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At least 19 recordsLinked to original sources

PubMed1977

Development of an intravenous gamma-globulin with Fc activities. II. Reconversion of S-sulfonated human gamma-globulin into the original gamma-globulin.

The reconversion of S-sulfonated antitetanus gamma-globulin (S-GG) into the original gamma-globulin was studied. S-sulfonate groups in S-GG could be converted into disulfide bonds in vitro. The conversion restored the greater part of both complement-fixing and skin-sensitizing activities. S-GG administered intravenously formed interchain disulfide bonds again in vivo, which was accompanied by restoration of the C-dependent passive hemolytic activity. Intravenous injection of S-GG did not cause a significant decrease in serum complement level.

Biotransformation↗

PubMed1976

[Prophylaxis and therapy with gamma globulin. General characterization and clinical use of gamma globulin preparations].

For accurate evaluation of the usefulness of gamma-globulin treatment, the clinical indications for passive immune prophylaxis and immunotherapy and the specific characteristics of commercially available gamma-globulin preparations have to be considered. Detailed investigations of currently used gamma-globulin preparations have shown that as yet no ideal product is available. Classical standard gamma-globulin and, in particular, enzymatically treated (Gamma-Venin, Veinoglobuline) or chemically modified preparations (Gamma-Globulin i.v. SRK, Intraglobin) for intravenous use have some deficiencies and involve potential risks for the patient. Nor is the infusion of "fresh frozen plasma" a safe and generally applicable alternative to the use of gamma-globulin concentrates. Thus from the outset the preconditions for effective treatment with gamma-globulin are not optimal. Standard and hyperimmune preparations, given once intramuscularly, are suitable for the prophylaxis of viral and bacteriotoxic diseases. In patients apt to react abnormally it is important to distinguish clearly between the few accepted indications and those that are more doubtful. Anti-D immunoglobulin is essential for the prevention of Rhesus sensitization after the delivery of a Rhesus-positive child. In general, gamma-globulin is recommended for substitution therapy and for the prophylaxis of recurrent acute bacterial infections in patients suffering from transient, congenital and acquired antibody-deficiency states. In such cases, high doses of an intravenously administrable preparation with a relatively long biologic half-life are recommended. The evidence for the effectiveness of gamma-globulin treatment of bacterial infections in patients without manifest disturbance of humoral immunity is equivocal. This is true, for example, of the oft-recommended combined use of antibiotics and high doses of intravenous gamma-globulin which is said to provide optimum antibacterial and antitoxic protection. There is even less chance of obtaining beneficial effects if gamma-globulin is given as an "ultimo ratio" in severe generalized bacterial infections resistant to antibiotic treatment. Localized and predominantly chronic infections are barely influenced by gamma-globulin. It is still too early to make a final assessment regarding the place and value of immunoglobulin concentrates for prophylactic and therapeutic purposes. This will only be possible if a preparation becomes available which contains all immunoglobulins in a biologically optimum state and concentration, is well tolerated and can be given in adequate doses both intramuscularly and intravenously.

Complement System Proteins↗

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↗

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↗

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↗

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↗

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↗

PubMed1978

[Modifications in alpha 2 globulins, gamma globulins and in rheumatoid factor during gold salt therapy in rheumatoid arthritis].

A total dose of g 1.071, given as hydrosoluble salts for a 12 month period, showed a significant decrease in serum gamma globulins along with clinical improvement in 17 patients affected with rheumatoid arthritis. A decrease in alpha 2 globulins and in rheumatoid factor titre was observed too, but it was not significant. The data suggest that in rheumatoid arthritis the gold therapy might also be effective on the immunological disease mechanism.

Adult↗

PubMed1977

Development of an intravenous gamma-globulin with Fc activities. I. Preparation and characterization of S-sulfonated human gamma-globulin.

S-sulfonated gamma-globulin (S-GG) was prepared by treating gamma-globulin with sulfite and tetrathionate ions. About four interchain disulfide bonds were selectively cleaved to give S-sulfonate groups. Although the above treatment strongly suppresses anticomplementary activity and nonspecific skin reactivity, the resulting S-GG retains high antibody activity. Furthermore, S-GG was found to maintain satisfactory levels for prolonged periods in vivo. The physicochemical and antigenic analyses of S-GG suggest that the S-sulfonation induces structural modification only at restricted sites.

Complement Fixation Tests↗

PubMed1976

Prostatic distribution of sex hormone-binding globulin and cortisol-binding globulin in benign hyperplasia.

