To analyze the role of the classical and alternative pathways of complement activation in the effector phase of arthritis, we have induced arthritis in C3-and factor B (FB)-deficient (C3 -/-and FB -/-) DBA/1J mice using well-defined monoclonal IgG2b and IgG2a antibodies to type II collagen. In control DBA/1J mice, severe swelling of the joints, destruction of cartilage and erosion of bone developed very rapidly with a 100% incidence and a peak on days 7-10. Although 75% of C3 -/-mice developed arthritis, the clinical severity was very mild and the onset was delayed. Severity of arthritis in FB -/-mice ranked intermediate in comparison with C3 -/-and control mice with an incidence of 100%. Immunohistochemical analysis of the inflamed joints demonstrated substantial reduction in macrophage and neutrophilic leukocyte infiltration in both C3 -/-and FB -/-mice, thereby confirming the clinical findings. We conclude that both the classical and the alternative pathways of complement activation are involved in the effector phase of arthritis.

Objective-To investigate the effect of complement deficiency on atherogenesis and lipidemia, we used mice deficient in the third complement component (C3Ϫ/Ϫ) or factor B (FBϪ/Ϫ). Methods and Results-Complement-deficient mice were crossed with mice deficient in both apolipoprotein E and the low-density lipoprotein receptor (ApoeϪ/Ϫ LDLRϪ/Ϫ). The percent lesion area in the aorta at 16 weeks, determined by en face analysis, was 84% higher in C3Ϫ/Ϫ mice than in controls (11.8%Ϯ0.4% versus 6.4%Ϯ0.8%, meanϮSEM, PϽ0.00005). The C3Ϫ/Ϫ mice also had 58% higher serum triglyceride levels (PϽ0.05) and a more proatherogenic lipoprotein profile, with significantly more low-density lipoprotein cholesterol and very-low-density lipoprotein triglycerides than control mice. The C3Ϫ/Ϫ mice weighed 13% less (PϽ0.01) and had a lower body fat content (3.5%Ϯ1.0% versus 13.1%Ϯ3.0%, PϽ0.01). There were no differences between FBϪ/Ϫ mice and controls. Key Words: atherosclerosis Ⅲ complement Ⅲ C3 Ⅲ factor B Ⅲ hyperlipidemia T he complement system plays an essential role in the humoral immune response. Soluble complement components are present in the blood in precursor forms and need to be activated to fulfill their specific physiological roles. Activated complement has diverse functions, including the initiation of inflammation, recruitment of leukocytes, clearance of immune complexes, neutralization of pathogens, regulation of antibody responses, and disruption of cell membranes. The complement cascade can be activated by 3 pathways. The classical activation pathway depends on assembly of complement factors at sites of antigen-antibody complexes. The lectin pathway is initiated by mannan-binding lectin bound to pathogen surfaces. Activation of the alternative pathway is triggered by a variety of pathogen surfaces and requires the interaction of third complement component (C3), factor B (FB), and factor D. Regardless of the pathway, activation leads to the cleavage of C3. This generates the smaller, proinflammatory C3a fragment and the larger C3b fragment. C3b can act as an opsonin and triggers the terminal part of the cascade, which culminates in the assembly of the terminal complement complex (TCC) on the target surface.C3-derived peptides have been implicated in the regulation of lipid metabolism. C3a and C3a des-Arg , a peptide formed when the C-terminal arginine is removed from C3a by carboxypeptidase N, can act as acylation-stimulating protein (ASP). 1 ASP has been implicated in adipose tissue function and maintenance of metabolic homeostasis. 2 ASP and C3a increase fat storage in adipocytes through increased triglyceride synthesis 3-5 and decreased intracellular lipolysis. 5 Mice that are deficient in C3, and therefore unable to synthesize ASP, have delayed triglyceride clearance, 6 -8 which can be normalized by administration of ASP. 7,9,10 However, Wetsel et al did not detect any impaired ability of C3Ϫ/Ϫ mice to clear triglycerides and free fatty acids from the circulation after an oral fat load. 11 FBϪ/Ϫ mice are viable and ferti...

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The advent of intensity-modulated radiation therapy makes it increasingly important to model the response accurately when large volumes of normal tissues are irradiated by controlled graded dose distributions aimed at maximizing tumor cure and minimizing normal tissue toxicity. The cell survival model proposed here is very useful and flexible for accurate description of the response of healthy tissues as well as tumors in classical and truly radiobiologically optimized radiation therapy. The repairable-conditionally repairable (RCR) model distinguishes between two different types of damage, namely the potentially repairable, which may also be lethal, i.e. if unrepaired or misrepaired, and the conditionally repairable, which may be repaired or may lead to apoptosis if it has not been repaired correctly. When potentially repairable damage is being repaired, for example by nonhomologous end joining, conditionally repairable damage may require in addition a high-fidelity correction by homologous repair. The induction of both types of damage is assumed to be described by Poisson statistics. The resultant cell survival expression has the unique ability to fit most experimental data well at low doses (the initial hypersensitive range), intermediate doses (on the shoulder of the survival curve), and high doses (on the quasi-exponential region of the survival curve). The complete Poisson expression can be approximated well by a simple bi-exponential cell survival expression, S(D) = e(-aD) + bDe(-cD), where the first term describes the survival of undamaged cells and the last term represents survival after complete repair of sublethal damage. The bi-exponential expression makes it easy to derive D(0), D(q), n and alpha, beta values to facilitate comparison with classical cell survival models.

Gas monitoring in human sinuses using tunable diode laser spectroscopyPersson, Linda; Andersson, Mats; Lewander, Märta; Svanberg, Katarina; Svanberg, Sune General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Abstract. We demonstrate a novel nonintrusive technique based on tunable diode laser absorption spectroscopy to investigate human sinuses in vivo. The technique relies on the fact that free gases have spectral imprints that are about 10.000 times sharper than spectral structures of the surrounding tissue. Two gases are detected; molecular oxygen at 760 nm and water vapor at 935 nm. Light is launched fiber optically into the tissue in close proximity to the particular maxillary sinus under study. When investigating the frontal sinuses, the fiber is positioned onto the caudal part of the frontal bone. Multiply scattered light in both cases is detected externally by a handheld probe. Molecular oxygen is detected in the maxillary sinuses on 11 volunteers, of which one had constantly recurring sinus problems. Significant oxygen absorption imprint differences can be observed between different volunteers and also left-right asymmetries. Water vapor can also be detected, and by normalizing the oxygen signal on the water vapor signal, the sinus oxygen concentration can be assessed. Gas exchange between the sinuses and the nasal cavity is also successfully demonstrated by flushing nitrogen through the nostril. Advantages over current ventilation assessment methods using ionizing radiation are pointed out. Gas monitoring in human sinuses