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[Serum globulin levels and activities of daily living in centenarians].

Serum globulin levels in 101 centenarians (77 women, 24 men) were analyzed by zonal electrophoresis and immunoglobulin assays. Six subjects showed an M band in electrophoretograms. Five M bands were immunoglobulin G (IgG) type and one was IgA. One subject was suspected to suffer from IgG-type multiple myeloma, and the others were thought to have essential (benign) monoclonal gammopathy. The relationship between serum globulin levels and activities of daily living (ADL) was studied in remaining 95 subjects. There were 21 rank-J (free-living), 25 rank-A (unable to go outside without help), 23 rank-B (bedridden but able to sit on the bed), and 26 rank-C (completely bedridden) centenarians. The mean serum alpha 1-, alpha 2-, and beta-globulin level in the rank-J centenarians was at the upper limit of the normal adult range. The mean alpha 1-globulin levels in rank-B (3.3 +/- 0.4%) and C (3.4 +/- 0.5%) subjects were significantly higher than those in rank-J (2.9 +/- 0.3%) centenarians. The mean serum gamma-globulin level of rank-J centenarians (16.9 +/- 3.7%) was within the normal range. The mean gamma-globulin levels in rank-B (21.0 +/- 2.7%) and C (22.8 +/- 4.9%) subjects were significantly higher than that in rank-J centenarians. The mean immunoglobulin G concentrations in rank-B (1.620 +/- 304 mg/dl) and C (1.720 +/- 392 mg/dl) subjects were significantly higher than those in rank-J centenarians (1.320 +/- 361 mg/dl) and in normal adults (1.150 +/- 235 mg/dl). IgA concentrations in all centenarians were higher than in normal controls. There was no significant difference in IgA or IgM concentration between rank-J subjects and those in other ranks. Serum globulin levels measured with electrophoresis, and the immunoglobulin concentrations, can be valuable indicators of the ability to perform activities of daily living, and may be useful predictors of subclinical diseases or morbidity in centenarians.

Activities of Daily Living↗

[Aseptic meningitis induced by high-dose gamma-globulin in an adult woman with antiphospholipid syndrome and chronic idiopathic thrombocytopenic purpura].

It is well known that the administration of high-dose gamma-globulin concentrate is effective in alleviating thrombocytopenia in patients with idiopathic thrombocytopenic purpura (ITP). However, treatment can sometimes induce aseptic meningitis. A 25-year-old Japanese woman with antiphospholipid syndrome and ITP was conditioned with high-dose gamma-globulin concentrate prior to splenectomy. Three days after the initial gamma-globulin course, she experienced severe headache, vomiting, and high-grade fever. Cerebrospinal fluid examination yielded a diagnosis of aseptic meningitis. The patient's clinical symptoms and abnormal cerebrospinal fluid findings disappeared immediately after the discontinuation of gamma-globulin therapy. Cases of aseptic meningitis induced by high-dose gamma-globulin therapy are uncommon in the literature, and most involve children. Moreover, to our knowledge, only 1 Japanese adult ITP case of gamma-globulin-induced aseptic meningitis has been reported to date. Aseptic meningitis may be one of the important adverse effects of the administration of high-dose gamma-globulin concentrate to pediatric as well as adult ITP patients.

Adult↗

[Electrophoretic study of albumins and globulins of 4 genotypes of Canavalia ensiformis].

