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PubMed1967

Studies of human anti-gamma-globulin factors reacting with pepsin-digested gamma-globulins.

Many sera from normal individuals as well as patients with various disease states contain agglutinating antibodies which show specificity for antigenic determinants of gamma-globulin revealed by pepsin digestion at pH 4.1. Sera containing such agglutinating activity as well as sera negative for these agglutinators contain low molecular weight (3S-5S) components of slow gamma-mobility which inhibit these agglutination reactions. Low molecular weight inhibitors show both auto- and isospecificity, and are antigenically related to the 5S pepsin fragment of gamma-globulin. A common situation is thereby revealed in which human anti-gamma-globulin antibodies showing specificity for pepsin-digested gamma-globulins are present in serum along with low molecular weight gamma-globulin components capable of inhibition. Autoreactivity or autospecificity of such anti-gamma-globulin factors is a phenomenon shared by both normal human sera and sera from patients with various disease states.

Adult↗
PubMedDate not supplied

Hepatitis B immune serum globulin and standard gamma globulin in prevention of hepatitis B infection among hospital staff: a preliminary report.

In May 1973 a controlled double-blind clinical trail with prophylactic injects of hepatitis B immune serum globulin (antibody titer by passive hemagglutination 1:355,000) and standard gamma globulin (1:100) was started in Sahlgren's Hospital, Göteborg, Sweden. The annual attack rate of clinical hepatitis B in the three departments studied had been 5 to 8 per cent during recent years. A total of 118 members of the hospital staff were prophylactically treated while 125 staff members were unwilling to participate and received no prophylactic treatment. During the first 20 months of study nine cases of clinical hepatitis B with jaundice occurred within the untreated group (7.2 per cent) while three cases (2.5 per cent) were observed in prophylactically treated individuals. After decoding it was found that 60 individuals had received specific hepatitis B immune serum globulin while 58 had received standard gamma globulin. Two of the three clinical cases of hepatitis B occurred within the standard gamma globulin group. Both groups included two individuals with transient antigenemia only and the standard gamma globulin group also included four individuals with antibody seroconversion.

Antibody Formation↗
PubMed1975

[Gamma globulin therapy of acute viral hepatitis. Studies on the therapeutic effect of gamma globulin on the course and late prognosis of manifested acute viral hepatitis in man].

In a prospective study 148 consecutive patients with biopsyproved acute viral hepatitis were observed serially and followed for 5 years. They were divided into three groups on the basis of being treated with high or low doses of gamma globulin and compared with a control group, not treated. As the efficacy of gamma globulin for the prophylaxis or modification of infectious hepatitis has been well documented by many investigators during the past 25 years, we were interested in evaluating the therapeutic effect of gamma globulin on the course of viral hepatitis. The purpose of the study was to determine the comparative efficacy of various doses of gamma globulin in preventing complications and in influencing the severity and the length of time of acute viral hepatitis and in preventing the development of chronic hepatitis and cirrhosis. For controlling the clinical, biochemical and histopathologic course 12 functional parameters were repeatedly measured under stable clinical conditions and 3--12 liver biopsies were performed in an individual patient using the Menghini needle with an intercostal approach. During the 5-year trial an overall of 825 liver biopsis were performed with this 148 patients. We conclude from this study, that in about 80% of patients with acute viral hepatitis recovery is complete, but takes several month's. A protracted course of 4 month's duration until recovery was found in 45 patients (30,4%), persistent hepatitis with recovery after 1--4 years duration occurred in 37 patients (25%), global liver necrosis with hepatic coma in 3 (2,3%), chronic hepatitis in 22 (14,8%), 8 of them as chronic aggressive hepatitis and cirrhosis in 3 (2,3%). The study demonstrated no therapeutic efficacy of gamma globulin in modifying the course or preventing complications of both AuAg+ and AuAg-neg. acute viral hepatitis in man. There was no striking difference in the groups treated with various doses of gamma globulin compared with a control group.

