High affinity uptake in neuronal and glial cells.
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Biomedical subjects
Publications and source records attributed to J Borg.
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Graded doses of marihuana were administered to five adults in a longitudinal repeated-measurements design. Speed of response was the basic parameter measured accross tests of increasing cognitive involvement. Marihuana produced significant dose-response effects of impaired performance in all test scores. However, single automatic motor abilities demonstrated greater sensitivity than tests of greater complexity. Evidence is presented for tolerance development.
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Islets of Langerhans isolated from rat pancreas were incubated at 37 degrees C(95% O(2)/5% CO(2)) in buffered medium containing 1.0 mg/ml glucose and leucine (3)H for 1 hr (1st hr), washed, and incubated for an additional hr (2nd hr) in low glucose medium (0.5-1.0 mg/ml) containing unlabeled leucine. A portion of the islets was then extracted with acid-ethanol and the remainder were transferred to medium containing 3.0 mg/ml glucose and incubated for 2 hr (3rd and 4th hr) at 37 degrees C. The medium was exchanged at 30-min intervals and portions of the islets were extracted at the 3rd and 4th hr. The total amounts and specific activities of the proinsulin and insulin in the islet extracts and medium samples were determined after fractionation on Biogel P-30 columns in 3 M acetic acid. Maximal release of newly synthesized insulin occurred between the 3rd and 4th hr of incubation, confirming the results of Howell and Taylor (Biochem. J.102: 922. 1967). The high glucose medium increased the secretion of insulin approximately three to fourfold. The ratio of the specific activities of the insulin in the medium to that in the islets was about 1/1 during incubation in low glucose, but it increased to 2.5/1 during incubation with high glucose. The peak occurred at the 3rd hr, i.e., 1 hr after exposure to high glucose. The ratio of labeled proinsulin to insulin was slightly lower in the medium than in the islets. Addition of sufficient cycloheximide after the 1st hr to inhibit protein synthesis did not inhibit these responses. The specific activity of the proinsulin in the medium was about the same as that in the islets, and both were about 10-fold higher than the specific activity of the insulin. High glucose did not alter the proinsulin specific activity, which tended to decline throughout the period of observation. With cycloheximide present, the concentration of proinsulin in the islets steadily declined while the specific activity of proinsulin remained high, indicating that the proinsulin pool is small and is turning over rapidly. In terms both of amount and radioactivity proinsulin amounted to 6-7% on a molar basis of the insulin in both the medium and the islets. Addition of dibutyryl cyclic 3',5'-adenosine monophosphate (DBCAMP) (0.002 M) with high glucose during the postlabeling period slightly increased the rate of insulin secretion (133% of control) but did not significantly alter the other parameters. The results suggest that while newly synthesized insulin and proinsulin may be preferentially secreted to a slight degree, about 90% of the insulin released during 3 hr in response to glucose, or to glucose and DBCAMP, is derived from pre-existing granule stores. There were no indications of the existence of independent or nongranule pathways of insulin or proinsulin secretion.
The voluntary discharge properties and axonal conduction velocity of single motor units were studied in patients with neuromuscular diseases with retained differentiation of the muscle fibers into type 1 and type 2, and in patients with late-onset hereditary distal myopathy in which muscle fibers have only intermediate histochemical properties. In the patients with muscle fiber differentiation, the findings were similar to those in normal subjects; that is, there was a continuum between motor units which fired tonically at low rates and had a low axonal conduction velocity, and motor units which fired phasically at high rates and had a high axonal conduction velocity. In the patients without muscle fiber differentiation, all motor units had intermediate firing properties and a low axonal conduction velocity. It is suggested that in chronic pathologic states, the differentiation of the muscle fiber histochemistry remains only as long as the differentiation of the motor neurons remains.
The axonal conduction velocity and voluntary discharge properties of single motor units of the extensor digitorum brevis were studied in elderly subjects. The results were compared with the findings of a previous study of younger subjects. The range of the axonal conduction velocities differed only slightly between the age groups, the elderly subjects having velocities of 25-52 m/sec and the younger subjects 30-54 m/sec. In both age groups, motor units firing tonically within the range of 10-30 Hz had axonal conduction velocities below 45 m/sec, and motor units firing mainly phasically within the range of 20-60 Hz had axonal conduction velocities above 40 m/sec. Motor units with an intermediate type of discharge pattern were more frequently seen in the elderly. In the elderly subjects, these motor units had axonal conduction velocities distributed within the whole range, while in the younger subjects, they had axonal conduction velocities in the middle of the range. An autopsy study showed an increased proportion of muscle fibers with intermediate characteristics of ATPase staining in the elderly subjects. It is suggested that the decreased differentiation of the muscle fiber histochemistry might be secondary to the decreased differentiation of the motoneuron firing properties.
In previous studies of schizophrenic patients, neuromuscular (histopathological and electrophysiological) and psychomotor (finger tapping) abnormalities were found. The present study was designed to investigate relationships between these abnormalities and a family history of psychosis in 14 schizophrenic patients and 25 unaffected first-degree relatives compared to 14 healthy controls. Muscle biopsies were performed in either m. tibialis anterior or m. lateralis. Macro EMG recordings were made from m. tibialis anterior. A finger tapping test was used to investigate psychomotor performance. Neuromuscular abnormalities (muscle biopsies and/or macro EMG) and/or aberrant psychomotor performance (finger tapping test) were found in 13 (93%) patients, 14 (56%) first-degree relatives and in three (21%) controls. A statistically significant relationship for the psychomotor, but not neuromuscular changes to a family history of psychosis was found using a logistic regression method. The percentage of patients, relatives and healthy controls exhibiting were 36/40/7% in the muscle biopsy, 50/20/0% in the macro EMG, and 71/82/14% in the finger tapping investigations. A higher frequency of neuromuscular and psychomotor abnormalities was found in patients with schizophrenia and their first-degree relatives compared to healthy controls. The relationship between psychomotor findings and a family history of psychosis indicate that central aspects of motor aberrations are associated with a hereditary disposition of psychosis. The neuromuscular as well as psychomotor changes indicate that schizophrenia may be a systemic disease involving the central nervous system as well as peripheral organs. An altered cell membrane is suggested to be an underlying factor based on the type of neuromuscular findings.
BACKGROUND: Sleep is a risk factor for respiratory failure in patients with chronic neuromuscular diseases (NMD). OBJECTIVE: To explore the diagnostic value of monitoring sleep parameters in addition to nocturnal respiratory parameters. METHODS: Thirty-one patients with chronic NMD underwent whole-night polysomnograms including EMG from accessory respiratory muscles. RESULTS: Sleep macrostructure was normal on average. The number of respiratory arousals per hour of sleep was above the upper limit observed in a control group (>2.1) in 71% of the patients, but was moderate in most cases. Nadir oxygen saturation <85% was the most common finding indicating respiratory dysfunction and was present in 80% of the patients. Noninvasive blood gas monitoring identified all but 2 patients with respiratory-induced sleep abnormalities. The respiratory arousal rate was correlated with the oxygen desaturation index, but otherwise there were no significant correlations between sleep and nocturnal respiratory parameters. Vital capacity was significantly positively correlated with obstructive apnea index and daytime base excess to nadir oxygen saturation. Inspiratory activity in accessory respiratory muscles was present during REM sleep and/or slow wave sleep in 70% of the patients. CONCLUSION: The severity of nocturnal respiratory dysfunction is not reflected in the extent of sleep impairment in patients with chronic neuromuscular diseases.
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