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At least 667 records · Page 37Linked to original sources

PubMed2000

Significance of soluble TNF receptor-I in acute-type fulminant hepatitis.

OBJECTIVE: Fulminant hepatitis is associated with apoptosis of hepatocytes, which is mediated via Fas and tumor necrosis factor (TNF) receptors. The clinical significance of apoptotic factors and these receptors was investigated in fulminant hepatitis. METHODS: Serum levels of TNF-alpha, soluble TNF receptor-I and -II, soluble Fas antigen, and Fas ligand were measured. Then, the relationships between these parameters and the severity or prognosis of fulminant hepatitis were studied. RESULTS: Serum levels of TNF-alpha, soluble TNF receptor-I, and soluble TNF receptor-II were increased in acute-type fulminant hepatitis. In particular, soluble TNF receptor-I was significantly higher than in patients with subacute-type fulminant hepatitis, severe acute hepatitis, acute hepatitis, or healthy controls. The soluble TNF receptor-I level continued to increase or remained high in patients who died of acute-type fulminant hepatitis, and eight of nine patients had a level >10 ng/ml. In contrast, the soluble TNF receptor-I level remained <10 ng/ml in survivors. Soluble Fas and soluble Fas ligand levels tended to increase in all types of acute liver disease and were not specific to fulminant hepatitis. CONCLUSION: Our findings suggested that monitoring the soluble TNF receptor-I level may help to assess the prognosis of acute-type fulminant hepatitis and that TNF might be associated with massive hepatic necrosis.

Acute Disease↗

PubMed1999

A mutation that improves soluble recombinant hemoglobin accumulation in Escherichia coli in heme excess.

High-level expression of soluble recombinant human hemoglobin (rHb) in Escherichia coli was obtained with several hemoglobin variants. Under identical conditions, two rHbs containing the Presbyterian mutation (Asn-108-->Lys) in beta-globin accumulated to approximately twofold less soluble globin than rHbs containing the corresponding wild-type beta-globin subunit accumulated. The beta-globin Providence(asp) mutation (Lys-82-->Asp) significantly improved soluble rHb accumulation compared to the wild-type beta-globin subunit and restored soluble accumulation of rHbs containing the Presbyterian mutation to wild-type levels. The Providenceasp substitution introduced a negatively charged residue into the normally cationic 2,3-bisphosphoglycerate binding pocket, potentially reducing the electrostatic repulsion in the absence of the polyanion. The average soluble globin accumulation when there was coexpression of di-alpha-globin and beta-Lys-82-->Asp-globin (rHb9.1) and heme was present in at least a threefold molar excess was 36% +/- 3% of the soluble cell protein in E. coli. The average total accumulation (soluble globin plus insoluble globin) was 56% +/- 7% of the soluble cell protein. Fermentations yielded 6.0 +/- 0. 3 g of soluble rHb9.1 per liter 16 h after induction and 6.4 +/- 0.2 g/liter 24 h after induction. The average total globin yield was 9.4 g/liter 16 h after induction. High-level accumulation of soluble rHb in E. coli depends on culture conditions, the protein sequence, and the molar ratio of the heme cofactor added.

Escherichia coli↗

PubMed2004

Interactions of foot-and-mouth disease virus with soluble bovine alphaVbeta3 and alphaVbeta6 integrins.

