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Biomedical subjects

J George

Publications and source records attributed to J George.

At least 109 records · Page 6Linked to original sources
PubMed1999

Cervical osteoarthropathy: an unusual cause of dysphagia.

PRESENTATION: A 72-year-old man complained of progressive dysphagia for solids associated with a sensation of foreign body in his throat for 2 years. A barium swallow showed a bridging osteophyte between C4 and C5 vertebrae indenting the oesophagus posteriorly and displacing it anteriorly. OUTCOME: He refused surgical intervention and was given dietary advice. After 6 months, his weight was steady and he was able to swallow semi-solid food without difficulty.

Aged↗
PubMed1999

Atheroma: links with antiphospholipid antibodies, Hughes syndrome and lupus.

Antiphospholipid antibodies (aPL) are found in a variety of autoimmune diseases, and are thought to predispose to arterial and venous thrombosis. These antibodies, when investigated in different assays in vitro, activate endothelial cells and promote uptake of modified LDL to macrophages. These observations suggest that aPL can contribute to atheroma development by targeting some of the sequential steps that constitute early atherogenesis. If substantiated by large-scale clinical trials, the pro-atherogenic properties of aPL may merit screening and intervention programs in selected populations.

Antibodies, Antiphospholipid↗
PubMed1999

Marked improvement of Churg-Strauss vasculitis with intravenous gammaglobulins.

Churg-Strauss vasculitis (CSV) is a systemic vasculitis usually treated with steroids and cytotoxic drugs. Herein, we describe the beneficial effect of intravenous immune globulin (IVIG) in a 50-year-old man with CSV. The IVIG therapy brought a marked clinical improvement, with impressive decline in the titers of antineutrophil cytoplasmic autoantibody.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1999

Activities of fluoroquinolones against Streptococcus pneumoniae type II topoisomerases purified as recombinant proteins.

Streptococcus pneumoniae topoisomerase IV and DNA gyrase have been purified from a fluoroquinolone-susceptible Streptococcus pneumoniae strain, from first-step mutants showing low-level resistance to ciprofloxacin, sparfloxacin, levofloxacin, and ofloxacin, and from two clinical isolates showing intermediate- and high-level fluoroquinolone resistance by a gene cloning method that produces recombinant proteins from Escherichia coli. The concentrations of ciprofloxacin, sparfloxacin, levofloxacin, or ofloxacin required to inhibit wild-type topoisomerase IV were 8 to 16 times lower than those required to inhibit wild-type DNA gyrase. Furthermore, low-level resistance to these fluoroquinolones was entirely due to the reduced inhibitory activity of fluoroquinolones against topoisomerase IV. For all the laboratory strains, the 50% inhibitory concentration for topoisomerase IV directly correlated with the MIC. We therefore propose that with S. pneumoniae, ciprofloxacin, sparfloxacin, levofloxacin, and ofloxacin target topoisomerase IV in preference to DNA gyrase. Sitafloxacin, on the other hand, was found to be equipotent against either enzyme. This characteristic is unique for a fluoroquinolone. A reduction in the sensitivities of both topoisomerase IV and DNA gyrase are required, however, to achieve intermediate- or high-level fluoroquinolone resistance in S. pneumoniae.

Anti-Infective Agents↗
PubMed1999

Serologic and clinical response to treatment of systemic vasculitis and associated autoimmune disease with intravenous immunoglobulin.

BACKGROUND: Autoimmune vasculitides cannot always be controlled by steroids and immunosuppressive drugs. Intravenous immunoglobulin (IVIg) treatment was found beneficial in several vasculitides including systemic and organ-specific diseases. In this article we tested whether the beneficial clinical response of IVIg treatment in vasculitides was accompanied by a decrease in vasculitis-associated autoantibody levels. METHODS: Ten patients diagnosed as having vasculitis were treated with high-dose (2 g/kg) IVIg monthly, in a 5-day schedule. In all the patients, other therapeutic measures failed to control disease progression prior to IVIg treatment. Each patient received between 1 and 6 treatment courses. All patients were evaluated for the levels of 5 autoantibodies (Abs) related to vasculitis before and after each treatment course. RESULTS: In 6 out of the 10 patients, a beneficial clinical response followed IVIg treatment. Moreover, no treatment-related adverse effects were observed in any of the patients. Anti-myeloperoxidase antibodies and cytoplasmic-antineutrophil cytoplasmic antibodies levels decreased concomitantly with the clinical improvement observed in the patients with Churg-Strauss vasculitis and Wegener's granulomatosis, respectively. Levels of cytoplasmic-antineutrophil cytoplasmic antibodies (ANCA) with specificity for bacteridial/permeability-increasing protein and human lysosomal-associated membrane protein increased after each treatment course, but returned to normal values before the following one. CONCLUSIONS: When other therapeutic measures, such as immunosuppressive therapy, fails to control disease manifestations in patients with vasculitides, IVIg is a possible effective intervention method with a high response rate. IVIg probably exerted its effects on disease progression via different mechanisms. Among these mechanisms, a decrease in relevant Ab levels is often found (probably by anti-idiotypes in IVIg), and thus ANCA levels are expected to associate with disease activity.

