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PubMed1962

The nature of Bence-Jones proteins. Chemical similarities to polypetide chains of myeloma globulins and normal gamma-globulins.

The chemical relations among Bence-Jones proteins, myeloma proteins, and normal gamma-globulins have been investigated by a variety of means. Starch gel electrophoresis in 8 M urea of reduced alkylated Bence-Jones proteins yielded patterns of bands corresponding to those of the light (L) polypeptide chains of the dissociated myeloma protein from the same patient. One instance in which this correspondence was found was chosen for extensive study. Chromatography on carboxymethylcellulose in 6 M urea was employed to isolate the light (L) polypeptide chains and heavy (H) polypeptide chains of the completely reduced and alkylated myeloma protein. Isolation of similarly treated Bence-Jones protein from the same patient corroborated the correspondence to the L chains of the myeloma protein. Amino acid analyses indicated that the compositions of the Bence-Jones protein and the L chains of the myeloma protein were identical. Moreover, the thermosolubility properties and spectrofluorometric behavior of the isolated L chains and Bence-Jones protein were similar. Ultracentrifugal analyses of the L chains of normal human 7S gamma-globulin showed that their molecular weight in 6 M urea was 20,000. In aqueous solution their molecular weight was 41,000, suggesting that they exist as dimers under these conditions. The L chains of normal human gamma-globulin were found to have reversible thermosolubility properties similar to those of Bence-Jones proteins. The H chains of normal human gamma-globulin did not share these properties. Using spectrofluorometric methods, characteristic molecular transitions were found upon heating Bence-Jones proteins and L chains. These transitions were indicated by an increase in the intensity of fluorescence at well defined temperatures as well as by reversible shifts in the wavelength of maximal emission. The findings suggest that Bence-Jones proteins are composed of L chains of the type found in normal and pathological gamma-globu]ins.

Bence Jones Protein↗

PubMed1966

Alpha globulin injections and decreased gamma globulin production in chickens.

Electrophoretic analysis shows a strong similarity in the blood serums of chickens subjected to egg parabiosis and of chickens repeatedly injected with fraction IV (alpha globulins). In both instances there is an evident rise in the albumin-plus alpha(1) titer and an evident decrease in the gamma globulin levels. These findings suggest that the injection of alpha globulins has the same serum effect on the animal as parabiotically induced blood chimerism, namely, a reduction in circulating gamma globulin (immunoglobulins?).

Alpha-Globulins↗

PubMed1992

Intravenous immune globulin for the prevention of nosocomial infection in low-birth-weight neonates. The Multicenter Group for the Study of Immune Globulin in Neonates.

BACKGROUND: Nosocomial infection is a major risk for premature infants with very low birth weights. One reason for their susceptibility to infection may be antibody deficiency, since there is little transfer of maternal IgG to the fetus before 32 weeks' gestation. METHODS: We conducted a multicenter, double-blind study of neonates weighing 500 to 1750 g at birth. A total of 588 neonates were randomly assigned, with stratification for birth weight, to receive periodic intravenous infusions of either immune globulin (500 mg per kilogram of body weight per day) or a placebo. Mortality, morbidity, and nosocomial infection during the next 56 days were assessed. RESULTS: The infusions were well tolerated; mild, reversible adverse reactions occurred in five infants in each group. There was a significant reduction in the risk of a first nosocomial infection in the recipients of immune globulin as compared with the placebo recipients (relative risk, 0.7; 95 percent confidence interval, 0.5 to 0.9). About 85 percent of the nosocomial infections were bacterial; the majority of these were caused by coagulase-negative staphylococci or Staphylococcus aureus. The neonates who received immune globulin had fewer mean days of hospitalization than the controls (62 vs. 68, P = 0.15); among the infants with infections, the difference in the mean length of the hospital stay was even greater (80 days vs. 101 days, P = 0.02). CONCLUSIONS: For premature infants weighing between 500 and 1750 g at birth, treatment with intravenous infusions of immune globulin is safe and reduces the risk of nosocomial infection.

Cross Infection↗

PubMed2004

Comparison of combined prophylaxis of cytomegalovirus hyperimmune globulin plus ganciclovir versus cytomegalovirus hyperimmune globulin alone in high-risk heart transplant recipients.

