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PubMedDate not supplied

Ascertainment of IgA1 (kappa)-transferrin complex in a case of multiple myeloma associated with hypersiderinemia.

IgA1(kappa)-transferrin complex was ascertained in a case of multiple myeloma with hypersiderinemia. On gel filtration, this complex disclosed an orange-colored protein with two peaks between the 19S and 7S fractions. On polyacrylamide gel electrophoresis and Western blotting analysis, the complex migrated at molecular weights of 430 and 700 kD in the non-reducing condition. A small amount of free transferrin was detected simultaneously. The complex was further separated into monoclonal IgA1(kappa) and transferrin at pH 4.5; these recombined at pH 7.2 after incubation (37 degrees C, 2 h). We also showed that the pepsin-digested F(ab')2 fragment of IgA1(kappa) combined with the transferrin. From these results it can be suggested that monoclonal IgA1(kappa) has an antibody activity for the transferrin. Clinically, this complex distributed the iron transport to erythroid cells in the bone marrow, resulting in hypersiderinemia, anemia, and iron deposits in the liver.

Aged↗
PubMed1995

Activation of phosphoinositide-specific phospholipase C by transferrin in porcine cerebral arterial smooth muscle cells.

The effect of transferrin on phosphoinositide metabolism was investigated in smooth muscle cells isolated from the porcine basilar artery. Ferric iron-bound transferrin induced a rapid increase in the level of inositol phosphates, the metabolic products of phosphoinositides through the phospholipase C pathway. Neither transferrin free of ferric iron nor ferric iron alone caused the activation of phospholipase C. This study suggests that ferric iron-bound transferrin is capable of eliciting receptor-mediated signal transduction in porcine cerebral arterial smooth muscle cells, which could result in the contraction of smooth muscle cells. Transferrin may be involved with the cerebral arterial narrowing in pathological conditions such as subarachnoid hemorrhage.

Animals↗
PubMed2006

Ferritin and transferrin are both predictive of the onset of hyperglycemia in men and women over 3 years: the data from an epidemiological study on the Insulin Resistance Syndrome (DESIR) study.

OBJECTIVE: The aim of the present work was to determine, in a cohort of men and women, whether ferritin and transferrin were associated with glucose metabolism and whether they were predictive of the onset of hyperglycemia (impaired fasting glycemia or type 2 diabetes) after 3 years of follow-up. RESEARCH DESIGN AND METHODS: Among 4,501 subjects from the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort, 1,277 subjects (644 men and 633 women) were randomly selected for the analysis of iron biomarkers at baseline and at 3 years. In addition, to determine whether these parameters were relevant to pathological changes, all 231 subjects normoglycemic at baseline and hyperglycemic 3 years later were analyzed for iron biomarkers. RESULTS: At baseline, plasma ferritin concentrations were positively correlated with fasting insulin and fasting glucose in the 1,277 subjects. Although transferrin and ferritin were negatively correlated, transferrin was also positively correlated with fasting insulinemia. Baseline ferritin concentration was an independent predictor of an increase in insulin concentration over a 3-year period (P = 0.002). Further, baseline ferritin and transferrin were independently associated with the onset of hyperglycemia over a 3-year period in the whole population (P < 0.001 for both) and in each sex. CONCLUSIONS: Although negatively correlated, both transferrin and ferritin were positively associated with the onset of abnormalities in glucose metabolism in a prospective study. These results further support the hypothesis of a causative role of iron metabolism in the onset of insulin resistance and type 2 diabetes.

Adult↗
PubMed1985

In vitro preparation of nonenzymatically glucosylated human transferrin, alpha 2-macroglobulin, and fibrinogen with preservation of function.

