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Biomedical subjects

T Chu

Publications and source records attributed to T Chu.

43 records · Page 3Linked to original sources

Induction of an immature T-cell phenotype in malignant helper T cells by cocultivation with epidermal cell cultures.

The possible inductive effect of epidermal cells on T-cell maturation has been examined employing an in vitro cocultivation technique. Mononuclear cells from 6 patients with cutaneous T-cell lymphoma (CTCL) and from 12 healthy volunteers were studied. In the 6 CTCL patients, all showed an expansion of the helper T-cell subpopulation and in one patient with leukemic CTCL, there was almost complete replacement of peripheral blood mononuclear cells by malignant cells with a helper T-cell phenotype. Epidermal cells derived from normal human skin were cultured to confluent monolayers, and were cocultivated with the mononuclear cells from CTCL patients or normal controls for 48 h at a density of 10(6)/ml. Following cocultivation, the surface phenotype of the cells from the 12 healthy volunteers and 5 of the patients with CTCL showed no significant phenotypic change. In the patient with leukemic CTCL, however, the surface phenotype of the malignant T cells had changed, with the acquisition of the T6 antigen by the majority of the cells. Cells cocultivated in medium alone and with human fibroblast monolayers showed no change in surface phenotype. The malignant T cells from the leukemic CTCL patient failed to react in a mixed lymphocyte culture to lymphocytes from 2 different healthy donors, and showed no phenotypic change following culture with these lymphocytes, indicating that the phenotypic change seen was not due to allogeneic stimulation.

Antigens, Differentiation, T-Lymphocyte↗

Video techniques for on-line portal imaging.

The application of on-line portal imaging techniques to the verification of treatment precision is reviewed. The design parameters for a video portal imaging system are described, and the optimization of image quality is discussed with particular emphasis on photon noise. On-line images are presented for a head phantom imaged on a 4 MV linac, and compared with a conventional portal film. The relative advantages of an on-line system are compared with conventional portal film analysis.

Humans↗

Estrogen (E2) and glucocorticoid (Gc) effects on microglia and A beta clearance in vitro and in vivo.

The accumulation of fibrillar aggregates of beta Amyloid (A beta) in Alzheimer's Disease (AD) brain is associated with chronic brain inflammation. Although activated microglia (mu glia) can potentially clear toxic amyloid, chronic activation may lead to excessive production of neurotoxins. Recent epidemiological and clinical data have raised questions about the use of anti-inflammatory steroids (glucocorticoids, Gcs) and estrogens for treatment or prevention of AD. Since very little is known about steroid effects on mu glial interactions with amyloid, we investigated the effects of the synthetic Gc dexamethasone (DXM) and 17-beta estradiol (E2) in vitro in a murine mu glial-like N9 cell line on toxin production and intracellular A beta accumulation. To determine whether the steroid alterations of A beta uptake in vitro had relevance in vivo, we examined the effects of these steroids on A beta accumulation and mu glial responses to A beta infused into rat brain. Our in vitro data demonstrate for the first time that Gc dose-dependently enhanced mu glial A beta accumulation and support previous work showing that E2 enhances A beta uptake. Despite both steroids enhancing uptake, degradation was impeded, particularly with Gcs. Distinct differences between the two steroids were observed in their effect on toxin production and cell viability. Gc dose-dependently increased toxicity and potentiated A beta induction of nitric oxide, while E2 promoted cell viability and inhibited A beta induction of nitric oxide. The steroid enhancement of mu glial uptake and impedence of degradation observed in vitro were consistent with observations from in vivo studies. In the brains of A beta-infused rats, the mu glial staining in entorhinal cortex layer 3, not associated with A beta deposits was increased in response to A beta infusion and this effect was blocked by feeding rats prednisolone. In contrast, E2 enhanced mu glial staining in A beta-infused rats. A beta-immunoreactive (ir) deposits were quantitatively smaller, appeared denser, and were associated with robust mu glial responses. Despite the fact that steroid produced a smaller more focal deposit, total extracted A beta in cortical homogenate was elevated. Together, the in vivo and in vitro data support a role for steroids in plaque compaction. Our data are also consistent with the hypothesis that although E2 is less potent than Gc in impeding A beta degradation, long term exposure to both steroids could reduce A beta clearance and clinical utility. These data showing Gc potentiation of A beta-induced mu glial toxins may help explain the lack of epidemiological correlation for AD. The failure of both steroids to accelerate A beta degradation may explain their lack of efficacy for treatment of AD.

Amyloid beta-Peptides↗

Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic mice.

We previously showed the non-steroidal anti-inflammatory drug (NSAID) ibuprofen suppresses inflammation and amyloid in the APPsw (Tg2576) Tg2576 transgenic mouse. The mechanism for these effects and the impact on behavior are unknown. We now show ibuprofen's effects were not mediated by alterations in amyloid precursor protein (APP) expression or oxidative damage (carbonyls). Six months ibuprofen treatment in Tg+ females caused a decrease in open field behavior (p < 0.05), restoring values similar to Tg- mice. Reduced caspase activation per plaque provided further evidence for a neuroprotective action of ibuprofen. The impact of a shorter 3 month duration ibuprofen trial, beginning at a later age (from 14 to 17 months), was also investigated. Repeated measures ANOVA of Abeta levels (soluble and insoluble) demonstrated a significant ibuprofen treatment effect (p < 0.05). Post-hoc analysis showed that ibuprofen-dependent reductions of both soluble Abeta and Abeta42 were most marked in entorhinal cortex (p < 0.05). Although interleukin-1beta and insoluble Abeta were more effectively reduced with longer treatment, the magnitude of the effect on soluble Abeta was not dependent on treatment duration.

Aging↗

Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology.

Both oxidative damage and inflammation have been implicated in age-related neurodegenerative diseases including Alzheimer's Disease (AD). The yellow curry spice, curcumin, has both antioxidant and anti-inflammatory activities which confer significant protection against neurotoxic and genotoxic agents. We used 22 month Sprague-Dawley (SD) rats to compare the effects of the conventional NSAID, ibuprofen, and curcumin for their ability to protect against amyloid beta-protein (Abeta)-induced damage. Lipoprotein carrier-mediated, intracerebroventricular infusion of Abeta peptides induced oxidative damage, synaptophysin loss, a microglial response and widespread Abeta deposits. Dietary curcumin (2000 ppm), but not ibuprofen, suppressed oxidative damage (isoprostane levels) and synaptophysin loss. Both ibuprofen and curcumin reduced microgliosis in cortical layers, but curcumin increased microglial labeling within and adjacent to Abeta-ir deposits. In a second group of middle-aged female SD rats, 500 ppm dietary curcumin prevented Abeta-infusion induced spatial memory deficits in the Morris Water Maze and post-synaptic density (PSD)-95 loss and reduced Abeta deposits. Because of its low side-effect profile and long history of safe use, curcumin may find clinical application for AD prevention.

Amyloid beta-Peptides↗

A technique for the evaluation of a missing tissue compensator system.

A two dimensional approach to the evaluation of a missing tissue compensator system has been developed and implemented. Quantitative descriptors of the dose area histograms generated by scanning films irradiated under a variety of compensated and uncompensated conditions are proposed. The method has been found to be useful during the acceptance testing of a commercial compensator system and the results of this exercise are presented.

Evaluation Studies as Topic↗