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.     

A socio-technical approach to post-occupancy evaluation: interactive adaptability in domestic retrofit

Understanding the process of domestic retrofit is important for learning and innovation. This is particularly the case for low carbon retrofits such as those undertaken under the UK's Retrofit for the Future (RftF) programme, with its aim to achieve an overall 80% carbon reduction by 2050. Current post-occupancy evaluation (POE) research has both theoretical and methodological limitations with implications for technical and behavioural research in the built environment. Drawing on relevant ideas and concepts from social practice theory and science and technology studies, principally prefiguration (constraints/enablement), black-boxing, heating and cooling practices, this paper demonstrates how the relationship between buildings and people could be reconceptualized as mutually constitutive and co-evolving through a process of ‘interactive adaptation’. The concept of ‘interactive adaptation’ is explored through a novel approach to integrating physical and social data collected from a sample of dwellings selected from the RftF programme. Analysis yields insights into the influences and pathways of interactive adaptation resulting from retrofit technology and practices. The implications of these insights for policy-makers, the research community and practitioners are discussed: end-use energy demand policy needs to be informed by a socio-technical approach.     

Real-time PCR detection of the thermostable direct hemolysin and thermolabile hemolysin genes in a Vibrio parahaemolyticus cultured from mussels and mussel homogenate associated with a foodborne outbreak

Molecular methods have become vital epidemiological tools in the detection and characterization of bacteria associated with a foodborne outbreak. We used both culture and real-time PCR to detect a Vibrio parahaemolyticus isolate associated with a foodborne outbreak. The outbreak occurred in July 2002 in Polk County, Florida, and originated at a Chinese buffet, with one person being hospitalized. The hospital isolated V. parahaemolyticus from the patient but destroyed the sample after diagnosis. From an onsite visit of the restaurant, food samples that possibly contributed to the outbreak were collected and sent to the Florida Department of Health, Tampa Branch Laboratory. Crab legs, crabsticks, and mussel samples were homogenized and incubated according to the Food and Drug Administration Bacteriological Analytical Manual culture protocol. Three sets of primers and a TaqMan probe were designed to target the tdh, trh, and tlh genes and used for real-time PCR. This study was successful in isolating V. parahaemolyticus from a mussel sample and detecting two of its genes (tdh and tlh) in food and pure culture by real-time PCR.     

Response latencies in auditory sentence comprehension: Effects of linguistic versus perceptual challenge.

Older adults with good hearing and with mild-to-moderate hearing loss were tested for comprehension of spoken sentences that required perceptual effort (hearing speech at lower sound levels), and two degrees of cognitive load (sentences with simpler or more complex syntax). Although comprehension accuracy was equivalent for both participant groups and for young adults with good hearing, hearing loss was associated with longer response latencies to the correct comprehension judgments, especially for complex sentences heard at relatively low amplitudes. These findings demonstrate the need to take into account both sensory and cognitive demands of speech materials in older adults' language comprehension. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.