OBJECTIVETo investigate the expression of beta-dystroglycan (beta-DG) and the roles of tissue inhibitor of metalloproteinases (TIMPs) on beta-DG in salivary adenoid cystic carcinoma (SACC).

METHODSbeta-DG in highly lung metastatic cell line ACC-M and lowly lung metastatic one ACC-2 was tested by immunocytochemistry with different concentrations (10, 15, 20, 25 micromol x L(-1)) of TIMPs, and that without the regulation of TIMPs was served as controls. beta-DG was detected in seven specimens of SACC and ten cases of normal salivary gland tissues which were considered as a comparison group by immunohistochemistry.

RESULTSThere was no positive beta-DG immune-staining at the ACC-2 and ACC-M cell lines without TIMPs in the cell culture. beta-DG expressed after the regulation of TIMPs. beta-DG expression was localized predominantly in basement membrane of the acinus, while the negative results were distributed in the carcinoma cells and around the cancer cell nests.

CONCLUSIONBeta-DG is widely expressed by transmembrane protein that plays important roles in connecting the extracellular matrix to the cytoskeleton, the fracture of this structure means that it is easy to invade and transfer, so restoration of beta-DG expression by TIMPs is considered to be critical for successful treatment of SACC.

Carcinoma, Adenoid Cystic ; Cell Line, Tumor ; Dystroglycans ; Humans ; Immunohistochemistry ; Salivary Gland Neoplasms ; Tissue Inhibitor of Metalloproteinases

BACKGROUND: The various medical treatments applied to myoclonus-dystonia patients with a mutation of the epsilon-sarcoglycan gene (SGCE) have not been beneficial in most cases. Most patients experience progressive deterioration or static clinical courses, with only rare cases of spontaneous remission. CASE REPORT: A 19-year-old girl presented with a 14-year history of myoclonus and dystonia that severely affected her left arm, neck, and trunk. Genetic studies showed a mutation in SGCE [deletion in exon 6 (c.771_772delAT, Cys258X)]. Both myoclonus and dystonia responded to anticholinergic treatment for 7 years and improved spontaneously. CONCLUSIONS: The possibility of spontaneous improvement should be kept in mind when considering the therapeutic strategy in myoclonus-dystonia patients, especially when contemplating deep-brain stimulation.
Arm ; Cholinergic Antagonists ; Dystonia ; Exons ; Humans ; Myoclonus ; Neck ; Remission, Spontaneous ; Sarcoglycans ; Young Adult

Walker-Warburg syndrome (WWS) is a rare autosomal recessive disorder characterized by congenital muscular dystrophy, brain (lissencephaly, hydrocephalus, cerebellar malformations) and retinal abnormalities, and is associated with mental retardation and seizures. In 1942, Walker was the first to report a case of WWS. As Fukuyama congenital muscular dystrophy or muscle-eye-brain disorder, it has been demonstrated that the glycosylation defects of alpha-dystroglycan which take a great role in muscle and neuron regeneration are at the root of these disorders. We report a five months old male patient who was presented with seizures as the chief complaint and was diagnosed with WWS, based on clinical criteria, MRI, muscular biopsy, ocular examination, and laboratory findings.
Biopsy ; Brain ; Dystroglycans ; Glycosylation ; Humans ; Hydrocephalus ; Intellectual Disability ; Lissencephaly ; Male ; Muscles ; Muscular Dystrophies ; Neurons ; Regeneration ; Retinaldehyde ; Seizures ; Walker-Warburg Syndrome

OBJECTIVETo study the association of DTNBP1 gene with some symptom factors of schizophrenia.

METHODSA total of 285 unrelated schizophrenic individuals were recruited from December 2004 to January 2009 for genetic analysis, and their symptom factors were assessed based on the Positive and Negative Syndrome Scale (PANSS). The quantitative trait test was performed by the UNPHASED program (version 3.0.12) to investigate the association between scored positive and negative symptoms and the single nucleotide polymorphisms (SNPs) in DTNBP1 gene.

RESULTSThe quantitative trait test showed allelic association of rs909706 with the excitement symptom of schizophrenia (P<0.05, adjusted by 10,000 permutations), while the genotype C/G of rs2619539 with a negative symptom, lack of spontaneity and flow of conversation (P<0.05, adjusted by 10,000 permutations).

