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Efficacy of prophylactic gamma-globulin in preventing non-A, non-B post-transfusion hepatitis.

Of 279 cardiac-surgery patients receiving a mean of twelve transfusions, 47 had significantly increased transaminase concentrations 14 to 180 days postoperatively and 10 were icteric. Preoperatively, each patient randomly received high-titre HbsAb gamma-globulin, normal gamma-globulin, or placebo and was followed at intervals for 9 months. Only 3 patients had serological evidence of hepatitis-B infection. 3 additional patients had serological evidence of cytomegalovirus infection, while none had evidence of hepatitis-A or Epstein-Barr infection. Less icteric hepatitis occurred in patients receiving the gamma-globulin preparations (P = 0-003), and the overall frequency of hepatitis was significantly reduced when compared with recipients of placebo. The protective effects of the two gamma-globulin preparations were not significantly different. Most post-transfusion hepatitis tody is neither viral hepatitis type B nor type A, and its severity and transmission are reduced by pre-transfusion gamma-globulin.

Adult↗

Partial reversal of alpha 2u globulin gene expression by thyroxine in the liver of diabetic rats.

Synthesis of alpha 2u globulin and its mRNA has been used as an index to monitor the effect of thyroxine on specific gene expression in the liver of hypoinsulinemic male rats. Administration of a physiological dose of thyroxine can partially reverse (to approximately 30% of the normal control) the marked reduction (more than 90%) in the hepatic levels of alpha 2u globulin and its mRNA during streptozotocin-induced diabetes. Estimation of newly synthesized alpha 2u globulin RNA transcripts from the native chromatin of isolated liver nuclei by "nuclear runoff experiments" showed that thyroxine can elevate the rate of transcription of alpha 2u globulin gene in the diabetic rat. Hypoinsulinemic diabetes is also found to be associated with an approximately 35% reduction in the thyroid hormone receptor level as compared to the normal control. The stimulatory effect of thyroxine on the synthesis of alpha 2u globulin and its mRNA was also evident in spontaneous diabetic Wistar "BB" rats. From these studies it can be concluded that severe hypoinsulinemia can cause a decrease in thyroid hormone action at the level of specific gene expression.

Alpha-Globulins↗

Amaranth globulin structure modifications induced by enzymatic proteolysis.

Globulin-P was partially hydrolyzed with papain under specific conditions to study the resulting structural modifications. Under mild hydrolytic conditions, globulin-P polymers were cleaved to render their unitary constituents (280 kDa molecules). Under stronger hydrolytic conditions these unitary molecules were 13% smaller than those from nonhydrolyzed globulin. Moreover, these molecules remained assembled even though they contained degraded polypeptides. The monomeric (M) subunit and the A chains were preferentially cleaved under mild and intermediate hydrolytic conditions, whereas B chains remained with the same size. These results suggest that the M and A polypeptides might be located at an exposed site of the molecules resembling the structure of the legumins. The M subunit may be participating in the stabilization of globulin-P polymers, on the basis that these two species disappeared under the same hydrolytic conditions. Similar events such as those described in this paper might be taking place on globulin-P during germination of amaranth grain.

Edible Grain↗

Possible nutritional implications of varietal influence on the 7S/11S seed globulin ratios in amaranth.

7S/11S seed globulin ratios were determined for seven currently available Amaranthus hybrid lines i.e., Amaranthus K266, K283, K343, K432, K433, K436 and MT-3. Of the seven Amaranthus lines investigated, four lines had 7S/11S globulin ratios ranging from 0.47 to 0.81, while three lines were found to contain exclusively the 11S globulin form. In general, 7S globulins contained lower levels of essential amino acids such as tryptophan, methionine, lysine, histidine, phenylalanine, valine and isoleucine than the 11S globulins.

Amino Acids↗

Expression of monocyte chemoattractant protein-1 in Kawasaki disease: the anti-inflammatory effect of gamma globulin therapy.

