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Biomedical subjects

S H Brown

Publications and source records attributed to S H Brown.

At least 37 records · Page 2Linked to original sources
PubMed1997

Rhythmic auditory-motor facilitation of gait patterns in patients with Parkinson's disease.

OBJECTIVES: The effect of rhythmic auditory stimulation (RAS) on gait velocity, cadence, stride length, and symmetry was studied in 31 patients with idiopathic Parkinson's disease, 21 of them on (ON) and 10 off medication (OFF), and 10 healthy elderly subjects. METHOD: Patients walked under four conditions: (1) their own maximal speed without external rhythm; (2) with the RAS beat frequency matching the baseline cadence; (3) with RAS 10% faster than the baseline cadence; (4) without rhythm to check for carry over from RAS. Gait data were recorded via a computerised foot switch system. The RAS was delivered via a 50 ms square wave tone embedded in instrumental music (Renaissance style) in 2/4 metre prerecorded digitally on a sequencer for variable tempo reproduction. Patients on medication were tested in the morning 60-90 minutes after medication. Patients off medication were tested at the same time of day 24 hours after the last dose. Healthy elderly subjects were tested during the same time of day. RESULTS: Faster RAS produced significant improvement (P < 0.05) in mean gait velocity, cadence, and stride length in all groups. Close synchronisation between rhythm and step frequency in the controls and both Parkinson's disease groups suggest evidence for rhythmic entrainment mechanisms even in the presence of basal ganglia dysfunction. CONCLUSIONS: The results are consistent with and extend prior reports of rhythmic auditory facilitation in Parkinson's disease gait when there is mild to moderate impairment, and suggest a technique for gait rehabilitation in Parkinson's disease.

Acoustic Stimulation↗
PubMed1997

Cross-institutional reuse of a problem statement knowledge base.

This article describes client and server applications for a problem statement knowledge base derived from a large corpus of provider entered terminology. The current status and potential for integration of the server into the Vanderbilt University Medical Center computing environment are discussed. Finally, an experiment in multiple dimensions of reuse for problem list terms is introduced, and possible strategies to mediate between free text and coded data are examined.

Artificial Intelligence↗
PubMed1996

A study of a series of recombinant fungal laccases and bilirubin oxidase that exhibit significant differences in redox potential, substrate specificity, and stability.

A series of fungal laccases (Polyporus pinsitus, Rhizoctonia solani, Myceliophthora thermophila, Scytalidium thermophilum) and one bilirubin oxidase (Myrothecium verrucaria) have been studied to determine their redox potential, specificity, and stability. Polyporus and Rhizoctonia laccases possess potentials near 0.7-0.8 V (vs. NHE), while other oxidases have potentials near 0.5 V. It is observed that higher redox potential correlates with higher activity. By EPR, no significant change in the geometry of type 1 copper (II) site is observed over this series. At the optimal pH, the two substrates studied, 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) and syringaldazine, show Km values ranging form 10 to 120 and from 1 to 45 microM; and kcat values ranging from 50 to 16 000 and 200 to 3000 per min, respectively. The enzymes are more stable in the neutral-alkaline pH range. The thermal stability is in the order of bilirubin oxidase equivalent to Myceliophthora laccase equivalent to Scytalidium laccase > Polyporus laccase > Rhizoctonia laccase. Based on these results and the sequence alignments made against Zucchini ascorbate oxidase it is speculated that structural differences in the substrate-activation site (a 'blue', type 1 copper center) control the redox potential range as well as substrate specificity, and the cystine content contributes to stability.

Electron Spin Resonance Spectroscopy↗
PubMed1996

The identification and characterization of four laccases from the plant pathogenic fungus Rhizoctonia solani.

Four distinct laccase genes, lcc1, lcc2, lcc3 and lcc4, have been identified in the fungus Rhizoctonia solani. Both cDNA and genomic copies of these genes were isolated and characterized. Hybridization analyses indicate that each of the four laccase genes is present in a single copy in the genome. The R. solani laccases can be divided into two groups based on their protein size, intron/exon organization, and transcriptional regulation. Three of these enzymes have been expressed in the fungus Aspergillus oryzae. Two of the recombinant laccases, r-lcc1 and r-lcc4, as well as the native lcc4 enzyme were purified and characterized. The purified proteins are homodimeric, comprised of two subunits of approximately 66kDa for lcc4 and 50-100kDa for the recombinant lcc1 protein. These laccases have spectral properties that are consistent with other blue copper proteins. With syringaldazine as a substrate, lcc4 has optimal activity at pH7, whereas lcc1 has optimal activity at pH6.

