Neil C. Porter

Costameres: repeating structures at the sarcolemma of skeletal muscle.

Costameres, structures at the plasma membrane of skeletal muscle, are present in a rectilinear array that parallels the organization of the underlying contractile apparatus. Costameres have three major functions: to keep the plasma membrane, or sarcolemma, aligned and in register with nearby contractile structures; to protect the sarcolemma against contraction-induced damage; and to transmit some of the forces of contraction laterally, to the extracellular matrix. These functions require that costameres link the contractile apparatus through the membrane to the extracellular matrix. Mutations to key components of costameres cause these structures to lose their rectilinear organization and can result in muscle weakness or death. This article summarizes the evidence that costameres are composed of large complexes of integral and peripheral membrane proteins that are linked to the contractile apparatus by intermediate filaments and to the extracellular matrix by laminin. They also present evidence that costameres are altered when key costameric components are missing, as in a murine form of muscular dystrophy.

Abnormal expression of mu-crystallin in facioscapulohumeral muscular dystrophy

To identify proteins expressed abnormally in facioscapulohumeral muscular dystrophy (FSHD), we extracted soluble proteins from deltoid muscle biopsies from unaffected control and FSHD patients and analyzed them using two-dimensional electrophoresis, mass spectrometry and immunoblotting. Muscles from patients with FSHD showed large increases over controls in a single soluble, 34 kDa protein (pI=5.08) identified by mass spectrometry and immunoblotting as mu-crystallin (CRYM). Soluble fractions of biopsies of several other myopathies and muscular dystrophies showed no appreciable increases in mu-crystallin. Mu-crystallin has thyroid hormone and NADPH binding activity and so may influence differentiation and oxidative stress responses, reported to be altered in FSHD. It is also linked to retinal and inner ear defects, common in FSHD, suggesting that its up-regulation may play a specific and important role in pathogenesis of FSHD.

Two populations of β-spectrin in rat skeletal muscle

We use immunoblotting, immunoprecipitation, and centrifugation in sucrose density gradients to show that the product of the erythrocyte β-spectrin gene in rat skeletal muscle (muscle β-spectrin) is present in two states, one associated with fodrin, and another that is not associated with any identifiable spectrin or fodrin subunit. Immunofluorescence studies indicate that a significant amount of β-spectrin without α-fodrin is present in the myoplasm of some muscle fibers, and, more strikingly, at distinct regions of the sarcolemma. These results suggest that α-fodrin and muscle β-spectrin associate in muscle in situ, but that some muscle β-spectrin without a paired α-subunit forms distinct domains at the sarcolemma. Cell Motil. Cytoskeleton 37:7–19, 1997.

Sarcolemmal Reorganization in Facioscapulohumeral Muscular Dystrophy

We examined the sarcolemma of skeletal muscle from patients with facioscapulohumeral muscular dystrophy (FSHD1A) to learn if, as in other murine and human muscular dystrophies, its organization and relationship to nearby contractile structures are altered.

A Pilot Study of Acupuncture in Treating Bortezomib-Induced Peripheral Neuropathy in Patients With Multiple Myeloma

Background. Peripheral neuropathy is the dose limiting toxicity of bortezomib in patients with multiple myeloma (MM). Objectives. To examine the safety, feasibility and efficacy of acupuncture in reducing bortezomib-induced peripheral neuropathy (BIPN) symptoms. Methods. Patients with MM experiencing persistent BIPN ≥grade 2 despite adequate medical intervention and discontinuation of bortezomib received 10 acupuncture treatments for 10 weeks (2×/week for 2 weeks, 1×/week for 4 weeks, and then biweekly for 4 weeks). Responses were assessed by the Clinical Total Neuropathy Score (TNSc), Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-Ntx) questionnaire, and the Neuropathy Pain Scale (NPS). Repeated-measures analysis of variance was used to test for monotonic decline in scores on each of the measures. Serial serum levels of proinflammatory and neurotrophic cytokines were obtained at baseline and weeks 1, 2, 4, 8, and 14. Results. Twenty-seven patients with MM were enrolled in the trial. There were no adverse events associated with the acupuncture treatments. TNSc data were deemed invalid and therefore were not reported. At weeks 10 and 14, FACT/GOG-Ntx and NPS showed significant reduction suggesting decreased pain, and improved function (P values were <.0001 for both FACT/GOG-Ntx and NPS at weeks 10 and 14). However, nerve conduction studies did not significantly change between baseline assessment and end of study. There was no correlation in serum cytokines for responders versus none responders. Conclusions. Acupuncture is safe, feasible and produces subjective improvements in patients’ symptoms. A follow-up randomized controlled trial is warranted.

Trigeminal Neuralgia: Viewpoint—Medical Management

Trigeminal neuralgia is a well-recognized neuropathic pain syndrome characterized by brief paroxysms of facial pain in the distribution of the trigeminal nerve. The syndrome can occur as a result of a number of medical conditions such as multiple sclerosis, basilar artery aneurysm, and brain tumor, but oftentimes is idiopathic. Treatment options include a number of neuropathic pain medications as well as neurosurgical and radiosurgical interventions. Medication remains the first-line therapy for almost all individuals, and the mainstay of treatment for most patients. Traditionally, Carbamazepine has maintained its role as the most effective first-line agent. While Baclofen has generally been considered the predominant second agent, its effectiveness is much less well established. Numerous additional agents are commonly in use for trigeminal neuralgia including a number of antiepileptic drugs, antidepressants, GABA-mimetic agents, local anesthetics, and narcotics. Use of these agents must be tailored to the personal needs and characteristics of the patients suffering with trigeminal neuralgia.

Rapidly worsening bulbar symptoms in a patient with spinobulbar muscular atrophy

X-linked spinobulbar muscular atrophy (Kennedy’s disease) affects muscles and motor neurons, manifesting as weakness and wasting of bulbar, facial, and proximal limb muscles due to loss of anterior horn cells in the brain and spinal cord. We present the case of a patient with X-linked spinobulbar muscular atrophy with rapidly worsening bulbar symptoms caused by laryngopharyngeal irritation associated with a viral upper respiratory tract infection, seasonal allergies and laryngopharyngeal reflux, who dramatically improved with multimodality therapy.

Trigeminal Neuralgia: Medical Management Perspective

Trigeminal neuralgia is a well-recognized neuropathic pain syndrome characterized by brief paroxysms of facial pain in the distribution of the trigeminal nerve. The syndrome can occur secondary to a number of medical conditions including multiple sclerosis, basilar artery aneurysm, and brain tumor [1]. The disorder can also be idiopathic, the latter instance being known as tic douloureux. Trigeminal neuralgia can strike persons of any age but typically affects older individuals. Treatment options include a number of neuropathic pain medications as well as neurosurgical and radiosurgical interventions. The mainstay of treatment for most individuals, however, remains medication.