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PubMed1976

Deficiency in plasma protein synthesis caused by x-ray-incuded lethal albino alleles in mouse.

Plasma protein synthesis was studied in mice bearing x-ray induced lethal mutations at the albino locus. Newborn albino mutants showed a decrease in each of the three principal plasma proteins, albumin, alpha-fetoprotein, and transferrin, when compared with colored littermate controls. Incorporation of [14C]leucine into plasma proteins of the newborn albinos 30 min after injection was only 1/5 that of the controls, but incorporation into total liver protein was only slightly diminished. Incorporation of [14C]leucine into an albumin fraction obtained by immunoprecipitation from livers incubated in vitro in an amino acid mixture was also strongly diminished. Thus, the liver of 18-day-old albino fetuses incorporated into this fraction 1/3 and that of newborn albinos 1/8 as much as the controls, but in both cases the incorporation into total liver protein was only 25% less than in the respective controls. These results indicate that the rather severe structural abnormalities observed in the mutants in the endoplasmic reticulum and the Golgi apparatus are not associated with a general deficiency of hepatic protein synthesis. Instead the data from this and previous work show that the progressive deficiency from fetal life to birth involves certain specific proteins represented by several perinatally developing enzymes and by plasma proteins. It is suggested that the mutational effects observed in these mice are due to deletions involving regulatory rather than structural genes at or near the albino locus.

Albinism↗
PubMed1976

The plasma protein binding and distribution of etomidate in dog, rat and human blood.

The interactions of etomidate and its major metabolite (R 28 141) with plasma proteins were studied by equilibrium dialysis with a multiple cell system. A 4% human serum albumin solution was able to bind 78.5% of the etomidate, and 60.5% of R 25 141, whereas a 1.5% human gamma globulin solution bound etomidate for not more than 3% and did not bind R 28 141 at all. The association constants and free binding energies for the binding of etomidate and R 28 141 to human serum albumin were determined. Plasma protein binding of etomidate was 75.4% in the dog and 76.5% in man; in rat plasma 79.5% of the radioactivity was bound to the plasma proteins, however the etomidate was partly hydrolyzed, even in the presence of sodium fluoride. In the rat 29.7% was distributed to the blood cells, 55.9% bound to plasma proteins and 14.4% was present in plasma water; in the dog the distribution percentages were 42.1%, 43.7% and 14.2% respectively, and in man 37.7%, 47.6% and 14.7% respectively. The major metabolite of etomidate was distributed for 26.3% to the human blood cells, 47.4% was bound to plasma proteins and 26.2% was present in the plasma water; its plasma protein binding amounted to 64.3%. Etomidate was bound at or in the blood cells, whereas R 28 141 was not.

Blood Proteins↗
PubMed2002

Toxic effect of tannic and related compounds on human plasma proteins.

OBJECTIVE: To investigate the toxicity of tannic acid related compounds such as gallic acid and polyphenol on the activity of plasma proteins in vitro. Their electrophoretic results show extremely important information, albumin and globulin levels are remarkably changed and characterized by disorder in their fractions avere which occurred frequently. METHODS: All plasma proteins samples of sets A, B and C were treated in sequences with known different concentrations of gallic acid, gallotannin and polypholes, which were separated chromatographically from phenolic extract of fruit peel of punicaceae. These were then treated, A, B and C were subjected to electrophoresis techniques, for identification and quantitation. RESULTS: The electrophoretic patterns of treated plasma proteins samples, sets A, B and C are arised with remarkable changes in their fraction levels, compared to normal. The results in were also characterized by disorders in their electrophoretic pattern. In this way 5 fractions of treated plasma proteins could be distinguished after sustaining which are ablumin and alpha1, alpha2 and beta and gamma globulins. CONCLUSION: The biological activity of tannic acid related compounds on plasma proteins in vitro, is important in determining their toxicity, and this toxicity may be depend upon their metabolic processes in the liver. In addition, the electrophoretic techniques used for separation and identification of plasma protein is extremely important for future work in the area.

Blood Proteins↗
PubMed1968

Direct measurement of the rates of synthesis of plasma proteins in control subjects and patients with gastrointestinal protein loss.

