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Biomedical subjects

E Gilbert

Publications and source records attributed to E Gilbert.

At least 19 recordsLinked to original sources
PubMed2006

Characterization and source assessment of heavy metals and polycyclic aromatic hydrocarbons (PAHs) in sediments of the Fosu Lagoon, Ghana.

The first results ever obtained on polycyclic aromatic hydrocarbon (PAHs) concentrations in the Fosu lagoon surface sediments are presented together with corresponding heavy metal (Fe, Mn, Cd, Zn and Ni) concentrations. Samples collected on a monthly basis from November 2003-April 2004 (Heavy metals) and December 2003-January 2004 (PAHs) at 8 locations, representing different anthropogenic sources of contamination to the lagoon, were analyzed. Concentrations of Cd and Ni in the lagoon sediment suggest greater contamination to the lagoon from industrial activities in the vicinity of the lagoon; 50% of the sediment samples exceeded some established sediment Cd guidelines for the protection of aquatic lives. Then, 15 PAHs were detected among the sediments from the different locations and the compositional pattern in decreasing order was 3-ring > 5-ring > 4-ring > 6-ring > 2-ring PAH compounds. Sigma PAH concentrations in the sediment samples ranged from 254 to 558 mg/kg, with a mean of 359.4 mg/kg. Two distinct areas were identified to be a major source of anthropogenic load of both heavy metals and PAH; the mechanical shop in the northeastern sector of the lagoon is the main location for the input of Cd and it's associated PAH compounds (e.g., acenapthylene, acenaphthene, naphthalene and benzo[a]fluoranthene) and to a lesser extent Ni. Both combustion and petroleum sources may account for PAH loads from this area. The residential area in the northern sector is responsible for high loads of Mn and its associated PAH compounds (e.g., phenanthrene, benzo[a]pyrene and anthracene). These chemicals seem to enter the lagoon mainly by the combustion of especially wood or coal.

Environmental Monitoring↗
PubMed2005

Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries.

OBJECTIVES: To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. DESIGN: Multinational retrospective cohort study of cancer mortality. SETTING: Cohorts of workers in the nuclear industry in 15 countries. PARTICIPANTS: 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. MAIN OUTCOME MEASUREMENTS: Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. RESULTS: The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv (< 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. CONCLUSIONS: These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.

Dose-Response Relationship, Drug↗
PubMed2004

Implementation of evidence based guidelines for paediatric asthma management in a teaching hospital.

AIMS: To evaluate a systematic approach to the development and implementation of evidence based asthma management guidelines. METHODS: Comparative study of children (2-18 years) with acute asthma; a control cohort (cohort 1) was recruited before implementation of the guidelines and two cohorts were recruited after implementation (cohorts 2 and 3). RESULTS: There was no difference in the proportion of patients who reattended in the six months following initial presentation for cohort 1 (21.5%), cohort 2 (27.8%), or cohort 3 (25.4%) and no difference in readmission rates (11.4%, 11.3%, 11.0% respectively). There was no difference in measures of asthma morbidity between the cohorts at 3 and 6 months across three domains: interval symptoms, exercise limitation, and bronchodilator use. Of those who did not have a management plan before presentation, one was provided to 46.9% of cohort 1, 74.8% of cohort 2, and 81.1% of cohort 3. There was no difference comparing cohort 2 or cohort 3 with cohort 1 regarding quality of life for either the subjects or their parents. CONCLUSIONS: Implementation of our evidence based guidelines was associated with the improved provision of asthma management plans, but there was no effect on reattendance or readmission to hospital, asthma morbidity, or quality of life. Future efforts to improve asthma management should target specific components of asthma care.

Acute Disease↗
PubMed2002

Influence of particles on sonochemical reactions in aqueous solutions.

Numerous publications deal with the possible application of ultrasound for elimination of organic pollutants as a tool for water pollution abatement. Most of the experiments were performed in pure water under laboratory conditions. For developing technologies that hold promise it is necessary to investigate the effect of ultrasound in natural systems or waste water where particulate matter could play an important role. In this paper the influence of quartz particles (2-25 microm) on the chemical effects of ultrasound in aqueous system using a high power ultrasound generator (68-1028 kHz, 100 W, reactor volume 500 ml) is reported. In pure water in dependence on particle size, concentration and frequency the formation rate of hydrogen peroxide under Ar/O2 (4:1) shows a maximum using 206 kHz in presence of 3-5 microm quartz particles (4-8 g/l). Under these conditions the yield of peroxide is higher than without quartz. Additionally under N2/O2 (4:1) besides hydrogen peroxide the formation of nitrite/nitrate was measured. Compared to pure water quartz particle depressed the formation of nitrite/nitrate up to 10-fold but not the formation of H2O2. According to the results of H2O2 formation the elimination of organic compounds by sonolysis (206 kHz) and the influence of quartz particles were investigated. As organic compounds salicylic acid, 2-chlorobenzoic acid and p-toluenesulfonic acid were used. The influence of quartz on the oxidation of organic compounds (206 kHz) is similar to that on the formation of H2O2.

