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Nuclear factors from expressing tissues interact in vitro with a rat alpha-2u globulin gene intron.

Members of the rat alpha 2u globulin gene family are expressed in a tissue-specific manner. Using a DNase I footprinting assay, we find that expressing tissues (liver, lachrymal, and salivary gland) contain nuclear proteins that interact specifically with two sites in the third intron of a cloned gene. These sequences are similar to a CCAAT-like sequence in the 5'-flanking region of the gene and the binding site for the transcription factor Sp1. Extracts of nonexpressing tissues (kidney, testis, brain, and spleen) do not show footprinting activity at these sites. Whereas hepatic expression of alpha 2u globulin is restricted to normal adult males, nuclear extracts of liver from all animals (adult and juvenile, male and female, intact and hypophysectomized) produce similar footprints. Footprints by extracts of lachrymal and salivary glands, tissues that express a subset of alpha 2u globulin genes distinct from the hepatic set, are also similar to the liver activity. The findings suggest that the third intron of an alpha 2u globulin gene contains sites that interact with tissue-specific factors to establish the potential for hormonal and developmental control of expression.

Alpha-Globulins↗

Testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex-hormone-binding globulin in pregnant alcohol abusers.

We compared serum concentrations of total and free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), and sex-hormone-binding globulin in 40 pregnant women exhibiting consistent alcohol abuse and in 20 abstinent pregnant controls. Sixteen drinkers gave birth to infants with fetal alcohol effects; the remaining 24 drinkers delivered healthy infants. Drinking patients with healthy infants had normal concentrations of total and free testosterone, sex-hormone-binding globulin, and DHEAS, but their levels of androstenedione increased between weeks 20-40 of pregnancy. Maternal drinking leading to fetal alcohol effects was accompanied by lowered concentrations of sex-hormone-binding globulin throughout pregnancy and by low total testosterone concentrations, although the latter difference reached statistical significance only at 16-20 weeks' gestation. In contrast, drinking leading to fetal damage was associated with higher free testosterone levels between weeks 16-20 of pregnancy and lowered concentrations of DHEAS between weeks 16-32 of gestation, whereas the androstenedione levels tended to be high throughout pregnancy. These changes in androgens can be explained in part by low sex-hormone-binding globulin concentrations, an insufficient supply of DHEAS by the adrenals, and reduced peripheral conversion of androstenedione to testosterone.

Adult↗

Studies on thyroid hormone-binding proteins. I. The subunit structure of human thyroxine-binding globulin and its interaction with ligands.

Thyroxine-binding globulin was isolated from human plasma by ammonium sulfate fractionation, chromatographic separations on diethylaminoethyl-Sephadex, gel chromatography, and two different electrophoretic procedures. The highly purified was homogeneous when subjected to polyacrylamide gel electrophoresis, ultracentrifugation analyses, and immunochemical determinations. The weight average molecular weight as determined by sedimentation equilibrium ultracentrifugations was 54,000 and by sedimentation diffusion data 55,000. Amino acid analyses indicated a minimum of 110 amino acid residues per molecule. By determination of the minimum in the curve for the fraction of maximum deviation from the amino acid analyses it was found that the minimum molecular weight for the polypeptide was 12,200. Carbohydrate analyses demonstrated the presence f equimolar amounts of amnnose, galactose, and glucosamine, and the carbohydrate portion constituted 7.5% of the total weight. The amino acid analyses suggested that thyroxine-binding globulin is composed of 4 subunits. Molecular weight determinations by gel chromatography in 6 M guanidine hydrochloride indicated the presence of three species of globulin with apparent molecular weights 52,000, 25,000, and 13,500, respectively. Prolonged storage in guanidine hydrochloride promoted a more than 60% yield of the monomeric species. Moreover, a half-molecule of thyroxine-binding globulin was isolated and shown to consist of two polypeptide chains of similar molecular weight...

Amino Acids↗

Catabolism physical, and immunologic properties of endocytosed isologous and heterologous iota-globulins by mouse macrophages.

