Biomedical subjects

A Ferrante

Publications and source records attributed to A Ferrante.

At least 127 records · Page 7Linked to original sources

PubMed1991

Early bone marrow transplantation in an infant with Wiskott-Aldrich syndrome.

The Wiskott-Aldrich Syndrome (WAS) is a rare X-linked immunohematological disorder characterized by eczema, profound thrombocytopenia, and progressive immunodeficiency. Severe hemorrhage, overwhelming sepsis, or lymphoreticular malignancy usually cause death in childhood. Recently, bone marrow transplantation (BMT) has been curative in some well-established cases, but there is no general agreement about the place of BMT in infants with WAS before the development of significant immunological abnormalities. We describe the successful use of early histocompatible BMT in a 10-month-old infant in whom WAS was diagnosed on the basis of eczema, thrombocytopenia, small platelets, and raised serum immunoglobulin A (Ig) and IgE, but before the development of immunodeficiency as evidenced clinically by recurrent infections, or immunologically by low serum IgM or consistently abnormal lymphocyte responses to mitogens. After an unstable period for several weeks posttransplantation when he developed marked hepatomegaly and severe interstitial pneumonitis, he made a good recovery. His eczema and thrombocytopenia resolved and he has shown no clinical or laboratory evidence of immunodeficiency. It is now over 2 years since his BMT. Because of the poor prognosis of WAS, where a histocompatible donor is available, BMT at the earliest opportunity, despite the inherent risks of such a procedure, may be the best option for an infant with WAS.

Age Factors↗

PubMed1991

Granulocyte-macrophage colony-stimulating factor augments neutrophil killing of Torulopsis glabrata and stimulates neutrophil respiratory burst and degranulation.

The effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the interaction between the fungus Torulopsis glabrata and human neutrophils was examined. Pre-incubation of neutrophils with GM-CSF increased the neutrophil fungal killing. The cytokine also increased the oxygen-dependent respiratory burst in response to opsonized fungi, measured by the lucigenin-dependent chemiluminescence assay and superoxide release. Under the same conditions the cytokine augmented release of constituents from both specific and azurophilic granules. Besides these priming effects, GM-CSF was a weak stimulus of the neutrophil respiratory burst and degranulation. The priming and stimulatory effects of GM-CSF were observed at 10-1000 U/ml with an optimal concentration of 100 U/ml.

Adult↗

PubMed1991

Free-living amoebae: pathogenicity and immunity.

Free-living amoebae causes three well-defined disease entities: (i) primary amoebic meningoencephalitis, caused by Naegleria fowleri, (ii) granulomatous amoebic encephalitis and (iii) chronic amoebic keratitis, caused by species of Acanthamoeba. Both Naegleria infections and chronic amoebic keratitis occur in healthy individuals while granulomatous amoebic encephalitis is often associated with patients with acquired immunodeficiencies. The different pathogenic behaviour of these organisms is associated with differences in life cycle, amoeboidal locomotion, enzyme composition (such as phospholipase A), and cytotoxins, as well as natural host immunity. Immunity against these amoebae (whether acquired or natural) involves a combination of complement, antibody and cell-mediated immunity. Evidence suggests that the major mechanisms of immunity against these amoebae is activation of phagocytic cells, especially neutrophils, by lymphokines and opsonization of the amoebae by antibody which promote an antibody dependent cellular destruction of the organism.

Acanthamoeba↗

PubMed1991

Effect of 22-32 carbon n-3 polyunsaturated fatty acids on superoxide production in human neutrophils: synergism of docosahexaenoic acid with f-met-leu-phe and phorbol ester.

Docosahexaenoic (22:6 n-3) and eicosapentaenoic acid (20:5 n-3) stimulated the oxygen-dependent respiratory burst in intact neutrophils in a dose-dependent manner as measured by either superoxide dismutase (SOD)-inhibitable cytochrome c reduction and lucigenin-dependent chemiluminescence. A number of longer chain hexaenoic acids isolated from ram testis (22 to 32 carbon fatty acids) showed a diminishing response with increasing carbon chain length. 22:6 acted synergistically to enhance the responses to two other neutrophil agonists, f-met-leu-phe (FMLP) and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Whereas 22:6-induced chemiluminescence was markedly inhibited by pre-treatment with cytochalasin B, the response to FMLP was augmented, while TPA-induced activation was largely unaffected by cytochalasin B. 22:6-induced activation of neutrophils is independent of protein kinase C, as 22:6, unlike TPA, did not cause the membrane translocation of this enzyme. Furthermore, the putative protein kinase C inhibitor H-7 [1-(5-isoquinolinylsulphonyl)-2-methylpiperazine] had little effect on 22:6-induced chemiluminescence. In contrast, 22:6-induced activation was extremely sensitive to the calmodulin antagonist W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide], indicating that calmodulin-dependent enzymes may be involved in the responses to 22:6. These results suggest that different mechanisms are involved in the 22:6-, FMLP- and TPA-induced activation of neutrophil NADPH-oxidase.

