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Biomedical subjects

H Sandberg

Publications and source records attributed to H Sandberg.

At least 37 records · Page 2Linked to original sources

Expression of coagulant activity in human platelets: release of membranous vesicles providing platelet factor 1 and platelet factor 3.

The relationship between the appearance of membrane-associated factor V-like activity (platelet factor 1, PF1) and phospholipid-like catalytic activity (platelet factor 3, PF3) has been examined, in vitro, in collagen-stimulated, human platelets. Both activities increased 7 fold upon collagen treatment relative to stirred controls. After sedimentation of stimulated platelets, 31% of total PF1 and 41% of PF3 remained in the supernatant fraction. PF1 eluted from a Sepharose CL-4B column in the same void volume fractions as PF3, phospholipid, and vesicular particles. These fractions had roughly 100 fold (lipid basis) or 1000 fold (protein basis) enhanced specific activity when compared to the stimulated platelet suspension. Freeze-fracture electron microscopy demonstrated that these void volume fractions contain two populations of membranous vesicles (80-200 nm and 400-600 nm in diameter). Upon centrifugation of the void volume fractions, PF1 and PF3 activities, phosphate-containing material, and ultraviolet-absorbing material all sedimented at the same rate, indicating that PF1 and PF3 are activities associated with one or both of the platelet-derived vesicle populations. Finally, we examined the effects of inhibitors on the appearance of PF1, PF3, platelet factor 4, total intrinsic factor V activity, and serotonin as well as on platelet aggregation. These studies suggest that the collagen-stimulated release of PF1 and PF3 is not coupled to either platelet aggregation or PF4 release but is probably a separate phase of the release reaction.

Blood Coagulation Factors↗

Purified human factor VIII procoagulant protein: comparative hemostatic response after infusions into hemophilic and von Willebrand disease dogs.

The procoagulant protein F.VIII:C is noncovalently bound to von Willebrand factor (vWF) to give the factor VIII macromolecular complex. New highly purified preparations of isolated human F.VIII:C, devoid of vWF and about 500,000-fold purified, were administered to hemophilia A and von Willebrand disease (vWD) dogs to determine their hemostatic effectiveness and survival in the circulation. Two preparations of F.VIII:C were used: peak 1, with active components of Mr 185,000-280,000, and peak 2, with a single component of Mr 170,000. In hemophilic dogs, with no plasma F.VIII:C but normal vWF, both preparations immediately elevated plasma F.VIII:C to expected levels, promptly stopped induced and spontaneous hemorrhages, and gave sustained plasma levels of F.VIII:C. The isolated F.VIII:C immediately complexed with endogenous vWF in hemophilic plasma and was eliminated exponentially, with a half-life (t1/2) of about 9 hr. Survival of peak 2 F.VIII:C was longer than that of peak 1 material. In contrast, F.VIII:C complexed to vWF in a therapeutic concentrate administered to hemophilic dogs was eliminated biexponentially with first-phase t1/2 of 3.2 hr and second-phase t1/2 of 9 hr. In vWD dogs with no vWF and reduced F.VIII:C levels, the isolated F.VIII:C produced supernormal levels of F.VIII:C without effect on induced bleeding. It was rapidly eliminated from plasma with a t1/2 of about 1 hr, as was the complexed F.VIII:C in the concentrate. These data indicate that isolated F.VIII:C promptly complexes with vWF and in this form is highly effective in controlling hemophilic hemorrhages with good survival in plasma. Without endogenous vWF with which to complex, the F.VIII:C is promptly eliminated.

Animals↗

Sports injuries of the knee ligaments--a prospective stress radiographic study.

Forty-six patients were entered into a prospective clinical and stress radiographic study done to assess the value of acute surgical treatment of injuries to the knee ligaments sustained during sports activities. After an average follow-up period of 5 1/2 years (range 4-6 1/2 years) medial instability was found only in two patients, both of whom were in the group with isolated rupture of the medial collateral ligament. Nine of the 29 patients in this group developed rotatory instability, but it was moderate and did not give rise to symptoms. Among the 17 patients with either injuries to the anterior cruciate ligament or combined injuries, anterior drawer instability persisted in seven, with an insufficient functional result in five. None of these 17 patients were able to resume competitive sport. Those patients who had not exercised physically just before the injury proved to have a significantly greater total instability than those who had. Therefore, routine limbering-up is recommended before sports activities.

