Investigations were performed concerning the elimination of the risk of hepatitis B transmission ... more Investigations were performed concerning the elimination of the risk of hepatitis B transmission of potentially infectious plasma derivatives by the addition of a low dose of hepatitis B immunoglobulin (HBIg). To this end, clotting factor VIII concentrate, prothrombin complex, C1 esterase inhibitor concentrate, plasminogen and antithrombin III were prepared from plasma strongly positive for hepatitis B surface antigen (HBsAg). To one half of every preparation, HBIg was added up to a final concentration of 0.4 IU anti-HBs/ml (test preparations), the other half was not treated (control preparations). Furthermore, to 10(-3) diluted infectious reference plasma (Bureau of Biologics, FDA, USA), an overdose HBIg was added to a final concentration of about 0.4 IU anti-HBs/ml. 6 chimpanzees, injected either with the control plasma derivatives or with the untreated infectious reference plasma, were infected with hepatitis B virus, whereas 5 chimpanzees, injected either with the test plasma de...
The Journal of laboratory and clinical medicine, 1980
Human factor VIII in plasma is a disperse protein consisting of a series of aggregates wih differ... more Human factor VIII in plasma is a disperse protein consisting of a series of aggregates wih different molecular weight. VIIR:Ag and VIII:C are present in all forms, but VIIR:WF is confined to the highest molecular weight forms only. After cryoprecipitation of plasma the latter are recovered in the precipitate, and the lowest molecular weight forms remain in the supernatant. Disaggregation of high molecular weight forms of factor VIII was found in vitro upon repeated cryoprecipitations. The disaggregation was detected only when the original low molecular weight forms were removed. The additional low molecular weight forms possessed VIII:C and VIIR:WF was lacking. The reverse process of aggregation of low molecular weight factor VIII to more highly aggregated forms was not observed. Exchange of VIII:C between high and low molecular weight fractions was demonstrated by gel chromatography of mixtures of hemophilic cryoprecipitate and normal concentrated cryosupernatant, and vice versa, a...
To evaluate the extent of denaturation of factor VIII-coagulant activity (VIII: C) during product... more To evaluate the extent of denaturation of factor VIII-coagulant activity (VIII: C) during production of factor VIII concentrates, the factor VIII-coagulant antigen (VIII: CAg)/VIII: C ratio was measured in plasma, cryoprecipitate and cryosupernatant from fresh and stored blood. This ratio was close to unity for both cryoprecipitate and other concentrates, suggesting that VIII: CAg is lost concurrently with VIII: C during cryoprecipitation and further fractionation. Storage of blood (18 h, 22 degrees C) before processing resulted in a 30% loss of VIII: C from the separated plasma; however, VIII: CAg was not affected. In cryoprecipitate prepared from this plasma, VIII: C and VIII: CAg both were 30% lower than when prepared from fresh plasma. In the corresponding cryosupernatant, however, more VIII: CAg but less VIII: C was present compared with fresh material. Gel chromatography revealed that the rise of VIII: CAg in cryosupernatant prepared from stored blood, was due to an increased ...
Current studies in hematology and blood transfusion, 1989
This study has shown that the principle of virus neutralization by specific antibodies is feasibl... more This study has shown that the principle of virus neutralization by specific antibodies is feasible at least in the case of hepatitis B. Virus neutralization is our preferred method since it entails no loss of functional activity and no risk of induction of neo-antigens in the plasma derivatives. Although double-blind clinical trials have not been performed, this study--in combination with some other studies - brought the conclusive evidence that virus neutralization in the case of hepatitis B transmission is efficacious. The suggested occurrence of side effects related to the formation of immune complexes during or after administration is not borne out by more than 7 years of experience with neutralized plasma derivatives with no reported side effects. Whether this method is useful for other viruses will depend on the availability of specific neutralizing antibodies.
The Journal of laboratory and clinical medicine, 1978
Recent observations suggest that plasma F VIII consists of a series of molecules with different m... more Recent observations suggest that plasma F VIII consists of a series of molecules with different molecular weights. The data described in this paper suggest that sup F VIII represents the molecules with relatively low molecular weights whereas the molecules with the highest molecular weights appear in cryo F VIII. Sup F VIII was associated with VIII:C and VIIIR:Ag, but ristocetin cofactor activity was lacking. Although the immunoprecipitation characteristics of sup F VIII with rabbit antifactor VIII were different from those of cryo F VIII, immunological identity was observed in immunodiffusion and crossed immunoelectrophoresis. In 0.8M NaCl sup F VIII dissociated into VIIIR:Ag of relatively high molecular weight and VIII:C of low molecular weight. No indications were obtained that the presence of sup F VIII was the result of proteolytic degradation of factor VIII. VIII:C of sup F VIII was more labile in vitro than VIII:C in plasma. It could be activated by traces of thrombin in a wa...
