Polyglutamine (polyQ) diseases are a group of hereditary neurodegenerative disorders caused by expansion of a glutamine repeat in responsible gene products. To date, the pathogenesis of polyQ diseases is still not very clear, but many researches suggest that phosphorylation of mutant proteins plays a critical role on the process of Huntington's disease, dentatorubral-pallidoluysian atrophy, spinal bulbar muscular atrophy, spinocerebellar ataxia1 and spinocerebellar ataxia 3/Machado-Joseph disease.
Heredodegenerative Disorders, Nervous System ; genetics ; metabolism ; Humans ; Huntington Disease ; genetics ; metabolism ; Machado-Joseph Disease ; genetics ; metabolism ; Muscular Atrophy, Spinal ; Peptides ; genetics ; metabolism ; Phosphorylation ; physiology ; Spinocerebellar Degenerations ; genetics ; metabolism ; Trinucleotide Repeat Expansion ; genetics ; physiology ; Trinucleotide Repeats ; genetics

OBJECTIVETo study muscle atrophy F-box (MAFbx) and muscle ring finger 1 (MuRF1) mRNA expression and its relationship with muscular contraction following free muscle transfer.

METHODSThe gracilis muscle was orthotopic transferred in adult rat to establish the animal model. The muscle at the unoperated side was used as control. The expression of MAFbx and MuRF1 mRNA, the muscle contraction and muscle function were measured by real-time PCR and multiple function physiological device. The relationship among the expression of MAFbx and MuRF1 mRNA, the muscle contraction and muscle function was analyzed.

RESULTSAfter muscle free transfer, muscle wet weight reservation, the maximum contraction and tetanus strength reduce first and increased later, but still lower than those at control side. The expression of MAFbx and MuRF1 mRNA reached peak level 3 - 4 weeks after muscle transfer which was 7.1 and 4.1 times as that at control side. It decreased later, but still higher than that at control side, showing a significant difference between them (P< 0. 05).

CONCLUSIONSPersistent over-expression of MAFbx and MuRF1 mRNA after muscle transfer has a close relationship with muscle atrophy and muscle dysfunction. MAFbx and MuRF1 can be used as markers for early muscle atrophy, and also as potential target for drug treatment of muscle atrophy.

Animals ; Female ; Muscle Contraction ; Muscle Proteins ; genetics ; Muscle, Skeletal ; pathology ; Muscular Atrophy ; genetics ; metabolism ; pathology ; RING Finger Domains ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; SKP Cullin F-Box Protein Ligases ; genetics ; Tripartite Motif Proteins ; Ubiquitin-Protein Ligases ; genetics

We report the first Korean patient with familial hemiplegic migraine type 1, with clinical and multimodal imaging findings. A 43-yr-old man was admitted for right hemianopia and aphasia, followed by coma. MRI showed only cerebellar atrophy. CT angiography showed mild vasodilation of intracranial blood vessels and increased vascularity in the left hemisphere and perfusion-weighted imaging showed elevated cerebral blood flow. Gene analysis of the patient and his mother led to the identification of a heterozygous point mutation (1997C-->T, T666M) in exon 16 of the CACNA1A gene. Familial hemiplegic migraine should be considered in patients with episodic neurological dysfunction with cerebellar atrophy.
Asian Continental Ancestry Group/*genetics ; Atrophy/genetics/metabolism ; Calcium Channels/*genetics ; Cerebellum/blood supply/*pathology ; Cerebral Angiography ; Coma/*diagnosis ; Exons ; Heterozygote ; Humans ; Magnetic Resonance Imaging ; Male ; Migraine with Aura/*diagnosis/genetics ; Point Mutation ; Republic of Korea ; Tomography, X-Ray Computed

BACKGROUNDLipid storage myopathy (LSM) is a genetically heterogeneous group with variable clinical phenotypes. Late-onset multiple acyl-coenzyme A dehydrogenation deficiency (MADD) is a rather common form of LSM in China. Diagnosis and clinical management of it remain challenging, especially without robust muscle biopsy result and genetic detection. As the noninvasion and convenience, muscle magnetic resonance imaging (MRI) is a helpful assistant, diagnostic tool for neuromuscular disorders. However, the disease-specific MRI patterns of muscle involved and its diagnostic value in late-onset MADD have not been systematic analyzed.

METHODSWe assessed the MRI pattern and fat infiltration degree of the lower limb muscles in 28 late-onset MADD patients, combined with detailed clinical features and gene spectrum. Fat infiltration degree of the thigh muscle was scored while that of gluteus was described as obvious or not. Associated muscular atrophy was defined as obvious muscle bulk reduction.

RESULTSThe mean scores were significantly different among the anterior, medial, and posterior thigh muscle groups. The mean of fat infiltration scores on posterior thigh muscle group was significantly higher than either anterior or medial thigh muscle group (P < 0.001). Moreover, the mean score on medial thigh muscle group was significantly higher than that of anterior thigh muscle group (P < 0.01). About half of the patients displayed fat infiltration and atrophy in gluteus muscles. Of 28 patients, 12 exhibited atrophy in medial and/or posterior thigh muscle groups, especially in posterior thigh muscle group. Muscle edema pattern was not found in all the patients.

