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PubMed1961

Specificity of the reaction between rheumatoid factors and gamma globulin.

Rheumatoid factors in the sera of patients with rheumatoid arthritis appear to be specifically directed against genetically determined "antigens" in human gamma-globulin. At least eight rheumatoid factors of differing specificity exist; usually several are present in combination in the same serum. The different rheumatoid factors can be readily detected through their pattern of reactivity with anti-Rh antibodies from different individuals. Rheumatoid factors in diseases other than rheumatoid arthritis were found to have a more restricted specificity, contrasted to the broader reactivity of the factors in most rheumatoid arthritis sera. A specificity similar to that for incomplete antibodies was not demonstrated for the reaction of rheumatoid factors with aggregated gamma-globulin or with gamma-globulin to form the "22S complex." In certain instances, using the anti-Rh system, rheumatoid factors were found to react poorly with the patient's own gamma-globulin, compared to that of other individuals of different genetic gamma-globulin types. These results, as well as additional indirect evidence, indicate that the rheumatoid factors can possess isospecificity. However, a certain degree of autospecificity was also found which was most clearly evident through complex formation with the patients own gamma-globulin and in the reaction with aggregates. The relevance of these findings to possible isoantibody as well as autoantibody concepts is discussed.

Antibodies, Anti-Idiotypic↗
PubMed1952

Experimental hyperglobulinemia; the effect of injected ribonucleotide on serum globulin levels in rabbits undergoing immunization.

It was shown, by means of salt fractionation procedures and electrophoresis that a marked and sustained hyperglobulinemia regularly resulted when sodium ribonucleate was injected subcutaneously at frequent intervals into rabbits undergoing immunization with horse serum. The hyperglobulinemia was characterized by a large increase in the gamma globulin levels, and a slight increase in the alpha and beta globulin levels. In control experiments done concurrently, the immunization of rabbits with horse serum, accompanied by subcutaneous injections of saline instead of ribonucleate, resulted in only moderate elevations in gamma globulin levels, while injections of ribonucleate alone brought about slight elevations in all three globulin components in some of the animals. Precipitin tests showed that the rabbits immunized with horse serum and simultaneously treated with ribonucleate developed antibody titers against horse serum that were no higher than those of the immunized controls given saline instead of ribonucleate. Indeed, some of the animals treated with horse serum and ribonucleate had globulin levels that were much higher and had antibody titers that were significantly lower than were those of several rabbits receiving horse serum and saline. Injections of ribonucleate alone did not result in the formation of specific antibodies detectable by means of precipitin tests. The results made it plain that the hyperglobulinemia of the animals treated with horse serum and ribonucleate was not due to an excessive production of specific antibodies. The findings as a whole provide further evidence that nucleotides play an important role in the formation of proteins in animals, and they indicate that an abnormally increased utilization of ribonucleotides by cells capable of producing globulins may be a causative factor in the pathogenesis of hyperglobulinemia.

Animals↗
PubMed1992

[The effect of ascitic fluid globulins on the growth of leukemia P388/DOX and Ehrlich's carcinoma in mice].

The study was performed to investigate the effect of ascitic fluid globulins of tumor on tumor growth and life span of mice. The globulins are shown to shorten the life span of Ehrlich tumor mice from 86.8 to 61.8 days, to increase 3-5-fold the growth rate of Ehrlich carcinoma and P388/DOX tumor. It was found that globulins of ascitic fluids and serum globulins of tumor have equal effects of tumor growth. It is proposed to use globulins of ascitic fluid to study the globulin role in tumor growth.

Animals↗
PubMed1964

EQUINE ANTIHAPTEN ANTIBODY. I. 7S BETA-2A- AND 1OS GAMMA-1- GLOBULIN COMPONENTS OF PURIFIED ANTI-BETA-LACTOSIDE ANTIBODY.