Human transferrin, alpha 2-macroglobulin, and fibrinogen were incubated with [3H]-glucose. After a 7-day, 37 degrees C incubation at 20 mM glucose, transferrin incorporated 1.1 mol of glucose/mol protein; alpha 2-macroglobulin, 10 mol of glucose/mol; and fibrinogen, 3.8 of glucose/mol, or approximately 14 mumol of glucose/g for each protein. These results were the same for glucose labeled in the 1 or 6 position. No radiolabel was incorporated into the proteins during incubations with glucose labeled in the 2 position. The rate and extent of iron binding were identical for both glucosylated and nonglucosylated transferrin. Glucosylated transferrin bound to Wil-2 human lymphoblast cells with a Kd = 33 nM and receptor number of 3.4 X 10(5) receptors/cell; nonglucosylated transferrin with a Kd = 31 nM and receptor number of 3.9 X 10(5) receptors/cell. Glucosylated and nonglucosylated alpha 2-macroglobulin showed the same conformational change as determined on native PAGE after reaction with trypsin, plasmin, or methylamine and had the same activity in the Ganrot assay after reaction with trypsin or plasmin. The clearance of 125I-labeled, methylamine-treated alpha 2-macroglobulin from the mouse circulation was identical for both glucosylated and nonglucosylated alpha 2-macroglobulin, t1/2 = 3 min. alpha 2-Macroglobulin that was first glucosylated then reacted with methylamine bound to mouse peritoneal macrophages with a Kd of 2.5 nM and receptor activity of 370 fmol/mg cell protein. alpha 2-Macroglobulin that was first reacted with methylamine and then glucosylated bound with a Kd of 3 nM and receptor activity of 320 fmol/mg cell protein. Glucosylated fibrinogen had the same clotting time as control fibrinogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Transferrin concentration in seminal plasma with special reference to serum hormone levels in infertile men.

The concentration of transferrin in seminal plasma and serum levels of LH, FSH, testosterone, and prolactin were measured in 94 male patients attending our infertility clinic. The concentration of transferrin in patients with azoospermia was lowest among azoospermia, oligozoospermia, and normozoospermia groups. There was significant positive correlation between the concentration of transferrin in seminal plasma and sperm density. However, seminal plasma transferrin was inversely correlated with serum levels of LH, FSH, and prolactin, respectively. It is suggested that transferrin in seminal plasma contributes to the activation of seminiferous tubules and can be used as a reliable index of Sertoli cell function.

Adult↗
PubMedDate not supplied

Changes in seminal plasma transferrin concentration following administration of clomiphene citrate.

This study was designed to investigate the functional changes in Sertoli cells following clomiphene citrate administration to patients with idiopathic infertility. The agent was administered to 44 oligozoospermic patients. Patients with improvement in sperm concentration after treatment (improvement group) showed significantly lower pretreatment follicle-stimulating hormone (FSH) levels in serum. Serum FSH and testosterone levels significantly increased in the improvement group after treatment (both p < 0.05). Seminal transferrin concentration significantly increased in the improvement group after treatment (p < 0.05), although there was no significant difference between pretreatment seminal transferrin concentration in the improvement group and that in patients with no improvement in sperm concentration. Seminal plasma transferrin concentration in patients in whom pretreatment luteinizing hormone level in serum was below 10 mIU/mL, and in those in whom the ratio of post- to pretreatment values was 1.5 or more, tended to increase after treatment. This group also contained a few more patients with improvement in sperm concentration than the other groups. The patients showing low pretreatment FSH levels and a high ratio of post- to pretreatment values demonstrated a significant increase in seminal plasma transferrin concentration after treatment (p < 0.01), and this group contained more patients with improvement than the other groups. It would appear that Sertoli cell stimulation may induce an increase in sperm concentration after clomiphene citrate administration, and the elevated transferrin secretion seems to be associated with the increase of serum FSH level after treatment.

Adult↗
PubMed1999

Levels of transferrin and alpha 2-HS glycoprotein in women with and without endometriosis.

The study objective was to test the hypothesis that elevated levels of transferrin and alpha 2-HS glycoprotein occur in the peritoneal environment of patients with endometriosis that may lead to the observed autoimmunity to these proteins. We set up a double sandwich enzyme-linked immunosorbent assay (ELISA) for measuring levels of transferrin and alpha 2-HS glycoprotein in the serum and peritoneal fluid samples from women with (n = 24-60) and without endometriosis (n = 35-49). Serum and peritoneal fluid levels of alpha 2-HS glycoprotein and peritoneal fluid levels of transferrin were significantly elevated in patients with endometriosis, in contrast to the controls. Serum levels of transferrin in patients, however, were significantly less in the patients than in controls. We conclude that transferrin and alpha 2-HS glycoprotein are present at high concentrations in the peritoneal fluids of patients with endometriosis. This may play a significant role in the autoimmune pathophysiology of endometriosis.

