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Biomedical subjects

E Roux

Publications and source records attributed to E Roux.

At least 55 records · Page 3Linked to original sources
PubMed1996

Human bronchial smooth muscle responsiveness after in vitro exposure to oxidizing pollutants.

The aims of this work were (1) to determine the dose-response relationship between ex vivo exposure to oxidizing pollutants such as nitrogen dioxide (NO2), the aldehyde acrolein, and ozone (O3), and the reactivity to agonists in isolated human bronchial smooth muscle; and (2) to investigate the alterations in the cellular mechanisms of human airway smooth muscle contraction induced by such exposures. Experiments were performed in isolated human bronchi obtained at thoracotomy. Isometric contraction in response to a variety of agonists was compared between pollutant-exposed preparations and paired controls. Short exposures to NO2, acrolein, or O3 altered the subsequent airway smooth muscle responsiveness in a dose-dependent manner. The cellular mechanisms producing the airway hyperresponsiveness observed in vitro are shared by the three pollutants and include alterations in airway smooth muscle excitation-contraction coupling as well as indirect effects on neutral endopeptidase activity.

Acrolein↗
PubMed1996

A prospective controlled study of low back school in the general population.

There are no data on the efficacy of a back school in primary prevention of back pain in the general population or on the characteristics of the population who volunteers. After announcement in the local press, 494 healthy adults volunteered and paid for a back school course in Switzerland. A total of 371 controls were matched for sex, age, profession, nationality and back pain. A statistically significant decrease in numbers of doctor's visits was found by the participants during the following 6 months compared with the controls. However, there were no significant between-group difference in the four remaining parameters (presence and intensity of back pain, drug intake and sick leave). Three-quarters of participants changed their attitudes after the back school. Volunteering for a back pain prevention programme was associated with the presence of back pain problems. Reasons for volunteering are further discussed. Overall, the results of this study showed that a back school for the general population may not solve the problem of low back pain, but improves self-help in a subgroup of the population.

Adult↗
PubMed1996

Human and rat airway smooth muscle responsiveness after ozone exposure in vitro.

We previously reported that NO2 and acrolein administered ex vivo to the lung altered the subsequent responsiveness of airway smooth muscle. The aim of this study was to determine the dose-response relationship for O3 in both human isolated bronchi and rat tracheae and to investigate the mechanisms underlying O3-induced airway responsiveness. Exposure to 1 ppm O3 for 15 min significantly increased the maximal response to carbachol of rat tracheal rings to 149.6 +/- 5.4% of the reference response to acetylcholine (ACh) compared with that of unexposed rings (131.3 +/- 2.4%, n = 6, P < 0.05). The change in maximal airway responsiveness to carbachol, when plotted against the product of exposure concentration and exposure time to O3, a surrogate for the dose, formed a bell-shaped curve. The peak of this dose-response curve was shifted to the right for human bronchi (50 ppm x min, n = 5) compared with that of rat tracheae (15 ppm x min, n = 6). In the rat trachea, responses to KCl were not altered by O3, whereas those to 5-hydroxytryptamine hydrochloride (5-HT) were significantly increased. Finally, in the absence of external Ca2+, O3 exposure still potentiated the maximal response to carbachol from 73.6 +/- 13.9 to 137.0 +/- 6.0% and that to 5-HT from 21.5 +/- 5.5 to 38.7 +/- 2.2% of the reference ACh response. These results indicate that O3 alters the subsequent in vitro airway responsiveness depending on 1) the dose, 2) the nature of the agonist, and 3) the species investigated. Because in vitro exposure to O3 increases responses to agonists that release intracellular Ca2+ and since this effect is maintained in Ca(2+)-free solution, the mechanism of O3-induced increase in airway smooth muscle responsiveness is likely to involve an enhancement in intracellular Ca2+ release.

Airway Resistance↗
PubMed1995

Elaboration of an oviductin by the oviductal epithelium in relation to embryo development as visualized by immunocytochemistry.