At least four members of the integrin family of receptors, alphaVbeta1, alphaVbeta3, alphaVbeta6, and alphaVbeta8, have been identified as receptors for foot-and-mouth disease virus (FMDV) in vitro. Our investigators have recently shown that the efficiency of receptor usage appears to be related to the viral serotype and may be influenced by structural differences on the viral surface (H. Duque and B. Baxt, J. Virol. 77:2500-2511, 2003). To further examine these differences, we generated soluble alphaVbeta3 and alphaVbeta6 integrins. cDNA plasmids encoding the individual complete integrin alphaV, beta3, and beta6 subunits were used to amplify sequences encoding the subunits' signal peptide and ectodomain, resulting in subunits lacking transmembrane and cytoplasmic domains. COS-1 cells were transfected with plasmids encoding the soluble alphaV subunit and either the soluble beta3 or beta6 subunit and labeled with [35S]methionine-cysteine. Complete subunit heterodimeric integrins were secreted into the medium, as determined by radioimmunoprecipitation with specific monoclonal and polyclonal antibodies. For the examination of the integrins' biological activities, stable cell lines producing the soluble integrins were generated in HEK 293A cells. In the presence of divalent cations, soluble alphaVbeta6 bound to representatives of type A or O viruses, immobilized on plastic dishes, and significantly inhibited viral replication, as determined by plaque reduction assays. In contrast, soluble alphaVbeta3 was unable to bind to immobilized virus of either serotype; however, virus bound to the immobilized integrin, suggesting that FMDV binding to alphaVbeta3 is a low-affinity interaction. In addition, soluble alphaVbeta3 did not neutralize virus infectivity. Incubation of soluble alphaVbeta6 with labeled type A12 or O1 resulted in a significant inhibition of virus adsorption to BHK cells, while soluble alphaVbeta3 caused a low (20 to 30%), but consistent, inhibition of virus adsorption. Virus incubated with soluble alphaVbeta6 had a lower sedimentation rate than native virus on sucrose density gradients, but the particles retained all of their structural proteins and still contained bound integrin and, therefore, were not exhibiting characteristics of a picornavirus A particle.

Animals↗

PubMed1975

Effects of calcium solubility on adsorption by rats with induced achlorhydria.

Gastric X-irradiated, achlorhydric rats and sham-operated controls were fed diets containing very soluble calcium chloride or calcium gluconate or slightly soluble calcium carbonate or tricalcium phosphate for 3 weeks. Calcium was absorbed more efficiently by achlorhydric rats from the very soluble salts from the slihtly soluble salts. The control rats absorbed calcium from the very soluble and slightly soluble calcium salts with similar efficiency. Achlorhydric rats fed slightly soluble calcium salts developed weaker bones with a lower mineral content than did those fed very soluble calcium. Apparently, the very soluble dietary calcium offset the impaired calcium absorption of achlorhydric rats. Calcium solubility had no significant effect on the bones of control animals.

Achlorhydria↗

PubMed2004

In silico estimation of DMSO solubility of organic compounds for bioscreening.

Solubility of organic compounds in DMSO is an important issue for commercial and academic organizations handling large compound collections or performing biological screening. In particular, solubility data are critical for the optimization of storage conditions and for the selection of compounds for bioscreening compatible with the assay protocol. Solubility is largely determined by the solvation energy and the crystal disruption energy, and these molecular phenomena should be assessed in structure-solubility correlation studies. The authors summarize our long-term experimental observations and theoretical studies of physicochemical determinants of DMSO solubility of organic substances. They compiled a comprehensive reference database of proprietary data on compound solubility (55,277 compounds with good DMSO solubility and 10,223 compounds with poor DMSO solubility), calculated specific molecular descriptors (topological, electromagnetic, charge, and lipophilicity parameters), and applied an advanced machine-learning approach for training neural networks to address the solubility. Both supervised (feed-forward, back-propagated neural networks) and unsupervised (Kohonen neural networks) learning methods were used. The resulting neural network models were validated by successfully predicting DMSO solubility of compounds in independent test selections.

Dimethyl Sulfoxide↗

PubMed2000

Partial solubility parameters of lactose, mannitol and saccharose using the modified extended Hansen method and evaporation light scattering detection.

