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J George

Publications and source records attributed to J George.

At least 163 records · Page 9Linked to original sources
PubMed1997

Smoking and immunity: an additional player in the mosaic of autoimmunity.

Autoimmune diseases are associated with a variety of predisposing factors. However, the relative contribution of each remains to be established. The purpose of the paper is to focus on cigarette smoking, a common Western habit, as a possible environmental factor for the emergence of autoimmunity. This association is described in view of several recent studies documenting increased susceptibility to autoimmune diseases among smokers.

Animals↗
PubMed1997

Rapid calpain I activation and cytoskeletal protein degradation following traumatic spinal cord injury: attenuation with riluzole pretreatment.

Immunocytochemical and immunoblotting techniques were used to investigate calpain I activation and the stability of the calpain-sensitive cytoskeletal proteins microtubule-associated protein 2 (MAP2) and spectrin at 1, 4, and 24 h after contusion injury to the spinal cord. Spinal cord injury resulted in the activation of calpain I at all time points examined, with the highest level of activation occurring at 1 h. At the same early time point, there was a loss of dendritic MAP2 staining in spinal cord sections, accompanied by pronounced perikaryal accumulation. The loss in MAP2 staining in the injured spinal cord progressed over the 24-h survival period to affect regions 3 mm distant to the site of injury. The presence of calpain I-specific spectrin degradation was apparent in neuronal cell bodies and fibers as early as 1 h after injury, with the most intense staining occurring within and juxtaposed to the injury site. Spectrin breakdown products in neuronal cell bodies declined rapidly at 4 h and were nearly undetectable at 24 h after injury. Immunoblot studies confirmed the immunocytochemical results by demonstrating a significant increase in calpain I activation, a significant decrease in MAP2 levels, and a significant increase in spectrin breakdown. Finally, treatment of animals with riluzole, an inhibitor of glutamate release, before surgery reduced significantly the loss of MAP2 levels observed at 24 h after injury. These results demonstrate that Ca2+-dependent protease activation and degradation of critical cytoskeletal proteins are early events after spinal cord injury and that treatments that minimize the actions of glutamate may limit their breakdown.

Animals↗
PubMed1997

Causes and prognosis of delirium in elderly patients admitted to a district general hospital.

BACKGROUND: delirium is common and is associated with a high early mortality, but less is known about the longer term prognosis. DESIGN: case-controlled prospective study. METHODS: all relevant wards were contacted weekly by a research nurse and the nurses were asked to report all patients presenting with confusion. Patients satisfying the American Psychiatric Association's Diagnostic and Statistical Manual III criteria were included. The diagnosis of delirium was confirmed by a consultant physician. Delirious patients were then followed-up throughout their hospital admission to ascertain the cause of their delirium, and assessed for visual and hearing impairment. The patients were assessed again at 6 and 12 months. Control patients, who were in hospital at the same time and on similar wards, but were not confused, were also examined and followed-up. RESULTS: 171 patients with delirium were identified (78 men and 93 women, mean age 81 years). The commonest cause of delirium was infection (34% of cases), but in 25% there were multiple equally contributory causes. Vision and hearing impairment was significantly more common in patients with delirium [odds ratio (OR) 12.62; confidence intervals (CI) 2.86-114.04, P < 0.001). After 1 year, patients presenting with delirium had an increased mortality (OR 2.30; 95% CI 1.25-4.35, P = 0.006), an increased institutionalization rate (OR 4.53; 95% CI 1.80-13.56, P = 0.001) and an increased likelihood of having been re-admitted (OR 2.05; 95% CI 1.19-3.54, P = 0.008). CONCLUSION: delirium has a poor long-term prognosis and may be a marker for functional deterioration and decline in elderly people.

