Aggressive drug therapy for rheumatoid arthritis

Recent data indicate that rheumatoid arthritis is more often systemic, progressive, and disabling than benign, and that it reduces life expectancy. The new evidence argues for a dramatic alteration in pharmacologic management. If several months of rest, exercise, and anti-inflammatory therapy are ineffectual, aggressive treatment with disease-modifying antirheumatic and immunosuppressive agents may be in order.     

Models of the self and other: Fundamental dimensions underlying measures of adult attachment.

Three studies, involving 146 undergraduates and 68 heterosexual couples, assessed the construct validity of the self- and other-model dimensions underlying the 4-category model of adult attachment. Five methods were used to assess the hypothesized dimensions: self-reports, friend-reports, romantic partner reports, trained judges' ratings of peer attachment, and trained judges' ratings of family attachment. Study 2 related the latent attachment dimensions to theoretically relevant outcome latent variables. As predicted, Ss' self models converged with direct measures of the positivity of their self-concepts, and Ss' other models converged with direct measures of the positivity of their interpersonal orientations. Study 3 related the latent attachment dimensions to 3 alternate self-report measures of adult attachment and showed that the 2 dimensions served as an organizing framework for the different measurement approaches. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The C-terminus of c-ABL is required for proliferation and viability signaling in a c-ABL/erythropoietin receptor fusion protein

Activated ABL oncogenes cause B-cell leukemias in mice and chronic myelogenous leukemia in humans. However, the mechanism of transformation is complex and not well understood. A method to rapidly and reversibly activate c-ABL was created by fusing the extra-cytoplasmic and transmembrane domain of the erythropoietin (EPO) receptor with c-ABL (EPO R/ABL). When this chimeric receptor was expressed in Ba/F3 cells, the addition of EPO resulted in a dose-dependent activation of c-ABL tyrosine kinase and was strongly antiapoptotic and weakly mitogenic. To evaluate the contributions of various ABL domains to biochemical signaling and biological effects, chimeric receptors were constructed in which the ABL SH3 domain was deleted (triangle upSH3), the SH2 domain was deleted (triangle upSH2), the C-terminal actin-binding domain was deleted (triangle upABD), or kinase activity was eliminated by a point mutation, K290M (KD). The mutant receptors were stably expressed in Ba/F3 cells and analyzed for signaling defects, proliferation, viability, and EPO-induced leukemia in nude mice. When compared with the ability of the full-length EPO R/ABL receptor to induce proliferation and support viability in vitro, the triangle upSH3 mutant was equivalent, the triangle upSH2 mutant was moderately impaired, and the triangle upABD and KD mutants were profoundly impaired. None of these cell lines caused leukemia in mice in the absence of pharmacological doses of EPO. However, in mice treated with EPO (10 U/d), death from leukemia occurred rapidly with wild-type and triangle upSH3. However, time to death was prolonged by at least twofold for triangle upSH2 and greater than threefold for triangle upABD. This inducible model of ABL transformation provides a method to link specific signaling defects with specific biological defects and has shown an important role for the C-terminal actin-binding domain in proliferation and transformation in the context of this receptor/oncogene.     

Polymerase chain reaction amplification analyses of clonality in T-cell malignancy including peripheral T-cell lymphoma

