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1.
Muscle Nerve ; 70(5): 1034-1039, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39267217

RESUMO

INTRODUCTION/AIMS: Hypogammaglobulinemia is a common yet under-recognized feature of myotonic dystrophy type 1 (DM1). The aims of our study were to determine the frequency of immunoglobulin G (IgG) deficiency in our cohort, to examine the association between immunoglobulin levels and cytosine-thymine-guanine (CTG) repeat length in the DMPK gene, and to assess whether IgG levels are associated with an increased risk of infection in DM1 patients. METHODS: We conducted a single-center, retrospective cross-sectional study of 65 adult patients with DM1 who presented to the Neuromuscular Clinic at Concord Repatriation General Hospital, Sydney, Australia, between January 2002 and January 2022. We systematically collected and analyzed clinical, laboratory, and genetic data for all patients with available serum electrophoresis and/or IgG level results. RESULTS: Forty-one percent of DM1 patients had IgG deficiency despite normal lymphocyte counts, IgA, IgM, and albumin levels. There was an association between CTG repeat expansion size and the degree of IgG deficiency (F = 6.3, p = .02). There was no association between IgG deficiency and frequency of infection in this group (p = .428). DISCUSSION: IgG deficiency is a frequent occurrence in DM1 patients and is associated with CTG repeat expansion size. Whether hypogammaglobulinemia is associated with increased infection risk in DM1 is unclear. A prospective multicenter cohort study is needed to evaluate this.


Assuntos
Agamaglobulinemia , Infecções , Distrofia Miotônica , Humanos , Distrofia Miotônica/complicações , Distrofia Miotônica/imunologia , Distrofia Miotônica/epidemiologia , Distrofia Miotônica/genética , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Transversais , Estudos Retrospectivos , Agamaglobulinemia/epidemiologia , Agamaglobulinemia/complicações , Infecções/epidemiologia , Idoso , Miotonina Proteína Quinase/genética , Expansão das Repetições de Trinucleotídeos , Imunoglobulina G/sangue , Adulto Jovem
2.
Immunol Med ; 47(2): 106-109, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38270551

RESUMO

Congenital Myotonic Dystrophy (CMD) is an autosomal dominant hereditary disease caused by mutations in the dystrophia myotonica protein kinase gene. Patients with CMD often exhibit low immunoglobulin (Ig) G levels. While Ig replacement therapy for low IgG levels has been reported in several adult cases, there have been no reports on pediatric patients. This study presents a first pediatric case where Ig replacement therapy effectively eliminated susceptibility to infections. The CMD patient, a 1-year-old Japanese female with a history of premature birth and necrotizing enterocolitis, developed recurrent severe bacterial infections due to hypogammaglobulinemia. Intravenous immunoglobulin (IVIG) (600 mg/kg/month) was administered but failed to maintain sufficient serum trough IgG levels. The dosage was increased to 2 g/kg/month, and later, the treatment shifted to subcutaneous immunoglobulin (SCIG), resulting in a stable serum trough IgG level above 700 mg/dL for one year. The cause of hypogammaglobulinemia in CMD patients remains unclear, but potential mechanisms, including IgG-mediated hypercatabolism by alterations in the neonatal Fc receptor, have been considered. Genetic testing ruled out common variable immunodeficiency, and other potential causes were excluded. The study suggests that higher doses of IVIG or SCIG can effectively prevent severe infections associated with CMD-induced hypogammaglobulinemia in children.


This case report sheds light on the efficacy of immunoglobulin therapy in pediatric congenital myotonic dystrophy (CMD). We anticipate that our findings will have a positive impact on clinical practice by providing insights into the prevention of severe infections associated with CMD-induced hypogammaglobulinemia. This research is of great interest to the readers of the journal as it addresses an unmet need in pediatric CMD management by providing a strategy for successful immunoglobulin therapy for the treatment of pediatric CMD.


