Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to assess typical early-onset complications following ischemic stroke in a large, hospital-based cohort to provide clinical data for future randomized trials and quality standards in clinical routine. 3,866 patients with acute ischemic stroke were prospectively documented in 14 Neurology Departments with an acute stroke unit. Within the first week after admission, increased intracranial pressure (7.6%) and recurrent cerebral ischemia (5.1%) were the most frequent neurological complications. Fever >38 degrees C (13.2%), severe arterial hypertension (7.5%) and pneumonia (7.4%) were the most frequent medical complications. Multivariate regression analysis yielded brain stem infarction and large-artery atherosclerosis as independent predictors for early recurrent ischemic stroke. This study provides representative data on onset and severity of early neurological and medical complications as well as possible predictors for early recurrent cerebral ischemia following acute ischemic stroke.
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PMID:Complications following acute ischemic stroke. 1237 29

Hyperlipidemia promotes the chronic inflammatory disease atherosclerosis through poorly understood mechanisms. Atherogenic lipoproteins activate platelets, but it is unknown whether platelets contribute to early inflammatory atherosclerotic lesions. To address the role of platelet aggregation in diet-induced vascular disease, we studied beta3 integrin-deficient mice (lacking platelet integrin alphaIIbbeta3 and the widely expressed nonplatelet integrin alphavbeta3) in two models of atherosclerosis, apolipoprotein E (apoE)-null and low-density lipoprotein receptor (LDLR)-null mice. Unexpectedly, a high-fat, Western-type (but not a low-fat) diet caused death in two-thirds of the beta3-/-apoE-/- and half of the beta3-/-LDLR-/- mice due to noninfectious pneumonitis. In animals from both models surviving high-fat feeding, pneumonitis was absent, but aortic atherosclerosis was 2- to 6-fold greater in beta3-/- compared with beta+/+ littermates. Expression of CD36, CD40L, and CD40 was increased in lungs of beta3-/-LDLR-/- mice. Each was also increased in smooth muscle cells cultured from beta3-deficient mice and suppressed by retroviral reconstitution of beta3. These data show that the platelet defect caused by alphaIIbbeta3 deficiency does not impair atherosclerotic lesion initiation. They also suggest that alphavbeta3 has a suppressive effect on inflammation, the loss of which induces atherogenic mediators that are amplified by diet-induced hyperlipidemia.
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PMID:Beta3 integrin deficiency promotes atherosclerosis and pulmonary inflammation in high-fat-fed, hyperlipidemic mice. 1274 2

Chlamydophila (Chlamydia) pneumoniae (C. pneumoniae) is the third most common cause of community-acquired pneumonia and is probably involved in the development of certain chronic inflammatory diseases, including atherosclerosis and adult-onset asthma. Histamine, synthesized by histidine decarboxylase (HDC) from L-histidine, plays an essential role in allergic and inflammatory processes and in cell differentiation. The effect of C. pneumoniae infection on the expression of HDC has not been examined. In the present study, normal Balb/c mice and HDC knockouts, and control mice with a CD1 background were infected intranasally with C. pneumoniae. On days 1, 3, 7, 16 and 31 after infection, the normal Balb/c mice were sacrificed and divided into three groups. In the homogenized lungs of the first group, C. pneumoniae titres were determined and demonstrated peak levels on day 7. HDC production was revealed by a Western blot assay throughout the observation period of 1-16 days, and cytokine concentrations were determined by ELISA. The interleukin-3 (IL-3) and interleukin-6 (IL-6) levels were highest on day 1 and on days 1-3, respectively; the interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels reached the maximum on day 7, but the quantity of IL-4 was still three times higher than that in the control group 16 days after infection. The lungs of the mice in the second group were processed for the in situ demonstration of HDC activity, while the lungs in the third group were stained for C. pneumoniae antigen. The HDC activity was increased predominantly in the bronchial epithelial cells, while C. pneumoniae antigens were expressed especially in the interstitial macrophages. The HDC knockout mice exhibited a higher survival rate after C. pneumoniae infection than did the control mice. These results point to a strong association between local histamine production and other inflammatory mediators and are novel in demonstrating the role of histamine in the pathomechanism of C. pneumoniae infections.
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PMID:Chlamydophila (Chlamydia) pneumoniae induces histidine decarboxylase production in the mouse lung. 1455 83

