Family Physicians
34 years of experience

Accepting new patients
Encanto
3330 N 2nd St
Ste 400
Phoenix, AZ 85012
602-631-4090
Locations and availability (2)

Education ?

Medical School Score Rankings
New York University (1976)
  • Currently 4 of 4 apples
Top 25%

Affiliations ?

Dr. Lopez is affiliated with 4 hospitals.

Hospital Affilations

Score

Rankings

  • St Joseph's Hospital
    350 W Thomas Rd, Phoenix, AZ 85013
    • Currently 4 of 4 crosses
    Top 25%
  • Banner Good Samaritan Regional Medical Center
    1111 E McDowell Rd, Phoenix, AZ 85006
    • Currently 4 of 4 crosses
    Top 25%
  • St Luke's Medical Center
    1800 E Van Buren St, Phoenix, AZ 85006
    • Currently 3 of 4 crosses
    Top 50%
  • St Lukes Behavioral Hospital
  • Publications & Research

    Dr. Lopez has contributed to 54 publications.
    Title Internal Mammary Artery Dilatation in a Patient with Aortic Coarctation, Aortic Stenosis, and Coronary Disease. Case Report.
    Date September 2011
    Journal Journal of Cardiothoracic Surgery
    Excerpt

    The ideal surgical approach is unclear in adult patients with coarctation of the aorta that is associated with other cardiovascular pathologies that require intervention. Standard median sternotomy allows simultaneous, coronary revascularization surgery, valve replacement and repair of aortic coarctation. However the collateral circulation and the anatomy of the mammary arteries must be determined, to avoid possible complications. We report a case of a 69 year-old man with aortic coarctation, aortic stenosis, coronary artery disease and internal mammary artery dilatation who underwent concomitant surgical procedures through a median sternotomy.

    Title Oxidized Cellulose As the Cause of an Acute Ischemic Event After Coronary Revascularization.
    Date January 2011
    Journal Interactive Cardiovascular and Thoracic Surgery
    Excerpt

    Absorbable topical hemostatic agents are commonly used in cardiac surgery. In this study, we report an unusual case of an acute ischemic event after coronary revascularization produced by interaction between oxidized cellulose and epsilon aminocaproic acid (EACA). An in vitro study was also performed to test the interaction between oxidized cellulose and EACA.

    Title Coronary Steal by Left Atrial Myxoma: a Case Report.
    Date January 2011
    Journal Cases Journal
    Excerpt

    This report describes a 41-year-old man who had atypical angina resulting from coronary steal by left atrial myxoma. The tumor was completely excised and the patient was symptoms free after operation.

    Title Pathophysiology of Beta2-glycoprotein I in Antiphospholipid Syndrome.
    Date June 2010
    Journal Lupus
    Excerpt

    Since beta(2)-glycoprotein I (beta(2)GPI) was described as the major antigenic target for antiphospholipid antibodies, many studies have focused their attention to the physiological role of beta(2)GPI and anti-beta(2)GPI antibodies on autoimmune-mediated thrombosis. Studies reporting the physiological role of beta(2)GPI have been numerous, but the exact mechanism of action(s) has yet to be completely determined. beta(2)GPI's epitopes for anti-beta(2)GPI autoantibodies have been characterized, however, not all of the heterogeneous anti-beta(2)GPI antibodies are pathogenic. The pathophysiologic role of beta(2)GPI has been reported in the fields of coagulation, fibrinolysis, angiogenesis, and atherosclerosis. Our understanding of the impact of beta(2)GPI, its metabolites and autoantibodies to beta(2)GPI on these physiological functions may contribute to the development of better therapeutic strategies to treat and prevent autoimmune-mediated atherothrombotic vascular disease.

    Title Oxidized-ldl/beta(2)-glycoprotein I Complexes Are Associated with Disease Severity and Increased Risk for Adverse Outcomes in Patients with Acute Coronary Syndromes.
    Date May 2010
    Journal American Journal of Clinical Pathology
    Excerpt

    Oxidized low-density lipoprotein (oxLDL)/beta(2)-glycoprotein I (beta2GPI) complexes have been implicated in atherogenesis. oxLDL/beta2GPI complexes were measured in 339 patients with suspected acute coronary syndromes. Approximately 68% had angiographically documented coronary artery disease (CAD) and significantly higher mean + or - SD levels of oxLDL/beta2GPI (3.75 + or - 6.31 U/mL) than patients with normal coronary arteries (2.21 + or - 3.03 U/mL; P = .0026). Patients with severe CAD had significantly higher mean + or - SD levels of oxLDL/beta2GPI (8.71 + or - 12.87 U/mL) compared with the overall mean of 3.25 U/mL (P < .05) and a significantly higher rate (28.9%) of adverse events than the overall rate of 11.2% (P < .05). Patients with adverse events had higher mean + or - SD levels of oxLDL/beta2GPI (4.05 + or - 5.38 U/mL) than patients without adverse events (3.15 + or - 5.53; P = .029). The relative risk for adverse events in higher oxLDL/beta2GPI quartiles was 3.1 (95% confidence interval, 1.0-9.1; P = .06) for quartile 3 and 3.5 (95% confidence interval, 1.2-10.4; P = .02) for quartile 4. Our results support the concept that oxLDL/beta2GPI complexes are associated with severity of CAD and a 3.5-fold increased risk for adverse outcomes.

    Title Autoimmunity, Infectious Immunity, and Atherosclerosis.
    Date February 2010
    Journal Journal of Clinical Immunology
    Excerpt

    Vascular inflammation is common in certain systemic autoimmune diseases and contributes to the oxidation of low-density lipoprotein (oxLDL) and oxLDL/beta2-glycoprotein I (beta2GPI) complex formation. These complexes have been implicated as proatherogenic autoantigens that participate in the development of atherosclerotic disease.

    Title Immunogenic Oxidized Low-density Lipoprotein/beta2-glycoprotein I Complexes in the Diagnostic Management of Atherosclerosis.
    Date October 2009
    Journal Clinical Reviews in Allergy & Immunology
    Excerpt

    Oxidized low-density lipoprotein (oxLDL) promotes atherosclerosis through a complex interaction of inflammatory and immunologic factors that lead to macrophage lipid uptake and foam cell formation. OxLDL interacts with beta2-glycoprotein I (beta2GPI) forming oxLDL/beta2GPI complexes. These complexes may be formed in the arterial intima during atherogenesis and released into the circulation. Autoantibodies against oxLDL/beta2GPI complexes have been demonstrated in patients with systemic lupus erythematosus and/or antiphospholipid syndrome, and shown to be significantly associated with arterial thrombosis. The observation that monoclonal autoantibodies against oxLDL/beta2GPI complexes significantly increased the oxLDL uptake by macrophages strongly suggests that such IgG autoantibodies are pro-atherogenic. In this article, we review the recent progress in our understanding of LDL oxidation, oxLDL/beta2GPI complex formation, and immune regulation of atherogenesis.

    Title Newer Antiphospholipid Antibodies Predict Adverse Outcomes in Patients with Acute Coronary Syndrome.
    Date September 2009
    Journal American Journal of Clinical Pathology
    Excerpt

    Antiphospholipid antibodies (aPLs) have been implicated in atherogenesis. We studied 344 patients with acute coronary syndromes; approximately 40% were aPL+ in 1 or more tests and 60% aPL-. In 215 patients, coronary artery disease (CAD) was angiographically documented, with 43.7% positive for aPL vs 34.9% of patients without CAD positive for aPLs. Anti-beta(2)-glycoprotein I (beta2GPI; 54%) and anti-oxidized low-density lipoprotein (oxLDL)/beta2GPI (48%) were most frequent, accounting for 87% of all aPL+ CAD cases. aPLs correlated with severity of CAD (P = .012). Adverse events occurred in 16.7% of patients with CAD, more frequently in patients who were aPL+ (P = .0006; relative risk, 2.9; 95% confidence interval, 1.5-5.6). Patients who were aPL+ with severe CAD had more adverse events than patients who were aPL- with severe CAD (P = .005) and aPL+ patients undergoing revascularization procedures (P = .001). Vascular events occurred in 21.7% of aPL+ patients compared with 7.1% of aPL- patients (P = .005). Anti-beta2GPI and anti-oxLDL/beta2GPI were associated with CAD severity and adverse outcomes.

