PubMed Health⌕ Search

Biomedical subjects

E Lien

Publications and source records attributed to E Lien.

At least 55 records · Page 3Linked to original sources
PubMed1996

Concomitant expression of hepatocyte growth factor/scatter factor and the receptor c-MET in human myeloma cell lines.

Myeloma cell line supernatants were screened for their ability to inhibit the activity of transforming growth factor-beta (TGFbeta) in the mink lung cell (Mv-1-Lu) bioassay. Supernatant from the human myeloma cell line JJN-3 contained potent TGFbeta antagonistic activity. This activity was isolated and found to be associated with a 72-78-kDa glycoprotein. Specific polyclonal and monoclonal antibodies were generated toward the 72-78-kDa protein, and these antibodies precipitated the TGFbeta inhibitory activity from JJN-3 supernatant. Upon amino acid sequencing the protein appeared to be identical to hepatocyte growth factor (HGF), and some of the generated antibodies directly blocked the action of recombinant HGF in various assays. By HGF-specific polymerase chain reaction we demonstrated that HGF mRNA was expressed in five out of five tested myeloma cell lines. The level of HGF protein in supernatants showed great variation from >500 ng/ml in JJN-3 supernatant to a few ng/ml in the supernatants from other myeloma cell lines. The same five cell lines were also screened for expression the HGF receptor c-MET. Four of them expressed the receptor as shown by reverse transcriptase-polymerase chain reaction and Western blot. The receptor was shown to be constitutively phosphorylated in the human myeloma cell line JJN-3. This receptor could be dephosphorylated by anti-HGF antibodies, indicating the existence of an autocrine HGF loop in this cell line. We propose that HGF/c-MET may play a role in multiple myeloma.

Animals↗
PubMed1996

Persistent activation of the tumor necrosis factor system in a subgroup of patients with common variable immunodeficiency--possible immunologic and clinical consequences.

In patients with common variable immunodeficiency (CVI), we have previously defined a subgroup of patients (CVIHyper) characterized by decreased numbers of CD4+ lymphocytes in peripheral blood, splenomegaly, and persistent immune activation in vivo, particularly of monocytes/macrophages. To further characterize this hyperactivity, parameters of activation of the tumor necrosis factor (TNF) system (TNF alpha and soluble TNF receptors [sTNFRs]) were measured in 24 patients with CVI and 20 healthy controls. Patients with CVI had significantly higher serum levels of TNF alpha and both types of sTNFRs, with the highest levels in the CVIHyper subgroup. In vitro, peripheral blood mononuclear cells (PBMC) and purified monocytes from CVIHyper patients spontaneously released significantly higher levels, and, after lipopolysaccharide (LPS) stimulation, significantly lower levels of TNF alpha and soluble p75-TNFR than cells from both other CVI patients and healthy controls. CVIHyper patients also had significantly higher TNF alpha:sTNFRs ratios in both serum and in unstimulated PMBC supernatants. The present study demonstrates persistent in vivo activation of the TNF system in CVI, particularly in the CVIHyper subgroup. This activation may contribute to the pathogenesis of both clinical and immunologic manifestations in CVI.

Adult↗
PubMed1996

Relationship between dietary supply of long-chain fatty acids and membrane composition of long- and very long chain essential fatty acids in developing rat photoreceptors.

The present study was designed to determine if dietary supply of long-chain fatty acid (LCFA, C20:4n-6, and/or C22:6n-3), reflecting levels that might be incorporated into infant formulas, influences the fatty acid composition of the visual cell membrane. The rod outer segment (ROS) of the retina was analyzed from rats fed diets varying in the ratio of 18:2n-6 to 18:3n-3 with or without 20:4n-6 [arachidonic acid (AA)] and 22:6n-3 (docosahexaenoic acid) from birth to six weeks of age. The level of very long chain fatty acids (VLCFA, C24-C36) was identified using gas chromatography and gas chromatography-mass spectrometry. In the ROS, the highest relative percent of AA was attained in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) of animals fed 1% AA diet, whereas feeding 0.7% docosahexaenoic acid (DHA) diet significantly increased the DHA level in PC, phosphatidylserine, and phosphatidylinositol compared to feeding diets containing AA. VLCFA of n-6 and n-3 up to C36 were found in PC, with the most abundant fatty acids being C32 and C34. In PC, phosphatidylserine and PE, the n-6 tetraenoic VLCFA level was highly increased in animals fed 1% AA compared to other dietary groups. This study suggests that dietary fat containing small amounts of AA or DHA is an important factor influencing membrane fatty acid composition of the visual cell during development.