Assuntos
Agamaglobulinemia , Imunoglobulina G , Imunoglobulinas Intravenosas , Distrofia Miotônica , Humanos , Feminino , Distrofia Miotônica/imunologia , Distrofia Miotônica/genética , Imunoglobulinas Intravenosas/administração & dosagem , Lactente , Agamaglobulinemia/etiologia , Agamaglobulinemia/terapia , Imunização Passiva
3.
Mikrobiyol Bul ; 44(4): 679-83, 2010 Oct.
Artigo em Turco | MEDLINE | ID: mdl-21063982

RESUMO

Microsporidium spp. may lead to a variety of clinical pictures like sinusitis, keratoconjunctivitis, hepatitis, myositis, peritonitis, nephritis, encephalitis and pneumonia in case of immune deficiencies. In this report, a case of diarrhea due to Microsporidium spp. has been presented. A four years old male patient who was followed with the diagnosis of myotonic dystrophia, was admitted to the hospital with the complaints of respiratory distress and fever. Due to the history of recurrent infections, further investigations was carried out to clarify the immunological status of the patient, and the total IgA and IgM levels were found as 14 mg/dl and 30 mg/dl, respectively (normal values were; 18-160 and 45-200 mg/dl, respectively). Following bronchoscopy done to enlighten respiratory distress, the patient developed high fever and watery diarrhea. Since bacteriological cultures of the stool yielded Shigella spp., antimicrobial therapy with ciprofloxacin was initiated. Parasitological examination of the stool done by Weber's modified trichrome dye, yielded Microsporidium spp. microscopically and albendazole was added to the treatment. Presence of Microsporidium spp. was confirmed by polymerase chain reaction with the use of C1 and C2 primers (Metabion, Germany) targeted to Microsporidium spp. and besides a 270 bp band specific for Encephalitozoon intestinalis was also obtained. This case emphasized that in case of diarrhea the stool samples of the immunocompromised patients should be evaluated in terms of Microsporidium spp. in addition to the routine parasitologic examinations.


Assuntos
Anti-Infecciosos/uso terapêutico , Diarreia/microbiologia , Fezes/microbiologia , Microsporídios não Classificados/isolamento & purificação , Microsporidiose/diagnóstico , Albendazol/uso terapêutico , Pré-Escolar , Ciprofloxacina/uso terapêutico , Diarreia/diagnóstico , Diarreia/tratamento farmacológico , Quimioterapia Combinada , Humanos , Hospedeiro Imunocomprometido , Masculino , Microsporídios não Classificados/genética , Microsporídios não Classificados/imunologia , Microsporidiose/tratamento farmacológico , Distrofia Miotônica/complicações , Distrofia Miotônica/imunologia , Shigella/isolamento & purificação
4.
Nat Commun ; 11(1): 2022, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32332745

RESUMO

The thymus is a primary lymphoid organ that plays an essential role in T lymphocyte maturation and selection during development of one arm of the mammalian adaptive immune response. Although transcriptional mechanisms have been well documented in thymocyte development, co-/post-transcriptional modifications are also important but have received less attention. Here we demonstrate that the RNA alternative splicing factor MBNL1, which is sequestered in nuclear RNA foci by C(C)UG microsatellite expansions in myotonic dystrophy (DM), is essential for normal thymus development and function. Mbnl1 129S1 knockout mice develop postnatal thymic hyperplasia with thymocyte accumulation. Transcriptome analysis indicates numerous gene expression and RNA mis-splicing events, including transcription factors from the TCF/LEF family. CNBP, the gene containing an intronic CCTG microsatellite expansion in DM type 2 (DM2), is coordinately expressed with MBNL1 in the developing thymus and DM2 CCTG expansions induce similar transcriptome alterations in DM2 blood, which thus serve as disease-specific biomarkers.


Assuntos
Proteínas de Ligação a DNA/genética , Distrofia Miotônica/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Timo/crescimento & desenvolvimento , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Expansão das Repetições de DNA , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Íntrons/genética , Masculino , Camundongos , Camundongos Knockout , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Distrofia Miotônica/sangue , Distrofia Miotônica/imunologia , Splicing de RNA/imunologia , RNA-Seq , Timo/imunologia , Adulto Jovem
5.
J Neurol Neurosurg Psychiatry ; 80(11): 1293-5, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19864666

