Biomedical subjects

Jacob George

Publications and source records attributed to Jacob George.

At least 73 records · Page 4Linked to original sources

PubMed2003

Inhibition of intimal thickening in the rat carotid artery injury model by a nontoxic Ras inhibitor.

BACKGROUND: Neointimal formation with and without previous vascular injury is common after balloon dilation and in transplant arteriosclerosis. It involves proliferation and migration of medial smooth muscle cells and inflammation, processes that are regulated by Ras proteins and their down-stream effectors. Farnesylthiosalicylate (FTS) is a Ras inhibitor that interferes with Ras membrane anchorage and affects Ras proteins in their active state. In the present study, we tested the hypothesis that systemic administration of FTS will suppress intimal thickening in the rat carotid injury model. METHODS AND RESULTS: The effects of FTS on rat vascular smooth muscle cells (VSMC) and splenocytes proliferation were evaluated in vitro. The in vivo effects of FTS on the neointima of balloon-injured male Wistar rats, treated daily for 2 weeks with FTS (5 mg/kg weight, intraperitoneally) were evaluated by determination of Ras, Ras-GTP, and active ERK levels (3 days after injury), and by quantitative determination of the extent of intimal thickening and immunohistochemistry for Ras, iNOS, NFkB, and Ki-67 (2 weeks after injury). FTS inhibited VSMC and splenocyte proliferation as well as interferon-gamma secretion by splenocytes in a dose-dependent manner. Compared with controls, FTS treatment resulted in a strong decrease in Ras-GTP and active ERK, and it significantly reduced intimal thickening after the injury. Ras expression appeared predominantly at areas of neointima regardless of the treatment group. NFkB and iNOS-positive cell numbers were reduced in sections of FTS treated rats. CONCLUSIONS: FTS appears to act as a potent inhibitor of intimal thickening in a model of experimental arterial injury.

Animals↗

PubMed2003

Number and adhesive properties of circulating endothelial progenitor cells in patients with in-stent restenosis.

OBJECTIVE: Intact endothelialization machinery is essential to facilitate vessel healing after stent placement and to prevent restenosis. Circulating endothelial progenitor cells (EPC) have been demonstrated in the peripheral blood and shown to display endothelial functional properties, along with the ability to traffic to damaged vasculature. We reasoned that robust in-stent intimal growth could be partially related to impaired endothelialization resulting from reduced circulating EPC number or function. METHODS AND RESULTS: Sixteen patients with angiographically-demonstrated in-stent restenosis were compared with patients with a similar clinical presentation that exhibited patent stents (n=11). Groups were similar with respect to the use of drugs that could potentially influence EPC numbers. Circulating EPC numbers were determined by the colony-forming unit assay, and their phenotype was characterized by endothelial-cell markers. Adhesiveness of EPC from both groups to extracellular matrix and to endothelial cells was also assayed. Patients with in-stent restenosis and with patent stents displayed a similar number of circulating EPC. Fibronectin-binding was compromised in patients with in-stent restenosis as compared with their controls exhibiting patent stents. Patients with diffuse in-stent restenosis exhibited reduced numbers of EPC in comparison with subjects with focal in-stent lesions. CONCLUSIONS: Reduced numbers of circulating EPC in patients with diffuse in-stent restenosis and impaired adhesion of EPC from patients with restenosis provides a potential mechanism mediating the exuberant proliferative process. These markers, if further validated, could provide means of risk stratifying patients for likelihood of developing in-stent restenosis.

Aged↗

PubMed2003

Cell and molecular regulation of endothelin-1 production during hepatic wound healing.

During hepatic wound healing, activation of key effectors of the wounding response known as stellate cells leads to a multitude of pathological processes, including increased production of endothelin-1 (ET-1). This latter process has been linked to enhanced expression of endothelin-converting enzyme-1 (ECE-1, the enzyme that converts precursor ET-1 to the mature peptide) in activated stellate cells. Herein, we demonstrate up-regulation of 56- and 62-kDa ECE-1 3'-untranslated region (UTR) mRNA binding proteins in stellate cells after liver injury and stellate cell activation. Binding of these proteins was localized to a CC-rich region in the proximal ECE-1 3' UTR base pairs (the 56-kDa protein) and to a region between 60 and 193 base pairs in the ECE-1 3' UTR mRNA (62 kDa). A functional role for the 3' UTR mRNA/protein interaction was established in a series of reporter assays. Additionally, transforming growth factor-beta1, a cytokine integral to wound healing, stimulated ET-1 production. This effect was due to ECE-1 mRNA stabilization and increased ECE-1 expression in stellate cells, which in turn was a result of de novo synthesis of the identified 56- and 62-kDa ECE-1 3' UTR mRNA binding proteins. These data indicate that liver injury and the hepatic wound healing response lead to ECE-1 mRNA stabilization in stellate cells via binding of 56- and 62-kDa proteins, which in turn are regulated by transforming growth factor-beta. The possibility that the same or similar regulatory events are present in other forms of wound healing is raised.