ABSTRACT 1.1. The incorporation of radioactivity from sodium acetate-1-14C into some classes of l... more ABSTRACT 1.1. The incorporation of radioactivity from sodium acetate-1-14C into some classes of lipids of Cucumaria planci, Holothuria tubulosa and Stichopus regalis was investigated.2.2. It was demonstrated that these animals are able to synthesize fatty acids and non-saponifiable lipids including 3β-sterols.3.3. It was supposed that all Holothurians are capable of synthesizing sterols, though biosynthesis is not likely to be the principal way by which Holothurians provide for their sterols.4.4. The sterol mixtures were analysed by means of gas-liquid chromatography. The proportional composition of the mixtures and the identity of the components were determined. The presence of some sterols, not met before in Holothurians was shown.
Succinylated human serum albumin (Suc-HAS) is a negatively charged neo-glycoprotein that binds to... more Succinylated human serum albumin (Suc-HAS) is a negatively charged neo-glycoprotein that binds to the positively charged V3-loop of HIV-1 gp120, acting as HIV-1-fusion inhibitor in vitro (IC50: 0.5-5.0 microg/ml). Suc-HSA was safe in rats and monkeys, and showed antiretroviral effect in a human-to-mouse model. We evaluated safety and pharmacokinetics of single and multiple doses of Suc-HSA in HIV-1-infected individuals. First, six untreated, chronically HIV-1-infected patients were randomized to a single dose of 1 or 10 mg/kg Suc-HSA intravenously. Second, five consecutive daily doses (10 mg/kg, based on the results of the single dose study) were given to four patients. Safety laboratory assessments, Suc-HSA plasma levels, plasma HIV-1 RNA (pVL), and CD4+ T-cell counts were determined. Increase of liver transaminases (grade 1/2) occurred in one of six patients in the single-dose phase and in three of four patients in the multiple-dosing phase. Suc-HSA plasma levels were undetectable...
Investigations were performed concerning the elimination of the risk of hepatitis B transmission ... more Investigations were performed concerning the elimination of the risk of hepatitis B transmission of potentially infectious plasma derivatives by the addition of a low dose of hepatitis B immunoglobulin (HBIg). To this end, clotting factor VIII concentrate, prothrombin complex, C1 esterase inhibitor concentrate, plasminogen and antithrombin III were prepared from plasma strongly positive for hepatitis B surface antigen (HBsAg). To one half of every preparation, HBIg was added up to a final concentration of 0.4 IU anti-HBs/ml (test preparations), the other half was not treated (control preparations). Furthermore, to 10(-3) diluted infectious reference plasma (Bureau of Biologics, FDA, USA), an overdose HBIg was added to a final concentration of about 0.4 IU anti-HBs/ml. 6 chimpanzees, injected either with the control plasma derivatives or with the untreated infectious reference plasma, were infected with hepatitis B virus, whereas 5 chimpanzees, injected either with the test plasma de...
The Journal of laboratory and clinical medicine, 1980
Human factor VIII in plasma is a disperse protein consisting of a series of aggregates wih differ... more Human factor VIII in plasma is a disperse protein consisting of a series of aggregates wih different molecular weight. VIIR:Ag and VIII:C are present in all forms, but VIIR:WF is confined to the highest molecular weight forms only. After cryoprecipitation of plasma the latter are recovered in the precipitate, and the lowest molecular weight forms remain in the supernatant. Disaggregation of high molecular weight forms of factor VIII was found in vitro upon repeated cryoprecipitations. The disaggregation was detected only when the original low molecular weight forms were removed. The additional low molecular weight forms possessed VIII:C and VIIR:WF was lacking. The reverse process of aggregation of low molecular weight factor VIII to more highly aggregated forms was not observed. Exchange of VIII:C between high and low molecular weight fractions was demonstrated by gel chromatography of mixtures of hemophilic cryoprecipitate and normal concentrated cryosupernatant, and vice versa, a...