Clonality in T-cell malignancy was investigated using T-cell receptor (TcR) V beta 1-20 family primers and polymerase chain reaction amplification (PCR) of cDNA prepared from tissue biopsies and blood involved with tumour. Secondary PCR amplification of the VDJ joints of primary PCR products was performed to distinguish clonal from polyclonal products, and clonal V beta gene products were confirmed by direct PCR sequencing in the majority of cases. In eight T-cell malignancies including T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell chronic lymphocytic leukaemia (T-CLL) shown to be clonal by Southern blot analysis, one or two primary PCR products were identified and shown to be clonal. In five cases of peripheral T-cell lymphoma (PTCL) all V beta 1-20 families were identified after primary PCR amplification, and clonal products were identified in two cases after secondary amplification; TcR V beta clonal families could not be demonstrated in the remaining three cases. These data were in agreement with previous Southern blot analysis of these cases, and confirmed the presence of reactive T cells in PTCL as well as providing further evidence for the genotypic heterogeneity of this entity. In the remaining case, a blood lymphocytosis, primary PCR amplification produced predominant TcR V beta 6 and V beta 12 family products, of which the V beta 6 family proved clonal after secondary PCR amplification. There was no evidence for overrepresentation of TCR V beta families by the tumour populations in this study, furthermore the data confirm the involvement of reactive cells in T-cell malignancy and the genetic heterogeneity of PTCL.     

Continuous and discontinuous fatigue crack growth of irradiated ultrahigh molecular mass polyethylene in saline solution at 37°C

To provide data for prosthesis design, the fatigue crack growth resistance of irradiated ultrahigh molecular mass polyethylene (UHMMPE) in saline solution at 37°C was determined from tests performed on compact tension specimens, comparable in size to the components in knee prostheses. The specimens were cyclically loaded by using a sinusoidal wave form at 1 Hz with a minimum-to-maximum load ratio of 0.1. Scanning electron microscopic fractography was used to examine the fracture surfaces. At higher stress levels, the Paris's Law was used to analyse the data, and a striation pattern with each striation corresponding to multi-cycles was observed. At lower stress levels, discontinuous fatigue crack growth was found, a phenomenon which dominated the fatigue life of the material and had not been reported previously in this material. A craze zone ahead of the crack tip was observed, which formed the discontinuous crack growth band with a length relevant to the Dugdale plastic zone length.     

100 mK bolometers for the submillimetre common-user bolometer array (scuba) I. Design and construction

We describe the design and construction of bolometric detectors for SCUBA - the Submillimetre Common-User Bolometer Array for the James Clerk Maxwell Telescope in Hawaii. The instrument contains 131 individual detectors, in two arrays, optimized for the submillimetre atmospheric transmission windows. The detectors are cooled by dilution refrigeration to a temperature of 100 mK, so that the receiver performance will be limited by photon noise from the sky and telescope background in all wavebands. A future paper will describe the performance of the detectors with reference to typical data obtained during the laboratory commissioning period.     

Tissue fixation security in transosseous rotator cuff repairs: a mechanical comparison of simple versus mattress sutures

The primary purpose of this investigation was to compare tissue fixation security by simple sutures versus mattress sutures in transosseous rotator cuff repair. These two repair techniques were each performed in 17 human cadaver shoulders, with two bone tunnels being used for the repair by two simple sutures and two other bone tunnels being used for the repair by one mattress suture. The repairs were loaded to failure in a servohydraulic materials test system. Rotator cuff repair by simple sutures was found to be significantly stronger than repair by mattress sutures (P = .0007). The average ultimate load to failure for the simple suture construct (189.62 N) was 39.72% greater than that for the mattress suture construct (135.71 N). Most of the failures occurred by suture breakage at the knot. Load-sharing by multiple suture tails and multiple knots in the simple suture configuration likely contributed to its superior strength characteristics compared with the mattress suture configuration.     

Shear numbers of protein beta-barrels: definition refinements and statistics

The original definition of shear number for a beta-barrel is not unique if it contains one or more uneven beta-bulges. We define the shear number of a beta-barrel as the minimal change of residue numbers in the backbone direction for all closed paths on the beta-barrel. We also discuss how to overcome some computational difficulties. It is pointed out that some closed beta-sheets should not be considered as beta-barrels. The pertinent statistics obtained from a representative list of the Protein Data Bank entries are summarized. All beta-barrels have positive shear numbers, i.e. they are right-twisted. The shear numbers of most beta-barrels are even, but exceptions do exist. The sizes of beta-ladders in a beta-barrel vary significantly. Most beta-barrels contain uneven beta-bulges, which may have important biological functions.