3' Untranslated Regions↗

PubMed2003

Effectiveness of interferon alfa-2b/ribavirin combination therapy for chronic hepatitis C in a clinic setting.

AIM: To determine effectiveness of treatment for hepatitis C outside clinical trials, by testing the hypothesis that apparent effectiveness and tolerability of interferon alfa-2b/ribavirin combination therapy would be less in a hospital liver clinic setting. DESIGN: Retrospective analysis of all patients in one centre commencing interferon alfa-2b/ribavirin therapy, but not in clinical trials, between 1998 and 2000. MAIN OUTCOME MEASURES: Effectiveness as sustained virological response (SVR); tolerability as premature discontinuation of treatment. RESULTS: The 121 patients had similar demographic and viral characteristics as those in Australian trials (age, 44 +/- 10 years; males, 66%; genotype 1, 44%; genotype 3, 36%), but 38% had advanced fibrosis, including 17% with cirrhosis. Sixty (50%) were previously untreated, 38 (31%) had relapsed after initial response (response relapse) and 23 (19%) were non-responders to interferon monotherapy. Sustained viral response (SVR) was achieved in 53% of patients overall: 47% of patients with genotype 1 HCV, 71% of patients with genotype 3. For patients with genotype 1 HCV, SVR was 43% in those previously untreated, 63% in response relapsers, and 38% in non-responders. Corresponding SVRs for genotype 3 were 65%, 87% and 33%. These results are similar to those obtained in published trials. Only 7% of our patients discontinued treatment because of adverse effects, fewer than reported in most clinical trials. Dose reduction was required in 18% of patients. CONCLUSIONS: In a hospital clinic setting the effectiveness of interferon alfa-2b/ribavirin combination therapy appears equivalent to published results from clinical trials.

Adult↗

PubMed2003

Interaction of iron, insulin resistance, and nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) has emerged as a ubiquitous liver disorder with occasional serious overtones. Although diabetes and obesity were initially held culpable, insulin resistance (IR) is now considered the fundamental operative mechanism. IR is probably the "first step" in nonalcoholic steatohepatitis (NASH). Oxidative stress may be the elusive "second" of possibly multiple steps in the progression of steatosis to fibrosing steatohepatitis. Because hepatic iron promotes oxidative stress, it was mooted as a contributory cofactor in NASH. This proposal was strengthened by an association with hepatic fibrosis. Subsequent studies have shown neither a significant increase in hepatic iron nor an association between hepatic iron and any of the histologic determinants in NASH. Likewise, the increased prevalence of hemochromatosis gene (HFE) mutations in some studies appears to be largely irrelevant to the development of hepatic fibrosis. Excess hepatic iron may occur in insulin resistance-associated iron overload (IRHIO), characterized by hyperferritinemia with normal to mild increases in transferrin saturation. Although patients with IRHIO have a high prevalence of IR-related metabolic disorders, the relationship of IRHIO to NASH is unclear. A recent study showed improvement in insulin sensitivity with the use of venesection in patients with NAFLD, but this approach cannot be implemented without extensive review.

Fatty Liver↗

PubMed2003

Safety of nitrate withdrawal in angina-free and hemodynamically stable patients with coronary artery disease.