The hamster oviduct secretes a high molecular weight antigen that belongs to the family of glycoproteins known as oviductins. In the present study, using immuno-electron microscopy, we examined the location of this hamster oviductin-1 (Hm Ov-1) in hamster oviductal oocytes and early embryos up to the blastocyst stage. The immunoreactive pattern of Hm Ov-1 changes markedly during the embryo development. In oviductal oocytes prior to fertilization, Hm Ov-1 was associated exclusively with the zona pellucida. Following fertilization, immunolabeling was detected in the perivitelline space and over the plasma membrane of 2-cell, 4-cell, and 8-cell embryos as well as young blastocysts. The change of the immunoreactive pattern was accompanied by the formation of an abundant number of coated pits, endocytic vesicles, multivesicular bodies, and lysosomal-like structures which were strongly labeled by gold particles. These immunogold-labeled cytoplasmic organelles characteristic of the endosomal-lysosomal apparatus were particularly evident in 2-cell, 4-cell, and 8-cell embryos and showed a decrease in number in the blastocysts. The close resemblance between the labeled flocculent material detected in the perivitelline space and that found in the zona matrix of early embryos and blastocysts suggested that the Hm Ov-1-associated electron-dense, flocculent material in the perivitelline space originated from the zona pellucida and was later endocytosed by the blastomeres through coated pits and endocytic vesicles. The detection of Hm Ov-1 in numerous multivesicular bodies and lysosomal structures indicated that the oviductin is eventually degraded. Although the exact functional role of Hm Ov-1 is not known, the presence of a copious amount of Hm Ov-1 in early hamster embryos may be ascribed to a special relationship between this particular oviductin and embryo development.

Animals↗
PubMed1995

Stage-specific immunolabeling for oviductin in the secretory granules of the oviductal epithelium of the golden hamster during the estrous cycle.

BACKGROUND: We have previously localized an antigen of oviductal origin in the zona pellucida of postovulatory hamster ova. This antigen is a high molecular weight glycoprotein secreted by the non-ciliated secretory cells of the oviduct and is later transferred to the zona pellucida of the oocyte during oviductal transit. This glycoprotein is rich in N-acetyl-D-galactosamine residues and has been designated Hamster Oviductin-1. In the present study, a monoclonal antibody (MAb) raised against this oviductin was used to detect the presence of this antigen in oviductal tissue during the estrous cycle. METHODS: Twenty mature female golden hamsters were used and were divided into five groups of five animals each according to the five different stages of the estrous cycle. Quantitative immunocytochemistry was performed on MAb-labeled thin sections of Lowicryl-embedded ampullary region of hamster oviducts. Control experiments were also carried out to assess the specificity of the immunolabeling. RESULTS: Quantitative analysis of the immunogold labeling indicated that maximum labeling for oviductin in the secretory granules of oviductal epithelial secretory cells was found around the time of ovulation, i.e., at estrus. The intensity of immunolabeling decreased from metestrus to diestrus 1, was at a minimum at diestrus 2, and started to increase at proestrus. CONCLUSION: Together, these quantitative results indicate that expression of oviductin in the secretory granules of the hamster oviductal secretory cells is stage specific. Maximum labeling for the antigen coincides with the time of ovulation suggesting an important role for the oviductal epithelium in contributing its secretory product to the zona pellucida of oocytes freshly released from the ovary. Since the oviduct is the site of sperm-egg interaction and where fertilization and early embryo development take place, the maximal production of oviductin at the time of ovulation may facilitate some of these crucial steps during the intricate process of reproduction.

Animals↗
PubMed1995

Missing T-cell receptor V beta families following blood transfusion. The role of HLA in development of immunization and tolerance.

