30 research outputs found
Effect of S-100 proteins and calmodulin on Ca2+-induced disassembly of brain microtubule proteins in vitro
Platelets Retain High Levels of Active Plasminogen Activator Inhibitor 1
The vascular fibrinolytic system is crucial for spontaneous lysis of blood clots. Plasminogen activator inhibitor 1 (PAI-1), the principal inhibitor of the key fibrinolytic enzyme tissue-type plasminogen activator (tPA), is present in platelets at high concentrations. However, the majority of PAI-1 stored in platelets has been considered to be inactive. Our recent finding (Brogren H, et al. Blood 2004) that PAI-1 de novo synthesized in platelets remained active for over 24 h, suggested that PAI-1 stored in the α-granules might be active to a larger extent than previously reported. To re-evaluate this issue, we performed experiments where the fraction of active PAI-1 was estimated by analyzing the tPA-PAI-1 complex formation. In these experiments platelets were lysed with Triton X-100 in the presence of serial dilutions of tPA and subsequently the tPA-PAI-1 complex was evaluated by Western blot. Also, using a non-immunologic assay, tPA was labeled with 125I, and 125I-tPA and 125I-tPA-PAI-1 was quantified by scintigraphy. Interestingly, both methods demonstrated that the majority (>50%) of platelet PAI-1 is active. Further analyses suggested that pre-analytical procedures used in previous studies (sonication or freezing/thawing) may have substantially reduced the activity of platelet PAI-1, which has lead to an underestimation of the proportion of active PAI-1. Our in vitro results are more compatible with the role of PAI-1 in clot stabilization as demonstrated in physiological and pathophysiological studies
Stent placement for renal arterial stenosis: where do we stand? A meta-analysis
PURPOSE: To perform a meta-analysis of renal arterial stent placement in
comparison with renal percutaneous transluminal angioplasty (PTA) in
patients with renal arterial stenosis. MATERIALS AND METHODS: Studies
dealing with renal arterial stent placement (14 articles; 678 patients)
and renal PTA (10 articles; 644 patients) published up to August 1998 were
selected. A random-effects model was used to pool the data. RESULTS: Renal
arterial stent placement proved highly successful, with an initial
adequate performance in 98% and major complications in 11%. The overall
cure rate for hypertension was 20%, whereas hypertension was improved in
49%. Renal function improved in 30% and stabilized in 38% of patients. The
restenosis rate at follow-up of 6-29 months was 17%. Stent placement had a
higher technical success rate and a lower restenosis rate than did renal
PTA (98% vs 77% and 17% vs 26%, respectively; P <.001). The complication
rate was not different between the two treatments. The cure rate for
hypertension was higher and the improvement rate for renal function was
lower after stent placement than after renal PTA (20% vs 10% and 30% vs
38%, respectively; P <.001). CONCLUSION: Renal arterial stent placement is
technically superior and clinically comparable to renal PTA alone
The Importance of Enzyme Inhibition Kinetics for the Effect of Thrombin Inhibitors in a Rat Model of Arterial Thrombosis
The effect of gossypol on fast axonal transport and microtubule assembly
Gossypol at micromolar concentrations (2 ÎŒM) was found to inhibit axonal transport and a microsomal ATPase activity in the frog sciatic nerve, although axonal microtubules and the neuronal content of AMP, ADP and ATP were not affected. At slightly higher concentrations (30-40 ÎŒM), gossypol also inhibited microtubule assembly and neuronal energy metabolism. Gossypol accumulated in the nerve and the results indicate that gossypol may act as a potent neurotoxin
Monitoring of Protein Conformational Changes Upon Interaction with Low Molecular Weight Compounds by QCM-D and its Application to Drug Discovery
Identification of the Binding Site for a Low-Molecular-Weight Inhibitor of Plasminogen Activator Inhibitor Type 1 by Site-Directed Mutagenesis
Effect of Estramustine Phosphate on the Assembly of Isolated Bovine Brain Microtubules and Fast Axonal Transport in the Frog Sciatic Nerve
Estramustine phosphate (0.01 to 0.5 nriM), an estradiol mustard derivative used in the therapy of prostatic carcinoma, inhibited the assembly of brain microtubule proteins in vitro and disassembled preformed microtubules. In the presence of estramustine phosphate, the minimum microtubule-protein concentration sufficient for the assembly of microtubules was increased. Low concentrations of taxoi (20 ÎŒM) completely reversed the inhibition of assembly by estramustine phosphate. The effects were specific to estramustine phosphate since neither estradiol 170-phosphate, the hormonal moiety of the drug, nor nornitrogen mustard, the alkylating moiety, had any effect on assembly. Estramustine phosphate (0.1 to 0.5 HIM) was also found to reversibly inhibit fast axonal transport in the frog sciatic nerve. The nerve content of adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate was not significantly affected by estramustine phosphate. Our results suggest that the cytotoxic action of estramustine phosphate could be dependent partially on an interaction with microtubules, probably via the microtubule-associated proteins