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Biomedical subjects

P Confalonieri

Publications and source records attributed to P Confalonieri.

At least 19 recordsLinked to original sources
PubMed2005

A post-marketing study on immunomodulating treatments for relapsing-remitting multiple sclerosis in Lombardia: preliminary results.

The preliminary results of a post-marketing study on relapsing-remitting multiple sclerosis patients treated with immunomodulating agents attending the Lombardia Region's Multiple Sclerosis Centers are presented. A total of 294 patients treated with Betaferon (67), Avonex (115), Rebif 22 (45), Rebif 44 (18) and Copaxone (49) were included. Relapse frequency consistently decreases at 1 year and continues to decrease after 5 years of treatment, without differences between therapeutic groups. Eighty-seven out of 294 patients (29.6%) discontinued treatment for different reasons. Forty-eight of them shifted to a second therapeutic agent. A different trend, to lower or higher doses of interferon or immunosuppression, according to reasons of discontinuation, was observed.

Adjuvants, Immunologic↗
PubMed2000

Increased expression of beta-chemokines in muscle of patients with inflammatory myopathies.

Idiopathic inflammatory myopathies (IIM) are muscle diseases of autoimmune pathogenesis characterized by mononuclear cell infiltration within muscle tissue. Since immune cell homing and accumulation at the site of antigenic challenge is usually mediated by chemokines, we evaluated the expression of 2 beta-chemokines--monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha)--by immunohistochemistry and polymerase chain reaction in muscles of polymyositis, inclusion body myositis, and dermatomyositis patients, and related their expression to immunopathological alterations in muscle. MCP-1 and MIP-1alpha transcripts were detected by PCR in all IIM muscles, but not in controls. By immunohistochemistry, the chemokines were found in all IIM muscle sections located in infiltrating inflammatory cells and also in neighboring extracellular matrix. The extent to which extracellular matrix was filled by each chemokine differed in each disease. In view of the known ability of chemokines to bind extracellular matrix and their possible synthesis by extracellular matrix components, we suggest that chemokine storage in the extracellular matrix can act as a microenvironmental factor amplifying lymphocyte activation and migration, thereby maintaining the autoimmune attack against unknown muscle antigens.

Chemokine CCL2↗
PubMed1999

Identification of three novel mutations in the major human skeletal muscle chloride channel gene (CLCN1), causing myotonia congenita.

Myotonia congenita (MC) is a genetic disease characterized by mutations in the CLCN1 gene (OMIM*118425) encoding the skeletal muscle voltage-gated chloride channel (ClC-1). Autosomal dominant and recessive forms are observed, characterized by impaired muscle relaxation after forceful contraction (myotonia), which is more pronounced after inactivity and improves with exercise. We report three novel and one known mutations of the CLCN1 gene in four unrelated MC families. In two families the mutations were missense: 803C>T (T268M) and 1272C>G (I424M) in exons 7 and 12, respectively. The third was a splice mutation in intron 5 (696+2T>A), which induced a frame shift with a stop codon in exon 6 (fs213X). In the fourth family the previously-reported missense mutation 689G>A (G230E) was found. We also report two known polymorphisms: 261C>T (T87T) and 2154T>C (D718D) in exons 2 and 17 of two MC families; also found in 14 (33%) and 28 (67%) of 42 healthy controls, respectively. These findings expand our knowledge of mutations responsible for myotonia congenita, reducing the proportion of MC patients in whom genetic alterations have not been found.

Chloride Channels↗
PubMed1999

Transforming growth factor-beta1 and fibrosis in congenital muscular dystrophies.

We evaluated transforming growth factor-beta1 (TGF-beta1) expression in the muscle of four laminin alpha2-negative, four laminin alpha2-positive and seven partial laminin alpha2-deficient congenital muscular dystrophy (CMD) patients, and compared it to Duchenne muscular dystrophy (DMD) patients and controls. TGF-beta1 mRNA levels in skeletal muscle from laminin alpha2-negative and laminin alpha2-positive CMD patients were significantly greater than in controls (P < 0.05 and P < 0.005, respectively), while in partial laminin alpha2-deficient muscular dystrophy patients the amount was not significantly higher than in controls (P > 0.1). The TGF-beta1 values were lower than those found in DMD, although the extent of fibrosis was greater in CMD than in DMD and controls. Our findings suggest that TGF-beta1 is involved in CMD muscle fibrosis, but differently from what we observed in DMD muscles as it seems not to be the major player in connective tissue proliferation.

