Evidence in support of a feedback-sensitive central timekeeper for an over-learned repetitive motor behavior (pencil shading).

PURPOSE: To demonstrate the presence of a CNS timekeeper for an over-learned repetitive voluntary movement (pencil shading), and to learn if the timekeeper is influenced by changes in sensory feedback. METHODS: Self-paced pencil shading; fast, maximally-fast, and slow hand waving, as well as enhanced physiologic tremor (EPT) were recorded on 3 separate occasions with a surface-mounted accelerometer placed on the hand in 9 normal volunteers. Variation in inter-trial peak frequency was calculated. Shading and EPT were also recorded with and without visual masking in 9 normals and in 2 deafferented patients. Variation in intra-trial beat-to-beat intervals, a measure of movement regularity, was calculated. RESULTS: Shading and maximally-fast waving displayed preferred frequencies with no more variability in peak frequency between trials than did EPT, while slow and fast waving had significant inter-trial variability. Variation in beat-to-beat intervals for the shading task was less in controls than for EPT, and less in controls than for the patients in both the masked and unmasked conditions. In addition, in the masked condition, pencil shading by the patients was performed with much higher amplitude and lower frequency than by the controls. CONCLUSIONS: These data support the hypothesis that certain repetitive voluntary movements, such as pencil shading, are paced by central timekeepers that are influenced by changes in sensory feedback.

Dystonia as a presenting feature of the 3243 mitochondrial DNA mutation.

A variety of neurologic phenotypes have been described in patients with mitochondrial disorders. We report a 32-year-old man in whom dystonia was the salient and presenting feature of a mitochondrial DNA mutation. He presented at age 23 with writer's cramp and progressed over 5 years to exhibit dystonia in facial muscles and lower limbs. He also has exercise intolerance, mild, bilateral ptosis, proximal muscle weakness, and sensorineural hearing loss. Molecular genetic analysis of blood, urine, and muscle biopsy demonstrated the presence of a heteroplasmic point mutation at nucleotide position 3243. The 3243 mtDNA mutation has pleomorphic manifestations, and dystonia should be added to the list of associated clinical features.

The cutaneous silent period is mediated by spinal inhibitory reflex.

High-intensity cutaneous stimuli inhibit tonically firing motor neurons resulting in a silent period (CSP) in EMG activity. To determine the central nervous system (CNS) circuitry of this inhibitory reflex, soleus H reflexes evoked by tibial nerve stimuli were conditioned by high-intensity sural stimuli in 5 normal men and 5 men with complete, traumatic cervical myelopathy. The sural-tibial interstimulus interval (ISI) was varied between 0 and 200 ms. In normals, the CSP in the tonically contracted soleus muscle began 90-100 ms after sural stimuli and had a duration of 60-80 ms. In the relaxed soleus, the conditioned soleus H-reflex amplitude was correspondingly reduced at ISIs of 60-120 ms. In patients, conditioned H-reflex amplitude was also reduced over the same ISI range, but the degree of inhibition was significantly less than in normals. These data support the hypothesis that the CSP is mediated by a spinal inhibitory reflex that is subject to supraspinal descending control.

Electromyography: do the diagnostic ends justify the means?

BACKGROUND: Physicians are sometimes reluctant to refer patients for electrodiagnostic studies (electromyography with nerve conduction studies [EMG/NCS]) believing the test is too painful and of little benefit. METHODS: We performed two separate surveys on 126 and 100 consecutive patients referred to our laboratory to determine if EMG/NCS was beneficial to the referring physician and to compare the level of anxiety experienced by patients before the study with the pain actually experienced during the study. RESULTS: The electrodiagnosis was discordant from the referring diagnosis in 39% of the patients with an abnormal EMG/NCS. Pretest anxiety levels were low in 59% of the patients, medium in 27%, and high in 14%. After the tests, 82% of the patients said that the test was not as bad as expected, and was generally only mildly painful. Ninety-three responded that they would have the test performed again. CONCLUSIONS: EMG/NCS often suggest alternative diagnoses, and the actual pain experienced during an EMG/NCS study is significantly less than expected.

Vitamin A and galactosyl transferase of tracheal epithelium.

