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PubMed1989

Loss of androgenic induction of alpha 2u-globulin gene family in the liver of NIH black rats.

Unlike all known strains of rat, the androgen-inducible alpha 2u-globulin gene family is totally silent in the liver of NIH black (NB) rats. No endocrinological or reproductive abnormalities are apparent, and the mRNA for the androgen-repressible hepatic protein SMP-2 is normally regulated in these animals. Furthermore, immunoblot analysis shows a normal level of the male-specific cytoplasmic androgen-binding protein. Cross-breeding of the NB male and Sprague-Dawley female shows that the hybrid male in the F-1 generation regains the androgen-dependent expression of alpha 2u-globulin in the liver. These results along with the observation of high constitutive level of alpha 2u-globulin mRNA in the preputial gland of NB rats indicate a tissue- and gene-specific regulatory defect which prevents androgenic induction of alpha 2u-globulin in the liver.

Alpha-Globulins↗

PubMed1989

Developmentally regulated male-specific transfactor(s) enable in vitro transcription of a cloned alpha 2u-globulin gene.

Selected members of the rat alpha 2u-globulin gene family are expressed in several tissues, manifesting characteristic developmental and endocrine transcriptional control. Studies are now underway to identify the responsible cis sequences and transacting factors. We recently reported that the cloned rat alpha 2u-globulin 207 gene manifests tissue-specific androgen-dependent expression; it is expressed in livers of male, but not female, transgenic mice. In the present study a portion of this gene (-639 to +1395) is used as an in vitro template in the presence of nuclear extracts derived from hepatic nuclei of prepubescent and mature male and female rats. alpha-Amanitin-sensitive in vitro transcription of the alpha 2u 207 gene by extracts derived from mature male rats is highly active and is at least 13 times as rapid as that with preparations from mature female or immature animals. In contrast, the rate of transcription of a control template, the adenoviral late promoter, is the same with all of these nuclear extracts. S1 nuclease analysis and the size of the transcript indicate that transcription is initiated in vitro at the same site as it is in vivo and that it continues to the 3' terminus of the alpha 2u-globulin template. Thus, cis sequences are present in this gene fragment which are controlled by developmentally regulated male transacting factors, enabling selective transcription of this alpha 2u-globulin gene. Mixing experiments indicate that this transcriptional control is positive.

Alpha-Globulins↗

PubMed2006

7S globulins from Phaseolus vulgaris L.: Impact of structural aspects on the nutritional quality.

7S globulins were extracted from common bean (Phaseolus vulgaris L.) seeds and characterized. SDS-PAGE showed major bands corresponding to the phaseolin subunits (43-53 kDa). An amino acid analysis indicated that, in spite of the limited amounts of sulphur amino acids and tryptophan, the globulins contained very high levels of essential amino acids. The protein solubility profiles of native and denatured (120 degrees C for 20 min) 7S globulins in water and in 0.5 M NaCl showed that NaCl had a limited effect on increasing the solubility of either the native or denatured proteins. The in vivo small intestinal digestibility of the 7S globulins was 90%, this being decreased to 86% after a thermal treatment. Fourier transform infrared spectroscopy revealed a high content of beta-sheet and beta-turn structures, together with a contribution at 1687 cm(-1) that was assigned to intramolecular beta-sheets. These features are diagnostic of a high propensity to irreversible aggregation that may be related to an adverse effect on the protein quality.

Amides↗

PubMed1996

Daily rhythmic and non-rhythmic variations of follitropin, lutropin, testosterone, and sex-hormone-binding globulin in men.

The circadian rhythmic variations of the serum concentrations of follitropin, lutropin, sex-hormone-binding globulin and testosterone, the ratio between the serum concentrations of testosterone and sex-hormone-binding globulin, and the salivary concentration of testosterone were investigated in a group of 13 apparently healthy men. Venous blood and salivary specimens were collected at 4-h intervals over a 24-h period. The circadian rhythms were studied by using a periodic function resulting from the sum of two cosine functions with periods of 24 and 12 h. The serum concentrations of follitropin and lutropin showed no significant rhythmic variations. For the salivary concentration of testosterone and for the ratio between the serum concentrations of testosterone and sex-hormone-binding globulin, only the cosine function with a period of 24 h was significant. Serum concentrations of sex-hormone binding globulin and testosterone were significantly affected by 24- and 12-h rhythmic components. Of the quantities studied, the salivary concentration of testosterone showed the greatest daily rhythmic variation (28.8% of the mean estimated over rhythm).