RESUMO

BACKGROUND: Myotonic dystrophy type 2 (DM2) is a dominantly inherited multisystem disorder, characterised by progressive proximal weakness, myotonia, cataracts and cardiac conduction abnormalities. Our clinical impression of an association between DM2 and autoimmune diseases or autoantibody formation has not been published previously. OBJECTIVE: The aim of the present study was to investigate the frequency of autoimmune diseases and serum autoantibodies in patients with DM2 compared with patients with adult onset myotonic dystrophy type 1 (DM1). METHODS: 28 genetically proven Dutch DM2 patients participated in the study and were compared with 51 age and sex matched adult onset DM1 patients. As the primary outcome measure, the presence of an autoantibody or autoreactive T cell associated autoimmune disorder was assessed. As a secondary outcome measure, the presence of autoantibodies in serum (nuclear and non-nuclear antibodies) was assessed in all patients. RESULTS: The frequency of autoimmune diseases (21% vs 2%) and the frequency of autoantibodies (25% vs 2%) were both significantly (p<0.01) higher in DM2 patients compared with DM1 patients. Data on DM1 patients were comparable with the general population. Results were not confounded by smoking, medication use, familial clustering, age or sex. CONCLUSION: The results provide new insight into the clinical picture of DM2. In addition, possible explanations for the association between DM2 and autoimmune diseases are proposed.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/complicações , Distrofia Miotônica/complicações , Doenças Autoimunes/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Distrofia Miotônica/diagnóstico , Distrofia Miotônica/imunologia
6.
J Med Case Rep ; 13(1): 338, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31744540

RESUMO

BACKGROUND: Myotonic dystrophy type 1 is an autosomal dominant disorder characterized by muscle weakness, myotonia, cataracts, and cardiac conduction defects; it is associated with expansions of cytosine-thymine-guanine repeats in the myotonic dystrophy protein kinase. Hypogammaglobulinemia is a lesser known association of myotonic dystrophy type 1 and the underlying pathogenesis of immunoglobulin G depletion remains unclear. CASE PRESENTATION: Here we report a kindred of two members (a 62-year-old white woman and a 30-year-old white man; mother and son) with myotonic dystrophy type 1-associated hypogammaglobulinemia associated with altered intravenous immunoglobulin elimination kinetics and reduced half-life. There was no history of systemic immunosuppression or renal or gastrointestinal protein loss in either patient, and no underlying case for a secondary immunodeficiency could be found. One patient required fortnightly intravenous immunoglobulin to maintain adequate trough immunoglobulin G levels. CONCLUSIONS: Ongoing study of myotonic dystrophy type 1-associated hypogammaglobulinemia using contemporary tools of genomic medicine may help to further delineate the pathogenesis of this entity.


Assuntos
Agamaglobulinemia/diagnóstico , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Mães , Distrofia Miotônica/diagnóstico , Núcleo Familiar , Adulto , Agamaglobulinemia/imunologia , Agamaglobulinemia/terapia , Feminino , Predisposição Genética para Doença , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Distrofia Miotônica/imunologia , Distrofia Miotônica/terapia
7.
Neuromuscul Disord ; 28(10): 878-880, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30197184

RESUMO

We report a patient with progressive proximal muscle weakness in her legs, early-onset cataract and perceptive hearing loss, who was recently diagnosed with myotonic dystrophy type 2 (DM2). She also had two autoimmune disorders in her history, namely Graves' disease and celiac disease. Previous studies have shown a high frequency of autoimmune diseases (21%) in patients with DM2. This is the first report of a patient with DM2 and two autoimmune diseases which both have not yet been described in DM2. The cause of this association might be explained at DNA, mRNA and protein levels, including genetic mutation in flanking genes and the toxic effect of the DM2 mutation on proteins involved in inflammation. This case report widens the spectrum of autoimmune diseases in DM2 and has implications both for clinical practice and for research.


Assuntos
Doença Celíaca/complicações , Doença de Graves/complicações , Distrofia Miotônica/complicações , Idoso , Doença Celíaca/diagnóstico , Doença Celíaca/imunologia , Diagnóstico Diferencial , Feminino , Doença de Graves/diagnóstico , Doença de Graves/imunologia , Humanos , Distrofia Miotônica/diagnóstico , Distrofia Miotônica/imunologia
8.
Sleep Med Rev ; 9(4): 269-310, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16006155

