Higher Transferrin Levels Research Articles

Cross-sectional and longitudinal associations of Iron biomarkers and cardiovascular risk factors in pre- and postmenopausal women: leveraging repeated measurements to address natural variability

BackgroundThe association between iron biomarkers and cardiovascular disease risk factors (CVD-RFs) remains unclear. We aimed to (1) evaluate the cross-sectional and longitudinal associations between iron biomarkers (serum ferritin, transferrin saturation (TSAT), transferrin) and CVD-RFs among women, and (2) explore if these associations were modified by menopausal status.MethodCross-sectional and longitudinal analyses including 2542 and 1482 women from CoLaus cohort, respectively. Multiple linear regression and multilevel mixed models were used to analyse the associations between Iron biomarkers and CVD-RFs. Variability of outcomes and iron markers between surveys was accessed using intraclass correlation (ICC).ResultsAfter multivariable adjustment, elevated serum ferritin levels were associated with increased insulin and glucose levels, while higher transferrin levels were linked to elevated glucose, insulin and total cholesterol, and systolic and diastolic blood pressure (p < 0.05). No association was observed between CVD-RFs and TSAT (p > 0.05). Iron biomarkers demonstrated low reliability across reproductive stages but exhibited stronger associations in the perimenopausal group. In longitudinal analysis, we found association only for transferrin with lower glucose levels [β = − 0.59, 95% CI (− 1.10, − 0.08), p = 0.02] and lower diastolic blood pressure [β = − 7.81, 95% CI (− 15.9, − 0.56), p = 0.04].ConclusionIn cross-sectional analysis, transferrin was associated with several CVD-RFs, and the associations did not change according to menopausal status. Conversely, in the longitudinal analyses, changes in transferrin were associated only with lower glucose and diastolic blood pressure levels. These differences might stem from the substantial longitudinal variation of iron biomarkers, underscoring the need for multiple iron measurements in longitudinal analyses.

Biochemical abnormalities among patients referred for celiac disease antibody blood testing in a primary health care setting

To investigate possible biochemical abnormalities associated with celiac disease (CD) antibody positivity in a primary health care setting and thereby identify predictors that could potentially reduce diagnostic delay and underdiagnosis of CD. This observational cohort study included measurements of CD antibodies in the Copenhagen Primary Care Laboratory (CopLab) database from 2000 to 2015; CD antibody positivity was defined as tissue transglutaminase antibody IgA or IgG ≥ 7 kU/L and/or deamidated gliadin peptide antibody IgG ≥ 10 kU/L. Individuals with a prior diagnosis of CD were excluded. We examined differences between individuals with positive and negative CD antibody tests regarding the results of biochemical tests performed six months before and one month after the date of the CD antibody test. We identified 76,265 measurements of CD antibodies during 2000–2015, and 57,061 individuals met the inclusion criteria (706 antibody-positive and 56,355 antibody-negative). We found lower ferritin, hemoglobin, cobalamin and folic acid levels and higher levels of transferrin, ALAT (alanine transaminase), and alkaline phosphate among individuals with a positive CD antibody test. Furthermore, we illustrated more measurements below the sex-specific reference intervals for hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), ferritin, cobalamin and folic acid among individuals with a positive CD antibody test. This study identified several biochemical abnormalities associated with CD antibody positivity among individuals referred to CD antibody testing. The pattern of abnormalities suggested that micronutrient deficiencies were prevalent among CD antibody-positive individuals, confirming malabsorption as a sign of CD. These findings illustrate the possibility of reducing diagnostic delay and underdiagnosis of CD.

Biochemical predictors of chronic kidney disease in children recovering from acute kidney injury

