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Biomedical subjects

B T Smith

Publications and source records attributed to B T Smith.

At least 37 records · Page 2Linked to original sources
PubMed1999

A study of shoulder motions as a control source for adolescents with C4 level SCI.

This study quantitatively examined and compared the shoulder motions of C4 level spinal cord injury (SCI), C5 level SCI, and able-bodied persons as a command source. The study was motivated by both the success of shoulder control in functional electrical stimulation (FES) systems designed for C5 level SCI people and the lack of quantitative information on the shoulder motion of persons with C4 level SCI. A dual-axis transducer was used to monitor the elevation/depression and protraction/retraction angles of each subject's shoulder while they performed three experimental sections which examined: the range of active shoulder motion; the ability to move incrementally to discrete positions with the aid of visual feedback; and the ability to hold discrete shoulder positions for an extended period without visual feedback. Results indicated that each group had the largest average shoulder displacements (abled = 23 degrees +/- 4 degrees, C5's = 14 degrees +/- 3 degrees, and C4's = 9 degrees +/- 3 degrees) while attempting to elevate and that on average the C4 group had the smallest range of active shoulder motion. No statistically significant differences between the groups were found in either the accuracy or stability of reaching discrete positions with the aid of visual feedback or in the accuracy of holding discrete shoulder positions for an extended period without visual feedback. The results suggest that within their limited range of motion the individuals with C4 level SCI retained shoulder control sufficient for use as an neuroprosthetic command interface.

Adolescent↗
PubMed1999

Implantable electrode lead in a growing limb.

An implantable electrode leadwire system used to provide limb function for individuals with spinal cord injuries (SCI's) was evaluated in a series of growing dogs to determine whether it could maintain its performance in the presence of growth. Thirty implantable electrodes (15 epimysial and 15 intramuscular) were implanted in the forelimb muscles of six young dogs. The electrodes' leads were tunneled subcutaneously and anchored proximally in the shoulder with excess lead incorporated into the subcutaneous space to accommodate growth. Six of the leads had some of this excess placed in pouches made from surgical membrane while the other 24 leads had excess placed freely within the subcutaneous space. Motor responses to the electrodes were tested before and after growth with tendon force transducers and were compared to the performance of new electrodes implanted to the same muscles of the mature dog during the explant procedure. Measured were the pulse duration at which a measurable force is first produced (threshold) and the percentage of the maximum force that could be attained from the target muscle before activation of adjacent muscles (usable force range). An analysis of variance indicated that there was no difference in the usable force range (p = 0.62) of the original electrodes before and after growth and that of the new electrodes placed at maturity. There was a difference in the threshold (p = 0.001) which can be attributed to an increase in the values measured from the original electrodes after growth. However, the increase in threshold with growth averaged 6 micros which is not clinically significant and can be accommodated through stimulation programming. Growth of the limb and unwinding of excess lead were quantified by radiograph. Extension of the freely placed excess lead was comparable to growth so that the pouch enclosures were found to be unnecessary for facilitating lead expansion. By radiograph and surgical observations, only two of 30 electrodes (both intramuscular) appeared to have been subjected to lead tension, although they continued to provide adequate motor responses. Insufficient excess lead was judged to be the cause of dislodgment for one of these electrodes. Results of this study suggest that for this implantable leadwire system, excess lead placed in the subcutaneous space can unwind on demand with limb growth such that an electrode will remain in position and provide a stable motor response.

Analysis of Variance↗
PubMed1999

Time-frequency analysis of the dispersion of Lamb modes.