Acute Disease↗
PubMed1987

Selection of an intravenous immune globulin for the immunoprophylaxis of cytomegalovirus infections: an in vitro comparison of currently available and previously effective immune globulins.

In an attempt to select an i.v. immune globulin to be used for the immunoprophylaxis of cytomegalovirus (CMV) infections in recipients of allogeneic bone marrow transplants, we conducted an in vitro comparison of three newly available commercial i.v. immune globulins with two CMV hyperimmune globulin products shown to be efficacious in previous CMV immunoprophylaxis studies. We compared these products for both CMV immunoreactive antibody titer by enzyme-linked immunosorbent assay (ELISA) and for in vitro functional activity by virus neutralization using both standard laboratory and wild clinical isolates of CMV. All five products had high titers of CMV-specific IgG when assayed by ELISA, ranging from 1:1600 to 1:25,600; the two hyperimmune products had the highest titers as expected. However, both hyperimmune products, despite having much higher CMV-IgG titers by ELISA, had CMV neutralizing antibody titers only equivalent to those found in two of the three standard i.v. immune globulin products tested (mean of 1:500-1:1000). One of the three commercial immune globulins tested had a lower mean neutralizing antibody titer in lots assayed compared to the other products (mean of 1:50). There was thus no direct or predictable correlation in any of the products tested between the quantity of CMV-IgG as measured by ELISA and in vitro functional activity as measured by virus neutralization. We also noted marked variation between different lots of the same product in all three commercially available immune globulin products. To insure that both current and future CMV immunoprophylaxis trials are standardized, the quantity as well as the functional activity of CMV-specific antibodies in products used need to be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗
PubMed1983

Post-gamma globulin. II. Radioimmunoassay determination of levels of post-gamma globulin and beta 2-microglobulin.

Post-gamma globulin previously isolated and partially sequenced in this laboratory was used for production of polyclonal and monoclonal (hybridoma) antibodies. A radioimmunoassay method was developed for quantitation of post-gamma globulin with either antibody. The titration curves obtained were treated statistically and found practically indistinguishable. The sensitivity of the method adopted for the quantitation of post-gamma globulin in a variety of biological fluids was 0.13 ng/ml and the upper limit of precision was 2.5 ng/ml. The following results were obtained (mean +/- 1 SD): normal sera, 0.96 +/- 0.20 microgram/ml; pregnancy sera, 1.08 +/- 0.28 micrograms/ml; cord blood 2.08 +/- 0.33 micrograms/ml; hospitalized patient's sera, 1.3 +/- 0.54 micrograms/ml; geriatric subjects' sera 2.26 +/- 1.10 micrograms/ml; cerebrospinal fluid, 5.37 +/- 3.36 micrograms/ml; saliva, 1.22 +/- 0.67 micrograms/ml; synovial fluid, 1.27 +/- 0.41 micrograms/ml and urine, 0.11 +/- 0.125 microgram/ml. To shed light on the catabolism of post-gamma globulin the levels of beta 2-microglobulin were also measured radiometrically. Correlative statistical analysis of all the data have shown that renal handling of post-gamma globulin and beta 2-microglobulin may be very similar but not necessarily identical.

Antibodies↗
PubMed2003

Interaction of serum proteins with CYP isoforms in human liver microsomes: inhibitory effects of human and bovine albumin, alpha-globulins, alpha-1-acid glycoproteins and gamma-globulins on CYP2C19 and CYP2D6.