CONCLUSIONSLate-onset MADD patients show a typical muscular imaging pattern of fat infiltration and atrophy on anterior, posterior, and medial thigh muscle groups, with major involvement of posterior thigh muscle group and gluteus muscles and a sparing involvement of anterior thigh compartment. Our findings also suggest that muscle MRI of lower limbs is a helpful tool in guiding clinical evaluation on late-onset MADD.

Adolescent ; Adult ; Age of Onset ; Child ; Child, Preschool ; Electron-Transferring Flavoproteins ; genetics ; Female ; Humans ; Lipid Metabolism, Inborn Errors ; genetics ; metabolism ; pathology ; Lower Extremity ; pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Muscle, Skeletal ; metabolism ; pathology ; Muscular Atrophy ; genetics ; metabolism ; pathology ; Muscular Dystrophies ; genetics ; metabolism ; pathology ; Mutation ; genetics ; Young Adult

PURPOSE: The purpose of this study was to examine the effects of Cu/Zn SOD on reduction of hindlimb muscular atrophy induced by cisplatin in rats. METHODS: Forty-two rats were assigned to three groups; control group, Cisplatin (CDDP) group and cisplatin with Cu/Zn SOD (CDDP-SOD) group. At day 35 hindlimb muscles were dissected. Food intake, activity, withdrawal threshold, muscle weight, and Type I, II fiber cross-sectional area (CSA) of dissected muscles were measured. Relative SOD activity and expression of MHC and phosphorylated Akt, ERK were measured after dissection. RESULTS: Muscle weight and Type I, II fiber CSA of hindlimb muscles in the CDDP group were significantly less than the control group. Muscle weight and Type I, II fiber CSA of hindlimb muscles, food intake, activity, and withdrawal thresholds of the CDDP-SOD group were significantly greater than the CDDP group. There were no significant differences in relative SOD activities of hindlimb muscles between the CDDP-SOD and CDDP groups. MHC expression and phosphorylated Akt, ERK of hindlimb muscles in the CDDP-SOD group were significantly greater than the CDDP group. CONCLUSION: Cu/Zn SOD attenuates hindlimb muscular atrophy induced by cisplatin through increased food intake and activity. Increment of phosphorylated Akt, ERK may relate to attenuation of hindlimb muscular atrophy.
Animals ; Body Weight/drug effects ; Cisplatin/*toxicity ; Disease Models, Animal ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Hindlimb ; Male ; Muscle, Skeletal/*drug effects/enzymology/metabolism ; Muscular Atrophy/*chemically induced/metabolism/pathology ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins/biosynthesis/genetics/pharmacology ; Superoxide Dismutase/genetics/metabolism/pharmacology ; Superoxides/metabolism

A pair of 19-year-old female identical twins was referred to our hospital with progressive visual loss. They exhibited bilateral chorioretinal atrophy involving the midperiphery on fundoscopy and fluorescein angiography. Bilateral visual field constriction was noted on dynamic Goldmann perimetry, and a markedly impaired response was observed on both photopic and scotopic electroretinograms. Cystoid macular edema was identified in both eyes on optical coherence tomography. Plasma levels of ornithine were elevated. Based on these observations, the patients were diagnosed with gyrate atrophy of the choroid and retina. The clinical diagnosis was confirmed by mutation analysis of the ornithine-delta-aminotransferase (OAT) gene. Patients were treated with a pyridoxine supplement (300 mg/day) and an arginine-restricted diet to lower plasma levels of ornithine, which were successfully reduced without progression of chorioretinal atrophy for 15 months. Our report describes the first case of gyrate atrophy in the Korean population diagnosed by OAT gene analysis and treated with vitamin B6 dietary supplementation.
DNA/*analysis ; DNA Mutational Analysis ; Diagnosis, Differential ; Electroretinography ; Female ; Fluorescein Angiography ; Fundus Oculi ; Gyrate Atrophy/*diagnosis/enzymology/genetics ; Humans ; *Mutation ; Ornithine-Oxo-Acid Transaminase/*genetics/metabolism ; Tomography, Optical Coherence ; Visual Acuity ; Young Adult

