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Biomedical subjects

A Ferrante

Publications and source records attributed to A Ferrante.

At least 145 records · Page 8Linked to original sources
PubMed1990

Immunoglobulin G subclass deficiency in children with high levels of immunoglobulin E and infection proneness.

Of 32 unrelated children with serum IgE greater than 1,000 U/ml, 17 were found to have infection proneness according to standard clinical criteria, and 15 were not infection prone. There were no statistical differences between these 2 groups of children with regard to age, sex, serum IgE levels or prevalence of asthma. However, the prevalence of eczema was significantly lower in the infection-prone group (p = 0.035). Of greater interest was the finding that 7 children in the infection-prone group had IgG subclass and/or IgA deficiency compared with none in the non-infection-prone group (p = 0.006). These results suggest that IgG subclass studies may be warranted in children with markedly elevated levels of serum IgE and proneness to infection.

Adolescent↗
PubMed1990

IgG subclass concentrations in absolute, partial and transient IgA deficiency in childhood.

Sixty-seven children with symptomatic IgA deficiency were studied on two separate occasions. Eighteen had aIgAd at presentation, and 49 had pIgAd. IgA concentrations had risen to the normal range for age in 22.2% of children presenting with aIgAd and 77.6% presenting with pIgAd when restudied at a median interval of 3.2 and 3.0 years, respectively. IgG subclass concentrations were measured by enzyme immunoassay in serum samples collected at enrollment from 12 children with aIgAd and 22 children with pIgAd. IgG2 and IgG4 concentrations for these 34 children were below the 5th centile for age and sex more frequently than expected (IgG2: chi square 5.8, P less than 0.025; IgG 4: chi square 18.4, P less than 0.0005). The prevalence of IgG2 deficiency or IgG4 deficiency did not differ significantly between those with aIgAd and those with pIgAd. IgG2 concentrations remained below the 5th centile more frequently than expected when retested in 31 children whose pIgAd had resolved (chi square 4.6, P less than 0.05). Children with aIgAd at presentation had IgG1 and IgG2 concentrations above the 95th centile more frequently than expected (IgG1: chi square 19.7, P less than 0.0005; IgG2: chi square 13.5, P less than 0.001) but this was not seen for IgG3 and IgG4 concentrations. Children with pIgAd did not have elevated IgG1 or IgG2 concentrations at presentation. High IgG1 and IgG2 concentrations in aIgAd may be a compensatory mechanism to afford protection from infection or could be part of a selective secondary response to repeated episodes of infection.

Adolescent↗
PubMed1990

Aspects of immunoglobulin replacement therapy.

Immunoglobulin replacement therapy appears to benefit some patients who have IgG subclass deficiencies. Because some patients with subnormal trough concentrations of IgG subclasses remain well, because other patients who have borderline/low normal concentrations of an IgG subclass are abnormally infection-prone and helped by immunoglobulin therapy and because infection proneness in individual patients does not always appear to parallel their IgG subclass concentrations, it is evident that IgG subclass concentrations, while a helpful guide, are not an absolute determinant of the need for immunoglobulin replacement therapy in infection-prone patients. Low IgG subclass concentrations may indicate impaired ability to produce certain "specific" antibodies and antibody replacement is likely to be the crucial factor in treatment rather than merely maintaining concentrations of IgG subclasses at particular levels.

Adolescent↗
PubMed1989

Altered neutrophils in mice immune to experimental Naegleria amoebic meningoencephalitis.

Naegleria fowleri is the cause of primary amoebic meningoencephalitis in man. The mouse is considered to be a suitable experimental model for this disease. The data presented shows that blood neutrophils from N. fowleri immune mice (immunised) that had received a 'recall' amoeba antigen had altered responses compared with those from similarly treated normal mice. The neutrophils from immune animals showed increased basal levels of oxygen-dependent respiratory activity, measured by the chemiluminescence response. These neutrophils also showed increased responses to formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), phorbol myristate acetate (PMA), and opsonized N. fowleri. The results are consistent with previous data suggesting that the neutrophil (and its activation) is important in defence against N. fowleri.

Amebiasis↗
PubMed1989

Mechanisms of human neutrophil-mediated cartilage damage in vitro: the role of lysosomal enzymes, hydrogen peroxide and hypochlorous acid.