Adult↗
PubMed1999

Enhancement of atherosclerosis in beta-2-glycoprotein I-immunized apolipoprotein E-deficient mice.

We have previously shown that low density lipoprotein receptor-deficient (LDL-RD) mice immunized with beta2-glycoprotein I (beta2GPI; a target of autoimmune anticardiolipin antibodies) developed enhanced early atherosclerosis, when fed a normal chow diet. The current study was undertaken to evaluate the effect of immunization with beta2GPI and the addition of a high fat diet on the progression of atherosclerosis in the apolipoprotein E (ApoE)-deficient mouse. Six-week-old female ApoE-deficient mice (n = 10) were immunized subcutaneously with either human beta2GPI or with ovalbumin, both emulsified in complete Freund's adjuvant and fed a high fat diet for 6 weeks. The beta2GPI-immunized mice were found to develop accelerated atherosclerosis when compared with their ovalbumin-immunized littermates (aortic lesion area of 137,500 +/- 13,801 vs. 72,444 +/- 14,465 microm2, respectively; p = 0.0067). The beta2GPI-immunized mice developed high titers of anti-beta2GPI antibodies, 10 days after the procedure, which were sustained until the sacrifice. LDL extracted from both study groups displayed similar susceptibility to ex vivo oxidation. These results confirm our previous study in which we found increased atherosclerosis in beta2GPI-immunized LDL-RD mice fed a chow diet. In the current study we show that the proatherogenic effect of beta2GPI immunization is maintained despite high cholesterol levels and is not associated with increased susceptibility of LDL to ex vivo oxidation.

Animals↗
PubMed1999

Enhanced fatty streak formation in C57BL/6J mice by immunization with heat shock protein-65.

Recent data suggest that the immune system is involved in atherogenesis. Thus, interest has been raised as to the possible antigens that could serve as the initiators of the immune reaction. In the current work, we studied the effects of immunization with recombinant heat shock protein-65 (HSP-65) and HSP-65-rich Mycobacterium tuberculosis (MT) on early atherogenesis in C57BL/6J mice fed either a normal chow diet or a high-cholesterol diet (HCD). A rapid, cellular immune response to HSP-65 was evident in mice immunized with HSP-65 or with MT but not in the animals immunized with phosphate-buffered saline (PBS) alone. Early atherosclerosis was significantly enhanced in HCD-fed mice immunized with HSP-65 (n=10; mean aortic lesion size, 45 417+/-9258 microm2) or MT (n=15; 66 350+/-6850 microm2) compared with PBS-injected (n=10; 10 028+/-3599 microm2) or nonimmunized (n=10; 9500+/-2120 microm2) mice. No fatty streak lesions were observed in mice fed a chow diet regardless of the immunization protocol applied. Immunohistochemical analysis of atherosclerotic lesions from the HSP-65- and MT-immunized mice revealed infiltration of CD4 lymphocytes compared with the relatively lymphocyte-poor lesions in the PBS-treated or nonimmunized mice. Direct immunofluorescence analysis of lesions from HSP-65- and MT-immunized mice fed an HCD exhibited extensive deposits of immunoglobulins compared with the fatty streaks in the other study groups, consistent with the larger and more advanced lesions found in the former 2 groups. This model, which supports the involvement of HSP-65 in atherogenesis, furnishes a valuable tool to study the role of the immune system in atherogenesis.

Animals↗
PubMed1999

Dietary beta-carotene and alpha-tocopherol combination does not inhibit atherogenesis in an ApoE-deficient mouse model.