    Title The Immunology of Atherothrombosis in the Antiphospholipid Syndrome: Antigen Presentation and Lipid Intracellular Accumulation.
    Date July 2009
    Journal Autoimmunity Reviews
    Excerpt

    The antiphospholipid syndrome (APS), characterized by elevated serum levels of antiphospholipid antibodies (aPL) and thromboembolic complications, is a common cause of acquired hypercoagulability. The plasma protein beta2-glycoprotein I (beta2GPI) is the most clinically relevant antigenic target for aPL. Recent experimental evidence from our laboratory substantiated the concept that IgG anti-beta2GPI immune complexes containing oxidized LDL (oxLDL) not only facilitated the intracellular accumulation of oxLDL in macrophages but also allowed the presentation of beta2GPI epitopes to pathogenic autoreactive T cells. Both mechanisms required FcgammaRI-mediated uptake by macrophages/monocytes. Furthermore, several clinical studies demonstrated that the presence of circulating oxLDL/beta2GPI complexes and IgG autoantibodies to these complexes was significantly associated with vascular inflammation (i.e. autoimmune-mediated atherothrombosis) in autoimmune patients. In this article, we review recent findings concerning the biochemical and immunologic mechanisms involved in autoimmune-mediated atherothrombosis in patients with APS.

    Title Atherosclerosis in Autoimmune Diseases.
    Date April 2009
    Journal Current Rheumatology Reports
    Excerpt

    Lipid peroxidation occurs frequently in patients with systemic autoimmune diseases and contributes to autoimmune vascular inflammation. Oxidized low-density lipoprotein (oxLDL) interacts with beta2-glycoprotein I (beta2GPI), forming oxLDL/beta2GPI complexes. Circulating oxLDL/beta2GPI complexes and autoantibodies to these complexes have been demonstrated in patients with systemic lupus erythematosus and antiphospholipid syndrome. These findings suggest an immunogenic nature of the complexes and an active proatherogenic role in autoimmunity. Biochemical characterization of the complexes and immunohistochemical studies of atherosclerotic lesions suggest that most of the complexes originate in the arterial wall and are released into circulation. The in vitro macrophage uptake of oxLDL/beta2GPI complexes increased significantly in the presence of antiphospholipid antibodies (anti-beta2GPI), suggesting that macrophage Fcgamma receptors are involved in the lipid intracellular influx that leads to foam cell formation. These findings provide an immunologic explanation for the accelerated development of atherosclerosis seen in systemic lupus erythematosus and antiphospholipid syndrome.

    Title Autoimmune-mediated Atherothrombosis.
    Date February 2009
    Journal Lupus
    Excerpt

    Autoimmune vascular inflammation and oxidative stress (lipid peroxidation) are common in systemic autoimmune diseases and contribute to the oxidative modification of low-density lipoprotein (oxLDL) and oxLDL/beta2GPI complex formation. Circulating oxLDL/beta2GPI complexes have been detected in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). The presence of antibodies to oxLDL/beta2GPI complexes indicates that these complexes are immunogenic, and the coexistence of complexes and antibodies has pointed to an active proatherogenic role in the development of autoimmune vascular complications. Immunohistochemical staining of atherosclerotic lesions suggest that these complexes are formed in the arterial wall and released into circulation. The in vitro macrophage uptake of oxLDL/beta2GPI complexes was significantly increased in the presence of antiphospholipid antibodies, either beta2GPI-dependent anticardiolipin or anti-beta2GPI antibodies, suggesting that macrophage Fcgamma receptors are involved in lipid intracellular influx and foam cell formation. These findings provide an explanation for the accelerated development of atherosclerosis seen in SLE and APS. The presence of circulating oxLDL/beta2GPI complexes and IgG antibodies to these complexes indicate significant vascular injury and oxidative stress as well as an active role in autoimmune-mediated atherothrombosis.

    Title Primary Antiphospholipid Syndrome: a Low-grade Auto-inflammatory Disease?
    Date December 2008
    Journal Rheumatology (oxford, England)
    Excerpt

    To test the inflammation and immune activation hypothesis in primary thrombotic APS (PAPS) and to identify clinical and laboratory factors related to inflammation and immune activation.

    Title Autoimmune Diseases and Infections: Controversial Issues.
    Date August 2008
    Journal Clinical and Experimental Rheumatology
    Excerpt

    The etiology and pathogenesis of certain types of disease remain controversial and stand like a bridge that crosses infectious, autoimmune and autoinflammatory pathways. Infection, for example, may initiate a disease, although it is the genetic regulation in the host, the interplay between virus or bacteria persistence and autoimmunity that produces the later phases of disease, the antigenic determinants responsible for inducing autoimmune disease, and the pathogenetic effector mechanisms. Infections agents cause pericarditis, but in 85% of cases it is "idiopathic". It has also been shown that persistent Clamydia pneumoniae, Porphyromonas gingivalis, and Helicobacter pylori infections cause host immunity and promote atherogenesis. A number of infectious agents have been suggested as potential triggers for primary biliary cirrhosis. Infections and vaccinations have also been linked to the pathogenesis of fibromyalgia syndrome, a common, chronic syndrome of widespread pain. Many factors are also responsible for fever of unknown origin such as: infections, autoimmunity disease, etc. However, it is difficult to determine a direct correlation between the infections agents in such a large group of diseases. The aim of this review is to analyze some of the controversies about the role of infections in autoimmune diseases.

    Title Preventing Autoimmune and Infection Triggered Atherosclerosis for an Enduring Healthful Lifestyle.
    Date April 2008
    Journal Autoimmunity Reviews
    Excerpt

    Atherosclerosis is a chronic inflammatory disease of the arteries associated with various risk factors that promote lipid abnormalities (i.e., dyslipidemia), development and progression of atherosclerotic lesions, plaque rupture, and vascular thrombosis. Experimental evidence from biochemical and clinical studies support the idea that arterial thrombosis is an autoimmune process resulting from 'autoantibody'-mediated pro-atherogenic mechanisms now seen in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). In addition, it has been shown that persistent infections of Chlamydia pneumoniae (C. pneumoniae), Porphyromonas gingivalis (P. gingivalis), and Helicobacter pylori (H. pylori) cause immune responses (infectious immunity) in their hosts that promote atherogenesis. In this article, we review recent progress in our understanding of immune- and infection-mediated atherosclerosis.

    Title Antiphospholipid Antibodies in Patients with Coronary Artery Disease: New Cardiac Risk Factors?
    Date October 2007
    Journal Annals of the New York Academy of Sciences
    Excerpt

    Antiphospholipid antibodies (aPL) have been implicated in the pathogenesis of coronary artery disease (CAD). We evaluated the presence of aPL in patients with chest pain/acute coronary syndromes (ACS) to determine if aPL were associated with the presence and severity of CAD, adverse outcomes, and other coronary risk factors. Patients with chest pain/ACS were evaluated for aPL prior to diagnostic and therapeutic investigations. Coronary angiograms were graded according to the severity of disease. Risk factors, including family histories, were assessed and patients were followed for adverse outcomes. To date, 232 patients (116 M, 116 F, mean age 63 years) with a mean follow-up of 9 months were studied. Thirty-seven percent (86/232) were positive for one or more aPL. More women, 49/86 (57%), were aPL positive versus men, 37/86 (43%). The presence of aPL appeared associated with both presence and severity of CAD (P = 0.176 women; P = 0.163 men). In patients undergoing procedures (angioplasty, stent, bypass), aPL was significantly associated with both an increase in adverse cardiac outcomes (P = 0.045) and extracardiac thrombotic events (P = 0.033). Anti-beta2 glycoprotein-1 (abeta2GP1) was the most frequent aPL, occurring in 68.5% of aPL-positive patients with CAD. Anticardiolipin antibody (aCL) occurred in only 7.4%. IgM isotypes were the most frequent for all categories of aPL (range 55-90%). Family history of antiphospholipid syndrome (APS)-related events was more significant in aPL-positive than aPL-negative individuals (P = 0.027).

