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Biomedical subjects

R Gerli

Publications and source records attributed to R Gerli.

At least 55 records · Page 3Linked to original sources
PubMed1996

Assessment of the European classification criteria for Sjögren's syndrome in a series of clinically defined cases: results of a prospective multicentre study. The European Study Group on Diagnostic Criteria for Sjögren's Syndrome.

OBJECTIVE: To assess the recently proposed preliminary criteria for the classification of Sjögren's syndrome (SS) in a multicentre European study of a new series of clinically defined cases. METHODS: The criteria included six items: I = ocular symptoms; II = oral symptoms; III = evidence of keratoconjunctivitis sicca; IV = focal sialoadenitis by minor salivary gland biopsy; V = instrumental evidence of salivary gland involvement; VI = presence of autoantibodies. Each centre was asked to provide five patients with primary SS, five with secondary SS, five with connective tissue diseases (CTD) but without SS, and five controls (patients with ocular or oral features that may simulate SS). The preliminary six item classification criteria set was applied to both the SS patients and the non-SS controls, and the performance of the criteria in terms of sensitivity and specificity was tested. RESULTS: The criteria set was tested on a total of 278 cases (157 SS patients and 121 non-SS controls) collected from 16 centres in 10 countries. At least four of the six items in the criteria set (limiting item VI to the presence of Ro(SS-A) or La(SS-B) antibodies) were present in 79 of 81 patients initially classified as having primary SS (sensitivity 97.5%), but in only seven of 121 non-SS controls (specificity 94.2%). When the presence of item I or II plus any two of items III-V of the criteria set was considered as indicative of secondary SS, 97.3% (71 of 73) of the patients initially defined as having this disorder and 91.8% (45 of 49) of the control patients with CTD without SS were correctly classified. CONCLUSION: This prospective study confirmed the high validity and reliability of the classification criteria for SS recently proposed by the European Community Study Group.

Adult↗
PubMed1995

Intracellular calcium levels are differentially regulated in T lymphocytes triggered by anti-CD2 and anti-CD3 monoclonal antibodies.

Antigen and/or mitogen-driven T-cell activation is mediated by a rise in intracellular free Ca2+, as second messenger. A regulatory key role for this process is represented by membrane-associated [Ca2+/Mg2+] ATP-ase that is mainly devoted to extrusion of intracellular ion excess. In the present study we have investigated the kinetics of CA2+ fluxes in both resting and already activated (Jurkat T-cell line) T lymphocytes after CD3 and CD2 (T11(2) and T11(3)) triggering and focused our attention on plasma membrane [Ca2+/Mg2+] ATP-ase activity. In both resting T cells and Jurkat cell line, the CD2 stimulation was able to determine a rise in intracellular free Ca2+ higher than that observed after CD3 triggering. In addition, this calcium signal was independent of negative feedback control exerted by [Ca2+/Mg2+] ATP-ase, as well as of IP3 generation. Thus the CD2 molecular system may, together with cell-adhesion properties, act as an amplifier of Ca2+ signals that, if delivered in the context of other molecular systems, such as CD3 or MHC class II antigens, are essentially devoted to the polyclonal co-stimulatory recruitment of a larger cellular repertoire.

Antibodies, Monoclonal↗
PubMed1995

High levels of the soluble form of CD30 molecule in rheumatoid arthritis (RA) are expression of CD30+ T cell involvement in the inflamed joints.

The CD30 is a surface molecule expressed by Th2-type lymphokine-producing T cells upon activation. CD30-expressing activated T cells release a soluble form of the molecule, which can be detectable both in vitro and in vivo. In the present study, high levels of soluble CD30 were found in peripheral blood and synovial fluid from patients with RA. However, CD30+ CD3+ cells, either CD4+ or CD8+, were significantly present in synovial fluid, but not in peripheral blood, of RA patients. Serum values of soluble CD30 were higher in active than inactive RA patients and directly correlated with rheumatoid factor serum titres. These data strongly support an involvement of CD30+ T cells in the immune processes of rheumatoid synovitis, and may suggest a relationship between Th2-type cytokine-secreting T cells and the pathological response in RA.

Adult↗
PubMed1995

Gamma delta T-cell subset distribution in human semen from fertile donors.

