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PubMed1984

Efficacy of orally administered immune serum globulin against type III group B streptococcal colonization and systemic disease in an infant rat model.

We established an experimental animal model of the gastrointestinal colonization and systemic disease following oral challenge of type III group B streptococcal strain in 3-day-old newborn rats. Two type III group B streptococcal strains isolated from the cerebrospinal fluid of septic newborn infants produced colonization in 57-87% of the challenged animals and 13-31% of these colonized animals developed systemic disease. Using this new animal model, we evaluated the effect of orally administered human immune serum globulin on the colonization and systemic disease. This antiserum contained 21 micrograms/ml of type III group B streptococcal antibody of human IgG class. Animals fed with immune serum globulin developed significantly lower rates of colonization and systemic disease than those of control (albumin or saline) (23 versus 71%, p less than 0.001 for colonization; 7 versus 31%, p less than 0.05 for systemic disease). However, rates of the development of systemic disease among the colonized animals were not significantly different between the two groups (33 versus 43%, p greater than 0.1). These findings suggest that orally administered immune serum globulin is beneficial in the prevention of colonization and systemic disease in this rat model and that this protective effect of oral immune serum globulin occurs primarily at the mucosal level.

Administration, Oral↗
PubMed1986

Fetal and maternal corticosterone and corticosteroid binding globulin in the diabetic rat gestation.

Delayed fetal lung development is a feature of the diabetic pregnancy. Since fetal glucocorticoids are important in the regulation of lung maturation, we measured corticosterone and corticosteroid-binding globulin binding capacity in streptozotocin-diabetic pregnant rats and their fetuses. Previous studies have demonstrated delayed fetal lung maturation in this animal model. In control fetuses, total corticosterone concentration increased through day 20 of gestation, then declined until day 22 (term). The unbound steroid, which accounted for 5-10% of the total, increased approximately 3-fold from day 18 to term. Corticosteroid-binding globulin binding capacity peaked on day 19 after which it decreased. Maternal total and unbound corticosterone levels and corticosteroid-binding globulin binding capacity remained relatively constant throughout the final week of normal gestation. When compared to controls, fetuses from diabetic pregnancies had significantly lower total corticosterone from day 19 through 22. Corticosteroid-binding globulin binding capacity was also significantly decreased in these fetuses for the last 4 days of gestation. Similar differences were noted in maternal samples. However, no significant differences in unbound, biologically active, corticosterone were seen when diabetic and control groups were compared. Thus, delayed fetal lung maturation observed in fetuses of streptozotocin-diabetic rats is associated with a decrease in total circulating corticosteroid levels late in gestation. However, since unbound corticosteroid levels were similar in fetuses of control and diabetic animals, it is likely that other mechanisms may be responsible for the observed delay in lung development in fetuses of diabetic pregnancies.

Animals↗
PubMed1992

Re-expression of thyroxine-binding globulin in post-weaning rats during protein or energy malnutrition.

Thyroxine-binding globulin, the highest affinity thyroid hormone binder of rat serum, was studied during 28 days of dietary protein restriction (6% protein vs 18% protein in isocaloric control diet) or energy restriction (60% intake of control diet). Studies were performed on male rats aged four weeks at the beginning of experiments: the animals had reached the ontogenic stage when the thyroxine-binding globulin had declined, after its high postnatal surge, to undetectable levels. Short-term administration (seven days) of one or the other restricted diet similarly induced resynthesis of the protein. Its serum concentrations reached 26-46% of those measured in eight-day pups (peak of the neonatal surge) and its liver mRNAs showed corresponding enhanced signals. Serum T4 binding activities were increased, although concomitantly transthyretin, second specific T4 carrier of the rat serum, decreased markedly (65-75% of controls) in response to the dietary restrictions. Longer-term diet administration (14 or 28 days) resulted in the further increase of the thyroxine-binding globulin in the protein-restricted rats, in contrast to its decline and eventual disappearance in the energy-restricted animals. Protein restriction was associated with increased total and free T3 serum concentrations, in contrast to energy restriction which little affected these parameters. These studies reveal rat thyroxine-binding globulin as a positive (increasing), highly sensitive reactant of malnutrition, able to discriminate between energy deficiency and composition dysequilibrium of diets. They suggest that up-regulation of its synthesis in the two dietary models involves differential mechanisms.