Although lipid oxidation plays a major role in atherogenesis, the role of antioxidants in the prevention and treatment of the process is not clear. Apolipoprotein (apo) E-deficient mice develop spontaneous atherosclerotic lesions in major arteries. The presence of oxidized lipoprotein epitopes in the lesion suggests that oxidation reactions are involved in atherogenesis in this mouse model, but the inhibitory effect of antioxidants on atherogenesis in the model is controversial. To test the effect of dietary antioxidants on atherogenesis, male apoE-deficient mice (n=15) were fed a standard chow diet supplemented with 0.05% alpha-tocopherol and 0.05% all-trans beta-carotene. A control group (n=15) received no antioxidant supplement. At the end of the trial, mice consuming vitamins had 5x more plasma vitamin E but undetectable beta-carotene levels. However, liver levels of the beta-carotene metabolite, retinyl palmitate, were higher in antioxidant-treated mice compared with control mice. The antioxidants had no effect on lipoprotein or on plasma anti-oxidatively modified low density lipoproteins (anti-oxLDL) antibody levels. The vitamins had a small but insignificant effect on lipoprotein resistance to ex vivo oxidation, determined by a longer lag period of conjugated diene formation. Atherosclerosis, determined by the lesion size at the aortic sinus, was insignificantly suppressed in antioxidant-treated mice (mean area+/-SE, 20 000+/-7129 versus 13 281+/-5861 micrometer(2); P=0.40). The aortic atherosclerotic lesion area was similar in both experimental groups (2.55+/-0.65% and 2.08+/-0.5% of total aortic area in the control and antioxidant group, respectively; P=0.58). The results of the current study suggest that moderate levels of synthetic antioxidant vitamins have no effect on atherogenesis in apoE-deficient mice.

Animals↗
PubMed1999

The Effect of Agmatine on Ischemic and Nonischemic Isolated Rat Heart.

OBJECTIVE: the natural polyamines play a protective role during ischemic injury. We studied the effects of agmatine on ischemic and nonischemic isolated rat hearts. METHODS: Thirty-one rats were randomly assigned to one of four experimental groups. Sixteen rats were injected with saline (group 1, n = 9; group 3, n = 7), and 15 rats were injected with 100 mg/kg of agmatine (group 2, n = 8; group 4, n = 7). Injections were given twice: 24 hours and 1 hour before the experiment. Using the modified Langendorf model, rat hearts were perfused with Krebs-Henseleit solution for 105 minutes during phase 1 of the experiment (groups 1 and 2). During phase 2, hearts were exposed to 45 minutes of global ischemia (groups 3 and 4). RESULTS: During phase 1, no statistically significant differences were observed between the agmatine and the control groups. During phase 2, agmatine caused a significant increase in left ventricular pressure (P <.003). At the end of reperfusion, P(max) was 111% +/- 10% from the baseline levels versus only 82% +/- 5% in the control group. After 20 minutes of reperfusion, dP/dt (first-time derivative of the ventricular pressure) in the agmatine group reached full recovery of 106% +/- 12% versus only 64% +/- 14% in the saline group (P =.059). Agmatine also caused a significant increase in coronary flow rate (P <.004) throughout the reperfusion period. Quantitative immunohistochemical staining disclosed reduced cell damage in the agmatine-treated hearts (P <.02) versus the control group. CONCLUSION: Agmatine injection given before induced ischemia improves hemodynamic recovery by mechanisms that may be attributed to its vasodilatory properties.

Journal Article↗
PubMed1999

Increased endothelial cell expression of alpha3beta1 integrin in cardiac valvulopathy in the primary (Hughes) and secondary antiphospholipid syndrome.

The objective of this work was to determine markers of endothelial cell activation in valves from patients with antiphospholipid syndrome (APS) and heart valve involvement, in order to establish a role for endothelial cells in the pathogenesis of the valvular disease. Sixteen valves from ten patients with APS, obtained from autopsies or removed during valve replacement, were studied. Two groups of valves were used as controls. One group included seven normal valves from patients who died from non-cardiac diseases. The other group of valves were obtained from patients with bacterial endocarditis during autopsies or valve replacement operations. Immunoperoxidase and immunofluorescence stainings with antibodies to human immunoglobulins, endothelial cells, alpha3beta1 integrin, collagen IV, laminin and fibronectin were employed. Three histopathological patterns were apparent: normal valves, valves with verrucous endocarditis and valves with fibrocalcific changes. In all the valves with verrucous endocarditis the following findings were observed: (1) increased expression of the alpha3beta1 integrin on the endothelial cells, (2) increased amount of collagen IV, laminin and fibronectin, (3) proliferation of blood vessels and (4) linear subendothelial deposition of immunoglobulins and complement. The valves with fibrocalcific changes were deformed and showed a thick layer of collagen IV, laminin and fibronectin, yet in two valves the indothelial cells showed an expression of the alpha3beta1 integrin. The control valves did not express the integrin and had only a thin subendothelial band of collagen IV. In valves from patients with APS, 1 markers of endothelial cell activation are upregulated while the inflammatory exudate is scant. There is also a prominent deposition of immunoglobulins in the valves from patients with APS, suggesting a possible association between the deposition of the antibodies and the activation of the endothelial cells in APS.