Human cytomegalovirus (HCMV) represents one of the most medically important human viruses and causes a wide spectrum of human diseases, including birth defects and mental retardation in newborns, common opportunistic infections in acquired immunodeficiency syndrome (AIDS) patients (e.g., CMV-associated retinitis and pneumonia), and possibly cardiovascular diseases such as atherosclerosis. This chapter describes the utilization of RNase P ribozyme-specifically, M1GS ribozyme, as a gene-targeting agent for blocking HCMV gene expression and growth. The target for the RNase P ribozyme is the overlapping region of the mRNAs that code for HCMV major transcription factors IE1 and IE2, which are essential for viral gene expression and replication. The methods described in this chapter focus primarily on i) construction of the retroviral vector for expression of M1GS ribozymes in cultured cells, ii) generation of stable cell lines expressing ribozymes, iii) determination of the expression of M1GS RNAs in human cells, and iv) evaluation of the efficacy of ribozymes in inhibiting HCMV IE1/IE2 expression and viral growth. Using these methods, we successfully constructed M1GS RNAs against the IE1/IE2 mRNA sequence and recently showed that a reduction of up to 150- to 3000-fold in HCMV growth is found in cells that express the ribozymes.
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PMID:RNase P ribozyme as an antiviral agent against human cytomegalovirus. 1501 69

Chlamydiae are obligate intracellular pathogens that replicate within a membrane-bound compartment (the inclusion) and are associated with important human diseases, such as trachoma, pneumonia, and atherosclerosis. We have examined the interaction of the host autophagic pathway with Chlamydia trachomatis serovar L2 by using the specific autophagosomal stain monodansylcadaverine, antibodies to autophagosome-associated markers, and traditionally used autophagic inhibitors, particularly 3-methyladenine and amino acids. Chlamydial inclusions did not sequester monodansylcadaverine, suggesting absence of fusion with autophagosomes. Interestingly, exposure of cultures infected for 19 h to 3-methyladenine or single amino acids until the end of infection (44 h) caused various degrees of abnormalities in the inclusion maturation and in the progeny infectivity. Incubation of host cells with chemicals throughout the entire period of infection modulated the growth of Chlamydia even more dramatically. Remarkably, autophagosomal markers MAP-LC3 and calreticulin were redistributed to the inclusion of Chlamydia, a process that appears to be sensitive to 3-methyladenine and some amino acids. The present data indicate the lack of autophagosomal fusion with the inclusion because it was devoid of monodansylcadaverine and no distinct rim of autophagosomal protein-specific staining around the inclusion could be observed. However, high sensitivity of Chlamydia to conditions that could inhibit host autophagic pathway and the close association of MAP-LC3 and calreticulin with the inclusion membrane still suggest a potential role of host autophagy in the pathogenesis of Chlamydia.
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PMID:Interaction of Chlamydia trachomatis serovar L2 with the host autophagic pathway. 1527 37

One of the major characteristics of Chlamydia spp. is its ability to cause prolonged, often subclinical infections. Chronic, persistent infection with Chlamydia pneumoniae has been implicated in the pathogenesis of several chronic diseases initially not thought to be infectious, including asthma, arthritis and atherosclerosis. C. pneumoniae is susceptible in vitro to a wide range of antimicrobial agents that target either protein or DNA synthesis, including macrolides, ketolides, tetracyclines, quinolones and rifamycins. Practically all treatment studies evaluating presented or published to date have used serology alone for diagnosis of C. pneumoniae infection, which only provides a clinical end point. The results of several treatment studies that did perform culture found that erythromycin, azithromycin (Zithromax, clarithromycin (Biaxin, levofloxacin (Levaquin and moxifloxacin (Avelox had a 70 to 90% efficacy in eradicating C. pneumoniae from the respiratory tract of children and adults with pneumonia. Persistence of the organism does not appear to be due to the development of antibiotic resistance. However, one cannot extrapolate from this experience to the treatment of chronic C. pneumoniae infection, especially cardiovascular disease. As there are no reliable serologic markers for chronic or persistent C. pneumoniae infection, it cannot be determined who is infected and who is not, which means that it cannot be assumed that any effect seen is due to successful treatment or eradication of C. pneumoniae.
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PMID:Advances in the management of Chlamydia pneumoniae infections. 1548 45

Chlamydia pneumoniae (CP) causes frequently nosocomial pneumonia and other inflammations of the upper and lower airways. Initially reports on the association between infection with CP and ischaemic heart disease (IHD) were published in 1988 by Saikku et al. who found a higher antibody titre against CP in acute myocardial infarction and sudden cardiac death as compared with a control group. The mechanism of this phenomenon is explained by the action of Chlamydiae on LDL-cholesterol, cytokines, the tumour necrotizing factor with a subsequent effect on the vascular wall. The authors assessed IgG and IgM antibodies in 39 elderly men using the immunofluorescent method. In addition they assessed the total cholesterol, LDL-cholesterol, triacylglycerol and fibrinogen. They divided the group into a sub-group with manifest IHD (n=22) and a control group without detectable IHD (n=17). In patients with IHD they found an insignificantly higher prevalence of Ig antibodies against CP as compared with the control group (31.8% and 29.4% resp.).IgM antibodes were found more frequently in the control group as compared with patients with IHD. Total cholesterol and triacylglycerol were insignificantly higher, HDL cholesterol was lower in patients with IHD as compared with controls. Fibrinogen was paradoxically insignificantly higher in controls as compared with patients with IHD. The authors explain these findings by the fact that the group was formed by elderly men (mean age 73 and 68 years resp.) who had an equal chance of CP infection. At this age arteriosclerosis is already developed and the differences are only in severity and site of the process. In the conclusiuon the authors state that the role of CP, as well as of other microorganisms in the pathogenesis of atherosclerosis is probable, although their investigation did not confirm it unequivocally. It is important to consider also possible interactions of many known and newly detected risk factors.
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PMID:[Chlamydia pneumoniae and the risk of ischaemic heart disease. Prevalence in a group of hospitalized elderly men]. 1564 Dec 38