Animals↗
PubMed2002

Recombinant human interleukin-1alpha increases serum albumin, Gc-globulin, and alpha1-antitrypsin levels in burned mice.

The response to thermal injury is a complex physiologic process requiring communication between sites of injury and distant target organs. The liver, one of these target organs, synthesizes a family of secretory proteins, the acute phase proteins, that carries out specific immunoprotective functions. In this study we investigated the effects of daily recombinant human interleukin-1alpha (rhIL-1alpha) administration on the serum levels of negatively regulated, i.e., albumin and Gc-globulin and positively regulated, i.e., alpha1-antitrypsin, acute phase proteins in a murine model of thermal injury. Adult CF-1 female mice underwent a 6.5-seconds, 20% total burn surface area, full thickness steam injury, and received either intraperitoneal rhIL-1alpha (20 microg x kg(-1) x day(-1)) or diluent for 10 days. Seven and 14 days after injury, mice were sacrificed, and serum albumin, Gc-globulin and alpha1-antitrypsin levels were measured by crossed immunoelectrophoresis technique. Thermal injury significantly lowered serum albumin levels, tended to decrease Gc-globulin levels, and increased serum alpha1-antitrypsin levels. Daily rhIL-1alpha administration after burn injury prevented hypoalbuminemia, and increased serum levels of Gc-globulin and alpha1-antitrypsin. IL-1 therapy might be helpful to maintain the homeostasis and immunity of the host after thermal injury.

Animals↗
PubMedDate not supplied

Neutralizing antibodies to rabies following injection of rabies immune globulin into gluteal fat or deltoid muscle.

BACKGROUND: This experiment was carried out to determine whether there is any difference in circulating rabies antibody when rabies immune globulin is administered into fat or muscle tissue. METHODS: Blood samples were taken at 24 and 48 hours after administering 40 IU/kg body weight of purified equine rabies immune globulin (ERIG) into deltoid muscle, or fatty gluteal tissue of grossly obese subjects. RESULTS: Both groups revealed barely detectable antibody levels. CONCLUSIONS: No conclusion was possible concerning the absorption kinetics of immune globulin from fat or muscle. However, it was evident that circulating antibody levels, using the recommended 40 IU/kg dose of ERIG, were extremely low and probably less than the required protective level at the possible bite site. This study supports current recommendations for local infiltration of virus inoculation sites with human or equine rabies immune globulin.

Animals↗
PubMed2002

Antithymocyte globulin for treatment of the bone marrow failure associated with myelodysplastic syndromes.

BACKGROUND: Almost half of the deaths that result from myelodysplastic syndromes are due to cytopenia associated with bone marrow failure. Treatment is mostly supportive care. OBJECTIVE: To determine whether treatment with antithymocyte globulin improves cytopenia and reverses dependence on red blood cell transfusions in patients with myelodysplastic syndromes. DESIGN: Single-treatment, prospective study. SETTING: Tertiary referral center. PATIENTS: 61 patients with myelodysplastic syndromes. INTERVENTION: Antithymocyte globulin, 40 mg/kg of body weight, given daily for 4 days. MEASUREMENTS: Evaluation of bone marrow, blood counts, transfusions, progression, and survival for a median of 30 months (range, 1 to 88 months). RESULTS: Within 8 months of treatment, 21 of 61 patients (34%) no longer required red blood cell transfusions. This independence from transfusions was maintained in 17 responders (81%) for a median of 36 months (range, 3 to 72 months). Ten of 21 patients (47.5%) with severe thrombocytopenia had sustained platelet count increases, and 6 of 11 patients (55%) with severe neutropenia had sustained neutrophil counts of greater than 1 x 10(9) cells/L. Characteristics favorable for response were younger patient age (P = 0.005) and lower platelet counts (P = 0.038). One of the 21 responders (5%) and 22 of the 40 nonresponders (55%) died before the end of the study (P = 0.008). One of the 21 responders (5%) and 13 of the 40 nonresponders (33%) had disease progression (P = 0.086). CONCLUSIONS: Although this study was a nonrandomized, single-treatment study, 34% of patients treated with antithymocyte globulin became transfusion independent. Response was associated with a statistically significant longer survival and an almost significant decreased time to disease progression. Treatment with antithymocyte globulin did not seem to be detrimental because historical overall median survival times were similar to those of nonresponders.