STUDY OBJECTIVES: To assess the consequences of nitrate withdrawal in angina-free and hemodynamically stable coronary patients. DESIGN: Prospective, open, intervention study. SETTING: Cardiology outpatient clinic of a university-affiliated municipal hospital. PATIENTS: Angina-free patients who were hemodynamically stable for at least 3 months before study onset were enrolled. They were all regularly receiving nitrates for symptom control. Those with significant reasons to avoid stopping nitrates, such as heart failure (ejection fraction <35%) or high BP (> 160 mm Hg systolic and/or > 100 mm Hg diastolic), and noncompliant patients were excluded. INTERVENTIONS: After providing informed consent and undergoing an exercise test (whenever possible), the participants were randomized to abruptly discontinue (study group) or continue (control group) nitrate treatment. Follow-up continued for at least 3 months after study entry. MEASUREMENTS AND RESULTS: Eighty patients were randomized to the study group and 40 patients to the control group (mean age [+/- 1 SD], 65.5 +/- 11 years and 66.1 +/- 10.9 years, respectively; p = not significant). The first month, eight study patients (10%) had a recurrence of anginal symptoms, compared with one control subject (2.5%) [p = not significant]. All eight patients responded promptly and favorably to the resumption of nitrate administration. CONCLUSIONS: Nitrate administration can be safely discontinued in angina-free and hemodynamically stable coronary patients who receive this medication on a regular basis. If relapse of anginal symptoms occurs, it will be within 1 month following nitrate withdrawal, and will resolve satisfactorily with reinstatement of treatment.

Aged↗

PubMed2003

Tyrphostin AG-556 reduces myocardial infarct size and improves cardiac performance in the rat.

TNF-alpha is a proinflammatory cytokine, abundantly expressed after myocardial infarction. It has been suggested that it exhibits myocardial suppressive and cytotoxic effects. AG-556 is a tyrosine kinase inhibitor synthesized based on its ability to reduce TNF-alpha production and cell toxicity, and to improve experimental models mediated by TNF-alpha (i.e., peritontitis and experimental autoimmune encephalomyelitis). Daily, for 7 days, rats were injected ip with either AG-556 dissolved in DMSO or with the control vehicle. Infarct size was determined in the hearts as well as in fibrous scar formation. Cardiac TNF-alpha expression was evaluated by ELISA and immunohistochemistry. Functional hemodynamic parameters were evaluated employing echocardiography prior to sacrifice. AG-556 treatment reduced MI size at 7 days with a parallel effect on fibrous tissue formation. TNF-alpha production by splenocytes was reduced upon AG-556 treatment, whereas no differences were evident between the groups with regard to myocardial cytokine expression. AG-556 attenuated the decrease in fractional shortening at the expense of preserving end systolic diameter. AG-556 has proven beneficial in reducing myocardial infarct size and attenuated consequent hemodynamic deterioration in the rat model. If reconfirmed, AG-556 may be of potential clinical use in post-MI patients.

Animals↗

PubMed2003

Immunity to heat shock protein 65--an additional determinant in intimal thickening.

Inflammation occurring consequent to vessel injury is thought to play an important role in atherosclerosis and restenosis. Autoimmunity to HSP65 has been shown to accelerate early atherogenesis in rabbits and mice, whereas in humans epidemiological data support this contention. In the current study, we explored the possibility of HSP65 influencing the extent of neointimal growth in the rat carotid injury model. Rats were either immunized with recombinant mycobacterial HSP65, heat killed preparation of Mycobacterium tuberculosis (MT), or with PBS, all emulsified in incomplete Freund's adjuvant. Animals were boosted with a similar protocol 3 weeks following the primary immunization and 2 weeks later carotid injury was applied in all animals by balloon inflation. Upon sacrifice 2 weeks later, sera were obtained for measurement of anti-HSP65 antibodies by ELISA, splenocytes were assessed for proliferative response to in vitro priming with HSP65, and carotid arteries were removed for evaluation of neointimal growth. Rats immunized with HSP65 exhibited a brisk and sustained humoral immune response to HSP65, and cellular immunity was also evident by thymidine uptake to splenocytes primed with the respective protein. Neointimal/medial ratio was significantly increased in HSP65 immunized rats, in comparison with MT injected and control animals. In conclusion, immunity to HSP65 can play a role in accelerating restenosis following arterial injury. These results should be further investigated in humans as they may provide a possible link between infections and restenosis/accelerated arteriosclerosis.

Animals↗

PubMed2003

Recent findings on natural products with erectile-dysfunction activity.

Viagra has had a profound influence on the search for natural products with erectile-dysfunction activity. To date the "natural" equivalent is not in existence but several pure compounds from nature, e.g., Yohimbine, Citrulline, two pyrano-isoflavones, berberine, forskolin and others, have either been re-examined or are new potential candidates. Intense activity exists in the area of testing semi-purified plant extracts for erectile dysfunction activity.

