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Biomedical subjects

R R Young

Publications and source records attributed to R R Young.

At least 19 recordsLinked to original sources
PubMed1995

Interlaboratory comparison: liver spontaneous mutant frequency from lambda/lacI transgenic mice (Big Blue) (II).

Spontaneous mutant frequency in livers of two transgenic mouse strains, each carrying identical lambda shuttle vectors with a lacI target gene, was evaluated by two laboratories. These studies investigated variability in spontaneous mutant frequency between animals and as a function of the number of phage screened. Liver DNA was independently isolated from 7-11 week old C57BL/6 and B6C3F1 Big Blue transgenic mice. At least 500,000 phage were screened for mutation at lacI for each animal using standardized assay procedures. In the two labs, the C57BL/6 liver spontaneous mutant frequency was 45 +/- 9 x 10(-6) and 41 +/- 7 x 10(-6). The B6C3F1 liver spontaneous mutant frequency was 42 +/- 10 x 10(-6) at one lab and 43 +/- 12 x 10(-6) and 41 +/- 8 x 10(-6) in two trials at the second lab. Mean mutant frequency data from both labs, calculated in increments of 100,000 plaque forming units (pfu) scored for each mouse strain, show stabilized mean mutant frequency and standard deviation after approximately 200,000-300,000 pfu screened. The frequency of spontaneous lacI mutants was reproducible both within and between labs and was comparable between the two transgenic mouse strains.

Animals↗
PubMed1995

Intralaboratory optimization and standardization of mutant screening conditions used for a lambda/lacI transgenic mouse mutagenesis assay (I).

A lambda/lacI shuttle vector transgenic mouse mutagenesis assay has been optimized and standardized for reproducible mutant detection. The mutagenic endpoints are blue lacI- phage plaques on a bacterial lawn resulting from the de-repression of beta-galactosidase activity acting on the chromogenic substrate X-gal. Non-mutant lacI phage plaques remain colorless. Factors demonstrated to affect mutant detection include X-gal concentration per assay tray, plaque density per assay tray, pH of plating agar, incubation time at 37 degrees C and the use of a red translucent screening filter over a light source to enhance mutant plaque visibility. In vivo mutant frequencies for liver in untreated animals using standard protocols and internal controls were repeatable in separate experiments using lambda/lacI B6C3F1 mice (4.3 +/- 1.2 x 10(-5) and 4.1 +/- 0.8 x 10(-5)). These studies analyze the use of internal controls to monitor the level of mutant phage plaque detection in a given experiment and evaluate the repeatability of observed mutant frequencies obtained when using standardized procedures.

Agar↗
PubMed1994

Tremor: classification, diagnosis and management.

Tremor can range from imperceptible physiologic movements to severely handicapping shaking. It can be a single entity, or it can occur in association with a disease that affects the basal ganglia, brainstem, cerebellum or peripheral nervous system. Tremors can be classified according to their anatomic location, the circumstances under which they occur, their frequency and amplitude, and whether they are physiologic or pathologic. As an isolated disorder, tremor should be treated only when it impairs the patient's ability to perform activities. Successful treatment requires the identification of precipitating factors, as well as associated signs and symptoms.

Humans↗
PubMed1994

Spasticity: a review.

This symposium is concerned with the treatment of spasticity and, in particular, with results from studies of tizanidine as a treatment for patients with MS and spinal cord injury. In this article, the definitions and pathophysiologies of spasticity are reviewed, and the issue of when and if to treat spasticity is evaluated. The merits of newer pharmacologic and invasive therapies are discussed relative to reduction of patient discomfort and the possibility of restored function.

Clonidine↗
PubMed1992

Genetic toxicology evaluation of commercial beers, III. SCE, chromosome aberrations, and forward mutation (HGPRT) of commercial beer products in CHO cells.

Concentrated organic residues extracted from 5 blended aliquots of commercial beers were evaluated for their ability to induce sister chromatid exchange (SCE), chromosomal aberrations and forward mutation in Chinese hamster ovary (CHO) cells. Each extract was prepared by blending 4 commercial beers of similar ingredients and brewing method, passing the beer pool over XAD-2 resin, extracting the resin and concentrating the extract. Studies were performed both with and without metabolic activation using variable amounts of reconstituted residues from 225-fold concentrates of the blended samples. CHO cultures were treated with 0.75 microliters/ml through 10.0 microliters/ml of the concentrates in the SCE assays, 1.0 microliters/ml through 10.0 microliters/ml of the extracts in the aberration assays and 2.5 microliters/ml up to 20 microliters/ml for forward mutation assays. In preliminary screening for SCE as an indicator of potential DNA damage, a significant increase was observed for 3 of 5 concentrated samples; however, no increase in SCE was induced by any of the 5 samples when S9 was added as a source of exogenous metabolic activation. More definitive tests for induction of genetic events, i.e., chromosome aberrations and forward HGPRT mutations, were negative for all 5 extracts whether or not S9 mix was present. Since SCE were not induced in tests with metabolic activation and since there was no concordant aberration or point mutation induction, the preliminary indication of potential DNA damage shown by elevated SCE under conditions without metabolic activation appears to have little biological significance.

