Subpopulations of motor and sensory neurons respond differently to brain-derived neurotrophic factor depending on the presence of the skeletal muscle.

The aim of our study was to assess the ability of brain-derived neurotrophic factor (BDNF) to rescue motor and sensory neurons from programmed cell death. It is clearly demonstrated that the administration of a single injection of a putative neurotrophic factor to mouse embryos in utero on embryonic day (E) 14.5 is sufficient to significantly reduce the death of motor neurons when assessed on E18.5. However, the trophic requirements of somatic neurons have not been unequivocally determined in a mammalian species in vivo. Indeed, the unexpectedly high numbers of surviving neurons observed in neurotrophin and tyrosine kinase receptor knockout mice are probably the consequence of functional redundancy between the neurotrophins and their receptors. We studied spinal cord and facial motor nucleus neurons and proprioceptive neurons in the dorsal root ganglion and mesencephalic nucleus. The action of BDNF was assessed in wild-type fetuses to gain insight into its ability to rescue neurons from naturally occurring programmed cell death. In addition, we used Myf5(-/-):MyoD(-/-) embryos, which completely lack skeletal musculature, to assess the ability of BDNF to rescue neurons from excessively occurring programmed cell death. We found that BDNF differentially rescued neurons from naturally vs. excessively occurring cell death and that its ability to do so varied among neuronal subpopulations.     

Beta-catenin abnormalities and associated insulin-like growth factor overexpression are important in phyllodes tumours and fibroadenomas of the breast

The aim of this study was to assess the expression of IGF-I and IGF-II in phyllodes tumours and fibroadenomas and to see if there is any correlation between nuclear beta-catenin expression and IGF-I and IGF-II expression in these tumours. In a previous study, it has been shown that Wnt signalling is important in the pathogenesis of phyllodes tumours of the breast. Epithelial Wnt5a overexpression and stromal Wnt2 overexpression were associated with abnormal, nuclear localization of beta-catenin in the stromal cells of these tumours. However, not all tumours with beta-catenin accumulation showed Wnt overexpression. One other possible cause of beta-catenin accumulation is overexpression of insulin-like growth factors (IGFs), as both IGF-I and IGF-II have been shown to stabilize beta-catenin. In this study, 30 fibroadenomas of the breast were assessed for beta-catenin expression using immunohistochemistry and the results were compared with previous data from 119 phyllodes tumours. In situ hybridization was used to assess IGF-I and IGF-II expression in 23 phyllodes tumours and 16 fibroadenomas. Nineteen phyllodes tumours (83%) showed widespread overexpression of IGF-II and 5/23 (22%) showed widespread overexpression of IGF-I. IGF-I expression correlated with nuclear beta-catenin staining in phyllodes tumours. Malignant phyllodes tumours showed no or little IGF-I expression. There was a degree of nuclear beta-catenin expression in the stroma (weak in 33%, moderate in 27%, and strong in 40%) in all fibroadenomas and nuclear beta-catenin staining correlated with IGF-I overexpression. Extensive IGF-II overexpression was also found in the majority of fibroadenomas (12/16). These results support the hypothesis that IGF-I and IGF-II overexpression may be important in the pathogenesis of fibroepithelial neoplasms of the breast and that IGF-I overexpression is likely to be contributing to the nuclear beta-catenin localization observed in the tumours.     

The importance of the motor nerve for the development of chemosensitivity at the neuromuscular junction

Experiments were performed on kittens to study the role of innervation on the development of the pharmacological responses of the neuromuscular junction. The importance of the nerve for the development of the differing properties of fast and slow muscles was also studied.It was confirmed that the different responses to depolarising drugs of the slow soleus and fast flexor hallucis longus muscles are not apparent during the first week of the animal's life.Even when the motor nerves to these muscles were crossed at this time the alien innervation did not affect the subsequent development of the different responses of fast and slow muscles to suxa- and decamethonium. This suggests that the different properties of the postsynaptic membrane are established very early in the animal's life and that they cannot be changed by altering the innervation.The neuromuscular junctions of these young animals are very insensitive to suxa- and decamethonium. When innervation is delayed, during the early postnatal period, the development of the high sensitivity of the neuromuscular junctions to the blocking and depolarising actions of these drugs was retarded. It is therefore concluded that the motor nerve induces the high chemosensitivity of the adult endplate region.     

Predicting Home and Work Blood Pressure Measurements from Resting Baselines and Laboratory Reactivity in Black and White Americans

The relationship between blood pressure in the laboratory (both at rest and in response to laboratory tasks) and ambulatory blood pressure at home and at work was evaluated. One hundred nineteen normotensive and unmedicated mild-moderate hypertensive black and white females and males participated in laboratory blood pressure monitoring at rest and during four challenging tasks (structured interview, video game, bicycle exercise, and cold pressor test) as well as ambulatory blood pressure monitoring while at home and at work. Baseline blood pressure taken while subjects were at rest was the strongest predictor of ambulatory systolic blood pressure (r = .64) and diastolic blood pressure (r = .77) at work. Among reactivity tasks the strongest predictors of ambulatory blood pressure in the total population were the structured interview and the video game (both psychological tasks) followed by the cold pressor test. Racial comparisons, however, determined that the cold pressor test predicted diastolic blood pressure significantly better for blacks (r = .73) than for whites (r = .40), suggesting a possible difference in blood pressure regulation.     

