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2.
Circulation ; 103(6): 806-12, 2001 Feb 13.
Article in English | MEDLINE | ID: mdl-11171787

ABSTRACT

BACKGROUND: Acute coronary syndromes present with an increased incidence from 6:00 AM to 12:00 noon. Whether endothelial function follows a diurnal rhythm and whether this rhythm is impaired in coronary artery disease (CAD) has not previously been studied. METHODS AND RESULTS: Diurnal variation in endothelium-dependent vasodilatation was examined in 10 CAD patients and 10 control subjects. Forearm blood flow responses to acetylcholine, sodium nitroprusside, and N(G)-monomethyl-L-arginine were determined by plethysmography at 8:00 AM, 2:00 PM, and 8:00 PM. Heart rate, blood pressure, plasma cortisol, and inflammatory markers were also determined. Heart rate and the low-frequency component of heart rate variability were greatest in the morning in control subjects, suggesting a diurnal variation in sympathetic activity. Basal forearm blood flows were significantly reduced in control subjects at 8:00 PM compared with 8:00 AM and 2:00 PM (1.2+/-0.2 versus 2.1+/-0.2 [8:00 AM] and 2.1+/-0.3 [2:00 PM] mL. 100 mL(-1). min(-1); P<0.05) but unchanged in the CAD group. Acetylcholine (37 microgram/min) responses were greater at 8:00 AM than at 8:00 PM in control subjects (12.5+/-3.7 versus 19.6+/-2.9 mL. 100 mL(-1). min(-1), respectively; P<0.05), but these responses were not time dependent in the CAD group. Responses to sodium nitroprusside were similar at all time points and between those with and without CAD. CONCLUSIONS: Thus, normal volunteers have a diurnal variation in their endothelium-dependent vasodilatation that may counteract other, potentially adverse, diurnal variations in hemodynamic and other parameters. In contrast, CAD patients who had presented with acute coronary syndromes showed a loss of this protective mechanism.


Subject(s)
Circadian Rhythm , Coronary Disease/physiopathology , Endothelium, Vascular/physiopathology , Hemodynamics , Acetylcholine , Acute Disease , Analysis of Variance , Blood Glucose/analysis , Blood Pressure , Carrier Proteins , Cholesterol/blood , Coronary Disease/blood , Cyclic AMP Receptor Protein/blood , Forearm/blood supply , Heart Rate , Humans , Hydrocortisone/blood , Interleukin-6/blood , Male , Middle Aged , Nitroprusside , Plethysmography , Triglycerides/blood , Vasodilation , omega-N-Methylarginine
3.
Pol Merkur Lekarski ; 11(63): 210-3, 2001 Sep.
Article in Polish | MEDLINE | ID: mdl-11761812

ABSTRACT

The levels of IL-6, CRP and TPS were measured in 38 patients with ovarian carcinoma in different histological types and clinical stages. The values IL-6, CRP and TPS were determined before and after chemotherapy. Pretreatment levels of IL-6, CRP and TPS were significantly increased in carcinoma patients relatively to the control group. The frequency of increased results and absolute value of IL-6 and TPS levels showed tendency to significant increase with the stage of disease. The highest values of IL-6 were observed in patients with serous and mucous carcinoma. The levels of IL-6, CRP and TPS were decreased above cut off values in patients with remission, and did not changed in patients with progression and stabilization disease. The results suggest that IL-6 especially in the combination with CRP and TPS may be useful in the diagnosis and the evaluation of therapy of patients with ovarian carcinoma.


Subject(s)
Carcinoma/blood , Cyclic AMP Receptor Protein/blood , Interleukin-6/blood , Ovarian Neoplasms/blood , Peptides/blood , Adult , Aged , Biomarkers, Tumor , Carcinoma/diagnosis , Carcinoma/drug therapy , Carrier Proteins , Enzyme-Linked Immunosorbent Assay , Female , Humans , Middle Aged , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/drug therapy , Treatment Outcome
4.
Biochemistry ; 39(19): 5797-807, 2000 May 16.
Article in English | MEDLINE | ID: mdl-10801330

