Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Transferrin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources
PubMed1991

Carbohydrate-deficient transferrin in serum: a new marker of potentially harmful alcohol consumption reviewed.

During the last 16 years an increasing number of studies have indicated a new diagnostic marker of alcohol abuse, unrelated to any of the conventional markers of alcoholism. This marker, now called carbohydrate-deficient transferrin, consists mainly of one or two isoforms of transferrin that are deficient in their terminal trisaccharides. Such isoforms have so far been detected by methods based on charge, i.e., isoelectric focusing, chromatofocusing, and anion-exchange chromatography of various designs combined with immunological detection techniques. This transferrin abnormality measures an accumulated effect of alcohol consumption, appearing after regular intake of 50-80 g of ethanol/day for at least one week and normalizing slowly during abstinence (half-life = about 15 days). To summarize all studies to date, approximately 2500 individuals have been examined, with a total clinical sensitivity of 82% and a specificity of 97%. False-positive results have only occasionally been reported: in a few patients with severe liver disease, usually primary biliary cirrhosis and chronic active hepatitis; in patients with genetic D variants of transferrin; and in patients with (and some carriers of) a recently identified inborn error of glycoprotein metabolism. The mechanism behind the transferrin abnormality is unknown but an acetaldehyde-mediated inhibition of glycosyl transfer has been suggested. Carbohydrate-deficient transferrin may thus offer a new possibility of diagnosing alcohol-related disorders. Its measurement is little affected by other conditions and, contrary to conventional markers of alcohol abuse, is apparently largely independent of concomitant liver disease.

Alcoholism↗
PubMed1991

Pathological changes of the mare endometrium and genotypes for transferrin and ELA.

Histological features of the endometrium, as assessed in biopsy samples, were related to Standardbred mare genotypes for transferrin, esterase (as a control) and equine leucocyte antigens (ELA). Pathological changes were found more frequently in each successively older age group of mares. Among mares aged 6-19 years, there were significant pathologic changes on first examination following an infertile breeding season for 46 of 90 (51%) of transferrin homozygotes and 50 of 146 (34%) of transferrin heterozygotes. The difference between the two groups was significant for the total data (chi 1(2) = 6.56, P = 0.010) and when the data were stratified for mare age at biopsy (chi 1(2) = 7.33, P = 0.0068). The effect of transferrin was similar in both trotters and pacers, especially for frequent genotypes commonly found in horses of both gaits. There was no effect of esterase and, in a smaller set of ELA-typed mares, no significant effect of ELA genotype on uterine biopsy category. Transferrin has a well-established microbiostatic and biocidal effect. Conceivably, heterozygotes for some combinations of transferrin variants could have a slower natural rate of endometrial deterioration than homozygotes.

Age Factors↗
PubMed1991

Mutational analysis of the cytoplasmic tail of the human transferrin receptor. Identification of a sub-domain that is required for rapid endocytosis.

It has been reported that the sequence Tyr20-X-Arg-Phe23 present within the cytoplasmic tail of the transferrin receptor may represent a tyrosine internalization signal (Collawn, J.F., Stangel, M., Kuhn, L.A., Esekogwu, V., Jing, S., Trowbridge, I.S., and Tainer, J. A. (1990) Cell 63, 1061-1072). However, as Tyr20 is not conserved between species (Alvarez, E., Gironès, N., and Davis, R. J. (1990) Biochem. J. 267, 31-35), the functional role of the putative tyrosine internalization signal is not clear. To address this question, we constructed a series of 32 deletions and point mutations within the cytoplasmic tail of the human transferrin receptor. The effect of these mutations on the apparent first order rate constant for receptor endocytosis was examined. It was found that the region of the cytoplasmic tail that is proximal to the transmembrane domain (residues 28-58) is dispensable for rapid endocytosis. In contrast, the distal region of the cytoplasmic tail (residues 1-27) was found to be both necessary and sufficient for the rapid internalization of the transferrin receptor. The region identified includes Tyr20-X-Arg-Phe23, but is significantly larger than this tetrapeptide. It is therefore likely that structural information in addition to the proposed tyrosine internalization signal is required for endocytosis. To test this hypothesis, we investigated whether a heterologous tyrosine internalization signal (from the low density lipoprotein receptor) could function to cause the rapid endocytosis of the transferrin receptor. It was observed that this heterologous tyrosine internalization signal did not allow rapid endocytosis. We conclude that the putative tyrosine internalization signal (Tyr20-Thr-Arg-Phe23) is not sufficient to determine rapid endocytosis of the transferrin receptor. The data reported here indicate that the transferrin receptor internalization signal is formed by a larger cytoplasmic tail structure located at the amino terminus of the receptor.

