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Biomedical subjects

L L Chen

Publications and source records attributed to L L Chen.

At least 73 records · Page 4Linked to original sources

Supplementary eye field contrasted with the frontal eye field during acquisition of conditional oculomotor associations.

1. The companion paper reported that a substantial proportion of cells in the supplementary eye field (SEF) of macaque monkeys show significant evolution of neuronal activity as subjects learn new and arbitrary stimulus-saccade associations. The purpose of the present study was to compare and contrast the activity of the SEF and the frontal eye field (FEF) during such conditional oculomotor learning. 2. In both SEF and FEF, we observed learning-dependent and learning-selective activity, defined as significant evolution of task-related activity as monkeys learned which of four saccades was instructed by a novel stimulus. By definition, in addition to changes as the monkeys learned the instructional significance of a novel instruction stimulus, learning-dependent activity also showed task-related modulation for trials instructed by familiar stimuli, whereas learning-selective activity did not. Of the 186 SEF neurons adequately tested, 81 (44%) showed one of these two categories of learning-related change. By contrast, of the 90 FEF neurons adequately tested, only 14 (16%) showed similar properties. This difference was highly statistically significant (chi 2 = 21.1; P < 0.001). 3. We also observed persistent differences in activity for trials with familiar versus novel instruction stimuli, which we termed learning-static effects. In some cases, the learning-static effect coexisted with learning-dependent or learning-selective changes in activity, although in others it did not. In the former cases, activity changed systematically during learning, but reached a level that differed from that for familiar stimuli instructing the same saccade. In the latter cases, the activity did not change significantly as the monkey learned new conditional oculomotor associations, but did show a significant difference depending upon whether a novel or familiar stimulus instructed a given saccade. Overall, 66 of 186 (35%) cells in the SEF and 17 of 90 (19%) cells in the FEF showed learning-static effects in one or more task periods. This difference was statistically significant (chi 2 = 7.9; P < 0.005). 4. The significant difference in the properties of SEF and FEF cells suggests a functional dissociation of the two areas during conditional oculomotor learning. In this respect, the FEF resembles the primary motor cortex, whereas the SEF resembles the premotor cortex.

Animals↗

Mantle-cell lymphoma in a patient with human immunodeficiency viral infection.

Rare cases of low-grade lymphomas have been described in patients with human immunodeficiency virus (HIV) infection. However, this is the first reported case of mantle-cell lymphoma, a type of low-grade lymphoma, in a patient who also had HIV infection. Salient clinical features included lymphocytosis, lymphadenopathy, splenomegaly, and involvement of the bone marrow and meninges. The disease proved to be unusually aggressive and response to chemotherapy was insignificant. The patient survived only 4 months.

Adult↗

Cytokine regulation of gelatinase production by head and neck squamous cell carcinoma: the role of tumor necrosis factor-alpha.

Gelatinases (GLs) belong to a family of enzymes known as matrix metalloproteinases (MMPs), which are produced by both normal and neoplastic cells. These enzymes have been implicated in tumor invasion and metastasis, although the mechanism of regulation of tumor MMP production is unknown. Since our previous studies have shown that numerous cytokines are present in the tumor microenvironment, our goal was to establish the effect of selected cytokines on GL production by both established tumor cell lines and primary cultures of head and neck squamous cell carcinoma (HNSCC). Supernatants of HNSCC cell lines SCC-25 and FADU stimulated with interleukin (IL)-1 alpha and IL-1 beta demonstrated modest induction of 92 kd GL production by zymogram analysis when compared with controls; IL-2, IL-6, and interferon-gamma had no consistent effect on MMP production. Stimulation of cell lines with tumor necrosis factor (TNF)-alpha (10(4) to 10 U/mL), however, dramatically enhanced production of 92 kd GL by both cell lines in a dose-dependent fashion, although tissue inhibitor of metalloproteinase (TIMP) expression was unaffected. Northern blot analysis showed that this enhancement of 92 kd GL occurred at the messenger RNA level. Stimulation of short-term primary tumor cultures with TNF-alpha resulted in significant enhancement of 92 kd GL expression in one of four cultures and enhancement of 72 kd GL expression in all cultures. The observed increase in GL expression by TNF-alpha suggests a role for this cytokine in the regulation of GL expression by tumor cells during invasion and metastasis.

Carcinoma, Squamous Cell↗

The role of amygdala norepinephrine in memory formation: involvement in the memory enhancing effect of peripheral epinephrine.