Adult↗

PubMed1989

Immunocytochemical localization of the sex hormone-binding globulin in a human hepatoma cell line.

The human hepatoma cell line HEP G2 was investigated in an indirect immunofluorescence study for localization of the sex hormone-binding globulin. Cells were grown directly to confluency on the slides used for the immunocytochemical staining. A fine granular cytoplasmatic fluorescence pattern revealed the presence of sex hormone-binding globulin. Chang-liver cells used as controls, incubated under the same conditions, did not fluoresce. The synthesis of the hormone-binding protein in HEP G2 cells, which could be stimulated by L-thyroxine in the culture medium, was monitored by either indirect immunofluorescence or by immunoradiometric determination of sex hormone-binding globulin in the supernatant. These studies demonstrate that immunofluorescence techniques are able to detect sex hormone-binding globulin in human hepatoma cells.

Carcinoma, Hepatocellular↗

PubMed1990

Effect of dihydrotestosterone on serum concentrations of alpha 2u-globulin and on spermatogenesis in melatonin-treated rats.

Adult male rats were given s.c. injections of melatonin (400 micrograms/100 g body weight per day) for 14 days. On day 15, the weights of the testis and accessory sex organs were less, testicular 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity was inhibited, spermatogenesis was suppressed and serum levels of gonadotrophins, testosterone and alpha 2u-globulin were decreased compared with control animals injected with vehicle. In a third group of rats given the same dose of melatonin for 14 days, administration of dihydrotestosterone (DHT) at a dose of 25 micrograms/100 g body weight per day on days 8-14 resulted in serum levels of alpha 2u-globulin, FSH, LH and testosterone and testicular 17 beta-HSD activity similar to those seen in vehicle-injected control animals. Weights of the testes and accessory sex organs and spermatogenesis were normal after administration of DHT in melatonin-treated rats. In another group of rats, the depressive effects of melatonin treatment on plasma gonadotrophins were reversed by the administration of alpha 2u-globulin on days 8-14. It was concluded that treatment with DHT prevents the depressive action of melatonin on testicular function by inducing the synthesis of alpha 2u-globulin.

17-Hydroxysteroid Dehydrogenases↗

PubMed2003

Inhibitory effect of serum globulins on the adhesion of Prevotella nigrescens to hydroxyapatite.

Prevotella nigrescens ATCC 25261 cells adhere well to protein-blocking hydroxyapatite (HA) which mimics a root surface in the periodontal pocket treated with proteases such as trypsin, proteinase K, chymotrypsin and papain. This study was done to clarify the inhibitory effect of alpha- and beta- serum globulins on the adhesion of P. nigrescens ATCC 25261 cells to trypsin-treated HA. The inhibitory effect was found to be caused by the alpha1-antitrypsin (alpha1-AT) of alpha-globulin and the low-density lipoprotein (LDL) of beta-globulin under experimental conditions. The most effective inhibition of alpha1-AT on P. nigrescens ATCC 25261 cell attachment to HA was achieved when alpha1-AT-treated trypsin was used. The most effective inhibition of LDL occurred when trypsin-treated HA was treated with LDL. Apo-transferrin (TF) and holo-TF, which are beta-globulins, did not affect the attachment of P. nigrescens ATCC 25261 cells to trypsin-treated HA.

Animals↗

PubMed1981

Influence of administered indigenous microorganisms on uptake of [iodine-125] gamma-globulin in vivo by intestinal segments of neonatal calves.