    Title Atherogenic Antiphospholipid Antibodies in Antiphospholipid Syndrome.
    Date October 2007
    Journal Annals of the New York Academy of Sciences
    Excerpt

    Macrophage uptake of oxidized LDL (oxLDL) plays a critical role in early stages of atherosclerosis. We previously reported that oxLDL forms stable complexes with beta2-glycoprotein I (beta2GPI), and that these complexes were frequently present in the sera of patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). oxLDL/beta2GPI complexes were shown to be antigenic targets for autoantibodies present in APS. To understand the role of autoantibodies in accelerated atherosclerosis of SLE and APS, we investigated the binding characteristics of beta2GPI and oxLDL to mouse macrophages, and the effect of anti-beta2GPI and anti-oxLDL autoantibodies on this macrophage binding. IgM anti-oxLDL antibody (derived from Apoe -/- mouse) showed inhibitory effect on oxLDL binding to macrophages. Although beta2GPI partly inhibited oxLDL binding to macrophages, IgG anti-beta2GPI autoantibody (derived from APS model mouse) showed pro-atherogenic property by promoting the binding of oxLDL/beta2GPI to macrophages.

    Title Determination of Oxidized Low-density Lipoproteins (ox-ldl) Versus Ox-ldl/beta2gpi Complexes for the Assessment of Autoimmune-mediated Atherosclerosis.
    Date October 2007
    Journal Annals of the New York Academy of Sciences
    Excerpt

    The immunolocalization of oxidized low-density lipoproteins (ox-LDL), beta2-glycoprotein I (beta(2)GPI), CD4(+)/CD8(+) immunoreactive lymphocytes, and immunoglobulins in atherosclerotic lesions strongly suggested an active participation of the immune system in atherogenesis. Oxidative stress leading to ox-LDL production is thought to play a central role in both the initiation and progression of atherosclerosis. ox-LDL is highly proinflammatory and chemotactic for macrophage/monocyte and immune cells. Enzyme-linked immunosorbent assays (ELISAs) to measure circulating ox-LDL have been developed and are being currently used to assess oxidative stress as risk factor or marker of atherosclerotic disease. ox-LDL interacts with beta(2)GPI and circulating ox-LDL/beta(2)GPI complexes have been demonstrated in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). It has been postulated that beta(2)GPI binds ox-LDL to neutralize its proinflammatory and proatherosclerotic effects. Because beta(2)GPI is ubiquitous in plasma, its interaction with ox-LDL may mask oxidized epitopes recognized by capture antibodies potentially interfering with immunoassays results. The measurement of ox-LDL/beta(2)GPI complexes may circumvent this interference representing a more physiological and accurate way of measuring ox-LDL.

    Title The Association of C-reactive Protein with an Oxidative Metabolite of Ldl and Its Implication in Atherosclerosis.
    Date June 2007
    Journal Journal of Lipid Research
    Excerpt

    C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with beta2-glycoprotein I (beta2GPI), implicating oxLDL/beta2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/beta2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/beta2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and beta2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of atherosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/beta2GPI complexes correlated with total cholesterol and hemoglobin A1c. Thus, the generation of CRP/oxLDL/beta2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/beta2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis.

    Title Anticardiolipin Antibodies in Scleroderma.
    Date February 2007
    Journal Journal of Clinical Rheumatology : Practical Reports on Rheumatic & Musculoskeletal Diseases
    Title Oxidative Modification of Low-density Lipoprotein and Immune Regulation of Atherosclerosis.
    Date January 2007
    Journal Progress in Lipid Research
    Excerpt

    Oxidized low-density lipoprotein (oxLDL) is thought to promote atherosclerosis through complex inflammatory and immunologic mechanisms that lead to lipid dysregulation and foam cell formation. Recent findings suggested that oxLDL forms complexes with beta2-glycoprotein I (beta2GPI) and/or C-reactive protein (CRP) in the intima of atherosclerotic lesions. Autoantibodies against oxLDL/beta2GPI complexes occur in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS) and significantly correlate with arterial thrombosis. IgG autoantibodies having similar specificity emerged spontaneously in non-immunized NZWxBXSB F1 mice, an animal model of APS, and a monoclonal autoantibody (WB-CAL-1; IgG2a) against complexed beta2GPI (oxLDL/beta2GPI complexes) was derived from the same mice. WB-CAL-1 significantly increased the in vitro uptake of oxLDL/beta(2)GPI complexes by macrophages. This observation strongly suggests that such IgG autoantibodies are pro-atherogenic. In contrast, IgM anti-oxLDL natural antibodies found in the atherosclerosis-prone mice (ApoE(-/-) and LDL-R(-/-) mice) have been proposed to be anti-atherogenic (protective). The presence of IgG anti-oxLDL antibodies in humans has been documented in many publications but their exact clinical significance remains unclear. In this article, we review recent progress in our understanding of the mechanisms involved in oxidation of LDL, formation of oxLDL complexes, and antibody mediated-immune regulation of atherogenesis.

    Title Atherogenic Oxidized Low-density Lipoprotein/beta2-glycoprotein I (oxldl/beta2gpi) Complexes in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome.
    Date January 2007
    Journal Lupus
    Excerpt

    Oxidized low-density lipoprotein (oxLDL) interacts in vitro with beta2-glycoprotein I (beta2GPI) via LDL-derived specific ligands forming oxLDL/beta2GPI complexes. Circulating oxLDL/beta2GPI complexes have been demonstrated in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Autoimmune vascular inflammation and oxidative stress contribute to oxLDL/beta2GPI complex formation. Immunohistochemical staining of atherosclerotic lesions suggest that these complexes are formed in the arterial wall and released into circulation. The demonstration of antibodies to oxLDL/beta2GPI complexes indicates that these complexes are immunogenic, and the coexistence of complexes and antibodies suggest an active pro-thrombotic/pro-atherogenic role in the development of autoimmune vascular complications. Circulating oxLDL/beta2GPI complexes can be measured by ELISA using a monoclonal antibody specific to complexed human beta2GPI to capture beta2GPI bound to oxLDL. An enzyme-conjugated monoclonal antibody to human Apo B 100 allows the specific detection of oxLDL/beta2GPI complexes. OxLDL/beta2GPI complexes were common in SLE and APS patients suggesting an underlying process of inflammation and oxidation. Using oxLDL/beta2GPI complexes as capture antigen, antibodies to oxLDL/beta2GPI can be measured by ELISA. Serum levels of IgG anti-oxLDL/beta2GPI antibodies were significantly higher in SLE patients with APS compared to SLE controls without APS. Further, high titers of these IgG antibodies were observed in APS patients with a history of arterial thrombosis. The presence of circulating oxLDL/beta2GPI complexes and IgG antibodies to these complexes indicates significant vascular injury and oxidative stress as well as an active role in autoimmune-mediated atherothrombosis.

    Title Accelerated Atheroma in the Antiphospholipid Syndrome.
    Date October 2006
    Journal Rheumatic Diseases Clinics of North America
    Excerpt

    Increased cardiovascular morbidity and mortality due to the pre-mature or accelerated development of atherosclerosis has been reported in patients with systemic autoimmune diseases such as systemic lupus erythematosus. These findings motivated a great deal of research into the role of autoimmunity in atherogenesis. The relationship between atherosclerosis and cholesterol metabolism to atherosclerosis has been well established. However, the participation of newer inflammatory and immunologic mechanisms are emerging as relevant factors for the initiation and progression of atherosclerotic lesions.