The modified extended Hansen method was tested for the first time to determine partial solubility parameters of non-polymeric pharmaceutical excipients. The method was formerly tested with drug molecules, and is based upon a regression analysis of the logarithm of the mole fraction solubility of the solute against the partial solubility parameters of a series of solvents of different chemical classes. Two monosaccharides and one disaccharide (lactose monohydrate, saccharose and mannitol) were chosen. The solubility of these compounds was determined in a series of solvents ranging from nonpolar to polar and covering a wide range of the solubility parameter scale. Sugars do not absorb at the UV-vis region, and the saturated solutions were assayed with a recent chromatographic technique coupled to an evaporative light scattering detector. This technique was suitable to determine the concentration dissolved in most solvents. The modified extended Hansen method provided better results than the original approach. The best model was the four parameter equation, which includes the dispersion delta d, dipolar delta p, acidic delta a and basic delta b partial solubility parameters. The partial solubility parameters obtained, expressed as MPa1/2, were delta d = 17.6, delta p = 28.7, delta h = 19, delta a = 14.5, delta b = 12.4, delta T = 32.8 for lactose, delta d = 16.2, delta p = 24.5, delta h = 14.6, delta a = 8.7, delta b = 12.2, delta T = 32.8 for mannitol and delta d = 17.1, delta p = 18.5, delta h = 13, delta a = 11.3, delta b = 7.6, delta T = 28.4 for saccharose. The high total solubility parameters delta T obtained agree with the polar nature of the sugars. The dispersion parameters delta d are quite similar for the three sugars indicating that the polar delta p and hydrogen bonding parameters (delta h, delta a, delta b) are responsible for the variation in the total solubility parameters delta T obtained, as also found for drugs. The results suggest that the method could be extended to determine the partial solubility parameters of other non-polymeric pharmaceutical excipients.

Chromatography, Liquid↗

PubMed2003

Sugar monomer and oligomer solubility: data and predictions for application to biomass hydrolysis.

Oligomer solubility could potentially play an important role in controlling the rates and yields in the thermochemical hydrolysis of hemicellulose as a pretreatment for subsequent enzymatic conversion of cellulose. However, limited data or models are available to describe the aqueous solubility of sugar monomers and oligomers. In this work, we measured the solubilities of sugars common to many biomass feedstocks in the temperature range of 25-30 degrees C. Then we reviewed solubility models for sugars from the open literature. Finally, we applied models to test their ability to describe this and other data reported in the literature. It was found that the solubility of sugar monomers was not well described by the ideal solubility law or other more complex models. However, with an empirical adjustment to the enthalpy of fusion, the ideal solubility law was able to approximately predict the solubility of cello-oligomers. Based on these results, solubilities for low molecular weight xylo-oligomers are predicted to investigate their possible importance in pretreatment and define further experimental measurements needed to improve our understanding of sugar and oligomer solubility.

Biomass↗

PubMed2005

Soluble adhesion molecules in the pathogenesis of rheumatoid arthritis.

Rheumatoid arthritis is chronic systemic inflammatory disease that is characterized by joint swelling and leukocyte recruitment into synovial tissue. Within the peripheral blood and synovial fluid of patients with rheumatoid arthritis there are many soluble mediators that function together to create an inflammatory environment ultimately responsible for the synovial pannus formation and subsequent joint destruction. One such group of soluble mediators present in the peripheral blood and synovial fluid of rheumatoid arthritic patients are soluble adhesion molecules. Soluble adhesion molecules are commonly formed as the result of cell surface adhesion molecule shedding due to cell stimulation, but may also be the result of de novo synthesis of truncated soluble forms of adhesion molecules. There has been debate over the function of soluble adhesion molecules in the inflammatory process. Soluble adhesion molecules have been shown to both enhance and inhibit different aspects of the inflammatory process. However, the preponderance of research studying rheumatoid arthritis has shown soluble adhesion molecules to be important regulators of leukocyte recruitment into the synovial tissue. This review will focus on the soluble adhesion molecules that have been studied in peripheral blood and synovial fluids of patients with rheumatoid arthritis. The role of different soluble adhesion molecules in the pathogenesis of rheumatoid arthritis will be discussed, as will the effects of common disease modifying anti-rheumatic therapies on their production.