Cartilage is a focal point of attack by cellular and molecular elements of the inflammatory response which occurs in arthritic diseases. Neutrophils damage articular cartilage by degrading matrix components and inhibiting their synthesis. The aim of this study was to elucidate mechanisms of this damage. Human neutrophils were isolated from blood by centrifuging through Ficoll-Hypaque and granule extract prepared from them. Articular cartilage from adult humans and cattle was maintained in organ culture. Cartilage degradation (release of 35S-labelled proteoglycan) or synthesis (incorporation of 35S into proteoglycan) was determined after various treatments. Human neutrophils and neutrophil granule extract degraded proteoglycan and inhibited proteoglycan synthesis. The specific leucocyte elastase inhibitor N-methoxysuccinyl-(ala)2-pro-val-chloromethylketone (MAAPVCMK) partially reversed these effects. H2O2, a product of the neutrophil respiratory burst, when added directly at 10(-6)mol/L, or generated by glucose oxidase (GO)/glucose inhibited proteoglycan synthesis but had no effect on degradation. Hypochlorous acid (OHCl), a product of the myeloperoxidase (MPO)/H2O2/Cl system at 50 mumol/L degraded proteoglycan and inhibited its synthesis. OHCl produced by granule extract (as a source of MPO) + GO-generated H2O2 + Cl- degraded proteoglycan. The results indicate that neutrophil-mediated proteoglycan degradation and inhibition of synthesis is largely attributable to elastase and secondarily to OHCl, whereas H2O2 impairs synthesis without affecting degradation of proteoglycan.

Animals↗
PubMed1989

IgG4 deficiency in IgA-deficient patients.

IgG subclass deficiency may be an important factor in the infection proneness of some IgA-deficient subjects. Although several studies on IgG subclass deficiency in IgA-deficient subjects have been reported, most have been unable to assess the incidence of IgG4 deficiency because the limitations of the assay methods used have often made a distinction between low normal and subnormal concentrations impossible. Having developed an enzyme-linked immunosorbent assay capable of measuring concentrations of all the IgG subclasses in healthy subjects of all ages and having established age-normal ranges for IgG subclasses using this assay, we measured IgG subclass concentrations in 73 IgA-deficient patients, the majority of whom were children with recurrent respiratory infections. The results showed that IgG4 deficiency occurred in 26% of the patients and was the most common IgG subclass deficiency found. IgG1, IgG2 and IgG3 deficiencies occurred, respectively, in 10, 12 and 8% of the patients. IgA-IgG4 deficiency occurred in 16% of the patients; IgA-IgG2-IgG4 in 4%; and IgG1-IgG2-IgG4, IgA-IgG1 and IgA-IgG2-IgG3 each occurred in 3%. Other subclass deficiencies or combinations of deficiencies were less frequent. Our results suggest that IgG4 deficiency even in the absence of IgG2 deficiency may be an important but hitherto largely unrecognized factor in infection proneness in some IgA-deficient patients.

Adolescent↗
PubMed1989

Augmentation of the neutrophil response to Naegleria fowleri by tumor necrosis factor alpha.

Conditioned medium from phytohemagglutinin-stimulated human mononuclear leukocytes, previously shown to activate neutrophils for amoeba killing, was found to contain high levels of tumor necrosis factor alpha (TNF-alpha) by an enzyme-linked immunosorbent assay. The effects of human recombinant TNF-alpha on the response of human neutrophils to the pathogenic free-living amoeba Naegleria fowleri was studied in vitro. The data showed that recombinant human TNF-alpha augmented the neutrophil respiratory burst (assessed by the cytochrome c reduction assay and lucigenin-dependent chemiluminescence assay) in response to amoebae opsonized with human serum. The priming effects of TNF-alpha were transient; marked enhancement was found with short 5- to 30-min preincubations of neutrophils with the cytokine. The enhancement of oxygen radical production was evident with 20 U of TNF-alpha per 10(6) neutrophils and continued to increase with up to 100 U. TNF-alpha also augmented the neutrophil lysosomal enzyme release in response to N. fowleri. The results support previous reports suggesting an important role of neutrophil cytokine activation for effective immunity against free-living amoebae.

Adjuvants, Immunologic↗
PubMed1989

Tumor necrosis factor alpha potentiates neutrophil antimicrobial activity: increased fungicidal activity against Torulopsis glabrata and Candida albicans and associated increases in oxygen radical production and lysosomal enzyme release.