Ten calves less than 14 h of age (average 8.6 h) were anaesthetized, and the intestine was ligated into segments 10 cm in length at 3-cm intervals beginning 1.8 m anterior of the ileocecal junction and proceeding proximally. Seven treatments were assigned in random order to segments in three successive sections of the small intestine. Segments received 1 ml of viable bacteria of intestinal origin, autoclaved bacteria of intestinal origin, or sterile microbiological broth at zero time; then after 4 h they were injected with iodine-125 labeled gamma-globulin. After an additional 1.5 h, the experiment was ended and uptake assayed. Two treatments measured anaerobic microbial growth after 4 h incubation with 1 ml of either sterile broth or live bacteria culture. Residual [iodine-125] gamma-globulin was measured in segments receiving 1 ml of sterile broth or live bacteria culture with 5.5-h incubation followed by 15-s exposure to labeled gamma-globulin. Uptake was lowest in segments receiving live bacteria as compared to segments receiving sterile inocula. Number of bacteria per gram of tissue was correlated negatively with uptake. Low corticosteroids in serum were associated with low uptake of gamma-globulin.

Animals↗

PubMed1981

Effects of dietary soybean globulins on plasma and liver lipids and on fecal excretion of neutral sterols in rats.

Effects of low-fat (1% corn oil) diets containing an isonitrogenous level (3.2%) of either casein, soybean protein isolate or three soybean globulin fractions (total, 11S and 7S globulins) on plasma and liver lipids and on the excretion of fecal neutral sterols were examined in rats. When diets free of cholesterol were fed, the concentration of plasma cholesterol was significantly lower in all groups of rats given different soybean proteins than in the animals given casein. 11S globulin tended to produce a lower level of plasma cholesterol as compared with the 7S counterpart. Although the net decrease due to feeding plant proteins in high density lipoprotein cholesterol was to some extent greater than that of very low and low density lipoprotein cholesterol, the percentage of the former to total cholesterol remained in the normal range. The concentration of liver cholesterol appeared to be lower in rats given soybean proteins. Rats fed soybean globulins, as compared with the animals fed casein, tended to excrete larger amounts of neutral sterol into the feces. These soybean-effects disappeared when cholesterol and cholic acid were added to diets. The results indicated that the antihypercholesterolemic effect of soybean protein was attributable to protein per se, and not to the carbohydrate components which were associated with the protein preparation.

Amino Acids↗

PubMed2026

Genetic Evidence Links Sex Hormone-binding Globulin to Total Body Bone Mineral Density at Age 45-60 Years: A Two-sample Mendelian Randomization Study.

The menopausal transition and early postmenopause represent important periods for women's skeletal health, but the genetic relevance of metabolic, behavioral, and hormone-related factors to bone mineral density during midlife remains incompletely understood. This study used publicly available genome-wide association study summary statistics to examine associations between body mass index, 25-hydroxyvitamin D, sex hormone-binding globulin, high-density lipoprotein cholesterol, smoking initiation, and alcohol intake frequency and total body bone mineral density at ages 45-60 years. Exposure genome-wide association study summary statistics were derived from large European-ancestry populations and were not restricted to midlife women, whereas the outcome genome-wide association study captured an age-stratified total body bone mineral density phenotype at age 45-60 years. This age range overlaps with the menopausal transition and early postmenopause in women. Univariable, reverse, and multivariable Mendelian randomization analyses were performed, with inverse-variance weighting as the primary method and complementary sensitivity analyses used to assess heterogeneity, pleiotropy, and result stability. Genetically predicted higher sex hormone-binding globulin was associated with lower total body bone mineral density (β = -0.111, 95% CI: -0.170 to -0.051; P = 0.0003). Reverse Mendelian randomization did not support reverse causation from bone mineral density to sex hormone-binding globulin. Multivariable analyses suggested that this association persisted after adjustment for selected metabolic biomarkers. The other examined exposures did not show consistent evidence of association. These findings provide genetic evidence linking sex hormone-binding globulin to total-body bone mineral density at ages 45-60 years. Further prospective and predictive studies are needed to evaluate its clinical relevance beyond established bone health assessment tools.

Humans↗

PubMed1980

Value of beta 1C/1A globulin serum levels as an early index of glomerular involvement in Schistosoma mansoni infection.

