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Biomedical subjects

Jacob George

Publications and source records attributed to Jacob George.

At least 37 records · Page 2Linked to original sources
PubMed2006

Neurohormonal and inflammatory markers as predictors of short-term outcome in patients with heart failure and cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy is a modality with proven morbidity and mortality benefit in advanced systolic heart failure. Nevertheless, not all patients respond favorably to CRT. Natriuretic peptides and inflammatory markers are elevated in congestive heart failure and reflect disease severity. OBJECTIVES: To test whether an early change in neurohormonal and inflammatory markers after implantation can predict the clinical response to CRT. METHODS: The study group included 32 patients with advanced symptomatic systolic heart failure and a prolonged QRS complex who were assigned to undergo CRT. Baseline plasma levels of B-type natriuretic peptide and high sensitivity C-reactive protein were determined in the peripheral venous blood and coronary sinus, Post-implantation levels were determined 2 weeks post-procedure in the PVB. Baseline levels and their change in 2 weeks were correlated with all-cause mortality and hospitalization for congestive heart failure. RESULTS: At baseline, coronary sinus levels of BNP but not hsCRP were significantly elevated compared to the PVB. Compared to baseline levels, BNP and hsCRP decreased significantly within 2 weeks after the implantation (BNP mean difference 229.1 +/- 102.5 pg/ml, 95% confidence interval 24.2-434, P< 0.0001; hsCRP mean difference 5.2 +/- 2.4 mg/dl, 95% CI 0.3-10.1, P= 0.001). During a mean follow-up of 17.7 +/- 8.2 months 6 patients died (18.7%) and 12 (37.5%) were hospitalized due to exacerbation of CHF. Baseline New York Heart Association and CSBNP levels predicted CHF-related hospitalizations. HsCRP levels or their change over 2 weeks did not predict all-cause mortality or hospitalizations. CONCLUSIONS: BNP levels in the CS and peripheral venous blood during biventricular implantation and 2 weeks afterwards predict clinical response and may guide patient management.

Acute Disease↗
PubMed2005

Transfer of endothelial progenitor and bone marrow cells influences atherosclerotic plaque size and composition in apolipoprotein E knockout mice.

OBJECTIVE: Recent clinical trials use cell therapy with bone marrow (BM) cells or endothelial progenitor cells (EPCs) for ischemic syndromes. We explored the effect of BM cell- or spleen cell-derived EPC transfer on plaque size and stability markers in the apolipoprotein E knockout (apoE KO) mouse model. METHODS AND RESULTS: ApoE KO mice aged 10 weeks served as recipients. Labeled BM cells and spleen cell-derived EPCs from age-matched apoE KO mice were injected intravenously to 2 groups of recipient mice each. Additional mice served as controls receiving saline. Both protocols were repeated 3 times at 2 weekly intervals. On killing, plaque size and character were studied, lipid profile analyzed, and serum and aortic cytokines assayed. Spleen cell-derived cells contained a significantly larger number of endothelial cell precursors. Labeled EPCs and BM cells were found abundantly in the spleens, yet also in the lesions of the recipient mice. Aortic sinus lesion size was significantly increased in mice receiving BM cells (n=10) in the EPC-treated group (n=10) compared with controls (n=10; a 54% and a 34% increase in aortic sinus plaque area, respectively). Mice receiving EPCs exhibited plaques with larger lipid cores and thinner fibrous caps and a higher number of infiltrating CD3 cells. RT-PCR analysis of aortas revealed reduced expression of mRNA for interleukin-10 (IL-10) in both cell transfer groups. Higher serum concentrations of IL-6 and monocyte chemoattractant protein-1 were found in sera from BM recipients, whereas lower IL-10 levels were found in mice transfused with spleen-derived EPCs. CONCLUSIONS: Transfer of BM cells and EPCs may result in an increase in atherosclerotic lesion size, whereas EPC transfer could also potentially influence plaque stability.

Animals↗
PubMed2005

Usefulness of anti-oxidized LDL antibody determination for assessment of clinical control in patients with heart failure.

