Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.16.3.1 (ceruloplasmin)
5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cerebrospinal fluid (CSF) contains the same proteins as blood plasma, but with a different pattern of concentrations. Protein concentrations in CSF are much lower than those in blood. CSF proteins are derived from blood or synthesized within the brain. The choroid plexus is an important source of CSF proteins. Transthyretin is the protein most abundantly synthesized and secreted by choroid plexus. It determines the distribution of thyroxine in the cerebral compartment. Synthesis of transthyretin first evolved in the brain, then later it became a plasma protein synthesized in the liver. Other proteins secreted by choroid plexus are serum retinol-binding protein, transferrin, caeruloplasmin, insulin-like growth factors, insulin-like growth factor binding proteins, cystatin C, alpha 1-antichymotrypsin, alpha 2-macroglobulin, prothrombin, beta 2-microglobulin and prostaglandin D synthetase. Species differences in expression of the genes for these proteins are outlined, and their developmental pattern, regulation and roles in the cerebral extracellular compartment are discussed.
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PMID:The cerebral expression of plasma protein genes in different species. 774 30

Children with cancer represent a high-risk group for protein-energy malnutrition due to side effects associated with treatment. Assessment of nutritional status at the time of diagnosis and during treatment is, therefore, essential for planning nutritional intervention. We studied the nutritional status of 25 children with leukemia [9 newly diagnosed/relapsed (D/R) leukemic patients and 16 children with leukemia in remission (REM)]. Plasma proteins (prealbumin, PA; albumin, Alb; transferrin, Tr; retinol-binding protein, RBP) and acute phase-reactant proteins (alpha 1-acid glycoprotein, AGP; C-reactive protein, CRP; ceruloplasmin, CER) were measured by radial immunodiffusion. Results show that there were no significant deficits in anthropometric measurements among leukemic children. In contrast, the mean levels of all plasma proteins, especially PA (P < 0.005), were significantly lower in the D/R group than in the REM group. All D/R children, compared to 59% of those in remission, had PA levels < 20 mg/dl. Only the D/R group had abnormal levels of RBP, Tr, and Alb. Children who were treated with prednisone had significantly higher mean levels of PA, RBP, and AGP than those who were not receiving prednisone. The mean levels of acute phase-reactant proteins in these leukemic children were comparable to those of healthy children. We conclude that mild/moderate malnutrition is common in leukemic patients at D/R and that PA seems to be the most sensitive indicator of visceral protein status.
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PMID:Nutritional status of children with leukemia. 907 29

Serum sex-hormone-binding globulin (SHBG), transferrin, prealbumin, retinol-binding protein, and ceruloplasmin concentrations were evaluated in 12 women with anorexia nervosa before and after weight gain and in 12 healthy women with normal weight. The serum SHBG concentrations were higher in patients with anorexia nervosa before weight gain than in control subjects and they returned to the normal range after weight gain. The changes of SHBG concentrations were not associated with any change in plasma testosterone, estradiol, or free thyroxin concentrations. The body mass index in our patients after weight gain was lower than in control subjects. Prealbumin, retinol-binding protein, ceruloplasmin, and transferrin in anorectic patients before weight gain did not differ from those of the control subjects and increased after weight gain. The changes of serum SHBG concentrations in patients with anorexia nervosa during weight gain make SHBG determination a reliable index of nutritional status in this type of eating disorder.
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PMID:Sex-hormone-binding globulin and protein-energy malnutrition indexes as indicators of nutritional status in women with anorexia nervosa. 843 64

Changes in the concentration of some serum acute phase proteins (alpha 1-antitrypsin, alpha 2-macroglobulin, complement C3, haptoglobin, ceruloplasmin, transferrin, albumin and hemopexin), thyroxine-binding globulin, retinol-binding globulin, plasminogen and Gc-globulin are reported in two separate series of Chinese, male schizophrenic patients and healthy controls. In the first series, 41 healthy blood donors and 98 schizophrenic patients in different stages of the disease were investigated. The second series consists of a random sample of 50 acutely ill schizophrenic patients and a second group of healthy subjects. The concentrations of these serum proteins were measured by rocket immunoelectrophoresis in agarose gel. Increased levels of serum alpha 1-antitrypsin, alpha 2-macroglobulin, haptoglobin, ceruloplasmin, and thyroxine-binding globulin were observed in both series of patients when compared to their respective controls. Albumin, transferrin and retinol-binding protein levels were reduced in patients in both series. Hemopexin levels were increased only in the acutely ill patients while complement C3 was decreased in the chronically ill patients. No changes were observed in the Gc-globulin levels of all groups of patients. With the exception of complement C3, the changes observed in the levels of these serum proteins were appropriate for that of an acute phase response.
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PMID:Acute phase proteins in male Chinese schizophrenic patients in Singapore. 895 1

