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PubMed1993

Fibrinogen and the albumin-globulin ratio in recurrent stroke.

BACKGROUND AND PURPOSE: In following patients initially recruited for a cross-sectional study of blood viscosity in ischemic cerebrovascular disease, it was noted that those having a low albumin-globulin ratio appeared to experience the majority of subsequent vascular events. Accordingly, a prospective study in which subjects were assigned to a high or low albumin-globulin cohort was undertaken to examine the relation between a low albumin-globulin ratio, the presence of clinical risk factors for stroke, and the occurrence of subsequent stroke, myocardial infarction, or vascular death. METHODS: Three groups of subjects were followed for an average of 1.5 +/- 0.8 years to ascertain vascular end points. Group 1 consisted of 126 patients with acute ischemic stroke; group 2 included 109 subjects matched with group 1 for age, medications, and recognized clinical risk factors for stroke; and group 3 was composed of 84 healthy volunteers, matched for age with groups 1 and 2. The median albumin-globulin ratio for group 1 at enrollment, 1.45, was used to dichotomize patients into two cohorts: all subjects with an albumin-globulin ratio of 1.45 or less were assigned to the "low" albumin-globulin cohort; those whose ratio was greater than 1.45 were assigned to the "high" albumin-globulin cohort. The occurrence of vascular end points was verified during subsequent hospitalizations and outpatient clinic visits and by telephone interviews of patients and providers. RESULTS: A total of 51 vascular events occurred, including 39 in group 1, 8 in group 2, and 4 in group 3. Subjects in either group 1 or 2 who were in the low albumin-globulin cohort had at least double the risk for a subsequent vascular event compared with their counterparts in the high albumin-globulin cohort (P < .01 and P < .03, respectively). In comparison with the high albumin-globulin cohort, significantly more patients in the low albumin-globulin cohort in group 1 had a history of prior stroke (P < .03). When groups 1 and 2 were combined, both a low albumin-globulin ratio and diabetes had a significant independent association with increased risk for subsequent vascular events in a Cox proportional-hazards model (P < .01 and P < .03, respectively). CONCLUSIONS: The results of this study indicate that significantly increased risk for subsequent vascular events in stroke patients and in subjects with clinical risk factors for stroke is associated with a shift in the concentrations of blood proteins to a prothrombotic environment characterized by lower levels of albumin and an increased concentration of globulins and fibrinogen.

Aged↗
PubMed1994

Detection and characterization of hepatitis C virus RNA in immune globulins.

BACKGROUND: Hepatitis C virus (HCV) RNA was measured in immune globulins and its chemical and physical properties were characterized. STUDY DESIGN AND METHODS: The study examined 69 immune globulin lots from 7 manufacturers, including 44 intravenous and 25 intramuscular immune globulin preparations. In addition, 8 experimental intravenous immune globulin preparations were investigated. Detection and quantitation of HCV RNA were achieved by reverse transcription and nested polymerase chain reaction at limiting dilution. A multi-antigen anti-HCV enzyme immunoassay was also used to test these immune globulins. RESULTS: The highest level of HCV RNA was found in an experimental immune globulin lot derived from a plasma pool made up of 186 anti-c100-3-reactive units. HCV RNA was detected only in 1 of 7 manufacturers' experimental intravenous immune globulin preparations derived from a pool made up of 2887 anti-c100-3-negative units. It was also detected in commercial intravenous immune globulin lots prepared by the same manufacturer from source plasma, but not from recovered plasma. More than half of the commercial intramuscular immune globulin lots, including specific immune globulin products, were HCV RNA positive. All immune globulin products examined were reactive for anti-HCV. Certain similarities were found for HCV RNA present in an immune globulin product and plasma. Ethanol at 20 or 25 percent had no effect upon the buoyant density of HCV RNA. CONCLUSION: Many immune globulin preparations contained HCV RNA, with levels depending upon both the type of starting plasma and the manufacturing process. Exposure to ethanol did not appear to affect the physical characteristics of HCV RNA.

Base Sequence↗
PubMed2001

Temporal profile of total, bound, and free Gc-globulin after acetaminophen overdose.

