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J George

Publications and source records attributed to J George.

At least 73 records · Page 4Linked to original sources
PubMed2000

Heat shock protein 60/65, beta 2-glycoprotein I and oxidized LDL as players in murine atherosclerosis.

We have made consecutive studies to prove that autoimmune factors can influence the progression of atherosclerosis in inbred and transgenic mice. C57BL/6 as well as LDL-receptor deficient mice were immunized with heat shock protein 65. LDL-RD and apolipoprotein E knockout (apoE KO) mice were immunized with human B-glycoprotein I. ApoE KO mice were immunized with oxidized LDL. In all immunized mice, a sustained humoral response to the provided antigen was elicited evident by high titers of antibodies by ELISA. A primary cellular immune response was also shown by thymidine incorporation studies employing the antigens in vitro. Immunization with hsp-65 and with beta 2-GPI served to enhance the progression atherosclerosis and led to an increase in the infiltration of CD3 in the subendothelial regions of the early plaques. Transfer of hsp-65 and beta 2-GPI reactive lymphocytes to syngenic mice led to enhancement of fatty streak formation. However, immunization with homologous oxLDL in apoE KO mice led to attenuation of lesion progression concomitant with the production of anti-oxLDL antibodies. Thus, autoimmune factors appear to influence early artherosclerosis progression in mice. If proven in humans these antigen specific responses may be harnessed for selective immunomodulation of the atherosclerotic plaque.

Animals↗
PubMed2000

Transforming growth factor-beta initiates wound repair in rat liver through induction of the EIIIA-fibronectin splice isoform.

A prominent feature of the hepatic response to injury is production of a fetal isoform of fibronectin, a splice variant containing the EIIIA region, which appears very early after injury and derives from sinusoidal endothelial cells. Previous studies have shown that it is instrumental in initiating the cellular response to injury, specifically the conversion of resting stellate cells to myofibroblast-like cells. The present work describes the regulation of this change in fibronectin expression. Using sinusoidal endothelial cells from normal or injured liver in primary culture, we show that exogenous transforming growth factor beta (TGFbeta) stimulates [EIIIA]Fn expression. To assess the role of TGFbeta in vivo, we used a chimeric IgG containing the extracellular portion of the TGFbeta type II receptor as a competitive inhibitor of the cytokine. Administered to animals at the time of injury, the inhibitor reduced expression of [EIIIA]Fn mRNA by 50% as compared to controls (P < 0.01). There was a corresponding decrease in [EIIIA]Fn protein production as judged by immunohistochemistry. Cell fractionation experiments indicated that the changes observed in whole-liver extracts were localized to sinusoidal endothelial cells. We conclude that TGFbeta initiates wound repair in part by stimulating endothelial expression of [EIIIA]Fn. Results with the soluble inhibitor of the TGFbeta type II receptor suggest a novel strategy for modulating wound repair in vivo.

Animals↗
PubMed2000

Biochemical abnormalities during the progression of hepatic fibrosis induced by dimethylnitrosamine.

OBJECTIVES: The pathogenesis of hepatic fibrosis is accompanied with several biochemical and metabolic abnormalities. To obtain more information about the alteration of biochemical and metabolic parameters during alcoholic liver fibrosis, we have monitored the changes of certain important biochemical compounds in experimentally induced hepatic fibrosis. DESIGN AND METHODS: The liver injury was induced in adult male albino rats by using dimethylnitrosamine (DMN) in doses of 1 mg/100 g body weight. Total collagen, total protein, cholesterol, lipid peroxides, glucose, urea, and inorganic phosphorus were monitored in liver and blood/serum samples on Days 0, 7, 14, and 21 after the start of DMN administration. Serum insulin levels were assayed by radioimmunoassay. The serum and urinary levels of hydroxyproline, uric acid, and creatinine were also monitored. RESULTS: The total collagen content in the liver was increased about 4-fold by Day 21 after the start of DMN administration. A significant increase was observed in lipid peroxide levels in both liver and blood samples. Although inorganic phosphorus level decreased in both serum and liver tissue, cholesterol was lowered only in the serum. Increased serum insulin level with impaired glucose tolerance was observed after 21 days. Serum hydroxyproline level increased throughout after the start of DMN administration. The urinary excretion of hydroxyproline was also significantly increased with a striking elevation on Day 7. Elevated uric acid levels were recorded in serum and urine samples during the latter periods of DMN treatment. No alteration was observed in blood urea and creatinine levels. CONCLUSIONS: The results of the present investigation demonstrated important alterations in metabolic parameters and biochemical abnormalities during experimentally induced liver damage. All alterations are compatible with the deterioration of liver functions during the pathogenesis of hepatic fibrosis.

