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Biomedical subjects

M Duse

Publications and source records attributed to M Duse.

At least 19 recordsLinked to original sources
PubMed2000

A video densitometric analysis of viral burden and follicular dendritic cell damage in lymph nodes in the latency phase of HIV infection.

BACKGROUND: The aim of this study was to collect quantitative data on damage to follicular dendritic cells (FDC) and on the structure of germinal centers (GC) in the early phase of HIV infection. METHODS: Lymph node sections from 10 HIV(+) subjects and from 5 HIV(-) control subjects were stained by immunohistochemistry for CD21, an FDC marker; gp24, to assess the HIV load; and IgM, to measure antibodies within the GC. RESULTS: The volume fraction (V(area)) and the logarithm of the inverse gray value (ArLIGV) of CD21 areas showed a highly significant decrease in HIV(+) specimens. The mean ArLIGV values ranged between 0.0916 +/- 0.01 and 0.3826 +/- 0.11 versus 0.6856 +/- 0.19 on average in controls (P < 0.001 for both). Six of 10 HIV(+) specimens were positive for gp24. Staining was limited to GC and showed a distribution pattern similar to that of CD21. CONCLUSIONS: FDC already undergo considerable damage during the latency phase of HIV infection. The pattern of CD21 indicates that, although FDC decrease in number, the staining intensity of positive cells is basically preserved. Video densitometric analysis, an approach requiring a strict standardized protocol, may help monitor disease course and evaluate response to therapy by quantifying viral burden and lymph node damage.

Dendritic Cells, Follicular↗
PubMed2000

Serum amyloid A is an activator of PMN antimicrobial functions: induction of degranulation, phagocytosis, and enhancement of anti-Candida activity.

Serum amyloid A (SAA) is a 12-kDa protein secreted in large amounts by liver cells during microbial infections or inflammatory diseases. We have recently reported that SAA induces chemotaxis of polymorphonuclear cells (PMN), monocytes, and T lymphocytes and stimulates their adhesion to endothelial monolayers. In this study, we investigated whether SAA regulates PMN antimicrobial activities. We found that recombinant SAA (rSAA), at concentrations comparable to serum levels attained during an acute phase response, is a potent activator of PMN. Stimulation of PMN by rSAA results in a rapid and transient increase of cytosolic calcium concentration and up-regulation of cell-surface expression of antigens involved in adhesion and microbial recognition such as CD11c and CD16. In addition, stimulation of PMN with rSAA increases secretion of lactoferrin, an antimicrobial protein that is contained in specific granules of PMN and enhances PMN phagocytic activity against heat-killed Candida albicans. Finally, activation of PMN with rSAA enhances their anti-Candida activity within 30 min of stimulation. These results suggest that SAA is involved in up-regulating PMN antimicrobial activities and that high circulating concentrations of SAA as seen in the acute phase response may constitute a potential host defense mechanism against fungal infections.

Acute-Phase Reaction↗
PubMed1999

Influence of maternal CD4 levels on the predictive value of virus load over mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1). Study Group for Vertical Transmission.

Forty-four anti-HIV seropositive pregnant women were enrolled in a study of maternal factors related to mother-to-infant human immunodeficiency virus type 1 (HIV-1) transmission. HIV-1 infection was documented in 11 of 45 infants (24.4%). Obstetric factors, maternal CD4 counts, and disease stage were not related to the risk of transmission. HIV-1 RNA levels at delivery were significantly higher in mothers who transmitted the infection (P = .024). A strong relationship between viral load and risk of transmission was observed in women with stage A1 (P= .006), but not in those with stages A2-A3. These results suggest that vertical transmission of HIV-1 is multifactorial and that viral load plays a major role in mothers with early-stage HIV-1 infection.

Adult↗
PubMed1999

Expression of inducible nitric oxide synthase in human granulomas and histiocytic reactions.

