Biomedical subjects

T L Williams

Publications and source records attributed to T L Williams.

At least 37 records · Page 2Linked to original sources

PubMed1997

Case report: unilateral mydriasis from topical Opcon-A and soft contact lens.

The use of topical ocular antihistamine/decongestant combinations to treat symptoms associated with allergic conjunctivitis is widespread, effective, and generally without adverse effects. Recently, these medications have become available without a prescription, possibly leading patients to the erroneous assumption that they are void of side effects. Likewise, patients may use these drugs for many ocular therapies for which they are unintended, possibly resulting in ocular complications. One significant adverse effect of these antihistamine/decongestant combinations when used inappropriately is pupillary dilation with associated blurry vision. Continued emphasis of the possible deleterious side effects by the clinician is recommended to circumvent these problems.

Adult↗

PubMed1996

Distribution of alpha 1A, alpha 1B and alpha 1E voltage-dependent calcium channel subunits in the human hippocampus and parahippocampal gyrus.

The distribution of voltage-dependent calcium channel subunits in the central nervous system may provide information about the function of these channels. The present study examined the distribution of three alpha-1 subunits, alpha 1A, alpha 1B and alpha 1E, in the normal human hippocampal formation and parahippocampal gyrus using the techniques of in situ hybridization and immunocytochemistry. All three subunit mRNAs appeared to be similarly localized, with high levels of expression in the dentate granule and CA pyramidal layer. At the protein level, alpha 1A, alpha 1B and alpha 1E subunits were differentially localized. In general, alpha 1A-immunoreactivity was most intense in cell bodies and dendritic processes, including dentate granule cells, CA3 pyramidal cells and entorhinal cortex pre-alpha and pri-alpha cells. The alpha 1B antibody exhibited relatively weak staining of cell bodies but stronger staining of neuropil, especially in certain regions of high synaptic density such as the polymorphic layer of the dentate gyrus and the stratum lucidum and radiatum of the CA regions. The alpha 1E staining pattern shared features in common with both alpha 1A and alpha 1B, with strong immunoreactivity in dentate granule, CA3 pyramidal and entorhinal cortex pri-alpha cells, as well as staining of the CA3 stratum lucidum. These findings suggest regions in which particular subunits may be involved in synaptic communication. For example, comparison of alpha 1B and alpha 1E staining in the CA3 stratum lucidum with calbindin-immuno-reactivity suggested that these two calcium channels subunits may be localized presynaptically in mossy fibre terminals and therefore may be involved in neurotransmitter release from these terminals.

Aged↗

PubMed1996

An immunocytochemical study of the distribution of AMPA selective glutamate receptor subunits in the normal human motor system.

Glutamate is the major mediator of fast excitatory neurotransmission in the mammalian central nervous system. Disturbances of this neurotransmitter system have been implicated in chronic degenerative neurological disease. Recently, major advances in our knowledge and understanding of the molecular biology of the glutamatergic receptor system have been made. It is now known that functional glutamate receptors consist of various combinations of some 20 identified subunits. A growing body of circumstantial evidence suggests that the non-N-methyl-D-aspartate subtype of glutamate receptors may mediate, at least in part, the selective motor neuron death seen in the human neurodegenerative disease amyotrophic lateral sclerosis. We have used subunit specific immunocytochemistry to study the distribution and potential subunit composition of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) selective glutamate receptors, (a subgroup of non-N-methyl-D-aspartate selective glutamate receptors formed by combinations of GluR1-4 subunits), in the human motor system. Motor neurons in the spinal cord, brainstem, and motor cortex were relatively strongly immunoreactive with the GluR2/3 subunit antibody, moderately so with the GluR4 subunit antibody, and showed relatively low levels of immunoreactivity with the GluR1 subunit antibody. This is the first detailed study of AMPA receptor subunit expression in the human motor system. Motor neurons express a distinct subunit profile when compared with other groups of neurons in the human nervous system. There were no significant differences in the pattern of relative AMPA subunit expression (GluR2/3 > or = GluR4 > GluR1) between groups of motor neurons typically affected (in the spinal cord and hypoglossal nucleus), or spared (oculomotor and Onufs nucleus) by the amyotrophic lateral sclerosis disease process. However, oculomotor motor neurons had higher levels of expression of all AMPA subunit proteins which may indicate greater AMPA mediated glutamatergic input in the normal function of this neuronal population. This study does not support a role for differential subunit composition of AMPA receptors in determining the selective vulnerability of motor neurons in amyotrophic lateral sclerosis. However, the overall density of receptors may be of importance.

