Muscle fiber types and function.

A major recent advance in the field of muscle fiber types has been the discovery that myogenic factors regulate fiber phenotypic properties. Myogenic influences occur in limb and trunk (somitic) muscle, but are particularly strong in jaw-closing muscles and extraocular muscles that express some unique myofibrillar proteins. In somitic muscles, a variant of fast fiber has been discovered, making four types of fibers: I, IIA, IIX, and IIB. These fibers express different isoforms of myofibrillar and other proteins. The speed and power of the four types of fibers are distinct and are controlled principally by their myosin heavy chains, which modulate the two regulatory steps in the crossbridge cycle, one controlling the rate of development of force, the other controlling the maximal velocity of shortening. Fast fibers have a higher threshold for Ca(2+)-activated force and a steeper force-pCa relation than do slow fibers. This difference is largely attributable to the cooperativity in the attachment of crossbridges and to the difference in Ca2+ binding capacity of their troponin C. Ca2+ initiates force development in muscle by increasing the rate of attachment of crossbridges. The phosphorylation of myosin light chain enhances this action. This effect of phosphorylation underlies the phenomenon of posttetanic potentiation of the isometric twitch in fast fibers.     

A protein kinase A-dependent molecular switch in synapsins regulates neurite outgrowth

Cyclic AMP (cAMP) promotes neurite outgrowth in a variety of neuronal cell lines through the activation of protein kinase A (PKA). We show here, using both Xenopus laevis embryonic neuronal culture and intact X. laevis embryos, that the nerve growth-promoting action of cAMP/PKA is mediated in part by the phosphorylation of synapsins at a single amino acid residue. Expression of a mutated form of synapsin that prevents phosphorylation at this site, or introduction of phospho-specific antibodies directed against this site, decreased basal and dibutyryl cAMP-stimulated neurite outgrowth. Expression of a mutation mimicking constitutive phosphorylation at this site increased neurite outgrowth, both under basal conditions and in the presence of a PKA inhibitor. These results provide a potential molecular approach for stimulating neuron regeneration, after injury and in neurodegenerative diseases.     

Analysis of myocilin mutations in 1703 glaucoma patients from five different populations

A glaucoma locus, GLC1A, was identified previously on chromosome 1q. A gene within this locus (encoding the protein myocilin) subsequently was shown to harbor mutations in 2-4% of primary open angle glaucoma patients. A total of 1703 patients was screened from five different populations representing three racial groups. There were 1284 patients from primarily Caucasian populations in Iowa (727), Australia (390) and Canada (167). A group of 312 African American patients was from New York City and 107 Asian patients from Japan. Overall, 61 different myocilin sequence variations were identified. Of the 61 variations, 21 were judged to be probable disease-causing mutations. The number of probands found to harbor such mutations in each population was: Iowa 31/727 (4.3%), African Americans from New York City 8/312 (2.6%), Japan 3/107 (2.8%), Canada 5/167 (3.0%), Australia 11/390 (2.8%) and overall 58/1703 (3. 4%). Overall, 16 (76%) of 21 mutations were found in only one population. The most common mutation observed, Gln368Stop, was found in 27/1703 (1.6%) glaucoma probands and was found at least once in all groups except the Japanese. Studies of genetic markers flanking the myocilin gene suggest that most cases of the Gln368Stop mutations are descended from a common founder. Although the specific mutations found in each of the five populations were different, the overall frequency of myocilin mutations was similar ( approximately 2-4%) in all populations, suggesting that the increased rate of glaucoma in African Americans is not due to a higher prevalence of myocilin mutations.     

Force: velocity pproperties of kitten muscles

1. The characteristics of isometric contractions and force:velocity properties of the extensor digitorum longus (EDL) and soleus (SOL) muscles of neonatal kittens were determined in situ.

2. The mean contraction time is 51 msec for EDL and 70 msec for SOL and the half-relaxation time is 51 msec for EDL and 109 msec for SOL.

3. The average maximum isometric tetanic tension per unit cross-sectional area of muscle is 1·27 kg/cm² for EDL and 1·17 kg/cm² for SOL.

4. The average twitch:tetanus ratio is 0·28 for EDL and 0·119 for SOL; the low value for SOL was found for both indirect and direct stimulation.

5. The average maximum speed of shortening of a sarcomere is 22·8 μ/sec for EDL and 12·7 μ/sec for SOL.

6. These properties of neonatal muscles are compared with those of adult cat muscles and discussed in connexion with differentiation of mammalian muscles into fast and slow types.

     

Increasing sampling density improves reproducibility of optical coherence tomography measurements.