Calmodulin↗

PubMed1991

Inhibition of tumour necrosis factor alpha (TNF-alpha)-induced neutrophil respiratory burst by a TNF inhibitor.

Tumour necrosis factor alpha (TNF-alpha) plays an important role in microbial defence and tissue damage by activating neutrophils. Therefore the ability of natural molecules to regulate the activity of TNF-alpha is likely to be of major importance in our understanding of the mechanisms of inflammation. We have examined the effects of a highly purified urine-derived TNF inhibitor (TNF inh) on the TNF-alpha-induced respiratory burst in human neutrophils. TNF-alpha inh-treated TNF-alpha was unable to stimulate a neutrophil lucigenin-dependent chemiluminescence response and superoxide formation. Treatment of TNF with the inhibitor also significantly reduced the priming ability of TNF-alpha for a response to the peptide f-met-leu-phe. These results show that the ability of TNF-alpha to induce a key neutrophil response is amenable to regulation by the TNF-alpha inh.

Cells, Cultured↗

PubMed1991

[Controversies about reconstruction after pancreatic resections in neoplasms of the periampullary area].

Extended pancreatic resections have still a significative morbidity: this explains all the technical alternatives proposed to the Whipple procedure. Treatment of the pancreatic stump after cephalic resection and the need of gastric resection are particularly debated today. The Authors, together with a wide literature review, report their experience with 45 patients who underwent cephalic (28 cases), subtotal (4 cases) or total (13 cases) pancreatectomy. Telescope pancreaticojejunostomy showed overall satisfying results (7% of dehiscences), inducing the Authors to use it in all cases. The role of pyloric preservation as proposed by Traverso and Longmire, which strongly reduces nutritional sequelae of pancreatectomy without negative effects on oncological radicality, is emphasized.

Duodenum↗

PubMed1991

Characterization of the major neutrophil-stimulating activity present in culture medium conditioned by Staphylococcus aureus-stimulated mononuclear leucocytes.

Culture medium conditioned by stimulating human mononuclear leucocytes (MNL) with killed Staphylococcus aureus (Scm) was found to contain a substantial amount of tumour necrosis factor-alpha (TNF-alpha) but no detectable tumour necrosis factor-beta (TNF-beta). Culture medium conditioned by MNL in the absence of bacteria contained no TNF-alpha activity. When Scm was fractionated by high-performance liquid chromatography (HPLC) on Bio-Sil TSK 250, TNF-alpha co-eluted with neutrophil-stimulating activity measured by chemiluminescence. Similarly, the ability of neutrophils to kill opsonized S. aureus was enhanced in fractions that contained this neutrophil-stimulating activity. The stimulating activity could be almost completely removed by pretreatment of the Scm with a TNF-alpha-specific monoclonal antibody (mAb). The ability of neutrophils to kill S. aureus in response to Scm was also substantially reduced by mAb to TNF-alpha. These results demonstrate that bacterial interaction with MNL leads to the release of neutrophil-stimulating activity that consists predominantly of TNF-alpha.

Antigens, Bacterial↗

PubMed1990

Neutrophil-mediated cartilage injury in vitro is enhanced by tumour necrosis factor alpha.

Neutrophil functions relevant to tissue damage are altered by cytokines such as tumour necrosis factor alpha (cachectin, TNF alpha), known to be present in inflammatory foci. In this study we examined the effect of TNF alpha on neutrophil-mediated cartilage damage in vitro. Human neutrophils were able to injure both human and bovine articular cartilage slices by degrading proteoglycan and inhibiting its synthesis. Recombinant human TNF alpha enhanced neutrophil-mediated degradation of proteoglycan, even when neutrophils were preincubated with TNF alpha and washed before incubating with cartilage. TNF alpha alone degraded proteoglycan and inhibited its synthesis. Neutrophil-mediated inhibition of proteoglycan biosynthesis was increased after incubating cartilage together with neutrophils and TNF alpha, but was unaltered when neutrophils were preincubated with TNF alpha. We conclude that TNF alpha enhances neutrophil injury to articular cartilage.

Adolescent↗

PubMed1990

Degradation of human cartilage by monocytes.

The effect of human peripheral blood monocytes on the degradation of human articular cartilage was studied in vitro using a radiometric assay to detect proteoglycan breakdown. The results showed that proteoglycan breakdown was increased by 60% after a 20 h exposure to monocytes (p less than 0.001).