Adult↗
PubMed1980

Epstein-Barr virus infection in renal transplant recipients. Effects of antithymocyte globulin and interferon.

We studied Epstein-Barr (EB) virus excretion and antibody in 41 renal transplant recipients enrolled in a placebo-controlled trial of human leukocyte interferon. Half the patients were also treated with antithymocyte globulin. Epstein-Barr virus excretion occurred more often in recipients of cadaver kidneys (P = 0.03) and those receiving antithymocyte globulin (P = 0.04) and less often in patients given interferon (P = 0.08). Antibody to viral capsid antigen increased fourfold or more in 12 of 22 patients treated with antithymocyte globulin and in none of the non-antithymocyte globulin-treated group (P = 0.0002). Antibody to the restricted component of early antigen rose fourfold or more in eight patients and appeared related to the occurrence of syndromes similar to those attributed to cytomegalovirus in transplant recipients. We conclude that increasing immunosuppression augments the rate of EB virus reactivation and that EB virus may be an important pathogen in heretofore ill-defined syndromes.

Antibodies, Viral↗
PubMed1983

Prevention of cytomegalovirus infection by cytomegalovirus immune globulin after marrow transplantation.

In an effort to prevent cytomegalovirus infection among seronegative patients having marrow transplants, a globulin with high antibody levels against cytomegalovirus was given before and for 11 weeks after transplantation in a randomized trial. Among 36 patients who received no prophylactic granulocyte transfusions, globulin recipients had significantly fewer infections than controls (2 of 17 versus 8 of 19, p = 0.05 by Fisher's exact test and p = 0.03 by Mantel-Cox test). Conversely, infection rates were high and unchanged by globulin use among patients who received granulocytes from seropositive donors (7 of 8 recipients versus 6 of 7 controls). The lack of effect of the globulin among patients receiving transfusions of granulocytes from seropositive donors may suggest that the dose of antibody was insufficient or that antibody is ineffective against virus transmitted in granulocytes. We conclude that cytomegalovirus infection can be prevented by immunoprophylaxis in seronegative patients having marrow transplants who are not given granulocyte transfusions.

Adolescent↗
PubMed2000

[Intravenously administered gamma-globulins in reactive hemaphagocytic syndrome. Multicenter study to assess their importance, by the immunoglobulins group of experts of CEDIT of the AP-HP].

Reactive hemophagocytic syndrome is characterized by systemic proliferation and activation of benign hemophagocytic cells of the monocyte-macrophage lineage. Treatment should be directed to the etiology, but successful treatment with high-dose gamma-globulin has been reported, especially in viral-associated hemophagocytic syndrome. We report 17 patients, of which 9 had infection-associated hemophagocytic syndrome, all treated with high-dose gamma-globulin. High-dose gamma-globulins appear to be more effective in infection-associated hemophagocytic syndrome, with a mean dose of 1.6gm/kg for one or two cycles. A multicentric randomized study is required to evaluate high-dose gamma-globulin in the treatment of reactive hemophagocytic syndrome.

Adolescent↗
PubMedDate not supplied

Gamma globulin inhibition of fibrin clot formation.