BACKGROUND: It has been suggested that oxidative stress may play a role in the pathogenesis of heart failure, this may have potential implications for therapeutic strategies. However, measures of oxidative stress are subject to confounding inaccuracies. IgG antibodies to oxidized LDL reflect exposure to the lipoprotein over an extended period and may thus mirror oxidative stress over a prolonged time frame. Therefore, we tested the hypothesis that anti-oxLDL antibodies correlate with the control of heart failure (HF), as manifested by hospital admissions for cardiac dysfunction. METHODS: One hundred and two consecutive patients attending the HF clinic with either systolic or diastolic HF were enrolled and the quality of clinical control was evaluated by assessing hospital admissions over the year prior to index determination of the oxidative stress marker. Antibodies to oxLDL were determined by ELISA and pro-BNP levels were also measured. RESULTS: Most patients (mean age 71.5 years) had systolic HF; mean NYHA functional class was 2.7 and mean left ventricular ejection fraction was 39.7%. Anti-oxLDL antibodies, but not pro-BNP, correlated significantly with mean NYHA score (averaged from all clinic visits in the year prior to blood testing), and with hospital admissions over the year prior to blood testing. Mean IgG anti-oxLDL antibody levels in patients with hospital admissions were 3.4 times higher than those in subjects not hospitalized over the previous year. CONCLUSION: IgG anti-oxLDL antibody levels correlate with the severity of HF.

Aged↗
PubMed2005

Hepascore: an accurate validated predictor of liver fibrosis in chronic hepatitis C infection.

BACKGROUND: Staging hepatic fibrosis by liver biopsy guides prognosis and treatment of hepatitis C, but is invasive and expensive. We sought to create an algorithm of serum markers that accurately and reliably predict liver fibrosis stage among hepatitis C patients. METHODS: Ten biochemical markers were measured at time of liver biopsy in 117 untreated hepatitis C patients (training set). Multivariate logistic regression and ROC curve analyses were used to create a predictive model for significant fibrosis (METAVIR F2, F3, and F4), advanced fibrosis (F3 and F4), and cirrhosis (F4). The model was validated in 104 patients from other institutions. RESULTS: A model (Hepascore) of bilirubin, gamma-glutamyltransferase, hyaluronic acid, alpha(2)-macroglobulin, age, and sex produced areas under the ROC curves (AUCs) of 0.85, 0.96, and 0.94 for significant fibrosis, advanced fibrosis, and cirrhosis, respectively. In the training set, a score > or = 0.5 (range, 0.0-1.0) was 92% specific and 67% sensitive for significant fibrosis, a score <0.5 was 81% specific and 95% sensitive for advanced fibrosis, and a score <0.84 was 84% specific and 71% sensitive for cirrhosis. Among the validation set, the AUC for significant fibrosis, advanced fibrosis, and cirrhosis were 0.82, 0.90, and 0.89, respectively. A score > or = 0.5 provided a specificity and sensitivity of 89% and 63% for significant fibrosis, whereas scores <0.5 had 74% specificity and 88% sensitivity for advanced fibrosis. CONCLUSIONS: A model of 4 serum markers plus age and sex provides clinically useful information regarding different fibrosis stages among hepatitis C patients.

Adult↗
PubMed2005

Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner.

