RM Davidson  PA Lingenbrink  LA Norton 《Canadian Metallurgical Quarterly》1996,59(6):500-504

G292 osteoblastic cells were cultured in dishes made with a flexible base of polytetrafluoroethylene (PTFE) and stretched ( approximately 1% strain level) continuously for 48 hours. Patch-clamp recording techniques were then used to monitor single channel currents of mechanosensitive ion channels in these cells. To stimulate mechanosensitive channels, we applied suction to the membrane, expressed as -cm Hg, directly through the patch pipette. GigaOhm seals were obtained on a total of 33 osteoblasts that contained a high-conductance ( approximately 180 pS) mechanosensitive channel, all in the cell attached configuration. Of these, 18 were obtained from cells that had been stretched for either 1 (n = 6), 24 (n = 4), or 48 (n = 8) hours, and 15 were obtained in control (nonstretched) cells at either 1 (n = 2), 24 (n = 5), or 48 (n = 8) hours. For unstrained cells, applied pressures ranging from -1 to -5 cm Hg increased the probability of channel opening (Popen) from 0.05 +/- 0. 01 (mean + SEM) to 0.12 +/- 0.07. By contrast, for the same values of applied pressure in stretched cells, Popen ranged from 0.06 +/- 0. 01 to 0.49 +/- 0.15. Our results suggest that intrinsic properties of mechanosensitive ion channels in the G292 osteoblastic cell may be modulated by continuous mechanical loading of the cell itself.  相似文献   

    

KW Mahaffey  CB Granger  R Collins  CM O'Connor  EM Ohman  SD Bleich  JJ Col  RM Califf 《Canadian Metallurgical Quarterly》1996,77(8):551-556

Intravenous heparin is routinely given after thrombolytic therapy for patients with acute myocardial infarction in the United States and in some, but by no means all, other countries. Several trials have documented improved infarct-artery patency in patients treated with heparin; however, none was large enough individually to assess the effect of heparin on clinical outcomes. We performed a systematic overview of the 6 randomized controlled trials (1,735 patients) to summarize the available data concerning the risks and benefits of intravenous heparin versus no heparin after thrombolytic therapy. Mortality before hospital discharge was 5.1% for patients allocated to intravenous heparin compared with 5.6% for controls (relative risk reduction of 9%, odds ratio 0.91, 95% confidence interval 0.59 to 1.39). Similar rates of recurrent ischemia and reinfarction were observed among those allocated to heparin therapy or control. The rates of total stroke, intracranial hemorrhage, and severe bleeding were similar in patients allocated to heparin; however, the risk of any severity of bleeding was significantly higher (22.7% vs 16.2%; odds ratio 1.55, 95% confidence interval 1.21 to 1.98). There was no significant difference in the observed effects of heparin between patients receiving tissue-type plasminogen activator and those receiving streptokinase or anisoylated plasminogen streptokinase activator complex, or between patients who did and did not receive aspirin. The findings of this overview demonstrate that insufficient clinical outcome data are available to support or to refute the routine use of intravenous heparin therapy after thrombolysis. It is not known if these findings are due to lack of statistical power, inappropriate levels of anticoagulation, or lack of benefit of intravenous heparin. Large randomized studies of heparin (and of new antithrombotic regimens) are needed to establish the role of such therapy.  相似文献   

    

RM Mohammad  A Maki  GR Pettit  AM al-Katib 《Canadian Metallurgical Quarterly》1996,49(5-6):262-272

It has been previously reported that Bryostatin 1 (Bryo1) induces differentiation of the human acute lymphoblastic leukemia (ALL) cell line, Reh, to a monocytoid B-cell stage. In this study we demonstrate that a novel protein, ubiquitin COOH-terminal hydrolase (UCH-L1), is associated with this differentiation. Reh cells were treated with 200 nmol/l of Bryo1 for 72 h and analyzed for changes in morphology, surface immunophenotype, acid phosphatase and terminal deoxynucleotidyl transferase. Protein patterns of the parent and differentiated cells, by two-dimensional polyacrylamide gel electrophoresis (2D PAGE), were studied. Bryo1-treated cells expressed morphologic, phenotypic and enzymatic features of the monocytoid B-cell stage. The UCH-L1 enzyme (MW-pl 34-5.3) was detected by 2 D PAGE in the differentiated, but not in parent cells. The presence of UCH-L1 in the Bryo1-treated cells was further confirmed by immunoblotting of 2 D PAGE using UCH-L1 polyclonal antibody. Ubiquitin expression was studied in parent and Bryo1-treated cells and was compared with 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated cells. Both agents, TPA and Bryo1, increased the level of ubiquitin expression as detected by flow cytometry. Sodium borohydride, an inhibitor of UCH-L1, inhibited the Bryo1-induced differentiating effect on Reh cells. To date, the mechanism by which Bryo1, exerts its B-cell differentiating effect is not fully understood. This study shows that UCH-L1 expression may play a major role in Bryo1-induced differentiation in pre-B-ALL.  相似文献   

    

TM Behr  WS Becker  RM Sharkey  ME Juweid  RM Dunn  HJ Bair  FG Wolf  DM Goldenberg 《Canadian Metallurgical Quarterly》1996,37(5):829-833