Adult↗
PubMed1999

A novel mutation (8342G-->A) in the mitochondrial tRNA(Lys) gene associated with progressive external ophthalmoplegia and myoclonus.

We describe a patient who suffered from impaired ocular motility from age 10 years and at 16 years developed ptosis, proximal weakness and progressive fatigability. At 35 years she developed massive myoclonic jerks, and head and distal tremor. A muscle biopsy showed a high percentage of cytochrome c oxidase negative fibers but no ragged-red fibers. A novel heteroplasmic mutation (8342G-->A) was found in the mitochondrial transfer RNA(Lys) gene by single-strand conformation polymorphism screening, followed by sequence and restriction fragment length polymorphism analysis. Approximately 80% of muscle mitochondrial DNA (mtDNA) harbored the mutation, while the mutation was absent in lymphocyte DNA of the proband, as well as of her mother, daughter and a maternal aunt. However, the pathogenicity of the mutation was confirmed by restriction fragment length polymorphism analysis of single muscle fibers, which revealed a significantly greater level of mutant mtDNA in cytochrome c oxidase negative over cytochrome c oxidase positive fibers.

Adenine↗
PubMed1998

The expression of co-stimulatory and accessory molecules on cultured human muscle cells is not dependent on stimulus by pro-inflammatory cytokines: relevance for the pathogenesis of inflammatory myopathy.

Specific activation of naive T cells requires TCR engagement plus interaction of CD28 on T cells with co-stimulatory B7-1/B7-2 on APCs. Since muscle cells may be directly involved in activating muscle-infiltrating T lymphocytes in polymyositis and inclusion body myositis, we analyzed B7 expression on myoblasts before and after treatment with pro-inflammatory cytokines. We found no expression of B7-1/B7-2, either constitutively or after stimulus with cytokines. Furthermore, myoblasts failed to stimulate alloreactive peripheral blood lymphocytes in mixed lymphocyte reactions. Lack of B7 expression was confirmed by immunostaining of polymyositis patients' muscle: only T and the few B lymphocytes present in inflammation areas expressed B7-1.

Antigens, CD↗
PubMed1998

Long-term selective IgG immuno-adsorption improves Rasmussen's encephalitis.

We report that long-term selective immunoglobulin G immunoadsorption by protein A (PAI) improved seizure frequency and neuropsychological deficits in a 16-year-old patient with severe treatment-resistant Rasmussen's encephalitis (RE). Clinical improvement correlated with reduction of antiglutamate receptor 3 antibodies. The efficacy of PAI in our patient supports the autoimmune hypothesis of RE and suggests its application to avoid, or at least delay, functional hemispherectomy in selected cases.

Adolescent↗
PubMed1997

Inflammatory myopathies and systemic disorders: a review of immunopathogenetic mechanisms and clinical features.

The inflammatory myopathies are a heterogeneous group of muscle diseases characterized by muscle degeneration mediated by inflammatory processes. They may be idiopathic, as in polymyositis, dermatomyositis and inclusion body myositis, or associated with systemic disorders such as malignancies, overlap syndromes, and retroviral infection. The pathogenesis of each disease is discussed together with more recent molecular and cellular immunology findings. Salient diagnostic, clinical and pharmacological features are also reviewed.

Dermatomyositis↗
PubMed1997

Transforming growth factor-beta 1 in polymyositis and dermatomyositis correlates with fibrosis but not with mononuclear cell infiltrate.

