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Biomedical subjects

G Pauli

Publications and source records attributed to G Pauli.

At least 163 records · Page 9Linked to original sources
PubMed1996

[Passive smoking and bronchial cancer: a difficult relation to establish].

There is a certain controversy over whether there is a relationship between passive smoking and bronchogenic cancer. The first epidemiology studies has found a small increase in the relative risk. Experimental work in animals have demonstrated that the smoke produced by a burning cigarette contains more cancerogenic agents than the smoke inhaled by a smoker. In man where only epidemiology studies are possible, the problem lies in quantifying exposure to passive smoking. Questionnaires or assay of markers such as CO and HbCO, thiocyanates, nicotine and its metabolite cotinine and certain adduits have been used. There are many possibilities for bias in such studies including classification of smokers among non-smokers, confounding factors (age, profession, eating habits), subjects' memory, and data collection errors. Meta-analyses have attempted to overcome the lack of power in many studies. Some of these meta-analyses have used correction factors to take into account publication bias. Meta-analyses have led to the conclusion that the risk for women exposed to their husband's tobacco smoke is somewhat increased compared with a non-smoking non-exposed population. The relative risk is about 2-fold higher and has been observed in Greece. The existence of a dose-intensity relationship has not been confirmed. Likewise, it is impossible to conclude concerning the role of passive smoking in children due to the small amount of data available.

Bronchial Neoplasms↗
PubMed1995

Spontaneous apoptosis of dendritic cells is efficiently inhibited by TRAP (CD40-ligand) and TNF-alpha, but strongly enhanced by interleukin-10.

In the lymphoid tissues, adaptive immune responses are initiated by the interaction of interdigitating dendritic cells (IDC) with naive T cells. To understand this interplay better, we used mature Langerhans cells (mLC), migrating from human epidermis, as the correlate of IDC ex vivo to evaluate the different effects of tumor necrosis factor (TNF)-alpha. TNF-related activation protein (TRAP; CD40-ligand) and interleukin-10 (IL-10) on induction or prevention of apoptotic cell death in these cells. Spontaneous decrease of mLC viability in culture was due to apoptosis, as determined by the appearance of typical morphological changes such as dilatation of the endoplasmic reticulum (ER), chromatin condensation and membrane blebbing. IL-10 strongly reduced mLC viability, whereas TRAP and TNF-alpha facilitated the survival of mLC. Spontaneous DNA fragmentation was detectable after 24 h in culture. IL-10 led to an earlier onset of DNA fragmentation, whereas TRAP and TNF-alpha delayed internucleosomal DNA cleavage. We found that IL-10-treated mLC were readily ingested and removed by macrophages. TNF-alpha and TRAP, in contrast, reduced engulfment of mLC by macrophages. Interestingly, IL-10, even at low concentrations, reverted the effects of TNF-alpha and TRAP in inhibiting mLC apoptosis. Furthermore, IL-10 led to the down-regulation of various surface antigens, especially of CD86 and CD54, whereas TNF-alpha and TRAP enhanced the expression of MHC class I and II antigens and of the accessory molecules CD40, CD54, CD80 and CD86. Taken together, these results show that mLC spontaneously undergo apoptosis in culture and that the progression of mLC to apoptosis is inhibited by TRAP and TNF-alpha, but accelerated by IL-10.

Apoptosis↗
PubMed1995

Determinants of HIV infection and recent risk behaviour among injecting drug users in Berlin by site of recruitment.

This study investigated differences in prevalence and determinants of HIV infection, and in recent risk behaviour (previous 6 months) among injecting drug users (IDUs) who are in contact with different types of services for IDUs in Berlin. Participants (n = 557) were recruited from drug-free long-term treatment centres, a storefront agency and a syringe exchange bus. HIV seroprevalence was lowest (3.9%) at the treatment centres, and highest among IDUs at the storefront agency (20.7%). In logistic regression, independent risk factors for HIV infection were duration of injecting drug use, borrowing syringes in prison, sex with HIV-positive partners, and prostitution. Syringe sharing in prison was the most important independent determinant of HIV infection among all three subpopulations of IDUs. Participants entering long-term treatment were most likely, and IDUs at the syringe exchange bus were least likely to have borrowed and passed on syringes in the previous 6 months. In logistic regression, site of recruitment was independently associated with recent borrowing of syringes, but not with condom use. Injection of drugs other than heroin only, and injecting in prisons, were also independent predictors of recent borrowing. The results indicate that IDUs entering treatment form an important target group for health education. There is a need for AIDS prevention measures in prisons. The comparatively low levels of recent injection risk behaviour among IDUs at the syringe exchange bus suggest that this type of intervention may be effective in harm reduction.