Accurate knowledge of the velocity dispersion of Lamb modes is important for ultrasonic nondestructive evaluation methods used in detecting and locating flaws in thin plates and in determining their elastic stiffness coefficients. Lamb mode dispersion is also important in the acoustic emission technique for accurately triangulating the location of emissions in thin plates. In this research, the ability to characterize Lamb mode dispersion through a time-frequency analysis (the pseudo-Wigner-Ville distribution) was demonstrated. A major advantage of time-frequency methods is the ability to analyze acoustic signals containing multiple propagation modes, which overlap and superimpose in the time domain signal. By combining time-frequency analysis with a broadband acoustic excitation source, the dispersion of multiple Lamb modes over a wide frequency range can be determined from as little as a single measurement. In addition, the technique provides a direct measurement of the group velocity dispersion. The technique was first demonstrated in the analysis of a simulated waveform in an aluminum plate in which the Lamb mode dispersion was well known. Portions of the dispersion curves of the A0, A1, S0, and S2 Lamb modes were obtained from this one waveform. The technique was also applied for the analysis of experimental waveforms from a unidirectional graphite/epoxy composite plate. Measurements were made both along and perpendicular to the fiber direction. In this case, the signals contained only the lowest order symmetric and antisymmetric modes. A least squares fit of the results from several source to detector distances was used. Theoretical dispersion curves were calculated and are shown to be in good agreement with experimental results.

Acoustics↗
PubMed1998

Magnetic resonance imaging data in the evaluation of effects of functional electrical stimulation on knee joints of adolescents with spinal cord injury.

Diagnostic imaging, consisting of roentgenograms and magnetic resonance images (MRIs), was performed as part of an evaluation of the effects of a functional electrical stimulation (FES) program on the knee joints of 29 adolescents with spinal cord injuries following implantation of fine-wire intramuscular electrodes in their lower extremity muscles. The subjects underwent a regimen consisting of stimulated exercise, standing and/or walking. The effects of FES on knee joints were prospectively studied by reviewing diagnostic imaging data. Evaluation of MRIs and plain radiographs showed no evidence of knee joint pathology secondary to FES exercise or weight bearing. In fact, based on follow-up of MRI scan, many of the joints improved following participation in the program. The MRI data supported the clinical examination of the knee joints of these children. Clinical examination appears adequate for screening for potential knee joint problems.

Adolescent↗
PubMed1998

Self-reported use of an implanted FES hand system by adolescents with tetraplegia.

The Freehand System, an eight-channel functional electrical stimulation (FES) system, was implanted in five adolescents with C-5 or C-6 tetraplegia to provide stimulated lateral pinch and palmar grasp. Following completion of inpatient training on how to use the Freehand System for predefined and self-selected activities of daily living (ADL), the adolescents were discharged to use their Freehand systems at home and school. A telephone survey was administered on a weekly basis to obtain information on the type of ADL performed with the Freehand System, reasons for not using the Freehand System, and perceived barriers and motivators to FES use. Twenty surveys were obtained on each adolescent, resulting in a total of 100 surveys. The most common type of activity performed with the Freehand System was self-care, which included tasks such as eating, grooming, and brushing teeth. The Freehand System was also used for productivity activities defined as writing, socialization, and manipulation of school and household objects. Motivators to Freehand System use included perceived need and importance to perform an ADL in an independent fashion, physical ease of using the Freehand System, and availability of social supports that facilitated Freehand System use. While there were several reported barriers to Freehand System use, incompatibility with multiple transfers to and from the wheelchair and lack of physical assistance during morning care to don the system were perceived as two of the more common reasons for nonuse.

Activities of Daily Living↗
PubMed1998

Mutagenesis and more: umuDC and the Escherichia coli SOS response.

The cellular response to DNA damage that has been most extensively studied is the SOS response of Escherichia coli. Analyses of the SOS response have led to new insights into the transcriptional and post-translational regulation of processes that increase cell survival after DNA damage as well as insights into DNA-damage-induced mutagenesis, i.e., SOS mutagenesis. SOS mutagenesis requires the recA and umuDC gene products and has as its mechanistic basis the alteration of DNA polymerase III such that it becomes capable of replicating DNA containing miscoding and noncoding lesions. Ongoing investigations of the mechanisms underlying SOS mutagenesis, as well as recent observations suggesting that the umuDC operon may have a role in the regulation of the E. coli cell cycle after DNA damage has occurred, are discussed.

Bacterial Proteins↗
PubMed1998

Lamb wave assessment of fiber volume fraction in composites.

Among the various techniques available, ultrasonic Lamb waves offer a convenient method of examining composite materials. Since the Lamb wave velocity depends on the elastic properties of a material, an effective tool exists to evaluate composites by measuring the velocity of these waves. Lamb waves can propagate over long distances and are sensitive to the desired in-plane elastic properties of the material. This paper discusses a study in which Lamb waves were used to examine fiber volume fraction variations of approximately 0.40-0.70 in composites. The Lamb wave measurements were compared to fiber volume fractions obtained from acid digestion tests. Additionally, a model to predict the fiber volume fraction from Lamb wave velocity values was evaluated.

