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Biomedical subjects

W Stephan

Publications and source records attributed to W Stephan.

At least 109 records · Page 6Linked to original sources
PubMed1983

A new hepatitis B vaccine containing HBeAg in addition to HBsAg.

A new vaccine is reported which contains HBeAg in addition to highly purified HBsAg. The rationale for this approach depends on the following data indicating that anti-HBe/anti-HBc may play an active role in prevention of HBV infection; (1) active immunization of chimpanzees with HBeAg(s) devoid of detectable HBsAg protected against subsequent challenge with HBV; (2) passive immunization of chimpanzees with an anti-HBe/anti-HBc intravenous immunoglobulin devoid of anti-HBs significantly delayed and appeared to attenuate HBV infection following subsequent challenge with HBV. The purification procedure utilized for production of the NYBC vaccine was designed to accomplish a high degree of purification with minimal use of complex equipment. This may facilitate eventual utilization of the vaccine on a mass scale for prevention of the HBV carrier state in high prevalence regions of the world. This procedure uses PEG precipitations and hydroxylapatite adsorption steps, followed by only a single isopycnic separation in a zonal rotor, to achieve a vaccine which is substantially free of serum proteins and detectable HBV DNA yet contains immunogenic quantities of HBsAg and HBeAg. The vaccine is inactivated by Tween 80 and formalin. Four lots have passed chimpanzee safety tests; two of them have been tested in clinical trials.

Animals↗
PubMed1983

[Beta-propiolactone as a sterilizing agent in the manufacture of intravenous immunoglobulin preparations].

It was demonstrated with phi X174, phi e and x phages that the beta-propiolactone step, which eliminated the anticomplementary activity of the intravenous immunoglobulin (IgG) preparation. Intraglobin, inactivates more than 10(6) viruses/ml. This means additional safety with respect to those viral diseases for which specific and sensitive diagnostic methods are not available at present.

Bacteriophages↗
PubMed1983

Factor VIII concentrate from cold sterilized human plasma.

beta-Propiolactone (beta-PL) in combination with UV irradiation (UV) is an established method for the sterilization of factor IX concentrate or stabilized human serum. Because of the extreme sensitivity of factor VIII to beta-PL, the standard beta-PL/UV procedure cannot be used to obtain hepatitis-safe factor VIII concentrate. It has been shown in chimpanzees that from a cryoprecipitate containing hepatitis non-A, non-B viruses in addition to hepatitis B viruses a factor VIII concentrate (160 U/10 ml) can be prepared by a modified beta-PL/UV procedure, which induces neither hepatitis B nor hepatitis non-A, non-B in experimental animals; the non-sterilized original cryoprecipitate proved to be infectious.

Animals↗
PubMed1983

Comparison of in vitro behaviour and in vivo efficacy of two 7S-immunoglobulin preparations for intravenous use.

Two intravenous 7S-immunoglobulin (IgG) preparations, beta-propiolactone(beta-PL)-treated (Intraglobin) and hydrochloric acid/pepsin-treated, were tested for their in vitro behaviour in haemagglutination, anticomplementary activity and binding to SPA-sepharose. These results were compared with the efficacy of these preparations in vivo, using mouse protection tests with Salmonella and Pseudomonas as a challenge. In spite of marked differences in the in vitro behaviour, both preparations showed almost the same efficacy in vivo. These results indicate that in vitro findings do not allow predictions of the in vivo efficacy of intravenous IgG preparations.

Animals↗
PubMed1982

Fractionation of cold-sterilized plasma. A new concept in production of non-infectious plasma proteins.

The hepatitis risk of protein fractions derived from pooled human plasma is eliminated by beta-propiolactone treatment and UV irradiation. The combination of this sterilization procedure with an adsorption and elution procedure leads to coagulation factor concentrates such as fibrinogen, factor VIII and factor IX concentrate and a stabilized serum preparation for intravenous use. This technology is carried out mostly at room temperature, without alcohol and minimum pollution. It seems, especially for developing countries, an attractive alternative to the widely used alcohol fractionation.