OBJECTIVES: Patients with congestive heart failure (CHF) suffer considerable morbidity and mortality despite advances in therapy. Treatment with erythropoietin (Epo) has shown promise in CHF patients, yet its mechanisms of action remain elusive. Endothelial progenitor cells (EPC) contribute to postnatal angiogenesis and vasculogenesis, and Epo was shown to promote EPC mobilization. We explored the effect of chronic treatment with Epo on the numbers and functional properties of EPC in CHF patients. METHODS AND RESULTS: Twenty-eight patients with CHF treated with Epo for a mean period of 28 months were compared to a matched group (n = 28) with regard to the number of circulating hematopoietic and endothelial stem cells (either CD34+, CD34+/CD45+, CD34+/CD133+, CD34+/VEGF-R2+ or CD34+/CD133+/VEGF-R2+) as well as their proliferative and adhesive capacity. In vitro, Epo was added to cultured EPC from healthy subjects to test proliferation and adhesion. No differences were observed in circulating numbers of hematopoietic and endothelial stem cells between CHF patients chronically treated with Epo or untreated. EPC from Epo-treated patients exhibited enhanced proliferation as well as a trend towards adhesion to cultured endothelial cells prior to and following stimulation with TNF-alpha. Addition of Epo to EPC from healthy subjects dose-dependently increased their proliferation and adhesion to fibronectin, cultured endothelial cells, and cardiomyocytes. These effects were significantly reduced in the presence of phosphatidylinositol (PI) 3-kinase inhibitors. CONCLUSIONS: Chronic Epo treatment is associated with an increase in the adhesive and proliferative properties of circulating EPC in patients with CHF.

Aged↗
PubMed2005

Circulating erythropoietin levels and prognosis in patients with congestive heart failure: comparison with neurohormonal and inflammatory markers.

BACKGROUND: Considerable morbidity and mortality are still associated with congestive heart failure (CHF) syndromes, despite improvement in therapy. Activation of neurohormonal, inflammatory, and oxidative mechanisms has been shown to contribute to the significant morbidity and mortality. Erythropoietin (EPO) is a cytokine known to regulate erythroid proliferation, attenuate apoptosis and oxidative stress, and promote angiogenesis. We prospectively evaluated the predictive value of baseline EPO, N-terminal pro-B-type natriuretic peptide, and C-reactive protein levels in patients with clinically controlled chronic CHF. METHODS: One hundred eighty-eight outpatients from a CHF clinic had baseline assessment of EPO, N-terminal pro-B-type natriuretic peptide, and C-reactive protein levels and a complete clinical data profile. These patients were followed up for 24 months for any hospitalization due to CHF or mortality. RESULTS: Circulating EPO levels were higher in CHF patients and increased in subjects with higher New York Heart Association scores. Levels of EPO (at a cutoff of 23 mU/mL) and N-terminal pro-B-type natriuretic peptide (cutoff at the median of 1556 pg/mL) were found to be strong predictors of mortality and CHF hospitalization, whereas C-reactive protein levels (cutoff of 10 mg/L) predicted CHF hospitalizations but not mortality. Left ventricular ejection fraction was found to be a predictor of mortality but not of CHF hospitalizations. Serum levels of EPO were significantly correlated with N-terminal pro-B-type natriuretic peptide and C-reactive protein levels but not with left ventricular ejection fraction. CONCLUSION: If confirmed in large-scale clinical studies, determination of circulating EPO levels may aid in predicting morbidity and mortality in patients with clinically controlled congestive CHF.

Aged↗
PubMed2005

A functional role for inducible costimulator (ICOS) in atherosclerosis.

BACKGROUND: Lymphocytes appear to influence atherosclerosis by altering cytokine production. Whereas primary lymphocyte activation requires T cell receptor ligation, costimulatory signals also appear requisite for generation of a functional T cell response. Inducible costimulator (ICOS) is a newly discovered T cell molecule with a dual role in immune mediated disorders. Herein, we tested the importance of ICOS in atherosclerosis. METHODS AND RESULTS: Atherosclerotic plaques from ApoE-KO mice were studied immunohistochemically for the presence and localization of ICOS and its receptors and its expression in splenocytes. ApoE-KO mice were immunized with human ICOS/Fc-chimera or non-fused Fc and either provided a chow diet for 6 weeks, or a high fat diet for 8 weeks. ICOS and its ligand were abundantly expressed within plaques from ApoE-KO mice: Spleen cells from atherosclerotic mice exhibited lowered constitutive expression of ICOS yet priming with oxLDL enhanced ICOS expression dose-dependently. In mice induced to develop fatty streaks and to generate ICOS blocking antibodies, early atherosclerosis was increased by approximately 77% whereas upon inducing more advanced lesions, the increase in plaque area upon ICOS blockade group was approximately 36%. IFN-gamma secretion by oxLDL-primed splenocytes in ICOS-immunized mice increased whereas IL-10 secretion diminished as compared to control animals. A similar trend in cytokine production was evident in the lesion by immunohistochemistry. CONCLUSION: ICOS appears as an influential costimulatory pathway in atherosclerosis that may play a protective rather that a proatherogenic role.

