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Investigation of putative androgen-like activity of alpha 2u-globulin in castrated and estrogen-treated male rats.

alpha 2u-Globulin, a male sex-dependent protein of the rat, was tested for its ability to produce androgenic or anabolic responses. Castrated rats were injected with alpha 2u-globulin isolated from urine or kidney and the effects on urinary nitrogen excretion, body weight, and weight of ventral prostate, seminal vesicles, and levator ani muscle were studied. alpha 2u-Globulin had no effect but testosterone propionate gave the expected stimulation of nitrogen retention, body growth, and growth of androgen-responsive tissues. alpha 2u-Globulin injected into estrogen-treated male rats (animals with suppressed serum levels of alpha 2u-globulin, gonadotropins, and testosterone) was also found to be without effect on body weight and on the weight of ventral prostate, seminal vesicles, levator ani muscle, and testes. We conclude that the alpha 2u-globulin molecule, by itself, is incapable of producing, directly or indirectly, androgenlike responses.

Alpha-Globulins↗

[Study on the therapeutic effects of interferon and gamma-globulin in experimental Pneumocystis carinii pneumonia].

This study was performed to observe the therapeutic effects of interferon-gamma(IFN-gamma) and gamma-globulin(gamma-globulin) in experimental Pneumocystis carinii pneumonia of immune suppressed mice. After 9 weeks, trimethoprim-sulfamethoxazole(TMP-SMZ; 10-50 mg/mouse/day), mouse IFN-gamma(5 x 10(4) units/mouse/day) and mouse gamma-globulin(20 mg/mouse/day) were administered to the mice for 3 weeks by the experimental group. The therapeutic efficacy was evaluated by body weights, histopathologic and electron microscopic findings of the lungs, and number of P. carinii cysts by Gomori's methenamine silver stain. Body weights of the mice were significantly increased in the group of combination therapy of TMP-SMZ with IFN-gamma or gamma-globulin, and in the group of TMP-SMZ treatment (p < 0.05), however, little effect was found in the group of gamma-globulin alone. Histopathologic findings of P. carinii pneumonia were much improved in the group of combination therapy of TMP-SMZ with IFN-gamma. Treatment with either TMP-SMZ or IFN-gamma significantly reduced the number of cysts in the P. carinii pneumonia, but gamma-globulin alone was ineffective. In electron microscopic findings of P. carinii pneumonia, the number of trophozoites and cysts were reduced by treatment with either TMP-SMZ or IFN-gamma, and most of the cysts were empty or containing one or two intracystic bodies. The present results suggested, that combination therapy of TMP-SMZ with IFN-gamma had synergistic effects in treatment of P. carinii pneumonia in experimental mice.

Animals↗

The utilization of an index for serum globulin compensation in diseases associated with decreased serum albumin.

The albumin globulin ratio (A/G ratio) is meant to represent the ratio of alterations in serum proteins, since, in liver disease, globulins (G) rise following serum albumin (SA) decrease. pathophysiological value, its' use has been limited. Alternatively, we have developed an index, the globulin compensation index (GCI) to measure the changes in serum globulins when albumin is decreased. The index is calculated as follows: G - 25 / 35 - SA. The GCI has been tested using retrospective patients' data from the Hospital Universiti Sains Malaysia. Analysis of the data shows that the GCI may be of potential value in showing the actual serum protein status, especially in cases where globulins are decreased along with albumin. Furthermore, globulin rise in cases with reduced albumin was found in 72.3% of cases of hepatic diseases, whereas this finding occurred in up to 32.3% of cases of non-hepatic, systemic diseases.

Humans↗

Identification of nuclear proteins that bind to the glucocorticoid regulatory region of a rat alpha 2u-globulin gene.