    Title Oxidized Low-density Lipoprotein/beta2-glycoprotein I Complexes and Autoantibodies in Patients with Type 2 Diabetes Mellitus.
    Date June 2006
    Journal Annals of the New York Academy of Sciences
    Excerpt

    Diabetes mellitus (DM) is associated with a high incidence of atherosclerotic cardiovascular complications that result from chronic metabolic abnormalities such as hyperglycemia-induced oxidative stress. The oxidative-modification of low-density lipoproteins (oxLDL) and oxLDL/beta(2)-GPI complex formation have been reported in patients with autoimmune disorders. OxLDL/beta(2)-GPI complexes and autoantibodies to these complexes were measured by ELISA in serum samples from 50 type 2 DM patients and 50 age/sex-matched healthy controls. Mean OD for oxLDL/beta(2)-GPI complexes in DM was 0.099 +/- 0.065 with 50% of patients reacting above the assay cutoff (P < 0.001 vs. controls). Mean OD for controls was 0.037 +/- 0.015 with 2% positives. Thirty-six (72%) DM patients were taking cholesterol-lowering statins and had a significantly lower mean OD complex level (0.092 +/- 0.071, P = 0.05) compared to patients not taking statins (0.112 +/- 0.05). Mean OD for IgG anti-oxLDL/beta(2)-GPI antibodies in DM was 0.157 +/- 0.112, similar to the controls (0.146 +/- 0.098, P = 0.328). Increased serum levels of oxLDL/beta(2)-GPI complexes may be a consequence of oxidative stress and LDL modification in DM. Lower levels of oxLDL/beta(2)GPI complexes in DM patients taking statins are in agreement with the antioxidant and antithrombotic properties of these drugs. No significant IgG autoantibody production was observed in this group of DM patients. The interaction of oxLDL with beta(2)-GPI in circulation suggests the intriguing possibility that oxLDL/beta(2)-GPI complexes may also play a role in the development of atherosclerosis and/or cardiovascular complications in DM.

    Title Pregnancy Loss and Endometriosis: Pathogenic Role of Anti-laminin-1 Autoantibodies.
    Date June 2006
    Journal Annals of the New York Academy of Sciences
    Excerpt

    Laminin-1 is a major multifunctional glycoprotein that forms an integral part of the scaffolding network of basement membranes, and is the earliest synthesized component during embryogenesis. This protein (alpha1beta1gamma1) plays an important role in basement membrane assembly and epiblast differentiation during embryonic development. Anti-laminin-1 autoantibodies are known to cause infertility and recurrent spontaneous abortion in animals. Recently, we reported that the presence of IgG anti-laminin-1 antibodies (Abs) in the blood is significantly associated with recurrent first-trimester miscarriages and subsequent negative pregnancy outcomes. Interestingly, these antibodies are also strongly associated with infertility, especially infertility caused by endometriosis. Laminin-alpha1, laminin-beta1, and laminin-gamma1 mRNAs were also detected in 90% of endometriotic lesions, and all laminin-alpha1, laminin-beta1, and laminin-gamma1 chains were localized to the basement membranes of glandular epithelium in endometriotic peritoneal lesions. ELISA showed specific reactivity of the autoantibodies to a particular region of the laminin-1 molecule, that is, the alpha1 chain G domain. IgM monoclonal anti-laminin-1 Abs, which we recently established, also recognized the G domain and cross-reacted with human alpha1 chain located in the basement membrane of the glandular epithelium of human endometrium. We also established an animal model that produced high titers of anti-laminin-1 Abs after immunization with mouse laminin-1. Anti-laminin-1 Abs from the immunized mice caused a higher fetal resorption rate with lower embryonic and placental weights. Thus, anti-laminin-1 Abs may be important in the development of autoimmune-mediated reproductive failures, and the assessment of the such antibodies may provide a novel means for noninvasive diagnosis of endometriosis.

    Title Oxldl/beta2gpi Complexes and Autoantibodies in Patients with Systemic Lupus Erythematosus, Systemic Sclerosis, and Antiphospholipid Syndrome: Pathogenic Implications for Vascular Involvement.
    Date June 2006
    Journal Annals of the New York Academy of Sciences
    Excerpt

    Oxidized low-density lipoprotein (oxLDL) interacts with beta2GPI, forming oxLDL/beta2GPI complexes. Autoimmune vascular inflammation (and oxidative stress) may promote the formation of these complexes. The coexistence of oxLDL/beta2GPI complexes with autoantibodies to these complexes suggests an active pro-atherogenic role in vascular thrombosis and atherosclerosis. Immunoglobulin G (IgG) anti-oxLDL/beta2GPI antibodies have been regarded as pro-atherogenic, whereas IgM antibodies are thought to be anti-atherogenic. For this study, oxLDL/beta2GPI complexes, IgG, and IgM anti-oxLDL/beta2GPI antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Measurements were taken in two patient groups: (1) those with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and rheumatoid arthritis (RA); and (2) those with primary and secondary antiphospholipid syndrome (APS). For oxLDL/beta2GPI complexes, SLE and SSc patients had the highest mean optical densities (ODs) (P <.001), followed by RA (P = .139) and healthy controls. IgG anti-oxLDL/beta2GPI antibody distribution followed the same pattern observed with oxLDL/beta2GPI complexes, SLE and SSc (P <.001), RA (P = .08), and controls. IgM antibodies showed a reverse pattern, with the highest mean OD in RA (P <.001), followed by SSc (P = .007) and SLE (P = 143). Both IgG and IgM anti-oxLDL/beta2GPI antibodies were significantly higher in secondary APS patients compared with SLE controls without APS. In addition, the highest mean OD and prevalence of IgG anti-oxLDL/beta2GPI antibodies were observed in APS patients with a history of arterial thrombosis. These results may reflect the widespread vascular involvement seen in SLE and SSc, in contrast to the relatively low vascular involvement in RA. In SLE and SSc, high serum levels and prevalence of circulating oxLDL/beta2GPI complexes and IgG anti-oxLDL/beta2GPI antibodies indicate significant vascular oxidative stress as well as a possible pathogenic role in autoimmune-mediated atherosclerosis.

    Title The Role of Innate and Adaptive Immunity to Oxidized Low-density Lipoprotein in the Development of Atherosclerosis.
    Date June 2006
    Journal Annals of the New York Academy of Sciences
    Excerpt

    Atherosclerosis is a chronic inflammatory process of the arterial wall associated with systemic and local immune responses to various antigens, oxidized low-density lipoprotein (oxLDL) being the most significant. Both IgM and IgG antibodies to oxLDL are produced during atherosclerosis. Some studies have shown that elevated levels of antibody to oxLDL correlate with the degree of atherosclerosis. Other studies reported that immunization of experimental animals with oxLDL induces high levels of antibodies to oxLDL, with decreased atherosclerosis, suggesting that the immune response to oxLDL may be antiatherogenic. The accelerated development of atherosclerosis has been observed in patients with systemic autoimmune diseases. In patients with antiphospholipid syndrome (APS), beta2-glycoprotein I (beta2GPI) is a major antigenic target for anticardiolipin antibodies (aCLs). We recently reported that oxLDL interacts with beta2GPI via oxLDL-derived specific ligands, such as 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) to form complexes. In vitro, anti-beta2GPI autoantibodies bind to oxLDL/beta2GPI complexes that are actively taken up by macrophages via Fcgamma receptors. Circulating oxLDL/beta2GPI complexes were detected in patients with systemic lupus erythematosus (SLE) and APS, at higher levels than in healthy individuals. Autoantibodies against these complexes were also present; however, IgG anti-oxLig-1/beta2GPI antibody levels in SLE patients with APS were significantly higher than those in SLE patients without APS and those in healthy individuals.