Although frequently asymptomatic, homozygous C2 deficiency (C2D) is known to be associated with severe infections and rheumatic disease. We describe the clinical findings in 40 persons with C2D from 33 families identified in Sweden over 25 years. Medical records covering 96% of the accumulated person-years were reviewed, giving a mean observation time of 39 years (range, 1-77 yr). Severe infection was the predominant clinical manifestation in the cohort: 23 patients had a past history of invasive infections, mainly septicemia or meningitis caused by Streptococcus pneumoniae, and 12 patients had repeated infections of this kind. Nineteen patients had at least 1 episode of pneumonia, and recurrent pneumonia was documented in 10 patients. Repeated infections occurred mainly during infancy and childhood. Systemic lupus erythematosus was found in 10 patients. Another 7 patients had undifferentiated connective tissue disease (n = 4) or vasculitis (n = 3). We found no correlation between susceptibility to invasive infection and rheumatologic disease. Cardiovascular disease occurred at a high rate, with a total of 10 acute myocardial infarctions and 5 cerebrovascular episodes in 6 patients. Causes of death among the C2D patients were infection (n = 5), acute myocardial infarction (n = 3), and cancer (n = 1). We suggest that severe infection may be the principal clinical manifestation of C2D. We also provide novel evidence for a possible role of C2D in the development of atherosclerosis consistent with findings in mannan-binding deficiency and experimental C3 deficiency. In addition, we confirm the well-known association between C2D and systemic lupus erythematosus.
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PMID:Hereditary C2 deficiency in Sweden: frequent occurrence of invasive infection, atherosclerosis, and rheumatic disease. 1564 97

While bronchiolitis obliterans organizing pneumonia (BOOP) has been associated with the use of sirolimus (SIR), the incidence in a consecutive group of patients given SIR to replace a calcineurin-inhibitor (CI) is unknown. Twenty-nine consecutive cardiac transplant recipients were switched from a CI to SIR to ameliorate CI-associated nephropathy or coronary graft atherosclerosis. Seven patients (24%) developed BOOP. The clinical characteristics and biopsy results of these patients are presented. The clinical course and response to withdrawal of SIR in all and steroids in four of seven patients suggested the diagnosis of BOOP. Chest X-rays and CT scans showed typical findings of BOOP in all seven patients. Infection was excluded in all patients. Biopsy results were characteristic of BOOP in six of seven patients. Six patients recovered and one died. BOOP is a common and potentially serious adverse event in cardiac transplant patients switched from a CI to SIR, especially when SIR is started late post-transplantation.
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PMID:BOOP is common in cardiac transplant recipients switched from a calcineurin inhibitor to sirolimus. 1588 46

The intracellular bacterium Chlamydia pneumoniae is involved in the inflammation process of atherosclerosis. We previously demonstrated that C. pneumonia infected monocytes (THP-1 cells) responded to stimulation by an increased respiratory burst linked to an increased NADPH oxidase (NOX) activity. We now tested agents acting on the assembly of the NOX subunits or on protein kinase C, a trigger of NOX activity. Apocynin, resveratrol, rutin, quercetin, curcumin, and tocopherols were tested. The cells were pre-incubated with Chlamydia and the agent for 19 h, and then stimulated with phorbol myristate acetate. The NOX activity was monitored by measuring the hydrogen peroxide production. Resveratrol and curcumin (10(-4)-10(-6) M) were better inhibitors than apocynin. alpha-Tocopherol was inactive, and gamma-tocopherol inhibitor at 10(-4) M only. Quercetin was inactive, and rutin a moderate but significant inhibitor. The inhibition by resveratrol was increased by 10(-6) M rutin or quercetin. Resveratrol and curcumin thus appeared to be interesting for atherosclerosis treatment.
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PMID:Resveratrol and curcumin reduce the respiratory burst of Chlamydia-primed THP-1 cells. 1593 98


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