The guanido carbon of hepatic arginine is the common precursor of urea and of the arginine of plasma proteins synthesized in the liver. It is possible to measure the momentary synthetic rates of plasma proteins by "pulse labeling" this arginine pool with bicarbonate-(14)C. In the current study, this method has been adapted in order to use urinary urea data and was applied to control subjects and patients with gastrointestinal protein loss. The assumptions required for this determination are discussed. There was close agreement between albumin synthetic rates measured by this method and albumin catabolic rates derived from simultaneous albumin-(131)I studies, supporting the validity of the method and suggesting that there is relatively little fluctuation in the rate of albumin synthesis from time to time. The albumin synthetic rates in six control subjects averaged 5.8 mg/kg per hr, while those of five patients with gastrointestinal protein loss averaged 7.2 mg/kg per hr. Thus in these patients, there was relatively little acceleration of albumin synthesis in response to continued loss of plasma proteins into the gastrointestinal tract. Fibrinogen synthetic rates averaged 1.9 mg/kg per hr in five control subjects and 3.2 mg/kg per hr in five patients with gastrointestinal protein loss. Transferrin synthetic rates exhibited considerable individual variation in both groups and averaged 0.24 mg/kg per hr in four control subjects and 0.31 mg/kg per hr in five patients with gastrointestinal protein loss. The method employed in this study offers several advantages in studying plasma protein metabolism. It provides a direct measurement of protein synthesis, applicable to several proteins simultaneously, does not require a long-term steady state in the metabolism of the proteins, and is capable of measuring short-term fluctuations in synthetic rates. Therefore, this approach is applicable to the investigation of the physiological factors controlling the rates of synthesis for plasma proteins.

Amyotrophic Lateral Sclerosis↗
PubMed1992

Partially hepatectomized rats: a model for the study of the effect of toxins on the plasma protein profiles of nascent hepatocytes.

A useful framework is proposed for unifying the synthesis of plasma proteins and their degradation by, or release from, liver cells of intact and partially hepatectomized rats, in which synthesis and release of acute-phase plasma proteins occur in synchrony with the internalization and catabolism of plasma and extracellular proteins. The catabolism of proteins and other hepato-intracellular glycoproteins during sepsis or trauma is essential to provide constituent amino acids and carbohydrates for the synthesis of acute-phase plasma proteins. Increases in the plasma levels of acute-phase response proteins in sham-operated rats reached a maximum between 1 and 2 d after mock surgery, and had returned virtually to control levels within 6 d. By contrast, acute-phase proteins in the plasma of partially hepatectomized rats were decreased by 10-20% of their initial values after 24 h. A maximum acute-phase response on d 7 after the operation was characterized by an increase of 181, 445, and 19% for alpha-1-acid glycoprotein, hepatoglobin, and hemopexin, whereas other acute-phase proteins remained below control levels, for example, by 11, 25, and 38% for albumin, transferrin, and prealbumin, respectively. This delayed response suggests that the nascent liver cells had inherited the capacity of the parent cells to respond to inflammatory signal and had synthesized acute-phase plasma proteins. Accordingly, a time frame for the application of toxin to nascent hepatocytes is suggested. An increased activity (300 +/- 50%) for both bound and free neuraminidase in remnant liver tissue 19 h post partial hepatectomy suggested that hepatic regenerating factor(s) were produced in liver tissue via the hepatic bound and/or free neuraminidase-mediated desialylation of humoral substrates. By contrast, circulating levels of lysosomal enzymes alpha-fucosidase and beta-N-acetyl-D-glucosaminidase were increased marginally after 24 h but had returned nearly to control levels after 7 d, suggesting that lysosomal acid hydrolases do not play a major role in regenerative DNA synthesis, mitosis, or in the synthesis of acute-phase plasma proteins.

Acute-Phase Proteins↗
PubMed1994

Regulation of lipid transfer between lipoproteins by an endogenous plasma protein: selective inhibition among lipoprotein classes.