BACKGROUND: Seronegative heart transplant recipients who receive an allograft from seropositive donors have a higher risk of developing cytomegalovirus (CMV) disease and cardiac allograft vasculopathy (CAV) and dysfunction. Neither CMV-specific hyperimmune globulin nor ganciclovir as sole CMV prophylaxis is sufficient to prevent CMV disease in high-risk patients. We retrospectively evaluated the efficacy of CMV-hyperimmune globulin with and without ganciclovir in 207 D+/R- heart transplant recipients. METHODS: The study population was divided into two groups: Group A was composed of 96 patients who received CMV hyperimmune globulin as sole CMV prophylaxis, and group B was composed of 111 patients who received combined CMV prophylaxis. All recipients were subjected to quadruple cytolytic immunosuppression. Primary and secondary end points included prevention of CMV-associated death, CMV disease and productive infection, CAV, and overall infection. RESULTS: There was no difference in overall survival between the two groups. Four patients in the group A died of CMV sepsis, whereas no CMV-associated death was observed in group B (P =0.0326). The actuarial incidence of CMV disease was significantly lower in patients who received double CMV prophylaxis (32.29 vs. 11.71, P =0.0003). Although no difference was observed with regard to productive CMV infection (53.12 vs. 65.77, P =not significant), CAV and overall infection rates were significantly higher in the first group (7.29 vs. 0.9, P =0.0157 and 70.83 vs. 62.16, P =0.03, respectively). CONCLUSIONS: Double CMV prophylaxis consisting of CMV hyperimmune globulin and ganciclovir is able to abolish CMV death and prevent CMV disease in high-risk heart transplant recipients. Therefore, the use of a combination regimen is recommended for seronegative recipients with seropositive donors.

Adolescent↗

PubMed1994

Successful bone marrow transplantation with rabbit anti-human thymocyte globulin in aplastic anemia. Report of a case previously treated with equine anti-human lymphocyte globulin.

Bone marrow transplantation is widely accepted as the first line therapy for patients with severe aplastic anemia. Patients with less severe forms of aplastic anemia are treated with immunosuppressive agents, hematopoietic growth factors or androgenic steroids. The use of rabbit anti-human thymocyte globulin allowed us to successfully transplant in a patient with a moderately severe form who once failed to respond to all conservative treatment including equine anti-human lymphocyte globulin. We propose that, given the availability of rabbit anti-human thymocyte globulin, marrow transplantation should be considered in non-severe aplastic anemia patients who are refractory to equine anti-human lymphocyte globulin.

Adult↗

PubMed1996

Alpha 2u-globulins in the urine of male rats: a reliable indicator for alpha 2u-globulin accumulation in the kidney.

Increases in kidney-type-alpha 2u-globulin (alpha G-K, molecular weight approximately 16 kDa) were detected in the urine of male adult rats treated with d-limonene by immunoblotting analysis using an antiserum which distinguishes native-type-alpha 2u-globulin (alpha G-N, molecular weight approximately 19 kDa) from alpha G-K. When male adult rats received d-limonene by gavage (0-300 mg/kg/day) for 14 consecutive days, dose-dependent increases in urinary excretion of alpha G-K were observed at a dosage level of more than 30 mg/kg/day. This was found to be directly correlated with alterations in the concentration of renal alpha G-K as well as the accumulation of hyaline droplets in proximal convoluted tubule (PCT) epithelial cells in the kidneys. Marked elevation of urinary alpha G-K was also noted following oral treatment of adult male rats with 2,2,4-trimethylpentane (TMP), 1,4-dichlorobenzene (DCB), decalin and isophorone (ISP) by gavage (1.5 mmol/kg/day) for 7 consecutive days, again in association with increased concentrations of renal alpha G-K and hyaline droplet accumulation in renal PCT epithelial cells. However, no such increases in urinary alpha G-K were observed for male adult rats treated with nephrotoxic chemicals such as puromycin aminonucleoside (PAN) (15 mg/kg/day, s.c., 14 consecutive days) or hexachloro-1,3-butadiene (HCBD) (100 mg/kg/day, p.o., 5 consecutive days), lacking the ability to cause kidney accumulation of the hyaline droplets and alpha G-K. The findings in this study thus indicate that measurement of urinary alpha G-K can give a reliable estimates not only of the potential to cause renal accumulation of alpha 2u-globulin but also of its magnitude.

Administration, Oral↗

PubMed2006

Single dose of anti-D immune globulin at 75 microg/kg is as effective as intravenous immune globulin at rapidly raising the platelet count in newly diagnosed immune thrombocytopenic purpura in children.