Animals↗

PubMed1991

Soybean protein solubility in potassium hydroxide: an in vitro test of in vivo protein quality.

Experiments were conducted to assess protein solubility in .2% KOH as an indicator of soybean protein quality for chicks and pigs and to assess effects of particle size on protein solubility. As the particle size (micron) of soybean meal (SBM) increased, protein solubility (%) decreased (b = -.0206). In two 9-d chick trials, dehulled SBM (48% CP) was subjected to various autoclaving times and then fed as the sole source of dietary protein to young chicks. Increasing autoclaving times from 0 to 40 min at 120 degrees C resulted in a quadratic decrease in protein solubility. A broken-line model was fitted wherein gain:feed of chicks was plotted as a function of protein solubility. The analysis showed no reduction in feed efficiency with solubilities greater than 59 +/- 1.5% (mean +/- SEM). When solubility was below 59%, however, gain:feed decreased 1.5% for each 1% decrease in protein solubility. The third trial (13 d) was conducted with 7.5-kg pigs fed autoclaved SBM (44% CP) as the primary source of protein. Feed efficiency was significantly decreased when protein solubility was less than 66%. This study showed that protein solubility in KOH was a good index of in vivo soybean protein quality, and that it is important to standardize SBM particle size when applying the KOH assay.

Animal Feed↗

PubMed1999

Production of soluble P-selectin by platelets and endothelial cells.

The distribution of a soluble form of a cell adhesion molecule, P-selectin, in human platelets and cultivated endothelial cells has been studied by enzyme-linked immunosorbent assay (ELISA). The concentration of soluble P-selectin in the blood plasma of healthy donors and patients with abnormal platelet count has also been determined. P-selectin was measured in the Triton X-100 lysate of platelets and endothelial cells (total P-selectin), in the 100,000g supernatant obtained after sedimentation of the membrane fraction from the homogenate of sonicated platelets and endothelial cells (intracellular soluble P-selectin), in the supernatant of activated and nonactivated platelets, and in the culture medium of endothelial cells. A soluble form of P-selectin which did not coprecipitate with the membrane fraction was detected in platelets and accounted for approximately 10% of the total P-selectin. Platelet activation by thrombin, ADP, or a thromboxane A2 analog resulted in the secretion of 30-50% of the intracellular soluble P-selectin. Measurements of P-selectin in endothelial cell culture revealed that endothelium from aorta contained about twofold more P-selectin than endothelium from umbilical vein. Intracellular soluble P-selectin was identified in both types of endothelial cells. In endothelial cells from the umbilical vein this form made up approximately 10% of the total P-selectin. Soluble P-selectin was also detected in the medium of cultivated endothelial cells, where its content correlated with the total cellular P-selectin. Concentration of P-selectin in blood plasma strongly correlated with the platelet count in the blood of healthy donors and patients with thrombocytosis and thrombocytopenia. These data indicate that platelets serve as one of the main source of plasma P-selectin. However, the presence of P-selectin in the plasma of patients with severe thrombocytopenia suggests that endothelium can also be involved in plasma P-selectin production. Thus, in vitro experiments as well as measurements of plasma P-selectin have shown that both platelets and endothelial cells can produce a soluble form of the protein. Platelet-derived soluble P-selectin and plasma P-selectin were shown to react with antibodies against the cytoplasmic domain of P-selectin. These data prove that at least part of soluble P-selectin is produced by synthesis employing special mRNA which lacks the sequence encoding the transmembrane domain, but not by the proteolytic shedding of the extracellular portion of membrane P-selectin.

Antibodies↗

PubMed1992

Lipid solubility of sedative-hypnotic drugs influences hypothermic and hypnotic responses of long-sleep and short-sleep mice.