Aged↗

PubMed1996

Effects of local oscillator frequency on intersegmental coordination in the lamprey locomotor CPG: theory and experiment.

1. Experiments have been performed on in vitro preparations of lamprey spinal cord bathed in D-glutamate, which induces a pattern of activity recorded from ventral roots that is similar to that seen in the intact animal during swimming. The frequency of fictive swimming increases with increasing D-glutamate concentration, but intersegmental phase lag remains unaffected. 2. The effects on intersegmental phase lags of unequal activation of the rostral and caudal halves of a preparation were determined. Unequal activation was produced by placing a diffusion barrier in the middle of the chamber and perfusing the two halves with different concentrations of D-glutamate. 3. Within the rostral compartment, the phase lag increased from control when the rostral D-glutamate concentration was higher than the caudal concentration, and decreased from control when it was lower. By contrast, the phase lags within the caudal compartment did not depend on the ratio of D-glutamate concentration between the two compartments. 4. The frequency of the ventral root activity during differential activation was not significantly different from that of control experiments that had the same concentration as in the rostral compartment. 5. The results are discussed within the context of the mathematical analysis of chains of coupled oscillators by Kopell and Ermentrout and other current theories about the mechanisms of intersegmental coordination in the lamprey.

Analysis of Variance↗

PubMed1995

Parkinsonism in motor neuron disease: case report and literature review.

This report describes a patient who had clinical features of both motor neuron disease and Parkinson's disease. Neuropathological examination and immunocytochemical studies showed that he had motor neuron disease of the progressive muscular atrophy type, and Lewy body Parkinson's disease, with intracytoplasmic inclusion bodies characteristic of both conditions. This is the first detailed description of these two diseases occurring concurrently in the same patient. A review of all previously reported cases of combined motor neuron disease and parkinsonism has led to the following conclusions: (1) that these two neuropathologically defined diseases occur together very infrequently, but (2) that parkinsonism and substantia nigra degeneration are not uncommon as part of the multi-system disease process underlying motor neuron disease.

Aged↗

PubMed1995

Distribution of AMPA-selective glutamate receptor subunits in the human hippocampus and cerebellum.

The distribution of AMPA-selective subunits, GluR1-4, was determined in the human hippocampus and cerebellum by in situ hybridization and immunocytochemistry. In the hippocampus, in situ hybridization revealed that GluR1 and GluR2 mRNAs were similarly distributed and highly expressed in the dentate gyrus, with lower levels in the CA regions. GluR3 and GluR4 mRNAs were expressed at very low levels. Immunocytochemical studies showed that GluR1- and GluR2/3-immunoreactivity were highest in the dentate molecular and granular layers. In the CA regions, GluR1 and GluR2/3 staining was observed in pyramidal cell bodies and surrounding neuropil and was more intense in CA4/3/2 compared with CA1. GluR4-immunoreactivity was low throughout the hippocampus. In the cerebellum, GluR1 and GluR4 transcripts were expressed in the granular and Purkinje cell/Bergmann glia layers. GluR2 mRNA was highly expressed in the granular layer and individual Purkinje cells, while GluR3 mRNA was not detectable in the cerebellum. GluR1- and GluR4-immunoreactivity were localized to Purkinje cells and putative Bergmann glia, as well as their processes extending into the molecular layer. GluR2/3 staining was intense in Purkinje cells, with moderate staining in the granular layer. Thus, GluR1-4 subunits are differentially distributed in the hippocampus and cerebellum. In addition, the distribution of subunit mRNA and protein correlate well with each other and with the glutamatergic neuroanatomy of the hippocampus and cerebellum.