Anti-p-azophenyl-beta-lactoside (Lac) antibody has been isolated from equine antiserum by specific precipitation with Lac-HSA (human serum albumin) and Lac-Hy (hemocyanin). Antibody was separated from antigen by chromatography on DEAE cellulose and zone electrophoresis in solvents containing lactose. Six antigenically distinct immunoglobulins have been identified in purified equine anti-Lac antibody: 7S beta(2A)-globulin, 19S gamma-globulin, a 10S gamma(1) globulin, and three antigenically distinct 7S gamma-globulins. The specific hapten-binding activity of the 7S beta(2A)-antibody and of the 10S gamma(1)-antibody has been demonstrated by equilibrium dialysis and by analytical ultracentrifugation using a combination of schlieren and absorption optics. The 10S gamma(1)-globulin antibody may be representative of a hitherto undescribed class of immunoglobulins.

Animals↗
PubMed1993

Gamma-globulin modulates growth of EBV-derived B-cell tumors in SCID mice reconstituted with human lymphocytes.

The effect of weekly gamma-globulin injection on the development of human B-cell tumors was studied in 120 mice with severe combined immunodeficiency (SCID). The mice were injected intraperitoneally (i.p.) with human peripheral mononuclear cells (PBMC) from 6 different Epstein-Barr virus (EBV)-seropositive donors. Animals repopulated with cells from 5 donors received gamma-globulin or saline for 20 weeks and were followed up to 24 weeks after reconstitution. A delay in the appearance of fata EBV-derived human B-cell tumors was noticed in the gamma-globulin-treated groups as compared to the controls. In a separate experiment, the effect of gamma-globulin treatment during the initial 4 weeks after reconstitution was compared to treatment from week 5 to week 8 as well as to a continuous 20-week treatment. The results from this experiment showed that B-cell tumor growth could be prevented just as efficiently when the animals were treated only during the first 4 weeks. In contrast, no preventive effect was seen when the first gamma-globulin dose was given at the beginning of week 5 after reconstitution. Our results indicate that gamma-globulin reduces the frequency of EBV-derived B-cell tumor development and suggest that SCID mice repopulated with human cells represent a useful in vivo model for evaluation of the prophylactic and/or therapeutic effects of immunomodulatory treatments in lympho-proliferative disorders associated with immunosuppression.

Animals↗
PubMed1993

Nucleotide sequence of an abundant rice seed globulin: homology with the high molecular weight glutelins of wheat, rye and triticale.

A cDNA clone corresponding to a 19 kD salt-soluble globulin of rice (Oryza sativa L.) was isolated by screening a lambda gt11 expression library of endosperm mRNA with antibodies raised against the purified rice seed alpha-globulin. The cDNA contained a single large open reading frame encoding a putative globulin precursor of molecular weight of 21 kD. The polypeptide consists of 182 amino acids and is devoid of lysine residues. Computer analysis of the NH2-terminal sequence of the globulin precursor protein indicated the presence of an 18 amino acid signal peptide. Segments of the amino acid sequence of the rice globulin were homologous with sequences in high molecular weight glutelins of wheat. Antibodies specific for rice seed globulin also cross-reacted with seed proteins from wheat, rye and triticale.

Amino Acid Sequence↗
PubMed2004

Sex-hormone-binding globulin is negatively correlated with femoral bone-mineral density in male cardiac-transplant recipients.

BACKGROUND: Osteoporosis and the subsequent increase in incidence of fractures are a common problem after cardiac transplantation. DESIGN: We performed a cross-sectional evaluation of male cardiac-transplant recipients in a late post-transplantation period (4.2 +/- 2.6 years after cardiac transplantation, n = 21). Bone-mineral density was measured by dual-energy X-ray absorptiometry and by quantitative heel ultrasound, and the endocrine characteristics of cardiac-transplant recipients with and without vertebral fractures were investigated. RESULTS: A significant negative correlation was observed between sex-hormone-binding globulin and femoral-neck bone-mineral density (rs = -0.699; p value = 0.001). Linear regression analysis controlling for age and body-mass index proved sex-hormone-binding globulin to be an independent negative predictor for femoral-neck bone-mineral density (r = -0.474; p value = 0.035). Patients with vertebral fractures had significantly lower femoral-neck bone-mineral density (pvalue = 0.035). However, sex-hormone-binding globulin, total and free testosterone, and estradiol did not exhibit significant associations with vertebral fractures in our patients. CONCLUSION: This investigation demonstrates for the first time an association between high sex-hormone-binding globulin levels and low femoral-neck bone-mineral density in a cohort of male cardiac-transplant recipients. Our data support the important role of sex-hormone-binding globulin in the pathogenesis of post-transplantation bone disease, although--possibly because of the small number of patients--we could not prove an interrelation of sex-hormone-binding globulin with vertebral fractures.

