A case of type 1 facioscapulohumeral muscular dystrophy (FSHD) with restrictive ventilatory defect and congestive heart failure

[Background] Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscle disease characterized by asymmetric involvement of muscles in the face, upper extremity, trunk, and lower extremity regions, with variable severity. It was recently reported that restrictive respiratory involvement is more frequent and severe than previously recognized, while cardiac dysfunction other than arrhythmia is still considered extremely rare in FSHD. [Case report] A 59-year-old man presenting with marked muscle atrophy in the trunk and asymmetrical muscle atrophy in the legs was hospitalized because of dyspnea and edema in the face and limbs. Shortness of breath with body movement started from approximately 40 years of age. Muscle biopsy revealed myopathic change with mild to moderate variation in fiber size. The diagnosis of FSHD was made by D4Z4 contraction to three repeats on genetic testing. A pulmonary function test revealed a decline of forced vital capacity (FVC) and a preserved FEV1/FVC indicating restrictive ventilatory defect (RVD). Ultrasonic echocardiogram (UCG) showed diffuse left ventricular hypokinesis, ventricular septum thickening, pericardial effusion, and decreased ejection fraction (LVEF 30%). [Conclusion] Although restrictive ventilatory defect and congestive heart failure are uncommon in FSHD, respiratory and cardiac evaluation may be necessary in patients with FSHD

Effect of intravenous immunoglobulin therapy on anti-NT5C1A antibody-positive inclusion body myositis after successful treatment of hepatitis C: A case report

Inclusion body myositis (IBM) is the commonest idiopathic inflammatory myopathy of older persons. Pathophysiological mechanism of IBM remains unknown; however, an association of IBM with chronic hepatitis C virus (HCV) infection and serum autoantibodies against skeletal muscle protein 5′-nucleotidase 1A (NT5C1A) has recently been reported. No effective treatment for IBM has yet been developed. We here present a 70-year-old man who was anti-NT5C1A antibody-positive in association with IBM and chronic hepatitis C. The initial treatment of ombitasvir/paritaprevir/ritonavir for his chronic hepatitis C was successful; however, his symptoms of IBM did not improve. On the contrary, his quadriplegic paralysis became more severe and he developed dysphagia. Next, steroid pulse therapy was initiated for IBM and, although his hyper-creatine phosphokinase-emia improved, his symptoms did not; indeed, they worsened. Subsequent intravenous immunoglobulin therapy (IVIg) resulted in obvious improvement in his dysphagia. Thereafter IVIg therapy was repeated at approximately 2-monthly intervals. His dysphagia remained improved for more than 1 year; however, his quadriplegia continued to progress slowly. Although IBM can reportedly be associated with hepatitis C, we inferred that there was no direct relationship between these conditions in our patient because his IBM did not improve after treatment of his hepatitis C. Although his IBM-associated quadriplegia did not improve, IVIg therapy did result in improvement in his dysphagia

Dysregulated Aire expression and autoimmunity

Deficiency for AIRE/Aire in both humans and mice results in the development of organ-specific autoimmune disease. We tested whether augmented and/or dysregulated AIRE/Aire expression might be also prone to the breakdown of self-tolerance. To define the effect of augmented Aire expression on the development of autoimmunity, antigen-specific clonal deletion and production of clonotypic regulatory T cells (Tregs) in the thymus were examined using mice expressing two additional copies of Aire in a heterozygous state (3xAire-knockin mice: 3xAire-KI). We found that both clonal deletion of autoreactive T cells and production of clonotypic Tregs in the thymus from 3xAire-KI were impaired in a T-cell receptor-transgenic system. Furthermore, 3xAire-KI females showed higher scores of experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein than wild-type littermates, suggesting that augmented Aire expression exacerbates organ-specific autoimmunity under disease-prone conditions. In humans, we found that one patient with amyopathic dermatomyositis showed CD3–CD19– cells expressing AIRE in the peripheral blood before the treatment but not during the remission phase treated with immunosuppressive drugs. Thus, not only loss of function of AIRE/Aire but also augmented and/or dysregulated expression of AIRE/Aire should be considered for the pathogenesis of organ-specific autoimmunity. We suggest that further analyses should be pursued to establish a novel link between organ-specific autoimmune disease and dysregulated AIRE expression in clinical settings

Guanidinylation of Chitooligosaccharides Involving Internal Cyclization of the Guanidino Group on the Reducing End and Effect of Guanidinylation on Protein Binding Ability

In order to synthesize a promising material for developing a novel peptide/protein delivery system, guanidinylation of chitooligosaccharides with 1-amidinopyrazole hydrochloride was investigated herein. The production of guanidinylated chitooligosaccharides was demonstrated by infrared spectroscopy (IR), nuclear magnetic resonance (NMR), and elemental analyses. Interestingly, we found that the reducing end in the guanidinylated chitooligosaccharides was converted to a cyclic guanidine structure (2-[(aminoiminomethyl)amino]-2-deoxy-d-glucose structure). This reaction was carefully proven by the guanidinylation of d-glucosamine. Although this is not the first report on the synthesis of the 2-[(aminoiminomethyl)amino]-2-deoxy-d-glucose, it has provided a rational synthetic route using the high reactivity of the reducing end. Furthermore, we found that the interaction between chitooligosaccharides and bovine serum albumin is weak when in a neutral pH environment; however, it is significantly improved by guanidinylation. The guanidinylated chitooligosaccharides are useful not only for the development of a novel drug delivery system but also as a chitinase/chitosanase inhibitor and an antibacterial agent

Cerebral syphilitic gumma mimicking a brain tumor that enlarged temporarily after commencing antibiotic treatment

In this case report, we describe a 60-year-old man who presented with headaches for 1 year and mild confusion for 3 weeks and was initially diagnosed as having a cerebral tumor on the basis of finding a round lesion in the right lenticular nucleus with ring enhancement on gadolinium-enhanced T1-weighted brain magnetic resonance imaging. However, the discovery of positive serology for Treponema pallidum infection on routine tests on admission prompted analysis of cerebrospinal fluid, which was also positive on Treponema pallidum hemagglutination (TPHA), rapid plasma reagin (RPR), and treponemal antibody absorption (FTA-ABS) tests. Thus, he was diagnosed as having an intracranial syphilitic gumma. After commencing treatment with penicillin G, the lesion temporarily increased in size, but subsequently resolved completely with continuing antibiotic treatment. In the present era of increasing prevalence of syphilitic infection and because they are eminently treatable, syphilitic gummas should be included in the differential diagnosis of apparent brain tumors. Additionally, temporary enlargement of a probable gumma after instituting antibiotic treatment should not prompt cessation or change of the antibiotics

Encouragement of Enzyme Reaction Utilizing Heat Generation from Ferromagnetic Particles Subjected to an AC Magnetic Field.

We propose a method of activating an enzyme utilizing heat generation from ferromagnetic particles under an ac magnetic field. We immobilize α-amylase on the surface of ferromagnetic particles and analyze its activity. We find that when α-amylase/ferromagnetic particle hybrids, that is, ferromagnetic particles, on which α-amylase molecules are immobilized, are subjected to an ac magnetic field, the particles generate heat and as a result, α-amylase on the particles is heated up and activated. We next prepare a solution, in which α-amylase/ferromagnetic particle hybrids and free, nonimmobilized chitinase are dispersed, and analyze their activities. We find that when the solution is subjected to an ac magnetic field, the activity of α-amylase immobilized on the particles increases, whereas that of free chitinase hardly changes; in other words, only α-amylase immobilized on the particles is selectively activated due to heat generation from the particles