Journal Article↗
PubMed2001

Analysis of the CD151-alpha3beta1 integrin and CD151-tetraspanin interactions by mutagenesis.

Transmembrane proteins of the tetraspanin superfamily are associated with various integrins and modulate their function. We performed mutagenesis analysis to establish structural requirements for the interaction of CD151 with the alpha3beta1 integrin and with other tetraspanins. Using a panel of CD151/CD9 chimeras and CD151 deletion mutants we show that the minimal region, which confers stable (e.g. Triton X-100-resistant) association of the tetraspanin with alpha3beta1, maps within the large extracellular loop (LECL) of CD151 (the amino acid sequence between residues Leu(149) and Glu(213)). Furthermore, the substitution of 11 amino acids (residues 195-205) from this region for a corresponding sequence from CD9 LECL or point mutations of cysteines in the conserved CCG and PXXCC motifs abolish the interaction. The removal of the LECL CD151 does not affect the association of the protein with other tetraspanins (e.g. CD9, CD81, CD63, and wild-type CD151). On the other hand, the mutation of the CCG motif selectively prevents the homotypic CD151-CD151 interaction but does not influence the association of the mutagenized CD151 with other tetraspanins. These results demonstrate the differences in structural requirements for the heterotypic and homotypic tetraspanin-tetraspanin interactions. Various deletions involving the small extracellular loop and the first three transmembrane domains prevent surface expression of the CD151 mutants but do not affect the CD151-alpha3beta1 interaction. The CD151 deletion mutants are accumulated in the endoplasmic reticulum and redirected to the lysosomes. The assembly of the CD151-alpha3beta1 complex occurs early during the integrin biosynthesis and precedes the interaction of CD151 with other tetraspanins. Collectively, these data show that the incorporation of CD151 into the "tetraspanin web" can be controlled at various levels by different regions of the protein.

Animals↗
PubMed2001

Lethal hepatitis after gene transfer of IL-4 in the liver is independent of immune responses and dependent on apoptosis of hepatocytes: a rodent model of IL-4-induced hepatitis.

The putative role of IL-4 in human and animal models of hepatitis has not yet been directly determined. We now report that direct expression of IL-4 in the liver of rats or mice using recombinant adenoviruses coding for rat or mouse IL-4 (AdrIL-4 and AdmIL-4, respectively) results in a lethal, dose-dependent hepatitis. The hepatitis induced by IL-4 was characterized by hepatocyte apoptosis and a massive monocyte/macrophage infiltrate. IL-4-induced hepatitis was independent of T cell-mediated immune responses. Hepatitis occurred even after gene transfer of IL-4 into nude rats, CD8-depleted rats, cyclosporine A-treated rats, or recombinase-activating gene 2(-/-) immunodeficient mice. Peripheral depletion of leukocytes using high doses of cyclophosphamide, and/or the specific depletion of liver macrophages with liposome-encapsulated dichloromethylene diphosphonate in rats did not block lethal IL-4-induced hepatitis. Direct transduction of hepatocytes with adenoviruses was not essential, since injection of AdrIL-4 into the hind limb induced an identical hepatitis. Finally, primary rat hepatocytes in culture also showed apoptosis when cultured in the presence of rIL-4. IL-4-dependent hepatitis was associated with increases in the intrahepatic levels of IFN-gamma, TNF-alpha, and Fas ligand. Administration of AdmIL-4 to IFN-gamma, TNF-alpha receptor type I, or TNF-alpha receptor type II knockout mice also resulted in lethal hepatitis, whereas a moderate protection was observed in Fas-deficient lpr mice. IL-4-dependent hepatocyte apoptosis could be abolished by treatment with caspase inhibitory peptides. Our results thus demonstrate that IL-4 causes hepatocyte apoptosis, which is only partially dependent on the activation of Apo-1-Fas signaling and is largely independent of any immune cells in the liver.

Acute Disease↗
PubMed2001

A multiplex real-time pcr assay for the detection of gene fusions observed in solid tumors.