Models, Theoretical↗
PubMed1997

Increasing cAMP attenuates induction of inducible nitric-oxide synthase in rat primary astrocytes.

Nitric oxide produced by inducible nitric-oxide synthase (iNOS) in different brain cells in response to various cytokines plays an important role in the pathophysiology of stroke and other neurodegenerative diseases. This study underlines the importance of cAMP in inhibiting the induction of NO production by lipopolysaccharide (LPS) and cytokines in rat primary astrocytes. Compounds (forskolin, 8-bromo-cAMP, and (Sp)-cAMP) that increase cAMP and activate protein kinase A (PKA) were found to inhibit LPS- and cytokine-mediated production of NO as well as the expression of iNOS, whereas compounds (H-89 and (Rp)-cAMP) that decrease cAMP and PKA activity stimulated the production of NO and the expression of iNOS in rat primary astrocytes. Forskolin, but not the inactive analogue 1,9-dideoxyforskolin, inhibited NO production and iNOS expression in a dose-dependent manner in astrocytes. The inhibition of LPS- and/or cytokine-induced NO production in rat C6 glial cells by forskolin suggest that similar to astrocytes, iNOS expression in C6 cells is also regulated by similar mechanisms. In contrast, in rat peritoneal macrophages the cAMP analogues stimulated the LPS- and cytokine-induced production of NO. In vitro, the PKA had no effect on iNOS activity in LPS-treated astrocytes or macrophages, suggesting that PKA modulates the intracellular signaling events associated with the induction of iNOS biogenesis rather than the post-translational modification of iNOS. The compounds which activate PKA activity, blocked the activation of NF-kappabeta in astrocytes but stimulated the activation of NF-kappabeta in macrophages. This differential regulation of NF-kappabeta activation in two different cell types (astrocytes and macrophages) by the same second messenger (cAMP) indicates that intracellular events or pathways in the activation of NF-kappabeta may be different. Moreover, this inhibition of iNOS expression in LPS- and cytokine-treated astrocytes by cAMP may be of therapeutic potential in NO-mediated cytotoxicity in neurodegenerative diseases.

Animals↗
PubMed1997

Implanted functional electrical stimulation hand system in adolescents with spinal injuries: an evaluation.

OBJECTIVE: To study the utility and functional benefits of an implanted functional electrical stimulation (FES) system for hand grasp and release in adolescents with tetraplegia secondary to spinal cord injuries. DESIGN: Intervention study with before-after trial measurement with each subject as his or her own control. SETTING: Nonprofit pediatric orthopedic rehabilitation facility specializing in spinal cord injury. PARTICIPANTS: A convenience sample of five adolescents between 16 and 18 years of age with C5 or C6 level tetraplegia at least 1 year after traumatic spinal cord injury. Key muscles for palmar and lateral grasp and release were excitable by electrical stimulation. INTERVENTIONS: A multichannel stimulator/receiver and eight electrodes were surgically implanted to provide stimulated palmar and lateral grasp and release. In conjunction with implantation of the FES hand system, surgical reconstruction in the form of tendon transfers, tendon lengthenings and releases, and joint arthrodeses was performed to augment stimulated hand function. Rehabilitation of the tendon transfers and training in the use of the FES hand system were provided. MAIN OUTCOME MEASURES: Measurements of pinch and grasp force, the Grasp and Release Test (GRT), and an assessment of six activities of daily living (ADL) were administered before implantation of the FES hand system and at regular follow-up intervals. Results of the stimulated response of individual muscles and surgical reconstruction were evaluated using standard and stimulated muscle testing techniques and standard assessment of joint range of motion. All subjects completed followup testing. RESULTS: Lateral and palmar forces were significantly greater than baseline forces (p = .043). Heavy objects on the GRT could only be manipulated with FES, and FES increased the level of independence in 25 of 30 ADL comparisons (5 subjects, 6 activities) as compared to baseline. After training, FES was preferred in 21 of 30 comparisons over the typical means of task completion. Of the 40 electrodes implanted, 37 continue to provide excellent stimulated responses and all of the implanted stimulators have functioned without problems. The surgical reconstruction procedures greatly enhanced FES hand function by either expanding the workspace in which to utilize FES (deltoid to triceps transfer), stabilizing the wrist (brachioradialis to wrist extensor transfer), or stabilizing joints (intrinsic tenodesis transfer, FPL split transfer). CONCLUSION: For five adolescents with tetraplegia, the combination of FES and surgical reconstruction provided active palmar and lateral grasp and release. Laboratory-based assessments demonstrated that the FES system increased pinch force, improved the manipulation of objects, and typically increased independence in six standard ADL as compared to pre-FES hand function. The study also showed that the five adolescents generally preferred FES for most of the ADL tested. Data on the benefits of the implanted FES hand system outside of the laboratory are needed to understand the full potential of FES.