Animals↗
PubMed1992

Assessment of the potential genotoxicity of perfluorodecanoic acid and chlorotrifluoroethylene trimer and tetramer acids.

Perfluoro-n-decanoic acid (PFDA) is a perfluorinated fatty acid that produces hepatomegaly and increased peroxisomal beta-oxidation when administered to rodents. Chlorotrifluoroethylene (CTFE) trimer acid and CTFE tetramer acid are metabolites of the six- and eight-carbon oligomers of CTFE, respectively. They are structurally related to PFDA, and CTFE tetramer acid has caused toxic effects in rodents that are similar to those observed following PFDA administration. Because of the correlation between peroxisome proliferation and hepatocarcinogenesis, CTFE trimer acid, CTFE tetramer acid, and PFDA were evaluated in in vitro and in vivo/in vitro bioassays to assess their potential genotoxic activity. The assays conducted were the Ames Salmonella/microsomal mutagenicity assay, the hypoxanthineguanine phosphoribosyltransferase (HGPRT) locus Chinese hamster ovary gene mutation assay, the sister chromatid exchange (SCE) assay, chromosomal aberration assay, and an in vivo/in vitro unscheduled DNA synthesis (UDS) and S-phase DNA synthesis assay. All test articles were negative in the Ames assay, the HGPRT assay, and the SCE assay. In the chromosomal aberration assay CTFE trimer acid and CTFE tetramer acid were negative in cultures with and without S9 metabolic activation. PFDA was also negative in the absence of metabolic activation, but chromosomal aberrations were observed when PFDA was incubated in the presence of S9 fraction. All test articles were negative for inducing UDS but all induced S-phase replicative DNA synthesis 16 hr after administration of the test article to the test animals; only CTFE tetramer acid and PFDA induced S-phase synthesis 48 hr after dosing: the usual timepoint examined for this response.

Animals↗
PubMed1992

Headaches in patients with traumatic lesions of the cervical spinal cord.

We established the occurrence of headache in a group of 20 patients with traumatic transections of the cervical spinal cord. All but two patients had complete sensory lesions at levels varying from C2-3 to C7-8. Only three patients claimed to have no headaches at all although one of them had nuchal pains with fever. Twelve patients had "bladder" or "bowel headaches" or had had them in the past. These headaches were mostly generalized, throbbing or pounding in nature and severe in intensity. They were caused by obstruction of urinary flow and fecal impaction, respectively, and were associated with autonomic dysreflexia. Otherwise the headaches reported by the patients were mild although frequent in four, i.e once per week or more. These headaches were also mostly bilateral and lasted a relatively short time, i.e. less than one or two hours. The causes of these headaches were nonspecific for the group studied except for stimulation of the body which, however, probably depended on a mechanism similar to that of the bladder and bowel headaches. Migraine, either classic or common, was not reported by any of the patients.

Adult↗
PubMed1992

Recurrent inhibition is increased in patients with spinal cord injury.

Mechanisms underlying the development of spasticity after spinal cord injury are not understood. One spinal interneuron likely to be affected is the Renshaw cell, which acts to produce recurrent inhibition in motor neurons as well as inhibiting Ia interneurons. Descending pathways exert both excitatory and inhibitory control over Renshaw cell activity. We studied Renshaw cell activity in normal subjects and in patients with varying levels of spasticity after spinal cord injury using the conditioned H-reflex technique of Pierrot-Deseilligny and Bussel. A submaximal stimulus to the tibial nerve is presented prior to a supramaximal stimulus so that action potential collision permits an H reflex (H') to be elicited in response to the supramaximal stimulus. The amplitude of this H' reflex is affected by activity in recurrent inhibitory pathways. Patients with both complete and partial spinal cord lesions were studied; date of injury ranged from 1 month to 216 months prior to evaluation. In the 18 patients in whom H reflexes could be recorded, H' reflexes were absent in 13, in contrast to their uniform presence in normal subjects. We conclude that recurrent inhibition via Renshaw cell activity is increased in spinal cord injury, and that measures of recurrent inhibition may correlate well with some clinical measures of spasticity.

Adult↗
PubMed1991

Innervation zone of orbicularis oculi muscle and implications for botulinum A toxin therapy.

Motor points (areas of maximal sensitivity to electrical stimulation) were found in constant locations over orbicularis oculi when measured in both eyes of six normal subjects. All subjects had a motor point at the lateral terminus of the upper lid crease and the medial extent of the lower lid crease. A study of the innervation zone [distribution of neuromuscular junctions (NMJ)] was conducted on strips of pretarsal and preseptal portions of the upper eyelid orbicularis that had been removed routinely during involutional ptosis surgery. There was no significant difference in NMJ concentration between the medial and lateral sections, as determined by cholinesterase staining. Therefore, we concluded that the innervation zone is diffuse for the orbicularis muscle within this portion of the upper eyelid. Single-point injections of botulinum toxin were then compared to the conventional multiple injection sites on separate eyes in 10 patients with benign essential blepharospasm. Eight of the 10 patients reported greater relief on the side given injections into multiple points; the other two patients experienced no difference between the two methods. Both histologic data and clinical observation of response to botulinum toxin injection suggest the innervation zone for the upper orbicularis is diffuse. Thus, we conclude that multiple injections are superior to the injection of a single motor point.