Inducible nitric oxide synthase (iNOS) is required in immune response against infections and is involved in granuloma formation in animals; in murine macrophages, iNOS is induced by lipopolysaccharide and interferon-gamma. In contrast, the role of iNOS in human immune response against infections is still questioned, and its expression in granulomas is poorly investigated. Using Western blotting and immunohistochemistry, we investigated iNOS expression in human lymph nodes with nonspecific reactions and in tissues containing granulomas caused by mycobacteria, Toxoplasma, Cryptococcus neoformans, Leishmania, Bartonella, noninfectious granulomas (sarcoidosis, foreign body), and other hystiocitic reactions (Kikuchi's disease, Omenn syndrome). iNOS was undetectable in nonspecific reactive lymphadenitis, foreign-body granulomas, and Omenn syndrome, whereas it was strongly expressed in infectious granulomas, sarcoidosis, and Kikuchi's diseases. Immunohistochemistry demonstrated that iNOS was selectively expressed by the epithelioid and multinucleated giant cells within the granulomas. Use of an anti-nitrotyrosine antibody, recognizing nitrosilated amino acid residues derived from nitric oxide production, revealed a consistent positivity within the cells expressing iNOS, thus suggesting that iNOS is functionally active. Detection of cytokines by reverse transcriptase-polymerase chain reaction demonstrated that tissues that were positive for iNOS, also expressed the Thl-type cytokine interferon-gamma mRNA, but not the Th2-type cytokine interleukin-4. Taken together, these results indicate that iNOS is involved in different human immune reactions characterized by histiocytic/granulomatous inflammation and associated with Th1-type cytokine secretion.

Adult↗
PubMed1998

IL-10 and IL-4 co-operate to normalize in vitro IgA production in IgA-deficient (IgAD) patients.

In the present study we evaluated in vitro immunoglobulin production from IgAD individuals and healthy controls. Peripheral blood mononuclear cells (PBMC) from IgAD and controls were cultured with anti-CD40 MoAb presented on a CDw32-transfected fibroblast cell line (CD40 system) in the presence of IL-10, IL-2, IL-4, transforming growth factor-beta (TGF-beta) alone as well as of IL-10 in combination with each of the other three cytokines. Only IL-10 added alone induced significant changes in baseline immunoglobulin production; marked increases in median supernatant levels of all three isotypes were observed in both groups. The most striking finding of this study was the synergizing effect of IL-4 on IgA production in the IgAD group when added with IL-10; median IgA supernatant level increased to a value superimposable on that found in the normal controls which remained about the same as when stimulated with IL-10 alone. The synergic effect of IL-4 and IL-10 was specific to the IgA isotype.

Adolescent↗
PubMed1998

Prospective study of mother-to-infant transmission of hepatitis C virus (HCV) infection. Study Group for Vertical Transmission.

Seventy-five women with anti-hepatitis C virus (HCV) antibody were enrolled prospectively during pregnancy or at delivery for study of mother-to-child transmission of HCV. Twenty-three women were coinfected with the human immunodeficiency virus (HIV). Seventy babies were monitored for at least 6 months. HCV infection was diagnosed in six infants (8.6%), four of whom were born to anti-HIV-positive mothers. HCV RNA was first detected between 2 and 6 months, and the genotypes of infected babies matched those of their mothers (type 1: n = 4; type 3: n = 2). Identical master sequences of the hypervariable region (HVR1) were detected in a mother-infant pair. In three babies coinfected with HCV and HIV, anti-HCV disappeared between 2 and 7 months, being persistently negative in two cases monitored for 11 and 26 months. Transmitting mothers did not differ significantly from those who did not transmit the infection with anti-HIV, HCV genotypes, and viral load at delivery, but had lower rate of reactivity to C100 by the recombinant immunoblot assay (RIBA) (P < .01). This prospective study confirms transmission of HCV from anti-HIV-negative mothers (4.4% in this series). Absence of anti-C100 antibodies at delivery is apparently related to increased risk of vertical transmission. Seronegative HCV infection can be observed in children coinfected with HIV.

Adult↗
PubMed1997

CD8+CD28- T cells in vertically HIV-infected children.

To evaluate whether vertical HIV infection interferes with the expression of CD28 on T lymphocytes, 25 HIV-infected children and 29 seroreverted children born to HIV+ mothers were studied. The percentage of CD28- cells among CD8+ T lymphocytes was higher in HIV-infected children than in controls (P < 0.001). In fact, in HIV-infected children, this percentage was elevated from the first year of life, while in healthy seroreverted children, the proportion of CD28- cells among CD8+ cells rose progressively with age (r = 0.49; P = 0.008). In HIV+ children, the CD8+ CD28-, but not CD8+ CD28+ cell proportion was significantly correlated with immunological markers of disease progression, such as CD4+ cell loss (r = -0.65; P < 0.001) and the level of in vitro spontaneous lymphocyte apoptosis (r = 0.53; P = 0.03).

