Resting respiratory tract dendritic cells preferentially stimulate T helper cell type 2 (Th2) responses and require obligatory cytokine signals for induction of Th1 immunity

Consistent with their role in host defense, mature dendritic cells (DCs) from central lymphoid organs preferentially prime for T helper cell type 1 (Th1)-polarized immunity. However, the "default" T helper response at mucosal surfaces demonstrates Th2 polarity, which is reflected in the cytokine profiles of activated T cells from mucosal lymph nodes. This study on rat respiratory tract DCs (RTDCs) provides an explanation for this paradox. We demonstrate that freshly isolated RTDCs are functionally immature as defined in vitro, being surface major histocompatibility complex (MHC) II lo, endocytosishi, and mixed lymphocyte reactionlo, and these cells produce mRNA encoding interleukin (IL)-10. After ovalbumin (OVA)-pulsing and adoptive transfer, freshly isolated RTDCs preferentially stimulated Th2-dependent OVA-specific immunoglobulin (Ig)G1 responses, and antigen-stimulated splenocytes from recipient animals produced IL-4 in vitro. However, preculture with granulocyte/macrophage colony stimulating factor increased their in vivo IgG priming capacity by 2-3 logs, inducing production of both Th1- and Th2-dependent IgG subclasses and high levels of IFN-gamma by antigen-stimulated splenocytes. Associated phenotypic changes included upregulation of surface MHC II and B7 expression and IL-12 p35 mRNA, and downregulation of endocytosis, MHC II processing- associated genes, and IL-10 mRNA expression. Full expression of IL-12 p40 required additional signals, such as tumor necrosis factor alpha or CD40 ligand. These results suggest that the observed Th2 polarity of the resting mucosal immune system may be an inherent property of the resident DC population, and furthermore that mobilization of Th1 immunity relies absolutely on the provision of appropriate microenvironmental costimuli.     

Chemotherapy in non-small cell lung cancer: a review

Lung cancer, of which non-small cell carcinoma is the most common, has been a significant therapeutic challenge for decades and will remain so for decades to come. Despite its prevalence, progress in the management of non-small cell lung cancer has been relatively slow. This is in part due to the pessimism of most physicians treating this disease, which has resulted in a relatively lackadaisical attitude with regards to clinical trials when compared to other solid tumours like breast or colorectal cancers. Nevertheless, the past decade has seen significant progress, specifically with regards to the management of locally advanced disease. Chemotherapy, though shown to be biologically active in non-small cell lung cancer, is considered an ineffective palliative tool in the setting of metastatic disease due to its toxicities and the "less than encouraging" response rates generated by the cisplatin-based combination regimen which is generally considered to be the most active currently available. The advent of new active agents such as paclitaxel and vinorelbine which are potentially less toxic may change this view. Conversely, the response rate of locally advanced disease to chemotherapy is significantly higher and this has resulted in numerous multimodality trials of neoadjuvant chemotherapy prior to surgery and/or radiation. To date, a number of randomised trials have shown that this approach can result in significant survival benefit for patients with locally advanced disease. An alternative approach makes use of the potential synergism between certain chemotherapeutic agents (such as cisplatin) and radiation when used concurrently. However, data on concurrent chemoradiotherapy in locally advanced disease have been largely based on single-arm studies and are inconclusive. Three randomised trials on concurrent chemoradiotherapy have been shown benefit for the use of combined modality in locally advanced disease. Hence, treatment of locally advanced disease should include chemotherapy as part of the combined modality approach. However, the optimal sequencing of these modalities would require well-designed randomised trials to determine.     

Long RT-PCR Amplification of the entire coding sequence of the polycystic kidney disease 1 (PKD1) gene

The peptidoglycan cortex of endospores of Bacillus species is required for maintenance of spore dehydration and dormancy, and the structure of the cortex may also allow it to function in attainment of spore core dehydration. A significant difference between spore and growing cell peptidoglycan structure is the low degree of peptide cross-linking in cortical peptidoglycan; regulation of the degree of this cross-linking is exerted by D,D-carboxypeptidases. We report here the construction of mutant B. subtilis strains lacking all combinations of two and three of the four apparent D, D-carboxypeptidases encoded within the genome and the analysis of spore phenotypic properties and peptidoglycan structure for these strains. The data indicate that while the dacA and dacC products have no significant role in spore peptidoglycan formation, the dacB and dacF products both function in regulating the degree of cross-linking of spore peptidoglycan. The spore peptidoglycan of a dacB dacF double mutant was very highly cross-linked, and this structural modification resulted in a failure to achieve normal spore core dehydration and a decrease in spore heat resistance. A model for the specific roles of DacB and DacF in spore peptidoglycan synthesis is proposed.     

