The hairpin region of WNT7A is sufficient for binding to the Frizzled7 receptor and to elicit signaling in myogenic cells.

Wnt signaling is essential for embryonic development and tissue homeostasis. So far, little is known about the importance and functional relevance of the different regions in WNT proteins including regions in their C-terminus identified as hairpin and linker. However, it was shown that the C-terminus of WNT7A comprising the linker and the hairpin region is sufficient to elicit signaling.

Stimulation of Non-canonical NF-κB Through Lymphotoxin-β-Receptor Impairs Myogenic Differentiation and Regeneration of Skeletal Muscle.

Myogenic differentiation, muscle stem cell functionality, and regeneration of skeletal muscle are cellular processes under tight control of various signaling pathways. Here, we investigated the role of non-canonical NF-κB signaling in myogenic differentiation, muscle stem cell functionality, and regeneration of skeletal muscle. We stimulated non-canonical NF-κB signaling with an agonistically acting antibody of the lymphotoxin beta receptor (LTβR).

Wnt7a Counteracts Cancer Cachexia.

Cancer cachexia is a complex metabolic disease so far lacking effective therapy, and it accounts for approximately one third of all cancer-related deaths worldwide. The extracellular ligand Wnt7a has a dual function in skeletal muscle, inducing the anabolic AKT/mammalian target of rapamycin (mTOR) pathway in myofibers and driving muscle stem cell expansion in skeletal muscle, making it a promising candidate for treatment of muscle wasting diseases. In murine and human myotubes, Wnt7a activates the anabolic AKT/mTOR pathway, thereby preventing cachexia-induced atrophy with a single application being sufficient to prevent atrophy independently of the tumor cell type causing cachexia.

The Puerto Rico study for the prevalence of multiple sclerosis.

This article review the results of a study conducted by the Puerto Rico Multiple Sclerosis Foundation. It presents the results of the first continuous patient registry of the Puerto Rico Multiple Sclerosis (MS) Foundation in the Island between the years 2003 and 2008. It describes the profile of patients with MS and the estimated prevalence.

Disseminated encephalomyelitis in adults.

Disseminated encephalomyelitis (DEM) is an inflammatory demyelinating disease that is common in children, but also appears in adults. It is often misdiagnosed as multiple sclerosis (MS) from which it differs in its clinical presentation, course of disease and prognosis. Some aspects of DEM overlap with neuromyelitis optica (NMO), another demyelination disease of CNS that was for a long time regarded as part of the MS spectrum, until discovery of the aquaporin-4 antibodies, claimed to be specific for NMO.

The accuracy of prevalence rates of multiple sclerosis: a critical review.

Review of the recent medical literature raises doubts about the reliability of reported prevalence rates of multiple sclerosis (MS). Many published prevalence rates are inflated. Some studies have shown that relying on clinical information and MRI interpretation leads to one third of incorrect MS diagnoses.

Disseminated encephalomyelitis and multiple sclerosis: two different diseases - a critical review.

The practice of initiating immunomodulatory treatment immediately after a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) emphasizes the need to distinguish between disseminated encephalomyelitis (DEM) and MS. Their clinical, genetic, imaging, and histopathological characteristics establish that they are distinct disease entities. Acute and recurrent DEM are more common in children, but also occur in adults.

The environment and the nervous system.

Multiple sclerosis (MS) is used as the best example to illustrate the interplay between genetic endowment and environmental effects. The former is widely considered as being the more important one, although there is mounting evidence that environmental factors influence genetic predisposition. The vast majority of environmental epidemiological studies have failed for two major reasons: they have lacked biological plausibility, and they have not considered possible environmental factors operative during the putative period of acquisition of the disease.

The multiple sclerosis trait and the development of multiple sclerosis: genetic vulnerability and environmental effect.

The remarkably low rate of concordance of multiple sclerosis (MS) in monozygotic twins has never been fully explained but it implies the possibility of a systemic condition called the multiple sclerosis trait (MST), which is quite different from asymptomatic MS. It results from the action of an antigenic challenge on the immune system of a genetically vulnerable person that does not cause damage to the nervous parenchyma; it may never evolve into the disease MS. A subsequent environmental viral-antigenic event in some MST-carriers can change the trait into the disease.

