Influence of COMT genotype and affective distractors on the processing of self-generated thought

The catechol-O-methyltransferase (COMT) enzyme is a major determinant of prefrontal dopamine levels. The Val¹⁵⁸Met polymorphism affects COMT enzymatic activity and has been associated with variation in executive function and affective processing. This study investigated the effect of COMT genotype on the flexible modulation of the balance between processing self-generated and processing stimulus-oriented information, in the presence or absence of affective distractors. Analyses included 124 healthy adult participants, who were also assessed on standard working memory (WM) tasks. Relative to Val carriers, Met homozygotes made fewer errors when selecting and manipulating self-generated thoughts. This effect was partly accounted for by an association between COMT genotype and visuospatial WM performance. We also observed a complex interaction between the influence of affective distractors, COMT genotype and sex on task accuracy: male, but not female, participants showed a sensitivity to the affective distractors that was dependent on COMT genotype. This was not accounted for by WM performance. This study provides novel evidence of the role of dopaminergic genetic variation on the ability to select and manipulate self-generated thoughts. The results also suggest sexually dimorphic effects of COMT genotype on the influence of affective distractors on executive function.     

Lines of Murine Oligodendroglial Precursor Cells Immortalized by an Activated neu Tyrosine Kinase Show Distinct Degrees of Interaction with Axons In Vitro and In Vivo

Replication-defective retroviruses expressing the t- neu oncogene, or a hybrid protein with the neu tyrosine kinase linked to the external region of the human epidermal growth factor receptor ( egfr-neu ), were used to establish lines of murine oligodendroglial precursor cells. Differentiation of the t- neu lines into myelin-associated glycoprotein (MAG)-positive oligodendrocytes was induced by dibutyryl cAMP, and the egfr-neu line showed limited differentiation in vitro upon withdrawal of epidermal growth factor. Cerebellar granule cell neurons expressed mitogens for the cell lines. Upon transplantation into demyelinated lesions, t- neu line cells engaged with the demyelinated axons whereas the egfr-neu line cells differentiated further and ensheathed the axons. These cell lines thus interact with neurons in vitro and in vivo and can be used as tools to define the molecules involved in different stages of neuron-glia interaction.     

Observations on the migratory behaviour of Schwann cells from adult peripheral nerve expiant cultures

Summary The migration of Schwann cells from adult sciatic nerve explant cultures has been examined by time-lapse photomicrography. Analysis of Schwann cell migratory behaviour indicates that the initial outwandering by individual Schwann cells was random. Although chance cell-cell contacts resulted in temporary immobilization of pairs of cells, stable multicellular structures did not form during this initial phase. As local cell densities increased, Schwann cells assembled networks within which Schwann cell movement continued to be observed.A second form of Schwann cell outgrowth was observed from degenerating fibres in which arrays of highly oriented Schwann cells migrated away from their basal laminai tubes onto the culture dish.These observations of Schwann cell random migration, network self-assembly and coordinated extratubal migration are considered to highlight aspects of Schwann cell behaviour, independent of axonal influences, which may have relevance to their role in peripheral nerve repair following nerve section.     

Plasma amino acid concentrations in geriatric control and hip-fracture patients.

Changes in plasma amino acids, 24-h nitrogen balances, and resting metabolic expenditures (RMEs) were measured in 10 geriatric patients (aged 70-92 y) with hip fracture 1 d after surgical fixation during both a 24-h fasting state and while receiving total peripheral parenteral nutrition (TPPN) for 24 h at 1.5 g amino acids.kg-1.d-1 and 29-30 kcal.kg-1.d-1 and compared with 19 healthy volunteer subjects (aged 70-84 y). RME and 24-h urinary nitrogen losses were also elevated in the trauma patients during both fasting and TPPN. Positive nitrogen balances were evident in both groups during TPPN. Plasma total amino acid concentration was significantly lower in the trauma patients because of lower plasma concentrations of the nonessential amino acids. Phenylalanine and methionine concentrations were significantly higher and lysine lower in the trauma group. In addition, evaluation of the essential amino acid ratios after fasting and TPPN reveal that there are no limiting amino acids during TPPN.     

Energy requirements for cancer patients and the effect of total parenteral nutrition

Limited data are available concerning resting metabolic expenditure (RME) in cancer patients and the effect of RME by varying glucose intake. This study describes the measurements on 21 patients with colorectal cancer while fasting and with incremental levels of standard TPN-glucose system by central vein. Following an overnight fast, the measured mean +/- SEM percent difference from the predicted RME for the male group was 4.13 +/- 1.67% and the female group, 2.09 +/- 2.09%. The overall mean percent difference of 2.95 +/- 1.45 suggests that colorectal cancer does not cause an increase in energy expenditure. Hepatic metastases in 11 of the patients did not influence RME. The data from the 21 patients indicate a statistically significant increase in RME with TPN compared to postabsorptive states in females of 37%, in males 21.88%, and combined of 29.88%. Progressively greater increases in RME were seen when calories provided incrementally exceeded the basal RME. Carbohydrate loading in excess of the patient's calorie need, as indicated by the respiratory quotient (RQ) greater than 1.0, results in fat synthesis and other energy-costing processes. The basal RME demonstrates that these cancer patients are not hypercatabolic, but do respond to high-level force-feeding with markedly increased metabolic expenditures.     

Tumor vascular signals in renal masses: detection with Doppler US

The vascularity of 49 renal masses (26 malignant and 23 benign lesions) was investigated with duplex Doppler ultrasound. Doppler signals obtained at the margins of renal masses were defined as "tumor signals" when the Doppler-shifted frequency of the lesion exceeded the frequency shift in the ipsilateral main renal artery. These exceeded 2.5 kHz with a 3-MHz insonating frequency. Among the 26 renal masses that subsequently proved to be malignant, tumor signals were obtained in 15 of 18 (83%) untreated renal cell carcinomas, in three of four Wilms tumors, and in two patients with metastases to the kidney, but not in the one patient with lymphoma. None of the 23 benign renal masses demonstrated tumor signals. Tumor vascularity in malignant lesions gives rise to abnormal, high-velocity, Doppler-shifted signals that can help in the differential diagnosis of renal masses.     

Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos

In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture environment differs from in-vivo conditions in that the oxygen concentration is higher, and in such conditions the mouse embryos show a higher concentration of reactive oxygen species (ROS) in simple culture media. ROS are believed to cause damage to cell membranes and DNA fragmentation in somatic cells. This study was conducted to ascertain the level of H2O2 concentration within embryos and the morphological features of cell damage induced by H2O2. A total of 62 human oocytes and embryos (31 fragmented, 15 non-fragmented embryos, 16 unfertilized oocytes) was obtained from the IVF-embryo transfer programme. The relative intensity of H2O2 concentrations within embryos was measured using 2',7'-dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence imaging and DNA fragmentation was observed with transmission electron microscopy and an in-situ apoptosis detection kit. The H2O2 concentrations were significantly higher in fragmented embryos (72.21 +/- 9.62, mean +/- SEM) compared to non-fragmented embryos (31.30 +/- 3.50, P < 0.05) and unfertilized oocytes (30.75 +/- 2.67, P < 0.05). Apoptosis was observed only in fragmented embryos, and was absent in non-fragmented embryos. Electron microscopic findings confirmed apoptotic bodies and cytoplasmic condensation in the fragmented blastomeres. We conclude that there is a direct relationship between increased H2O2 concentration and apoptosis, and that further studies should be undertaken to confirm these findings.