The induction of rat alpha 2u-globulin by glucocorticoids is a secondary response to the hormone, that is protein synthesis is absolutely required for induction. Using the DNase I protection assay, we have identified three proteins present in rat liver nuclei that bind in or near the regulatory region of a cloned alpha 2u-globulin gene. One protein which we term alpha 2u-globulin nuclear factor 1 (alpha 2uNF1), binds to precisely the sequence we have previously shown to be required for hormonal induction. Genes containing linker-scanning mutations in this region show diminished binding to this nuclear factor and display greatly reduced or abolished glucocorticoid response. alpha 2uNF1 was detected in nuclei from several sources, and its level is apparently unaffected by glucocorticoids. Its recognition sequence is unlike those of previously reported transcription factors. We detect two other proteins, alpha 2uNF2 and alpha 2uNF3, that bind near the alpha 2u-globulin regulatory region. A mutant alpha 2u-globulin promoter which does not bind alpha 2uNF2 shows increased inducibility by glucocorticoids in transfected mouse L-cells. The binding of alpha 2uNF3 is not required for alpha 2u-globulin induction by the hormone.

Alpha-Globulins↗

[The effect of human gamma globulin on tbe production of antibodies to the surface antigen of the hepatitis B virus in an experiment on animals].

The biological assay for the determination of HBsAg in gamma globulin is proposed. The assay is based on the immunizing action of immune complexes and some specific features of secondary immune response. For this purpose, the highly purified preparation of HBsAg is injected into guinea pigs. Subsequently the animals receive human gamma globulin. An increase in the titer of anti-HBsAg antibodies in the animals preimmunized with the antigen is indicative of the presence HBsAg in human gamma globulin. In accordance with another variant of this assay, human gamma globulin is introduced into mice and 21 days later the animals are immunized with HBsAg. The appearance of anti-HBsAg antibodies in the animals, previously treated with gamma globulin, on day 4 after the injection of the antigen indicate that the animals experience the second penetration of HBsAg, i. e. its presence in previously injected human gamma globulin.

Animals↗

High-dose intravenous gamma-globulin therapy in Kawasaki disease.

The efficacy for reduction of coronary aneurysm in Kawasaki disease was studied from 1984 to 1988 in Taiwan. One hundred and six children with Kawasaki disease were treated by one of the following regimens: regimen I: aspirin and 130-200 mg/kg/day of intravenous gamma-globulin (group I = 7), regimen II: 201-400 mg/kg/day of intravenous gamma-globulin with aspirin (group II = 49) and regimen III: aspirin alone (group III = 43) and no treatment (group IV = 7). By using two-dimensional echocardiography and aortography, the coronary arterial aneurysms noted in group I, II, III and IV were 42.9%, 49.0%, 44.2% and 16.7% respectively within 4 weeks of the illness and were 28.6%, 18.4%, 16.4% and 16.7% respectively during the follow-up period of 11.4 +/- 8.2 months. The incidence of coronary aneurysm was reduced significantly (p less than 0.005) in patients with high-dose gamma-globulin therapy and with aspirin therapy alone. However, there was no difference between group II and III, probably due to delays in the time of start of prophylactic gamma-globulin therapy. There was also significant lower incidence of the giant coronary aneurysm in children with high dose gamma-globulin therapy and with aspirin therapy. (p less than 0.05) The incidences of giant aneurysm in groups I, II, III and IV were 28.6%, 2.0%, 4.7% and 14.3% respectively. These results suggest that even with delay in the time of start of prophylactic gamma-globulin therapy, it still can reduce the formation of giant coronary aneurysm.

Adolescent↗

Dynamic changes of horse serum T-globulin immunization with snake venoms, tetanus and diphtheria toxoids.

In course of immunizing horses with snake venoms, tetanus and diphtheria toxoids, a new serum component, T-globulin, was formed and migrated between the beta- and gamma-globulins. The T-globulin content was parallel with the antibody titre after the middle course of immunization. There were many components in snake antivenin and T-globulin was composed of most of those components. The components of diphtheria T-globulin were the same as those of crude antitoxin and tetanus T-globulin except one precipitin.

