Topographic organization of connections between the hypothalamus and prefrontal cortex in the rhesus monkey

Prefrontal cortices have been implicated in autonomic function, but their role in this activity is not well understood. Orbital and medial prefrontal cortices receive input from cortical and subcortical structures associated with emotions. Thus, the prefrontal cortex may be an essential link for autonomic responses driven by emotions. Classic studies have demonstrated the existence of projections between prefrontal cortex and the hypothalamus, a central autonomic structure, but the topographic organization of these connections in the monkey has not been clearly established. We investigated the organization of bidirectional connections between these areas in the rhesus monkey by using tracer injections in orbital, medial, and lateral prefrontal areas. All prefrontal areas investigated received projections from the hypothalamus, originating mainly in the posterior hypothalamus. Differences in the topography of hypothalamic projection neurons were related to both the location and type of the target cortical area. Injections in lateral eulaminate prefrontal areas primarily labeled neurons in the posterior hypothalamus that were equally distributed in the lateral and medial hypothalamus. In contrast, injections in orbitofrontal and medial limbic cortices labeled neurons in the anterior and tuberal regions of the hypothalamus and in the posterior region. Projection neurons targeting orbital limbic cortices were more prevalent in the lateral part of the hypothalamus, whereas those targeting medial limbic cortices were more prevalent in the medial hypothalamus. In comparison to the ascending projections, descending projections from prefrontal cortex to the hypothalamus were highly specific, originating mostly from orbital and medial prefrontal cortices. The ascending and descending connections overlapped in the hypothalamus in areas that have autonomic functions. These results suggest that specific orbitofrontal and medial prefrontal areas exert a direct influence on the hypothalamus and may be important for the autonomic responses evoked by complex emotional situations.     

Effects of low radiation doses on Chinese hamster cells

The induction of cytogenetic damages after irradiation with single dose of gamma-rays (0.1-2 Gy) have been studied. It is shown non-linear curve for the induction of chromosome aberrations, detected by anaphase method. After irradiation in S-stage of the cell cycle at dose below 0.2 Gy the cells were more radiosensitive than after irradiation with doses 0.3-2 Gy. Between the phases of high radiosensitivity and radioresistance the reversal dose-effect relation was observed. This phenomenon was not marked for the cells after irradiation in G2-stage of the cell cycle. It is possible, this results could reflect an induced radioresistance at low dose of irradiation.     

Marker selection for the transmission/disequilibrium test, in recently admixed populations

Various analytical, iterative and rebinning algorithms have been proposed for 3D reconstruction in positron emission tomography. This paper examines execution times of five analytical and rebinning algorithms. Meaningful comparisons are obtained by using similar software modules in all implementations. Reconstruction times are shown to differ by vast amounts: the Favor algorithm of Defrise et al is more than twice as fast as the widely used reprojection algorithm of Kinahan and Rogers; the Fourier rebinning algorithm (Fore) recently developed by Defrise is more than 15 times faster than the reprojection algorithm.     

Overexpression of human superoxide dismutase inhibits oxidation of low-density lipoprotein by endothelial cells

Oxidation of LDL in the subendothelial space has been proposed to play a key role in atherosclerosis. Endothelial cells produce superoxide anions (O2.-) and oxidize LDL in vitro; however, the role of O2.- in endothelial cell-induced LDL oxidation is unclear. Incubation of human LDL (200 microg/mL) with bovine aortic endothelial cells (BAECs) for 18 hours resulted in a 4-fold increase in LDL oxidation compared with cell-free incubation (22.5+/-1.1 versus 6.3+/-0.2 [mean+/-SEM] nmol malondialdehyde/mg LDL protein, respectively; P<0.05). Under similar conditions, incubation of LDL with porcine aortic endothelial cells resulted in a 5-fold increase in LDL oxidation. Inclusion of exogenous copper/zinc superoxide dismutase (Cu/ZnSOD, 100 microg/mL) in the medium reduced BAEC-induced LDL oxidation by 79%. To determine whether the intracellular SOD content can have a similar protective effect, BAECs were infected with adenoviral vectors containing cDNA for human Cu/ZnSOD (AdCu/ZnSOD) or manganese SOD (AdMnSOD). Adenoviral infection increased the content and activity of either Cu/ZnSOD or MnSOD in the cells and reduced cellular O2.- release by two thirds. When cells infected with AdCu/ZnSOD or AdMnSOD were incubated with LDL, formation of malondialdehyde was decreased by 77% and 32%, respectively. Two other indices of LDL oxidation, formation of conjugated dienes and increased LDL electrophoretic mobility, were similarly reduced by SOD transduction. These data suggest that production of O2.- contributes to endothelial cell-induced oxidation of LDL in vitro. Furthermore, adenovirus-mediated transfer of cDNA for human SOD, particularly Cu/ZnSOD, effectively reduces oxidation of LDL by endothelial cells.     

