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Biomedical subjects

M Mosca

Publications and source records attributed to M Mosca.

At least 19 recordsLinked to original sources
PubMed2006

Anti-signal recognition particle autoantibodies: marker of a necrotising myopathy.

OBJECTIVE: To elucidate the clinical importance of the anti-signal recognition particle (SRP) autoantibody in patients with myositis. METHODS: Retrospective systematic assessment of the clinical, laboratory and histological characteristics of 23 anti-SRP-positive patients from six European centres. Data were compared with a large group of anti-SRP-negative patients with myositis published previously. RESULTS: Clinically, patients with anti-SRP autoantibodies often had a severe symmetric proximal muscle weakness resulting in marked disability, dysphagia and highly elevated levels of serum creatine kinase. Three patients had typical dermatomyositis rashes. The disease was associated with the occurrence of extramuscular signs and symptoms including interstitial lung disease. No association was found with an increased risk of cardiac involvement, and the disease carried a reasonably favourable prognosis with most patients responding to treatment. None of the patients had the typical histological features of myositis. Most muscle biopsy specimens showed the presence of necrotic muscle fibres and no inflammatory infiltrates. CONCLUSIONS: Anti-SRP autoantibodies are associated with a syndrome of a necrotising myopathy in the spectrum of immune-mediated myopathies that differs from typical polymyositis. Further studies are needed to elucidate the pathogenesis and to clarify the role of the anti-SRP autoantibodies in this unique disease.

Adult↗
PubMed2006

Undifferentiated connective tissue diseases (UCTD).

The term undifferentiated connective tissue diseases is used to define conditions characterized by the presence of signs and symptoms suggestive of a systemic autoimmune disease that do not satisfy the classificative criteria for defined connective tissue diseases (CTD) such as systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), rheumatoid arthritis (RA) and others. A small percentage of patients presenting with an undifferentiated profile will develop during the first year follow up of a full blown CTD, however an average of 75% will maintain an undifferentiated clinical course. These patients may be defined as having a stable undifferentiated connective tissue diseases (UCTD). The most characteristic symptoms of UCTD are represented by arthritis and arthralgias, Raynaud's phenomenon, leukopenia, while neurological and kidney involvement are virtually absent. Eighty percent of these patients have a single autoantibody specificity, more frequently anti-Ro and anti-RNP antibodies. Stable UCTD are considered as distinct clinical entities and therefore it has been proposed to define those conditions as UCTD. Classificative criteria have also been proposed and a work to better define them is still under way.

Autoantibodies↗
PubMed2006

Functional and isokinetic assessment of muscle strength in patients with idiopathic inflammatory myopathies.

OBJECTIVE: To assess muscle strength in patients with idiopathic inflammatory myopathies (IIM) using neuromuscular scales and isokinetic testing. METHODS: Muscle function was evaluated in 27 IIM patients being followed at the Rheumatology Unit of the University of Pisa using: (i) a modified version of the grading system used to assess Duchenne dystrophy, (ii) the four-stage grading system of Henriksson and Sandstedt, (iii) an isokinetic muscle strength test (Kin Com, Chatanooga) and (iv) the Health Assessment Questionnaire (HAQ). RESULTS: The neuromuscular scales showed normal or only mildly impaired muscle strength in 60% (Duchenne scale) and 80% (Henriksson and Sandstedt scale) of the patients, respectively, whereas isokinetic testing detected moderate to severe reductions in muscle strength in almost 70% of the patients. No correlations were observed between muscle strength and disease activity, therapy, age at evaluation and disease duration. There was a correlation between the results of the HAQ and neuromuscular testing, but not the isokinetic test. CONCLUSIONS: Although less easy and more expensive to administer, isokinetic testing appears to be a more sensitive instrument than the standard neuromuscular tests for assessing muscle function in IIM patients. In particular, it can detect small reductions in muscle strength.

Adrenal Cortex Hormones↗
PubMed2006

Clinical characteristics of patients with myositis and autoantibodies to different fragments of the Mi-2 beta antigen.