PROBLEM: Gamma delta T-cell subset distribution has not been fully investigated in normal human semen. METHODS: We therefore carried out experiments by using a direct immunofluorescence staining technique followed by two-color cytofluorimetric analysis on mononuclear cell (MC) suspensions from ejaculates of ten healthy, fertile volunteers. Autologous peripheral blood MC were simultaneously analyzed and the results used for statistical comparison. RESULTS: The proportion of normal human semen lymphocytes bearing the gamma delta T-cell receptor for antigen was greatly increased compared with autologous circulating counterparts. Interestingly, the rise was mainly due to an overexpansion of cells expressing V delta 1 gene-encoded determinants on their surface. This contrasts with the normal blood picture, where most gamma delta T cells express V delta 2 conformational epitopes. CONCLUSIONS: The numerical and phenotypical differences in semen gamma delta T lymphocytes provide further evidence of a defined migrating lymphocyte subset balance in anatomically and physiologically distinct areas of the body. Their functional role, in terms of both helper and suppressor-cytotoxic activities in the nonsterile proximal portions of the male genital tract, now needs to be explored in detail.

Adult↗
PubMed1995

Gamma delta T lymphocytes in mumps meningitis patients.

Flowcytometric analysis on T-cell subpopulations in the blood and cerebrospinal fluid (CSF) of 10 children with mumps meningitis (MM) revealed that the proportion of lymphocytes which bore the gamma delta T-cell receptor for antigen was significantly higher in CSF than in autologous and heterologous blood samples. gamma delta T-cell values in CSF of MM patients were also significantly higher than those calculated in CSF specimens from nine children with non-inflammatory neurological disorders. Whether and how the expanded CSF gamma delta T-lymphocyte subset, either CD8+ or double-negative (CD4-/CD8-), contributes to the eradication of mumps virus infection from the central nervous system represents a central focus of our ongoing research.

Antigens, CD↗
PubMed1995

Peripheral blood gamma delta T cells in human listeriosis.

A phenotypical analysis carried out by direct immunofluorescence and two-colour cytofluorometry showed that the number of lymphocytes bearing the gamma delta T-cell receptor heterodimer was increased in the blood of eight children with Listeria monocytogenes infection, mainly due to an expansion of cells identified by monoclonal antibodies which recognize V delta 2 gene products. These findings are further evidence that gamma delta T cells are in some way involved in the immune response directed against human intracellular pathogens.

Female↗
PubMed1995

Long term treatment of rheumatoid arthritis with high doses of intravenous immunoglobulins: effects on disease activity and serum cytokines.

OBJECTIVE: To evaluate the effects of long term treatment of rheumatoid arthritis (RA) with high doses of intravenous immunoglobulins (IVIg). METHODS: Ten patients with active RA and prior unsuccessful treatment with at least one slow acting antirheumatic drug were treated with 400 mg/kg of IVIg for the first three days and then once a month for 12 months. Clinical evaluation and laboratory analysis were performed every month. Serum levels of tumour necrosis factor alpha (TNF alpha), soluble interleukin-2 receptor (sIL-2R), IL-1 alpha, IL-1 beta, IL-6 and interferon gamma (IFN gamma) were measured at baseline and at three monthly intervals for 15 months. RESULTS: Although laboratory parameters were not influenced by the treatment, a late but significant clinical improvement was observed after six months. Serial measurement of cytokines revealed a rapid and persistent decrease in serum TNF alpha and a late and significant reduction in sIL-2R concentrations. CONCLUSION: This study suggests that IVIg can ameliorate the symptoms and improve the functional capability of RA patients. This effect is associated with a partial modulation of serum concentrations of inflammatory cytokines and, more interestingly, with a late decrease in sIL-2R which correlated with the late reduction in disease activity.

Adult↗
PubMed1995

CD26 and CD31 surface antigen expression on human colostral T cells.

The expression levels of CD26 and CD31 surface antigens, two adhesion/activation molecules with helper and suppressor activities, respectively, were found to be significantly higher on human colostral T cells (CD3+) than in autologous peripheral blood samples. These findings provide further phenotypical evidence that immune system T lymphocytes are compartmentalized in the mammary gland late in pregnancy and during lactation. The question of whether these overexpanded T lymphocyte populations in breast milk modulate in situ, either by enhancing or suppressing, the cellular and/or humoral immune response of the suckling infant remains to be answered. Additional studies are, therefore, needed to explore this intriguing field concerning the immunology of the colostrum.

