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Biomedical subjects

R Giorno

Publications and source records attributed to R Giorno.

At least 19 recordsLinked to original sources
PubMed2000

Application of Staphylococcal enterotoxin B on normal and atopic skin induces up-regulation of T cells by a superantigen-mediated mechanism.

BACKGROUND: The skin of patients with inflammatory skin diseases such as atopic dermatitis is frequently colonized with Staphylococcus aureus. Colonization with S aureus has been reported to exacerbate atopic dermatitis. Recent studies have demonstrated that S aureus isolated from the skin of patients with atopic dermatitis releases bacterial toxins that act as superantigens. We have previously applied the staphylococcal superantigen staphylococcal enterotoxin B (SEB) on intact human skin and found that the application led to induction of dermatitis. OBJECTIVE: The purpose of the study was to determine whether superantigen-induced dermatitis is primarily due to a T cell-superantigen-mediated reaction or represents nonspecific cytokine-driven inflammation. METHODS: We applied SEB, vehicle, and sodium lauryl sulfate on normal skin in healthy (n = 6) and atopic subjects (n = 6) and biopsy specimens were taken from all treated areas. The biopsy specimens from all subjects and peripheral blood from the atopic subjects were analyzed for the T-cell receptor (TCR) Vbeta repertoire with mAbs against TCR Vbeta 2, 3, 8.1, 12, 14, and 17. RESULTS: From all subjects, both healthy and patients with atopic dermatitis, skin biopsy specimens from SEB-treated areas demonstrated selective accumulation of T cells expressing SEB-reactive TCR Vbeta 12 and 17 (P <.05). This selective up-regulation was not found in the sodium lauryl sulfate-treated areas. CONCLUSION: Our data strongly support that superantigen-induced T-cell activation is involved in the dermatitis seen after experimental application of SEB on intact skin.

Administration, Topical↗
PubMed1997

Increased nitric oxide production accompanied by the up-regulation of inducible nitric oxide synthase in vascular endothelium from patients with systemic lupus erythematosus.

OBJECTIVE: To investigate whether systemic lupus erythematosus (SLE) is accompanied by increased serum nitrite levels, whether active compared with inactive disease is associated with greater nitric oxide (NO) production, and whether endothelial cells or keratinocytes serve as cellular sources of NO by virtue of their increased expression of either constitutive nitric oxide synthase (cNOS) or inducible NOS (iNOS). METHODS: Fifty-one serum samples (46 from patients with SLE) were analyzed for NO production by measuring nitrite levels in a calorimetric assay. Skin biopsy samples from 21 SLE patients and 11 healthy volunteers were evaluated immunohistochemically, using monoclonal antibodies, for endothelial cell and keratinocyte cNOS and iNOS expression. RESULTS: Serum nitrite levels were significantly elevated in the 46 patients with SLE (mean +/- SEM 37 +/- 6 microM/liter) compared with controls (15 +/- 7 microM/liter; P < 0.01), and were elevated in patients with active SLE compared with those with inactive disease (46 +/- 7 microM/liter versus 30 +/- 7 microM/liter; P < 0.01). Serum nitrite levels correlated with disease activity (r = 0.47, P = 0.04) and with levels of antibodies to double-stranded DNA (r = 0.35, P = 0.02). Endothelial cell expression of iNOS in SLE patients (mean +/- SEM score 1.5 +/- 0.2) was significantly greater compared with controls (0.6 +/- 0.2; P < 0.01), and higher in patients with active disease compared with those with inactive SLE (1.7 +/- 0.2 versus 1.2 +/- 0.2; P < 0.01). Keratinocyte expression of iNOS was also significantly elevated in SLE patients (0.9 +/- 0.1) compared with controls (0.4 +/- 0.1; P < 0.001). With regard to expression of cNOS, there were no differences between patients with active SLE, those with inactive SLE, and normal controls in either the vascular endothelium or the keratinocytes. CONCLUSION: NO production is increased in patients with SLE, and 2 potential sources of excessive NO are activated endothelial cells and keratinocytes via up-regulated iNOS.

