of pertussis toxin (PT), suggesting the involvement of a guanine-nucleotide-binding regulatory protein (G-protein) in mediating TGF beta 1-induced growth inhibition. To characterize further this G-protein dependence, we have isolated, by chemical mutagenesis, a CCL64 variant (CCL64-D1) that is resistant to TGF beta 1. Whereas in the parental CCL64 cells TGF beta 1 stimulates both GTP[35S] (guanosine 5'-[gamma-[35S]thio]triphosphate) binding and GTPase activity, in the CCL64-D1 variants TGF beta 1 is without effect. Quantitative immunoblotting with antisera for G-protein alpha- and beta-subunits, as well as PT-catalysed ADP-ribosylation analyses, revealed no appreciable changes in the level of G-protein expression in the CCL64-D1 variants compared with parental cells. In contrast with another TGF beta-resistant clone, MLE-M, which we show lacks detectable type I receptor protein, the CCL64-D1 cells retain all three TGF beta cell-surface binding proteins. On the basis of these studies, we propose that a necessary component of TGF beta 1-mediated growth inhibition in CCL64 epithelial cells is the coupling of TGF beta 1 receptor binding to G-protein activation.

Animals↗
PubMed1990

Distinct pathways regulate transforming growth factor beta 1-stimulated proto-oncogene and extracellular matrix gene expression.

The effect of pertussis toxin (PT) on transforming growth factor beta 1 (TGF beta 1)-induced proto-oncogene expression was investigated in AKR-2B fibroblasts. PT substantially abolished c-sis and c-myc mRNA expression following TGF beta 1 stimulation. This inhibitory effect was specific for TGF beta 1-stimulated proto-oncogene expression and associated with the ADP-ribosylation of a 41-kDa substrate. Actinomycin D decay and nuclear run-on experiments demonstrated that the inhibitory effects of PT are a result of decreased transcriptional activation and not to an increased decay of proto-oncogene message. PT did not, however, affect TGF beta 1-stimulated fibronectin and collagen mRNA accumulation nor did it have any inhibitory effect on TGF beta 1-induced morphological transformation. These data indicate that TGF beta 1-stimulated gene expression is coupled to multiple pathways distinguished by their sensitivity to PT.

Adenosine Diphosphate↗
PubMed1990

What do women want? Facialmetric assessment of multiple motives in the perception of male facial physical attractiveness.

The multiple motive hypothesis of physical attractiveness suggests that women are attracted to men whose appearances elicit their nurturant feelings, who appear to possess sexual maturity and dominance characteristics, who seem sociable, approacheable, and of high social status. Those multiple motives may cause people to be attracted to individuals who display an optimal combination of neotenous, mature, and expressive facial features, plus desirable grooming attributes. Three quasi-experiments demonstrated that men who possessed the neotenous features of large eyes, the mature features of prominent cheekbones and a large chin, the expressive feature of a big smile, and high-status clothing were seen as more attractive than other men. Further supporting the multiple motive hypothesis, the 2nd and 3rd studies indicated that impressions of attractiveness had strong relations with selections of men to date and to marry but had a curvilinear relation with perceptions of a baby face vs. a mature face.

Beauty↗
PubMed1989

Regulation of transforming growth factor beta 1 action by multiple transducing pathways: evidence for both G protein-dependent and -independent signaling.

