Is there a genetic susceptibility locus for Parkinson's disease on chromosome 22q13?

The cytochrome P450 mono-oxygenase gene, CYP2D6 on chromosome 22q13 (ch22q13), has been inconsistently associated with Parkinson's disease. Associations with CYP2D6 have either been absent altogether or have involved more than one polymorphism, many of which have the same metabolic effect on gene expression. We examined the association between CYP2D6 polymorphisms and Parkinson's disease in a case-control study and included 10 polymorphic dinucleotide repeat markers linked to CYP2D6 to determine whether the association was present or due to linkage disequilibrium. There was no association between any polymorphism of CYP2D6 and Parkinson's disease, but two of 10 dinucleotide repeat markers linked to CYP2D6 were associated with the disease. These results provide evidence to suggest that there may be an unidentified locus for susceptibility to Parkinson's disease that is in linkage disequilibrium with dinucleotide repeat markers mapping near CYP2D6 on ch22q13.     

Matching neural and muscle oscillators: control by FMRFamide-like peptides

Stomatogastric nervous systems of the shrimp, Palaemon serratus, were stained with antisera raised against the peptide FMRFamide. FMRFamide-like immunoreactivity was found in fibers in the input nerve to the stomatogastric ganglion (STG), in several STG somata, in dense neuropil in the STG, in the motor nerves that innervate the dilator muscles of the pyloric region, but not in the pyloric dilator (PD) motor neurons. FMRFamide and several FMRFamide-like peptides elicited sequences of rhythmic depolarizations and contractions of the pyloric dilator muscle. As peptide concentrations were increased, a discrete threshold for contraction was found, above which contractions were initiated with a decreasing latency in an all-or-none fashion. Muscles stopped rhythmically contracting after many seconds to several minutes of activity; the duration of spontaneous oscillatory activity in peptide was proportional to the concentration of applied peptide. In the absence of peptide, each motor neuron discharge evoked small graded muscle contractions. During peptide-induced oscillations, motor neuron activity did not always entrain muscle oscillations. After spontaneous oscillations had stopped, when the motor neurons were stimulated in the presence of the peptide, each motor neuron burst evoked large amplitude contractions as a result of the peptide-induced regenerative properties of the muscle membrane.     

T2 hyperintense foci on magnetic resonance images of schizophrenic patients and controls.

High resolution magnetic resonance imaging (MRI) of the brain was performed on 18 male schizophrenic patients and 15 male normal control subjects using an identical imaging protocol. The number and size of T2 hyperintense foci were clinically quantified by an academic radiologist. Large foci (greater than or equal to 3 mm in diameter) were observed more frequently on patient images (7/18) than on control images (1/15). The imaging protocol detected high rates of focal hyperintensities, but no differences between patients and controls were noted in the total affected brain area (sum of focal areas) or in the presence or absence of foci.     

Reconstruction of the lateral ankle ligaments. A biomechanical analysis.

The purpose of this study was to perform a biomechanical analysis of several commonly performed operative procedures used to stabilize the lateral ankle. We performed the Evans, Watson-Jones, and Chrisman-Snook procedures on 15 cadaveric ankles and tested the ankles for stability, motion, and isometry of graft placement. The Evans procedure allowed increased anterior displacement, internal rotation, and tilt of the talus when compared to ankles with intact ligaments. Subtalar joint motion was restricted by the Evans procedure. The Watson-Jones procedure controlled internal rotation and anterior displacement of the talus, but was less effective in controlling talar tilt and also restricted subtalar joint motion. The Chrisman-Snook procedure allowed increased internal rotation and anterior displacement of the talus when compared to ankles with intact ligaments. The procedure was effective in limiting talar tilt, but restricted subtalar joint motion. Based on the biomechanical data obtained, we devised a lateral ankle reconstruction with bone tunnels that reproduce the anatomic orientation of both the anterior talofibular and calcaneofibular ligaments. This ankle ligament reconstruction resists anterior displacement, internal rotation, and talar tilt without restricting subtalar joint motion. Clinical relevance: We found considerable mechanical differences among the more commonly performed lateral ankle reconstructions. It is possible to locate bone tunnels and graft placement so that a more anatomic configuration is achieved.     

Construction and validation of a Parkinson's disease mutation genotyping array for the Parkin gene.

