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An anti-heart immune serum (IS) has been tested to prevent digitalis intoxication in guinea-pig atrial and papillary muscle. The results show a good protector effect of the IS against the cardiotoxic effects of digitoxin. The hypothesis of an interaction between the IS and the affinity binding sites of the cardiotonic glycosides can be retained.
Column ion exchange chromatographic processes were developed for the production of immune serum globulin (ISG) for intravenous use. Sequential chromatography on two cross-linked agarose gel anion exchangers yielded the same immunoelectrophoretic pure ISG as a single column DEAE-Sephadex procedure with the advantage of repeated 'in column' cycling. ISG with a low content of aggregated IgG and low anticomplementary activity was prepared from plasma with 53-69% efficiency. The ISG prepared by these processes was characterized with respect to the content of IgA, prekallikrein activator (PKA), plasminogen, fragmentation, and heavy chain subclass distribution.
Three sequential serum samples collected from each of 20 young children with a naturally acquired primary rotavirus infection were assayed by the radioimmunoprecipitation technique for immunoglobulin G antibodies to rotavirus structural and nonstructural proteins of the four major human rotavirus serotypes G1, P1A; G2, P1B; G3, P2; and G4, P2. Fourteen children were infected with a serotype G1 rotavirus strain and six children were infected with a serotype G4 rotavirus strain. Sera were collected from each child in the acute and convalescent periods postinfection and also approximately 4 months later. Serum immune responses to rotavirus core antigens VP2 and VP3, to the major inner capsid antigen VP6, to nonstructural proteins NS35, NS28, and NS26, and to the outer capsid neutralization antigen VP4 of all test strains were detected in the majority of patients. These responses do not appear to be influenced by the G type or P type of the rotavirus strain used in the reactions. Homologous responses to the main neutralization antigen VP7 were detected in 93% of patients with serotype G1 infections and 50% of patients with serotype G4 infections. Heterologous VP7 responses were less frequently detected and were restricted to G1, G3, and G4 serotype rotavirus strains. No responses to VP7 of the serotype G2 rotavirus strain were detected in any patients. Heterotypic immune responses to the neutralization antigens, at least following serotype G1 and G4 infections, therefore appear to consist primarily of responses to VP4 rather than to VP7.
A comparison was made of immune serum from rabbits, sheeps, pigs and cattle. Pure IgG was prepared by the Rivanol sulphate method and immune electrophoresis. Optimum protein quality, conjugation time under various conditions and using two preparations of fluorescein isothiocyanate were studied. Conjugate purified by DEAE-Sephadex A-50 and concentrated to 1% protein by ultrafiltration was freeze-dried and then tested for activity and the degree of non-specific fluorescence. Evaluation by yield of immuno-electrophoretically pure IgG, conjugation time, antibody content, degree of non-specific fluorescence and the intensity of specific fluorescence before and after dilution showed that pig serum was the best, followed by cattle and sheep serum; rabbit serum was the least suitable for conjugate preparation.
Neutralizing antibodies to selected non-polio enteroviruses were found in three lots of human immune serum globulin (ISG) prepared from the sera of persons from different geographic regions. Reciprocal titers to coxsackieviruses B3 and B4 ranged from 400 to greater than or equal to 2000, whereas titers to coxsackievirus A9 and ECHO viruses 5 and 9 ranged from 100 to 400 in all three lots of ISG. The presence of neutralizing antibodies to commonly occurring (coxsackieviruses B1 to B5 and A9 and ECHO viruses 3, 4 and 9) and infrequently encountered (ECHO viruses 5 and 13) serotypes, coupled with the increasing evidence that antibodies are an important factor in preventing illness, support recommending the administration of ISG to those at high risk for serious disease.
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The efficacy of an Indian preparation of immune serum globulins (ISG) was evaluated among pregnant women during an epidemic of hepatitis E in Karad, Western India from January to March 1993. Ten of 55 women receiving ISG developed immunoglobulin M (IgM) antibodies to hepatitis E virus (anti-HEV) during the 1 month of follow-up compared with 18 out of 53 control subjects. Although the total number of recent HEV infections was significantly less in the ISG-treated group, no significant difference could be shown in the proportion of clinical hepatitis E cases because of the very small numbers of patients who developed clinical disease. The observed marginal beneficial effect of ISG might be the result of a low immunoglobulin G (IgG) anti-HEV IgG titre (1:500) of the ISG preparation used. Preparation and testing of high-titred ISG should be a high priority for protecting pregnant women during epidemics of hepatitis E.
Serologic evidence now confirms epidemiologic evidence that human immune serum globulin (ISG) protects susceptible patients from hepatitis A provided it is administered prior to exposure to the virus. In two wards of young patients housed at the Lynchburg (Virginia) Training School and Hospital for the mentally retarded, 44 out of 60 patients had no detectable antibody to hepatitis A prior to an epidemic which took place there in 1970; 12 of 19 non-immunized susceptible patients contracted the disease, while only four of 25 patients receiving ISG developed hepatitis. These four were probably infected with the virus prior to ISG administration. Of the 16 patients with pre-existing antibody, none showed any signs of symptoms of hepatitis.