The effects of serum proteins on the in vitro hydroxylation pathways of mephenytoin (CYP2C19) and debrisoquine (CYP2D6) were studied to enhance the predictability of in vivo drug metabolism from in vitro assays. Both CYP substrates are known to be weakly bound to albumin and the applicability of the free drug hypothesis was further appraised. Since bovine serum albumin (BSA) is used widely in in vitro assays, a comparison between human and bovine proteins was made. Four major serum proteins were studied: albumin, alpha1-acid glycoprotein (AGP), alpha- and gamma-globulins. Human serum albumin (HSA) inhibited both CYP activities about 20% more than BSA. The addition of human alpha-globulins, but not the bovine protein, resulted in marked reduction of 86% and 41% in CYP2C19 and CYP2D6 activities, respectively. This reduction of activity was strikingly greater than the fraction bound (14 and 22%, respectively). The inhibition was of the competitive type and the Ki values of human alpha-globulins on CYP2C19 and CYP2D6 were found to be 0.45% (4.5 mg/ml) and 3.5% (35 mg/ml), respectively. The effect of both human and bovine gamma-globulins on CYP isoforms was negligible. The Ki values of human and bovine AGP for CYP2C19 were 1.84% (420 microM) and 0.93% (210 microM), respectively. For HSA, human alpha-globulins and human and bovine AGP, the strongly decreased CYP activities in vitro cannot be explained by the free drug hypothesis. A direct interaction of these serum proteins with CYP enzymes is postulated. Differential effects of bovine and human serum proteins and CYP specific inhibition were observed.

Alpha-Globulins↗
PubMed1964

ON THE RELATIONSHIPS BETWEEN THE GAMMA-GLOBULIN GENES OF THE GM SYSTEM. A STUDY OF GM GENE PRODUCTS IN SERA, MYELOMA GLOBULINS, AND SPECIFIC ANTIBODIES WITH SPECIAL REFERENCE TO THE GENE GM.

Gm types of sera from Caucasians and Negroes, of myeloma globulins, and of specific antibodies were investigated. In particular the relationship between the recently identified gene Gm(f) and other Gm genes was analyzed. 1. Caucasians were, with rare exceptions, either Gm(b+f+) or Gm(b-f-). 2. In Negroes, on the other band, type Gm(b+f-) was found to be common. 3. No myeloma globulins appeared to contain the product of more than 1 of the 3 genes Gm(a), Gm(b), and Gm(f), even though the large majority of normal individuals, as well as myeloma patients, possess 2 or all 3 of these genes. 4. The types Gm(a+b-f-) and Gm(a-b-f+) represented the 2 major groups among the gamma(2)-myeloma globulins; each comprised roughly 40 per cent. The types Gm(a- b+f-) and Gm(a-b-f-) are minor groups. 5. All Gm(x+) myeloma globulins were also Gm(a+). Approximately half of the Gm(a+) myeloma globulins were Gm(x+). 6. In the majority, but not in all, of Gm(a+) sera the anti-Rh antibodies were clearly Gm(a+). Similarly, the anti-Rh antibodies of Gm(f+) sera were most often, but not always, also Gm(f+). In contrast, only a minor proportion of Gm(b+) anti-Rh sera sensitized red cells to anti-Gm(b).

Antibodies↗
PubMed1990

Protein binding of active ingredients and comparison of serum ethinyl estradiol, sex hormone-binding globulin, corticosteroid-binding globulin, and cortisol levels in women using a combination of gestodene/ethinyl estradiol (Femovan) or a combination of desogestrel/ethinyl estradiol (Marvelon) and single-dose ethinyl estradiol bioequivalence from both oral contraceptives.

Results from two clinical pharmacokinetic studies are given. The first study was an observational study in oral contraceptive users who took either a combination of gestodene and ethinyl estradiol (pill A, Femovan) or desogestrel and ethinyl estradiol (pill B, Marvelon). A total of 69 women (39 receiving pill A and 30 receiving pill B) were evaluated to determine serum ethinyl estradiol, sex hormone-binding globulin, corticosteroid-binding globulin, and cortisol levels. Samples were obtained on 1 day during the tenth to twenty-first days of pill intake. All women received the respective oral contraceptive for at least 3 months. The test power was such that an 80% difference of 1 standard deviation of each target variable would have been detected (alpha = 0.05; beta = 0.1). No statistically significant differences were found in sex hormone-binding globulin, corticosteroid-binding globulin, or cortisol serum levels between both groups. Time and height of maximum ethinyl estradiol levels were identical as was the area under the curves. Ex vivo protein-binding analysis of the progestins revealed a free portion of 0.6% for gestodene and 2.5% for 3-ketodesogestrel as the active metabolite of desogestrel. Sex hormone-binding globulin-bound portions were much higher for gestodene (75.3% +/- 9.1%) than for 3-ketodesogestrel (31.6% +/- 12%). The remaining fractions were bound to albumin. In a second study, ethinyl estradiol-bioequivalence from pills A and B was investigated in 18 women in a controlled, single-dose, randomized, crossover design. The area under the ethinyl estradiol serum levels were identical up to 4 hours after pill intake between both treatments. According to the relatively low variation in data in this group of women, a 10% difference in ethinyl estradiol-availability could have been detected. Both studies indicate that the pharmacokinetics of ethinyl estradiol were independent of the concomitantly administered progestin, that is, desogestel and gestodene.

