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PubMed1992

Prophylactic intravenous administration of standard immune globulin as compared with core-lipopolysaccharide immune globulin in patients at high risk of postsurgical infection.

BACKGROUND: Infections and their sequelae are a major cause of death among patients admitted to the surgical intensive care unit (ICU). Studies of passive immunotherapy with standard intravenous immune globulin and hyperimmune globulin directed against gram-negative core lipopolysaccharide to prevent gram-negative infections and their serious systemic complications have had equivocal results in such patients. METHODS: We performed a double-blind study to assess the efficacy of standard immune globulin and core-lipopolysaccharide hyperimmune globulin in preventing infections in surgical patients at high risk. The patients received standard immune globulin (400 mg per kilogram of body weight), hyperimmune globulin (400 mg per kilogram), or placebo (25 percent albumin, 8 ml per kilogram) weekly, for a maximum of four doses while in the ICU. RESULTS: A total of 352 patients were enrolled, and 329 could be evaluated. The number of patients in whom infections developed was significantly lower in the group receiving standard immune globulin than in the placebo group (36 of 109 vs. 53 of 112 patients, P = 0.03), as was the incidence of pneumonia (15 vs. 30 cases, P = 0.04), especially pneumonia due to gram-negative bacteria (5 vs. 16 cases, P = 0.02). The number of days spent in the ICU and the total days spent in the hospital were lower in the standard immune globulin group (medians of 2 and 7.5 days fewer; P = 0.02 and 0.06, respectively). In contrast, the hyperimmune globulin had no detectable prophylactic effect on infections (50 of 108 patients, with 25 cases of pneumonia). The rate of systemic infections and shock was similar in the three study groups, and hospital mortality did not differ significantly among them. CONCLUSIONS: Intravenous immune globulin given prophylactically to selected high-risk patients in the surgical ICU can reduce the incidence of infection. Core-lipopolysaccharide hyperimmune globulin is not effective in preventing gram-negative infections and their systemic complications.

Bacteremia↗
PubMed1960

Immunological studies of human gamma-globulin. Relation of the precipitin lines of whole gamma-globulin to those of the fragments produced by papain.

Two major antigenic fragments were obtained from various purified gamma-globulin preparations after papain treatment. One, the F component, had a mobility faster than the original gamma-globulin and the second, the S component, had a slower mobility. Similar F and S components were also obtained with certain homogeneous myeloma proteins which were closely related to gamma-globulin immunologically. Additional minor antigenic components were detected with certain antisera. The technique of immunoelectrophoresis was particularly useful for bringing out the different antigenic constituents obtained after papain treatment. The F and S components as well as a midfraction were isolated by chromatography on DEAE-cellulose. These were immunologically homogeneous and could be utilized to absorb F and S antibodies from various antisera. The relative amount of F and S antibodies varied in different antisera from individual rabbits immunized with whole gamma-globulin. Whole gamma-globulin was separated by zone electrophoresis into a fast migrating and a more slowly migrating fraction. Each of these gave rise to F and S components after splitting with papain. The F components of the two gamma-globulins were similar in mobility, while the S components showed marked mobility differences although antigenically they were very similar. The mobility differences of the parent gamma-globulin appeared to be primarily related to the differences in the S component. Certain antisera against pathological gamma-globulins were found to give double lines with a wide variety of gamma-globulin preparations in agar diffusion. These were shown to be related to the F and S antigenic determinants of gamma-glubulin. This relationship was evident by a number of procedures utilizing both Ouchterlony plate techniques and immunoelectrophoresis. The question of whether these findings indicate heterogeneity of gamma-globulin in relation to the F and S antigenic components, or whether different antigenic groups on one molecule can give rise to separate lines in certain instances, is discussed.

Antibodies↗
PubMed1991

Behavior of alpha 2u-globulin accumulating in kidneys of male rats treated with d-limonene: kidney-type alpha 2u-globulin in the urine as a marker of d-limonene nephropathy.

Effects of d-limonene on alpha 2u-globulin in the kidneys, urine and serum were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis. Treatment of male rats with d-limonene by gavage for 14 consecutive days (300 mg/kg/day) caused accumulation of hyaline droplets in renal proximal tubule cells, and a marked intensification of a protein band corresponding to the kidney-type alpha 2u-globulin, with a molecular weight calculated to be approximately 16 kDa. However, no significant changes in the serum alpha 2u-globulin (native-type) band, of approximately 19 kDa, were observed between treated rats and controls, suggesting that circulating alpha 2u-globulin levels were not affected by the d-limonene administration. While the molecular weight of the major alpha 2u-globulin in the urine from control rats was the same as that in the serum (native-type), marked increase in the protein band corresponding to kidney-type-alpha 2u-globulin was observed in the urine from treated rats. The results were indicative of elimination of alpha 2u-globulin from the kidney to urine, the appearance of kidney-type-alpha 2u-globulin in urine implying disruption or exfoliation of proximal tubule cells. Therefore, it is suggested that the presence of the alpha 2u-globulin (kidney-type) in the urine might be used as an indicator of chemically induced alpha 2u-globulin nephropathy.