Antibodies, Monoclonal↗
PubMed1995

Initial lymph vessels of the skin and elastic fibres form an integral morphofunctional structure.

Little has been published on the histochemical and cytochemical properties of anchoring filaments of the initial lymph vessels. Previous research suggests that the microfibrils of the anchoring filaments have ultrastructural, histochemical and cytochemical characteristics similar to those of the microfibrils associated with the elastic fibres. With the aim of further investigating the histological identity of anchoring filaments, we performed an immunohistochemical study in human skin lymphatics, using the antibody HB8, specific for elastic fibre microfibrils. There is now a body of evidence suggesting a new concept in the framework of the lymphatic system. It unifies the initial lymph vessels, the anchoring filaments and the satellite elastic fibres in a single and integral entity.

Adolescent↗
PubMed1994

Activation of cord T lymphocytes. IV. Analysis of surface expression and functional role of 1F7 (CD26) molecule.

A role for CD26 surface antigen (Ag) in both CD3- and CD2-mediated T cell activation has been previously demonstrated. To analyze the functional role of CD26 in the CD3- and CD2-induced activation pathways of cord T cells, which represent the most reliable source of Ag-unprimed T cells, we employed a newly developed anti-CD26 monoclonal antibody, termed anti-1F7, anti-CD3 and anti-CD2 in activating T lymphocytes. The results showed that CD26 Ag is expressed on the surface of almost all resting cord T cells and that its fluorescence intensity is enhanced by activation. The binding of anti-1F7 induced a decrease in CD26 membrane expression, with no detectable effect on the surface expression of other cord T cell-related molecules. Moreover, the modulation of CD26 resulted in an increase in anti-CD3-mediated cord T cell activation through an enhancement in intracellular calcium levels, IL-2 receptor expression, and IL-2 synthesis, whereas it had no effect on cord T cell activation induced by anti-CD2 or anti-CD2 plus exogenous IL-2. The fact that the selective involvement of CD26 in the activation pathway triggered by anti-CD3, but not anti-CD2, could be reversed by prior stimulation of cord T cells with anti-CD3 suggests that this functional feature, which resembles that of mature thymocytes, may be linked to the Ag-unprimed cell phenotype of cord T lymphocytes.

Antibodies, Monoclonal↗
PubMed1994

Expression and functional role of 1F7 (CD26) antigen on peripheral blood and synovial fluid T cells in rheumatoid arthritis patients.

The expression and the functional role of the CD26 (1F7) T cell surface molecule, an ectoenzyme which seems to represent a functional collagen receptor of T lymphocytes and to have a role in T cell activation, were analysed in both peripheral blood (PB) and synovial fluid (SF) T cell samples from patients with active and inactive rheumatoid arthritis (RA). Although patients with active disease displayed higher percentages of PB CD26+ CD4+ T cells than inactive RA and control subjects, CD26 antigen expression on RA SF T lymphocytes was low. The anti-1F7 binding to the T cell surface, that led to CD26 antigen modulation and enhancement of both IL-2 synthesis by, and 3H-TdR incorporation of, anti-CD3- or anti-CD2-triggered PB T cells in RA and control subjects, was unable to affect significantly both expression and functional activity of RA SF T lymphocytes. Since the 1F7 antigen spontaneously reappeared on the surface of unstimulated SF T cells after 2-5 days of culturing, the low 1F7 antigen expression of anti-1F7 in the SF T cell compartment may be the result of in vivo molecule modulation exerted by the natural ligand in the joint, with important implications for T cell activation and lymphokine synthesis.

Adolescent↗
PubMed1994

CD26 surface antigen expression on peripheral blood T lymphocytes from children with Down's syndrome (trisomy 21).

A phenotypical analysis carried out by two-colour flow cytometry showed that the proportion of circulating CD4+ T lymphocytes co-expressing the membrane-associated ectoenzyme dipeptidyl peptidase IV (CD26 antigen), a functional collagen receptor involved in T-cell triggering through its interaction with the CD45 protein tyrosine phosphatase, was significantly lower in 28 children with non-translocated trisomy 21 (Down's syndrome) (DS) than that calculated in the bloodstream of 27 age- and sex-matched healthy controls. Agonist anti-CD26 monoclonal antibodies (MoAbs), such as anti-1F7, not only modulate the surface expression of this molecule, but also enhance the proliferative activity of normal human T cells via the CD3- and CD2-mediated activation pathways. T-lymphocyte proliferation induced by antigen or polyclonal T-cell activators, including anti-CD3 or -CD2 MoAbs, is severely impaired in DS. Although the physiological ligand of CD26 surface structure is unknown, the fact that CD4+ T lymphocytes found in the blood of trisomic subjects are mostly CD26- (anti-1F7-) suggests that their faulty mitogenic response may be due to phenotypical and, perhaps, strictly correlated functional abnormalities.