Animals↗
PubMed1996

Disseminated Mycobacterium avium complex infection in AIDS: immunopathogenic significance of an activated tumor necrosis factor system and depressed serum levels of 1,25 dihydroxyvitamin D.

Disseminated Mycobacterium avium complex (MAC) infection is associated with considerable morbidity and mortality in patients with AIDS. Because both tumor necrosis factor-alpha (TNF-alpha) and 1,25-dihydroxyvitamin D3 (1,25D) may be involved in the normal control of MAC infection, these parameters were studied in AIDS patients with disseminated MAC infection. Of 53 AIDS patients studied, 24 had no clinical events, 11 had disseminated MAC infection, and 18 had other clinical events. Patients with disseminated MAC infection had significantly higher serum levels of both TNF-alpha and soluble TNF receptors compared with other AIDS patients; almost half of the MAC-infected patients had TNF bioactivity in serum. MAC-infected patients also had severely decreased serum 1,25D levels compared with all other AIDS patients. The activation of the TNF system was significantly correlated with the degree of 1,25D deficiency. These findings may reflect interaction between vitamin D and the TNF system in the pathophysiology of disseminated MAC infection in AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1996

Detection of soluble receptors for tumor necrosis factor, interleukin-2 and interleukin-6 in retroplacental serum from normal pregnant women.

Soluble cytokine receptors (R) may regulate the activities of the cytokines present. We have studied the occurrence of soluble receptors for the cytokines tumor necrosis factor (TNF), interleukin-2 (IL-2) and interleukin-6 (IL-6) in normal pregnant women. Levels of TNFR and IL-2R were higher in retroplacental serum (RPS) than in the corresponding peripheral serum (PS) samples. TNFR, but neither IL-2R nor IL-6R, concentrations in PS from pregnant women were elevated compared to that in nonpregnant women. RPS inhibited TNF-mediated cytotoxicity, with the inhibitory effect being reduced after the removal of 55 kD TNFR from RPS. Our data reveal that soluble cytokine receptors are present in RPS and may contribute to the adjustment of intrauterine cytokine activities during pregnancy.

Antigens, CD↗
PubMed1995

Polymorphonuclear granulocytes enhance lipopolysaccharide-induced soluble p75 tumor necrosis factor receptor release from mononuclear cells.

Lipopolysaccharide (LPS), a part of the Gram-negative bacteria cell wall, is a potent inducer of tumor necrosis factor (TNF). TNF is an important mediator in Gram-negative infections such as meningococcal septic shock, but its harmful action can be prevented by the natural occurring soluble (s) TNF receptors (sTNFR) sp55 and sp75. In this study, the effect of LPS on release of sTNFR was investigated. First, we found a selective increase in human whole-blood sp75 TNFR levels following LPS stimulation, accompanied by no increase in sp55. Separating the different blood cell populations, mononuclear cells (PBMC) selectively released sp75 upon LPS stimulation, while LPS induced a minor increase in sp75 release from polymorphonuclear granulocytes. Interestingly, in co-cultures of PBMC and granulocytes, the release of LPS-induced sp75 TNFR was enhanced. Second, adherent monocytes were also found to selectively release sp75 TNFR upon LPS stimulation, where Neisseria meningitidis LPS was found to be 100-1000 times more potent in inducing sp75 release than Escherichia coli LPS. Using flow cytometry, the monocyte membrane distribution of both TNFR were found to be increased after LPS stimulation. Third, human umbilical vein endothelial cells selectively released sp55 TNFR after stimulation with LPS. We conclude that mononuclear and endothelial cells might be the main sources of soluble p75 and p55 TNFR, respectively, observed in Gram-negative sepsis, although these receptors are released in vivo more rapidly than they are in vitro.