Alpha-Globulins↗
PubMed1975

[Effect of gamma globulin on reactivity of the organism. V. Types of biological activity of gamma globulin preparations].

Biological activity of 110 series of commercial gamma-globulin preparations was studied; they were found to contain placental antigens, group-specific blood substances, gonadotropic hormones and antibodies to them. Placental antigens were found in 12% of placental and abortive gamma-globulin batches in titres of 1 : 2--1 : 16; no placental protein was revealed in donor gamma-globulin. There were group-specific blood substances in all the batches of placental and abortive gamma-globulin studied (in titres of 1 : 138--A, 1 : 112 B in the placental gamma-globulin and in titres of 1 : 48.9--A, 1 : 32--B in the abortive gamma-globulin). In the preparations from the venous blood group-specific substances were either absent or present in lowe titres only (1 : 2). The value of gonadotropic hormones in the placental gamma-globulin batches constituted 873+/-157, and in the abortive--991.4+/-147 IU/l; no gonadotropins were revealed in donor gamma-globulin. The mean titres of antibodies to gonadotropin hormone in the gamma-globulin preparations made of placental blood constituted 1 : 236+/-32, of abortive--1 : 131+/-16.6, and of the venous blood--1 : 46+/-24.7. The presence of biologically-active substances in the gamma-globulin preparations pointed to the necessity of increased requirement of their quality; additional requirements to its standardization proved to be also necessary.

Antibodies↗
PubMed1998

HIV hyperimmune globulin or intravenous immune globulin inhibits response to an HIV vaccine.

The murine model was developed to assess the effects of maternally transferred HIV hyperimmune globulin or human intravenous immune globulin on the immunization of the offspring at 18-21 days of age with rgp 120SF2-complete Freund's adjuvant. Either HIV hyperimmune globulin or intravenous immune globulin was administered intraperitoneally to post-partum BALB/c mice and was transferred via milk to the offspring. Both HIV hyperimmune globulin and intravenous immune globulin inhibited the offspring anti-rgp 120SF2 IgG response to the vaccine. The HIV hyperimmune globulin inhibition persisted for 28 days after immunization while the intravenous immune globulin inhibition was still present at 63 days after immunization. In addition, the intravenous immune globulin had a more generalized immunosuppressive effect, inhibiting the IgG response to both rpg 120SF2 and an additional protein antigen, hen egg-white lysozyme. Effects of maternal or exogenously administered pre-existing antibody, including control antibodies (intravenous immune globulin), on the newborn response to HIV and other vaccines must be carefully evaluated when vaccine studies proceed in newborns.

AIDS Vaccines↗
PubMed1996

Effects of passive immunization against alpha-2u-globulin and supplementation with alpha-2u-globulin on serum gonadotrophins and testicular activity.

The purpose of the present study was to evaluate the effects of anti-alpha-2U-globulin on pituitary-gonadal functions in male rats. Adult male rats were given injections of anti-alpha-2u-globulin (1 mg/day) for 14 days, when they were killed 7 days after the last injection, serum levels of gonadotrophins and testosterone measured by radioimmunoassays, were less, testicular delta 3 beta- and 17 beta-hydroxy-steroid dehydrogenase (3 beta- and 17 beta-HSD) activities were suppressed, spermatogenesis was inhibited and serum level of alpha-2u-globulin was decreased in anti-alpha-2u-globulin treated rats. Administration of alpha-2u-globulin (1.5 mg/day) for 7 days to anti-alpha-2u-globulin treated rats reversed the 3beta-HSD and 17beta-HSD activities and serum levels of gonadotrophins, testosterone and alpha-2u-globulin, while spermatogenesis was restored to normal. The results indicate that changes in testicular steroidogenesis and spermatogenesis in rats after passive immunization against alpha-2u-globulin may be due to decrease in availability of endogenous alpha-2u-globulin.

17-Hydroxysteroid Dehydrogenases↗
PubMed1964

THE IMMUNOGLOBULINS OF MICE. II. TWO SUBCLASSES OF MOUSE 7S GAMMA-2-GLOBULINS: GAMMA-2A- AND GAMMA-2B-GLOBULINS.

