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Human antirabies gamma globulin.

To obviate the foreign protein reactions experienced with the use of hyperimmune serum in rabies-exposed individuals, an attempt was made to produce a rabies antiserum of human origin.Five doses of an inactivated rabies virus duck-egg vaccine were administered to 34 volunteers at 4-day intervals (i.e., on days 0, 4, 8, 12 and 16). An additional dose of chick-embryo attenuated virus vaccine-Flury HEP (high egg passage)-was given on the 46th day, followed by a final booster dose of duck-egg vaccine on the 288th day. Twenty-four days later, i.e., on the 312th day after the first dose, the participants were bled and the serum pooled and converted to gamma globulin.These volunteers, having no initial antibody, responded with variable titres, the pooled serum having a titre of 1: 100 against 50 LD(50) of rabies virus in neutralization tests and the gamma globulin prepared from this pool a titre of 1: 300.In five individuals inoculated with the antirabies gamma globulin, blood samples tested at intervals for residual antibody showed significant titres through 21 days.While the passive antibody levels resulting from the administration of a more potent immune horse serum were much higher than those achieved by the weaker human antirabies gamma globulin used, the decrease in titre was more gradual with the human globulin. With more booster inoculations in a larger group of human volunteers, it is believed that a human rabies immune gamma globulin could be produced which would be equal in effect to immune horse serum. The advantages of a human source of antibody in rabies prophylaxis are discussed.

Animals↗

Prognostic value of an index for serum globulin compensation in colon and breast cancers.

INTRODUCTION: Decreased serum albumin (SA) levels have been used extensively as prognostic indicators in many chronic debilitating diseases. The decrease may be partly compensated by globular proteins. The failure of globulins to compensate may reflect advanced disease. We examined the prognostic value of the level of serum globulins in colorectal and breast cancers. METHODS: Data of 80 patients with advanced colon and breast cancers were analysed. Of these, 46 patients died within six months of measurement of their serum proteins, and the rest were followed-up for more than six months after measurements of their serum proteins were taken. A mathematical formula, representing the globulin compensation index (GCI), was recently developed from the measured SA levels and globulins. Patients were then classified into three categories: negative GCI and negative compensation; GCI of 0 to less than 1.0 with partial compensation; and GCI equal or greater than 1.0 with full compensation. RESULTS: Among the deceased patients, 45.7 percent had negative GCI, compared to 26.5 percent of patients in the survivors group. For partial compensation, 30.4 percent of patients were from the deceased group, and 32.4 percent were from the survivors group. For full compensation (elevated GCI), 23.9 percent of patients were from the deceased group, compared to 41.1 percent from the survivors group (p-value equals 0.031). CONCLUSION: Patients with low GCI are more likely to have bad prognoses, whereas those with higher GCI have more favourable prognoses. Globulin compensation may be a reliable prognostic factor in advanced colorectal and breast cancers, and possibly in other chronic illnesses. The GCI may serve as a useful tool in the measurement of this compensation.

Breast Neoplasms↗

[Serum sex hormone-binding globulin levels in thyroid diseases].

Synthesis of "sex-hormone binding globulin" is influenced by the thyroid hormones and its concentration in the serum may be a marker of the thyroid hormone effect at the peripheral tissue (liver) level. Compared to euthyroid controls serum "sex-hormone binding globulin" concentration is elevated in overt hyperthyroidism (141.6 +/- 37.6 vs 48.3 +/- 16.2 nmol/l; p less than 0.001), conversely, its mean level is decreased in the hypothyroid group of patients (24.9 +/- 14.8 vs 48.3 +/- 16.2; p less than 0.001). In the group of subclinical hyperthyroidism the mean value of "sex-hormone binding globulin" corresponds to that in control subjects (47.4 +/- 16.8), while its serum level is near the lower border of the normal range in subclinical hypothyroidism (33.6 +/- 6.1 vs 48.3 +/- 16.2; p less than 0.01). During thyroid hormone replacement for hypothyroidism measurement of serum "sex-hormone binding globulin" may help to assess the response of the target organs to the hormone therapy. In patients with peripheral thyroid hormone resistance serum "sex-hormone binding globulin" level is within the normal range (51.3 +/- 9.8), its determination supports the diagnosis of this disease.

Adult↗

[The usefulness of the refractometer in the assessment of colostrum and various factors affecting serum gamma globulin levels in newborn calves].