The significance of argyrophilia in human breast carcinomas

Summary The significance of demonstrating argyrophilia in human breast carcinomas is a complex issue, although there is general agreement that true carcinoid tumours of the breast are rare.A predominantly unselected series of breast carcinomas has been investigated for evidence of argyrophilia using the Churukian Schenk method (Churukian and Schenk 1979), alpha lactalbumin and prealbumin, a marker of neuroendocrine cells.Argyrophilia has been detected in 25% of carcinomas, including all of mucinous types. However, only 4 of the 68 tumours had a diffuse cytoplasmic reaction typical of that seen in neuroendocrine cells. The others showed a focal or subluminal/ peripheral reaction. Those argyrophilic carcinomas with demonstrable alpha lactalbumin had this latter pattern of reactivity, although the milk protein was always detected in lesser amounts by comparison. Prealbumin was only found to varying degrees in eight tumours and the majority of these had a diffuse or focal cytoplasmic argyrophilic reaction.It would appear that in only a small number of breast carcinomas, approximately six percent, does the presence of argyrophilia probably represent neuroendocrine differentiation, whilst in others it is related to the secretory nature of the tumour cells.     

Evaluating self-generated information: anterior prefrontal contributions to human cognition

The anterior or rostrolateral prefrontal cortex (RLPFC) is frequently recruited during complex cognitive tasks across a wide range of domains, including reasoning, long-term memory retrieval, and working memory. The authors report an event-related functional MRI study, indicating that the RLPFC is specifically involved in the evaluation of internally generated information--or information that cannot be readily perceived from the external environment but has to be inferred or self-generated. The findings are consistent with a hierarchical model of lateral prefrontal organization, with RLPFC contributing only at the highest orders of cognitive transformations. This characterization of RLPFC function may help explain seemingly disparate findings across multiple cognitive domains and could provide a unified account of this region's contribution to human cognition.     

Liposome-mediated gene transfer and expression via the skin

A ß-galactosidase gene expression construct was usedto investigate the effectiveness of gene delivery and expressionwhen DNA/liposome complexes were topically applied to mouseskin in vivo. DNA was complexed with a commercial preparationof N-[1-(2,3-dioleoyloxy) propyl]-N, N, N-trimethyl-ammonium-methyl-sulphate(DOTAP) in a ratio of 1:1.6 (w/w). The DNA rapidly penetratedthe skin and was expressed in the epidermis, dermis and hairfollicles. A DNA concentration of 267 µg/ml DNA was foundto be optimal for efficient transfection. Expression was seenas early as 6 h post-application, persisted at high levels 24and 48 h post-treatment, but was markedly reduced by 7 daysafter application. In conclusion, utilising a commercially availableliposome preparation, topically-applied DNA/liposome complexescan be efficiently delivered and expressed in several cell typeswithin the skin. This simple, non-invasive technique may haveimplications for a number of gene therapy applications.     

N-methyl-D-aspartate receptors in the cortex and hippocampus of baboon (Papio anubis and Papio papio)

In vitro autoradiography was used to examine the N-methyl-D-aspartate receptor in the brain of a baboon species, Papio anubis, and compared to that of Papio papio which exhibits a photosensitive epilepsy. The epilepsy originates in the frontal cortex and is accompanied by an enhanced sensitivity to N-methyl-D-aspartate. In both Papio anubis and Papio papio, the density of N-methyl-D-aspartate receptors was greatest in the hippocampus, followed by associational areas including frontal cortex, and low in primary sensory areas such as the visual cortex. The receptors were concentrated in the outer cortical layers I-III, very low in layer IV except in primary visual cortex, and of intermediate density in layer V. The density of binding sites was approximately two-fold lower than previously observed in the rodent brain, whereas the affinity of the receptor for [3H]L-glutamate was greater in the primate versus the rodent brain. Glycine potentiated the binding of [3H]L-glutamate in both cortex and hippocampus. No significant differences in the properties of N-methyl-D-aspartate receptors were observed between the two baboon species, suggesting that the photosensitivity of Papio papio is not due to alterations in the binding of L-glutamate to the N-methyl-D-aspartate receptor complex.     

Sensitivity of FL cells to polio- and adenoviruses

Summary Poliovirus plaque counts on the FL strain of human amnion cells were almost double the counts on rhesus monkey kidney for the same virus preparation, repeatedly assayed over more than six months. FL cells gave more consistent results in virus assay than monkey kidney cells. Plaque counts obtained with FL cells were 2 1/2 to 5 times higher than those obtained with HeLa, Chang's conjunctiva and Detroit-6 cells.Using the chick embryo-adapted MEF-1 strain of poliovirus, FL cells and primary human amnion cells reacted similarly in respect to plaque count and morphology, while no distinct plaques were seen on monkey kidney or HeLa monolayers under comparable conditions. For infectivity assays of adenovirus suspensions based on cytopathogenic effect, FL cells were found suitable, although no plaque formation was obtained.Aided by American Cancer Society Grant E-82 and a grant from the National Foundation.