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PubMed1983

Activation of purified cytoplasmic 17 beta-hydroxysteroid dehydrogenase from human placenta by human albumin and globulin.

The cytoplasmic 17 beta-hydroxysteroid dehydrogenase of human placenta, purified more than 2500-fold, was activated by small amounts of human albumin and globulin. This activation was dependent on substrate concentration. At 20 microM estradiol (10 X KM) and two different concentrations of enzyme (0.01 and 2 micrograms/ml), the activation was greatest at albumin or globulin concentrations between 0 and 30 micrograms/ml. At "low" concentrations of estradiol (20 nM = 10(-2) X KM) and enzyme (0.01 microgram/ml), maximal activity occurred at approximately 10 micrograms/ml. Higher concentrations of albumin and globulin led to a decline in activity.

17-Hydroxysteroid Dehydrogenases↗
PubMed1988

The role of alpha-2u-globulin in corticosteroidogenesis in male rats.

Administration of estradiol-17 beta for 7 days to the adult male rat results in adrenal hyperplasia, decreased serum corticosterone along with elevation in serum ACTH and inhibition of adrenal 5-ene-3 beta-hydroxysteroid dehydrogenase activity (5-ene-3 beta-HSD). Treatment with alpha 2u-globulin for following 14 days of estrogen-treated rats reversed the effects of estrogen while in normal rats alpha 2u-globulin treatment increased adrenal 5-ene-3 beta-HSD activity and serum corticosterone level while causing a fall in serum ACTH. It is concluded that alpha 2u-globulin may play a role in ACTH secretion by inducing corticosterone synthesis.

3-Hydroxysteroid Dehydrogenases↗
PubMed1989

Plasma levels of estradiol, estrone, estrone sulfate and sex hormone binding globulin in patients receiving rifampicin.

Plasma estrone, estradiol, estrone sulfate, androstenedione, testosterone and sex hormone binding globulin were measured in 14 patients (3 postmenopausal women, 11 men) with tuberculosis who received rifampicin. During treatment a moderate, but significant increase in the plasma level of estradiol (mean increase 32%, P less than 0.01) and estrone (mean increase 13%, P less than 0.01) were seen. In contrast, plasma estrone sulfate was significantly reduced (mean reduction of 25%, P less than 0.05). No alteration in plasma testosterone was observed, but there was a slight (mean 15%) increase in plasma androstenedione of borderline significance (P = 0.052). In eight patients, from whom all tuberculostatic treatment except rifampicin had been withdrawn, plasma sex hormone binding globulin was found to be increased by 75% by rifampicin treatment. Further, the results obtained in this part of the study confirmed the alteration in plasma estrone sulfate to be caused by rifampicin alone without any contribution from other tuberculostatic drugs. While plasma estradiol could be increased due to elevation of sex hormone binding globulin, plasma estrone was probably increased secondary to the increase in plasma androstenedione. A reduced plasma estrone sulfate level suggests that rifampicin enhances the rate of estrone sulfate metabolism. The possibility that treatment with drugs which reduce plasma estrone sulfate might be beneficial for hormone dependent cancers is discussed.

Adult↗
PubMed1977

Oligoclonal gamma-globulin banding of cerebrospinal fluid in patients with subacute sclerosing panencephalitis. Comparison of the electrophoretic pattern with that in multiple sclerosis and congenital infections.

Lumbar cerebrospinal fluid (CSF) of 8 patients with subacute sclerosing panencephalitis (SSPE) was examined by agarose gel electrophoresis. In comparison with normal controls and children with different neurological diseases (including infections, tumours and degenerative diseases) the quantitative evaluation of the pherograms by an analog computer revealed an extreme change of the gamma-globulin profile. All cases showed 6-7 abnormal subfractions consisting of 2-4 tall, markedly protruding spikes and several small intermediate fractions. The oligoclonal gamma-globulin contributed 20.1-42.5% to total protein. This particular gamma-globulin profile seems to be highly indicative of the diagnosis of SSPE. It can be distinguished from the oligoclonal pattern in patients suffering from multiple sclerosis (MS) and congenital infections. The CSF protein profile of 13 patients with MS was different from that in SSPE in that it showed 1-5 monoclonal gamma-fractions in every case with none or only one peak protuding more markedly. The percentage of all subfractions amounted to 4.5-23.8% of total protein. As in MS, the aspect of oligoclonality in 9 children with congenital infections (cytomegalic inclusion body disease, toxoplasmosis and rubella) was quite variable, as again 1-5 abnormal subfractions were detected. Their relative concentrations, on the whole ranging from 0.6-12% of total protein, was considerably lower than in SSPE.