Adult↗
PubMed1982

Post-gamma globulin : tissue distribution and physicochemical characteristics of dog post-gamma globulin.

An animal model (dog) was established to investigate physicochemical and biological parameters of a basic low molecular mass protein---post-gamma globulin (p-gamma). In this study the distribution of this 11 000 daltons (11 kdaltons) protein was determined in extracts of the number of tissues. Extracts of parotid gland, brain and kidney contained high amounts of "free" p-gamma globulin (11 kdaltons). Two higher molecular mass forms (34k and 27 kdaltons) of this protein were demonstrated in the kidney and brain extracts. Extracts of ovary and uterus were devoid of the 27 k moiety and kidney extracts lacked the "free" p-gamma globulin (11k). These studies indicate that p-gamma globulin may be a part of a much larger molecule or that p-gamma globulin may be associated with another yet unknown protein. These findings may be important for clinical and pathological studies in human kidney and central nervous system (CNS) diseases.

Animals↗
PubMed1985

Neutralizing antibody to hepatitis A virus in immune serum globulin and in the sera of human recipients of immune serum globulin.

We determined the titer of neutralizing antibody to hepatitis A virus in five lots of immune serum globulin and in the sera of human recipients of immune globulin using a new and sensitive procedure, the radioimmunofocus inhibition assay. The neutralizing antibody titer of four immune globulin lots ranged from 1:170,000 to 1:406,000, and was approximately 100-fold the antibody titer determined by radioimmunoassay. The neutralizing antibody titer of a Bureau of Biologics reference immunoglobulin was 1:794,000. Sera collected from 18 healthy men who had undergone prophylaxis with immune globulin (0.02 ml/kg body wt) were negative when tested by radioimmunoassay. However, 2 of 18 sera collected before administration of immune globulin and sera from all 18 men collected 3 and 55 days later contained detectable neutralizing antibody. The measurement of neutralizing antibody should prove useful for standardizing passive immunoprophylaxis against hepatitis A as well as for evaluating the potential efficacy of new hepatitis A virus vaccines.

Antibodies, Viral↗
PubMed2000

Use of a single method in the extraction of the seed storage globulins from several legume species. Application to analyse structural comparisons within the major classes of globulins.

In this study, a single, improved methodology was used to extract, fractionate and purify the 11S (legumin-type or related to the alpha-conglutin from Lupinus albus L.), 7S (vicilin-type or related to the beta-conglutin from L. albus) and 2S (related to the gamma-conglutin from L. albus) families of proteins from eight legume species: L. albus, Glycine max (L.) Merr., Pisum sativum L., Vicia faba L., Cicer arietinum L., Phaseolus vulgaris L., Lens culinaris Med. and Arachis hypogaea L. The sedimentation coefficients obtained varied from 1.9 to 8.1 for the gamma-conglutin-related proteins, from 5.1 to 10.5 for the beta-conglutin-related proteins and from 12.0 to 14.9 for the alpha-conglutin-related globulins. The gamma-conglutin-related proteins is the most heterogeneous group. Antibodies produced against each type of gamma-conglutin polypeptide chain recognize the other polypeptide chain as well as other polypeptides in the corresponding globulins from all species examined. The 7S globulins are typically composed of a large number of polypeptides, covering a wide range of molecular masses (10 to 70 kD). The presence of disulphide bonds is apparently absent and the occurrence of glycopolypeptides is not widespread. Finally, the 11S globulins are characteristically formed by a limited number of polypeptides that may be divided into a lighter group (20-25 kD) and a heavier group (35-50 kD). The presence of disulphide bonds is apparently widespread but the occurrence of glycopolypeptides seems to be relatively rare. Both the 7S family and the 11S globulins studied by immunoblotting exhibit a low level of structural similarity.

