Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q16637 (SMA)
 8,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BACKGROUND AND PURPOSE The antiakinetic effect of internal Globus pallidus deep brain stimulation (Gpi-DBS) in Parkinson's disease is not clear and not either how this effect is modulated by L-dopa. METHODS Left Gpi-DBS and/or L-dopa effect was studied with auditory paced right-handed sequential movements on (15)O-butanol positron emission tomography (PET) in five patients. Rest and for conditions during movements (DBS off/L-dopa off; DBS on/L-dopa off; DBS off/L-dopa on; DBS on/L-dopa on) were compared with statistical parametric mapping. RESULTS Gpi-DBS activated the right supplementary motor area/premotor (SMA/PMC), and right insular cortex (IC), and as L-dopa decreased the left sensorimotor cortex (M1/S1) activity. L-dopa increased the left ventrolateral thalamus (VLTH), and decreased the left superior parietal cortex (PC) activity. Gpi-DBS and L-dopa interaction showed right SMA/PMC, IC, and left PC activation, decrease of left VLTH, PMC, and dorsolateral prefrontal cortex (PFC) activity. CONCLUSIONS The improvement of bradykinesia with Gpi-DBS is secondary and contributed to the regress of M1/S1-related rigidity and compensatory SMA/PMC, and IC activation. L-dopa and Gpi-DBS alone each reduces M1/S1 overactivity. Interaction ignores this effect, moreover has akinetic effect in the left VLTH, PMC, and PFC. Motor improvement possibly related to left PC and compensatory right SMA/PMC, and IC activation.
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PMID:Pallidal deep brain stimulation and L-dopa effect on PET motor activation in advanced Parkinson's disease. 1902 48

Spinal muscular atrophy (SMA) is one of the leading genetic causes of infant mortality with an incidence of 1:10,000. The recently-introduced antisense oligonucleotide treatment improves the outcome of this disease, in particular when applied at an early stage of progression. The genetic cause of SMA is, in >95% of cases, a homozygous deletion of the survival motor neuron 1 (SMN1) gene, which makes the low-cost detection of SMA cases as part of newborn screening programs feasible. We developed and validated a new SALSA MC002 melting curve assay that detects the absence of the SMN1 exon 7 DNA sequence without detecting asymptomatic carriers and reliably discriminates SMN1 from its genetic homolog SMN2 using crude extracts from newborn screening cards. Melting curve analysis shows peaks specific for both the SMN1 gene and the disease modifying SMN2 homolog. The detection of the SMN2 homolog, of which the only clinically relevant difference from the SMN1 gene is a single nucleotide in exon 7, was only used to confirm a correct reaction in samples that lacked the SMN1 gene, and not for SMN2 quantification. We retrieved 47 DBS samples from children with genetically-confirmed SMA, after informed consent from parents, and 375 controls from the national archive of the Dutch National Institute for Public Health and the Environment (RIVM). The assay correctly identified all anonymized and randomized SMA and control samples (i.e., sensitivity and specificity of 100%), without the detection of carriers, on the three most commonly-used PCR platforms with melting curve analysis. This test's concordance with the second-tier 'golden standard' P021 SMA MLPA test was 100%. Using the new P021-B1 version, crude extracts from DBS cards could also be used to determine the SMN2 copy number of SMA patients with a high level of accuracy. The MC002 test showed the feasibility and accuracy of SMA screening in a neonatal screening program.
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PMID:Validation of a Fast, Robust, Inexpensive, Two-Tiered Neonatal Screening Test algorithm on Dried Blood Spots for Spinal Muscular Atrophy. 3307 80