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Biomedical subjects

C Gimenez

Publications and source records attributed to C Gimenez.

At least 19 recordsLinked to original sources

[Acute pulmonary toxicity due to gemcitabine: a role for asbestos exposure?].

INTRODUCTION: Gemcitabine is an important drug in the treatment of non-small cell lung cancer. Myelosuppression is the most common toxic effect but its use sometimes leads to severe pulmonary toxicity by means of diffuse alveolar damage or sub-acute interstitial pneumonitis. METHODS: A retrospective study was made of all the patients treated in our department with this drug, alone or in combination. Episodes of acute dyspnoea during the course of chemotherapy were identified, and data were collected concerning the past history, the illness and the treatment in patients who had developed a respiratory failure attributable to gemcitabine. RESULTS: 312 patients had been treated with gemcitabine over a 5 year period and 18 had developed episodes of acute dyspnoea, of which 6 (1.9%) were attributed to the drug itself. Of these patients 4 had notifiable industrial disease (no. 30bis) secondary to asbestos exposure (odds ratio=85, 95% confidence interval 13-546) and 5 were active smokers. The possible role of intracellular ATP pool depletion secondary to asbestos exposure or smoking as a predisposing factor in the development of gemcitabine pulmonary toxicity is discussed. CONCLUSION: Smoking and asbestos exposure should be taken into account in future studies of gemcitabine pulmonary toxicity.

Acute Disease↗

[Tolerance of fiberoptic bronchoscopy by self-administered questionnaire: in the words of the patients].

INTRODUCTION: Fibreoptic bronchoscopy is currently undertaken by the majority of respiratory physicians, but under varying conditions. Though complications are rare the tolerance of this examination is sometimes poor, particularly when it is performed under local anaesthesia. The undesirable effects may reduce the value of the examination as well as causing discomfort for the patient. METHODS: A prospective study of the tolerance of the endoscopic examination was made on 100 consecutive patients by self-administered questionnaire. RESULTS: There were no major and 7 minor complications (7%). 45% of the patients were anxious but the experience of the operator tended to reassure them (p=0.07). 30% of the patients reported some pain, which tended to be exacerbated by anxiety (44% vs 18%, p=0.008) and the supine position (57% vs 43%, p=0.047). 37% of patients reported nausea, and 50% dyspnoea, without any significant predictive factor. 79% would agree to a repeat examination under the same conditions and 92% said that they had received information appropriate to the examination undergone. CONCLUSION: The tolerance of fibreoptic bronchoscopy under local anaesthesia is poor and perhaps overestimated by respiratory physicians. Patient information is essential. A national enquiry could lead to the standardisation of techniques.

Anesthesia, Local↗

Familial osteoarthritis and Milwaukee shoulder associated with calcium pyrophosphate and apatite crystal deposition.

OBJECTIVE: To characterize and define the phenotypes observed in a large Italo-Argentinean kindred with osteoarthritis, chondrocalcinosis, and Milwaukee shoulder (MS). METHODS: Seventy-five members were evaluated with a history, examination, and radiographs of shoulders, spine, hands, and knees. Superior subluxation of the glenohumeral joint was graded using shoulder radiographs and tomography and nuclear magnetic resonance imaging and 3 dimensional computed tomography was performed on selected members. In 31 family members peripheral blood DNA was utilized for genetic linkage analysis of several candidate gene loci previously linked to chondrocalcinosis phenotypes, as well as those implicated in the proper patterning of skeletal elements and cartilage differentiation. In addition, direct sequence analysis of type II collagen gene (COL2A1), the gene that codes for the major structural protein of cartilage, was undertaken in 3 affected and 3 unaffected members of the family. RESULTS: MS was seen in one member of the first generation and 6 members of the 2nd generation, while 8 members of the 3rd generation showed an incomplete form of MS. Isolated superior subluxation of the shoulder was seen in 16 other family members of the 3rd and 4th generations. Osteoarthritis of the spine and peripheral joints was seen in 31 affected members, while chondrocalcinosis was observed in 6 members of the first generation. Shoulder synovial fluid from 2 patients showed the presence of both apatite and calcium pyrophosphate dihydrate crystals. Direct analysis of the COL2A1 gene indicated no known disease determining mutations in affected members, thus excluding this gene as a candidate gene in this family. Genetic linkage to several candidate loci, including the chondrocalcinosis loci on chromosomes 5p and 8q, as well as loci for HOX A and C were also excluded. Linkage analyses of other loci for the HOX B and D genes and the PAX 1 and 9 genes were uninformative in this kindred. CONCLUSION: This kindred illustrates an unusual type of osteoarthritis with secondary intraarticular and periarticular calcification and MS in the most severely affected elderly members. A search for linkage to some potential candidate genes was either excluded or uninformative. Further linkage analysis to identify potential candidate genes is in progress.

