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T R Scott

Publications and source records attributed to T R Scott.

At least 19 recordsLinked to original sources
PubMed2006

Use of pairwise marker combination and recursive partitioning in a pharmacogenetic genome-wide scan.

The objective of pharmacogenetic research is to identify a genetic marker, or a set of genetic markers, that can predict how a given person will respond to a given medicine. To search for such marker combinations that are predictive of adverse drug events, we have developed and applied two complementary methods to a pharmacogenetic study of the hypersensitivity reaction (HSR) associated with treatment with abacavir, a medicine that is used to treat HIV-infected patients. Our results show that both of these methods can be used to uncover potentially useful predictive marker combinations. The pairwise marker combination method yielded a collection of marker pairs that featured a spectrum of sensitivities and specificities. Recursive partitioning results led to the genetic delineation of multiple risk categories, including those with extremely high and extremely low risk of HSR. These methods can be readily applied in pharmacogenetic candidate gene studies as well as in genome-wide scans.

Adult↗
PubMed2006

Monoclonal antibodies against chicken interleukin-6.

Monoclonal antibodies (mAb) were produced against a recombinant (r) chicken interleukin-6 (IL-6). Eight mAbs produced were tested for isotype; ability to inhibit recombinant forms of chicken (ch), human (h) and murine (m) IL-6; and recognition of rchIL-6 by Western immunoblotting. The mAb isotypes were represented by IgG1 (one), IgG2a (six) and IgG2b (one). In a mouse B9 hybridoma cell bioassay with rmIL-6, four mAbs effectively inhibited activity of rmIL-6. Further bioassays with the four mAbs at varying concentrations showed that two of these mAbs (1.20.7 and 1.26.4) were quite effective at inhibiting rmIL-6. Recombinant forms of ch, h and mIL-6 were all tested in a bioassay with the most potent inhibiting mAb (1.26.4), and this mAb was effective in inhibiting all three recombinant IL-6 proteins. Western immunoblotting revealed identification of the original IL-6 immunogen used for mAb production. Based upon inhibition of IL-6 activity in a standard bioassay and IL-6 recognition by Western immunoblotting, mAb 1.26.4 was judged the most useful antibody for future studies and applications.

Animals↗
PubMed2006

Memory-dependent c-Fos expression in the nucleus accumbens and extended amygdala following the expression of a conditioned taste aversive in the rat.

Retrieving the memory of a conditioned taste aversion involves multiple forebrain areas. Although the amygdala clearly plays a role in the expression of a conditioned taste aversion, critical regions, downstream from the amygdala remain to be defined. To this end, Fos immunoreactivity was used in the rat to explore forebrain structures associated with retrieval that have an anatomical relationship with the amygdala. The results showed that expression of a conditioned taste aversion to 0.5 M sucrose elicited neuronal activation in the nucleus accumbens and in a complex of structures collectively referred to as the extended amygdala. The posterior hypothalamus and parasubthalamic nucleus, which receive inputs from the extended amygdala, were also activated upon re-exposure to the sucrose conditioned stimulus. Fos immunoreactivity did not increase in these regions in response to an innately aversive tastant, quinine hydrochloride (conditioned stimulus control), nor to LiCl-induced visceral stimulation in unconditioned animals (unconditioned stimulus control). In addition, these regions did not respond to the sucrose conditioned stimulus in sham-conditioned animals. These results suggest that conditioned and innately aversive tastes are differentially processed in the forebrain circuitry that includes the nucleus accumbens and extended amygdala.

Amygdala↗
PubMed2005

Positioning prostanoids of the D and J series in the immunopathogenic scheme.