The catabolism of completely endocytosed isologous and heterologous gamma-globulins by mouse macrophages was studied in vitro. Mouse, human, and rabbit 125-I-IgG were coupled to mouse, human, or sheep erythrocytes either as antibodies or by covalent binding. They were exposed to macrophages for 1 hr and the non-endocytosed erythrocytes were then removed with a Ficoll gradient centrifugation. Catabolism was evaluated after 2, 5, and 18 hr in culture by measuring the radioactivity released into the culture medium as well as the radioactivity that remained associated with cells. It was found that all iota-globulins were catabolized in a similar fashion, and that the type of carrier erythrocytes (isologous or heterologous) had no influence on catabolism. Some of the material that remained associated with macrophages was on the cell membrane and could be removed by trypsin. Some of the material that was released by macrophages was completely degraded but some was either not degraded or only partially degraded. Sucrose density gradient analysis and SDS-polyacrylamide gel electrophoresis showed that this material had kept some physical properties of native iota-globulins. It was also found with the antigen-binding inhibition test and incubation with erythrocytes that the released material contained molecules carrying Fab determinants and was able to bind specifically to erythrocytic antigens. Taken together, these observations show that iota-globulins phagocytosed in the form of antigen-antibody complexes are only incompletely degraded and that the material associated with plasma membrane of macrophages or found in the culture medium is a product of cell catabolism.

Animals↗

[Immunosuppressive effect of a human serum ferroprotein of hepatic origin, alpha 2 H globulin. Study on blastic transformation of normal lymphocytes in the presence of phytohemagglutinin].

The alpha2 H globulin, a glycoferroprotein, has been found in the serum of patients with malignant diseases. Its level varies according to the evolution of the disease. The activity of this protein has been studied on the normal lymphocytes cultivated in presence of phytohemagglutinin. This study has showed that 5 mug/ml of alpha2 H globulin can inhibit the blastic transformation. The inhibitory effect is proportional to the amount of alpha2 H globulin added as judged by the tritiated thymidin incorporation. The study of morphological aspects of the lymphocytes shows that alpha2 H globulin acts upon the synthesis of the cytoplasmic proteins.

Alpha-Globulins↗

Zoster immune globulin prophylaxis of disseminated zoster in compromised hosts. A randomized trial.

Herpes zoster can be a severe, and sometimes fatal, virus infection in its disseminated form in immunocompromised hosts. Previous studies have suggested that delay in appearance of antibody to varicella-zoster virus occurs as one defect in such patients. In this study, pooled gamma-globulin (normal serum globulin [NSG]) and zoster immune globulin ([ZIG] prepared from convalescent zoster patients) were compared for their ability to prevent dissemination of early localized zoster in immunocompromised hosts. Either agent was given intramuscularly in randomized double-blind fashion within nine days of onset of zoster in 97 patients. Despite greater than 100-fold differences in titer of anti-varicella-zoster virus antibody, ZIG did not appear superior to NSG in prophylaxis of dissemination or diminishing postherpetic pain in zoster in immunocompromised hosts. Zoster immune globulins should be reserved for prophylaxis and modification of varicella, where its beneficial effect has been demonstrated.

Antibodies, Viral↗

[Advisability of carrying out mass prevention of infectious hepatitis with gamma globulin].

In Vilnius 15,183 pupils in 20 schools were observed for two years; in October, 1966, gamma globulin prophylaxis of infectious hepatitis was carried out among all the pupils of these schools. 17.062 pupils in 27 schools, who received no gamma globulin, were used for control. At the end of the first year of observation morbidity rate among the immunized children was found to be considerably lower than among the school children of the control group. During the second year of observation morbidity rate among the children of the "old" immunized group increased 3.5-fold and did not significantly differ from morbidity rate among the children of the control group. The latter increased 1.8-fold. The authors have come to the conclusion that the effect of gamma globulin prophylaxis on the epidemic process depends on the method of such prophylaxis. The method of prophylaxis by introducing gamma globulin immunization with universal coverage, as the use of the former method is not followed by an increase in total morbidity (i.e. among both immunized and nonimmunized children) during the second year after immunization, which is observed after prophylaxis by universal immunization.

Child↗

Effect of antisomatostatin gamma-globulin on gastrin release in rats.

In order to determine the mechanism of endogenous gastric somatostatin in the regulation of gastrin release, antisomatostatin rabbit gamma-globulin was administered in vivo and in vitro in the rat. First, in rats anesthetized by chloral hydrate, intravenous injection of 1 ml antisomatostatin rabbit gamma-globulin had no significant effect on plasma gastrin levels. Second, basal gastrin release from the isolated perfused rat stomach was not affected by the administration of antisomatostatin rabbit gamma-globulin (1:99 and 1:1 dilutions). Third, the addition of antisomatostatin rabbit gamma-globulin (1:99) to incubated rat antral mucosa, however, significantly increased the basal gastrin release. From these results, it is concluded that antral somatostatin exerts its inhibitory effect on basal gastrin release mainly not through the circulation but via paracrine pathways.

Animals↗

[Natural antibodies against Pseudomonas aeruginosa in human gamma globulin preparations].