Adult↗
PubMed1996

Candida albicans induces selective expansion of human T lymphocytes expressing the T-cell receptor variable region V beta 5.1.

Candida albicans is a common pathogen which can present major problems as an opportunistic skin pathogen in patients with immunodeficiency. The exact nature of the T cell responses to C. albicans is poorly understood. The purpose of this study was to determine whether C. albicans could stimulate the selective expansion of T lymphocytes expressing particular V beta gene segments. Human T lymphocytes stimulated in vitro with an extract of C. albicans were analyzed for T cell receptor V beta gene expression by using a quantitative PCR technique. We found that stimulation of peripheral blood mononuclear cells (PBMC) produced a selective increase in the expression of V beta 5.1 and 5.2 gene transcripts. Using cytofluorographic analysis with available anti-V beta monoclonal antibodies, we verified that there was a significant selective expansion (P = 0.035) of V beta 5.1 positive T lymphocytes in PBMC from six subjects stimulated in vitro with C. albicans. PCR analysis of V beta 5.1 expansion in 10 subjects showed increases in V beta 5.1 gene transcripts in 7/10 subjects. More importantly, analysis of the T cell infiltrate 48 h after intradermal injections with C. albicans also showed significant expression of V beta 5.1 in the infiltrates, along with the infiltration of V beta 8.1 + T cells. The selective expansion of V beta 5.1 bearing T lymphocytes in PBMC stimulated with C. albicans and in skin test reactions to C. albicans suggests that a restricted population of T cells react to C. albicans. Furthermore, our present data raise the provocative possibility that one or more antigens in C. albicans can act as a superantigen, producing selective expansion of a population of T lymphocytes bearing a particular V beta specificity.

Antibodies, Monoclonal↗
PubMed1995

Evidence for a streptococcal superantigen-driven process in acute guttate psoriasis.

Recent studies have suggested that T cells play a critical role in the pathogenesis of psoriasis. Guttate psoriasis is a well-defined form of psoriasis frequently associated with streptococcal throat infection. This study tested the hypothesis that T cells in acute guttate psoriasis skin lesions may be activated by streptococcal superantigens. Peripheral blood as well as lesional and perilesional skin biopsies were analyzed for T cell receptor V beta repertoire using monoclonal antibodies against 10 different V beta families. Skin biopsies from all patients with acute guttate psoriasis, but not skin biopsies from patients with acute atopic dermatitis or inflammatory skin lesions induced in normal subjects with sodium lauryl sulfate, demonstrated selective accumulation of V beta 2+ T cells (P < 0.05). The expansion of V beta 2+ T cells occurred in both the CD4+ and the CD8+ T cell subsets. Sequence analysis of T cell receptor beta chain genes of V beta 2-expressing T cells from skin biopsies of patients with guttate psoriasis showed extensive junctional region diversity that is more compatible with a superantigen rather than a conventional (nominal) antigen-driven T cell response. All streptococcal isolates from patients with guttate psoriasis secreted streptococcal pyrogenic exotoxin C, a superantigen known to stimulate marked V beta 2+ T cell expansion. These data support the concept that acute guttate psoriasis is associated with superantigenic stimulation of T cells triggered by streptococcal superantigen(s).

Acute Disease↗
PubMed1994

Up-regulation of endothelial cell adhesion molecules characterizes disease activity in systemic lupus erythematosus. The Shwartzman phenomenon revisited.