CONCLUSIONDTNBP1 variations are possibly associated with some symptoms of schizophrenia, which could partly explain the relationship between the susceptibility gene DTNBP1 and that disease.

Adult ; Base Sequence ; Carrier Proteins ; genetics ; China ; DNA Primers ; Dysbindin ; Dystrophin-Associated Proteins ; Ethnic Groups ; Female ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Schizophrenia ; ethnology ; genetics

Recent reports indicate that the dysbindin gene located on chromosome 6p22.3 is a major susceptibility gene for schizophrenia. In the brain, the dysbindin gene may influence glutamatergic neurotransmission by multiple post- and pr- synaptic mechanisms. This paper reviews the research progress on the dysbindin gene in schizophrenia, including the dysbindin gene and its product, the possible pathogenic mechanisms, the association study of the dysbindin gene with schizophrenia, and the cognitive decline caused by the dysbind in variations.
Brain ; metabolism ; Carrier Proteins ; genetics ; physiology ; Cognition Disorders ; genetics ; physiopathology ; Dysbindin ; Dystrophin-Associated Proteins ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Schizophrenia ; genetics ; metabolism ; pathology

OBJECTIVES: This study was designed to investigate the association of schizophrenia and P1320, P1325, P1635, P1655, P1763 and SNP A polymorphisms on dystrobrevin binding protein 1(DTNBP1) gene in Korean patients. METHODS: We analyzed P1320, P1325, P1635, P1655, P1763 and SNP A polymorphisms on DTNBP1 gene from their DNAs extracted from their blood in 388 Korean schizophrenic patients (male 198, female 190) and 372 control subjects(male 247, female 125). We compared the differences of genotype and allele distributions of the six polymorphisms on DTNBP1 gene between the Korean schizophrenic patient group and the normal control group. RESULTS: There were no statistically significant differences of genotype and allele distributions of the P1320, P1325, P1635, P1655, P1763 and SNP A polymorphisms on DTNBP1 gene between the schizophrenic patient group and the normal control group. CONCLUSION: The results of this study suggest that P1320, P1325, P1635, P1655, P1763 and SNP A polymorphism on DTNBP1 gene do not have influence on the risk of the schizophnenic in the Korean population.
Alleles ; Carrier Proteins ; DNA ; Dystrophin-Associated Proteins ; Female ; Genotype ; Humans ; Polymorphism, Genetic ; Schizophrenia

The muscular dystrophies are a diverse group of inherited muscle disorders characterized by progressive muscle weakness and wasting with characteristic histologic abnormalities such as degeneration, necrosis, and regeneration of muscle fibers. With progress in molecular genetics methods, new discoveries of dystrophin and related molecules have dramatically changed the understanding and diagnosis of a large group of muscular dystrophy patients. Dystrophin and its related molecular associates are tightly associated and form an essential cytoskeletal system (dystrophin-glycoprotein complex) at the muscle fiber surface membrane, which is critical for maintaining the integrity of the sarcolemma and muscle fibers. Deficiency of one of these sarcolemmal proteins, including dystrophin, dystroglycans, sarcoglycans, and laminin-2, leads to the breakdown and instability of muscle fibers and to clinically observed progressive muscle weakness. Identification of the molecular cause of muscular dystrophies would allow a genetic oriented classification and diagnosis using DNA or protein analysis. However, definition of the molecular pathogenesis of muscular dystrophies has not been completely possible until now. Future advances in this field should allow the exact diagnosis and treatment of muscular dystrophies.
Classification ; Diagnosis* ; DNA ; Dystroglycans ; Dystrophin ; Humans ; Membranes ; Molecular Biology ; Muscle Weakness ; Muscular Diseases ; Muscular Dystrophies* ; Myotonic Dystrophy ; Necrosis ; Regeneration ; Sarcoglycans ; Sarcolemma