Age Factors↗
PubMed1997

T cell activity and cytokine production in X-linked agammaglobulinemia: implications for vaccination strategies.

In the 5 X-linked agammaglobulinemia (XLA) patients studied we show that memory T cells are present and that T lymphocytes proliferate normally to mitogens, monoclonal antibodies and, in particular, to recall antigens demonstrating normal in vivo T cell priming despite the absence of B cells. Furthermore, in vitro T cell activation in response to both T cell receptor-independent and T-cell receptor-dependent signals leads to a pattern of cytokine production characteristic of primed T cells and necessary for normal T cell function. These data are in good agreement with results obtained in gene-targeted mice and further support the concept that the absence of B cells does not impair induction of in vivo T cell memory and effector function which is generally considered to be of great importance in conferring protection against viral infections. Thus, while there is no risk of inducing infections in XLA patients by administering vaccines containing killed viruses or recombinant viral proteins, stimulation of T cell immunity by such vaccines may be of potential benefit particularly in the defense against infections with viruses such as the hepatitis B virus to which hypogammaglobulinemic patients are particularly exposed.

Adolescent↗
PubMed1996

Defective expression of HLA class I and CD1a molecules in boy with Marfan-like phenotype and deep skin ulcers.

We report the case of a boy with low expression of HLA class I molecules on peripheral blood mononuclear cells, which is associated with immunodeficiency. The patient, who had a Marfan-like phenotype, had chronic deep skin ulcers and sinobronchiectasis. Immunohistologic examination of the ulcerated skin showed a dense perivascular infiltrate composed of normal mature lymphocytes and macrophages. All cells in the infiltrate showed an apparently normal expression of HLA class I molecules, but intraepidermal dendritic Langerhans' cells were negative for CD1a, an antigen that is a highly specific marker for these cells and is abundantly expressed in some self-healing forms of cutaneous lesions. It is therefore speculated that a defective expression of CD1a molecules can contribute to the chronic persistence of deep skin ulcers, which have already been reported in association with defective expression of HLA class I molecules.

Adolescent↗
PubMed1996

Intravenous immune globulin in the treatment of intractable childhood epilepsy.

Many clinical and experimental data strongly support the role of immune mechanisms in the pathogenesis of childhood epilepsy. Following Pechadre's first observations with intramuscular immune globulin (IMIG), intravenous immune globulin (IVIG) has been employed in some forms of intractable childhood epilepsy (ICE), mainly in West syndrome (WS) and Lennox Gastaut syndrome (LGS), with good results. So far, 373 children suffering from ICE have been treated in 29 studies and 174 have responded favourably. Although these studies are heterogeneous and controls are lacking, most authors report similar responsiveness ranging from 30% to 50%. Several mechanisms have been suggested to account for the efficacy of IVIG in ICE including antiviral effect, substitutive therapy in patients with concomitant humoral immunodeficiency, idiotype-anti-idiotype interaction or a neuromodulant effect. To better define the real efficacy of IVIG in ICE in paediatric patients, a randomized, multicenter, double-blind clinical trial was started in 1993, including only patients suffering from WS and LGS. To date, only one double-blind trial had been carried out (with both adult and paediatric patients); it showed a clear trend in favour of IVIG treatment but lacked statistical significance, perhaps because of the small and heterogeneous sample. Controlled multicentre studies on well-defined populations are needed and patients with WS and LGS are probably the best candidates.

Adolescent↗
PubMed1995

Effect of HIV vertical transmission on the ontogeny of T cell antigens involved in the regulation of humoral immune response.

HIV infection causes progressive impairment of humoral immunity, including defective specific antibody production. To evaluate whether vertical HIV infection interferes with the expression on CD4+ lymphocytes of developmentally regulated molecules, that play a crucial role in the generation of immunological memory (CD45 isoforms) and in attainment of antibody responses (CD40L), 22 HIV-infected children and 36 seroreverted children born to HIV+ mothers were studied. The percentage of CD40L+ PBMC after activation in vitro with phorbol myristate acetate (PMA) plus ionomycin was lower in HIV-infected children than in controls (P < 0.004). This correlated with the depletion of CD4+ lymphocytes (r = 0.75; P < 0.001). CD40L expression rose progressively with age (r = 0.36; P = 0.03) in seroreverted children, but not in HIV-infected children, suggesting that while in normal children in vivo antigen stimulation results in progressive attainment of CD40L expression (and thus to effective T-B cell cooperation), this process is largely defective in HIV-infected children, contributing to the genesis of humoral immune deficiency. The proportion of CD4+ cells bearing the CD45RO isoform was increased among HIV-infected infants during the first years of life. However, the percentage of CD4+ CD45RO+ peripheral blood mononuclear cells (PBMC) progressively increased with age in controls (r = 0.69; P = 0.03), but not in HIV-infected children, showing that while vertical transmission of HIV does not prevent CD45RO expression early in life, it is associated with a disturbance of the physiological process of antigen priming, contributing to poor immunological memory to T cell-dependent antigens.