The present study examined the roles of amygdala alpha 1 and beta noradrenergic receptors in memory formation as well as their involvement in the memory enhancing effect of peripheral epinephrine (E). Male Sprague-Dawley rats with cannulae implanted into the amygdala were trained on the one-trial inhibitory avoidance task and tested for retention 24 hrs later. Immediately after training, they received various treatments to alter amygdala noradrenergic functions and/or peripheral adrenergic functions. Separate groups of animals were decapitated 10 min after training for assays of monoamine levels in various brain regions by the HPLC-EC method. Results indicated that, when infused into the amygdala immediately after training, isoproterenol and 8-bromo-cAMP enhanced retention, while propranolol impaired retention. On the other hand, phenylephrine or prazosin failed to produce statistically significant effects. Posttraining intra-amygdala infusion of propranolol, but not prazosin, abolished the memory enhancing effects of norepinephrine (NE) infused into the amygdala or E given subcutaneously to the adrenal demedullated rats. Depletion of amygdala NE by the selective neurotoxin DSP-4 also abolished the memory modulatory effects of E. These findings support that amygdala noradrenergic beta, but not alpha 1, receptors are involved in both central and peripheral memory modulatory processes. However, since the postmortem tissue NE levels in the amygdala and other brain regions did not differ among various groups, the inhibitory avoidance training and peripheral E may only activate a transient functional increase in the amygdala NE activity.

Amygdala↗

Tat-mediated delivery of heterologous proteins into cells.

The Tat protein of human immunodeficiency virus 1 (HIV-1) can enter cells efficiently when added exogenously in tissue culture. To assess if Tat can carry other molecules into cells, we chemically cross-linked Tat peptides (residues 1-72 or 37-72) to beta-galactosidase, horseradish peroxidase, RNase A, and domain III of Pseudomonas exotoxin A (PE) and monitored uptake colorimetrically or by cytotoxicity. The Tat chimeras were effective on all cell types tested, with staining showing uptake into all cells in each experiment. In mice, treatment with Tat-beta-galactosidase chimeras resulted in delivery to several tissues, with high levels in heart, liver, and spleen, low-to-moderate levels in lung and skeletal muscle, and little or no activity in kidney and brain. The primary target within these tissues was the cells surrounding the blood vessels, suggesting endothelial cells, Kupffer cells, and/or splenic macrophages. Tat-mediated uptake may allow the therapeutic delivery of macromolecules previously thought to be impermeable to living cells.

ADP Ribose Transferases↗

Phospholipid metabolite expression by head and neck squamous cell carcinoma.

OBJECTIVE: To characterize the presence and production of various phospholipid metabolites by head and neck squamous cell carcinoma (HNSCC) and squamous cell carcinoma cell lines in vitro and in vivo. DESIGN: The HNSCC tumor homogenates and supernatants of HNSCC tumor cultures and established squamous cell carcinoma cell lines were assayed for prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and platelet activating factor (PAF). In vitro experiments were carried out under baseline conditions or with exposure to several known immunomodulators (epidermal growth factor, bacterial lipopolysaccharide, and interleukin 1). PATIENTS: The HNSCC tumor tissue was obtained from primary tumor or cervical lymph node metastasis of surgical resections. MAIN OUTCOME MEASURES: Prostaglandin E2, LTB4, and PAF were measured in tumor homogenates and cell culture supernatants using standardized radioimmunoassay kits. RESULTS: All tumor homogenates (eight of eight) contained detectable levels of PGE2 (range, 324 to 2258 pg/g of tumor tissue) and LTB4 (range, 790 to 41,900 pg/g of tumor tissue); PAF was detected in six of eight homogenates (range, 7362 to 40,788 pg/g of tumor tissue). All of the short-term primary HNSCC tumor cultures and squamous carcinoma lines produced PGE2 (range, 90 to 1160 pg/10(6) cells), and half of the cultures produced LTB4 (range, 100 to 1700 pg/10(6) cells); none of the cultures or cell lines produced detectable levels of PAF. Interleukin 1 significantly enhanced production of PGE2 by tumor cultures (P < .02). Characterization of tumor cultures with a fibroblast antibody marker, BR2, revealed that 26% to 64% of tumor culture cells were fibroblasts. CONCLUSIONS: Prostaglandin E2, LTB4, and PAF are present in the tumor microenvironment, where they may be involved in the local immunosuppression phenomenon seen in HNSCC. Both PGE2 and LTB4 were produced in vitro by tumor cultures and squamous cell carcinoma cell lines; PAF was not produced by tumor cultures in vitro and therefore may be a product of local immune cells in HNSCC in vivo. Interleukin 1 and PGE2 may interact in immunoregulation in the HNSCC tumor microenvironment.

Aged↗

Head-direction cells in the rat posterior cortex. I. Anatomical distribution and behavioral modulation.

