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Pathophysiological Significance (pathophysiological + significance)
Selected AbstractsPathophysiological significance of senescence marker protein-30GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 2010Naoki Maruyama A novel rat liver protein of 30 kDa, SMP30 decreases with aging. This protein is expressed most prominently in the liver and kidneys among the various organs. Its gene is located on the X chromosome. No functional domain was recognized in the entire amino acid sequence. Recently, we found a homology between rat SMP30 and two species of bacterial gluconolactonase (EC 3.1.1.17). The lactonase reaction with l -gulono-,-lactone is the penultimate step in vitamin C (l -ascorbic acid) biosynthesis. SMP30-knockout (KO) mice fed a vitamin C-deficient diet displayed symptoms of scurvy. In SMP30-KO mice, hepatocytes were more susceptible to apoptosis induced by TNF-, plus actinomycin D than hepatocytes from wild-type mice. Two morphological features considered to be a hallmark of senescence are apparent in SMP30-KO mice. At 12 months of age, SMP30-knockout mice had clearly visible deposits of lipofuscin and senescence-associated ,-galactosidase (SA-,-GAL) in their renal tubular epithelia. These features are compatible with high electron dense deposits in lysosomes. This observation suggests that the SMP30-knockout mouse is a useful model of ordinal senescence. Geriatr Gerontol Int 2010; 10 (Suppl. 1): S88,S98. [source] Collateral desmitis of the distal interphalangeal joint in conjunction with concurrent ossification of the cartilages of the foot in nine horsesEQUINE VETERINARY EDUCATION, Issue 9 2008T. S. Mair Summary The purpose of this study was to describe the frequency of occurrence of severe ossification of the collateral cartilages (sidebone) coexistent with collateral desmitis of the distal interphalangeal joint (DIPJ) in lame horses. Sidebone was diagnosed and graded on standard radiographs and soft tissue injuries of the foot were diagnosed using standing low-field magnetic resonance imaging (MRI). Of 15 horses with forelimb lameness and severe sidebone, 9 had evidence of concurrent collateral desmitis of the DIPJ. All 15 horses had damage to other structures (including the deep digital flexor tendon, distal sesamoidean impar ligament, collateral sesamoidean ligament, navicular bone and distal phalanx) within the affected feet as identified on MRI. The clinical and pathophysiological significance of concurrent collateral desmitis of the DIPJ and sidebone is currently uncertain. However, this study shows that injuries to multiple structures within the foot are common and that collateral desmitis of the distal interphalangeal joint is frequently seen in lame horses in conjunction with severe ossification of the collateral cartilages. [source] Enhanced expression of Mcm proteins in cancer cells derived from uterine cervixFEBS JOURNAL, Issue 6 2003Yukio Ishimi Minichromosome maintenance proteins (Mcm) 2,7 play essential roles in eukaryotic DNA replication. Several reports have indicated the usefulness of Mcm proteins as markers of cancer cells in histopathological diagnosis. However, their mode of expression and pathophysiological significance in cancer cells remain to be clarified. We compared the level of expression of Mcm proteins among human HeLa uterine cervical carcinoma cells, SV40-transformed human fibroblast GM00637 cells and normal human fibroblast WI-38 cells. All the proteins examined were detected in HeLa and GM cells at 6,10 times the level found in WI-38 cells on average. This increase was observed both in total cellular proteins and in the chromatin-bound fraction. Consistently, Mcm2 mRNA was enriched in HeLa cells to approximately four times the level in WI-38 cells, and the synthesis of Mcm4, 6 and 7 proteins was accelerated in HeLa cells. Immunohistochemical studies of surgical materials from human uterine cervix showed that Mcm3 and 4 are ubiquitously expressed in cancer cells. Further, the positive rate and level of Mcm3 and 4 expression appeared to be higher in cancer cells than in normal proliferating cells of the uterine cervix and dysplastic cells, suggesting that they can be useful markers to distinguish these cells. [source] Soluble vascular cell adhesion molecule-1 induces human eosinophil migrationALLERGY, Issue 5 2009S. Ueki Background:, Tissue eosinophilia is one of the hallmarks of allergic diseases and Th2-type immune responses including asthma. Adhesion molecules are known to play an important role in the accumulation of eosinophils in allergic inflammatory foci, and they contribute to eosinophil activation. Elevated levels of the soluble forms of adhesion molecules in the body fluid of asthmatic patients have been observed, although their pathophysiological significance remains to be fully elucidated. Methods:, Peripheral blood eosinophils were purified, and the effect of soluble vascular cell adhesion molecule-1 (sVCAM-1) on eosinophil migration was investigated using in vitro systems. Results:, We found that sVCAM-1 (1 to 10 ,g/ml) induced eosinophil chemotaxis, rather than chemokinesis, in a concentration-dependent fashion. In addition, sVCAM-1 induced cell shape change and actin polymerization, which are necessary for cell movement. Manipulations with very late antigen (VLA)-4-neutralizing antibody and signal inhibitors indicated that the sVCAM-1-induced chemotaxis was mediated through ligand-dependent activation of tyrosine kinase Src, p38 mitogen-activated protein kinase (MAPK), and extracellular signal-regulated kinase (ERK) MAPK. Rapid phosphorylation of these signaling molecules was observed using a bead-based multiplex assay. Conclusion:, Our results raise the possibility of sVCAM-1 in the fluid phase as a significant contributor to the heightened eosinophilic inflammatory response. [source] Bacterial translocation studied in 927 patients over 13 yearsBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 1 2006J. MacFie Background: Bacterial translocation (BT) describes the passage of bacteria from the gastrointestinal tract to normally sterile tissues such as the mesenteric lymph nodes (MLNs) and other internal organs. The clinical and pathophysiological significance of BT remains controversial. This report describes results obtained over a 13-year period of study. Methods: MLNs were obtained from 927 patients undergoing laparotomy. Nasogastric aspirates were obtained from 458 (49·4 per cent) of 927 patients for culture; pH was measured in 172 (37·6 per cent) of 458. Preoperative clinical variables were evaluated and factors that influenced BT were included in a multivariate logistic regression analysis. Results: BT was identified in 130 (14·0 per cent) of 927 patients. Postoperative sepsis was more common in patients with BT (42·3 versus 19·9 per cent; P < 0·001). Independent preoperative variables associated with BT were emergency surgery (P = 0·001) and total parenteral nutrition (TPN) (P = 0·015). Gastric colonization was confirmed in 248 (54·1 per cent) of 458 patients, and was associated with both BT (P = 0·015) and postoperative sepsis (P = 0·029). A gastric pH of less than 4 was associated with a significant reduction in gastric colonization (53 versus 80 per cent; P < 0·001) and postoperative sepsis (46 versus 70·3 per cent; P = 0·018) but not BT. Conclusion: BT is associated with postoperative sepsis. Emergency surgery and TPN are independently associated with an increased prevalence of BT. Copyright © 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] | ||||||||||