Low admission values of the actin scavenger Gc-globulin are associated with an adverse outcome in acetaminophen (paracetamol) overdose. This prospective longitudinal study including 84 patients with acetaminophen overdose characterizes the temporal profile of Gc-globulin during the entire length of hospitalization. Serum Gc-globulin (total, actin bound, and free) levels and actin-complex ratio were measured on admission and every 12 hours until discharge. In 32 patients without hepatotoxicity (non-HEPTOX group; peak transaminase levels < 1,000 U/L), total and free Gc-globulin levels and complex ratio remained within normal range during hospitalization. Among 52 patients with hepatotoxicity (HEPTOX group; peak transaminase levels > 1,000 U/L), 15 patients had hepatic encephalopathy (HE), and 37 patients did not. In these 2 groups, total and free Gc-globulin levels decreased to 97 and 50 mg/L and 148 and 86 mg/L, respectively (normal mean, 340 and 299 mg/L), the nadir occurring at 72 hours postoverdose. Complex ratio peaked at 60 hours at levels more than 3-fold greater than normal. Conversely, bound Gc-globulin remained within normal levels for all patients throughout the observation period. At day 2, a total Gc-globulin cutoff value of less than 120 mg/L correctly predicted HE in 75%, and a value greater than 120 mg/L correctly predicted the absence of HE in 91% of patients. In conclusion, Gc-globulin is severely stressed in patients with hepatotoxicity. Extreme values occurred at 60 to 72 hours postoverdose, a period in which Gc-globulin protection against actin toxicity may be inadequate. A total Gc-globulin level less than 120 mg/L on day 2 is a good predictor of later HE. Bound Gc-globulin is maintained at constant levels independent of total Gc-globulin levels, suggesting a balanced upregulation of the removal of bound Gc-globulin even under conditions with increased actin release.

Acetaminophen↗
PubMed2001

Increased turnover of Gc-globulin in patients with hepatic encephalopathy.

BACKGROUND: A low serum level (< 100 mg/L) of the actin-scavenger Gc-globulin is a prognostic marker of non-survival in fulminant hepatic failure (FHF). It is unknown whether decreased production or increased consumption (or both) is responsible for the low Gc-globulin levels. METHODS: Ten patients with FHF and four patients with acute or chronic liver disease (AOCLD) with hepatic encephalopathy (HE) grades II-IV were included. Eight patients with cirrhosis (chronic liver disease, CLD) without HE served as controls. Total, free, and actin-bound Gc-globulin were measured in samples from an artery, a central vein, and a hepatic vein. In 12 patients (9 FHF, 3 AOCLD), concentrations were measured before and after high volume plasmapheresis (HVP). RESULTS: Total Gc-globulin was reduced to 21%, 40%, and 43% of the normal level in the FHF, AOCLD, and CLD groups, respectively, whereas bound Gc-globulin was within normal range in all patients. The Gc:actin complex ratio was increased 3.8, 2.5, and 1.9-fold compared with normal levels. Total, free, and bound serum Gc-globulin levels did not differ among arterial, systemic venous, or hepatic venous blood. Total Gc-globulin rose to >100 mg/L in all patients after HVP, whereas bound Gc-globulin remained unchanged. The Gc-globulin production rate in FHF and AOCLD patients was increased to 4.1 +/- 1.3 mg/min compared to literature values of 0.6 mg/min in healthy individuals. The estimated half-life of total Gc-globulin was shorter in the patients compared to healthy individuals (127 +/- 56 min and 870 min, respectively). CONCLUSIONS: Gc-globulin levels were reduced in patients with FHF and AOCLD because a 7-fold increase of Gc-globulin production rate could not compensate for the accelerated clearance. Bound Gc-globulin was maintained within normal levels in all circumstances studied, indicating a possible regulatory role of this parameter in the clearance of actin.

Adult↗
PubMed2006

Genetic variation in pea seed globulin composition.