RESUMO

Human narcolepsy is a chronic sleep disorder affecting 1:2000 individuals. The disease is characterized by excessive daytime sleepiness, cataplexy and other abnormal manifestations of REM sleep, such as sleep paralysis and hypnagogic hallucinations. Recently, it was discovered that the pathophysiology of (idiopathic) narcolepsy-cataplexy is linked to hypocretin ligand deficiency in the brain and cerebrospinal fluid (CSF), as well as the positivity of the human leukocyte antigen (HLA) DR2/DQ6 (DQB1*0602). The symptoms of narcolepsy can also occur during the course of other neurological conditions (i.e. symptomatic narcolepsy). We define symptomatic narcolepsy as those cases that meet the International Sleep Disorders Narcolepsy Criteria, and which are also associated with a significant underlying neurological disorder that accounts for excessive daytime sleepiness (EDS) and temporal associations. To date, we have counted 116 symptomatic cases of narcolepsy reported in literature. As, several authors previously reported, inherited disorders (n=38), tumors (n=33), and head trauma (n=19) are the three most frequent causes for symptomatic narcolepsy. Of the 116 cases, 10 are associated with multiple sclerosis, one case of acute disseminated encephalomyelitis, and relatively rare cases were reported with vascular disorders (n=6), encephalitis (n=4) and degeneration (n=1), and hererodegenerative disorder (three cases in a family). EDS without cataplexy or any REM sleep abnormalities is also often associated with these neurological conditions, and defined as symptomatic cases of EDS. Although it is difficult to rule out the comorbidity of idiopathic narcolepsy in some cases, review of the literature reveals numerous unquestionable cases of symptomatic narcolepsy. These include cases with HLA negative and/or late onset, and cases in which the occurrences of the narcoleptic symptoms are parallel with the rise and fall of the causative disease. A review of these cases (especially those with brain tumors), illustrates a clear picture that the hypothalamus is most often involved. Several cases of symptomatic cataplexy (without EDS) were also reported and in contrast, these cases appear to be often associated with non-hypothalamic structures. CSF hypocretin-1 measurement were also carried out in a limited number of symptomatic cases of narcolepsy/EDS, including narcolepsy/EDS associated with tumors (n=5), head trauma (n=3), vascular disorders (n=5), encephalopathies (n=3), degeneration (n=30), demyelinating disorder (n=7), genetic/congenital disorders (n=11) and others (n=2). Reduced CSF hypocretin-1 levels were seen in most symptomatic narcolepsy cases of EDS with various etiologies and EDS in these cases is sometimes reversible with an improvement of the causative neurological disorder and an improvement of the hypocretin status. It is also noted that some symptomatic EDS cases (with Parkinson diseases and the thalamic infarction) appeared, but they are not linked with hypocretin ligand deficiency. In contrast to idiopathic narcolepsy cases, an occurrence of cataplexy is not tightly associated with hypocretin ligand deficiency in symptomatic cases. Since CSF hypocretin measures are still experimental, cases with sleep abnormalities/cataplexy are habitually selected for CSF hypocretin measures. Therefore, it is still not known whether all or a large majority of cases with low CSF hypocretin-1 levels with CNS interventions, exhibit EDS/cataplexy. It appears that further studies of the involvement of the hypocretin system in symptomatic narcolepsy and EDS are helpful to understand the pathophysiological mechanisms for the occurrence of EDS and cataplexy.


Assuntos
Distúrbios do Sono por Sonolência Excessiva/metabolismo , Distúrbios do Sono por Sonolência Excessiva/fisiopatologia , Hipotálamo/metabolismo , Hipotálamo/fisiopatologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Narcolepsia/líquido cefalorraquidiano , Narcolepsia/fisiopatologia , Neuropeptídeos/metabolismo , Receptores de Neuropeptídeos/metabolismo , Criança , Doença Crônica , Síndrome de Coffin-Lowry/líquido cefalorraquidiano , Síndrome de Coffin-Lowry/fisiopatologia , Traumatismos Craniocerebrais/líquido cefalorraquidiano , Traumatismos Craniocerebrais/fisiopatologia , Distúrbios do Sono por Sonolência Excessiva/imunologia , Antígenos HLA-DQ/imunologia , Antígenos HLA-DR/imunologia , Humanos , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/imunologia , Esclerose Múltipla/fisiopatologia , Distrofia Miotônica/líquido cefalorraquidiano , Distrofia Miotônica/imunologia , Distrofia Miotônica/fisiopatologia , Narcolepsia/imunologia , Doenças Neurodegenerativas/líquido cefalorraquidiano , Doenças Neurodegenerativas/fisiopatologia , Doenças de Niemann-Pick/líquido cefalorraquidiano , Doenças de Niemann-Pick/imunologia , Doenças de Niemann-Pick/fisiopatologia , Receptores de Orexina , Orexinas , Doença de Parkinson Pós-Encefalítica/líquido cefalorraquidiano , Doença de Parkinson Pós-Encefalítica/fisiopatologia , Síndrome de Prader-Willi/líquido cefalorraquidiano , Síndrome de Prader-Willi/imunologia , Síndrome de Prader-Willi/fisiopatologia , Receptores Acoplados a Proteínas G , Doenças Vasculares/líquido cefalorraquidiano , Doenças Vasculares/fisiopatologia
9.
Arch Intern Med ; 145(5): 919-20, 1985 May.
Artigo em Inglês | MEDLINE | ID: mdl-3994468

