TRAIL induces apoptosis and activation of NFkappaB

TRAIL (TNF-related-apoptosis-inducing-ligand) was found as a new member of the TNF family which mediates cell death in a wide variety of malignant cell lines and primary tumor cells. TRAIL induces two different signals, cell death mediated by caspases and gene induction mediated by NFkappaB. Inhibition of TRAIL-induced activation of NFkappaB augments apoptosis induction by TRAIL and attenuates apoptosis resistance.     

Exploiting similarities across multiple dimensions for author name disambiguation

Scientometrics - In bibliometric analysis, ambiguity in author names may lead to erroneous aggregation of records. The author name disambiguation techniques attempt to address this issue by...     

Mycobacterium avium complex and Mycobacterium tuberculosis in patients infected with the human immunodeficiency virus

Primary care physicians play an important role in identifying and treating bacterial infections in adults infected with the human immunodeficiency virus (HIV). Mycobacterium avium complex and Mycobacterium tuberculosis are pathogens that can cause systemic or local infection in these patients. We review the epidemiology, pathogenesis, clinical presentation, and principles of treatment for these two mycobacterial pathogens. Because M tuberculosis disease is preventable and curable and yet communicable, physicians should maintain a high degree of suspicion for tuberculosis in HIV-infected adults. In comparison, the goal of treating M avium complex in patients with advanced HIV disease is to reduce constitutional symptoms and improve survival.     

Association with terminal exons in pre-mRNAs: a new role for the U1 snRNP?

Psoralen cross-linking experiments in HeLa cell nuclear extracts have revealed the binding of U1 snRNA to substrates containing the SV40 late and adenovirus L3 polyadenylation signals. The sites of U1 cross-linking to the substrates map different distances upstream of the AAUAAA sequence to regions with limited complementarity to the 5' end of U1 snRNA. U1 cross-linking to the same site in the SV40 late pre-mRNA is enhanced by the addition of an upstream 3' splice site, which also enhances polyadenylation. Examination of different nuclear extracts reveals a correlation between U1 cross-linking and the coupling of splicing and polyadenylation, suggesting that the U1 snRNP participates in the coordination of these two RNA-processing events. Mutational analyses demonstrate that U1/substrate association cannot be too strong for coupling to occur and suggest that the U1 snRNP plays a similar role in recognition of internal and 3' terminal exons. Possible mechanisms for communication between the splicing and polyadenylation machineries are discussed, as well as how interaction of the U1 snRNP with 3' terminal exons might contribute to mRNA export.     

Comparative analysis of the pC194 group of rolling circle plasmids

pC194-type plasmids have been isolated from widely divergent species of bacteria: Gram positive, Proteobacteria, Spirochaetes and Cyanobacteria. We have examined the three essential replication elements of these plasmids, i.e., the Rep protein, and the origins of double and single stranded synthesis. Comparative analysis of Rep protein sequences from these plasmids indicates that they are highly divergent. Those isolated from Gram positive species fall into five groups: a Bacillus group, a Lactobacillus group, a Streptococcus group and two Staphylococcus aureus groups. The two S. aureus clusters are quite separate, suggesting that there has been at least one plasmid transfer between divergent Gram positive species. The double stranded origin of replication and the active site of the Rep protein display similarities across species indicating that these motifs can function in very divergent hosts. In contrast the single stranded origin of replication is typical of the host from which the plasmid is isolated. This is exemplified by (i) pKYM where the single stranded origins are similar to the minus origins found on the single-stranded coliphages, and (ii) pTD1 (isolated from a Spirochaete), pNostoc, pMA1 and pRF1 (all isolated from Cyanobacteria) which have no sequence homology to the minus origins identified in Gram positive or Gram negative species. This points to the single stranded origin as a feature critical to the determination of the host range of the plasmid.     