We have previously described the major components of rat serum (Electrophoresis 1998, 19, 1484-1492 and 1493-1500). In this report we examine sex-related differences in protein concentrations, both in control animals and upon experimentally induced inflammation. Under baseline conditions approximately one third of the spots resolved in serum by two-dimensional electrophoresis (2-DE) are expressed at levels > or =25% higher in female rats than in male rats and a further 10% at levels > or =25% lower. Inflammation increases the expression of the positive acute-phase reactants: hemopexin, ceruloplasmin, alpha1-antitrypsin (all approximately 2-fold), C-reactive protein (3- to 5-fold), serine protease inhibitor-3 (4- to 5-fold), thiostatin (> 5-fold in females, >20-fold in males), clusterin, orosomucoid, haptoglobin chains and alpha2-macroglobulin. The baseline level of the last four markers is below the detection limit, hence no percent increase can be computed. Conversely, negative acute-phase reactants are reduced on inflammation: alpha1-inhibitor III, alpha2-HS-glycoprotein, kallikrein-binding protein and transthyretin (all reduced to between 1/2 to 1/3 of the baseline levels), retinol-binding protein (to about 1/2 to 1/4) and albumin (to 2/3). Except for thiostatin, the changes in acute-phase protein levels are similar in male and female rats.
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PMID:Proteins of rat serum: III. Gender-related differences in protein concentration under baseline conditions and upon experimental inflammation as evaluated by two-dimensional electrophoresis. 1034 56