Adult↗
PubMed2001

Differential tissue-specific expression of cysteine proteinases forms the basis for the fine-tuned mobilization of storage globulin during and after germination in legume seeds.

The temporal and spatial distribution of cysteine proteinases (CPRs) was analyzed immunologically and by in situ hybridization to identify the CPRs involved in the initiation of storage-globulin degradation in embryonic axes and cotyledons of germinating vetch (Vicia sativa L.). At the start of germination several CPRs were found in protein bodies in which they might have been stored in the mature seeds. Cysteine proteinase 1 was predominantly found in organs like the radicle, which first start to grow during germination. Cysteine proteinase 2 was also present at the start of germination but displayed a less-specific histological pattern. Proteinase B was involved in the globulin degradation of vetch cotyledons as well. The histological pattern of CPRs followed the distribution of their corresponding mRNAs. The latter were usually detected earlier than the CPRs but the in situ hybridization signals were histologically not as restricted as the immunosignals. Proteolytic activity started in the radicle of the embryonic axis early during germination. Within 24 h after imbibition it had also spread throughout the whole shoot. At the end of germination, newly synthesized CPRs might have supplemented the early detectable CPRs in the axis. In the cotyledons, only the abaxial epidermis and the procambial strands showed proteinase localization during germination. Both CPR1 and CPR2, as well as the less common proteinase B, might have been present as stored proteinases. Three days after imbibition, proteolytic activity had proceeded from the cotyledonary epidermis towards the vascular strands deeper inside the cotyledons. The histochemical detection of the CPRs was in accordance with the previously described histological pattern of globulin mobilization in germinating vetch [Tiedemann J, et al. (2000)]. A similar link between the distribution of CPRs and globulin degradation was found in germinating seeds of Phaseolus vulgaris L. The coincidence of the histological patterns of globulin breakdown with that of the CPRs indicates that at least CPR1, CPR2 and proteinase B are responsible for bulk globulin mobilization in the seeds of the two legumes.

Biological Transport, Active↗
PubMed1981

A possible variant of thyroxine-binding globulin in Australian Aborigines.

We have recently described a major variation from the normal levels of serum thyroxine-binding globulin in many Australian Aborigines [1]. Subsequently we presented evidence that affected individuals were widely distributed throughout Australia, that "low values of thyroxine-binding globulin were not caused by environmental or health factors, but were inherited in an autosomal dominant fashion [2]. Refetoff [3] has shown that the cause of genetically determined low thyroxine-binding globulin levels in Caucasians is alteration in synthesis rate without any structural variation of the protein. Since however the "low" thyroxine-binding globulin of Aborigines is vastly more prevalent and genetically distinct from the X-linked type, we investigated the possibility that this may be a structural variant. Evidence suggestive of this includes results from heat inactivation, competitive binding of thyroxine to thyroxine-binding globulin to measure affinity, and use of a radioimmunoassay different from that used in the original work. The "Low thyroxine-binding globulin of Aborigines may be a protein with a structural variation at or near the binding site for thyroxine, resulting in low affinity for thyroxine and hence "low" results with assay methods which depend upon the thyroxine binding site. Since the Australoid peoples, to whom Australian Aborigines are racially related, are distributed widely throughout the southern hemisphere it is important to establish whether this variant is found outside Australia in order to avoid the likelihood of misdiagnosis of thyroid disease in such subjects.

Australia↗
PubMed1989

Involvement of reversible binding to alpha 2u-globulin in 1,4-dichlorobenzene-induced nephrotoxicity.