Lipid transfer protein (LTP) remodels plasma lipoproteins by promoting mass transfers of cholesteryl ester (CE) and triglyceride between lipoproteins. We have investigated the capacity of an additional plasma protein, lipid transfer inhibitor protein (LTIP) to modify the functional activity of LTP in a complex mixture of lipoproteins. Transfer assays containing isolated LTP, LTIP, and the three major lipoprotein classes, and assays with intact human plasma supplemented with exogenous LTIP were used. In both assays, the inhibition of CE transfer by LTIP varied markedly depending on the lipoproteins involved and was dependent on LTIP concentration. Inhibition of lipid transfer between a given pair of lipoproteins was similar. However, between lipoprotein pairs the extent of inhibition was very different, varying up to 7-fold. Inhibition followed the order of very low density lipoprotein (VLDL)-low density lipoprotein (LDL) transfers > LDL-high density lipoprotein (HDL) transfers > VLDL-HDL transfers. Consistent with the preferential inhibition of transfer events involving LDL, LTIP was shown by gel filtration studies to associate primarily with LDL in plasma. The addition of LTIP to native plasma stimulated the LTP-mediated efflux of CE from HDL to VLDL; this occurred at the expense of LDL CE depletion. Thus, LTIP alters the pattern of lipid transfer reactions in plasma by uniquely affecting the individual transfer events mediated by LTP. By preferentially diminishing transfer events involving LDL, especially those between VLDL and LDL, LTIP enhances the ability of LTP to remove CE from HDL, and thus alters HDL metabolism.

Blood Proteins↗
PubMed1995

Effects of various risk factors on plasma protein and serum immunoglobulin concentrations of calves at postpartum hours 10 and 24.

In an attempt to identify important predictors of failure of passive immunoglobulin transfer (< 800 mg of IgG/dl), identify calves with failure of passive immunoglobulin transfer, and determine the effects of a colostrum supplement, blood samples were collected from 263 calves at postpartum hours 10 and 24. Calves of dams diagnosed with mastitis had lower mean plasma protein and IgG concentrations at 10 (P < 0.05) and 24 (P < 0.01) hours. Plasma protein and IgG concentrations were similar for single and twin calves at 10 hours, but IgG concentration at 24 hours was higher (P < 0.01) in twin calves. Calves born to dams that had dystocia had numerically lower mean plasma protein and IgG concentrations than did calves born to dams that had normal delivery. However, observed differences were small and, after adjustment for other important factors, these differences were not significant. Age of dam was associated with plasma protein (P < 0.05) and IgG (P < 0.10) concentrations at 10 hours, but had no effect at 24 hours. Plasma protein and IgG concentrations decreased as calves were born later in the calving season, although the association of birth date with IgG concentration at 24 hours was marginal (P = 0.07). Calf sex, dam body condition score, and birth weight were not related to plasma protein or IgG values. The sensitivity and specificity of a cutoff value of 4.8 g of protein/dl of plasma, measured at 10 hours, for diagnosing failure of passive immunoglobulin transfer at 10 hours were 78 and 94%, and for diagnosing failure of passive immunoglobulin transfer at 24 hours were 88 and 73%, respectively. A colostrum supplement administered to calves with low plasma protein concentration at 10 hours had no effect on plasma protein or IgG values at 24 hours or on preweaning morbidity and mortality.

Aging↗
PubMed1976

Increased plasma protein binding and lower metabolic clearance rate of aldosterone in plasma of low cortisol concentration.

During ACTH or cortisol infusion in ten recumbent normal men taking dexamethasone, the metabolic clearance rate of aldosterone increased by 50% as plasma cortisol was raised from low (2 mug/dl) to high concentration (50 mug/dl). Since splanchnic blood flow did not change, a greater efficiency of removal of aldosterone must have occurred, by means of displacement of aldosterone from high-affinity sites on plasma protein. At 37 C, equilibrium dialysis of low-cortisol plasma showed one-third of plasma aldosterone bound to albumin, and 24 to 28% bound to higher-affinity sites on other protein. As plasma cortisol increased, a progressively smaller fraction was tightly bound, approaching zero as transcortin was saturated with cortisol. The addition of large amounts of aldosterone to low-cortisol plasma displaced 14C-cortisol from transcortin binding sites. The results support earlier evidence that a significant fraction of plasma aldosterone is bound to transcortin, from which it is readily displaced by cortisol, resulting in an increased metabolic clearance rate of aldosterone by making a larger fraction available for removal from plasma.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

[Interaction of human blood plasma proteins with glycosaminoglycans].