Amino Acid Sequence↗
PubMed1996

Purification, characterization, molecular cloning, and expression of two laccase genes from the white rot basidiomycete Trametes villosa.

Two laccases have been purified to apparent electrophoretic homogeneity from the extracellular medium of a 2,5-xylidine-induced culture of the white rot basidiomycete Trametes villosa (Polyporus pinsitus or Coriolus pinsitus). These proteins are dimeric, consisting of two subunits of 63 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and have typical blue laccase spectral properties. Under nondenaturing conditions, the two purified laccases have different pIs; purified laccase forms 1 and 3 have pIs of 3.5 and 6 to 6.5, respectively. A third purified laccase form 2 has the same N terminus as that of laccase form 3, but its pI is in the range of 5 to 6. The laccases have optimal activity at pH 5 to 5.5 and pH < or = 2.7 with syringaldazine and ABTS [2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid)] as substrates, respectively. The genes lcc1 and lcc2 coding for the two purified laccases (forms 1 and 3) have been cloned, and their nucleotide sequences have been determined. The genes for lcc1 and lcc2 have 8 and 10 introns, respectively. The predicted proteins are 79% identical at the amino acid level. From Northern (RNA) blots containing total RNA from both induced and uninduced cultures, expression of lcc1 is highly induced, while the expression of lcc2 appears to be constitutive. Lcc1 has been expressed in Aspergillus oryzae, and the purified recombinant protein has the same pI, spectral properties, stability, and pH profiles as the purified native protein.

Amino Acid Sequence↗
PubMed1996

Basal ganglia and cerebellar impairment differentially affect the amplitude and time scaling during the performance of forearm step tracking movements.

Forearm step tracking movements of different amplitudes were analysed in nine patients with cerebellar and five patients with parkinsonian symptoms in comparison to six normal subjects. Movements were made under two instructions: 1) track "as fast as possible" and 2) "as precisely as possible". Movement duration, acceleration duration and peak velocity increased with increasing amplitude. The ratio between acceleration and deceleration duration was independent of movement amplitude in the parkinsonian patients and the normal subjects. In the cerebellar patients, however, this ratio decreased with increasing amplitude. This impairment of the relative timing between acceleration and deceleration duration implies that, in contrast to parkinsonian patients, cerebellar patients cannot anymore utilize physiological scaling mechanisms when performing movements of different amplitudes.

Adult↗
PubMed1995

Fusarium graminearum A 3/5 as a novel host for heterologous protein production.

We describe a novel fungal expression system which utilizes the Quorn myco-protein fungus Fusarium graminearum A 3/5. A transformation system was developed for F. graminearum and was used to introduce the coding and regulatory regions of a trypsin gene from Fusarium oxysporum. The protein was efficiently expressed, processed and secreted by the recombinant host strain. In addition, the promoter and terminator of the F. oxysporum trypsin gene have been successfully utilized to drive the expression of a cellulase gene from Scytalidium thermophilum and a lipase gene from Thermomyces lanuginosus in F. graminearum.

Base Sequence↗
PubMed1994

Aspirin and nonsteroidal anti-inflammatory drug use and the risk of subsequent colorectal cancer.