Amino Acid Sequence↗
PubMed1991

Turnover of the transferrin receptor is not influenced by removing most of the extracellular domain.

We treated intact cells with trypsin to remove most of the external domain of the transferrin receptor and investigated what effect the absence of the external domain had on the turnover of the fragment that remained associated with the cells. To detect the cell-associated tryptic fragment, which contains a small amount of the external domain, the transmembrane domain, and the cytoplasmic domain, we prepared an anti-peptide antibody against a segment of the cytoplasmic domain. This antibody specifically immunoprecipitated the intact transferrin receptor as well as a 21-kDa peptide from trypsin-treated HeLa cells. Several lines of evidence indicated that the 21-kDa peptide was the cell-associated tryptic fragment of the transferrin receptor. The fragment was only present in trypsin-treated cells; the fragment migrated as a dimer in nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis, as it should if it were derived from the transferrin receptor; a goat antibody prepared to the purified human transferrin receptor also precipitated the 21-kDa peptide from trypsinized cells. In addition, treating the tryptic fragment with neuraminidase increased the electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels, suggesting the fragment contained O-linked carbohydrate. When cells were trypsinized and then incubated at 37 degrees C, the half-life of the tryptic fragment (15 +/- 4 h) was not significantly different than the half-life of the intact receptor (19 +/- 6 h). This indicates that removing 95% of the external domain of the transferrin receptor has little effect on processes operating in the turnover of the receptor.

Amino Acid Sequence↗
PubMedDate not supplied

[The use of monoclonal antibodies for determining the transferrin content of the urine].

The authors used monoclonal antibodies to human transferrin for the development of a high-sensitive test system for the assessment of transferrin levels in urine with enzyme immunoassay. The conditions of the immunoassay performance were optimized. The sensitivity of the test system enabled the authors to define the levels of transferrin up to 1 ng/ml. Tests for the detection of transferrin in patients with chronic pyelonephritis and chronic renal failure were performed. The designed test system permitted transferrin to be revealed in the urine of those patients who had negative results during a radial immunodiffusion. The authors demonstrated the possibility of using the developed monoclonal antibodies in laser nephelometry for the detection of blood and urinary transferrin levels.

Antibodies, Monoclonal↗
PubMed1991

Cytotoxic activity of an anti-transferrin receptor immunotoxin on normal and leukemic human hematopoietic progenitors.

