MR imaging: Arthropathies and infectious conditions of the elbow, wrist, and hand

The superior soft tissue contrast and multiplanar capability of MR imaging has contributed to earlier diagnosis and implementation of effective treatment for a variety of arthropathies and infectious conditions of the elbow, wrist, and hand. Because of overlapping clinical signs and symptoms, MR imaging plays an important role in delineating the features and staging of each of these conditions. This article discusses the seropositive and seronegative inflammatory arthropathies, with emphasis on early detection and surveillance, as well as gout, synovial osteochondromatosis, pigmented villonodular synovitis, tenosynovitis, and de Quervain's tenosynovitis. Certain noninflammatory arthritides and infectious conditions are also reviewed.     

Enhanced expression of stem cell antigen-1 (Ly-6A/E) in lymphocytes from lupus prone mice correlates with disease severity

B6.Sle1 mice, congenic for the NZM2410-derived lupus susceptibility locus, Sle1 on chromosome 1 exhibit many of the features seen in human lupus including activated lymphocytes and high titers of antinuclear autoantibodies. Among the different surface molecules that were aberrantly expressed on the B6.Sle1 lymphocytes was Ly-6A/E. Splenic B- and T-lymphocytes but not myeloid cells from B6.Sle1 mice exhibited enhanced levels of Ly-6A/E compared to B6 controls. In particular, MZ B cells, GC B cells and B-cell blasts expressed the highest levels of Ly-6A/E in both strains, with the levels being even higher on B6.Sle1 derived cells. Following stimulation with LPS or anti-IgM, there was a profound up-regulation in Ly-6A/E, particularly on MZ B cells and B-cell blasts. CD4 and CD8 T cells also up-regulated Ly-6A/E after stimulation with anti-CD3 and anti-CD28. These studies were extended to additional autoimmune strains including B6.Sle3, B6.Sle1.lpr and BXSB. Importantly, Ly-6A/E levels on lymphocytes were commensurate with the degree of disease exhibited by these lupus strains. Finally, it appears that increased interferon levels, in addition to antigen receptor stimulation, may also be a factor accounting for elevated Ly-6A/E in lupus. Given these observations it is important to elucidate the functional role of Ly-6A/E in lupus in future studies.     

Human genetic approaches to diseases of lymphocyte activation

Our laboratory focuses on the study of the molecular regulation of T lymphocyte homeostasis, particularly as it relates to immunological tolerance, apoptosis, and autoimmune diseases. Through intense molecular research on the regulation of lymphocyte fate, the Fas receptor and other tumor necrosis factor receptors as well as their ligands have emerged as key regulators of T lymphocyte apoptosis. We are studying genetic abnormalities of this death pathway, particularly in the context of autoimmune lymphoproliferative syndrome (ALPS) and other non-ALPS conditions affecting lymphocyte homeostasis. These studies have led to further investigations of the regulation of the NF-kappaB signaling pathway, the molecular basis for programed cell death and viral cytopathicity, mechanisms of autoimmunity, and the regulation of mature T-cell tolerance. Our investigations promise to provide insight into the molecular mechanisms behind the regulation of immune response and contribute to the development of novel diagnostic and treatment methods for autoimmune diseases.     

Anomalous flexor digiti minimi brevis in Guyon's canal

In an adult male cadaver, the flexor digiti minimi brevis, a muscle of the hypothenar eminence, was found to arise from the superficial transverse septum (between the superficially placed flexor carpi ulnaris, palmaris longus, and flexor carpi radialis muscles, and the deeply placed flexor digitorum superficialis muscle) in the distal fourth of the flexor aspect of the left forearm. The muscle exhibited two strata of muscle fibers at its origin. The superficial stratum was a thin layer of transversely running fibers confined to the forearm, which has not been previously reported. The deep stratum, a thick layer of longitudinally running fibers, formed the bulk of the muscle. It traversed Guyon's canal superficial to the ulnar nerve and vessels to reach the hypothenar eminence. Its course through Guyon's canal could be a cause for ulnar tunnel syndrome. The ulnar nerve trunk innervated not only the anomalous flexor digiti minimi brevis muscle, but also abductor digiti minimi and palmaris brevis. This may be due to the common phylogeny of these three muscles from the same muscle mass.     

Deletion of MCL-1 causes lethal cardiac failure and mitochondrial dysfunction

MCL-1 is an essential BCL-2 family member that promotes the survival of multiple cellular lineages, but its role in cardiac muscle has remained unclear. Here, we report that cardiac-specific ablation of Mcl-1 results in a rapidly fatal, dilated cardiomyopathy manifested by a loss of cardiac contractility, abnormal mitochondria ultrastructure, and defective mitochondrial respiration. Strikingly, genetic ablation of both proapoptotic effectors (Bax and Bak) could largely rescue the lethality and impaired cardiac function induced by Mcl-1 deletion. However, while the overt consequences of Mcl-1 loss were obviated by combining with the loss of Bax and Bak, mitochondria from the Mcl-1-, Bax-, and Bak-deficient hearts still revealed mitochondrial ultrastructural abnormalities and displayed deficient mitochondrial respiration. Together, these data indicate that merely blocking cell death is insufficient to completely overcome the need for MCL-1 function in cardiomyocytes and suggest that in cardiac muscle, MCL-1 also facilitates normal mitochondrial function. These findings are important, as specific MCL-1-inhibiting therapeutics are being proposed to treat cancer cells and may result in unexpected cardiac toxicity.     

Bioactive actinomycetes from Krishna River sediments of Andhra Pradesh

Sediment samples from Krishna River at Nagayalanka of Andhra Pradesh, India were investigated as a source of actinomycetes to screen for the production of novel bioactive compounds. During our investigation on fresh water actinomycetes from 5 different river sediment samples, a total of 80 actinomycetes were isolated. Out of these 80 isolates, 30 isolates which showed distinct macromorphological characteristics were selected. The antimicrobial and enzymatic activities were studied for all the 30 isolates. The preliminary study for antimicrobial activity by cross streak method indicated that 16 isolates (53.3%) have excellent antagonistic properties. All these 16 isolates were subjected to detailed submerged fermentation studies. It was observed that 12 isolates (40.0%) exhibited antibacterial activity, 9 isolates (30.0%) showed antifungal activity while 5 isolates (16.6%) showed both antibacterial and antifungal activities. All the 30 isolates were also subjected for the determination of enzymatic activities 25 isolates (83.3%) exhibited amylolytic activity while 27 isolates (90.0%) showed proteolytic activity. Among these isolates, six promising isolates were selected for detailed morphological, cultural, physiological and biochemical studies. It was established that these isolates belong to the Streptomyces genus by virtue of their cell wall composition pattern and were identified as strains of different Streptomyces species like S. rochei, S. alanosinicus, S. erumpens, S. griseoplanus, S. gancidicus and S. nigrogriseolus.     

Peribulbar oncocytoma: high-frequency ultrasound with histopathologic correlation.

The clinical, ultrasonographic, and histopathologic characteristics of an oncocytoma of the conjunctiva are described. A 49-year-old woman presented with a red-orange lesion adjacent to the caruncle in her left eye. A clinical examination including high-frequency ultrasound was performed prior to excisional biopsy of her tumor. High-frequency ultrasound demonstrated an epibulbar tumor with low internal reflectivity and a cystic component. There was no involvement of the underlying sclera. Multiple hypoechoic components of the tumor stroma were correlated to multiple cystic glandular structures on histopathologic evaluation. The excised tumor was diagnosed to be an oncocytoma.