Actins↗
PubMed1999

A study of 20 SLE patients with intravenous immunoglobulin--clinical and serologic response.

OBJECTIVE: To test the clinical response of systemic lupus erythematosus (SLE) patients to intravenous immunoglobulins (IVIg), and whether the clinical response of IVIg treatment in SLE is accompanied by modification of SLE-associated autoantibodies/antibodies (Abs) and complement levels. METHODS: Twenty SLE patients were treated with high-dose (2 g/kg) IVIg monthly, in a 5-d schedule. Each patient received between 1-8 treatment courses. They were evaluated for the clinical response, Systemic Lupus Activity Measure (SLAM) score before and after IVIg, levels of antinuclear antibody (ANA), dsDNA (double-stranded DNA), SS-A or SS-B, ENA (extractable nuclear antigens), C3 and C4 levels before and after the treatment, and before and after each treatment course. RESULTS: A beneficial clinical response following IVIg treatment was noted in 17 out of 20 patients (85%). Few clinical manifestations responded more to treatment: arthritis, fever, thrombocytopenia, and neuropsychiatric lupus. In 9 patients evaluated before and after IVIg, mean SLAM score decreased from 19. 3+/-4.7 to 4+/-2.9 (P<0.0001). There was a tendency towards abnormal levels of complement and Abs before IVIg courses among the treatment responders compared with the non-responders, and similarly the former tended to have normalization of their abnormal levels more than the latter. These differences were found statistically significant only with respect to C4 and SS-A or SS-B levels before IVIg courses. CONCLUSION: IVIg has a high response rate among SLE patients. A combination of clinical manifestations, Abs and complement levels may aid in the future in predicting who among SLE patients will benefit more from IVIg treatment.

Adult↗
PubMed1999

Beta2 glycoprotein I containing immune-complexes in lupus patients: association with thrombocytopenia and lipoprotein (a) levels.

In this study we determined the prevalence and clinical associations of immune-complexes-containing beta-2-glycoprotein I (beta2GPI) in randomly selected SLE patients. We studied 38 consecutive SLE patients attending the Rheumatology Unit. Previous arterial or venous-thrombosis were documented by the appropriate diagnostic test. Lipid profile including total cholesterol, LDL, VLDL, HDL and Lp(a) levels were determined from the sera of the fasting patients. Antibodies to cardiolipin, oxidized LDL and beta2GPI were detected employing ELISA. Beta2GPI containing IgG immune-complexes were assayed by using a dot-blot assay. Fourteen SLE patients (36.8%) were found to be positive for the presence of IgG anti-beta2GPI antibodies. Ten of the SLE patients (26.3%) were found to have high levels of beta2GPI containing immune-complexes. There was a positive correlation between beta2GPI-IC levels and the occurrence of thrombocytopenia in the patients (P < 0.05). Furthermore, patients with SLE and venous thrombosis had higher levels of beta2GPI-IC when compared with thrombosis-free patients or with healthy controls (P < 0.05). Patients with higher Lp(a) levels (> 50 mg/dl) possessed higher levels of beta2GPI-IC as compared with patients with lower Lp(a) concentration (< 20 mg/dl) (P < 0.05). These results suggest that IC-containing beta2GPI can help in defining a subpopulation of SLE patients with increased risk of thrombocytopenia and further aid in resolving mechanisms of immune-mediated tissue damage.

Adult↗
PubMed1999

Atherosclerosis-related markers in systemic lupus erythematosus patients: the role of humoral immunity in enhanced atherogenesis.