A quantitative characterization of seeds from 59 pea (Pisum sativum L.) lines and relative taxa with various external characteristics and wide geographical origin was performed to explore the genetic variation of pea concerning its starch and protein contents and globulin composition. Pea lines, which produce round, wrinkled, flat, and round-dimpled seeds, have starch as the major reserve, with an average content of 46%. Protein content varied from 13.7 to 30.7% of the seed dry matter, with an overall average of 22.3%. Densitometric quantification of the individual globulins (legumin, vicilin, convicilin, and globulin-related proteins) based on SDS-PAGE gels showed no lines lacking any particular globulin. Among the lines tested, variation was shown in both their total globulins content and their globulin composition. The total globulin content ranged from 49.2 to 81.8% of the total pea protein extract (TPPE). Legumin content varied between 5.9 and 24.5% of the TPPE. Vicilin was the most abundant protein of pea, and its content varied between 26.3 and 52.0% of the TPPE. Both processed and nonprocessed vicilins occurred. The processed vicilin was the predominant one, with values between 17.8 and 40.8%, whereas the nonprocessed ones constituted between 3.1 and 13.5% of the TPPE. Convicilin was the least abundant globulin, and its content ranged from 3.9 to 8.3%. Finally, the globulin-related proteins were present in amounts ranging from 2.8 to 17.3%. They were less abundant in comparison with legumin and vicilin, but they showed the largest relative variation of the four globulin classes. Correlations between the different external characteristics and globulin composition were determined. Comparison with soybean showed that pea lines show more variety in the abundance of globulin proteins, enabling a wider range of food application.

Electrophoresis, Polyacrylamide Gel↗
PubMed1987

Sex-independent synthesis of alpha 2u-globulin and its messenger ribonucleic acid in the rat preputial gland: biochemical and immunocytochemical analyses.

alpha 2u-Globulin is the principal urinary protein of the mature male rat. The major urinary source of this protein is the liver where it is synthesized and secreted by hepatocytes under hormonal regulation. High levels of alpha 2u-globulin and its messenger RNA (mRNA) are also present in the preputial gland of both male and female rats, and neither castration nor ovariectomy significantly alters the preputial concentration of this protein and its mRNA. Per unit mass of RNA and protein, the preputial gland as compared to liver contains about 3-fold higher level of alpha 2u-globulin mRNA and about 300-fold higher level of alpha 2u-globulin. Despite a 3-fold (300%) difference in the content of alpha 2u-globulin mRNA, nuclear run-off experiments show only a 30% higher rate of alpha 2u-globulin gene transcription in the preputial gland than in the liver. Immunocytochemical analyses reveal that the liver possesses two alpha 2u-globulin cell populations, one showing higher immunoreactivity than the other. In contrast, the preputial gland contains only one type of alpha 2u-globulin containing acinar cells, and a large amount of alpha 2u-globulin accumulates in the ductal lumen. From these results we conclude that the 300% higher level of alpha 2u-globulin mRNA in the preputial gland is not due to a corresponding difference in the rate of transcription of alpha 2u-globulin gene. Such a difference may represent tissue-specific regulation at a posttranscriptional level of mRNA metabolism. Furthermore, the huge difference in the alpha 2u-globulin content of the preputial gland and the liver is primarily due to the cellular and ductal accumulation of this protein in the preputial gland vs. its rapid secretion by the liver.

Alpha-Globulins↗
PubMed2000

Roles of gamma-Globulin in the Dynamic Interfacial Behavior of Mixed Dipalmitoyl Phosphatidylcholine/gamma-Globulin Monolayers at Air/Liquid Interfaces.

This study investigated the roles of gamma-globulin in the dynamic interfacial behavior of dipalmitoyl phosphatidylcholine (DPPC)/gamma-globulin monolayers at air/liquid interfaces at 25 degrees C. The surface tension behavior demonstrated that gamma-globulin had a large adsorption time scale. Moreover, the surface pressure-area hysteresis behavior of adsorbed gamma-globulin monolayers suggested that no significant desorption occurred during the compression stage, and the respreading of gamma-globulin molecules at the interface during the expansion stage was slow. From the hysteresis behavior of adsorbed gamma-globulin monolayers with spread DPPC molecules, it was found that gamma-globulin molecules were expelled from the interface as DPPC molecules were in a condensed state. The squeeze-out of gamma-globulin molecules seemed to induce the loss of DPPC molecules at the interface with the extent depending on the initial gamma-globulin surface concentration. Furthermore, the expelled gamma-globulin molecules re-entered the monolayer and participated in the surface pressure increase during the following expansion stage. The exclusion of gamma-globulin associated with the removal of DPPC during monolayer compression and the re-entry of gamma-globulin during subsequent monolayer expansion represented a mechanism for DPPC depletion and gamma-globulin enrichment at the interface, which may explain the inhibitory effect of certain proteins on the surface activity of DPPC. Copyright 2000 Academic Press.