Prostaglandin D(2) (PGD(2)) is produced by a variety of immune and non-hematopoietic cells and appears to function in both an inflammatory and homeostatic capacity. Two genetically distinct PGD(2)-synthesizing enzymes have been identified to date, including hematopoietic- and lipocalin-type PGD synthases (H-PGDS and L-PGDS, respectively). Though the inter-species expression profiles of these two enzymes vary widely, H-PGDS is generally localized to the cytosolic aspect of immune and inflammatory cells, whereas L-PGDS is more resigned to tissue-based expression. PGD(2) activity is principally mediated through two unique G protein-coupled receptors (GPCR), designated DP(1) and DP(2). These receptors exhibit overlapping binding profiles, yet their respective agonists elicit generally distinctive responses. Additional to DP receptors, the PGD(2) metabolite 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) binds the nuclear peroxisome proliferator-activated receptor gamma (PPARgamma) and has the facility to initiate a variety of anti-inflammatory phenotypes either through or independent of PPARgamma association. This review highlights the collective relevance of PGD(2) and its respective synthases, receptors, and metabolites in immunopathologic responses.

Animals↗
PubMed2005

Hematopoietic prostaglandin D2 synthase in the chicken Harderian gland.

The Harderian gland (HG), a sero-mucous secreting organ in the eye orbit, has long been recognized as immunologically important in chickens. During experimentation to characterize immune components of the gland, proteomics analysis revealed the presence of hematopoietic prostaglandin D synthase (H-PGDS). Extraction of total RNA followed by RT-PCR produced cDNA of 597 base pairs. DNA sequencing revealed nucleic acid and predicted amino acid sequences that were 99% aligned with the one published sequence for chicken H-PGDS of the spleen. Alignment with murine, rat, and human H-PGDS were 69, 69, and 66%, respectively. Ocular vaccination of chickens with a Newcastle Disease/Infectious Bronchitis vaccine (Mass.-Ark. Strain) induced an increase in H-PGDS expression determined by real-time PCR. Furthermore, immunohistochemistry of frozen HG sections showed positive stained cells for both H-PGDS and mast cell tryptase in the sub-epithelial cell layers of the HG ducts. Based on the potent vasoactive role of PGD(2), it appears that the chicken HG is a site of active mucosal immunity partially mediated by PGD(2) synthesized by H-PGDS in the gland.

Amino Acid Sequence↗
PubMed2004

Our current understanding of humoral immunity of poultry.

With the inception of the modem era of avian immunology in the mid-1950s following the discovery of the role of the bursa of Fabricius (BF), steady and persistent research has been conducted by scientists. Findings that have advanced our knowledge of humoral immunity (HI) include the distinct role of B cells in antibody production, explanation of antibody diversity by gene rearrangement and conversion, identification of a bursal secretory dendritic cell and dendritic cells of the spleen, characterization of cytokine factors, and mapping of MHC class II genes. Numerous experiments have been conducted to evaluate the HI responses of poultry through antibody titer determination and quantitation of immunoglobulin concentrations in the humors. Antibody studies have included the genetics of HI regarding both quantity and persistence of responses as influenced by multiple genes and MHC haplotypes. In the past decade, emergence of monoclonal antibody reagents to identify cell surface markers on B cells and accessory cells has allowed for discrimination of HI functions of cells by immunohistochemistry, flow cytometry, and other techniques. The signaling mechanisms of avian B cells are becoming better understood. Continued work in avian immunity has led to more advances in identification, characterization, and gene sequencing of important cytokines. Additional work is required to identify and sequence genes for many more cytokines that have direct effects on B cells. A brief history of research published on avian B cells is presented with an examination of some of the important research findings reported in recent years.

Allergy and Immunology↗
PubMed2002

Production and characterization of a turkey sperm mitochondrial monoclonal antibody and its usefulness for assessment of sperm integrity.

A monoclonal antibody (4C7/2E4) that binds to an antigen located on the midpiece of turkey spermatozoa has been produced and characterized. The antibody was also reactive to antigens on the midpiece of chicken, Japanese quail, and bobwhite quail spermatozoa but was unreactive to spermatozoa from guinea fowl, human, horse, boar, and bull. Immunogold transmission electron microscopy of turkey spermatozoa showed that the antibody was associated with the outer mitochondrial membrane. Titratable antibody binding was observed for extracts of turkey spermatozoa and isolated mitochondria. The antibody did not recognize proteins separated by SDS-PAGE, but on Western blots of proteins separated by native gradient-PAGE, the antibody recognized a broad band greater than 660 kDa. No effects on fertilizing capacity, embryonic mortality, or hatchability of eggs were observed when the antibody was added to turkey semen prior to insemination. When semen stored for 0, 3, 6, 24, and 48 h was immunolabeled with 4C7/2E4, the percentage of spermatozoa with unlabeled midpieces was significantly increased by 6 h of storage. The number of free mitochondria and damaged midpieces also significantly increased with storage.