Acetylcholinesterase↗
PubMed1991

Abnormal most-rapid isometric contractions in patients with Parkinson's disease.

Fast isometric elbow flexor muscle contractions of specified amplitude in six normal subjects were compared with those of 11 patients with Parkinson's disease. Despite treatment, all patients exhibited deficits in this motor task. Three patients were able to produce rapid force pulses with normal contraction times, but the variability of their force responses was increased in comparison with the highly stereotyped responses produced by normal subjects. The other eight patients had prolonged contraction times and segmentation of the force profiles. The integrated area of the first agonist EMG burst and the rate of development of force (dF/dt) were less at any target level than what was needed to produce a fast response. The area of the EMG burst, however, did increase with target amplitude, and the relative increase of dF/dt, with target amplitude, was normal. It is concluded that the motor program subserving fast muscle contraction is preserved in Parkinson's disease, but its execution is characterised by improper scaling of motor output.

Adult↗
PubMed1991

The clinical diagnosis of disorders of the spinal cord.

Disease of the spinal cord or cauda equina may cause pain, motor abnormalities, sensory disturbance, alteration of reflexes and muscle tone, and bladder dysfunction. These five neurologic abnormalities occur in various combinations, evolve rapidly or slowly, and result in one of eight possible spinal cord syndromes. When a particular syndrome is defined by neurologic history and examination, differential diagnosis is limited to only a few possible disorders. An appropriate neuroradiologic or electrophysiologic procedure done at this point will usually provide the correct diagnosis.

Humans↗
PubMed1988

Motor unit synchronization in physiologic, enhanced physiologic, and voluntary tremor in man.

Synchronization between pairs of single motor units simultaneously recorded from wrist extensor muscles was quantitated in 3 normal subjects during physiologic tremor (PT), beta-adrenergically enhanced physiologic tremor (EPT), and fast voluntary wrist flexion-extension movements mimicking tremor (VT). Cross-correlation histograms generated from the two spike trains of each motor unit pair demonstrated central or paracentral peaks in 13/19 recordings during PT, 22/36 during EPT, and 6/7 during VT. Relative peak area was used as a quantitative index of synchronization between the two motor units of each pair. It was lowest in PT, progressively increased in EPT as tremor amplitude increased, and highest in VT. In PT and lower amplitude EPT, the synchronization indexes were higher between motor units that discharged at the same or nearly the same frequency. In contrast, in higher amplitude EPT and VT, motor units with different firing frequencies were sometimes strongly synchronized as a consequence of double discharges in faster-firing motor units that had burst repetition rates in the range of slower-firing motor units discharging as singlets. Greater motor unit synchronization with increasing tremor amplitude in EPT may be secondary to a simultaneous increase in muscle spindle afferent activity from the tremulous muscle. Greatest synchronization in VT presumably reflects near maximal supraspinal and segmental common synaptic input onto motoneurons that generate VT. These results support a longstanding hypothesis that synchronization of motor units is the physiological basis for higher amplitude tremor.

Electromyography↗
PubMed1987

Lumbrical sparing in carpal tunnel syndrome: anatomic, physiologic, and diagnostic implications.

Motor axons supplying lumbrical muscles are less severely affected than axons supplying thenar muscles in the carpal tunnel syndrome; sometimes lumbrical motor fibers are less affected than digit 2 sensory fibers. This pattern is consistent with compression of both the anterior and posterior aspects of the median nerve in the carpal tunnel because nerve fibers responsible for thenar, lumbrical, and digit 2 functions lie in an anterior-posterior gradient within the distal median nerve. Recognition of lumbrical sparing supports the electrodiagnosis of carpal tunnel syndrome when the distal latency to thenar muscles or the palm-to-wrist mixed median nerve conduction velocity is normal.

Action Potentials↗
PubMed1987

Physiologic and pharmacologic approaches to spasticity.

The term spasticity is used to describe many relatively unrelated syndromes and, because they share few common pathophysiologic mechanisms, it is not possible to define the physiology or pharmacology of spasticity. In patients with spastic paresis, it is the latter negative symptom (rather than the spasticity) that accounts for almost all the functional disability. Clinical neurophysiologic techniques are useful for categorization of patients with clinically identical syndromes into subgroups which respond to different therapies. Fusimotor or spindle primary afferent hyperactivity have not been demonstrated in spastic patients; reduction in central inhibitory mechanisms probably accounts for spastic hyper-reflexia. Increased passive muscle stiffness may also be clinically significant. Therapies for spasticity include elimination of causative or enhancing factors, frequent muscle stretching, surgical approaches and chemotherapy. The latter includes dantrolene (which weakens muscles), baclofen (particularly useful for reduction of flexor spasms and flexor dystonia in patients with spinal lesions) and diazepam.

Animals↗