Ascitic Fluid↗
PubMed2000

In vitro and in vivo efficacy of acid-sensitive transferrin and albumin doxorubicin conjugates in a human xenograft panel and in the MDA-MB-435 mamma carcinoma model.

Acid-sensitive transferrin and albumin conjugates with doxorubicin have recently been developed with the aim of circumventing the systemic toxicity and improving the therapeutic efficacy of this anticancer agent. The in vitro activity of two acid-sensitive transferrin and albumin doxorubicin conjugates and free doxorubicin was evaluated in twelve human tumour xenografts using a clonogenic assay. The inhibitory effects and the activity profile of the conjugates was, in general, comparable to that of doxorubicin (mean IC(70) -value for doxorubicin approximately 0.1 microM and 0.1 - 0.4 microM for the conjugates). Subsequently, the efficacy of an acid-sensitive transferrin and albumin doxorubicin conjugate, which both incorporated a phenylacetyl hydrazone bond as a predetermined breaking point, was evaluated in the xenograft mamma carcinoma model MDA-MB-435 in comparison to free doxorubicin (dose, i.v.: 2 x 4, 8 and 12 mg/kg). The conjugates showed significantly reduced toxicity (reduced lethality and body weight loss) with a concomitantly stable or slightly improved antitumour activity compared to free doxorubicin. At the dose of 12 mg/kg mortality was unacceptably high in the doxorubicin treated group ( approximately 80%); in contrast, no mortality was observed with the conjugate treated animals with body weight loss < 10 %. In a further experiment, therapy with the acid-sensitive doxorubicin albumin conjugate at 3 x 12 mg/kg in the MDA-MB-435 model resulted in a significantly improved antitumour activity over free doxorubicin at its optimal dose of 2 x 8 mg/kg. In conclusion, acid-sensitive transferrin and albumin doxorubicin conjugates can be administered at higher doses than free doxorubicin in nude mice models with a concomitant improvement in antitumour activity. Interestingly, there is no pronounced difference between identically constructed transferrin and albumin doxorubicin conjugates with regard to in vitro or in vivo efficacy.

Animals↗
PubMed1993

Studies on the transfer of DNA into cells through use of avidin-polylysine conjugates complexed to biotinylated transferrin and DNA.

A simple procedure has been developed for studying the transfer of DNA into cells using the process of receptor-mediated endocytosis. Poly-L-lysine 460 was covalently attached to the carbohydrate chains of avidin via periodate oxidation and NaBH4 reduction to give avidin-pLys460. Following purification through Sephacryl S-300, the conjugate was reacted with biotinylated transferrin. The resulting avidin-pLys460-[bio-transferrin] could be either fractionated by Superose 12 gel chromatography or used directly in experiments with DNA. Determination of the interaction between avidin-pLys460-]bio-transferrin] and DNA was carried out by nitro cellulose filter binding and agarose gel retardation assays. The conjugate was shown to bind DNA strongly, giving stable complexes soluble in 0.15-0.2 M salt solutions. Gene transfer using avidin-pLys460-[bio-transferrin] and the luciferase plasmid pRSVL was accomplished with Hela cells, alpha T3 pituitary cells and a human melanoma cell line used in the present study. Transfection was dependent on bio-transferrin and stimulated by the lysosomotropic agent chloroquine. The results are consistent with a receptor-mediated endocytosis mechanism of DNA delivery for Hela cells and a combination of receptor and adsorptive endocytosis for the alpha T3 pituitary and melanoma T-5 cell lines.

Avidin↗
PubMed2003

Transferrin C2 variant does confer a risk for Alzheimer's disease in caucasians.

Several gene mutations are associated with an increased risk of Alzheimer's disease. Previous studies reported higher transferrin C2 allele frequencies in Alzheimer's disease compared with normal controls. However, potential interactions between transferrin C2 and APOE (epsilon 4), have not been extensively investigated and have been the subject of controversial reports from several laboratories. We have carried out a case-control study on the association between Alzheimer's disease and transferrin C2 and APOE epsilon 4 alleles. epsilon 4 allele was associated with a four fold increase in the risk of disease, and transferrin C2 allele was significantly associated with Alzheimer's disease only in epsilon 4 negative subjects. These results suggest that apoE and transferrin may be part of a complex mechanism in the pathogenesis of Alzheimer's disease.