Animals↗

PubMed2003

Lipid peroxidation, stellate cell activation and hepatic fibrogenesis in a rat model of chronic steatohepatitis.

BACKGROUND/AIMS: We explored the involvement of cell types, cytokines and lipid peroxidation in a rat dietary model of fibrosing steatohepatitis. METHODS: Male rats were fed a high fat diet deficient in methionine and choline (MCD) for up to 17 weeks. Whole liver, hepatocytes and non-parenchymal cells were analysed for reduced glutathione (GSH) levels, products of lipid peroxidation (thiobarbituric acid reactive substances, TBARS), liver injury, and fibrosis. RESULTS: MCD diet-fed rats developed hepatic steatosis at week 2 and focal necroinflammatory change by week 5, while pericellular fibrosis evolved and progressed between weeks 12 and 17. Collagen alpha(1)(1) gene expression was upregulated by week 5 and increased fivefold by week 17. Stellate cells were the unique source of collagen gene expression. TIMP-1 and -2 were increased at week 12. Livers of MCD diet-fed rats exhibited lowered levels of GSH and elevated TBARS. Hepatocytes were the source of lipid peroxidation, and mRNA levels for TGFbeta1 were increased only in this cell type. CONCLUSIONS: The MCD model of 'fibrosing steatohepatitis' replicates the histologic features of human steatohepatitis, and the sequence of steatosis, inflammatory cell injury and fibrogenesis. The temporal sequence is consistent with a concept for involvement of oxidative injury in inflammatory recruitment and pathogenesis of hepatic fibrogenesis.

Animals↗

PubMed2003

Transjugular liver biopsy effecting changes in clinical management.

Although transjugular liver biopsies are frequently performed in patients with impaired blood coagulation, their impact on effecting changes in clinical management has not been assessed. We reviewed our experience with 43 consecutive transjugular liver biopsies performed over 3 years (1998-2000) at Westmead Hospital, Sydney, Australia. The technical success, procedural complication rates and subsequent management of these patients were ascertained from the medical case records. Forty-two (28 men) patients were studied. The indications for liver biopsy were as follows: assessment of hepatitis/cirrhosis status (n = 21), evaluation of liver dysfunction following bone marrow transplantation (n = 19) and miscellaneous (n = 2). All liver biopsies were performed with a Cook 20-G transjugular cutting needle device. Adequate histological samples were obtained in 42 (98%) of the 43 biopsies performed. The pre-biopsy diagnoses were confirmed by histology in 28 cases (65%). A change in clinical diagnosis was observed in 12 (28%) patients, and there were changes to subsequent management in all 12 patients. Four patients developed procedural complications, including small neck haematomas in two patients and a self-limiting biliary fistula in one. The only major complication was an extracapsular bleed from a hepatic laceration. This patient required emergency surgery but recovered. Transjugular liver biopsies can be effectively and safely performed in high-risk patients with impaired coagulation. They aid accurate histological appraisal of liver dysfunction in these patients and influence clinical decision-making.

Adult↗

PubMed2003

Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression [corrected].

BACKGROUND & AIMS: Chronic hepatitis C virus infection is associated with an increased prevalence of type 2 diabetes. We hypothesized that virus-induced insulin resistance may be a mechanism for fibrogenesis in chronic hepatitis C virus infection. METHODS: In 260 hepatitis C virus-infected subjects, we examined the relationship between histological findings and anthropometric and biochemical data, including insulin resistance determined by the homeostasis model assessment (HOMA-IR). We also compared fasting serum insulin, C peptide, and HOMA-IR levels between the subset of 121 hepatitis C virus patients with stage 0 or 1 hepatic fibrosis and 137 healthy volunteers matched by sex, body mass index, and waist-hip ratio. RESULTS: Hepatitis C virus-infected subjects with stage 0 or 1 hepatic fibrosis had higher levels of insulin, C peptide, and HOMA-IR (all P < or = 0.01) compared with matched healthy controls. In the 250 hepatitis C virus patients (fibrosis stage 0 to 4), viral genotype and portal, but not lobular, inflammation were univariate predictors of HOMA-IR. By multiple linear regression analysis, independent predictors of HOMA-IR included body mass index (P < 0.001), previous failed antiviral treatment (P < 0.001), portal inflammatory grade (P < 0.001), and genotype 3 status (P = 0.01). Genotype 3 had significantly lower HOMA-IR than other genotypes (which were comparable when adjusted for effects of the remaining independent predictors). HOMA-IR was an independent predictor for the degree of fibrosis (P < 0.001) and the rate of fibrosis progression (P = 0.03). CONCLUSIONS: Hepatitis C virus may induce insulin resistance irrespective of the severity of liver disease, and this effect seems to be genotype specific. Further, our findings support the hypothesis that insulin resistance may contribute to fibrotic progression in chronic hepatitis C virus infection.