OBJECTIVES: To assess the clinical implications of autoantibodies directed against different parts of the Mi-2 beta autoantigen in patients with myositis. METHODS: A systematic assessment of the clinical, laboratory, and histological characteristics of 48 anti-Mi-2 positive patients from six European centres was made. Anti-Mi-2 autoantibodies were determined with an ELISA using four overlapping fragments spanning the entire amino acid sequence of the autoantigen. Data were compared with results for a large group of anti-Mi-2 negative patients with myositis published previously. RESULTS: Anti-Mi-2 autoantibodies were found in dermatomyositis, polymyositis, and inclusion body myositis. In general, myositis with anti-Mi-2 autoantibodies was characterised by relatively mild disease, sometimes accompanied by extra-muscular symptoms, including arthralgia, arthritis, Raynaud's phenomenon, and interstitial lung disease. Cardiac disease was not seen, and treatment response was fair. No differences were found between patients with autoantibodies to different fragments of the Mi-2 beta antigen, except for a potentially increased risk of cancer in patients with antibodies directed to the N-terminal fragment of the autoantigen. CONCLUSIONS: Anti-Mi-2 autoantibodies are not a marker of a specific subtype of myositis. No significant differences between patients with autoantibodies to different fragments of the Mi-2 beta autoantigen are found, with the possible exception of an increased risk of cancer in patients with antibodies to the N-terminal fragment.

Adenosine Triphosphatases↗
PubMed2004

Distinct thymocyte subsets express the vanilloid receptor VR1 that mediates capsaicin-induced apoptotic cell death.

Herein, we provide the first evidence on the capsaicin (CPS) receptor vanilloid receptor type-1 (VR1) by rat thymocytes, and its involvement in CPS-induced apoptosis. VR1 mRNA was identified by quantitative RT-PCR in CD5(+) thymocytes. By immunofluorescence and flow cytometry, we found that a substantial portion of CD5+ thymocytes, namely CD4+ and double negative (DN) cell subsets, express VR1 that was present on plasma membrane on discrete spots. By Western blot, VR1 protein was identified as a single band of 95 kDa. We also described that CPS could trigger two distinct pathways of thymocyte death, namely apoptosis and necrosis depending on the dose of CPS exposure. CPS-induced apoptosis involved intracellular free calcium (Ca2+) influx, phosphatidylserine exposure, mitochondrial permeability transmembrane pore (PTP) opening and mitochondrial transmembrane potential (Delta Psi m) dissipation leading to cytochrome c release, activation of caspase-9 and -3 and oligonucleosomal DNA fragmentation. VR1 was functionally implicated in these events as they were completely abrogated by the VR1 antagonist, capsazepine (CPZ). Finally, we demonstrated that VR1 expression on distinct thymocytes was associated with the selective ability of CPS to trigger DNA fragmentation in VR1+ CD4+ and DN thymocytes. Overall, our results suggest that the expression of VR1 on thymocytes may function as a sensor of harmful stimuli present in the thymic environment.

Animals↗
PubMed2004

Risk factors for osteoporosis in female patients with systemic lupus erythematosus.

In the last years it has been recognized that patients with systemic lupus erythematosus (SLE) are at high risk of osteoporosis (OP) and fractures, both occurring through disease-specific (chronic arthritis, reduced physical activity, induction of cytokines promoting bone resorption, renal impairment, endocrine factors) and nondisease-specific mechanisms (sunshine avoidance with consequent vitamin D deficiency, glucocorticoids, immunosuppressants and chronic anticoagulants). Regarding anticoagulants, subcutaneous heparin is crucial against the risk of recurrent thromboembolism or pregnancy loss, specifically in patients with SLE and anti-phospholipid syndrome (APS). Thus heparin-induced OP represents one of the hazards of this treatment, first because heparin must be used long-term and secondly because pregnancy and lactation themselves may predispose to OP and fractures. Current data suggest the use of prophylaxis with calcium and vitamin D in all patients treated with heparin during pregnancy. Nevertheless glucocorticoid-induced OP (GIOP) is considered the most serious risk factor for OP and fractures in SLE patients. All guidelines recommend general measures and supplementation with calcium and vitamin D in all patients. However when considering premenopausal patients, there is no generally recommended treatment. Bisphosphonates, which are considered the first choice therapy for the prevention and treatment of GIOP, should be used 'cautiously' in these patients. Therefore the potential risks and lack of efficacy data on fracture risk reduction in premenopausal patients must be weighed against their proven efficacy in postmenopausal patients.

Female↗
PubMed2003

Recombinant birch allergens (Bet v 1 and Bet v 2) and the oral allergy syndrome in patients allergic to birch pollen.

