[Bronchial peptidergic control and concepts of neurogenic inflammation].
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Biomedical subjects
Publications and source records attributed to G Pauli.
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Owing to a technical analysis enabling the detection of mineral elements present in trace amounts in small volumes, an analysis of the liquid obtained in 148 broncho-alveolar lavages could be studied. The elements consistently recovered were as follows: iron, copper, zinc, nickel, lead and titanium. Normal values were established. In the absence of exposure, there was no significant difference distinguishing the different pulmonary diseases studied. In occupational disease, the presence of iron in large quantities, tungsten, nickel and rare earths could be shown objectively, as well as the persistence of gold or iodine after medical absorption. However, this preliminary work does not allow one to establish a formal correlation between the alveolar concentrations obtained and the pulmonary disease observed.
Allergy reactions may be regarded as resulting from exposure to allergens of subjects who are genetically predisposed to synthesize IgE. The presence of allergens in the environment is necessary to acquire sensitization. With some allergens, sensitization seems to develop very rapidly. The introduction or presence in the environment of certain allergens, such as house dust mites, may increase the prevalence of asthma. Despite conflicting reports, in atopic subjects exposure to pet animals also is a risk factor. Introducing foreign proteins prematurely into infant's food has been considered a factor that facilitates the development of allergic diseases. Contact with occupational allergens results in allergic manifestations in less than one-third of the subjects exposed, which suggests that genetic factors play a predisposing role. Beside exposure to allergens, non-specific environmental factors, such as chronic inhalation of tobacco smoke or atmospheric pollutants (e.g. ozone, SO2, NO2, particles of burnt fuels) might contribute to sensitization. The part played by viral infections (RSV or influenza virus) in the triggering of allergic diseases has often been reported. Interactions between irritants and allergens may encourage the development of respiratory allergy.
Muscarinic receptor subtypes in human, guinea pig and rat lung tissue were characterized by radioligand binding, and functional studies were carried out on guinea pig and rat tissues. Control binding experiments were performed with membranes from human tissues rich in M1 (hippocampus), M2 (pons-medulla) and M3 (salivary gland) receptor subtypes. Competitive binding experiments with atropine and 4-diphenylacetoxy-N-methylpiperidine methobromide did not reveal any tissue selectivity of these ligands. Pirenzepine, a selective M1 antagonist with 11-2[[2-[(diethylamino)methyl]-1-piperidinyl] acetyl]-5, 11-dihydro-6H-pyrido[2,3-b] [1,4]-benzodiazepine-6-one (AF-DX116), a selective M2 antagonist, made it possible to characterize muscarinic subtypes. In hearts from the three species, the low affinity for pirenzepine and the high affinity for AF-DX116 were related to M2 receptors. In rat lung, the high affinity for AF-DX116 and the intermediate affinity for pirenzepine indicate M2 and M3 subtypes. Guinea pig and human lung tissues contain 48 and 67%, respectively, of muscarinic binding sites with high affinity for pirenzepine (M1). The second muscarinic receptor population in human lung might be classified as M3 in view of the cardioselectivity of AF-DX116, but the occurrence of M2 cardiac-type receptors could not be excluded. In guinea pig lung, both M2 and M3 subtypes might occur in addition to M1 receptors. Muscarinic stimulation led to the contraction of guinea pig and rat lung strips but did not significantly affect human lung strips. We suggest that presynaptic M2-muscarinic receptors modulated the M3-induced contraction in the guinea pig lung smooth muscle.
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The organization of envelope projections (knobs) of four different isolates of the human immunodeficiency virus types 1 and 2 (HIV-1 and -2) was studied using surface replica and thin section electron microscopy (EM) in combination with rotational image enhancement. All HIV strains show an identical organization of knobs on the virus envelope. The surface of an "ideal", well-preserved HIV particle is studded with 72 knobs arranged in a T = 7 laevo symmetry. The role of the p 17 protein, which is coating the inner leaflet of the viral envelope, is discussed as a matrix protein functioning as a scaffold for the envelope and its projections during morphogenesis as well as with mature virions.
A library of subgenomic fragments of bovine herpesvirus type 2 (BHV-2) DNA was constructed in the expression cloning vector lambda gt11 and screened with monoclonal antibodies to the glycoprotein gb BHV-2, which is homologous to glycoprotein gB (gB-1) of herpes simplex virus type 1 (HSV-1). Lambda gt11 clones containing gB BHV-2-specific sequences were used to identify lambda EMBL3 vectors with DNA inserts which contained the complete gB BHV-2 gene. Nucleotide sequencing revealed that the gB BHV-2 gene is highly conserved compared to gB-1. The amino acid sequences and the predicted secondary structures of both glycoproteins are very similar. Two further open reading frames (ORF) in close vicinity to the gene encoding gB BHV-2 showed considerable homology to HSV-1 genes. They code for the major DNA-binding protein (dbp) of BHV-2 and a putative 72-kDa polypeptide. The gene of the latter protein corresponding to ICP18.5 of HSV-1 is interspersed between the ORFs of gB BHV-2 and the dbp of BHV-2. All three genes map in the unique long region of the genome. Their homology and the colinear arrangement compared to HSV-1 indicate a close relationship between the two viruses.