    Title Oxidized Low-density Lipoprotein and Beta2-glycoprotein I in Patients with Systemic Lupus Erythematosus and Increased Carotid Intima-media Thickness: Implications in Autoimmune-mediated Atherosclerosis.
    Date June 2006
    Journal Lupus
    Excerpt

    Oxidative stress and LDL modification (oxLDL) are early pro-atherogenic events. OxLDL binds beta2GPI producing immunogenic oxLDL/beta2GPI complexes. Antibodies to these complexes have been associated with arterial thrombosis in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Circulating oxLDL/beta2GPI complexes, IgG and IgM antibodies to these complexes were measured by ELISA in 30 SLE patients asymptomatic for cardiovascular disease (mean age 31 years) and 27 age/sex matched healthy controls. Carotid intima-media thickness (IMT) was measured by ultrasound in all patients and controls. Forty-seven percent of SLE presented plaques (median IMT of 0.65 +/- 0.12 mm) while only 7% of the controls had plaques (median IMT of 0.50 +/- 0.04 mm, P < 0.001). Median optical density (OD450nm) for oxLDL/beta2GPI complexes in SLE was 0.244 +/- 0.07, higher than controls (0.174 +/- 0.09, P < 0.001). Median OD for IgG anti-oxLDL/beta2GPI antibodies was also higher in SLE (0.297 +/- 0.26) compared to controls (0.194 +/- 0.07, P < 0.001) while the median OD for IgM antibodies in SLE (0.444 +/- 0.46) was not different than controls (0.326 +/- 0.22, P = 0.267). There was no correlation between IMT and oxLDL/beta2GPI complexes, IgG or IgM antibodies, possibly reflecting the complex interrelationship between these serologic elements and tissue factors in the arterial wall. These results support the hypothesis that oxLDL/beta2GPI complexes and IgG (not IgM) anti-oxLDL/beta2GPI antibodies contribute to the development of autoimmune-mediated atherosclerosis.

    Title Antibodies Against Beta2-glycoprotein I Complexed with an Oxidised Lipoprotein Relate to Intima Thickening of Carotid Arteries in Primary Antiphospholipid Syndrome.
    Date June 2006
    Journal Clinical & Developmental Immunology
    Excerpt

    To explore whether antibodies against beta2-glycoprotein I (beta2GPI) complexed to 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) and to oxidised low-density lipoproteins (oxLDL) relate to paraoxonase activity (PONa) and/or intima media thickness (IMT) of carotid arteries in primary antiphospholipid syndrome (PAPS). As many as 29 thrombotic patients with PAPS, 10 subjects with idiopathic antiphospholipid antibodies (aPL) without thrombosis, 17 thrombotic patients with inherited thrombophilia and 23 healthy controls were investigated. The following were measured in all participants: beta2GPI-oxLDL complexes, IgG anti-beta2GPI-oxLig-1, IgG anti-beta2GPI-oxLDL antibodies (ELISA), PONa, (para-nitrophenol method), IMT of common carotid (CC) artery, carotid bifurcation (B), internal carotid (IC) by high resolution sonography. Beta2GPI-oxLDL complex was highest in the control group (p < 0.01), whereas, IgG anti-beta2GPI-oxLig1 and IgG anti-beta2GPI-oxLDL were highest in PAPS (p < 0.0001). In healthy controls, beta2GPI-oxLDL complexes positively correlated to IMT of the IC (p = 0.007) and negatively to PONa after correction for age (p < 0.03). PONa inversely correlated with age (p = 0.008). In PAPS, IgG anti-beta2GPI-oxLig-1 independently predicted PONa (p = 0.02) and IMT of B (p = 0.003), CC, (p = 0.03) and of IC (p = 0.04). In PAPS, PONa inversely correlated to the IMT of B, CC and IC (p = 0.01, 0.02 and 0.003, respectively). IgG anti-beta2GPI-oxLig-1 may be involved in PAPS related atherogenesis via decreased PON activity.

    Title Oxidized Ldl/beta2-glycoprotein I Complexes: New Aspects in Atherosclerosis.
    Date December 2005
    Journal Lupus
    Excerpt

    beta2-glycoprotein I (beta2GPI) is a major antigenic target for antiphospholipid antibodies. Oxidized low-density lipoprotein (oxLDL) is the principal lipoprotein found in atherosclerotic lesions, and it colocalizes with beta2GPI and immunoreactive lymphocytes. oxLDL/beta2GPI complexes appeared in the blood circulation of patients with diseases, such as systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), systemic sclerosis, diabetes mellitus and chronic renal diseases. Thus, the complexes may be associated with systemic and chronic inflammation of the vasculature. IgG anti-oxLDL/beta2GPI complexes autoantibodies and their immune complexes were detected only in SLE/APS patients and in its animal model and were strongly associated with arterial thrombosis. The oxLDL/beta2GPI complexes were internalized by macrophages via IgG anti-beta2GPI antibody-mediated phagocytosis. In contrast, IgM anti-oxLDL antibodies derived from hyperlipidemic mice reduced the incidence of atherosclerosis. The distribution patterns of IgG and IgM anti-oxLDL antibodies in patients suggest the different roles of these antibodies.

    Title Factor Xiii in Primary Antiphospholipid Syndrome.
    Date September 2005
    Journal The Journal of Rheumatology
    Excerpt

    To evaluate the clinical significance of factor XIII (FXIII) in primary antiphospholipid syndrome (APS).

    Title Characterization of a Murine Anti-laminin-1 Monoclonal Antibody (ak8) Produced by Immunization with Mouse-derived Laminin-1.
    Date May 2005
    Journal Clinical & Developmental Immunology
    Excerpt

    Laminin-1 is a structural glycoprotein that forms an integral part of the scaffolding of basement membranes, and plays an important role during embryonic development. We have recently demonstrated a significant association between anti-laminin1 antibodies (Abs) and reproductive failure, such as recurrent spontaneous abortions and infertility-associated endometriosis in both human and mouse studies. In the present study, we established an IgM (micro, kappa) monoclonal anti-laminin-1 Ab (AK8) by immunizing mice with mouse Engelbreth-Holm-Swarm sarcoma (EHS)-derived laminin-1. The AK8 monoclonal antibody (mAb) reacted with particular peptide sequences from the globular G domain of mouse laminin-alpha1 chain of using ELISA and Western blot techniques. The peptide tertiary structure of the epitope recognized by AK8 mAb was predicted using eight synthesized domain peptide sequences and three consensus sequences obtained by phage displayed random peptide library. Basement membranes of endometrium of pregnant mice and humans were immunostained with AK8 mAb. Thus, AK8 mAb recognized a common structure present in the G domain of the laminin-alpha1 chain in both mice and humans. The passive immunization of mice with AK8 mAb may represent a suitable animal model for anti-laminin-1 Ab-mediated reproductive failure.

    Title Igg Autoantibodies Against Beta2-glycoprotein I Complexed with a Lipid Ligand Derived from Oxidized Low-density Lipoprotein Are Associated with Arterial Thrombosis in Antiphospholipid Syndrome.
    Date February 2005
    Journal Clinical & Developmental Immunology
    Excerpt

    We recently reported [J. Lipid Res. 42 (2001), 697; 43 (2002), 1486; 44 (2003), 716] that [beta2-glycoprotein I (beta2GPI) forms complexes with oxidized LDL (oxLDL) and autoantibodies against these complexes are present in patients with SLE and antiphospholipid syndrome (APS). The relationship of beta2GPI/oxLDL complexes and IgG autoantibodies against beta2GPI complexed with oxLig-1 (an oxLDL-derived ligand) with clinical manifestations of APS was studied in 150 APS and SLE patients. The beta2GPI/oxLDL levels of APS patients were similar to those of SLE patients without APS, but they were significantly higher than healthy individuals. There was no difference in the complex levels among the patients with arterial, venous thrombosis, or pregnancy morbidity. IgG anti-beta2GPI/oxLig-1 levels of APS were significantly higher than those of SLE without APS and healthy individuals. Further, antibody levels of APS patients with arterial thrombosis were significantly higher than those patients with venous thrombosis and pregnancy morbidity. Thus, oxidation of LDL leads the complex formation with beta2GPI in SLE and APS patients. In contrast, anti-beta2GPI/oxLig-1 autoantibodies were generated only in APS and were strongly associated with arterial thrombosis. These results suggest that autoantibodies against beta2GPI/oxLDL complexes are etiologically important in the development of atherosclerosis in APS.