The effects of a number of factors on the concentration of gamma globulins in the serum of newborn calves were studied in 181 calves from six different dairy farms as was also the use of the refractometer test in controlling the ingestion of colostrum. The refractometer test was found to be reliable in controlling the concentration of gamma globulins in the serum of calves up to the sixth day of life. The factors 'time the first colostrum was ingested', 'amount of first colostrum ingested' and the 'concentration of gamma globulins in the colostrum' were found to account for 23.5 per cent of the variations in serum gamma globulin concentration; this became 42.4 per cent when the 'system of administration' and the 'farm-bound factors' were also taken into account. The first colostrum is best ingested when it is offered in a pail or bottle provided with a nipple. Calves of heifers were found to show a lower concentration of gamma globulins in the serum than did calves of older cows.

Animal Feed↗

[Comparative analysis of gamma globulin preparations isolated by means of DEAE-Sephadex and DEAE-cellulose].

Preparations of rabbit gamma-globulin obtained with the aid of ion-exchange chromatography on DEAE-Sephadex contained an admixture of other serum proteins revealed by disc-electrophoresis in acrylamide gel. This impurity can be eliminated by rechromatography of gamma-globulin preparations of DEAE-cellulose in the same buffer solutions which were used for purification of gamma-globulin on DEAE-Sephadex. Better purification of gamma-globulin on DEAE-cellulose can supposedly be attributed to the effective absorption on cellulose basis of euglobulin aggregates which form in the solutions with a low ionic power used for chromatographic isolation of gamma-globulin on ion-exchangers.

Animals↗

Investigation of the serum level of pregnancy-associated alpha2-globulin during contraceptive treatment by means of radial immunodiffusion method.

The serum level of pregnancy-associated alpha2-globulin was studied in 70 healthy women taking three different types of oral contraceptives [40 Bisecurin: containing 1.0 mg of Ethynodiol diaceticum +0.05 mg Ethynilestradiol; 20 Infecundin: containing 2.5 mg of Norethynodrel +0.1 mg of Mestranol; 10 Cervicundin: containing of 0.5 mg Ethynodiol diaceticum]. Elevated amounts of serum level of pregnancy associated alpha2-globulin could be detected in 37 of the 40 women taking Bisecurin and in all 20 taking Infecundin. Cervicundin however, failed to induce any change in the serum protein pattern of the 10 subjects studied. Serum levels of pregnancy-associated alpha2-globulin were higher in the Infecundin-taking (53 mg %), than in the Bisecurin-taking group (29 mg %). This shows the oestrogen dependency of the pregnancy-associated alpha2-globulin and points to a possible implication of this globulin in the immunosuppressive processes.

Alpha-Globulins↗

[Physico-chemical characteristics of human neurospecific beta 2 globulin].

Neurospecific beta 2-globulin was found to be a protein with molecular mass 20,000 +/- 2,000 daltons, exhibiting electrophoretic mobility of beta 2-globulins (0.29 +/- 0,05). Contrary to the S-100 protein the globulin was readily precipitated by ammonium sulfate at 30-60% of saturation. No carbohydrate and lipid components were found in the globulin. The beta 2-globulin appears to be a typical polypeptide.

Beta-Globulins↗

Effect of variations in globulin concentrations on serum radioimmunoassay results, as exemplified by choriogonadotropin.

Variations in serum protein concentrations can affect results of radioimmunoassay of human choriogonadotropin involving either polyethylene glycol or double-antibody methods of separation. Relative to the maximal binding of choriogonadotropin in the presence of normal (30 g/L) globulin concentrations, globulin concentrations of 10 to 60 g/L were associated with maximal binding ranging from 84.9 to 115.6% in the polyethylene glycol system, and from 109.9 to 92.5% in the double-antibody system. This effect was quantitatively much the same throughout the standard curve in the polyethylene glycol system, but diminished with the higher standard concentrations in the double-antibody system. In assays involving polyethylene glycol separation, an increase in globulin was associated with a linear increase in nonspecific binding, but no detectable effect of globulin on nonspecific binding was observed in the double-antibody system. Determination and compensation for nonspecific binding of individual samples (rather than for mean assay nonspecific binding) eliminated the globulin effect in the polyethylene glycol system but not in the double-antibody system.

Chorionic Gonadotropin↗

[Effect of multiple gamma globulin administration on the effectiveness of seroprophylaxis in hepatitis A].

The data provided by immunological and epidemiological studies carried out to determine the influence of the multiple injections of 10% commercial gamma globulin on the level of antigamma globulin formation and, in this connection, on the effectiveness of the prophylaxis of hepatitis A are discussed. A sharp increase in the titers of antigamma globulin in persons receiving multiple gamma globulin injections is shown. The increased amount of antibodies to gamma globulin, appearing as the result of the multiple use of this preparation, decreases the effectiveness of the seroprophylaxis of hepatitis A.

