Biomedical subjects

P Bonnet

Publications and source records attributed to P Bonnet.

At least 73 records · Page 4Linked to original sources

PubMed1996

Synergistic action of NS-004 and internal Ca2+ concentration in modulating pulmonary artery K+ channels.

Considering the singular vasomotor behavior of the pulmonary artery, we were interested to test NS-004 (1-(2'-hydroxy-5'-chlorophenyl)-5-trifluoromethyl-2(3H)-benzimidazolo ne) on pulmonary artery smooth muscle cells. Using the patch clamp technique, we identified a delayed rectifier K+ current and a Ca(2+)-activated K+ current. With a low free intracellular Ca2+ concentration ([Ca2+]i), 10-50 microM NS-004 activated a noisy outward current which was blocked by iberiotoxin. 50 microM NS-004 also inhibited a smooth inactivating outward current. Under these conditions, 10 microM NS-004 induced no change in the resting membrane potential. With a higher free [Ca2+]i, 10 microM NS-004 was 3.5 times more efficacious in increasing the noisy current and it induced a hyperpolarization. We concluded that increasing free [Ca2+]i induced potentiation of the NS-004-induced activation of high conductance Ca(2+)-sensitive K+ channels and of the NS-004-induced hyperpolarization of the cell. The delayed rectifier K+ channel was inhibited by NS-004 as well as by an increased free [Ca2+]i.

4-Aminopyridine↗

PubMed1996

Extracellular matrix and beta 1 integrin expression in nodal and extranodal T-cell lymphomas.

Since non-Hodgkin's lymphoma (NHL) cells interact with surrounding structures similarly to their normal counterparts, micro-environmental changes and the aberrant expression of adhesion molecules are considered to be of importance in lymphomagenesis. In this immunohistochemical study, the composition of several extracellular matrix (ECM) components and the expression of their beta 1 integrin receptors were examined in nodal and extranodal T-cell NHLs. Except for the T-lymphoblastic NHLs, almost all T-NHLs displayed abundant deposition of matrix and considerable expression of the alpha 4 and beta 1 integrin chains. This is in contrast to B-cell NHLs, which show ECM patterns comparable to those in reactive lymphoid tissue or, in cases of high-grade malignancy, active matrix degradation and very low expression or absence of beta 1 integrins, as previously described. This difference is probably based on distinct cytokine production in B- and T-cell malignancies. As in B-NHL, nodal and extranodal T-NHLs of the same morphological subtype exhibit identical ECM patterns, which suggests that malignant lymphoid cells of both B and T origin create at least part of their own specific micro-environment.

Collagen↗

PubMed1996

Distinctive adhesion pathways are involved in epitheliotropic processes at different sites.

Intraepithelial migration of lymphoid cells (epitheliotropism) is a biological process that can be observed under various physiological and pathological conditions. Recently, epitheliotropism was proposed to be a multi-step process, involving interactions of lymphoid cells with both epithelial basement membrane (EBM) and epithelial cells. In the present study we analysed by immunohistochemistry the adhesion mechanisms that are potentially involved in epitheliotropism of lymphoid cells in various disorders, such as tonsillar hyperplasia, coeliac disease, malignant lymphomas of mucosa-associated lymphoid tissue (MALTomas), and mycosis fungoides (MF). The combinations of adhesion molecules expressed on the participating lymphoid and epithelial cells varied among these disorders. These findings suggest that the adhesion pathways utilized in epitheliotropism may be associated with the nature of the lymphoid cell (reactive or neoplastic/B or T) and/or the site of the epithelium involved. In some cases the specificity of the process was determined by the adhesion mechanism involved in the lymphocyte-EBM interaction, as in the case of alpha 3 beta 1 integrin/laminin-5 in MF, and in others by the adhesion mechanisms involved in the interaction between lymphoid and epithelial cells, such as alpha 4 integrin/VCAM-1 in tonsillar hyperplasia and alpha E beta 7/E-cadherin in coeliac disease.

Celiac Disease↗

PubMed1996

Developmental toxicity of inhaled ethylene oxide in rats following short-duration exposure.

The developmental toxicity of ethylene oxide (EtO) was examined in Sprague-Dawley rats following inhalation exposure during Days 6 to 15 of gestation. Two different exposure regimens were used: (1) exposure for 0.5 hr once a day to 0, 400, 800, or 1200 ppm EtO; or (2) exposure for 0.5 hr three times a day to 0, 200, or 400 ppm EtO or 0, 800, or 1200 ppm EtO. Repeated brief exposures (3 x 0.5 hr/day) to EtO caused fetal toxicity indicated by reduced fetal weight at 800 and 1200 ppm, and overt maternal toxicity manifested as reduced body weight gain at 1200 ppm. Neither embryolethality nor teratogenicity occurred following any exposure regimen.