SUMMARY: Specific gene fusions observed in solid tumors are extremely useful diagnostic markers. We report the development of a method based on real-time PCR which enables the detection upon identical PCR conditions of the different fusions specifically observed in Ewing tumors (ET), alveolar rhabdomyosarcoma (ARMS), synovial sarcoma (SS), small round cell desmoplastic tumors (SRCDT), extraskeletal myxoid chondrosarcoma, malignant melanoma of soft parts, congenital fibrosarcoma, and anaplastic large cell lymphoma. A simple assay, based on multiplexing of primers and probes, is described for the routine genetic diagnosis of small round cell tumors of children. It enables the detection of the five EWS-ETS, the two PAX-FKHR, the three SYT-SSX, and the EWS-WT1 fusions of ET, ARMS, SS, and SRCDT, respectively. The sensitivity of this test is high enough to detect all fusions, including the large EWS-FLI-1 transcripts, with the equivalent of 100 tumor cells as a starting material. This multiplex fluorescent analysis of chromosome translocations (MFACT) was validated in comparison with conventional RT-PCR on a series of 79 tumors. A major advantage of this method is that it completely abolishes the manipulation of PCR-products. It, therefore, considerably lowers the risk of cross-contamination linked to carry-over of RT-PCR products. It also constitutes an important step toward the complete automation of the detection of cancer-specific gene fusions.

Artificial Gene Fusion↗
PubMed2001

B-cell function in chronic heart failure: antibody response to pneumococcal vaccine.

BACKGROUND: Several immune system abnormalities have been noted in patients with chronic heart failure (CHF) including autoantibody production and abnormalities in tumor necrosis factor, interleukin 2, interleukin 6, natural killer cells, helper/inducer lymphocytes, lymphocyte reactivity, and subtherapeutic responses to the influenza vaccination. Patients with CHF have a higher risk of nosocomial infections, mainly pulmonary. Immune function abnormalities in patients with CHF raise concern over the ability of patients with symptomatic CHF to mount an effective and protective B-cell response. METHODS AND RESULTS: B-cell function was assessed by measuring antibody production in response to pneumococcal vaccination. Antibody levels were increased markedly for all serotypes tested (P <or= .001), and all patients had an increase in the number of serotypes for which they had protective antibody levels from a mean of 7.9 to 10.5 of 12 serotypes tested (P <or= .001). These responses are consistent with normal responses to vaccination. CONCLUSIONS: Despite evidence of multiple immune system abnormalities, patients with CHF seem to have an intact B-cell function and the etiology of CHF does not affect antibody response. The normal response to vaccination confirms the potential utility of the vaccination.

Adult↗
PubMed2001

Acoustic neuroma surgery outcomes.

OBJECTIVE: The outcomes of surgery for acoustic neuromas have improved dramatically since the development of modern surgical techniques, the operating microscope, magnetic resonance imaging (MRI), and cranial nerve monitoring. The goals of acoustic neuroma surgery are now preservation of facial nerve function and, when feasible, hearing preservation. Many large series do not report standardized hearing and facial function grading, and they include patients who did not benefit from the most modern techniques. The purpose of this study was to present the results of acoustic neuroma surgery using the most modern techniques and equipment, using standardized grading systems. STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: 97 patients who underwent surgical removal of acoustic neuromas from 1992 to 1998. INTERVENTION: All patients underwent acoustic neuroma surgery and had preoperative audiograms and MRI with contrast. In addition, all patients had preoperative and postoperative facial function graded by the House-Brackmann scale and intraoperative facial nerve monitoring. Hearing preservation was attempted in patients with tumors of any size who had preoperative function of grade A or B according to the Committee on Hearing and Equilibrium guidelines for reporting results of acoustic neuroma surgery. MAIN OUTCOME MEASURES: Hearing preservation was considered successful if the patient retained serviceable hearing grade A or B. House-Brackmann grade 1 or 2 was considered excellent facial function. Complications were recorded. RESULTS: Facial nerve integrity was preserved in 96 of 97 patients (99%). Eight of 8 (100%) patients with intracanalicular tumors had excellent facial nerve function (HB 1-2). Fifty-two of 55 (95%) of patients with small tumors had excellent facial nerve function, and 15 of 24 (63%) with medium tumors had HB grade 1-2. Hearing was preserved in 29% of patients with tumors under 2 cm. The overall complication rate was 20%; cerebrospinal fluid leak was the most common. CONCLUSION: These results show that with modern imaging and surgical techniques, acoustic neuroma surgery is extremely safe and outcomes are very good. Surgery remains the treatment of choice for most tumors until alternative therapies, such as gamma knife, use uniform grading scales and show long-term facial and hearing results.