RESUMO

A 53-year-old man had myotonic dystrophy, hyperthyroidism, and Addison's disease, an association not previously reported, to our knowledge. In the literature, at least five cases of hyperthyroidism associated with myotonic dystrophy have been described, but none also had Addison's disease. The presence of thyroid anti-microsomal antibodies and anti-adrenal antibodies suggests that the two endocrine disorders may be autoimmune. In our case, the treatment of the two endocrinopathies caused a reduction of myotonic symptoms.


Assuntos
Doença de Addison/fisiopatologia , Hipertireoidismo/fisiopatologia , Distrofia Miotônica/fisiopatologia , Autoanticorpos/análise , Humanos , Hipertireoidismo/imunologia , Masculino , Pessoa de Meia-Idade , Distrofia Miotônica/imunologia
10.
Neuromuscul Disord ; 6(3): 203-10, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8784809

RESUMO

Myotonic dystrophy (DM) is an autosomal dominant multisystem disorder associated with expansion of the CTG repeat within the 3' non-coding region of the myotonin protein kinase (MT-PK) gene. CTG repeat length has been shown to correlate with the clinical category and age at onset of the disease. The relationship between CTG repeat length and immunological parameters were analyzed in this study. We determined CTG repeat length in 14 DM patients and 15 normal controls using Southern and PCR analyses, and then correlated their CTG repeat lengths with their serum immunoglobulin (IgG, IgA, IgM) levels and the number of peripheral white blood cells, including lymphocyte subsets. In DM patients, increasing CTG repeat lengths correlated significantly with decreasing serum IgG levels, decreasing total lymphocyte counts, and decreasing CD2+, CD3+, and CD4+ cell counts. Immunological parameters were also influenced by the expansion of CTG repeat in DM patients.


Assuntos
Imunoglobulina G/sangue , Distrofia Miotônica/genética , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases , Linfócitos T/imunologia , Repetições de Trinucleotídeos , Adulto , Idoso , Antígenos CD/sangue , Sequência de Bases , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina M/sangue , Contagem de Linfócitos , Subpopulações de Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Distrofia Miotônica/sangue , Distrofia Miotônica/imunologia , Miotonina Proteína Quinase , Reação em Cadeia da Polimerase , Valores de Referência , Análise de Regressão , Mapeamento por Restrição
11.
J Neuroimmunol ; 144(1-2): 100-4, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14597103

RESUMO

The length of the CTG repeat in the 3' untranslated region of the DMPK gene is considered to be associated with clinical severity in type 1 Dystrofia Myotonica (DM1) and has also been suggested to correlate with the degree of deficiency of IgG noted in these patients. Total serum level of IgG and IgG subclasses was therefore measured in 61 Swedish patients with DM1, the largest number of patients investigated to date in this respect. Almost half (44%) of the DM1 patients showed a serum concentration of IgG below the normal range. Deficiency of IgG1, IgG2 or IgG3 was noted in 26%, 7% and 20% of the patients, respectively. As transcription of genes 3' of the DMPK gene on chromosome 19 is reduced in DM1 patients, a decreased expression of the alpha chain of the receptor involved in IgG catabolism, FcRn, may theoretically be responsible for the low serum IgG in DM1 patients. No correlation was however found between the number of CTG repeats, levels of FcRn transcripts in either muscle tissue or lymphocytes and serum IgG levels.