Previously, we showed that donor-specific CTL nonresponsiveness occurs in transfused recipients sharing one HLA haplotype (or at least one HLA-B and one HLA-DR antigen) with the blood donor. The aim of the present study was to disclose the distinct effects of BT on the T-cell receptor repertoire and to analyze which factors determine the tolerizing versus immunizing properties of BT. We show here that recipients of HLA-sharing BT develop not only donor-specific CTL nonresponsiveness posttransfusion, but also a significant decrease in the usage of one to three V beta families as shown by PCR. In contrast, recipients of non-HLA-sharing BT remained donor-specific CTL responders and did not decrease the usage of V beta families. In addition, these patients generated high-affinity CTL for donor antigens which could not be blocked by anti-CD8 mAb. Our results show that major alterations occur in the CTL and TCR V beta repertoire following BT. We hypothesize that the fate of transfused allogeneic lymphocytes in the host is based on the degree of sharing of HLA antigens with the host. This relationship determines the ultimate outcome of BT: immunization versus tolerization.

Base Sequence↗
PubMed1995

Application of a polymorphic Y microsatellite to the detection of post bone marrow transplantation chimaerism.

A highly sensitive Y-microsatellite amplification system was developed for the detection of post bone marrow transplantation (BMT) chimaerism. The system is able to detect the DNA equivalent of a single male cell in a background of 10(5) female cells. For clinical applications it has the distinct advantage that the polymorphic nature of the PCR product allows the checking of the genuineness of a positive PCR signal by reference to its allelic type. This extra degree of precision enhances the accuracy of Y-PCR for clinical diagnosis.

Alleles↗
PubMed1995

Transfusion-associated graft-versus-host disease in a patient treated with Cladribine (2-chlorodeoxyadenosine): demonstration of exogenous DNA in various tissue extracts by PCR analysis.

Transfusion-associated graft-versus-host disease can occur in both immunocompetent and immunocompromised hosts. Cladribine is a synthetic analogue of adenine used in the treatment of lymphoid malignancies, commonly associated with a decrease in T lymphocytes. Cladribine was given for a low-grade non-Hodgkin's lymphoma with thrombocytopenia as the main side-effect. Six units of pooled non-irradiated platelets were transfused from six unrelated donors; 10 d later a clinical picture typical of graft-versus-host disease resulted. Polymerase chain reaction of the highly polymorphic DNA minisatellites and HLA-DR oligotyping were used to demonstrate the exogenous DNA. In the patient's blood and tissues, only the pattern of donor 5 was found. The patient (DRB1*0301/1101; DRB3*0101/02) and this donor (DRB1*0301/1104; DRB3*02) by chance shared a partial common haplotype. This complication highlights the sensitivity of DNA minisatellite analysis. It further raises the question of transfusion and of prophylactic irradiation of all blood products in immunosuppressed patients and those treated with cladribine. This case represents a previously unreported situation where an immunosuppressed patient was able to eliminate cells from five totally HLA-DR dissimilar donors but not from one heterozygous donor with strong HLA-DR similarity.

Aged↗
PubMed1994

Acquired C1 inhibitor deficiency as a result of an autoantibody to the reactive center region of C1 inhibitor.

An autoantibody that we hypothesize to react with the reactive center of the plasma serine proteinase inhibitor, C1 inhibitor (C1INH), has been found in a patient with acquired C1INH deficiency. The Ab blocks the ability of C1INH to inhibit the hydrolysis of N-carbobenzyloxy-L-lysine thiobenzylester by purified C1s. A cryoprecipitate from the patient's plasma as well as the Ig fraction were able to block C1INH inhibition of C1s. The immunoaffinity purified Ab to C1INH from the patient's plasma Ig fraction neutralizes the inhibitory activity of C1INH in a dose-dependent manner and blocks the ability of normal C1INH to form a complex with C1s. The neutralizing activity of the purified Ab is reversed by a synthetic peptide that corresponds to the amino acid sequence in the P1 to P15 positions of the reactive center of C1INH but not by a 34-amino-acid trypsin peptide or 37-amino-acid elastase peptide derived from the C-terminus of C1INH. Western blot analysis indicated that the Ab is an oligoclonal Ig with kappa light chains.

