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Biomedical subjects

G Pauli

Publications and source records attributed to G Pauli.

At least 181 records · Page 10Linked to original sources
PubMed1994

[Monoclonal antibodies and bronchial cancer].

Techniques of production of monoclonal antibodies (MoAb) have provided powerful tools to study biological lung cancer behavior. Immunochemistry is more sensitive than conventional light microscopy examination to detect tumour cells in sputum or pleural effusion, or small cell lung cancer metastases in bone marrow. Immunochemistry is also helpful for the differential diagnosis of carcinoma versus lymphoma or sarcoma, using antibodies directed against antigens such as cytokeratins, vimentin, EMA, LCA, SP100, CEA. In lung cancer, immunochemistry may detect neuroendocrine differentiation, or help to distinguish metastatic carcinoma from primary lung cancer. A positive immunostaining with CEA, Leu-M1, SP1, B72-3 supports the diagnosis of pleural metastatic adenocarcinoma versus mesothelioma. Immunoscintigraphy is a non invasive imaging technique which allows local and distant disease evaluation and could replace in the future the present staging work up. To evaluate the potential therapeutic efficacy of MoAbs in Lung cancer, phase I studies have been performed. Therapeutic effect is based on: 1) indirect cytotoxicity (cells are killed by ADCC or K cells) or direct cytotoxicity (MoAb are carriers of toxins, radioisotopes or drugs). 2) Immune response modulation by anti-idiotypic Ab. 3) Interferences with growth factors. Results of most of phase I trials are disappointing. Improvement of MoAb selectivity, improvement of conjugates stability, reduction of humoral response to MoAb, enhanced tumour localisation, and reduction of nonspecific captation should lead to a better efficacy.

Animals↗
PubMed1994

Monoclonal antibodies directed against tick-borne encephalitis virus with neutralizing activity in vivo.

Monoclonal antibodies (MoAbs) were raised against the tick-borne encephalitis (TBE) virus, strain K23. The reactivities of 14 selected MoAbs were characterized by ELISA, Western blot analysis, haemagglutination inhibition, immunoprecipitation, in vivo protection and in vitro neutralization tests. All MoAbs reacted only with the glycoprotein E. The binding epitope of one MoAb could be delimited by a synthetic peptide to amino acids 306-339 representing one immunodominant loop structure of the glycoprotein E. The MoAbs exhibited individual reactivities against 13 different TBE virus isolates in ELISA and immunoblot test ranging from type-specific reactions to a broad reactivity with all isolates. Four MoAbs also showed a cross-reaction with other flaviviruses like West Nile virus and/or Yellow fever virus in immunoblot analysis. By competition ELISA the MoAbs could be divided into five different reaction patterns. Four MoAbs showed neutralizing activity with titers in the range 1:140 to 1:5,000 in an in vitro assay. These neutralizing activities could be confirmed by an in vivo mouse challenge model. The MoAbs are useful for diagnostic purposes and for differentiation of TBE virus strains and other flaviviruses.

Amino Acid Sequence↗
PubMed1994

[Non-allergenic bronchial hyperreactivity and occupational agents].

The relationship between occupational asthma (OA) and non-specific bronchial responsiveness (NSBR) is reviewed. Natural or laboratory exposure to ubiquitous allergens can induce or increase NSBR. Reduction of exposure has an opposite effect. Preliminary results suggest that NSBR is not a predisposing factor to OA. NSBR assessment can be useful in screening for OA, before employment to document baseline levels and serially afterwards, alone or combined to immediate skin reactivity to the occupational agent, to document the onset of OA. Showing NSBR is essential to the diagnosis of OA. Although specific broncho-provocation tests in a hospital laboratory still represent the gold standard to confirm OA, the demonstration of changes in peak expiratory flow rates, in particular if such changes are coupled to NSBR, is an important diagnostic tool. NSBR assessment is also an interesting guide to specific bronchoprovocation in the laboratory. Several studies have documented a reduction in NSBR in some cases of OA after removal from exposure to the causal agent. The degree of NSBR is one of the criteria that have been suggested in setting permanent disability in subjects with OA. Increased NSBR can exist in other occupational conditions and represents an essential feature of Reactive Airways Dysfunction Syndrome (RADS).

Adult↗
PubMed1993

Sequence specific binding of the transcription factor c-Ets1 to the human immunodeficiency virus type I long terminal repeat.