Adult↗

Recanalization of thrombosed superficial femoral arteries with a hydraulic thrombectomy catheter in a canine model.

OBJECTIVE: This experiment was conducted to evaluate efficacy and safety of the Oasis thrombectomy catheter on arterial thrombosis in dogs. MATERIALS AND METHODS: Thrombosis was induced in 18 femoral arteries of nine mongrel dogs. Recanalization of the thrombosed femoral artery was performed using a thrombectomy catheter 7-10 days after thrombus induction. Pre- and postprocedural arterial status was documented by angiography. After mechanical thrombectomy, the animals were sacrificed and the femoral arteries were harvested and examined macro- and microscopically. Additionally, in vitro fragmentation was carried out to determine particle size and distribution from the recovered effluent. RESULTS: Subacute thrombosis was successfully created in 15 femoral arteries. Full recanalization was achieved in 80% (12/15) of the thrombosed femoral arteries without any residual thrombus. No significant downstream embolization was documented angiographically. Endothelial denudation was observed in all the treated arteries along with occasional disruption of the internal elastic lamina. No medial injury was seen. Ninety-eight percent of thrombus was liquefied, defined as particles smaller than 15 microm, by the catheter. Particles larger than 400 microm represented 0.27% of the original clot weight. CONCLUSION: Occluded femoral arteries with 7- to 10-day-old thrombus can be efficiently recanalized with the Oasis catheter in dogs without any significant complication. This thrombectomy catheter appears to be highly effective and safe and requires no sophisticated equipment. Blood loss was our major concern regarding use of this catheter but can be minimized by strictly controlling activation time and restricting the inflow into the vascular segment being treated.

Animals↗

Enhanced MHC class II-restricted presentation of measles virus (MV) hemagglutinin in transgenic mice expressing human MV receptor CD46.

This study analyzes the role of the measles virus (MV) receptor, i.e. the human CD46 molecule, in the MHC class II-restricted presentation of MV hemagglutinin (H). We generated transgenic mice ubiquitously expressing CD46, with a similar level of transgene expression on the surface of antigen-presenting cells (APC), i.e. B cells, dendritic cells (DC) and macrophages. APC isolated from transgenic mice and nontransgenic controls were tested for their ability to present MV H to H-specific CD4+ I-Ed-restricted T cell hybridomas. All three populations of APC were capable of presenting MV to T cell hybridomas, DC being the most efficient. Expression of CD46 on B lymphocytes increased MHC class II-dependent presentation of MV H up to 100-fold, while CD46-transgenic DC stimulated H-specific T cell hybridomas up to 10-fold better than nontransgenic DC. Interestingly, expression of CD46 did not change the presentation efficiency of transgenic macrophages, indicating that CD46-dependent enhancement of antigen presentation depends on the nature of the APC. Furthermore, a single injection of UV-inactivated MV particles into CD46-transgenic mice, but not nontransgenic controls, induced generation of MV-specific T lymphocytes and production of anti-H antibodies, suggesting a role for CD46 in the efficient capture of MV in vivo. These results show for the first time that one ubiquitously expressed cell surface receptor, like CD46, could function in receptor-mediated antigen presentation both in vitro and in vivo and its performance depends on the type of APC which expresses it.

Animals↗

Increased chromosome abnormalities in human preimplantation embryos after in-vitro fertilization in patients with recurrent miscarriage.

