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Biomedical subjects

V Daniel

Publications and source records attributed to V Daniel.

At least 73 records · Page 4Linked to original sources
PubMed1994

Isotypes and IgG subclasses of anti-Fab antibodies in human immunodeficiency virus-infected hemophilia patients.

We reported recently that anti-Fab autoantibodies of the IgG isotype are associated with the decrease of helper/inducer (CD4+) lymphocytes in human immunodeficiency virus-infected (HIV+) hemophilia patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). In the present study we investigated the subclass distribution of IgG-anti-Fab autoantibodies, and whether anti-Fab antibodies of the IgA and IgM isotypes also are associated with the development of AIDS. Sera of HIV+ patients with AIDS had significantly higher IgA-anti-Fab activity than HIV+ patients with ARC (p < 0.02), HIV+ patients without AIDS/ARC (p < 0.0001), HIV-negative (HIV-) patients (p < 0.001), or healthy controls (p < 0.0001). An inverse association was found between IgA-anti-Fab activity and CD4+ cell counts (r = -0.396, p < 10(-6)). In contrast, no association of CD4+ cell counts was observed with IgM-anti-Fab. However, IgM-anti-Fab was significantly increased in patients with thrombocytopenia. We found a significant association between IgA-anti-Fab activity and serum neopterin concentrations (r = 0.310, p < 10(-5)). IgG-anti-Fab activity was detected mainly in the IgG3 fraction, although in HIV+ patients with AIDS/ARC various IgG subclasses were present. Affinity-purified anti-Fab antibodies isolated from sera of AIDS patients bound to rgp120-preincubated CD4+ cells of a healthy individual, supporting our hypothesis that anti-Fab antibodies and free circulating gp120 molecules are involved in the elimination of uninfected CD4+ cells. Removal of anti-Fab autoantibodies from the circulation by immune adsorbance might be a useful approach in the treatment of AIDS.

AIDS-Related Complex↗
PubMed1994

Induction of AP-1 (Fos/Jun) by chemical agents mediates activation of glutathione S-transferase and quinone reductase gene expression.

A regulatory element, EpRE, was found to be responsible for the induction of mouse glutathione S-transferase (GST) Ya gene expression by a variety of chemical agents such as planar aromatic hydrocarbons, diphenols, phorbol ester, phenobarbital and electrophilic compounds. The EpRE is composed of two adjacent AP-1-like binding sites and was recently found to be activated by Fos/Jun heterodimeric complex (AP-1). In this report we show that regulatory elements ARE, previously demonstrated to mediate the chemical induction of rat GST Ya and quinone reductase genes, have a similar structure with EpRE and are activated by Fos/Jun complex. The activation of GST Ya and quinone reductase genes by a variety of chemical inducers is found to be associated with an increase in AP-1 binding activity. We present evidence that chemical agents induce expression of c-fos and c-jun proto-oncogenes and an enhanced synthesis of protein components of AP-1 complex. We suggest that the increased synthesis of AP-1 complex followed by an AP-1-mediated transcriptional activation of GST Ya and quinone reductase genes may provide a molecular mechanism for the induction of these drug-metabolizing enzymes by chemical agents.

Arsenates↗
PubMed1993

A new method for determining anti-B cell antibodies and their specificity using flow cytometry.

We describe a new flow cytometric B cell crossmatch method with improved sensitivity and specificity. It is based on the coating of B cell surface immunoglobulins with an unconjugated polyvalent anti-human immunoglobulin antibody. The method also provides a means for determining the specificity of anti-B cell antibodies and, potentially, for anti-HLA class II antibody specificity differentiation (DR, DQ or DP) in a binding inhibition test using mouse monoclonal antibodies directed against human HLA class II antigens.

Antibody Specificity↗
PubMed1993

Sequence analysis suggests a recent duplication of the growth hormone-encoding gene in Tilapia nilotica.