Animals↗
PubMed2000

Interleukin (IL)-4 deficiency does not influence fatty streak formation in C57BL/6 mice.

Abundant data is present to implicate oxidatively modified low-density lipoprotein (oxLDL) in enhanced atherogenesis. Among the factors involved in LDL oxidation, an important role has been attributed to human 15-lipoxygenase (LO) and its murine analog 12-LO. The expression of these peroxidizing enzymes is under the control of cytokines, the principal of which is IL-4. In the present study we tested the hypothesis that knocking out the IL-4 gene from C57BL/6 mice would result in suppression of fatty streaks. For this purpose, we have fed 45 female IL-4 transgenic knockout (IL-4T KO) and 45 wild-type (WT) mice an atherogenic diet for 15 weeks. Consecutive determinations of the lipid profile from both study groups were performed at monthly intervals, and fatty streak formation was assessed at the aortic sinus level, upon sacrifice. The two study groups did not differ significantly with respect to the lipid profile or the uptake and degradation of iodinated oxLDL by their peritoneal macrophages. We found that the endogenous deficiency of IL-4 did not confer protection from early atherosclerosis in the IL-4T KO as compared to their WT littermates (determined at the aortic sinus). Immunohistochemical studies, Western blots and 12/15-LO activity assays revealed the presence and activity of 12/15-LO in macrophages of WT mice as well as in IL-4T KO mice. Both did not differ significantly between the study groups. The data from this study imply that deficiency in IL-4 does not affect early atherosclerosis in C57BL/6 mice fed a high-cholesterol diet.

Animals↗
PubMed2000

The effects of N-6 polyunsaturated fatty acid supplementation on the lipid composition and atherogenesis in mouse models of atherosclerosis.

Despite numerous studies, the precise role of dietary n-6 polyunsaturated fatty acids in the pathogenesis of atherosclerosis remains controversial. It has been shown that feeding an n-6-enriched diet resulted in decreased atherosclerosis in African green monkeys and was associated with a reduction in LDL levels. However, other authors reported that n-6 supplementation increased the oxidative stress and the susceptibility of LDL to undergo in vitro oxidation, thus potentially enhancing atherosclerosis. The present study was designed to investigate the effect of dietary supplementation of n-6 polyunsaturated fats (safflower oil), as compared with a saturated fat-rich diet (Paigen), on the blood lipid profile and atherosclerosis in two mouse models. In the first experiment, female C57BL/6 mice (n=23-30 per group) were fed a cholate containing Paigen diet, a safflower oil-rich diet (with cholate), or normal chow for 15 weeks. No significant differences between the high fat diet groups were evident with respect to total cholesterol, LDL, HDL or triglyceride levels. The extent of aortic sinus fatty streaks did not differ significantly between the two groups. In the second experiment, LDL-receptor-deficient (LDL-RD) mice (n=20-30 per group) were randomized into similar dietary regimens. Mice consuming a safflower oil-enriched diet developed significantly less atherosclerosis, in comparison with Paigen diet-fed mice. A reduction in LDL levels, although not of a similar magnitude as the reduction in atherosclerosis, was evident in the safflower oil-fed mice when compared to the Paigen diet-fed littermates. In both mouse models of atherosclerosis, LDL isolated from the plasma of mice on the n-6 polyunsaturated diet was rendered slightly more susceptible to oxidation in vitro, as indicated by a shorter lag period for diene formation. Thus, the effects of n-6 fatty acids on the lipoprotein composition and other potential influences may have contributed to the anti-atherogenic effect in the LDL-RD mouse model.