The effects of cholera toxin (CT) on transforming growth factor beta 1-stimulated protooncogene expression, [gamma-35S]GTP binding, GTPase activity and growth under anchorage-independent and -dependent conditions were studied in AKR-2B fibroblast cells. CT was shown to inhibit TGF beta 1-stimulated c-sis and c-myc mRNA expression. Actinomycin D decay and nuclear runon experiments demonstrated that this inhibition was not due to an increased decay of protooncogene message, but to a decreased transcriptional activation. These inhibitory effects were not secondary to changes in the ability of TGF beta 1 to bind to its receptor(s) since radioreceptor assays and affinity labeling studies demonstrated that CT had no effect on TGF beta 1 binding. ADP ribosylation of AKR-2B plasma membranes with [alpha-32P]NAD+ revealed a Mr 45,000 protein as the major CT substrate. The labeling of this Mr 45,000 protein in membranes could be inhibited by prior pretreatment of the cells with increasing concentrations of CT. Treatment of membranes with nanogram concentrations of CT abolished the increase in [gamma-35S]GTP binding following addition of TGF beta 1 as well as decreased basal binding. Similarly, CT pretreatment of membranes inhibited TGF beta 1-stimulated GTPase activity. Unexpectedly however, the stimulatory effects of TGF beta 1 on anchorage-independent growth in soft agar were unaffected by CT. Only pertussis toxin was able to inhibit TGF beta 1-induced colony formation in soft agar in a dose-dependent manner. Furthermore, differential effects of both CT and pertussis toxin were observed on TGF beta 1-stimulated monolayer growth; CT was inhibitory, whereas pertussis toxin was without effect. These results suggest that the diverse biological effects of TGF beta 1 are mediated through multiple intracellular pathways distinguishable by their toxin sensitivities.

Animals↗
PubMed1989

Mid-G1 arrest and epidermal growth factor independence of ras-transfected mouse cells.

Transfection of C3H/10T1/2 cells with either a c-myc or an activated c-Ha-ras gene decreased the cellular dependence for serum-derived factors to proliferate in monolayer. The c-myc-transfected cells did, however, require a high plasma concentration for significant growth, while the ras transfectants grew extremely well in either low or high concentrations of either plasma or serum. Stimulation of quiescent cultures with purified growth factors demonstrated that c-myc transfection did not alter qualitatively or quantitatively the requirement for both epidermal growth factor (EGF) and insulin to progress to DNA synthesis. Cells transfected with either a ras gene alone or a combination of ras plus c-myc lost their dependence on EGF for DNA synthesis; cultures became committed to S phase in serum-free medium supplemented with insulin alone. The ras transfectants arrested in mid-G1, 6 h prior to S phase. The EGF independence of the ras transfectants is consistent with the mid-G1 arrest of these cells at a point(s) distal to the primary action of EGF in early G0-G1.

Animals↗
PubMed1989

Interferon alpha/beta modulation of growth-factor-stimulated mitogenicity in AKR-2B fibroblasts.

Growth factor-stimulated mitogenicity in mouse embryo-derived AKR-2B cells was inhibited in a dose-dependent fashion by a mixture of alpha and beta mouse interferons (IFN). A 60% decrease in epidermal growth factor (EGF) and insulin-stimulated DNA synthesis was observed with 10 kU/ml IFN, and half-maximal inhibition was seen at 1 kU/ml. Likewise, the mitogenic effect of 5% fetal bovine serum (FBS) was inhibited by 60% with 10 kU/ml IFN and by 38% with 1 kU/ml IFN. IFN inhibition of DNA synthesis was paralleled by a decrease in monolayer growth of AKR-2B cells by 60% on the 3rd day of culture and by 40% on the 6th day of culture. Soft agar growth of two AKR-2B derived lines, AKR-MCA and AKR-2B (clone 84A), was also inhibited significantly with the addition of 1-10 kU/ml of IFN. The effect of IFN on EGF receptors was also examined. Treatment of AKR-2B cells with 10 kU/ml IFN resulted in a 35% decrease in EGF binding to cell surface receptors. The reduced binding of EGF to cells treated with IFN was due to a loss of EGF receptors as determined by Scatchard analysis. IFN treatment of AKR-2B cells neither altered the affinity of the EGF receptor for its ligand nor affected receptor internalization. Nuclear transcription and actinomycin D decay analysis indicated that within 2 hr, IFN reduced c-myc messenger RNA levels at the level of transcription with no affect on message decay.

Animals↗
PubMed1988

fMLP provokes coronary vasoconstriction and myocardial ischemia in rabbits.

