Cellular and developmental patterns of expression of Ret and glial cell line-derived neurotrophic factor receptor alpha mRNAs

 Glial cell line-derived neurotrophic factor (GDNF) has recently been shown to signal by binding to GDNF receptor-alpha (GDNFR-α), after which the GDNF-GDNFR-α associates with and activates the tyrosine kinase receptor Ret. We have localized Ret messenger RNA (mRNA) in the developing and adult rodent and compared with to the expression of GDNF and GDNFR-α mRNA. Ret mRNA is strongly expressed in dopamine neurons and α-motorneurons as well as in thalamus, ruber and occlumotor nuclei, the habenular complex, septum, cerebellum, and brain stem nuclei. Ret mRNA was also found in several sensory systems, in ganglia, and in nonneuronal tissues such as teeth and vibrissae. Very strong Ret mRNA signals are present in kidney and the gastrointestinal tract, where Ret and GDNF mRNA expression patterns are precisely complementary. The presence of Ret protein was confirmed in adult dopamine neurons using immunohistochemistry. GDNFR-α mRNA was strongly expressed in the developing and adult dopamine neurons. It was also found in neurons in deep layers of cortex cerebri, in hippocampus, septum, the dentate gyrus, tectum, and the developing spinal cord. In the kidney and the gastrointestinal tract, GDNFR-α mRNA and Ret mRNA distribution overlapped. Dorsal root ganglia, cranial ganglia, and developing peripheral nerves were also positive. GDNFR-α was additionally found in sensory areas and in developing teeth. Sensory areas included inner ear, eye, olfactory epithelium, and the vomeronasal organ, as well as developing tongue papillae. The temporospatial pattern of expression of GDNFR-α mRNA did not always match that of Ret mRNA. For instance, GDNFR-α mRNA was also found in the developing ventral striatum, including the olfactory tubercle, and in hippocampus. These areas seemed devoid of Ret mRNA, suggesting that GDNFR-α might also have functions unrelated to Ret. Received: 2 January 1997 / Accepted: 26 February 1997     

Simulating activations with cytoarchitecture

Cytoarchitectonic delineation of areas in post-mortem human brains provides the precise location of these areas. It has been possible to study the size and location of areas between post-mortem brains with multi-subject cytoarchitectonic data. If the structure–function relationship is assumed to be a one-to-one mapping for the purposes of inter-subject variability, then functional areas in the cortex will also adhere to the structure, and therefore, the location and size of cytoarchitectonic areas in the brain. Thus, it is possible to use the cytoarchitectonic data as being representative of the size and location of functional activations. Under this assumption, we simulated activations in cytoarchitectonic areas from ten post-mortem brains in this study. We then treated these data as we would a normal PET experiment. The purpose of this study is to demonstrate a standard PET image analysis on a simulated ten-subject PET study using cytoarchitecture to localize the activations. By doing so, we simulate activations with real inter-subject variability with the size and location of each area. Significant activations were obtained for activations simulated in areas 3a and 3b. A voxel-wise conjunction between simulated data and experimental data was made to better determine the underlying areas activated by the experimental tasks. This study presents a novel technique for demonstrating the effect of standard image analysis on the location and size of simulated activations as determined by cytoarchitectonic data from multiple subjects. Furthermore, this technique has been applied to better determine the underlying areas activated in an experiment.     

Production of prostaglandin E2 in monocytes stimulated in vitro by Chlamydia trachomatis, Chlamydophila pneumoniae, and Mycoplasma fermentans

Chlamydia trachomatis (CT) as well as Chlamydophila pneumoniae (CP) cause chronic inflammatory diseases in humans. Persistently infected monocytes are involved in the pathogenesis by inducing mediators of inflammation. An in vitro system of chlamydial persistence in human peripheral blood monocytes (HPBM) was used to investigate prostaglandin E(2) (PGE(2)) production and the expression of the key enzyme for prostaglandin production, cyclooxygenase-2 (COX-2). PGE(2) production was determined by PGE(2)-ELISA of HPBM-culture supernatants. Cox-2 mRNA expression was measured by real-time RT-PCR of total RNA isolated from HPBM. Both, CT and CP, stimulated PGE(2) production of HPBM in vitro. Equivalent numbers of CT per host cell induced a higher PGE(2)-response compared to CP. The amount of synthesized PGE(2) depended on the chlamydial multiplicity of infection (MOI). Even at an MOI of 10 the amount of CT- and CP-induced prostaglandin, respectively, was lower than the amount of prostaglandin induced by E. coli lipopolysaccharide (LPS) at a concentration of 10microg/ml. In contrast to stimulation with LPS, Chlamydia-induced PGE(2) production as well as cox-2 mRNA decreased after day 1 post infection (p.i.). These data indicate that Chlamydia stimulate PGE(2) production in human monocytes. Since Chlamydia are often contaminated by mycoplasma, the influence of mycoplasma on the prostaglandin production was investigated additionally. Mycoplasma fermentans (MF) also stimulated PGE(2) production. The co-infection of mycoplasma and Chlamydia resulted in an additive effect in the production of PGE(2). Thus it is important to use host cells and Chlamydia free of mycoplasma contamination for the analysis of Chlamydia-induced prostaglandin production.     