We developed an assay for galactosyl transferase (uridine diphosphategalactose:glycoprotein galactosyltransferase, EC 2.4.1.22) in microsomes of rat tracheal epithelium and characterized the properties of this enzyme system. We found that vitamin A deficiency greatly depressed galactosyl transferase activity. Activity could be restored within 48 h by dosing the animal with retinyl acetate. Adding retinol to the microsomes from tracheal epithelium of vitamin A-deficient rats also restored galactosyl transferase activity to some extent. Full restoration was achieved by pre-incubating retinol with the microsomal preparation for 30 min. Optimal concentration of pre-incubated retinol was 10(-8) M. Pre-incubation with retinyl phosphate and retinoic acid stimulated galactosyl transferase activity in microsomes from tracheas of deficient rats; pre-incubation with dolichyl phosphate, anhydroretinol and the dimethylacetylcyclopentenyl analog of retinoic acid did not. We concluded that vitamin A is involved in the galactosyl transferase system of rat tracheal epithelium, possibly by being linked to galactose.

Galactosyl transferase activity in rat bladder transitional cell carcinoma lines and in exfoliated cells in urine during carcinogenesis and reversible hyperplasia.

Cultured cells of rat bladder transitional cell carcinoma line AY-27, in suspension, were assayed for galactosyl transferase (GT) by measurement of the transfer of [3H]galactose from uridine diphosphate-[3H]galactose to desialylated ovine submaxillary mucin (OSM-NANA). The assay was optimized with respect to time and to protein, uridine diphosphate galactose, OSM-NANA and Triton X-100 concentrations. This assay was then applied weekly to suspensions of exfoliated bladder cells collected from urines of rats fed the bladder carcinogen N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide, and of control rats. Increases in activity over controls appeared 42 weeks after feeding the carcinogen, at a stage when bladder tumors were already microinvasive or deeply invasive, and activities at 52 weeks were about 10-fold greater than normal values. In contrast, a bladder cytotoxic agent inducing reversible hyperplasia was injected into rats, and exfoliated cells were collected from urines: these cells showed no greater GT activity than normal. Bladder tumor tissue from a transplanted tumor had the same high specific enzymatic GT activity as exfoliated cells from tumor-bearing rats.

Galactosyl transferase activity in human transitional cell carcinoma lines and in benign and neoplastic human bladder epithelium.

Cultured cells of human transitional cell carcinoma line MGH-U1, in suspension, were assayed for galactosyl transferase by measurement of the transfer of [3H]galactose from uridine diphosphate:[3H]galactose to desialylated ovine submaxillary mucin. The assay was optimized with respect to time and to protein, uridine disphosphate:galactose, desialyated ovine submaxillary mucin, and Triton X-100 concentrations. This assay was then applied to fresh specimens of benign, inflamed, and neoplastic bladder epithelium from 33 patients who under went cold-cup biopsies at cytoscopy. Transitional cell carcinoma specimens gave values in the range of 24.7 to 184.8 cpm [3H]galactose transferred per microgram protein per hr [72.0 +/- 44.7 (S.D.); n = 25]; normal and inflamed specimens ranged from 0.8 to 46.1 cpm/microgram protein per hr [8.3 +/- 8.4 (S.D.); n = 35]. By using a known method of cell rupture, cell ghosts, representing cell-surface membranes, were isolated both from the cultured cell line and from two biopsy specimens of transitional cell carcinoma. Although a complete enzymatic and electron microscopic analysis was not undertaken, the coincidence of an enzyme marker with the cell ghost fraction containing the elevated galactosyl transferase made it appear probable that this enzyme is located in the cell surface.

Uridine 5'-diphosphate galactose: glycoprotein galactosyl transferase activity in exfoliated bladder epithelial cells in rats fed N-(4-(5-nitro-2-furyl)-2-thiazolyl) formamide.

Urine samples of normal male Fischer rats or rats fed 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide for 6,8 or 30 weeks were collected and centrifuged 50 weeks after beginning treatment. After being sonicated and assayed (with purified desialylated ovine submaxillary mucin as acceptor glycoprotein), the exfoliated bladder cells obtained from the urines of treated rats showed uridine 5'-diphosphate galactose:glycoprotein transferase activity. The specific enzymatic activity of the enzyme from cells of 30-week-treated rats was about 10 times higher than from normal rats. The enzyme from cells of hyperplastic rats (treated 6 or 8 weeks) was only slightly higher in specific activity than that of normal rats. A similar was obtained at a later stage of bladder tumor induction, when the urines from 30-week-treated rats contained blood. A correction was made for protein contributed by the blood clot. The possibility that the blood clot contributed galactosyl transferase activity was excluded. Activity of the enzyme was detected in normal rat bladder tissue and in normal human urine.