Two subclasses of mouse 7S gamma(2)-globulins are identified, and are designated gamma(2a)- and gamma(2b)-globulins. They are distinguished from 7S gamma(1)-globulins, gamma(1A) (beta(2A))-globulins, and gamma(1M)-globulins of mouse serum. Antibody activity was detected among the gamma(2a)-globulins and gamma(2b)-globulins of hyperimmune mouse serum. gamma(2a)- and gamma(2b)-myeloma proteins were identified. The genetically determined isoantigen, Iga-1, was present on gamma(2a)-myeloma proteins, but not on gamma(2b)-myeloma proteins. These findings indicate a complexity among the 7S gamma(2)-globulins which must be taken into account in structural, functional, and genetic studies of immunoglobulins.

Animals↗
PubMed1960

Gamma globulin and antibody formation in vitro. I. Gamma globulin formation in tissues from immature and normal adult rabbits.

Gamma globulin formation in vitro by various tissues was studied using the incorporation of C(14)-L-lysine into a protein precipitable by a specific anti rabbit gamma globulin serum prepared in a sheep. It was demonstrated that the rate of gamma globulin formation in similar numbers of spleen cells is much higher if taken from an immunized rabbit at the height of antibody formation than that in normal spleen cells. Besides spleen, other tissues shown to form gamma globulin in normal adult rabbits were: peripheral lymph nodes, bone marrow, lung, mesenteric lymph nodes, appendix, and thymus. In tissues from newborn rabbits gamma globulin formation could not be demonstrated. Rabbits 1 week old already showed a beginning of significant gamma globulin formation in appendix tissue, followed approximately 3 weeks later by gamma globulin synthesis in spleen and thymus. Histological observations on these tissues were described and correlated with findings on gamma globulin formation. In the discussion an attempt has been made to relate these observations on newborn and immature rabbits to those available in the literature on antibody formation in newborn animals.

Animals↗
PubMed1984

Immune globulin and hepatitis B immune globulin. Prophylactic measures for intimate contacts exposed to acute type B hepatitis.

We studied the relative prophylactic efficacies of recently derived immune globulin containing antibody to hepatitis B surface antigen (anti-HBs) and hepatitis B immune globulin in 60 intimate contacts exposed to acute type B hepatitis. Forty susceptible contacts were randomly assigned to treatment with either a single intramuscular dose of immune globulin or hepatitis B immune globulin (0.06 mL/kg of body weight), following which observation was maintained over a 12-month period. Twenty additional contacts received the equivalent of twice the dose of immune globulin given to the first group, and follow-up was maintained for six months. Neither the hepatitis B virus (HBV) attack rates (11% to 19%) nor the frequency of clinical illness (0% to 4.8%) was substantially different in the three groups. When compared with average frequencies reported in the literature, significantly lower illness rates were noted for immune globulin recipients. These data indicate that currently derived immune globulin as well as hepatitis B immune globulin may confer protection from illness (le, passive-active immunity) in the setting of intimate exposure to HBV.

Acute Disease↗
PubMed1990

Immunological quantitation of rat and mouse thyroxine-binding globulins. Ontogenesis and sex-dependence of the circulating levels of the thyroxine-binding globulins.

We describe the preparation of monospecific antisera against a thyroxine-binding globulin partially purified from immature rat sera by affinity chromatography on thyroxine-Sepharose. The antisera are used for the rocket immunoelectrophoresis assay of rat thyroxine-binding globulin and also, owing to their partial cross-reactivity with mouse thyroxine-binding globulin, for the quantitation of this serum binding protein in the mouse. The thyroxine-binding globulin is measured in developing rats and in sexually mature male and female rats and mice. The results of the ontogenetic study confirm the postnatal surge of serum thyroxine-binding globulin levels, formerly demonstrated with binding techniques. They allow further to define the correlations, dependent on age, of the immunoquantitated thyroxine-binding globulin and transthyretin levels with the abilities of the sera to bind thyroxine. In sexually mature rats and mice we demonstrate an opposite sex-dependence of thyroxine-binding globulin levels, characterized by increased levels of the protein in the female rats versus increased levels of the protein in the male mice. This is the first report of immunological quantitation of rat and mouse thyroxine-binding globulins.

Aging↗
PubMed1995

The utilization of lupin (Lupinus angustifolius) and faba bean globulins by rats is poorer than of soybean globulins or lactalbumin but the nutritional value of lupin seed meal is lower only than that of lactalbumin.