Mitoxantrone combined to vincristine,cyclophosphamide and fluorouracil in advanced breast cancer

Summary In our wide experience of treating advanced breast carcinoma with chemotherapy, the combination of doxorubicin (DOX), vincristine (VCR), cyclophosphamide (CPM) and fluorouracil (FU) gave a complete plus partial response rate of over 60%, with 100% alopecia and frequent cardiac toxicity depending on total dose.After the EORTC Clinical Screening Group phase II trial we have conducted an expected difference method comparative phase II trial using the combination DOX, VCR, CPM, FU and the combination of MTX (10mg/m²), VCR, CPM and FU on a population of 50 breast carcinoma patients similar to those taking part in the first study.The reasons for similarity of action will be presented and discussed.     

The use of blood components in surgical transfusion therapy

Blood components can be prepared either by separation of ordinary whole blood units or, selectively, by apheresis techniques. In recent years, new methods for improvement of quality and length of storage have been developed. The additive solution approach is now being applied increasingly. Its advantages and the difference between some available systems are described. Blood component therapy must be integrated into the patients' water/electrolyte balance and nutrition schedule. An outline is given of the role of blood components in the treatment of shock. The question of excessive bleeding, the possibilities of making the diagnosis of its cause(s) in the individual case, and the use of blood components is described. Coronary pulmonary bypass is used as an example of a complicated situation that can be handled effectively by a limited number of diagnostic and therapeutic tools.

---

Resumen Los componentes sanguíneos pueden ser preparados bien por separación de unidades ordinarias de sangre total o, selectivamente, por técnicas de aferesis. Estas últimas tienen la ventaja de permitir la selección de donantes particularmente apropiados en relación a compatibilidad inmunológica o a la ausencia de agentes infecciosos transmisibles, así como a la posibilidad de que un mismo donante pueda ser usado en forma repetida dentro de un período de tiempo corto. Nuevos métodos de mejoramiento y prolongación del período de almacenamiento han sido desarrollados. El enfoque de las soluciones aditivas es empleado con creciente frecuencia; se describen sus ventajas y las diferencias con otros métodos disponibles en la actualidad.La terapia con componentes sanguíneos debe ser parte integral del manejo del equilibrio de agua y electrolitos y del programa de soporte nutricional. Se provee una guía sobre el uso de componentes sanguíneos en el tratamiento del shock.Se describe el problema del sangrado excesivo, la posibilidad de establecer el diagnóstico de su causa en cada caso individual, y el uso de los componentes sanguíneos. El bypass coronario es presentado como ejemplo de una situación compleja que puede ser manejada en forma efectiva por medio de un número limitado de métodos de diagnóstico y tratamiento.

---

Résumé Les constituants du sang peuvent être isolés soit par séparation des unités de sang total ordinaire, soit sélectivement par techniques d'apharèse. Au cours des récentes années des méthodes pour améliorer la qualité et la durée du stockage ont été mises au point. Pour ce faire, l'emploi d'additifs est largement répandu. Les avantages et les différences entre quelques méthodes disponibles sont décrits par les auteurs. Le traitement par constituants du sang doit être associé à l'équilibre hydroélectrolytique et nutritif. Le rôle des différentes parties constituantes du sang dans le traitement du choc est souligné. La question de l'hémorragie excessive, les possibilités de faire le diagnostic de ses causes dans les cas individuels et l'emploi des parties constituantes adéquates du sang sont décrits. A titre d'exemple le By pass pulmo-coronarien, situation particulièrement délicate, peut être contrôlé efficacement par un nombre limité de méthodes diagnostiques et thérapeutiques.

     

Patient involvement in oral hygiene cooperation: a factor analytic study

In a previous study the concept "patient involvement" was found to be strongly predictive of therapy outcome. On the basis of a questionnaire concerning patients' background and motivation, 82 patients were interviewed before treatment. To cover the concept "patient involvement" 16 variables were considered as relevant measures. In a factor analysis four factors accounted for 90% of the common variance. The factors were interpreted in terms of: initial attitudes, attendance, self-confidence and teeth-mindedness.     

Conceptual problems in establishing the critical concentration of cadmium in human kidney cortex

The definition of the "critical concentration" for cadmium is compared with the concepts used to establish this measure in some recent publications. The term has not been clearly defined on a population basis and this has given rise to certain confusion. Different groups of investigators therefore have arrived at different estimates of the "critical concentration" for cadmium in human kidney cortex. A new measure, the "population critical concentration" (PCC) with a clearly defined response rate, is suggested. A reanalysis of the published data indicates that the PCC-10 (10% response rate) for cadmium in kidney cortex is likely to be in the range 180-220 micrograms/g and the PCC-50 is likely to be about 25% higher.     

Clinical utility of PTSD,resilience, sleep,and blast as risk factors to predict poor neurobehavioral functioning following traumatic brain injury: A longitudinal study in U.S. military service members

Quality of Life Research - This study examined the clinical utility of post-traumatic stress disorder (PTSD), low resilience, poor sleep, and lifetime blast exposure as risk factors for predicting...