Age Factors↗
PubMed1994

Hemidystonia secondary to acquired toxoplasmosis in a non-immunodeficient patient.

We discuss the unusual presentation of acquired toxoplasmosis in a girl with severe and transient hemidystonia as a unique symptom. Serum titres of anti-toxoplasma antibodies increased whereas no specific antibody response in the CSF was observed. While symptomatic drugs were inefficacious, specific anti-toxoplasmosis therapy led to complete and permanent recovery within 2 months.

Cerebrovascular Disorders↗
PubMed1994

X-linked agammaglobulinemia, growth hormone deficiency and delay of growth and puberty.

Coinheritance of X-linked agammaglobulinemia and growth hormone deficiency (XLA/GHD) has been classified as an independent primary immune deficiency. We evaluated the pattern of growth and endocrine function in seven XLA subjects (ages 10.9-20.1 years); four belonged to two different XLA pedigrees and three represented sporadic XLA cases. Three had reached adulthood (final stature 176.0, 173.5 and 165.0 cm, respectively) and their retrospective growth showed delay in growth and puberty during adolescence. In the other four subjects, growth hormone production was measured by growth hormone pharmacological stimulation tests (clonidine, arginine): three of four patients had insufficient growth hormone responses (peak growth hormone < 10 micrograms/l); all three had delayed puberty; their growth hormone responses increased after "priming" with testosterone, reaching values > 10 micrograms/l in two of them and allowing diagnosis of "true" growth hormone deficiency in the third. The fourth was a normally growing subject who showed a normal growth hormone response both before and after testosterone priming. Six out of the seven subjects showed a growth pattern consistent with delay in growth and puberty. Our results suggest that true XLA/GHD is rarer than previously supposed and that subnormal responses to growth hormone stimulation tests may be found without sex steroid priming of the test in adolescence. The most probable growth pattern in XLA appears to be delay in growth and puberty, as has already been described for other chronic diseases.

Adult↗
PubMed1993

Extensive deletion of immunoglobulin heavy chain constant region genes in the absence of recurrent infections: when is IgG subclass deficiency clinically relevant?

This report describes two children with undetectable serum levels of IgA1, IgG2, IgG4, and IgE due to a homozygous deletion encompassing the A1-E genes. The father is a heterozygous carrier of the same deletion and the mother a heterozygous compound carrying the deletion on one chromosome and duplication on the other. In both children, serum IgG, IgG1, and IgG3 were higher than in normal children and IgG antibody response to tetanus toxoid and polysaccharide antigens was normal with increased IgG1 and IgG3 response compared to controls. The latter can be interpreted as a compensatory mechanism for the subclass deficit and may explain the lack of significant infections in both children. The importance of distinguishing IgG subclass deficiency due to gene deletion from that due to immunoregulatory dysfunction is discussed.

Adolescent↗
PubMed1993

Intravenous immunoglobulin in two children with Guillain-Barré syndrome.

Two children with Guillain-Barrè syndrome were successfully treated with high-dose intravenous immunoglobulin (IVIG) and no relapses occurred over a 1 year follow up. No side-effects were observed. These data provide further evidence that IVIG may be safely and effectively employed in children with Guillain-Barrè syndrome.

Adolescent↗
PubMed1993

The lesson of agammaglobulinemia 40 years after Bruton's discovery.

Forty years after Bruton's discovery, the spectrum of primary defects of immunoglobulins has been largely extended and characterized. An increasingly more accurate recognition of the basic pathogenetic mechanisms of disease has helped to design more effective drugs and therapeutic strategies for patients with both primary and secondary immune deficiencies. In recent years, major advances in molecular biology have allowed characterization of the genetic basis of many primary immunodeficiencies, resulting in more accurate genetic counseling and leading to the first successful application of genetic therapy to the treatment of a human disease.

Agammaglobulinemia↗