Abnormalities, Drug-Induced↗

PubMed1996

Distribution of laminin variants and their integrin receptors in human secondary lymphoid tissue. Colocalization suggests that the alpha 6 beta 4-integrin is a receptor for laminin-5 in lymphoid follicles.

Laminins are a family of multifunctional basement membrane glycoproteins. Over the last years, many laminin isoforms have been characterized, which were shown to be composed of distinct combinations of variant alpha, beta and gamma chains. Some of these isoforms show remarkable tissue specificity, which suggests functional involvement in local processes. In this study the previously described mAb 4C7, which recognize epithelial basement membranes as well as endothelial basement membranes in lymphoid follicles, was identified as an anti-laminin-5 antibody. Using a set of mAbs against various variant laminin chains we established that specifically the gamma 2 chain of laminin-5 was confined to the endothelial basement membranes of vessels in lymphoid follicles, whereas other variant laminin chains were also expressed elsewhere in the lymphoid follicles, whereas other variant laminin chains were also expressed elsewhere in the lymphoid tissue. Additionally, the expression of the known integrin receptors of laminin-5 was also examined. The alpha 6 beta 4 integrin-receptor for laminin was found to be colocalized with the laminin-5 gamma 2 chain on the abluminal surface of endothelial cells, whereas the alpha 3 integrin chain could not be detected in lymphoid follicles. This finding suggests that the alpha 6 beta 4 integrin (and not the alpha 3 beta 1 integrin) serves as a laminin-5 receptor on endothelial cells in the follicular compartment of lymphoid tissue. Furthermore, alpha 6 beta 4 was also found in the same punctuated pattern on FDCs as laminin-5. The function of the laminin-alpha 6 beta 4 complex in this particular localisation is still obscure, but a role in the maintainance of the follicular compartment via hemidesmosome-like attachment sites is postulated.

Antibodies, Monoclonal↗

PubMed1996

Mycosis fungoides with extracutaneous localization in the breast.

We report a patient with mycosis fungoides (MF) and transformation to anaplastic (CD30+) lymphoma, who developed an unusual manifestation in the breast. Cutaneous and extracutaneous tumour cells both showed marked intraepithelial migration, but had distinct expression patterns of epitheliotropism-associated integrins. Intraepidermal and dermal lymphoma cells in the skin expressed most of the integrins that are presumed to be involved in epitheliotropism, such as leucocyte functional antigen-1 (LFA-1), alpha 1 beta 1, alpha 3 beta 1, alpha 4 beta 1 and alpha 6 beta 1. In the breast, most of the extraepithelial tumour cells only expressed the laminin-5 ligand alpha 3 beta 1 (strong) and the collagen ligand alpha 1 beta 1 (weak). However, on the intraepithelial tumour cells in the mammary ducts and glands LFA-1, alpha 4 and alpha E could also be detected. In view of these findings we propose epitheliotropism of the MF cells in the breast to be a multistep process in which tumour cell-epithelial basement membrane (EBM) interaction, predominantly mediated by alpha 3 beta 1 and laminin-5, is the primary event. Adhesion to and subsequent infiltration of the neoplastic lymphoid cells into the EBM may, either directly or indirectly, lead to upregulation and/or activation of other integrins that amplify interaction with epithelial cells.

Breast Neoplasms↗

PubMed1995

Assessment of the developmental toxicity and placental transfer of 1,2-dichloroethane in rats.