Assuntos
Deficiência de IgG/imunologia , Imunoglobulina G/sangue , Distrofia Miotônica/genética , Distrofia Miotônica/imunologia , Expansão das Repetições de Trinucleotídeos/genética , Adolescente , Adulto , Idoso , Regulação para Baixo/imunologia , Feminino , Antígenos de Histocompatibilidade Classe I , Humanos , Deficiência de IgG/genética , Imunoglobulina G/classificação , Subpopulações de Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Distrofia Miotônica/classificação , Receptores Fc/biossíntese , Receptores Fc/sangue , Receptores Fc/genética , Índice de Gravidade de Doença
12.
J Neurol ; 213(4): 305-8, 1976 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-62029

RESUMO

A 48-year-old man with myotonic dystrophy did well until the age of 37, when he developed the first of many remissions and exacerbations of multiple sclerosis. The only serum value done while the patient was infection free, revealed serum hypogammaglobulinemia. Three determinations of the relative concentration of gama globulin in the cerebrospinal fluid over 11 years, yielded markedly elevated levels. Previous work on the immunological abnormalities in both disease entities is discussed. This is the only published case in which these two diseases were manifested in the same patient.


Assuntos
Esclerose Múltipla/complicações , Distrofia Miotônica/complicações , Humanos , Imunoglobulina G/análise , Imunoglobulina G/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Distrofia Miotônica/imunologia
13.
J Neurol Sci ; 73(1): 1-10, 1986 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3009720

RESUMO

A 52-year-old Caucasian male with typical features of myotonic dystrophy (MD) developed a lung abscess and was found to have a mild atypical cyclic neutropenia. Granulocyte function testing revealed a defect in phagocytosis, bactericidal activity and chemotaxis. The defects were less severe at the nadir of the granulocyte counts. Skin windows demonstrated that the granulocyte defects were not just an in vitro artifact. The patient was treated with lithium carbonate and improved. Mobilization into a skin window and clinical MD were unchanged. Studies of his 10 children and 2 siblings, including granulocyte function tests and complete neurological evaluations were obtained. The 4 children with abnormal parameters of granulocyte function all had definite evidence of MD. Two children had equivocal findings of MD and the others were normal. There was minimal evidence of granulocyte dysfunction in these children. Twelve of 19 unrelated patients with MD had evidence of impaired granulocyte function with the most consistent defect being chemotaxis in response to bacterial factor. Mild granulocyte dysfunction is frequently associated with MD, but severe dysfunction with many defects is uncommon but can occur, as in this family. There was a tendency for the more severely afflicted members of this family to have more pronounced granulocyte dysfunction. Longitudinal testing in this family may determine any relationship between the granulocyte dysfunction and the onset of MD, as well as any correlation with the progression of the disorder. MD patients who develop infection should have granulocyte function tests as part of their evaluation.


Assuntos
Granulócitos/fisiologia , Distrofia Miotônica/sangue , Adolescente , Adulto , Agregação Celular , Movimento Celular , Quimiotaxia de Leucócito , Criança , Feminino , Humanos , Contagem de Leucócitos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Distrofia Miotônica/genética , Distrofia Miotônica/imunologia , Peroxidase/metabolismo , Fagocitose
14.
J Neurol Sci ; 140(1-2): 96-100, 1996 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-8866433

RESUMO

Intracytoplasmic inclusion bodies of the thalamus in eight patients with myotonic dystrophy (MyD) were studied immunohistochemically. The intracytoplasmic inclusion bodies of the thalamus (thalamic inclusions, TIs) were strongly immunostained with anti-ubiquitin antibody (Ab) and some of them were mildly stained with anti-microtubule associated protein 1 (MAP 1) and anti-MAP 2 antibodies. However, TIs did not react with any of the following: anti-neurofilament protein Ab, anti-tau Ab, anti-paired helical filament Ab, anti-tubulin Abs (alpha and beta), anti-neuron-specific enolase Ab, anti-glial fibrillary acidic protein Ab, anti-synaptophysin Ab, anti-myelin basic protein Ab, anti-actin Ab and anti-phosphorylated epitope of neurofilaments Ab. Thus, our study demonstrates the unique immunohistochemistry of TIs in MyD which differentiates them from other intracytoplasmic inclusions in various neurodegenerative disorders.