Human immunodeficiency virus type I (HIV-1) long terminal repeat (LTR) driven transcription is regulated by a variety of cellular transcription factors. Most work has focused on the two nuclear factor kappa B (NF-kB) elements indispensable for HIV-1 LTR enhancer function. We demonstrate here the specific binding of the transcription factor c-Ets1 to an U3 region of the HIV-1 LTR (nt -141 to -149) using electrophoretic mobility shift analysis with T-cell nuclear extract and in vitro translated protein. This previously not identified Ets binding site is highly conserved among different HIV-1 isolates and maps to an U3 region recently shown to be necessary for viral growth in vitro. The c-Ets proto-oncogene family of transcription factors has yet been associated with HTLV-I and HIV-2 transcription. Our present analysis suggests an important role of c-Ets proteins in HIV-1 transcription.

Base Sequence↗
PubMed1993

[Viral infections and asthma].

Respiratory tract viruses have been held responsible for the genesis and aggravation of asthma in both children and adults. The relationship between asthma and viruses is looser in adults than in children, but it has been demonstrated that viral infections can generate a peripheral obstructive disorder on the one hand, and a transient non-specific bronchial hyperreactivity in healthy subjects on the other hand. Current data are insufficient to define clearly the alterations induced by viral infections and responsible for bronchial inflammation and non-specific bronchial hyperreactivity. Numerous studies have concluded to a complex mechanism involving bronchial epithelium lesions, imbalance of the autonomic nervous system in bronchial tone regulation, occurrence of immediate hypersensitivity reaction with facilitation of its delayed component, and cytokines produced during viral infection.

Adolescent↗
PubMed1993

Sensitivity of HIV antibody detection in saliva.

To assess the sensitivity and specificity of HIV antibody detection in saliva we tested matched serum and saliva samples from HIV-infected and uninfected individuals. Saliva specimens were collected by two different devices of the Salivette system and stored at different temperatures. Samples were tested for HIV antibodies by two commercially available enzyme-linked immunosorbent assays (ELISAs; Wellcome, Biotest). HIV antibodies were detected in 98.5% (Wellcome) and 97.8% (Biotest) of the saliva samples (standard Salivettes) from 135 seropositive individuals. Using the Salivettes flavoured with citric acid the sensitivity was only 22.9%. No reactions in ELISA were found in saliva from HIV-seronegative individuals. Salivary HIV-specific IgA was detected in 90% of seropositive individuals. All positive saliva samples stored at room temperature were still reactive after 20 days; of those stored at 37 degrees C, 23 out of 24 were positive when retested on day 5. Sensitivity of HIV antibody detection in saliva samples dried onto filter paper was 100% when a minimum of 100 microliters of saliva was used. HIV antibody testing in saliva is an efficient tool for large scale epidemiological studies when standard Salivettes are used for sample collection. Saliva samples can be stored in Salivettes or dried onto filter paper for several days at room temperature and under tropical conditions (37 degrees C).

Enzyme-Linked Immunosorbent Assay↗
PubMed1993

Fine mapping of HIV-1 Nef-epitopes by monoclonal antibodies.

A panel of newly isolated murine monoclonal antibodies is described which are specific for the Nef protein of the human immunodeficiency virus type 1 (HIV-1). Epitope mapping using recombinant Nef-related proteins, synthetic peptides and lipopeptides showed 3 independent antigenic determinants located within the regions of amino acids 83-93, 175-190 and 86-166 of the Nef protein. None of the monoclonal antibodies reacted with recombinant Nef proteins of HIV-2.

Amino Acid Sequence↗
PubMed1993

Receiver operating characteristic analysis: a useful method for a comparison of the clinical relevance of two in vitro IgE tests.

BACKGROUND: The objectives of this study were to demonstrate the usefulness of Receiver Operating Characteristic (ROC) analysis in the definition of a positive threshold in the comparison of two in vitro tests for detecting IgE antibodies and to determine the clinical relevance of specific IgE tests according to the sensitivity and specificity determined by ROC analysis. METHODS: Specific IgE levels were compared with the use of both MATRIX (Abbott Laboratories, Chicago, Ill.) and PHADEZYM (Pharmacia, Uppsala, Sweden) tests in 109 patients: 86 allergic patients and 23 control subjects. All allergic patients had a clinical history of allergy to mite, cat, grass pollen, or birch pollen and positive skin prick test results to the suspected allergen. Using various levels of specific IgE, we determined the points of the ROC curves with the best ratio of true positives to false positives for four aeroallergens (i.e., mite, cat, grass pollen, and birch pollen). RESULTS: Except for mite allergen there was no correspondence between the positive threshold values determined by ROC analysis with MATRIX and PHADEZYM tests. In terms of class, when ROC analysis was used, the threshold was class III with the MATRIX test and class II with PHADEZYM test for cat, grass pollen, and birch pollen and class III for mite. According to the threshold value, sensitivity and specificity for MATRIX and PHADEZYM tests were similar except for cat, for which the PHADEZYM test had a lower sensitivity (0.71) than the MATRIX test (0.90). With mite allergen the predictive value of only one positive MATRIX test result was 0.96. The specificities of MATRIX and PHADEZYM tests were 100% in both nonatopic and atopic control groups. CONCLUSIONS: We conclude that ROC analysis is a reliable method for comparing IgE in vitro tests and that it emphasizes the lack of correspondence between arbitrary units given for each in vitro test. ROC analysis appears to be a good method for helping to standardize IgE in vitro tests.