The anesthetic potency of many agents, including alcohols, barbiturates and other sedative-hypnotic drugs, is influenced by lipid solubility. Previous studies from our laboratory, however, have demonstrated that genetic factors influence this relationship. We have reported that mouse lines selectively bred for differences in duration of ethanol-induced anesthesia, the long-sleep (LS) and short-sleep (SS) mice, differ in sleep-time response to water-soluble, but not lipid-soluble, sedative-hypnotic drugs. The studies described here sought to determine whether this same relationship exists for the hypothermic response produced by 17 sedative-hypnotic drugs in the LS and SS mice. Dose-response and time course relationships for hypothermic actions were determined and were compared with the dose-related anesthetic effects of the drugs. Hypothermic potencies increased along with lipid solubility for both the LS and SS mouse lines, but the rate of change differed for the two mouse lines. LS mice were more responsive to ethanol and other water-soluble drugs whereas the SS were more responsive to lipid-soluble drugs; significant correlations were obtained between lipid solubility (log P-octanol-water partition coefficient) and relative LS-SS responsiveness to both the hypothermic and hypnotic actions of the 17 test drugs. Thus, both hypnotic and hypothermic actions of sedative-hypnotic drugs are correlated with lipid solubility. Possible explanation for these correlations include greater LS central nervous system sensitivity to water-soluble drugs and LS-SS differences in distribution of lipid-soluble drugs.

Animals↗

PubMed1990

T-cell activation in Crohn's disease. Increased levels of soluble interleukin-2 receptor in serum and in supernatants of stimulated peripheral blood mononuclear cells.

Serum levels of soluble interleukin-2 receptor were determined in 29 patients with active and quiescent Crohn's disease. In addition, the ability of peripheral blood mononuclear cells of 23 of these patients to generate soluble interleukin-2 receptor following mitogenic stimulation was studied in vitro. Serum soluble interleukin-2 receptor concentrations of patients with active Crohn's disease (n = 19) were significantly elevated (757 +/- 438 U/ml) compared with levels in patients with inactive disease (n = 10; 412 +/- 120 U/ml) and healthy control individuals (n = 40; 375 +/- 102 U/ml; p less than 0.003 and p less than 0.0005, respectively). Serial determinations of serum soluble interleukin-2 receptor concentration in a follow-up of 11 hospitalized patients treated for highly active disease showed a decrease from 1252 +/- 494 U/ml to 527 +/- 193 U/ml (p less than 0.004) that corresponded to clinical improvement, as assessed by Crohn's disease activity index and a reduction of inflammatory parameters. In vitro phytohemagglutinin stimulation of peripheral blood mononuclear cells derived from patients with Crohn's disease resulted in elevated soluble interleukin-2 receptor production not only in patients with active disease (3987 +/- 2439 U/ml), but also in patients with inactive disease (3297 +/- 2282 U/ml), compared with the amount of soluble interleukin-2 receptor produced by mononuclear cells of healthy individuals (1523 +/- 1152 U/ml; p less than 0.005 and p less than 0.02, respectively). In addition, cultivation of mononuclear cells without mitogen resulted in higher soluble interleukin-2 receptor production in patients with active disease than in patients with inactive disease (p less than 0.02). However, patients suffering from active ulcerative colitis also had significantly increased serum levels of soluble interleukin-2 receptor (1080 +/- 400 U/ml) compared with the levels in patients with chronic disease (455 +/- 140 U/ml; p less than 0.0025). In addition, peripheral blood mononuclear cells derived from patients with ulcerative colitis produced significantly more soluble interleukin-2 receptor upon mitogenic stimulation with phytohemagglutinin (2314 +/- 936 U/ml), than cells from healthy controls (1523 +/- 1152 U/ml; p less than 0.05). The finding of elevated soluble interleukin-2 receptor serum levels in patients with active Crohn's disease and its increased production by mononuclear cells of patients with both active and inactive disease is a further example of an alteration of the immune system in this condition; however, this alteration can also be found in other inflammatory bowel diseases.

Adult↗

PubMed1988

The malignant B cells from B-chronic lymphocytic leukemia patients release TAC-soluble interleukin-2 receptors.

