Autoimmunity in atherosclerosis. The role of autoantigens.
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Animals↗
Biomedical subjects
J George
Publications and source records attributed to J George.
Effect of hyperglycemia and hyperlipidemia on atherosclerosis in LDL receptor-deficient mice: establishment of a combined model and association with heat shock protein 65 immunity.
Diabetes and atherosclerosis have been proposed to be influenced by immune and autoimmune mechanisms. A common incriminated antigen in both disorders is the heat shock protein (HSP)-60/65. In the current study, we established a model combining hyperglycemia with hyperlipidemia in LDL receptor-deficient (LDL-RD) mice and assessed its possible influences on lipid profile, HSP60/65, and atherogenesis. LDL-RD mice were injected either with streptozotocin to induce hyperglycemia or with citrate buffer (control). When hyperglycemia was induced, both study groups were challenged with a high-fat (Western) diet for 6 weeks. Plasma fasting glucose, lipid profile, and antibody levels to HSP65 and oxidized LDL were assessed. At death, the spleens from both groups were evaluated for their proliferative response to HSP65 and the consequent cytokine production. The extent of atherosclerosis was assessed at the aortic sinus. Plasma glucose, cholesterol, and triglyceride levels were elevated in mice injected with streptozotocin compared with control mice. Atherosclerotic lesions were significantly larger in the streptozotocin-injected hyperglycemic LDL-RD mice (132 +/- 23 x 10(5) microm2) in comparison to their normoglycemic litter-mates (20 +/- 6.6 x 10(5) microm2; P < 0.0001). Both humoral and cellular immune response to HSP65 was more pronounced in streptozotocin-injected mice. When challenged with HSP65 in vitro, splenocytes from streptozotocin-injected mice favored the production of the T-helper (TH)-1 cytokine gamma-interferon. In conclusion, we have established a mouse model that combines hyperglycemia with diet-induced hyperlipidemia in LDL-RD mice and studied its effect on atherosclerosis progression. The accelerated atherosclerotic process is associated with heightened immune response to HSP65 and a shift to a TH1 cytokine profile.
Animals↗
Predictors of liver-related complications in patients with chronic hepatitis C.
Chronic hepatitis C is the leading cause of decompensated liver disease requiring liver transplantation and a major cause of hepatocellular carcinoma (HCC). In liver clinic series, about 20% of those chronically infected with hepatitis C virus (HCV) develop cirrhosis over 20 years. From epidemiological data, however, it is clear that certain subgroups of patients are more likely to develop liver-related complications than others. Both host and viral factors have been implicated in individual susceptibility to adverse outcomes. The impact of host factors, such as alcoholism, is now well defined, and viral factors, such as genotype and viral load, appear to be less influential than previously considered. Coinfections with HIV, hepatitis A virus (HAV) and hepatitis B virus (HBV) may influence the rate of fibrotic progression and the subsequent development of complications in patients with chronic hepatitis C. The stage of fibrosis on biopsy and biochemical markers, such as a low serum albumin, can help identify patients who are more likely to develop complications. The role of the immune system in modifying the course of HCV is only now being defined. This editorial explores the role of host and viral factors in the development of liver-related complications in HCV-infected individuals.
Hepacivirus↗
[Endogenous aspergillus endophthalmitis: a case repport].
We report a case of endogenous aspergillus endophthalmitis. This infection occurred in a young immunocompromised boy of 6 years old. The localisation of the chorioretinitis was unusual because out of the posterior area. The evolution was favorable with recovering of the visual acuity under general treatment and intravitreous injections.
Amphotericin B↗
Cercarial dermatitis in India.
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Animals↗
Follow-up among women with an abnormal mammogram in an HMO: is it complete, timely, and efficient?