Antigens, CD↗
PubMed1994

Increased levels of cytokines and cytokine activity modifiers in normal pregnancy.

Accumulating evidence suggests that cytokines are major participants in human reproduction. Cytokines may have beneficial or negative influence on pregnancy outcome, depending on the cytokine level present. Thus, successful reproduction appears to depend on a tight regulation of cytokine activities. The present study raised the question whether normal pregnancy is associated with an activation of native cytokine buffer mechanisms. Soluble interleukin 6 receptors (IL-6Rs) and soluble interleukin 1 receptor antagonists (IL-1RAs) may modify the activity of IL-6 and IL-1, respectively. The production of soluble IL-6R and IL-1RA in pregnancy was studied by assessing the IL-6R and IL-1RA concentrations in serum samples from healthy pregnant women at different gestational ages. At delivery, both maternal and umbilical blood was obtained. Concentrations of IL-6 and IL-1 in the samples were determined to study the influence of cytokines on the activity level of the corresponding buffer mechanism. Serum levels of both IL-6R and IL-1RA were increased in pregnant women, as were levels of IL-6 and IL-1. Cytokine levels did not demonstrate a significant correlation with the concentration of the corresponding activity modifier. IL-1RA and IL-6 increased with gestational age and with labor activity. A significant correlation was observed between the levels of IL-6 and IL-1RA.

Female↗
PubMed1994

Serum levels of tumor necrosis factor-alpha (TNF alpha) and soluble TNF receptors in human immunodeficiency virus type 1 infection--correlations to clinical, immunologic, and virologic parameters.

Two EIAs (Medgenix and Quantikine) and a bioassay were used to measure tumor necrosis factor-alpha (TNF alpha) in serum samples from 73 human immunodeficiency virus type 1 (HIV-1)-seropositive patients and in samples from 2 control groups. All clinical groups of HIV-1-infected patients, regardless of concurrent illness, had significantly elevated levels of both types of soluble TNF receptors (sTNFRs) and immunoreactive TNF alpha (Medgenix EIA), with the highest concentrations among the AIDS patients. These TNF parameters were significantly correlated with reduced CD4+ lymphocyte counts. Only a few HIV-1-infected patients had detectable TNF alpha levels measured by the Quantikine EIA. TNF alpha bioactivity was significantly raised only in the AIDS group. Serially measured sTNFRs, expressed as sTNFR slopes, were significantly associated with survival in the patient group. The raised levels of immunoreactive TNF alpha and sTNFRs strongly indicate activation of the TNF alpha system during HIV-1 infection. Levels increase with disease progression and degree of immunodeficiency; thus, serially measured sTNFRs may give useful prognostic information in HIV-1 infection.

Adult↗
PubMed1994

Tumor necrosis factor-alpha inhibits stem cell factor-induced proliferation of human bone marrow progenitor cells in vitro. Role of p55 and p75 tumor necrosis factor receptors.

Stem cell factor (SCF), a key regulator of hematopoiesis, potently synergizes with a number of hematopoietic growth factors. However, little is known about growth factors capable of inhibiting the actions of SCF. TNF-alpha has been shown to act as a bidirectional regulator of myeloid cell proliferation and differentiation. This study was designed to examine interactions between TNF-alpha and SCF. Here, we demonstrate that TNF-alpha potently and directly inhibits SCF-stimulated proliferation of CD34+ hematopoietic progenitor cells. Furthermore, TNF-alpha blocked all colony formation stimulated by SCF in combination with granulocyte colony-stimulating factor (CSF) or CSF-1. The synergistic effect of SCF observed in combination with GM-CSF or IL-3 was also inhibited by TNF-alpha, resulting in colony numbers similar to those obtained in the absence of SCF. These effects of TNF-alpha were mediated through the p55 TNF receptor, whereas little or no inhibition was signaled through the p75 TNF receptor. Finally, TNF-alpha downregulated c-kit cell-surface expression on CD34+ bone marrow cells, and this was predominantly a p55 TNF receptor-mediated event as well.