Adult↗
PubMed1993

A double-blind, placebo controlled trial of solidified benzyl benzoate applied in dwellings of asthmatic patients sensitive to mites: clinical efficacy and effect on mite allergens.

BACKGROUND: The aim of this double-blind, randomized study was to investigate the effectiveness of an acaricidal cleaning product in modifying both clinical symptoms and mite allergen levels over a period of at least 1 year. METHODS: Twenty-six asthmatic patients with proven Dermatophagoides pteronyssinus (Dp) asthma were selected; three were withdrawn from the trial. The patients' homes were divided into two groups; 11 homes were treated with solidified benzyl benzoate and tenside agents (A), and 12 were treated with a placebo (P). Two applications were performed at the beginning of the trial and at least 6 months later. Patients were examined 1 month before the trial, at the beginning of the trial, and every 3 months over a period of 1 year. Indoor mite exposure was evaluated by three methods: semiquantitative guanine determinations, quantitative guanine determinations, and the measurement of Der p I + Der f 1 (antigen P, of Dp + antigen F1 of D. farinae) levels. RESULTS: The symptom scores established at the beginning of the trial and 12 months later showed a statistically significant improvement only in the A group (p < 0.01). The visual analog scale also showed a statistically significant difference both in the A (p < 0.05) and P groups (p < 0.01). No statistical differences were found between medication scores in the A or P groups. A statistically significant increase was also observed for forced expiratory volume in 1 second and maximal expiratory flow rate 25/75 in the two groups (p < 0.05 for P group; p < 0.01 for A group). The mean decreases in Der p I + Der f 1 in patient mattresses between the beginning of the trial and after 12 months were 20% for the acaricide group and 17% for the placebo group, respectively (NS). For house dust samples with origins other than the patients' mattresses we found significant decreases in Der p I+Der f 1 in the A group (p < 0.01 for carpets and p < 0.05 for upholstery elements).

Adolescent↗
PubMed1993

Can we predict very short term survival in small cell lung cancer?

We retrospectively reviewed the charts of 151 consecutive patients diagnosed as small cell lung cancer in our department and who had at least one course of chemotherapy. Nineteen patients died during the first 2 months, of the probability were reported to construct a receiver operating characteristic curve i.e. 13% of the population. The probability of dying within 2 months was investigated through a stepwise logistic regression. A performance status < or = 70 (Karnofsky index), an age > 60, a platelet count < or = 150,000/mm3, elevated alkaline phosphatase and a sodium < or = 135 mmol/l were independent predictors of a very short term survival and contributed to the equation for the probability of dying within a 2-month period. Sensitivity and specificity for various cutoff points characteristic curve allowing one to determine for a given patient his risk of being a very short term survivor. Such an approach could prevent inclusion of patients with high risk of early death in clinical trials and help to choose appropriate treatments for such poor risk patients.

Aged↗
PubMed1993

Neuropathologic analysis of postmortal brain samples of HIV-seropositive and -seronegative i.v. drug addicts.

Between 1987 and 1992 we performed forensic-pathologic and neuropathologic examinations on 70 cases of i.v. drug addicts who died of an overdose. In almost 25% of the cases HIV-positivity was revealed by serological examinations. In all the cases, irrespective of the result of the serological examination, a diffuse, reactive astrocytosis was the most prominent histologic alteration, accompanied by more or less pronounced regressive changes of this cell type in the deep layers of the white matter. Furthermore, also in all the cases, a slight to moderate, reactive proliferation of microglia could be assessed. In a few cases of the HIV-seropositive group a lymphocytic meningitis, viz. meningoencephalitis was found; these changes may indicate an early invasion of the central nervous system (CNS) by the HIV. In spite of these inflammatory alterations, in the latter cases no HIV-specific antigens (p24 and gp41) could be demonstrated in the brain, most probably because of the small number of infectious particles. In order to reveal the earliest phase of invasion of the CNS by the HIV, we performed a search for HIV-specific nucleic acid sequences by the aid of the polymerase chain reaction (PCR) in 8 HIV-seronegative and 8 normal control cases. Although, most probably due to contamination, also the control cases exhibited some PCR-signals, these were more pronounced and appeared with more primer-pairs within the group of HIV-seronegative drug addicts. It is conceivable that HIV penetrates the CNS and is harboured in it in latent form shortly after the primary infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Diseases↗
PubMed1993

Inability of serum neuron-specific enolase to predict disease extent in small cell lung cancer.

