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Biomedical subjects

G Pauli

Publications and source records attributed to G Pauli.

At least 217 records · Page 12Linked to original sources

Inhibition of viral replication by monoclonal antibodies directed against human immunodeficiency virus gp120.

Monoclonal antibodies (MAbs) were raised against the glycoprotein gp120 of human immunodeficiency virus type 1 (strain HTLV-IIIB). The reactivity of five selected MAbs was characterized in several tests: ELISA, immunostaining of Western blots, immunofluorescence, immunoprecipitation, immunoelectron microscopy, alkaline phosphatase-anti-alkaline phosphatase assay and neutralization. The binding region was delimited by sequential overlapping Escherichia coli fusion proteins of the gp120 sequence between amino acids (aa) 49 and 280. In the ELISA, when using sequential overlapping 15 aa peptides, the binding epitopes were localized between aa 64 and 78 for three MAbs and between aa 114 and 123 for the fourth Mab. The fifth Mab showed multiple reactions with different peptides possibly indicating a reaction with a discontinuous epitope. In virus growth inhibition assays, all five MAbs inhibited the spread of HIV-1 infection in cell cultures after a single or repeated treatment at a concentration of 63 micrograms/ml of the purified MAbs. All MAbs showed low but significant neutralizing activity at concentrations of 100 micrograms/ml.

Amino Acid Sequence↗

Human choriogonadotropin (hCG) and placental lactogen (hPL) inhibit interleukin-2 (IL-2) and increase interleukin-1 beta (IL-1 beta), -6 (IL-6) and tumor necrosis factor (TNF-alpha) expression in monocyte cell cultures.

The effect of the human trophoblast hormones chorionic gonadotropin (hCG) and placental lactogen (hPL) on the expression of cytokines in peripheral blood mononuclear cell cultures was followed under a variety of culture conditions, (a) phytohemagglutinin stimulated cells (PHA-MSC), (b) allogenic mixed cells (AMC) and (c) spontaneously proliferating cells (SPC). A dose dependent enhanced release of IL-6, IL-1 beta and TNF-alpha by hCG and hPL was observed under all culture conditions. However, an inhibitory effect on the IL-2 release was seen in PHA-MSC by hPL and in AMC by hPL and hCG. The role of the suppression of IL-2 production/release on cytotoxicity towards trophoblast is discussed. These results suggest a sensitive, dose dependent hormonal control of the modulation of the immune response during pregnancy and strengthen the concept of a distinct regulation of monocytes and lymphocyte subpopulation by trophoblast hormones.

Cells, Cultured↗

[Loop diuretics and the treatment of asthma].

Current data in the literature show a protective effect of loop diuretics in relation to certain types of experimental bronchospasm. This action has sometimes been observed after the administration of diuretics as aerosols in less severe cases of asthma. The initial observations on bronchospasm induced by physical stimuli (exercise, distilled water and hyperventilation), have been extended to bronchospasm provoked by allergens or certain chemical stimuli (metabisulphide, adenosine 5'-monophosphate, and salicylic acid). On the other hand provocation tests using histamine or acetylcholine are modified, either a little or not at all by diuretics. The proposed mechanisms of action are multiple, but are still very hypothetical: an action on ionic fluxes in the epithelial cells, in mastocytes, in nerve cells and in muscle cells inducing the secretion of prostaglandin. Diuretics certainly have opened some interesting patho-physiological approaches, but current data concerning their efficacy in asthmatics are still fragmentary and do not, at the current time, allow them to take a significant place in the therapeutic arsenal of asthma drugs.

Administration, Inhalation↗

[Occupational asthma caused by ebony wood].

A case of occupational asthma to ebony wood dust is described in a violin and stringed instrument maker, who was sanding and filing ebony to make the finger boards of violins and cellos. The diagnosis was confirmed using a realistic provocation test; after sanding and smoothing the ebony for 20 minutes the patient developed bronchial spasm with fall of the force expired volume in one second (VMS) of 45% which was reversible following the inhalation of beta 2 agonists. A delayed reaction was seen at 3 hours and 6 hours and at 20 hours after the test. The observations of occupational asthma or rhinitis to ebony wood are very rare. To our knowledge there are two publications at the present time. It has been recognised as an occupational disease (see table 47 of occupational diseases) and an exclusion order has been effected.