Animals↗
PubMed2000

Intravenous immunoglobulin treatment of lupus nephritis.

OBJECTIVE: To evaluate the clinical response of treatment-resistant membranous and membranoproliferative lupus nephritis to intravenous immunoglobulin (IVIg). METHODS: Seven lupus nephritis patients who failed to respond to at least prednisone and cyclophosphamide were studied. A kidney biopsy showing either membranous or membranoproliferative glomerulonephritis was available in six patients. They were treated with six courses (patients 1 and 2) or 1 or 2 courses (patients 3 through 7) of high-dose IVIg. For patients 3 through 7, the plasma levels of albumin, total cholesterol, urea, creatinine, dsDNA antibody titers, and daily proteinuria were measured just before the IVIg therapy, immediately on completion, and 6 months later. RESULTS: All seven patients had a beneficial response to IVIg. In patient 1, decrease in proteinuria was evident 2 weeks after IVIg was started, nephrotic syndrome gradually disappeared, and she had no proteinuria in 3 years' follow-up. Decline in proteinuria was evident in patient 2 after the 4th IVIg course, but proteinuria reached the pretreatment level 4 months after the therapy ended. In patients 3 through 7, the mean daily proteinuria before IVIg (5.3 +/- 2.1 g) decreased after 1 or 2 IVIg courses (3.3 +/- 1.4 g), and further decreased when measured 6 months later (2.1 +/- 1.3 g). Similarly, the plasma cholesterol level decreased while the plasma albumin level increased after IVIg. CONCLUSIONS: IVIg might be effective in treatment-resistant membranous or membranoproliferative lupus nephritis. Future studies should concentrate on determining the preferred treatment protocol of IVIg for the various classes of lupus nephritis.

Adolescent↗
PubMed2000

Ultrasound biomicroscopy of sclerotomy sites after pars plana vitrectomy for diabetic vitreous hemorrhage.

OBJECTIVE: This study was aimed at assessing changes at the sclerotomy site using the ultrasound biomicroscope (UBM) in eyes that underwent primary pars plana vitrectomy for complications of proliferative diabetic retinopathy. DESIGN: Prospective, observational case series. PARTICIPANTS: Eighty-six eyes of 84 patients with vitreous hemorrhage caused by proliferative diabetic retinopathy. INTERVENTION: Three-port pars plana vitrectomy followed by UBM evaluation of all sclerotomy sites between 6 and 8 weeks after surgery. Correlation with intraoperative findings done in case of reoperations. Forty-one eyes had repeat UBM at 6 months. MAIN OUTCOME MEASURES: The changes at the sclerotomy site were classified into six groups: well healed, gape, plaque, vitreous incarceration, fibrovascular proliferation, and anterior hyaloidal fibrovascular proliferation (AHFVP). The UBM characteristics of each of the groups were defined. The findings at 6 months were compared with those at 6 to 8 weeks. RESULTS: At 6 to 8 weeks after surgery, most sclerotomies were well healed or had either moderate to high reflective plaques bridging the site. Wound gape was seen in 22.1% of active ports, 32.6% of light ports, and 25.6% of infusion ports. Vitreous incarceration was seen most often at the infusion port (18. 6% of eyes). Fibrovascular proliferation was seen in 9.3% of active ports, 12.8% of light ports, and 15.1% of infusion ports. Thirteen eyes had recurrent vitreous hemorrhage 6 to 8 weeks after surgery. Cases with rebleeding and no fibrovascular proliferation at the sclerotomy on UBM did well with outpatient fluid-air exchange (two eyes) or observation only (three eyes). Those with fibrovascular proliferation on UBM (eight eyes) required more extensive surgery. CONCLUSIONS: UBM is helpful in detecting complications at the sclerotomy sites after pars plana vitrectomy and is an invaluable tool in the assessment of the patient before reoperation.

Diabetic Retinopathy↗
PubMed2000

A double-blind randomised comparison of ropivacaine 0.5%, bupivacaine 0.375% - lidocaine 1% and ropivacaine 0.5% - lidocaine 1% mixtures for cataract surgery.