Cartilage, Articular↗

PubMed1990

Killing of Plasmodium falciparum by cytokine activated effector cells (neutrophils and macrophages).

Macrophages display natural antibody independent killing of asexual blood stages of Plasmodium falciparum in vitro. In contrast, the neutrophil killing of P. falciparum requires the presence of antibodies. Cytokines such as TNF alpha have very little effect on the macrophage-induced antiplasmodial activity, but significantly increase the damage of parasites by neutrophils. Cytokines, TNF alpha, IFN-gamma and TNF beta at very high concentrations were not toxic to P. falciparum in culture. It is postulated that the basis for cytokine modulated antiplasmodial activity of leukocytes is increased expression of Fc and complement receptors, which leads to a more efficient interaction between the parasite and neutrophils. It is also postulated that the parasite evades natural macrophage killing mechanisms by inducing factors which suppress this macrophage activity. Cytokine inhibitors may be induced during the course of a malarial infection. These could be involved in attempts to attain a balance between the host and the parasite, by protecting the parasite from the damaging effect of the immune system and protecting the host from the deleterious effects of cytokines.

Animals↗

PubMed1990

Prevalence of anti-group B streptococcal type III capsular IgG antibodies in the United Kingdom and an analysis of their specific IgG subclasses.

Neonatal infection due to group B streptococcus (GBS) has a higher incidence in the USA than in the United Kingdom. A British population was investigated to ascertain the proportion of women who have protective anti-GBS type III IgG levels. Thirty-one (34%) of 90 pregnant women, 10 (43%) of 23 nonpregnant women, and 5 (50%) of 10 mothers of healthy colonized infants had anti-type III IgG greater than or equal to 2 micrograms/ml. Of 19 mothers who had infants infected with GBS type III, 17 (89%) had low specific IgG levels; of the other 2, the infants themselves had low IgG levels. The proportion of women in the UK with protective antibody levels is higher than in the USA. Sera (12) were assayed for anti-type III IgG isotypes; all contained IgG2, 6 had detectable IgG1, and 1 had IgG4.

Antibodies, Bacterial↗

PubMed1990

Immunoglobulin G subclass deficiency and predisposition to infection in Down's syndrome.

Serum immunoglobulins and IgG subclasses were measured in 26 children with Down's syndrome using an enzyme-linked immunosorbent assay and monoclonal antibodies. Eighteen (69%) of the children had increased susceptibility to infection. None of the children had deficiencies of total IgG and IgM, and only one had an IgA deficiency. IgG4 deficiency was diagnosed in 14 (54%) children. One child had a deficiency of IgG2. There were no children with deficiencies of either IgG1 or IgG3. There was a significant correlation between IgG subclass deficiency and predisposition to infection (P less than 0.05). Ninety percent of the patients with severe infections had low IgG4 whereas only 25% of those with no infections had low concentrations of IgG4. These results suggest that it is important to screen patients with Down's syndrome who have frequent systemic or respiratory infections for IgG subclass deficiencies because this may not be apparent from the assay of total IgG.

Adolescent↗

PubMed1990

Polyamine oxidase activity in rheumatoid arthritis synovial fluid.

Oxidation of polyamides by polyamine oxidases (PAO) leads to the generation of highly reactive aminoaldehydes which have been shown to have a variety of effects, including killing of pathogenic microorganisms and regulation of leucocyte functions. Data presented here show that PAO are present in synovial fluid from patients with rheumatoid arthritis. This finding may have important implications in the various properties attributed to synovial fluid which includes anti-inflammatory activity.

Arthritis, Rheumatoid↗

PubMed1990

Tetrandrine, a plant alkaloid, inhibits the production of tumour necrosis factor-alpha (cachectin) hy human monocytes.

Human mononuclear leucocytes (MNL) or the adherent fraction (monocytes) produced tumour necrosis factor-alpha (TNF-alpha) (by ELISA) in culture when stimulated with killed Staphylococcus aureus. The bisbenzylisoquinoline alkaloid, tetrandrine inhibited the capacity of MNL and monocytes to produce TNF-alpha at a concentration range of 0.1 to 5 micrograms/ml. Tetrandrine may be potentially useful in the treatment of inflammatory diseases in which TNF-alpha plays a major role.

Alkaloids↗

PubMed1990

Augmentation of the human monocyte/macrophage chemiluminescence response during short-term exposure to interferon-gamma and tumour necrosis factor-alpha.