Adult↗
PubMed1994

Homogeneity in the distribution of matrix components in the hamster zona pellucida as revealed by backscattered electron imaging fracture-label.

BACKGROUND: Backscattered electron imaging fracture-label (BEI-FL), an adaptation of the fracture-label method for scanning electron microscopy, offers the advantage of providing information about the distribution of antigenic and receptor sites with respect to the three-dimensional organization of tissues and cells over relatively large surfaces. Recently, using post-embedding cytochemistry on thin-sections of Lowicryl-embedded oocytes, a homogenous distribution of glycoproteins in the zona pellucida (ZP) was demonstrated (Kan et al., 1989. Biol. Reprod., 40:585-598, Anat. Rec., 226:37-47; Roux and Kan, 1991. Anat. Rec., 230:347-360). However, it can be argued that the chemical nature of resins and the physical conditions of tissue processing required for post-embedding cytochemistry may introduce changes in the tissue components and result in altered distribution of components. On the other hand, freeze-fracture exposes constituents in a minimally denaturing manner and, since no embedding media are used, binding sites are sterically available to the probe. We have, therefore, applied BEI-FL to examine the distribution of matrix glycoproteins in the ZP of hamster oocytes. METHODS: Ovaries and cumulus masses obtained from superovulated female golden hamsters were fixed by immersion in 2.5% glutaraldehyde and processed for fracture-label. Tissues were labeled, respectively, with Wheat germ agglutinin (WGA) followed by ovomucoid-colloidal gold, Ricinus communis agglutinin I (RCA I)-colloidal gold or a monoclonal antibody against Hamster Oviductin-1 followed by protein A-gold, and then examined in the scanning electron microscope. RESULTS: Backscattered electron imaging revealed a homogenous distribution of WGA and RCA I binding sites throughout the cross-fractured matrix of the ZP of ovarian and postovulatory oocytes. Hamster Oviductin-1, an oviductal glycoprotein which is transferred to the ZP of oocytes during oviductal transit, was also found to be uniformly distributed throughout the ZP of postovulatory oocytes. CONCLUSIONS: Our results indicate that BEI-FL can be advantageously used to examine extracellular matrices and are consistent with the concept that glycoproteins are uniformly distributed throughout the ZP of the hamster oocyte.

Animals↗
PubMed1994

Molecular and biological characterization of human 4-1BB and its ligand.

4-1BB was originally described as a cDNA expressed by activated murine T cells and subsequently demonstrated to encode a member of the tumor necrosis factor receptor family of integral membrane proteins. Recently, we identified and cloned a murine ligand for 4-1BB (mu4-1BB-L) and demonstrated it to be a member of an emerging family of ligands with structural homology to tumor necrosis factor. To characterize further the role of 4-1BB in the immune response we undertook to clone the human homologue of 4-1BB-L. However, attempts to isolate a cDNA encoding the human 4-1BB-L by cross-hybridization with the murine cDNA were unsuccessful. Therefore we first utilized cross-species hybridization to isolate a cDNA encoding human 4-1BB (hu4-1BB). A fusion protein consisting of the extracellular portion of hu4-1BB coupled to the Fc region of human immunoglobulin G1 (hu4-1BB.Fc) was then used to identify and clone a gene for human 4-1BB-L from an activated CD4+ T cell clone using a direct expression cloning strategy. Human 4-1BB-L shows 36% amino acid identity with its murine counterpart and maps to chromosome 19p13.3. Scatchard analysis demonstrated high-affinity binding of hu4-1BB.Fc to either native or recombinant human 4-1BB-L. Both monoclonal antibody to hu4-1BB and cells transfected with hu4-1BB-L induced a strong proliferative response in mitogen co-stimulated primary T cells. In contrast, ligation of 4-1BB on T cell clones enhanced activation-induced cell death when triggered by engagement of the TCR/CD3 complex.

Amino Acid Sequence↗
PubMed1994

Regulation of apoptosis and T cell activation by Fas-specific mAb.