The pressing question today is to find early informative markers for kidney interstitial injury in reconvalescents of acute kidney injury (AKI). The aim of the study was to determine the informativeness of transferrin (TF), ceruloplasmin (CP) presence and activity level of lysosomal enzymes in urine as predictors of chronic kidney disease. Materials and methods. The contents of TF, CP and N-acetyl-β-Dgluosaminindase (NAG) and β-galactosidase (ß-GAL) in the urine of 41 children after AKI were determined. All patients were divided into 2 groups depending on the disease duration – group 1 included 22 patients with 12 months’ duration, group 2 – 19 children with the disease duration of 2 years and more. The control group consisted of 28 conditionally healthy children. Results. The levels of NAG and ß-GAL were 8 and 3 times increased, respectively, in the patients from group 1 in comparison with the control group (P &lt; 0.001). In the group 2 children, the enzyme levels were 4 times higher than the control, and albuminuria was observed at normal GFR (P &lt; 0.001). An inverse correlation was established between GFR indices and activity levels of NAG (r = -0.473) and ß-GAL (r = -0.333), and a direct correlation between activity indices of GAG and ß-GAL (r = 0.845). The presence and high levels of TF in 18.8 % of children in group 1 and in 21.0 % in group 2, as well as urine CP in 72.7 % of patients in group 1 and in 78.9 % in group 2, is indicative of a progressive damage to the kidney glomerular apparatus. Conclusions. The presence and increased quantitative parameters of TF and CP in the urine of children after AKI are early signs of damage to the kidney glomerular apparatus. Four times increased levels of the enzyme activity and albuminuria at unchanged GFR indicate an interstitial kidney injury (P &lt; 0.001). The examinations conducted are non-invasive, relatively low cost and easy to use for children of all ages.

Health and Nutritional Status of Vegetarian Candidates for Bariatric Surgery and Practical Recommendations.

Data on vegetarianism and bariatric surgery (BS) are scarce. We herein describe the health and nutritional status of vegetarian patients who plan to undergo BS and propose combined recommendations for vegetarian patients who undergo BS, based on our clinical experience and current scientific literature in both nutrition fields. Cross-sectional analysis of a prospectively maintained database of all primary laparoscopic sleeve gastrectomies (LSG) performed at a bariatric center of excellence between January 2014 and November 2016 was carried out querying patients who declared a vegetarian or vegan lifestyle before surgery. Preoperative data collected included demographics, anthropometrics, dietary patterns, supplementation use, physical activity, smoking habits, co-morbidities, and blood tests. Each vegetarian was matched to five different omnivores based on age, gender, and BMI. During the study period, 1470 patients underwent primary LSG surgery (63.7% females). Twenty-one declared a vegetarian or vegan lifestyle (1.4%) pre-surgery. Most were classified as lacto-ovo (57.1%) and were driven from ethical reasons (85.7%). No differences were found between vegetarian and omnivore LSG candidates regarding co-morbidities and nutritional deficiencies, except for lower prevalence of impaired fasting glucose (14.3 vs. 47.1%;P=0.007), lower ferritin levels (54.3±50.5 vs. 96.8±121.8ng/ml; P=0.052) and higher transferrin levels (313.9±42.7 vs. 278.4±40.4mg/dl; P=0.009) among the vegetarian cohort. Preoperative use of vitamin B12 and iron supplementation was higher among vegetarian LSG candidates than their omnivore counterparts (57.1 vs. 6.7%;P<0.001 and 23.8 vs. 6.7%; P=0.015, respectively). Vegetarians have comparable health status and nutritional deficiencies, lower iron stores, and higher supplementation use before surgery compared to omnivore LSG candidates.

Deferoxamine’s Influence on Iron Metabolism, the Rheological Properties of Blood, Endothelial Dysfunction in an Experimental Model of Ischemia/Reperfusion

Objectives. Prevention of violations of microcirculation should take into account the massive entry of hemolysis products into the bloodstream and the related subsequent activation of free radical oxidation. Results. By simulating ischemia/reperfusion on rats we demonstrated the positive effect of deferoxamine on iron metabolism parameters (higher levels of transferrin, less ferritin and free iron, which received the drug group), also observed a decrease in the concentration of von Willebrand factor, as a measure of endothelial dysfunction. Blood viscosity parameters in the deferoxamine group was the closest to the control group parameters. Conclusion. Thus, we can conclude about the positive effect of deferoxamine on the parameters of iron metabolism, microcirculation and blood rheology in critical conditions involving ischemia/reperfusion.