The effects of short-term (30 min) pre-incubation of human monocytes and macrophages (3-day cultured monocytes) with leucocyte-derived human interferon-gamma (IFN-gamma) and recombinant human tumour necrosis factor-alpha (rTNF-alpha) were examined. Pre-incubation of either monocytes or macrophages with rTNF-alpha or IFN-gamma (100 U/5 x 10(5) cells) augmented their respiratory burst to formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), measured by the luminol- and lucigenin-dependent chemiluminescence assay. In addition, both cell types showed a burst of respiratory activity in the presence of rTNF-alpha or IFN-gamma only. The effects of IFN-gamma were removed by adsorption with an anti-IFN-gamma monoclonal antibody and those of rTNF-alpha were abolished by heating at 100 degrees C, or by the addition of anti-TNF-alpha monoclonal antibody. The results demonstrate that both IFN-gamma and rTNF-alpha are stimulators of monocytes and macrophages, and rapidly alter the capacity of the cells to respond to fMLP, which binds to cell surface receptors.

Cells, Cultured↗

PubMed1990

Production of tumor necrosis factors alpha and beta by human mononuclear leukocytes stimulated with mitogens, bacteria, and malarial parasites.

Tumor necrosis factors alpha and beta (TNF-alpha and TNF-beta) are multifaceted polypeptide cytokines which may mediate some of the significant changes in cellular homeostasis which accompany the invasion of the mammalian host by viruses, bacteria, and parasites. Although it is well established that bacterial lipopolysaccharide is a potent inducer of TNF-alpha, there is still very little known of the types of agents which can trigger the production of TNFs in mononuclear leukocytes. Using an enzyme-linked immunosorbent assay for measuring TNF-alpha and TNF-beta, we examined the capacity of various T-lymphocyte and beta-lymphocyte mitogens as well as microbial components to stimulate production of these cytokines in culture. The mitogens phytohemagglutinin, concanavalin A, and pokeweed mitogen induced production of both TNF-alpha and TNF-beta, while whole-killed Staphylococcus aureus and Bordetella pertussis, like lipopolysaccharide, were potent inducers of TNF-alpha but failed to stimulate TNF-beta production. TNF-alpha production was detectable within 1 h after stimulation, while TNF-beta production was not detected until after 8 h of culture. The bacterial products tetanus toxoid, purified protein derivative, pertussis filamentous hemagglutinin, and pertussis toxin were all able to induce TNF-alpha and TNF-beta production. Disrupted (frozen-thawed) Plasmodium falciparum-infected erythrocytes were also potent inducers of TNF-alpha and TNF-beta. The results demonstrated that a wide variety of microbial components are inducers of TNF-alpha. Some may not only be more effective than lipopolysaccharide but can also induce TNF-beta production. Furthermore, evidence is presented showing that TNF-beta but not TNF-alpha production correlates with lymphoproliferation.

Animals↗

PubMed1990

Tumor necrosis factor enhances neutrophil-mediated killing of Plasmodium falciparum.

We developed a radiometric assay by which the antiplasmodial effects of phagocytic cells can be quantitated. This assay was used to examine the effects of recombinant human tumor necrosis factor alpha (TNF-alpha) on the killing of Plasmodium falciparum by human neutrophils. Data presented demonstrated that neutrophils engulf and destroy P. falciparum, but substantial killing of parasites required the presence of either heat-labile or heat-stable opsonins. While recombinant TNF-alpha at concentrations of 5 to 50,000 U/ml showed no direct effects on the parasite, this cytokine augmented the antimalarial activity of neutrophils at doses of 20 to 250 U/10(6) neutrophils. The results suggest that TNF-alpha is an important component of the immune phagocytic effector mechanisms which are involved in destruction of the malarial parasite.

Animals↗

PubMed1990

Studies of chemotactic, chemotactic movement-inhibiting and random movement-inhibiting effects of interleukin-1 alpha and beta, tumour necrosis factors alpha and beta and interferon gamma on human neutrophils in assays using 'sparse-pore' polycarbonate (Nuclepore) membranes in the Boyden chamber.

Interleukin-1 alpha and beta (IL-1 alpha and beta), tumour necrosis factors alpha and beta (TNF alpha and beta) and interferon gamma (IFN gamma) were tested for their chemotactic effects, their effects on chemotactic movement towards N-formyl-methionyl-leucyl-phenylalanine (FMLP) and their effects on random locomotion of human peripheral blood neutrophils through polycarbonate membranes in Boyden-type chambers. Both IL-1 alpha and beta, but no other cytokine tested were chemotactic for neutrophils using 'sparse-pore' polycarbonate membrane. Both TNFs, but no other cytokine, inhibited neutrophil chemotactic movement towards FMLP using the same membrane. No cytokine influenced random migration of neutrophils through polycarbonate membrane of standard pore density. These results suggest that IL-1 may have a role as a chemotactic mediator of inflammation, but that TNFs may inhibit chemotactic migration of neutrophils into inflammatory lesions.

Biological Factors↗