Similarly to unleaded gasoline, 1,4-dichlorobenzene (1,4-DCB) administered for 2 years caused a dose-related increase in the incidence of renal tumors in male but not in female rats or in either sex of mice. Unleaded gasoline and 2,2,4-trimethylpentane (TMP), a component of unleaded gasoline, increased protein droplet formation and cell proliferation in male but not in female rat kidneys. These protein droplets contained, alpha 2u-globulin, a male rat-specific low-molecular-weight protein and 2,4,4-trimethyl-2-pentanol, a metabolite of TMP that was reversibly bound to this protein. Studies were undertaken to determine if 1,4-DCB produced similar effects; 1,2-DCB was used for comparison since it did not produce renal carcinogenesis in male rats. Gel filtration chromatography of a 116,000g supernatant prepared from kidneys of 1,4-[14C]DCB-treated rats showed that radiolabel coeluted with alpha 2u-globulin as one sharp peak as opposed to a multipeak pattern observed for 1,2-[14C]DCB; the maximal quantity of radiolabel for 1,4-DCB was twice that for 1,2-DCB. Equilibrium dialysis of kidney cytosol in the presence or absence of sodium dodecyl sulfate demonstrated that the radiolabel was reversibly bound to alpha 2u-globulin; the amount for 1,4-[14C]DCB-treated rats was almost twice as much as that for 1,2-[14C]DCB-treated rats. 1,2-DCB was also shown to be covalently bound to renal alpha 2u-globulin, and covalently bound to liver and plasma high-molecular-weight proteins. 1,4-DCB and, to a minor extent, 2,5-dichlorophenol, the major metabolite of 1,4-DCB, were reversibly bound to renal alpha 2u-globulin from 1,4-DCB-treated rats. 1,4-DCB increased protein droplet formation in male but not in female rat kidneys, whereas equimolar doses of 1,2-DCB showed no effect in either sex. Renal cell proliferation, measured by [3H]thymidine incorporation into renal DNA, was increased after 1,4-DCB but not after 1,2-DCB treatment. Nephrotoxicity and biochemical alterations induced by 1,4-DCB resemble those of unleaded gasoline and suggest that a similar mechanism is involved in the induction of alpha 2u-globulin nephropathy in male rats.

Alpha-Globulins↗
PubMed1983

Tissue-specific control of alpha 2u globulin gene expression: constitutive synthesis in the submaxillary gland.

Synthesis of alpha 2u globulin, previously thought to occur only in the male rat liver, has now been demonstrated in the submaxillary salivary gland. Unlike liver, submaxillary synthesis of alpha 2u globulin mRNA is constitutive--that is, independent of the endocrine state, age and sex. Liver and submaxillary alpha 2u globulin mRNAs are of similar size, and their 5' ends map to the same region of the gene. Isoelectric focusing of in vitro translation products revealed that submaxillary mRNA encodes a more acidic subset of alpha 2u globulins than does liver. Salivary alpha 2u globulin mRNA manifests 5% nucleotide divergence, encoding 20 amino acid substitutions, which specifies a more acidic polypeptide than its hepatic counterpart. Thus the liver and submaxillary gland synthesize alpha 2u globulin from different sets of genes that are subject to very different developmental and hormonal control.

Alpha-Globulins↗
PubMed1980

Grafting of different glycosides on the surface of liposomes and its effect on the tissue distribution of 125I-labelled gamma-globulin encapsulated in liposomes.

Different glycosides were grafted on the surface of liposomes containing 125I-labelled gamma-globulin by two ways: (1) by using glycolipid and (2) by covalent coupling of p-aminophenyl-D-glycosides to phosphatidylethanolamine liposomes using glutaraldehyde. The distribution of 125I-labelled gamma-globulin was determined in mouse tissues from 5-60 min after a single injection of these liposomes. The liver uptake of encapsulated 125I-labelled gamma-globulin was highest from liposomes having galactose and mannose on the surface. Competition experiments and cross-inhibition studies indicate that this uptake are mediated by specific recognition of the surface galactose and mannose residues of liposomes by the receptors present on the plasma membrane of liver cells. Stearylamine-containing liposomes were found to be more efficient in mediating the uptake of 125I-labelled gamma-globulin by the lung, whereas in the case of spleen, phosphatidylethanolamine liposomes were more efficient. The extent of uptake of 125I-labelled gamma-globulin from all types of liposome decreases as the amount of given liposomes increases. The uptake of 125I-labelled gamma-globulin from liposomes containing asialogangliosides depends upon the phospholipid/glycolipid ratio. These experiments clearly demonstrate that enhanced liposome uptake by liver cells could be achieved by grafting galactose and mannose on the liposomal surface.

Animals↗
PubMed2006

Do Rh-negative women with first trimester spontaneous abortions need Rh immune globulin?

