Search PubMed⌕ Search

Biomedical subjects

T D Lee

Publications and source records attributed to T D Lee.

At least 55 records · Page 3Linked to original sources
PubMed1998

Dose-dependent enhancing and inhibitory effects of A77 1726 (leflunomide) on cytotoxic T lymphocyte induction.

Leflunomide is an immunosuppressive prodrug which prevents allograft rejection in several animal model systems and may, therefore, have clinical application in organ transplant recipients. Although cytotoxic T lymphocytes (CTL) are an important component of the allograft rejection response, the effect of leflunomide on CTL development has not been thoroughly explored. In this study we have determined the effect of A77 1726, the active metabolite of leflunomide, on CTL induction in C57BL/6 mouse T cell cultures stimulated with anti-CD3 monoclonal antibody. Conjugate formation with P815 target cells, granzyme B enzymatic activity in CTL lysates, and P815 cytolysis in a 51Cr-release assay were used as determinants of in vitro CTL function. At high concentrations (10-20 microM), A77 1726 strongly inhibited CTL generation. In contrast, a low concentration (0.5 microM) of A77 1726 promoted CTL development. These dose-dependent opposing effects of A77 1726 on CTL induction could not be attributed to alterations in CD8+ lymphocyte percentages, interleukin-2 or CD25 expression, or the ability to conjugate with P815 target cells. However, both interferon-gamma and granzyme B expression were significantly decreased when CTL were induced in the presence of 10-20 microM A77 1726, and were slightly, but not always significantly, elevated in the presence of 0.5 microM A77 1726. We conclude that at high concentrations A77 1726 is a potent inhibitor of CTL induction, but a low concentration of A77 1726 enhances CTL development.

Animals↗
PubMed1998

Rapid protein identification using a microscale electrospray LC/MS system on an ion trap mass spectrometer.

A methodology has been developed for the rapid identification of gel separated proteins. Following in gel protein digestion with trypsin, the resulting peptide mixture is analyzed by on-line liquid chromatography, electrospray mass spectrometry (LC/MS). The mass spectral data containing either accurate mass values or sequence specific fragment ion information is then matched to a database of known protein sequences. Key features of the LC/MS system are the use of a novel integrated, microscale LC column-electrospray interface and variable flow solvent delivery to optimize the efficiency of sample loading and gradient elution. With these enhancements, only 10 min is required to analyze each sample. The method is routine for sample amounts ranging from 50 to 500 fmol. The analysis parameters for the ion trap mass spectrometer have to be carefully adjusted in order to keep pace with the rapidly eluting LC peaks. Although designed for rapid LC separations, the integrated column-electrospray interface is also able to provide extended analyses of selected components using a technique known as "peak parking".

Amino Acid Sequence↗
PubMed1998

On the dynamics of motor learning research.

In this paper I have attempted to conceptualize the dynamical pattern view of learning (Zanone & Kelso, 1992, 1994, 1997) in terms of some historical similarities to the dynamic pattern perspective, unique contributions, and potential problems to be addressed in future research and theory. For researchers interested in motor learning issues, all three of these points can be viewed only as positive advances to the field of study.

Behavior↗
PubMed1998

Adhesion of tumoricidal eosinophils to MCA-38 colon adenocarcinoma cells involves protein tyrosine kinase activation and is diminished by elevated cyclic AMP in the effector cell.

Although eosinophils have been implicated in immune responses to certain types of tumors, the mechanisms of anti-tumor activity by eosinophils are poorly understood. We show here that mouse eosinophils kill allogeneic MCA-38 colon adenocarcinoma cells in the absence of specific anti-body. Eosinophil adhesion to MCA-38 monolayers occurred within 15 min and plateaued at 90 min. Although mouse eosinophils express alphaL (CD11a), alphaM (CD11b), and alpha4 (CD49d) integrin chains, blocking antibody studies revealed that these molecules are not involved in eosinophil binding to MCA-38 cells. Adhesion was also fibronectin-independent. Binding was inhibited when eosinophils, but not MCA-38 cells, were pretreated with methyl 2,5-dihydroxycinnamate (MDHC), a selective inhibitor of protein tyrosine kinases, or 8-Br-cAMP-Na, a cell-permeable cyclic AMP analogue. Adhesion was unaffected by calphostin C, a specific inhibitor of protein kinase C, and wortmannin, a selective inhibitor of phosphatidylinositol 3-kinases.

Adenocarcinoma↗
PubMed1997

Aortic valve grafts in the rat: evidence for rejection.