Aged↗
PubMed1997

Immunologic characterization and functional properties of murine antibodies raised against deleted mutants of human beta 2-glycoprotein I.

beta 2-Glycoprotein I (beta 2GPI) is a 50 kDa molecule proposed as a principal target of 'autoimmune' antiphospholipid antibodies (aPL). We have used deleted mutants (DM) representing different domains of beta 2GPI (I-IV, IV-V and V) for immunization of naive mice and studied the characteristics of the respective murine IgG preparations in comparison with affinity-purified IgG from two patients with primary antiphospholipid syndrome. Immunization with beta 2GPI and with the DM produced anti-beta 2GPI antibodies, part of which reacted with negatively charged phospholipids (PL), whereas reactivity with cardiolipin was evident only in the IgG from mice immunized with beta 2GPI. These results are consistent with the presumption that aPL are induced following the in vivo association of beta 2GPI (used for immunization) with resident negatively charged PL. Accordingly, DM which either lack the PL binding site or aPL attachment locus did not elicit, upon immunization, antibodies reactive with PL. Further, murine anti-beta 2GPI IgG and human 'autoimmune' aPL were similar, albeit not identical, in terms of DM requirement for PL binding and charge dependency. Murine antibodies and human aPL, regardless of their binding characteristics, were found to bind significantly to platelets upon their activation with thrombin and to promote platelet activation. The results of the current study emphasize the dissimilarities between human 'autoimmune' aPL and murine anti-beta 2GPI. Thus, anti-beta 2GPI antibodies to different DM as well as human aPL are capable of binding and activating human platelets provided beta 2GPI is present.

Animals↗
PubMed1997

The bactericidal activity of levofloxacin compared with ofloxacin, D-ofloxacin, ciprofloxacin, sparfloxacin and cefotaxime against Streptococcus pneumoniae.

The bactericidal activity of levofloxacin was compared with that of four other quinolones and one cephalosporin against four strains of Streptococcus pneumoniae with varying degrees of penicillin G susceptibility. Levofloxacin was found to be the most bactericidal quinolone at its optimum bactericidal concentration, followed by ofloxacin, ciprofloxacin, sparfloxacin and D-ofloxacin, in that order. There was no correlation between quinolone-susceptibility and penicillin-susceptibility with any quinolone tested. To allow a comparison between the bactericidal activity of the quinolones and cefotaxime to be made a bactericidal index was used. Against two penicillin-sensitive pneumococci and a penicillin-intermediate pneumococcus, cefotaxime was the most potent antibacterial agent tested, followed by levofloxacin. However, against the penicillin-resistant pneumococcus, levofloxacin was considerably more potent than cefotaxime. The remaining quinolones tested were inferior to levofloxacin. Levofloxacin has enhanced activity against pneumococci compared with clinically available quinolones. In addition, levofloxacin may be the future quinolone of choice in the treatment of penicillin-resistant pneumococci.

Anti-Infective Agents↗
PubMed1997

Infections and Wegener's granulomatosis--a cause and effect relationship?

The association of infections and autoimmune disease has been noted by various authors. Several mechanisms have been proposed to explain this, with no current consensus. Wegener's granulomatosis (WG) is an autoimmune disease involving predominantly the pulmonary and renal systems, and is associated with a distinct autoantibody-the anti neutrophil cytoplasmic antibody (ANCA). Although no solid evidence implicates infections in the emergence of WG, direct and circumstantial data suggest this relation. We review this evidence and discuss possible underlying mechanisms. We emphasize the relationship between infections and ANCA, and their role in the maintenance of the 'on-going' inflammatory response.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

'Autoantibody dominance' pattern following idiotypic manipulation of naive mice by immunization with anti-U1RNP antibodies.

OBJECTIVE: To study the immune response and clinical findings in mice immunized with different epitope-specific anti-U1RNP antibodies purified from the sera of mixed connective tissue disease (MCTD) patients with various clinical manifestations. METHODS: BALB/c mice were immunized with anti-U1RNP-IgG preparations from 3 patients with MCTD. Group 1 was immunized with U1 70 kD A-positive IgG, group 2 with U1 70 kD-negative, U1A, U1C, B-B'-positive IgG and group 3 with U1 70 kD, U1A, U1C-positive IgG. The induced autoantibody response in the mice was studied by ELISA and immunoblots and the clinical findings of MCTD in humans were assessed. RESULTS: Immunoblot assays showed that mice immunized with different human anti-U1RNP antibodies developed predominantly autoantibodies directed against U1 68-70 kD epitope. This 'autoantibody dominance' pattern was not associated with clinical findings. CONCLUSIONS: The restricted murine autoimmune response may provide clues to the diversified autoantibody production in autoimmune diseases and explain in part the changing patterns of clinical findings in individuals with MCTD.