Aged↗
PubMed2004

Targeted delivery of RNA-cleaving DNA enzyme (DNAzyme) to tumor tissue by transferrin-modified, cyclodextrin-based particles.

Short nucleic acid sequences specific to oncogene targets such as bcl-2, bcr-abl, and c-myc have been shown to exhibit specific anti-cancer activity in vitro through antigene or antisense activity. Efficient in vivo delivery of oligonucleotides remains a major limitation for the therapeutic application of these molecules. We report herein on the preparation of transferrin-modified nanoparticles containing DNAzymes (short catalytic single-stranded DNA molecules) for tumor targeting as well as their biodistribution using various methods of administration in the mouse. Linear, beta-cyclodextrin-based polymers are complexed with DNAyzme molecules to form sub-50 nm particles termed "polyplexes". The surface properties of the cyclodextrin-containing polyplexes are modified by exploiting the ability of the beta-cyclodextrin substructure and adamantane to form inclusion complexes. Accordingly, conjugates of adamantane with poly(ethylene glycol) (PEG) are prepared and combined with the polyplexes. The adamantane form inclusion complexes with the surface cyclodextrins of the polyplexes to provide a sterically stabilizing layer of PEG. The stabilized polyplexes are also modified with transferrin for increasing targeting to tumor cells expressing transferrin receptors. The preparation, characterization, and in vitro application of these nanoparticles are discussed. The transferrin-polyplexes containing fluorescently-labeled DNAzyme molecules are administered to tumor-bearing nude mice and their biodistribution and clearance kinetics are monitored using a fluorescence imaging system. Four methods of administration are studied: intraperitoneal bolus and infusion, intravenous bolus, and subcutaneous injection. DNAzymes packaged in polyplex formulations are concentrated and retained in tumor tissue and other organs, whereas unformulated DNAzyme is eliminated from the body within 24 hours post-injection. Intravenous and intraperitoneal bolus injections result in the highest fluorescent signal (DNAzyme) at the tumor site. Tumor cell uptake is observed with intravenous bolus injection only, and intracellular delivery requires transferrin targeting.

Adamantane↗
PubMed1999

Is serum transferrin receptor a sensitive marker of iron repletion in patients with iron-deficiency anemia and hemodialysis patients?

BACKGROUND: Serum transferrin receptor (sTfR) concentration has been recognized as a reliable laboratory indicator of iron deficiency in recent years. But its response to iron supplementation has not been investigated. METHODS: We evaluated the sTfR concentrations in 15 patients diagnosed with iron-deficiency anemia, in 30 patients receiving maintenance hemodialysis (HD) with iron repletion and in 31 healthy controls. The serial changes of sTfR concentration and their correlation with serum ferritin in patients with iron deficiency under iron repletion were also examined in three patients. RESULTS: In patients with iron-deficiency anemia, the sTfR concentration was 5.6 +/- 2.4 mg/ml, significantly higher than that in the control group (1.8 +/- 0.4 mg/ml) and patients receiving maintenance HD with iron repletion (1.7 +/- 0.5 mg/ml). The three patients with iron-deficiency anemia who received eight to 16 weeks of iron supplementation showed steady and significant decreases in sTfR concentration and significant increases in serum ferritin and transferrin saturation. However, the decreases in sTfR concentration did not occur immediately, as did the increases in serum ferritin and transferrin saturation, following iron repletion. There was a four-week delayed response in the decrease of sTfR concentrations as measured against serum ferritin and transferrin saturation. CONCLUSIONS: sTfR concentration may not be as effective as an early index of iron repletion compared with serum ferritin and transferrin saturation.

Adult↗
PubMed2000

Targeting rat anti-mouse transferrin receptor monoclonal antibodies through blood-brain barrier in mouse.