We investigated the expression of monocyte chemoattractant protein-1 (MCP-1) mRNA, protein, and its bioactivity in plasma, mononuclear cells (MNC) and polymorphonuclear leukocytes (PML) in patients with Kawasaki disease, including those who were treated with intravenous gamma globulin. MCP-1 mRNA expression was increased in the MNC and the plasma level of MCP-1 and monocyte chemotactic activity in plasma in the acute phase as compared with healthy control levels and decreased after the gamma globulin therapy. The infused gamma globulin contained MCP-1 protein with monocyte chemotactic activity and did not show a neutralising effect against MCP-1 protein in vitro. Our results suggest that the infusion of gamma globulin may reduce the production of MCP-1 in MNC in patients with Kawasaki disease, subsequently reducing its level in plasma. The changes in MCP-1 level after gamma globulin therapy may serve to alleviate the symptoms in the acute phase in patients with Kawasaki disease.

Acute Disease↗

Evidence of sex hormone binding globulin binding sites in the medial preoptic area and hypothalamus.

We have demonstrated a high density of both radiolabeled progesterone and estradiol conjugated to bovine serum albumin binding sites in the medial preoptic area and hypothalamus. Infusions of sex hormone binding globulin into the medial preoptic area of rats increased their female sexual receptivity similarly to the effect of estradiol conjugated to bovine serum albumin, suggesting sex hormone binding globulin acts at binding sites for estradiol conjugated to bovine serum albumin. In this study sex hormone binding globulin was used to displace radiolabeled progesterone conjugated to bovine serum albumin from plasma membrane fractions from the medial preoptic area-anterior hypothalamus and medial basal hypothalamus of ovariectomized rats injected with either 5 microg estradiol benzoate or sesame oil vehicle. We found that sex hormone binding displaced radiolabeled progesterone conjugated to bovine serum albumin in both areas and that in vivo estradiol treatment greatly increased the relative displacement by sex hormone binding globulin in the medial preoptic area-anterior hypothalamus. We interpret these data as indicating the presence of sex hormone binding globulin receptors in brain plasma membranes and further suggest that endogenous steroid conditions may alter these receptors.

Animals↗

Superinduction of alpha 2u globulin by actinomycin D: evidence for drug-mediated increase in alpha 2u mRNA.

Actinomycin D, an inhibitor of DNA-dependent RNA synthesis, increased the hepatic concentration of alpha 2u globulin, an androgen-inducible protein in the rat. Spayed female rats with a marginally induced state of alpha 2u synthesis showed an approximately 5-fold increase in hepatic alpha 2u globulin within 3-6 hr after treatment with actinomycin D. Initial treatment of these animals with 5 alpha-dihydrotestosterone, followed by actinomycin D, resulted within 2-3 hr in a more than 2-fold increase in hepatic alpha 2u globulin compared to animals treated with the androgen alone. In spite of inhibition of hepatic synthesis of poly(A)-containing RNA to less than 25% of control, superinduction with actinomycin D resulted in a parallel increase in the translatable mRNA for alpha 2u globulin. These results showing increase in both alpha 2u globulin and its translatable mRNA after superinduction with actinomycin D support the concept of post-transcriptional repression of alpha2u synthesis.

Alpha-Globulins↗

Immunocytochemical study of gamma globulin in liver in hepatitis and postnecrotic cirrhosis.

Gamma globulin was demonstrated by immunocytochemical fluorescence technique in many reticuloendothelial cells of the hepatic sinusoids and of the fibrous tracts in various forms of hepatitis and in postnecrotic cirrhosis. In other liver diseases and in normal livers, even in the presence of hypergammaglobulinemia, few if any gamma globulin-containing cells were found. In contrast, spleen and lymph nodes showed no difference between postnecrotic cirrhosis or hepatitis and other types of cirrhosis or non-hepatic hypergammaglobulinemias. The gamma globulin-containing cells in the liver are on cytologic grounds considered reticuloendothelial cells showing transition to plasma cells and exhibiting little or no phagocytosis of tissue breakdown products. These cells are assumed to form rather than engulf gamma globulin. The possibility that the gamma globulin formed represents antibody to liver cell breakdown products is discussed.