OBJECTIVE: To test the hypothesis that the regular use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is negatively associated with the risk of subsequent colorectal cancer. DESIGN: Case-control study with four age- and sex-matched control subjects for each incident colorectal cancer case. POPULATION AND SETTING: Patient population of a large municipal teaching hospital in Atlanta, Ga. MAIN OUTCOME MEASURE: Odds of colorectal cancer as a function of aspirin, nonaspirin NSAIDs, and acetaminophen dispensed to the study population in the 4 years prior to incident colorectal cancer diagnosis. MAIN RESULTS: The risk of colorectal cancer estimated by odds ratios decreased with increasing days of exposure to aspirin linearly in a dose-dependent fashion (likelihood ratio statistic: for cumulative days, P < .001; for cumulative dose, P < .001). The coefficient for days of exposure to aspirin was highly significant even when modeled as a continuous variable (P = .001). There appeared to be a threshold above which nonaspirin NSAIDs afforded protection (likelihood ratio statistic: for cumulative days, P = .021; for cumulative dose, P = .019). Acetaminophen conferred no risk reduction. CONCLUSION: The results of previous experimental animal models, interventional case studies, and some but not all epidemiological investigations and the present data point toward a causal relationship between NSAID use and the prevention of cancer of the large bowel and rectum. Because of the potential gastrointestinal and renal side effects of NSAID use, particularly in the elderly, chemoprevention trials are now needed to allow risk-benefit analysis in populations at high risk for colorectal cancer.

Acetaminophen↗
PubMed1994

Movement-related phasic muscle activation. III. The duration of phasic agonist activity initiating movement.

To test the hypothesis that phasic muscle activation is related to the acceleration-deceleration characteristics of the resulting movement, we examined the relation between the duration of the acceleratory phase of a variety of movement types and the duration of the phasic muscle activity producing the acceleration (the initial agonist burst, AG1). Movements of five types were studied: (1) step-tracking movements of different amplitudes (10-90 deg) and durations (200-800 ms), (2) movements of the same amplitude (40 deg) and duration (600 ms) varying only in their symmetry ratio (SR, ratio of acceleration to deceleration durations), (3) movements in which acceleration duration was changed while acceleration magnitude was held constant, (4) oscillatory movements of different frequencies and peak amplitudes, (5) step-tracking movements against different inertial loads. Subjects made movements about the elbow joint in the horizontal plane. Surface electromyographic (EMG) activity was recorded from the biceps and the lateral head of the triceps muscles. Under all movement conditions tested and with acceleration duration ranging from 100 to 500 ms, acceleration duration varied linearly with the duration of AG1. Correlation coefficients for the linear regression lines ranged from 0.8 to 0.99. The slope of the best fit linear regression lines ranged from 0.5 to 1.6 and tended to be higher for extensions than flexions. The variations in slope may arise from differing mechanical properties of the biceps and triceps muscles, as well as from active forces produced in the antagonist. AG1 duration was unchanged by inertial loading when subjects kept acceleration duration constant. If subjects responded to an increase in inertial load with an increase in acceleration duration, there was a corresponding increase in AG1 duration. The data demonstrate a general relation between one characteristic of muscle activation (AG1 duration) and the resulting movement. The linear form of the relation is invariant across movement amplitude (range 10-90 deg), speed, duration (range 200-800 ms) and temporal profile (SR range 0.3-2.7), and is also independent of movement type (step, oscillatory). Such a general and simple relation between EMG and movement suggests that, at least to a first approximation, the nervous system can rather simply determine the muscle activation patterns needed to produce movements with desired characteristics.

Acceleration↗
PubMed1994

Effects of gravitational forces on single joint arm movements in humans.

We have examined the kinematics and muscle activation patterns of single joint elbow movements made in the vertical plane. Movements of different amplitudes were performed during a visual, step-tracking task. By adjusting shoulder position, both elbow flexion and extension movements were made under three conditions: (a) in the horizontal plane, (b) in the vertical plane against gravity, and (c) in the vertical plane with gravity. Regardless of the gravitational load, all movements were characterized by time symmetric velocity profiles. In addition, no differences were found in the relationships between movement duration, peak velocity, and movement amplitude in movements with or against gravity. The pattern of muscle activation was influenced however, by the gravitational load. Both flexion and extension movements made with gravity were characterized by a reciprocally organized pattern of muscle activity in which phasic agonist activity was followed by phasic antagonist activity. Flexion and extension movements made against gravity were characterized by early phasic antagonist activity occurring at about the same time as the initial agonist burst. These findings suggest that EMG patterns are modified in order to preserve a common temporal structure in the face of different gravitational loads.

Adult↗
PubMed1993

Regulation of ribosomal RNA transcription by growth rate of the hyperthermophilic Archaeon, Pyrococcus furiosus.