Journal Article↗
PubMed2001

Three novel mutations causing complete T(4)-binding globulin deficiency.

Inherited T(4)-binding globulin deficiency is caused by mutations in the T(4)-binding globulin gene located on the X chromosome. We describe herein three novel mutations in three different families producing complete T(4)-binding globulin deficiency. The proposita of a family from Harwichport is a female with XO Turner's syndrome who expressed only the mutant T(4)-binding globulin allele. Her T(4)-binding globulin sequence has a 19-nucleotide deletion in the distal portion of exon 4. This causes a frameshift and a premature stop at codon 384 of the mature protein. Structure analysis with the Swiss PDB-Viewer revealed that this mutation removes beta-strand s5B from the core of the T(4)-binding globulin molecule, leading to a severe folding defect that is likely to prevent synthesis and secretion. The propositi of complete T(4)-binding globulin deficiency 7 and 8 were 7-month-old and 3-wk-old male infants who were identified because of low serum T(4) levels detected during neonatal screening. Sequencing of complete T(4)-binding globulin deficiency 7 revealed a single nucleotide deletion, a G at position 2690 in exon 3. This leads to an alteration of the amino acid sequence starting at codon 283 and a premature stop at codon 301. Complete T(4)-binding globulin deficiency 8 also has a deletion of the first nucleotide of exon 4, a G at position 3358. This leads to a frameshift and a premature stop at codon 374. As in the case of complete T(4)-binding globulin deficiency J, which has also a nucleotide deletion but downstream (position 3421) and a stop at codon 374, these two T(4)-binding globulin mutants undoubtedly have a defect in intracellular transport and therefore fail to be secreted. This explains the lack of T(4)-binding globulin in the hemizygous affected subjects.

Adolescent↗
PubMed2003

Globulins enhance in vitro iron but not zinc dialysability: a study on six legume species.

The study was addressed to evaluate the in vitro iron and zinc dialysability from the globulin fraction of six legumes. Five legume species including white bean, mottled bean (Taylor bean), chickpea, lentil, lupin, and a modified mottled bean variety, selected by back-crossing to obtain seeds with globulins composed by G1 fraction only, were used. Globulins (G1 + G2) were extracted from the seeds and analysed for their in vitro iron and zinc dialysability. The highest globulin concentration was detected in lentil (89%). The percentage of globulins in the modified variety of Taylor bean (G1 only) was higher than that of the commercial variety (G1 + G2). The highest concentration of iron was found in Taylor bean globulins. The modified variety of Taylor bean contained 2.6-fold higher iron concentration than the whole seed, and the commercial variety had 1.8-fold higher iron only. The highest zinc concentration was found in lentil globulins. Also iron dialysability from globulins was markedly higher than that of the respective whole seed. The highest value of iron dialysability was found in lentil (10.8%). Zinc dialysability was generally high (above 20%), but no significant differences between whole seed and globulins were detected. The results showed that globulins enhanced iron but not zinc dialysability. Lupin and the modified variety of Taylor bean showed a different behaviour in terms of mineral dialysability compared to the other legumes. The amino acid composition of the digestion products of whole seeds and globulins failed to evidence any direct influence on iron and zinc availability.

Amino Acids↗
PubMed2004

Surface physicochemical properties of globulin-P amaranth protein.