This study evaluated the efficacy and side-effects of plain ropivacaine compared with ropivacaine-lidocaine and bupivacaine-lidocaine mixtures for peribulbar blocks in cataract surgery. Ninety patients were randomly allocated to three groups and received peribulbar blockade using one of the three solutions. Speed of onset and quality of blockade were assessed using akinesia, surgical satisfaction and patient satisfaction. Complications and cardiovascular side-effects were noted. There was a slower onset of akinesia using ropivacaine alone, although at 10 min after injection all groups were equal in this respect. There was no difference in surgical or patient satisfaction between the groups. There were no differences in pain on injection, preblock and postblock blood pressure, heart rate or oxygen saturation. The optimal time to surgical incision after peribulbar blockade is not less than 15 min and plain ropivacaine fulfils this criterion.

Aged↗
PubMed2000

Radiological classification of meniscocapsular tears of the anterolateral portion of the lateral meniscus of the knee.

In an arthroscopic-MRI correlation study of acute injuries to the knee it was found that anterolateral meniscocapsular separations of the lateral aspect of the knee were missed on MRI reporting. Eighty sports-related injuries of the knee were seen by experienced orthopaedic surgeons at the University of Malaya Medical Centre and at the National Sports Centre, Malaysia from January 1996 to July 1997. Fifty of the patients were suspected to have meniscal tears that were either lateral or medial on clinical examination and they were sent for MRI. Many of these patients were tertiary referrals. Magnetic resonance imaging examinations in 27 of the 50 patients were reported as not showing any intrasubstance or obvious meniscocapsular tears, but arthroscopy performed on them revealed anterolateral meniscocapsular tears of the lateral meniscus of varying degrees in nine of these patients. In retrospect the tears could be seen on MRI, and a pattern to the tears was noted and classified as follows. Type 0, normal; type 1, torn inferior or superior meniscocapsular attachment; type 2, both meniscofemoral and meniscotibial ligaments torn but with minimal separation of meniscus and capsule by fluid or synovitis; and type 3, marked separation of meniscus and capsule by fluid (> 3 mm). Ten patients who did not undergo arthroscopy for various personal and financial reasons underwent MRI which showed type 1 and type 2 tears, and were treated conservatively. These patients were all asymptomatic after 4-6 weeks with regard to clinical signs, suggesting a lateral meniscal tear. Magnetic resonance imaging therefore does reveal minor degrees of meniscocapsular tears anterolaterally when one understands the normal anatomy in this region.

Arthroscopy↗
PubMed2000

Captopril and L-arginine have a synergistic cardioprotective effect in ischemic-reperfusion injury in the isolated rat heart.

OBJECTIVES: The present study was designed to evaluate the possible effect of the combined administration of both captopril (Cap) and L-arginine (L-a) in the isolated ischemic rat heart model. BACKGROUND: Recent studies suggest that L-arginine and angiotensin-converting enzyme (ACE) inhibitors possess independent cardioprotective effects in ischemic hearts. The pharmacological effect of the combination of both drugs has not yet been investigated in the ischemic myocardium. METHODS: Using the modified Langendorf model, rats were perfused with either Cap 360 micromol/L (n = 6) or (L-a) 3mmol/L (n = 6), both captopril and L-arginine (Cap+L-a) (n = 8), or saline control (Con) (n = 8). The study design included 30 minutes of perfusion, 30 minutes of global ischemia, and 30 minutes of reperfusion thereafter. RESULTS: Hearts treated with both Cap+L-a demonstrated an improved performance in all parameters. After 10 minutes of reperfusion, the P(max) in the Cap+L-a group was 98 +/- 8 mmHg (P <.001), 59 +/- 14 mmHg in the Cap group (P <.02), and 44.3 +/- 10 mmHg in the L-a group (P = NS), compared with only 42 +/- 8 mmHg in the control. After 10 minutes of reperfusion the dP/dt(min) was: in the Cap+L-a group: -1,650 +/- 223 mmHg/s (P <. 006); in the Cap group: -1,051 +/- 302 mmHg/s (P <.03); in the L-a group: -870 +/- 131 mmHg/s (P = NS), compared with only -487 +/- 131 mmHg/s in the control. Coronary flow was significantly increased in all 3 groups: Cap+L-a group: 22.3 +/- 1.5 mL/min (P <.001); Cap group: 18 +/- 1.6 mL/min (P <.01); L-a group: 19.8 +/- 0.9 mL/min (P <.02), compared with 12.6 +/- 0.9 mL/min in the Con group. Total NO level was significantly increased in the Cap+L-a group: 13.4 +/- 2 micromol (P <.03) vs. 6.1 +/- 1 micromol for the L-a group. NO levels of both the Cap group and the Con group were beneath detectable values. CONCLUSION: Combined administration of captopril and L-arginine has a synergistic, protective effect on heart function and coronary flow that may be mediated by enhanced NO production.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Biotechnological production of plant-based insecticides.