Adolescent↗
PubMed1994

Effect of erythromycin administration on upper gastrointestinal motility in scleroderma patients.

BACKGROUND: Gastrointestinal involvement is frequent in patients with scleroderma. Erythromycin, a macrolide antibiotic, has been shown to accelerate gastric emptying in normal subjects and diabetic patients. The present study investigated the effects of acute erythromycin administration on gastric and gallbladder motility in patients with scleroderma and gastrointestinal involvement. METHODS: Twelve scleroderma patients and 14 healthy subjects were investigated. Each subject was investigated on 4 different days. Gastric and gallbladder emptying and gastric motility were determined by sonography and manometry, and the effect of 2 mg/kg/h erythromycin in fasted patients or after semisolid meal evaluated. RESULTS: The half-time of gastric emptying in response to semisolid meal was 121.3 +/- 14.0 min (SE) in scleroderma patients and 45.7 +/- 10.4 min in healthy subjects (P < 0.01). The peak of gallbladder emptying occurred later in scleroderma patients (95.0 +/- 5.0 min) than in healthy subjects (45.0 +/- 8.0 min) (P < 0.01). Erythromycin stimulated gastric and gallbladder motility in fasted subjects, as shown by manometry and sonography, and accelerated gastric and gallbladder emptying when administered immediately before the meal (P < 0.01). CONCLUSIONS: Erythromycin accelerates gastric and gallbladder emptying in scleroderma patients and might be helpful in the treatment of gastrointestinal motor abnormalities in these patients.

Adult↗
PubMed1994

Effect of erythromycin on gastric and gallbladder emptying and gastrointestinal symptoms in scleroderma patients is maintained medium term.

OBJECTIVES: Scleroderma patients frequently present esophageal and gastric emptying abnormalities and small bowel dysfunction. Erythromycin, a macrolide antibiotic, has been found to accelerate gastric and gallbladder emptying in both healthy subjects and diabetic patients. Our objective was to investigate the effects of 4-wk oral erythromycin administration on the gastric and gallbladder emptying, gastrointestinal symptoms (early satiety, abdominal pain, nausea, bloating, vomiting, and constipation), and motilin plasma levels of patients with scleroderma. METHODS: 12 scleroderma patients were investigated before and after 4-wk treatment with 250 mg oral erythromycin three times a day. The effect of a single i.v. dose of 2 mg/kg/h erythromycin on gastric and gallbladder emptying before starting the oral treatment was also evaluated. Gastric and gallbladder emptying after a solid meal were evaluated by sonography. RESULTS: Single i.v. administration of erythromycin before the meal reduced gastric emptying T1/2 from 121.3 +/- 14.0 to 45.5 +/- 7.3 min (p < 0.01) and accelerated gallbladder emptying without affecting the peak. Four-week oral administration of erythromycin reduced gastric emptying T1/2 from 121.3 +/- 14.0 min to 46.5 +/- 8.3 min (p < 0.01). Peak gallbladder emptying was also significantly accelerated, while total emptying remained unchanged (p < 0.01). Furthermore, 4-wk erythromycin administration reduced both motilin plasma levels (from 223.4 +/- 53.8 to 145.4 +/- 67.2 pmol/L, p < 0.01) and symptoms of nausea, vomiting, and abdominal pain (p < 0.01), and increased bowel movements in a subset of scleroderma patients with intestinal pseudo-obstruction. CONCLUSIONS: Erythromycin stimulates gastrointestinal motility in patients with scleroderma. Administered medium-term, it accelerates gastric and gallbladder emptying and alleviates gastrointestinal symptoms.

Drug Administration Schedule↗
PubMed1993

Activation of cord T lymphocytes. III. Role of LFA-1/ICAM-1 and CD2/LFA-3 adhesion molecules in CD3-induced proliferative response.

