2,472 research outputs found

    Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD)

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    Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) is currently under investigation as a photosensitizer for photodynamic therapy (PDT). Since BPD exhibits rapid pharmacokinetics in plasma and tissues, we assessed damage to tumour and muscle microvasculature when light treatment for PDT was given at short times after injection of photosensitizer. Groups of rats with chondrosarcoma were given 2 mg kg−1 of BPD intravenously 5 min to 180 min before light treatment of 150 J cm−2 690 nm. Vascular response was monitored using intravital microscopy and tumour cure was monitored by following regrowth over 42 days. For treatment at 5 or 30 min after BPD injection, blood flow stasis was limited to tumour microvasculature with lesser response in the surrounding normal microvasculature, indicating selective targeting for damage. No acute changes were observed in vessels when light was given 180 min after BPD injection. Tumour regression after light treatment occurred in all animals given PDT with BPD. Long-term tumour regression was greater in animals treated 5 min after BPD injection and least in animals given treatment 180 min after drug injection. The correlation between the timing for vascular damage and cure implies that blood flow stasis plays a significant role in PDT-induced tumour destruction. © 1999 Cancer Research Campaig

    Where Snow is a Landmark: Route Direction Elements in Alpine Contexts

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    Route directions research has mostly focused on urban space so far, highlighting human concepts of street networks based on a range of recurring elements such as route segments, decision points, landmarks and actions. We explored the way route directions reflect the features of space and activity in the context of mountaineering. Alpine route directions are only rarely segmented through decision points related to reorientation; instead, segmentation is based on changing topography. Segments are described with various degrees of detail, depending on difficulty. For landmark description, direction givers refer to properties such as type of surface, dimension, colour of landscape features; terrain properties (such as snow) can also serve as landmarks. Action descriptions reflect the geometrical conceptualization of landscape features and dimensionality of space. Further, they are very rich in the semantics of manner of motion

    Design and methods of a longitudinal study investigating the impact of antiretroviral treatment on the partnerships and sexual behaviour of HIV-infected individuals in rural KwaZulu-Natal, South Africa

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    BACKGROUND: Diagnosed HIV-infected people form an increasingly large sub-population in South Africa, one that will continue to grow with widely promoted HIV testing and greater availability of antiretroviral therapy (ART). For HIV prevention and support, understanding the impact of long-term ART on family and sexual relationships is a health research priority. This includes improving the availability of longitudinal demographic and health data on HIV-infected individuals who have accessed ART services but who are not yet ART-eligible.DESIGN AND METHODS: The aim of the study is to investigate the impact of ART on family and partner relationships, and sexual behaviour of HIV-infected individuals accessing a public HIV treatment and care programme in rural South Africa. HIV-infected men and women aged 18 years or older attending three clinics are screened. Those people initiating ART because they meet the criteria of WHO stage 4 or CD4 ? 200 cells/?L are assigned to an 'ART initiator' group. A 'Monitoring' group is composed of people whose most recent CD4 count was >500 cells/?L and are therefore, not yet eligible for ART. During the four-year study, data on both groups is collected every 6 months during clinic visits, or where necessary by home visits or phone. Detailed information is collected on social, demographic and health characteristics including living arrangements, past and current partnerships, sexual behaviour, HIV testing and disclosure, stigma, self-efficacy, quality of family and partner relationships, fertility and fertility intentions, ART knowledge and attitudes, and gender norms. Recruitment for both groups started in January 2009. As of October 2010, 600 participants have been enrolled; 386 in the ART initiator group (141, 37% male) and 214 in the Monitoring group (31, 14% male). Recruitment remains open for the Monitoring group.DISCUSSION: The data collected in this study will provide valuable information for measuring the impact of ART on sexual behaviour, and for the planning and delivery of appropriate interventions to promote family and partner support, and safe sexual behaviour for people living with HIV in this setting and elsewhere in sub-Saharan Africa

    Borrelia valaisiana resist complement-mediated killing independently of the recruitment of immune regulators and inactivation of complement components