Antibodies, Anti-Idiotypic↗

Preventing rhesus isoimmunization. Antepartum Rh immune globulin prophylaxis versus a sensitive test for risk identification.

The controversial proposal to use Rho (D) immune globulin (human) prophylactically in pregnancy should not detract from the most expedient approach to further reduction of Rh disease; that is, to ensure that every eligible woman is given Rho (D) immune globulin (human) after delivery, abortion, or ectopic pregnancy. Family planning by Rh-negative women at risk and limiting the number of pregnancies in women already immunized will be additional effective ways to reduce the current incidence of hemolytic disease in most communities. Present evidence shows that blanket antepartum Rho (D) immune globulin (human) prophylactic treatment will be very costly and will place many subjects at potential risk while offering benefit to only a few. Sensitive and practical laboratory testing for fetomaternal hemorrhage is presently only a research tool but will soon be clinically available to provide new data on fetomaternal hemorrhage. In the near future, pregnant women truly at risk for Rh isoimmunization may be identified by analysis of their blood, and this will be a rational basis for antepartum Rho (D) immune globulin (human) treatment. There are compelling advantages in cost, risks, and benefits for an approach of selective antepartum Rho (D) immune globulin (human) therapy as opposed to routine prophylaxis for all Rh-negative gravid women.

Australia↗

Thyroxine-protein interactions. Interaction of thyroxine and triiodothyronine with human thyroxine-binding globulin.

The effect of temperature on the binding of thyroxine and triiodothyronine to thyroxine-binding globulin has been studied by equilibrium dialysis. Inclusion of ovalbumin in the dialysis mixture stabilized thyroxine-binding globulin against losses in binding activity which had been found to occur during equilibrium dialysis. Ovalbumin by itself bound the thyroid hormones very weakly and its binding could be neglected when analyzing the experimental results. At pH 7.4 and 37 degrees in 0.06 M potassium phosphate/0.7 mM EDTA buffer, thyroxine was bound to thyroxine-binding globulin at a single binding site with apparent association constants: at 5 degrees, K = 4.73 +/- 0.38 X 10(10) M-1; at 25 degrees, K = 1.55 +/- 0.17 X 10(10) M-1; and at 37 degrees, K = 9.08 +/- 0.62 X 10(9) M-1. Scatchard plots of the binding data for triiodothyronine indicated that the binding of this compound to thyroxine-binding globulin was more complex than that found for thyroxine. The data for triiodothyronine binding could be fitted by asuming the existence of two different classes of binding sites. At 5 degrees and pH 7.4 nonlinear regression analysis of the data yielded the values n1 = 1.04 +/- 0.10, K1 = 3.35 +/- 0.63 X 10(9) M-1 and n2 = 1.40 +/- 0.08, K2 = 0.69 +/- 0.20 X 10(8) M-1. At 25 degrees, the values for the binding constants were n1 = 1.04 +/- 0.38, K1 = 6.5 +/- 2.8 X 10(8) M-1 and n2 = 0.77 +/- 0.22, K2 = 0.43 +/- 0.62 X 10(8) M-1. At 37 degrees where less curvature was observed, the estimated binding constants were n1 = 1.02 +/- 0.06, K1 = 4.32 +/- 0.59 X 10(8) M-1 and n2K2 = 0.056 +/- 0.012 X 10(8) M-1. When n1 was fixed at 1, the resulting values obtained for the other three binding constants were at 25 degrees, K1 = 6.12 +/- 0.35 X 10(8) M-1, n2 = 0.72 +/- 0.18, K2 = 0.73 +/- 0.36 X 10(8) M-1; and at 37 degrees K1 = 3.80 +/- 0.22 X 10(8) M-1, n2 = 0.44 +/- 0.22, and K2 = 0.43 +/- 0.38 X 10(8) M-1. The thermodynamic values for thyroxine binding to thyroxine-binding globulin at 37 degrees and pH 7.4 were deltaG0 = -14.1 kcal/mole, deltaH0 = -8.96 kcal/mole, and deltaS0 = +16.7 cal degree-1 mole-1. For triiodothyronine at 37 degrees, the thermodynamic values for binding at the primary binding site were deltaG0 = -12.3 kcal/mole, deltaH0 = -11.9 kcal/mole, and deltaS0 = +1.4 cal degree-1 mole-1. Measurement of the pH dependence of binding indicated that both thyroxine and triiodothyronine were bound maximally in the region of physiological pH, pH 6.8 to 7.7.

Binding Sites↗

Studies of enteric pathogens and gamma-globulin levels of neonatal calves in Sweden.