PURPOSE: Published series of peripapillary retinal nerve fiber layer (RNFL) measurements using optical coherence tomography (OCT) have sampled 100 evenly distributed points on a 360 degrees peripapillary circular scan. The goal of this study was to determine whether a four-fold increase in sampling density improves the reproducibility of OCT measurements. METHODS: Complete ophthalmic examinations, achromatic automated perimetry, and OCT imaging were performed in all patients. The OCT scanning consisted of three superior and inferior quadrantic scans (100 sampling points/quadrant) and three circular scans (25 points/quadrant). The RNFL thickness measurements and coefficient of variation (CV) were calculated for the superior and inferior quadrants for each sampling density technique. RESULTS: The study included 22 eyes of 22 patients (3 control subjects; 2 patients with ocular hypertension; and 17 patients with glaucoma). Quadrants with associated glaucomatous visual field loss on automated achromatic perimetry had thinner RNFLs than quadrants without functional defects for both the 25- and 100-points/quadrant scans. For quadrants associated with normal visual hemifields (n = 22), there was no difference between the 25- and 100-points/quadrant scans in mean RNFL thickness and CV. Among quadrants with visual field defects (n = 22), RNFL thickness measurements were thinner in the 25-points/quadrant scans than in the 100-points/quadrant scans. The CV for the 25-points/quadrant scans (25.9%) was significantly higher than that for the 100-points/quadrant scans (11.9%). CONCLUSION: Increasing the sampling density of OCT scans provides less variable representation of RNFL thickness. The optimal sampling density to achieve maximal reliability of OCT scans remains to be determined.     

Paraneoplastic optic neuropathy in nasopharyngeal carcinoma--report of a case

A 31-year-old Chinese man developed left optic neuritis with left sectorial field loss as a remote effect of nasopharyngeal carcinoma. The field defect showed interesting fluctuations in response to the dosage of systemic steroid therapy. Neuropathologic findings from an exploratory craniotomy did not show any gross tumour mass around the left optic nerve nor any histological evidence of tumour infiltration. This case illustrates that "optic neuritis" could be a paraneoplastic effect of nasopharyngeal carcinoma.     

Multimodality treatment of nongalenic arteriovenous malformations in pediatric patients

OBJECTIVE: Previously reported series of arteriovenous malformations (AVMs) in pediatric patients have primarily used a single-modality treatment approach of either surgery, radiosurgery, or embolization, with significant treatment-related morbidity and mortality. At our institution, we have used a combined multidisciplinary team approach of all three treatment modalities, alone or in combination, to minimize complications and to maximize efficacy in the management of these lesions. METHODS: We retrospectively reviewed 40 consecutive pediatric patients with AVMs seen at our institution from 1991 to 1999. A multidisciplinary team planned the treatment for each AVM. The treatment modality consisted of the following approaches: surgery alone in 14 patients, a combination of endovascular embolization and surgery in 6 patients, radiosurgery alone in 11 patients, a combination of endovascular embolization and radiosurgery in 2 patients, and a combination of radiosurgery and surgery in 2 patients. Four patients are receiving ongoing multistaged treatment for reduction of the nidus size for eventual surgical resection or radiosurgical obliteration of large, complex lesions. In one patient, no treatment was recommended. RESULTS: The clinical outcomes for the overall series were 95.0% excellent or good (Glasgow Outcome Scale score 5 or 4), 2.5% fair (Glasgow Outcome Scale score 3), and 2.5% dead. Radiographic efficacy in the patients who have completed treatment was 92.9% complete obliteration of their AVMs and 7.1% incomplete obliteration. Of the 10 patients who had seizures, 9 are seizure-free. CONCLUSION: A combined multimodality approach of surgery, radiosurgery, and embolization in managing AVMs in pediatric patients can improve outcomes and minimize morbidity and mortality.     

Estimating time to full uterine cervical dilation using genetic algorithm

The objectives of this study were to provide new parameters to better understand labor curves, and to provide a model to predict the time to full cervical dilation (CD). We studied labor curves using the retrospective records of 594 nulliparas, including at term, spontaneous labor onset, and singleton vertex deliveries of normal birth weight infants. We redefined the parameters of Friedman's labor curve, and applied a three-parameter model to the labor curve with a logistic model using the genetic algorithm and the Newton-Raphson method to predict the time necessary to reach full CD. The genetic algorithm is more effective than the Newton-Raphson method for modeling labor progress, as demonstrated by its higher accuracy in predicting the time to reach full CD. In addition, we predicted the time (11.4 hours) to reach full CD using the logistic labor curve using the mean parameters (the power of CD = 0.97 cm/hours, a midpoint of the active phase = 7.60 hours, and the initial CD = 2.11 cm). Our new parameters and model can predict the time to reach full CD, which can aid in the forecasting of prolonged labor and the timing of interventions, with the end goal being normal vaginal birth.