Animals↗
PubMed1997

Familial Mediterranean fever and hyperimmunoglobulinemia D syndrome: two diseases with distinct clinical, serologic, and genetic features.

OBJECTIVE: To determine whether the 2 periodic febrile syndromes familial Mediterranean fever (FMF) and hyperimmunoglobulinemia D syndrome (HIDS) are distinct diseases. METHODS: Clinical manifestations of the diseases were analyzed by physicians experienced with FMF and HIDS. Serum immunoglobulin (Ig) levels were studied in 70 patients with FMF using nephelometry or ELISA and compared with Ig levels in 50 patients with HIDS. Genetic linkage of HIDS with the chromosome 16 polymorphic locus RT70, currently used for refined localization of the FMF susceptibility gene (MEFV), was studied in 9 HIDS families (18 patients) using polymerase chain reaction amplification and gel electrophoresis. RESULTS: The main clinical features distinguishing FMF from HIDS were lymphadenectomy, skin eruption, and symmetrical oligoarthritis in HIDS, and monoarthritis, peritonitis, and pleuritis in FMF. Increased IgG levels were found in 12 patients with FMF (17%), IgA in 16 (23%), IgM in 9 (13%), and IgD in 9 (13%), significantly lower than the prevalence reported for HIDS. We found no evidence for genetic linkage between HIDS and the chromosome 16 marker RT70. CONCLUSION: HIDS and FMF are different entities, clinically, immunologically, and genetically.

Chromosomes, Human, Pair 16↗
PubMed1997

The emerging concept of pathogenic natural autoantibodies.

Natural autoantibodies (NAA) are self-reacting antibodies found in the serum. NAA do not require antigenic or mitogenic stimuli for their synthesis. These low affinity antibodies are found in the sera of normal healthy subjects and animals and are thought to constitute part of the innate immunity by providing a first line of defense against foreign invading pathogens. In this paper we summarize the recently accumulated data which points to the pathogenic potential of NAA, challenging the paradigm of nonharmful antibodies.

Animals↗
PubMed1997

Atherosclerosis in LDL-receptor knockout mice is accelerated by immunization with anticardiolipin antibodies.

Atherosclerosis is a process initiated by accumulation of macrophages in distinct areas of endothelial cell damage and uptake of large amounts of lipids. Recently, it has been shown that the immune system plays an active part in the progression of the atherosclerotic plaque although its precise role has not yet been elucidated. Anticardiolipin antibodies (aCL) are generally found in the sera of patients with the antiphospholipid syndrome (APS) and are associated with a prothrombotic state. Several authors have demonstrated that aCL can activate platelets and endothelial cells as well as increase oxidized low density lipoprotein (LDL) uptake by macrophages. In the present study we sought to assess the effect of immunization with aCL (Ab1, leading to the production of mouse aCL-Ab3) on the progression of atherosclerosis. Two groups of 8-weeks old female LDL-receptor knockout mice (n = 13 per group) were immunized with IgG purified from the serum of an APS patient or with normal human IgG, respectively. The aCL immunized mice developed high titres of 'self' aCL (detected using the standard aCL ELISA) as compared with the normal human IgG immunized mice, whereas no differences were noted between both study groups with respect to the serum lipid levels. The extent of fatty streak formation was significantly higher in the aCL immunized mice in comparison with the human IgG injected mice (mean aortic lesion size of 5308 +/- 471 microns2 vs 1027 +/- 184 microns2, respectively, P < 0.01). The immunohistochemical analysis of the atherosclerotic plaques from both mouse groups did not display differences in cellular composition. The results of the study show that mouse aCL induced by immunization with human aCL from an APS patient enhance atherogenesis in LDL-RKO mice and imply that these antibodies may play a role in atherosclerosis development in patients with the APS.