Drug targeting through the brain capillary endothelium, which forms the blood-brain barrier (BBB) in vivo, may be achieved with peptidomimetic monoclonal antibodies that target peptide transcytosis systems on the BBB in vivo. Murine monoclonal antibodies to the rat transferrin receptor, such as the OX26 monoclonal antibody, are targeted through the BBB on the transferrin receptor in the rat. However, the present studies show the OX26 monoclonal antibody is not an effective brain delivery vector in mice. The emergence of transgenic mouse models creates a need for brain drug-targeting vectors for this species. Two rat monoclonal antibodies, 8D3 and RI7-217, to the mouse transferrin receptor were evaluated in the present studies. Both the RI7-217 and the 8D3 antibody had comparable permeability-surface area products at the mouse BBB in vivo. However, owing to a higher plasma area under the concentration curve, the mouse brain uptake of the 8D3 antibody was higher, 3.1 +/- 0.4% of injected dose [(ID)/g] compared with the brain uptake of the RI7 antibody, 1.6 +/- 0.2% ID/g, at 60 min after i.v. injection. Conversely, the mouse brain uptake of the OX26 antibody, which does not recognize the mouse transferrin receptor, was negligible, 0.06 +/- 0.01% ID/g. The RI7-127 antibody was more selective for brain because this antibody was not measureably taken up by liver. The capillary depletion technique demonstrated transcytosis of the RI7-217 antibody through the mouse BBB in vivo. The brain uptake of the 8D3 antibody was saturable, consistent with a receptor-mediated transport process. In conclusion, these studies indicate rat monoclonal antibodies to the mouse transferrin receptor may be used for brain drug-targeting studies in mice such as transgenic mouse models.

Animals↗
PubMed1997

[Study on the synthesis and secretion rate of transferrin in hepatoma and peritumor hepatocytes].

OBJECTIVE: To study the changes of synthesis and secretion of transferrin (Tf) in human hepatocellular carcinoma (HCC) cells and search the causes of reduced membrane-bond transferrin in HCC tissue. METHODS: By radioisotope incorporation and immunoprecipitation to determine the synthesis and secretion rate of transferrin in human HCC cells and peritumor hepatocytes. RESULTS: When compared with peritumor hepatocytes the quantity of transferrin synthesized was not changed in HCC cells, but its secretion rate was accelerated significantly while the transferrin storage was significantly decreased. CONCLUSION: The results suggest that HCC growth might be enhanced by increased Tf secretion and help explain the decreased membrane-bond form of Tf in HCC tissue.

Carcinoma, Hepatocellular↗
PubMed2000

Mean cell volume and gamma-glutamyl transferase are superior to carbohydrate-deficient transferrin and hemoglobin-acetaldehyde adducts in the follow-up of pregnant women with alcohol abuse.

BACKGROUND AND OBJECTIVE: To compare the usefulness of carbohydrate-deficient transferrin (CDT), the ratio of CDT to total transferrin, and hemoglobin-acetaldehyde adducts with mean cell volume (MCV) and gamma-glutamyl transferase (GGT) in the follow-up of alcohol abuse during pregnancy. METHODS: Forty-four pregnant drug and alcohol abusing female patients attending a special outpatient clinic were followed from the 8th to 24th gestational week onwards. A population of sixty-two healthy pregnant women was recruited to assess the effect of gestation on the markers. RESULTS: Eight of thirteen heavy drinking (> or =8 drinks/week) patients delivered infants with fetal alcohol effects (FAE). MCV and GGT were higher among heavy drinking patients than in moderately drinking (<8 drinks/week) patients (92+/-4 vs 90+/-3 fl and 31+/-34 vs 16+/-10 U/ L, respectively), and in patients delivering infants with FAE compared with patients delivering healthy infants (95+/-3 vs 90+/-3 fl and 34+/-26 vs 15+/-10 U/L, respectively). Hemoglobin-acetaldehyde adducts, CDT, and the ratio of CDT to total transferrin were neither associated with the reported level of alcohol consumption nor with the occurrence of FAE. In the receiver operating characteristics analysis MCV was found to be superior to CDT and the adducts, and GGT superior to the adducts, in identifying heavy drinking and in predicting FAE. In the control population, both CDT and total transferrin were found to rise during pregnancy, whereas the ratio of CDT to total transferrin was found to decline. The upper reference range of 33 U/L for CDT was considerably higher than that of non-pregnant women (26 U/L). CONCLUSION: MCV and GGT appear to be the most efficient laboratory markers for detecting excessive alcohol consumption and the adverse effects of alcohol on the fetus.