Bovine herpesvirus 2 (BHV-2) specifies a glycoprotein of 130 kDa (gB BHV-2) which shows extensive homology to glycoprotein B (gB-1) of herpes simplex virus 1 (HSV-1). The BHV-2-specific 130-kDa glycoprotein is able to induce cross-reacting antibodies, some of which even cross-neutralize HSV-1. In order to determine the genome localization of gB BHV-2 and in order to identify conserved antigenic domains in both glycoproteins, we established libraries of subgenic fragments of BHV-2 and HSV-1 DNA in the prokaryotic expression vector lambda gt11 and screened them with cross-reacting monoclonal antibodies which allowed us to identify recombinant lambda gt11 clones expressing gB fusion protein. Nucleotide sequencing of inserted DNA fragments within these recombinant lambda gt11 clones revealed that they originated from the carboxy-terminal part of the major DNA-binding proteins (dbp) of BHV-2 (dbp BHV-2) and its counterpart ICP8 in HSV-1. Antisera raised against the beta-galactosidase fusion protein of recombinant phage lambda-113/2 coding for an 84 amino acid (aa) polypeptide originating from dbp BHV-2 neutralized infectivity of BHV-2 and HSV-1 in the presence of complement and precipitated [3H] glucosamine-labeled gB BHV-2 and gB-1. This antiserum also reacts with ICP8 and presumably with dbp BHV-2. Two hypotheses are discussed to explain this unexpected result: (i) epitopes in the carboxy-terminal part of gB BHV-2 and gB-1 are similar to antigenic determinants in the amino-terminal region of the gBs, thus providing cross-reacting antibody-binding sites; (iii) during gene expression a carboxy-terminal part of dbp BHV-2 and ICP8 genes might be spliced to the amino-terminal region of the glycoproteins gB BHV-2 and gB-1.
Envelope proteins of bovine herpesvirus type 2 (BHV-2) and herpes simplex virus types 1 and 2 (HSV-1, -2) share cross-reacting determinants. Monoclonal antibodies directed against epitopes of a 130K glycoprotein of BHV-2 detect determinants on the surface of infected cells and react either with cytoplasmic or nuclear antigens. Biological and biochemical characterization of the proteins recognized by these antibodies revealed that the BHV-2 specific 130K glycoprotein and the gB of HSV share common epitopes. Some of them are involved in the neutralization of HSV and BHV-2.
The production and properties of monoclonal antibodies raised against herpes simplex virus type 1 (HSV-1)-infected cell nuclei are described. Biological and immunochemical assays revealed that these antibodies recognize four different proteins in HSV-1-infected cells. Four antibodies reacted with the major DNA-binding protein (ICP8) and six with the 65K DNA-binding protein. Two antibodies detected the ICP35 family of proteins and one antibody bound to a protein with an apparent mol. wt. of 60K. Immune electron microscopy showed that the major DNA-binding protein had a patchy distribution, whereas the 65K DNA-binding protein was evenly spread in the infected cell nuclei. The 60K protein as well as the polypeptides of the ICP35 family were preferentially found associated with the viral capsid.
Monoclonal antibodies (MAbs) were raised against gag proteins of human immunodeficiency virus type 1 (HIV-1), strain HTLV-IIIB. One of 29 antibodies was specific for p17 of HIV-1. Twenty of 28 MAbs reactive with the major core protein p24 of HIV-1 showed cross-reactivity with HIV-2, and five of these also detected the corresponding antigens of simian immunodeficiency virus (SIVmac). The MAbs were reactive in several tests, i.e. ELISA, immunostaining of Western blots, immunofluorescence, alkaline phosphatase-anti-alkaline phosphatase immunocytochemistry and immunoelectron microscopy. The submembrane protein p17 was clearly localized within the virion.