Adult↗
PubMed1994

Distinct and direct synergistic effects of IL-1 and IL-6 on proliferation and differentiation of primitive murine hematopoietic progenitor cells in vitro.

While interleukin-1 (IL-1) and IL-6 have been demonstrated to synergize with colony-stimulating factors (CSFs) and stem cell factor (SCF) to stimulate myeloid colony formation of primitive hematopoietic progenitor cells, it has not yet been established whether these effects are directly mediated. In the present study, direct effects of IL-1 and IL-6 were examined on primitive Lin-Sca-1+ murine bone-marrow progenitor cells that were cultured and plated individually. IL-1 and IL-6 showed not only overlapping, but also distinct, patterns of direct synergy. While IL-1 or IL-6 had no proliferative effects as single growth factors, IL-1, in combination with granulocyte-macrophage CSF (GM-CSF), IL-3, CSF-1, and SCF, but not granulocyte-CSF (G-CSF), enhanced the cloning frequency of Lin-Sca-1+ progenitors three- to five-fold, whereas IL-6 increased the cloning frequency in response to all four CSFs and SCF two- to seven-fold. In all cases, the size of the colonies observed were increased as well. Furthermore, the combined action of IL-1 and IL-6 resulted in additive or synergistic enhancement of CSF- and SCF-stimulated colony formation of Lin-Sca-1+ high proliferative potential colony-forming cells (HPP-CFCs). Finally, IL-6, but not IL-1, enhanced the number of immature blast cells observed in CSF- and SCF-stimulated cultures.

Animals↗
PubMed1993

The release of soluble p55 TNF receptor from U937 cells studied by a new p55 immunoassay.

A highly specific and sensitive immunoassay for soluble p55 tumor necrosis factor receptor (TNFR) has been established. The immunoassay was based on a newly developed monoclonal antibody (IV4E) recognizing a non-TNF-binding site of the p55 TNFR. The IV4E antibody immunoprecipitated a 55 kDa TNF binding protein from HL-60 cells. No binding of IV4E to the p75 TNFR could be detected. Bound TNFR to IV4E was detected with digoxigenin (DIG) labeled TNF. This assay could detect down to 300 pg/ml of soluble p55, which represents an 8-10-fold increase in sensitivity compared to earlier developed immunoassays. The assay was specific for soluble p55 TNFR present in serum and cell culture supernatants, since addition of excess unlabeled TNF together with DIG labeled TNF inhibited the signal. TNF concentrations up to 10 ng/ml in the TNFR sample did not affect the assay, indicating that TNFRs can be measured in samples containing TNF. The new immunoassay was used to study the mechanisms underlying the release of soluble p55 TNFR from U937 cells stimulated with TPA. The TPA induced release of soluble p55 TNFR from U937 cells occurred in two phases. First, a rapid increase of soluble p55 was observed after the addition of TPA. Later, the release of p55 occurred at a slower rate, and this release was inhibited by known inhibitors of protein synthesis and intracellular transport. Addition of TPA increased the p55 mRNA expression in U937 cells. The results suggest that TPA induces both release and new synthesis of p55 in U937 cells.

Animals↗
PubMed1993

High concentrations of the soluble p55 tumour necrosis factor receptor in human seminal plasma.

Soluble TNFRs (tumour necrosis factor receptors) inhibit in-vivo and in-vitro bioactivities of TNF, and thus the secretion of soluble TNFRs could be a physiological principle to attenuate the bioactivities of TNF. Two types of TNFR have been identified and both forms can be released from cells. In this study, soluble TNFRs in seminal plasma from three groups of men were analysed: from men with normal semen quality (n = 32), with reduced semen quality (n = 7) and vasectomized men (n = 3). Sensitive and specific enzyme-linked immunosorbent assays were utilized to detect soluble TNFRs in seminal plasma, based on capture antibodies directed against non-TNF-binding sites of the TNFRs and digoxigenin (DIG)-labelled TNF. The mean +/- standard deviation levels of p55 TNFR were 56.4 +/- 20, 64.4 +/- 17 and 45.4 +/- 5 ng/ml in the three groups, respectively. The concentration of p75 TNFR was < 1 ng/ml in all groups. The results suggest an exclusive existence of high amounts of the soluble p55 TNFR in seminal plasma. Seminal plasma from vasectomized men contained p55 TNFR at approximately the same levels as the specimen from the two other groups, indicating that the source of p55 TNFR is not the testis but rather some tissue more distal in the male genital tract, such as the prostate or the seminal vesicles. The soluble p55 TNFR was purified from human seminal plasma, using affinity and gel filtration chromatography. Further characterization of the purified p55 revealed a protein with a molecular weight of approximately 22 kDa, both under reducing and non-reducing conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Affinity↗
PubMed1993