Animals↗
PubMed1997

The role of 67gallium scintigraphy and high resolution computed tomography as predictors of disease activity in sputum smear-negative pulmonary tuberculosis.

SETTING: University Hospital, Kuala Lumpur, Malaysia. OBJECTIVE: To determine whether 67Gallium (Ga) scintigraphy and high resolution computed tomography (HRCT) of the lung improve the diagnostic accuracy of sputum smear-negative active pulmonary tuberculosis. DESIGN: Patients suspected of having active pulmonary tuberculosis but who were sputum smear-negative underwent 67Ga scintigraphic and HRCT scanning of the lung. Results of these scans were correlated with results of bacteriology and histopathology as well as clinical data on follow-up. RESULTS: Although none of the patients was culture-positive for Mycobacterium tuberculosis, 14 were considered to have active disease either because of positive direct smears of respiratory tract specimens other than sputum, positive histopathology, or clinical and radiological improvement following antituberculosis chemotherapy. A positive 67Ga scan had a sensitivity of 100% and a specificity of 83% for active pulmonary tuberculosis. Of the HRCT findings, the presence of centrilobular lesions had a 93% sensitivity and 100% specificity in determining disease activity in this group of patients. CONCLUSION: Both 67Ga scintigraphic and HRCT scans are helpful in determining disease activity in sputum smear-negative pulmonary tuberculosis.

Female↗
PubMed1997

Antibiotic susceptibility of Neisseria gonorrhoeae in Trinidad and Tobago.

Treatment failures with standard doses of penicillin have been observed in the Sexually Transmitted Diseases (STD) clinics in Trinidad and Tobago. In the absence of an ongoing surveillance system, the antimicrobial susceptibility of 518 Neisseria gonorrhoeae strains was determined in order to guide treatment. 39 (7.6%) strains were resistant to penicillin, including 27 (5.2%) positive for beta-lactamase; that is penicillinase-producing Neisseria gonorrhoeae (PPNG). 51 (10%) strains were resistant to tetracycline, with 26 (5.0%) of these exhibiting high levels of resistance compatible with tetracycline resistant Neisseria gonorrhoeae (TRNG). Six strains showed evidence of having both PPNG and TRNG plasmids, and five strains showed chromosomally-mediated resistance to both penicillin and tetracycline. The overall resistance rate to penicillin and tetracycline was 17.7%. There was no resistance to spectinomycin, cefuroxime, ceftriaxone and norfloxacin. The resistance rates demonstrated in this study are sufficiently significant to preclude the use of penicillin and tetracycline in the STD clinics and to justify the use of newer antimicrobials. It is essential that resistance patterns be monitored by continued surveillance.

Female↗
PubMed1996

The effect of patient and physician reminders on use of screening mammography in a health maintenance organization. Results of a randomized controlled trial.

BACKGROUND: Despite its demonstrated efficacy in reducing breast carcinoma mortality, screening mammography remains underutilized and its promotion in the primary care setting provides an important opportunity for intervention. METHODS: A randomized controlled trial was conducted in two sites of a health maintenance organization (HMO) serving an urban, minority population to evaluate the impact of patient and physician reminders on site visitation and mammography use. Eligible women (n = 2368) were randomly assigned to 1 of 4 intervention combinations (patient and physician reminders individually, together, or neither). The patient reminder letter invited mammography-due women to visit. The physician reminder was a notice placed in the medical record of mammography-due women. Logistic analysis and survival analysis were used to investigate the relationship of intervention status to visitation, time to a visit, and mammography use. RESULTS: The patient reminder intervention had no effect upon rates of study year visitation or mammography at either site. However, among HMO Site 2 enrollees with entitlement insurance, the median time to the next visit was reduced from 12 to 9 weeks in association with assignment to patient reminder intervention. The physician reminder intervention was also effective in increasing the rate of completed mammography at Site 2 among all assignees (36% vs. 22% for those with vs. those without physician reminders) and among assignees who visited (59% vs. 43%). CONCLUSIONS: Patient reminder letters had limited impact on visitation in this setting. Physician reminders are more effective but sites vary in their responsiveness. Further improvement in mammography utilization will require a better understanding of the determinants of patient and physician behavior.