The idiopathic inflammatory myopathies are diseases of unknown etiology characterized by T cell-mediated myocytotoxicity in polymyositis and complement-mediated angiopathy of muscle fibers in dermatomyositis. A variable degree of fibrosis is present in muscles in these conditions both perimysially and endomysially. We evaluated the expression of TGF-beta 1, a pleiotropic cytokine with fibrogenic and immunomodulating activity, by means of quantitative-polymerase chain reaction and immunocytochemistry in DM and PM muscle biopsies. TGF-beta 1 mRNA was significantly higher in DM compared with controls, whereas in PM the values were not significantly different when compared with controls and DM. TGF-beta 1 was localized in connective tissue but did not correspond with mononuclear cell infiltrates. These findings suggest a correlation between TGF-beta 1 and connective tissue proliferation in inflammatory myopathy, while its immunomodulatory role remains to be elucidated.

Adolescent↗
PubMed1997

Emerging treatments in myopathies.

Outstanding improvement has been made in the molecular understanding of several muscle diseases with the application of molecular biological techniques to the investigation of human disorders. The identification of genetic mutations has improved considerably the diagnostic approach to muscular dystrophies, mitochondrial myopathies and ion channel disorders. Important results have been achieved in the field of inflammatory myopathies. With a few exceptions, therapies available are nonspecific and rarely represent a cure for the disease. Molecular medicine offers an opportunity to design new therapeutic strategies based on the pathogenic mechanisms underlying each disease.

Animals↗
PubMed1995

Expression of transforming growth factor-beta 1 in dystrophic patient muscles correlates with fibrosis. Pathogenetic role of a fibrogenic cytokine.

Duchenne muscular dystrophy is a fatal disorder characterized by progressive muscular weakness, wasting, and severe muscle contractures in later disease stages. Muscle biopsy reveals conspicuous myofiber degeneration and fibrosis substituting muscle tissue. We quantitatively determined mRNA of the potent fibrogenic cytokine transforming growth factor-beta 1 by quantitative PCR in 15 Duchenne muscular dystrophy, 13 Becker muscular dystrophy, 11 spinal muscular atrophy patients, and 16 controls. Higher transforming growth factor-beta 1 expression was greater in Duchenne muscular dystrophy patients than controls (P = 0.012) and Becker patients (P = 0.03). Fibrosis was significantly more prominent in Duchenne muscular dystrophy than Becker muscular dystrophy, spinal muscular atrophy, and controls. The proportion of connective tissue in muscle biopsies increased progressively with age in Duchenne muscular dystrophy patients, while transforming growth factor-beta 1 levels peaked at 2 and 6 yr of age. Transforming growth factor-beta 1 protein was also detected by immunocytochemistry and immunoblotting. Our findings suggest that transforming growth factor-beta 1 stimulates fibrosis in Duchenne muscular dystrophy. Expression of transforming growth factor-beta 1 in the early stages of Duchenne muscular dystrophy may be critical in initiating muscle fibrosis and antifibrosis treatment could slow progression of the disease, increasing the utility of gene therapy.

Age Factors↗
PubMed1994

Changes in peripheral blood lymphocyte subset frequencies in myasthenia gravis patients are related to immunosuppression.

Surface antigens on peripheral blood lymphocytes from myasthenia gravis patients were investigated. The expression of DR+ and CD8+/DR+ T lymphocytes was increased and the expression of CD4+ T cells reduced. Neither thymectomy, clinical condition nor anti-acetylcholine receptor antibody titre correlated with any of the changes in peripheral blood lymphocyte subsets observed. However, immunosuppressive therapy correlated with the significant reduction in CD4+ and CD2+/CD4+ T cells in these patients.

Adolescent↗
PubMed1994

The POEMS syndrome: report of six cases.

We report six patients affected by POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes), a peculiar multiorgan disease frequently associated with osteosclerotic myeloma or other plasma cell disorders. Sensorimotor polyneuropathy was associated with multisystem involvement in all of the patients, with osteosclerotic myeloma in 2 cases, monoclonal gammopathy of undetermined significance in 2 cases and Castleman's disease in the final two. In all of the patients, sural nerve biopsy findings were consistent with a mixed, axonal and demyelinating neuropathy. Increased levels of Interleukin-6 were found in two cases, but the pathogenesis of the disease is far from established.

Aged↗