Coordination dynamics in Parkinson's disease patients and healthy subjects quantified by the coordination dynamics recording method and sEMG

Coordination dynamics were measured in Parkinson's disease patients to quantify central nervous system (CNS) dysfunction. The low-load coordination dynamics in the patients were impaired by 56% for forward and 44% for backward moving in comparison to a control group of similar age. Exercising at higher load was only partly possible. When the disease preferentially affected one side of the body, the coordination dynamics were worse for the affected side. A dexterity test showed that coordination of hand and arm movements could be improved in the short-term memory when exercising on the special coordination dynamics recording and therapy device. Simultaneously taken surface EMG (sEMG) showed that the motor pattern was impaired in the Parkinson's disease patients. sEMG recordings showed further that the fast fatigable muscle fibre activation was impaired. FF-type muscle fibres were already activated for low load in one and not at all in another muscle. In conclusion, coordination between motoneuron firings and between arm and leg movements were found to be impaired in Parkinson's disease patients.     

Isolation of a new clathrin heavy chain gene with muscle-specific expression from the region commonly deleted in velo-cardio-facial syndrome

Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DGS) are developmental disorders characterized by a spectrum of phenotypes including velopharyngeal insufficiency, conotruncal heart defects and facial dysmorphology among others. Eighty to eighty-five percent of VCFS/DGS patients are hemizygous for a portion of chromosome 22. It is likely that the genes encoded by this region play a role in the etiology of the phenotypes associated with the disorders. Using a cDNA selection protocol, we isolated a novel clathrin heavy chain cDNA (CLTD) from the VCFS/DGS minimally deleted interval. The cDNA encodes a protein of 1638 amino acids. CLTD shares significant homology, but is not identical to the ubiquitously expressed clathrin heavy chain gene. The CLTD gene also shows a unique pattern of expression, having its maximal level of expression in skeletal muscle. Velopharyngeal insufficiency and muscle weakness are common features of VCFS patients. Based on the location and expression pattern of CLTD, we suggest hemizygosity at this locus may play a role in the etiology of one of the VCFS-associated phenotypes.      

Formaldehyde in cryoprotectant propanediol and effect on mouse zygotes

Cryopreservation of human zygotes and embryos has been routinely performed by in-vitro fertilization clinics for many years. Karran and Legge (1996) first reported that formaldehyde (FA) present in the cryoprotective solutions can have a deleterious effect on mouse oocytes. FA is a cytotoxic, carcinogenic and mutagenic chemical. The effect of FA on mouse zygotes was investigated. In addition, the concentrations of FA in propanediol (PROH) obtained from various sources were determined. Pooled 1-cell embryos were dispensed into droplets of modified Ham's F10 or human tubal fluid containing various concentrations of FA. Since bovine serum albumin (BSA) may minimize toxicity additional trials were done as above in the absence of BSA. FA concentration in the standard 1.5 M PROH, from different sources in water, was measured in the same assay using a standard curve of 0-100 microM FA. FA in a complex medium had a significant deleterious effect on embryo development and hatching but only at 1 mM concentration (P < 0.000001; see Tables I-III). There was no significant effect of FA at 100 microM. However, in a simple medium even 50 microM FA decreased embryo hatching. FA was present in 1.5 M PROH from different sources (range 1.0-35.3 microM concentration). It appears that FA concentrations do not increase with storage because FA concentrations were low even after opening and storage for 3 years on the shelf. This suggests that FA is a contaminant during the manufacturing process and may vary from manufacturer to manufacturer and batch to batch. Until further studies are done to confirm the lack of toxicity to embryos during cryopreservation (with or without FA scavengers) it may be prudent to screen all batches of cryoprotectants for FA as part of quality control.      

Integrative re-organization mechanism for reducing tremor in Parkinson's disease patients

A special movement therapy, called coordination dynamics therapy, has been reported to have the potential to improve central nervous system (CNS) functioning in Parkinson's disease patients. Electromyography using surface electrodes (sEMG) showed that the rhythmic muscle activity leading to Parkinsonian tremor was generated in the patients by the impairment of two kinds of inhibition. First, some premotor spinal oscillators organized themselves in the CNS neuronal networks without strong adequate input and second, the oscillators synchronized their firing to give rise to rhythmic muscle activity and tremor. In this paper it will be shown that highly coordinated arm and leg movements, generated when exercising on a special coordination dynamics therapy device, can reduce Parkinsonian tremor in amplitude and frequency and improve CNS functioning in the short-term memory. sEMG measurements showed upon exercising on the special coordination dynamics therapy device that the motor program improved in the short-term memory and tremor muscle activity became coordinated with the volitional motor program and reduced in size and frequency. Higher load exercising seemed to better reduce tremor muscle activity, probably because the physiologic CNS organization was more integrative then and could 'bind' stronger simultaneous pathologic tremor activity. Moreover, the rhythmic synchronized motor unit firing in different arm and leg muscles was synchronized or coordinated and changed in frequency and amplitude. It is concluded that the integrative re-organization mechanism to reduce Parkinsonian tremor is the phase and frequency coordination between neuron firing of the physiologic neuronal network state, generated by the highly coordinated arm and leg movements, and the simultaneous pathologic tremor network state, generated by the uninhibited neurons, firing synchronized oscillatory.