Polyacrylamide gel electrophoresis (PAGE) and PAGE-SDS were used to study seed albumins and globulins of Canavalia ensiformis. In PAGE the concentration of acrylamide used in the upper gel was 4.0% with a pH of 6.7 and in the lower gel 7.5% and 10% of acrylamide were used with a pH of 8.9. In PAGE-SDS the concentration of acrylamide was 4.4% with a pH of 6.8 in the upper gel and 7.5% and 12.6% with a pH of 8.8 in the lower gel. The material used were the Venezuelan genotypes Tovar, Yaracuy, Original and U-02. The albumins and globulins were extracted with a 0.5 M NaCl solution and then separated by dialysis against water and lyophilized. These protein fractions represented 84.85% of the total amount of protein in seeds. The albumins were separated in PAGE with 7.5% acrylamide into five fractions and globulins into six, with similar electrophoretic patterns between genotypes. In a similar manner, the patterns obtained in PAGE with 10% acrylamide were the same for all genotypes, showing five bands for albumins and three bands for globulins. With PAGE-SDS containing 7.5% of acrylamide, albumins were separated into as many as eight components, and globulins into as many as seven bands with mobilities between 0.2981 and 0.9932, with different patterns for each genotype. Also the patterns PAGE-SDS at 12.6% of acrylamide were different for the genotypes, separating proteins into a greater number of bands. The albumins showed as many as twenty-one bands with mobilities between 0.2603 and 0.7398, and globulins as many as sixteen bands with mobilities between 0.2454 and 0.7390. The PAGE patterns of the genotypes analyzed did not show differences between them. However, with PAGE-SDS different electrophoretic patterns were obtained which varied in the number and intensity of the bands, making it possible to distinguish the genotypes studied. The molecular weight of the albumins varied between 76,000 and 12,000 daltons and of the globulins between 80,000 and 12,000 daltons.

Albumins↗

Alpha-1-acute phase globulin in the blood of tunicamycin-injected rats. Isolation of the non-glycosylated form, its inhibitory properties and synthesis in liver slices.

Plasma of rats injected with tunicamycin (2 micrograms/g body wt) shows on crossed immunoelectrophoresis the presence of an additional, slowly migrating component of alpha 1-acute-phase globulin (alpha 1-AP-globulin). The native and modified forms of alpha 1-AP-globulin were jointly isolated on the column of immobilized antibodies and then separated by chromatofocusing on polybuffer exchanger. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate demonstrated that tunicamycin-induced form of rat alpha 1-AP-globulin has Mr of 50,000 and is devoid of carbohydrates as inferred from the lack of staining with Schiff reagent. However, during incubation with papain in vitro it is only slightly less effective than mature glycosylated alpha 1-AP-globulin (Mr 68 000) in inhibiting hydrolysis of CBZ-Lys-ONp. Incubation of liver slices from control and tunicamycin-injected rats with 14C-leucine demonstrated that tunicamycin reduces synthesis and release to the medium of alpha 1-AP-globulin and some other plasma proteins, but the proportion of aglyco-alpha 1-AP-globulin is higher than in plasma.

Acute-Phase Proteins↗

Effects of the serum gamma globulin fraction of patients with allergic asthma and dilated cardiomyopathy on chronotropic beta adrenoceptor function in cultured neonatal rat heart myocytes.

Spontaneously beating cardiomyocytes of newborn rats were exposed in culture to the gamma globulin fraction from the blood serum of patients with allergic asthma and dilated cardiomyopathy. The gamma globulin fraction of the asthmatics inhibited in a dose-dependent fashion the positive chronotropic response of lactate or pyruvate-treated myocytes to clenbuterol, an adrenergic agonist that acted via stimulation of beta 2 adrenoceptors. The gamma globulin fraction of the cardiomyopathic patients increased the rate of beating. This effect was stereoselectively inhibited by the beta blocker (-)-propranolol, indicating an involvement of beta adrenoceptors. The serum gamma globulin fraction from healthy persons had no effect on the beating rate. The effects of both the asthmatic and cardiomyopathic gamma globulin fractions were abolished by immunoprecipitation with antihuman gamma globulin and antihuman IgG. The chronotropic effects of the gamma globulin fraction may be attributed to the presence of autoantibodies to beta-adrenergic receptors, more specifically beta 2 receptors in the case of the asthmatics and beta 1 receptors in the case of the cardiomyopathic patients.

Adrenergic beta-Agonists↗

Immunosuppresive effect of a human hepatic glycoferroprotein, alpha2H globulin. A study on the transformation of normal human lymphocytes.

