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PubMed1975

The pathogenesis of Vaccinia virus toxicity. I. The role of virus-platelet interaction.

When mice are injected intravenously with a large dose of vaccinia virus, prepared in the Ehrlich ascites carcinoma of the mouse, there is a precipitous loss of plasma fibrinogen and blood platelets. Death occurs usually within 24 hours. A specific role of the virus in this toxic syndrome can be demonstrated when heparin is employed to circumvent intravascular coagulation and fibrinogen loss. Heparin does not prevent a profound thrombocytopenia from occurring, but it modifies the rate of platelet loss. Toxicity is prevented when heparinized virus preparations are pretreated with beta-propiolactone or specific antibody, although a mild thrombocytopenia occurs. Thrombocytopenia does not occur in mice injected with heparinized material prepared from uninfected tumors. These studies indicate that the basic mechanism of vaccinia virus toxicity is an early interaction between infectious virus and blood platelets, with marked thrombocytopenia and consequential pathophysiologic changes.

Afibrinogenemia↗
PubMed1977

Studies on human KC cell syncytia formation induced by Mason-Pfizer monkey virus.

Human KC cell monolayer inoculated with concentraten Mason-Pfizer monkey virus (MPMV) showed syncytia formation within an hour. The cell fusion was blocked by the treatment of the MPMV with neutralizing antiserum. Treatment of the MPVM with beta-propiolactone resulted in the loss of infectivity although KC cell fusion ability of the virus still remained. KC cells inoculated with unconcentrated MPMV showed no cell fusion even after several transfers, although a chronic MPMV infection was established. The virus-producing KC cells were refractory to fusion by MPMV. Human embryonic lung cells (HEL) were infected by serially diluted MPMV harvested from virus-producing culture, transferred twice, then cultivated together with KC cells for syncytia formation to examine the end point dilution titer of the virus. HEL infected by 10(-4)-diluted MPMV still induced syncytia formation by cocultivation with KC cells.

Animals↗
PubMed1991

Effect of inactivated viral vaccines (human) on frequency of micronuclei in bone marrow erythrocytes of mice.

Cytogenetic effects of the two inactivated viral vaccines (polio and antirabies) were studied in adult male mice by the micronucleus test. Polio salk vaccine did not induce micronuclei formation at both human (0.5 ml) and 1/5th human doses. Antirabies vaccine induced micronuclei in poly and total erythrocytes only at human dose of 2 ml. Beta-propiolactone (BPL) induced micronuclei at higher dose of 5.7 mg, but not at 0.57 mg (approximate concentration present in 2 ml of rabies vaccine). The P/N ratio was not affected in vaccinated and BPL inoculated animals. Antirabies vaccine induced micronuclei percentage was more than the BPL value.

Animals↗
PubMedDate not supplied

Evaluation of different methods of inactivation of Newcastle disease virus and avian influenza virus in egg fluids and serum.

Viruses conveyed in shipments of eggs, viral diagnostic reagents, or avian serum samples are a potential hazard for susceptible poultry. Different methods of treatment of those materials to eliminate the hazard of virulent and avirulent strains of Newcastle disease virus (NDV) or avian influenza virus (AIV) were evaluated. The NDV strains tested were more thermostable than the AIV strains. The results suggest that standard pasteurization methods would not reliably inactivate the concentrations of NDV used. beta-Propiolactone (BPL) (greater than or equal to 0.025%) inactivated NDV or AIV in allantoic fluid, but higher concentrations were needed to inactivate virus diluted in serum. Hemagglutination (HA) of NDV and AIV and hemolysis (HL) activity of NDV were reduced or eliminated by 0.4% BPL. Formalin (greater than or equal to 0.04%) inactivated either virus but adversely affected HA and HL activity. NDV or AIV was inactivated by binary ethylenimine (BEI) (0.01 M) with no adverse effect on HA or HL. Heat (56 C) or BEI (0.01 M) had no apparent effect on hemagglutination-inhibition (HI) titers of NDV and AIV antisera, the effect of formalin (0.1%) was variable, and BPL (greater than or equal to 0.25%) depressed the HI titers of both antisera. The optimum method should achieve virus inactivation without harming the treated material.