Adult↗
PubMed2000

Treatment-associated leukemia following testicular cancer.

BACKGROUND: Men with testicular cancer are at an increased risk of leukemia, but the relationship to prior treatments is not well characterized. The purpose of our study was to describe the risk of leukemia following radiotherapy and chemotherapy for testicular cancer. METHODS: Within a population-based cohort of 18 567 patients diagnosed with testicular cancer (from 1970 through 1993), a case-control study of leukemia was undertaken. Radiation dose to active bone marrow and type and cumulative amount of cytotoxic drugs were compared between 36 men who developed leukemia and 106 matched control patients without leukemia. Conditional logistic regression was used to estimate the relative risk of leukemia associated with specific treatments. All P values are two-sided. RESULTS: Radiotherapy (mean dose to active bone marrow, 12.6 Gy) without chemotherapy was associated with a threefold elevated risk of leukemia. Risk increased with increasing dose of radiation to active bone marrow (P for trend =.02), with patients receiving radiotherapy to the chest as well as to the abdominal/pelvic fields accounting for much of the risk at higher doses. Radiation dose to active bone marrow and the cumulative dose of cisplatin (P for trend =.001) were both predictive of excess leukemia risk in a model adjusted for all treatment variables. The estimated relative risk of leukemia at a cumulative dose of 650 mg cisplatin, which is commonly administered in current testicular cancer treatment regimens, was 3.2 (95% confidence interval = 1.5-8.4); larger doses (1000 mg) were linked with statistically significant sixfold increased risks. CONCLUSIONS: Past treatments for testicular cancer are associated with an increased risk of leukemia, with evidence for dose-response relationships for both radiotherapy and cisplatin-based chemotherapy. Statistically nonsignificant excesses are estimated for current radiotherapy regimens limited to the abdomen and pelvis: Among 10 000 patients given a treatment dose of 25 Gy and followed for 15 years, an excess of nine leukemias is predicted; cisplatin-based chemotherapy (dose, 650 mg) might result in 16 cases of leukemia. The survival advantage provided by current radiotherapy and chemotherapy regimens for testicular cancer far exceeds the small absolute risk of leukemia.

Adult↗
PubMed2000

Foamy cells with oligodendroglial phenotype in childhood ataxia with diffuse central nervous system hypomyelination syndrome.

Childhood ataxia with diffuse central nervous system hypomyelination syndrome (CACH) is a recently described leukodystrophy of unknown etiology. To characterize the neuropathological features and gain insight as to the pathogenesis of this disorder, we studied cerebral tissue from six patients with the CACH syndrome. Evaluation of toluidine blue-stained, semithin sections of white matter from CACH patients disclosed unusual cells with "foamy" cytoplasm, small round nuclei and fine chromatin. Electron microscopy (EM) revealed cells in the white matter with abundant cytoplasm containing many mitochondria and loosely clustered, membranous structures, but lacking the lysosomal structures seen in macrophages. Further analysis of tissue sections with antibodies and special stains demonstrated that the abnormal cells with abundant cytoplasm labeled with oligodendroglial markers, but did not react with macrophage or astrocytic markers. Double immunolabeling with macrophage and oligodendroglial markers clearly distinguished macrophages from the "foamy" oligodendroglial cells (FODCs). Proteolipid protein (PLP) mRNA in situ hybridization demonstrated PLP mRNA transcripts in a high proportion of oligodendrocytes in CACH patients compared to control patients, and PLP mRNA transcript signal in cells, morphologically consistent with FODCs. Normal and pathological brain control tissues did not contain FODCs. These neuropathological findings will be useful pathological identifiers of CACH, and may provide clues to the pathogenesis of this disorder.

Ataxia↗
PubMed2000

Dual labeling with green fluorescent proteins for confocal microscopy.

We report a dual labeling technique involving two green fluorescent protein (GFP) variants that is compatible with confocal microscopy. Two lasers were used to obtain images of (i) mixed cultures of cells, where one species contained GFPuv and another species contained GFPmut2 or GFPmut3, and (ii) a single species containing both GFPuv and GFPmut2 in the same cell. This method shows promise for monitoring gene expression and as a nondestructive and in situ technique for confocal microscopy of multispecies biofilms.

Biofilms↗
PubMed2000

Commensal interactions in a dual-species biofilm exposed to mixed organic compounds.

