Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinity

<p>Abstract</p> <p>Background</p> <p>The collagen antibody-induced arthritis (CAIA) model, which employs a cocktail of monoclonal antibodies (mAbs) to type II collagen (CII), has been widely used for studying the pathogenesis of autoimmune arthritis. In this model, not all mAbs to CII are capable of inducing arthritis because one of the initial events is the formation of collagen-antibody immune complexes on the cartilage surface or in the synovium, and subsequent activation of the complement by the complexes induces arthritis, suggesting that a combination of mAbs showing strong ability to bind mouse CII and activate the complement may effectively induce arthritis in mice. In the present study, we examined the relationship between the induction of arthritis by the combination of IgG2a (CII-6 and C2A-12), IgG2b (CII-3, C2B-14 and C2B-16) and IgM (CM-5) subclones of monoclonal antibodies (mAb) of anti-bovine or chicken CII and the ability of mAbs to activate complement and bind mouse CII.</p> <p>Methods</p> <p>DBA/1J mice were injected with several combinations of mAbs followed by lipopolysaccharide. Furthermore, the ability of mAbs to activate the complement and bind mouse CII was examined by ELISA.</p> <p>Results</p> <p>First, DBA/1J mice were injected with the combined 4 mAbs (CII-3, CII-6, C2B-14, and CM-5) followed by lipopolysaccharide, resulting in moderate arthritis. Excluding one of the mAbs, i.e., using only CII-3, CII-6, and C2B-14, induced greater inflammation of the joints. Next, adding C2A-12 but not C2B-16 to these 3 mAbs produced more severe arthritis. A combination of five clones, consisting of all 5 mAbs, was less effective. Histologically, mice given the newly developed 4-clone cocktail had marked proliferation of synovial tissues, massive infiltration by inflammatory cells, and severe destruction of cartilage and bone. Furthermore, 4 of the 6 clones (CII-3, CII-6, C2B-14, and C2A-12) showed not only a strong cross-reaction with mouse CII but also marked activation of the complement <it>in vitro</it>.</p> <p>Conclusion</p> <p>The combination of 4 mAbs showing strong abilities to activate the complement and bind mouse CII effectively induced arthritis in DBA/1J mice. This <it>in vitro </it>system may be useful for the selection of mAbs associated with the development of arthritis.</p

Relaxation kinetics of photoinduced surface relief grating on azopolymer films

This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. This article appeared in Tatsunosuke Matsui, Shin-ichiro Yamamoto, Masanori Ozaki, Katsumi Yoshino, and Francois Kajzar, Journal of Applied Physics 92, 6959 (2002) and may be found at https://doi.org/10.1063/1.1516264

Solid phase epitaxy of molecular beam deposited amorphous GaAs on Si

Solid phase epitaxial (SPE) crystallization of amorphous GaAs on (100) Si tilted by 4° toward formed by molecular beam deposition (MBD) was first achieved by cw Kr laser irradiation for short durations. The ratio of As to Ga (y/x) in deposited amorphous GaxAsy films was varied from 0.4 to 1.2. During the laser irradiation, movement of the amorphous/crystalline interface was measured using time-resolved optical reflectivity (TROR). It was found from TROR and micro-Raman scattering measurements that hetero-SPE is attained in samples with As/Ga ratios ranging from 0.8 to 1.1 and that the interface roughness is larger than that observed in homo-SPE (e.g., MBD GaAs on GaAs and P+ ion-implanted GaAs)

Inflammation induced by bacterial cell wall fragments in the rat air pouch. Comparison of rat strains and measurement of arachidonic acid metabolites.

Streptococcal cell wall fragments, suspended in phosphate-buffered saline, were injected into a preformed subcutaneous air pouch in rats. The advantage of the air pouch model is the capacity for quantitation of exudative, cellular, and proliferative responses and soluble mediators. Accumulation of pouch fluid containing many leukocytes occurred during the first 3 days. Granulation tissue separable from the surrounding subcutaneous tissue developed by 6 days. Immunofluorescence and immunoperoxidase staining showed the presence of cell walls in inflammatory cells both in pouch fluid and in pouch tissue. Histologic features of this inflammation included an acute exudative phase with a predominantly neutrophil infiltration followed by a chronic phase characterized by fibroblast proliferation, formation of blood vessels, and infiltration with mononuclear cells. The lining of the pouch before injection of cell wall developed morphologic features of synovial membrane, which became more evident during the chronic phase of induced inflammation. Outbred Sprague-Dawley and inbred Lewis rats developed more pouch fluid, cell numbers in the pouch fluid, and granulation tissue than inbred Buffalo rats. The arachidonic acid metabolites, prostaglandin E2 and leukotriene B4, were measured in the pouch fluid, and more of each was produced in the Lewis than in the Buffalo strain. These measurements of inflammation are consistent with the relative susceptibility of these strains to cell-wall-induced arthritis. This model of inflammation can be used in the examination of the regulatory mechanisms of evolving chronic inflammation

