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At least 397 records · Page 22Linked to original sources

The role of aldose reductase in sugar cataract formation: aldose reductase plays a key role in lens epithelial cell death (apoptosis).

Since aldose reductase is localized primarily in lens epithelial cells, osmotic insults induced by the accumulation of sugar alcohols occur first in these cells. To determine whether the accumulation of sugar alcohols can induce lens epithelial cell death, galactose-induced apoptosis has been investigated in dog lens epithelial cells. Dog lens epithelial cells were cultured in Dulbecco's modified Eagle's mimimum essential medium (DMEM) supplemented with 20% fetal calf serum (FCS). After reaching confluence at fifth passage, the medium was replaced with the same DMEM medium containing 50 mM D-galactose and the cells were cultured for an additional 2 weeks. Almost all of the cells cultured in galactose medium were stained positively for apoptosis with the terminal deoxynucleotidyl transferance-mediated biotin-dUTP nick end labeling (TUNEL) technique. Agarose gel electrophoresis of these cells displayed obvious DNA fragmentation, known as a ladder formation. All of these apoptotic changes were absent in similar cells cultured in galactose medium containing 1 microM of the aldose reductase inhibitor AL 1576. Addition of AL 1576 also reduced the cellular galactitol levels from 123+/-10 microgram/10(6) cells (n=5) to 3.9+/-1.9 microgram/10(6) cells (n=5). These observations confirm that galactose induced apoptosis occurs in dog lens epithelial cells. Furthermore, the prevention of apoptosis by an aldose reductase inhibitor suggests that this apoptosis is linked to the accumulation of sugar alcohols.

Aldehyde Reductase↗

Role of leukocytes in ethanol-induced microvascular injury in the rat brain in situ: potential role in alcohol brain pathology and stroke.

Effects of acute and chronic alcohol ethanol administration on in vivo microvascular-leukocyte dynamics was studied in brains of naive and leukocyte-depleted rats by direct, quantitative intravital high-resolution TV microscopy, fluorescence microscopy and myeloperoxidase staining. Administration of alcohol produced dose-dependent venular vasospasm, and rolling and adherence of leukocytes to venular walls; leukocyte velocity concomitantly decreased. Intermediate to high doses of ethanol resulted in infiltration of leukocytes and macrophages across venular walls, and concentration-dependent increases in myeloperoxidase staining in parenchyma, and rupture of postcapillary venules with focal hemorrhages. Use of phosphorus 31-nuclear magnetic resonance spectroscopy on intact animals revealed that the latter were associated with whole brain losses in intracellular levels of ATP and phosphocreatine with concomitant rises in intracellular inorganic phosphate and hydrogen ion concentration. Vinblastine-depletion of circulating leukocytes prevented or ameliorated greatly the alcohol-induced microvascular damage and proinflammatory-like reactions. These new results, when viewed in light of other recent findings, suggest that alcohol-induced cerebral vascular and brain damage is dependent, to a large extent, on recruitment of leukocytes.

Animals↗

Results of surgical treatment of stage III lung carcinoma with carinal proximity. The role of sleeve lobectomy versus pneumonectomy and the role of sleeve pneumonectomy.

Sleeve lobectomy in specific situations can be an alternative to pneumonectomy. Sleeve pneumonectomy is an aggressive resection for carcinoma involving the tracheobronchial angle, carina, or lower trachea and lung. Sleeve lobectomy is questioned because of its technical difficulties and its postoperative complications. Sleeve pneumonectomy is controversial in that its postoperative mortality and long-term survival rates are similar, it is a technically difficult procedure, and its mortality rate is greater than that of standard pneumonectomy. The indications for the procedures and patient selection are discussed.

Adult↗

A genome-wide housekeeping role for TFIID and a highly regulated stress-related role for SAGA in Saccharomyces cerevisiae.

TFIID and SAGA share a common set of TAFs, regulate chromatin, and deliver TBP to promoters. Here we examine their relationship within the context of the Saccharomyces cerevisiae genome-wide regulatory network. We find that while TFIID and SAGA make overlapping contributions to the expression of all genes, TFIID function predominates at approximately 90% and SAGA at approximately 10% of the measurable genome. Strikingly, SAGA-dominated genes are largely stress induced and TAF independent, and are downregulated by the coordinate action of a variety of chromatin, TBP, and RNA polymerase II regulators. In contrast, the TFIID-dominated class is less regulated, but is highly dependent upon TAFs, including those shared between TFIID and SAGA. These two distinct modes of transcription regulation might reflect the need to balance inducible stress responses with the steady output of housekeeping genes.

DNA-Binding Proteins↗

The role of imagination in the disease process: pre-Cartesian histroy (the role of imagination in the disease process).

Ancient and Renaissance physicians implicated the soul's imaginative faculty in the genesis and remission of disease. The theory stated that images of objects of desire or aversion aroused emotions, which in turn set up humoral imbalances, disturbing digestion and other vital functions, culminating in various forms of pathology. This concept explained the therapeutic efficacy of 'placebos' in forms such as spells, charms and talismans. The theory merits close attention by contemporary physicians and researchers.

History of Medicine↗

Dimerization of MoMuLV genomic RNA: redefinition of the role of the palindromic stem-loop H1 (278-303) and new roles for stem-loops H2 (310-352) and H3 (355-374).

Genomic RNAs from retroviruses are packaged as dimers of two identical RNA molecules. In Moloney murine leukemia virus, a stem-loop structure (H1) located in the encapsidation domain Psi (nucleotides 215-564) was postulated to trigger RNA dimerization through base pairing between auto complementary sequences. The Psi domain also contains two other stem-loop structures (H2 and H3) that are essential for RNA packaging. Since it was suspected than H1 is not the only element involved in RNA dimerization, we systematically investigated the dimerization capacity of several subdomains of the first 725 nucleotides of genomic RNA. The efficiency of dimerization of the various RNAs was estimated by measuring their apparent dissociation constants, and the specificity was tested by competition experiments. Our results indicate that the specificity of dimerization of RNA nucleotides 1-725 is driven by motifs H1-H3 in domain Psi. To define the relative contributions of these elements, RNA deletion mutants containing different combinations of H1-H3 were constructed and further analyzed in competition and kinetic experiments. Our results confirm the importance of H1 in triggering dimerization and shed new light on the mechanism of dimerization. H1 is required to provide a stable dimer, probably through the formation of extended intermolecular interactions. However, H1-mediated association is a slow process that is kinetically enhanced by H3, and to a lesser extent by H2. We suggest that they facilitate the recognition between the two RNAs, most likely through their conserved GACG loops. Our results reinforce the idea that dimerization and packaging are two closely related processes.

Animals↗

The role of ascorbic acid role in the differentiation of sclerotia in Sclerotinia minor.

Sclerotinia minor in culture produces ascorbic acid in levels dependent on oxidative growth conditions and stage of development. During differentiation reduced/oxidized ascorbate ratio decreased by 12 and 6 fold at high and low oxidative stress, respectively. Exogenous ascorbate caused a concentration-dependent decrease of oxidative stress (lipid peroxidation), inhibition of sclerotial differentiation (up to 100%) and delay of differentiatlon (up to 10 days). Ascorbic acid may be produced to help the fungus reduce oxidative stress during growth. The data of this study support our theory proposing that oxidative stress is the inducing factor of sclerotial differentiation in fungi.

Antioxidants↗