OBJECTIVE: To examine whether literature supports the use of Rh immune globulin in Rh-negative women with first trimester spontaneous abortions to prevent maternal sensitization to the fetal Rh antigen and subsequent fetal morbidity and mortality. METHODS: We searched MEDLINE (1966-2005), the Cochrane Central Register of Controlled Trials, EMBASE (1990 to 2005), and the reference sections of the articles found. The search is considered updated to December of 2005. Search terms included vaginal bleeding, Rh negative, Rh immune globulin, RhoGAM, isoimmunization, sensitization, first trimester pregnancy, threatened, and spontaneous abortion. RESULTS: The evidence to support the use of Rh immune globulin for a diagnosis of first trimester spontaneous abortion is minimal. There is a paucity of well-designed research that examines maternal sensitization or hemolytic disease of the newborn as an outcome in patients receiving, versus not receiving, Rh immune globulin in first trimester bleeding. There is significant evidence to demonstrate fetomaternal hemorrhage in first trimester spontaneous abortions; yet, no studies demonstrate subsequent maternal sensitization or development hemolytic disease in the fetus as a result of this hemorrhage. CONCLUSION: In summary, there is minimal evidence that administering Rh immune globulin for first trimester vaginal bleeding prevents maternal sensitization or development of hemolytic disease of the newborn. The practice of administering Rh immune globulin to Rh-negative women with a first trimester spontaneous abortion is based on expert opinion and extrapolation from experience with fetomaternal hemorrhage in late pregnancy. Its use for first trimester bleeding is not evidence-based.

Abortion, Spontaneous↗
PubMed1980

Effects of diethylstilbestrol and estramustine phosphate on serum sex hormone binding globulin and testosterone levels in prostate cancer patients.

Serum testosterone-estradiol binding globulin and total testosterone were measured in 2 groups of male controls (less than 50 and more than 65 years old) and in 7 groups of prostatic cancer patients treated with various endocrine manipulation procedures, including orchiectomy, and estramustine phosphate and diethylstibestrol therapy. There were 133 individuals studied. Total serum testosterone levels were significantly higher in the younger versus the older control group and testosterone-estradiol binding globulin levels were significantly higher in the older men. Whereas orchiectomy reduced serum testosterone to low concentrations (72 plus or minus 11 ng. per 100 ml.) testosterone-estradiol binding globulin levels were not altered. In contrast, estramustine phosphate and diethylstilbestrol therapy, when administered to intact or castrated patients, resulted in depressed testosterone and markedly elevated testosterone-estradiol binding globulin serum levels, particularly in those patients receiving estramustine phosphate (less than 35 ng. per 100 ml. and more than 6 micrograms per 100 ml., respectively). These studies led to the conclusion that diethylstilbestrol or estramustine phosphate therapy is significantly more effective than orchiectomy in eliciting a concomitant elevation of testosterone-estradiol binding globulin and a depression of total testosterone. Even though free serum testosterone was not measured in the present study the law of mass action would indicate that in those patients with high testosterone-estradiol binding globulin (more than 5 microgram. per 100 ml.) and low total testosterone levels (less than 80 ng. per 100 ml.) the availability of biologically active (unbound steroid) testosterone would be negligible.

Adult↗
PubMed2002

Increased serum albumin, gamma globulin, immunoglobulin IgG, and IgG2 and IgG4 in autism.

BACKGROUND: Research on the biological pathophysiology of autism has found some evidence that immune alterations may play a role in the pathophysiology of that illness. As a consequence we expected to find that autism is accompanied by abnormalities in the pattern obtained in serum protein electrophoresis and in the serum immunoglobulin (Ig) and IgG subclass profile. METHOD: We examined whether subjects with autism showed changes in total serum protein (TSP) and the serum concentrations of albumin, alpha1 globulin, alpha2 globulin, beta globulin and gamma globulins, IgA, IgM and IgG and the IgG subclasses IgG 1, IgG2, IgG3 and IgG4, compared with normal controls. RESULTS: We found significantly increased concentrations of TSP in autistic subjects, which were attributable to increased serum concentrations of albumin and gamma globulin. Serum IgG, IgG2 and IgG4 were also significantly raised. In autism there were significant and positive correlations between social problems and TSP and serum gamma globulin and between withdrawal symptoms and TSP and serum albumin and IgG. CONCLUSIONS: The results suggest that autism is characterized by increased TSP, a unique pattern obtained in serum protein electrophoresis, i.e. increased serum albumin and IgG, and by a specific IgG subclass profile, i.e. increased serum IgG2 and IgG4. The increased serum concentrations of IgGs in autism may point towards an underlying autoimmune disorder and/or an enhanced susceptibility to infections resulting in chronic viral infections, whereas the IgG subclass skewing may reflect different cytokine-dependent influences on autoimmune B cells and their products.