The sequence of two growth hormone(GH)-encoding genes from tilapia fish (Tilapia nilotica) is reported. Our data indicate that the presence of two GH in the tilapia genome is a consequence of a relatively recent duplication event. The two genes are highly homologous, having a similar intron (five)/exon (six) arrangement, and both encode an identical polypeptide. Sequence similarity extends up to bp -628 upstream to the transcription start point, after which the sequences of the two genes are not related to each other. The presence of two GH in the tilapia genome is supported both by the nucleotide sequence and by genomic DNA blot hybridization analysis. Tilapias, like salmonids, contain an extra intron compared with the mammalian GH structure. We suggest that within the superorder Teleostei, the insertion of intron 5 into GH took place after the evolutionary separation of Cyprinoidea, but before Isospondyli (salmonids) and Acanthopterygii (tilapias) were separated. Thus, the additional intron which is probably present in many teleost fish GH may provide an excellent natural marker for evolution and classification studies.

Amino Acid Sequence↗
PubMed1993

Phenobarbital induction of AP-1 binding activity mediates activation of glutathione S-transferase and quinone reductase gene expression.

Phenobarbital is an inducer of xenobiotic-metabolizing enzymes, such as cytochrome P-450, glutathione S-transferases (GSTs) and NAD(P)H:quinone reductase, as well as being a promoter of hepatocarcinogenesis. The molecular mechanisms regulating these biological activities are, however, unknown. In this paper we show that induction by phenobarbital of GST Ya and quinone reductase gene expression is mediated by regulatory elements, EpRE and ARE respectively, which are composed of two adjacent AP-1-like binding sites. EpRE was recently found to be activated by a Fos/Jun heterodimeric complex (AP-1). Here we show that phenobarbital induces an increase in AP-1 binding activity in nuclear extracts of cultured hepatoma cells. Furthermore, we observe that the induction of chloramphenicol acetyltransferase (CAT) activity from an EpRE Ya-cat gene construct and of AP-1 binding activity by phenobarbital is inhibited by the thiol compounds N-acetyl-L-cysteine and glutathione. These results suggest that the phenobarbital induction of AP-1 activity, leading to the AP-1-mediated transcriptional activation of the GST Ya and quinone reductase genes, may involve production of reactive oxygen species and an increase in intracellular oxidant levels, which is prevented by thiol compounds. In view of the involvement of AP-1 in the control of cell proliferation and transformation, the induction by phenobarbital of AP-1 binding activity observed here provides a possible molecular mechanism for the tumour-promoting activity of this drug.

Acetylcysteine↗
PubMed1993

Recombinant carp (Cyprinus carpio) growth hormone: expression, purification, and determination of biological activity in vitro and in vivo.

Carp growth hormone (cGH) cDNA (Koren et al., 1989) was cloned under the control of lambda-phage PLOL promoter and lambda cll ribosomal binding site into pBR322 plasmid to enable its expression in Escherichia coli A1645 that produces constitutively the thermolabile lambda repressor c1857. Temperature shift to 42 degrees abolished the repression, resulting in a high level of cGH expression. The bacterially expressed cGH protein, contained within the refractile body pellet, was solubilized in 4.5 M urea, refolded, and purified on Q-Sepharose column by stepwise elution with NaCl. The bioactive fraction was eluted at 0.2 M NaCl at a yield of 10-15%. This fraction contained predominantly (95%) 21.5-kDa monomeric cGH. The activity of cGH in vitro was bioassayed using Nb2-11C lymphoma cells (containing lactogenic receptors) and 3T3-F442A preadipocyte cells (containing somatogenic receptors). Bioactivity was found to be 0.01 and 6-10% that of human GH, respectively. In vivo cGH activity was measured by weekly ip injection in juvenile carp fed a low (23%) protein diet. Over a 6-week period, cGH increased the growth rate by 38% compared to fish injected with vehicle only. Identical injections with bovine GH yielded only a 21% increase.

Adipose Tissue↗
PubMed1993

Complementarities and network interactions in AIDS.