Aged↗

PubMed1995

Interactions between muscle activation, body curvature and the water in the swimming lamprey.

The travelling wave of curvature which propels a fish forward arises from the interaction of the patterns of motoneurone activity generated by the spinal cord with the mechanical properties of (1) the muscle, (2) the skin, bone and connective tissues of the body, and (3) the water in which it is swimming. Furthermore, in the lamprey, a powerful feedback system has been demonstrated which allows local body curvature to influence the timing of the activity pattern generated by the spinal cord. The relative timing between activation and curvature are illustrated for both closed- and open-loop conditions, using data from intact swimming lampreys and from an in vitro preparation of lamprey spinal cord and notochord. The mechanical behaviour of a lamprey has been simulated with a mathematical model based on springs, dashpots, light rods, point masses and power units incorporating properties of lamprey muscle. Results are presented which illustrate the behaviour of a lamprey out of water. To anticipate the inclusion of the lamprey body model in the computation of the fluid dynamics, a hydrodynamical model has been developed in which the body motion and the forward swimming have been prescribed by mathematical functions. Results are presented to illustrate the hydrodynamic vortex structure as predicted by a two-dimensional, time-dependent numerical solution of the Navier-Stokes equations, including both viscous and inertial terms.

Animals↗

PubMed1994

Anguilliform body dynamics: a continuum model for the interaction between muscle activation and body curvature.

A two dimensional continuum model for the body mechanics of the lamprey is derived from a simple discrete rod and pivot structure. Each element in the discrete structure consists of two smoothly jointed light rods with perpendicular extensions at each of the midpoints between which is fixed a quasi muscle segment. The muscle segment is attributed with the viscous and elastic properties of all the animal tissue plus the ability to produce force. The travelling wave of muscle activation in the real animal is modelled by a corresponding time dependent forcing term at each segment. A linearisation of the ensuing continuum model, corresponding to low curvature dynamics, is investigated. The profiles obtained compare favourably with those of a lamprey moving out of water on a smooth surface. In addition the phase difference at each point on the body between the wave of muscle activation and the mechanical wave observed on the body indicates that the mechanical wave progresses slower than, but at the same frequency as, the wave of activation; this is a property that is also observed in the freely swimming lamprey.

Animals↗

PubMed1994

Intersegmental phase lags in the lamprey spinal cord: experimental confirmation of the existence of a boundary region.

A critical feature of the motor pattern generated by the lamprey spinal cord is an intersegmental delay that is constant down the cord and scales with cycle duration. This has been modelled as the output of a chain of coupled oscillators, within a general mathematical framework developed by Kopell and Ermentrout (1986, 1988). The analysis predicts that for asymmetric coupling of equally-activated oscillators, the intersegmental phase lag will be uniform along the chain except in a boundary layer at one end. Here we provide experimental evidence that a boundary layer does occur at the rostral end of an isolated preparation of lamprey spinal cord. In the context of the mathematical analysis, this indicates that ascending coupling is dominant in the control of intersegmental phase lag in the lamprey.

Animals↗

PubMed1993

Matrix effects and accuracy assessment. Identifying matrix-sensitive methods from real-time proficiency testing data.

Retrospective proficiency testing data may be used to screen for matrix effect, which is suspected when significant methodologic bias is detected. Prioritization is centered on those situations where relatively high unacceptability rates are associated with high bias. Before attributing high unacceptability rates to methodologic bias, factors such as peer grouping strategies, number of participants in peer groups, analyte concentration, evaluation limits, and interparticipant precision, all of which affect scoring, need to be considered. When bias-associated high unacceptability rates are detected, methods are candidates for further evaluations to identify the causes of bias, to determine if matrix effect is present. Using outputs from the College of American Pathologists Survey Management Enhancement Program, we have presented data from the 1991 Comprehensive Chemistry Survey to demonstrate methodology to study this problem, and have selected examples of method performance in which tabular and graphic information contribute to its study. For the analytes studied, unacceptability rates tend to be greatest in association with high methodologic bias and/or between-participant imprecision relative to external evaluation limits, samples at the upper extreme of analyte concentration, low numbers of participants in peer groups, grading by comparative method, and concentration-independent fixed evaluation limits. Specific examples of significant bias that is possibly matrix induced are presented for uric acid, glucose, creatinine, and total protein.