Assuntos
Corpos de Inclusão/patologia , Distrofia Miotônica/imunologia , Tálamo/patologia , Idoso , Feminino , Humanos , Imuno-Histoquímica , Proteínas de Filamentos Intermediários/análise , Masculino , Pessoa de Meia-Idade , Distrofia Miotônica/metabolismo , Distrofia Miotônica/patologia , Proteínas do Tecido Nervoso/análise
15.
J Neurol Sci ; 201(1-2): 59-64, 2002 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-12163195

RESUMO

An imbalance of TNF system activity has been reported in patients with myotonic dystrophy type 1 (DM1). Nevertheless, the question whether TNF-alpha action is directly implicated in the pathogenesis of DM1 or is a simple marker of disease activity is still open. Therefore, the present study was aimed to investigate serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 levels in association with the disease stage, cytosine-thymine-guanine (CTG) expansion and cardiac function of 56 patients with DM1 (40+/-14 years) and 28 healthy controls (42+/-12 years). All subjects were submitted to resting electrocardiogram (EKG), Signal-averaged EKG (SA-EKG), and M-mode/2-D echocardiography. TNF-alpha levels were higher in patients compared to controls (p<0.0003) and were associated to disease stage (p<0.02). Significant correlation were observed between TNF and CTG expansion (p<0.005) or PQ intervals (p<0.0005). Ventricular late potentials (VLPs) occurred in 54% of cases. In these patients, TNF-alpha levels were higher compared to those without VLPs (p<0.05). We may conclude that TNF-alpha levels might represent and adjunctive criterion for disease staging in patients with myotonic dystrophy type 1, and that elevated TNF levels in DM1 may lead to cardiac fibrosis affecting diastolic function, conduction, and automaticity.


Assuntos
Distrofia Miotônica/imunologia , Distrofia Miotônica/patologia , Fator de Necrose Tumoral alfa/metabolismo , Adolescente , Adulto , Idoso , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/imunologia , Arritmias Cardíacas/patologia , Progressão da Doença , Eletrocardiografia , Feminino , Fibrose , Humanos , Interleucina-1/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Distrofia Miotônica/etiologia
16.
Rinsho Shinkeigaku ; 34(8): 788-92, 1994 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-7994985

RESUMO

Low serum concentration of IgG in myotonic dystrophy (MyD) has been well documented and has been considered to be due to accelerated breakdown of IgG. However, the catabolic rate of IgG is tightly regulated by serum IgG level and basal metabolic rate. The serum IgG level and basal metabolic rate in the patient with MyD is reported to be significantly low. One possible explanation for this fact is presence of disproportion in IgG subclasses; if the level of one or some subclasses is high, catabolism of total IgG could be accelerated regardless of decreased total IgG. In this study, we examined serum concentration of all four IgG subclasses by sandwich ELISA methods in 43 patients with MyD and 24 healthy age- and sex-matched controls. Serum levels of al IgG subclasses were lower in MyD than those in normal controls, especially the levels of IgG1 and IgG3 were significantly low (p < 0.01) as compared to those in normal controls. These results, combined with our previous studies, suggest that accelerated catabolism is inadequate as a cause of low serum concentration of IgG in MyD. Further studies are required to approach the mechanism of low serum concentration of IgG in the patients with MyD.


Assuntos
Imunoglobulina G/sangue , Distrofia Miotônica/imunologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Allerg Immunol (Paris) ; 21(10): 377, 379-80, 1989 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2624674

RESUMO

We evaluated some immunological parameters in a group of 24 patients affected with myotonic dystrophy (MD). IgG, IgA, IgM immunoglobulin serum levels resulted decreased in most of the patients. Anti-smooth-muscle antibodies have been found in 10 out of 24 patients (45.5%). Moreover in some of them decreased C3 and C4 complement fraction serum levels have been found. Our data confirm the existence of some immunological abnormalities in a great number of subjects affected with the disease. Besides, these data evidence for most of the subjects the presence of autoantibodies non-organ-specific direct against myocellular antigens. These autoantibodies could be considered the expression of suffering of muscular fibres.