Increased levels of soluble tumor necrosis factor-alpha receptors in serum from pregnant women and in serum and urine samples from newborns.

Secretion of soluble cytokine receptors has been suggested as a mechanism of regulating cytokine activity in vivo. In this study, the presence of soluble receptors for tumor necrosis factor-alpha (TNF-alpha) in serum samples from pregnant women and newborn babies was examined by using TNF-alpha receptor-specific immunoassays. Serum from pregnant women contained the 55-kD TNF-alpha receptor p55 [6.4 micrograms/L, interquartile range, i.e. the difference between the 25th and 75th percentile, (IQR) 7.2 micrograms/L], whereas p55 was not detected in control sera from nonpregnant, fertile women. The levels of p55 were also elevated in serum from newborns (3.2 micrograms/L, IQR 0.7 micrograms/L). Furthermore, first-voided urine from newborns contained high levels of p55 (44.6 micrograms/L, IQR 96.6 micrograms/L). The concentration of p55 in the neonatal period was significantly higher than that of children later in childhood (p < 0.05). The concentration of p55 was 7.3 micrograms/L, IQR 13.8 micrograms/L, in urine samples from a group of preschool children (1 mo < age < 5 y) and 6.9 micrograms/L, IQR 2.9 micrograms/L, in urine samples from children in a higher age group (5 y < age < 10 y). The concentration of the 75-kD TNF-alpha receptor in urine did not differ significantly between the different age groups studied. The elevated p55 serum levels of pregnant women and neonates are suggestive of a pregnancy-associated release of soluble receptors. The high concentration of p55 in neonatal urine may reflect a postpartum elimination of soluble receptors shed during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1992

p55 and p75 tumor necrosis factor receptors in patients with chronic lymphocytic leukemia.

We studied the expression of the two tumor necrosis factor (TNF) receptors, p55 and p75, on B cells from patients with chronic lymphocytic leukemia (CLL), and the presence of soluble TNF receptors in serum. Expression of membrane-associated receptors was quantified by double labeling of peripheral blood mononuclear cells (PBMC) with monoclonal antibodies against CD19 and p55/p75 TNF receptors and flow cytometry. A high fraction of the CD19+ cells expressed the p55 receptor (44% +/- 34% [SD]) and p75 receptor (61% +/- 31%). In healthy controls, 0% to 1% of the CD19+ cells expressed the p55 receptor and 0% to 10% expressed the p75 receptor. Incubation of CD19+ cells with 10 ng/mL of TNF increased the incorporation of thymidine in 11 patients tested, and this was decreased to 65% (P < .05) by antibodies to the p55 receptor or the p75 receptor, and to 35% +/- 7% (P < .001) when both antibodies were combined. With an enzyme-linked immunoassay, we measured soluble TNF receptors in serum from CLL patients. The mean level of p55 receptors was increased to 12.9 +/- 8.9 ng/mL (P < .000001 v normal). The mean level of p75 receptors was increased to 13 +/- 24 ng/mL (P = .01 v normal). The membrane expression of the two receptors was positively correlated (r +/- 97, P < .01); however, there was no correlation between membrane expression and serum concentration of either receptor. Autologous serum containing high levels of soluble TNF receptors inhibited TNF-induced proliferation of CD19+ cells. In conclusion, we have demonstrated that neoplastic cells from patients with CLL have increased expression of p55 and p75 TNF receptors, and that both receptors mediate signal to proliferation. Furthermore, serum from CLL patients has elevated levels of soluble TNF receptors, which may counteract the proliferative effect of TNF.