Fas was initially described as a molecule expressed on the surface of certain cell lines that could mediate programmed cell death (apoptosis) subsequent to ligation by specific mAb. To determine whether mAb to other epitopes on the Fas molecule might mediate other functions, we generated a panel of mAb to the extracellular portion of human Fas. Significant lysis of Fas-expressing target cells was only observed when the new mAb were first bound to a solid-phase support and not when the mAb were added in solution. However, several of these mAb inhibited the killing of target cells induced by the prototypic Fas-specific mAb, CH-11. Those mAb that inhibited apoptosis of target cells mediated by the CH-11 mAb also blocked lysis of target cells mediated by cells expressing Fas ligand. Finally, some of the Fas-specific mAb were found to co-stimulate proliferation of peripheral blood T cells in the presence of immobilized CD3 mAb. Thus, the data indicate the existence of a complex set of interactions mediated by Fas in both normal and transformed lymphoid cells that may have important implications regarding the role(s) of this molecule in regulation of immune responses.

Animals↗
PubMed1994

Kaposi's sarcoma following allogeneic bone marrow transplantation.

Localised Kaposi's sarcoma (KS) was diagnosed 240 days after allogeneic bone marrow transplantation (BMT) in a severely immunosuppressed HIV negative patient with genetic predisposition. The tumour was of host origin, based on PCR amplification of DNA minisatellites. Treatment with radiotherapy prompted almost complete regression of the lesions. However the patient subsequently died with relapsed acute myelogenous leukaemia. Contrary to the incidence observed after organ allografts, the advent of KS appears to be exceptional after BMT, since only one case has been reported to date, following reinfusion of autologous marrow.

Bone Marrow Transplantation↗
PubMed1994

Androcur 50 in the treatment of prostatic carcinoma. Belgian multicentric study with the participation of 30 urologists.

Androcur 50 was administered as monotherapy (n = 73) or as combined therapy with LH-RH agonists (n = 130) in 203 patients during a 6 month period. Eighty two patients had a local invasive disease, 119 had metastatic disease and 2 had a tumor confined to the prostate. Quality of life could be evaluated in 164 patients considered as valid cases for efficacy analysis. General well being improved in 41% of the patients, appetite was better in 34% of the patients and weight increased in 36%. Pain due to metastatic disease decreased or stabilised in 96% of the patients. Of the 203 patients, 8 patients had objective metastatic progression which led to death in one patient. The incidence of side effects observed in all 203 is as follows: 9% gynaecomastia, 6.5% gastro-intestinal disorders. Hot flushes were reported in 2% of the patients in the monotherapy and in 13% of the patients in the combined treatment. This open not controlled trial shows that the use of Androcur 50 in monotherapy or in combined treatment is an effective drug for prostatic carcinoma, improves quality of life and is generally well tolerated.

Aged↗
PubMed1993

Fas transduces activation signals in normal human T lymphocytes.

The Fas gene encodes a cell surface molecule that is a member of the the nerve growth factor/tumor necrosis factor receptor family of proteins and can mediate programmed cell death (apoptosis) in certain transformed cell lines. To characterize further the biological function of Fas, particularly with regard to its function in normal cells, a panel of monoclonal antibodies (mAbs) was generated against the extracellular portion of human Fas. Some of these mAbs induced apoptosis in transformed cell lines expressing Fas, but only when immobilized on the culture vessel. One of the new Fas mAbs (M38) was used for studies on normal lymphoid cells and found to stimulate the proliferation of purified human T cells and thymocytes when immobilized on culture wells along with CD3 antibody. T cell proliferation induced by Fas mAb was largely interleukin 2 independent and was demonstrated to be due to a direct effect on the precursor T cell. Thus, the data demonstrate that in addition to a role in the induction of apoptosis in certain transformed cell lines, the Fas protein may also play an important role in the activation and proliferation of normal T cells.

Antibodies, Monoclonal↗