Globulin-P, the polymerized 11S amaranth globulin, is composed of 280 kDa unitary molecules (UM, 23%) and aggregates larger than 500 kDa (A, 70%). Antibodies against these proteins were prepared to study their surface characteristics and to assess their homology with other storage proteins. Results showed that globulin-P unitary molecules and aggregates had similar reactive surfaces. A polypeptide of 56 kDa was found to be the most reactive to the antibodies assayed, followed by the acidic polypeptides. Such results support previous information, according to which these polypeptides appeared to be the most exposed on the molecule surface. Globulin-P fraction presented cross-reactivity with the remaining amaranth protein fractions: 11S-globulin, glutelins, and albumins. Globulin-P and 11S-globulin showed similar reactive surfaces whereas glutelin and albumins presented a lower cross-reactivity. The reactivity of the glutelin fraction depended on its sequence. Globulin-P fraction presented cross-reactivity with quinoa globulins, and to a lesser extent with globulins of sunflower and rice. Moreover, the anti-Gp serum was unable to detect either conformational or sequence epitopes in globulins of soybean, wheat, buckwheat, rice, and rye.

Amaranthus↗
PubMed1998

Analysis of alpha2u-globulin in rat urine and kidneys by liquid chromatography-electrospray ionization mass spectrometry.

A quantitative method was developed for determination of alpha2u-globulin in urine and kidney samples collected from male rats using liquid chromatography-electrospray ionization mass spectrometry (LC-ESI/MS). Samples prepared from urine and kidney homogenates using size exclusion filters were subject to reversed-phase liquid chromatography and the effluent passed into an electrospray ionization source. Quantitative analysis using external standard calibration was based upon selected ion monitoring of protonated molecular ions by the mass spectrometer. Linear calibration curves were developed over the range of approximately 4. 6-370 microg of alpha2u-globulin/microL for spiked urine standards and over the range of approximately 4.6-550 microg of alpha2u-globulin/microL for spiked kidney standards. The precision (relative standard deviation) for repeated injection (using urine samples) and intra-assay precision (using both urine and kidney samples) were within +/-10.4% and +/-13.2%, respectively. Using spiked urine standards, inter-assay precision, intra-assay accuracy, and inter-assay accuracy were within +/-20%, +/-20%, and +/-15%, respectively. Using spiked kidney standards, intra-assay accuracy was within +/-15%. The limits of detection (LOD) for the determination of alpha2u-globulin in urine and kidney samples were approximately 0.41 pg/nL (1.0 fmol injected) and 25 pg/nL ( approximately 13 fmol injected), respectively. The limits of quantitation (LOQ) for determination of alpha2u-globulin in urine and kidney samples were calculated as 1.4 pg/nL (3.7 fmol injected) and 83 pg/nL (45 fmol injected), respectively. Applicability of the LC-ESI/MS method was demonstrated by determination of alpha2u-globulin in both urine and kidney samples collected from male Fischer 344/N rats dosed intravenously with cis-Decalin at concentrations of 0, 2.5, 5.0, 10, and 20 mg/kg. A dose-dependent relationship was found between the amount of cis-Decalin administered and alpha2u-globulin accumulation in kidney samples, whereas no significant change in the urinary levels of alpha2u-globulin occurred. These observations are consistent with excessive accumulation of alpha2u-globulin occurring in protein droplets in renal proximal tubule epithelial cells as a result of decreased catabolic activity due to formation of ligand-protein complexs with Decalin and its metabolite(s). This report demonstrates that LC-ESI/MS may be routinely applied for quantitative analysis of alpha2u-globulin in rat urine and kidney samples to address alpha2u-globulin accumulation and its role in the development of nephrotoxicity associated with chemical exposures.

Alpha-Globulins↗
PubMed1981

Specific binding of thyroid-stimulating hormone by human serum globulins.

Globulin preparations (41) from patients with Graves's disease (positive to thyroid stimulating immunoglobulins; TSI) and 12 from healthy persons (TSI-negative) were tested for their specific thyrotrophin (TSH)-binding properties. Globulins from both groups possessed binding sites for 131I-labelled TSH. The mean dissociation constant (Kd) was 6.8 pmol/1 per mg globulin and the maximum specific binding (Bmax) was 3.0 pmol/mg globulin per 1 for the TSI-negative control group. Twenty-four (58.5%) globulin preparations from the TSI-positive group had similar TSH-binding characteristics with mean Kd of 7.2 pmol/1 per mg globulin and Bmax of 3.6 pmol/mg globulin per 1 (A-type binding) but the remaining 17 (41.5%) bound TSH in a different fashion with Kd of 71.5 pmol/1 per mg globulin and Bmax of 13.6 pmol/mg globulin per 1 (B-type binding). Both types of specific TSH binding reached the maximal level within 1 h of incubation and had an optimum pH of 7--8. There was a linear correlation between the amount of bound TSH and the globulin content of the samples. Both types of binding were reversible by the addition of an excess of TSH and gonadotrophins, ACTH, prolactin and insulin competed with TSH for the binding sites only when in relatively high concentrations. The binding sites were associated with macromolecules; they emerged with the void volume after chromatography on Sephadex G-200 and migrated with immunoglobulin G (IgG) on paper electrophoresis. The binding capacity of the globulin preparations could be decreased by preincubation with antiserum to human IgG or with human thyroid membranes.