Adult↗
PubMed1996

Lack of induction of chromosome aberrations and micronuclei by N-(1,3-dimethylbutyl)-N-phenylparaphenylenediamine in mouse bone marrow cells.

N-(1,3-Dimethylbutyl)-N-phenylparaphenylenediamine (DMPPD) is a derivative of phenylenediamine (PPD) which is widely used in the rubber industry as an antioxidant. DMPPD which is a strong allergen, is least studied for its clastogenic potency. This study evaluated the genotoxic property of DMPPD in Swiss albino mice bone marrow cells by using chromosomal aberration and micronuclei assay. Three concentrations of DMPPD, i.e., 100, 150 and 200 mg/kg body wt. did not significantly increase the micronuclei in polychromatic erythrocytes or the ratio of poly to normochromatic erythrocytes. Chromosome aberration studies using 100 mg and 200 mg/kg body wt. showed that DMPPD is a non-inducer of chromosome aberrations. The results indicated non-clastogenicity of DMPPD in mice marrow cells up to a concentration of 200 mg/kg body wt. under our experimental conditions.

Animals↗
PubMed1996

Antimutagenic and anticarcinogenic activity of natural and synthetic curcuminoids.

Five synthetic curcuminoids and three natural curcuminoids were investigated for their antimutagenic and anti-promotional activity. The natural curcuminoids, curcumin I (diferuloylmethane), curcumin II (feruloyl-p-hydroxycinnamoylmethane) and curcumin III (bis-(p-hydroxycinnamoyl)methane) isolated from Curcuma longa were found to be potent inhibitors of mutagenesis and crotean oil-induced tumour promotion. Curcumin III produced 87.6% inhibition to 2-acetamidofluorene (2-AAF) induced mutagenesis, at a concentration of 100 micrograms/plate, curcumin II and curcumin I produced 70.5% and 68.3% inhibition at the same concentration. All the synthetic curcuminoids were found to inhibit 2-AAF-induced mutagenicity among which salicyl- and anisylcurcuminoids were the most active. Curcumin III was the most effective anti-promotor among natural curcuminoids. While 90% of the control animals were having papillomas on the 10th week of tumour initiation, only 10% of the curcumin III-treated animals, 20% of the curcumin II-treated animals, and 40% of the curcumin I-treated animals were having papillomas. Salicylcurcuminoid, which was causing no papillomas by the 10th week, was the most potent anti-carcinogen among the synthetic curcuminoids. Piperonal curcuminoid also exhibited anti-promotional activity.

Animals↗
PubMed1996

Pathogenic role of anti-endothelial cell antibodies in vasculitis. An idiotypic experimental model.

Idiotypic manipulation of naive mice has previously been used for induction of systemic autoimmune diseases (e.g., antiphospholipid syndrome, systemic lupus erythematosus, and Wegener's granulomatosis). The aim of this study focused on the utilization of this technique to induce the production of anti-endothelial cells Abs (AECA) and autoimmune vasculitis in a murine model. AECA were derived from a Wegener's granulomatosis patient's plasma. IgG was purified by absorption on a proteinase-3 affinity column resulting in the depletion of anti-neutrophil cytoplasmic Ab activity. The absorbed IgG fraction displayed a high titer of AECA as evidenced by a cyto-ELISA against unfixed human umbilical vein endothelial cells. BALB/c mice were actively immunized with the purified AECA. Three months after a boost injection with the human AECA, mice developed endogenous AECA (AB), but not Abs to proteinase-3, cardiolipin, or DNA. Histologic examination of lungs and kidneys revealed both lymphoid cell infiltration surrounding arterioles and venules; as well as deposition of Igs at the outer part of blood vessel walls. This experimental animal model of vasculitis, a product of our method of idiotypic manipulation, provides the first direct proof for the pathogenicity of AECA.

Animals↗