OBJECTIVE: The histopathologic changes of fresh rat aortic valve allografts over time and the effect of cryopreservation were examined. METHODS: Fifty-six syngeneic and allogeneic rat aortic valves were transplanted, either fresh or after cryopreservation, and then at different time points they were explanted and histologically examined in a blinded fashion. RESULTS: Histopathologic changes in the first week are similar in syngeneic and allogeneic grafts. Fresh syngeneic grafts and leaflets retained normal structure up to 56 days. Allogeneic grafts showed retrovalvular thrombus formation with leaflet ghosts and neointimal proliferation. Cryopreservation did not alter this process. CONCLUSIONS: Cardiac allograft valves in the rat model undergo changes that are characteristic of cell-mediated rejection and lead to valve failure.

Animals↗
PubMed1997

Prevention of postsurgical adhesions with N,O-carboxymethyl chitosan: examination of the most efficacious preparation and the effect of N,O-carboxymethyl chitosan on postsurgical healing.

BACKGROUND: Adhesion formation after operation can result in major complications. We have previously demonstrated that N,O-carboxymethyl chitosan (NOCC) is an effective inhibitor of postsurgical peritoneal adhesion formation. However, the optimal form of NOCC (i.e., cross-linked gel versus solution), as well as the best time of administration for optimal reduction in adhesion development, was not investigated. In addition, because adhesion formation and normal wound healing are related events and weakening of wound healing would be a serious drawback to the use of NOCC clinically, we wished to assess the effect of NOCC on the healing of surgical incisions. METHODS: Three surgical models were used: (1) an abdominal aortic anastomosis, (2) a large bowel anastomosis, and (3) an abdominal skin incision. In the first model Sprague-Dawley rats received an abdominal aortic transection and repair. NOCC solution or gel was administered at different time points throughout the procedure. Control and NOCC-treated animals were killed 14 days after operation. The condition of the anastomosed vessel was examined, and adhesion frequency and intensity in the abdomen were scored. In the second model Sprague-Dawley rats underwent large bowel transection and repair. Control and NOCC-treated animals were killed on postoperative days 4, 7, and 14, and strength of repair was assessed by removal of the large bowel and measurement of the bursting strength of the repaired incision. In the third model rats received an abdominal incision and were immediately closed. Control and NOCC-treated animals were killed 14 days after operation, and the skin tensile strength of the wound was measured with a tensiometer. RESULTS: In all three models studied, NOCC treatment did not adversely affect the strength of the repaired incision. NOCC solution administered before operation did not greatly reduce adhesion formation, whereas the delivery of both NOCC gel and solution after operation was most efficacious. CONCLUSIONS: The administration of both NOCC gel and solution after operation is most efficacious, and NOCC does not compromise postsurgical healing in rats at doses that prevent peritoneal adhesion formation.

Abdomen↗
PubMed1997

Characterization of myomodulin-related peptides from the pulmonate snail Helix aspersa.

Three myomodulin-related peptides--pQLSMLRLamide, PMSMLRLamide, and SLGMLRLamide--have been purified and sequenced from extracts of whole snails. The level of immunoreactive myomodulin was shown by HPLC and RIA to be widely distributed among 26 different snail tissues, with the highest levels (higher even than those in the central ganglia) occurring in certain male reproductive organs. Synthetic pQLSMLRLamide modified either the spontaneous rhythmic activity or the resting tone of several isolated muscular organs: the aorta, ventricle, upper gut, epiphallus, flagellum, and spermatheca; but the retractor muscles of the pharynx, penis, and tentacle were unaffected.

Animals↗
PubMed1997

Learning a new bimanual coordination pattern: reciprocal influences of intrinsic and to-be-learned patterns.

According to dynamic pattern theory, intrinsically stable bimanual coordination patterns affect, and are affected by, the acquisition of a new coordination pattern. In Experiment 1, subjects practiced either a 45 degrees or a 135 degrees relative phase pattern for 4 days; in Experiment 2, they practiced a 90 degrees relative phase pattern over 6 days. Retention tests were conducted 4 weeks after the last practice session in both experiments. Performance on both the in-phase (0 degree) and anti-phase (180 degrees) patterns was also measured on each day. Contrary to predictions, the experiments revealed that reciprocal effects between the intrinsic patterns and the new pattern were only temporary, and did not affect learning in any permanent way. As well, learning a new pattern was not differentially affected by its relation to an intrinsic pattern.

Adult↗
PubMed1997

Purification, identification, concentration and bioactivity of (Z)-7-dodecen-1-yl acetate: sex pheromone of the female Asian elephant, Elephas maximus.