Myeloma gamma globulins have been reported to interfere with fibrinogen-fibrin conversion. A patient with multiple myeloma is described with a gamma globulin IgG1lambda concentration of 11 g per dl, prolonged thrombin time and poor clot retraction. Purified gamma globulin from the patient's serum and from normal serum caused prolongation of the thrombin time and reptilase clotting time assays in both normal plasma and in solutions of bovine fibrinogen. In addition, fibrin clots formed during the thrombin time assays were found to be ultrastructurally abnormal. This data suggests that the interaction of gamma globulin in the polymerization of fibrin may, in at least some cases, be due to nonspecific protein interaction.

Aged↗
PubMed1992

[Gadolinium-MRI findings of two adrenoleukodystrophy cases treated with gamma-globulin].

Two cases of adrenoleukodystrophy were reported. We treated them with intravenous gamma-globulin infusion. MRI with gadolinium enhancement was performed before and after the therapy to evaluate the effect of gamma-globulin. Case 1 was a 19-year-old boy, who noticed left hemianopsia when he was 18 years old. Case 2 was a 36-year-old man, who developed ataxic gait and character change when he was 33 years old. Very long chain fatty acids in plasma and RBC membrane were elevated in both cases. On T2-weighted image of MRI, high signal lesions were seen in the white matter of occipital lobe in case 1, cerebellum, internal capsule, and around the corpus callosum in case 2. On T1-weighted image, the rim of every lesion was enhanced by gadolinium infusion. After the gamma-globulin therapy, gadolinium enhancement of the rim remarkably reduced in case 1. No reduction was observed in case 2. MRI findings of case 1 indicate the possibility that gamma-globulin may suppress the inflammation of the adrenoleukodystrophy.

Adrenoleukodystrophy↗
PubMed1986

Activity of intravenous immune globulins against Klebsiella.

Seven commercial intravenous immune globulin (IVIG) preparations and an experimental hyperimmune globulin (Klebsiella immune-IVIG) were analyzed for antibody levels to Klebsiella capsular polysaccharides, opsonic activity, and protective capacity against Klebsiella. With one exception, all IVIGs reacted immunologically with the various capsular antigens, although titers between the preparations varied considerably. Klebsiella immune-IVIG possessed substantially higher titers (32-fold to 128-fold) than the commercial preparations. Only the hyperimmune globulin was capable of promoting the phagocytosis and killing of six Klebsiella test strains. When prophylactically administered, a commercial IVIG afforded significant protection (P less than 0.01) against fatal experimental Klebsiella sepsis only at a dose of 500 mg/kg. Klebsiella immune-IVIG provided a similar level of protection at a dose of 5 mg/kg. Whereas the commercial IVIG was ineffective when used therapeutically, the hyperimmune globulin was highly protective. Combined antibiotic-immunoglobulin therapy was most effective at reducing mortality.

Animals↗
PubMed1984

Antibody to the hepatitis B virus-associated delta-agent in immune serum globulins.

Fifty lots of immune serum globulin prepared by four United States manufacturers between 1944 and 1977 were tested for the presence and titer of antibody to the hepatitis B virus-associated delta-agent. Anti-delta was detected in 28 of the 50 lots (56%) of immune serum globulin at titers ranging from 1:10 to 1:400. Anti-delta was present in 75% (6 of 8) of lots produced between 1962 and 1965, in 77% (17 of 21) produced between 1967 and 1970, in 45% (5 of 11) produced between 1971 and 1972 and in none (0 of 9) produced since 1973. A single lot of globulin prepared from plasma that was collected in 1944 from United States Army soldiers also contained detectable anti-delta. These data indicate that delta-infection has been occurring among hepatitis B surface antigen (HBsAg) carriers in the United States since the 1940s. The decrease in prevalence of anti-delta in immune serum globulin lots coincided with the start of routine HBsAg screening of blood and plasma. The elimination of HBsAg-positive units from plasma pools has reduced levels of HBsAg and anti-delta and should have decreased the risk of transmission of both type B hepatitis and delta-hepatitis by plasma products.