Animals↗
PubMed2005

Transient hydroureteronephrosis caused by a Foley's catheter tip in the right ureter.

We report a case of unilateral hydronephrosis following urethral catheterization in a patient with T6 complete paraplegia at the Physical Medicine and Rehabilitation Department in a tertiary care teaching hospital, India. Diagnosis was established by an abdominal ultrasound. The misplaced catheter tip was withdrawn from the ureteric orifice and hydronephrosis was resolved. Foley's catheterization, a widely practiced clinical procedure, is not without its attendant risks of an inadvertent placement in the ureter leading to transient hydronephrosis. Inadequate drainage through a catheter should thus alert one to this potentially hazardous complication that can be diagnosed by an early ultrasound. This complication can be avoided by gently tugging on the catheter after inflating the catheter bulb.

Adolescent↗
PubMed2005

The involvement of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in atherosclerosis.

OBJECTIVES: Herein, we determined the significance of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in atherosclerotic vascular disease. BACKGROUND: Inflammation is associated with the pathogenesis of atherosclerosis. The TNF-related apoptosis-inducing ligand/APO-2L, a member of the TNF superfamily, has a role in apoptosis induction and is recognized for its immunomodulatory properties. METHODS: Stable and vulnerable atherosclerotic human plaques and aortas from atherosclerotic mice were assayed for the presence of TRAIL, and its inducibility was assayed by immunoblot and real-time polymerase chain reaction on peripheral mononuclear cells incubated with oxidized low-density lipoprotein (oxLDL). Enzyme-linked immunosorbent assay was used for the determination of soluble TRAIL levels in atherosclerotic patients. RESULTS: Tumor necrosis factor-related apoptosis-inducing ligand is present in stable atherosclerotic lesions, is increased in vulnerable plaques, and is found to colocalize with CD3 cells and oxLDL. The TNF-related apoptosis-inducing ligand messenger ribonucleic acid (mRNA) and protein expression was up-regulated in peripheral blood mononuclear cells after incubation with oxLDL. Serum levels of soluble TRAIL but not TNF-alpha or Fas-ligand were reduced significantly in patients with unstable angina as compared with patients with stable atherosclerotic disease and healthy subjects. A negative correlation was demonstrated between soluble TRAIL and C-reactive protein levels but not with levels of mRNA of TRAIL in peripheral blood mononuclear cells. CONCLUSIONS: Tumor necrosis factor-related apoptosis-inducing ligand is expressed in plaque-infiltrating CD3 cells and induced by oxLDL, whereas levels of soluble TRAIL are reduced in patients with acute coronary syndromes and negatively correlate with C-reactive protein levels. These results support a possible role for TRAIL in atherosclerosis.

Animals↗
PubMed2005

Intermediate colloidal formation and the varying width of periodic precipitation bands in reaction-diffusion systems.

The mechanism of rhythmic pattern formation in reaction-diffusion systems is investigated theoretically by introducing a new concept. The boundary that separates the two reacting species virtually migrates as the diffusion proceeds into the gelatinous medium. Based on this boundary migration scenario, all the well-established relations on Liesegang patterns could be proved, in a rather modified way. The idea of formation of intermediate colloidal haze prior to patterning along with the moving boundary model proved to be efficient in predicting the concentration dependence of the width of the spatiotemporal patterns. The experimental observations support the width law relation developed.

Journal Article↗
PubMed2005

The effect of tyrphostin AG-556 on intimal thickening in a mouse model of arterial injury.