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The relationship between asymptomatic fecal carriage of enterotoxigenic bacteria (ETB), diarrhea and serum immune response in children has not been systematically explored. We studied 40 babies between birth and two years with weekly health histories, weekly fecal samples and serum samples every six months and with diarrhea. Toxigenic bacteria and fecal toxin were identified by ELISA (cholera toxin) and Y-1 cell assay. Serum antitoxin was identified by ELISA (IgG and IgM) and toxin neutralization (Y-1 assay). Thirty-eight babies had fecal ETB 457 weeks; 36 of them had toxigenic E. coli (ETEC) 220 weeks. Twenty babies had 36 episodes of diarrhea within one week of isolation of ETB or demonstration of fecal toxin. Nineteen (53%) episodes in 11 (55%) babies were followed by an antibody response within one to three weeks. Sixty-one sera were positive. Forty-three (69%) of the positives were preceded within one month by toxin and diarrhea. Ten (17%) were preceded by diarrhea but no toxin; five were preceded by toxin but no diarrhea; three were preceded by neither. Twenty-four (64%) of the babies who carried ETB had a serologic response to toxin at some time during the observation period. Antibody responses followed identification of toxigenic E. coli in 17 instances, Klebsiella in four, Citrobacter in two, colony pools in four, and fecal water in 21. Asymptomatic carriage of enterobacteria which elaborated toxin immunologically and functionally similar to cholera toxin was common among these babies but serum antibody responses were significantly more common following toxin-related diarrhea.
In a further analysis of a randomized, double-blind study of 107,803 U.S. soldiers receiving either immune serum gamma globulin (ISG) or placebo, serum specimens from the first week of clinical illness from 210 soldiers consecutively hospitalized with icteric hepatitis were reexamined by using modern immunologic methods to test for evidence of hepatitis A and B. Prophylactic intramuscular injection of 5 or 10 ml of ISG containing antibody to hepatitis A virus and antibody to hepatitis B surface antigen provided significant protection against development of endemic type A, type B, and non-A, non-B icteric hepatitis for six months if it was administered before exposure. Failure to receive a second injection of either 5 or 10 ml of ISG permitted an occurrence of hepatitis that was not significantly different from that among subjects who failed to receive a second placebo injection. ISG at 2 ml appeared equally effective in preventing hepatitis A but may be less effective in preventing hepatitis B and non-A, non-B hepatitis.
Since 1969, extensive use of immune serum globulin in the Israel Defence Force for prophylaxis against hepatitis A virus (HAV) infection has produced a sharp decline in the incidence of the disease. However, it is not clear whether this policy has affected the susceptibility of Israeli adults to HAV infection. In this study, we examined the effect of the immunisation policy on the incidence of hepatitis A virus infection in the civilian population in the 15-44 year age group, which includes all those who have completed compulsory military service since vaccination was introduced. The incidence of viral hepatitis in the Jewish civilian population aged 15-44 increased by approximately 50% 3-4 years after the implementation of the immunisation policy. This rise was not seen in the non-Jewish population of the same age nor among Jews aged 45-64. These findings strongly suggest that the immunisation policy in the military prevents both clinical and sub-clinical disease, but has had the effect of producing more susceptible people at an older age in the civilian population.
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A method for calibrating proteins by Western blot analysis is described. Rabbit immune serum, specific for seven protein molecular weight standards, and goat anti-rabbit horseradish peroxidase conjugate are used to visualize standards after electrotransfer onto nitrocellulose. This method can be used as a reagent and procedure control.
A methodological investigation of the procedure used by Beaumont et al for measuring a "serum immune complex" precipitated by 25% ammonium sulfate and alleged to contain an ethynyl-estradiol binding immunoglobulin has found major problems with reproducibility and with the correlation of total protein as measured by the Lowry method and the IgG content as determined by a specific nephelometric procedure.
We reviewed the efficacy of three agents advocated as ancillary therapy in myeloma patients. Intramuscularly administered immune serum globulin (gamma globulin) was ineffective in preventing infection. Hemoglobin level was improved in some myeloma patients receiving androgens. However, the response rate and the degree of leukopenia or thrombocytopenia were not superior with androgen-melphalan-prenisone combination therapy, as compared with those resulting from the two-drug combination without androgen. A controlled study evaluating androgen plus melphalan has not been done. The long-term administration of fluoride, supplemented by calcium and androgen, induced radiologically apparent bone fluorosis, but strengthening of lytic bone was not observed. Neither objective nor subjective benefit was demonstrated in a controlled study comparing the effects of fluoride (without calcium supplement) with those of the placebo.
Previous studies have shown that the administration of immune serum globulin (ISG) before exposure to hepatitis A virus prevents infection. The precise dose needed and the duration of the protection conferred are unclear, however. In this study, ISG doses of 2 mL and 5 mL were used for preexposure prophylaxis, and their efficacies in reducing the attack rate of hepatitis A among Israel Defence Forces troops serving in field units were compared. The attack rate during the first 4 months of follow-up was low and was similar regardless of the dose administered (0.11/10,000 and 0.15/10,000 for 2 mL and 5 mL, respectively; P = 1.0). In the second and third 4-month intervals after immunization, attack rates were higher (but not significantly so) among soldiers given 2 mL than among those given 5 mL. Twelve months after immunization, the cumulative attack rate for hepatitis A was significantly different for the two groups (2.78/10,000 vs. 1.30/10,000; P < .05). Our data suggest that preexposure immunization with 2 mL of ISG is as effective as that with 5 mL in preventing hepatitis A for 4 months. The advantage of the 5-mL dose is evident 5-12 months after administration.