Recurrent miscarriage is a pathological condition induced by maternal and embryonic causes. This paper describes a prospective study to determine the real incidence of aneuploidy for autosomes 13, 16, 18, 21, 22, and gonosomes in preimplantation human embryos obtained from patients with recurrent pregnancy loss after ovarian stimulation in an IVF-ET programme. Our results indicate that aneuploidy for the chromosomes analysed are abnormally higher in embryos obtained after IVF from recurrent abortion patients (58%) compared to non-recurrent abortion patients undergoing IVF. Furthermore, monosomies are six times more frequent than trisomies (47:8) in preimplantation embryos from recurrent abortion patients. Based on the present study, preimplantation genetic diagnosis (PGD) of embryos obtained from patients with recurrent miscarriage could prove advantageous in diagnosing abnormal embryos and selecting normal embryos for transfer.

Abortion, Habitual↗

Neuronal dependency of the glycine transporter GLYT1 expression in glial cells.

Two membrane-localized transporter proteins (GLYT1 and GLYT2) are responsible for removal of extracellular glycine in the mammalian CNS. Whereas GLYT1 seems to be expressed mainly in glial cells, GLYT2 is neuronal. The highest concentrations of both transporters are found in glycinergic areas of the nervous system. The expression of these proteins may be under regulatory control. We demonstrate here that GLYT1 is not expressed in pure glial cultures, but it is expressed by diverse types of glial cells in mixed neuronal/glial cultures. In these mixed cultures, the glial expression of GLYT1 is down-regulated after selective elimination of the neurons. The absence of expression in pure glial cultures and the observed reduction in the GLYT1 expression after neuronal loss support the existence of a regulatory cross-talk between neurons and glia to initiate and sustain the glial expression of GLYT1.

Amino Acid Transport Systems, Neutral↗

Congenital and acquired lung hernias.

Lung hernia is defined as a protrusion of lung parenchyma beyond the confines of the musculoskeletal thorax. Lung hernias can be classified according to location (i.e., cervical, thoracic, or diaphragmatic) and etiology. Approximately 80% of reported cases of lung hernia are acquired, usually related to trauma or surgery. Symptoms are few, infrequent, and vague. A painless, local, and inconstant bulging is evident on physical examination. The diagnosis of a lung herniation is accomplished using chest radiographs in the most cases. Surgery is usually reserved for large hernias or incarcerated hernias.

Hernia↗

Type III bare lymphocyte syndrome: lack of HLA class II gene expression and reduction in HLA class I gene expression.

The bare lymphocyte syndrome (BLS) consists of an association between a combined immunodeficiency disease and a significantly reduced expression of either human histocompatibility leukocyte antigens (HLA) class I (HLA-A, -B, -C) or HLA class II (HLA-DP, -DQ, -DR) at the cell surface. BLS type III, the more frequent form of this syndrome, is characterized by impaired expression of both class I and class II antigens on patients' cells, in particular on leukocytes. We describe herein the demonstration that expression of HLA class I molecules was reduced by approximately half on Epstein-Barr virus-transformed B cells (LCL) derived from type III BLS patients. HLA class I mRNA level was also decreased to the same extent. Expression of HLA class I molecules was also very significantly reduced at the surface of these fibroblasts as was mRNA specific for HLA class I. Simultaneously, the expression of HLA-DR molecules on LCL was even more greatly decreased, and the expression of HLA-DQ antigens was virtually abolished. Molecular analysis demonstrated an absence of mRNA for the alpha- and beta-chains of HLA-DQ and HLA-DR in the patients' lymphocytes. In general, such patients present with an association of an absence of expression of HLA class II antigens and a significantly reduced expression of HLA class I antigens. The mechanism of this association is still uncertain.

Child↗

Chronic and acute respiratory effects among grain mill workers.