Hepatitis↗

Studies on structural units of the gamma-globulins.

When human and rabbit 7S gamma-globulins were reduced in strong urea solutions by a number of procedures, their molecular weights fell to approximately (1/3) of the original values. Partial separation of the reduction products was achieved using chromatography and starch gel electrophoresis in urea solutions. One of the components of reduced human 7S gamma-globulin was isolated by chromatography, identified by starch gel electrophoresis, and subjected to amino acid analyses. The amino acid composition of this component differed from that of the starting material and also from that of the remaining components. A reduced pathological macroglobulin dissociated to components with an average molecular weight of 41,000. Several reduced human myeloma proteins, when subjected to starch gel electrophoresis, yielded individual patterns that nevertheless had features in common with those of reduced normal gamma-globulins. Reduction of normal and abnormal gamma-globulins was accompanied by the appearance of titratable sulfhydryl groups. Chemical treatments other than reduction were used to determine the type of bond holding the subunits together. It was tentatively concluded that they were linked by disulfide bonds. An hypothesis is presented to relate the structural features of the various gamma-globulins in terms of the multiplicity of polypeptide chains in these molecules.

Amino Acids↗

Presence of HTLV-III antibodies in immune serum globulin preparations.

The authors tested 15 immune serum globulin pharmaceutical preparations for antibody reactivity to human T cell lymphotrophic virus type III (HTLV-III) by the Abbott immunoenzymometric assay (IEMA). Although no evidence of HTLV-III infectivity has appeared after injection of similar preparations into humans, the authors found all samples IEMA reactive. Upon dilution, the authors demonstrated parallel decreases of antibody reactivity among two samples of gamma globulin, the Abbott-positive control, and a markedly reactive patient specimen. Gamma globulin isolated from sera of six animal species was nonreactive in the Abbott assay. All samples were nonreactive with the H-9 cell line antigen. Antibody reactivity to HTLV-III was confirmed in 13 of 15 gamma globulin samples when tested by the Electro-Nucleonics IEMA, and 14 samples contained at least the p24 band on Western blot analysis. Although false positivity occurs in IEMA assays possibly because of elevated protein concentrations and nonspecific binding, the authors, results show that in most circumstances immune serum globulin preparations tested do contain true reactivity to HTLV-III.

Antibodies, Viral↗

A polyvalent human gamma-globulin immune to Pseudomonas aeruginosa: passive protection of mice against lethal infection.

As a means to development of guidelines for therapeutic application to human disease, preparations of human polyvalent gamma-globulin immune to Pseudomonas aeruginosa (PG) were studied in acute infections in mice. PG was highly effective in controlling lethal infections induced in mice by the major immunotypes of P. aeruginosa; greater than or equal to 10 microgram of of gamma-globulin per mouse protected against challenge with less than or equal to 10(6) 50% lethal doses of P. aeruginosa. PG was less than or equal to 57 times more effective than normal human gamma-globulin. The active antibody component is specific for each immunotype; it is of the IgG type and undoubltedly is directed against the O-antigen. PG was was not protective against challenge with Escherichia coli, Enterobacter cloacae, Proteus mirabilis, or Klebsiella pneumoniae; a low degree of cross-protection was seen against Serratia marcescens. In a model infection involving mice in a terminal stage of advanced P. aeruginosa infection, human plasma immune to P. aeruginosa proved ineffective, but the gamma-globulin component showed moderate activity. The apparent irreversibility of this late-stage infection is not clearly ascribable to a toxin. It is postulated that the successful treatment of advanced P. aeruginosa infections in humans would require multiple therapeutic approaches, including passive immunization with a high-potency, specifically immune globulin.

Animals↗

Changes in the concentration of globulins in naive guinea pigs during feeding by the immature stages of Rhipicephalus evertsi evertsi (Acari: Ixodidae).