In attempting the early detection of glomerular abnormalities in patients with the hepatosplenic form of Schistosoma mansoni infection, the serum concentration of beta 1C/1A globulin was determined in 17 patients without clinical evidence of nephropathy. Renal biopsies were obtained during splenectomy in all of them. The serum levels of beta 1C/1A globulin were below the normal limit in eight patients; of these, two had histological evidence of focal proliferative glomerulonephritis, two others had membranoproliferative glomerulonephritis, and one showed focal sclerosing glomerulonephritis. Of nine patients with normal serum levels of beta 1C/1A globulin, eight had no glomerular abnormalities demonstrated by light microscopy. Determination of the serum concentration of beta 1C/1A globulin proved to be a valuable index for the detection of early glomerulopathy in patients with hepatosplenic schistosomiasis, since a low level correlated well with the histologic demonstration of glomerular involvement by light microscopy.

Adolescent↗

PubMed2000

Policies and procedures related to weak D phenotype testing and Rh immune globulin administration. Results from supplementary questions to the Comprehensive Transfusion Medicine Survey of the College of American Pathologists.

OBJECTIVE: To determine and evaluate policies and procedures related to weak D phenotype testing and terminology and the administration of Rh immune globulin in selected clinical situations. Design, Setting, and Participants.-Institutions participating in the College of American Pathologists 1999 J-A Comprehensive Transfusion Medicine Survey program were asked to respond to a series of supplementary questions related to weak D phenotype testing and Rh immune globulin administration. More than 3500 institutions and transfusion services participated. RESULTS: Most supplementary questions elicited more than 3000 responses. Despite no clinical or regulatory mandate, 58. 2% of transfusion services routinely perform an antiglobulin test for the weak D phenotype in patients who test negative with anti-D reagents. Significant differences were found concerning the transfusion of blood components to patients with the weak D phenotype and the administration of Rh immune globulin to these individuals. At least one patient with the weak D phenotype with anti-D alloantibody formation was observed during a 12-month period by 31.8% of transfusion services. CONCLUSIONS: Significant variability concerning policies and procedures related to weak D typing and terminology was found in this survey. Transfusion of blood components to patients with the weak D phenotype and the administration of Rh immune globulin also demonstrated variations. Anti-D alloantibody formation by patients with the weak D phenotype may not be as rare as previously thought. Additional study related to the clinical significance of these results is warranted.

Blood Banks↗

PubMed1976

L-Asparaginase: effect on 7S gamma globulin extents and germinal centers in spleen and lymph-nodes.

Administration of L-asparaginase may cause remission in a high percentage of acute lymphocytic leukemias and lymphomas, either in experimental animals or in human beings. This enzyme is able to depress immune reactions like lymphocyte blastogenesis and delayed hypersensitivity, and to impair gamma-globulin synthesis. L-asparaginase also has antigenic properties, and may cause the formation of anti-L-asparaginase antibodies. This study reports observations on the effect of L-asparginase on the 7S gamma-globulin levels and on the behaviour of the germinal centers in spleen and lymph nodes. It has been found that after administration of low or intermediate doses of L-asparginase, a decrease in the size of the follicular marginal zones occurred. This was accompanied by an enlargement of the germinal centers. Furthermore the spleen weight decreased and the concentration of 7S gamma-globulin diminished slightly. In animals given high doses of L-asparaginase, germinal centers were enlarged even more but marginal zones appeared repopulated although not to the degree of the controls. The spleen weight of these enzyme-injected animals reached almost the normal values, while a statistically significant decrease of 7S gamma-globulin concentrations was found.

Animals↗

PubMed1979

Interference of iodine-125 ligands in radioimmunoassay: evidence implicating thyroxine-binding globulin.