Adult↗
PubMed1995

Replication pattern of human immunodeficiency virus type 1 in mature Langerhans cells.

Langerhans cells (LC), the dendritic antigen presenting cells of the skin, mature into potent immunostimulatory cells during migration to regional lymph nodes, where they are identified as interdigitating cells (IDC). Since mature Langerhans cells (mLC) resemble IDC in phenotype and immunostimulatory capacity, we examined whether these cells were susceptible to infection with macrophagetropic and lymphotropic strains of human immunodeficiency virus type 1 (HIV-1). Highly purified cell preparations of mLC migrating from human epidermis expressed high amounts of major histocompatibility complex (MHC) class I and II antigens and of the accessory molecules CD40, CD80 and CD86, indicative of the phenotype of potent immunostimulatory cells. CD4 expression was upregulated on mLC during cultivation, independent of the presence of tumour necrosis factor alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the culture medium. The macrophagetropic HIV-1 strain SF162 replicated to higher titres in mLC than the lymphotropic strain IIIB. Both strains induced syncytia, with SF162 showing a more rapid cytopathic effect. Addition of TNF-alpha enhanced virus production, due to better cell viability under TNF-alpha treatment, whereas GM-CSF did not significantly influence viability of cells and replication pattern of the virus. These findings suggest that in the infected individual IDC in lymph nodes may function as target cells for HIV-1.

Antibodies, Monoclonal↗
PubMed1995

First report of anaphylactic reaction after fig (Ficus carica) ingestion.

We report an anaphylactic reaction which occurred very shortly after ingestion of a fresh fig. The IgE-dependent mechanism was demonstrated on the basis of positivity of the prick test performed with fresh fig (Ficus carica) extract. In addition, we were able to detect specific IgE to the same extract in the serum. The patient did not demonstrate sensitization to other common allergens involved in respiratory and food allergies. However, detection of specific IgE to F. benjamina indicated a sensitization to weeping fig. The CAP F. benjamina was partially inhibited by preincubation of the serum with fig extract, suggesting that these two species of Ficus share some common allergens. In this context, the assumption can be made that weeping fig was responsible for the initial sensitization in this patient.

Aged↗
PubMed1995

Potential for lung sound monitoring during bronchial provocation testing.

BACKGROUND: The use of lung sound monitoring during bronchial provocation testing has not been clearly demonstrated. The appearance of wheeze and changes in inspiratory breath sound intensity have been analysed and related to changes in spirometric parameters and to airways hyperresponsiveness. METHODS: Lung sounds were recorded in 38 patients undergoing a routine carbachol airway challenge (CAC) test. Spirometric testing was performed before and after the inhalation of each of five cumulative doses of 320 micrograms carbachol; a fall in forced expiratory volume in one second (FEV1) by 20% or more was considered as significant. Lung sound analysis was carried out using a computerised system. RESULTS: The CAC test was positive (CAC+) in 21 patients and negative (CAC-) in 17. At the final stage of the challenge, wheeze was identified in 10 positive patients (48%) and in one negative patient (6%); in non-wheezers the inspiratory breath sound intensity decreased significantly from baseline in 11 CAC+ patients (mean (SD) change -35 (24%)) but not in 16 CAC- patients (mean (SD) change 5 (24%)). In all non-wheezers a linear relationship was found between breath sound intensity and the squared inspiratory airflow (r = 0.53-0.92) which became looser after the inhalation of carbachol. CONCLUSION: When unertaking bronchial provocation testing the accurate identification of wheeze may prove useful in avoiding or shortening the test because of the presumed relationship between wheeze and airways hyperresponsiveness. Changes in breath sound intensity may also be useful, but further studies are required to define the threshold for significant changes in this index.

Adult↗
PubMed1995

Systemic sarcoidosis initially presenting as an orbital tumour.

A 73 year old woman presented with redness, itching and painless proptosis of the left eye. Clinical examination and computed tomographic (CT) scan of the orbit revealed a postero-ocular mass, the biopsy of which showed a noncaseating, giant cellular, epithelioid granuloma compatible with sarcoidosis. The patient had no respiratory complaints, but the thoracic CT scan showed multiple bilateral hilar and mediastinal adenopathies. Gallium scan showed increased uptake in both hilar regions, in the left orbit and in the right parotid gland. Multiple bronchial biopsies revealed sarcoid granulomas, with a bronchoalveolar lavage (BAL) cytological pattern of active sarcoidosis. The evolution was favourable with prednisolone given at a dose of 0.5 mg.kg-1 daily. It is suggested that in an unusual presentation of sarcoidosis, a thorough search should be made for localization at other sites, lungs in particular, even in the absence of respiratory complaints.

Aged↗
PubMed1995

[Metrology of airborne particles carrying the principal air allergens].