Guanine is the major nitrogenous waste product in arachnids. It may serve as an indicator for allergenic mite faecal pellets. The present study assesses the correlation between the mit allergenicity of different house dust (HD) samples and their guanine content. Guanine content in HD samples was evaluated either by the Acarex-Test or determined quantitatively, especially for in-vitro methods. Using intradermal tests in selectively sensitized Dermatophagoides pteronyssinus (Dpt) patients, we evaluated the mite allergenicity of eight extracts obtained from HD samples with varying guanine contents. The weal area appeared to be proportional to the HD samples' guanine content. A three-fold increase in skin reactivity was observed when the guanine content varied from 0.06% to more than 1%. Patients allergic to HD but not to Dpt had no significant reactions with HD extract prepared from a guanine-rich HD sample. For eighteen different HD samples coupled to paper discs, the percentage Dpt RAST binding values obtained with a Dpt-selectively sensitized patient serum pool was correlated with the guanine concentrations of HD samples (P less than 0.01). The potencies of different HD extracts obtained from HD samples that varied in guanine content were also clearly distinguished on histamine-release titration curves. House dust obtained from homes at high altitude or from hospitals was generally guanine free. The HD sample guanine contents in homes where twelve Dpt-sensitized patients experienced symptoms were significantly higher than in homes where these patients were symptom free. The guanine colour test, a quick and easy technique, represents an important new development in indoor environmental investigations. It makes it possible to demonstrate mite faecal exposure and can be used to monitor the effectiveness of mite allergen avoidance measures.
The month of birth distribution for 1301 French patients born between 1953 and 1975 with at least one positive skin test was compared to that of the whole population. A chi-square test was performed, and the expected birth month distribution of the groups calculated from the INSEE* data for 1953-1975. All patients underwent skin testing with house dust, Dermatophagoides pternyssinus (Dpt), cat and dog allergens, grass, tree and weed pollens, and moulds. The only study criterion was a positive skin test unrelated to any specific disorder. A significant difference in month of birth distribution was observed 1) for patients with positive skin test to grass pollen, with a high rate of births from January to May, and 2) for patients with mould sensitization, with a low rate of births in April, May and December. Tree and weed pollens, house dust and Dpt showed no significant relation with month of birth. For cat and dog allergens, the observed and expected distributions of birth month were similar. For the whole sensitized population the birth rate tended to be low in December except for the cat and dog sensitized. Our study confirms the well-known seasonal peak of births in the first 5 months of the year for grass pollen sensitized patients. No consistent monthly or seasonal tendency could be statistically demonstrated for other allergens except moulds.
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The diagnosis of occupational asthma requires the integration of a multiplicity of data; the history, cutaneous skin tests, respiratory function tests and non-specific tests of bronchial hyper-reactivity and specific bronchial provocation tests. The history remains fundamental in the investigation of occupational asthma. It should particularly search for the presence of an atopic trait, the occurrence of similar disorders in members of the same firm and also the timing of symptoms in relation to the occupational activities. Cutaneous tests are particularly helpful in IgE-mediated asthma in relation to the inhalation of animal or vegetable materials of glycoprotein origin. For haptens, the need for their prior coupling to a protein carrier causes problems which have not been entirely resolved. Laboratory tests (RAST, histamine liberation, TDBH...) run into the same snags. Respiratory function and non specific bronchial provocation tests confirm the diagnosis of asthma and enable the medium and long term progress to be assessed. Specific bronchial provocation tests are the most appropriate tests to establish an aetiological diagnosis in occupational asthma. Different technical methods are possible: quantitative administration of allergen, aerosols, and realistic tests using exposure chambers to achieve true test doses and to obtain dose dependent responses. The products responsible for occupational asthma are multiple and are gathered into two tables. The different substances are characterised in a simplified manner. First animal matter (mammalian and arthropod allergens), secondly substances of vegetable origin (roots, leaves, flowers, grain and flour, wood and its derivatives) and finally chemical products. The chemical products are primarily from the pharmaceutical and metal industries and above all from the plastics industry.
Forty-five patients with severe, poorly controlled asthma, including 23 corticosteroid-dependent patients, were treated with a preparation of beclomethasone dipropionate aerosol delivering 250 mcg per puff. The daily dose ranged from 1000 to 2000 mcg. The mean follow-up period was 14 +/- 7 months, and 11 patients have now been followed up for more than 2 years. Forty-two patients were improved, and total withdrawal of continuous steroid therapy could be achieved in 13 cases. Treatment remained effective in long term use, provided a minimum of 1000 mcg/day was given. However, despite clinical improvement the obstructive syndrome persisted in 65% of the patients.
The commercial availability of high-dose inhaled corticosteroid preparations for the treatment of asthma offers an occasion for reviewing the different mechanisms of action of glucocorticoids notably glucocorticoids, notably their interference with lipocortin protein synthesis and arachidonic acid metabolism. A favourable effect on bronchial hyper-reactivity and on delayed hypersensitivity reactions has also been observed. The problems raised by the various preparations responsible for varying degrees of systemic activity, the difficulties inherent in the use of inhalers and the side-effects of these products are discussed. The effectiveness and safety of the current high-dose inhaled preparations are emphasized.