Activities of Daily Living↗
PubMed1997

Cytochrome P-450 2E1 in rat liver peroxisomes: downregulation by ischemia/reperfusion-induced oxidative stress.

Cytochrome P-450 containing enzymes, known to be present in the endoplasmic reticulum and mitochondria, catalyze the oxidation of various compounds. In this study we have used highly purified peroxisomes (> 95%) to provide evidence by analytical cell fractionation, enzyme activity, Western blot, and immunocytochemical analysis that cytochrome P-450 2E1 (Cyp 2E1) is present in peroxisomes. Similar specific activities of aniline hydroxylase, a Cyp 2E1-dependent enzyme, in purified peroxisomes (0.72 +/- 0.03 nmol/min/mg protein) and microsomes (0.58 +/- 0.03 nmol/min/mg protein) supports the conclusion that peroxisomes contain significant amount of Cyp 2E1. This peroxisomal Cyp 2E1 was also induced in acetone-treated rat liver. The status of microsomal and peroxisomal Cyp 2E1 was also examined following ischemia/reperfusion-induced oxidative stress. Ischemia alone had no effect; however, reperfusion following ischemia resulted in decrease in Cyp 2E1 both in microsomes and peroxisomes. This demonstration of cytochrome P-450 2E1 in peroxisomes and its downregulation during ischemia/reperfusion describes a new role for this organelle in cytochrome P-450 related cellular metabolism and in oxidative stress induced disease conditions.

Aniline Compounds↗
PubMed1997

Plasma lipid and lipoprotein responses to dietary fat and cholesterol: a meta-analysis.

Quantitative relations between dietary fat and cholesterol and plasma lipid concentrations have been the subject of much study and some controversy during the past 40 y. Previous meta-analyses have focused on the most tightly controlled, highest-quality experiments. To test whether the findings of these investigations are generalizable to broader experimental settings and to the design of practical dietary education interventions, data from 224 published studies on 8143 subjects in 366 independent groups including 878 diet-blood lipid comparisons were subjected to weighted multiple-regression analysis. Inclusion criteria specified intervention studies published in English between 1966 and 1994 reporting quantitative data on changes in dietary cholesterol and fat and corresponding changes in serum cholesterol, triacylglycerol, and lipoprotein cholesterol concentrations. Regression models are reported for serum total cholesterol, triacylglycerol, and low-density-high-density-, and very-low-density-lipoprotein cholesterol, with multiple correlations of 0.74, 0.65, 0.41, 0.14, and 0.34, respectively. Interactions of dietary factors, initial dietary intakes and serum concentrations, and study and subject characteristics had little effect on these models. Predictions indicated that compliance with current dietary recommendations (30% of energy from fat, < 10% from saturated fat, and < 300 mg cholesterol/d) will reduce plasma total and low-density-lipoprotein-cholesterol concentrations by approximately 5% compared with amounts associated with the average American diet.

Adolescent↗
PubMed1996

The bacillus subtilis dinR gene codes for the analogue of Escherichia coli LexA. Purification and characterization of the DinR protein.