OBJECTIVE: To conduct a randomized prospective trial of immune globulin treatment for 105 Rh+ children with newly-diagnosed immune thrombocytopenic purpura and a platelet count<20,000/microL, to determine whether anti-D immune globulin (anti-D) is as effective as intravenous immune globulin (IVIg). STUDY DESIGN: Eligible patients received either a single intravenous dose of 50 microg/kg anti-D (anti-D50), 75 microg/kg anti-D, (anti-D75), or 0.8 g/kg IVIg, (IVIg). Patients were monitored for response to treatment and adverse events. RESULTS: By 24 hours after treatment 50%, 72%, and 77% of patients in the anti-D50, anti-D75, and IVIg groups, respectively, had achieved a platelet count>20,000/microL (P=.03). By day 7, hemoglobin concentrations decreased by 1.6 g/dL, 2 g/dL, and 0.3 g/dL in the anti-D50, anti-D75, and IVIg groups, respectively. Headache, fever, or chills occurred least often in the anti-D50 group. CONCLUSIONS: A single 75 microg/kg dose of Anti-D raised the platelet count in children with newly diagnosed immune thrombocytopenic purpura more rapidly than standard-dose anti-D and as effectively as IVIg, with an acceptable safety profile.

Adolescent↗

PubMed1999

Increase in serum concentrations of thyroxine-binding globulin and of cortisol-binding globulin after the induction of normal thyroid function in previously hyperthyroid patients.

Serum concentrations of thyroxine-binding globulin (TBG) were determined in 36 female patients with hyperthyroidism due to either Graves' disease (n = 33), or autonomous thyroid adenomas (n = 3). After the induction of euthyroidism by antithyroid drugs, serum concentrations of TBG rose from 13.7 +/- 2.4 ng/mL to 17.1 +/- 2.8 ng/mL (p < 0.001) whereas those of sex hormone-binding globulin (SHBG) fell from 142.2 +/- 66.4 nmol/L to 53.6 +/- 21.8 nmol/L (p < 0.001). Serum concentrations of cortisol-binding globulin (CBG) rose to 42.9 +/- 10.3 microg/mL (basal: 36.8 +/- 9.4 microg/mL; p < 0.001) but serum concentrations of total and of free cortisol remained unchanged. Thus, thyroid hormones exert different effects on the production of various carrier proteins in vivo. Whereas they stimulate the production of SHBG, they suppress the level of CBG and of their own carrier protein, TBG.

Antithyroid Agents↗

PubMed1975

Radioimmune assay of heterologous serum gamma-globulin in patients receiving rabbit antihuman thymocyte globulin.

A radioimmune assay (RIA) method for detecting heterologous serum rabbit gamma-globulin (RG) and antibody to this protein is described. The methodology is used for monitoring serum levels of rabbit globulin in patients receiving rabbit ATG (RATG). In 7 cardiac recipients receiving RATG, maximum serum levels of RG were achieved 1-3 days after administration of final dose. RG half-life subsequent to peak serum levels was rapid (X = 36 hr) in 4 patients and prolonged (X = 18 days) in 3 patients. Patient antibody to rabbit gamma-globulin was detectable only in those patients with short RG half-life. Antirabbit antibody titers in these patients were extremely low and barely detectable by RIA.

Animals↗

PubMed1989

Polyclonal rabbit gamma globulins against a human cytotoxic CD4+ T cell clone. I. Clone characteristics and antiblast globulin preparation.

Antihuman lymphocyte rabbit (or horse) gamma globulins used in recipients of organ transplantation are prepared against thymocytes or immortalized cell lines, the only two sources so far allowing enough antigen preparation. These cells lack, however, the surface determinants characteristic of alloreactive blasts involved in the rejection process. We have derived long-term cultures of a panel of alloreactive (untransformed) clones from a rejected kidney. Among them, clone 1E7 has been chosen as a cytotoxic CD4+ (CD2+ CD3+ TCR alpha beta+) clone proliferating against HLA-DR8 targets. This clone (clonality assessed on T cell receptor genomic rearrangements) has been grown using weekly stimulations with the kidney donor-derived EBV cell line and recombinant IL-2. Clone cultures have been adapted to mass production after optimization of culture conditions satisfying pharmaceutical requirements. This procedure warranted a reproducible source of antigen since the functional and phenotypic characteristics of the immunizing 1E7 cells remained identical through the life span of the culture. In addition, the study of the total growth capacity of 1E7 cells showed consistent expansion until the 40th cell cycle, ensuring a progeny that will satisfy the large-scale requirement for a clinical trial. Rabbits were injected with 100 x 10(6) 1E7 cells (21, 14, and 7 days before bleeding). Sera were depleted of agglutinin by red blood cell absorption and globulin antiblast (GAB) prepared by SO4Na precipitation and ion exchange chromatography; 50% complement-mediated target cell lysis and 50% inhibition of E rosette formation and alloproliferation were obtained at GAB dilutions of about 1:250-1:500. Prescreened on cynomolgus monkeys, GAB could significantly prolong skin grafts when given prophylactically. Finally GAB have been used in human recipients of kidney grafts for prophylaxis of early rejection. Results of this pilot study are given in a separate report in this issue. In conclusion we have, for the first time, set up a large-scale preparation of polyclonal globulin against a normal human alloreactive clone, and this new reagent should present several advantages over classic antilymphocyte or antithymocyte sera because it contains specificities against activation antigens and has less crossreactivity variation among batches.