A macroglycoferroprotein of hepatic orgin, alpah2H globulin, the serum level of which increases a few weeks or months before local recurrence of metastases, has been essayed for its immunosuppressive activity. The study was carried out using the lymphoblastic transformation test and was judged by tritiated thymidine incorporation and microscopic examination. PHA-induced blast transformation of 97 per cent of normal donor lymphocytes is inhibited by 100 mug/ml of alpha2H globulin. This inhibitory effect is proportional to the quantity of added alpha2H globulin. In is obvious with a concentration of 2-5 mug/ml, a frequently observed level in the serum of patient with tumours. Preincubation of lymphocytes with alpha2H globulin renders more effective the inhibitory action on PHA-induced transformation. A mechanism of competition between PHA and alpha2H globulin is suggested by preincubation and the inhibitory effect related to the doses. However, microscopic observation shows that alpha2H globulin acts on the earliest events occurring to the stimulated lymphocytes, by inhibiting cytoplasmic RNA and protein synthesis. The alpha2H globulin effect may not only have an immunosuppresive activity but it may have a more general effect, for example blocking or modifying cellular respiration.

Alpha-Globulins↗

[Level of viral antibodies in normal and specific swine and bovine gamma globulin preparations].

Studied were 15 series of normal bovine gamma-globulin, 5 series of normal swine gamma-globulin, 7 series of Aujeszky gamma-globulin, 6 series of specific gamma-globulin against edema disease of pigs, 4 series of specific gamma-globulin against paratyphus, 5 series of Mixoglobulin-70, and one series of swine poly-globulin. All series of gamma-globulin preparations were studied for the presence of antibodies against Mixovirus parainfluenza-3 through the hemagglutinationinhibition reaction, antibodies against adenoviruses through the precipitation reaction in agar gel, and antibodies against the virus of Aujeszky's disease through the virus-neutralization reaction in tissue cultures.

Adenoviridae↗

[Effect of immunization on the quantitative behavior of gamma globulins in the blood serum of cattle following whole-body x-ray irradiation].

Five experiment series were applied to 38 calves, aged between two-and-a-half and four months, using whole-body exposure to X-ray treatment based on median lethal doses (MLD) between 1.2 Gy and 1.7 Gy. Various methods of immunisation were simultaneously applied, and their effects on irradiation-caused response of gamma globulin concentrations in blood serum were studied. Gamma globulin levels were determined by Kunkel's zinc sulphate turbidity test. Immunisation applied between 14 and 21 days prior to irradiation resulted on obvious stimulation of gamma globulin production. In two experiments with parenteral antigen application, gamma globulin levels increased through about 14 days in apparently irradiated animals declined, after that period of time, but they continued to rise in really irradiated probands. A high lethal dose of 1.7 Gy, however, was followed by significant drop, three weeks after irradiation, that is in concomitance with the climax of the radiation syndrome. When 1.5 Gy were used, rise in gamma globulin concentration was recordable also following oral administration of antigen. Response of irradiated animals was even more clearly pronounced by secondary reaction of antibody formation, following booster action due to experimental infection with homologous germs. The stimulating effect of irradiation upon gamma globulin levels in blood serum, when oral or parenteral immunisation had taken place, prior to irradiation, has been attributed to reaction of the immune-globulin producing system to the release of tissue proteins or tissue antigens. Immunisation, prior to irradiation, stimulated the immunological system which underwent stronger regeneration, after irradiation, or had obviously acquired higher resistance to radiation.

Animals↗

[Immunochemical identification of ferritin and its immunological analogs beta-fetoprotein and alpha 2H-globulin].

Immunochemistry techniques were made use of to identify the immunological analogs of ferritin - beta-fetoprotein and alpha 2H-globulin. Direct correlation of the test systems for ferritin, beta-fetoprotein and alpha-globulin demonstrated their complete identity. Electrophoretic mobility of beta-fetoprotein was found to be identical to that of ferritin, corresponding with blood serum alpha 2-globulins. alpha 2H-Globulin was obtained from human kidney tumors according to the method devised by the author. The glycoprotein component of alpha 2H-globulin isolated from the preparation alpha 2H-globulin did not prove identical to kidney tumor ferritin and was thus signed to serum alpha 2-macroglobulins of healthy subjects. Since there are no differences between ferritin and its immunological analogs, it is suggested that beta-fetoprotein and alpha 2H-globulin be termed ferritin.

Alpha-Globulins↗

Triphasic pills: variability of endocrine parameters and of sex steroid-binding globulins.