The liver lobule is formed by parenchymal cells, i.e., hepatocytes and nonparenchymal cells. In contrast to hepatocytes that occupy almost 80% of the total liver volume and perform the majority of numerous liver functions, nonparenchymal liver cells, which contribute only 6.5% to the liver volume, but 40% to the total number of liver cells, are localized in the sinusoidal compartment of the tissue. The walls of hepatic sinusoid are lined by three different cell types: sinusoidal endothelial cells (SEC), Kupffer cells (KC), and hepatic stellate cells (HSC, formerly known as fat-storing cells, Ito cells, lipocytes, perisinusoidal cells, or vitamin A-rich cells). Additionally, intrahepatic lymphocytes (IHL), including pit cells, i.e., liver-specific natural killer cells, are often present in the sinusoidal lumen. It has been increasingly recognized that both under normal and pathological conditions, many hepatocyte functions are regulated by substances released from neighboring nonparenchymal cells. Liver sinusoidal endothelial cells constitute the lining or wall of the hepatic sinusoid. They perform important filtration function due to the presence of small fenestrations that allow free diffusion of many substances, but not of particles of the size of chylomicrons, between the blood and the hepatocyte surface. SEC show huge endocytic capacity for many ligands including glycoproteins, components of the extracellular matrix (ECM; such as hyaluronate, collagen fragments, fibronectin, or chondroitin sulphate proteoglycan), immune complexes, transferrin and ceruloplasmin. SEC may function as antigen-presenting cells (APC) in the context of both MHC-I and MHC-II restriction with the resulting development of antigen-specific T-cell tolerance. They are also active in the secretion of cytokines, eicosanoids (i.e., prostanoids and leukotrienes), endothelin-1, nitric oxide, and some ECM components. Kupffer cells are intrasinusoidally located tissue macrophages with a pronounced endocytic and phagocytic capacity. They are in constant contact with gut-derived particulate materials and soluble bacterial products so that a subthreshold level of their activation in the normal liver may be anticipated. Hepatic macrophages secrete potent mediators of the inflammatory response (reactive oxygen species, eicosanoids, nitric oxide, carbon monoxide, TNF-alpha, and other cytokines), and thus control the early phase of liver inflammation, playing an important part in innate immune defense. High exposure of Kupffer cells to bacterial products, especially endotoxin (lipopolysaccharide, LPS), can lead to the intensive production of inflammatory mediators, and ultimately to liver injury. Besides typical macrophage activities, Kupffer cells play an important role in the clearance of senescent and damaged erythrocytes. Liver macrophages modulate immune responses via antigen presentation, suppression of T-cell activation by antigen-presenting sinusoidal endothelial cells via paracrine actions of IL-10, prostanoids, and TNF-alpha, and participation in the development of oral tolerance to bacterial superantigens. Moreover, during liver injury and inflammation, Kupffer cells secrete enzymes and cytokines that may damage hepatocytes, and are active in the remodeling of extracellular matrix. Hepatic stellate cells are present in the perisinusoidal space. They are characterized by abundance of intracytoplasmic fat droplets and the presence of well-branched cytoplasmic processes, which embrace endothelial cells and provide focally a double lining for sinusoid. In the normal liver HSC store vitamin A, control turnover of extracellular matrix, and regulate the contractility of sinusoids. Acute damage to hepatocytes activates transformation of quiescent stellate cells into myofibroblast-like cells that play a key role in the development of inflammatory fibrotic response. Pit cells represent a liver-associated population of large granular lymphocytes, i.e., natural killer (NK) cells. They spontaneously kill a variety of tumor cells in an MHC-unrestricted way, and this antitumor activity may be enhanced by the secretion of interferon-gamma. Besides pit cells, the adult liver contains other subpopulations of lymphocytes such as gamma delta T cells, and both "conventional" and "unconventional" alpha beta T cells, the latter containing liver-specific NK T cells. The development of methods for the isolation and culture of main liver cell types allowed to demonstrate that both nonparenchymal and parenchymal cells secrete tens of mediators that exert multiple paracrine and autocrine actions. Co-culture experiments and analyses of the effects of conditioned media on cultures of another liver cell type have enabled the identification of many substances released from non-parenchymal liver cells that evidently regulate some important functions of neighboring hepatocytes and non-hepatocytes. To the key mediators involved in the intercellular communication in the liver belong prostanoids, nitric oxide, endothelin-1, TNF-alpha, interleukins, and chemokines, many growth factors (TGF-beta, PDGF, IGF-I, HGF), and reactive oxygen species (ROS). Paradoxically, the cooperation of liver cells is better understood under some pathological conditions (i.e., in experimental models of liver injury) than in normal liver due to the possibility of comparing cellular phenotype under in vivo and in vitro conditions with the functions of the injured organ. The regulation of vitamin A metabolism provides an example of the physiological role for cellular cross-talk in the normal liver. The majority (up to 80%) of the total body vitamin A is stored in the liver as long-chain fatty acid esters of retinal, serving as the main source of retinoids that are utilized by all tissues throughout the body. Hepatocytes are directly involved in the uptake from blood of chylomicron remnants, and the synthesis of retinol-binding protein that transfers retinol to other tissues. However, more than 80% of the liver retinoids are stored in lipid droplets of hepatic stellate cells. HSC are capable of both uptake and release of retinol depending on the body's retinol status. The activity of some major enzymes of vitamin A metabolism have been found to be many times higher per protein basis in stellate cells than in hepatocytes. Despite progress in the understanding of the roles played by these two cell types in hepatic retinoid metabolism, the way in which retinoids move between the parenchymal cells, stellate cells, and blood plasma has not been fully elucidated. Sinusoidal blood flow is, to a great extent, regulated by hepatic stellate cells that can contract due to the presence of smooth muscle alpha-actin. The main vasoactive substances that affect constriction or relaxation of HSC derive both from distant sources and from neighboring hepatocytes (carbon monoxide, leukotrienes), endothelial cells (endothelin, nitric oxide, prostaglandins), Kupffer cells (prostaglandins, NO), and stellate cells themselves (endothelin, NO). The cellular cross-talk reflected by the fine-tuned modulation of sinusoidal contraction becomes disturbed under pathological conditions, such as endotoxemia or liver fibrosis, through the excess synthesis of vasoregulatory compounds and the involvement of additional mediators acting in a paracrine way. The liver is an important source of some growth factors and growth factor-binding proteins. Although hepatocytes synthesize the bulk of insulin-like growth factor I (IGF-I), also other types of nonparenchymal liver cells may produce this peptide. Cell-specific expression of distinct IGF-binding proteins observed in the rat and human liver provides the potential for specific regulation of hepatic IGF-I synthesis not only by growth hormone, insulin, and IGF-I, but also by cytokines released from activated Kupffer (IL-1, TNF-alpha, TGF-beta) or stellate cells (TGF-alpha, TGF-beta). Hepatic stellate cells may affect turnover of hepatocytes through the synthesis of potent positive as well as negative signals such as, respectively, hepatocyte-growth-factor or TGF-beta. Although hepatocytes seem not to produce TGF-beta, a pleiotropic cytokine synthesized and secreted in the latent form by Kupffer and stellate cells, they may contribute to its actions in the liver by the intracellular activation of latent TGF-beta, and secretion of the biologically active isoform. Many mediators that reach the liver during inflammatory processes, such as endotoxins, immune-complexes, anaphylatoxins, and PAF, increase glucose output in the perfused liver, but fail to do so in isolated hepatocytes, acting indirectly via prostaglandins released from Kupffer cells. In the liver, prostaglandins synthesized from arachidonic acid mainly in Kupffer cells in a response to various inflammatory stimuli, modulate hepatic glucose metabolism by increasing glycogenolysis in adjacent hepatocytes. The release of glucose from glycogen supports the increased demand for energetic fuel by the inflammatory cells such as leukocytes, and additionally enables enhanced glucose turnover in sinusoidal endothelial cells and Kupffer cells which is necessary for effective defense of these cells against invading microorganisms and oxidative stress in the liver. Leukotrienes, another oxidation product of arachidonic acid, have vasoconstrictive, cholestatic, and metabolic effects in the liver. A transcellular synthesis of cysteinyl leukotrienes (LTC4, LTD4, and LTE4) functions in the liver: LTA4, an important intermediate, is synthesized in Kupffer cells, taken up by hepatocytes, converted into the potent LTC4, and then released into extracellular space, acting in a paracrine way on Kupffer and sinusoidal endothelial cells. Thus, hepatocytes are target cells for the action of eicosanoids and the site of their transformation and degradation, but can not directly oxidate arachidonic acid to eicosanoids. (ABSTRACT TRUNCATED)
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PMID:Cooperation of liver cells in health and disease. 1172 49