Chemical Fractionation↗
PubMed1970

Synthesis, assembly, and secretion of gamma globulin by mouse myeloma cells. I. Adaptation of the Merwin plasma cell tumor-11 to culture, cloning, and characterization of gamma globulin subunits.

MPC-11 myeloma tumor cells were adapted to growth in continuous culture. The cultured cells resembled the parent tumor in that they produced the fully assembled gamma globulin molecules as well as six unassembled molecules. Although cultured and tumor cells synthesized excess light chains, the molar ratio of light (L) to heavy (H) chains was approximately 1.7:1 in the culture, and 3.5:1 in the tumor. The cultured cells also produced fewer half molecules and free light chains than the parent tumor. Peptide column analysis did not reveal differences in the primary structure of the H chains derived from the parent tumor and the culture. The L chains may have differed by a minor peptide. As much as 20% of the newly labeled cytoplasmic proteins and almost 100% of the proteins secreted by the cultured myeloma cells could be precipitated by specific antiserum. The immune precipitates contained seven different gamma globulin molecules, six of which were characterized according to their molecular size and H and L chain content as fully assembled molecules (H(2)L(2)), heavy chain dimers (H(2)), half molecules (HL), H, light chain dimers (L(2)), and L chains. All gamma globulin subunits as well as the complete H(2)L(2) molecule were produced and secreted by splenic clones of the parent MPC-11 tumor, and agar clones of the cultured cells. This indicates that the various gamma globulin subunits were produced by the same cell and did not reflect cellular heterogeneity with respect to gamma globulin synthesis.

Animals↗
PubMed1984

Monoclonal antibodies to alpha 2u-globulin and immunocytofluorometric analysis of alpha 2u-globulin-synthesizing hepatocytes during androgenic induction and aging.

Stable hybridomas generated by fusion of spleen cells from hyperimmunized mice and mouse myeloma cells were cloned to prepare monoclonal antibodies to alpha 2u-globulin, an androgen-dependent urinary protein of hepatic origin. One of these monoclonal antibodies was used as a probe for immunocytofluorometric analysis of alpha 2u-globulin producing hepatocytes during androgenic induction and aging through fluorescence-activated cell sorting (FACS). FACS patterns of hepatocytes from mature male rats that produce high levels of alpha 2u-globulin showed tow distinct peaks, arbitrarily designated as peak I (weakly fluorescent) and peak II (brightly fluorescent). In the mature male rat, peak II represented about 40% of the total hepatocytes, and the fluorescence intensity of this subpopulation decreased in direct correspondence with the gradual decline of alpha 2u-globulin synthesis during aging. Similarly the androgenic induction of this protein in ovariectomized female rats was associated with an increase in the fluorescence intensity of the hepatocyte subpopulation under peak II rather than an increase in the relative number of these cells. From these results we conclude that the androgen-dependent synthesis of alpha 2u-globulin and its alteration during aging are confined to a specific subpopulation of hepatocytes within the liver.

Aging↗
PubMed1978

Correlation of free thyroxine index and thyroxine: thyroxine-binding globulin ratio with the free thyroxine concentration as measured by the thyroxine and thyroxine-binding globulin radioimmunoassays.