The weight of Rhipicephalus evertsi evertsi Neumann nymphs, which as larvae and nymphs completed the entire blood meal on the same individual guinea pig, was significantly lower than the weight of those that as larvae and nymphs fed on two separate naive hosts. Nymphs of the latter category spent 1 wk (from unfed larvae to unfed nymphs) on one animal before their transfer to the second host to complete the blood meal. The albumin concentration of the host blood decreased and was related to the time that the immature ticks spent on the hosts. The albumin/globulin ratio also decreased. The alpha 1 globulin fraction increased soon after the guinea pigs were infested with ticks. No further changes in the levels of the alpha 1 globulin fraction were observed with time. The concentration of serum beta globulins increased only in guinea pigs infested with immature ticks for the entire larval and nymphal feeding period. A second infestation of those guinea pigs with larvae of R. e. evertsi resulted in further increases in the levels of serum beta globulins. The relationships among serum beta globulin levels, the weight of engorged nymphs, and host immunity are discussed.

Animals↗

RNA metabolism and membrane-bound polysomes in relation to globulin biosynthesis in cotyledons of developing field beans (Vicia faba L.).

In cotyledon cells of developing field beans the RNA content per cell does not change in the second half of developmental period 2, whereas globulin biosynthesis continues. The constant RNA content per cell results from an equilibrium between RNA synthesis and degradation. All types of RNA are synthesized until the end of globulin biosynthesis, but poly(A)-containing RNA was preferentially labelled during maximum globulin formation. During stage 2 of seed development of poly(A)-containing RNA fraction represents a discrete peak in the 12--18-S region on agarose gels and corresponds to the peak of poly(A)-containing RNA isolated from polysomes. alpha-Amanitin inhibits selectively the labelling of poly(A)-containing RNA and concomitantly globulin formation. Translation of total poly(A)-containing RNA, free and membrane-bound polysomes in a cell-free wheat germs demonstrates that the globulins are preferentially produced on membrane-bound polysomes and that poly(A)-containing RNA includes the mRNA for both vicilin and legumin.

Amanitins↗

Different forms of alpha 2u-globulin in male and female rat urine.

alpha 2u-Globulin is usually considered to be present only in male rat urine. This study demonstrates that a very similar protein exists in female rat urine and compares its properties with those of the male form. Isoelectric focusing followed by immunofixation reveals considerable microheterogeneity of alpha 2u-globulin in male and female rat urine. Important sex differences are noted in the banding pattern. The isoelectric point of the major male component (pI approximately equal to 5.3) is considerably higher than that of the major female components (pI approximately equal to 4.6). In addition, the female form of alpha 2u-globulin has a somewhat higher mobility on sodium dodecyl sulphate/polyacrylamide gel electrophoresis than its male counterpart. These sex differences are preserved after purification of alpha 2u-globulin from male and female rat urine by affinity chromatography and enrichment of the major male and female components by ion-exchange chromatography. Immunologically no differences are observed between these purified components and their amino acid composition reveals only minor differences. A slightly higher carbohydrate content is observed in the major female component than in the major male component. Finally evidence is presented that oestrogen treatment suppresses the male forms of alpha 2u-globulin but has no effect on the female forms. The observed differences between the male and female forms and their different hormonal control suggest that they are encoded by different genes.

Alpha-Globulins↗

Nucleotide sequence of cloned cDNA coding for pumpkin 11-S globulin beta subunit.

cDNA coding for preproglobulin beta, a precursor protein of 11-S globulin beta subunit, was cloned and the nucleotide sequence has been determined. The sequence covers the whole coding region (1440 base pairs) with 5' and 3' noncoding region (30 and 214 base pairs, respectively). The deduced amino acid sequence of preproglobulin beta consists of a 21-amino-acid N-terminal signal peptide, preceding the acidic gamma polypeptide region (275 amino acids) and the subsequent basic delta region (184 amino acids). The site for post-translational cleavage of the precursor polypeptide to make the gamma and delta chains is estimated to be located between the asparagine-glycine residues. The N-terminal amino acid of the gamma chain of mature 11-S globulin beta subunit was reported to be blocked by 5-oxoproline (pyroglutamic acid) [Ohmiya et al. (1980) Plant Cell Physiol. 21, 157-167]. It was shown that the blocked N-terminal amino acid is coded as a glutamine residue. The derived amino acid sequence was also compared with those of precursor proteins of other 11-S globulins such as soybean glycinin, cotton beta globulin, pea legumin and rape 11-S globulin by dot matrix analysis.