Bias↗

PubMed1992

Phase coupling by synaptic spread in chains of coupled neuronal oscillators.

Many neural systems behave as arrays of coupled oscillators, with characteristic phase coupling. For example, the rhythmic activation patterns giving rise to swimming in fish are characterized by a rostral-to-caudal phase delay in ventral root activity that is independent of the cycle duration. This produces a traveling wave of curvature along the body of the animal with a wavelength approximately equal to the body length. Here a simple mechanism for phase coupling in chains of equally activated oscillators is postulated: the synapses between the cells making up a "unit oscillator" are simply repeated in neighboring segments, with a reduced synaptic strength. If such coupling is asymmetric in the rostral and caudal directions, traveling waves of activity are produced. The intersegmental phase lag that develops is independent of the coupling strength over at least a tenfold range. Furthermore, for the unit oscillator believed to underlie central pattern generation in the lamprey spinal cord, such coupling can result in a phase lag that is independent of frequency.

Animals↗

PubMed1992

cis-bis(pyridine)platinum(II) organoamides with unexpected growth inhibition properties and antitumor activity.

The platinum(II) organoamides [Pt(NRCH2)2L2] (L = pyridine (py), R = p-HC6F4, C6F5,p-IC6F4,p-CIC6F4,p-C6F5C6F4; L = 4-methylpyridine, R = p-HC6F4) and [Pt(NRCH2CH2NR')(py)2] (R = p-HC6F4, R' = C6F5, p-BrC6F4, or p-MeC6F4) inhibit the growth of murine L1210 leukemia cells in culture with ID50 values for continuous exposure in the range 0.6-2.7 microM. Representative complexes are also active against L1210 cells in 2-h pulse exposures, as well as against the cisplatin-resistant variant L1210/DDP and human colonic carcinoma cell lines HT 29 and BE. Three complexes [Pt(NRCH2)2L2] (R = p-HC6F4, C6F5, or p-IC6F4) have good activity (T/C greater than or equal to 180%) against P388 leukemia in mice, and all other compounds tested are active except when R = p-C6F5C6F4, L = py. Although the molecular basis of the biological activity of these complexes is not known, the observation of good activity for amineplatinum(II) compounds with no hydrogen substituents on the nitrogen donor atoms introduces a new factor in the anticancer behavior of platinum(II) complexes.

Animals↗

PubMed1992

Yeast killer virus transcription initiation in vitro.

Killer virions isolated from infected Saccharomyces cerevisiae cells contain an RNA polymerase activity which catalyzes the transcription in vitro of positive polarity RNAs from the L-A and M double-stranded RNA genomic segments of the virus. The RNA polymerase can initiate transcription in vitro with gamma-thio-GTP, whose thiophosphate group is found on the 5' terminus of transcripts. Transcripts produced in vitro by the virion-associated RNA polymerase in the presence of 7mGpppG are significantly more active as translational templates than are transcripts produced in its absence. However, unlike Escherichia coli RNA polymerase transcripts from viral cDNA made in the presence of 7mGpppG, transcripts produced by viral RNA polymerase in the presence of 7mGpppG fail to bind to antibody against 7mG.

DNA-Directed RNA Polymerases↗

PubMed1992

Modelling of intersegmental coordination in the lamprey central pattern generator for locomotion.

Rhythmic motor activity requires coordination of different muscles or muscle groups so that they are all active with the same cycle duration and appropriate phase relationships. The neural mechanisms for such phase coupling in vertebrate locomotion are not known. Swimming in the lamprey is accomplished by the generation of a travelling wave of body curvature in which the phase coupling between segments is so controlled as to give approximately one full wavelength on the body at any swimming speed. This article reviews work that has combined mathematical analysis, biological experimentation and computer simulation to provide a conceptual framework within which intersegmental coordination can be investigated. Evidence is provided to suggest that in the lamprey, ascending coupling is dominant over descending coupling and controls the intersegmental phase lag during locomotion. The significance of long-range intersegmental coupling is also discussed.