Animals↗

Age-dependent regulation of the polymorphic forms of alpha 2u-globulin.

Hepatic synthesis of alpha 2u-globulin in the male rat shows a gradual decline and ultimate loss during aging and senescence. Northern blot analysis with a cloned cDNA probe showed that the decrease in alpha 2u-globulin synthesis during aging is associated with a corresponding decrease in the concentration of its hepatic mRNA. By means of two-dimensional gel electrophoresis, alpha 2u-globulin is resolved into a family of proteins. A monoclonal mouse antibody can identify at least five major isoelectric variants of alpha 2u-globulin within the total protein synthesized by rat hepatocytes. These isoelectric variants are also present in the in vitro translation products of hepatic mRNA. An examination of the hepatic synthesis of the isoelectric variants of alpha 2u-globulin during aging showed a differential regulation of the variant forms of this protein. Variant 2 (pI 6.1, the most prominent form) is the first to appear at puberty (40 days). The weakest member of the five major isoelectric forms (variant 4, pI 4.1) is the last to disappear at senescence. Although the overall decline in alpha 2u-globulin synthesis during aging seems to be due to an age-dependent decrease in the androgen responsiveness of hepatocytes, it is postulated that the differential regulation of the isoelectric variants may represent changes at the level of the genes coding for this protein.

Aging↗

Generation of suppressor cells by aggregated human globulin.

We have studied the capacity of aggregated human globulin, a model for immune complexes, to induce suppressor cells which modulate a predominantly T cell response, i.e. the proliferative response of autologous mononuclear cells to concanavalin A. We utilized a soluble aggregated human globulin preparation depleted of both high molecular weight (greater than 4 x 10(6) daltons) insoluble aggregates and monomeric IgG. The mean per cent suppression induced by mononuclear cells preincubated with aggregated human globulin for 96 hr was 39 +/- 8%; monomeric IgG did not induce significant suppression (4 +/- 6%). We found a close correlation between the magnitude of suppression induced by preincubation for 96 hr with aggregated human globulin and that induced by preincubation with concanavalin A. Kinetic analysis indicated that suppressor cell induction by aggregated human globulin required 48 hr of preincubation; suppressor cell induction by concanavalin A required 24 hr. Aggregated human globulin-induced suppression was not associated with DNA synthesis as measured by 3H-thymidine uptake. The findings suggest that immune complexes can modulate immunoregulation.

Adult↗

[Content of micro- and macro-elements, lead and cadmium in albumins and globulins of fresh and stored, dried seeds of the Faba bean].

The content of micro/macroelements, lead and cadmium in Faba bean proteins from the seeds after their harvest and from the seeds stored (2 months, 6-8 degrees C) and dried (6h at 35 degrees C up to 15-15% moisture) was determined. Proteins were extracted with water (pH 8.0). Globulins were precipitated from water protein extract at pH 4.2. The microelements (Cu, Mn, Fe and Zn) content in albumins and globulins from the seeds after their harvest and from stored and dried seeds were as follows: 37.4 and 27.1; 46.7 and 35.8; 15.4 and 18.9; 179.2 and 229.7 micrograms/g (albumins) and 24.9 and 31.9; 20.0 and 28.1; 92.1 and 205.4; 68.7 and 102.9 micrograms/g (globulins). These findings indicate that Faba bean albumins and globulins form the labile and neutral nucleo-glycoprotein complexes with Cu, Mn, Fe and Zn. The process of storage and drying caused the migration of the micro and macroelements between albumins and globulins. Generally, one may say that Faba bean albumins and globulins are the source of the biologically active micro- and macroelements.

Albumins↗

Evaluation of the prophylactic effect of gamma globulin in meningococcal infection.