Animals↗
PubMed1990

Production of alpha-interferon by human leukocytes.

We examined the capacity of human leukocytes to produce alpha-interferon subtypes following viral induction. It was shown that the beta-propiolactone inactivated viral inductor stimulated the production of a complete set of native alpha-interferon subtypes. Acid treatment of native interferon at pH 2.0 inactivated the acid-labile portion of alpha-interferon. Its exposure to 37 degrees C for 5 days and repeated acid treatment at pH 2.0 resulted in additional inactivation of some interferon pool fractions. The acid-labile subtypes of human alpha-interferon were formed in a nonadherent mononuclear cell fraction.

Humans↗
PubMed1977

Non-infectious antigen for laboratory diagnosis of Japanese encephalitis.

Sucrose-acetone suckling mouse brain antigens of Na-kayama NIH, JaGAr-01 and Peking-1 strains of Japanese encephalitis (JE) virus treated with beta-propiolactone (BPL) retained their ability to specifically react in haemagglutination inhibition (HI) tests with antibody to JE virus, as demonstrated with convalescent sera. BPL treatment abolished the infectivity but did not affect the haemagglutinating activity of the virus of the pH optimum of the haemagglutination (HA) test.

Adolescent↗
PubMed1986

Cyclophosphamide and dimethyl dioctadecyl ammonium bromide immunopotentiate the delayed-type hypersensitivity response to inactivated enveloped viruses.

Immunization of BALB/c mice with measles virus inactivated with beta-propiolactone and mixed with 100 micrograms of the cationic surface-active lipid dimethyl dioctadecyl ammonium bromide (DDA) primes for a strong virus-specific delayed-type hypersensitivity (DTH) response that peaks 1 week later. Optimal immunization and challenge doses were found to be 8 and 4 micrograms/mouse, respectively, and pretreatment with 200 mg of cyclophosphamide/kg 2 days prior to immunization significantly enhanced the DTH response. When compared to Freund's complete and incomplete adjuvants, DDA was superior for induction of DTH to inactivated purified measles virus. As DDA could be administered to animals at a site different from the measles virus antigens, or 1 day previously, and still significantly enhance the DTH response, DDA is probably acting more as an immune modulator than as a simple adjuvant. The conditions for an optimal DTH response to measles virus were also shown to be applicable to other enveloped viruses, for example, a strong DTH response was similarly generated to inactivated purified influenza PR8 virus and to herpes simplex virus type I antigens present in plasma membranes isolated from infected Vero cells.

Adjuvants, Immunologic↗
PubMed1987

Inhibition of in vitro hematopoiesis by hepatitis A virus.

Inoculation of human bone marrow with hepatitis A virus (HAV) resulted in a dose- and duration-of-incubation-dependent suppression of hematopoietic progenitor (CFU-GM, BFU-E, CFU-Mix) growth in vitro. Monocytic progenitors appeared to be least affected. While HAV inactivation by heat or beta-propiolactone and neutralization by specific antibodies completely abrogated hematopoietic inhibition, depletion of adherent bone marrow cells, and enrichment of progenitors did not alter the pattern of suppression, which also seemed to be independent of HuIFN-alpha, -beta, -gamma, and TNF. These findings support the concept that direct infection of progenitor cells by HAV may be responsible for hematologic changes commonly seen during early phases of infectious hepatitis and possibly for some cases of bone marrow failure.

Adult↗
PubMed1988

Differences among available immunoglobulin preparations for intravenous use.

Today almost all IgG preparations for intravenous use (IVIG) fulfill the basic requirements for a preparation given intravenously (sterility, pyrogenicity, antibody content but also anticomplementary activity, etc.). However, there are still marked differences among such preparations caused by the method of preparation: (1) Enzymatically treated IVIGs (by pepsin and plasmin) have a shorter biologic half-time and a disturbed IgG subclass composition; (2) in chemically treated IVIGs (beta-propiolactone, reduced or sulfonated IgGs) the IgG3 subclass is lacking and some of the Fc-related functions are altered; and (3) the IVIGs purified by anion exchangers are poor in the IgG4 subclass. The three main preparations sold in the United States (Gamimune N, Gammagard and Sandoglobulin) belong to the nonmodified preparations and, with the exception of the IgG subclass representation, show similar Fab- and Fc-related properties (antibody content, interaction with Fc receptors on monocytes, phagocytosis-promoting activity, etc.) In none of these preparations, an elevated level of undesired contaminants (prekallikrein activator, irregular anti-erythrocyte antibodies) are found.