OBJECTIVE: To test the hypothesis that during exacerbations of systemic lupus erythematosus (SLE), endothelial cells are activated to increase their expression of adhesion molecules. METHODS: Endothelial cell expression of E-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) was quantitated immunohistochemically in 20 biopsy specimens from nonlesional, non-sun-exposed skin from 16 SLE patients. Disease activity was evaluated with the SLE Disease Activity Index (SLEDAI) and with measurements of complement components C3a desArg, C3, and C4. RESULTS: The mean expression of all 3 adhesion molecules was significantly elevated in patients with SLE versus healthy controls, as well as in patients with active versus inactive SLE. The mean C3a desArg level was significantly higher in patients with active SLE compared with those with inactive SLE. The SLEDAI scores correlated directly with C3a desArg levels and inversely with C3 and with C4 levels. Evaluation of serial biopsy specimens demonstrated loss of endothelial cell adhesion molecules and reduction of C3a levels with clinical improvement. CONCLUSION: Our findings demonstrate up-regulation of the surface expression of 3 distinct adhesion molecules, E-selectin, VCAM-1, and ICAM-1, in patients with SLE. The abnormal expression of these endothelial cell adhesion molecules is most marked in patients with active disease characterized by significant elevations of the complement split product C3a desArg. We suggest that in certain SLE patients, excessive complement activation in association with primed endothelial cells induces leukocyte-endothelial cell adhesion and leuko-occlusive vasculopathy.

Cell Adhesion Molecules↗
PubMed1993

A potential role for superantigens in the pathogenesis of psoriasis.

Psoriasis is a complex inflammatory skin disease in which local vascular changes, T-cell activation, abnormal keratinocyte proliferation and differentiation, and neutrophil activation all contribute to the ongoing disease process. Because of recent interest in T-cell activation as a trigger for psoriatic lesions, we hypothesized that psoriasis may be triggered by superantigens, e.g., toxins of microbial origin that stimulate T cells expressing particular T-cell receptor (TCR) beta chain variable (V beta) gene segments. Lesional skin biopsies and peripheral blood from two patients with acute exacerbations of their psoriasis that appeared to be triggered by infection were analyzed for TCR V beta gene expression using monoclonal antibodies directed against V beta 5.1, 5.2, 6.7, 8.1, and 12. Skin biopsies from both patients demonstrated a different pattern of V beta expansion that correspond to the V beta pattern expected to be induced by the type of superantigen expressed during the infection. In contrast, using immunofluorescence and flow cytometry, peripheral blood T cells from these patients did not demonstrate any expansion of the 5 V beta subsets studied. These observations support the hypothesis that local activation of cutaneous T cells in psoriasis may be caused by a superantigen and provides a new direction for investigating the pathogenesis of this complex and fascinating skin disorder.

Adult↗
PubMed1989

Inflammatory myopathy and acquired immunodeficiency syndrome.

A 33-year-old black woman with advanced acquired immunodeficiency syndrome (AIDS) presented with rapidly progressive muscle weakness and serologic and radiologic evidence of central nervous system Toxoplasma infection. Muscle biopsy revealed an inflammatory infiltrate predominantly composed of macrophages and T suppressor/cytotoxic cells. Human immunodeficiency virus major core protein (p24) was also detected in macrophages and damaged muscle cells around the inflammatory infiltrates. The patient improved clinically with glucocorticoid therapy for polymyositis and pyrimethamine and clindamycin therapy for toxoplasmosis.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Ultrastructural evidence for mast cell activation in a case of neurofibromatosis.

Neurofibromas contain fibroblasts and many mast cells, and recent hypotheses have linked fibrous tissue growth to activated mast cells. We describe the ultrastructure of mast cells and fibroblasts in a case of neurofibromatosis. Mast cells were numerous and showed extensive signs of activation. Mast cells were often intimately associated with fibroblasts, and mast cell granules could be seen inside fibroblasts ('transgranulation'). The fibroblasts were also activated. These results suggest that interactions between mast cells and fibroblasts may be important in the prominent collagen production that takes place in these tumors.

Adult↗
PubMed1988

Mast cells and neurofibromatosis.