We examined the behavioral modulation of head-directional information processing in neurons of the rat posterior cortices, including the medial prestriate (area Oc2M) and retrosplenial cortex (areas RSA and RSG). Single neurons were recorded in freely moving rats which were trained to perform a spatial working memory task on a radial-arm maze in a cue-controlled room. A dual-light-emitting diode (dual-LED) recording headstage, mounted on the animals' heads, was used to track head position and orientation. Planar modes of motion, such as turns, straight motion, and nonlocomotive states, were categorized using an objective scheme based upon the differential contributions of movement parameters, including linear and angular velocity of the head. Of 662 neurons recorded from the posterior cortices, 41 head-direction (HD) cells were identified based on the criterion of maintained directional bias in the absence of visual cues or in the dark. HD cells constituted 7 of 257 (2.7%) cells recorded in Oc2M, 26 of 311 (8.4%) cells in RSA, and 8 of 94 (8.5%) cells in RSG. Spatial tuning of HD cell firing was modulated by the animal's behaviors in some neurons. The behavioral modulation occurred either at the preferred direction or at all directions. Moreover, the behavioral selectivity was more robust for turns than straight motions, suggesting that the angular movements may significantly contribute to the head-directional processing. These behaviorally selective HD cells were observed most frequently in Oc2M (4/7, 57%), as only 5 of 26 (19%) of RSA cells and none of the RSG cells showed behavioral modulation. These data, taken together with the anatomical evidence for a cascade of projections from Oc2M to RSA and thence to RSG, suggest that there may be a simple association between movement and head-directionality that serves to transform the egocentric movement representation in the neocortex into an allocentric directional representation in the periallocortex.

Animals↗

Head-direction cells in the rat posterior cortex. II. Contributions of visual and ideothetic information to the directional firing.

This study investigated the effects of visual and ideothetic cues on the spatial tuning of head-direction (HD) cells recorded in the rat posterior cortices. Extracellular, single unit responses were recorded from animals performing each of two different tasks, a spatial working memory task on a radial-arm maze and a passive rotation task on a modified "lazy Susan" platform. The influence of visual cues was assessed by manipulating the position of one white and three black cue-cards placed around the maze. We found three major categories of HD cells based on their response to cue manipulations in the maze tasks. Type A cells (10/41) rotated their preferred directions along with the rotation of the cues. The majority (type B, 25/41) of the HD cells were unaffected by the rotation of visual cues, maintaining their established preferred direction. Type C cells (6/41) showed complex responses to cue rotation, with the preferred direction reflecting either a combination of both type A and type B responses or an unpredictable response. The results indicate that the internal representation of directionality can be calibrated by visual cues and that some mnemonic processes may have been involved in the registration of the previous cue locations. Eleven cells were tested in both the maze task and the passive rotation task. Most (9/11) showed a significant directionality in the former task, but showed either no or weak directionality in the latter task, suggesting that movement-related ideothetic cues may be used in supporting the directional firing of these cells. Only two cells showed significant directionality in both tasks. Their established preferred directions did not rotate along with the cues in the maze task, but did rotate with the cues in the passive rotation task. We conclude that the dynamic aspect of the directional tuning in these cortical HD cells may represent on-line calibration of an angular coordinate representation.

Animals↗

An accurate impression method for implant prosthesis fabrication.

The long-term success of an implant prosthesis depends not only on the development of osseointegration, but also on the maintenance of osseointegration after the prosthetic phase. To achieve this, a passive superstructure must be fabricated. Errors that result from the impression transfer method of implant position during the impression procedures often made it necessary to section and solder metal frameworks repeatedly. This article presents a modified impression technique intended to deal with the problems of more traditional impressions with the aim of achieving a more accurate master cast.

Dental Casting Technique↗

Patterns of abnormal myogenesis in human cleft palates.

To test the hypothesis that soft palate muscles are abnormal in cleft palate, we compared soft palate morphogenesis in fetuses with cleft palate (n = 4) to age-matched (n = 3) and nonmatched (n = 1) control specimens. The morphologic status of all soft palate and masticatory structures were classified into one of six stages based on the level of histogenesis. At 54 mm crown-rump length (CRL), the levator veli palatini (L), palatopharyngeus (PP), and palatoglossus (PG) in cleft subjects demonstrated mesenchymal condensation into myoblastic fields, lagging behind the control specimens (97 mm CRL), which displayed definitive fields of myoblasts and myotube formation. In the 175 mm and 225 mm cleft and the 170 mm and 192 mm control specimens, muscular morphology was similar and had reached its postnatal appearance for the tensor veli palatini (175 m only) and L, PP, PG (225 mm only). Muscle fiber directions were, however, disoriented and disorganized, especially close to the medial epithelial edge of the cleft. The levator veli palatini, could not be distinguished as a discrete muscle in the cleft specimens, and what we believed to be the PP and PG seemed "normal" at the level of light microscopy, but malpositioned in a superior direction. This preliminary study demonstrates for the first time that early myogenesis in cleft palates differs from normal.