Adult↗

Pharmacokinetic and preliminary metabolic fate of navelbine in humans as determined by high performance liquid chromatography.

The pharmacokinetics and metabolism of Navelbine (NVB) were investigated in 20 patients by a specific high performance liquid chromatographic methodology allowing the monitoring of NVB, deacetyl-NVB, and N-oxide NVB. After the i.v. (15 min) administration of 30 mg/m2 of drug, blood and urine samples were collected for, respectively, 144 and 48 h. NVB is characterized by a three compartmental kinetics, with a Cmax of 1130 +/- 139 (SEM) ng/ml. The total body clearance and apparent volume of distribution, as defined by high performance liquid chromatography, are 1.26 +/- 0.09 liter/h/kg (48.6 +/- 4.1 liters/h/m2) and 75.6 +/- 9.2 liters/kg (2918.4 +/- 307.2 liters/m2). No metabolite could be detected in serum; the urinary excretion of NVB represented 11% of the administered dose. Deacetyl-NVB could be identified as a minor urinary metabolite when no N-oxide NVB appeared in the urine samples. Two additional peaks appeared in most of urinary chromatograms as trace amounts. Thus, the major pathway of NVB, as for other Vinca alkaloids, should be hepatic clearance, as biliary elimination and/or hepatic biotransformation.

Adult↗

Borna disease virus-specific antigens: two different proteins identified by monoclonal antibodies.

A variety of cells originating from different species, including man, can be infected with Borna disease (BD) virus. Two different virus infection-specific antigens with molecular weights of 24 kD and 35/38 kD (double band) could be demonstrated using antigen preparations from persistently infected cells and rat brains, and polyvalent antisera from naturally and experimentally infected animals. Three different monoclonal antibodies were selected. One was specific for the 24-kD protein and two others reacted with the 35/38-kD antigen. The 24- and 35/38-kD antigens could be monitored concomitantly with the appearance of newly synthesized infectious virus. Both antigens could be detected at the same time during the infection cycle, and showed identical distribution in the cell. Their relationship to one another and their possible function is discussed.

Animals↗

Oral manifestations of AIDS-associated non-Hodgkin's lymphomas.

While B-cell lymphomas are frequently found in AIDS patients, reports on oral manifestations are rare. Among a group of 465 HIV-infected patients 5 presented with primary oral manifestations of a malignant B-cell lymphoma. The primary site of manifestation was the maxilla in 3 cases and the mandible in 2 cases. Based on the histological and immunohistochemical examination the tumors were differentiated as Burkitt's lymphoma (n = 1), as anaplastic large cell (ALC) lymphoma of the B-cell type (n = 1), as high-grade non-Hodgkin's lymphoma not classifiable according to the Kiel classification (n = 1), as immunoblastic-plasmoblastic lymphoma (n = 1), and as centroblastic lymphoma (n = 1). Serum samples were negative for HTLV-I antibodies in 5/5 cases.

Acquired Immunodeficiency Syndrome↗

Epitopes of the HIV-1-negative factor (nef) reactive with murine monoclonal antibodies and human HIV-1-positive sera.

Murine monoclonal antibodies (MAbs) raised against a recombinant nef protein fragment of human immunodeficiency virus type 1 (HIV-1) strain BH10 were characterized by an epitope mapping system using overlapping decapeptides. Four different immunogenic regions were identified. Ten human HIV-1-positive sera were tested in the same epitope mapping system, seven of these were reactive with four immunogenic regions. Two of the nef-specific epitopes recognized by human sera overlapped with the epitopes defined by the murine monoclonal antibodies. The reactivity of the monoclonal antibodies with the recombinant nef protein and with infected and uninfected cells were investigated in a variety of test systems. The results are discussed with respect to homologous regions of nef and cellular proteins.

Amino Acid Sequence↗

A case of classical mycosis fungoides associated with human T-cell lymphotropic virus type I.