Exposure to flour dust may induce chronic respiratory manifestations as well as acute ventilatory effects. We compared the prevalence of respiratory symptoms, ventilatory impairment, and variations in pulmonary function over the workshift in a group of mill workers exposed to wheat flour and in referent workers. One hundred and forty-two men exposed to flour in a mill and 37 referent workers were included in this study. Each subject completed a standardized questionnaire. Pulmonary function tests were performed before and after the workshift. The assessment of environmental exposure to flour showed high concentrations during some jobs with a high percentage of inhalable particles and a low concentration of respirable particles. The exposed workers had a significantly higher prevalence of usual cough and usual phlegm than the referents. The prevalence of asthma, based on the questionnaire, was similar. Before the workshift, the exposed workers had significantly lower mean lung function values for peak flow rate and forced expiratory flow rate at 75% of the vital capacity than the referents. After the workshift, all the lung function values showed a slight decrease, significant for forced vital capacity and forced expiratory volume during 1 s in both groups. Among the exposed workers, the asthmatic subjects had a significantly higher decrease across the shift than the nonasthmatic workers. This result is probably linked to bronchial hyperreactivity. Among nonasthmatic subjects, the decrease was larger in nonexposed workers than in exposed workers. A higher prevalence of respiratory symptoms and lower pulmonary function values were observed among mill workers by comparison with referents. Moreover, the data suggest that asthmatic status and the time of spirometric measurements need to be taken into account in epidemiological studies on exposure to airborne allergens. In addition, the study does not exclude a healthy worker effect with selection of dust-resistant subjects or better identification of asthmatic subjects among the workers exposed to an allergenic substance than among the nonexposed workers.

Adult↗

Cell-to-cell contact via measles virus haemagglutinin-CD46 interaction triggers CD46 downregulation.

CD46 downregulation by measles virus (MV) occurs after expression of virus haemagglutinin (H) protein on the surface of the infected cell and is a consequence of CD46-H interaction on the cell membrane. To assess whether CD46 downregulation also occurs after CD46-H interaction when these two molecules are expressed on distinct cells, we used human T cell line Jurkat (expressing CD46) and transfected murine fibroblast line L stably expressing MV-H protein (L.H). FACS analysis shows that cell-to-cell contact of 1 h at 37 degrees C triggers a reduction of CD46 cell surface labelling as detected by MCI20.6, GB24 and J4-48 monoclonal antibodies. This reduction is similar to that observed after MV infection or after infection with recombinant vaccinia virus encoding MV-H protein. By contrast, MV-H protein was downregulated only when CD46-H interaction occurred on the same cell membrane. CD46 downregulation is specific for CD46-H interaction because it was not observed after coincubation of Jurkat cells with either L cells expressing MV nucleoprotein (L.NP) or L cells. Moreover, this downregulation could be blocked by either anti-CD46 or anti-H antibodies. The H-mediated CD46 downregulation is reversible and restricted to CD46 since expression of other surface markers (CD3, CD14, CD47 and CD63) is unaffected. It is apparently not mediated in a protein kinase (PK) A- or PKC-dependent manner. Altogether, our results provide an unequivocal demonstration that interaction between the extracellular domains of CD46 and MV-H is sufficient to trigger CD46 downregulation.

1-Methyl-3-isobutylxanthine↗

Invariant chain expression similarly controls presentation of endogenously synthesized and exogenous antigens by MHC class II molecules.

I-Ak- and I-Ed-transfected L fibroblasts were supertransfected with cDNA coding for hen egg lysozyme (HEL) or measles virus hemagglutinin (HA). Well-defined cell culture conditions allowed us to obtain L cells with either no detectable endogenous Ii mRNA or a high level of endogenous Ii mRNA induced by serum starvation. Cells supertransfected with mouse Ii chain gene stably expressing a high level of Ii chain were also used as APC in parallel experiments. Class II presentation of endogenously secreted HEL or an ER-retained form of HEL to the HEL-specific I-Ak-restricted 3A9 T cell hybridoma was found to be strongly enhanced in cell transfectants expressing Ii chain. Similar results were obtained with the presentation of transmembrane HA to the HA-specific I-Ed-restricted TH5.143 T cell hybridoma. These findings correlate with those obtained with the presentation of exogenous HEL and HA. In addition, as reported to be the case for exogenous antigen, expression of a large amount of endogenous HA by the APC supplants the requirement for Ii chain expression in the enhancement of antigen presentation. These data demonstrate that presentation by MHC class II molecules of a given antigen, either exogenously provided or endogenously synthesized, is controlled in a similar manner by the Ii chain.