Binding of human blood plasma proteins with hyaluronic acid, chondroitin-4-SO4 and heparin was studied. Chondroitin-4-SO4 was not involved in the reaction, whereas heparin and hyaluronic acid formed complexes with the proteins at very low concentrations. The intensity of binding correlated with concentration of carbohydrates in blood plasma proteins. Heparin displaced hyaluronic acid in the complexes. Biological importance of the interactions between glycosaminoglycans and glycoproteins, incorporated into blood plasma as well as into cell membranes of various tissues, is discussed.

Blood Proteins↗
PubMed1987

Plasma protein extravasation induced by mammalian tachykinins in rat skin: influence of anaesthetic agents and an acetylcholine antagonist.

The effect of mammalian tachykinins on plasma protein extravasation was assessed in the rat dorsal skin. Substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) increased vascular permeability in a dose-related manner with a threshold dose of about 0.07 pmol in sodium pentobarbitone-anaesthetized animals. Plasma protein extravasation induced by the tachykinins was 100-500 times less in magnitude in animals anaesthetized with urethane. Plasma protein extravasation induced by SP (66 pmol) was significantly reduced (63%; P less than 0.001) by atropine (a muscarinic inhibitor) while that induced by NKA or NKB was unaffected by the inhibitor suggesting that a cholinergic component might only be involved in the vascular permeability elicited by SP. The rank order of potency for the tachykinins on plasma protein extravasation was: NKB greater than SP greater than NKA (in absence of atropine) and NKB greater than NKA greater than SP (in presence of atropine), suggesting that this vascular response is mediated by a SP-E receptor type. The amplitudes of the plasma protein extravasation induced by NKB and its hydrophilic analogue [Arg degrees]NKB were similar, indicating that the lipophilic features of the native peptide cannot account for its potent biological activity. Plasma protein extravasation was enhanced by the SP analogue [D-Pro4,Lys6,D-Trp7,9,10,Phe11]SP (4-11), thus showing the limitation of such SP analogues (antagonists) for characterizing the tachykinin receptors involved in vascular permeability.

Anesthetics↗
PubMed2002

Value of the plasma protein and hemoglobin concentration in the diagnosis of pulmonary edema in scorpion sting patients.

OBJECTIVE: To investigate the value of measuring total plasma protein and hemoglobin concentrations for the diagnosis of pulmonary edema secondary to scorpion envenomation. DESIGN AND SETTING: Retrospective study over a 4-year period in the medical intensive care unit of a university hospital. PATIENTS: 67 patients older than 3 years admitted in the intensive care unit for scorpion envenomation and stratified into two groups according to the presence of pulmonary edema assessed by a medical committee that took into account clinical, radiological, and blood gas data at admission and after treatment. Total plasma protein and hemoglobin concentrations were analyzed separately. RESULTS: At admission all patients with and without pulmonary edema exhibited polypnea and tachycardia. The mean plasma protein and hemoglobin concentrations were higher in patients with pulmonary edema (74+/-6 and 14.2+/-2.0 g/dl, respectively) than in those without pulmonary edema (64+/-6 and 12.3+/-1.4 g/dl). After 24 h plasma protein and hemoglobin concentrations decreased in the pulmonary edema group (-11 and -1.9 g/dl) despite a negative fluid balance (-500 ml). A plasma protein concentration of 70 g/l or more predicted the presence of pulmonary edema with a sensitivity of 80% a specificity of 96%, a positive predictive value of 97%, and negative predictive value of 77%. CONCLUSIONS: In scorpion-envenomed patients with cardiorespiratory manifestations high plasma protein and hemoglobin concentrations suggest the presence of pulmonary edema.

Adolescent↗
PubMed2006

Altered expression and glycosylation of plasma proteins in rheumatoid arthritis.