Adolescent↗
PubMed1987

The effects of low-protein diet and testosterone on sex hormone-binding globulin capacity in male rabbits.

The effects of a low-protein high-carbohydrate (LPHC) diet (8% protein 65% to 72% carbohydrate) were compared to those of regular rabbit chow (14% to 16% protein 57% to 64% carbohydrate) on sex hormone-binding globulin (SHBG) capacity in 12 male rabbits. The six rabbits who were fed the LPHC diet for 8 weeks showed a significant increase in their mean SHBG capacity (mean +/- SE: from 70 +/- 16 nmol/L to 332 +/- 45 nmol/L, P less than .01) whereas the six rabbits fed the standard diet showed a slight decrease (from 106 +/- 22 nmol/L to 76 +/- 20 nmol/L, NS). These changes in SHBG capacity were mirrored by a decrease in percent-free T (from 2.64 +/- 0.26% to 1.64 +/- 0.16%, P less than .01) in the LPHC diet group and no change in percent-free T in the regular diet group (from 2.36 +/- 0.21% to 2.19 +/- 0.10%). The changes in SHBG capacity and percent-free T were not associated with significant changes in testosterone (T), free T, estradiol (E2), thyroxine, triiodothyronine, thyroxine-binding globulin, or cortisol binding globulin levels. In a subsequent experiment, testosterone cyclopentyl propionate (TCP) was administered to six male rabbits while on regular rabbit chow and again after 6 weeks of the LPHC diet. TCP administration did not cause any significant change in the SHBG capacity, but the LPHC resulted again in a significant (P less than .05) increase in SHBG capacity from 80 +/- 18 nmol/L. to 198 +/- 22 nmol/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The comparative pathobiology of alpha 2u-globulin nephropathy.

alpha 2u-Globulin nephropathy is an important toxicologic syndrome that occurs in male rats following exposure to a number of important industrial and environmental chemicals. A low, but significant incidence of renal neoplasia develops in male rats as a chronic sequela to the disease. Studies on the pathogenesis of alpha 2u-globulin nephropathy have demonstrated that this protein is produced in large amounts in the male rat, that reversible binding occurs between chemicals and/or their metabolites and alpha 2u-globulin, and that this complex is resistant to proteolytic hydrolysis, leading to accumulation in renal lysosomes and subsequent cytotoxicity and cell death. This results in marked exposure-related increases in cell proliferation that persist for at least one year, providing exposure continues. This sustained increase in renal cell proliferation can promote initiated cells to form preneoplastic foci and renal neoplasia in male rats. Since this syndrome is highly species and sex specific, it is important to determine the relevance of these data for human risk assessment. The scientific considerations involved in high to low dose and species to species extrapolation are discussed.

Alpha-Globulins↗
PubMed1991

Quantitation of urinary alpha 2u-globulin and albumin by reverse-phase high performance liquid chromatography.

A rapid, reproducible, and sensitive high-performance liquid chromatography (HPLC) method for the quantitation of alpha 2u-globulin, the major urinary protein excreted by adult male rats, and albumin has been developed. Total urinary proteins, isolated by a simple Sephadex G-25 gel filtration step, are separated and quantitated by reverse-phase HPLC on a C4 Macrosphere 300 column. The proteins are separated and eluted with a two-step gradient of acetonitrile in aqueous trifluoroacetic acid. Detection limits of 9 and 25 micrograms/mL of urine were established for albumin and alpha 2u-globulin, respectively. Quantitation of urinary excretion of the two proteins in young adult male and female rats and aging male rats showed that values obtained with this method compared favorably with values from previously developed immunological techniques. To quantitate total urinary protein excretion, we modified the Bradford protein assay to use rat urinary protein as standard. Given the established importance of alpha 2u-globulin in the development of male rat-specific nephrotoxicity and nephrocarcinogenicity, these methods should be useful for studying the renal handling of this protein under normal and nephrotoxic conditions.