This study evaluates the developmental toxicity and placental transfer of 1,2-dichloroethane (DCE) in rats. Sprague-Dawley rats were given 0-2.4 mmol DCE kg-1 day-1 by gavage, or were exposed for 6 hr per day to 0-300 ppm DCE by inhalation, from Day 6 to 20 of gestation. Maternal toxicity was observed after inhalation exposure to 300 ppm DCE and oral administration of 2.0 or 2.4 mmol DCE kg-1. There was no evidence of altered growth nor teratogenic effects after either inhalation or oral administration of DCE at any concentration tested. The time course disposition of 14C was examined over a 48-hr period in 12- and 18-day pregnant rats after a single oral dose of 1.6 mmol [14C]DCE kg-1. Peak concentrations of radiocarbon occurred between 2 and 4 hr postdose. Conceptus (Day 12) and fetal (Day 18) tissues accounted for 0.06 and 0.4% of the administered dose, respectively. Up to 4 hr, levels of radiocarbon in placenta and fetus were slightly less than in maternal plasma of 18-day pregnant rats and were two to five times higher at later periods. At 2 hr, unchanged DCE accounted for most of radioactivity (78-86%) recovered in maternal plasma, placenta, and fetus. Acidic metabolites and radioactivity bound to macromolecules increased up to 24 hr (0.01 mumol-eq DCE g-1) in either placental or fetal tissues. Thereafter, their levels declined more slowly than those in the maternal plasma. Results from this developmental toxicity study in rats confirm embryonic exposure to radiocarbon associated with [14C]DCE and/or its metabolites and has demonstrated the lack of observable teratogenic effects.

Administration, Inhalation↗

PubMed1995

Rat heart-aorta cluster transplantation: a novel model to study transplant rejection.

The purpose of this study was to develop a microsurgical cluster model of heart plus entire thoracic aorta transplantation and to compare it to the isolated model of heart transplantation as a tool to study transplant rejection. Thirty-six syngeneic (DA x DA and Lew x Lew) and allogeneic (DA x PVG and DA x Lew) cluster heart-aorta transplants were compared to 43 syngeneic and allogeneic isolated heart grafts. Graft survival, recipient survival and histological data on myocardial and aortic tissues were assessed. There was no statistically significant difference in graft survival between the two models studied (P > 0.05). In the cluster transplants, the aortic component was spared the severity of acute rejection noted for the myocardial counterpart. In conclusion, the results demonstrated that the cluster model was technically feasible and highly reproducible. Additionally, it was possible to apply this model to the study of experimental allograft rejection using novel immunosuppressants. The success of the cluster model in strongly mismatched transplant strain combinations underscores its potential for application in slower rejection combinations, making it particularly suited for chronic rejection studies. The inherent capacity for sampling a broader range of vessel sizes in one animal makes the cluster model more suitable than the isolated models of aorta or heart for application to experimental protocols.

Animals↗

PubMed1995

Elicitin produced by an isolate of Phytophthora parasitica pathogenic to tobacco.

Elicitin was prepared from a Phytophthora parasitica culture isolated from tobacco in Australia. The protein with elicitor activity was purified and sequenced. This protein, which contains 98 amino acid residues, shows full homology with an elicitin produced by a completely unrelated isolate from carnation, indicating conservation of elicitin sequence within a single species.

Amino Acid Sequence↗

PubMed1995

Distribution of extracellular matrix components and their receptors in human lymphoid tissue and B-cell non-Hodgkin lymphomas.

In this study the distribution patterns of various extracellular matrix components and their receptors (i.e. beta 1 integrins) in B-cell non-Hodgkin lymphomas were examined and compared to those in reactive lymphoid tissue. Neoplastic follicles within follicular lymphomas showed similar patterns to that observed in reactive follicles, which appeared to be strongly associated with the presence of follicular dendritic cells. Diffuse lymphomas of low and intermediate malignancy grade revealed features comparable to those of interfollicular areas of reactive lymphoid tissue, irrespective to which compartment the tumour cells were related. Highly malignant lymphomas, however, displayed unique extracellular matrix configurations, resulting from active matrix degradation by macrophages; this may support rapid tumour growth. Extranodal lymphomas showed virtually the same matrix patterns as their nodal counterparts, suggesting that (malignant) lymphoid cells generate (at least partly) their own specific microenvironment. In reactive lymphoid tissue beta 1 integrins were mainly found on resident cells and except for alpha 4, alpha 5 (and beta 1) the lymphoid cells expressed very little, if any, beta 1 integrins. In comparison, expression of these integrins on lymphoma cells was reduced (follicular lymphomas) or could not be detected at all (diffusely growing lymphomas); this might contribute to the growth pattern and metastatic properties of the tumours.

Cell Adhesion Molecules, Neuronal↗

PubMed1995

Antiandrogenic properties of nomegestrol acetate.