Antibodies, Monoclonal↗
PubMed1992

Addition of long-chain polyunsaturated fatty acids to formula for very low birth weight infants.

Thirty-four premature infants who were appropriate for gestational age and weighing less than 1500 g at birth were fed "preemie" SMA-24 formula, "preemie" SMA-24 formula manufactured to contain C20 and C22 omega 6 and omega 3 fatty acids (LCPE-SMA), or expressed milk (EBM). Blood samples were drawn from a small arm vein during the first week of life and after 28 days of feeding. The fatty acid content of plasma phospholipids was determined. Infants fed SMA-24 had a high content of 18:2 omega 6 in plasma phospholipids. Feeding LCPE-SMA normalized plasma phospholipid levels of C20 and C22 omega 6 and omega 3 fatty acids to be similar to levels of C20 and C22 omega 6 and omega 3 fatty acids found in infants fed EBM, and significantly higher than characteristic levels for infants fed SMA-24. Feeding LCPE-SMA or EBM results in a balanced incorporation of C20 and C22 omega 6 and omega 3 fatty acids into phospholipids derived from the liver or perhaps the small intestine.

Fatty Acids↗
PubMed1992

Feeding preterm infants a formula containing C20 and C22 fatty acids simulates plasma phospholipid fatty acid composition of infants fed human milk.

Thirty-four premature infants weighing less than 1500 grams at birth were fed preterm formula (formula), preterm infant formula manufactured to contain a balance of C20 and C22 omega 6 and omega 3 fatty acids within the range characteristic of human milk (LCPE-formula) or their mothers' expressed breast milk (EBM). Blood samples were obtained during the first week of life and after 28 days of feeding to determine the effect of feeding C20 and C22 omega 6 and omega 3 fatty acids on plasma lipids. Fatty acid analyses of red blood cell phospholipids indicated few differences between dietary treatment and age. Fatty acid content of plasma cholesterol esters indicated a high plasma cholesterol linoleate level for infants fed formula and a reduced content of C20 and C22 omega 6 and omega 3 fatty acids. For infants fed the modified formula (LCPE-formula) the levels of 20:4 omega 6, 20:5 omega 3 and 22:6 omega 3 were higher than observed for the formula group and similar to those observed for infants fed EBM. By the fifth week of life, feeding the modified formula resulted in plasma phospholipid levels of C20 and C22 omega 6 and omega 3 fatty acids similar to levels of C20 and C22 omega 6 and omega 3 fatty acids found in infants fed EBM and significantly higher than levels characteristic of infants fed formula. It is concluded that infants fed LCPE-formula illustrate an overall balance between C20 and C22 omega 6 to omega 3 fatty acids in the plasma similar to that characteristic of infants fed human milk.

Fatty Acids↗
PubMed1987

Subclinical left ventricular abnormalities in young subjects with long-term type 1 diabetes mellitus detected by digitized M-mode echocardiography.

Noninvasive studies in patients with type 1 diabetes mellitus suggest subclinical left ventricular (LV) impairment, but the studies differ with regard to methods, patient selection and results. Thus, digitized M-mode echocardiograms were recorded in 24 persons younger than 50 years with long-term (more than 12 years) type 1 diabetes but without overt heart disease and in 28 control subjects. To improve accuracy, measurements were adjusted for body surface area, LV size and the influence of heart rate, as appropriate. Diabetics had a higher heart rate and systolic and diastolic blood pressure than control subjects. LV end-diastolic and stroke dimensions were smaller, duration of systole longer and preejection period/LV ejection time ratio higher than in control subjects, whereas fractional shortening and peak shortening rate were similar. In diabetics, diastole was shorter, peak filling rate was lower and the rapid filling period was prolonged, while percent filling during the rapid filling period and atrial contribution to filling were higher. Thus, in a well defined study population of relatively young persons with long-term type 1 diabetes, subclinical LV systolic and diastolic dysfunction were found. The diastolic abnormalities suggest reduced LV compliance, while those in systole may be secondary to an increased afterload or decreased myocardial contractility.

Adult↗