Albuminuria↗
PubMedDate not supplied

Influence of glucocorticoid, aspirin, and gamma globulin on interleukin-6 production in the hepatoma cell line.

The current study was designed to observe the effects of drugs used for the treatment of inflammatory diseases (glucocorticoid, aspirin, and gamma globulin) on interleukin 6 (IL-6) production in the liver which may be involved in acute phase protein stimulation. The HUH-7 hepatoma cell line was used in which the IL-6 gene is expressed and produces IL-6 in vitro. The cells were cultured in RPMI 1640 supplemented with 1% fetal calf serum for 12 h prior to addition of these drugs. We collected the cells and supernatants at 24 h, 48 h, and 72 h after addition of glucocorticoid, aspirin, and gamma globulin. IL-6 mRNA in the cells was measured by Northern blot hybridization, while the IL-6 activity in culture supernatants was measured by enzyme-linked immunosorbent assay. At 48 h after addition of glucocorticoid and aspirin, there was a suppression of IL-6 activity in the culture supernatants, which was associated with a decrease of mRNA level in the cells. However, suppression by gamma globulin was not observed. These data demonstrate that glucocorticoid and aspirin are potent regulators of IL-6 synthesis in the hepatoma cell. These components may decrease acute phase protein production via the suppression of IL-6 production in the liver during inflammation.

Aspirin↗
PubMed1988

Chromatographic purification of gamma-globulin from human serum on ferric oxide-agarose columns.

A fast chromatographic procedure for the purification of the gamma-globulin fraction of human serum on ferric oxide-containing agarose has been developed. The presence of ferric oxide (to which gamma-globulin is absorbed) increases the rigidity of the beads. They can therefore be used at high flow rates without troublesome crosslinking. The separation has been performed on a 14-ml column and on a 1.5-ml disposable column. The yield is 87 +/- 6% and the gamma-globulin fraction is homogeneous in agarose gel electrophoresis.

Chromatography, Agarose↗
PubMed1982

Synthesis and processing of the dimorphic forms of rat alpha 2u-globulin.

alpha 2u-Globulin the androgen-dependent male rat urinary protein, can be resolved into two distinct molecular forms by SDS-polyacrylamide slab gel electrophoresis. These two forms designated as alpha 2u-A (M, 18,800) and alpha 2u (Mr 18,100) are found both in urine and in the liver cells. Translation of rat liver mRNA in the rabbit reticulocyte lysate produced two preprotein forms of alpha 2u-globulin, designated as alpha 2uA' (Mr 20,300) and alpha 2uB' (Mr 19,600). Cell-free translation of rat liver mRNA in the presence of dog pancreas microsomal membrane or in Xenopus oocytes produced the two processed forms of alpha 2u-globulin (alpha 2uA and alpha 2uB). Quantitation of alpha 2uA and alpha 2uB within the in vitro translation products of the hepatic mRNA from albino rats of Yale, Sprague-Dawley and Fischer strains showed genetic differences in the proportion of translatable mRNA for alpha 2uA and alpha 2uB. The ratio of alpha 2uA: alpha 2uB in the translation products of liver mRNA from Yale rats was found to be 1:2.5 while in the case of both Sprague-Dawley and Fischer rats, the ratio was 1:4. A small portion of the alpha 2uA and alpha 2uB synthesized in the cultured hepatocytes, in the Xenopus oocytes or in the membrane-supplemented cell-free system appeared as two additional forms, designated as alpha 2uA" (Mr 21,200) and alpha 2uB" (Mr 20,600). Unlike alpha 2uA and alpha 2uB both alpha 2uA" and alpha 2uB" were found to bind to Con A-Sepharose, suggesting their glycoprotein nature.

Alpha-Globulins↗
PubMed1986

Electrophoretic variants of alpha 2u-globulin in the livers of adult male rats: a possible polymorphism.

Two-dimensional polyacrylamide gel electrophoresis has been used to examine the microsomal fractions from the livers of 32 adult male Alpk/AP (Wistar-derived) rats for the presence of alpha 2u-globulin variants of differing isoelectric point. Three major such isoelectric variants are described. Different combinations of these three forms were found in the population examined, with one-half of the animals expressing all three variants in approximately equal proportions and with one variant being present in all the animals examined. An understanding of the relevance of such different alpha 2u-globulin profiles to the individual animal must now await the assignment of a biological role for alpha 2u-globulin.