Animals↗
PubMed2001

Synergistic control of stimulated pronosupination with the stimulated grasp of persons with tetraplegia.

The control of stimulated forearm pronosupination in concert with stimulated hand grasp of persons with tetraplegia has been investigated. It has been shown that hand grasp stability increased as supination was achieved. In accordance with this, a strategy of object acquisition has been proposed incorporating pronosupination and hand grasp. It has been proposed that, after object acquisition in the pronated posture, that supination be used to increase grasp stability. Three types of pronosupination control which act in synchrony with grasp were implemented incorporating this principle. The three types used were position-controlled pronator stimulation, touch-controlled pronator stimulation, and constant pronation stimulation. These controllers played a supporting role to the separate user control of hand grasp and release. The three controllers were evaluated and compared using a standardized test procedure that incorporated stimulated pronosupination control with stimulated grasp. Such methods of pronosupination control are likely to provide enhanced options for improving upper extremity function using electrical stimulation.

Adult↗
PubMed2000

Taste as a factor in the management of nutrition.

The sense of taste lies at the interface between the external and internal milieux, at the point at which the animal must decide which chemicals from the environment to incorporate into itself. Accordingly, taste is organized along a neural dimension of nutrients versus toxins, which corresponds to a behavioral dimension of acceptance versus rejection, and to a hedonic dimension of appetitive versus aversive qualities. Reflexive responses, cognitive analyses, and hedonic reactions appear to be managed at different levels of the nervous system. At the first central relay, the nucleus of the solitary tract, somatic reflexes for acceptance or rejection, and autonomic reflexes anticipating digestion are orchestrated. At the second, the parabrachial nucleus of the rodent, associative mechanisms important to the development of conditioned aversions and sodium appetite are manifested. In the thalamic taste relay, gustatory memories associated with non-visceral events may be formed. Primary taste cortex appears to be the site for a cognitive evaluation of gustatory quality and intensity. Finally, a hedonic assessment of the chemical may be made in secondary taste cortex and in the ventral forebrain sites to which it projects. With this assessment comes integration of the gustatory signal with those from other senses, perhaps to create a perception of flavor. Therefore, a sequence that begins with an analysis of the molecular structure of a chemical in the mouth serves to incorporate that gustatory component into an appreciation of flavor, and to participate in the control of motivational processes that guide dietary selection.

Animals↗
PubMed2000

Ultrastructure of spermatozoa from Japanese quail.

A monoclonal antibody (mAb) to epitopes on mitochondria from turkey spermatozoa cross-reacted with Japanese quail spermatozoal mitochondria. However, the pattern of binding was different from that observed for turkey sperm. The ultrastructure of quail spermatozoa was examined to determine the reason for this difference in antibody binding pattern. Light microscopy, as well as scanning (SEM) and transmission (TEM) electron microscopy, were used to study the morphology of spermatozoa from Japanese quail. Japanese quail had a sauropsid type of sperm cell, which is typical of nonpasserine birds. The spermatozoa were vermiform in shape, with a maximum width of 0.6 microm and an overall length between 230 and 250 microm. An acrosome (3.7 to 4.5 microm), nucleus (20.8 to 23.8 microm), midpiece (160 to 170 micro/m), and tail (40 to 60 microm) were observed. The TEM showed an acrosomal cap surrounding a perforatorium that inserted into the nucleus at the posterior end. Only a distal centriole was observed, which gave rise to a central axoneme with a 9+2 microtubular structure. The axoneme was encased by a spiraled mitochondrial sheath in the midpiece region (64 to 74% of the overall length of the sperm), and mitochondria numbers were estimated to be greater than 1,400 per sperm. In contrast, turkey sperm contain short midpieces with only 20 to 30 mitochondria per sperm. Differences in binding patterns of the mAb to turkey mitochondria between quail and turkey sperm were due to the presence of mitochondria on the exceptionally long midpieces of quail sperm.