Although there is abundant published evidence that radioiodinated antigens interfere in digoxin radioimmunoassays, other radioimmunoassays are similarly affected. We investigated the relationship of radioiodinated antigen structure to its function in the immunoassay. Carrier-free 125I-labeled iodotyrosine and iodohistamine derivatives were incubated with human serum, and the bound and free fractions were separated. We demonstrated that diiodotyrosyl analogs bind avidly to serum proteins. Because protein binding could be reduced with competitors that inhibit thyroxine-binding globulin, such as 1,8-anilinonaphthalene sulfonate and thyroxine, thyroxine-binding globulin was clearly implicated. Diiodotyrosyl compounds also bound to solutions of purified thyroxine-binding globulin, and this binding was inhibited by the same two competitors. We postulate that thyroxine-binding globulin is the major source of the heretofore unexplained interference of radioiodinated haptens. We present recommendations for eliminating or minimizing such interference.

Digoxin↗

PubMed1954

Prevention of infections hepatitis by gamma globulin.

Infectious hepatitis, a viral disease, has become increasingly more important in recent years. It is believed that the great increase in reported cases is not due entirely to better reporting, but that there has been an actual increase in the incidence of this disease. The comparatively long incubation period in infectious hepatitis, the high incidence in persons in close contact with patients who have the disease, and the fact that in most instances contact between persons is the mode of spread, makes this disease particularly suitable for the use of an immunizing agent which would be administered after exposure. From the studies reviewed it is apparent that gamma globulin is of value in preventing hepatitis both when administered as mass prophylaxis in an epidemic, and when given to persons in close contact with a person who has the disease. Widespread use of gamma globulin prophylactically among persons who have been in close contact with the occasional patients with infectious hepatitis seen by practicing physicians might often obviate the need for mass immunization. It should be stated that there is little evidence for the effectiveness of gamma globulin in the therapy of infectious hepatitis. In a study in which very large amounts (average dose 45 cc.) of gamma globulin were given very early in the disease, no significant difference was observed between those injected and a control group.

Biomedical Research↗

PubMed1962

Local application of antirabies gamma-globulin in dried form for the prevention of rabies.

The authors report on guinea-pig experiments conducted to determine the effect of dried antirabies gamma-globulin in the local treatment of wounds infected with street rabies.The results showed that local application of dried gamma-globulin within 30 minutes of the time of infection of the wound protected the majority of animals and resulted in a considerably longer incubation period in the remainder than in the controls. When the preparation was applied later than 30 minutes after infection, the therapeutic effect was slight or absent. Optimum protection in these experiments was obtained through rapid application of gamma-globulin, followed by vaccination every other day for six days.Dried antirabies gamma-globulin exerts a specific, local action on the rabies virus and is entirely painless and non-destructive to body tissues.

Animals↗

PubMed1978

Serum albumin and total globulin levels in common liver diseases in Accra (Ghana).

Serum albumin and total globulin were determined in 22 healthy people, 29 patients with acute viral hepatitis, 27 patients with cirrhosis and 27 patients with primary hepatocellular carcinoma to see if they might be of discriminating value. The mean serum albumin values were found to be highest in the healthy subjects followed by acute viral hepatitis, primary hepatocellular carcinoma and cirrhosis, in that order. The mean serum total globulin values on the other hand, were found to be lowest in the healthy subjects followed by acute viral hepatitis, primary hepatocellular carcinoma and cirrhosis, in that order. Both the mean albumin and mean total globulin of each group of subjects were significantly different from the respective means of the other three groups. A probable explanation for the higher serum albumin and lower globulin levels found in primary hepatocellular carcinoma, as compared to cirrhosis, is that hepatocellular carcinoma occurs in reasonably well-compensated cases of cirrhosis.

Adult↗

PubMed1988

[The nature of serum factor precipitating autologous alpha-globulins in rabbits].

The nature of serum factor, resulted from the immune response to human albumin being a precipitant of auto-alpha-globulins in rabbits, have been studied. The use of ion exchange, immunoaffinity chromatography and immunoelectrophoresis has shown, that antibodies to human albumin, carrying the binding site to alpha-globulin in antigen-binding fragment are the factor responsible for alpha-globulin precipitation. The synthesis of antibodies cross-reacting to alpha-globulin gives the evidence of the selective derangement of tolerance to one of organism self antigens during the immune response to heterologous antigen.

Alpha-Globulins↗