Both membrane (p55) and soluble (p45) forms of TAC-reactive interleukin-2 receptor (IL-2R) are expressed and/or released by activated lymphocytes or monocytes. Previous work has detected increased levels of circulating, TAC-soluble IL-2R (soluble TAC antigen) in the serum of most B-cell chronic lymphocytic leukemia (B-CLL) patients. We detected soluble TAC antigen in B-CLL patients (mean of 3,332 U/mL v 410 for controls). Serum soluble TAC antigen levels increased with stage (mean value of 1,187 U/mL for stage 0 v 2,527 for stage 2 and 5,410 for stages 3 and 4). We next attempted to determine whether the elevated serum levels of soluble TAC antigen in B-CLL patients might result from shedding or secretion of the receptor from the circulating, malignant B cells. Purified, malignant B cells from B-CLL patients were capable of producing easily detectable soluble TAC antigen after 48 hours of in vitro culture (range of 60 to 1,563 U/mL). IL-2R production by CLL B cells was dose dependent in most patients over a concentration of 10 x 10(6) to 60 x 10(6)/mL. In contrast, there was little or no detectable soluble TAC antigen when highly purified T cells from the same patients were cultured. Finally, despite elaboration of soluble IL-2R by CLL B cells, membrane expression of B-cell IL-2R was detected in only six of 11 patients. Thus, the cellular source of the elevated serum IL-2R levels is the malignant CLL B cell. Taken together these data suggest that (a) the malignant CLL B cell is "activated" in terms of release of soluble IL-2R and may serve as a tumor marker in this disease and (b) the elevated levels of circulating IL-2R may be an associated factor in the cellular immunodeficiency noted in B-CLL patients.

B-Lymphocytes↗

PubMed1975

Membrane bound and soluble adenosine triphosphatase of Escherichia coli K 12. Kinetic properties of the basal and trypsin-stimulated activities.

Basal and trypsin-stimulated adenosine triphosphatase activities of Escherichia coli K 12 have been characterized at pH 7.5 in the membrane-bound state and in a soluble form of the enzyme. The saturation curve for Mg2+/ATP = 1/2 was hyperbolic with the membrane-bound enzyme and sigmoidal with the soluble enzyme. Trypsin did not modify the shape of the curves. The kinetic parameters were for the membrane-bound ATPase: apparent Km = 2.5 mM, Vmax (minus trypsin) = 1.6 mumol-min-1-mg protein-1, Vmax (plus trypsin) = 2.44 mumol-min-1-mg protein-1; for the soluble ATPase: [S0.5] = 1.2 mM, Vmax (-trypsin) = 4 mumol-min-1-mg protein-1; Vmax (+ trypsin) = 6.6 mumol-min-1-mg protein-1. Hill plot analysis showed a single slope for the membrane-bound ATPase (n = 0.92) but two slopes were obtained for the soluble enzyme (n = 0.98 and 1.87). It may suggest the existence of an initial positive cooperativity at low substrate concentrations followed by a lack of cooperativity at high ATP concentrations. Excess of free ATP and Mg2+ inhibited the ATPase but excess of Mg/ATP (1/2) did not. Saturation for ATP at constant Mg2+ concentration (4 mM) showed two sites (groups) with different Kms: at low ATP the values were 0.38 and 1.4 mM for the membrane-bound and soluble enzyme; at high ATP concentrations they were 17 and 20 mM, respectively. Mg2+ saturation at constant ATP (8 mM) revealed michealian kinetics for the membrane-bound ATPase and sigmoid one for the protein in soluble state. When the ATPase was assayed in presence of trypsin we obtained higher Km values for Mg2+. These results might suggest that trypsin stimulates E. coli ATPase by acting on some site(s) involved in Mg2+ binding. Adenosine diphosphate and inorganic phosphate (Pi) act as competitive inhibitors of Escherichia coli ATPase. The Ki values for Pi were 1.6 +/- 0.1 mM for the membrane-bound ATPase and 1.3 +/- 0.1 mM for the enzyme in soluble form, the Ki values for ADP being 1.7 mM and 0.75 mM for the membrane-bound and soluble ATPase, respectively. Hill plots of the activity of the soluble enzyme in presence of ADP showed that ADP decreased the interaction coefficient at ATP concentrations below its Km value. Trypsin did not modify the mechanism of inhibition or the inhibition constants. Dicyclohexylcarbodiimide (0.4 mM) inhibited the membrane-bound enzyme by 60-70% but concentrations 100 times higher did not affect the residual activity nor the soluble ATPase. This inhibition was independent of trypsin. Sodium azide (20 muM) inhibited both states of E. coli ATPase by 50%. Concentrations 25-fold higher were required for complete inhibition. Ouabain, atebrin and oligomycin did not affect the bacterial ATPase.