OBJECTIVE: To describe the extent to which women with seriously abnormal mammograms complete indicated follow-up, the timeliness of this follow-up, and variations in the pattern of use of diagnostic procedures. STUDY DESIGN: Retrospective chart review. PATIENTS AND METHODS: Ninety-two women enrolled in a single urban health maintenance organization (HMO) with an abnormal index mammogram (mass or suspicious calcifications) during 1995 or 1996 were identified by review of all HMO mammography reports. Data were abstracted from medical records concerning all clinical services received over the 11 months after the date of the abnormal mammogram. Procedure costs were estimated based on 1997 Medicare relative-value units. Logistic regression and a multivariate accelerated failure-time model were used to evaluate the association between predictor variables and the occurrence and timing of completion of follow-up. RESULTS: Follow-up was not completed by 31 (34%) of the 92 study women and was delayed beyond 60 days for another 32 (35%). In adjusted analysis, factors associated with completion within 60 days included age less than 50 years and inclusion of a specific follow-up recommendation in the mammogram report. Completion by the end of the study (a minimum of 11 months after the index mammogram) was associated only with the presence of a specific follow-up recommendation. The follow-up process (i.e., the diagnostic procedures used) was highly variable but almost always included surgical evaluation. The average cost among those completing follow-up was about $1900 (in 1997 dollars). CONCLUSIONS: Incomplete follow-up after a potentially seriously abnormal mammogram constitutes an important barrier to breast cancer control efforts in the study HMO, but its explanation remains incompletely understood. The follow-up process itself is highly variable, and improvement in its efficiency and timely completion will require a better understanding of its determinants.
Adult↗
Autoantibodies associated with atherosclerosis.
Atherosclerosis is a multifactorial pathological process. In recent years, the immune factors associated with its initiation and progression have been investigated intensively. Several autoantigens and their respective autoantibodies have been suggested as factors in atherogenesis. This manuscript provides a review of autoantibodies directed towards oxidized low-density lipoprotein (oxLDL), cardiolipin, beta2-glycoprotein-I and heat-shock protein 60/65, and their association with human and murine atherosclerosis.
Animals↗
In vivo inhibition of rat stellate cell activation by soluble transforming growth factor beta type II receptor: a potential new therapy for hepatic fibrosis.
Transforming growth factor beta (TGF-beta) is a well characterized cytokine that appears to play a major role in directing the cellular response to injury, driving fibrogenesis, and, thus, potentially underlying the progression of chronic injury to fibrosis. In this study, we report the use of a novel TGF-beta receptor antagonist to block fibrogenesis induced by ligation of the common bile duct in rats. The antagonist consisted of a chimeric IgG containing the extracellular portion of the TGF-beta type II receptor. This "soluble receptor" was infused at the time of injury; in some experiments it was given at 4 days after injury, as a test of its ability to reverse fibrogenesis. The latter was assessed by expression of collagen, both as the mRNA in stellate cells isolated from control or injured liver and also by quantitative histochemistry of tissue sections. When the soluble receptor was administered at the time of injury, collagen I mRNA in stellate cells from the injured liver was 26% of that from animals receiving control IgG (P < 0.0002); when soluble receptor was given after injury induction, collagen I expression was 35% of that in control stellate cells (P < 0.0001). By quantitative histochemistry, hepatic fibrosis in treated animals was 55% of that in controls. We conclude that soluble TGF-beta receptor is an effective inhibitor of experimental fibrogenesis in vivo and merits clinical evaluation as a novel agent for controlling hepatic fibrosis in chronic liver injury.
Animals↗
Anti-oxidized low density lipoprotein antibody determination as a predictor of restenosis following percutaneous transluminal coronary angioplasty.
Recent data suggests that autoimmune factors play an important role in the pathogenesis of atherosclerosis. In this context several autoantigens have been shown to elicit an immune response that results in accelerated atherosclerotic plaque formation. In the present study, we investigated whether elevated titers of anti-oxidized low density lipoprotein (oxLDL), anticardiolipin and antibodies to beta2-glycoprotein I (beta2GPI) can predict subsequent restenosis in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). A total of 74 consecutive patients (52 males, 22 females) with coronary artery disease were enrolled in the study. All patients underwent successful PTCA prior to which blood was drawn for the antibody analysis. The PTCA was followed by a clinical evaluation. Patients with recurrent chest pains underwent a repeated angiography and 34 of the 74 patients (46%) experienced restenosis. Patients positive for the presence of anti-oxLDL antibodies were more likely to develop restenosis within 6 months when compared with patients with no subsequent restenosis (relative-risk of 1.87; P< 0.05). Presence of anti-oxLDL antibodies was associated with hyperlipidemia (r = 0.25; P < 0.05) but not with other risk factors for atherosclerosis. Positivity for anticardiolipin or anti-beta2GPI antibodies which associate with a prothrombotic state, was not effective in predicting lumen narrowing. Thus, the presence of elevated levels of anti-oxLDL antibodies is associated with a higher risk for coronary restenosis following PTCA.
Aged↗
Immunolocalization of beta2-glycoprotein I (apolipoprotein H) to human atherosclerotic plaques: potential implications for lesion progression.