BACKGROUND: Inflammation has been shown to play an important role in promoting the response to arterial injury and proinflammatory cytokines, such as tumor necrosis factor (TNF) alpha, are candidate mediators. AG-556 is a tyrosine kinase inhibitor proven to be effective in a model of multiple sclerosis-like syndrome in mice due to its immunomodulating effect. In the current study, we investigated the effect of the tyrphostin AG-556 on neointimal thickening and cytokine profile in a model of arterial injury in the mouse. METHODS: Injury was induced by external cuff placement on the left femoral artery of wild-type C57BL/6 mice. AG-556 dissolved in DMSO was injected intraperitoneally daily to the injured mice in a dosage of 2 mg/mouse. Control mice received DMSO injections. Histological analysis was carried out to assess neointimal formation. Splenocytes were cultured in the absence and presence of a mitogen for evaluation of thymidine incorporation and cytokine production. RESULTS: AG-556 treatment significantly attenuated intimal thickening (43,000+/-17,000 microm2; n=11) when compared to DMSO administration (286,000+/-127,000 microm2; n=10; P<0.05). Basal interferon-gamma production by splenocytes from AG-556-treated mice was increased by approximately 20-fold in comparison with levels in DMSO-treated animals, whereas Con-A induced secretion of the cytokine was similar between both groups. Levels of TNF-alpha, IL-4 and IL-10 in the culture supernatant from treated and non-treated animals did not differ significantly. CONCLUSION: The tyrosine kinase inhibitor AG-556 may have a role in the reduction of intimal thickening. The effect could be mediated via an immune modulating effect involving a significant increase in the smooth muscle cell inhibitory cytokine IFN-gamma.

Animals↗
PubMed2005

Circulating matrix metalloproteinase-2 but not matrix metalloproteinase-3, matrix metalloproteinase-9, or tissue inhibitor of metalloproteinase-1 predicts outcome in patients with congestive heart failure.

BACKGROUND: Extracellular matrix remodeling is thought to play an important role in the progression of heart failure (HF). Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are matrix-degrading enzymes that have been demonstrated to influence left ventricular properties and serve as targets of potential anti-remodeling agents. Herein we evaluated the potential significance of circulating MMP and TIMP levels in patients with congestive HF (CHF) speculating it may assume prognostic value. METHODS: Serum samples were obtained from 88 consecutive patients attending the outpatient HF clinic and analyzed for MMP-2, -3, -9, and TIMP-1 as well as N-terminal probrain natriuretic peptide (NT-ProBNP). Patients were followed up for the occurrence of either mortality or hospitalizations due to CHF or either of each. RESULTS: Circulating levels of MMP-2, -9, and TIMP-1 but not of MMP-3 were increased in patients with CHF as compared with age-matched controls. Only MMP-2 and NT-ProBNP levels correlated significantly with New York Heart Association class. Matrix metalloproteinase-2 and NT-ProBNP levels did not correlate. Patients with circulating MMP-2 above 352 ng/mL were 4.2 times more likely to die, 2.2 times more likely to be hospitalized because of CHF, and 2.3 times more likely to experience either of the 2 end points as compared with patients with MMP-2 concentrations below this threshold. Both MMP-2 and NT-ProBNP were found to be independent predictors of mortality over a 24-month follow-up period. CONCLUSIONS: Matrix metalloproteinase-2 but not MMP-3, -9, or TIMP-1 serum levels is an independent predictor of mortality in patients with CHF.

Adult↗
PubMed2005

Serum levels of interleukin-18 in patients with stable and unstable angina pectoris.