Adsorption↗
PubMed1982

Activity and storage stability of proteins in a hepatitis-free human serum preparation.

The activity of certain selected serum proteins was investigated in Biseko, a product prepared from beta-propiolactone/UV treated, pooled human plasma. It was shown that the biological activity of the immunoglobulins, transport proteins and inhibitor proteins was not affected by the manufacturing process. With the exception of alpha 1-antitrypsin and coeruloplasmin, the biological activity of the proteins studied proved to be preserved on storage at 37 degrees C.

Antibodies↗
PubMed1981

Long-term tolerance and recovery of beta-propiolactone/ultraviolet (beta PL/UV) treated PPSB in chimpanzees.

Recent experiments have shown that a preparation of PPSB (factor IX concentrate) derived form beta PL/UV treated plasma was not infectious in chimpanzees with respect to hepatitis B and non-A, non-B. To answer the question whether the beta PL/UV treatment influences the tolerance and efficacy of the PPSB-concentrate, long-term application of PPSB-Biotest was carried out in chimpanzees. After 10 applications of 25 U factor IX/kg at weekly intervals, no signs of intolerance were observed by measurement of blood pressure during i.v. application and by means of skin-testing. Determination of coagulation factor activity during the application period revealed the same factor IX recovery at the beginning and at the end of the study.

Animals↗
PubMed1981

Effect of combined treatment of serum containing hepatitis B virus with beta-propiolactone and ultraviolet irradiation.

The effect of cold sterilization by beta-propiolactone (beta-PL) and ultraviolet (UV) irradiation of serum contaminated with infectious hepatitis B virus (HBV) was investigated in chimpanzee. Chimpanzees given 0.1 ml/kg of the undiluted HBV serum estimated to contain 10(7)-10(8) CID50/ml developed acute hepatitis B infection 4 weeks after inoculation. Chimpanzees injected with the same undiluted hepatitis serum treated with beta-PL/UV developed hepatitis B infection 14 weeks later. Based on the published linear relationship between log dose of HBV and incubation period in chimpanzees this indicates a 10(6)-fold reduction in infectivity titer. Animals inoculated with the serum diluted 1:1,000 showed manifest hepatitis B infection 11 weeks later. Animals inoculated with serum diluted 1:1,000 and then cold sterilized with beta-PL/UV showed no signs of hepatitis B infection. Sensitive proteins are not denatured by beta-PL/UV cold sterilization.

Animals↗
PubMed1981

On the mutagenicity and immunogenicity of a beta-propiolactone-treated therapeutic IgG-preparation.

During the production of Intraglobin, an i.v. tolerable IgG-immunoglobulin preparation, fraction Cohn II is treated with beta-propiolactone. Thereby the IgG-molecules are chemically modified thus preventing an increase in secondary aggregates which could give rise to adverse reactions in the patients treated with the IgG-preparation. The safety tests described here neither showed any evidence for the presence of unhydrolysed mutagenic-beta-propiolactone in the final product nor that neoantigenic determinants had been created by the reaction of beta-propiolactone with the protein molecules.

Animals↗
PubMed1981

A clinical study of the tolerance and safety of a beta-propiolactone-treated immunoglobulin.

In an open clinical study, 31 healthy volunteers were each given three i.v. infusions of 50 ml of a immunoglobulin preparation (Intraglobin) from three different production batches. During a 35-week observation period every three weeks blood specimens were drawn from the participants and analysed for serological (HBsAg, anti-HBs, anti-HBc, HBeAg and anti-HBe) and clinico-chemical parameters of hepatitis (SGOT, SGPT, gamma-GT and bilirubin levels). In no case evidence of the development of hepatitis arose, nor did the participants suffer from any side-effects during or after the infusions. Ten out of the 31 subjects then received another 150 ml infusion followed by an intradermal application of the new immunoglobulin in a 1:10 dilution four weeks later. No signs of immediate or delayed hypersensitivity reactions could be observed in the volunteers.