BACKGROUND: IgE cross-reactivity between pollen and food allergens represents the molecular basis for oral allergy syndrome (OAS). OBJECTIVE: To evaluate specific IgE for Bet v 1 and Bet v 2 in the serum of patients sensitized to birch pollen and to identify whether IgE antibodies to Bet v 1 and Bet v 2 were predictors of OAS. METHODS: Thirty-three patients with skin prick test results and radioallergosorbent assay test results positive to birch pollen, 12 (36%) of whom had OAS symptoms, were enrolled in the study. Serum levels of specific IgE were determined by the fluoroenzyme immunoassay technique. RESULTS: The t test revealed significantly higher serum IgE levels against Bet v 1, Bet v 2, and birch pollen in the 12 symptomatic patients with respect to those without OAS (32.4 vs 12.4 kU/L, 7.6 vs 1.3 kU/L, and 42.3 vs 17.3 kU/L, respectively). Attempts to establish a threshold value of serum IgE antibirch pollen and the appearance of OAS revealed that a level of 20 kU/L or more yields an efficiency of the test equal to 70%. CONCLUSIONS: In our study, quantitative birch specific IgE level proved useful in predicting clinical allergy symptoms with birch exposure.

Adult↗
PubMed2003

Molecular analysis of V(H)I+ B lymphocytes in hepatitis C patients.

BACKGROUND AND AIMS: Hepatitis C virus infection is often associated with lymphoproliferative disorders such as essential mixed cryoglobulinemia and B-cell non-Hodgkin lymphoma, which show preferential expression of VHI family products. By analyzing immunoglobulin heavy chain usage, we addressed the question of whether or not clonal B-cell expansion occurrs in patients free of essential mixed cryoglobulinemia or non-Hodgkin lymphoma. PATIENTS AND METHODS: Four hepatitis C virus-positive patients, all undergoing liver transplantation, were studied. Peripheral blood, intra-hepatic, and lymph node lymphocytes were used as a source of B cells. A patient with hepatocellular carcinoma and fresh blood from four healthy donors were used as negative controls. VHI family sequences were cloned and analyzed by reverse transcription-polymerase chain reaction. RESULTS: Immunoglobulin heavy chain sequences from clonally expanded B lymphocytes were identified in three out of four hepatitis C virus-infected patients. The clonally expanded B lymphocyte populations showed a broad spectra of immunoglobulin heavy chain gene usage. CONCLUSIONS: HCV infection can induce B-cell expansion with larger clonal variation. The restricted V gene usage in hepatitis C virus-associated non-Hodgkin lymphoma suggests that there may be selection mechanisms to develop non-Hodgkin lymphoma from non-malignant, clonally expanded B-cell populations in hepatitis C virus-infected patients.

B-Lymphocytes↗
PubMed2003

Correlations of Y chromosome microchimerism with disease activity in patients with SLE: analysis of preliminary data.

BACKGROUND: Recently it has been suggested that microchimerism may have a significant role in the aetiopathogenesis of some autoimmune diseases. OBJECTIVES: To evaluate the incidence of microchimerism in systemic lupus erythematosus (SLE), to quantify the phenomenon, to evaluate changes of microchimerism during follow up, and to correlate these data with clinical and laboratory variables. METHODS: Patients were selected for the study on the basis of the following criteria: (a) pregnancy with at least one male offspring; (b) no history of abortion and blood transfusion. Microchimerism was detected using a competitive nested polymerase chain reaction for a specific Y chromosome sequence and an internal competitor designed ad hoc. Disease activity and organ involvement were also evaluated. RESULTS: Sixty samples from 22 patients with SLE and 24 healthy controls were examined. Microchimerism was seen in 11 (50%) patients and 12 (50%) controls. The mean number of male equivalent cells was 2.4 cells/100 000 (range 0.1-17) in patients with SLE and 2.5 (range 0.2-1.8) in healthy controls. No differences in the incidence of microchimerism or in the number of microchimeric cells were found between patients and healthy controls. Patients with a history of lupus nephritis had a higher mean number of fetal cells than patients with no such history. Disease activity did not appear to correlate with microchimerism. CONCLUSIONS: The preliminary data suggest that microchimerism does not interfere with the disease course of SLE, although further analysis on larger groups will be necessary to confirm these observations.

Adolescent↗
PubMed2002

Dosage-related bifidogenic effects of galacto- and fructooligosaccharides in formula-fed term infants.