Results of two controlled epidemiological tests evaluating the prophylactic effect of gamma globulin of Monogolian and Soviet production against meningococcal infection are presented. Observations were carried out on children aged 3 months to 4 years, not attending children's establishments. The results of the observation revealed the following prophylactic effect of gamma globulin of Mongolian production in the first two months after administration: index of efficiency--5.0, coefficient of efficiency--80%, P greater than 0.01. The efficiency of the prophylactic effect of Soviet gamma globulin was limited to one month: the index of efficiency amounted to 5.3, the coefficient of efficiency to 82.2%, P greater than 0.01. The course of meningococcal infection in the children who had received gamma globulin was less severe than in the children of the control group. Lethal outcome was recorded only in the group of children who had not received gamma globulin. The duration of the prophylactic effect of gamma globulin was found to depend on the height of the titres of specific antibodies in the preparation. The preparations are recommended as prophylactic means for children aged from 3 months to 4 years in doses of 1.5 ml (one dose) in the foci of meningococcal infection.

Child, Preschool↗

Lower total serum protein, albumin, and beta- and gamma-globulin in major and treatment-resistant depression: effects of antidepressant treatments.

Strong evidence has recently been reported that major depression is accompanied by an acute phase response (APR), characterized by elevated levels of positive acute phase proteins (APPs) and decreased levels of negative APPs. The APR is also reflected in lowered total serum protein (TSP) and specific changes in the major electrophoretically separated protein fractions. The present study examined pretreatment and posttreatment serum TSP and the concentrations and percentages of the major electrophoretically separated serum protein fractions in 37 major depressed subjects, of whom 29 had treatment-resistant depression (TRD), and in 29 normal controls. We found that TSP and the percentage and concentration of serum albumin (Alb) and gamma-globulin fraction were significantly lower in major depression and TRD than in normal controls. Serum beta-globulin concentrations were significantly lower in major depressed and TRD subjects than in normal controls. The percentages of the alpha 1- and alpha 2-globulin fractions were significantly higher in major depressed subjects than in normal controls. There were no significant effects of subchronic treatment with antidepressants on TSP, the percentage or concentration of the major electrophoretically separated protein fractions, i.e. alpha 1-, alpha 2- and beta-globulin. There was a significant increase in percentage of the gamma-globulin fraction after subchronic treatment with antidepressants. The results support the hypothesis that major depression and TRD are accompanied by a chronic APR.

Acute-Phase Proteins↗

THE IMMUNOGLOBULINS OF MICE. I. FOUR MAJOR CLASSES OF IMMUNOGLOBULINS: 7S GAMMA-2-, 7S GAMMA-1-, GAMMA-1A (BETA-2A)-, AND 18S GAMMA-1M-GLOBULINS.

Two classes of 7S gamma-globulins are identified in normal mouse serum and are designated 7S gamma(2)-globulins and 7S gamma(1)-globulins. These two immunoglobulin classes are similar in size. They differ in range of electrophoretic mobility, in specific antigenic determinants, and in genetically determined isoantigens. Four classes of immunoglobulins in mouse serum, i.e. 7S gamma(2)-, 7S gamma(1)-, gamma(1A) (beta(2A)), and gamma(M)-globulins, were shown to have antibody activity. Each class was characterized and shown to have distinctive immunochemical and physicochemical properties. The genetically determined isoantigens, Iga-1 and Iga-2, were shown to be present only on 7S gamma(2)-globulin molecules.

Animals↗

Impact of respiratory syncytial virus immune globulin in 1996-1997: a local controlled comparison.