Adolescent↗
PubMed1975

Hormonal regulation of the hepatic messenger RNA levels for alpha2u globulin.

The messenger RNA rat alpha2u globulin has been identified and quantitated in a cell-free translational system derived from Krebs II ascites cells. Hepatic tissue of the mature male rats which normally produce alpha2u globulin was also found to contain a high level of alpha2u mRNA. Approximately 1.6 per cent of all poly(A) containing RNA of the adult male rat liver could be accounted for alpha2u messenger activity. Female rats do not produce alpha2u globulin and no alpha2u mRNA activity could be detected in the poly(A) containing RNA fraction obtained from the livers of these animals. However, androgen treatment to spayed female rats was found to induce the parallel appearance to both alpha2u globulin and its corresponding mRNA. Both hypophysectomy and adrenalectomy which are known to reduce the level of alpha2u globulin in the urine of male rats were found also to reduce the hepatic level of alpha2u mRNA. The results indicate that hormonal control of alpha2u globulin synthesis in rat liver is achieved primarily through regulation of its translatable mRNA level and that more than one hormone may participate in this regulation.

Alpha-Globulins↗
PubMed1999

Role of disulfide bonds upon the structural stability of an amaranth globulin.

Analysis of globulin-P, the polymerized amaranth globulin, gave a low amount of free sulfhydryls (10.2 +/- 0.5 micromol/g) from which 7 +/- 1 micromol/g was buried inside the molecule. In addition, its disulfide content was high (51 +/- 1 micromol/g) and similar to soybean 11S globulin content. The more exposed disulfide bridges were found to be stabilizing polymers, whereas the less reactive bridges were either linking P(20) and P(30) polypeptides or forming intrachain linkages. It was found that the buried bonds participate in the stabilization of folded polypeptides and the quaternary structure of the globulin. In turn, the dissociation of polymers and disruption of the quaternary structure by the action of 2-mercaptoethanol reverted upon removal of the reducing agent. This demonstrates that the polymerized state and the quaternary structure of the molecules are most favorable from the thermodynamic point of view. The similar content of SH and SS in globulin-P and globulin-S found in this laboratory suggests that the differences between these proteins may be ascribed to other compositional differences.

Calorimetry↗
PubMed2003

First-trimester sex hormone binding globulin and subsequent gestational diabetes mellitus.

OBJECTIVE: We sought to examine the association between early pregnancy levels of sex hormone binding globulin and subsequent gestational diabetes mellitus, an association that has not been studied previously. STUDY DESIGN: We conducted a nested case-control study of 44 patients with gestational diabetes mellitus and 94 women with negative third-trimester screening for gestational diabetes mellitus. Sex hormone binding globulin levels were measured from serum samples that had been collected in the first trimester, and clinical data were ascertained from prospectively collected electronic medical records. RESULTS: Compared with women without gestational diabetes mellitus, first-trimester sex hormone binding globulin levels were lower among women in whom gestational diabetes mellitus subsequently developed (187 +/- 82 nmol/L vs 233 +/- 92 nmol/L, P <.01). In logistic regression analysis that was adjusted for body mass index, age, race, smoking, blood pressure, serum testosterone and estradiol levels, and gestational age at serum collection, sex hormone binding globulin levels remained independently associated with subsequent gestational diabetes mellitus. For every 50-nmol/L increase in sex hormone binding globulin, the odds of gestational diabetes mellitus fell by 31% (odds ratio, 0.69; 95% CI: 0.48, 0.99). CONCLUSION: Sex hormone binding globulin offers a potential early marker to target women who are at risk for gestational diabetes mellitus.

Birth Weight↗