Nomegestrol acetate (NOM-Ac; TX 066, 17 alpha-acetoxy-6-methyl-19-nor-4,6-pregnadiene-3,20-dione, CAS 58652-20-3), a 19-nor-progesterone derivative showed a significant antiandrogenic effect on ventral prostate and seminal vesicles weights of immature castrated rats treated with testosterone. However, this effect was 20 times less potent than that of cyproterone acetate (CYP-Ac). In contrast to norethindrone acetate, a 19-nor-testosterone derivative. NOM-Ac was totally devoid of androgenic effect on male accessory sex organs. Relative binding affinity against 3H-testosterone for androgen receptor of rat ventral prostate showed an IC50 of 22.6 +/- 4.0 and 21.1 +/- 5.3 nmol/l for NOM-Ac and CYP-Ac, respectively, while Dixon analysis disclosed a Ki of 7.58 +/- 0.94 and 4.30 +/- 0.17 nmol/l. Then, Scatchard plot analysis of 3H-NOM-Ac binding revealed a KD of 20.9 +/- 3.1 nmol/l and a Bmax of 217 +/- 27 fmol/mg protein.

Androgen Antagonists↗

PubMed1994

Hypoxia increases the activity of Ca(2+)-sensitive K+ channels in cat cerebral arterial muscle cell membranes.

The cellular mechanisms mediating hypoxia-induced dilation of cerebral arteries have remained unknown, but may involve modulation of membrane ionic channels. The present study was designed to determine the effect of reduced partial pressure of O2, PO2, on the predominant K+ channel type recorded in cat cerebral arterial muscle cells, and on the diameter of pressurized cat cerebral arteries. A K(+)-selective single-channel current with a unitary slope conductance of 215 pS was recorded from excised inside-out patches of cat cerebral arterial muscle cells using symmetrical KCl (145 mM) solution. The open state probability (NPo) of this channel displayed a strong voltage dependence, was not affected by varying intracellular ATP concentration [(ATP]i) between 0 and 100 microM, but was significantly increased upon elevation of intracellular free Ca2+ concentration ([Ca2+]i). Low concentrations of external tetraethylammonium (0.1-3 mM) produced a concentration-dependent reduction of the unitary current amplitude of this channel. In cell-attached patches, where the resting membrane potential was set to zero with a high KCl solution, reduction of O2 from 21% to < 2% reversibly increased the NPo, mean open time, and event frequency of the Ca(2+)-sensitive, high-conductance single-channel K+ current recorded at a patch potential of +20 mV. A similar reduction in PO2 also produced a transient increase in the activity of the 215-pS K+ channel measured in excised inside-out patches bathed in symmetrical 145 mM KCl, an effect which was diminished, or not seen, during a second application of hypoxic superfusion. Hypoxia had no effect on [Ca2+]i or intracellular pH (pHi) of cat cerebral arterial muscle cells, as measured using Ca(2+)- or pH-sensitive fluorescent probes. Reduced PO2 caused a significant dilation of pressurized cerebral arterial segments, which was attenuated by pretreatment with 1 mM tetraethylammonium. These results suggest that reduced PO2 increases the activity of a high-conductance, Ca(2+)-sensitive K+ channel in cat cerebral arterial muscle cells, and that these effects are mediated by cytosolic events independent of changes in [Ca2+]i and pHi.

Animals↗

PubMed1994

Nasal and pulmonary toxicity of glutaraldehyde in mice.

A concentration-dependent expiratory bradypnea, indicative of sensory irritation, occurred during a 15-min oronasal exposure of mice to glutaraldehyde in the concentration range of 0.7-4.5 ppm. The level of exposure which led to a 50% decrease in the respiratory rate (RD50) was found to be 2.6 ppm. For assessment of nasal toxicity, mice were exposed to glutaraldehyde vapours with concentrations of 2.6, 1.0, 0.3 ppm for periods of 6 h/day over the course of 4, 9 and 14 days and were immediately killed. Recovery was studied with another group of mice exposed to 1.0 ppm for 14 days and sacrificed after 1, 2 and 4 weeks rest time. Control groups were concurrently exposed to clean filtered air. The earliest lesions were observed in the respiratory epithelium of the septum, the naso- and maxilloturbinates, after 4 days of exposure to 0.3 ppm. Severe histopathological changes were still observed 2 weeks after the end of the exposure to 1.0 ppm. No exposure-related histological abnormalities were detected in the trachea and lungs. In conclusion, this experiment demonstrates that repeated exposure to 1/10 RD50 is associated with upper respiratory tract damage in mice, and this value does not seem to be an acceptable concentration limit for occupational exposure.

Administration, Inhalation↗

PubMed1994

Persistent polyclonal lymphocytosis with binucleated B lymphocytes: a genetic predisposition.