Alanine Transaminase↗
PubMed1980

Evaluation of the effect of betapropiolactone/ultraviolet irradiation (BPL/UV) treatment of source plasma on hepatitis transmission by factor IX complex in chimpanzees.

To evaluate the safety of a beta-Propiolactone/Ultraviolet (BPL/UV), irradiated Factor IX complex preparation we inoculated 8 chimpanzees with 25 units Factor IX/Kilo from a pool of 5 production lots which had been treated in this manner. These lots were derived from approximately 1,000 donors. Animals were followed with weekly tests for hepatitis B serologic markers and transaminases, and biweekly liver biopsies, for 6 months. No evidence of transmission of hepatitis B, or non-A, non-B viruses was observed. To further evaluate the BPL/UV procedure a plasma pool was intentionally contaminated with hepatitis B virus and one half of the pool treated with BPL/UV. Factor IX complex was isolated from the treated and untreated pools and each was inoculated into 4 chimpanzees. The Factor IX derived from untreated plasma infected all four animals with an average incubation period of 10.5 weeks, whereas that prepared from PBL/UV treated plasma infected only one of four animals with an incubation period of 21 weeks. These results were interpreted as suggesting that BPL/UV can inactivate approximately 99.9% of hepatitis B virus infectivity.

Animals↗
PubMed1980

Fluctuations of barrier structure in ionic channels.

In rate-theory analysis of ion transport in channels, the energy of binding sites and the height of activation barriers are usually considered to be time-independent and not influenced by the movement of the ion. The assumption of a fixed barrier structure seems questionable, however, in view of the fact that proteins may exist in a large number of conformational states and may rapidly move from one state to the other. In this study, some of the effects of multiple conformational states of a channel on ion transport are analyzed. In the first part of the paper, the ion permeability of a channel with n binding sites is treated on the assumption that interconversion of channel states is much faster than ion transfer between binding sites. Under this condition, the form of the flux equation remains the same as for a channel with fixed barriers, provided that the rate constants for ion jumps are replaced by weighted averages over the rate constants for the individual conformational states. In the second part, a channel with two (main) barriers and a single (main) binding site is considered, with the rates of conformational transitions being arbitrary. This case, in particular, includes the situation where a jump of the ion is followed by a slow transition to a more polarized state of the binding site. Under this condition, the conductance of the channel exhibits a nonlinear dependence on ion concentration which is different from a simple saturation behavior. Under non-stationary conditions damped oscillations may occur.

Biological Transport↗
PubMed1980

[Tolerance of beta-propiolactone-treated and UV-irradiated rat serum].

beta-Propiolactone-treated and UV-irradiated rat serum was injected into rats to investigate its ability to generate new immunogenic determinants. No inflammatory/cytotoxic reaction was observed and antibodies directed against the beta-propiolactone-treated and UV-irradiated serum could not be detected.

Animals↗
PubMed1979

Theory of single-file noise.

A general theoretical approach to the analysis of electric fluctuations generated by the so-called single-file diffusion through narrow channels is presented. The formalism is a slight extension of an approach to electric fluctuations in discrete transport systems with negligible interactions between the particles recently developed by one of the authors. In the single-file transport mechanism interactions between the particles must be taken into account. Three main results of principal interest are: (a) the electric fluctuations around stationary states (at equilibrium and non-equilibrium) are determined by the time-dependent solutions of the macroscopic single-file transport equations, (b) as a direct consquence of the interactions between the ions in the single-file transport the macroscopic time-dependent current and the autocorrelation function of the microscopic current fluctuations can exhibit damped oscillatory behavior, and the current noise spectrum can show peaking, (c) the number of binding sites for the ions within the pores seems to have a strong influence on the oscillatory behavior: with increasing number of binding sites the damping of the oscillations decreases and the peaking of the spectrum becomes stronger.

Binding Sites↗