Binding, Competitive↗
PubMed2002

Effects of providing a water-soluble globulin in drinking water and diet complexity on growth performance of weanling pigs.

Two experiments were conducted to evaluate the effects of providing a water-soluble globulin in the drinking water on growth performance of weanling pigs. In Exp. 1, 360 weanling pigs (5.0 +/- 1.2 kg; 17 +/- 3 d of age; PIC) were blocked by initial weight and allotted to one of six treatments in a 2 x 3 factorial arrangement. Treatments included three diet complexity regimens with or without water-soluble globulin (3 and 1.5% solutions; d 0 to 7 and d 0 to 14, respectively) provided in the drinking water. The 35-d study was divided into three phases (d 0 to 7, 7 to 14, and 14 to 35) with corresponding lysine levels of 1.6, 1.5, and 1.35%. Soybean meal replaced specialty protein and lactose sources to provide three different complexity regimens. From d 0 to 7, a water-soluble globulin x diet complexity interaction (P < 0.05) was observed for average daily gain (ADG) and gain:feed (G/F). Increasing diet complexity increased ADG and G/F for pigs provided water, whereas the medium diet complexity regimen optimized performance for pigs offered water-soluble globulin. From d 0 to 14, pigs fed the two more complex regimens had greater ADG and G/F (P < 0.01) than the pigs fed the least complex regimen. Pigs offered water-soluble globulin had decreased (P < 0.01) ADFI, but increased (P < 0.001) G/F from d 0 to 14. For overall performance (d 0 to 35), increasing diet complexity increased (P < 0.03) ADG and ADFI, whereas water-soluble globulin offered from d 0 to 14 had no effect. In Exp. 2, 360 weanling pigs (5.2 +/- 1.6 kg; 19 +/- 4 d of age) were used in a 21-d growth assay. The trial was arranged as a 2 x 3 factorial with pigs fed the low- or medium-complexity diets (Exp. 1) with water or a 3% solution of water-soluble globulin offered for 4 or 8 d after weaning. From d 0 to 4, pigs offered water-soluble globulin had increased (P < 0.001) ADG and G/F compared with pigs provided water, whereas from d 4 to 8, pigs provided water had increased (P < 0.05) ADG and G/F compared with pigs offered water-soluble globulin. Pigs fed the medium-complexity diet had increased ADG and G/F (d 4 to 8 and d 8 to 12) compared with pigs fed the low-complexity diet. From d 0 to 8 and d 0 to 21, pigs provided water-soluble globulin for 4 or 8 d after weaning had improved G/F compared with pigs provided water. Results demonstrate that providing water-soluble globulin through the water source of weanling pigs improves ADG and G/F immediately after weaning.

Animal Feed↗
PubMed1984

Thyroxine-binding globulin in serum and milk specimens from puerperal lactating women.

The whey fraction of human milk contains a thyroxine-binding protein analogous to serum thyroxine-binding globulin. To assess the method by which this binding protein appears in milk over the course of lactation, paired serum and milk specimens from 45 healthy, euthyroid women were assayed for thyroxine-binding globulin and whey thyroxine-binding globulin using a highly specific thyroxine-binding globulin-radioimmunoassay. Elevated serum levels (39.2 +/- 4.72 micrograms thyroxine-binding globulin/mL; mean + SD, N = 5) were found in samples drawn at less than two weeks post partum. These levels normalized rapidly over the next three weeks post partum (26.0 +/- 3.3 micrograms/mL, P less than .005, N = 5), and by five weeks, no further significant decreases were observed. As was the case for serum thyroxine-binding globulin, whey thyroxine-binding globulin was present in its highest concentrations (79.3 +/- 13.4 micrograms/dL, N = 7) in the colostrum and transitional milk. These levels are equivalent to approximately 2 to 3% of serum concentrations. In contrast to serum thyroxine-binding globulin levels, however, whey thyroxine-binding globulin declined logarithmically over a protracted 12-week period, and no further significant changes in whey thyroxine-binding globulin concentrations were observed up to 20 weeks post partum, at which time they were approximately equal to 1% of serum thyroxine-binding globulin levels. A strong linear correlation between serum and whey thyroxine-binding globulin was found within the first five weeks post partum (r2 = .95, P less than .0005, N = 14).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1994