Parkin mutations account for the majority of familial and sporadic early onset Parkinson's disease (EOPD) cases with a known genetic association. More than 100 mutations have been described in the Parkin gene that includes homozygous, compound heterozygous, and single heterozygous mutations. We have designed a Parkin mutation genotyping array (gene chip) that includes published Parkin sequence variants and allows their simultaneous detection. The chip was validated by screening 85 PD cases and 47 controls previously tested for Parkin mutations. Similar genotyping microarrays have been developed for other genetically heterogeneous diseases including age-related macular degeneration. Here, we show the utility of a genotyping array for Parkinson's disease by analysis of 60 subjects from the Genetic Epidemiology of Parkinson Disease (GEPD) study that includes 15 early-onset PD case probands and 45 relatives.     

Efficacy of Intraoperative Cooling Methods

Background: Patients may require perioperative cooling for a variety of reasons including treatment of a malignant hyperthermia crisis and induction of therapeutic hypothermia for neurosurgery. The authors compared heat transfer and core cooling rates with five cooling methods.

Methods: Six healthy volunteers were anesthetized with desflurane and nitrous oxide. The cooling methods were 1) circulating water (5 [degree sign] Celsius, full-length mattress and cover), 2) forced air (10 [degree sign] Celsius, full-length cover), 3) gastric lavage (500 ml iced water every 10 min), 4) bladder lavage (300 ml iced Ringer's solution every 10 min), and 5) ice-water immersion. Each method was applied for 40 min or until the volunteers' core temperatures approached 34 [degree sign] Celsius. The volunteers were rewarmed to normothermia between treatments. Core cooling rates were evaluated using linear regression.

Results: The first volunteer developed abdominal cramping and diarrhea after gastric lavage. Consequently, the technique was not again attempted. Bladder lavage increased heat loss 10 [nearly =] 10 W and decreased core temperature 0.8 +/- 0.3 [degree sign] Celsius/h (r2 = 0.99 +/- 0.002; means +/- SD). Forced-air and circulating-water cooling comparably increased heat flux, [nearly =] 170 W. Consequently, core cooling rates were similar during the two treatments at 1.7 +/- 0.5 [degree sign] Celsius/h (r2 = 0.99 +/- 0.001) and 1.6 +/- 1.1 [degree sign] Celsius/h (r2 = 0.98 +/- 0.02), respectively. Immersion in an ice water slurry increased heat loss [nearly =] 600-800 W and decreased core temperature 9.7 +/- 4.4 [degree sign] Celsius/h (r sup 2 = 0.98 +/- 0.01). Immersion cooling was associated with an afterdrop of [nearly =] 2 [degree sign] Celsius.     

Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease

Background

Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated pathogenic variants rather than sequencing the whole gene, which may leave carriers of PD-associated GBA variants undiscovered.

Peptidergic modulation of a multioscillator system in the lobster. I. Activation of the cardiac sac motor pattern by the neuropeptides proctolin and red pigment-concentrating hormone

1. The cardiac sac motor pattern consists of slow and irregular impulse bursts in the motor neurons [cardiac sac dilator 1 and 2 (CD1 and CD2)] that innervate the dilator muscles of the cardiac sac region of the crustacean foregut. 2. The effects of the peptides, proctolin and red pigment-concentrating hormone (RPCH), on the cardiac sac motor patterns produced by in vitro preparations of the combined stomatogastric nervous system [the stomatogastric ganglion (STG), the paired commissural ganglia (CGs), and the oesophageal ganglion (OG)] were studied. 3. Bath applications of either RPCH or proctolin activated the cardiac sac motor pattern when this motor pattern was not already active and increased the frequency of the cardiac sac motor pattern in slowly active preparations. 4. The somata of CD1 and CD2 are located in the esophageal and stomatogastric ganglia, respectively. Both neurons project to all four of the ganglia of the stomatogastric nervous system. RPCH elicited cardiac sac motor patterns when applied to any region of the stomatogastric nervous system, suggesting a distributed pattern generating network with multiple sites of modulation. 5. The anterior median (AM) neuron innervates the constrictor muscles of the cardiac sac. The AM usually functions as a part of the gastric mill pattern generator. However, when the cardiac sac is activated by RPCH applied to the stomatogastric ganglion, the AM neuron becomes active in antiphase with the cardiac sac dilator bursts. This converts the cardiac sac motor pattern from a one-phase rhythm to a two-phase rhythm. 6. These data show that a neuropeptide can cause a neuronal element to switch from being solely a component of one neuronal circuit to functioning in a second one as well. This example shows that peptidergic "reconfiguration" of neuronal networks can produce substantial changes in the behavior of associated neurons.