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531.
532.
533.
Dramatically different phenotypes in mouse models of human Tay-Sachs and Sandhoff diseases 总被引:4,自引:2,他引:4
Phaneuf D; Wakamatsu N; Huang JQ; Borowski A; Peterson AC; Fortunato SR; Ritter G; Igdoura SA; Morales CR; Benoit G; Akerman BR; Leclerc D; Hanai N; Marth JD; Trasler JM; Gravel RA 《Human molecular genetics》1996,5(1):1-14
We have generated mouse models of human Tay-Sachs and Sandhoff diseases by
targeted disruption of the Hexa (alpha subunit) or Hexb (beta subunit)
genes, respectively, encoding lysosomal beta-hexosaminidase A (structure,
alpha) and B (structure, beta beta). Both mutant mice accumulate GM2
ganglioside in brain, much more so in Hexb -/- mice, and the latter also
accumulate glycolipid GA2. Hexa -/- mice suffer no obvious behavioral or
neurological deficit, while Hexb -/- mice develop a fatal neurodegenerative
disease, with spasticity, muscle weakness, rigidity, tremor and ataxia. The
Hexb -/- but not the Hexa -/- mice have massive depletion of spinal cord
axons as an apparent consequence of neuronal storage of GM2. We propose
that Hexa -/- mice escape disease through partial catabolism of accumulated
GM2 via GA2 (asialo- GM2) through the combined action of sialidase and
beta-hexosaminidase B.
相似文献
534.
Antithrombotic effect of a monoclonal antibody to the platelet glycoprotein IIb/IIIa receptor in an experimental animal model 总被引:8,自引:1,他引:8
A murine monoclonal antibody directed at the platelet glycoprotein IIb/IIIa complex, which blocks platelet aggregation ex vivo, was tested for its antithrombotic effects in an established animal model of acute platelet thrombus formation in partially stenosed arteries. Infusion of 0.7 to 0.8 mg/kg of the F(ab')2 fragment of the antibody completely blocked new thrombus formation despite multiple provocations, making it the most potent antithrombotic agent tested in this model. 相似文献
535.
JAK2 is associated with the c-kit proto-oncogene product and is phosphorylated in response to stem cell factor 总被引:5,自引:1,他引:5
Weiler SR; Mou S; DeBerry CS; Keller JR; Ruscetti FW; Ferris DK; Longo DL; Linnekin D 《Blood》1996,87(9):3688-3693
Stem cell factor (SCF) is a hematopoietic growth factor that interacts with the receptor tyrosine kinase, c-kit. We have found that SCF- stimulates rapid and transient tyrosine phosphorylation of JAK2 in human and murine cell lines, as well as in normal human progenitor cells. JAK2 and c-kit were associated in unstimulated cells with further recruitment of JAK2 to the c-kit receptor complex after SCF stimulation. Treatment of cells with JAK2 antisense oligonucleotides resulted in a 46% decrease in SCF-induced proliferation. These data demonstrate that SCF induces tyrosine phosphorylation of JAK2 and suggest that JAK2 is a component of the SCF signal transduction pathway. 相似文献
536.
Homocysteine inhibits von Willebrand factor processing and secretion by preventing transport from the endoplasmic reticulum 总被引:10,自引:2,他引:10
Intracellular protein transport in endothelial cells is selectively inhibited by homocysteine, a thiol amino acid associated with both thrombosis and atherosclerosis. In a previous study, homocysteine decreased cell surface expression of the surface transmembrane glycoprotein thrombomodulin without decreasing secretion of another endothelial cell protein, plasminogen activator inhibitor-1. To define further the effects of homocysteine on protein transport, we examined the processing and secretion of the multimeric glycoprotein von Willebrand factor (vWF) in human umbilical vein endothelial cells. Incubation with 2 mmol/L homocysteine resulted in complete loss of vWF multimers and prevented asparagine-linked oligosaccharide maturation, propeptide cleavage, and secretion; these effects are consistent with impaired exit from the endoplasmic reticulum (ER). Dimerization was only partially inhibited, suggesting that homocysteine causes retention of provWF in the ER without preventing dimer formation. In pulse-chase incubations, intracellular provWF was degraded before exiting the ER in homocysteine-treated cells. Homocysteine also inhibited the processing and secretion of a carboxyl-terminal truncation mutant of human provWF expressed in rat insulinoma cells, indicating that retention in the endoplasmic reticulum can be mediated by regions of provWF apart from the carboxyl-terminal 20-Kd segment. These results suggest that retention of secretory proteins in the ER is regulated by redox mechanisms and imply that the intracellular transport of multiple endothelial cell proteins may be altered in patients with homocystinuria. 相似文献
537.