Plasma Protein Biomarkers of the Geriatric Syndrome of Frailty

Frailty is a geriatric syndrome associated with physical decline with aging. Using a proteomics-based screening method to screen plasma for potential biomarkers, we previously found inflammatory glycoproteins to be increased with frailty. The purpose of this study was to confirm if plasma levels of these glycoproteins, as well as of interleukin-6, are increased with frailty in a larger sample (n = 65) of community-dwelling older adults. Plasma levels of transferrin, fibrinogen, haptoglobin, and interleukin-6 were determined with enzyme-linked immunosorbent assay. Differences in protein concentrations by frailty status were determined using analysis of variance. Higher levels of transferrin (p < .001), fibrinogen (p < .0001), and interleukin-6 (p = .0035) were associated with frailty status (nonfrail, prefrail, or frail) and frailty score (0-5) in this sample even after adjustment for age and sex. Haptoglobin did not differ by frailty status (p = .05). Our findings largely confirmed the findings of our nontargeted approach that inflammatory glycoproteins are increased with frailty. Future studies should include larger examinations of these associations and consider the potential usefulness of these glycoproteins as biomarkers for frailty.

Factors associated with iron deficiency in pregnant women seen at a public prenatal care service

OBJECTIVE: This study aimed to determine the frequency of iron deficiency and its association with socioeconomic, obstetric, and nutritional factors in pregnant women. METHODS: This cross-sectional study included women on the second trimester of pregnancy seen at a public prenatal care facility of Cuiabá, Mato Grosso, Brazil from May 2008 to May 2009. Socioeconomic, nutritional, and obstetric data were compared with markers of iron stores. RESULTS: During the study period, 146 pregnant women met the inclusion criteria. The frequency of anemia characterized by abnormal hemoglobin level, hematocrit, and mean corpuscular volume varied from 3% to 5%. However, 11% of the women had high transferrin levels and 39% had low ferritin levels. Before pregnancy, 21% of the women were underweight and 29% were overweight or obese. During pregnancy, the percentage of overweight or obese women rose to 40%. History of miscarriages, higher gestational age, and excess weight before pregnancy were associated with markers of iron stores at abnormal levels. Consumption of specific food groups was not associated with abnormal marker levels. CONCLUSION: Serum ferritin was the most sensitive indicator of iron deficiency. Excess weight and anemia were concomitant.

The Effect of Fetal and Early Postnatal Iron Deficiency on Iron Metabolism in Adult Rats

Undernutrition during pregnancy and/or lactation plays an important role on the overall health of offspring later in life. Using a rodent model, the present study was conducted to examine the effect of fetal and early postnatal iron deficiency on iron metabolism in adult animals. Rats were treated with three stages of low or normal iron diets from gestation until the end of the study. During the first stage (4 weeks prior to 3 weeks after pregnancy, total 7 weeks), two groups of adult females (dams) were fed with either a low-iron (7.4 mg iron/kg, group LD) or control-iron (274 mg/kg, group CD) diet. During the second stage (from 3 to 13 weeks of age, total 10 weeks), all pups from stage 1 (both the LD and CD groups) were placed on a control-iron diet for 10 weeks (groups LD-CD and CD-CD, respectively). During the third stage (from 13 to 29 weeks of age, total 16 weeks), both LD-CD and CD-CD groups from stage 2 were fed with a low-iron (named LD-CD-LD and CD-CD-LD groups, respectively). We found that the live birth rate of the offspring of the LD dams (84.7 %) was significantly lower than that of the CD dams (95.4 %). During stage 2, the mean body weight of the LD-CD male or LD-CD female rats exceeded the CD-CD male rats (p < 0.05). Compared with the CD-CD-LD rats, the LD-CD-LD rats had significantly increased total iron binding capacity, and higher levels of transferrin, serum erythropoietin (EPO), renal EPO mRNA, duodenal divalent metal transporter-1, and renal transferrin receptors. These findings indicate that rats with an early-life experience of iron deficiency (during pregnancy and the nursing period) can develop stronger iron absorption capabilities in adulthood.

Is Hepcidin-25 a Clinically Relevant Parameter for the Iron Status in Hemodialysis Patients?