The relationship between exposure to aeroallergens and the acquisition of allergy and asthma has been shown over the past ten years. Thanks to new developments for detecting major allergens amongst the principle aeroallergens, in future it will be possible to measure their airborne concentration and to determine the particle size of particles carrying them. We report the results obtained from three studies in which we have shown that airborne mites Group I and II and cockroaches Bla g 1 and Bla g 2 allergens have a broadly similar airborne behaviour. That is to say that they are not measurable unless the atmosphere is artificially disturbed and they are carried principally on particles of > 10 microns. On the other hand, 30-40% of cat allergens are carried on particles < 5 microns and measurable in the air without any artificial disturbance. According to our data and those of the literature, we propose a different classification for aeroallergens according to characteristic aerodynamics. Although some progress in the standardisation of techniques for sampling airborne allergens may have been accomplished, other studies are required to improve their reliability in order that airborne measurements can become a marker of allergic exposure in both domestic and occupational environment.

Air↗
PubMed1995

Cell specific uptake of antiretroviral drugs: AZT coupled to LDL inhibits HIV replication in human macrophages.

Macrophages, besides helper T-lymphocytes, are target cells for the human immunodeficiency virus (HIV). We report on a mechanism to deliver selectively antiretroviral drugs to cells of the monocyte/macrophage lineage. These cells and cells of the endothelium express scavenger receptors which mediate the transport of modified low density lipoprotein (LDL). LDL modified by covalently bound azidothymidine (AZT), a potent inhibitor of HIV replication, is internalized via this pathway into human macrophages. Treatment of HIV-1 infected human macrophages with AZT-LDL showed in vitro efficient inhibition of viral replication. In contrast, HIV replication in T-lymphocytes (Molt 4/8), which do not express scavenger receptors, is not inhibited by AZT-LDL but by free AZT.

Antiviral Agents↗
PubMed1995

[Importance of measuring exposure to the principal indoor allergens in allergic asthma].

Domestic allergens, such as mite and cat allergens, are a leading cause of allergic asthma. Allergen exposure is a risk factor for sensitization. Allergens also play a major role in the development of inflammation and non specific bronchial hyperreactivity as well as in the apparition and modulation of symptomatic asthma. The development of new means of detecting allergens (i.e. immunochemical assays including monoclonal antibodies, quantitative and semiquantitative guanine measurements for mite allergens) has made possible to identify allergens sources and reservoirs. The form in which domestic allergens become airborne is important. The group I and II allergens from mites, the major cockroach allergens are carried on large particles (mean size > 10 microns diameter); in contrast, the major cat allergens are airborne on small particles (40% < 5 microns). Guanine, a metabolic excretion product of mites, is used as a marker for mite feces and is correlated with the presence of major allergens from mites. A colorimetric method (Acarex-TestR) provides a simple and inexpensive method of assaying indoor mite allergen exposure for both doctor and patient alike. By using Acarex-TestR it is possible to evaluate the mite allergen exposure for a population in a particular country. The detection of allergens sources and reservoirs, the quantification of domestic allergens has enabled the evaluation of the effect of a reduction in allergen exposure to be better assessed. Recognition of the risks, environmental control and reduction in allergen loads, should be among the objectives of asthma management.

Air Pollution, Indoor↗
PubMed1994

CD4 expressing human 293 cells as a tool for studies in HIV-1 replication: the efficiency of translational frameshifting is not altered by HIV-1 infection.

An adherent human cell line (293) was made susceptible for HIV-1 infection by transfer of a CD4 expression plasmid. These cells could be infected with HIV-1 and produced infectious virus up to a titer of 10(6) TCID50/ml releasing p24 protein up to 1 micrograms/ml. Since they can be efficiently transfected with reporter genes, these cells are a suitable model system to monitor biochemical events during productive infection of HIV-1 and can be used for antiviral drugs. Translational frameshifting determines the balance of the structural Gag versus the catalytic Pol proteins which is probably crucial for correct virus assembly. We have genetically engineered CD4 expressing 293 cells with a sensitive in vivo reporter system to monitor the extent of frameshifting in HIV-1-infected versus uninfected cells. During the time course of productive HIV-1 infection the low efficiency of ribosomal frameshifting is not altered.

CD4 Antigens↗
PubMed1994

Determination of the size of HIV using adenovirus type 2 as an internal length marker.

The size of a virion is a key criterion to its proper classification and may have implications in many practical aspects. Size determinations by thin section electron microscopy often result in length aberrations of more than 10% because of a number of preparative and instrumental inaccuracies, e.g. specimen shrinkage or swelling and unreliable calibration. Using adenovirus type 2 as an isometric size marker for internal calibration, we have determined the diameters of mature and immature HIV-1 to be 110 to 128 and 132 to 146 nm, respectively. The marker had been used either as a purified particle suspension added to the HIV producing culture, or adenovirus had been propagated together with HIV by infecting HIV producing cells. Using well characterized isometric markers, e.g. an icosahedral virus, in thin section electron microscopy appears to be a suitable technique for viral size determinations.