Recombinant modified vaccinia virus Ankara-simian immunodeficiency virus gag pol elicits cytotoxic T lymphocytes in rhesus monkeys detected by a major histocompatibility complex class I/peptide tetramer

The utility of modified vaccinia virus Ankara (MVA) as a vector for eliciting AIDS virus-specific cytotoxic T lymphocytes (CTL) was explored in the simian immunodeficiency virus (SIV)/rhesus monkey model. After two intramuscular immunizations with recombinant MVA-SIVSM gag pol, the monkeys developed a Gag epitope-specific CTL response readily detected in peripheral blood lymphocytes by using a functional killing assay. Moreover, those immunizations also elicited a population of CD8+ T lymphocytes in the peripheral blood that bound a specific major histocompatibility complex class I/peptide tetramer. These Gag epitope-specific CD8+ T lymphocytes also were demonstrated by using both functional and tetramer-binding assays in lymph nodes of the immunized monkeys. These observations suggest that MVA may prove a useful vector for an HIV-1 vaccine. They also suggest that tetramer staining may be a useful technology for monitoring CTL generation in vaccine trials in nonhuman primates and in humans.     

Transforming growth factor beta: a matter of life and death

A wide variety of functions, many of which represent opposing activities, have been attributed to TGF-beta, a molecule implicated in embryogenesis, development, and immune and inflammatory processes. This paradoxical behavior of promoting or inhibiting cell growth and function, while important in normal physiology and homeostasis, can contribute to or interrupt pathologic sequelae, making TGF-beta a particularly intriguing molecule for study. New transgenic mouse models displaying targeted alterations in TGF-beta 1 expression offer novel and unique opportunities to determine the essential function(s) of TGF-beta.     

On the question of an electrokinetic requirement for phospholipase C action

The phospholipase C of clostridium welchii (alpha toxin) has an absolute requirement for trace quantities of Ca2+. It attacks pure phosphatidylcholine particles (smectic mesophases) having a close-packed bilayer structure only when their surface zeta potential is made positive by the addition of certain divalent ions (e.g., Ca2+) to the aqueous phase or by the presence of low concentrations of long chain cations to the lipid. Alternatively, if the rotational freedom of individual phospholipid molecules is increased by the insertion of short n-alkanols (e.g., hexanol) into the bilayer or when a monolayer of the substrate at an air/water interface is expended, enzymic hydrolysis can occur without any requirement for a net postive charge on the surface.     

Leg function after radiotherapy for Ewing's sarcoma

Twenty-nine patients with Ewing's sarcoma of the lower extremity who survived for two or more years following therapy (5000 rad locally and systemic chemotherapy) were studied to assess functional status of the affected leg. Twenty-two of twenty-nine were alive and were reexamined; the deceased patients were evaluated by record review. Twenty-two of the twenty-nine had serial radiographs, which were reviewed to assess growth change induced by radiation. The living patients were divided on the basis of clinical examination into four functional groups with Group I comprising patients with minor functional limitations and leg length discrepancy 1.5 cm or less. Group II patients had moderate functional limitations with 2.5-cm leg-length discrepancy or less. Group III patients had severe functional limitations with up to 4-cm leg length discrepancy. Group IV patients had severe complications, sufficient enough to warrant amputation. Thirteen of twenty-two patients were classified as functional Group I, five as Group II, three as Group III, and one as Group IV. Radiographic changes in growing bone did not correlate with functional results. Although a femoral fracture and an age less than 16 years at diagnosis were found to be less favorable prognostic factors for the functional treatment result, these results show that neither femoral location nor young age justify primary amputation for Ewing's sarcoma of the lower leg extremity.