A controlled trial of venlafaxine in trichotillomania: interim phase I results

Vibrio vulnificus, a particularly virulent halophilic vibrio, has been isolated from the blood and skin necrotic lesion of a hemodialyzed patient with sepsis. The patient has had exposure of the skin to seawater. Various chronic conditions including renal failure have a great risk for developing septicemia due to V vulnificus. It is necessary to inform persons with liver diseases or immunocompromising conditions of hazards associated with the consumption of undercooked seafood and seawater exposure.     

Mathematical models for motile bacterial transport in cylindrical tubes

Mathematical models considering motile bacterial transport within a geometrically restrictive cylindrical tube were developed. Two macroscopic transport parameters, the random motility coefficient as a self-diffusion coefficient of the cell population and the chemotactic velocity as a chemical-induced velocity, were derived. The three-dimensional cell balance equation was reduced to forms similar to Segel's one-dimensional phenomenological cell balance equations with additional modifications for bacteria-wall interactions. Two conceptually different approaches accounting for such interactions were presented. The first approach parallels treatments in the gas kinetic theory by viewing bacterial interactions with walls as collisions and subsequent diffusive/specular reflections, which led to the Bosanquet formula for the bacterial diffusion coefficient. Based on the experimental observation that bacterial swimming motion is guided by a straight tube, the second approach considered modifications in the bacterial swimming orientation as a consequence of various long-range interactions with the tube surface. A phenomenological turning model capable of aligning bacterial motion along a tube axis was proposed. The model predicts that under the geometrical restriction of a small cylindrical tube, the macroscopic bacterial transport resulting from the proposed turning model can exhibit behavior that ranges from dimensionally reduced diffusion to pure wave propagation, depending on the influence of the tube diameter on the reversal probability in the bacterial swimming motion. Our theoretical model provides explicit equations that explain how such a transition can occur. The predicted results were then qualitatively compared with experimental data from the literature. As a preliminary comparison, we concluded that bacterial transport in cylindrical tubes of diameter 10 micrometers remains in the mode of a dimensionally reduced diffusion, and shifts to a wave motion when the tube diameter decreases to 6 micrometers.     

Cognitive ability and cerebral lateralisation in transsexuals

INTRODUCTION: The application of high-frequency current to the AV junctional area results in a temperature rise in the myocardium and may cause accelerated junctional rhythm (AJR). The aim of the study was to characterize heat-induced AJR in an in vitro animal model. METHODS AND RESULTS: Studies were performed in isolated perfused pig and rabbit hearts. Using a small heating probe, we could induce AJR from a discrete area located in the middle of the triangle of Koch, which was smaller than the area from which RF energy application could elicit AJR. Histology showed that the heat-sensitive area was located over, or close to, the compact AV node. It did not correspond with the areas where double potentials were found or with the site(s) of earliest atrial activation during VA conduction. Microelectrode recordings revealed that AJR arose in nodal-type cells. Heat increased the slope of the phase 4 depolarization and shortened the action potential duration. Two types of AJR were observed: the first one was regular and the second one showed irregularity in the intervals. Interaction of multiple foci and the presence of conduction block between the foci and the His bundle caused the irregularity of the His-His intervals during the second type of AJR. CONCLUSION: AJR observed during heat and RF application in the AV nodal area results from the effect of heat on AV nodal cells with underlying pacemaker activity. The heat-sensitive area is located over, or very close to, the compact AV node.     

The effect of adrenergic agonists on the systemic response to hemorrhage

An in vivo antitumor screening of extracts of Gomphrena martiana indicated positive activity in the petroleum ether extract, and its further bioactivity-directed fractionation resulted in a lipophilic flavonoid fraction. Upon inoculation of various doses of 5,6,7-trisubstituted flavones on two murine tumor lines, Sarcoma 180 and Ehrlich's carcinoma, a decrease of tumor growth was observed. An in vitro KB cultured cell screen indicated cytotoxicity.