Complement System Proteins↗
PubMedDate not supplied

Efficacy of experimental inactivated mycoplasma gallisepticum oil-emulsion bacterin in egg-layer chickens.

Six groups of white leghorn pullets were studied to determine the ability of beta-propiolactone-inactivated Mycoplasma gallisepticum (MG) oil-emulsion bacterins to counteract reductions in egg production caused by MG infection. The pullets were inoculated with 0.5 ml of MG bacterin subcutaneously in the neck at about 20 weeks of age and were challenged with MG near 28 weeks of age, when they were in peak egg production. Various challenge schemes with infectious bronchitis virus were used at the time of MG challenge to increase the reduction in egg production. MG bacterins afforded protection against moderate drops in egg production in at least three of the studies, where the unvaccinated challenged control hens exhibited reduced egg production.

Animals↗
PubMed1987

Induction of thymic lymphomas and squamous cell carcinomas following topic application of isopropyl methanesulfonate to female Hsd:(ICR)BR mice.

The goal of these experiments in female Hsd:(ICR)Br mice was to determine whether the direct-acting SN1 alkylating carcinogen isopropyl methanesulfonate (IMS) is carcinogenic and to compare its effects with those of the direct-acting SN2 methyl homologue, methyl methanesulfonate (MMS). The compounds were administered by topical application and s.c. injection. Analysis at the 288th day of mice receiving s.c. injections of IMS and MMS was the subject of a previous report (A. Segal et al., Proc. Soc. Exp. Biol. Med., 183: 132-135, 1986). The s.c. and topical application experiments were terminated at the 450th day and the final results are reported in this paper. In mice treated by s.c. injection with IMS, thymic lymphomas were observed in at least 20 of 32 mice, the first at the 40th day, and neoplasms were not observed at the injection site. Of the 30 MMS-treated mice, 11 developed sarcomas at the injection site and one thymic lymphoma was observed. In mice treated topically with IMS, thymic lymphomas were observed in 20 of 30 treated mice, the first at the 102nd day, and squamous cell carcinomas at the injection site were observed in 9 mice. Neither squamous cell carcinomas nor thymic lymphomas were observed in 30 mice following topical application of MMS. The direct-acting SN2 aklylating carcinogen beta-propiolactone was also administered by topical application. At the 450th day, at the same dose used for MMS (40 mumol/application), papillomas of the skin were observed in 25 of 30 treated mice, squamous cell carcinomas of the skin were seen in 17 mice, and one thymic lymphoma was observed. The results suggest that the rapid induction of thymomas by IMS may be related to its ability to alkylate exocyclic oxygen atoms in DNA of hemopoietic cells and also to a sensitivity of these cells to such lesions.

Administration, Topical↗
PubMed1988

[Monitoring of sterilization procedures for plasma derivatives using bacteriophages].

Since 1968 the combination of beta-propiolactone (beta-PL) plus UV-inactivation for the sterilization of plasma derivatives is in use at Biotest. In 1981, a bacteriophage test system was established for routine monitoring of the efficacy of this sterilization procedure, using the bacteriophages phi x 174, phi e, Kappa and f2. In the period of 1981 to 1986, 88 control experiments were performed under production conditions demonstrating a mean inactivation of these test viruses of greater than or equal to 6.7 log10. This constant and high efficacy of the beta-PL/UV sterilization procedure guarantees the longstanding safety of beta-PL/UV sterilized blood derivatives. Bacteriophages are also useful experimental viruses for monitoring the efficacy of pasteurization processes.

Blood Preservation↗
PubMed1987

Inhalation carcinogenesis of various alkylating agents.