BACKGROUND: beta2-Glycoprotein I (beta2GPI) is a major antigenic target of antiphospholipid antibodies, which possesses natural anticoagulant properties. The aim of the present study was to determine its presence and localization within human atherosclerotic plaques and to study its association with endothelial cells and monocyte macrophages in vitro. METHODS AND RESULTS: Human atherosclerotic lesions were obtained after carotid endarterectomies and studied immunohistochemically with anti-beta2GPI as well as antibodies to CD4/CD8, macrophages, and adhesion molecules. In vitro, human umbilical vein endothelial cells (HUVECs) and U937 (myelomonocytic cell line) cells were investigated for their ability to associate with radiolabeled beta2GPI. We found beta2GPI to be abundantly expressed within the subendothelial regions and intimal-medial borders of human atherosclerotic plaques and to colocalize with CD4-positive lymphocytes. This observation was confirmed by Western blot applied on homogenates of atherosclerotic lesions with anti-beta2GPI antibodies. Both HUVECs and U937 cells bound labeled beta2GPI, and the process was inhibited by oxidized LDL and not by native LDL. CONCLUSIONS: The abundant presence of human beta2GPI within the lesions, its association with endothelial cells and macrophages, and its colocalization with CD4-positive lymphocytes suggests that it may serve as a target for an immune-mediated reaction that can influence lesion progression.
Animals↗
[Hyperhomocysteinemia--a risk factor or vascular disease?].
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Homocysteine↗
Comparison of ThinPrep and conventional preparations: urine cytology evaluation.
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Evaluation Studies as Topic↗
Reactivity of peripheral blood lymphocytes to oxidized low-density lipoprotein: a novel system to estimate atherosclerosis employing the Cellscan.
BACKGROUND: The assumption that atherosclerosis involves an autoimmune response to oxidized LDL (oxLDL) is based on the presence of immunocompetent cells and immunoglobulin deposition in the atherosclerotic lesions by successful immunomodulation of the atherosclerotic process and by inhibition of experimental atherosclerosis by antioxidants. The Cellscan system is a multiparameter laser-based static cytometer that enables repeated monitoring of the fluorescence intensity (FI) and polarization (FP) of individual living cells. Analysis of intracellular fluorescein fluorescence polarization (IFFP) has previously been used to define activated lymphocyte population. HYPOTHESIS: In this study, the Cellscan apparatus has been used to monitor cellular response to oxLDL in patients with atherosclerosis and in controls. METHODS: The FI and FP of fluorescein diacetate (FDA)-labeled peripheral lymphocytes were measured following exposure to oxLDL in vitro. Using cluster analysis we were able to identify subpopulations of cells that were characterized by their FI and FP. Forty-two subjects were studied: 22 patients with severe coronary heart disease and 22 control individuals, either healthy or with other diseases. RESULTS: Fluorescence intensity of fluorescein-labeled peripheral blood lymphocytes (PBL) was markedly decreased upon exposure to high doses (> 25 micrograms/ml) of oxLDL concurrently with an increase in FP. A specific and dose-dependent reduction in FP of the high-intensity cell subpopulations, accompanied by higher FI, was evident in patients with ischemic heart disease upon exposure to low doses of oxLDL (up to 25 micrograms/ml). Maximal depolarization was shown upon triggering with 2 micrograms/ml oxLDL. The polarization ratio (the mean polarization value of the specific cell population with and without activation) obtained for patients' lymphocytes was significantly lower (p < 0.01) than that of the control group (0.936 +/- 0.05 and 1.028 +/- 0.055, respectively). CONCLUSION: These data suggest that PBL from patients with active ischemic heart disease show an increased reactivity to oxLDL. A 73% positivity rate was found for ischemic heart disease patients compared with 5% in the control subjects. One of the future prospects of this study might be the advent of a simple and rapid noninvasive test that could assess the extent of atherosclerosis, and possibly even the response to therapy, by monitoring the reactivity of PBL to oxLDL.
Aged↗
The involvement of beta2-glycoprotein I (beta2-GPI) in human and murine atherosclerosis.