Persistent lymphocytosis is usually associated with a malignant lymphoproliferative disease (MLPD). We report six female patients presenting a chronic, moderate lymphocytosis of 2-16 years duration with atypical binucleated lymphocytes on peripheral blood smears. Further investigation showed a polyclonal increase in serum IgM and HLA-DR7 phenotype in all patients. The B cells were polyclonal because Southern hybridization of DNA and polymerase chain reaction failed to demonstrate a clonal rearrangement of immunoglobulin heavy chain genes. Peripheral blood examination showed binucleated lymphocytes in a family member of two of the cases; taken together with the association with HLA-DR7 these data suggest a genetic predisposition. The identification of this benign syndrome is important in order to prevent its misdiagnosis as a MLPD.

Adult↗

PubMed1994

Hypoxia activates a potassium current in isolated smooth muscle cells from large pulmonary arteries of the rabbit.

Severe hypoxia (< 10 mmHg) induced relaxation of precontracted rings obtained from large diameter (3-4 mm) pulmonary arteries of the rabbit but had no effect upon their basal tone nor upon the length of enzymatically isolated smooth muscle cells. In isolated smooth muscle cells severe hypoxia increased a voltage-gated K+ current. The magnitude of this response depended upon the degree of intracellular Ca2+ buffering, being abolished by 10 mM EGTA. The hypoxic response of K+ currents demonstrates a direct effect of hypoxia on pulmonary artery smooth muscle cells via a modulation of potassium channel activity.

Animals↗

PubMed1994

A new monoclonal antibody (3A5) that recognises a fixative resistant epitope on tissue macrophages and monocytes.

AIMS: To develop a monoclonal antibody specific for human macrophages in routinely processed material. METHODS: The monoclonal antibody was derived from a mouse popliteal lymph node after subcutaneous immunisation in the footpad with fragments of human spleen depleted of lymphocytes and erythrocytes. RESULTS: 3A5 is a monoclonal antibody reactive with macrophages, monocytes, and histiocytes in routinely processed (formalin fixed, paraffin wax embedded) human tissue specimens. Unlike the well known panmacrophage marker KP1 (CD68), neither dendritic cells (interdigitating cells, Langerhans' cells, and microglia) nor myeloid, lymphoid, or epithelial cells stained with 3A5. CONCLUSION: As the staining pattern of 3A5 is restricted, compared with other macrophage markers and the recognised epitope survives common fixation and embedding procedures, 3A5 is a valuable marker for histiocytes and macrophages in routine diagnostic applications.

Animals↗

PubMed1994

Effects of lipoxygenase products of arachidonate metabolism on parathyroid hormone secretion.

High extracellular Ca2+ (Ca2+ ec) stimulates the formation of inositol phosphates and diacylglycerol and activates phospholipase A2 in porcine parathyroid cells. Ca2+ ec action is also coupled to the formation of arachidonic acid, the precursor of both the cyclooxygenase and lipoxygenase (LO) pathways. We previously reported that LO pathway products might act as second messengers and play a part in regulating PTH secretion by Ca2+ ec. We have now investigated the effects of hydroxyeicosatetranoic acids (HETEs) on PTH secretion. Collagenase-dispersed porcine parathyroid cells were incubated in low [Ca2+] (0.5 mM, maximal stimulation) with or without HETEs for three 15-min periods. 12- and 15-HETEs inhibited PTH secretion in a dose-dependent manner from 10(-12) to 10(-9) M. Maximal inhibition was with 10(-9) M. Since 12- and 15-HETEs are the metabolic reduction products of 12- and 15-HPETEs, we also examined the effect of those precursors on PTH release. 12- and 15-hydroxyperoxyeicosatetranoic acids (HPETEs) were more potent inhibitors of PTH secretion. The threshold concentrations of both HPETEs that inhibited PTH release were lower than those for HETEs: 10(-9) M suppressed PTH secretion. This effect is comparable to that of high [Ca2+] (2 mM). This provides new evidence that products of 12-LO and 15-LO pathways are potent inhibitors of PTH secretion.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1994

The experience of the CHU Liège with conservative surgery in the management of upper urinary tract tumors.

A review of 20 cases of conservative surgery for urothelial tumors of the upper tract is presented. The morbidity is limited; the recurrence rate is around 15% in the ipsilateral urinary tract with a mean follow up of 41 months. Conservative surgery does not seem to carry a higher fatal risk as compared to more radical surgery. It has indications in some cases which are defined.

Adult↗