Psychosocial functioning in patients with treatment-resistant depression after group cognitive behavioral therapy

<p>Abstract</p> <p>Background</p> <p>Although patients with Treatment Resistant Depression (TRD) often have impaired social functioning, few studies have investigated the effectiveness of psychosocial treatment for these patients. We examined whether adding group cognitive behavioral therapy (group-CBT) to medication would improve both the depressive symptoms and the social functioning of patient with mild TRD, and whether any improvements would be maintained over one year.</p> <p>Methods</p> <p>Forty-three patients with TRD were treated with 12 weekly sessions of group-CBT. Patients were assessed with the Global Assessment of Functioning scale (GAF), the 36-item Short-Form Health Survey (SF-36), the Hamilton Rating Scale for Depression (HRSD), the Dysfunctional Attitudes Scale (DAS), and the Automatic Thought Questionnaire-Revised (ATQ-R) at baseline, at the termination of treatment, and at the 12-month follow-up.</p> <p>Results</p> <p>Thirty-eight patients completed treatment; five dropped out. For the patients who completed treatment, post-treatment scores on the GAF and SF-36 were significantly higher than baseline scores. Scores on the HRSD, DAS, and ATQ-R were significantly lower after the treatment. Thus patients improved on all measurements of psychosocial functioning and mood symptoms. Twenty patients participated in the 12-month follow-up. Their improvements for psychosocial functioning, depressive symptoms, and dysfunctional cognitions were sustained at 12 months following the completion of group-CBT.</p> <p>Conclusions</p> <p>These findings suggest a positive effect that the addition of cognitive behavioural group therapy to medication on depressive symptoms and social functioning of mildly depressed patients, showing treatment resistance.</p

Methotrexate-associated lymphoproliferative disorder with multiple pulmonary nodules and bilateral cervical lymphadenopathy

As has been well recognized, methotrexate (MTX) leads to a state of immunosuppression and can provide a basis for the development of lymphoproliferative disorders (LPDs). MTX-associated LPDs can affect nodal sites as well as extranodal sites, though the manifestation of an LPD in the form of multiple pulmonary nodules is rare. Here, we report two cases of MTX-associated LPD with multiple bilateral pulmonary nodules, which was a finding suggestive of lung cancer, and bilateral cervical lymphadenopathy. After withdrawal of MTX, the multiple bilateral pulmonary nodules and bilateral cervical lymphadenopathy disappeared without chemotherapy in both cases. From these results, patients with pulmonary nodules and cervical lymphadenopathy should be examined for head and neck malignant tumors. Also, physicians should carefully check the administration of MTX. In patients with an MTX-associated LPD, we need to make an early diagnosis and consider discontinuing the administration of MTX as soon as possible

Fine tuning Exo2, a small molecule inhibitor of secretion and retrograde trafficking pathways in mammalian cells

The small molecule 4-hydroxy-3-methoxybenzaldehyde (5,6,7,8-tetrahydro[1]benzothieno[2,3- d]pyrimidin-4-yl)hydrazone (Exo2) stimulates morphological changes at the mammalian Golgi and trans-Golgi network that are virtually indistinguishable from those induced by brefeldin A. Both brefeldin A and Exo2 protect cells from intoxication by Shiga(-like) toxins by acting on other targets that operate at the early endosome, but do so at the cost of high toxicity to target cells. The advantage of Exo2 is that it is much more amenable to chemical modification and here we report a range of Exo2 analogues produced by modifying the tetrahydrobenzothienopyrimidine core, the vanillin moiety and the hydrazone bond that links these two. These compounds were examined for the morphological changes they stimulated at the Golgi stack, the trans Golgi network and the transferrin receptor-positive early endosomes and this activity correlated with their inherent toxicity towards the protein manufacturing ability of the cell and their protective effect against toxin challenge. We have developed derivatives that can separate organelle morphology, target specificity, innate toxicity and toxin protection. Our results provide unique compounds with low toxicity and enhanced specificity to unpick the complexity of membrane trafficking networks