BACKGROUND: Immune globulin containing high titers of neutralizing antibodies specific for respiratory syncytial virus (RSV) is clinically used to prevent hospitalizations for RSV-related respiratory infections among high-risk infants. However, recommendations regarding which patient populations should receive RSV immune globulin are inconsistent. OBJECTIVE: To compare hospitalization rates for prematurely born infants with and without chronic lung disease who received RSV immune globulin with similar infants whose parents refused such treatment during the 1996-1997 winter season. DESIGN: Inception cohort study. PARTICIPANTS: Infants born at less than 35 weeks' gestation and less than 6 months old without lung disease and children who had been born prematurely, had chronic respiratory disease, and were less than 2 years old at the onset of the RSV season. MAIN OUTCOME MEASURE: Hospitalization for an RSV-related respiratory illness. RESULTS: Seventy-six infants (66 [87%] with chronic lung disease and 10 [13%] born prematurely without lung disease) received RSV immune globulin; 65 infants (18 [28%] with chronic lung disease and 47 [72%] born prematurely without lung disease) did not. Three (4%) of the treated group and 2 (3%) of the untreated group were hospitalized for RSV infections. Of those with chronic lung disease, 5% (3/66) of those treated with RSV immune globulin were hospitalized, compared with 11% (2/18) of those untreated. Of those born prematurely without lung disease, no infant in the treated (0/10) or untreated (0/47) group was hospitalized. CONCLUSIONS: The risk of hospitalization of infants born prematurely who are younger than 6 months without lung disease is low. Current recommendations for preventing RSV illness in this group by using RSV immune globulin may require inclusion of more specific clinical characteristics rather than gestational age alone.

Chronic Disease↗

Human cytomegalovirus hyperimmune globulin not only neutralizes HCMV infectivity, but also inhibits HCMV-induced intracellular NF-kappaB, Sp1, and PI3-K signaling pathways.

Inhibition of virus-induced intracellular signaling pathways and viral infectivity are our ultimate goals in the development of effective antiviral agents to control human cytomegalovirus (HCMV) infections. The HCMV hyperimmune globulin may meet such criteria. In a human embryonic lung (HEL) fibroblast culture model, pretreatment of Towne strain HCMV with HCMV hyperimmune globulin was shown to inhibit viral infectivity successfully, as measured by a standard plaque assay. The extracellular viral titers and extracellular viral DNA, as measured by plaque assay and PCR, respectively, were also decreased. In addition, the HCMV hyperimmune globulin prevented HCMV from inducing the intracellular activation of NF-kappaB, Sp-1, and PI3-K signaling pathways. The PI3-K pathway was examined by following phosphorylation (activation) of two of its downstream kinases, Akt and p70S6K. HCMV hyperimmune globulin also prevented the production of immediate early, early, and late viral proteins. These studies show that HCMV hyperimmune globulin neutralization of HCMV prevents the earliest known events observed after viral envelope glycoproteins bind their cell membrane receptors, i.e., NF-kappaB, Sp-1 and PI3-K activation. This suggests that HCMV hyperimmune globulin not only can inhibit viral infectivity, but can also prevent the abnormal cellular signaling that may induce unwanted cellular proliferation or cytokine synthesis.

Capsid↗

Evaluation of the safety and immunogenicity of a new, heat-treated human rabies immune globulin using a sham, post-exposure prophylaxis of rabies.