Mast cells are in close contact with other cells in neurofibromatosis, e.g. neural cells and fibroblasts. Secretory products of mast cells may be important in the regulation of collagen synthesis by fibroblasts and Schwann cells. Newer methods of detecting mast cells by avidin staining of granules and localization of membrane Fc receptors for IgE have been exploited in at least one experimental model of fibrosis (murine chronic graft-versus-host disease). Such approaches should help in understanding parameters involved in modulation of cell growth in neurofibromas. Future directions for the study of cellular dynamics in neurofibromas should include detection of activated (degranulated) mast cells, Schwann cells and effects of mast cell products on collagen gene expression.

Fibrosis↗
PubMed1987

Cutaneous mast cell depletion and recovery in murine graft-vs-host disease.

Mast cells as studied by light microscopy with metachromatic staining, have been noted to "disappear" from the skin of mice with chronic graft-vs-host disease (GVHD) produced across minor histocompatibility barriers. This mast cell disappearance is accompanied by ultrastructural evidence of loss of granule contents. In this study, we followed cutaneous mast cells in chronic GVHD over 9 mo by three methods: Light microscopy of toluidine blue-stained sections showed that mast cells not seen at day 42 reappeared between days 94 and 125, were supramaximal at days 146 and 164, and returned to normal levels at days 195 and 280. Double immunofluorescent staining of mast cells for the presence of surface IgE receptors and cytoplasmic granules (avidin) revealed IgE receptor-bearing cells that lacked avidin-binding granules at the time when mast cells were not apparent on light microscopy. By electron microscopy, reappearing mast cells have the morphology of immature dermal mast cells. Ultrastructural abnormalities of mast cells persist some 150 days after GVHD induction. The possible relationship of these mast cell changes to the development of dermal fibrosis in chronic GVHD is discussed.

Animals↗
PubMed1987

Simultaneous in situ detection of IgE receptors and cytoplasmic granules in murine cutaneous mast cells.

A method is described for the simultaneous in situ detection of surface receptors and cytoplasmic granules in mast cells of frozen sections of mouse skin. Surface IgE receptors are detected after saturation of the receptors with a murine monoclonal antibody of IgE isotype. The latter is subsequently detected by monospecific rabbit anti-mouse IgE (purified on protein A-Sepharose) followed by FITC-conjugated goat anti-rabbit IgG. Cytoplasmic granules are localized by staining with TRITC-avidin conjugate. Normal cutaneous mast cells show green surface fluorescence and red intracellular granules. The method is specific for mast cells; other cells with Fc receptors for IgE are not seen. This method should be useful in the study of situations in which mast cells may have become degranulated.

Animals↗
PubMed1987

Monoclonal antibody analysis of skin in chronic murine graft vs host disease produced across minor histocompatibility barriers.

Chronic graft vs host disease (GVHD) across minor histocompatibility barriers was produced in BALB/c mice by the injection of spleen cells from B10.D2 mice. Changes in the skin were analyzed in frozen sections using a panel of monoclonal antibodies detected by immunoperoxidase methods. Compared to control animals, a number of changes occurred in the skin of animals with chronic GVHD. In the epidermis, there were increased numbers of Thy-1-positive dendritic cells; keratinocytes expressed Thy-1 and Ia antigens. T lymphocytes appeared in both dermis and epidermis. In the early stages, cells with "helper" and "suppressor" phenotypes were present, while at later times "helper" cells remained in the epidermis and "suppressor" cells remained in the dermis. Cells bearing markers of macrophages were prominent in both dermis and epidermis after the second week. Of great interest was the appearance of spindle-shaped cells in the dermis which expressed Thy-1 and Ia. These cells resembled fibroblasts which may be activated to produce the excess collagen seen in the skin of chronic GVHD.

Animals↗
PubMed1987

Spectrum of inclusion body myositis.