Serum neuron-specific enolase (NSE) levels were measured before treatment in 112 patients diagnosed as having small cell lung cancer in our department. All these patients underwent exhaustive staging procedures: 53 had limited disease (LD) and 59 extensive disease (ED). Serum NSE was elevated in 83% of the patients (i.e. 71% of the patients with LD and 93% of the patients with ED). Mean values of NSE differed significantly according to disease extent. A receiver-operating characteristic curve was constructed with different cut-off levels of serum NSE in order to determine the accuracy of NSE for identifying ED. There was no level of NSE capable of predicting with sufficient accuracy the presence of ED. The best compromise was given by a threshold of 35 micrograms/l: 60% of the ED patients had a serum NSE above 35 micrograms/l but 30% of the LD patients also had a serum NSE above 35 micrograms/l.

Adult↗
PubMed1993

Characterization of murine monoclonal antibodies directed against the submembrane protein p17 of HIV-1.

Monoclonal antibodies (MAbs) were raised against the gag protein of human immunodeficiency virus type 1 (HIV-1). The reactivity of the selected Mabs with the matrix protein p17 of HIV-1 were investigated in several tests, i.e. ELISA, immunostaining of Western blots, and alkaline phosphatase anti-alkaline phosphatase immunocytochemistry (APAAP). All three Mabs reacted exclusively with HIV-1 and showed specific binding to the virus surface in pre-embedding immuno-electron-microscopy and useful as diagnostic agents. In an "in vitro" cultivation experiment the MAbs showed antiviral activity in concentrations in the range of 25-100 micrograms/ml. No binding region could be defined using overlapping peptides consisting of the p17 protein sequence of HIV-1 in an epitope mapping system and therefore we concluded, that the MAbs recognize a conformational epitope.

Animals↗
PubMed1993

The HIV-1 Nef protein shares an antigenic determinant with a T-cell surface protein.

OBJECTIVE: To characterize antigens on uninfected T lymphocytes reactive with monoclonal antibodies (MAb) directed against the HIV-1 Nef protein, and to search for antibodies directed against this epitope in HIV-1-infected individuals. DESIGN: Murine MAb directed against an epitope of Nef defined by amino acids 60-73 reacted with cell surface antigens of normal peripheral blood lymphocytes and permanent human T-cell lines. METHODS: The specificity of the MAb reaction was investigated by flow cytometry and immunofluorescence. The antigen was precipitated from lysates or uninfected cells using MAb or sera from HIV-1-infected individuals and analysed by Western blot and isoelectrofocusing. RESULTS: An antigen with an apparent relative molecular mass of 137,000 and an isoelectric point of 8.45 was immunoprecipitated with the cross-reactive MAb from uninfected human T cells. Sera from HIV-positive individuals recognizing a Nef epitope partially overlapping with the binding site of the cross-reactive MAb stained the 137 kD protein precipitated with the MAb in Western blot analysis, while HIV-positive sera without antibodies to this Nef region and sera from uninfected individuals were negative. CONCLUSION: The induction of autoantibodies cross-reactive with cellular surface proteins may play a role in the pathogenesis of AIDS.

Amino Acid Sequence↗
PubMed1993

Mite allergen content in mattress dust of Dermatophagoides-allergic asthmatics/rhinitics and matched controls.

It has been suggested that the mites Dermatophagoides pteronyssinus and D. farinae are important indoor environmental factors facilitating both the sensitization of atopic subjects and asthmatic attacks of house dust-sensitive patients. Contradictory results have been reported about the current exposure to mites or their allergens among patients and control groups of atopic or non-atopic subjects. In order to determine whether there is a difference in mite exposure levels between D. pteronyssinus-sensitized asthmatics and/or rhinitis and control subjects we considered a case-control study of 70 patients with asthma and/or rhinitis and positive skin test reactions to D. pteronyssinus and twice as many control subjects who were matched as to age and sex. The first control subject for each patient was an immediate neighbour of the patient and the second was patient arbitrarily chosen among hospitalized patients. Mite allergen exposure was measured in mattress dust collected under standardized conditions, by measuring Der p I+Der fI content and by performing a semiquantitative guanine determination (Acarex-test). The content of Der p I and Der fI was very high both in the homes of patients and those of healthy individuals: 69% of the total samples contained more than 10 micrograms Der pI+Der fI/g of dust. There was no significant difference between cases and controls with respect to Der p I, Der fI, Der p I+Der fI content and Acare class distributions. The calculated odds-ratios associated with the Acarex test and the mite allergens did not differ significantly from the level 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