Altered glycosylation of plasma proteins has been directly implicated in the pathogenesis of rheumatoid arthritis (RA). The present study investigated the changes in the Concanavalin-A (Con-A)-bound plasma proteins in the RA patients in comparison to that of the healthy controls. Two proteins (MW approximately 32 kDa and approximately 62 kDa) showed an alteration in expression while an altered monosaccharide profile (high mannose) was observed in the approximately 62 kDa protein in the samples collected from RA patients. The 2-dimensional polyacrylamide gel electrophoresis analysis of the Con-A-bound plasma samples showed a large number of protein spots, a few of which were differentially expressed in the RA patients. Some unidentified proteins were detected in the RA patients which were absent in the control samples. The present study, therefore, enunciates the role of carbohydrates as well as that of the acute phase response in the disease pathogenesis.

Adult↗
PubMed1993

Acute-phase plasma protein response to cholera intoxication in healthy and diabetic rats.

The aim of the present study is twofold: to establish the response of hepatic machinery of plasma protein biosynthesis to cholera intoxication, and to examine the same response of alloxan-diabetic hepatocytes with minimal capacity of synthesis of plasma proteins. Direct lesion of hepatic plasma membranes via ip administration of cholera toxin to male rats resulted in a typical acute-phase response (APR) of plasma proteins, which had regressed to levels similar to those of healthy controls approximately at 240 h postintoxication. The d 2 response to a single 0.16 mg/kg body weight dose was typified by a 23% reduction in the level of albumin, but a 6- and 24-fold increase in the levels of fibrinogen and alpha-1-acid glycoproteins, respectively. This response was similar (in direction but not in magnitude) to the acute-phase reaction to a simple subcutaneous administration of carrageenan. The intoxication was accompanied by a massive leakage, into the peritoneal cavity, of plasma fluid, which embraced the complete profile of acute-phase reactants. A three-step mechanism is proposed to account for the observations as follows: (1) There is a rapid formation of a stable complex between subunit B of the toxin and ganglioside GM1 of hepatic plasma membrane. An APR is induced in response to the alteration(s) of hepatic plasma membranes. (2) The release, from the choleragen-membrane complex, of polypeptide A1 and its subsequent penetration of the hepatic membrane result in both activation of adenylate cyclase and increased vascular permeability of hepatic membranes. This leads, in turn, to exudation of components of plasma fluid in the peritoneal cavity of intoxicated rats. An alternate rationale for this exudation is the slow leakage of plasma proteins out of the blood vascular system (possibly through microvesicles) into the peritoneal cavity of cholera intoxicated rats. The spectrum of acute-phase hepatic secretory components was mirrored in the corresponding peritoneal exudate. (3) The increased hepatic membrane flow provides the continued renewal of plasma membrane proteins required for its eventual repair by either endocytosis or sloughing off the toxin-bound membrane segments into the circulatory system, thus producing regression of APR. Livers of diabetic rats, an already established model in terms of APR, responded to ip administration of cholera toxin by increased biosynthesis of the identified plasma proteins and a marked reduction in total free-glucose in serum.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute-Phase Proteins↗
PubMed1979

Pharmacokinetics of quinidine related to plasma protein binding in man.

The disposition and plasma protein binding of quinidine after intravenous administration were studied in 13 healthy subjects. Plasma protein binding, expressed as the fraction of quinidine unbound ranged from 0.134--0.303 (mean 0.221). Elimination rate constant (beta) varied from 0.071 to 0.146 h-1 (mean 0.113), and apparent volume of distribution (Vbeta) varied from 1.39--3.20 1 . kg-1 beta (mean 2.27). Total body clearance was 2.32--6.49 ml min-1 . kg-1. There was a positive linear correlation between the plasma fraction of unbound quinidine and both V beta (r = 0.885, p less than 0.01) and total body clearance (r = 0.668, p less than 0.05). No significant correlation existed between the fraction of unbound quinidine in plasma and the elimination rate constant. The results show that both the apparent volume of distribution and total body clearance of quinidine are proportional to the unbound fraction in plasma. This implies that the total plasma concentration of quinidine at steady state will change with alterations in plasma binding, whilst the concentration of unbound compound and its elimination rate will remain unaffected.

Blood Proteins↗
PubMed2004

Interaction of fibronectin type II proteins with membranes: the stallion seminal plasma protein SP-1/2.