Assuntos
Autoanticorpos/imunologia , Distrofia Miotônica/imunologia , Adolescente , Adulto , Proteínas do Sistema Complemento/análise , Feminino , Humanos , Imunoglobulinas/análise , Masculino , Pessoa de Meia-Idade
18.
Nihon Rinsho ; 57(4): 917-26, 1999 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-10222790

RESUMO

We investigated whether the degree of (CTG)n expansions is correlated with the extent of multisystemic disorders in 40 patients with myotonic dystrophy (DM). We examined the endocrinological disorders with both the Ellsworth-Howard(EH) test and thyrotropin releasing hormone (TRH) tolerance test. His-ventricular(HV) interval on the His bundle electrogram was analyzed as one of the cardiac conduction disorders. Serum IgG levels and the proliferative response of lymphocyte to concanavalin(Con). A mitogen were investigated as the immunological disorders and both intelligence quotient (IQ) and apnea index(AI) also as the disorders of central nervous systems. Moreover, the extent of muscular involvement was evaluated by muscle disability score, horizontal saccadic velocity using ENG, myopathy index(MI) estimated by quantitative EMG, and pulmonary function test consisting of % vital capacity (% VC) and peak flow. Southern blot were made of the DNAs as described previously. Briefly, the genomic DNAs extracted from the leukocytes were digested with Eco RI then hybridized with a 32P-labeled cDNA25 probe. The results of the EH test (p < 0.05), TRH tolerance test (p < 0.01), HV interval (p < 0.01), serum IgG levels (p < 0.05), and the proliferative response to Con A mitogen (p < 0.01) were all significantly correlated with (CTG)n length. The values of AI (p < 0.01) and IQ (p < 0.01) were significantly correlated with (CTG)n length. In addition, the extent of muscular involvement based on the disability score (p < 0.001), horizontal saccadic velocity (p < 0.001). MIs of Tibialis anterior (p < 0.05), and Biceps brachii (p < 0.02), % VC (p < 0.05) and peak flow (p < 0.01) also was significantly correlated with (CTG)n length. From the above results, it was considered that (CTG)n length was well correlated with disease severity in DM.


Assuntos
Distrofia Miotônica/genética , Distrofia Miotônica/fisiopatologia , Repetições de Trinucleotídeos/genética , Apneia/etiologia , Glândulas Endócrinas/fisiopatologia , Coração/fisiopatologia , Humanos , Inteligência , Músculos/fisiopatologia , Distrofia Miotônica/imunologia
19.
Free Radic Res ; 48(4): 503-10, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24472045

RESUMO

Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy affecting adults and is due to trinucleotide sequence (CTG) in the 3' UTR region of DMPK gene located at 19q13.3 chromosome. The pathogenic mechanisms of multisystemic involvement of DM1 are still unclear. The increased levels of reactive oxygen species/free radicals and lipid peroxides and decreased antioxidant levels play an important role in the pathogenesis of DM1. Present study includes 20 DM1 patients and 40 age- and sex-matched controls. Malonilaldehyde (MDA), superoxide dismutase (SOD), glutathione peroxidise (GPX), glutathione-S-transferase (GST), reduced glutathione (GSH), and TAS levels were measured and its association with clinical phenotype were evaluated. Results revealed significantly higher levels of MDA (p = 0.002), SOD (p = 0.006), and TAS p = 0.004) and lower level of GPX (p = 0.003), GST (P < 0.001) and GSH (P = 0.016) in DM1 patients. A significant negative correlation of MDA level with dyspepsia and CK-MB and GST level with serum SCK, CK-MB, and diabetes were observed. However, a significant positive correlation of SOD level with serum CK-MB, CK-MM, and diabetes and negative correlation with facial weakness were noted. Though, GSH level had significant positive correlation with learning and writing disability, speech, and languages disability yet found negative correlation with duration of disease. The GPX and TAS showed no correlation with any clinical findings. Our data further support the pathogenic role of oxidative stress in DM1 of Indian origin and support the opportunity to undertake clinical trials with antioxidants in this disorder.


Assuntos
Antioxidantes/metabolismo , Distrofia Miotônica/imunologia , Oxidantes/metabolismo , Humanos , Peroxidação de Lipídeos , Distrofia Miotônica/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio
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