The process of cellular iron uptake involves a specific receptor for the plasma carrier transferrin and a pathway of receptor-mediated endocytosis. Transferrin receptor expression is closely related to the rate of cell proliferation, and conjugates between anti-transferrin receptor monoclonal antibodies and toxins have been shown to have potent cytotoxic activity. We have constructed an anti-transferrin receptor immunotoxin by conjugating the anti-transferrin receptor monoclonal antibody B3/25 to a ribosome-inactivating protein, the saporin-6 (SO6), which is derived from the seeds of the plant Saponaria officinalis. The immunotoxin B3/25-SO6 was tested for in vitro cytotoxic activity against the human cell lines K-562 and HL-60 and against normal human bone marrow hematopoietic progenitors and acute myeloid leukemia clonogenic cells. The immunotoxin proved to be an effective inhibitor of K-562 and HL-60 clonogenic cell growth, in vitro colony formation being completely inhibited at immunotoxin concentrations ranging from 10(-7) to 10(-10) M. B3/25-SO6 markedly reduced the recloning efficiency of HL-60 clonogenic cells at 10(-12) M. Exposure of HL-60 cells in suspension culture to 10(-9) M B3/25-SO6 for 48-72 h completely abolished their clonogenic potential. The immunotoxin was also found to be cytotoxic against normal human bone marrow progenitor cells (burst-forming unit-erythroid and colony-forming unit-granulocyte, macrophage) in a dose-dependent manner. However, exposure of normal colony-forming unit-granulocyte, macrophage in suspension culture to 10(-9) M B3/25-SO6 for 72 h resulted in only 50% suppression of their clonogenic potential. Finally, B3/25-SO6 was found to be a potent inhibitor of in vitro growth of acute myeloid leukemia clonogenic cells. The cytotoxic effects of B3/25-SO6 were shown to be specific, since both saporin alone and irrelevant immunotoxins did not have any effect in the cellular systems examined. We conclude that the immunotoxin B3/25-SO6 has dose-related cytotoxic effects on both normal and leukemic human hematopoietic progenitors. Since there are substantial differences between normal and leukemic progenitors with respect to the proportion of cycling cells and the expression of transferrin receptors, B3/25-SO6 or similar immunotoxins may have clinical application in bone marrow-purging procedures.

Antibodies, Monoclonal↗
PubMed1991

Purification of transferrins and lactoferrin using DEAE affi-gel blue.

1. A simple method for purifying transferrins and lactoferrin is described. 2. The method consists of a preliminary step of dye-ligand chromatography using DEAE Affi-Gel Blue as the gel matrix at pH 7.5. In this chromatographic step, the transferrins and lactoferrin were readily separated from the bulk of the other proteins by start buffer elution. 3. Differences in the chromatographic behaviour of the various serum transferrins (monkey, human, rabbit, pig, chicken and duck) and ovotransferrin upon DEAE Affi-Gel Blue chromatography can be attributed to differences in the anionic charge of the transferrins in 0.02 M potassium phosphate buffer, pH 7.5, thus resulting in the differential retardation of these protein molecules by the gel matrix. 4. The result of DEAE Affi-Gel Blue chromatography of human lactoferrin is different from that for the transferrins. This may possibly reflect the differences in the strength of interaction between lactoferrin and transferrin with this gel matrix.

Amino Acid Sequence↗
PubMed1990

Colorimetry and constant-potential coulometry determinations of transferrin-bound iron, total iron-binding capacity, and total iron in serum containing iron-dextran, with use of sodium dithionite and alumina columns.

After the parenteral administration of iron-dextran (imferon), the increased total iron concentrations in serum can be determined by atomic absorption spectroscopy and by colorimetric methods involving sodium dithionite, which reductively dissociates iron from the dextran complex. We report that constant-potential coulometry detects only about 55-70% of dextran-bound iron before dithionite reduction and variable amounts after reaction with the reducing agent. In addition, we have developed a procedure for determining transferrin-bound iron, total iron-binding capacity (TIBC), total iron, and dextran-bound iron with the Kodak Ektachem colorimetric system. In determining total serum iron, the sample is first mixed with sodium dithionite, which rapidly dissociates all dextran-bound iron, but does not remove iron from either transferrin or hemoglobin. After the mixture is applied to an Ektachem slide, transferrin-bound iron is released at pH 4 and is detected together with the iron previously bound to dextran. TIBC is determined by mixing serum with ferric citrate in moderate excess and filtering through a small alumina (Al2O3) column, which binds excess free iron and iron-dextran; the iron in the column eluate represents the TIBC. Transferrin-bound iron is determined by applying diluted serum without added ferric citrate to an alumina column and measuring the iron in the column eluate. Dextran-bound iron is equivalent to the difference between total and transferrin-bound iron. Using this method, we found that transferrin iron-binding sites are saturated in vitro by excess iron-dextran less efficiently than by ferric citrate.