The capacity of human tumor necrosis factor alpha (TNF-alpha) to modulate the killing of the opportunistic pathogens Torulopsis glabrata and Candida albicans by human neutrophils was studied. TNF-alpha significantly enhanced neutrophil fungicidal activity in a concentration-dependent manner and was evident in a range of neutrophil-fungus ratios. Enhanced killing of T. glabrata required much lower TNF-alpha concentrations than were required for enhancement of killing of C. albicans. Maximal enhancement of killing occurred with 20 and 100 U of TNF-alpha per 5 x 10(6) neutrophils for T. glabrata and C. albicans, respectively. The fungal killing kinetics demonstrated that TNF-alpha augmentation of fungicidal activity was evident within 1 h and persisted for an incubation period of at least 22 h. Preincubation of neutrophils with TNF-alpha was essential for the enhancement of killing. Maximal stimulation of killing was observed within 1 h of preincubation with TNF-alpha, and poor stimulation of killing was observed when TNF-alpha was added at time zero. Associated with the increase in fungicidal activity was an increased production of superoxide and an enhanced degranulation of enzymes and other proteins from azurophilic and specific granules in response to the fungi. The results demonstrate that TNF-alpha augments the neutrophil oxidative respiratory burst and the degranulation induced by opsonized fungi and that it increases the neutrophil fungicidal activity.

Adjuvants, Immunologic↗
PubMed1989

Alterations in function and subpopulations of peripheral blood mononuclear leukocytes in children with portal hypertension. Leukocyte subtypes and function in portal hypertension.

Children with advanced portal hypertension usually have splenomegaly (often associated with hypersplenism) which may lead to a decreased life span of circulating blood leukocytes. In a group of 6 children (age range 4-15 years; mean age 8.5 years) with portal hypertension, we examined peripheral blood mononuclear leukocytes for possible changes in their proportions, numbers and function. Compared to normal subjects, children with portal hypertension had a marked reduction in the percentages and absolute numbers of T lymphocytes (CD3+), T 'helper/inducer' (CD4+) and T 'suppressor/cytotoxic' (CD8+) cells. However, the percentages of B lymphocytes (FMC1+), natural killer cells (Leu 11+) and monocytes (morphological) were increased, and the absolute numbers of B cells were significantly increased in these patients. Lymphocyte responsiveness to phytohemagglutinin, pokeweed mitogen and concanavalin A were depressed in the patients, while the natural killer cell cytotoxicity was slightly increased. Thus, children with portal hypertension show changes in the relative proportions and absolute numbers of peripheral blood mononuclear blood leukocyte subpopulations as well as changes in mononuclear leukocyte function.

Adolescent↗
PubMed1989

Suppression of human monocyte interleukin 1 production by the plant alkaloid tetrandrine.

The bisbenzylisoquinoline alkaloid, tetrandrine, was shown to affect some important human monocyte functions. The drug caused significant inhibition of random movement, chemotaxis, superoxide anion generation and interleukin 1 (IL-1) production. By contrast, degranulation and hexose-monophosphate shunt activity were unaffected. Tetrandrine may be of value in the treatment of chronic inflammatory diseases where IL-1 has a major role as an inflammatory mediator.

Alkaloids↗
PubMed1989

Staphylococcus aureus-stimulated mononuclear leucocyte-conditioned medium increases the neutrophil bactericidal activity, and augments oxygen radical production and degranulation in response to the bacteria.

Conditioned medium produced by human mononuclear leucocytes (MNL) stimulated with formalin-fixed, heat-killed Staphylococcus aureus enhanced the killing of opsonized S. aureus by human neutrophils. This enhancement was not seen when conditioned medium from non-stimulated MNL or medium cultured in the absence of both bacteria and MNL was used. There was a five-fold decrease in survival of bacteria when neutrophils were treated with conditioned medium. Conditioned medium-treated neutrophils showed increased initial rate of killing but after 20-30 min the rate of killing was similar to that of non-conditioned medium-treated leucocytes. The neutrophils treated with conditioned medium showed increased production of chemiluminescence, superoxide and lysosomal enzyme release (from both azurophilic and specific granules) in response to opsonized S. aureus. The results demonstrate that bacterial interaction with MNL leads to the release of mediators (cytokines) which potentiate the anti-bacterial function of neutrophils.

Blood Bactericidal Activity↗
PubMed1988

Purification of human monocytes/macrophages by adherence to cytodex microcarriers.