The renal uptake of radiolabeled antibody fragments and peptides presents a problem in radioimmunodetection and therapy, compromising lesion sensitivity, especially with intracellularly-retained isotopes. Previously, we showed that cationic amino acids and their derivatives are capable of significantly reducing kidney uptake in animals. We report our initial clinical results of successful renal uptake reduction in five patients who underwent cancer radioimmunodetection with 99mTc-anti-CEA Fab' fragments. METHODS: The patients were infused with two liters of a commercially-available nutritive amino acid solution (containing approximately 2.25 g/liter lysine-glutamate and 2.50 g/liter arginine), whereas 75 control patients received the same volume of saline (quantification of organ and tumor kinetics from conjugate whole-body views by ROI technique). RESULTS: The renal uptake in the amino acid group was significantly lower (p<0.05) than in the control group (11.1 +/- 2.0% injected dose versus 17.7 +/- 7.0% injected dose at 24 hr postinjection), whereas the uptake of all other organs remained unaffected. Gel filtration chromatography of the urine taken from amino-acid-treated patients showed that a significantly higher amount of excreted activity was bound to intact Fab' (53% of excreted activity) in contrast to only less than 10% in the control group. CONCLUSION: The renal uptake of monoclonal antibody fragments in patients can be reduced significantly by amino acid infusion, even at considerably lower doses than those that were safe and effective in animals. As was found in animals, the mechanism seems to rely on an inhibition of the re-absorption of tubularly-filtered proteins by the proximal tubule cells. These results encourage further clinical trials to lower the renal uptake experienced in radioimmunodetection, as well as in therapeutic trials with antibody fragments and peptides.  相似文献   

    

G Mochloulis  RM Irving  HR Grant  RF Miller 《Canadian Metallurgical Quarterly》1996,110(11):1034-1037

Over a period of 10 years 17 human immunodeficiency virus(HIV)-infected patients with laryngeal Kaposi's sarcoma were seen and treated at University College London Hospitals. All patients had advanced HIV disease. Their presentation was with symptoms of upper airway obstruction in the majority of cases and the diagnosis was made by fibreoptic examination of the larynx. Biopsy was associated with brisk haemorrhage in one patient, who required a temporary tracheostomy, and was not performed in the other 16 cases. The commonest site of laryngeal involvement was the supraglottis in 11 patients, with glottic lesions noted in eight patients: subglottic lesions were seen in only three. Treatment of laryngeal Kaposi's sarcoma was, in general, conservative, five patients received low dose radiotherapy to the larynx and 10 were treated with systemic chemotherapy for disseminated Kaposi's sarcoma. Laryngeal Kaposi's sarcoma did not contribute to patient mortality.  相似文献   

    

T Dunzendorfer  VW Lee  S Levine  AD Morenas  RM Beazley  S Chipkin 《Canadian Metallurgical Quarterly》1996,41(11):2233-2237

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JJ Uil  RM van Elburg  CJ Mulder  HS Heymans 《Canadian Metallurgical Quarterly》1996,49(2):68-72

Absorbable stapling devices have been described by several groups for the creation of continent urinary diversions. Experience with these devices in the creation of the LeBag ileocecal orthotopic pouch is described. Use of the staplers simplifies pouch construction and yields functional results similar to hand-sewn reservoirs.  相似文献   

    

MB Bolster  RM Silver 《Canadian Metallurgical Quarterly》1993,7(1):79-97

Scleroderma (SSc) is a disease characterized by skin fibrosis but it is the end-organ effect of microvascular injury and fibrosis that is important prognostically. Pulmonary involvement in SSc patients, either of parenchymal fibrosis and/or pulmonary hypertension, is a major cause of morbidity and mortality. Interstitial lung disease occurs more commonly in patients with diffuse SSc and is associated with a loss of lung volume, as well as a defect of gas exchange. Parenchymal fibrosis may also cause pulmonary hypertension. Isolated pulmonary hypertension occurs exclusively in patients with limited SSc and is detectable by a reduced DCO. The early identification of either manifestation is difficult. Patients may have minimal symptoms, unremarkable physical findings, normal chest radiographs and/or minimally abnormal pulmonary function tests at a time when significant lung pathology is present. It is essential to attempt to identify pulmonary disease early, at a potentially reversible stage. Multiple therapeutic endeavours have yielded only short-term or minimal benefits in symptoms and pulmonary function, and thus a major alteration in SSc pulmonary prognosis has not been achieved. Further study of the pathogenesis of this disease manifestation will be helpful in its earlier identification and intervention.  相似文献   

    

T Hong  TJ Watson-Yang  X Guo  AJ Freeman  T Oguchi  Jh Xu 《Canadian Metallurgical Quarterly》1991,43(3):1940-1947

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RM Hendry  CV Hanson  V Bongertz  M Morgado  A Duarte  J Casseb  L Brigido  E Sabino  R Diaz  B Galv?o-Castro 《Canadian Metallurgical Quarterly》1996,91(3):347-348

The influence of noncompetitive (MK-801), competitive (AP-7) and the antagonist of polyamines site of NMDA receptor (arcaine) on the central activity of angiotensin II (A II) was studied. The open field test, conditioning of active avoidance responses (CARs) and passive avoidance situation was used to investigate learning and memory in rats. All used antagonists decreased beneficial action of A II on these processes.  相似文献