Adenoviruses, Human↗
PubMed1994

Inhibition of infectious human immunodeficiency virus type 1 particle formation by Gag protein-derived peptides.

Sequential overlapping Gag protein-derived oligopeptides of human immunodeficiency virus type 1 (HIV-1) 22 to 24 amino acids long, were synthesized and tested in vitro for antiviral activity. Two synthetic peptides, one derived from the matrix protein p17 (NPGLLETSEGCRQ, amino acids 47 to 59) and one located in the capsid protein p24 (PAATLEEMMTA, amino acids 339 to 349) inhibited the production of infectious virus when added to HIV-1-infected cultures when used in the range of 20 to 200 micrograms/ml. As shown by thin section electron microscopy, peptide treatment resulted in the release of immature, deformed virus particles suggesting that the two peptides interfered with assembly and maturation. Other Gag protein-derived oligopeptides had little or no influence on virus production. To characterize further the functionally active regions we synthesized peptide derivatives with three consecutive amino acids substituted by alanine; they did not cause inhibition. Therefore the regions responsible for inhibition were located between amino acids 50 to 61 in p17, and 342 to 350 in p24. These observations might lead to the development of a new antiviral strategy affecting the late stage of virus replication.

Amino Acid Sequence↗
PubMed1994

Breath sound intensity in patients with airway provocation challenge test positive by spirometry but negative for wheezing: a preliminary report.

Wheeze detection has been proposed as an indicator of bronchial responsiveness during airway provocation challenge (APC) test. However, there is evidence that wheeze may be occasionally absent in subjects whose APC is positive by spirometry. We tested the hypothesis that, in this case, inspiratory breath sound intensity (BSI) over the chest is noticeably decreased. Six patients (3 asthmatics and 3 patients with atopic rhinitis) were selected, whose forced expiratory volume in 1 s (FEV1) fell by 20% or more at the end point of the challenge in the absence of concurrent wheezing. Lung sounds were recorded at the right posterior lung base and analysed by computer. Inspiratory BSI at the end point of the challenge was markedly decreased in all patients, a change almost completely reverted by the inhalation of 200 micrograms of salbutamol in all of them but one. These results support the view that BSI monitoring is potentially useful as an indicator of bronchoconstriction during bronchial provocation testing. However, further studies are necessary to confirm this hypothesis.

Adolescent↗
PubMed1994

HLA class II alleles in isocyanate-induced asthma.

Studying genetic factors that control human immune responsiveness may further our understanding of specific types of asthma in which the role of immune factors is uncertain to date. HLA Class II gene products are involved in the control of immune responses. Therefore, we investigated whether HLA Class II genetic markers contribute to susceptibility or resistance to isocyanate-induced asthma (IAA) in exposed workers. We collected venous blood samples from two groups of unrelated white adults: (1) patients with isocyanate-induced asthma documented by a positive inhalation challenge; and (2) exposed individuals with no history of IAA. The second exon of DQA1, DQB1, DPB1, and DRB genes was selectively amplified by the polymerase chain reaction (PCR) method. HLA typing was carried out by the PCR-RFLP method, which allowed discrimination of most HLA DQA1, DQB1, DPB1, and DRB alleles. No significant difference was found in the distribution of DPB1 alleles between patients and control subjects. Allele DQB1*0503 and allelic combination DQB1*0201/0301 were associated with susceptibility to the disease. Conversely, allele DQB1*0501 and the DQA1*0101-DQB1*0501-DR1 haplotype conferred significant protection to exposed healthy control subjects. Our results are consistent with the hypothesis that immune mechanisms are involved in isocyanate-induced asthma and that specific genetic factors may increase or decrease the risk of developing IAA in exposed workers.

Adult↗
PubMed1994

From allergen sources to reduction of allergen exposure.

Allergen exposure plays a major role in the development of sensitization, inflammation and symptomatic asthma. The development of new means of detecting allergens has enabled the evaluation of the effect of a reduction in allergen exposure to be better assessed. In order to prevent allergen exposure it is necessary to determine the allergen sources and reservoirs to which avoidance measures should be directed. The allergen sources and reservoirs of mite, cat, dog, cockroach, rodent, mould and pollen allergens are briefly reviewed. The relationships between allergen exposure, sensitization, nonspecific bronchial hyperreactivity and asthma symptoms are discussed. Recognition of the risks, environmental control, and reduction in allergen loads should be among the objectives of asthma management.

Allergens↗