The effect of heparin as a reversing agent of multidrug resistance (MDR) was tested on normal mononuclear cells from 24 healthy volunteers and leukaemic cells from 12 acute myeloid leukaemia, five chronic myeloid leukaemia, five acute lymphoid leukaemia and three chronic lymphoid leukaemia patients. Two cell lines were used as controls, the human erythroleukaemia K562 and its vincristine-resistant derivative K562-Lucena 1. Heparin was not cytotoxic by itself as determined using a MTT assay and cell counts. MDR modulation was assessed by Rhodamine 123 extrusion using flow-cytometry. Modulation of the resistant cell line was produced by the classical reversing agent verapamil and also by heparin, the same being observed in normal and leukaemic cells and being independent of the type of leukaemia. Our work suggests that heparin may be considered a potential MDR modulator.

Cell Line↗

PubMed1996

Central role of immunoglobulin (Ig) E in the induction of lung eosinophil infiltration and T helper 2 cell cytokine production: inhibition by a non-anaphylactogenic anti-IgE antibody.

Elevated levels of immunoglobulin (Ig) E are associated with bronchial asthma, a disease characterized by eosinophilic inflammation of the airways. Activation of antigen-specific T helper (Th) 2 cells in the lung with the subsequent release of interleukin (IL) 4 and IL-5 is believed to play an important role in the pathogenesis of this disease. In this study, we have used a non-anaphylactogenic anti-mouse-IgE antibody to investigate the relationship between IgE, airway eosinophil infiltration, and the production of Th2 cytokines. Immunization of mice with house dust mite antigen increased serum levels of IgE and IgG. Antigen challenge of immunized but not control mice induced an infiltration of eosinophils in the bronchoalveolar lavage associated with the production of IL-4 and IL-5 from lung purified Thy1.2+ cells activated through the CD3-T cell receptor complex. Administration of the anti-IgE monoclonal antibody (mAb) 6h before antigen challenge neutralized serum IgE but not IgG and inhibited the recruitment of eosinophils into the lungs and the production of IL-4 and IL-5 but not interferon gamma. Studies performed using an anti-CD23 mAb, CD23 deficient and mast cell deficient mice suggest that anti-IgE mAb suppresses eosinophil infiltration and Th2 cytokine production by inhibiting IgE-CD23-facilitated antigen presentation to T cells. Our results demonstrate that IgE-dependent mechanisms are important in the induction of a Th2 immune response and the subsequent infiltration of eosinophils into the airways. Neutralization of IgE, for example, non-anaphylactogenic anti-IgE mAbs may provide a novel therapeutic approach to the treatment of allergic airway disease.

Anaphylaxis↗

PubMed1996

A study of the fibrinolytic response in healthy men and women following a brief exposure to venous occlusion.

In this study, 176 healthy men and women between the ages of 18 and 25 yrs were tested for fibrinolytic activity before and after a 5 min period of venous occlusion (VO) at 100 mm Hg. Using this protocol, 140 demonstrated an increase in fibrin plate lysis following this brief period of venous occlusion and were classified as "Responders." There were 36 individuals in the study who showed either a decrease or no change in fibrin plate lysis after 5 min of venous occlusion and they were classified as "Non-Responders." Responders showed a decrease in PAI-1 following VO. However, neither Responders nor Non-Responders demonstrated any significant differences in the levels of plasminogen, antiplasmin, protein C, free t-PA, or total t-PA following this brief exposure to venous occlusion. When comparing women and men in this study, women had significantly greater fibrin plate lysis both before and after 5 min of VO. They also demonstrated higher pre- and post-VO levels of circulating plasminogen. Also, women had less PAI-1 pre- and post-VO than men. When examining Responders and Non-Responders according to gender, women who were Responders had significantly greater fibrin plate lysis before and after VO than male Responders. Also, women Responders demonstrated a significant decrease in PAI-1 following 5 min of VO when compared to men who were Responders in this study.

Adolescent↗

PubMed1996

A new frameshift mutation 460delG in exon 4 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

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Adult↗

PubMed1996

Comparison between conventional hemodynamic monitoring and polarographic tissue pO2-monitoring of the liver in early septicemia of the pig.

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Animals↗

PubMed1996

A monoclonal blocking-ELISA for detection of orthopoxvirus antibodies in feline sera.

A double sandwich blocking-ELISA using a genus-specific neutralizing monoclonal antibody (MAb) against the vaccinia virus 32 kD adsorption protein (D8L open reading frame: ORF) was developed to detect orthopoxvirus (OPV) antibodies in sera. A collection of 2173 feline serum samples was examined in an epidemiological study. The blocking-ELISA revealed 44 (2%) sera with positive titres of 1:2-1:256. ELISA results were confirmed by the plaque-reduction test. A close correlation between titres of both assays could be observed (r = 0.986). In general, the sensitivity of the blocking ELISA was two to four times higher. Neutralizing OPV-antibodies were found in nine sera with ELISA-titres > 1:4. Antibody specificity to OPV was also demonstrated by Western blotting analysis with selected feline sera. The epidemiographical distribution of the ELISA-positive sera and case histories of 37 seropositive cats available from the referring veterinarians are demonstrated. The blocking-ELISA enables a rapid serological diagnosis and can be used in veterinary and human medicine. It allows OPV-antibody screening in human and other animal species.

Animals↗