Acrosome↗
PubMed2000

Ultrastructure of spermatozoa from Japanese quail.

A monoclonal antibody (mAb) to epitopes on mitochondria from turkey spermatozoa cross-reacted with Japanese quail spermatozoal mitochondria. However, the pattern of binding was different from that observed for turkey sperm. The ultrastructure of quail spermatozoa was examined to determine the reason for this difference in antibody binding pattern. Light microscopy, as well as scanning (SEM) and transmission (TEM) electron microscopy, were used to study the morphology of spermatozoa from Japanese quail. Japanese quail had a sauropsid type of sperm cell, which is typical of nonpasserine birds. The spermatozoa were vermiform in shape, with a maximum width of 0.6 microm and an overall length between 230 and 250 microm. An acrosome (3.7 to 4.5 microm), nucleus (20.8 to 23.8 microm), midpiece (160 to 170 microm), and tail (40 to 60 microm) were observed. The TEM showed an acrosomal cap surrounding a perforatorium that inserted into the nucleus at the posterior end. Only a distal centriole was observed, which gave rise to a central axoneme with a 9+2 microtubular structure. The axoneme was encased by a spiraled mitochondrial sheath in the midpiece region (64 to 74% of the overall length of the sperm), and mitochondria numbers were estimated to be greater than 1,400 per sperm. In contrast, turkey sperm contain short midpieces with only 20 to 30 mitochondria per sperm. Differences in binding patterns of the mAb to turkey mitochondria between quail and turkey sperm were due to the presence of mitochondria on the exceptionally long midpieces of quail sperm.

Acrosome↗
PubMed2000

Quantitative evaluation of two methods of control of bilateral stimulated hand grasps in persons with tetraplegia.

Electrical stimulation has been applied to the paralyzed muscles of both hands of two persons with tetraplegia using percutaneous and implantable electrodes. Two separate methods of user control were being investigated. The first monitored the myoelectric signals from the user's own sternocleidomastoid muscles and the second monitored wrist joint angle. These signals were used as commands to modify the stimulated grasps. The hands were instrumented to detect the degree of hand closure and grip force and the users matched these to specific target parameters using the controller during tracking tasks. Performance in these tracking tasks was measured quantitatively. Wrist control was found to be less sensitive to the direction of hand opening/closing required than the myoelectric control. The user's performance with the myoelectric control demonstrated sensitivity to the target size and the speed of hand movement in response to the command control. The wrist controller required less training than the myoelectric controller for users to become proficient in its use. Based on these results, the wrist controller and the myoelectric controller both provide successful control of bilateral hand grasp and release. Of the two controllers, the wrist controller is likely to provide the greater ease of use, although it is only available to the population of users with active wrist extension.

Electric Stimulation Therapy↗
PubMed2000

Detection of fatigue in the isometric electrical activation of paralyzed hand muscles of persons with tetraplegia.

Paralyzed muscle fatigue is the eventual depression of force due to either prolonged or repetitive electrical stimulation of motor units. The robustness and safety of future functional electrical stimulation (FES) systems will rely on their ability to detect the onset of muscle fatigue. The relative degree of muscle activation can be estimated by monitoring the M-wave. The aim of this study was to test a proposed method of quantitative fatigue assessment that detects muscle force output and its corresponding M-wave measured concurrently. The detection of force and M-wave concurrently allows any reduction in muscle force output to be attributed to either changes in the fatigue state of the stimulated muscle or changes in the degree of stimulus activation of that muscle. The fatigue assessment scheme can thereby accommodate the corresponding changes in muscle force caused by an alteration in the stimulation intensity during fatigue. The Extensor Digitorum Communis (EDC), Extensor Pollicis Longus (EPL), and Flexor Pollicis Longus (FPL) muscles of two C5/C6 tetraplegic men were studied. Stimulation recruitment tests over the pulsewidth range from 0 to 200 micros, were performed at intervals during 20 min of maximal stimulation (200 micro/s). Muscle force correlated to the M-wave parameter, second phase area, with mean correlation coefficients of greater than 0.82, when the muscle was in either a nonfatigued or fatiguing state. After the initial force, likely to be primarily due to the fast glycolytic (FG) motor units, had declined the M-wave demonstrated only minor changes throughout the fatigue of muscle force during 20 min of constant maximal stimulation. The second phase area and root-mean-square (rms) of the M-wave [see Fig. 2(a) reflected muscle activation during modulated stimulation and also remained relatively constant during the fatigue-related force decline when the muscle was stimulated at a constant intensity. This detection of M-wave parameters satisfies the defined requirement for a myoelectric parameter that indicates electrical activation, but is relatively invariant to muscular fatigue. Index Terms-Electrical stimulation, electromyography (EMG), functional electrical stimulation (FES), muscle fatigue, spinal cord injury, tetraplegia.