Case-Control Studies↗

[Pharmacological actions of hyphae body of Auricularia auricula (L. ex Hook) Underw and its alcoholic extract].

The percent peripheral blood T lymphocytes were elevated and HC50 reduction induced by cyclophosphamide was recovered after the hyphae body of Auricularia auricula had been ip administered in mice. The action of blood platelet agglutination in rats induced by ADP was inhibited and the time of erythrocytic electrophoresis in mice was shortened after the alcoholic extract had been ig administered.

Animals↗

[Studies on the isolation of endogenous sleep factors from Tupaia Belangeri Chinensis (TBC) after sleep deprivation].

The present study was undertaken to explore endogenous sleep factors isolated from 48-72 h sleep deprived (SD) male Tupaia belangeri chinensis (TBC). Only drink ad libitum (10% glucose) was available within 24 h before collection of urine. Controlled "clean" urinary samples were pooled and stored at 20 C. Fraction I-V from the urine were determined after ultrafiltration and Sephadex-G15. Amino-acid analysis of each fraction was automatically done by a 835 Amino-acid Analyzer, respectively. Bioassay was performed in 40 adult rabbits weighing 2.5-3.5 kg of either sex. Experiments were undertaken via the mesodiencephalic intraventricular infusion. Results show that S2C (Fraction-III) (50 micrograms/rabbit, i.c.v.) exhibited significant delta-enhancing effect compared to the controls. Further purification was done with Sephadex G-25 and Sephadex LH-20. The more purified S4B (50 micrograms/rabbit, i.c.v.) also exhibited significant delta-enhancing effect compared to the controls. The amino-acid analysis of Fraction-III revealed that the compositional contents of S2C and S4B are different from what have been known with Factor S, DSIP and SPS.

Acetylmuramyl-Alanyl-Isoglutamine↗

Altered epidermal growth factor signal transduction in activated Ha-ras-transformed human keratinocytes.

Epidermal growth factor (EGF) can stimulate proliferation and 92 kDa gelatinase/matrix metalloproteinase (MMP-9) expression. The induction of MMP-9 is not only pathologically significant for invasion and metastasis, but also serves as a semiquantitative measure of EGF signal transduction. In order to examine the role of mutated ras p21 in EGF signal transduction, an activated Ha-ras-transformed human keratinocyte cell line was developed and characterized. Overexpression of the mutated Ha-ras p21 in these cells was demonstrated. Our results showed that EGF induced 92 kDa MMP-9 secretion was doubled in the ras-transformed keratinocytes in comparison to the parent cells. The karyotype, the expression of EGF receptor (EGFR) and transforming growth factor (TGF) alpha at the mRNA level remained unchanged. These results suggest that the presence of high levels of mutated ras p21 may be responsible for the aberrant EGF signal transduction and contributes to transformation. In addition, a reduction of TGF beta expression at mRNA level by 70% was found in the activated Ha-ras-transformed keratinocytes when compared to the parent cells.

Cell Line, Transformed↗

Enflurane inhibits NMDA, AMPA, and kainate-induced currents in Xenopus oocytes expressing mouse and human brain mRNA.

Effects of enflurane, an inhalational anesthetic, on NMDA, AMPA, and kainate-gated currents were examined in Xenopus laevis oocytes expressing mouse or human brain mRNA. In oocytes expressing mouse mRNA, enflurane at an anesthetic concentration (1.8 mM) inhibited the NMDA-, AMPA-, and kainate-induced currents by 29-40%, 30-33%, and 20-27%, respectively, suggesting that all three glutamate ionotropic receptors are susceptible to suppression by inhalational anesthetics. Furthermore, inhibition by enflurane was independent of the concentrations of the agonists (NMDA, AMPA, and kainate) or the NMDA-coagonist (glycine). This suggests that enflurane inhibition does not result from a competitive interaction at glutamate or glycine binding sites. Enflurane also suppressed the oscillation and apparent desensitization of NMDA currents, suggesting an inhibition of Ca2+ influx through the NMDA channel. In oocytes expressing human brain mRNA, only kainate produced observable currents. Kainate currents of human channels were smaller in size than those of the mouse; however, the kainate concentration-response curve and percent inhibition (27-29%) by enflurane were similar for mice and humans. The results suggest that human and mouse kainate receptors have similar pharmacological characteristics.

Aged↗