The concentration of thyroxine-binding globulin in the serum can now be measured by a simple and specific radioimmunoassay. Triiodothyronine uptake and measurement of total thyroxine have been combined to yield a free thyroxine index which has been found to correlate with the clinical state of the patients. An estimate of the free thyroxine concentration, as measured by the thyroxine and thyroxine-binding globulin radioimmunoassays, provided a good correlation with the free thyroxine index and the thyroxine: thyroxine-binding globulin ratio. However, the thyroxine: thyroxine-binding globulin ratio is inaccurate when thyroxine-binding globulin concentrations are high or low.

Adult↗
PubMed1993

Prophylactic administration of respiratory syncytial virus immune globulin to high-risk infants and young children. The Respiratory Syncytial Virus Immune Globulin Study Group.

BACKGROUND: Infants with cardiac disease or prematurity are at risk for severe illness caused by respiratory syncytial virus. Immune globulin with a high titer of antibodies against respiratory syncytial virus may offer infants and young children at risk protection from this serious, common respiratory illness. METHODS: We studied 249 infants and young children (mean age, eight months) who had bronchopulmonary dysplasia due to prematurity (n = 102), congenital heart disease (n = 87), or prematurity alone (n = 60). Respiratory syncytial virus immune globulin was given monthly to some of these children in either a high dose (750 mg per kilogram of body weight; n = 81) or low dose (150 mg per kilogram; n = 79); 89 controls received no immune globulin. Group assignments were random. Assessments of respiratory illness and management were conducted without knowledge of the children's group assignments. RESULTS: There were 64 episodes of respiratory syncytial virus infection: 19 in the high-dose group, 16 in the low-dose group, and 29 in the control group. In the high-dose group there were fewer lower respiratory tract infections (7, vs. 20 in the control group; P = 0.01), fewer hospitalizations (6, vs. 18 in the control group; P = 0.02), fewer hospital days (43, vs. 128 in the control group; P = 0.02), fewer days in the intensive care unit (P = 0.05), and less use of ribavirin (P = 0.05). In the low-dose group there was a significant reduction only in the number of days in the intensive care unit (P = 0.03). Adverse events during the 580 infusions were generally mild and included fluid overload (in five children), oxygen desaturation (eight), and fever (six). Six children died: three in the high-dose group, three in the low-dose group, and none in the control group (P = 0.15), but no death was attributed to the use of immune globulin or to illness caused by respiratory syncytial virus. CONCLUSIONS: Administration of high doses of respiratory syncytial virus immune globulin is a safe and effective means of preventing lower respiratory tract infection in infants and young children at high risk for this disease.

Antibodies, Viral↗
PubMed2002

The interaction of human and bovine serum proteins with CYP3A in human liver microsomes: inhibition of testosterone 6beta-hydroxylation by albumin, alpha-globulins, alpha(1)-acid glycoprotein and gamma-globulins.

The effects of human and bovine serum proteins on CYP3A activity, using testosterone as the probe substrate, were investigated in human liver microsomes. Serum albumin, alpha-globulins, and alpha(1)-acid glycoprotein (alpha(1)-AGP) of both species significantly inhibited testosterone 6beta-hydroxylation. When the inhibitory effects of serum proteins were compared with serum protein binding data, human alpha-globulins, with a ratio (relative metabolic activity/unbound fraction) of 0.3, showed higher, and bovine alpha(1)-AGP, with the ratio of 1.4, showed lower inhibitory effects than those expected from protein binding of testosterone. The effects of the other serum proteins were close to those expected from protein binding, according to the free drug hypothesis. The K(i) values obtained from the Dixon plots were 0.32% (w/v, 48 microM) for human serum albumin (HSA), 0.48% for human alpha-globulins, and 0.23% (52 microM) for human alpha(1)-AGP. K(i) values of bovine serum albumin, bovine alpha-globulins and bovine alpha(1)-AGP were 3-5 times higher than those of the respective human proteins. The results suggest a direct interaction of some of these serum proteins with the active site of the CYP3A isoform. Since the bovine serum proteins showed weaker inhibitory effects than human serum proteins, the wide use of BSA, which is viewed as interchangeable with HSA, needs to be cautioned.

Alpha-Globulins↗