Animals↗

PubMed1994

Stimulation of sex hormone-binding globulin mRNA and attenuation of corticosteroid-binding globulin mRNA by triiodothyronine in human hepatoma cells.

We examined the time course and dose response of the triiodothyronine (T3) effect on mRNAs for sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) in cells of the human hepatoma line HepG2. After 7 h of exposure to a saturating dose of T3, SHBG mRNA was unchanged but increased to 1.5 +/- 0.1 times the unstimulated control at 22 h. Maximal stimulation (2.3 +/- 0.6) was observed at 2-3 days. Corticosteroid-binding globulin mRNA was unchanged for 22 h after exposure to T3 but diminished thereafter to 64% by day 3. At 3-4 days of exposure, the changes in both SHBG mRNA and CBG mRNA were dose-responsive to the T3 concentration. For both mRNAs, half-maximal response occurred between 10 and 20 pmol/l bioavailable T3. Cortisol-binding proteins secreted by HepG2 cells after 3 days in culture also were T3 dose-responsive. No re-uptake of secreted CBG by the cells was observed, suggesting that the T3 effect on CBG secretion occurs during production of the mature protein. These data suggest that T3 stimulates the expression of the SHBG gene and attenuates the expression of the CBG gene. The effects of T3 on these genes are consistent with the increase in circulating SHBG and decrease in circulating CBG observed in hyperthyroidism. The HepG2 cells may be a useful human cell line in which to study the diversity of the molecular mechanisms of T3 action.

Carcinoma, Hepatocellular↗

PubMed1995

Opposite effects of thyroid hormones on binding proteins for steroid hormones (sex hormone-binding globulin and corticosteroid-binding globulin) in humans.

Sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) levels were evaluated in euthyroid (N = 111), hyper- (N = 58) and hypothyroid (N = 38) men, in pre- and postmenopausal women (study 1) and in hyper- (N = 24) and hypothyroid (N = 15) patients before and after treatment with carbimazole or levothyroxine therapy (study 2). The SHBG levels are increased in hyper- and decreased in hypothyroid patients, whereas CBG levels are increased in hypo- and decreased in hyperthyroid patients. The SHBG levels are higher in women than in men with similar thyroid status. Plasma SHBG levels are correlated positively whereas CBG levels are correlated negatively with free thyroid hormone concentrations in men as well as women. In hypothyroid patients, SHBG concentrations increased (p < 0.01) and CBG concentrations decreased (p < 0.01) during levothyroxine treatment. In hyperthyroid patients, SHBG concentrations decreased (p < 0.01) and CBG concentrations increased (p < 0.01) during antithyroid treatment. The SHBG and CBG concentrations in treated hypo- and hyperthyroid patients were not significantly different from those of euthyroid controls. Our data indicate that SHBG and CBG levels depend on thyroid status. Corticosteroid-binding globulin is an index of thyroid hormone action at the liver level whose changes are opposite to those of SHBG in hyper- and hypothyroidism.

Adult↗

PubMed1989

Combined hepatitis B immune globulin and vaccine for postexposure prophylaxis of accidental hepatitis B virus infection in hemodialysis staff members: comparison with immune globulin without vaccine in historical controls.