A total of 191 batches of commercial human gamma globulin were studied with the aim of detecting natural antibodies by means of cross and countercurrent electrophoresis, immunodiffusion in agar gel and the passive hemagglutination test. Commercial human gamma globulin preparations were found to contain, to a greater or lesser extent, natural antibodies to the cell-wall O-antigen of Ps. aeruginosa and the antigens of its extracellular slime (capsule); the titers of these antibodies were 1 : 64 to 1 : 256 in 75-85% of cases, 1 : 512 and greater in 10-11% of cases. Commercial gamma globulin preparations also contained antibodies protecting mice from experimental Pseudomonas infection. No correlation was detected between the degree of serological activity and the protective activity of gamma globulin preparations.

Animals↗

[Prevention of viral hepatitis B with specific gamma globulin. Results of 2 years' experience in a hemodialysis center].

Prophylaxis with gamma globulins specific for virus hepatitis B was carried out at the Trieste Haemodialysis Centre from December 1979 to December 1981. Since no clear distinction could be drawn between HBsAg-positive dialysed subjects, all staff and patients at the Centre were regarded as constantly at risk for contagion, and hence in the post-exposure state. Those who refused prophylaxis were excluded, together with surface antigen carriers and subjects with antibodies. Specific gamma globulins (Uman-Big) were given at a dose of 0.06 cc/kg at intervals of 90-105 days, together with 0.02 cc/kg standard gamma globulins for conjectured protection against non-A and non-B hepatitis. No allergic reactions worthy of not were observed. Only one patient positivised of all those who underwent continuous prophylaxis. New carriers of HBsAg gradually decreased in number from 1976 to 1981, initially due to the adoption of disposable filters, subsequently owing to partial separation of Au-positives, and finally, in a significant manner, with the introduction of prophylaxis with specific gamma globulins.

Hepatitis B↗

Antibodies to meningococcus polysaccharides in nonspecific gamma-globulins from different regions of the world.

Seventy-one batches of nonspecific gamma-globulin obtained from France, USSR and Mongolia were studied for presence of specific antibody to group A and C meningococcus polysaccharide. Specific activity was tested by two methods: radioimmunoassay (Lyon) and reaction of passive haemagglutination inhibition (Moscow). Antibodies were detected in all the gamma-globulin batches tested, in some of them at high titres. The summary results indicated that approximately equal levels of specific A antibodies were present in preparations obtained from the different regions of the world. Antibodies to group C polysaccharide showed considerable variation in level from selection country to country; the highest level of C antibodies was in gamma-globulin from France. The authors feel entitled by the results to recommend testing of nonspecific gamma-globulin, selection of batches with a high level of specific antimeningococcus antibodies, and their judicious use.

Antibodies, Bacterial↗

Effect of long-term administration of paromomycin sulfate on the level of serum albumin and gamma-globulin in human cirrhosis.

The efficacy of administration of oral paromomycin sulfate on serum albumin and gamma-globulin levels was studied in cirrhotic patients. After an observation period of 3 months, paromomycin sulfate at 2.0 g per day or a placebo was administered for 6 months, and changes in serum albumin and in gamma-globulin levels were examined every three months. Out of 16 cirrhotic patients treated with paromomycin, 11 (68.8%) showed significant increases in serum albumin compared with one out of 16 in the placebo group. Concerning gamma-globulin, seven (43.8%) patients in the paromomycin group showed significant decreases compared with one in the placebo group. In addition, among the 11 cirrhotics whose endotoxemia decreased after paromomycin administration, eight (72.7%) showed significant increases in albumin level. It was suggested that paromomycin improves the serum albumin and gamma-globulin levels in cirrhosis through the alleviation of endotoxemia caused by intestinal bacteria.

Clinical Trials as Topic↗

[Immunoglobulin FAB-fragments: specific activity and reactogenicity. III. Comparative study of the antigenic properties of anti-encephalitic gamma-globulin and FAB-fragments isolated from it].

Parenteral administration of antiencephalytic gamma-globulin and of the Fab-fragments, extracted from it, to rabbits stimulated the formation of specific antibodies. The maximal blood serum specific antibody level in rabbits reimmunized with Fab-fragments was much lower than that following the reimmunization of rabbits with gamma-globulin. Antibodies specific to gamma-globulin and Fab-fragments were concentrated in the gamma-globulin fraction of the immune sera and could be referred to the immunoglobulins of G class.

Animals↗

[Experimental analysis of the complement-binding activity of gamma-globulin].