OJ Old SR Kulkarni TJ Hardy FJ Slim LG Emerson RA Bulbulia MR Whyman KR Poskitt 《Annals of the Royal College of Surgeons of England》2015,97(2):120-124
Introduction
Totally extra-peritoneal (TEP) inguinal hernia repair allows identification and repair of incidental non-inguinal groin hernias. We assessed the prevalence of incidental hernias during TEP inguinal hernia repair and identified the risk factors for incidental hernias.Materials and Methods
Consecutive patients undergoing TEP repair from May 2005 to November 2012 were the study cohort. Inspection for ipsilateral femoral, obturator and rarer varieties of hernia was undertaken during TEP repair. Patient characteristics and operative findings were recorded on a prospectively collected database.Results
A total of 1,532 TEP repairs were undertaken in 1,196 patients. Ninety-three patients were excluded due to incomplete data, leaving 1,103 patients and 1,404 hernias for analyses (1,380 male; 802 unilateral and 301 bilateral repairs; median age, 59 years). Among the 37 incidental hernias identified (2.6% of cases), the most common type of incidental hernia was femoral (n=32, 2.3%) followed by obturator (n=2, 0.1%). Increasing age was associated with an increased risk of incidental hernia, with a significant linear trend (p<0.01). The risk for patients >60 years of age was 4.0% vs 1.4% for those aged <60 years (p<0.01). Incidental hernias were found in 29.2% of females vs 2.2% of males, (p<0.0001). Risk of incidental hernia in those with a recurrent inguinal hernia was 3.0% vs 2.6% for primary repair (p=0.79).Conclusions
Incidental hernias during TEP inguinal hernia repair were found in 2.6% of cases and, though infrequent, could cause complications if left untreated. The risk of incidental hernia increased with age and was significantly higher in patients aged >60 years and in females. 相似文献538.
M Wilson M Dordea A Light MP Serra SR Aspinall 《Annals of the Royal College of Surgeons of England》2015,97(3):198-203
Introduction
Immediate breast reconstruction (IBR) is performed increasingly following mastectomy for breast cancer. The literature suggests higher reconstructive failure and poorer cosmesis in the subgroup of patients receiving postmastectomy radiotherapy (PMRT) following IBR. We set out to determine the accuracy of a multidisciplinary team (MDT) discussion in predicting PMRT.Methods
Preoperative MDT discussions were recorded prospectively over a 12-month period (from February 2011) in a symptomatic breast unit. The estimated need for PMRT was stratified into ‘PMRT not required’, ‘PMRT possibly required’, ‘PMRT probably required’ and ‘PMRT required’ groups.Results
Of 156 referrals included in the study, 76 patients (49%) underwent mastectomy: 61 simple mastectomy, 10 skin sparing mastectomy (SSM) and delayed-immediate breast reconstruction, 3 SSM and implant-based IBR, and 2 mastectomy IBR with an autologous flap. The IBR rate was therefore 19.7%. The proportion of patients who received PMRT was 14% (3/21) in the ‘PMRT not required’, 30% (7/23) in the ‘PMRT possibly required’, 65% (9/14) in the ‘PMRT probably required’ and 94% (17/18) in the ‘PMRT required’ groups. Assigning a linear numerical score (1–4) to these groups (higher score representing greater likelihood of receiving PMRT), the predicted need for PMRT correlated with the proportion of patients who ultimately received PMRT (linear regression r2=0.98, p=0.01).Conclusions
This study has examined the factors influencing MDT discussions regarding IBR, demonstrating that the MDT is reasonably accurate at predicting need for PMRT. Whether such accuracy is clinically adequate and/or reproducible across units is debatable. 相似文献539.
Andressa Tomazini Borghardt Thiago Nascimento do Prado Thiago Moura de Araújo Noemi Marisa Brunet Rogenski Maria Edla de Oliveira Bringuente 《Revista latino-americana de enfermagem》2015,23(1):28-35
AIMS:
to evaluate the accuracy of the Braden and Waterlow risk assessment scales in critically ill inpatients.METHOD:
this prospective cohort study, with 55 patients in intensive care units, was performed through evaluation of sociodemographic and clinical variables, through the application of the scales (Braden and Waterlow) upon admission and every 48 hours; and through the evaluation and classification of the ulcers into categories.RESULTS:
the pressure ulcer incidence was 30.9%, with the Braden and Waterlow scales presenting high sensitivity (41% and 71%) and low specificity (21% and 47%) respectively in the three evaluations. The cut off scores found in the first, second and third evaluations were 12, 12 and 11 in the Braden scale, and 16, 15 and 14 in the Waterlow scale.CONCLUSION:
the Braden scale was shown to be a good screening instrument, and the Waterlow scale proved to have better predictive power. 相似文献540.
Platelet kinetics in patients with bone marrow hypoplasia: evidence for a fixed platelet requirement 总被引:6,自引:4,他引:6
We have studied 16 normal subjects and 27 patients with stable, untreated thrombocytopenia secondary to bone marrow failure and platelet counts ranging from 12,000 to 70,000/microL. Autologous platelets were labeled with 51Cr for measurement of mean platelet life span in the normal subjects and in 20 patients. Labeled donor cells were used in the remaining subjects. Platelet survival, as determined with both autologous and homologous platelets, correlated directly with platelet count in the thrombocytopenic patients. Platelet life span was only modestly reduced in patients having counts in the range of 50,000 to 100,000/microL (7.0 +/- 1.5 days v 9.6 +/- 0.6; P less than .01) but was markedly reduced when the count fell below 50,000/microL (5.1 +/- 1.9 days, P less than .001). The recovery of donor platelets in severely thrombocytopenic recipients (60% +/- 15%) was equivalent to control values (66% +/- 8%; P greater than .2). The recovery of autologous platelets was normal when the platelet count exceeded 50,000/microL (74% +/- 15%) but was reduced in patients with lower counts (50% +/- 22%; P less than .01). All patient and normal data were well correlated by a model predicting a maximum platelet life span of 10 1/2 days and a fixed requirement for 7,100 platelets per microliter of blood per day, or about 18% of the normal rate of platelet turnover, which averaged 41,200 platelets per microliter per day. We conclude that although relatively few platelets are used to support vascular integrity, this requirement is reflected by a reduced platelet life span in marrow hypoplasia and may contribute to the shortening of platelet survival observed in other thrombocytopenias. 相似文献