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    Spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato complex differ in their resistance to complement-mediated killing, particularly in regard to human serum. In the present study, we elucidate the serum and complement susceptibility of B. valaisiana, a genospecies with the potential to cause Lyme disease in Europe as well as in Asia. Among the investigated isolates, growth of ZWU3 Ny3 was not affected while growth of VS116 and Bv9 was strongly inhibited in the presence of 50% human serum. Analyzing complement activation, complement components C3, C4 and C6 were deposited on the surface of isolates VS116 and Bv9, and similarly the membrane attack complex was formed on their surface. In contrast, no surface-deposited components and no aberrations in cell morphology were detected for serum-resistant ZWU3 Ny3. While further investigating the protective role of bound complement regulators in mediating complement resistance, we discovered that none of the B. valaisiana isolates analyzed bound complement regulators Factor H, Factor H-like protein 1, C4b binding protein or C1 esterase inhibitor. In addition, B. valaisiana also lacked intrinsic proteolytic activity to degrade complement components C3, C3b, C4, C4b, and C5. Taken together, these findings suggest that certain B. valaisiana isolates differ in their capability to resist complement-mediating killing by human serum. The molecular mechanism utilized by B. valaisiana to inhibit bacteriolysis appears not to involve binding of the key host complement regulators of the alternative, classical, and lectin pathways as already known for serum-resistant Lyme disease or relapsing fever borreliae

    The Stromal Processing Peptidase of Chloroplasts is Essential in Arabidopsis, with Knockout Mutations Causing Embryo Arrest after the 16-Cell Stage

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    Stromal processing peptidase (SPP) is a metalloendopeptidase located in the stroma of chloroplasts, and it is responsible for the cleavage of transit peptides from preproteins upon their import into the organelle. Two independent mutant Arabidopsis lines with T-DNA insertions in the SPP gene were analysed (spp-1 and spp-2). For both lines, no homozygous mutant plants could be detected, and the segregating progeny of spp heterozygotes contained heterozygous and wild-type plants in a ratio of 2∶1. The siliques of heterozygous spp-1 and spp-2 plants contained many aborted seeds, at a frequency of ∼25%, suggesting embryo lethality. By contrast, transmission of the spp mutations through the male and female gametes was found to be normal, and so gametophytic effects could be ruled out. To further elucidate the timing of the developmental arrest, mutant and wild-type seeds were cleared and analysed by Nomarski microscopy. A significant proportion (∼25%) of the seeds in mutant siliques exhibited delayed embryogenesis compared to those in wild type. Moreover, the mutant embryos never progressed normally beyond the 16-cell stage, with cell divisions not completing properly thereafter. Heterozygous spp mutant plants were phenotypically indistinguishable from the wild type, indicating that the spp knockout mutations are completely recessive and suggesting that one copy of the SPP gene is able to produce sufficient SPP protein for normal development under standard growth conditions

    Applying refinement to the use of mice and rats in rheumatoid arthritis research

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    Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

    The Whole Atmosphere Community Climate Model Version 6 (WACCM6)

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    The Whole Atmosphere Community Climate Model version 6 (WACCM6) is a major update of the whole atmosphere modeling capability in the Community Earth System Model (CESM), featuring enhanced physical, chemical and aerosol parameterizations. This work describes WACCM6 and some of the important features of the model. WACCM6 can reproduce many modes of variability and trends in the middle atmosphere, including the Quasi‐Biennial Oscillation, Stratospheric Sudden Warmings and the evolution of Southern Hemisphere springtime ozone depletion over the 20th century. WACCM6 can also reproduce the climate and temperature trends of the 20th century throughout the atmospheric column. The representation of the climate has improved in WACCM6, relative to WACCM4. In addition, there are improvements in high latitude climate variability at the surface and sea ice extent in WACCM6 over the lower top version of the model (CAM6) that come from the extended vertical domain and expanded aerosol chemistry in WACCM6, highlighting the importance of the stratosphere and tropospheric chemistry for high latitude climate variability
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