A hundred and twenty healthy women who did not desire pregnancy were selected to check the effects of triphasic oral contraceptives on endocrine parameters and on plasma levels of steroid-binding proteins. Three groups of 40 women each were treated with 3 different pills containing different doses of ethynilestradiol in combination with noretistherone or levonorgestrel or gestodene, for a 6-month period. Serum concentrations of pituitary, ovarian and adrenal hormones, sex-hormone binding globulin and corticosteroid binding globulin were measured, basally and after the 6th cycle. Triiodothyronine and thyroxine were also tested. After 6 cycles the three oral contraceptives determined the inhibition of gonadotropins, ovarian steroids and Dehydroepiandrosterone Sulphate as well as an increase in Cortisol, triiodothyronine, thyroxine, sex hormone binding globulin and corticosteroid binding globulin. Prolactin levels did not vary. In the groups that receive the pills containing noretistherone, levonorgestrel and gestodene, sex hormone binding globulin increased by 138-136 and 156 per cent respectively, while corticosteroid binding globulin increased by 89-75 and 82 per cent respectively. The higher increase in sex hormone binding globulin, caused by gestodene-containing pill, testifies to the selectivity of this progestogen towards a lower androgenicity than norethisterone and levonorgestrel.

Adolescent↗

[Gc-globulin in paracetamol poisoning].

Gc-globulin scavenges actin liberated from necrotic cells. We measured serum Gc-globulin and the degree of complexing with monomeric actin (complex ratio) in the initial phase of paracetamol (acetaminophen) intoxication and related this to the severity of liver necrosis and the clinical course. In eighteen patients with paracetamol intoxication serial measurements of serum Gc-globulin and complex ratio were determined from admission and every three hours thereafter. Eight patients developed hepatic encephalopathy (HE) and two of them died. On admission all patients had significantly reduced serum Gc-globulin levels compared to normal individuals, and patients with HE had significantly lower values than patients without HE. All patients with HE had at least three samples, where Gc-globulin was below 120 mg/l (35% of normal). Complex ratio on admission did not differ significantly in the patients with and those without HE. The peak complex ratio was higher in patients with HE than in patients without HE, and three of four patients with peak complex ratio above 75% had HE. In conclusion, Gc-globulin levels were found to be decreased in patients with paracetamol intoxication; this decrease correlated with the most severe sign of liver dysfunction, HE. Serum Gc-globulin below 120 mg/l and peak complex ratios above 75% may be critical values.

Acetaminophen↗

Treatment of Guillain-Barré syndrome with high-dose immune globulins combined with methylprednisolone: a pilot study. The Dutch Guillain-Barré Study Group.

In an open study 25 patients with Guillain-Barré syndrome were treated for 5 days with intravenous immune globulins in a dose of 0.4 gm/kg of body weight/day and 0.5 gm of methylprednisolone intravenously per day. The results of this combined treatment were compared with the results from a group of 74 patients who were treated with immune globulins only in a recent Dutch Guillain-Barré trial. In the methylprednisolone-immune globulin treatment group, 19 of 25 patients (76%) improved by one or more functional grades after 4 weeks, as compared with 39 (53%) of 74 patients treated with immune globulin alone (p = 0.04). Also the median time required to the stage of walking independently was reduced in the methylprednisolone-immune globulin treatment group. This pilot study suggests that combined treatment with methylprednisolone and immune globulins in patients with the Guillain-Barré syndrome is more effective than treatment with immune globulins alone; a randomized clinical trial might confirm this.

Autoantibodies↗

Clinical response to cold insoluble globulin replacement in a patient with sepsis and thermal injury.

Cold insoluble globulin (fibronectin, alpha 2-surface binding glycoprotein) is a naturally occurring substance necessary for optimal stimulation of the reticuloendothelial system. While this globulin depends on macrophages as the effector cells for its opsonic function, as is true of both antibody and complement, it is neither part of nor dependent on these systems for its opsonic activity. A relatively simple bioassay developed at the Medical College of Georgia substantiated that cold insoluble globulin is severely depleted in sepsis. Cryoprecipitate, properly processed and stored, is an exogenous source of cold insoluble globulin. Infused into septic patients 10 units thawed at 2 degrees C and reconstituted to 250 ml with saline solution can temporarily restore cold insoluble globulin levels and enhance activity of the reticuloendothelial system. Proper current use dictates measurement of cold insoluble globulin levels in the infusate as well as levels in the patient and the clinical response to infusion. Our bioassay and a septic patient's response to infusion of cold insoluble globulin are reported herein.