The contribution of autoimmune phenomena to the development of AIDS is not fully understood. In this paper we provide new evidence that idiotypic network interactions are operative in the development of AIDS. We furthermore present a model that involves two groups of antibodies and other molecules that are related to each other by a network of specific complementarities. We define Group I molecules to include antibodies and other molecules that have direct or indirect similarities with class I MHC molecules, and Group II substances that have similarities with class II MHC. We observe an inverse relationship between Group I antibodies (including anti-Fab) and Group II antibodies (including anti-anti-gp120, anti-anti-CD8 and anti-rCD4). The potential roles of members of these two groups in AIDS pathogenesis and/or protection are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Biodegradation and brain tissue reaction to poly(D,L-lactide-co-glycolide) microspheres.

The therapeutic application of neuroactive molecules in neuroscience is limited, due to the problems posed by the administration of these drugs (peripheral metabolism, systemic effect and passage of the blood-brain barrier). One solution is the implantation in the brain of biodegradable polymer devices with controlled release of a neuroactive drug. The biodegradation and tissue reaction of the copolymer poly(D,L-lactide-co-glycolide) microspheres prepared by the solvent evaporation method, radiosterilized and stereotactically implanted in the rat brain were studied by routine staining, immunohistochemistry and transmission electronic microscopy. The brain tissue reaction observed was a non-specific astrocytic proliferation and a macrophagous-microglial cell reaction, typically found following damage to the central nervous system. Some foreign-body giant cells were observed and the inflammatory and macrophagous reaction decreased dramatically after 1 month and almost ended after 2 months when the microspheres were totally biodegraded. The copolymer poly(D,L-lactide-co-glycolide) microspheres may be considered biocompatible to the brain tissue.

Animals↗
PubMed1993

IgA-anti-Fab autoantibodies and disease progression in AIDS.

There is increasing evidence that autoimmune phenomena contribute to the pathogenesis of the acquired immunodeficiency syndrome (AIDS). We investigated the relationship between IgA autoantibodies directed against the Fab part of the IgG molecule and disease progression in 87 HIV-infected hemophilia patients. AIDS patients demonstrated a significantly higher serum IgA-anti-Fab activity than HIV-positive (HIV+) patients with AIDS-related complex (ARC) (P < 0.02), HIV+ patients without AIDS/ARC (P < 0.0001), HIV negative (HIV-) patients (P = 0.0001), or healthy controls (P < 0.0001). Moreover, an inverse association was observed between serum IgA-anti-Fab activity and CD4+ cell counts (r = -0.396, P < 10(-6)). This close association was confirmed in longitudinal studies of symptomatic patients. IgA-anti-Fab antibodies are suggested to play an important role in the immunopathogenesis of AIDS, and their determination may be helpful in the monitoring of HIV-infected patients.

AIDS-Related Complex↗
PubMed1993

Defective IL-6 secretion in HIV-infected haemophilia patients.

To study the role of IL-6 in HIV-induced B cell defects, in vitro B cell responses and IL-6 secretion were determined simultaneously in 67 haemophilia patients. Twenty-three patients were HIV- (Group 1), 27 HIV+ stage CDC II, III (Group 2), and 17 were HIV+ stage CDC IV (Group 3). Pokeweed mitogen (PWM) was used for T cell-dependent and Staphylococcus aureus Cowan I (SAC I) for T cell-independent B cell stimulation. B cell differentiation was assessed in a reverse haemolytic plaque assay and by ELISA determination of IgG and IgM in culture supernatants. An ELISA was used to measure IL-6 in plasma and culture supernatants. HIV- patients showed impaired immunoglobulin-secreting cell (ISC) responses after T cell-independent and T cell-dependent stimulation (P < 0.0001 and P < 0.01, respectively), whereas IL-6 secretion, IgM and IgG responses were comparable to those in healthy controls. HIV+ patients at stage CDC II, III or IV demonstrated significantly reduced mitogen-stimulated IL-6 secretion (P < 0.05, PWM; P < or = 0.001, SAC I) as well as impaired ISC and IgG responses (P < 0.01, PWM; P < or = 0.0001, SAC I). CDC IV patients showed reduced IgM responses in addition (P < 0.02, PWM; P < 0.0005, SAC I). Plasma IL-6 levels were elevated both in HIV+ patients (CDC II, III patients: 165 +/- 73 pg/ml, P < 0.005; CDC IV patients: 58 +/- 18 pg/ml, P < 0.0001) and in HIV- patients (283 +/- 65 pg/ml, P < 0.0001) which appeared to be a T cell effect induced by treatment with haemophilia factor concentrates. Our data provide evidence for different types of B cell deficiencies in HIV- patients (impaired ISC response only) and HIV+ patients (impaired ISC as well as IL-6 and IgM/IgG responses). The defective IL-6 secretion in HIV+ patients is likely to affect terminal B cell differentiation and this may explain the reduced immunoglobulin secretion in these patients in response to antigenic challenge.