A controlled trial of intravenous immune globulin to reduce nosocomial infections in very-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network.

BACKGROUND: Nosocomial infections are a major cause of morbidity and mortality in premature infants. As a rule, their low serum gamma globulin levels at birth subsequently decline to hypogammaglobulinemic values; hence, prophylactic administration of intravenous immune globulin may reduce the rate of hospital-acquired infections. METHODS: In this prospective, multicenter, two-phase controlled trial, 2416 infants were stratified according to birth weight (501 to 1000 g and 1001 to 1500 g) and randomly assigned to an intravenous immune globulin group (n = 1204) or a control group (n = 1212). Control infants were given placebo infusions during phase 1 of the study (n = 623) but were not given any infusions during phase 2 (n = 589). Infants weighing 501 to 1000 g at birth were given 900 mg of immune globulin per kilogram of body weight, and infants weighing 1001 to 1500 g at birth were given a dose of 700 mg per kilogram. The immune globulin infusions were repeated every 14 days until the infants weighed 1800 g, were transferred to another center, died, or were sent home from the hospital. RESULTS: Nosocomial infections of the blood, meninges, or urinary tract occurred in 439 of the 2416 infants (18.2 percent): 208 (17.3 percent) in the immune globulin group and 231 (19.1 percent) in the control group (relative risk, 0.91; 95 percent confidence interval, 0.77 to 1.08). Septicemia occurred in 15.5 percent of the immune globulin recipients and 17.2 percent of the controls. During phase 1 the rate of nosocomial infections was 13.4 percent in the immune globulin group and 17.8 percent in the control group; the respective rates during phase 2 were 21.0 percent and 20.4 percent. The predominant organisms included gram-positive cocci (53.0 percent), gram-negative bacilli (22.4 percent), and candida species (16.0 percent). Adverse reactions were rarely observed during the infusions. Immune globulin therapy had no effect on respiratory distress syndrome, bronchopulmonary dysplasia, intracranial hemorrhage, the duration of hospitalization, or mortality. The incidence of necrotizing enterocolitis was 12.0 percent in the immune globulin group and 9.5 percent in the control group. CONCLUSIONS: Prophylactic use of intravenous immune globulin failed to reduce the incidence of hospital-acquired infections in very-low-birth-weight infants.

Adult↗
PubMed2001

High-dose intravenous immune globulin for stiff-person syndrome.

BACKGROUND: Stiff-person syndrome is a disabling central nervous system disorder with no satisfactory treatment that is characterized by muscle rigidity, episodic muscle spasms, high titers of antibodies against glutamic acid decarboxylase (GAD65), and a frequent association with autoimmune disorders. Because stiff-person syndrome is most likely immune-mediated, we evaluated the efficacy of intravenous immune globulin. METHODS: We assigned 16 patients who had stiff-person syndrome and anti-GAD65 antibodies, in random order, to receive intravenous immune globulin or placebo for three months, followed by a one-month washout period and then by three months of therapy with the alternative agent. Efficacy was judged by improvements in scores on the distribution-of-stiffness index and heightened-sensitivity scale from base line (month 1) to the second and third month of each treatment phase. Direct and carryover effects of treatment were compared in the two groups. RESULTS: Among patients who received immune globulin first, stiffness scores decreased significantly (P=0.02) and heightened-sensitivity scores decreased substantially during immune globulin therapy but rebounded during placebo administration. In contrast, the scores in the group that received placebo first remained constant during placebo administration but dropped significantly during immune globulin therapy (P=0.01). When the data were analyzed for a direct and a first-order carryover effect, there was a significant difference in stiffness scores (P=0.01 and P<0.001, respectively) between the immune globulin and placebo groups, and immune globulin therapy had a significant direct treatment effect on sensitivity scores (P=0.03). Eleven patients who received immune globulin became able to walk more easily or without assistance, their frequency of falls decreased, and they were able to perform work-related or household tasks. The duration of the beneficial effects of immune globulin varied from six weeks to one year. Anti-GAD65 antibody titers declined after immune globulin therapy but not after placebo administration. CONCLUSIONS: Intravenous immune globulin is a well-tolerated and effective, albeit costly, therapy for patients with stiff-person syndrome and anti-GAD65 antibodies.