Burns↗

Interaction of myasthenic serum globulin with the acetylcholine receptor.

A serum factor from patients with myasthenia gravis which inhibited the binding of 125I-labeled alpha-bungarotoxin to acetylcholine receptor extracted with Triton X-100 from rat muscle has been studied in detail. The inhibitory activity was localized to the IgG fraction based upon the fractionations by sodium sulfate precipitation and DEAE chromatography as well as reaction with anti-IgG globulin. The myasthenic globulin inhibited toxin binding to receptors extracted from degenerated muscle but did not inhibit toxin binding to normal junctional receptors. At saturation levels of myasthenic globulin, the number of denervated acetylcholine receptors available for toxin binding was reduced approx. 50 percent. The myastehnic globulin was found to bind to denervated acetylcholine receptors but not to normal acetylcholine receptors by a radioimmunoassay technique in which myasthenic globulin incubated with 125I-labeled alpha bungarotoxin-receptor complexes was precipitated by anti-IgG serum. The globulin binding was saturable over the same range as inhibition of toxin binding. The data suggest that the myasthenic IgC binds to a site on the receptor complex juxtaposed to the acetylcholine receptor site. The myasthenic globulin appears to be a useful probe for investigation differences between acetylcholine receptors extracted from normal and denervated muscle and for investigating the pathogenesis of myasthenia gravis.

Acetylcholine↗

The cold-insoluble globulin of human plasma: studies of its essential structural features.

These investigations were directed at furnishing information on the essential structural features of the cold-insoluble globulin of human plasma. Amino acid and carbohydrate analyses showed that it is a glycoprotein (1.2% sialic acid, 1.8% hexose, 2.1% hexosamine) containing all of the amino acids usually found in proteins. Circular dichroic spectral analysis suggested that cold-insoluble globulin contained a very high proportion of beta-structure; no evidence for the presence of alpha-helix was found. Sedimentation velocity experiments at pH 7.0, in the presence or absence of dithiothreitol, plus related gel electrophoretic experiments at pH 8.4, indicated that the integrity of certain disulfide bridges was necessary for its solubility under "physiologic" conditions. In experiments in urea-containing solution, two sedimenting peaks were observed. The major one, amounting to more than 95% of the total, had an s20,w of 5.6 S, the minor peak had an s20,w of 7.3 S. Following disulfide bridge reduction a single symmetrical peak of 3.9 S was formed. Such behavior suggested that cold-insoluble globulin is a multichain molecule whose subunit chains are linked by disulfide bridging. Strong support for this conclusion was obtained from electrophoretic analyses in gels containing dodecylsulfate, in that cold-insoluble globulin manifested an increased rate of migration after reduction of disulfide bridges. The reduced cold-insoluble globulin band could be resolved into a closely spaced doublet, the components of which had molecular weights of 220 000 and 215 000, respectively. Since in sedimentation equilibrium experiments the molecular weight of the unreduced molecule was estimated to be 450 000, values in this range for the size of the subunit chain suggested that each cold-insoluble globulin molecule is composed of two covalently linked chains. The nature of the size heterogeneity of the reduced subunit chains is uncertain. However, the finding of a single type of NH2-terminal sequence ([Glu-Ala) in cold-insoluble globulin preparations, is consistent with the speculation that the smaller subunit may be a catabolic intermediate arising via release of peptide material containing the COOH-terminus of a parent chain.

Amino Acids↗

Similarity of antigelatin factor and cold insoluble globulin.

