The present study measured the normal blink rate (BR) variations in relation to behavioral tasks in 150 healthy volunteers (70 males and 80 females; aged 35.9 +/- 17.9 years, range 5-87 years). The subjects were videotaped in a standard setting while performing three different tasks: resting quietly, reading a short passage, talking freely. The mean BR was computed during each task; the data were compared by means of analysis of variance and Student's t tests. Mean BR at rest was 17 blinks/min, during conversation it increased to 26, and it was as low as 4.5 while reading. As compared with rest, BR decreased by -55.08% while reading (p < 1 x 10(-15)) and increased by 99.70% during conversation (p < 1 x 10(-9)). As compared with reading, BR increased during conversation by 577.8% (p < 1 x 10(-17). The distribution curves were highly reproducible in each task. The best curve fit was represented by a log-normal distribution, with the upper tail of each curve having a normal distribution. Eye color and eyeglass wearing did not influence BR. Women had higher BR than men just while reading. No age-related differences were found. The most common BR pattern was conversation > rest > reading, which occurred in 101 subjects (67.3%); 34 subjects (22.7%) had the pattern rest > conversation > reading; 12 (8.0%) had the pattern conversation > reading > rest. This study identified three normal behavioral BR patterns and showed that BR is more influenced by cognitive processes than by age, eye color, or local factors. The present findings provide a normal reference for the analysis of BR in movement disorders such as dystonia or tics.

Dystrophin is the scaffold of a protein complex, disrupted in inherited muscular dystrophies. At the last 3 terminus of the gene, a protein domain is encoded, where syntrophins are tightly bound. These are a family of cytoplasmic peripheral membrane proteins. Three genes have been described encoding one acidic (␣1) and two basic (␤1 and ␤2) proteins of ϳ57-60 kDa. Here, we describe the characterization of two novel putative members of the syntrophin family, named ␥1-and ␥2-syntrophins. The human ␥1-syntrophin gene is composed of 19 exons and encodes a brain-specific protein of 517 amino acids. The human ␥2-syntrophin gene is composed of at least 17 exons, and its transcript is expressed in brain and, to a lesser degree, in other tissues. We mapped the ␥1-syntrophin gene to human chromosome 8q11 and the ␥2-syntrophin gene to chromosome 2p25. Yeast two-hybrid experiments and pull-down studies showed that both proteins can bind the C-terminal region of dystrophin and related proteins. We raised antibodies against these proteins and recognized expression in both rat and human central neurons, coincident with RNA in situ hybridization of adjacent sections. Our present findings suggest a differentiated role of a modified dystrophin-associated complex in the central nervous system.Since the identification of dystrophin, the product of the Duchenne muscular dystrophy gene at Xp21, molecular genetics has moved quickly (1, 2). The deficiency of dystrophin in Duchenne muscular dystrophy (DMD) 1 and its first animal model, the mdx mouse, leads to a dramatic reduction in a group of previously unknown proteins identified as the dystrophinassociated protein complex.In the last few years, the dystrophin-associated protein complex proteins have been isolated; their genes have been cloned; and the following model of the complex has been hypothesized (3-5). Dystrophin is a large rod-shaped protein, primarily localized beneath the muscle cell membrane. Its actinin-like N terminus binds F-actin (6), whereas its C terminus is anchored to the transmembrane protein, ␤-dystroglycan, which is linked through ␣-dystroglycan to the extracellular merosin (laminin-2) (7). Then, this complex bridges the muscle membrane from the cytoskeleton to the extracellular matrix. In addition, dystroglycan is the receptor for agrin, a protein with a pivotal role in the clustering of acetylcholine receptors at the neuromuscular junction (8 -10) and a fundamental element of the basal lamina (11). At the muscle membrane, this complex is associated with the hydrophobic sarcospan DAP25 (dystrophinassociated protein; A5) (12) and the sarcoglycan complex, which is composed of at least four interacting transmembrane glycoproteins: ␣-sarcoglycan (DAG50 (dystrophin-associated glycoprotein), A2, adhalin) (13, 14), ␤-sarcoglycan (DAG43, A3b) (15, 16), ␥-sarcoglycan (DAG35, A4) (17), and ␦-sarcoglycan (18). Mutations in the laminin-␣2 gene are responsible for congenital muscular dystrophy (19); mutations in the ␥-, ␣-, ␤-, and ␦-sarcoglycan genes cause limb-girdle mus...

Two brothers with myopathic coenzyme Q10 (CoQ10) deficiency responded dramatically to CoQ10 supplementation. Muscle biopsies before therapy showed ragged-red fibers, lipid storage, and complex I + III and II + III deficiency. Approximately 30% of myofibers had multiple features of apoptosis. After 8 months of treatment, excessive lipid storage resolved, CoQ10 level normalized, mitochondrial enzymes increased, and proportion of fibers with TUNEL-positive nuclei decreased to 10%. The authors conclude that muscle CoQ10 deficiency can be corrected by supplementation of CoQ10, which appears to stimulate mitochondrial proliferation and to prevent apoptosis.

By defining the functional defect in a congenital myasthenic syndrome (CMS), we show that the third transmembrane domain (M3) of the muscle acetylcholine receptor governs the speed and efficiency of gating of its channel. The clinical phenotype of this CMS results from the mutation V285I in M3 of the alpha subunit, which attenuates endplate currents, accelerates their decay and causes abnormally brief acetylcholine-induced single-channel currents. Kinetic analysis of engineered alpha V285I receptors demonstrated a predominant effect on channel gating, with abnormally slow opening and rapid closing rates. Analysis of site-directed mutations revealed stereochemical and volume-dependent contributions of alpha V285 to channel gating. Thus, we demonstrate a functional role for the M3 domain as a key component of the nicotinic acetylcholine receptor channel-gating mechanism.

We describe four patients affected by chronic inflammatory demyelinating polyneuropathy (CIDP) in a pure motor form. Selective involvement of motor fibers was suggested by the absence of sensory symptoms, normal sensation at neurological examination and normal findings on electrophysiological testing of sensory fibres and sural nerve biopsy. The onset of the disease occurred at a young age (3-29 years) and the clinical course was relapsing-remitting. Over a follow-up period of 1.5-14 years, periodical clinical and electrophysiological examinations showed that selective involvement of motor fibers remained a constant feature. Electromyography and nerve conduction studies continued to show a purely demyelinating neuropathy without signs of axonal impairment. All patients were steroid-unresponsive, whereas they considerably improved after being treated with immunoglobulins. Two patients were treated with interferon alpha and showed a good response. In conclusion, the occurrence in our four patients of pure motor involvement over a long period of time during which several relapses occurred, suggests that pure motor CIDP may represent the result of a specific immunological process rather than of a random distribution of inflammation throughout peripheral nerves.