Accumulating data suggest potential clinical relevant relationships between hepcidin-25 levels, iron stores, erythropoiesis effectiveness, and epoetin dose. The immunometric methods and mass spectroscopy are currently used to measure hepcidin-25, but no standard exists, and values, although similar in trends, differ in absolute value. To investigate hepcidin levels and their relationship with peripheral iron indices, inflammation, and anemia therapy in patients on hemodialysis (HD). A cross-sectional study in 78 patients from a single HD center. Hepcidin-25 was measured with enzyme-linked immunosorbent assay (ELISA), using a commercial kit (Bachem, UK). Hepcidin-25 levels were similar to those previously reported in studies using the same antibody (median 113 [95% CI; 107-122 ng/mL]) and significant but weak correlations of hepcidin with transferrin (R2=0.06; p<0.04) and ferritin (R2=0.09; p<0.01) were found. A model of multiple regression analysis explained 57% of variation along hepcidin quartiles. Lower hepcidin levels were associated with higher transferrin levels (odds ratio 1.05 [1.01-1.09]), bigger iron doses (odds ratio 1.09 [1.02-1.15]), and an increased darbepoetin resistance index (odds ratio 4.3E+15 [11.15-1.6E+30]). An elevated serum C reactive protein was associated with increased hepcidin levels (odds ratio 0.70 [0.49-0.99]), while a higher ultrafiltration volume (odds ratio 4.30 [1.28-14.51]) and the male sex (odds ratio 0.04 [0.00-0.80]) were related to lower hepcidin levels. Cohort number and composition. Hepcidin-25 ELISA assay. A low hepcidin level in hemodialysis patients with high epoetin resistance index could be a useful marker of iron-restricted erythropoiesis, but confirmation by a therapeutical trial is necessary.

Levels of Transferrin in Bronchoalveolar Lavage Fluid in Sarcoidosis

There has been only one report showing high levels of transferrin (Tf) in bronchoalveolar lavage fluid (BALF) in patients with sarcoidosis. This study was designed to assess the levels of Tf in both BALF and serum and to examine the relationship between the levels of Tf and other disease markers in sarcoidosis. Subjects were 64 sarcoidosis and 10 healthy controls. Tf in BALF and serum was measured by nephelometric assay. Median Tf levels in BALF from sarcoidosis was 0.70 (range, 0.00-3.97) mg/dl, which was significantly higher compared with controls (0.36 (range, 0.00-1.02) mg/dl; p = 0.005). In contrast, median Tf levels in serum from sarcoidosis was 258 (range, 171- 383) mg/dl, which was significantly lower compared with controls (322 (range, 234-356) mg/dl; p = 0.003). Tf levels in BALF were significantly correlated with both the percentage of lymphocytes (r = 0.617, p = 0.001) and serum angiotensin-converting enzyme activity (r = 0.363, p = 0.003) and serum soluble interleukin-2 receptor (r = 0.450, p = 0.001) in sarcoidosis. Levels of Tf in BALF from patients with sarcoidosis were not influenced by smoking status. The levels of Tf in sarcoidosis are high in BALF, but low in serum. Increased levels of Tf in BALF may reflect the disease activity.

Hemokromatose – fra underdiagnostisert kuriositet til folkesykdom

Hemochromatosis is a common disease with a good prognosis, when diagnosed early and treated appropriately. The aim of this overview is to give updated information on hemochromatosis with special focus on biochemical features, diagnosis and treatment. This article is based on our own experience and a review of available literature in various databases such as PubMed and Medline. Hereditary hemochromatosis is an autosomal recessive disease characterized by iron overload due to increased intestinal iron uptake over many years. Hemochromatosis is often discovered through coincidental detection of high levels of transferrin and/or ferritin. The early symptoms are asthenia and joint pain. About 85 % of patients with hereditary hemochromatosis are homozygote for the C282Y mutation in the HFE: gene, but the majority of homozygotes remain asymptomatic. With ferritin levels > 500 microg/, both hereditary hemochromatosis and iron overload (of unknown cause) are treated with blood-letting. The pathogenesis is not fully elucidated but recent reports indicate that the protein hepcidin (produced in the liver) plays a key role in the development of hemochromatosis. Iron overload may also be secondary to other diseases such as thalassemia and other conditions requiring multiple long-term blood transfusions. The goal is to maintain ferritin values at approximately 20 - 50 microg/L.