Alpha-Globulins↗
PubMed1991

NCI-Black-Reiter (NBR) male rats fail to develop renal disease following exposure to agents that induce alpha-2u-globulin (alpha 2u) nephropathy.

The NCI-Black-Reiter (NBR) rat is the only strain of male rat known not to synthesize the hepatic form of the low molecular weight protein, alpha 2u-globulin. In previous studies, NBR rats were shown not to develop renal disease when exposed to decalin, a compound known to induce alpha 2u-globulin nephropathy in other rat strains. The objective of this study was to show that the presence of alpha 2u-globulin (alpha 2u) is essential for the development of this syndrome in rats exposed to 2,2,4-trimethylpentane (TMP), 1,4-dichlorobenzene (DCB), isophorone (IP), PS-6 unleaded gasoline (UG), and d-limonene (d-L). The induction of alpha 2u-nephropathy in F344 male rats with lindane was used as a positive control and this response was contrasted to male NBR and female F344 rats treated with lindane. Five to seven 11-week-old male NBR rats were exposed to TMP (500 mg/kg/day), DCB (500 mg/kg/day), IP (1000 mg/kg/day), UG (500 mg/kg/day), d-L (1650 mg/kg/day), or lindane (10 mg/kg/day) and five 11-week-old male and female F344 rats were exposed to lindane (10 mg/kg/day) by oral gavage on 4 consecutive days. NBR male and F344 male and female rats gavaged with corn oil were incorporated in the study as vehicle controls. The presence of hyaline droplets was assessed in perfusion-fixed kidneys by staining paraffin sections with Mallory-Heidenhein stain and in GMA sections with Lee's methylene basic blue fuchsin stain. Paraffin sections were also analyzed immunohistochemically for the presence of alpha 2u. Under exposure conditions that clearly induce alpha 2u-nephropathy in male F344 rats, no lesions, hyaline droplets, or alpha 2u were detectable in treated or control male NBR and female F344 rats. It is thus concluded that the presence of alpha 2u is causal to the development of renal disease in rats exposed to TMP, DCB, IP, UG, d-L, and lindane.

Alpha-Globulins↗
PubMedDate not supplied

Albumins and globulins in developing maize grains.

Quantitative and qualitative (amino acid composition) changes of albumins and globulins in developing grain of normal and opaque-2 (o2) maizes were examined in proteins extracted sequentially with water and 0.5 M NaCl, and isolated by salting out with trichloroacetic acid. The amount of albumins per grain reached a maximum at mid-development the declined. Globulins, virtually absent in very young grain, increased in level until maturity. The variations were more marked for o2 than normal maize. Amino acid compositions changed little with development. The selectivity and exhaustiveness of sequential extraction, and the physiological role of albumins and globulins in grain are discussed.

Albumins↗
PubMed1982

Serum gamma-globulin concentration in different stages of sexual activity in females of common vole, Microtus arvalis, Pall.

1. In young and adult females of common vole low gamma-globulin levels at the greatest individual variability in the estrous phase were observed. 2. In natural population when the nonactive females were probably not under hormonal suppression (northern Poland, late summer) they had significantly higher level of gamma-globulins than pregnant, lactating and post partum ones. 3. It is suggested that decreases of gamma-globulin concentration may be an important physiological consequences of hormonal events and influence the viability of females in natural population during reproduction period.

Animals↗
PubMed1994

Effects of dietary rhIGF-I in neonatal calves on the appearance of glucose, insulin, D-xylose, globulins and gamma-glutamyl transferase in blood.