A 72-year-old male patient from north-eastern Iran developed the typical clinical and histopathological features of mycosis fungoides with lymphadenopathy, but without any other systemic involvement. Human T-cell lymphotropic virus (HTLV-I) antibodies were detected in the patient's serum by two different ELISAs and by Western blot using purified viral particles from MT-2 culture supernatants. Cultured peripheral blood lymphocytes were positive for labelling with anti-HTLV-I serum. Southern blot hybridization of DNA extracted from a skin tumour and from an involved lymph node revealed integrated proviral DNA with identical restriction patterns. This case supports a relationship between mycosis fungoides and HTLV-I and may indicate a new region of endemic HTLV-I infection.

Aged↗

Characterization of murine monoclonal antibodies directed against the core proteins of human immunodeficiency virus types 1 and 2.

Monoclonal antibodies (MAbs) raised against the core proteins of human immunodeficiency virus type 1 (HIV-1; laboratory strain HTLV-IIIB) and HIV-2 (strain ROD) were investigated in a variety of tests, e.g., enzyme-linked immunosorbent assay (ELISA), immunostaining of Western immunoblots, immunofluorescence, immunoprecipitation, and alkaline phosphatase anti-alkaline phosphatase assay. The MAbs were grouped according to their cross-reactions. Seven HIV-1-specific MAbs reacted exclusively with HIV-1, and five showed cross-reactivity with HIV-2 and simian immunodeficiency virus of macaques in ELISA. Four of the 15 MAbs against HIV-2 reacted only with the HIV-2 protein p26. Six showed cross-reactivity with HIV-1, and five showed a broad reaction with all three viruses. Overlapping 30-amino-acid-long peptides derived from the p24 protein sequence of HIV-1 were used in an epitope-mapping system. Three different immunogenic regions (A, B, and C) could be defined. Specific regions where anti-HIV-1 and -HIV-2 MAbs cross-reacted were mapped with shorter oligopeptides.

Amino Acid Sequence↗

Comparison of four anti-HIV screening assays which belong to different test generations.

There are three different test generations of enzyme-linked immunosorbent assays (ELISA) for the detection of human immunodeficiency virus (HIV) infection, depending on whether virus lysate, recombinant proteins or synthetic peptides are used as solid phase antigen. Four different assays, i.e., three sandwich ELISAs and one competitive test, were used to demonstrate differences between the three systems with regard to the content of different diagnostically relevant virus proteins. The sensitivities and specificities of these assays were compared by using 312 anti-HIV positive sera and 500 sera of healthy blood donors. The highest sensitivity and specificity were achieved by the competitive ELISA based on recombinant proteins, and by the sandwich ELISA based on synthetic peptides.

Blotting, Western↗

[Is chemotherapy with cisplatin useful in non small cell bronchial cancer at staging IV? Results of a randomized study].

The benefit of chemotherapy for patients with disseminated non small cell lung cancer (NSCLC) is controversial. The introduction of cisplatinum in the combination chemotherapy for NSCLC gave rise to higher response rates. To study the question of the usefulness of cisplatinum-based chemotherapy in disseminated NSCLC we conducted a prospective randomized trial comparing best supportive care to vindesine + cisplatin. Between December 1985 and March 1988, 49 patients with stage IV NSCLC were enrolled. Of the 46 eligible patients 24 were in the chemotherapy group and 22 in the best supportive care group. The treatment groups were not significantly different in terms of age, performance status, histology. Toxicity on the chemotherapy arm grade 3 or more was observed in 17.5% for neutropenia, in 8.75% for vomiting. There was one death related to treatment. The overall response rate in the chemotherapy group was 41.7%. Patients of the chemotherapy group had a median survival time of 199 days and the patients of the best supportive care group had a median survival time of 73 days. The difference in survival is highly significant (p less than 0.001).

Adult↗

[Specific provocation tests].

The authors describe the methodology of allergen challenge tests, with special attention to some particular aspects, such as the allergenic extracts and their biological activity, and the methods used in aerosol administration and in measurements of bronchial obstruction. They present the results of their personal experience, concerning interindividual variations in a sensitized population and the reproducibility of the immediate reaction revealed by dose-response curves. Comparisons of allergen tests with exposure to allergens under physiological conditions are discussed. In occupational asthma the exposure tests sometimes constitute the only diagnostic method, owing to ignorance of the responsible mechanisms and to the multiplicity of incriminated substances. However, these tests are not without danger and must be performed by well-trained medical and paramedical teams.

Allergens↗