Twenty-three staff members serving in a hemodialysis unit were exposed accidentally to needlestick contaminated with blood containing hepatitis B surface antigen and hepatitis B e antigen, as well as high levels of DNA polymerase activity (greater than 100 cpm). They received hepatitis B vaccine (20 micrograms) simultaneously with hepatitis B immune globulin (5 ml, 200 IU per ml) within 48 hr after the exposure, and the vaccination was repeated at 1 and 3 months. The protective efficacy was compared with that in a past study in the same unit in which 33 members were given hepatitis B immune globulin alone within 48 hr after the exposure to blood with similarly high levels of DNA polymerase activity. No differences were noted in age or sex between the staff members who were vaccinated and those who were not, nor were there any differences between their inocula in the titers of hepatitis B virus markers. During 12 months after the accident, only one (4%) of the 23 vaccinated members contracted hepatitis B virus infection, at a frequency significantly lower than 11 (33%) of the 33 members who did not receive vaccine (p less than 0.02). These results indicate that hepatitis B vaccine, when given in combination with hepatitis B immune globulin, is efficacious for postexposure immunoprophylaxis of accidental infection.

Adult↗

PubMed1984

A preparation of modified immune serum globulin (human) suitable for intravenous administration. Further characterization and comparison with pepsin-treated intravenous gamma globulin.

Numerous methods have been used in previous attempts to prepare a human gamma globulin solution suitable for intravenous administration. These include fractionation schemes, enzyme digestion, manipulations of pH, and various combinations of these methods. The selective reduction and alkylation process that we have developed for Gamimune causes a controlled and reproducible modification of a limited number of disulfide bonds in the hinge region of IgG, resulting in a functional antibody molecule of undiminished molecular weight and possessing complement-binding properties suitable for intravenous administration. Subtle changes in molecular structure or properties that may be caused by trace enzyme hydrolysis or extremes of pH and temperature are avoided. The biochemical characterization of immune globulin intravenous (Gamimune) is described herein, and the attributes of this chemically modified IgG are compared with some of the other intravenous gamma globulin preparations.

Chemical Phenomena↗

PubMed1984

Varicella zoster antibody titers after the administration of intravenous immune serum globulin or varicella zoster immune globulin.

Varicella is a serious infection in the immunocompromised patient. Prophylaxis with varicella zoster immune globulin is known to decrease the incidence of severe varicella infection. The titers of antibody to varicella zoster virus were compared in patients who received either varicella zoster immune globulin or intravenous immune globulin, 4 ml or 6 ml/kg per dose. The titers of antibody to varicella zoster virus were comparable in each group.

Adolescent↗

PubMed1978

Bovine thyroxine-binding globulin. Purification and comparison of molecular weight and amino acid composition with human thyroxine-binding globulin.

Bovine and human thyroxine-binding globulin were purified from serum by a three-step purification procedure which comprised affinity chromatography consecutively on thyroxine- and Concanavalin A--Sepharose and finally preparative polyacrylamide gel electrophoresis. The molecular weights of the two proteins were similar (54 000) as well as their carbohydrate contents while some differences in amino acid composition were found. Rabbit antiserum against bovine thyroxine-binding globulin reacted with human thyroxine-binding globulin with no sign of spur formation.

Amino Acids↗

PubMed1990

Unforeseen effect of thyroxine binding globulin when using the microencapsulated antibody method to determine free thyroxine (FT4): misleading results due to circulating unsaturated thyroxine binding globulin.

The effect of varying concentrations (0-52 mg/l) of purified thyroxine binding globulin (TBG) on the microencapsulated antibody method for free thyroxine was investigated. The results demonstrated that the free thyroxine values were strongly influenced by the concentration of thyroxine binding globulin in the samples. The standard curve could no longer be distinguished at a concentration of purified thyroxine binding globulin of 52 mg/l. In the clinical application, we observed that the values obtained using the microencapsulated antibody method were significantly higher than the expected values in patients receiving triiodothyronine treatment after total thyroidectomy (theoretically nil) and in patients with untreated primary hypothyroidism with negligible thyroxine (less than 12.9 nmol/l). These false positive values are considered to be due to the methodological problem mentioned above, i.e. the microcapsule membrane is not efficient and therefore must be improved. Consequently, any data based on this method should be interpreted with caution.

Adult↗

PubMed1981

Polyclonal gammopathy with beta-globulin-gamma-globulin bridging. Two unusual cases.

Polyclonal gammopathy with beta-globulin-gamma-globulin (beta-gamma) bridging has been classically, though not exclusively, described with cirrhosis. We studied two unusual cases that exhibited polyclonal gammopathy with beta-gamma bridging. In the first case, the coexistence of Kaposi's sarcoma appeared with angioimmunoblastic lymphadenopathy. In the second, liver disease developed as a complication of alpha 1-antitrypsin deficiency and retroperitoneal malignant fibrous histiocytoma involving the porta hepatis.

Aged↗