The effects of dietary sweet lupin (Lupinus angustifolius, Unicrop) seed meal or its insoluble fiber (nonstarch polysaccharides + lignin) on performance, digestibility and nitrogen utilization in growing rats were studied in four experiments. Globulin proteins isolated from lupin, faba bean (Vicia faba L. minor) or soybean (Glycine max) were also incorporated into purified diets as replacements for lactalbumin (control) and the nutritional effects were evaluated. Isocaloric, legume-based diets supplemented with amino acids were used. Final weight gain, gain:feed ratios, nitrogen retention and net protein utilization of the animals fed whole lupin meal-based diets for 10 d were inferior to those of controls. In contrast, adding lupin insoluble fiber to a control diet produced no adverse effects. Ileal starch and apparent nitrogen digestibilities, and fecal digestibility of starch in lupin-fed rats were higher than those of controls, but fecal true nitrogen digestibility was lower. Replacement of lactalbumin with globulin proteins from lupin or faba bean depressed food intake and protein utilization, but only performance was affected by consumption of soybean globulins. Rats consuming lupin or faba bean globulins excreted significantly more nitrogen, particularly as urea through the urine. This did not occur in rats fed soybean globulins. Urea concentration in plasma was higher in rats fed diets containing lupin meal or legume globulins. The concentrations of urea, arginine and ornithine in plasma increased significantly compared with control values after 3 to 9 h of a lupin diet. After 9 h, plasma lysine was also decreased. We concluded that the main reasons for the low nutritional value of sweet lupin seed meal are likely to be related to the chemical structure of the globulin proteins and their adverse effects on growth and nitrogen metabolism, and not to any known antinutritional factor or poor digestibility.

Amino Acids↗
PubMed1984

Complement interaction with immune serum globulin and immune globulin intravenous.

Three complement assays, C1q binding activity, C3 activation in normal human serum, and enhancement of alternative pathway activity, have been used to evaluate the in vitro anticomplementary activity of untreated and heat-aggregated (63 degrees C, 10 minutes) immune serum globulin and immune globulin intravenous prepared by partial reduction and alkylation. Unheated immune globulin intravenous marginally activated endogenous C3 in normal serum, had a fivefold lower affinity for 125I C1q but was very similar to immune serum globulin in enhancing complement alternative pathway activity. Heat-aggregated immune globulin intravenous was about twofold less effective than heat-aggregated immune serum globulin in the activation of C3 in normal serum and had approximately a threefold lower affinity for 125I C1q. The ability of immune globulin intravenous to retain specific complement receptor activity suggests that it would also retain in vivo efficacy in complement-mediated amplification of host defense reactions but that it is safe for intravenous use due to a lower capacity to initiate nonspecific complement activation.

Complement Activating Enzymes↗
PubMed1996

Antenatal management of alloimmune thrombocytopenia with intravenous gamma-globulin: a randomized trial of the addition of low-dose steroid to intravenous gamma-globulin.

OBJECTIVES: Our purposes were to investigate maternal infusions of intravenous gamma-globulin, to prevent intracranial hemorrhage, and to determine whether 1.5 mg dexamethasone and 60 mg prednisone per day add to the effect of intravenous gamma-globulin. STUDY DESIGN: Fifty-four women with alloimmune thrombocytopenia and thrombocytopenic fetuses were randomized to intravenous gamma-globulin 1 gm/kg per week with or without dexamethasone. Nonresponders after 4 to 6 weeks received continued intravenous gamma-globulin plus 60 mg of prednisone per day ("salvage"). RESULTS: Dexamethasone did not add to the effect of intravenous gamma-globulin. Overall, there was a mean platelet increase from the first to the second fetal blood sampling of 36,000/microliters (n = 47) and from the first fetal blood sampling to birth of 69,000/microliters (n = 54). A total of 62% to 85% of fetuses responded. There were no intracranial hemorrhages. "Salvage" increased the platelet count in 5 of 10 nonresponders to intravenous gamma-globulin. CONCLUSION: Intravenous gamma-globulin treatment is appropriate for thrombocytopenic fetuses with alloimmune thrombocytopenia before use of weekly in utero platelet transfusions, even in severe thrombocytopenia.

Cerebral Hemorrhage↗
PubMed2004

Gc globulin (vitamin D-binding protein) levels: an inhibition ELISA assay for determination of the total concentration of Gc globulin in plasma and serum.

Gc globulin, also called vitamin D-binding protein, is a plasma protein involved in the actin-scavenger system. In this study, the total Gc globulin concentration in serum or plasma samples was determined using a new, fast, solid-phase inhibition assay. Included in the study were 228 healthy volunteers (131 M, 97 F), 22 pregnant women, 90 cancer patients and 9 patients with chronic liver disease. Moreover, the degree of complexing with actin was determined in selected samples using crossed immunoelectrophoresis. The Gc globulin level in healthy controls was in the range 176-623 mg/L, showing no age dependency. The median level was found to be significantly higher in women than in men. Gc globulin concentrations were raised during pregnancy, showing a median value of 541 mg/L in the first trimester, and slightly raised to 574 mg/L in the second trimester. Cancer patients showed no changes in Gc globulin level, and there was no sign of increased amounts of complexing with actin. Chronic liver patients showed increased levels of Gc globulin following transplantation, but no signs of complexing with actin. This new solid-phase inhibition assay is fast, it is a good complement to the existing quantification methods, and it is especially suitable for determination of the Gc globulin status in acute liver patients before and during treatment.

Actins↗