The application of diffusion tensor imaging (DTI) to the evaluation of developing brain remains an area of active investigation. This review focuses on the changes in DTI parameters which accompany both brain maturation and injury. The two primary pieces of information available from DTI studies-water apparent diffusion coefficient and diffusion anisotropy measures-change dramatically during development, reflecting underlying changes in tissue water content and cytoarchitecture. DTI parameters also change in response to brain injury. In this context, not only does DTI offer the possibility of detecting injury earlier than conventional imaging methods, but also appears more sensitive to disruption of white matter than any other imaging method. DTI offers unique insight into brain injury and maturation, and does so in a fashion that can be readily applied in a clinical setting.

Adolescent↗

PubMedDate not supplied

The maintained discharge of neurons in the cat lateral geniculate nucleus: spectral analysis and computational modeling.

The maintained discharge of neurons along the early visual pathway in mammals constitutes the "noise" from which the visual signal must be discriminated. The statistics of this background noise in cat retinal ganglion cells (RGCs) have been shown to conform to that of a gamma-distributed renewal process (Kuffler et al., 1957; Barlow & Levick, 1969), and power spectrum analysis reveals that this property allows for low noise levels at the temporal-frequency range (0-10 Hz) most important for visual performance (Troy & Robson, 1992). In this study, we compare the statistics of the maintained discharge of cat lateral geniculate neurons with those of its RGC input by simultaneous recordings of spikes and S-potentials in single relay cells of the cat lateral geniculate nucleus (LGN). We demonstrate that, during primarily tonic spiking activity, the LGN maintained discharge preserves the renewal process statistics of its RGC input and also generates relatively little noise at the temporal frequencies important for vision. However, during burst spiking activity, the renewal process model breaks down and increased noise is generated at 2-10 Hz. This suggests that optimization of the visual signal/noise ratio is not a prime consideration in the behavioral states associated with bursting activity in the LGN. The occurrence of burst spikes in LGN relay cells is dependent on the activity of T-type calcium channels in their plasma membranes (Jahnsen & Llinas, 1984a,b). We show that a computational model of LGN relay cells that incorporates T-channel kinetics (Mukherjee & Kaplan, 1995) can correctly simulate LGN maintained discharge statistics during both tonic and bursty firing conditions, and indicates an essential role for this ion channel in determining the dynamic noise properties of the LGN. We also use the computational model to predict how the burstiness of the LGN maintained discharge is affected by the statistics of its RGC input.

Action Potentials↗

PubMedDate not supplied

MUC1-specific CTLs are non-functional within a pancreatic tumor microenvironment.

Pancreatic cancer is a highly aggressive, treatment refractory disease and is the fourth leading cause of death in the United States. In humans, 90% of pancreatic adenocarcinomas over-express altered forms of a tumor-associated antigen, MUC1 (an epithelial mucin glycoprotein), which is a target for immunotherapy. Using a clinically relevant mouse model of pancreas cancer that demonstrates peripheral and central tolerance to human MUC1 and develops spontaneous tumors of the pancreas, we have previously reported the presence of functionally active, low affinity, MUC1-specific precursor cytotoxic T cells (pCTLs). Hypothesis for this study is that MUC1-based immunization may enhance the low level MUC1-specific immunity that may lead to an effective anti-tumor response. Data demonstrate that MUC1 peptide-based immunization elicits mature MUC1-specific CTLs in the peripheral lymphoid organs. The mature CTLs secrete IFN-gamma and are cytolytic against MUC1-expressing tumor cells in vitro. However, active CTLs that infiltrate the pancreas tumor microenvironment become cytolytically anergic and are tolerized to MUC1 antigen, allowing the tumor to grow. We demonstrate that the CTL tolerance could be reversed at least in vitro with the use of anti-CD40 co-stimulation. The pancreas tumor cells secrete immunosuppressive cytokines, including IL-10 and TGF-beta that are partly responsible for the down-regulation of CTL activity. In addition, they down-regulate their MHC class I molecules to avoid immune recognition. CD4+ CD25+ T regulatory cells, which secrete IL-10, were also found in the tumor environment. Together these data indicate the use of several immune evasion mechanisms by tumor cells to evade CTL killing. Thus altering the tumor microenvironment to make it more conducive to CTL killing may be key in developing a successful anti-cancer immunotherapy.

Adoptive Transfer↗

PubMedDate not supplied

Comparative evaluation of antiproliferative activity and induction of apoptosis by some fluoroquinolones with a human non-small cell lung cancer cell line in culture.

Lung cancer is the leading cause of cancer- related death in the world today. Since the effective management of drug resistant lung cancer, and particularly non-small cell lung carcinomas is a major problem, attempts need to be made to identify new potential anticancer drugs that can kill non-small cell lung cancer cells efficiently. In the present study, a human non-small cell lung carcinoma NCI-H460 cell line was used to evaluate the antiproliferative activity of Fluoroquinolones like Enoxacin, Norfloxacin, Ciprofloxacin and Levofloxacin. As determined by Sulphorodhamine B assay (SRB assay), all Fluoroquinolones caused cellular growth inhibition in a concentration and time-dependent manner. Enoxacin was found to be the most effective Fluoroquinolone followed by Norfloxacin, Ciprofloxacin and Levofloxacin. Growth inhibitory effects were also found to be independent of the concentrations of serum growth factors in culture medium or variation of initial cell seeding density and proved to be irreversible in nature. Appearance of rounded cells with altered morphology and cell surface blebbing indicated cell killing by apoptosis. Cell shrinkage, nuclear condensation & fragmentation, and cytoplasmic blebbing as indicated by MGG staining confirmed this to be the case. Thus, this investigation clearly demonstrated that the NCI-H460 human non-small cell lung carcinoma cell line is highly sensitive to Fluoroquinolone treatment. The Fluoroquinolones used in this study which are clinically used as antibacterial agents, can also inhibit tumor cell growth suggesting their potential use in a strategy for cancer treatment which might help in controlling cancer.

Apoptosis↗