The morphology of synovial grooves (Fossae synoviales) in joints of cattle of different age groups

The joint cartilage of the head of the radius, the metacarpal bone, the tibial cochlea, the proximal trochlea of the talus and the metatarsal bone of 26 cattle in the age groups fetuses, 0 days, 2-5 weeks, 2-5 months, 7-13 months, 2-3.5 years, and 5-7 years were examined macroscopically and histologically. Synovial grooves developed on all joint surfaces examined, but at different times. At some locations the development of the grooves began prenatally. During the groove development the same features were in principle observed on all joint surfaces: Degeneration and progressive thinning of the joint cartilage, invasion of connective tissue into the cartilage, cessation of the endochondral ossification, and depression of the groove area into the subchondral bone. The findings indicated that the synovial grooves should be considered as being part of the normal morphology of the joints. In 4 animals aged from 3 weeks to 13 months dyschondroplastic (osteochondrotic) lesions were observed in the joint cartilage both inside and outside the groove areas on one or more joint surfaces.     

A comparison of topical non-steroidal anti-inflammatory drugs to steroids for control of post cataract inflammation

Fifty patients undergoing phacoemulsification with posterior chamber intraocular lens implantation were randomly assigned to receive either diclofenac sodium 0.1% eye drops (Voltaren Ophthalmic, CibaVision Ophthalmics, Duluth, GA) or prednisolone acetate 1.0% eye drops (Pred Forte, Allergan Pharmaceuticals, Irvine, CA) as their postoperative anti-inflammatory medication. The patients were examined one day, one week, and one month after surgery, and their postoperative inflammation was evaluated both by slit lamp assessment of cell and flare, and by objective measurement of cell and flare with the Kowa FC-1000 laser cell and flare meter. At each visit, the level of postoperative inflammation was the same for the two study groups. Thus diclofenac sodium was as effective an anti-inflammatory agent for postoperative inflammation as prednisolone acetate.     

Isoflurane alters proximal tubular cell susceptibility to toxic and hypoxic forms of attack

BACKGROUND: Fluorinated anesthetics can profoundly alter plasma membrane structure and function, potentially impacting cell injury responses. Because major surgery often precipitates acute renal failure, this study assessed whether the most commonly used fluorinated anesthetic, isoflurane, alters tubular cell responses to toxic and hypoxic attack. METHODS: Mouse proximal tubule segments were incubated under control conditions or with a clinically relevant isoflurane dose. Cell viability (lactate dehydrogenase release), deacylation (fatty acid, such as C20:4 levels), and adenosine triphosphate (ATP) concentrations were assessed under one or more of the following conditions: (a) exogenous phospholipase A2 (PLA2) or C20:4 addition, (b) Ca2+ overload (A23187 ionophore), (c) increased metabolic work (Na ionophore), and (d) hypoxia- or antimycin A-induced attack. Isoflurane's effect on NBD phosphatidylserine uptake (an index of plasma membrane aminophospholipid translocase activity) was also assessed. RESULTS: Isoflurane alone caused trivial deacylation and no lactate dehydrogenase release. However, it strikingly sensitized to both PLA2- and A23187-induced deacylation and cell death. Isoflurane also exacerbated C20:4's direct membrane lytic effect. Under conditions of mild ATP depletion (Na ionophore-induced increased ATP consumption; PLA2-induced mitochondrial suppression), isoflurane provoked moderate/severe ATP reductions and cell death. Conversely, under conditions of maximal ATP depletion (hypoxia, antimycin), isoflurane conferred a modest cytoprotective effect. Isoflurane blocked aminophospholipid translocase activity, which normally maintains plasma membrane lipid asymmetry (that is, preventing its "flip flop"). CONCLUSIONS: Isoflurane profoundly and differentially affects tubular cell responses to toxic and hypoxic attack. Direct drug-induced alterations in lipid trafficking/plasma membrane orientation and in cell energy production are likely involved. Although the in vivo relevance of these findings remains unknown, they have potential implications for intraoperative renal tubular cell structure/function and how cells may respond to superimposed attack.