Faecal and blood samples were taken from 10-30% of calves, 36 hours to 14 days old, in 47 dairy herds in different regions of Sweden from September 1987 to October 1988 (Olsson et al. 1993). Faecal samples from 279 calves were analysed for the presence of Escherichia coli (K99+), rotavirus and Cryptosporidium sp. Twenty (7.2%) of these samples were from diarrhoeic calves. An ELISA was developed and used for the rotavirus analysis. E. coli K99+ was detected in 11.5%, Cryptosporidium sp. in 6.1% and rotavirus in 5.4% of the faecal samples. The presence of rotavirus alone and the combination rotavirus and E. coli (K99+) was found to be associated with diarrhoea (p < 0.001 and p < 0.01 respectively). Blood samples from 327 calves were analysed for the level of total protein and gamma-globulin. In 43 of these samples (13%) gamma-globulin did not separate from the beta 2-region by electrophoresis. The mean total protein concentration was 53.6 g/l in calves free from diarrhoea. The mean gamma-globulin concentration, adjusted to 7 days age was 5.9 g/l. The 20 diarrhoeic calves had lower levels of both total protein and gamma-globulin, compared with calves without diarrhoea, but the difference was not significant. One litre more of colostrum at the first feed increased the level of total protein of the calves' sera by 1.4 g/l (p = 0.05). Calves born between May and September had a 2.0 g/l higher (p < 0.001) serum concentration of gamma-globulin than calves born between October and April.

Animals↗

[Correlation between serum globulin levels and hepatitis C virus antibody].

BACKGROUND: some studies have suggested that the elevation of serum globulins in patients with chronic autoimmune hepatitis, paraproteinemias and rheumatoid arthritis could affect the determination of false positive hepatitis C virus antibodies (anti-HCV). AIM: to study the relationship between positive anti-HCV and serum levels of globulins in patients with liver disease. PATIENTS AND METHODS: one hundred thirty one patients with liver disease, 49 alcoholic, 38 cryptogenetic, 17 autoimmune and 27 with other causes, were studies prospectively measuring simultaneously anti-HCV and serum levels of total, gamma and immuno-globulins (IgA, IgG and IgM). These levels were compared between anti-HCV positive and negative groups and correlated with the ratio between serum optical density/cutoff optical density of the anti HCV assay. RESULTS: Twenty eight patients (21.3%) were anti-HCV positive, no differences in serum globulins between these patients and anti-HCV negative patients and no correlations between serum globulins and anti-HCV optical densities were observed. CONCLUSIONS: the hypergamma-globulinemia observed in these patients with liver diseases would not be responsible for positive hepatitis C virus antibodies.

Enzyme-Linked Immunosorbent Assay↗

Long-term oral administration of ginseng extract decreases serum gamma-globulin and IgG1 isotype in mice.

Effects of long-term oral administration of ginseng extract on serum protein profile and immunoglobulin (Ig) isotypes were studied in mice. Ginseng extract was orally administered to healthy female mice for 52 days at doses of 30 and 150 mg/kg per day and serum protein electrophoretograms and Ig isotypes levels were evaluated. Serum level of gamma-globulin was decreased dose dependently to 82% (P < 0.05) and 56% (P < 0.01) of control values at the doses of 30 and 150 mg/kg per day, respectively. Levels of total protein, albumin, alpha2- and beta-globulin fractions, as well as the ratio of albumin to globulin (A/G) did not change significantly. However, the alpha1-globulin level increased by 24% (P < 0.05) at the doses of 30 and 150 mg/kg per day. Among the Ig isotypes, including IgG1, IgG2a, IgG2b, IgG3, IgM and IgA, serum IgG1 was dose dependently decreased to 68% (P < 0.05) of control values at the dose of 150 mg/kg per day without significant changes in other Ig isotypes. As IgG1 isotype is rarely cytotoxic and can act as a blocking antibody, it is suggested that the selective decrease in serum IgG1 induced by ginseng extract without changes in the cytotoxic antibodies such as IgG2a may be helpful for the prevention and inhibition of cancer.

Administration, Oral↗

Open controlled therapeutic trial of intravenous immune globulin in relapsing-remitting multiple sclerosis.

