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Biomedical subjects

I George

Publications and source records attributed to I George.

At least 19 recordsLinked to original sources
PubMed2005

Sound processing in the auditory-cortex homologue of songbirds: functional organization and developmental issues.

Recent literature on the Field L of songbirds, showing that some neurons present a clear selectivity towards complex sounds, especially conspecific songs, is reviewed. Furthermore, studies on European starlings have revealed a complex functional organization in this central auditory area, with subareas exhibiting different response features. Interestingly, both the functional organization and the neuronal specialization can be drastically affected by early deprivation, clearly showing the existence of a developmental plasticity. Some recovery seems to remain possible at later stages, and social factors may be involved.

Acoustic Stimulation↗
PubMed2005

New insights into the auditory processing of communicative signals in the HVC of awake songbirds.

In the present study, using a systematic recording method and a variety of stimuli, we determined the proportion of responsive sites and their response features in the vocal control nucleus HVC of awake-restrained starlings, a species with multiple song types. Responsive sites were classified into three groups, according to the number of stimuli to which they responded. Sites in the three groups showed responses to individual-specific songs, with sites in the group that showed responses to only one stimulus responding mostly to a bird's own song. In comparison, very few sites exhibited responses to universal species-specific songs and to artificial nonspecific sounds. By contrast, data obtained in the same birds under urethane anesthesia show that, although the total proportion of responsive sites was similar, numerous responses to a universal species-specific song and to an artificial nonspecific pure tone could be observed.

Acoustic Stimulation↗
PubMed2004

Environmental genomics: exploring the unmined richness of microbes to degrade xenobiotics.

Increasing pollution of water and soils by xenobiotic compounds has led in the last few decades to an acute need for understanding the impact of toxic compounds on microbial populations, the catabolic degradation pathways of xenobiotics and the set-up and improvement of bioremediation processes. Recent advances in molecular techniques, including high-throughput approaches such as microarrays and metagenomics, have opened up new perspectives and pointed towards new opportunities in pollution abatement and environmental management. Compared with traditional molecular techniques dependent on the isolation of pure cultures in the laboratory, microarrays and metagenomics allow specific environmental questions to be answered by exploring and using the phenomenal resources of uncultivable and uncharacterized micro-organisms. This paper reviews the current potential of microarrays and metagenomics to investigate the genetic diversity of environmentally relevant micro-organisms and identify new functional genes involved in the catabolism of xenobiotics.

Bacteria↗
PubMed2002

Multicenter evaluation of a nonweekend reading schedule for radiometric pyrazinamide susceptibility testing of Mycobacterium tuberculosis.

Pyrazinamide (PZA) is an integral component of the short-course chemotherapy regimen for tuberculosis. The BACTEC 460TB PZA susceptibility test for Mycobacterium tuberculosis with a daily (D) reading schedule has been available for more than 10 years, but weekend laboratory staffing is necessary. A nonweekend (NW) reading schedule has not been validated in a multicenter study. This prospective multicenter study compares the interlaboratory reproducibility of PZA susceptibility results by following both the D and NW schedules. A total of 181 cultures were shared among four laboratories. Isolates were selected based on resistance or borderline resistance to at least one streptomycin-isoniazid-rifampin-ethambutol drug or PZA. One laboratory used a D reading schedule, and three laboratories used a NW schedule. Both reading schedules are based on the standard BACTEC 460TB PZA protocol. With the NW schedule, the growth index (GI) is not available for test interpretation on Saturday, Sunday, and Monday. Of the 181 shared cultures, 154 were found to be susceptible by all laboratories, 19 were found to be resistant, and 8 had discordant results. The overall pairwise interlaboratory agreement was 97.7%. The discrepancies were not associated with the type of reading schedule used. However, the median control GI was significantly higher for the NW schedule (321) than for the D schedule (259) (P < 0.0001) although results were available on average in about 7 days from setup for both schedules. These results show that the NW schedule is a suitable alternative for laboratories that do not read and interpret PZA susceptibility tests on weekends.

Antitubercular Agents↗
PubMed2002

Multicenter evaluation of ethambutol susceptibility testing of mycobacterium tuberculosis by agar proportion and radiometric methods.