Sex hormone-binding globulin-(SHBG) and cortisol-binding globulin-(CBG) like proteins have been demonstrated in prostatic tissue surgically removed from patients with benign prostatic hyperplasia. These proteins are not easily removed by superfusion of tissue slices. Epithelial tissue was separated from stroma and found not to contain the SHBG- or CBG-like proteins. Substantial amounts of these proteins, however, remained associated with the stroma. It is suggested that they may be constituents of interstitial fluid in this tissue compartment. The possible significance of this in benign prostatic hyperplasia is discussed.

Binding Sites↗

PubMed1975

Lack of B lymphocyte depletion from murine spleen cell populations by a human gamma-globulin, anti-human gamma-globulin column system.

It has been reported previously that enriched populations of mouse thymus-dependent (T) lymphocytes could be prepared by the use of a column procedure that is believed to remove selectively cells with receptors for antigen-antibody complexes. In our hands, this procedure does not selectively remove B lymphocytes but rather masks the surface immunoglobulin. Analysis of the column-passed cells revealed an apparent decrease in the percentage of immunoglobulin-bearing cells but little decrease in either the percentage of complement receptor lymphocytes or the mitogenic response to lipopolysaccharide. Furthermore, rabbit immunoglobulin could be detected on the surface of 35 to 45% of the cells emerging from the columns prepared with rabbit anti-human gamma-globulin (HGG). After overnight incubation, 30 to 40% of the emerging cells reexpressed mouse immunoglobulin on their surfaces. Adsorption of the antisera used to make the columns with mouse gamma-globulin (MGG) diminished the depleting capacity of the columns. We conclude from these observations that antibodies in the anti-HGG sera, cross-reactive with mouse immunoglobulin, account for the spacious depletion of B lymphocytes observed when cells are passed over these antigen-antibody complex columns.

Animals↗

PubMed1977

[Influence of combined application of antilymphocyte globulin and plasmatic alpha-globulin fraction on precipitin formation in rabbits (author's transl)].

In the experiments on rabbits immunized with human albumin the effect of combined application of both antilymphocyte globulin (ALG) and plasmatic alpha-globulin fraction (agf) on antibody formation was studied. The course of immune response had been compared to groups administered the above preparation alone, and to controls which had been applied saline. It was found that both ALG alone and AGF were capable to a certain extent of suppressing precipitin formation; a pronounced suppression appeared following the combined effect of both drugs. A strong suppression, however, was likewise attained when a high dose of AGF alone was applied. These findings are discussed in association with other statements that under given experimental conditions the combined application of both drugs, besides the immunosuppressive effect on the formation of antibodies against the antigen used (albumin) showed also an adverse side effect. The latter resulted in a considerably increased level of antibodies against ALG as compared to the group receiving ALG only. The authors point out the necessity of a further follow-up this interesting experience and, unless a more feasible pattern is found which would eliminate the side effects, warn against eventual clinical use of this drug combination under study.

Alpha-Globulins↗

PubMed1979

Isolation, characterization and radioimmunoassay of corticosteroid-binding globulin (CBG) in human serum -- clinical significance and comparison to thyroxine-binding globulin (TBG).

Isolation of the corticosteroid-binding globulin CBG was achieved by 5 chromatographical steps on cortisol Sepharose, QAE-Sephadex A-50, Con A-Sepharose and hydroxylapatite. The purity of the isolated CBG was demonstrated in polyacrylamide gel electrophoresis, SDS electrophoresis, immunodiffusion and ultracentrifugation. Microheterogeneity was shown in isoelectric focusing by 5 bands in the pH range of 3.7--4.2, which could be reduced to one major band after neuraminidase treatment. The equimolar binding of cortisol to CBG was demonstrated by binding studies. The association constant for cortisol was 2.8 x 10(8)M-1, for progesterone 1.7 x 10(6)M-1. From analytical ultracentrifugation, the molecular weight was calculated on 50 700; the sedimentation coefficient was 3.6 S, the partial specific volume 0.690 ml/g, the Stokes radius 38 A and the frictional coefficient ratio 1.5. A specific radioimmunoassay for CBG was established using the purified CBG for immunization, radioiodination and for calibration standards. The normal range of CBG levels in human serum was 2.4--4.4 mg/100 ml (mean +/- 2 SD). Studies were performed to compare the levels of CBG and thyroxine-binding globulin (TBG). No sex differences but a significant biphasic age dependence were observed for both proteins. In pregnancy and under oestrogen treatment of women and men, CBG was demonstrated to be the more distinct indicator of oestrogenic activity as compared with TBG, whereas the sensitivity of TBG was more pronounced to supposedly antioestrogenic substances like Danazol, and in severe disease. No coincidence of genetic CBG and TBG deficiencies have been found so far.

Amino Acids↗

PubMed1976

Reconstruction of intact gamma-globulin from S-sulfonated gamma-globulin in vivo.