Cow colostrum is rich in insulin-like growth factors IGF-I and II, thus the dietary effects of recombinant human (rh) rhIGF-I on the newborn were of interest. The objective of this study was to examine the effect of dietary IGF-I upon selected blood components and gut absorptive development. Calves were blocked by birth weight and fed two times per d for a total of four times with the initial restricted diet. The initial feeding was 1.5 l and the remaining three feedings were at 2 l with one of three experimental diets; 1) milk replacer plus isolated colostrum derived globulins (MR-), 2) same as 1 above plus 750 ng/ml rhIGF-I (MR+), 3) pooled cow colostrum (COL). Thereafter, all animals received only milk replacer at 5% of body weight (BW)/feeding two times per d with only treatment 2 having continued addition of 750 ng/ml rhIGF-I until experimental completion at 6 to 7 d after birth. At feeding three, animals were fed D-xylose (0.5 g/kg BW) and 5,000 U of bovine kidney membrane gamma-glutamyl transferase as indicators of gut absorptive capacity. Colostrum-fed animals received 5,000 U of natural occurring gamma-glutamyl transferase activity in the 1.5 l first feeding. Blood samples taken over time were collected and saved as frozen plasma. All diets were analyzed for nutrient composition and endogenous levels of test hormones. Colostrum fed calves had greater globulin concentration (P < 0.01) than MR- or MR+ fed calves. Recombinant hIGF-I feeding had no effect (MR- vs. MR+) upon total protein, albumin or globulin blood levels. Absorption of colostrum gamma-glutamyl transferase at first feeding resulted in a peak total blood U of 4.5% of that fed. Although enzyme absorption was greatly reduced by the third feeding (0.5% of total fed), MR+ fed calves exhibited no significant difference in enzyme absorption when compared with the controls (MR- vs. MR+). However, pharmacokinetic analysis of D-xylose absorption at the third feeding showed diet effect upon absorption of D-xylose. Dietary rhIGF-I may change development or activity of sugar transporters and also may alter absorption of macromolecules (closure) in neonatal calves.

Animal Feed↗
PubMed1996

Rasmussen syndrome and long-term response to gamma globulin.

Rasmussen syndrome (RS) is a severe and progressive focal epilepsy of unknown etiology that leads to deterioration of motor and cognitive function. We report a 14-year-old girl who developed epilepsia partialis continua involving the left hand, mild hemiparesis, and secondarily generalized seizures. RS was confirmed by brain biopsy. The patient has been treated with intravenous gamma globulin every 4 months for 46 months. The clinical course throughout this time has been distinctly atypical for RS, with no progression in motor or cognitive deficits and rare secondarily generalized seizures. Although the mechanism for action for gamma globulin in RS is not known, an immunomodulatory role has been postulated. Evidence of an immunologically mediated process in RS and clinical experience with a growing number of patients who benefit from immunomodulatory therapy suggest that a systematic study of the efficacy of gamma globulin in comparison with other forms of medical therapy is warranted.

Adult↗
PubMedDate not supplied

The effect of the administration of human gamma globulins in a model of BCG infection in mice.

The effect of the administration of a commercial preparation of human gamma globulins has been evaluated in a mouse model of intranasal infection with BCG. First, we demonstrated the passage of specific antibodies to saliva and lung lavage following the intranasal or intraperitoneal administration to mice of human gamma globulins. This treatment of mice inhibited BCG colonization of the lungs (p < 0.01). A similar inhibitory effect was observed after infection of mice with gamma globulin opsonized BCG organisms (p < 0.01). These results are relevant for the development of new strategies for the control and treatment of tuberculosis.

Administration, Intranasal↗
PubMed1985

Purification of human serum gamma globulins by hydrophobic interaction high-performance liquid chromatography.

Fresh, whole human serum was fractionated on a Bio-Rad Protein Chromatography System, equipped with a Bio-Gel TSK Phenyl-5PW column, by utilizing a descending linear gradient of ammonium sulfate in 0.1 M sodium phosphate buffer, pH 7.0, at 0 degree C. Two major peaks were isolated corresponding to albumin and gamma globulin. The identity of these protein peaks was substantiated by chromatography of an albumin-gamma globulin standard mixture. The purity of the individual fractions was verified by high-performance size exclusion chromatography (HPSEC) on either a Bio-Sil TSK-250 or a Bio-Gel TSK-40 column. The applicability of these HPSEC columns to the molecular weight characterization of the Bio-Gel TSK Phenyl-5PW column fractions was compared. Typically, the Bio-Gel TSK Phenyl-5PW column (75 X 7.5 mm I.D.) was used to purify gamma globulin from 100 microliter of plasma. This corresponded to approx. 1.5-2.0 mg of the globin fraction. Unidentified contaminants in this fraction had molecular weights of approx. 1000-3000 daltons and 260 000-300 000 daltons.

Chromatography, Gel↗