Acetaldehyde↗
PubMed1975

[Oral loading test with a preparation which frees iron gradually in the intestine. Behavior of blood iron and transferrin].

Blood iron, total transferrin, iron-bound transferrin and transferrin iron saturation percentage were determined in non-anaemic subjects after oral administration of 1 and 2 tablets of a commercial preparation (Ferro-grad) containing ferrous sulphate and ensuring slower release of iron in the intestine. After 1 tablet, blood iron and transferrin saturation reached their peaks after 4 hr and returned to start levels after 10 hr. Higher increases were achieved, though later, with 2 tablets and the return to start levels presumibly occurred within 14 hr. There was a slight increase in total transferrin 2 hr after 1 tablet and values remained high throughout the experiment. When 2 tablets were given values fluctuated considerably, with minima coinciding with maximum blood iron values.

Adult↗
PubMed1975

In vivo evidence for the functional heterogeneity of transferrin-bound iron. II. Studies in pregnant rats.

Iron atoms from the two iron-binding sites of transferrin in the maternal plasma were selectively transferred to fetal tissues across the placenta of the pregnant rat. Rat serum transferrin was selectively double-labeled with 55Fe bound to the A-site and 59Fe bound to the B-site and injected intravenously into pregnant rats at 11 to 20 days gestation. Ratios of 55Fe to 59Fe were measured in various maternal and fetal tissues sampled from 30 to 120 minutes after injection. In the maternal tissues preponderance of A-site 55Fe was observed in circulating red blood cells and in heme extracted from bone marrow and spleen; B-site 59Fe predominated in the liver parenchymal cells and proximal small intestine. As predicted by the Fletcher-Huehns hypothesis, placental transfer of radioiron resulted in a selective concentration of A-site 55Fe in all the fetal tissues including the fetal placenta, yolk sac, whole fetus, and in the separately analyzed liver heme and ferritin and in fetal blood. When the placenta was bypassed by direct injection of the selectively double-labeled transferrin into the umbilical vein, a reversal of the 55Fe/59Fe ratios of heme extracted from the fetal liver was observed. These studies confirm the concept of functional heterogeneity of iron atoms bound to transferrin and indicate that the placenta of rats between the eleventh and twentieth day of pregnancy selectively removes erythroblast-oriented iron from transferrin and diverts it to fetal tissues.

Animals↗
PubMed2002

Transferrin-mediated targeting of hypericin embedded in sterically stabilized PEG-liposomes.

Over the last few decades, photodynamic therapy evolved to a promising new treating modality for cancer. The photosensitizers used, induce light sensitivity to a normal light insensitive chemical or physical process. Third generation photosensitizers are derivatives of second generation photosensitizers introduced into or attached to chemical devices. This modification increases the biological specificity to deliver photosensitizers to a defined cell type. The aim of this study was to improve the specificity of hypericin for tumor cells using transferrin-conjugated PEG-liposomes. Transferrin was used as tumor-seeking molecule, since many tumor cells, among which HeLa cells, overexpress transferrin receptors on their surface. Hypericin, a potent second generation photosensitizer, was integrated in the lipid bilayers of the liposomes. The antiproliferative effect of the targeted PEG-liposomes was determined and compared with the results of non-targeted PEG-liposomes and free hypericin. Additionally, the intracellular accumulation assay was performed. All manipulations were done on HeLa cells. To interpret the results, the data were supplemented by findings concerning embedding stability. Targeting hypericin by transferrin-conjugated PEG-liposomes did not significantly favour the photocytotoxicity and the intracellular accumulation of hypericin, in comparison with non-targeted PEG-liposomes or free hypericin. Embedding stability experiments showed only limited stable embedding. Despite of their proven efficiency as a targeting carrier system, transferrin-conjugated PEG-liposomes seem less effective in targeting hypericin to tumor cells due to the amount of hypericin leaking out of the PEG-liposomes.

Anthracenes↗