ABSTRACT

The newly described adapter molecule p130 Crk-associated substrate (Cas) has been reported to contribute to cytoskeletal organization through assembly of actin filaments and to be pivotal in embryonic development and in oncogene-mediated transformation. We characterized the regulation of Cas tyrosine phosphorylation in highly differentiated, anucleate platelets. Phospholipase C-activating receptor agonists, including collagen, thrombin receptor-activating peptide (TRAP), and U46619 (a thromboxane A2 analogue), and A23187 (a Ca2+ ionophore) induced rapid Cas tyrosine phosphorylation in platelets. 12-O-Tetradecanoylphorbol 13-acetate and 1-oleoyl-2-acetyl-sn-glycerol, protein kinase C (PKC) activators, also induced Cas tyrosine phosphorylation, albeit sluggishly. Cas tyrosine phosphorylation induced by collagen or TRAP was transient in aggregating platelets; Cas became dephosphorylated in a manner dependent on integrin alpha IIb beta 3-mediated aggregation. While BAPTA-AM (an intracellular Ca2+ chelator) inhibited Cas phosphorylation induced by collagen or TRAP, Ro31-8220 (a PKC inhibitor) rather prolonged it. Under the conditions, this PKC inhibitor suppressed platelet aggregation but not intracellular Ca2+ mobilization. In contrast to Cas involvement in focal adhesions in other cells, platelet Cas phosphorylation preceded the activation of focal adhesion kinase (FAK), and blockage of alpha IIb beta 3-mediated platelet aggregation with a GRGDS peptide resulted in prolongation of stimulation-dependent Cas tyrosine phosphorylation but in suppression of FAK tyrosine phosphorylation. Furthermore, TRAP-induced Cas phosphorylation was insensitive to cytochalasin D, an actin polymerization inhibitor. The failure of FAK to associate with Cas in immunoprecipitation studies also suggests that Cas tyrosine phosphorylation is independent of FAK activation. Of the signaling molecules investigated in this study, Src seemed to associate with Cas. Finally, Cas existed mainly in cytosol and membrane cytoskeleton fractions in the resting state, and remained unchanged during platelet aggregation, when FAK translocated to the cytoskeletal fraction. Our findings on platelet Cas suggest that (i) rapid Cas tyrosine phosphorylation occurs following phosphoinositide turnover by receptor-mediated agonists and may be mediated by intracellular Ca2+ mobilization; (ii) PKC activation, by itself, may elicit sluggish Cas phosphorylation; (iii) Cas tyrosine dephosphorylation, but not phosphorylation, is dependent on integrin alpha IIb beta 3-mediated aggregation; and (iv) Cas is not involved in cytoskeletal reorganization. Anucleate platelets seem to provide a unique model system to fully elucidate the functional role(s) of Cas.


Subject(s)
Blood Platelets/metabolism , Cytoskeleton/physiology , Phosphoproteins/blood , Platelet Aggregation , Platelet Glycoprotein GPIIb-IIIa Complex/physiology , Proteins , Signal Transduction , Tyrosine/blood , Blood Platelets/drug effects , Blood Platelets/enzymology , Blood Platelets/physiology , Blood Proteins/metabolism , Calcium/blood , Carrier Proteins , Crk-Associated Substrate Protein , Cyclic AMP/agonists , Cyclic AMP/blood , Cyclic AMP Receptor Protein/agonists , Cyclic AMP Receptor Protein/blood , Cytochalasin D/pharmacology , Cytoskeleton/drug effects , Cytoskeleton/metabolism , Enzyme Activation , Focal Adhesion Kinase 1 , Focal Adhesion Kinase 2 , Focal Adhesion Protein-Tyrosine Kinases , Humans , Intracellular Fluid/metabolism , Phosphoproteins/physiology , Phosphorylation/drug effects , Platelet Activation/drug effects , Platelet Aggregation/drug effects , Protein Kinase C/blood , Protein-Tyrosine Kinases/blood , Receptors, Cell Surface/agonists , Retinoblastoma-Like Protein p130 , Signal Transduction/drug effects , Subcellular Fractions/enzymology , Subcellular Fractions/metabolism , src Homology Domains
5.
Respirology ; 5(4): 315-20, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11192540

ABSTRACT

OBJECTIVE: To clarify the clinical significance of autoantibodies (auto-Ab) to interleukin-1alpha (IL-1alpha) in rheumatoid arthritis (RA) with interstitial lung disease (ILD), we examined the IL-1alpha auto-Ab level in serum of patients with RA with/without ILD. METHODOLOGY: We investigated the level of IL-1alpha auto-Ab in serum of 70 patients with RA with/without ILD and 40 control patients (CP). Levels of IL-1alpha auto-Ab were measured by radioimmunoassay, and serum was regarded as IL-1alpha auto-Ab positive at an auto-Ab level of more than 5 ng/mL. RESULTS: Interleukin-1alpha auto-Ab was detected in the serum of 30 out of 70 RA patients (42.9%), and six out of 40 CP (15%) (P < 0.05). Interleukin-1alpha auto-Ab were detected in the serum of 18 out of 32 patients with RA with ILD (56.2%) and 12 out of 38 patients with RA without ILD (31.5%). The positive rate of these autoantibodies in RA with ILD was significantly higher than that in RA without ILD (P < 0.05). Although C-reactive protein, immunoglobulin G, rheumatoid factor and rheumatoid arthritis particle agglutination levels in serum from patients with RA with ILD were not significantly different between the IL-1alpha auto-Ab-positive and -negative groups, the lactate dehydrogenase level (LDH) and AaDO, in the IL-1alpha auto-Ab-positive group were significantly higher than those in the negative group (LDH: P < 0.001, AaDO2: P < 0.05). CONCLUSION: These results suggest that IL-1alpha auto-Ab are generated in response to the immunoinflammatory process of ILD in RA, and these autoantibodies may neutralize and regulate the IL-1alpha activity.


Subject(s)
Arthritis, Rheumatoid/complications , Autoantibodies/blood , Interleukin-1/immunology , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/immunology , Adult , Aged , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Rheumatoid/drug therapy , Blood Sedimentation , Carrier Proteins , Case-Control Studies , Cyclic AMP Receptor Protein/blood , Female , Humans , L-Lactate Dehydrogenase/blood , Lung Diseases, Interstitial/blood , Male , Middle Aged , Steroids
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