There is limited knowledge of interspecies interactions in biofilm communities. In this study, Pseudomonas sp. strain GJ1, a 2-chloroethanol (2-CE)-degrading organism, and Pseudomonas putida DMP1, a p-cresol-degrading organism, produced distinct biofilms in response to model mixed waste streams composed of 2-CE and various p-cresol concentrations. The two organisms maintained a commensal relationship, with DMP1 mitigating the inhibitory effects of p-cresol on GJ1. A triple-labeling technique compatible with confocal microscopy was used to investigate the influence of toxicant concentrations on biofilm morphology, species distribution, and exopolysaccharide production. Single-species biofilms of GJ1 shifted from loosely associated cell clusters connected by exopolysaccharide to densely packed structures as the p-cresol concentrations increased, and biofilm formation was severely inhibited at high p-cresol concentrations. In contrast, GJ1 was abundant when associated with DMP1 in a dual-species biofilm at all p-cresol concentrations, although at high p-cresol concentrations it was present only in regions of the biofilm where it was surrounded by DMP1. Evidence in support of a commensal relationship between DMP1 and GJ1 was obtained by comparing GJ1-DMP1 biofilms with dual-species biofilms containing GJ1 and Escherichia coli ATCC 33456, an adhesive strain that does not mineralize p-cresol. Additionally, the data indicated that only tower-like cell structures in the GJ1-DMP1 biofilm produced exopolysaccharide, in contrast to the uniform distribution of EPS in the single-species GJ1 biofilm.

Biofilms↗
PubMed2000

Detection of chromosome imbalances in retinoblastoma by parallel karyotype and CGH analyses.

We have studied a series of 20 primary retinoblastomas by karyotypic analysis and comparative genomic hybridization (CGH), to perform an exhaustive evaluation of chromosome imbalances in this tumor. In addition, 4 tumors were studied by CGH only. On the whole, CGH results were largely in agreement with those of karyotypic analysis and with known cytogenetic data. The most frequent imbalances were +6p (13/24 cases), +1q (12/24), -16/-16q (11/24), and +2p (9/24). Recurrent high-level amplifications were observed in 2p23-25 and 1q21. Amplification of 2p23-25, present in 4 cases among which 3 showed double-minute chromosomes, was related to MYCN amplification, as demonstrated by FISH and PCR. No evident correlation was found in this small series between any of the imbalances identified and either the differentiation or the histoprognostic risk.

Adolescent↗
PubMed1999

Paradoxical inhibition of c-myc-induced carcinogenesis by Bcl-2 in transgenic mice.

Here, we investigated changes in apoptosis during tumor progression by analyzing the effect of coexpressing various antiapoptotic genes on the multistage process of c-myc-induced hepatocarcinogenesis in transgenic mice. Whereas continuous c-myc gene overexpression in the liver led to cellular hepatocarcinoma, the coexpression of the bcl-2 gene inhibited the emergence of liver tumors, by inhibiting a pretumoral phase characterized by increased proliferation and apoptosis. This antioncogenic effect was specific to Bcl-2 and was not shared by other antiapoptotic genes such as bcl-xL and a dominant negative form of p53. Thus, we have shown that Bcl-2 can have a tumor suppressor effect in vivo on c-myc-induced hepatocarcinogenesis during the emergence of neoplastic foci.

Animals↗
PubMed1998

Fas ligand, tumor necrosis factor-alpha expression, and apoptosis during allograft rejection and tolerance.

BACKGROUND: Cytotoxic T cells can induce target cell lysis and apoptosis by different pathways. The interactions of CD95 antigen (Fas) with its ligand (CD95L) and of tumor necrosis factor (TNF)-alpha with its receptor (TNF-R1) lead to apoptotic cell death. Recently, conflicting studies have been published concerning the expression and the role of CD95L in allograft rejection and tolerance. METHODS: In this study, the intragraft expression of CD95/CD95L and TNF-alpha and the frequency and distribution of apoptotic cells were compared in a model of heterotopic cardiac allograft in the rat in which recipients were either not treated (acute rejection) or pretreated with donor-specific blood transfusion (tolerant). RESULTS: In the acutely rejected allografts, a peak in the expression of CD95L and TNF-alpha and in the number of apoptotic cells was observed during the first week after transplantation; apoptotic cells were confined to graft-infiltrating cells. In the tolerated allografts, however, levels of graft-infiltrating cell apoptosis and CD95L and TNF-alpha expression during the same period of time were dramatically lower. The expression of Fas was constitutive and was not modulated during acute rejection or tolerance. CONCLUSION: This down-regulation of CD95L and TNF-alpha in allografts rendered tolerant by donor-specific transfusion suggests a role for apoptosis-inducing pathways in acute allograft rejection.

Acute Disease↗