The demand for natural and nonpersistent insecticides is increasing day by day. Plant cell cultures could be an alternative to conventional methods of production of insecticides from field-grown plants. In vitro cultured plant cells produce a wide array of insecticides as a part of their secondary metabolism. Their ability to synthesize key enzymes and the manipulation of these could lead to the enhanced production of many insecticides of industrial importance. The development of a high-yielding hairy root culture system for thiophenes, nicotine, and phytoecdysones is of considerable interest. In this article, the current literature on various factors that influence the growth, production, and secretion of six insecticidal compounds, namely, pyrethrins, azadirachtin, thiophenes, nicotine, rotenoids, and phytoecdysones which have been prospects for the scale-up of cell cultures, genetic engineering to obtain transgenic plants, and metabolically engineered plants for increased production of bio-molecules, has been discussed. Environmental safety clearance and the future prospects of application of biomolecules for plant-derived insecticides are presented.

Biotechnology↗
PubMed2000

Bronchoscopic photodynamic diagnosis and therapy for lung cancer.

Photodynamic diagnosis and therapy have exciting potential in lung cancer management. Fluorescence bronchoscopy enhances the detection of preinvasive lesions and early invasive carcinomas involving the central airways, whereas photodynamic therapy (PDT) provides an effective method for treating these lesions with preservation of lung tissue. However, the natural history of preinvasive lesions is poorly understood and so the value of treatment remains unclear. Although treatment for early invasive carcinomas'is not open to question, the possibility of undetected nodal disease means that PDT is unlikely to replace surgical resection in patients who are fit for thoracotomy. PDT also provides an effective method of palliating patients with advanced obstructing endobronchial tumors. Although it is considered superior to simple tumor debulking, its usefulness is limited by transient but potentially severe skin photosensitivity. There is therefore a need to develop new photosensitizing drugs with less severe side effects.

Bronchoscopy↗
PubMed2000

Mammography use among women as a function of age and patient involvement in decision-making.

OBJECTIVE: To assess the extent to which self-reported patient involvement in decision-making for initiation of mammography differs with age. DESIGN: Data from the 1992 National Health Interview Survey (NHIS) Cancer Control Supplement were evaluated. Prevalences were weighted and variances were adjusted using SUDAAN software to account for the complex, multistage sampling probability design of the NHIS. Logistic regression was used to evaluate the relative likelihood of self-reported involvement in the decision to have a mammogram within the preceding year as a function of age and other covariates. PARTICIPANTS: Mammography use was assessed among 3,863 NHIS female respondents 40 years of age or older. The analysis of decision-making was restricted to the subgroup of 1,064 women who reported a screening mammogram within the preceding year and who provided information on the other relevant variables. MEASUREMENTS AND MAIN RESULTS: The probability of reported mammography use within the preceding year declines among older groups of interviewees. Among women with a mammogram in the preceding year, the weighted percentage of women reporting active involvement in the decision (patient decision or decided jointly with a physician) declines from 51% among women 40 to 45 years of age to 19% among those aged 75 years or older. The adjusted odds ratio comparing the likelihood of participating in the decision to have a mammogram for the oldest women, compared with the youngest, was 0.31 (95% confidence interval 0.15 to 0.61). CONCLUSIONS: Older women are substantially less likely than younger women to report active involvement in the mammography decision-making process. Increased use of screening mammography among older women will require greater promotion by physicians. Other interventions, such as directed educational efforts, may also be needed to increase mammography demand among older women.