Adenosine Diphosphate↗

PubMed1996

Soluble forms of CD44 and CD54 (ICAM-1) cellular adhesion molecules are released by human prostatic cancer cell lines.

We have identified that human prostatic cancer cell lines DU145, PC3, ND1, ALVA31 and JCA1 released soluble CD44 molecules and DU145, PC3 and ND1 released soluble CD54. Both soluble and surface CD44 were not found in LNCaP, and both forms of CD54 were not expressed in LNCaP and JCA1. CD54 was found to be highly expressed on cell surface in ALVA31, but these cells did not release soluble CD54. Expression of both cell surface and soluble forms were examined after treatment of cells with IFN-gamma, TGF-beta 1, or culturing in serum-free media. The concentration of soluble CD54 in supernatants changed to small extent after treatment with TGF-beta 1 and increased after treatment with IFN-gamma or in serum-free media. Cell surface expression of CD54 however, changed only minimally after treatment. The levels of cell surface and soluble CD44 also changed minimally after treatment with IFN-gamma and TGF-beta 1 but decreased in serum-free media and this was accompanied by marked elevation of soluble CD44 in supernatants. These data indicate that soluble CD44 might be released from cell surface by shedding whereas alternative splicing is the most likely mechanism of soluble CD54 release.

Cell Adhesion Molecules↗

PubMed1994

Levels of soluble interleukin-2 receptor-alpha are elevated in serum and ascitic fluid from epithelial ovarian cancer patients.

OBJECTIVE: The purpose of the study was to determine whether ovarian cancer patients have activated lymphocytes as indicated by the presence of soluble interleukin-2 receptor-alpha and to compare soluble interleukin-2 receptor-alpha with other markers in ovarian cancer. STUDY DESIGN: Ascites and serum from patients with advanced active ovarian cancer was tested for the presence of elevated levels of soluble interleukin-2 receptor-alpha and compared with normal controls. Levels of soluble interleukin-2 receptor-alpha were also compared with levels of CA 125 and macrophage colony-stimulating factor in the same patients, to evaluate the correlation between different markers. RESULTS: Elevated levels of soluble interleukin-2 receptor-alpha were detected in 86 of 86 (100%) ascites samples and 67 of 85 (79%) serum samples from patients with advanced epithelial ovarian cancer. In contrast, only 12 of 25 (48%) benign ascites samples and one of 88 (1%) serum samples from controls had elevated levels. There was no obvious correlation between levels of soluble interleukin-2 receptor-alpha and levels of CA 125; however, levels of soluble interleukin-2 receptor-alpha did correlate with levels of macrophage colony-stimulating factor. Concurrent measurement of serum-soluble interleukin-2 alpha and CA 125 levels detected 100% of patients with epithelial ovarian cancer. CONCLUSION: The detection of elevated levels of soluble interleukin-2 receptor-alpha in serum and ascites indicates the presence of activated lymphocytes in patients with epithelial ovarian cancer. Ascites and serum levels of soluble interleukin-2 receptor-alpha are elevated in patients with advanced ovarian cancer and warrant assessment as a potential complementary marker to CA 125 for early detection of ovarian cancer and management of patients with advanced ovarian cancer.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1999

Soluble thrombomodulin as a predictor of incident coronary heart disease and symptomless carotid artery atherosclerosis in the Atherosclerosis Risk in Communities (ARIC) Study: a case-cohort study.