Adolescent↗

Prospective stress radiography in 38 old injuries of the ligaments of the knee joint.

In a prospective clinical and stress radiographic study comprising 38 patients, the course of chronic ligament injuries in the knee joint was evaluated. All but five patients had isolated ligament injuries, 16 of which affected the anterior cruciate ligament. The operations were performed from 18 days to 20 years after the injury had occurred. In 13 patients primary suture could be carried out, 12 patients underwent exploratory arthrotomy, and the remainder had relevant ligament repair. After a follow-up period of 7 years the instability had been cured in all patients with medial laxity and in one of two patients with lateral laxity. Nineteen patients had a drawer sign preoperatively. The anterior drawer sign disappeared in practically all patients, while a posterior drawer sign was a constant sequel to injury affecting the posterior cruciate ligament. It was difficult to prevent the development of rotatory instability--which was present in six preoperatively and in 14 at follow-up--and the rotatory instabilities were predominantly marked (greater than 6 mm). Nevertheless, only a few patients had an annoying sensation of instability. By means of ligament reconstruction, it was possible to reduce the preoperative instability appreciably. Passive instability had completely subsided in 40 per cent (15/38). The subjective result was good, only 16 per cent (6/38) having troublesome loss of function.

Adolescent↗

Isolation and characterization of lipid-protein particles containing platelet factor 3 released from human platelets.

Lipid-protein particles with platelet factor 3 measured by the Stypven clotting-time test [Hardisty & Hutton (1966) Br. J. Haematol. 12, 764-776] have been isolated from platelet-release supernatant. Starting material was washed platelets, which were released by treatment with collagen. Purification of the particles from other components in the release material was accomplished by gel filtration on Sepharose CL-4B followed by affinity chromatography on poly-L-lysine-Sepharose CL-4B gel. Chemical characterization showed that the particles were composed of 40% protein, 42% phospholipids, 13% cholesterol and 5% triacylglycerols. The phospholipid composition was 38% phosphatidylcholine, 25% phosphatidylethanolamine, 9% phosphatidylserine, 2% phosphatidic acid and 26% sphingomyelin. No carbohydrate was detected. Electron-microscopic studies revealed the presence of membranous particles with diameters between 70 and 170 nm.

Blood Coagulation Factors↗

Prospective stress radiographic study of knee ligament injuries in 62 patients treated by acute repair.

A prospective clinical and stress radiographic study comprising 62 patients was performed to assess the value of acute repair of 35 isolated collateral ligament injuries and 27 major injuries. After a follow-up period of 6 years there was no lateral or medical instability in 42 out of 46 patients. This included 31 out of 33 patients in the group with medial collateral ligament injuries. Among the patients with major injuries 16 (60 per cent) had drawer signs, but in only 6 was there significant instability (greater than 6 mm). In the total material it proved difficult to prevent the development of rotatory instability. This was present in 10 patients preoperatively and in 19 at follow-up. However, this instability was on the whole slight and was experienced as annoying by only 4 patients. Measurement of passive instability showed that 55 per cent (34/62) had become completely stable, but this applied to only 30 per cent (8/27) of patients with major injuries. The functional end result was unsatisfactory in 8 patients (13 per cent). Although several patients could compensate muscularly for a marked passive instability, there was a significant correlation between instability and functional loss.

Adolescent↗

Studies of the thromboplastic effect of human plasma lipoproteins.

Human plasma lipoprotein fractions were prepared by flotation in the ultracentrifuge. Addition of these fractions to platelet-rich, platelet-poor and platelet-free plasma affected the partial thromboplastin and Stypven clotting times to various degrees. Addtion of high density lipoprotein (HDL) to platelet-poor and platelet-free plasma shortened both the partial thromboplastin and the Stypven time, whereas addition of low density lipoprotein and very low density lipoprotein (LDL + VLDL) fractions only shortened the Stypven time. The additions had little or no effect in platelet-rich plasma. Experiments involving the addition of anti-HDL antibodies to plasmas with different platelet contents and measuring of clotting times produced results that were in good agreement with those noted when lipoprotein was added. The relation between structure and the clot-promoting activity of various phospholipid components is discussed.

Antibodies↗