Enlargement of the spinal cord: inflammation or neoplasm?

Intramedullary spinal tumours are uncommon lesions that can cause significant difficulties in the differential diagnosis between inflammatory diseases such as multiple sclerosis and acute disseminated encephalomyelitis, and vascular malformations or neoplasms. We report five cases in which the history and the clinical symptoms suggested an inflammatory process of the spinal cord but the MRI characteristics were those of neoplastic lesions. Both non-neoplastic and neoplastic intramedullary lesion may have very similar symptoms, and even CSF abnormalities, but in every one of our cases, a more detailed history and longer observation of the clinical course would have led to the correct diagnosis; in such problem cases, empirical treatment and a follow-up MRI after a month's observation would be a more prudent approach providing that the patient is not rapidly deteriorating.

Psychiatric manifestations of multiple sclerosis and acute disseminated encephalomyelitis.

It is unusual for acute disseminated encephalomyelitis and multiple sclerosis to present as purely psychiatric disorders. We report five patients with such demyelinating diseases and symptoms of psychosis, depression or anxiety. The importance of excluding demyelination as the basis for these psychiatric disturbances is emphasized, especially in the presence of unexplained neurologic findings.

An adult case of Leigh disease.

Leigh's disease is a mitochondrial disease of infancy and early childhood, and is rare in adults. Following a febrile illness, a 21-year-old woman developed ataxic paraparesis and was originally diagnosed as multiple sclerosis. Her illness progressed to somnolence and quadriparesis.

Cerebral demyelination in Wegener's granulomatosis.

A 38-year-old woman with a history of a granulomatous lesion of the nose, developed blurred vision, ataxic gait, and spastic tetraparesis. The presence of demyelination on the brain MRI led to the diagnosis of cerebral demyelination associated with Wegener's granulomatosis. Pulse cyclophosphamide administration resulted in some clinical of improvement of her condition.

Sudden onset aphasic hemiplegia: an unusual manifestation of disseminated encephalomyelitis.

The association of the sudden onset of aphasia with hemiplegia, hemisenosry defect, and facial palsy, with MRI evidence of white matter lesions, requires differentiation between multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). We have observed eight patients with such a syndrome, all of whom were originally diagnosed as multiple sclerosis, but who, on closer examination, turned out to be instances of disseminated encephalomyelitis. The patterns of demyelination seen in T2-weighted MRI are quite different in both conditions.

The nature of multiple sclerosis.

Multiple sclerosis (MS) has recently been classified according to its clinical course. Despite relapses and remissions, its course is invariably progressive, and the observed progression from the remitting-relapsing to the secondary progressive form represents the accumulation of permanent damage to the nervous system. Discussions of the nomenclatural position of Schilder's, Marburg's, and Baló's diseases, ignore the fact that the unique, pathognomonic, sharp-edged plaque of MS, is also the pathologic end-result in the three variants.

Diagnostic criteria for multiple sclerosis: an historical review.

Starting with Charcot, diagnostic criteria for multiple sclerosis (MS) have evolved to reflect advances in our understanding of the disease and the development of new diagnostic techniques, and from purely clinical considerations to increasing dependency upon imaging of the central nervous system. The MS diagnostic process was revolutionized by the 1981 introduction of magnetic resonance imaging (MRI), but the increasing reliance upon this technique has led to a surge in erroneous diagnoses, mostly because of the failure to distinguish between MS and disseminated encephalomyelitis (DEM), as well as mounting disregard for the data obtained from the traditional history and physical examination. The most recent scheme of McDonald et al.

Multiple sclerosis trait: the premorbid stage of multiple sclerosis. A hypothesis.

The unexpectedly low rate of concordance in monozygotic (MZ) twins with multiple sclerosis (MS) suggests that they share a systemic condition called the multiple sclerosis trait. This trait constitutes the premorbid stage of the disease and is quite distinct from asymptomatic MS. It results from the action of an antigenic challenge to the immune system of a genetically susceptible person but is short of producing lesions of the central nervous system parenchyma; in fact, the disease may never develop in people with the trait.