Aluminum Oxide↗
PubMed1987

[Detection of beta 2-transferrin with agarose gel electrophoresis, immunofixation and silver staining in cerebrospinal fluid, secretions and other body fluids].

A method is described for the detection of beta 2-transferrin (asialotransferrin) in 1 microliter cerebrospinal fluid. Owing to its low content of sialic acid, beta 2-transferrin migrates more slowly than the main transferrin component (beta 1-transferrin) in electrophoresis. The high sensitivity and specificity of the test depend on immunofixation of the electrophoretically separated transferrin in the agarose gel, and on the visualization of the immune complex by staining with alkaline silver nitrate solution. Since beta 2-transferrin occurs practically only in cerebrospinal fluid and not in other body fluids, its detection in secretions from the nose or ear can be used for the diagnosis of rhinoor otoliquorrhoea. Even under unfavourable conditions, 10% cerebrospinal fluid can be detected in a secretion. Operator time for investigation of a secretion sample is 110 minutes and the analysis time is 5 hours. The direct costs are 95 German marks. Forty two secretions have been investigated so far. Eighteen were shown to contain cerebrospinal fluid, and this was confirmed by subsequent operative findings on the patients.

Asialoglycoproteins↗
PubMedDate not supplied

Seminal plasma transferrin concentration in normozoospermic fertile men and oligozoospermic men associated with varicocele.

Seminal plasma transferrin concentration has been reported a useful clinical marker for Sertoli cell function. In the present study, to investigate if transferrin production in the testis is decreased in oligozoospermic men associated with visible varicocele, seminal plasma transferrin concentrations in two groups -12 normozoospermic fertile men and 14 oligozoospermic varicocele patients--were measured and the values compared. Seminal plasma transferrin concentration in the oligozoospermic varicocele group was 29.9 +/- 6.8 micrograms/mL, and the concentration in the normozoospermic fertile group was 75.5 +/- 39.3 micrograms/mL. There was a significant difference between the two groups (P less than .001). The results indicate that transferrin production in the testis of oligozoospermic varicocele patients must be decreased, and also suggest that decreased transferrin production may be related to disturbed spermatogenesis in varicocele patients.

Adult↗
PubMedDate not supplied

Expression of transferrin receptors on lymphocytes: its correlation with T-helper/T-suppressor cytotoxic ratio and rejection in heart transplant recipients.

Forty-one heart transplant recipients were monitored serially for the expression of transferrin receptors and T-helper/T-suppressor cytotoxic ratios on circulating lymphocytes during the hospitalization periods after heart transplantations (60.5 +/- 18.9 days). These values were retrospectively correlated with the patients' clinical status with respect to rejection and infection. During clinically stable periods the average values of percentage of transferrin receptor-positive lymphocytes and T-helper/T-suppressor cytotoxic ratios were 5.9 +/- 4.3 and 1.5 +/- 1.0, respectively. The percentage of transferrin receptor-positive lymphocytes increased to a level of 12.0 +/- 5.4 (p less than 0.001) during the early prerejection phase and remained at this level throughout the rejection period. T-helper/T-suppressor cytotoxic ratios increased to 1.96 +/- 0.92 during the early prerejection phase (p less than 0.05), peaked at 2.30 +/- 1.21 during the late prerejection phase (p less than 0.01), but began to decline by the rejection period. After rejection treatment percentage of transferrin receptor-positive lymphocytes decreased to 8.4 +/- 5.3 (p less than 0.05), and T-helper/T-suppressor cytotoxic ratios decreased to normal levels. In contrast, in patients with infectious complications, a remarkably elevated percentage of transferrin receptor-positive lymphocytes (20.7 +/- 11.7) and relatively low T-helper/T-suppressor cytotoxic ratios (1.3 +/- 0.5) were noted. The data show an association between the clinical status, such as rejection and infection, and these immunologic measurements as transferrin receptor-positive lymphocytes and T-helper/T-suppressor cytotoxic ratios in heart transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

[A study on the antibacterial activity of amniotic fluid--the significance of intraamniotic transferrin].