BACKGROUND: Human milk oligosaccharides have been shown to stimulate selectively the growth of Bifidobacteria and Lactobacilli in the intestine. In this study, the bifidogenic effect of an experimental prebiotic oligosaccharide mixture consisting of low-molecular-weight galactooligosaccharides and high-molecular-weight fructooligosaccharides was analyzed in 90 term infants. METHODS: Two test formulas were supplemented with either 0.4 g/dL or with 0.8 g/dL oligosaccharides. In the control formula, maltodextrin was used as placebo. At study day 1 and study day 28, the fecal species, colony forming units (cfu) and pH were measured and stool characteristics, growth, and side effects were recorded. RESULTS: At study day 1, the median number of Bifidobacteria did not differ among the groups (0.4 g/dL group, mean [interquartile range] 8.5 [1.9] cfu/g; 0.8 g/dL group, 7.7 [6.1] cfu/g; and the placebo group, 8.8 [6.1] cfu/g) (figures in square brackets are interquartile range). At the end of the 28-day feeding period, the number of Bifidobacteria was significantly increased for both groups receiving supplemented formulas (the 0.4 g/dL group, 9.3 [4.9] cfu/g; the 0.8 g/dL group, 9.7 [0.8] cfu/g) versus the placebo group (7.2 [4.9] cfu/g, P < 0.001). This effect was dose dependent (0.4 g/dL versus 0.8 g/dL, P < 0.01). The number of Lactobacilli also increased significantly in both groups fed the supplemented formulas (versus placebo, P < 0.001), but there was no statistically significant difference between the group fed formula with 0.4 g/dL oligosaccharides and the group fed formula with 0.8 g/dL oligosaccharides. The dosage of supplement significantly influenced the change in fecal pH (P < 0.05) (placebo, pH 5.5-6.1; 0.4 g/dL formula, pH 5.48-5.44; 0.8 g/dL formula, pH 5.54-5.19). Slight changes in the stool frequency resulted in a significant difference between the placebo group and the group fed the 0.8 g/dL formula at day 28 (P < 0.01). Supplementation had a significant dose-dependent influence on stool consistency (0.8 g/dL versus placebo, P < 0.0001; 0.8 g/dL versus 0.4 g/dL, P < 0.01). Supplementation had no influence on the incidence of side effects (crying, regurgitation, vomiting) or growth. CONCLUSIONS: These data indicate that supplementation of a term infant's formula with a mixture of galacto- and fructooligosaccharides has a dose-dependent stimulating effect on the growth of Bifidobacteria and Lactobacilli in the intestine and results in softer stool with increasing dosage of supplementation.

Bifidobacterium↗
PubMed2002

Pregnancy outcome in patients with undifferentiated connective tissue disease: a preliminary study on 25 pregnancies.

Undifferentiated connective tissue disease (UCTD) is a group of systemic autoimmune conditions not fulfilling the classification criteria for a definite connective tissue disease (CTD). While an average of 20% of UCTD patients develop a defined CTD during follow-up, the remaining patients maintain an undefined disease. Since pregnancy is considered to be an important factor that may alter the course of autoimmune diseases, we examined 25 pregnancies in 20 UCTD patients being followed at our unit in order to evaluate: (i) the pregnancy outcome; (ii) whether pregnancy is associated with flares of disease activity; and (iii) whether pregnancy may be a trigger for the development of a defined CTD. Twenty-two pregnancies (88%) were successfully brought to term, while the remaining three (12%) ended in an abortion in the first trimester. Obstetric complications were observed in six out of the 22 successful pregnancies (27%). Six patients (24%) experienced a disease flare during pregnancy or puerperium, one of whom presented a major flare and developed systemic lupus erythematosus. In the other five patients the manifestations at flare were mild and included arthritis, fever and skin rash. The incidence of flares in a control population of non-pregnant UCTD patients over a period of 1 year was 7%. Although UCTD is a mild condition, the risk of flares during pregnancy appears increased and therefore careful monitoring is as necessary as in other CTD patients. Further prospective studies will be necessary to confirm these preliminary observations.

Adult↗
PubMed2001

Treatment of systemic lupus erythematosus.

The treatment of systemic lupus erythematosus (SLE) is mainly based on a number of "traditional" drugs such as corticosteroids, antimalarials, azathioprine and cyclophosphamide. However, this scenario is rapidly changing due to the introduction of new compounds. Some of these new agents have been successfully used in other diseases, while others are being specifically designed to interfere with the immune abnormalities seen in SLE. As our knowledge on the mechanisms of immune response increases, new drugs that can interfere with T and B cell interaction and activation, production of anti-dsDNA autoantibodies, immune-complexes deposition and cytokine activation have been developed and some of these are now under investigation in SLE. Although initial data regarding their safety and efficacy are encouraging, caution must be taken before these drugs are considered as the treatment of choice for specific SLE manifestations. Specifically, controlled clinical trials with sufficient number of patients are necessary. If the promising results already available are confirmed, the use of these drugs might represent the keystone in the future management of SLE and other autoimmune diseases.

Adjuvants, Immunologic↗