In their natural ecosystems, adult male and female Asian elephants, Elephas maximus, live separately. For several weeks prior to ovulation, female elephants release a substance in their urine which elicits a high frequency of non-habituating chemosensory responses, especially flehmen responses, from male elephants. These responses occur prior to, and are an integral part of, mating. Using bioassay-guided fractionation, quantitatively dependent on these chemosensory responses, a specific sex pheromone was isolated and purified by an alternating series of organic and/or aqueous extractions, column chromatography, gas chromatography and high-performance liquid chromatography. Using primarily 1H-proton nuclear magnetic resonance (NMR) spectrometry and gas chromatography-mass spectrometry (GC-MS) of the urine-derived pheromone and its dimethyl disulfide derivative, we determined the structure of the active compound to be (Z)-7-dodecen-1-yl acetate (Z7-12:Ac). Concentrations of Z7-12:Ac in the female urine increased from non-detectable during the luteal phase to 0.48 microgram/ml (0.002 mM) early in the follicular phase and to 33.0 micrograms/ml (0.146 mM) just prior to ovulation. Bioassays with commercially available authentic synthetic Z7-12:Ac, using 10 Asian male elephants at several locations in the US, demonstrated quantitatively elevated chemosensory responses that were robust during successive tests, and several mating-associated behaviors. Bioassays with Z7-12:Ac with adult male elephants dwelling in more natural social situations in forest camps in Myanmar revealed some differing contextual pre-mating behavioral components. The remarkable convergent evolution of this compound suggests that compounds identified in mammalian exudates that are also present in pheromone blends of insects should be re-evaluated as potential mammalian chemosignals.

Animals↗
PubMed1997

Effects of aging and reduced relative frequency of knowledge of results on learning a motor skill.

Although there is evidence for age-related changes in both cognition and motor control, very little is known about the effect of age on learning of new motor skills. The present experiment addressed the interaction between aging and the role of knowledge of results (KR) on a motor learning task. Using a three-segment task on which each segment had specific timing goals, three different manipulations of relative frequency of information about performance were compared in younger and older adults. The three conditions were (a) 100% KR in which information about performance on each segment was provided after every trial, (b) 67% KR in which the performance information was faded over trials, and (c) 67% KR in which the performance information was faded over the segments within each trial. Following 90 acquisition trials, all subjects performed retention, transfer, and reacquisition tests. There were age-related differences for movement accuracy and consistency on acquisition and on the retention tests but not on the transfer test. However, none of these differences interacted with the frequency of KR manipulations. Surprisingly, there was no effect due to the fading schedules of KR. In general, these results indicated that younger and older adults use KR in a similar way to learn a motor skill.

Adult↗
PubMed1997

Dissociated contextual interference effects in children and adults.

24 7-yr.-old children and 24 university-age adults practiced a ballistic aiming task under either low contextual interference (blocked practice) or high contextual interference (random practice). All subjects performed 90 acquisition trials, followed by 20 transfer trials and 15 retention trials. Similar to previous findings, the adults performed the acquisition trials better under blocked than under random conditions, yet performed the retention and transfer tests better after random than blocked practice. No differences in acquisition were found between blocked and random practice conditions for the children; nevertheless, the random group performed the retention and transfer tests better than the blocked group. The results are discussed in relation to applied and theoretical issues of contextual interference.

Adult↗
PubMed1996

Neuropeptide Y 3-36 is an endogenous ligand selective for Y2 receptors.

Neuropeptide Y (NPY 1-36) binds to Y1 and Y2 receptors with similar affinity. No endogenous molecular form of NPY with selectivity for Y1 or Y2 receptors has been described so far. We report the presence of an endogenous fragment of NPY in porcine brain, NPY 3-36, which lacks the amino-terminal dipeptide Tyr-Pro of NPY 1-36. NPY 3-36 accounts for 35% of NPY-like immunoreactivity in porcine brain. We have compared binding of NPY 3-36 and NPY 1-36 in model systems of Y1-like (SK-N-MC cells) and Y2-like receptors (CHP234 cells). NPY 3-36 and NPY 1-36 had similarly high affinity for Y2-like receptors on CHP234 cells, but NPY 3-36 had a 1000-fold lower affinity than NPY 1-36 for Y1-like receptors on SK-N-MC cells. Thus amino-terminal cleavage of NPY 1-36 generating NPY 3-36 converts an unselective Y1/Y2 receptor ligand into a highly Y2 selective ligand. This may be a means of fine tuning NPY biological actions.

Animals↗