Reproducibility of ethambutol (EMB) susceptibility test results for Mycobacterium tuberculosis has always been difficult for a variety of reasons, including the narrow range between the critical breakpoint for EMB resistance and the MIC for susceptible strains, borderline results obtained with the BACTEC 460TB method, the presence of microcolonies determined using the agar proportion (AP) method, and a lack of agreement between these two testing methods. To assess the frequency of these problems, M. tuberculosis drug susceptibility data were collected in a multicenter study involving four laboratories. Resistant, borderline, and susceptible isolates were shared among the laboratories to measure interlaboratory test agreement. Half of isolates determined by BACTEC 460TB to be resistant were determined to be susceptible by the AP method. Isolates determined to be resistant to EMB by both BACTEC 460TB and AP methods were almost always resistant to isoniazid. Results from isolates tested by the BACTEC 460TB method with an EMB concentration of 3.75 micro g/ml in addition to the standard 2.5 micro g/ml did not show improved agreement by the AP method. While these results do not indicate that the AP method is more accurate than the BACTEC 460TB method, laboratories should not report EMB monoresistance based on BACTEC 460TB results alone. Monoresistance to EMB should only be reported following confirmation by the AP method. Microcolonies could not be confirmed as resistant by the BACTEC 460TB method or by repeat testing with the AP method and do not appear to be indicative of resistance.

Agar↗
PubMed2002

Using semi-automated image processing and desktop systems to incorporate actual patient volumetric data in immersive surgical planning and viewing systems for multiple patients.

This paper describes how patient specific volumetric data are managed from image acquisition through final processing for the purposes of creating a 3D VR rendering of user selected and manipulated 3D models. The system described here allows for the development of quick, inexpensive, and clinician manipulated patient-specific models. The utility of this process is demonstrated by being able to move VRML models to desktop or immersive environments for both pre-operative planning and patient-specific surgical and anatomical training.

Computer Simulation↗
PubMed2001

Regulation of class II expression in monocytic cells after HIV-1 infection.

Human macrophage hybridoma cells were used to study HLA-DR expression after HIV-1 infection. HLA-DR surface expression was lost 2 wk after infection that was associated with decreased mRNA transcription. Transfecting HLA-DR-alpha and HLA-DR-beta cDNA driven by a nonphysiological CMV promoter restored expression, suggesting that regulatory DNA-binding proteins may be affected by HIV-1 infection. There was no protein binding to conserved class II DNA elements (W/Z/S box, X-1 and X-2 boxes, and Y box) in a HIV-1-infected human macrophage hybridoma cell line, 43(HIV), and in primary monocytes that lost HLA-DR expression after HIV-1(BaL) infection. PCR analysis of the HIV-1-infected cells that lost HLA-DR expression revealed mRNA for W/Z/S (RFX-5), X-1 (RFX-5), X-2 (hX-2BP), and one Y box DNA-binding protein (NF-YB), and CIITA, a non-DNA-binding protein necessary for class II transcription. There was no mRNA for the Y box-binding protein, NF-YA. However, HLA-DR expression could be restored by transfection with NF-YA driven by a CMV promoter, although HLA-DR failed to localize in either the late endosomes, lysosomes, or acidic compartments. This was associated with a loss of class II-associated invariant chain peptide and leupeptin-induced protein in the 43(HIV) cells. To address this further, non-HIV-1-infected 43 cells were infected with vaccinia virus containing HIV-1 gag, nef, pol, and env proteins. HLA-DR failed to localize in neither the late endosomes, lysosomes, or acidic compartments in the vaccinia-infected cells containing HIV-1 env protein. HIV-1 appears to have multiple effects on class II expression in monocytic cells that may contribute to the immune defects seen in HIV-1-infected patients.

Antigens, Differentiation, B-Lymphocyte↗
PubMed2001

Enhanced T cell apoptosis in common variable immunodeficiency: negative role of the fas/fasligand system and of the Bcl-2 family proteins and possible role of TNF-RS.