    Title Anti-laminin-1 Autoantibodies, Pregnancy Loss and Endometriosis.
    Date January 2005
    Journal Clinical & Developmental Immunology
    Excerpt

    Laminin-1 is a major component and multifunctional glycoprotein of basement membranes that consists of three different subunits, alpha1, beta1 and gamma11 chains. It is the earliest synthesized network-forming protein during embryogenesis and plays an important role in embryonic development, embryonic implantation and placentation. We have recently shown that IgG anti-laminin-1 antibodies were significantly associated with recurrent first-trimester miscarriages and with subsequent pregnancy outcome. Interestingly, these antibodies were also observed in patients with endometriosis-associated infertility but not in patients with other causes of infertility, including tubal factors, hormonal and uterine abnormalities. Laminin-alpha1, -beta1 and -gamma1 mRNAs have been detected in 90% of endometriotic lesions and all laminin-alpha1, -beta1 and -gamma1 chains were localized in the basement membranes of glandular epithelium in endometriotic peritoneal lesions. Western blot analysis showed that anti-laminin-1 antibodies from those patients reacted with all laminin-1's chains. ELISA also confirmed that one of the target epitopes for these antibodies was located in a particular region of the laminin-1 molecule, i.e. the carboxyl-terminal globular G domain of alpha1 chain. IgM monoclonal anti-laminin-1 autoantibody, that we recently established, also recognized the G domain. Anti-laminin-1 antibodies from mice immunized with "mouse" laminin-1, caused a higher fetal resorption rate with lower embryonic and placental weights. Thus, anti-laminin-1 antibodies may be important in development of autoimmune-mediated reproductive failures and the assessment of the antibodies may provide a novel non-invasive diagnosis of endometriosis.

    Title Are Oxidized Ldl/beta2-glycoprotein I Complexes Pathogenic Antigens in Autoimmune-mediated Atherosclerosis?
    Date September 2004
    Journal Clinical & Developmental Immunology
    Excerpt

    The oxidative modification of low-density lipoprotein (LDL) in the intima of arteries contributes to the initiation and progression of atherosclerotic lesions. We have previously reported that oxidized LDL (oxLDL) interacts with an endogenous plasma protein, beta2-glycoprotein I (beta2GPI), to form complexes and that the interaction is mediated by oxLDL specific ligands. We have also demonstrated the presence of oxLDL/beta2GPI complexes in the blood stream of patients with systemic inflammatory and autoimmune diseases. These findings implicate that oxLDL/beta2GPI complexes are possible atherogenic autoantigens. Autoantibodies to oxLDL/beta2GPI complexes have been associated with arterial thrombosis. Further, circulating IgG immune complexes containing oxLDL and beta2GPI were also detected in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). Although many unanswered questions remain about the exact pathogenic mechanism(s) involved, oxLDL/beta2GPI complexes may be described as metabolic products relevant in atherogenesis and as significant participants in autoimmune-mediated atherosclerosis.

    Title Oxidized Low-density Lipoprotein/beta2-glycoprotein I Complexes and Autoantibodies to Oxlig-1/beta2-glycoprotein I in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome.
    Date April 2004
    Journal American Journal of Clinical Pathology
    Excerpt

    Oxidized low-density lipoprotein (oxLDL) interacts with beta2-glycoprotein I (beta2-GPI) via oxLDL-derived specific ligands (oxLig-1) forming complexes. The prevalence and significance of oxLDL/alpha2-GPI complexes and antibodies to oxLig-1/alpha2-GPI were evaluated in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). The oxLDL/beta2-GPI complex was 69% positive (above mean + 3 SD of control subjects) in 97 consecutive patients with SLE, 62% in 40 patients with SLE with secondary APS, and 60% in 50 control patients with SLE without APS. IgG anti-oxLig-1/beta2-GPI antibody was positive in 31 (32%) of 97 consecutive patients with SLE, in 26 (65%) of 40 patients with SLE with secondary APS, and in 6 (19%) of 32 control patients with SLE. Anti-oxLig-1/beta2-GPI antibodies were 93.7% specific with a positive predictive value of 90.0% for APS, better than anticardiolipin antibodies (80.0% specific, 71.4% predictive value). These results confirm that oxLDL/beta2-GPI complexes are common in SLE and suggest a possible immunogenic role in APS. In contrast, IgG anti-oxLig-1/beta2-GPI antibodies not only are associated with but also are clinically useful risk factors for APS.

    Title Anti-beta 2-glycoprotein I and Antiphosphatidylserine Antibodies Are Predictors of Arterial Thrombosis in Patients with Antiphospholipid Syndrome.
    Date February 2004
    Journal American Journal of Clinical Pathology
    Excerpt

    The predictive value (PV) and association of 4 antiphospholipid antibodies with clinical manifestations of the antiphospholipid syndrome (APS) were evaluated in 90 patients with systemic lupus erythematosus (SLE) and 100 with APS. Patients with APS were classified into arterial thrombosis, venous thrombosis, and pregnancy morbidity subgroups. IgG, IgM, and IgA anticardiolipin (aCL), antiphosphatidylserine (aPS), anti-beta 2-glycoprotein I (anti-B2GPI), and antiprothrombin (aPT) antibodies were determined by enzyme-linked immunosorbent assay. Individually, anti-B2GPI and aPS antibodies had the strongest PV for APS (86.4%-94.1%; P < .001) in patients with SLE. The PV for APS reached 100% when 2 or more antibodies were present. Similarly, anti-B2GPI and aPS antibodies had a stronger PV and association for arterial thrombosis (87%-95%; P < .001) compared with venous thrombosis (80%-92%; P = .01). Weak PV and association with pregnancy morbidity were seen with all antibodies. These results suggest an important pathogenic role of anti-B2GPI antibodies in arterial thrombosis. In addition, anti-B2GPI and aPS antibodies seem to provide the best diagnostic value for the laboratory assessment of APS.

    Title Clinical Performance (sensitivity and Agreement with Thrombosis) of Four Antiphospholipid Antibody Assays.
    Date June 2002
    Journal American Clinical Laboratory
    Title Logical Responses to Youth Who Run Away from Home: Implications for Psychiatric Mental Health Nursing.
    Date July 1995
    Journal Journal of Psychosocial Nursing and Mental Health Services
    Excerpt

    1. Runaway youths do not fit into a typical profile; they are adolescents of every race, ethnic group, and religious orientation; they are representative of every socioeconomic status and geographic location in America. 2. Psychosocial events including physical and sexual abuse are common antecedents to runaway behaviors. 3. Implications for psychiatric mental health nursing practice include working with community programs focused on reducing runaway episodes; implementing preventive measures focused on strengthening parenting and problem-solving skills for reducing conflict with families with adolescent children; and promoting responsible sexuality through adequate and responsible sex education and counseling.