We have studied the single rRNA gene cluster from the Archaeon, Pyrococcus furiosus. This isolate grows optimally at 100 degrees C and is thus a hyperthermophile. In P. furiosus, transcription of 16S rRNA is subject to regulation over a 7.5-fold range in response to a 20-fold increase in growth rate. The single cluster encoding the 16S and 23S rRNA genes of P. furiosus was cloned and the 1.9 kb region upstream of the 16S rRNA gene was sequenced.

Archaea↗
PubMed1993

Role of the cerebellum in visuomotor coordination. I. Delayed eye and arm initiation in patients with mild cerebellar ataxia.

The initiation of coupled eye and arm movements was studied in six patients with mild cerebellar dysfunction and in six age-matched control subjects. The experimental paradigm consisted of 40 deg step-tracking elbow movements made under different feedback conditions. During tracking with the eyes only, saccadic latencies in patients were within normal limits. When patients were required to make coordinated eye and arm movements, however, eye movement onset was significantly delayed. In addition, removal of visual information about arm versus target position had a pronounced differential effect on movement latencies. When the target was extinguished for 3 s immediately following a step change in target position, both eye and arm onset times were further prolonged compared to movements made to continuously visible targets. When visual information concerning arm position was removed, onset times were reduced. Eye and arm latencies in control subjects were unaffected by changes in visual feedback. The results of this study clearly demonstrate that, in contrast to earlier reports of normal saccadic latencies associated with cerebellar dysfunction, initiation of both eye and arm movements is prolonged during coordinated visuomotor tracking thus supporting a coordinative role for the cerebellum during oculo-manual tracking tasks.

Adult↗
PubMed1993

Enzymes from high-temperature microorganisms.

Enzymes derived from microorganisms growing at extreme temperatures are of biotechnological use as highly thermostable biocatalysts and should provide insight into the intrinsic basis of protein stability. So far, only DNA polymerases from these organisms have been put to commercial use, although the application of other classes of highly thermostable enzymes is being considered. Problems in the cultivation of high-temperature microorganisms and in the production of their enzymes still hampers progress in this field.

Archaea↗
PubMed1993

Characterization of Amylolytic Enzymes, Having Both alpha-1,4 and alpha-1,6 Hydrolytic Activity, from the Thermophilic Archaea Pyrococcus furiosus and Thermococcus litoralis.

Extracellular pullulanases were purified from cell-free culture supernatants of the marine thermophilic archaea Thermococcus litoralis (optimal growth temperature, 90 degrees C) and Pyrococcus furiosus (optimal growth temperature, 98 degrees C). The molecular mass of the T. litoralis enzyme was estimated at 119,000 Da by electrophoresis, while the P. furiosus enzyme exhibited a molecular mass of 110,000 Da under the same conditions. Both enzymes tested positive for bound sugar by the periodic acid-Schiff technique and are therefore glycoproteins. The thermoactivity and thermostability of both enzymes were enhanced in the presence of 5 mM Ca, and under these conditions, enzyme activity could be measured at temperatures of up to 130 to 140 degrees C. The addition of Ca also affected substrate binding, as evidenced by a decrease in K(m) for both enzymes when assayed in the presence of this metal. Each of these enzymes was able to hydrolyze, in addition to the alpha-1,6 linkages in pullulan, alpha-1,4 linkages in amylose and soluble starch. Neither enzyme possessed activity against maltohexaose or other smaller alpha-1,4-linked oligosaccharides. The enzymes from T. litoralis and P. furiosus appear to represent highly thermostable amylopullulanases, versions of which have been isolated from less-thermophilic organisms. The identification of these enzymes further defines the saccharide-metabolizing systems possessed by these two organisms.

Journal Article↗
PubMed1990

The hyperthermophilic archaebacterium, Pyrococcus furiosus. Development of culturing protocols, perspectives on scaleup, and potential applications.

From this brief discussion, it is clear that there are many obstacles to overcome before hyperthermophilic archaebacteria will be an important aspect of biotechnology. Nevertheless, the prospects are intriguing. The nature of the environments that harbor these organisms and the consequent requirements for their controlled culture suggest that chemical and biochemical engineers can play an important role in elucidating their scientific and technological aspects.

Archaea↗