Adolescent↗

PubMed2003

Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C.

Data on the long-term outcome of nonalcoholic steatohepatitis (NASH)-associated cirrhosis are few, and most reports describe cases of cryptogenic cirrhosis associated with risk factors for NASH but without histologic definition. In this prospective cohort study, we describe the long-term morbidity and mortality of 23 patients with NASH-associated cirrhosis defined by strict clinicopathologic criteria. Outcomes were compared with 46 age- and gender-matched patients with cirrhosis from chronic hepatitis C virus (HCV) infection: 23 untreated and 23 nonresponders to antiviral therapy. During follow-up (mean, 84 months; median, 60 months; range, 5-177 months), 9 of the 23 NASH-associated cirrhosis cases developed liver-related morbidity (8 ascites and/or encephalopathy, 1 variceal bleeding). The probability of complication-free survival was 83%, 77%, and 48% at 1, 3, and 10 years, respectively, and the cumulative probability of overall survival was 95%, 90%, and 84% at 1, 3, and 10 years, respectively. Five deaths were from liver failure, 1 from a non-liver-related cause. By multivariate analysis, bilirubin (P =.02) and platelet (P =.04) were independent predictors of complication-free survival; bilirubin (P =.05) was the only predictor for overall survival. After controlling for these factors, there was no difference in complication-free or overall survival between the NASH-cirrhosis cohort and either group of HCV-cirrhosis. However, 8 cases of liver cancer occurred in the HCV-cirrhosis groups compared with none among NASH cases. In conclusion, liver failure is the main cause of morbidity and mortality in NASH-associated cirrhosis. The prognosis is either similar or less severe than HCV-cirrhosis, except that HCC appears less common.

Adult↗

PubMed2003

Changes in antipyrine clearance and platelet count, but not conventional liver tests, correlate with fibrotic change in chronic hepatitis C: value for predicting fibrotic progression.

OBJECTIVE: We tested whether fibrotic progression in chronic hepatitis C could be predicted by liver tests, antipyrine clearance, or platelet count. METHODS: In 58 patients (6 untreated, 52 interferon-treated), a second liver biopsy was taken median 4.5 yr after first histologic diagnosis. We used receiver operating characteristic curves to determine whether changes in conventional liver tests, antipyrine clearance, or platelet count were predictive of altered hepatic fibrosis score. RESULTS: Apart from a weak association with change in ALT, conventional liver tests (albumin, bilirubin, prothrombin time) failed to correlate with changes (Delta) in hepatic fibrosis, but there were significant correlations between deltaantipyrine clearance or deltaplatelet count and deltafibrosis score (p < 0.01). As indicated by areas under the receiver operating characteristic curves, the diagnostic accuracy of deltaantipyrine clearance for fibrotic progression was 68%; for Deltaplatelet count it was 80%. With defined cut-off values (-0.05 ml/min/kg for deltaantipyrine clearance; -41 x 10(9)/L for deltaplatelet count), the negative predictive values for fibrotic progression were 85% with antipyrine clearance and 89% with platelet count. Corresponding positive predictive values were 48% and 91%, respectively. CONCLUSIONS: Changes in antipyrine clearance and platelet count are more sensitive than conventional tests for indicating fibrotic change in chronic hepatitis C. Both could be used to reliably identify those who do not have fibrotic progression, and platelet count also has a high positive predictive value for disease progression.