Blood Donors↗
PubMed1981

TSH binding by globulins from patients with Graves' disease.

Forty one globulin preparations from patients with Graves' disease were tested for their specific TSH binding properties and compared with their TSI activity in: 1. human thyroid membrane competition assay; 2. adenylate cyclase stimulation; 3. colloid droplet formation. The preparations tested were divided into two well distinguishable groups according to their specific TSH binding: 25 samples out of 41 contained thyrotropin binding sites similar to the globulins from normal healthy persons (A-type binding, Kd: 1.2 pmol-1 g and Bmax: 0.8 pmol g-1) and 17 samples bound TSH with lower affinity but higher capacity (B-type binding mean Kd: 15.3 pmol-1 g, mean Bmax: 2.7 pmol g-1). both A- and B-type TSH binding globulins containing samples were active in binding to human thyroid membrane, in droplet formation and adenylate cyclase stimulation. However, there was a linear correlation between the potential THS binding capacity of a B-type sample and the percentage adenylate cyclase stimulation and droplet formation, whereas the reverse correlation was found with their thyroid membrane binding activity. It was concluded that B-type TSH binding globulins may play a role in the formation and/or modification of the pathogenetic TSH action.

Adenylyl Cyclases↗
PubMed1995

Clinical impact of replacing Minnesota antilymphocyte globulin with ATGAM.

In August 1992, we replaced Minnesota antilymphocyte globulin (MALG) with lymphocyte immune globulin, antithymocyte globulin (equine) (ATGAM) in our immunosuppression protocols. The clinical impression of increased graft rejection prompted our assessment of the effect of this change on patient and graft outcome. The initial study group consisted of 426 renal transplant recipients transplanted between October 1, 1987, and September 21, 1993. After exclusions, 388 transplant events, with a minimum 8-month follow-up, made up the final study cohort: 323 patients received MALG and 65 received ATGAM. Immunosuppression included intravenous methylprednisolone, oral prednisone, oral AZA, CsA in some cases, and intravenous MALG or ATGAM, 15 mg/kg/day, for 7 to 14 days. Acute rejection was treated with high dose intravenous steroids and steroid-resistant episodes were treated additionally with either MALG or OKT3. Statistical comparisons were stratified for multiple patient characteristics and treatment variations. There was a greater incidence of rejection in general, and a higher incidence of steroid-resistant episodes requiring subsequent antilymphocyte globulin therapy (P = 0.0073) in patients receiving ATGAM versus MALG. No difference was seen in the incidence of CMV infection or blood-borne sepsis. Lymphoma occurred in 3 MALG and 2 ATGAM recipients. MALG recipients were significantly less likely to experience rejection within the first 60 days after transplant (P = 0.0127 using unstratified data; P < 0.0001 when data were stratified for patient characteristics). The relative risk of acute rejection for posttransplant days 5, 7, 10, and 14 was consistently higher for ATGAM-treated patients. We conclude that MALG and ATGAM are not equivalent drugs, and that MALG is a more effective immunosuppressant, and is just as safe as ATGAM in our protocol environment.

Adult↗
PubMed1994

Testing for antibody to hepatitis A to decrease the cost of hepatitis A prophylaxis with immune globulin or hepatitis A vaccines.