Recent evidence suggests that atherosclerosis is an inflammatory disorder in which cytokines appear to play an important role. Special attention centered over the possible contribution of cytokines to the destabilization of the plaque. IL-18 is a proinflammatory cytokine of the IL-1 family, recognized for its ability to promote IFN-gamma secretion. It has recently been detected in human plaques and its administration was associated with increased atherosclerosis in apolipoprotein E (apoE) mice concomitant with an increase in plaque infiltrating inflammatory cells. In our study, we investigated whether patients with established atherosclerosis, with either stable or unstable angina, possessed high levels of IL-18. Patients with stable angina (n=48) were from the outpatient clinic whereas patients with unstable angina (n=73) were recruited upon admission and prior to performance of coronary angiography. Control patients (n=19) were healthy subjects with no evidence of coronary artery disease. Serum levels of IL-18 were assayed by ELISA. Patients with stable and unstable angina exhibited higher serum levels of IL-18 (77.1+/-7.2 and 61.5+/-5.1 pg/ml, respectively) in comparison to control subjects (p=0.002 and p=0.02, respectively). However, levels of IL-18 did not differ significantly between patients with stable and unstable angina. No differences were evident in the serum concentrations of IL-18 in patients with unstable angina (n=17) upon admission and 1-3 months later when the angina was already controlled. Although IL-18 serum levels appear elevated in the presence of coronary atherosclerosis, there is no evidence to associate this progression towards plaque instability.

Adult↗
PubMed2005

Transfer of endothelial progenitor cells improves myocardial performance in rats with dilated cardiomyopathy induced following experimental myocarditis.

Endothelial progenitor cells (EPCs) home to sites of tissue injury and differentiate into mature endothelial cells. Their transfer feasibility has been proven in models of hindlimb ischemia and myocardial infarction. We investigated, the effect of delivery of spleen-derived EPC in a rat model of inflammatory-mediated myocardial damage. Male Lewis rats (N=25) were immunized against myosin. Healthy donor Lewis rats were sacrificed, their spleens harvested, separated on Ficoll gradient centrifugation, and grown on fibronectin coated plates with endothelial cell medium for 5 days. Ten days after myosin immunization, spleen cell derived EPC were collected, and labeled 2 x 10(7) cells per rat were injected into the femoral vein of diseased rats. Cell transplantation was repeated twice, 2 and 4 weeks after initial cell transfer. Rats with inflammatory-mediated cardiomyopathy exhibited a significant mobilization of EPC from the bone marrow to the periphery and their ability to adhere to fibronectin, mature endothelial cells and cultured cardiomyocytes was significantly reduced when compared to healthy rats. Transfer of EPC resulted in a functional improvement in cardiac performance evident by higher fractional shortening by echocardiography (a 15% increase). Histological studies exhibited reduced scar tissue and thickened ventricular walls in rats receiving EPC as compared with untreated animals. EPC transfer is effective in attenuating myocardial damage in a model of non-ischemic dilated cardiomyopathy.

Animals↗
PubMed2005

NF-kappaB activation, rather than TNF, mediates hepatic inflammation in a murine dietary model of steatohepatitis.

BACKGROUND & AIMS: We explored the roles of nuclear factor-kappaB (NF-kappaB) and tumor necrosis factor (TNF) alpha (TNF-alpha) as mediators of inflammation in a nutritional model of steatohepatitis. METHODS: Wild-type (wt), TNF null -/-, and TNF receptor (R)-1-/- mice were fed a methionine- and choline-deficient (MCD) diet for up to 5 weeks. Liver injury (serum alanine aminotransferase [ALT]), hepatic inflammation, triglycerides, and lipid peroxide levels were determined. Hepatic NF-kappaB activation and expression of TNF and intercellular adhesion molecule-1 (ICAM-1) were assayed. RESULTS: Irrespective of genotype, MCD diet-fed mice developed hepatic lipid peroxidation and serum ALT elevation; at day 10, livers from wt, TNF-/-, and TNFR-1-/- mice showed equivalent steatohepatitis. NF-kappaB/DNA binding was enhanced in hepatic nuclear fractions from MCD diet-fed wt mice compared with dietary controls; there were corresponding increases of ICAM-1 and TNF messenger RNA (mRNA). Likewise, NF-kappaB activation and ICAM-1 expression were enhanced by MCD dietary feeding in TNF-/- and TNFR-1-/- mice compared with respective controls. To establish whether NF-kappaB is a primary mediator of inflammation in experimental steatohepatitis, we over-expressed a mutant, nondegradable IkappaB (mIkappaB), delivered by adenovirus in vivo. As expected, hepatic mIkappaB expression reduced NF-kappaB/DNA binding induced by MCD dietary feeding, with resultant abrogation of ICAM-1 and TNF synthesis. Such blockade of NF-kappaB transcriptional activation substantially protected against development of steatohepatitis, with significant reductions in liver injury and hepatic inflammation. CONCLUSIONS: In the MCD dietary model of steatohepatitis, NF-kappaB is activated early and is an important proinflammatory mediator of lesion development, but steatohepatitis occurs independently of TNF synthesis and TNFR-1 activation.