Animals↗

PubMed1990

Effects of bicuculline and strychnine on synaptic inputs to edge cells during fictive locomotion.

Edge cells are mechanoreceptive neurones located in the lateral tracts of the lamprey spinal cord. Phasic activation of these cells by lateral bending can entrain the activity of the locomotor central pattern generator. During fictive locomotion induced by bath-applied NMDLA (N-methyl-D,L-aspartate) or sensory stimulation, edge cells receive synaptic input. In this paper we provide evidence that the tonic inhibition received during sensory-induced fictive locomotion is glycinergic. We also show that during fictive locomotion induced by application of NMDLA to the spinal cord, bicuculline unveils phasic synaptic activity in edge cells. During sensory-evoked fictive locomotion, by contrast, only tonic synaptic activity is apparent in the presence of bicuculline.

Action Potentials↗

PubMed1990

GABAergic control of rhythmic activity in the presence of strychnine in the lamprey spinal cord.

Rhythmic ventral root activity has been induced in the spinal cord of the lamprey in vitro in the presence of strychnine. Bicuculline (a GABAA blocker) increases the initial frequency and decreases the episode duration of such activity, whereas diazepam (which potentiates GABA action) has the opposite effect. In addition, bicuculline slows the depolarisation of ventral horn neurones. However, voltage clamp at potentials positive to the interburst potential does not reveal net outward current, even in the presence of diazepam, indicating that the effects of GABA on the rhythmic activity must be presynaptic to the impaled cells.

Action Potentials↗

PubMed1990

Forcing of coupled nonlinear oscillators: studies of intersegmental coordination in the lamprey locomotor central pattern generator.

1. This paper reports the results of an investigation of the basic mechanisms underlying intersegmental coordination in lamprey locomotion, by the use of a combined mathematical and biological approach. 2. Mathematically, the lamprey central pattern generator (CPG) is described as a chain of coupled nonlinear oscillators; experimentally, entrainment of fictive locomotion by imposed movement has been investigated. Interpretation of the results in the context of the theory has allowed conclusions to be drawn about the nature of ascending and descending coupling in the lamprey spinal CPG. 3. Theory predicts and data show that 1) the greater the number of oscillators in the chain, the smaller is the entrainment frequency range and 2) it is possible to entrain both above and below the rest frequency at one end but only above or below at the other end. 4. In the context of the experimental results, the theory indicates the following: 1) ascending coupling sets the intersegmental phase lags, whereas descending coupling changes the frequency of the coupled oscillators; 2) there are differences in the ascending and descending coupling other than strength; and it also suggests that 3) coupling slows down the oscillators.

Afferent Pathways↗

PubMed1989

Endogenous activation of glycine and NMDA receptors in lamprey spinal cord during fictive locomotion.

Strychnine is shown to abolish left-right alternation in fictive locomotion induced by sensory stimulation. Robust rhythmic activity, characterized by left-right coactivation at each segmental level, is seen in the presence of strychnine at all doses used (0.5-20 microM). The proportion of the cycle occupied by the ventral root bursts and the rostral-caudal coordination is similar to that seen in the absence of strychnine. Furthermore, the rhythm is abolished by cis-2,3-piperidine dicarboxylic acid (PDA), 2-amino-5-phosphonovalerate (APV), or the removal of Mg2+ from the perfusate, as in the absence of strychnine. Voltage clamp was applied to ventral horn neurons during stimulation in the presence of strychnine, with holding potentials negative to the plateau potential associated with a ventral root burst but positive to the potential in the interburst. Inward current was seen during the ventral root burst, but no outward current was seen at burst termination or during the interburst. The results indicate that in fictive locomotion induced by endogenous release of NMDA receptor agonists, left-right alternation is dependent on glycinergic transmission. Furthermore, evidence is provided that in the absence of glycinergic transmission, burst termination may depend on NMDA receptor-linked voltage-sensitive processes.

Animals↗