CVI is a primary immunodeficiency characterized by a failure of B cell differentiation associated with an array of T cell defects, such as enhanced T cell apoptosis. In this study we investigated the mechanisms underlying CVI enhanced T cell death. We analysed both the expression of Fas using flow cytometry techniques and the expression of FasL mRNA using RT-PCR in CVI T cells. We could not find any significant differences between CVI and normal subjects with regard to Fas expression, although there was a subgroup of CVI patients with very high Fas expression which was accompanied by an up-regulation of FasL mRNA. However, attempts to induce Fas-mediated apoptosis in these high Fas expressing cells, as evaluated by propidium iodide staining and APO2.7 staining, were unsuccessful. We also investigated intracellular levels of Bcl-2, bcl-xl and bax in CD4(+) and CD8(+) CVI T cells, as well as the bax/Bcl-2 ratio, using flow cytometry techniques but could not detect any differences between CVI and normal subjects. Finally we analysed TNF-RI and TNF-RII mRNA expression in CD4(+) and CD8(+) CVI T cells using semiquantitative RT-PCR and found a significant increase in expression of both TNF-Rs in CD4(+) T cells from CVI patients. Our data suggest that the increased expression of both TNF-Rs on T cells may be one of the mechanisms responsible for the accelerated T cell apoptosis in CVI.

Adolescent↗
PubMed2001

Use of rapid enzymatic assays to study the distribution of faecal coliforms in the Seine river (France).

In 1997 and 1998 faecal contamination of the Seine river and its estuary was studied for the first time by rapid enzymatic methods, based on the presence of the beta-D-glucuronidase enzyme in E. coli, in parallel with traditional plate counts of faecal coliforms on specific culture medium. Our study focused on a 450 km stretch of the river, including the Parisian area, and presenting highly variable levels of faecal pollution. Both methods showed that wastewater outfalls of the Parisian area and the presence of a maximum turbidity zone (at the mouth of the estuary) had a strong impact on the abundance of faecal coliforms in the river. Downstream from the Parisian outfalls, beta-D-glucuronidase activity measurements decreased 5-6x less rapidly than plate counts suggesting that rapid enzymatic assays could detect enzymatically-active but non-culturable bacteria.

Biological Assay↗
PubMed2001

Use of beta-D-galactosidase and beta-D-glucuronidase activities for quantitative detection of total and fecal coliforms in wastewater.

Two enzymatic methods based on the measurement of the beta-D-galactosidase activity of total coliforms and the beta-D-glucuronidase activity of Escherichia coli were used to assess coliform levels in wastewater alongside traditional culture-based techniques, which can be biased by the aggregation of bacteria or their attachment to particles. Enzymatic methods were precise (i.e., coefficients of variation were 9%-15%), rapid (response in 20 min), and correlated well (in log units) with traditional techniques for raw and treated sewage (r2 > 0.75). They were used for rapid assessment of coliform removal efficiency in two different wastewater treatments. These methods could be useful for the estimation of the abundance of coliforms in domestic sewage and their removal by wastewater treatment processes.

Bacteriological Techniques↗
PubMed2000

Enhanced apoptosis of T cells in common variable immunodeficiency (CVID): role of defective CD28 co-stimulation.

CVID is a primary immune disorder in which hypogammaglobulinaemia may be associated with a number of T cell defects including lymphopenia, anergy, impaired lymphocyte proliferation and deficient cytokine secretion. In this study we show that T cells of CVID subjects, in comparison with control T cells, undergo spontaneous apoptosis in culture and markedly accelerated apoptosis after gamma-irradiation. Although costimulation of the CD28 receptor following engagement of the TCR/CD3 receptor normally provides a second signal necessary for IL-2 secretion, CD28 costimulation in CVID does not significantly increase IL-2 production, nor does this combination of activators enhance the survival of irradiated CVID T cells, as it does for cultured normal T cells. Addition of IL-2 enhances CVID T cell survival, suggesting that the IL-2 signalling pathways are normal. CVID T cells have similar expression of Bcl-2 to control T cells. CD3 stimulation up-regulates T cell expression of bcl-xL mRNA for normal T cells, but anti-CD28 does not augment bcl-xL expression for CVID subjects with accelerated apoptosis. Defects of the CD28 receptor pathway, leading to cytokine deprivation and dysregulation of bcl-xL, could lead to poor T cell viability and some of the cellular defects observed in CVID.

Adolescent↗
PubMed2000

Use of enzymatic methods for rapid enumeration of coliforms in freshwaters.