Atherosclerosis is a multifactorial process, the hallmark of which is fat deposition in the vessel wall. Autoimmune factors have recently been shown to play an important role in the initiation and progression of atherosclerosis; candidate autoantigens are oxidized lipids and heat shock proteins. beta2-glycoprotein I (beta2-GPI) is a highly glycosylated plasma protein that serves as a major antigenic target for autoimmune type antiphospholipid antibodies. Its major relevant property is binding to negatively charged phospholipids/surfaces. In the set of studies presented in this paper, we provide evidence pointing towards beta2-GPI as an influential determinant in murine and human atherogenesis. Thus, immunization of transgenic atherosclerosis-prone mice (apolipoprotein E and low-density lipoprotein receptor knockouts) with human beta2-GPI results in a brisk and sustained respective response that extends to cross-react with the 'self' murine beta2-GPI. Atherosclerosis is accelerated in both strains concomitant with the infiltration of CD4 lymphocytes in the aortic sinus of the mice. When human plaques were studied, it was found that beta2-GPI resides in the subendothelial regions and co-localizes with CD4 lymphocytes. Thus, the immune response towards beta2-GPI may play an important role in atherogenesis, serving as a possible target for antigen specific therapies.
Animals↗
Influence of Polyamines on Growth of Hairy Root Cultures of Witloof Chicory (Cichorium intybus L. cv. Lucknow Local) and Formation of Coumarins.
The effect of polyamines (putrescine, spermidine, and spermine) was examined for growth and production of two coumarins, esculetin and esculin, in the hairy roots of chicory (Cichorium intybus L. cv. Lucknow local). Of the polyamines administered, 1.5 mm putrescine alone resulted in a 2.3-fold higher increase in the growth of hairy roots as well as in the production of esculetin and esculin, which was 3.37 times more than that of the control on day 21. The endogenous level of conjugated putrescine was more than fivefold that of free putrescine levels in untreated samples. The production of esculetin and esculin in hairy root cultures strictly correlated with growth in all of the treatments. Putrescine at 1.5 mm resulted in a greater length of primary root (18.29 +/- 1.37 cm) compared with the control (10.96 +/- 0.82 cm) and more secondary and tertiary roots. This study also provides insight into the morphogenetic changes that occur in roots in response to the external supply of polyamines.Key Words. Cichorium intybus L. cv. Lucknow local-Hairy root cultures-Polyamines-Coumarinshttp://link.springer-ny.com/link/service/journals/00344/bibs/18n1p33.html
Journal Article↗
A randomized design for repeated binary outcomes used to evaluate continued effectiveness of a breast cancer control intervention strategy.
The literature has not discussed in detail design and evaluation strategies for the assessment of continued effectiveness of intervention strategies. In this article we present an approach to evaluating continued effectiveness with two repeated binary outcomes that are related to the use of preventive services. We present a two-stage design with independent randomization procedures for each of two successive controlled trials and discuss the implications of the randomization plan for the statistical evaluation. Intervention effectiveness for each year is determined by an adjusted odds ratio that compares the odds of procedure use for those who received the intervention to those who did not. Changes in the two adjusted odds ratios between successive years are assessed within the context of a regressive logistic model. We demonstrate these methods by applying them to the Metropolitan Detroit Project to Reduce Avoidable Mortality from Breast Cancer. In this project, computer-generated physician mammography reminders placed prominently in medical records were used to promote mammography referrals among women visiting primary care clinics during a 2-year intervention period. An assessment of the change in intervention effectiveness as well as an adjusted estimate of the overall intervention effectiveness for the 2 years were obtained from a multivariate regressive logistic model. The advantage of this approach was its potential for reducing bias and producing a balanced comparison between intervention groups during the second year of intervention. This issue was important because previous work indicated that having had a mammogram had a significant impact on subsequent mammography use. An important component in the implementation of this design was an information management system that facilitated doing two randomization procedures efficiently. As information and computer technology advance, and as more sophisticated information systems are used for data management, designs such as these become reasonable alternatives to consider.
Adult↗
Utility of a microcomputer as an external memory aid for a memory-impaired head injury patient during in-patient rehabilitation.
Memory deficit is one of the most frequent cognitive complications encountered after brain injury. It is recognized as difficult to treat. Over the past decades, various strategies of memory remediation have been used. Among them, prosthetic devices, such as notebooks and alarms, have shown some benefit. This study describes the case of a 22-year-old man who demonstrated deficits in memory and executive function. In an in-patient rehabilitation setting, a microcomputer was introduced as an external memory aid. With this intervention, the patient demonstrated an immediate improvement in the ability to attend every therapy and ask for every medication on his schedule. This case study demonstrates the usefulness of a microcomputer as an external memory aid for a memory-impaired head injury survivor.
Adult↗
Community hospitals...and district general hospitals.
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Hospitals, Community↗