B-Lymphocytes↗
PubMed1993

Association of T cell and macrophage dysfunction with surface gp 120-immunoglobulin-complement complexes in HIV-infected patients.

The mechanism of CD4+ cell depletion and functional T helper cell inhibition in HIV-infected individuals is poorly understood. The present study demonstrates that immune complex-covered CD4+ cells are associated with T cell inhibition and macrophage stimulation. We studied 30 patients with ARC/AIDS and 35 asymptomatic HIV+ haemophilia patients. Overall, 20 +/- 3% of peripheral CD4+ lymphocytes were covered with gp120 (range 0-94%). gp120+ cells also exhibited surface-bound IgG (P = 0.0001), IgM (P = 0.0001), and complement (P = 0.0001). Decreased in vitro lymphocyte proliferation was associated with the immune complex load of CD4+ cells. The higher the percentage of CD4+ gp 120+ cells in the blood, the lower the T cell response in vitro (P = 0.001). Moreover, an association was found between immune complex-positive cells and plasma neopterin (P = 0.01). Patients with increased plasma neopterin levels had decreased in vitro responses to pokeweed mitogen (PWM) (P = 0.006), phytohaemagglutinin (PHA) (P = 0.004), concanavalin A (Con A) (P = 0.09), and anti-CD3 MoAb (P = 0.03), and decreased CD4+ cell counts in the blood (P = 0.006). Since maximally 1% of CD4+ lymphocytes are infected with HIV, T cell dysfunction and T cell depletion in HIV-infected patients may also be caused by the release of free gp120 that binds to uninfected CD4+ cells. Our data suggest that the functional inhibition and subsequent elimination of uninfected CD4+ lymphocytes with surface gp120-immunoglobulin-complement complexes may be a pathomechanism in the manifestation of AIDS.

Antigen-Antibody Complex↗
PubMed1993

CD4+ lymphocyte depletion in HIV-infected patients is associated with gp120-immunoglobulin-complement attachment to CD4+ cells.

The mechanism of CD4+ lymphocyte depletion, which is the main immunological feature in HIV-infected patients, is unclear. We investigated whether gp120-immunoglobulin-complement complexes on the surface of CD4+ cells might be involved in the elimination of CD4+ lymphocytes. The results obtained in 63 HIV-infected patients show that gp120 is attached to a variable degree to CD4+ cells. Importantly, the percentage of CD4+gp120+ lymphocytes is inversely associated with CD4+ lymphocyte counts in the peripheral blood (p = 0.0004). CD4+gp120+ blood lymphocytes bind IgM (p = 0.0027) and IgG antibodies (p = 0.0001) and complement (p = 0.0005). These results suggest that immune complex-mediated cell elimination is an important mechanism of CD4+ cell depletion in patients with AIDS.

Antigen-Antibody Complex↗
PubMed1993

Molecular mimicry between HIV-1 and antigen receptor molecules: a clue to the pathogenesis of AIDS.

There is increasing evidence that autoimmune phenomena play an important role in the immunopathogenesis of AIDS. We found a high degree of sequence homology between HIV-1 and antigen receptor molecules, immunoglobulins and T cell receptors. Based on recent findings that the appearance of anti-Fab autoantibodies and attachment of gp120/immunoglobulin/complement complexes on CD4+ T cells are associated with the decrease of CD4+ T cells in HIV-infected patients, we hypothesize herein that cross-reactive anti-F (ab')2 autoantibodies and circulating gp120 molecules are responsible for a destabilization of the immune network and the elimination of CD4+ T cells.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Glutathione S-transferases: gene structure and regulation of expression.