Amino Acid Sequence↗

Proteinase A, a storage-globulin-degrading endopeptidase of vetch (Vicia sativa L.) seeds, is not involved in early steps of storage-protein mobilization.

Proteinase A is a papain-like cysteine endopeptidase of vetch (Vicia sativa L.) which was assumed to initiate storage-globulin breakdown just after the onset of seed germination. This enzyme was purified from cotyledons of vetch seedlings. On gelatin-containg SDS gels, active proteinase A migrated with an apparent molecular mass of 21 kDa, whereas after heat denaturation its molecular size on SDS/PAGE was 29 kDa. Although proteinase A is capable of hydrolyzing storage globulins in vitro it could not be localized in the protein-body fraction of cotyledons from germinating seeds. cDNA clones encoding proteinase A precursor have been obtained by PCR. The precursor is composed of an N-terminal signal sequence followed by a propeptide, the region encoding mature proteinase A, and a C-terminal KDEL sequence. Mature proteinase A with a derived molecular mass of 25,244 Da does not have the KDEL sequence. The derived amino acid sequence of the proteinase A precursor is 78.2% identical to sulfhydryl-endopeptidase (SH-EP), a cysteine endopeptidase from germinating Vigna mungo seedlings. Northern blot analysis indicated that proteinase A mRNA appears de novo in cotyledons of 1-day-germinated vetch seeds, where its amount increases up to day 6. No proteinase A mRNA was detected in other vetch organs, not even in the embryo axis, which contains stored globulins. By means of antibodies raised against the purified and against recombinantly produced proteinase A, the 29-kDa bands of mature proteinase A were detected in cotyledon extracts of 6-day-germinated seeds when globulin degradation has already far proceeded. The reported data do not agree with the proposed triggering role of proteinase A in storage-globulin breakdown during germination.

Amino Acid Sequence↗

Effect of continual light deprivation and alpha-2u-globulin replacement therapy on serum concentration of gonadotropins and testicular activity in rats.

Prolonged darkness caused a fall in testicular 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity and diminished spermatogenesis, serum levels of gonadotropins, testosterone and alpha 2u-globulin. Administration of alpha 2u-globulin at a dose of 1.5 mg rat-1 per day for 7 days after 68 days of light deprivation, reversed the 17 beta-HSD activity and serum levels of gonadotropins, testosterone and alpha 2u-globulin, while spermatogenesis was restored to normal. The animals kept in prolonged darkness for 68 days and then received saline (7 days in light-dark cycle, 14 L: 10 D), showed no significant changes of testicular activity, serum levels of gonadotropins, testosterone and alpha 2u-globulin, when compared with dark-exposed animals (68 days) receiving rabbit serum (7 days in light-dark cycle, 14 L: 10 D). These results suggest that alpha 2u-globulin plays an important role in testicular function in dark-exposed rats by inducing gonadotropins and testosterone secretion.

Alpha-Globulins↗

Treatment of severe pertussis by administration of specific gamma globulin with high titers anti-toxin antibody.

Our patient presented with severe respiratory distress and marked pleocytosis. She was mechanically ventilated and received gamma globulin with high titers of anti-pertussis toxin and anti-filamentous hemagglutinin. Her clinical signs improved and a notable decrease in white blood cell count was observed. Ten months after treatment, the patient showed normal physical and mental development and anti-pertussis toxin and anti-filamentous hemagglutinin titers were significantly increased. Recently, the effectiveness of gamma globulin therapy has been emphasized again. Our experience supports the use of iv gamma globulin infusion. Also, gamma globulin did not influence the patient's own immunologic response to pertussis. Gamma globulin therapy with high anti-pertussis toxin titers could be considered for treatment of severe pertussis.

Antitoxins↗