Tissue plasminogen activator mutants lacking the growth factor domain and the first kringle domain: II

1991 ◽  
Vol 5 (1) ◽  
pp. 31-41 ◽  
Author(s):  
K. Wikström ◽  
C. Mattsson ◽  
C. Sterky ◽  
G. Pohl
1991 ◽  
Vol 5 (1) ◽  
pp. 17-29 ◽  
Author(s):  
G. Pohl ◽  
C. Sterky ◽  
A. Attersand ◽  
E. Nyberg ◽  
B. Löwenadler ◽  
...  

2006 ◽  
Vol 104 (1) ◽  
pp. 79-84 ◽  
Author(s):  
Hiroyuki Katano ◽  
Ken Kamiya ◽  
Mitsuhito Mase ◽  
Motoki Tanikawa ◽  
Kazuo Yamada

Object Chronic subdural hematomas (CSDHs) recur in 7 to 18% of cases. The present study was conducted to determine whether serum or lesion concentrations of coagulofibrinolytic and angiogenic factors, which have been reported to be potential markers of CSDH development, might predict such recurrences. Methods Sixty consecutive patients (mean age 71.5 years) with CSDHs (74 affected sides) were studied. Samples of serum in preoperative peripheral venous blood and of hematomas (obtained during surgery) were collected and analyzed. The CSDH recurred in six (8.1%) of the 74 affected sides in six patients. None of the values of the coagulative factors or tests in serum showed significant variation between cases with and those without recurrence. Among coagulofibrinolytic factors, tissue plasminogen activator (TPA) in hematomas demonstrated significantly greater levels in recurrent than in nonrecurrent cases; a similar tendency was noted for α2-plasmin inhibitor–plasmin complex in hematomas. Both factors were greater in the lesions than in the serum. Among the angiogenic factors, levels of hepatic growth factor (HGF) and vascular endothelial growth factor (VEGF) in hematomas were significantly greater than in serum, whereas those of basic fibroblast growth factor were rather lower. Note that comparisons between recurrent and nonrecurrent cases revealed no significant difference. Conclusions Patients harboring CSDHs with high TPA concentrations on sampling at the initial surgery have a relatively high probability of recurrence and require follow up with computerized tomography scanning. Angiogenic factors, such as HGF and VEGF, might be candidate markers of CSDH enlargement but are not useful as predictors of recurrence.


2017 ◽  
Vol 1 (1) ◽  
pp. 34-40 ◽  
Author(s):  
Enchun M. Liu ◽  
Rithwick Rajagopal ◽  
Bradley T. Smith ◽  
M. Gilbert Grand

Purpose: To assess the outcomes of patients with large submacular hemorrhage (SMH) due to age-related macular degeneration in this era of anti-vascular endothelial growth factor (VEGF). Methods: Retrospective analysis of 149 eyes of 149 patients receiving pars plana vitrectomy, subretinal tissue plasminogen activator, and gas injection (“surgical group”; n = 80) or anti-VEGF alone (“anti-VEGF group”; n = 69). Changes in visual acuity (VA), number of anti-VEGF injections, and percentage of patients with ≥3 line VA gains are compared between groups. Results: Patients in the surgical group had larger SMH than those in the anti-VEGF group, 30.35 versus 14.57 mm2 ( P < .0001). Both groups experienced similar visual gains (−0.35 logarithm of the minimal angle of resolution [logMAR] vs −0.23 in logMAR, surgical vs anti-VEGF group; P = .36). The percentage of patients gaining ≥3 lines of VA was 55% in the surgical group and 54% in the anti-VEGF group. The surgical group achieved best-recorded VA sooner (3.7 compared to 4.6 months; P = .04) and required fewer injections (3.4 injections vs 4.7 in the anti-VEGF group; P = .001). Conclusion: Surgical intervention was favored for larger hemorrhages of shorter duration. Despite extensive hemorrhage and poor baseline VA, both groups showed similar rate of significant VA improvement.


2020 ◽  
Vol 8 ◽  
pp. 2050313X2097033
Author(s):  
Athanasios Karamitsos ◽  
Vasileios Papastavrou ◽  
Tsveta Ivanova ◽  
David Cottrell ◽  
Kevin Stannard ◽  
...  

The objective of this case series is the evaluation of the efficacy and visual outcomes after displacement of subretinal hemorrhage using intravitreal injection of recombinant tissue plasminogen activator, expansile gas, and in some cases an anti-vascular endothelial growth factor agent. A case series of 28 eyes of 28 patients (16 men and 12 women with age range 67–95 years) suffering from subretinal hemorrhage (duration range 1–15 days) caused by age-related macular degeneration or retinal macroaneurysm is presented. All the patients were treated with intravitreal injection of recombinant tissue plasminogen activator and gas and some of them received an anti-vascular endothelial growth factor agent between January 2013 and December 2016. The outcomes assessed were visual acuity (preoperatively 1 week, and 1 month postoperatively) with respect to duration and dimension of hemorrhage, displacement of hemorrhage, and possible complications of the procedure. Successful displacement of hemorrhage was achieved in 25 patients (89.3%), 18 of 28 patients had significant improvement in visual acuity 1 week after the treatment, and 22 of 28 patients had significant improvement in visual acuity 1 month after the treatment. The mean improvement of all patients with anatomical displacement of the hemorrhage in visual acuity was 0.7 ± 0.5 (LogMAR) in 1 month. Two patients developed vitreous hemorrhage after the procedure and one retinal detachment. Visual outcome a month after therapy displayed week correlation with duration, diameter, and thickness of hemorrhage. The results lead to the conclusion that intravitreal treatment of recombinant tissue plasminogen activator and expansible gas with or without injection of anti-vascular endothelial growth factor agent is effective in improving visual acuity and displacing submacular hemorrhage secondary to age-related macular degeneration and retinal macroaneurysm. The best functional outcomes can be expected in patients regardless of the size and duration of the hemorrhage.


1994 ◽  
Vol 41 (1) ◽  
pp. 25-34 ◽  
Author(s):  
T Pietrucha ◽  
W J Stec ◽  
A Okruszek ◽  
B Uznański ◽  
M Koziołkiewicz ◽  
...  

To examine whether the epidermal growth factor (EGF)-like domain Pro47-Asp87 is involved in the interaction of tissue plasminogen activator (t-PA) with platelets, we have expressed this domain in E. coli. The peptide fragment was produced from a plasmid expression vector as a fusion protein with beta-galactosidase Met1-Val444 at high yield in eight clones of E. coli. The fusion protein was purified and subjected to mild acid hydrolysis with formic acid, then the peptide Pro47-Asp87, identified by immunoblotting using specific antibodies to t-PA, was isolated by HPLC. After incubation with blood platelets spin labelled with 16-doxylstearic acid or 5-doxylstearic acid, the Pro47-Asp87 peptide fragment reduced fluidity of the membrane lipid bilayer to the same extent as did intact t-PA as indicated by ESR measurements. Our data suggest that the EGF-like domain of t-PA can directly interact with blood platelets and thus it seems to contain those sites of the t-PA molecule that bind the platelet membrane components.


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