The conversion of the S-surfonate group in a peptide to a disulfide bond has been observed in vitro. This paper reports that the conversion of this group in human S-sulfonated gamma-globulin (S-GG) appeared to occur in vivo judging from the change in molecular weight of S-GG observed in the presence of sodium dodecyl sulfate (SDS) and the restoration of hemolytic activity.

Animals↗

PubMed1977

Role of urinary alpha1-globulin fraction in formation of urinary calculi. With special reference to aggregating effect of serum alpha1-globulin on calcium carbonate suspension.

The present study was undertaken to determine if urinary protein can produce urinary stones and what types of protein have such an effect. Normal human serum was fractionated first with ammonium sulfate and then with DEAE-cellulose. The stone-forming action of each fraction was estimated by calculating their ability to alter the sedimentation rate and zeta-potential of a calcium carbonate suspension. Finally, the proteins in each fraction were identified by cellulose acetate electrophoresis. The most marked aggregating and precipitating effect on a CaCO3 suspension was observed with a mixture of proteins of alpha1-globulin and albumin fractions. However, beta- and gamma-fractions had little aggregating effect on the CaCO3 suspension.

Alpha-Globulins↗

PubMed1976

Metabolism of thyroxine-binding globulin in man. Abnormal rate of synthesis in inherited thyroxine-binding globulin deficiency and excess.

It has been previously suggested that inherited thyroxine-binding globulin (TBG) abnormalities in man may be due to mutations at a single X-chromosome-linked locus controlling TBG synthesis. However, abnormalities in TBG degradation have not been excluded. The availability of purified human TBG and its successful labeling with radioiodide allowed us to examine such possibility. Human TBG was purified by affinity chromatography, labeled under sterile conditions with 131I or 125I,, and mixed with [125I]thyroxine (T4) or [131I]T4, respectively, before their intravenous injection. Blood and urine samples were collected over a 10-day period, and the turnover parameters were calculated. In eight normal volunteers mean values +/-SD for TBG and T4 respectively, were as follows: Half time (t1/2) 5.3 +/- 0.4 and 7.0 +/- 0.6 days; distribution space (DS) 7.2 +/- 1.0 and 10.8 +/- 1.2 liters; and total daily degradation (D) 0.211 +/- 0.053 and 0.088 +/- 0.011 mumol/day. In all subjects, t1/2 of TBG was shorter than that of T4; and the DS was smaller. 2.4 mol of TBG was degraded for each mole of T4. In five of six subjects from four families, comprising hemizygous and heterozygous carriers of TBG absence, decrease, and excess, the t1/2 and DS for TBG were within the normal range. The D of TBG was proportional to the serum concentration of the protein. Changes in the T4 kinetics in these patients were compatible with euthyroidism and with the known alterations in the extrathyroidal T4 pool associated with the changes in serum TBG concentration. A striking decrease in the t1/2 of TBG was found only in a patient with acquired diminution in TBG concentration and in patients with thyrotoxicosis or other conditions apparently unrelated to thyroid dysfunction. TBG t1/2 was 2.5 days in a patient with multiple myeloma and 3.6 days in two patients with thyrotoxicosis. Decreased TBG t1/2 was also observed in three of six patients with nonthyroidal pathology and was associated with an increase in TBG D disproportionate to their level of serum TBG. These studies indicate that changes in TBG concentration in patients with X-chromosome-linked TBG abnormalities are due to alterations in its rate of synthesis. In other conditions, abnormalities of TBG degradation and/or rate of synthesis may be found.

Adult↗

PubMed1977

Suppression of tumor-specific cell-mediated cytotoxicity by immunoregulatory alpha-globulin and by immunoregulatory alpha-globulin-like peptides from cancer patients.

The suppression of tumor-specific cell-mediated cytotoxicity by human immunoregulatory alpha-globulin (IRA), by a peptide fraction derived from IRA, and by IRA-like peptides from the serum of cancer patients was studied in a syngeneic murine tumor-host system. Splenic lymphocytes from tumor-immunized mice were cytotoxic specific tumor cells in vitro as measured by the [125]-iododeoxyuridine release microcytotoxicity assay. However, this effect was significantly depressed if 1.25 to 5 mg of IRA per ml were added to the cultures. Pooled lyophilized normal human serum protein was inactive. IRA peptide and IRA-like peptide fractions from cancer patients were also highly suppressive of cell-mediated cytotoxicity at much lower concentrations (0.05 to 0.5 mg/ml). Control human serum peptide, which failed to inhibit the induction of hemolytic plaque-forming cells in sheep erythrocyte-injected mice, had no effect on cell-mediated cytotoxicity. IRA and IRA-like peptide fractions were not cytotoxic to the effector lymphocytes or to the target cells at the concentrations used.

Alpha-Globulins↗