This study aims to investigate the effect of modified Danggui Shaoyao Powder on the suppressor of cytokine signaling 3(SOCS3)/Toll-like receptor 4(TLR4) signaling pathway in gastric tissue of rats with chronic atrophic gastritis(CAG).Sixty SPF-grade SD rats were randomly assigned into the normal group, model group, Moluo Pills group, and high-, medium-, and low-dose groups of modified Danggui Shaoyao Powder.The rats in other groups except the normal group were treated with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) to establish the CAG model.After 12 weeks of modeling, the rats in each group were administrated with corresponding drugs by gavage for 8 weeks.After the last administration, the histopathological changes of rat gastric mucosa were observed via hematoxylin-eosin(HE) staining.The serum levels of IL-6, TNF-α, and CRP were determined by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of SOCS3 and TLR4 were determined by real-time PCR.The protein levels of SOCS3, TLR4, JAK2, p-JAK2, STAT3, and p-STAT3 in rat gastric tissue were measured by Western blot.Immunohistochemical method was employed to determine the protein levels of NF-κB, MyD88, NLRP3, Bcl-2, Bax, and Bad in rat gastric tissue.The results showed that modified Danggui Shaoyao Powder alleviated gastric mucosal atrophy of rats, significantly lowered the levels of IL-6, TNF-α, and CRP in rat serum, up-regulated the mRNA level of SOCS3, and down-regulated the mRNA level of TLR4 in rat gastric tissue.Furthermore, modified Danggui Shaoyao Powder up-regulated the protein level of SOCS3, down-regulated the protein levels of TLR4, p-JAK2, p-STAT3, NF-κB, MyD88, NLRP3, Bax, and Bad, and promoted the expression of Bcl-2 protein.Therefore, modified Danggui Shaoyao Powder may mitigate the gastric mucosal atrophy of rats by regulating the SOCS3/TLR4 signaling pathway.
Animals ; Atrophy ; Gastritis, Atrophic/genetics* ; Interleukin-6/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; NF-kappa B/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Powders ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Suppressor of Cytokine Signaling 3 Protein/metabolism* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; bcl-2-Associated X Protein/metabolism*

Spinal muscular atrophy has been classified into four groups based on the age of onset and clinical severity of the disease. Homozygous deletion in SMN1 gene causes the disease but the clinical severity may be modified by copy number of homologous gene SMN2 as well as the extent of deletion at SMN locus. In the view of scarcity of genotype and phenotype correlation data from India, this study has been undertaken to determine that correlation in SMA patients by using the SMN and NAIP genes and two polymorphic markers C212 and C272 located in this region. Two to four alleles of the markers C212 and C272 were observed in normal individuals. However, majority of Type I patients showed only one allele from both markers whereas in Type II and III patients, 2-3 alleles were observed. The SMN2 copy number in our type III patients showed that patients carry 3-5 copies of SMN2 gene. Our results suggest that extent of deletions encompassing H4F5, SMN1, NAIP and copy number of SMN2 gene can modify the SMA phenotype, thus accounting for the different clinical subtypes of the disease.
Adolescent ; Adult ; Alleles ; Apoptosis ; Child ; Child, Preschool ; Chromosomes, Human, Pair 5/*genetics ; Comparative Study ; DNA Mutational Analysis ; DNA-Binding Protein, Cyclic AMP-Responsive/*genetics ; Enzyme Inhibitors/metabolism ; Female ; Gene Deletion ; *Genetic Markers ; Genotype ; Homozygote ; Humans ; India ; Infant, Newborn ; Male ; Muscular Atrophy, Spinal/*genetics/pathology ; Nerve Tissue Proteins/*genetics ; Phenotype ; RNA-Binding Proteins/*genetics ; Variation (Genetics)

Spinal muscular atrophy (SMA) is an autosomal recessive disorder, caused by homozygous absence of the survival motor neuron gene (SMN1) in approximately 94% of patients. Since most carriers have only one SMN1 gene copy, several SMN1 quantitative analyses have been used for the SMA carrier detection. We developed a reliable quantitative real-time PCR with SYBR Green I dye and studied 13 patients with SMA and their 24 parents, as well as 326 healthy normal individuals. The copy number of the SMN1 gene was determined by the comparative threshold cycle (Ct) method and albumin was used as a reference gene. The homozygous SMN1 deletion ratio of patients was 0.00 and the hemizygous SMN1 deletion ratio of parents ranged from 0.39 to 0.59. The delta delta Ct ratios of 7 persons among 326 normal individuals were within the carrier range, 0.41-0.57. According to these data, we estimated the carrier and disease prevalence of SMA at 1/47 and 1/8,496 in Korean population, respectively. These data indicated that there would be no much difference in disease prevalence of SMA compared with western countries. Since the prevalence of SMA is higher than other autosomal recessive disorders, the carrier detection method using real-time PCR could be a useful tool for genetic counseling.
Adult ; Aged ; Aged, 80 and over ; DNA Mutational Analysis/*methods ; Female ; Genetic Predisposition to Disease/epidemiology ; Genetic Screening/*methods ; Heterozygote ; Heterozygote Detection/methods ; Humans ; Korea/epidemiology ; Male ; Middle Aged ; Muscular Atrophy, Spinal/*epidemiology/genetics/*metabolism ; Nerve Tissue Proteins/*genetics ; Polymorphism, Genetic ; *Quantitative Trait, Heritable ; Reverse Transcriptase Polymerase Chain Reaction/*methods ; Risk Assessment/*methods ; Risk Factors