Blood contamination in children's saliva: Prevalence, stability, and impact on the measurement of salivary cortisol, testosterone, and dehydroepiandrosterone

The prevalence, stability, and impact of blood contamination in children's saliva on the measurement of three of the most commonly assayed hormones were examined. Participants were 363 children (47% boys; ages 6-13 years) from economically disadvantaged families who donated saliva samples on 2 days in the morning, midday, and late afternoon. Samples (n=2178) were later assayed for cortisol (C), testosterone (T), and dehydroepiandrosterone (DHEA). To index the presence of blood (and its components) in saliva, samples were assayed for transferrin. Transferrin levels averaged 0.37 mg/dl (SD=0.46, range 0.0-5.5, Mode=0), and were: (1) highly associated within individuals across hours and days, (2) positively correlated with age, (3) higher for boys than girls, (4) higher in PM than AM samples, and (5) the highest (>1.0 mg/dl) levels were rarely observed in samples donated from the same individuals. Transferrin levels were associated with salivary DHEA and C, but less so for T. As expected, the relationships were positive, and explained only a small portion of the variance. Less than 1% of the statistical outliers (+2.5 SDs) in salivary hormone distributions had correspondingly high transferrin levels. We conclude that blood contamination in children's saliva samples is rare, and its effects on the measurement of salivary hormones is small. Guidelines and recommendations are provided to steer investigators clear of this potential problem in special circumstances and populations.

Recombinant human protein C expression in the milk of transgenic pigs and the effect on endogenous milk immunoglobulin and transferrin levels.

Colostrum and milk are natural vehicles for acquiring passive immunity and are valuable tools for decreasing neonatant mortality from diarrheal disease. The effects of recombinant human protein C (rhPC) expression levels on endogenous immunoglobulin and transferrin content of the milk of different lineages of transgenic pigs were studied. The levels of rhPC in the milk ranged from 40 to 1200 microg/ml. Transgenic pigs with rhPC expression levels less than 500 microg/ml had no significant differences in milk protein composition with respect to nontransgenic pigs. A line of transgenic pigs having rhPC expression levels of 960-1200 microg/ml had two- to three-fold higher IgG, IgM, and secretory IgA concentrations compared to other transgenic and nontransgenic pig groups (P < 0.05), and four- to five-fold higher transferrin levels than nontransgenic pigs (P < 0.05). Changes in milk protein composition were not associated with mastitis or other pathologic disruption of epithelial cell junctions as indicated by normal casein and albumin levels in milk. Since IgG, IgM, secretory IgA, and transferrin are transported into the milk by transcytosis, higher levels of these proteins indicate that transcyctosis in the mammary epithelial cell was likely upregulated in pigs having high rhPC expression levels. This study is the first that shows a statistically significant example that mammary tissue specific expression of a heterologous protein can enhance endogenous phenotypic characteristics of milk.

Two dimensional protein patterns of bronchoalveolar lavage fluid from non-smokers, smokers, and subjects exposed to asbestos.

Bronchoalveolar lavage (BAL) fluid contains a large number of proteins which comprise a potential resource for studying respiratory effects due to occupational and environmental exposures. A study was undertaken to compare protein patterns of BAL fluid from non-smokers, smokers, and subjects exposed to asbestos. BAL fluid samples were analysed with two dimensional gel electrophoresis (2-DE). The separated proteins were detected, quantified, and pattern-matched between different individuals with a computerised imaging system designed for evaluations of 2-DE patterns. About 200 different protein spots were detected in each sample of BAL fluid. As is the case with blood plasma, the BAL fluid samples contained large amounts of albumin, transferrin, and immunoglobulins. Higher levels of basic proteins were found in smokers than in non-smokers, while subjects exposed to asbestos had increased amounts of several high molecular weight proteins as well as basic proteins. Lower levels of albumin and higher levels of immunoglobulins were found in smokers than in non-smokers, while higher levels of transferrin were found in asbestos exposed subjects than in unexposed subjects. Moreover, in the group exposed to asbestos differences were found between patients with pleuritis and patients with pleural plaque, and one protein spot was found only in two patients with progressive pleural disease. These results suggest that both smokers and asbestos exposed subjects have significant changes in their airway protein expression compared with non-smokers and unexposed subjects. It is inferred that analysis of protein patterns in the BAL fluid with 2-DE may be used to detect and characterise, at a molecular level, respiratory effects due to occupational and environmental exposures.