Rapid enumeration methods based on the enzymatic hydrolysis of 4-methylumbelliferyl-beta-D-galactoside and 4-methylumbelliferyl-beta-D-glucuronide were optimized for freshwaters. The enzymes beta-D-galactosidase (GALase) and beta-D-glucuronidase (GLUase) were shown to be already induced in freshwaters when tested, respectively, with the inducers isopropyl-beta-D-thiogalactopyranoside and methyl-beta-D-glucuronide. Both enzymatic activities were compared, respectively, with plate counts of total and faecal coliforms in freshwaters. Enzymatic methods and reference plate counts were significantly correlated in log-log plots. Moreover, the GLUase method allowed the detection of viable (presenting a detectable GLUase activity) but nonculturable Escherichia coli.

Bacteriological Techniques↗
PubMed2000

ETA receptor blockade induces fibrosis of the clipped kidney in two-kidney-one-clip renovascular hypertensive rats.

BACKGROUND: In two kidney-one clip renovascular hypertension (2K1C), blood flow is reduced in the clipped kidney leading to ischaemia. The non-clipped kidney is characterized by increased shear stress. Circulating Ang II is elevated. All these factors are stimuli of the paracrine renal endothelin system. Indeed, we demonstrated an activation of the renal endothelin system in the 2K1C rat model. METHODS: We analysed the effects of chronic treatment with the ETA receptor antagonist BQ-123 on blood pressure, heart rate, plasma renin activity, and on the progression of glomerulosclerosis, interstitial fibrosis and vascular remodeling in the clipped and non-clipped kidney. RESULTS: Long-term treatment with BQ-123 led to a fibrotic atrophy of the clipped kidney characterized by a significantly reduced weight of the clipped kidney compared to the clipped kidney of the placebo-treated group. Computer-aided image analysis revealed a markedly enhanced interstitial fibrosis of these clipped kidneys after long-term ETA blockade. The effects of ETA receptor antagonists on the non-clipped kidney were less pronounced. Neither blood pressure nor plasma renin activity were significantly altered by BQ-123 treatment. CONCLUSIONS: The present study indicates that long-term blockade of the activated endothelin system in the clipped kidney of rats with renovascular hypertension using an ETA receptor antagonist led to a fibrotic atrophy of the clipped kidney.

Animals↗
PubMed2000

Survival of Escherichia coli in freshwater: beta-D-glucuronidase activity measurements and characterization of cellular states.

A rapid enzyme assay measuring beta-D-glucuronidase activity of Escherichia coli was tested in survival experiments after discharge of E. coli in river water. Enzyme activity was compared with several analyses performed to characterize cellular states under stressful conditions. Enzyme activity remained stable under starvation and light stress conditions despite losses of culturability, respiratory activity, and cytoplasmic membrane integrity. beta-D-Glucuronidase activity followed the pattern of genetic and morphologic cell integrity. The tested enzyme assay seems well adapted to study the fate of fecal coliforms in survival experiments, and appears to be a rapid and efficient way to estimate the microbiological quality of surface waters.

Bacteriological Techniques↗
PubMed1999

Endothelin system-dependent cardiac remodeling in renovascular hypertension.

The aim of the present study was to analyze whether the cardiac endothelin system contributes to cardiac remodeling in rats with 2-kidney, 1 clip (2K1C) renovascular hypertension. The endothelin system seems to be a promising candidate for cardiac remodeling because endothelin (ET)-1 promotes growth of cardiomyocytes in vitro and induces cardiac collagen synthesis. The activity of the cardiac endothelin system was analyzed by measuring cardiac tissue big ET-1 and ET-1 concentrations as well as by estimating the cardiac expression of the ETA and ETB receptors 10 days, 4 weeks, and 12 weeks after the renal artery was clipped. The effects of long-term treatment with ETA, ETB, and combined ETA/ETB receptor antagonists on cardiac hypertrophy, media/lumen ratio of intracardiac arteries, and left ventricular fibrosis were also analyzed. This study demonstrated that the overall left ventricular cardiac endothelin system has a similar activity in the early, middle, and late stages of 2K1C renovascular hypertension compared with sham-operated controls. Fibrosis of the left ventricle and hypertrophy of intracardiac arteries, however, were markedly altered after long-term treatment with endothelin receptor antagonists in a blood pressure-independent manner. These 2 effects are mediated by different subtypes of endothelin receptors. ETA receptor blockade completely normalized the hypertrophy of intracardiac arteries (P<0. 01 compared with 2K1C without treatment) in renovascular hypertension, whereas the ETB antagonist reduced cardiac fibrosis of the left ventricle (P<0.001 compared with 2K1C without treatment) to baseline values. This study demonstrates that the cardiac endothelin system plays an important role in the development of cardiac fibrosis as well as in hypertrophy of intracardiac arteries in 2K1C renovascular hypertensive rats.