    Title Clinical Significance of Immunoglobulin A Versus Immunoglobulins G and M Anti-cardiolipin Antibodies in Patients with Systemic Lupus Erythematosus. Correlation with Thrombosis, Thrombocytopenia, and Recurrent Abortion.
    Date November 1992
    Journal American Journal of Clinical Pathology
    Excerpt

    Serum levels of immunoglobulins (Ig) A, G, and M anti-cardiolipin (aCL) antibodies were determined by enzyme-linked immunosorbent assay in a group of selected systemic lupus erythematosus female patients. Patients were divided into three groups based on their clinical history of thrombosis with or without thrombocytopenia (group I), thrombocytopenia alone (group II), and neither of these (group III). After the aCL antibody levels were determined, the patients' obstetric histories of pregnancies and abortions were reviewed. A high incidence of one or more abortions was seen only in group I patients. A high prevalence of elevated levels of IgA and IgG (but not IgM) aCL antibodies was observed in group I patients. However, among the patients in group II, only the levels of IgA aCL antibodies were increased. In both groups, the addition of the IgA aCL determination--to the classical IgG and IgM aCL assays--increased the prevalence of positive reactors in 31.6%. These results indicate that high levels of IgA aCL antibodies correlated better with thrombocytopenia than either IgG or IgM. Also, the importance of including the determination of IgA aCL antibodies to assess properly the risk of thrombosis, thrombocytopenia, and recurrent abortions in systemic lupus erythematosus patients is demonstrated.

    Title Reduction of Intra-oral Demineralization of Enamel After Single Exposures to Sodium Fluoride.
    Date June 1992
    Journal Journal of Dental Research
    Excerpt

    Studies demonstrated the effects of single rinses with low concentrations of NaF on the intra-oral demineralization of enamel. Blocks of bovine enamel were covered with Streptococcus mutans IB1600, mounted in palatal appliances, and worn in the mouths of volunteers for specified times. Subjects rinsed with solutions of NaF, with or without sucrose. Demineralization was determined as changes in iodide penetrability (delta Ip) of the enamel, while the pH and F of the streptococcal plaque, and enamel F, were determined with ion-specific electrodes. Delta Ip was reduced by about 80% (from 14.5 +/- 2.7 to 2.8 +/- 2.3 units) when 250 micrograms F/mL was added to the sucrose rinse. Corresponding plaque pH's were 4.1 +/- 0.5 and 4.2 +/- 0.3, consistent with a lack of effect on bacterial acidogenesis. Protection against mineral loss was concentration-dependent. Administration of sucrose at different times after NaF revealed that the effect of F persisted for at least 60 min. Analyses of plaque F demonstrated an initial elevation and concentration within the cells, followed by a drop to stable, baseline values. Enamel F increased slowly to almost 500 micrograms/g enamel after 105 min. The protective effect of F appeared to be manifested in two stages, the first related to a high plaque F and the second to F that became incorporated into the enamel. Analysis of the data suggested that F was transferred from plaque to enamel during the experimental period.

    Title Adolescents' Attitudes Toward Mental Illness and Perceived Sources of Their Attitudes: an Examination of Pilot Data.
    Date January 1992
    Journal Archives of Psychiatric Nursing
    Excerpt

    This exploratory descriptive pilot study examined the attitudes of 89 Floridian adolescents toward mental illness and found significant differences according to gender and education about mental illness. Responses to social distance items showed that adolescents tended to be less accepting as they were proposed relationships that suggested greater intimacy with the mentally ill. The mass media, personal experience with someone who had a mental illness, and parents were perceived by the adolescents as the most important sources of their attitudes. The major implications for nursing practice with adolescents, and particularly in the school system, are discussed with suggested interventions.

    Title Lack of Correlation Between Food Retention on the Human Dentition and Consumer Perception of Food Stickiness.
    Date December 1991
    Journal Journal of Dental Research
    Excerpt

    When dental health professionals advise that sticky foods be avoided, it is left to the consumer to choose correctly among different foods. In this study, comparisons were made among consumer ratings of stickiness of 21 commercially available foods and objective measurements of tooth retention of each of the foods. No correlation was found between the two, and neither the rates of clearance of food particles from the teeth nor the rates of clearance of food-derived sugars from the saliva correlated with ratings of food stickiness. Cookies, crackers, and potato chips were most retentive, whereas caramels, jelly beans, raisins, and milk chocolate bars were among those poorly retained. Clearance rates appeared to vary inversely with initial retention. However, chocolate-caramel bars exhibited high initial retention and a very rapid rate of clearance from the teeth. The findings show that consumers cannot accurately assess the retentiveness of foods and, thus, the advise simply to avoid sticky ones is inadequate.

    Title Prevention of Sucrose-induced Demineralization of Tooth Enamel by Chewing Sorbitol Gum.
    Date April 1989
    Journal Journal of Dental Research
    Excerpt

    Measurements were made of the effect of chewing sorbitol gum on the intra-oral demineralization induced by rinsing with 10% sucrose solutions. Blocks of bovine enamel were covered with a layer of Streptococcus mutans IB1600, and mounted on palatal appliances that were worn by five subjects for defined periods of time. Enamel demineralization was determined by following changes in iodide penetrability (delta Ip) of the enamel surfaces. Delta Ip increased to a maximum of about 15 units between 30 and 45 min, while the pH of the S. mutans plaque dropped to below 4 by 15 min. Plaque pH returned to 4.9 by 60 min. Chewing sorbitol gum after the sucrose rinse minimized further increases in delta Ip and brought about a more rapid return of the S. mutans plaque pH toward neutrality. The effect of chewing gum was greater when chewing was initiated earlier so that, when gum was given at five min after the sucrose rinse, demineralization was only 37% of that obtained without gum. The findings confirm earlier reports on the effect of gum on plaque pH, and directly demonstrate the profound protective effects that chewing sorbitol gum can have on tooth enamel.

    Title Nursing Research--the Content.
    Date October 1988
    Journal The Florida Nurse
    Title Lymphocytotoxic Antibodies and Intermediate Immune Complexes in Hypergammaglobulinemic Purpura of Waldenström.
    Date August 1988
    Journal Annals of Allergy
    Excerpt

    Immune complexes, lymphopenia, and lymphocytotoxic antibodies were detected in two patients with hypergammaglobulinemic purpura of Waldenström. These abnormalities were further characterized in one patient. Ultracentrifugation analysis of this patient's serum showed an intermediate peak likely representing medium sized immune complexes. Circulating IgG-containing immune complexes (2-ME resistant Clq binding material) and IgM rheumatoid factor (2-ME sensitive) were also detected. A sequential study of cold reactive IgM lymphocytotoxic antibodies revealed a significant inverse correlation between antibody levels and peripheral lymphocyte counts. The possible implications of these findings in the pathogenesis of hypergammaglobulinemic purpura are discussed.

    Title Immediate Skin Test Reactivity to Common Aeroallergens in Patients with Respiratory Allergies: a Comparative Analysis of Allergen-induced Skin Reactions and Their Histamine Controls.
    Date July 1988
    Journal The Journal of Allergy and Clinical Immunology
    Excerpt

    The results of the immediate skin test response to a panel of 16 common aeroallergens performed in a group of 659 consecutive patients with symptoms suggestive of a respiratory allergy were analyzed. A group of 108 healthy individuals served as control subjects. Ninety-four percent of the patients and 87% of the control subjects had at least one allergen-induced reaction (wheal greater than or equal to 2 by 2 mm). The prevalence of positive skin reactions to each aeroallergen was equally high in both groups. However, if a skin reaction is considered as positive only when an allergen-induced wheal is equal or larger compared to the 50% of the wheal obtained with the histamine control in that individual, 70% of the patients had positive skin reactions and only 38% of the control subjects were positive (p less than 0.05). Similarly, the prevalence rates to five aeroallergens (pollen, Fusarium, Mucor, Pullularia, and Curvularia) in the patient group were reduced to those levels observed with the control group, suggesting they are clinically less important. The age and not the sex influenced both the prevalence rates (p less than 0.001) and the mean size (p less than 0.01) of allergen and histamine-induced skin reactions. Lower prevalence rates and mean size values were observed in the youngest group (0 to 9 years). Moreover, there was an inverse relationship between lower skin reactivity with more younger subjects in our patient population. These results indicate that patients and healthy individuals have similar mechanisms for skin reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Cryoglobulinemia and Cutaneous Vasculitis in Human Brucellosis.
    Date February 1988
    Journal Journal of Clinical Immunology
    Excerpt

    We report the occurrence of cryoglobulinemia and cutaneous vasculitis in three patients with brucellosis caused by Brucella melitensis. The isolated cryoglobulins were characterized as mixed polyclonal or type III. Brucella agglutinin activity was not detected in any of the cryoglobulins analyzed. However, the same agglutinin titer and the presence of precipitin lines of identity in immunodiffusion gels were observed in the supernatant of the cryoglobulins and the serum. Rheumatoid-factor activity was present in all the cryoprecipitates tested. Resolution of the purpuric lesions with therapy coincided with a decrease in serum cryoglobulins and, in one patient, with normalization of his serum C3 levels. These findings suggest that the immunological abnormalities manifested by our patients were the direct consequence of the brucellosis infection and provide additional evidence to support the role for immunological mechanisms in the pathogenesis of human brucellosis.