The current knowledge about the structure of GST genes and the molecular mechanisms involved in regulation of their expression are reviewed. Information derived from the study of rat and mouse GST Alpha-class, Ya genes, and a rat GST Pi-class gene seems to indicate that a single cis-regulatory element, composed of two adjacent AP-1-like binding sites in the 5'-flanking region of these GST genes, is responsible for their basal and xenobiotic-inducible activity. The identification of Fos/Jun (AP-1) complex as the trans-acting factor that binds to this element and mediates the basal and inducible expression of GST genes offers a basis for an understanding of the molecular processes involved in GST regulation. The induction of expression of Fos and Jun transcriptional regulatory proteins by a variety of extracellular stimuli is known to mediate the activation of target genes via the AP-1 binding sites. The modulation of the AP-1 activity may account for the changes induced by growth factors, hormones, chemical carcinogens, transforming oncogenes, and cellular stress-inducing agents in the pattern of GST expression. Recent observations implying reactive oxygen as the transduction signal that mediates activation of c-fos and c-jun genes are presently considered to provide an explanation for the induction of GST gene expression by chemical agents of diverse structure. The possibility that these agents may all induce conditions of oxidative stress by various pathways to activate expression of GST genes that are regulated by the AP-1 complex is discussed.

Animals↗
PubMed1992

Structure and sequence of the growth hormone-encoding gene from Tilapia nilotica.

We report here the nucleotide (nt) sequence of the growth hormone (GH)-encoding gene (GH) of the tilapia fish (Tilapia nilotica). The T. nilotica GH gene, similar to that of the salmonidae fish, Atlantic salmon and rainbow trout, contains six exons and five introns. However, despite the presence of an additional intron (intron V), the size of the primary transcript of T. nilotica GH (1666 nt) is significantly shorter than that of all other currently characterized fish GH genes. Comparison of sequences upstream from the transcription start point of the tilapia, carp, rainbow trout and Atlantic salmon GH genes shows a region of high homology preceding the typical TATA box. This homology does not seem to extend to the regions further upstream of the compared fish GH genes and is not observed to be present in the corresponding region of the mammalian GH genes. A sequences search for putative DNA-binding domains for transcription factors shows the presence of short nt stretches similar to those considered to be involved in the tissue-specific expression of mammalian GH genes.

Amino Acid Sequence↗
PubMed1992

Striking inverse association of IgG-anti-Fab gamma antibodies and CD4 cell counts in patients with acquired immunodeficiency syndrome (AIDS)/AIDS-related complex.

The contribution of autoimmune phenomena to the pathogenesis of acquired immunodeficiency syndrome (AIDS) is poorly understood. We investigated the relationship between IgG-anti-Fab gamma autoantibodies and the main immunologic feature of AIDS, the decrease of CD4+ helper lymphocytes. Sera of 33 human immunodeficiency virus (HIV) infected (HIV+) hemophilia patients with AIDS/AIDS-related complex (ARC), 57 HIV+ patients without AIDS/ARC, 23 HIV-negative (HIV-) patients, and 76 healthy controls were tested for antibody activity against the Fab region of IgG. Patients with AIDS/ARC had significantly higher IgG-anti-Fab gamma activity than HIV+ patients without AIDS/ARC, HIV- patients, or controls (P less than .0001). A striking inverse association was found between IgG-anti-Fab gamma and CD4+ cell counts (r = -.69; P less than 10(-6)). Sequential testing in 16 AIDS/ARC patients showed that an increase in the IgG-anti-Fab gamma activity was invariably accompanied by a decrease in the CD4+ cell count. IgG-anti-Fab gamma antibodies may play an important role in the immunopathogenesis of AIDS.

AIDS-Related Complex↗