Animals↗
PubMed1999

Antigen trafficking and accessory cell function in respiratory epithelial cells.

We investigated accessory cell function, antigen (Ag) trafficking, and uptake of immune complexes in isolated nasal epithelial cells (NEC) and airway epithelial cells (AEC), as well as in the two respiratory epithelial cell lines A549 and BEAS-2B. The NEC and AEC were capable of supporting Ag-specific as well as phytohemagglutinin-induced and anti-CD3 antibody-induced T-cell proliferation. We colocalized fluorescein isothiocyanate (FITC)-labeled Ags with human leukocyte antigen (HLA)-DR in A549 and BEAS-2B, utilizing laser confocal microscopy. Respiratory epithelial cells stimulated and unstimulated with interferon (IFN)-gamma were pulsed with FITC-labeled Ags for varying periods and evaluated for their ability to internalize Ag. In the unstimulated cells, intracellular punctate staining was evident at 60 min and persisted up to 120 min. In the IFN-gamma-stimulated cells (100 U/ml for 48 h), uptake occurred at 30 min, was maximal at 60 min, and diminished at 120 min. We conducted kinetic studies in the A549 and BEAS-2B cells, utilizing electron microscopy with colloidal gold-conjugated Ags (Au-OVA). At 15 min, Au-OVA was evident in the early compartments resembling the compartment of uncoupling of receptor and ligand. At 30 min, multivesicular bodies were labeled with Au-OVA, and by 60 min Au-OVA was present in the primary and secondary lysosomes. The FITC-labeled Ags colocalized with an early endosomal marker (anti-cathepsin D), a late endosomal marker (M6PR), a lysosomal marker (CD63), and with 3-(2, 4-dinitroanilino)-3'-aminomethyldipropylamine, a marker of acidic vesicles. The BEAS-2B and A549 cells, and NEC and AEC, expressed surface Fcgamma receptor and internalized IgG immune complexes. The NEC and AEC also expressed the costimulatory molecules CD80 and CD86 as determined with flow cytometry, the reverse transcription-polymerase chain reaction for RNA, and immunohistochemistry, and T-cell proliferation could be blocked by treating NEC and AEC with anti-CD80 and anti-CD86 antibodies. Our findings suggest that respiratory epithelial cells may have a role in local Ag presentation.

Antigen-Antibody Complex↗
PubMed1998

Chronically HIV-1-infected monocytic cells induce apoptosis in cocultured T cells.

We have previously developed a human macrophage hybridoma model system to study the effect of HIV-1 infection on monocytic function. Upon coculture of one chronically (35 days postinfection) HIV-1-infected human macrophage hybridoma cell line, 43HIV, there was a dose-dependent decrease in the viability of cocultured Ag-stimulated T cells associated with an increase in DNA strand breaks. Enhanced apoptosis was determined by labeling with biotinylated dUTP and propidium iodide, increased staining with annexin V, increased side light scatter and expression of CD95, and decreased forward light scatter and expression of Bcl-2. There was also increased DNA strand breaks as determined by propidium iodide staining in unstimulated T cells cocultured with 43HIV and in T cells stimulated with anti-CD3 mAb and PHA. Pretreatment with 5145, a human polyclonal anti-gp120 Ab that recognizes the CD4 binding region, as well as with an anti-Fas ligand mAb blocked apoptosis in CD4+ T cells but not in CD8+ T cells. A soluble factor with a Mr below 10,000 Da was defined that induced apoptosis in CD4+ and CD8+ T cells and B cells. SDS-PAGE analysis of the active fractions revealed a band of 6000 Da that, after electroelution, had proapoptotic activity. The pI of the activity was estimated to be between 6.5 and 7.0. In conclusion, chronically HIV-1-infected monocytic cells induce apoptosis in bystander-, Ag-, anti-CD3-, and mitogen-stimulated T cells by multiple factors, which may contribute to the depletion of lymphocytes induced by HIV-1.

Apoptosis↗