Adult↗
PubMed2000

Alphavirus RNA genome repair and evolution: molecular characterization of infectious sindbis virus isolates lacking a known conserved motif at the 3' end of the genome.

The 3' nontranslated region of the genomes of Sindbis virus (SIN) and other alphaviruses carries several repeat sequence elements (RSEs) as well as a 19-nucleotide (nt) conserved sequence element (3'CSE). The 3'CSE and the adjoining poly(A) tail of the SIN genome are thought to act as viral promoters for negative-sense RNA synthesis and genome replication. Eight different SIN isolates that carry altered 3'CSEs were studied in detail to evaluate the role of the 3'CSE in genome replication. The salient findings of this study as it applies to SIN infection of BHK cells are as follows: i) the classical 19-nt 3'CSE of the SIN genome is not essential for genome replication, long-term stability, or packaging; ii) compensatory amino acid or nucleotide changes within the SIN genomes are not required to counteract base changes in the 3' terminal motifs of the SIN genome; iii) the 5' 1-kb regions of all SIN genomes, regardless of the differences in 3' terminal motifs, do not undergo any base changes even after 18 passages; iv) although extensive addition of AU-rich motifs occurs in the SIN genomes carrying defective 3'CSE, these are not essential for genome viability or function; and v) the newly added AU-rich motifs are composed predominantly of RSEs. These findings are consistent with the idea that the 3' terminal AU-rich motifs of the SIN genomes do not bind directly to the viral polymerase and that cellular proteins with broad AU-rich binding specificity may mediate this interaction. In addition to the classical 3'CSE, other RNA motifs located elsewhere in the SIN genome must play a major role in template selection by the SIN RNA polymerase.

3' Untranslated Regions↗
PubMed2000

Overexpression of 15-lipoxygenase in vascular endothelium accelerates early atherosclerosis in LDL receptor-deficient mice.

To study the possible role of the human lipid-oxidizing enzyme 15-lipoxygenase (15-LO) in atherosclerosis, we overexpressed it specifically in the vascular wall of C57B6/SJL mice by using the murine preproendothelin-1 promoter. The mice overexpressing 15-LO were crossbred with low density lipoprotein (LDL) receptor-deficient mice to investigate atherogenesis. High levels of 15-LO were expressed in the atherosclerotic lesion in the double-transgenic mice as assessed by immunohistochemistry. The double-transgenic, 15-LO-overexpressing, LDL receptor-deficient mice (LDLR-/-/15LO) developed significantly larger atherosclerotic lesions at the aortic sinus compared with lesions in the LDL receptor-deficient (LDLR-/-) mice after 3 and 6 weeks (107,000 versus 28,000 microm(2) [P:<0.001] and 121,000 versus 87,000 microm(2) [P:<0.05], respectively) of an atherogenic diet. LDL from the LDLR-/-/15LO mice was more susceptible to oxidation than was the LDL from the control LDLR-/- mice, as shown by a shorter lag period for copper-induced conjugated diene formation. On the other hand, no differences were found in the levels of serum anti-oxidized LDL antibodies between the study groups. There were also no differences with respect to the density of macrophages and T lymphocytes infiltrating the lesions in both experimental groups. Taken together, these results support the hypothesis that 15-LO overexpression in the vessel wall is associated with enhanced atherogenesis.

Animals↗
PubMed2000

Autoimmunity in atherosclerosis: lessons from experimental models.

The modern view of atherosclerosis is of a chronic inflammatory disorder. In accord with this paradigm, the process of uninhibited influx of fat to the vessel wall results from an 'adequate' response to various forms of injury (i.e. turbulence, infections, modified lipoproteins). This idea has been further extended by several groups, to assume that the atherosclerotic lesion can be the target of an autoimmune mediated attack. According to this hypothesis, the site of initiation of the plaque should bear/express the target autoantigen, whereas concomitantly a respective immune response is generated in the periphery. The examples illuminating this notion are beta2GPI as a target autoantigen, HSP60/65 an oxidized-LDL. Herein we present evidence to support the involvement of autoimmune mechanisms in atherogenesis based on the experience from experimental models and human studies.

Animals↗