BACKGROUND: Small amounts of soluble thrombomodulin in plasma are thought to reflect endothelial damage. In a case-cohort study, we examined whether soluble thrombomodulin is a predictor of incident coronary heart disease and carotid artery atherosclerosis. METHODS: The study population consisted of 14,170 black and white participants from the Atherosclerosis Risk in Communities (ARIC) study, who did not have cardiovascular disease at the start of the study and who we followed up for 6 years. After appropriate exclusions, we analysed 258 cases of incident coronary heart disease and 449 cases of carotid atherosclerosis. A stratified random sample of 753 individuals from the ARIC cohort was used as the comparison group. We used EIA to measure soluble thrombomodulin in plasma samples from both groups. For the analysis, we used quintiles of soluble thrombomodulin concentrations (< 24.7, 24.8-30.6, 30.7-40.2, 40.3-55.2, and > or = 55.3 ng/mL). FINDINGS: Soluble thrombomodulin showed a strong, graded, inverse association with incident coronary heart disease (p=0.005). The adjusted rate ratio of the highest quintile of soluble thrombomodulin compared with the lowest quintile was 0.29 (95% CI 0.15-0.57). The association with carotid atherosclerosis, however, tended to be positive, especially among white participants (odds ratio 2.94 [1.15-7.51] for highest vs lowest quintile). The relation of soluble thrombomodulin to incident coronary heart disease and carotid atherosclerosis was dependent on factor VIII coagulant activity (p=0.06 and 0.003, respectively). INTERPRETATION: The prospective association of soluble thrombomodulin with incident coronary heart disease differs from its cross-sectional association with carotid atherosclerosis. In healthy people, plasma concentrations of soluble thrombomodulin may reflect endothelial expression of thrombomodulin. High concentration of soluble thrombomodulin may be associated with decreased risk of coronary heart disease.

Analysis of Variance↗

PubMed1996

Serum levels of soluble interleukin-2 receptor in patients with perennial allergic rhinitis before and after immunotherapy.

BACKGROUND: Interleukin-2 receptor (IL-2R) exists in soluble form in sera, and the rate of release of the soluble form of IL-2R (soluble IL-2R) reflects T cell activation in vivo. Since T lymphocytes play a central role in respiratory allergic disorders, the measurement of serum levels of soluble IL-2R may be useful in analyzing the disease state of allergic disorders. OBJECTIVE: To investigate the serum concentrations of soluble IL-2R in 48 patients with perennial allergic rhinitis and 14 nonatopic healthy controls, with special reference to the possible changes following long-term immunotherapy. METHODS: This retrospective study included 48 patients who had had variable periods of long-term immunotherapy with Dermatophagoides farinae extracts. The duration of immunotherapy ranged from 5 to 15 years. Serum samples were collected twice from each patient, before the initiation of immunotherapy and at the time of clinical assessment of immunotherapy. All the serum samples were simultaneously used for determination of soluble IL-2R concentrations, by the use of an enzyme-linked immunosorbent assay. To serve as controls, 14 nonallergic subjects of the same age range and sex were chosen. RESULTS: Patients with allergic rhinitis before immunotherapy had significantly higher serum levels of soluble IL-2R than nonatopic subjects. Elevated serum levels of soluble IL-2R decreased significantly following immunotherapy and the serum levels of soluble IL-2R in patients with allergic rhinitis after immunotherapy were not statistically different from those of nonatopic subjects. In addition, the percent decrease in serum soluble IL-2R correlated significantly with the duration of immunotherapy. CONCLUSIONS: Hyperactivity of helper T cells of atopic patients is altered after long-term immunotherapy, and such immunoregulatory changes could be theoretically involved in the mechanisms of immunotherapy.

Adolescent↗