As cord T cells, a model of antigen (Ag)-unprimed cell, display a functional defect when stimulated through the CD3 molecule, the role of lymphocyte function-associated antigen 1(LFA-1)/intercellular adhesion molecule 1 (ICAM-1) and CD2/lymphocyte function-associated antigen 3 (LFA-3) receptor-ligand pairs in cord CD3-triggered T-cell activation was analyzed using specific monoclonal antibodies (mAb) against each adhesion molecule. The addition of anti-CD11a, anti-CD18, or anti-CD2 to both adult and cord peripheral blood mononuclear cells (PBMC) cultures led to a decrease in CD3-induced proliferation. In contrast, CD3-stimulated cord, but not adult, PBMC proliferation was markedly enhanced when anti-CD54 or anti-CD58 were added. Despite the fact that ICAM-1 and LFA-3 molecules were virtually absent on cord resting T cells, mAb against these two molecules boosted both mitogenesis of and interleukin (IL)-2 production by purified cord T cells stimulated with plastic immobilized anti-CD3. Cord T-cell supernatant levels of interferon-gamma (IFN-gamma) were undetectable with CD3 stimulation, slightly raised with CD58/CD3 costimulation, but normal when T cells were preincubated with IL-2 for 24 hr before being costimulated with anti-CD3/CD58. Evidence that IL-2 and IFN-gamma play a pivotal role in fully activating cord T cells came from the demonstration that IL-2 and IFN-gamma are able to bypass the CD3-proliferative defect through differential up-regulation of the adhesion molecules. It would, therefore, seem that ICAM-1 and LFA-3 molecules are crucially implicated in the CD3-activation pathway of Ag-unprimed T cells.

Adult↗
PubMed1993

Interferon-alpha in mixed cryoglobulinemia patients: a randomized, crossover-controlled trial.

The effects of interferon-alpha (IFN-alpha) on clinical and serologic manifestations of mixed cryoglobulinemia (MC) were investigated by randomized, crossover-controlled trial in 26 patients. The trial alternated 6 months with and 6 months without IFN-alpha therapy (2 x 10(6) IU daily for a month, then every other day for 5 months). In 22 patients, pretreatment steroid dosage remained unchanged during the study. Six patients dropped out (three because of side effects), whereas another 20 patients experienced a significant improvement of purpura (P < .02) and serum transaminases (P < .005) during IFN-alpha treatment. The presence of clinical improvement was supported by the outcome measurements of several immunologic parameters. In particular, serum cryoglobulins were significantly reduced (P < .04) during IFN-alpha therapy. A rebound phenomenon of clinical and serologic parameters was observed after IFN-alpha discontinuation. In addition, no variations were recorded during 6 months without therapy. Hepatitis C virus (HCV) RNA was detected in 91% (20/22) of our MC patients; in 2/13 cases HCV RNA was no longer detectable in serum samples after IFN-alpha therapy. Thus, IFN-alpha could be considered as treatment for MC in patients with HCV seropositivity.

Alanine Transaminase↗
PubMed1993

Lymphocytes bearing the gamma delta T cell receptor in acute Brucella melitensis infection.

A phenotypical analysis carried out by indirect immunofluorescence and two-color cytofluorometry showed that the number of lymphocytes bearing the gamma delta T cell receptor (TcR) heterodimer was dramatically increased in the blood of six children with Brucella melitensis infection. Most in vivo expanded gamma delta T cells reacted with a monoclonal antibody which identifies V delta 2 gene products and a significant proportion expressed CD25 and HLA-DR activation antigens. In addition, whereas only a few gamma delta T lymphocytes were CD8+, nearly all were CD4-. Highly enriched populations of both alpha beta and gamma delta T cells were obtained by negative immunoselection from three subjects with brucellosis sampled during convalescence. Despite the different form of their TcR, the proliferation of these two major T cell subsets in response to a mitogenic anti-CD3 monoclonal reagent (OKT3) was optimal. In contrast, alpha beta, but not gamma delta, T lymphocytes proliferated vigorously in response to the antigenic stimulus elicited by heat-killed Brucella. Further studies are, therefore, needed to determine whether the selective expansion of the gamma delta T cell subpopulation observed during the clinical course of the infection is driven by antigenic determinant(s) borne by the pathogen in vivo or is due to host-derived stimuli, such as autologous heat-shock proteins expressed on the surface of the infected cells.

Acute Disease↗