Recent pathological studies of coronary arteries from humans with suspected coronary spasm have revealed an augmented intramural burden of inflammatory cells. To test the hypothesis that inappropriate activation of inflammatory cells participates in the evolution of coronary vasospasm, the present experiments employed a newly developed coronary arteriographic technique for use in pentobarbital-anesthetized rabbits to evaluate the coronary vasomotor actions of the nonselective inflammatory cell stimulant, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). In 10 of 10 animals, selective left intracoronary injection of 200 ng fMLP evoked profound left coronary narrowing accompanied in all cases by ST segment deviation and dysrhythmias. Thallium-201 scintigraphy demonstrated hypoperfusion of the left ventricular free wall and septum supplied by the spastic coronary artery. The fMLP-induced epicardial vaso-constriction, ischemic electrocardiogram (ECG) changes, and thallium perfusion defects were reversed by intravenous nitroglycerin. Neither the right coronary artery nor its distribution were influenced by left coronary injection of fMLP. Additional experiments in isolated, salt solution-perfused rabbit hearts demonstrated that fMLP failed to exert direct coronary vasoconstrictor effects. These observations indicate that the non-selective inflammatory cell stimulant, fMLP, provokes arteriographically demonstrable coronary spasm with attendant myocardial hypoperfusion and ischemic ECG changes in anesthetized rabbits. Such a model may be useful in exploring the dynamic role of inflammatory cells in development of coronary spasm.

Angiography↗
PubMed1987

Coronary arteriography in the intact rabbit: demonstration of coronary vasomotor and electrocardiographic effects of ergonovine and indomethacin in rabbits after abrupt cessation of prolonged nitroglycerin treatment.

Abrupt withdrawal of chronic nitroglycerin treatment may predispose the coronary circulation to spasm. To test this hypothesis directly, we developed a technique for performing selective coronary arteriography in the intact rabbit with images obtained by video-based methods or cineangiographic film. Experiments were then conducted in rabbits treated three times daily with topical nitroglycerin ointment for 6 weeks and in age- and sex-matched control animals. Forty hours after cessation of treatment, animals were anesthetized, and ECG and coronary vasoactive effects (determined by coronary arteriography) of ergonovine, 0.2 mg/kg (intravenous) and indomethacin, 25 mg/kg (intravenous) were assessed. Of six nitroglycerin-treated rabbits, one died of ventricular fibrillation prior to arteriographic study. The remaining five developed ECG abnormalities (single ventricular premature beats, nonsustained ventricular tachycardia, and ST segment deviation) upon challenge with ergonovine or indomethacin. Neither agent evoked ECG changes in control rabbits. In contrast, the degree of luminal diameter reduction in epicardial coronary arteries provoked by ergonovine or indomethacin did not differ between control and nitroglycerin-treated animals. Focal coronary artery spasm was not observed in any rabbit. Our results demonstrate that selective coronary arteriography in rabbits is feasible and that changes in vessel caliber may be assessed from images thus obtained. Data from this study indicate that ergonovine- and indomethacin-induced ECG abnormalities observed in nitroglycerin-treated rabbits cannot be ascribed to epicardial coronary artery spasm.

Animals↗
PubMed1975

To comply or not comply: testing the self-perception explanation of the "foot-in-the-door" phenomenon.

A field experiment was conducted to test the self-perception explanation of the "foot-in-the-door" phenomenon of increased compliance with a substantial request after prior compliance with a smaller demand. In this study, some subjects were first approached with a small request (answer 8 questions in a telephone survey) the size of which was virtually certain to guarantee compliance. Other subjects were first approached with a request sufficiently large to guarantee noncompliance (answer 50 questions). Subjects in both of these conditions were subsequently approached with a moderately sized request (30 questions sponsored by a different public service organization). As predicted by self-perception theory, subjects in the small-initial-request condition showed a higher rate of compliance to the second request (.519), whereas subjects in the large-initial-request condition showed a lower rate of compliance (.219) than subjects in the no-initial-request control condition (.333).

Attitude↗