Adult↗

PubMed2003

Pharmacotherapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the more common causes of cancer death worldwide. It occurs on a background of chronic liver disease or viral hepatitis in the vast majority of cases, with hepatitis C being mostly responsible for its continuing rise in western countries. With the screening of at-risk groups, up to 70% of HCC lesions will be detected at a treatable stage but at best, only 20-30% will benefit from potentially curative hepatic resection or transplantation. How best to treat the remaining nonsurgical patients is an area of much debate and no ideal treatment is yet available. This review summarises some of the therapeutic modalities used for HCC, with an emphasis on pharmacological therapies.

Antineoplastic Agents↗

PubMed2003

Management of lupus nephritis.

Management of lupus nephritis is relatively nonspecific and includes various immunosuppressive drugs, cytotoxic agents and other modalities directed against the aberrant immune response. Treatment decisions are influenced by the clinical features, histology, response to treatment, relapses, patient consent and tolerance to medications. Guidelines based on available evidence, as to how best to manage lupus nephritis and possible future interventions are discussed.

Anti-Inflammatory Agents↗

PubMed2003

[The role of cytokines secreted by T cells in the pathogenesis of angina pectoris].

Recent evidence suggests that an inflammatory process has a significant role in the evolution of atherosclerosis. A chronic inflammatory response in the blood vessel's wall causes the formation of a lesion that narrows the artery's lumen and may cause such conditions as stable angina (SA). Destabilization of the atheromatous lesion, blood clot formation and rapid narrowing of the artery lumen may appear as part of an acute process, superimposed on the chronic inflammation. Such an acute process may be the mechanism underlying acute conditions such as unstable angina (UA) or myocardial infarction. Recent studies are trying to shed light on the process which causes destabilization of the atheromatous lesion. These studies implicate T lymphocytes and, especially, T helper 1 (Th1) cells (a sub-population of T lymphocytes) as having an important role in the destabilization of the lesion. Interferon gamma, an important cytokine secreted by Th1 cells, diminishes the production of collagen by smooth muscle cells and activates macrophages which destroy collagen and elastin. Furthermore, interferon gamma encourages clot formation and disrupts production of nitric oxide by endothelial cells. These qualities of interferon gamma support the hypothesis by which Th1 cells play a significant role in the evolution of UA. Unlike Th1 cells, Th2 cells, another sub-population of T lymphocytes, may help protect the atheromatous lesion from destabilization. This hypothesis is supported by the qualities of interleukin 10, one of the important cytokine secreted by Th2 cells. Interleukin 10 diminishes the secretion of interferon-gamma, inhibits the secretion of enzymes which destroy connective tissue in the atheromatous lesion and interferes with clot formation on the unstable lesion.

Angina Pectoris↗

PubMed2002

Oral tolerance with heat shock protein 65 attenuates Mycobacterium tuberculosis-induced and high-fat-diet-driven atherosclerotic lesions.

OBJECTIVE: The goal of this study was to explore the efficacy of oral tolerance with heat shock protein (HSP) 65 in two apparently non-overlapping models of murine atherosclerosis. BACKGROUND: Atherosclerosis is considered to be a chronic inflammatory process. Autoimmune mechanisms have been shown to influence atherogenesis in experimental animal models. Heat shock protein 65 is a candidate antigen thought to drive a proatherogenic immune-mediated response. Mucosal tolerance is a therapeutic means of accomplishing immune unresponsiveness toward a given antigen by feeding it before active induction of the disorder. METHODS: Low-density lipoprotein receptor deficient mice were fed with different doses of HSP65 every other day for 10 days. Feeding with either bovine serum albumin (BSA) or phosphate buffered saline (PBS) served as control. One day after the last feeding, mice were challenged either by immunization with heat killed Mycobacterium tuberculosis or by a high fat diet. RESULTS: Lymphocyte reactivity from mice fed with HSP65 and immunized either against HSP65 or M. tuberculosis was significantly reduced in comparison with BSA-fed mice. Moreover, co-incubation of splenocytes-from mice with tolerance induced with HSP65 but not BSA-with HSP65-reactive lymphocytes resulted in the suppression of HSP65 reactivity by the latter cells. Interleukin-4 production by HSP65-fed and immunized mice was increased upon priming with respective protein. Early atherosclerosis was attenuated in HSP65-fed mice, compared with either BSA- or PBS-fed mice, regardless of the method employed to induce fatty streaks (M. tuberculosis immunization or high-fat diet). CONCLUSIONS: Oral tolerance induced with HSP65 could prove to be a novel means of suppressing atherogenesis.

Administration, Oral↗