In order to study the antimicrobial activity of amniotic fluid, attempts were made to evaluate the in vivo growth of bacteria in amniotic fluid and the role of transferrin in antibacterial activity. The bacteria chosen for these experiments were Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus faecalis, respectively. The results obtained were as follows: Amniotic fluid was shown have an antibacterial effect on Escherichia coli and Staphylococcus aureus, while Pseudomonas aeruginosa and Streptococcus faecalis proliferated readily in amniotic fluid. Individual difference in each sample appeared to be responsible for the inconsistent potency of the inhibitory effect observed. When amniotic fluid was heated at 100 degrees C for 5 minutes, the antibacterial activity was lost. The level of transferrin in amniotic fluid obtained at term was determined to be 29.1 +/- 17.6mg/dl (N = 90). The value correlated with neither those measured in cord sera nor maternal sera. The antimicrobial activity was restored by adding transferrin into heat-treated amniotic fluid at a concentration of 250mg/dl or higher. Simultaneous addition of transferrin and a sufficient concentration of iron made it possible to form a transferrin-iron complex. A subsequent decrease in unbound transferrin resulted in the loss of antibacterial properties.

Amniotic Fluid↗
PubMedDate not supplied

Increase in seminal transferrin following antiandrogen treatment.

Seminal plasma transferrin was determined by radioimmunoassay in normal and infertile men under basal conditions and after manipulations of FSH and testosterone known to stimulate Sertoli cell activity and transferrin secretion in vitro. Normal volunteers were given the antiandrogens cyproterone acetate or flutamide, or a combination of 19-nortestosterone together with medroxyprogesterone. Severely oligozoospermic patients were treated with pulsatile GnRH to decrease elevated FSH levels. No close correlation between seminal transferrin and any of the serum hormones could be detected under basal conditions. However, antiandrogen treatment increased transferrin in seminal plasma, although from the in vitro studies a decrease or no effect would have been expected. No effect on seminal transferrin was detected in the patients receiving GnRH treatment. Since seminal transferring after hormonal treatment did not parallel transferrin secretion by Sertoli cells under hormonal stimulation in vitro, its role as a diagnostic marker for Sertoli cell function remains questionable.

Adult↗
PubMed1988

Characterization of the transferrin receptor in tunicamycin-treated A431 cells.

The transferrin receptor undergoes extensive co- and post-translational modifications during its biosynthesis. In this study, the functional and structural properties of the transferrin receptor from tunicamycin-treated A431 cells were examined. Incubation of A431 cells with this inhibitor of asparagine-linked glycosylation results in a shift of the apparent molecular weight of the transferrin receptor from 94,000 to 79,000. The electrophoretic mobility of the receptor from treated cells is that of a monomer under nonreducing conditions, whereas the transferrin receptor in untreated cells has the mobility of a dimer under identical conditions. This result indicates a lack of disulfide bond formation between subunits of the receptor from tunicamycin-treated cells. In solution no dimers can be detected with cross-linking studies. This unglycosylated receptor does not appear to stably bind transferrin as demonstrated by a lack of isolation of this form of the receptor with transferrin-linked Sepharose. It is not transported to the surface of A431 cells.

Cell Line↗
PubMed1988

Uptake of iron from transferrin by isolated rat hepatocytes. A redox-mediated plasma membrane process?