Adult↗
PubMed1997

Reduced serum Gc-globulin concentrations in patients with fulminant hepatic failure: association with multiple organ failure.

OBJECTIVE: To evaluate the association between admission serum concentrations of the actin-scavenger, Gc-globulin, and the subsequent development of multiple organ failure in patients with fulminant hepatic failure. DESIGN: Retrospective study. SETTING: A hepatologic intensive care unit. PATIENTS: Seventy-nine patients with hepatic encephalopathy grade 3 or 4. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum admission concentrations of both total and nonactin-complexed (free) Gc-globulin were determined. The development of cardiovascular failure, renal failure, pulmonary failure, intracranial hypertension, and infections were recorded in each patient. Both total and free Gc-globulin values were significantly lower in the patients, compared with normal controls. The Gc-globulin values were significantly reduced in patients who subsequently developed cardiovascular failure (p < .01), intracranial hypertension (p < .001), and infections (p < .001), compared with those patients who did not. No differences were found between patients with and without pulmonary or renal failure. Patients with total Gc-globulin values in the lowest quintile had on average 2.6 organ failures, whereas patients with Gc-globulin concentrations in the highest quintile had 0.9 organ failures. The corresponding figures for the lowest and highest quintiles of free Gc-globulin were 3.0 and 1.1 organ failures, respectively. Both total and free Gc-globulin were inversely correlated to the number of organ failures (p < .005 in both cases). Patients with multiple organ failure (> or = 2 organ failures) had significantly reduced Gc-globulin values compared with patients without multiple organ failure (p < .0001). CONCLUSIONS: In patients with fulminant hepatic failure, the lowest admission Gc-globulin concentrations were associated with the subsequent development of cardiovascular failure, intracranial hypertension, and infections. Lack of Gc-globulin correlated significantly with the development of multiple organ failure and may be pathogenetically involved in this condition.

Adolescent↗
PubMed1998

Serum Gc-globulin in the early course of multiple trauma.

OBJECTIVES: In patients with multiple trauma, actin released from damaged cells may cause severe circulatory disturbance due to thrombi formation. The aim of this study was to evaluate serum concentrations of the actin scavenger, Gc-globulin, in relation to the severity of injury and outcome. DESIGN: Prospective, longitudinal, observational study. SETTING: Trauma center at a university hospital. PATIENTS: Twelve patients with multiple trauma, consecutively included, according to defined criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum Gc-globulin concentrations were measured at the time of admission and daily thereafter for 1 wk or until death. In all patients, the Gc-globulin concentration was significantly low (p < .0001), and the proportion of Gc-globulin bound to actin was already increased compared with normal values (p < .0001) by the time of hospital arrival. There was an inverse correlation between the mean concentration of serum Gc-globulin in the first week after trauma and the Injury Severity Score (r = -0.72, p < .05). Surviving patients had a significantly (p < .05) higher concentration of serum Gc-globulin in the first week after trauma compared with nonsurvivors. CONCLUSIONS: Serum concentrations of Gc-globulin were significantly low in trauma patients. The reduction took place within 60 mins after injury. Because the normal half-life of Gc-globulin is almost 48 hrs, our observations suggest a marked consumption of Gc-globulin immediately after the trauma. This finding could be the first clinical evidence that Gc-globulin plays a role in the systemic inflammatory response syndrome after trauma. This result is supported by the finding that lack of Gc-globulin was related to nonsurvival and the severity of the trauma.

Actins↗