A series of earlier studies showed that inhalation exposures of rats to three water-reactive electrophilic compounds produced brisk yields of nasal cancer even when the animals were exposed for only 30 days (6 hr/day X 5 day/wk). In addition, carcinogenic potencies of the compounds appeared to relate to their chemical reactivities as measured by hydrolysis rates. For a further study of this phenomenon, inhalation exposures were conducted with five additional water-reactive compounds: beta-propiolactone [(BPL) CAS: 57-57-8], methylmethane sulfonate [(MMS) CAS: 66-27-3], ethylchloroformate [(ECF) CAS: 541-41-3], dichloroacetyl chloride [(DCAC) CAS: 79-36-7], and propylene oxide [(PO) CAS: 75-56-9] on male Sprague-Dawley rats. The hydrolysis rates of these compounds span 6 orders of magnitude. The compounds were administered for 30 days (6 hr/day X 5 days/wk) with the use of exposure concentrations that were inversely proportional to the respective hydrolysis rates. With this protocol, all compounds except PO (the slowest reacting compound) produced nasal cancer in rats. The concentrations of MMS and BPL employed in the studies produced similar nasal cancer yields, indicating that the carcinogenic potencies of these compounds in rat nasal mucosa were proportional to their hydrolysis rates. The nasal cancer yields of DCAC and ECF were less than expected. DCAC hydrolyzes so rapidly at in vivo temperatures (half-life much less than 0.01 min) that it may not reach target DNA in reactive form. Why the exposures to ECF produced yields of nasal cancer not predicted by its reactivity is currently under investigation. These results combined with our earlier results demonstrate that the carcinogenic potencies of some inhaled reactive electrophilic compounds are related to their hydrolysis rates.

Acetates↗
PubMedDate not supplied

The longevity of sterilized aortic valve homografts 1966-1972.

Between 1966 and 1972 seventy-two adult patients underwent aortic valve replacement with unstented aortic valve homografts prepared by chemical beta-propiolactone sterilization and storage. There were 5 hospital deaths and 6 foreign patients are lost to follow-up. Of the remaining 61, there have been 7 late deaths. Thirty-one patients have needed re-operation and 6 of them died. To date, 13 patients still have their homografts--none take anticoagulants and endocarditis has not occurred. The technique for valve preparation is not currently used anywhere, but the results, especially with respect to freedom from endocarditis and from calcification compare most favourably with current methods. The relative freedom from calcification suggests that it may still have relevance to the problems of aortic and pulmonary valve replacement in children.

Adult↗
PubMedDate not supplied

Influence of several chemical reagents on lymphocytic choriomeningitis and Tacaribe viruses.

The sensitivity of lymphocytic choriomeningitis virus (LCMV) and Tacaribe virus to several chemical reagents was investigated. The viruses were sensitive to lipid solvents (ether, chloroform) and to detergents (sodium desoxycholate and Triton X-100); they were rapidly inactivated by formalin, beta-propiolactone, hydrogen peroxide and chloramine B. The results obtained contribute to a more complete characterization of the biological features of the arenavirus group and may be useful for scientific research and manufacturing of viral preparations.

Animals↗
PubMed1985

[Properties and efficacy of a human immunoglobulin M preparation for intravenous administration].

From Cohn fraction III a new immunoglobulin (Ig) preparation (Pentaglobin) was prepared. This preparation contains 72% IgG and is enriched in IgM (12%) and IgA (16%). Due to a treatment with beta-propiolactone it is suitable for intravenous application. This IgM-enriched immunoglobulin preparation is prominent in high antibody titers (passive hemagglutination) against gram-negative as well as gram-positive germs and shows significantly higher efficacy in mouse protection tests than intravenous standard IgG. The high IgM content of this preparation in particular is responsible for the binding of bacterial antigens. Thus a marked advancement in the treatment of bacterial infections is to be expected by this new intravenously tolerable immunoglobulin preparation.

Animals↗
PubMed1975

Conventional immunoglobulin therapy.

Concentrated gamma globulin as a substitute for deficient B-cell function is usually given by the intramuscular route. The intravenous administration would be preferable, but presents major difficulties, mainly with shock-life reactions. Most of them are due to rapid activation of the complement system by aggregated IgG. The attempts to avoid such reactions include exposure of gamma globulin concentrates to pepsin, plasmin, low pH, beta-propiolactone, polymers, salts and millipore filtration. The results improved slowly, but they are still not entirely satisfactory.

Absorption↗