BACKGROUND: Recent genetic analyses have shown that Miyoshi myopathy (MM) is caused by a mutation in the DYSF, which induces the dysfunction of dysferlin. We identified the deficiency of dysferlin by immunohistochemistry and Western blot in four patients with clinically diagnosed MM, and investigated the clinical and pathological characteristics of MM. METHODS: A muscle biopsy was performed in four patients who were diagnosed with MM by clinical and electrophysiological study. Immunostaining of muscle specimens for dyferlin, dystrophin, alpha, beta, gamma, sigma-sarcoglycan, beta-dystroglycan, and caveolin-3 were performed in all four patients. We analyzed the quantitative analysis for dysferlin by Western blot in three of four patients. RESULTS: All four patients showed clinical onset during adolescence or early adulthood (15-26 year old), a slowly progressive course, and a relatively high serum creatine kinase level (2240-6400 IU/L). Routine pathological studies showed non-specific myopathic changes. On immunocytochemistry, there was negative immunoreacticity for dysferlin on muscle specimens in all patients. The immunoreactivities for dystrophin, alpha, beta, gamma, sigma-sarcoglycan, beta-dystroglycan, and caveolin-3 were normal. On Western blotting, complete loss of dysferlin was noted in all three patients with MM CONCLUSIONS: Identification of isolated deficiency of dysferlin on immunocytochemistry or Western blot is important for the confirmative diagnosis of MM.
Adolescent ; Biopsy ; Blotting, Western* ; Caveolin 3 ; Creatine Kinase ; Diagnosis ; Dystroglycans ; Dystrophin ; Humans ; Immunohistochemistry ; Muscular Diseases*

Schizophrenia (MIM 181500) is a complex disorder affecting approximately 1% of the population worldwide. Epidemiologic evidences, together with recent linkage and association studies, have clearly demonstrated the high heritability of schizophrenia (up to 80%). Uncovering the genetic mechanism of schizophrenia has became one of the greatest challenges for both psychiatry and genetics. In recent years, remarkable advances in the genetics of this disorder has been achieved with the rapid growth of human genome information and experiment technologies. Several candidate genes within some of the best-supported linkage regions have been reported and, more importantly, replicated. Moreover, these genes present a significant connection in the signaling pathways implicated in the development of schizophrenia, especially NMDA receptor-mediated glutamate transmission. In this review, we summarize the recent advances in the genetics of schizophrenia, focusing particularly on linkage disequilibrium analysis and the latest understanding of the neurobiology of the disorder.
Acyltransferases ; genetics ; Carrier Proteins ; genetics ; Dysbindin ; Dystrophin-Associated Proteins ; Humans ; Membrane Proteins ; genetics ; Nerve Tissue Proteins ; genetics ; Neuregulin-1 ; Receptors, N-Methyl-D-Aspartate ; genetics ; Schizophrenia ; genetics

BACKGROUND: For the differential diagnosis between the various subtypes of muscular dystrophy, the analysis of the protein expression pattern from the biopsied skeletal muscle tissue is essential. Authors performed the immunohistochemical study (IHC) using sets of antibodies for the differentiation of subtypes of muscular dystrophy. METHODS: Antibodies against dystrophin C-terminal, dystrophin rod domain, dystrophin N-terminal, alpha-, beta-, gamma-sarcoglycans, laminin alpha2 chain, dysferlin, and beta-dystroglycan were used for the IHC study in 43 patients with muscular dystrophy. The reactivity against the specific antibodies was graded and the clinical findings were assessed. RESULTS: We found 15 cases of dystrophin deficiency and 7 cases of dysferlin deficiency. Those with dystrophin deficiency were clinically classified previously as follows, 11 cases with Duchenne's muscular dystrophy (DMD), two with congenital muscular dystrophy (CMD), one with Becker's muscular dystrophy (BMD), and a female patient with limb-girdle muscular dystrophy (LGMD). Those with dysferlin deficiency consisted of 4 cases with LGMD phenotype and 3 with distal myopathy. CONCLUSIONS: The results of our study confirm the dystrophin immunostain is essential for the identification of dystrophinopathies among the various subtypes of muscular dystrophy. Also, the identification of 7 cases with dysferlin deficiency suggests dysferlinopathy is the common cause of muscular dystrophy in Korea.
Antibodies ; Diagnosis, Differential ; Distal Myopathies ; Dystroglycans ; Dystrophin ; Female ; Humans ; Immunohistochemistry ; Korea ; Laminin ; Muscle, Skeletal ; Muscular Dystrophies* ; Muscular Dystrophies, Limb-Girdle ; Muscular Dystrophy, Duchenne ; Phenotype ; Sarcoglycans