To evaluate the extent of denaturation of factor VIII-coagulant activity (VIII: C) during product... more To evaluate the extent of denaturation of factor VIII-coagulant activity (VIII: C) during production of factor VIII concentrates, the factor VIII-coagulant antigen (VIII: CAg)/VIII: C ratio was measured in plasma, cryoprecipitate and cryosupernatant from fresh and stored blood. This ratio was close to unity for both cryoprecipitate and other concentrates, suggesting that VIII: CAg is lost concurrently with VIII: C during cryoprecipitation and further fractionation. Storage of blood (18 h, 22 degrees C) before processing resulted in a 30% loss of VIII: C from the separated plasma; however, VIII: CAg was not affected. In cryoprecipitate prepared from this plasma, VIII: C and VIII: CAg both were 30% lower than when prepared from fresh plasma. In the corresponding cryosupernatant, however, more VIII: CAg but less VIII: C was present compared with fresh material. Gel chromatography revealed that the rise of VIII: CAg in cryosupernatant prepared from stored blood, was due to an increased ...
Current studies in hematology and blood transfusion, 1989
This study has shown that the principle of virus neutralization by specific antibodies is feasibl... more This study has shown that the principle of virus neutralization by specific antibodies is feasible at least in the case of hepatitis B. Virus neutralization is our preferred method since it entails no loss of functional activity and no risk of induction of neo-antigens in the plasma derivatives. Although double-blind clinical trials have not been performed, this study--in combination with some other studies - brought the conclusive evidence that virus neutralization in the case of hepatitis B transmission is efficacious. The suggested occurrence of side effects related to the formation of immune complexes during or after administration is not borne out by more than 7 years of experience with neutralized plasma derivatives with no reported side effects. Whether this method is useful for other viruses will depend on the availability of specific neutralizing antibodies.
The Journal of laboratory and clinical medicine, 1978
Recent observations suggest that plasma F VIII consists of a series of molecules with different m... more Recent observations suggest that plasma F VIII consists of a series of molecules with different molecular weights. The data described in this paper suggest that sup F VIII represents the molecules with relatively low molecular weights whereas the molecules with the highest molecular weights appear in cryo F VIII. Sup F VIII was associated with VIII:C and VIIIR:Ag, but ristocetin cofactor activity was lacking. Although the immunoprecipitation characteristics of sup F VIII with rabbit antifactor VIII were different from those of cryo F VIII, immunological identity was observed in immunodiffusion and crossed immunoelectrophoresis. In 0.8M NaCl sup F VIII dissociated into VIIIR:Ag of relatively high molecular weight and VIII:C of low molecular weight. No indications were obtained that the presence of sup F VIII was the result of proteolytic degradation of factor VIII. VIII:C of sup F VIII was more labile in vitro than VIII:C in plasma. It could be activated by traces of thrombin in a wa...
ABSTRACT 1.1. The incorporation of radioactivity from sodium acetate-1-14C into some classes of l... more ABSTRACT 1.1. The incorporation of radioactivity from sodium acetate-1-14C into some classes of lipids of Cucumaria planci, Holothuria tubulosa and Stichopus regalis was investigated.2.2. It was demonstrated that these animals are able to synthesize fatty acids and non-saponifiable lipids including 3β-sterols.3.3. It was supposed that all Holothurians are capable of synthesizing sterols, though biosynthesis is not likely to be the principal way by which Holothurians provide for their sterols.4.4. The sterol mixtures were analysed by means of gas-liquid chromatography. The proportional composition of the mixtures and the identity of the components were determined. The presence of some sterols, not met before in Holothurians was shown.
Succinylated human serum albumin (Suc-HAS) is a negatively charged neo-glycoprotein that binds to... more Succinylated human serum albumin (Suc-HAS) is a negatively charged neo-glycoprotein that binds to the positively charged V3-loop of HIV-1 gp120, acting as HIV-1-fusion inhibitor in vitro (IC50: 0.5-5.0 microg/ml). Suc-HSA was safe in rats and monkeys, and showed antiretroviral effect in a human-to-mouse model. We evaluated safety and pharmacokinetics of single and multiple doses of Suc-HSA in HIV-1-infected individuals. First, six untreated, chronically HIV-1-infected patients were randomized to a single dose of 1 or 10 mg/kg Suc-HSA intravenously. Second, five consecutive daily doses (10 mg/kg, based on the results of the single dose study) were given to four patients. Safety laboratory assessments, Suc-HSA plasma levels, plasma HIV-1 RNA (pVL), and CD4+ T-cell counts were determined. Increase of liver transaminases (grade 1/2) occurred in one of six patients in the single-dose phase and in three of four patients in the multiple-dosing phase. Suc-HSA plasma levels were undetectable...
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