The clinical, laboratory, and biopsy features are described for a large group of patients with inclusion body myositis (IBM) (15 men and four women; mean age, 63 years). A quantitative histopathologic analysis of muscle biopsy specimens revealed less fiber necrosis and endomysial and perivascular inflammation in IBM than in polymyositis (PM) and dermatomyositis, but a more frequent occurrence of dark-angular and hypertrophied fibers. Rimmed vacuoles were present in 3.4% of all fibers and 15- to 18-nm filaments were identified in the biopsy specimens of nine of 11 patients. A panel of monoclonal antibodies immunoreactive with lymphocytes and cells of monocyte/macrophage lineage suggested that the inflammatory reaction in IBM was similar to that in PM (but not dermatomyositis) and mediated by cellular immune responses. These studies confirm the clinical and histopathologic distinctions between IBM and chronic PM, and that differentiation between these disorders is often difficult.

Adult↗
PubMed1986

Immunohistochemical analysis of human peripheral blood and lymphoid tissues using monoclonal antibodies immunoreactive with non-lymphoid cells.

Immunoperoxidase methods were used to study human peripheral blood and lymphoid tissues using a panel of monoclonal antibodies to non-lymphoid cells. The majority of peripheral blood monocytes were immunoreactive for LeuM1, LeuM2, LeuM3 and LeuM5. Rare peripheral blood monocytes were immunoreactive for R4/23. The different antibodies showed characteristic patterns of immunoreactivity in peripheral lymphoid tissues. LeuM1 was immunoreactive with scattered cells in the paracortex of lymph node and tonsil and with many cells in the marginal zone of the spleen. LeuM2 was immunoreactive with endothelial cells in lymph node and tonsil. A few cells in the red pulp of the spleen were immunoreactive for LeuM2. LeuM3 and R4/23 showed distinctive immunoreactivity in germinal centers of secondary follicles, giving a "lacy" pattern. LeuM3 was also immunoreactive with endothelium in lymph node and tonsil and with sinus lining cells in lymph node. LeuM5 was immunoreactive with macrophages in the germinal center, fibroblastic reticulum cells in the mantle zone and interdigitating reticulum cells in the paracortex of lymph node and tonsil.

Antibodies, Monoclonal↗
PubMed1986

Analysis of macrophages, activated cells and T cell subsets in inflammatory myopathies using monoclonal antibodies.

The availability of monoclonal antibodies which react with lymphocytes and cells of the MPS permits the construction of panels of reagents for immunophenotypic analysis of infiltrating cells in IM. We used immunohistochemical methods to immunophenotype inflammatory cells in muscle biopsies of patients with PM, DM and IBM. The cases of PM and IBM contained an intense MPS cell infiltrate in perivascular and endomysial areas, closely surrounding muscle fibers and occasionally included within the muscle fiber itself; an infiltrate of Leu-6+ cells with a morphology consistent with MPS cells in perivascular and endomysial distribution and occasionally closely apposed to muscle fiber membranes; lymphocytes and MPS cells expressing the IL2-R, and approximately equal numbers of T cells of helper-inducer and suppressor-cytotoxic phenotypes. DM cases had fewer MPS cells and relatively more B cells than T cells.

Antibodies, Monoclonal↗
PubMed1985

Immunohistochemical analysis of the distribution of vimentin in human peripheral lymphoid tissues.

The distribution of the intermediate filament protein vimentin in peripheral lymphoid tissues was determined using a monoclonal antibody. Frozen sections of tissue were stained using an avidin-biotin immunoperoxidase method. The antibody stained endothelial cells in spleen, lymph node, and tonsil. Unusual rod-like structures were revealed in the sinusoid-lining cells of the spleen. A variety of reticulum cells was detected, including fibroblastic reticulum cells, histiocytic reticulum cells (tingible body macrophages), and splenic marginal zone macrophages. Very few lymphocytes were immunoreactive. Only weak cytoplasmic immunoreactivity was observed in lymphocytes of the periarteriolar lymphocyte sheath of the spleen. The monoclonal antibody employed appears to be of limited usefulness in detecting normal lymphocytes, but is strongly reactive with endothelial structures and some types of reticulum cells.

Histocytochemistry↗