Adherence to cytodex microcarries was used as a means of purifying and culturing human monocytes. Mononuclear leukocytes obtained from centrifugation of blood on Hypaque-Ficoll medium could be enriched for monocytes/macrophages by adherence to cytodex microcarriers. Using this system it was possible to obtain monocytes/macrophages in high yields and viability, and good purity. Detachment of the monocytes from the microcarriers was simply achieved by a 1-2 min agitation of the contents. Cells which had been cultured up to 30 days on the microcarriers could be similarly detached. Functional studies on the detached monocytes macrophages showed the cells to respond well to stimuli such as zymosan and fMLP, and were capable of killing opsonized bacteria.

Blood Bactericidal Activity↗
PubMed1988

Neutrophil stimulating activity released by Staphylococcus-stimulated mononuclear leukocyte conditioned medium. Further characterization and partial purification.

Culture medium conditioned by human mononuclear leukocytes (MNL) stimulated with formalin fixed heat-killed Staphylococcus aureus induces a small respiratory burst in human neutrophils, and dramatically increases the response of neutrophils to stimuli such as N-formyl-L-methionyl-L-leucyl-L-phenylalanine. The data presented show that the activity is not unique to Staphylococcus aureus. Similar neutrophil modulating activities were produced by medium conditioned by MNL cultured in the presence of Streptococcus pneumonia, and Group B streptococcus. The activity was relatively resistant to heating; significant reduction of activity was observed only when 80 degrees C was reached. Neutrophil stimulating activity production by stimulated MNL was dependent on protein and RNA synthesis and the activity appeared to be released by the non-adherent fraction of the MNL, suggesting that it is not of macrophage origin. The activity was not sensitive to soya bean trypsin inhibitor, but was sensitive to trypsin and was not removed when stimulated conditioned medium was depleted of immunoglobulin and albumin by affinity chromatography. Purification by gel filtration on Sephadex G-100 and high-performance liquid chromatography with Bio-Sil TSK250 columns showed that the major activity had an apparent molecular weight of 35,000-43,000 under conditions in which ionic interactions and association with albumin were reduced; by using polyethylene glycol or high salt (0.46 M Na+) in the elution buffer.

Cell Adhesion↗
PubMed1988

Effects of cytochalasin B, N-formyl peptide and plasma on polarisation, zeiosis (blebbing) and degranulation of polymorphonuclear leukocytes in suspension.

The effects were studied of cytochalasin B and N-formyl peptide (FMLP) in various concentrations on the morphology and degranulation (release of the granule contents lysozyme and beta-glucuronidase) of polymorphonuclear leukocytes (PMN) suspended in either Hanks' solution or 100% fresh heparinised plasma. PMN in low concentrations of FMLP in Hanks' solution or in plasma alone showed "long" polarisation and did not degranulate. Cytochalasin B caused the PMN in low concentrations of FMLP or in plasma to become spherical, but no degranulation of the cells occurred. High concentrations of FMLP in Hanks' solution induced "short" polarisation of PMN with slight degranulation of the cells. Cytochalasin B together with high concentrations of FMLP in Hanks' solution induced zeiosis ("blebbing") and marked degranulation of the cells. However, cytochalasin B and high concentrations of FMLP in plasma caused PMN to exhibit "short" polarised morphology and markedly degranulate. These results suggest that degranulation of PMN can be associated with either the "short" polarised shape of the cells or zeiosis, but not the "long" polarised form. Furthermore, the results indicate that plasma, although capable of causing "long" polarisation of the cells, inhibits zeiosis without affecting the degranulation of the cells induced by cytochalasin B.

Blood↗
PubMed1988

Tumour necrosis factor-beta modulates human neutrophil-mediated cartilage damage.

Human neutrophils, when cultured with human articular cartilage coated with heat-aggregated immunoglobulin G, degraded proteoglycan and inhibited its synthesis. Neutrophil-mediated degradation of cartilage was potentiated by recombinant human tumour necrosis factor-beta (TNF beta), although TNF beta alone did not alter proteoglycan degradation. This effect was seen when TNF beta, neutrophils, and cartilage were incubated together, and also when neutrophils were preincubated with TNF beta and washed before being added to cartilage. Similar results were obtained with living and killed cartilage. In contrast, pretreatment of neutrophils with TNF beta abrogated the neutrophil-mediated inhibition of proteoglycan biosynthesis. There was no effect of TNF beta alone on synthesis of proteoglycan.

Cartilage↗