A serum‐free, pyruvate‐free medium that supports neonatal neural/glial cultures

Tissue culture media with serum generally cause excessive astrocyte proliferation in neonatal brain cultures, and often fail to support neonatal neurons. Published serum-free media for brain cultures contain sodium pyruvate, which interferes with lactate dehydrogenase (LDH) assays for cell death. We wanted to use neonatal neural-glial cultures in LDH assays while avoiding astrocyte proliferation, so we developed a serum-free medium without sodium pyruvate. Our initial medium was based on that of Romijn et al. (J Neurosci Methods 23:75-83, 1988), testing selected additives. Cell survival in 8-10-day-old cultures was measured using 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). N-acetylcysteine, citrate, superoxide dismutase, ascorbate, supplemental amino acids, and high levels of transferrin improved survival. The optimized medium supported neonatal brain cells in reaggregates or in monolayers of 400 cells/mm2 for several weeks with large, healthy-appearing neurons and very little astrocyte proliferation. Neurons stained strongly for the neuronal marker class III beta-tubulin and the synapse marker synaptophysin. Electron microscopy of reaggregate cultures demonstrated abundant neurons with synapses in a dense neuropil. This medium will be useful for various in vitro applications, especially those using LDH assays or requiring the use of neonatal cells.

Synthesis of Transferrin and Transferrin mRNA in Bovine Sertoli Cells in Culture and in Vivo: Sequence of Partial cDNA Clone for Bovine Transferrin1

Techniques were developed for generating enriched cultures of bovine Sertoli cells and indifferent supporting cells (immature Sertoli cells). The [35S]methionine and [35S]sulfate-labeled proteins secreted by cultured cells were analyzed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and fluorography. The electrophoretic pattern of the major Sertoli cell-secreted proteins was distinct from that of the major proteins secreted by cultured peritubular cells (the predominant contaminating cell type). Five major polypeptides ranging in molecular mass from 22 kDa to 77 kDa were resolved by 2D-PAGE in reducing conditions and were assigned numbers for reference purposes. Polypeptides 1 and 2 appeared to be analogous to two rat Sertoli cell-secreted proteins, sulfated glycoprotein-1 and sulfated glycoprotein-2, because of similar molecular mass, isoelectric point, subunit composition, sulfation, and sialation characteristics. Transferrin was detected in conditioned medium by immunoprecipitation using an antibody to bovine serum transferrin. Cultured Sertoli cells isolated from prepubertal bulls secreted higher levels of transferrin than did cells isolated from infant bulls. An 850 bp cDNA corresponding to the 3' portion of bovine transferrin mRNA was cloned and sequenced. Transferrin message was shown to be present in testicular tissue isolated from infant and prepubertal bulls and it increased as bulls matured. Levels of testicular transferrin mRNA were subsequently shown to correlate with daily sperm production in yearling beef bulls.

Seminal plasma transferrin concentration in idiopathic oligozoospermia

To investigate whether or not transferrin production is decreased in the testis of idiopathic oligozoospermia, the seminal plasma transferrin concentration was measured and the values were compared in two groups (15 men of pregnancy-proved normozoospermia and 22 patients with idiopathic oligozoospermia). Seminal plasma transferrin concentration in the pregnancy-proved normozoospermic group was 78.5 ± 37.9 μg/mL, and the concentration in the patients with idiopathic oligozoospermia was 44.4 ± 37.6 μg/mL. There was a significant difference between them (P < 0.01). The patients with idiopathic oligozoospermia could be divided into two subgroups according to seminal plasma transferrin concentration and serum gonadotropin levels. One group had high transferrin levels with elevated serum gonadotropin levels. The results indicate that the determination of seminal plasma transferrin concentration is one of the useful parameters for evaluation of testicular function and also suggest that additional studies may allow for the subdivision of the patients with so-called idiopathic oligozoospermia.

The regulation by low-density lipoproteins of the activation of oxidative enzyme-primed lymphocytes is governed by transferrin