BACKGROUND: The introduction of new vaccines to prevent hepatitis A infection raises the question of the cost of these vaccines relative to immune globulin when short-term protection against hepatitis A is required. Since the prevalence of hepatitis A antibodies (anti-HAV) in the US population increases rapidly with age, testing for anti-HAV may decrease the cost of vaccination programs. METHODS: A cost-analysis model was developed that incorporates the cost of immune globulin or hepatitis A vaccine, the number of doses of vaccine, the cost of testing for anti-HAV in either commercial or public-sector laboratories, and the prevalence of anti-HAV in the general population by age. RESULTS: In comparison with hepatitis A vaccines, with expected costs between $10 and $25 per dose, use of immune globulin for postexposure prophylaxis or preexposure short-term (< or = 6 months) prophylaxis is much less expensive for all age groups. Testing for anti-HAV does not significantly diminish the cost of immune globulin regimens. In contrast, if anti-HAV testing is performed in a public-sector laboratory at $10 per test, and hepatitis A vaccine costs $10 per dose, testing reduces vaccination costs in those 40 years of age or older for a two-dose vaccine regimen and in those 30 years of age or older for a three-dose regimen. At the other end of the spectrum, if vaccine costs $35 per dose, commercial testing for anti-HAV at $25 per person reduces the costs in those 30 years of age or older if either a two- or three-dose regimen is elected. However, vaccine savings are realized in those 10 years and older if public-sector testing is performed and three doses of vaccine at $35 per dose are utilized. In an intermediate scenario of public-sector testing and vaccines costing $25 per dose, the cost would also be reduced in those 30 years old or older. CONCLUSIONS: Testing for anti-HAV in frequent travelers, international government, business, and volunteer workers, military personnel, etc, may be an effective means of decreasing costs of hepatitis A prevention.

Adolescent↗
PubMed1976

Rh-immune globulin after amniocentesis for genetic diagnosis.

The procedure of amniocentesis during the second trimester of pregnancy for genetic diagnosis creates the potential for Rh sensitization secondary to fetomaternal bleeding. We have advised administration of Rh-immune globulin after such amniocentesis whenever the pregnancy may be Rh-incompatible. Of 56 patients who received Rh-immune globulin there has been only 1 case of Rh sensitization, which occurred in a patient who underwent a second amniocentesis 2 weeks after the first attempt without receiving a second dose of Rh-immune globulin. There have been no developmental problems detected to date which could be ascribed to Rh-immune globulin.

Adult↗
PubMed1996

Mechanisms of immunosuppression induced by antithymocyte globulins and OKT3.

OKT3 monoclonal antibody and polyclonal antithymocyte or antilymphocyte globulins are among the most potent immunosuppressive agents which have been used in organ transplantation for many years. Both induce a rapid and profound lymphocytopenia classically attributed to several mechanisms, such as complement-dependent cytolysis, cell-mediated antibody-dependent cytolysis, as well as opsonization and subsequent phagocytosis by macrophages. However, the relative contribution of these three Fc-dependent mechanisms in vivo is difficult to ascertain and may be less important than previously thought. In addition OKT3 induces T-cell receptor modulation in vivo and modulated T cells no longer interact with antigen-presenting cells. Modulation of the T-cell receptor complex has not been documented for antithymocyte and antilymphocyte globulins as yet. The monoclonal antibody OKT3, which is directed against the epsilon chain of the CD3 molecule on the T-cell surface, but also antithymocyte and antilymphocyte globulins, which contain antibodies directed against CD3 and other functional molecules on the surface of T and B cells, generate various transduction signals to the target cells which can affect their functions in different ways. Recent in vitro studies suggest that these antibodies interfere with activation signals. Indeed, antithymocyte and antilymphocyte globulins, at low concentrations, inhibit T-cell activation induced by alloantigens, whereas they induce polyclonal T-cell activation at higher concentrations. Mitogenic antibodies can trigger an activation-induced cell death phenomenon as documented with anti-CD3 antibodies. Anti-CD3 antibodies can also induce a state of specific unresponsiveness (clonal anergy) which may contribute to their long-lasting immunosuppressive effect. One may hypothesize from in vitro data that in spite of their nonspecific immunosuppressive effects which may result in severe iatrogenic immunodeficiency, antilymphocyte antibodies may also act on stimulated alloreactive T-cell clones and therefore contribute to donor-specific graft adaptation.

Antibodies↗