A double-blind, controlled, randomized trial was conducted to evaluate the safety and immunogenicity of a new human rabies immune globulin (HTRIG). This product, manufactured by Pasteur Merieux Connaught, PMC, has undergone a heat-treatment step (10 h at 60 degrees C) and removal of mercurothiolate. The corresponding unheated product available from the same manufacturer (human rabies immune globulin, HRIG, IMOGAM RABIES[spr2]) was used for comparison. These two rabies immune globulins (RIGs) were administered either alone or in association with the human diploid cell rabies vaccine (HDCV, IMOVAX[spr2] RABIES, PMC) according to a standard, post-exposure rabies prophylaxis schedule. Sixty-four healthy adults were randomly assigned to four groups of 16 to receive either HRIG/placebo, HTRIG/placebo, HRIG/HDCV or HTRIG/HDCV. RIG was administered at the recommended dose of 20 IU/kg by three intramuscular (i.m.) injections in the gluteus. HDCV or placebo was given on day (D) 0, D3, D7, D14, and D28 into the deltoid by the intramuscular (i.m.) route. Any local reaction from D0 to D3 at the immune globulin injection site, and any systemic reaction from D0 to D42, were monitored by subject diaries. Rabies-neutralizing serum antibody levels were assessed by the rapid fluorescent focus inhibition test (RFFIT) before treatment and on D3, D7, D14, D28, D35, and D42. No serious adverse reactions and, in particular, no allergic-type reactions were reported. The safety profiles of HTRIG and HRIG were similar, except that complaints of pain, or tenderness at the injection site were half as common in the HTRIG group. Most of the local reactions were mild or moderate. After the administration of HTRIG/placebo or HRIG/placebo, 60% of subjects had detectable rabies antibodies levels, but by D42 all titres were below the seroprotective level (i.e. below 0.5 IU/ml). In the groups HTRIG/HDCV and HRIG/HDCV, the antibody titres rose markedly from D7, and reached a maximum value of 19 IU/ml (95% CI, 11 to 38 IU/ml) and 31 IU/ml (95% CI, 20 to 48 IU/ml), respectively, on day 14. All subjects who received RIG and vaccine maintained a protective antibody level from D14 to D42. No significant difference in immunogenicity results between these two groups (HTRIG/HDCV and HRIG/HDCV) was observed, and no interference of immune globulin with vaccine was reported. The safety and immunogenicity profiles of PMC HTRIG appear comparable with the current reference product. The heat-treatment step will enhance the safety by further reducing the probability of virus transmission through immune globulin treatment. The low levels of rabies antibodies obtained by intramuscular administration of either PMC HTRIG or of PMC HRIG support the recommendations that call for local infiltration of wounds with RIG.

Adolescent↗

A novel cereal storage protein: molecular genetics of the 19 kDa globulin of rice.

A lambda gt11 cDNA library, constructed from poly(A)+ RNA isolated from immature rice seed endosperm, was screened with affinity-purified antibodies against the rice storage protein called alpha-globulin (previously), or the 19 kDa globulin (our term). A positive clone was isolated and sequenced and shown to encode a 21 kDa precursor for the 19 kDa globulin, based on the identity of portions of the inferred amino acid sequence and the sequence of three cyanogen bromide peptides of the 19 kDa globulin. Analysis of genomic DNA by Southern blotting using the cDNA clone probe revealed one hybridizing band in Eco RI, Hind III, and Bam HI digests. This strongly suggests that the 19 kDa globulin is encoded by a single-copy gene. Because of its single-copy nature and its abundance of Arg and lack of Lys, the 19 kDa rice globulin appears to be a particularly attractive target for genetically engineering increased Lys content in rice seeds.

Amino Acid Sequence↗

Modulation of functional activity of human polymorphonuclear and mononuclear phagocytes by intravenous gamma globulin.

Intravenous gamma-globulin was tested in a range of concentrations compatible with the increments obtained after therapeutic infusions for modulation of phagocytic functions of human polymorphonuclears (PMNs) and monocytes. Intravenous gammaglobulin in concentrations of 3.0 mg/ml or more increased adhesiveness and suppressed chemotaxis of PMNs. There was marked dose-dependent enhancement of opsonization of gram-positive and gram-negative microorganisms. Preincubation of PMNs with intravenous gamma-globulin caused enhancement of the total bacteria ingested, total bacteria killed, phagocytosis, and phagocytic index, when gram-positive and gram-negative bacteria were tested. During phagocytosis, there was no release of LDH or lysozyme; however, there was release of beta-glucuronidase. No significant difference in phagocytic enhancement was found when filtered and native intravenous gamma-globulin preparations were compared. There was marked enhancement of the superoxide anion generation by intravenous gamma-globulin above the concentration of 0.01 mg/ml. Intravenous gamma-globulin also markedly enhanced phagocytic activity of monocytes. Therefore, intravenous gamma-globulin modulates not only opsonization-related phenomena, but also exerts a complex influence on other aspects of phagocytic activity.

Blood Bactericidal Activity↗