The activation of T lymphocytes was regulated in vitro by low-density lipoproteins (LDL). Not all prereplicative events induced by the oxidative enzymatic mitogens neuraminidase and galactose oxidase (NAGO) were susceptible to inhibition by LDL. The accessory cell-independent early blastogenic response was not suppressed. LDL suppressed accessory cell-dependent responses, and the extent of LDL suppression, depended on the concentration of transferrin. A gradient of transferrin determined the point in the cell cycle at which NAGO-primed lymphocytes were suppressed by LDL. When transferrin was low (0–10 μg/ml) and in serum-free medium (SFM), LDL suppressed the expression of cell surface receptors for interleukin-2 (IL-2R) and transferrin (TfR), the late blastogenic response prior to DNA replication (72 hr), and DNA replication. At higher levels of transferrin, about 100 μg/ml, the LDL-suppressed cells were IL-2R +, TfR + and responsive to IL-2, but did not enter S phase. LDL suppression could be ablated by IL-2 and by high levels of transferrin (250–1000 μg/ml). In RPMI medium containing serum (FBS), the pattern of LDL suppression was different from that in SFM: fully activated IL-2R +, TfR + lymphocytes were unresponsive to exogenous IL-2, suggesting that they were blocked at the G 1/S boundary. This block was also relieved by transferrin (> 100 μg/ml). The data suggest that the interplay between transferrin and LDL is a critical factor in the NAGO-induced stimulation of T lymphocytes. LDL and transferrin exert negative and positive control of lymphocyte activation, respectively. In SFM, LDL appear to alter transferrin utilization by accessory cells; in RPMI-FBS, by fully activated T lymphocytes.

Protein Abnormalities in Adult Respiratory Distress Syndrome, Tuberculosis, and Cystic Fibrosis Sera

Crossed immunoelectrophoresis (X-IEP) revealed several abnormalities in serum proteins from patients with adult respiratory distress syndrome (ARDS), tuberculosis (TB), and cystic fibrosis (CF). The two quite different kinds of pulmonary disease, one acute (ARDS) and the other chronic (TB and CF) exhibited serum changes specific for each disease and abnormalities associated with inflammation and pathogenesis, in general. In ARDS sera, most proteins were extremely low, presumably due to leakage into the lungs through damaged tissue, while the acute-phase proteins, orosomucoid, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and haptoglobin, were markedly high when compared to the overall protein pattern. The extremely high alpha 1-antichymotrypsin values were not seen in corresponding TB and CF sera. Numerous TB patients had elevated alpha 1-antitrypsin, alpha 1-antichymotrypsin, and haptoglobin, but only the alpha 1-antitrypsin population mean was significantly different from normal. Gc-globulin, ceruloplasmin, and beta-lipoprotein were higher and alpha 1-lipoprotein and inter-alpha-trypsin inhibitor lower than normal. All other quantitative serum changes were not statistically significant. Surprisingly, all TB patients belonged to the Gc-1-1 genotype in contrast to the Gc-1-1, Gc-1-2, Gc-2-2 polymorphisms of the other populations. CF homozygote sera revealed statistically significant increases in the acute-phase proteins, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and haptoglobin, while orosomucoid, transferrin, IgA, and IgG tended to be higher than normal. The tendency for higher levels of transferrin indicated possible iron deficiency in some patients. In contrast, prealbumin, alpha 1-lipoprotein, and inter-alpha-trypsin inhibitor were significantly depressed in CF patients. CF heterozygotes shared the decrease of alpha 1-lipoprotein with the patients while exhibiting small but significant depressions of alpha 2-macroglobulin and IgG. Though not statistically significant, lowered concentrations of alpha 1-antitrypsin were evident for the heterozygotes.

Transferrin in foetal and adult mouse tissues: synthesis, storage and secretion

Transferrin is an important growth-promoting serum glycoprotein synthesized chiefly in the liver in adults. The transferrin found in the mouse foetus is thought to be wholly a product of the foetus itself and its synthesis starts at lest as early as the 7th day of gestation. The major sites of synthesis in mouse foetuses are the visceral yolk sac (VYS) and liver (Adamson, 1982). We now report that other murine foetal tissues synthesize readily detectable amounts, namely lung, spleen, spinal cord and rib cage. Very low levels are also synthesized by the brain, muscle and pancreas. We can detect no synthesis of transferrin in late foetal thymus, heart or skin although mid-gestation foetal skin may make a very small amount. No synthesis of transferrin can be detected in adult brain, lung and spleen, but approximately equal rates of synthesis are detected in adult liver and adult ear pinna. Transferrin is accumulated by foetal and adult tissues in widely varying amounts and these have been measured by enzyme-linked immunosorbent assays of extracts. In addition to VYS and liver, high levels of transferrin are found in foetal skin, lung and rib cage with lower amounts in spinal cord, spleen and muscle tissues. Tissues of the 15th day foetus accumulate the highest concentrations of transferrin. A role for the mediation of transferrin in the stimulation of growth and differentiation by interaction tissues is discussed.