Iron deficiency and marginal vitamin A (VA) deficiency frequently coexist and affect billions of people, mostly children and women, worldwide. The effects of these micronutrient deficiencies alone and in combination on hematologic, biochemical and molecular indices of iron and VA status were investigated in a 2 x 2 randomized blocked study conducted in growing male Sprague-Dawley rats. From 3-8 wk of age, rats were fed one of four purified diets that were either adequate or restricted in iron (Fe) and adequate or marginal in VA: (+)Fe(+)VA, 20.3 and 0.367 micro g/g, respectively, denoted control diet; (-)Fe(+)VA, 3.34 and 0.405 micro g/g; (+)FeVA(m), 22.2 and 0.051 micro g/g; or (-)FeVA(m), 3.03 and 0.055 micro g/g. Weight-matched rats fed adequate micronutrients were included to control for possible confounding effects of Fe deficiency on growth and feed efficiency. Iron restriction reduced (P < 0.05) weight gain, feed efficiency, blood hemoglobin and hematocrit. Plasma and liver iron and plasma transferrin saturation were reduced by approximately 50%, whereas liver transferrin mRNA and protein and transferrin receptor mRNA were elevated, as was liver ferritin light-chain protein and light-chain mRNA. Liver heavy-chain ferritin mRNA, hemopexin, ceruloplasmin and cellular retinol-binding protein mRNA were not affected by iron or VA restriction. Although marginal VA deficiency did not exacerbate indices of poor iron status during iron deficiency, iron deficiency was associated with lower plasma retinol and elevated liver VA concentrations. These results are consistent with an impaired mobilization of liver retinol during iron deficiency as well as multiple alterations in iron metabolism.
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PMID:Iron deficiency and marginal vitamin A deficiency affect growth, hematological indices and the regulation of iron metabolism genes in rats. 1246 96