The Bacillus subtilis dinR gene encodes a 23-kDa protein that shares about 34% homology with the Escherichia coli LexA protein. We have purified the dinR gene product to near homogeneity, and we describe its activities. The purified DinR protein binds specifically to the promoter regions of three B. subtilis SOS genes: dinB, dinC, and recA. Electrophoretic mobility of DinR-promoter complexes in each case is identical to that of promoters bound by the B. subtilis SOS repressor (Lovett, et al., (1993) J. Bacteriol. 175, 6842-6849). Analysis of hydroxyl radical footprints of DinR bound to the dinC promoter indicates that DinR interacts with one side of the DNA providing access to the consensus operator site (5'-GAACN4GTTC-3') within two adjacent major grooves. Consistent with its proposed role as a transcriptional repressor, purified DinR displaces B. subtilis RNA polymerase from the recA promoter and represses transcription of the recA gene in vitro. We also show that purified DinR protein undergoes general base-catalyzed autodigestion as well as RecA-mediated cleavage at the peptide bond between Ala-91 and Gly-92. Corresponding to its cleavage by activated RecA following DNA damage, the level of DinR is significantly reduced in RecA+ B. subtilis cells following exposure to mitomycin C. Thus, the DinR protein is structurally and functionally analogous to the E. coli LexA protein, and accordingly, we propose renaming the protein B. subtilis LexA.

Bacillus subtilis↗
PubMed1996

Quantitative comparison of grasp and release abilities with and without functional neuromuscular stimulation in adolescents with tetraplegia.

In this study, a functional neuromuscular stimulation (FNS) hand system designed by Case Western Reserve University (CWRU) was implemented in 5 adolescents with C5 tetraplegia and hand function with FNS was evaluated and compared to tenodesis abilities using a grasp and release test designed specifically for this purpose. The test involved the unilateral acquisition, movement and release of 6 objects of various sizes and weights. During a single test session, five 30-second trials were performed with each object with and without the FNS system where the number of completions and failures were recorded for each trial. At least 4 and as many as 8 test sessions were conducted with each subject over periods of 1.5 to 3 years. For each subject, test performance with FNS was compared statistically to tenodesis performance and session-to-session consistency was analyzed. Of 30 comparisons (5 subjects and 6 test objects), FNS was more effective in 23 cases (77%), tenodesis was better in 5 instances (17%) and in 2 cases (6%) there was no difference. Subjects were able to manipulate the 3 heaviest test objects only with FNS and in 60% of all cases involving the 3 lighter test objects there were significantly more trials in which there were more completions or fewer failures with FNS. Performance with FNS and tenodesis was generally inconsistent across sessions; possible reasons for these variations are discussed. Overall, the results of this study support those of the only previous investigation that used the grasp and release test to evaluate hand function with FNS in C5 and C6 tetraplegia.

Activities of Daily Living↗
PubMed1996

Development of an upper extremity FES system for individuals with C4 tetraplegia.

The application of functional electrical stimulation (FES) to provide upper extremity function for individuals with C4 tetraplegia is under investigation. In this study, a FES system was designed that allowed one individual with complete C4 tetraplegia to coordinate stimulated lateral or palmar prehension with stimulated arm movements using contralateral shoulder position. The system consisted of percutaneous intramuscular electrodes implanted to muscles for hand grasp and release, supination, elbow flexion, and extension and arm adduction. Due to peripheral denervation, transposition and subsequent stimulation of the paralyzed latissimus dorsi muscle provided elbow flexion and transfer and stimulation of the paralyzed extensor carpi ulnaris muscle provided forearm supination. A suspended sling provided shoulder joint stability. The subject controlled stimulation proportionally using contralateral shoulder motion sensed by a position transducer. Control of stimulated hand grasp and release were coupled with stimulated arm motions so that hand-to-mouth activities could be accomplished with one motion of the contralateral shoulder. With this system, the subject was able to grasp a milk carton placed in the hand and lift and lower it from his mouth to drink from a short straw. He could also scoop a semisolid substance with an adapted spoon and lift and lower it from the work surface to his mouth to eat. The subject required assistance to place the milk carton or spoon in his hand and position the plate for scooping. Further investigation is needed to generate the necessary arm movements to make completion of these tasks possible without assistance and to expand the range of activities possible with the FES system.

Accidents, Traffic↗
PubMed1996

Epoxide hydrolase in human and rat peroxisomes: implication for disorders of peroxisomal biogenesis.