It was experimentally demonstrated that the anticomplimentary characteristics of gamma-globulin perparations was associated with disturbances of the colloid condition of the serum system and the absence of any stabilizing action of albumin and other serum proteins. It is also expressed as a result of a high complement-binding activity of protein aggregates. The anticomplementary characteristics of the nonaggregated part of protein in commercial preparations of gamma-globulin could be depressed by the addition of albumin or fresh serum; as to the anticomplementary characteristics of protein aggregates -- it remains unchanged. An intermolecular electrostatic interaction exists between albumin and gamma-globulin; it prevents sorption of the complement on Fc-fragment of IgG, whose destruction leads to the manifestation of the gamma-globulin complement-binding activity.

Blood Proteins↗

[Detection of alpha2H-globulin in the blood serum in myocardial infarct].

The content of alpha2H-globulin in the plasma of 53 patients with macrofocal and 33 patients with microfocal myocardial infarction was determined in dynamics by the immunochemical method, with due account for the form and severity of the disease, the extent of involvement of the heart muscle, and the presence of complications and concomitant pathologic conditions of the lungs and kidneys. The frequency of alpha2H-globulin detection was 62% in macrofocal and 21% in microfocal myocardial infarction. In transmural myocardial infarction alpha2H-globulin is detected within the first 3 days of the disease in 37.5% of cases. The appearance of alpha2H-globulin in the blood plasma of patients with myocardial infarction is evidently associated with hypoxia and cell regeneration.

Adult↗

Rabies immune globulin (human) in the prevention of rabies.

The development of rabies immune globulin of human origin is discussed. Antirabies serum of equine origin when used in conjunction with rabies vaccine, enhances significantly the chances of survival after a severe bite by a rabid animal. However, those who receive the equine serum may develop serum sickness or even anaphylaxis. To circumvent this risk, while preserving the benefit, many workers have attempted to develop rabies immune globulin of human origin. Success was impeded by the difficulty in obtaining rabies immune plasma with the needed antibody level. Despite this and other obstacles, production of the human globulin on a scale sufficient to satisfy clinical needs has been finally realized. At the appropriate dosage, this globulin was demonstrated to interfere minimally, if at all, with the expression of active immunity induced by vaccination.

Animals↗

Within- and between-subject biological variations of follitropin, lutropin, testosterone, and sex-hormone-binding globulin in men.

The within-subject and between-subject biological variation of the serum concentrations of follitropin, lutropin, sex-hormone-binding globulin, and testosterone; the ratio between the serum concentrations of testosterone and sex-hormone-binding globulin; and the concentration of testosterone in saliva have been studied in a group of 20 men during 12 months. The between-subject coefficients of variation (CVs) were 36.0% for follitropin, 37.0% for lutropin, 42.7% for sex-hormone-binding globulin, 21.3% for testosterone in serum, 28.8% for testosterone in saliva, and 51.6% for the ratio between serum concentrations of testosterone and sex-hormone-binding globulin. The medians of the within-subject CVs for the respective analyses and ratio were 17.3%, 24.0%, 12.1%, 10.9%, 17.3%, and 9.4%. These data were used to calculate the desirable imprecision, the critical difference for significant change detection, and the index of individuality.

Adult↗

[Isoelectrofocusing on polyacrilamide gel in the study of gamma-globulin changes during neurological illnesses (author's transl)].

Isoelectrofocusing on polyacrilamide gel in the analysis of cerebrospinal fluid proteins is particularly suitable for investigations of gamma-globuline changes in the course of various neurological conditions. This technique makes it possible to recognise three patterns besides the normal one. The first is characterized by a diffuse increase in gamma-globulines with a great number of high density fractions showing uniform distribution in the alkaline pH area. It was observed in a case of Guillain-Barrè syndrome and in two cases of intramedullary tumours. It seems to be due to an alteration in the permeability of the blood-brain barrier. The second pattern shows a diffuse increase in the number of fractions and appears uneven owing to a certain amount of higher density bands which stand out clearly. This was observed in one case of tubercolous meningo-encephalytis, in one case of chickenpox encephalytis and one case of cryptococcal meningitis in a patient affected by lymphogranuloma. This pattern is probably due to an alteration of blood-brain as well as of immunological systems. The third pattern presents a clear fractionation of gamma-globulins gathered in a certain number of highly coloured bands, mainly in the most alkaline area of gel. This was observed in all the ten cases of multiple sclerosis and in the only case of subacute sclerosing panencephalitis. This may be attributed to the intrathecal production of oligoclonal gamma-globulines (Ig.G.).

Blood-Brain Barrier↗