Animals↗

Sephadex filtration and human serum albumin gradients do not select spermatozoa by sex chromosome: a fluorescent in-situ hybridization study.

Fluorescent in-situ hybridization (FISH) of decondensed sperm nuclei has been used directly to evaluate the enrichment efficiency of human sperm separation using Sephadex gel filtration and human serum albumin (HSA) gradients. Control and processed spermatozoa were fixed and their nuclei decondensed. In-situ hybridization was carried out with a Y-specific DNA probe (DYZ1). Sephadex filtration yielded 52.5% Y-chromosome-bearing spermatozoa, HSA separation resulted in 49.4% Y-chromosome-bearing spermatozoa and in the untreated control sample the percentage of Y spermatozoa was 49.3%. Statistical analysis revealed no significant differences between the selection methods employed and the controls, and no real enrichment for X- or Y-bearing spermatozoa was detected for any of the selection methods assayed. The usefulness of the protocols reported for selection of spermatozoa by sex chromosome in couples at risk for X-linked diseases is discussed.

Cell Separation↗

Inhibition of high-affinity gamma-aminobutyric acid uptake in primary astrocyte cultures by phorbol esters and phospholipase C.

The effects of phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C (PKC), on high-affinity Na(+)-dependent gamma-aminobutyric acid (GABA) uptake were investigated in primary cultures of neurons and glial cells from rat brain cortex. Incubation of glial cells with PMA led to concentration- and time-dependent decreases in the GABA transport in glial cells. This effect could be completely suppressed by addition of the PKC inhibitor H7. The PMA effects could be mimicked by oleoylacetylglycerol, the diacylglycerol kinase inhibitor R59022 and exogenous phospholipase C. Treatment with PMA did not affect GABA transport in neuronal cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Arachidonic acid inhibits glycine transport in cultured glial cells.

The effects of arachidonic acid on glycine uptake, exchange and efflux in C6 glioma cells were investigated. Arachidonic acid produced a dose-dependent inhibition of high-affinity glycine uptake. This effect was not due to a simple detergent-like action on membranes, as the inhibition of glycine transport was most pronounced with cis-unsaturated long-chain fatty acids, whereas saturated and trans-unsaturated fatty acids had relatively little or no effect. Endogenous unsaturated non-esterified fatty acids may exert a similar inhibitory effect on the transport of glycine. The mechanism for this inhibitory effect has been examined in a plasma membrane vesicle preparation derived from C6 cells, which avoids metabolic or compartmentation interferences. The results suggest that part of the selective inhibition of glycine transport by arachidonic acid could be due to the effects of the arachidonic acid on the lipid domain surrounding the carrier.

Arachidonic Acid↗

Na+ dependence of tyrosine transport across the synaptosomal membrane reflects changes in the morphology of synaptosomes.

The Na+ dependence of tyrosine uptake into rat brain synaptosomes and synaptosomal plasma membrane vesicles (SPMV) was examined in the present study. At low tyrosine concentrations, the isoosmotic substitution of Na+ by sucrose in the incubation medium led to an increase of tyrosine uptake in synaptosomes and to a decrease in SPMV. The removal of extracellular Ca2+ and Mg2+ and addition of isoosmotic sucrose completely prevented the augmented tyrosine uptake in Na+-free incubated synaptosomes. Morphological differences were found at the electron-microscopic level when synaptosomes were incubated in Na+-free and Na+-containing media. The internal volume measured for synaptosomes incubated in a Na+-free medium was almost half of that obtained in a Na+-containing medium, in good agreement with the observations made with the electron microscope. Also, the omission of Ca2+ and Mg2+ resulted in a specific swelling of only the synaptosomes incubated in Na+-free medium. When synaptosomes and SPMV were preloaded with several neutral amino acids, the tyrosine uptake rate was greatly increased, indicating fully operational exchange mechanisms for these amino acids. We propose that the enhancement of high-affinity synaptosomal tyrosine uptake observed in Na+-free medium is a consequence of a specific shrinkage of the synaptosomes and a parallel increase of the exchange rate with endogenous neutral amino acids.

Animals↗