Ten patients with relapsing-remitting multiple sclerosis were treated with intravenous immune globulin, 0.4 g/kg per day for 5 consecutive days, and then with additional booster doses of immune globulin of 0.4 g/kg, once every 2 months, for the next 12 months. Ten untreated patients with relapsing-remitting multiple sclerosis who were matched with the study patients for age, disease duration, and number of attacks per year served as controls. Immune globulin treatment was well tolerated, with no side effects. The exacerbation rate decreased from 3.7 +/- 1.2 exacerbations per year before treatment to 1.0 +/- 0.7 exacerbations per year during the treatment in the immune globulin-treated patients, while it remained unaltered in the controls. The posttreatment Kurtzke Expanded Disability Status Scale score decreased from a mean of 4.45 to 4.15, whereas in controls it increased from 3.55 to 3.75. The results suggest that immune globulin suppresses the ongoing pathologic process in multiple sclerosis and may be a promising treatment to prevent disease exacerbations.

Adult↗

Elevation of serum free triiodothyronine, total triiodothyronine, thyroxine-binding globulin, and total thyroxine levels in combat-related posttraumatic stress disorder.

BACKGROUND: This study was designed to assess both central and peripheral aspects of thyroid function in combat-related posttraumatic stress disorder (PTSD), with the particular purpose of finding a mechanistic explanation for an imbalance between serum levels of free thyroxine (T4) and total T4 previously observed in pilot work. METHODS: A total of 96 male combat veterans with PTSD diagnosed by DSM-III-R (72 from the West Haven, Conn, Veterans Affairs Medical Center and 24 from the Menlo Park, Calif, Veterans Affairs Medical Center) were compared with 24 male control subjects. One or more serum samples were analyzed by radioimmunoassays for levels of total T4, free T4, total triiodothyronine (T3), free T3, T4-binding globulin, and thyrotropin. RESULTS: The pilot observation of moderately elevated total T4 levels with no elevation in free T4 levels in patients with PTSD was confirmed, suggesting the hypotheses that (1) there may be an increased peripheral conversion of free T4 by deiodination to T3 or (2) there may be an increased binding of T4 secondary to elevated T4-binding globulin levels. Our findings support both hypotheses. The PTSD groups all showed a marked and sustained elevation in levels of both total T3 and free T3, as well as elevated T3/T4 ratios, supporting the increased T3 conversion hypothesis. The PTSD groups also showed a marked and sustained increase in T4-binding globulin levels, supporting the increased binding hypothesis. Thyrotropin levels did not differ between PTSD and control groups. CONCLUSIONS: These findings demonstrate an unusual pattern of thyroid alterations, featuring substantial elevations in total T3, free T3, and T4-binding globulin levels, in combat-related PTSD that differs from established endocrinopathies, such as classic hyperthyroidism, T3 thyrotoxicosis, or chronic T4-binding globulin elevation.

Adult↗

Light chain heterogeneity of 19S and 7S anti-gamma-globulins in rheumatoid arthritis and subacute bacterial endocarditis.

Both 19S and 7S anti-gamma-globulins in rheumatoid arthritis sera are enriched in kappa light chain bearing antibody molecules when compared to total 19S and 7S globulins from the same individuals. In patients with subacute bacterial endocarditis 19S anti-gamma-globulins are also, to a degree, enriched in kappa light chains, whereas the 7S anti-gamma-globulins have kappa to lambda light chain ratios indistinguishable from total 7S globulin.

Antibodies, Anti-Idiotypic↗

Simultaneous passive and active immunization against hepatitis B: noninterference of hepatitis B immune globulin with the anti-HBs response to reduced doses of heat-inactivated hepatitis B vaccine.

The effect of simultaneous administration of hepatitis B immune globulin on the antibody response to a low dose of heat-inactivated hepatitis B vaccine was investigated in 175 health care workers. Subjects were divided into four groups: Groups I and II received 3 monthly injections of a reduced dose (0.6 microgram) of a heat-inactivated hepatitis B vaccine (the usual dose being 3 micrograms) along with 500 IU of hepatitis B immune globulin simultaneously with the first injection of vaccine; Groups III and IV received the vaccine only. In addition, Groups I and III received a final booster injection with 0.6 microgram of the vaccine 8 months after the initial injection. Anti-HBs passively acquired from hepatitis B immune globulin did not interfere with the development of an active antibody response to the vaccine: the anti-HBs conversion rates were similar in persons treated with the combined regimen (89%) as in those who received the vaccine only (91%). At 3 and 5 months after the first injection, however, anti-HBs titers in the recipients of vaccine alone were slightly but statistically significantly higher than those of persons who received both hepatitis B immune globulin and vaccine; but at 8 months, this difference was no longer statistically significant. After a booster inoculation at 8 months, the geometric mean titer of anti-HBs increased 7- to 8-fold in antibody-positive vaccinees, regardless of whether hepatitis B immune globulin had been given earlier. Moreover, 6 of 13 nonresponders to the initial three vaccine injections developed anti-HBs after the booster inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