Animals↗
PubMed2005

Functional T-lymphocyte dichotomy in the peripheral blood of patients with unstable angina.

OBJECTIVES: Herein, we investigated the percentage of T-helper (Th1) and Th2 cells among the general T-cell population in the peripheral blood of patients with stable angina (SA) and unstable angina (UA). BACKGROUND: Recent evidence suggests that Th1 cells and the cytokines that they secrete (especially IFN-gamma) have a role in the activation of macrophages, promotion of clot formation and destabilization of atherosclerotic plaques. Thus, Th1 cytokines may contribute to the initiation and progression of UA. In contrast, cytokines secreted by Th2 cells (e.g. IL-10) are known to inhibit activation and proliferation of Th1 cells and the secretion of IFN-gamma, lysosomal enzymes and metalloproteinases. Therefore, we sought to examine whether the ratio of IFN-gamma to IL-10 secreting cells is altered in patients with UA. METHODS: The percentage of Th1 and Th2 cells among the general T-cell population was determined by fluorescent intracellular cytokine staining (IFN-gamma and IL-10, out of the total CD3 positive cells). RESULTS: The percentage of T-cells positive for intracellular IFN-gamma was significantly higher in patients with UA (n = 22) in comparison with SA (n = 20) patients (39.0+/-2.8% and 29.6+/-2.7%, respectively. P = 0.02). There was no significant difference in intracellular IL-10 positive cells between the two groups. In addition, there was no significant difference in the ratio between the intracellular IFN-gamma positive cells and the intracellular IL-10 positive cells. CONCLUSIONS: There is an increased activity of Th1 cells in patients with UA in comparison with patients with SA. There is no evidence of heightened activity of Th2 cells in either group. Thus, IFN-gamma secreted by peripheral blood T-lymphocytes,may be an important immunomodulator contributing to destabilization of the atheromatous plaque lying at the base of the etiopathogenesis of unstable angina.

Aged↗
PubMed2005

Hepatic steatosis and the risk of hepatocellular carcinoma in chronic hepatitis C.

BACKGROUND AND AIM: Obesity associated hepatic steatosis has been suggested to have a premalignant potential. We determined whether hepatic steatosis predisposes to liver cancer in persons with chronic hepatitis C virus (HCV) infection. METHODS: We compared the histological severity of steatosis in the index liver biopsies of 25 patients with chronic hepatitis C who subsequently developed hepatocellular carcinoma (HCC) with matched controls who did not. Cases were aged (mean) 54.7 years, 84% males, 76% genotype 1, and 64% fibrosis stage 4; and controls were matched for these characteristics. Those with a sustained virologic response to antiviral therapy were excluded. RESULTS: Duration of HCV infection, concomitant alcohol intake, body mass index and indices of past hepatitis B virus (HBV) infection were comparable between the groups. Controls were followed for a longer period after the index liver biopsy than were cases (113 months vs 55 months, P < 0.001). As determined by percentage area of biopsy core occupied by steatosis on computer assisted morphometric evaluation, and graded by semiquantitative histological assessment, steatosis was comparable among cases and controls. The odds of developing HCC among those with steatosis grades 1 and 2 did not differ significantly from those without steatosis. There was no association between increasing morphometric percentage area occupied by steatosis and the subsequent development of HCC. Neither steatosis grade or percent area of steatosis on biopsy were selected in multivariate regression analysis as independent predictors for the development of HCC. CONCLUSIONS: Hepatic steatosis does not augment the risk of hepatocarcinogenesis in patients with chronic HCV infection.

Carcinoma, Hepatocellular↗