Action Potentials↗
PubMed2000

The use of bilateral stimulated hand grasp in the bimanual activities of persons with tetraplegia.

Grasp and release has been provided to both upper extremities of subjects with tetraplegia using percutaneous and fully implanted stimulation. This is to determine quantitatively the performance of these subjects in three bimanual tests using two handed stimulation. Their performance here is compared with two separate cases: the same tests using single handed stimulation assisted by a nonstimulated hand and using two unstimulated hands. It was found that bilateral stimulation significantly improved the efficacy of performing the bimanual tests assessed over that using unilateral stimulation assisted by the nonstimulated hand (in two of three tests) or no stimulation three of three tests). These results show quantitative evidence of the benefits of providing bilateral stimulation for the completion of bimanual tasks for persons with tetraplegia who are appropriate candidates for stimulated grasp. These benefits were observed especially in cases where the ability of the subject in completing the task using unilateral stimulation was not strong.

Activities of Daily Living↗
PubMed2000

Rapid induction of sodium appetite modifies taste-evoked activity in the rat nucleus of the solitary tract.

Sodium-deprived rats develop a salt appetite and show changes in gustatory responses to NaCl in the periphery and brain stem; salt-sensitive neurons respond less to hypertonic NaCl than do corresponding cells in replete controls. By administering DOCA and renin, we generated a need-free sodium appetite quickly enough to permit us to monitor the activity of individual neurons in the nucleus of the solitary tract before and after its creation, permitting a more powerful within-subjects design. Subjects received DOCA pretreatment followed by an intracerebroventricular infusion of renin. In animals that were tested behaviorally, this resulted in elevated intake of 0.5 M NaCl. In neural recordings, renin caused decreased responding to hypertonic NaCl across all neurons and in the salt-sensitive neurons that were most responsive to NaCl before infusion. Most sugar-sensitive cells, in contrast, gave increased phasic responses to NaCl. These results confirm that sodium appetite is accompanied by decreased responding to NaCl in salt-sensitive neurons, complemented by increased activity in sugar-sensitive cells, even when created rapidly and independently of need.

Acids↗
PubMed1999

Taste in the monkey cortex.

The sense of taste in humans differs substantially from that of rodents, from which a preponderance of gustatory electrophysiology derives. To establish a more appropriate neural model for human gustation, we recorded the activity of single neurons in the primary taste cortex in 11 alert cynomolgus macaques. Taste cells composed 6% of all neurons encountered. Another 24% responded during mouth and jaw movements, and 4% were sensitive to tactile stimulation of the mouth. Smaller numbers responded during olfactory or visual stimulation, or when the monkey extended his tongue. Taste cells could be divided into four statistically independent groups, corresponding to those most responsive to glucose (38%), NaCl (34%), quinine (22%), or HCI (5%). The location of a taste cell did not predict its response profile, i.e., there was no clear topographic organization of taste sensitivity. We established neural thresholds and intensity-response functions to the basic stimuli and determined that-with the exception of HCl, to which the macaque is relatively insensitive-they were similar to those reported by human subjects. We then turned to the coding of taste quality, as inferred in macaques from the patterns of neural activity elicited by each of greater than 100 stimuli. The results proved generally faithful to human reports of the perceived qualities of these same tastants. Finally, an investigation of taste mixtures revealed a degree of mixture suppression and interaction among basic qualities similar to those reported by humans. We conclude that the alert macaque offers a reliable neural model for human gustation.

Animals↗