Antigelatin factor, a protein capable of complexing denatured collagen, was separated from human serum by adsorption onto immobilized collagen. Antiserum raised against the material binding to denatured collagen permitted the development of a radioassay for the determination of antigelatin factor in which the complex of antigelatin factor and denatured 125I-labeled collagen is precipitated with this antiserum. Further purification of antigelatin factor was achieved by chromatography on DEAE-cellulose yielding an electrophoretically homogeneous protein. Its migration rate in dodecyl sulfate-polyacrylamide gel electrophoresis was identical with that of cold insoluble globulin (molecular weight approx. 440 000) prepared from human plasma by a published procedure amended by DEAE-cellulose chromatography. Reduction of disulfide bonds yielded subunits of molecular weight approx. 220 000, indistinguishable from those of cold insoluble globulin. The amino acid composition of both proteins was very similar. Immunological identity of both proteins was demonstrated by gel diffusion against monospecific anti-cold insoluble globulin antiserum. Closely related binding curves were obtained if denatured 125I-labeled collagen was reacted with increasing amounts of either cold insoluble globulin or antigelatin factor and the complexes formed were precipitated with anti-cold insoluble globulin antiserum. In addition, antigelatin factor and cold insoluble globulin mediated the fixation of denatured 125I-labeled collagen to trypsinized macrophages in the same way. Therefore, it is concluded that antigelatin factor and cold insoluble globulin are identical or very closely related proteins.

Amino Acids↗

The use of intravenous immune globulin in collagen vascular disorders: a potentially new modality of therapy.

During the last several years, there has been increasing interest in the use of intravenous immune globulin for immunosuppression. Although the mechanism(s) of action remains to be delineated, immune globulin therapy has been shown to be effective in some antibody-mediated disorders. In Rh disease, antibody-induced cytopenias, myasthenia gravis, and the clotting disorder associated with anti-factor VIII antibody, intravenous immune globulin has had therapeutic benefit. It was of interest that intravenous immune globulin may partially ameliorate the tendency toward dilation of the coronary vessels in Kawasaki disease. If this disorder represents a vasculitis of the small feeding vessels of the coronary arteries, could this agent influence other forms of collagen vascular disease? Pilot studies in dermatomyositis and polymyositis and systemic juvenile rheumatoid arthritis indicate benefit from intravenous immune globulin therapy. In these studies we used a high-dose protocol consisting of 1 gm/kg/day of immune globulin for 2 days every 4 weeks. In patients with either myositis or systemic juvenile rheumatoid arthritis, beneficial effects were seen. In the former group of patients, increased proximal muscle strength and reduction in creatine kinase levels were observed. In the latter group of patients a marked reduction in systemic features was observed. The amount of corticosteroids required was reduced in both groups of patients. These studies indicate the potential for intravenous immune globulin in collagen vascular disorders and the need for carefully controlled trials of this form of therapy.

Arthritis, Juvenile↗

Effectiveness of immune globulins in preventing infectious hepatitis and hepatitis A: a systematic review.

OBJECTIVE: To assess the effectiveness and safety of immune globulins in preventing infectious hepatitis and hepatitis A. STUDY DESIGN: Systematic review with meta-analysis. DATA SOURCES: We searched the Cochrane Library, MEDLINE, EMBASE, Biological Abstracts and Science Citation Index to December 2002. Vaccine manufacturers were contacted for additional data. REVIEW METHODS: We included randomised controlled trials comparing effectiveness of hepatitis A immune globulins with no intervention or placebo, and carried out a meta-analysis. RESULTS: We included six studies (two in Russian). Tested immune globulins show higher effectiveness than placebo or do-nothing against infectious hepatitis both in primary prevention and in prevention after exposure (effectiveness 83%; RR: 0.17; 95% CI: 0.15-0.19; and effectiveness 69%; RR: 0.31; 95% CI: 0.20-0.47, respectively). We found considerable heterogeneity among studies, possibly due to different methodology, background rates of disease and immune globulins dosage and concentrations. No safety data were reported in the studies. CONCLUSIONS: Immune globulins are efficacious in preventing infectious hepatitis and hepatitis A, but included studies do not report data about their safety. Average length of passive protection was three months. Given the notable heterogeneity of performance of immune globulins, short protection conferred and absence of trial safety data, the only indications for the use of immune globulins may be in situations in which inadequate supplies of vaccine are available or when the eight-day window of opportunity for vaccine use is past.

Chi-Square Distribution↗