    Title The Hypocomplementemic Urticarial-vasculitis Syndrome: Therapeutic Response to Hydroxychloroquine.
    Date June 1984
    Journal The Journal of Allergy and Clinical Immunology
    Excerpt

    We report a patient with hypocomplementemic urticarial-vasculitis syndrome. This case illustrates the continuum between urticaria and purpura characteristic of hypocomplementemic urticarial-vasculitis syndrome. Clq precipitin was demonstrated in the patient's serum and in the diethylaminoethylcellulose-ion exchange fraction containing only IgG. A skin biopsy specimen of urticarial and purpuric lesions demonstrated leukocytoclastic vasculitis and granular deposition of C3 and Clq in the basement membrane with IgA, IgM, C3, and Clq in postcapillary venules. Serial total hemolytic complement activity and Clq determinations were performed, and the response to several treatment regimens is presented. Symptomatic and serologic improvement was observed only with hydroxychloroquine.

    Title Gastrointestinal Involvement in Leukocytoclastic Vasculitis and Polyarteritis Nodosa.
    Date February 1981
    Journal The Journal of Rheumatology
    Excerpt

    The records of 106 consecutive patients referred to the University of Colorado Medical Center (UCMC) vasculitis study group during a 5-yr period were evaluated for gastrointestinal (GI) manifestations attributable to vasculitis. There were 3 groups: 18 with leukocytoclastic vasculitis (LCV) on skin biopsy younger than 16 yr of age; 75 with LCV older than 16 yr of age; and 13 with polyarteritis nodosa (PAN). Significant GI manifestations at presentation or exacerbation of vasculitis occurred in 38 of 106 (36%) patients. These were more frequent in LCV patients younger than 16 yr (66%), than older LCV patients (26%) or PAN patients (46%). The commonest complaint was abdominal pain (79%), followed by nausea (63%), vomiting (37%) and diarrhea (23%). GI bleeding was present in 52% and acute abdomen in 21% of patients. No consistent radiologic findings were noted. Duodenal and peritoneal biopsies suggested vasculitis in 6 LCV patients. Seven exploratory laparotomies were performed in 4 LCV and 3 PAN patients. Intestinal infarction was found in 3 patients with PAN, but in one of the LCV patients. Two patients with LCV with an acute abdomen were not explored and responded promptly to iv corticosteroids. Thus, systemic vasculitis frequently involves the GI tract. In patients with LCV, recognition of this association and treatment with corticosteroids can avoid surgery. In our patients with PAN, however, acute abdominal signs indicated infarction requiring surgery and resection.

    Title Perspectives in International Neurosurgery: Neurosurgery in Puerto Rico.
    Date August 1979
    Journal Neurosurgery
    Title The Requirement of Viable Thymocytes for Species-specific Attachment to and Release from Macrophages.
    Date December 1977
    Journal Journal of Immunology (baltimore, Md. : 1950)
    Excerpt

    The role of the thymocyte in its species-specific binding to macrophages has been explored. Although formalin treatment of macrophages resulted in loss of binding to thymocytes, formalin treatment of thymocytes did not have this effect. However, two differences between living and formalin-treated thymocytes were noted. Formalin-treated thymocytes bound to macrophages of any species whereas the binding of living thymocytes was species specific. Living thymocytes attained maximum binding in approximately 1 hr and then the fraction bound gradually diminished. Formalin-treated thymocytes remained bound to the macrophage and appeared to be phagocytized. Released thymocytes did not bind to fresh macrophages, but released macrophages bound to fresh thymocytes. The results suggest that the binding of thymocytes to macrophages results in maturation of thymocytes.

    Title Immunological Survey in High Altitude: Effect on Antibody Production and the Complement System.
    Date August 1976
    Journal Annali Sclavo; Rivista Di Microbiologia E Di Immunologia
    Excerpt

    In order to asses the effect of acute exposure to natural high altitude on some immunological mechanisms of mice, the primary response to SRBC was studied by the direct Hemolytic Plaque and Hemagglutination Tests. A control group was studied in Lima, Peru, 150 m. At high altitude (Ticlio, Peru, 4843 m), we found fewer spleen plaque-forming cells (PFC) and the maximal peak of PFC was delayed 1 day, as compared with the response at a lower altitude. Conversely, there was a higher serum concentration of 2-ME sensitive and resistant hemagglutinin antibodies at high altitude and the 19-S (2-ME sensitive) response was predominant during the first days at high altitude while the 7-S response was retarded. These results are interpreted as a stimulating effect of hypoxia on the 19-S antibody production rather than a cellular proliferation as far as the SRBC system is concerned. Serum concentrations of Igs G, M, A and the fraction C'3 of the Complement (B1C/B1A globulin) were determined in normal natives from three cities at different altitude levels: Morococha-Ticlio, 4680 m; La Oroya, 3700 m; and Tarma, 3051 m by the Radial Immunodiffusion Test. The serum concentration of C'3 was correlated with the total hemolytic activity of Complement (C'H50 method) in a group of natives from Morococha. The control group was of normal natives from Lima. No significant differences were found between resum concentration of Igs G, M and A in both groups, but there was a tendency for higher values of IgA at higher altitudes, and most sera in the high altitude group were above the normal IgG values for adults. The resum concentration of C'3 and the hemolytic activity of Complement were wound to be diminished in the high altitude group. These results are interpreted as an inhibitory effect of the altitude on the sequential activation and/or lysing capability rather than a reduction in the C'3 concentration.

    Title Thymocytes, Macrophages, and Erythrocytes.
    Date July 1974
    Journal The Journal of Allergy and Clinical Immunology
    Title Antiphospholipid Antibodies and Antiphospholipid Syndrome: Role in Portal Vein Thrombosis in Patients With and Without Liver Cirrhosis.
    Date
    Journal Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/hemostasis
    Excerpt

    The antiphospholipid syndrome (APS) has been associated with portal vein thrombosis (PVT). This study explored the contribution of antiphospholipid antibodies (aPL) to PVT in cirrhotic and noncirrhotic patients. Patients and methods: A total of 50 patients with liver cirrhosis and PVT, 50 patients with liver cirrhosis without PVT, 50 consecutive PVT without liver cirrhosis, and 50 controls. aPL tests: lupus anticoagulants (LAs), immunoglobulin G (IgG) anti-cardiolipin antibodies (aCL), IgG anti-beta-2-glycoprotein-I (beta2GPI), and IgG beta2GPI-complexed with oxidized low-density lipoprotein antibodies (ox-LDL). Results: Lupus anticoagulants were negative in all patients. A titre of IgG aCL >40 IgG phospholipid units (GPL) was present in 2% of patients with liver cirrhosis and in none of the other groups. In all, 4% of patients with PVT without cirrhosis were positive for IgG beta2GPI in the absence of any other positive aPL and labelled as primary APS. Conclusions: aPL play no role in PVT associated with liver cirrhosis but can be tested in idiopathic PVT.


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