The uptake of iron from transferrin by isolated rat hepatocytes varies in parallel with plasma membrane NADH:ferricyanide oxidoreductase activity, is inhibited by ferricyanide, ferric, and ferrous iron chelators, divalent transition metal cations, and depends on calcium ions. Iron uptake does not depend on endosomal acidification or endocytosis of transferrin. The results are compatible with a model in which iron, at transferrin concentrations above that needed to saturate the transferrin receptor, is taken up from transferrin predominantly by mechanisms located to or contiguous with the plasma membrane. The process involves labilization and reduction of transferrin-bound iron by cooperative proton and electron fluxes. A model which combines the plasma membrane mechanism and the receptor-mediated endocytosis mechanism is presented.

Animals↗
PubMed1987

Plasma iron and transferrin iron-binding capacity evaluated by colorimetric and immunoprecipitation methods.

We evaluated plasma iron (PI) and total iron-binding capacity (TIBC) or transferrin in normal individuals and in patients with iron imbalance. The standard colorimetric measurements of PI and TIBC and the standard isotope-dilution measurement of TIBC were compared with an immunoprecipitation method and also with immunoelectrophoresis of transferrin. PI concentrations as measured by the standard and immunoprecipitation methods agreed closely for all individuals except those with saturated transferrin, where nontransferrin iron increased the results in the standard assay. This excess iron in saturated plasma may be derived from either free iron or iron-bearing ferritin. There were also differences in TIBC between the two methods. Iron-deficient sera gave higher values for transferrin when measured by immunoelectrophoresis. Unsaturated iron-binding capacity was increased in the isotope-dilution method in some iron-saturated plasma, compounding errors when added to erroneously high PI values to compute TIBC. Perhaps some exchange of iron occurred between added iron and transferrin iron in the isotope-dilution method. These measurements confirm the accuracy of the standard colorimetric method of measuring PI and TIBC except in iron-saturated plasma. However, the greater specificity of a polyclonal immunoprecipitation method of measuring PI and TIBC makes it particularly useful in differentiating transferrin-bound iron from nontransferrin iron.

Colorimetry↗
PubMed1986

Structure and function of transferrin receptors and their relationship to cell growth.

The transferrin receptor binds the major serum iron-transport protein, transferrin, and mediates cellular iron uptake. The receptor is a major immunodominant cell surface glycoprotein of cultured cells and its expression on the cell surface is co-ordinately regulated with cell growth. Recent structural and functional studies of the transferrin receptor are reviewed. The properties of monoclonal antibodies against the transferrin receptor that inhibit transferrin-mediated iron uptake are described. Studies with these antibodies establish that the transferrin receptor plays an important role in cell growth and suggest that monoclonal antibodies that interfere with the function of growth-related receptors may be useful in regulating tumour cell growth.

Animals↗
PubMed1987

Distribution of transferrin synthesis in brain and other tissues in the rat.

Levels of transferrin mRNA were measured by hybridization to transferrin cDNA in extracts from various areas of rat brain and other tissues. The highest concentrations of transferrin mRNA were found in the liver and the choroid plexus of the lateral and third ventricles. Lower concentrations were observed in the medulla and thalamus, choroid plexus of the fourth ventricle, cortex, hypothalamus, cerebellum, pituitary, testis, placenta, stomach, spleen, kidney, muscle, and heart. Yolk sac, small intestine, and adrenal glands did not contain detectable transferrin mRNA levels. The size of transferrin mRNA was the same in liver, brain, and testis. Upon incubation of choroid plexus pieces with [14C]leucine in vitro, about 4% of the radioactive protein secreted into the medium was found to be transferrin. Together with previous data (Dickson, P.W., Howlett, G.J., and Schreiber, G. (1985) J. Biol. Chem. 260, 8214-8219; Dickson, P.W., Aldred, A.R., Marley, P.D., Bannister, D., and Schreiber (1986) J. Biol. Chem. 261, 3475-3478) the obtained data suggest that the choroid plexus plays a role in maintenance of homeostasis in the microenvironment of the central nervous system by synthesizing and secreting plasma proteins.

Animals↗