Systemic Lupus Erythematosus (SLE) patients experience premature atherosclerosis. A deranged lipid metabolism and use of immunosuppressive medications accounts partially for the accelerated process. The role of autoimmunity in atherosclerosis has recently been highlighted. Autoantigenic determinants thought to play a role in the development of atherosclerosis include: modified lipoproteins, heat shock proteins and beta2-glycoprotein I (a target of 'autoimmune' anticardiolipin antibodies). In this present work we determined autoimmune markers which may be associated with premature atherosclerotic process found in SLE patients. We have found that antibodies to oxLDL were raised in the sera of lupus patients and cross-reacted with cardiolipin and with beta2GPI. OxLDL containing immune-complexes of the IgG and IgM isotypes were both elevated in the SLE patients as compared with healthy controls. Patients with high Lipoprotein (a) concentrations (>30 mg/dl) had higher levels of IgM oxLDL-containing immune-complexes. IgM but not IgG anti-HSP-65 antibodies were elevated in the lupus patients and levels of oxLDL containing immune-complexes correlated positively with the presence of anti-HSP 65 antibodies. Lysophosphatidylcholine (LPC) is a peroxide-derivative formed during LDL oxidation, was shown to evoke a humoral response in healthy subjects. Antibodies to lysophosphatidylcholine of the IgG but not the IgM isotype were reduced in SLE patients compared with controls, suggesting it may be 'consumed' into oxLDL containing immune complexes. Therefore, SLE patients exhibit a humoral autoimmune response towards the antigenic candidates incriminated in the progression of atherosclerosis. These findings may help identify factors that are involved in accelerating atherogenesis in SLE patients.

Adult↗
PubMed1999

Anti-cardiolipin, anti-endothelial-cell and anti-malondialdehyde-LDL antibodies in uremic patients undergoing hemodialysis: relationship with vascular access thrombosis and thromboembolic events.

Patients with chronic renal failure requiring regular hemodialysis are known to be prone to thromboembolic events due to a hypercoagulable state. Vascular access thrombosis (VAT; including thrombosis of the vascular shunt or graft) represents a serious complication and jeopardizes life in these patients. In the current study, conducted on 81 consecutive patients from the Hemodialysis Unit, we have employed ELISA for the estimation of various autoantibody levels (anti-endothelial cell antibodies, anti-cardiolipin, anti-beta 2GPI and anti-modified LDL antibodies) and correlated them with the occurrence of thromboembolic events in general, and VAT in particular. We have found that the levels of antibodies reactive with human umbilical vein endothelial cells (HUVEC) but not with other EC lines (microvascular or EaHy 929) were significantly higher in hemodialysed patients with VAT in comparison with patients with no VAT (p = 0.001). A weaker but yet positive correlation was observed between the levels of anti-HUVEC and anti-cardiolipin antibodies and the occurrence of thromboembolic events including deep vein thrombosis, pulmonary infarction, cerbrovascular events and VAT (both p-values equal 0.02). Anticardiolipin antibodies (aCL) were not cross reactive with beta 2GPI or with HUVEC. Antibodies to modified LDL, although higher in hemodialyzed patients, did not correlate with thromboembolic events. The results of this study suggest that antibodies to HUVEC may prove as a fairly good marker of VAT in hemodialysis. High levels of aCL are weakly associated with thromboembolic events and antibodies to modified LDL do not correlate with a prothrombotic state.

Adult↗
PubMed1999

Elevated homocysteine levels in patients with Raynaud's syndrome.

OBJECTIVE: Patients with Raynaud's phenomenon (RP) have vasomotor dysregulation, the etiology of which has not yet been elucidated. We investigated plasma levels of homocysteine and folate in patients with primary or secondary RP in comparison with healthy subjects. METHODS: Plasma from patients with RP, either primary (n = 10) or secondary to scleroderma (n = 10), and from healthy subjects (n = 20) was obtained for homocysteine determination using high performance liquid chromatography. RESULTS: Patients with primary and secondary RP had significantly higher homocysteine concentrations (mean 15.5 +/- 4.1 and 11.6 +/- 6.2 micromol/l, respectively; p < 0.05) compared to healthy individuals (mean 5.9 +/- 2.0 micromol/l). Patients with primary RP had significantly lower plasma levels of folate in comparison with patients with secondary RP or healthy individuals. CONCLUSION: This is the first study to show higher plasma levels of homocysteine in patients with RP. Given the obscure etiology of this disorder, these findings may provide new clues in the understanding of vasomotor dysfunction in RP.

Adult↗