The IFCC Committee on Plasma Proteins has been investigating regional differences for commonly assayed plasma proteins to determine whether universal reference intervals can be applied. As a part of this study, we launched an Asian project analyzing the concentrations of 13 serum proteins whose values are standardized to CRM470, and five newer analytes: retinol-binding protein (RBP), cystatin C (CysC), light-chain-kappa (L-kappa), and light-chain-lambda (L-lambda). In Tokyo, Seoul, Kuala Lumpur, Hong Kong, Taipei and Shanghai, serum samples were collected from 146 to 415 apparently healthy individuals with nearly equal gender ratios. All assays were performed in Tokyo on a Behring Nephelometer II (BN II). Seven chemical analytes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (gammaGT), creatinine, total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)) were also measured. These results were used for excluding individuals with possible latent clinical disorders. Positive acute phase reactants were consistently lower, and negative ones were higher, in Tokyo than those in other cities. The most conspicuous difference was observed in C-reactive protein (CRP). There were no regional differences in transferrin, albumin, or CysC. Creatinine was much lower in Tokyo despite comparable CysC levels. ALT and gammaGT were higher in Shanghai, Taipei and Seoul; gammaGT and TG were higher in Shanghai; and HDL-C was higher in Tokyo. Gender-related differences in reference intervals were observed for immunoglobulin (Ig)M, haptoglobin, RBP, transferrin, alpha2-macroglobulin (A2M), transthyretin, alpha1-acid glycoprotein, CysC, and C4 in all cities. Slight age-related differences were observed, irrespective of the region, in IgA and ceruloplasmin (increase) and A2M (decrease). Environmental factors and lifestyle seem to have a great influence on many commonly measured analytes.
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PMID:Diagnostic and epidemiological implications of regional differences in serum concentrations of proteins observed in six Asian cities. 1532 16

A longitudinal study based on a serum sample bank was carried out in Finland to find out the association between biochemical substances and the subsequent risk of cancer. The objective was to evaluate the consistency between means of individually estimated levels of these compounds and levels based on pooling. Levels of alpha-tocopherol, beta-carotene, retinol, retinol-binding protein, and ceruloplasmin were estimated by primary site and sex and partly by age and morphology. The concentrations in pooled samples were consistently lower than the averages of the individual samples. On the basis of individual samples, all the five biochemical compounds had a rather consistent protective effect on the risk of cancers at most primary sites. This protective effect disappeared in the pool analyses, and more than half of exposure contrasts showed an opposite sign. For ceruloplasmin, the effect of pooling was smaller but not negligible. The results of this study emphasize the demand to standardize the collecting, handling, and analysing of samples in serum banks. They are, furthermore, consistent with the hypothesis that pooling of biochemical samples affects the levels of the substances and may affect the conclusions of epidemiological studies on causes of diseases.
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PMID:Blood biochemistry and the risk of cancer. 1554 87

There is evidence that organic food often contains relatively high amounts of natural toxic compounds produced by fungi or plants, whereas corresponding conventional food tends to contain more synthetic toxins such as pesticide residues, but only a few studies have evaluated the impact of their consumption on health. This study proposes a novel approach to evaluate the potential health risk of organic compared to conventional food consumption, that is, the assay of sensitive markers of cell function in vulnerable conditions. The markers utilized were intestinal and splenic lymphocyte proliferative capacity and liver acute-phase reaction, both responding to the presence of toxins. The vulnerable conditions in which body defenses can be less efficient were weaning and protein-energy malnutrition. This study reports the results of a pilot experiment on one sample of eight varieties of organically and conventionally grown wheat. Weaned rats were assigned to two groups fed conventional (CV) or organic (ORG) wheat for 30 days. Each group was divided in two subgroups of well-nourished (WN) or protein-energy-malnourished (PEM) rats. For each rat, the lymphocyte proliferation was assayed by [(3)H]thymidine incorporation after stimulation of cells with a mitogen, in a culture medium containing either commercial fetal calf serum (FCS) or the corresponding rat serum (RS) to mimic the in vivo proliferative response. The acute-phase proteins (albumin, transthyretin, transferrin, ceruloplasmin, retinol-binding protein) were measured in plasma by Western blotting and immunostaining with specific antibodies. The proliferative response of lymphocytes cultured with FCS and the amount of acute-phase proteins of rats fed the ORG wheat sample, either WN or PEM, did not differ from those of rats fed the CV wheat sample. However, the proliferative response of lymphocytes cultured with RS was inhibited in PEM-CV compared with PEM-ORG. The content of mycotoxins was highest in the organic sample, and therefore the immunotoxic effect was probably due to other contaminants in the CV wheat. In conclusion, these results indicate that the conventional wheat sample tested represented a higher risk for lymphocyte function than the wheat sample organically grown, at least in vulnerable conditions.
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PMID:Novel approach for food safety evaluation. Results of a pilot experiment to evaluate organic and conventional foods. 1556 30


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