To understand the basis of excretion of excessive amounts of epoxydicarboxylic fatty acids (EDFA) in urine of patients with disorders of peroxisomal biogenesis (Pitt, J. J., and A. Poulos. 1993. Clin. Chim. Acta. 223: 23-29), the activity of epoxide hydrolase (EH) was measured in cultured skin fibroblasts from control subjects and patients with peroxisomal disorders. EH activity was approximately 40% lower in fibroblasts that lack intact peroxisomes (Zellweger syndrome), whereas the activity in other peroxisomal disorders (X-adrenoleukodystrophy and rhizomelic chondrodysplasia punctata) with intact peroxisomes was similar to control. To identify the specific enzyme/organelle that represents the decrease in EH activity in Zellweger cells, we have analyzed this activity in different subcellular organelles from control and Zellweger skin fibroblasts. EH activity was enriched in peroxisomes from control fibroblast. EH activity in isolated mitochondria, microsomes, or cytosol from Zellweger fibroblast was similar to that of control fibroblast. These observations indicate that deficient activity of EH in cells from Zellweger patients is due to lack of peroxisomal EH activity. The peroxisomal EH is differentially induced to a higher degree by ciprofibrate, a hypolipidemic agent and peroxisome proliferator, than EH activity in other organelles and cytoplasm. The high specific activity of EH in peroxisomes and differential induction of EH activity in peroxisomes as compared to other organelles, and the excretion of EDFA in patients who lack peroxisomes suggests that peroxisomal EH may be responsible for the detoxification of EDFA, and that this enzyme in peroxisomes may be a different protein than the EH found in other organelles.

Animals↗
PubMed1995

Ketoconazole and other imidazole derivatives are potent inhibitors of peroxisomal phytanic acid alpha-oxidation.

The imidazole antimycotics like ketoconazole, clotrimazole, bifonazole, miconazole and CO, known as powerful inhibitors of cytochrome P-450, are potent inhibitors of peroxisomal phytanic acid alpha-oxidation to pristanic acid suggesting the possible involvement of the cytochrome P-450 mono-oxygenase system in this oxidation. In contrast to the inhibition of the oxidation of [1-14C]phytanic acid, [1-14C]phytanoyl-CoA and [(2,3)-3H]phytanic acid, these drugs and CO have no effect on the oxidation of [1-14C]alpha-hydroxy phytanic acid indicating that these drugs and CO inhibit only the alpha-hydroxylation of phytanic acid. These studies using purified peroxisomes from liver and cultured human skin fibroblasts and Hep G2 cells clearly demonstrate that alpha-hydroxylation, an intermediate step in the alpha-oxidation of phytanic acid found to be impaired in Refsum Disease, is mediated by cytochrome P-450 containing enzyme.

Carbon Monoxide↗
PubMed1995

Generation of polyclonal catalytic antibodies against cocaine using transition state analogs of cocaine conjugated to diphtheria toxoid.

Six novel transition state analogs (TSAs) of cocaine (10-14 and 17) and one non-cocaine, p-aminophenylphosphonyl ester of cyclohexanol (19), were synthesized and characterized by 1H- and 13C-NMR and FAB-MS. (1R)-ecgonine methyl ester or cyclohexanol were subjected to phenylphosphonylation in the presence of dicyclohexyl carbodiimde (DCC) and 4-N,N-dimethyl aminopyridine (4-DMAP). TSA-IV (10), however, was synthesized from norcocaine which was protected with dibromoethane to yield 4 before acid hydrolysis, esterification and phenylphosphonylation were carried out. TSA-III (11) TSA-I (12) and (19), using various length spacer arms, were coupled with the immunogenic protein, diphtheria toxoid (DT). The TSAs coupled with DT were used to immunize mice and after appropriate boosts their sera were tested for the presence and titer of anti-TSA polyclonal antibodies using ELISA. Preliminary results show that the mice immunized with these TSAs produced high titers of polyclonal catalytic antibodies, except for (19), with the ability to hydrolyze the substrate 125I-4'-iodococaine in an in vitro assay, even in the presence of noncatalytic anti-TSA antibodies.

4-Aminopyridine↗