Seminal plasma of mammalians contains, among others, proteins that are characterized by the fibronectin (Fn) type II module. Our knowledge about the structure and the physiological function of seminal Fn type II proteins mainly originates from studies on PDC-109, the bovine representative of this protein family. The present work focuses on the equine protein SP-1/2 (also named HSP-1/2) with particular emphasis on its interaction with lipid membranes by employing the intrinsic protein fluorescence and a number of spin-labeled and fluorescent lipid analogues. The results indicate that the interaction of SP-1/2 with (lipid) membranes is similar to that of PDC-109 which can be explained by homologous amino acid sequences of both proteins. Like PDC-109, SP-1/2 has a specificity for phospholipids with the phosphocholine headgroup. Upon binding to lipid vesicles, the protein intercalates into the hydrophobic membrane core, resulting in a rigidification of the lipid phase and, at higher concentration, in a perturbation of membrane structure. However, compared with PDC-109, the impact of SP-1/2 on membranes is less intense in that the degree of protein-mediated immobilization of lipids was lower. Furthermore, different to PDC-109, SP-1/2 was not able to extract lipids from human red blood cells. The data are discussed with regard to similarities and species-specific differences of the function of seminal Fn type II proteins in the genesis of sperm cells.

Amino Acid Motifs↗
PubMed1995

Fasting plasma glucose and glycosylated plasma protein at 24 to 28 weeks of gestation predict macrosomia in the general obstetric population.

The purpose of this study was to modify the traditional gestational diabetes screening process in order to provide a test that might more reliably detect those women at risk of delivering a macrosomic infant despite a negative test for gestational diabetes mellitus (GDM). Pregnant women (n = 160) were screened for GDM at 24 to 28 weeks' gestation using the traditional 50 g glucose challenge test (GCT). In addition, glycosylated hemoglobin, glycosylated serum protein, and glycosylated plasma protein (GPP) were analyzed from blood drawn at this same time. If the patient's challenge test was positive (140 mg/dL or higher), a 100 g oral glucose tolerance test (OGTT) was performed. Twenty-three women had a positive GCT (14.4%) and five (3.13%) were excluded from further study because they received treatment for gestational diabetes based on a positive OGTT. None of the GCT-negative or the GCT-positive-OGTT-negative patients received treatment. Gestational age at delivery, infant gender, and birthweight were retrieved from birth records. Although several correlations with infant birthweight were found, the fasting plasma glucose (FPG) and GPPs proved most significant. The FPG on the OGTT significantly correlated with infant birthweight (p < 0.001; r = 0.94). A value greater than 90 mg/dL proved to be 100% sensitive and 64% specific for infant birthweight more than 4000 g. The relationship of the GPP and subsequent infant birthweight was also significant (p < 0.001; r = 0.81). A GPP greater than 23% proved to be 100% sensitive in predicting birthweight above 4000 g (11 of 11 infants); however, the test had a 52% specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗
PubMed1996

Binding of sulphamethazine to pig plasma proteins and albumin.

The interaction of sulphamethazine (SMZ) with pig plasma proteins and albumin was studied by ultrafiltration and equilibrium dialysis. Binding to pig plasma proteins was monophasic (affinity approximately 9.0 mol/L x 10(3)) and the main binding protein was albumin. At 37 degrees C and pH 7.4, the affinity of SMZ for albumin was about 8.0 mol/L x 10(3) and the number of binding sites was estimated as 1.4. Increasing the temperature from 4 to 45 degrees C resulted in a seven-fold decrease in affinity, and increasing pH from 6.0 to 8.0 enhanced affinity for pig albumin ten-fold. The free energy of binding (-delta G) and enthalpy change (-delta H) were around 5.5 and 5.1 Kcal/mol, respectively. The total entropy change (delta S) was small and positive, around 2 cal/mol/degree K. Studies with the fluorescent probes warfarin and dansylsarcosine, suggest that these bind to separate sites on porcine albumin. SMZ displaced both probes and inhibited the deacetylation of p-nitrophenyl acetate by pig albumin. We conclude that: (1) binding of SMZ to pig plasma proteins and albumin is weak; (2) the interaction with albumin is exothermic and enthalpy driven, and (3) pig albumin, like other mammalian albumins, appears to possess discrete binding sites for warfarin and dansylsarcosine. SMZ interacts with both these loci.

Analysis of Variance↗