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PubMed1994

Serum-soluble interleukin-2 receptor concentrations in patients with gastric cancer.

BACKGROUND: Serum concentrations of soluble interleukin-2 receptor (IL-2R) were found to be high in patients with autoimmune diseases, lung cancer, malignant lymphoma, tuberculosis, and other diseases. Serum-soluble IL-2R was evaluated as a tumor maker in patients with gastric cancer. METHODS: Preoperative concentrations of serum-soluble IL-2R were examined in 40 patients with gastric cancer. The authors investigated the correlations of serum-soluble IL-2R concentrations with various characteristics of this cancer (disease stage, gross appearance, depth of the tumor, lymph node metastasis, liver metastasis, peritoneal metastasis, histopathologic grade, serum carcinoembryonic antigen (CEA), alpha-fetoprotein (alpha-FTP), carbohydrate antigen 19-9 (CA19-9), and immunosuppressive acidic protein (IAP). Serum soluble IL-2R concentrations were measured with an enzyme-linked immunosorbent assay. RESULTS: Levels of serum-soluble IL-2R in patients with gastric cancer were significantly higher than those of normal control subjects. Serum concentrations of IL-2R in patients with lymph node metastasis were also significantly higher than those of patients without lymph node metastasis. There were no significant differences in histopathologic findings (grade, lymphatic invasion, venous invasion). Moreover, serum concentrations of soluble IL-2R in patients who were IAP positive were significantly higher than those who were IAP negative. CONCLUSIONS: Preoperative serum-soluble IL-2R concentrations in patients with gastric cancer reflect the occurrence of regional lymph node metastases. Preoperative evaluation of serum soluble IL-2R concentrations may be a valuable parameter of indicating the probability of lymph node metastasis preoperatively.

Aged↗

PubMed1994

Two inhibitors of pro-inflammatory cytokine release, interleukin-10 and interleukin-4, have contrasting effects on release of soluble p75 tumor necrosis factor receptor by cultured monocytes.

The biological activity of the pro-inflammatory cytokine, tumor necrosis factor (TNF)-alpha depends on the level of TNF-alpha itself, the expression of the p55 and p75 cell surface receptors for TNF on target cells and the concentrations of the natural inhibitors of TNF-alpha, the soluble p55 and p75 TNF receptors (TNF-R). Interleukin (IL)-10 and IL-4 are known to inhibit TNF-alpha production by monocytes. We, therefore, investigated the effects of IL-10 and IL-4 on the cell surface expression and release of TNF-R by human monocytes to determine whether these cytokines also indirectly modulated the biological activity of TNF-alpha. Exposure to IL-10 (1-10 U/ml) for 24 or 48 h increased soluble p75 TNF-R expression and concomitantly reduced surface expression of p75 TNF-R. Further, IL-1 alpha-stimulated production of TNF-alpha was diminished by IL-10 and only a small proportion of this TNF-alpha was bioactive, consistent with increased production of inhibitory soluble TNF-R. IL-10 also induced down-regulation of surface p55 TNF-R on monocytes, and increased release of soluble p55 TNF-R. However, the expression of soluble p55 TNF-R was much lower than soluble p75 TNF-R, indicating that it contributed less importantly to neutralization of TNF-alpha under these conditions. Like IL-10, IL-4 supressed the release of TNF-alpha by monocytes. In contrast to IL-10, however, IL-4 (0.1-10 ng/ml) supressed the release of soluble p75 TNF-R from monocytes in a dose-dependent manner. Release of soluble p55 TNF-R was also supressed by IL-4. IL-10, therefore, reduces the pro-inflammatory potential of TNF in three ways: by down-regulating surface TNF-R expression whilst increasing production of soluble TNF-R and inhibiting the release of TNF-alpha itself. This suggests that IL-10 may be useful in the treatment of diseases where overexpression of TNF-alpha occurs.

Cells, Cultured↗

PubMed1997

The effects of anticoagulation and processing on assays of IL-6, sIL-6R, sIL-2R and soluble transferrin receptor.

Levels of plasma cytokines, their receptors or immune-related peptides, are used in experimental and clinical medicine. However, no standards are available regarding the use of anticoagulants or blood processing including the technique of blood collection or time delay between blood sampling and centrifugation. Blood was collected from 10 patients in order to assay interleukin 6, soluble interleukin 6 receptor, soluble interleukin 2 receptor and soluble transferrin receptor by enzyme-linked immunosorbent assay (ELISA). At the time of sampling, five different collecting tubes were used: allowing coagulation, in the presence of EDTA, with EDTA being administered to the serum after its separation, in citrated and in heparinized blood. Blood was centrifuged 10 min after collection and separated serum or plasma was immediately frozen at -20 degrees C. To study the effect of time delay between blood sampling and processing, blood from 11 other patients was sampled, allowing coagulation; or in EDTA tubes and stored at 4 degrees C. The blood was centrifuged 10 min, 8 h and 24 h later, and the separated serum or EDTA plasma was stored at -20 degrees C until thawed for protein determination. Plasma interleukin 6 and soluble interleukin 6 receptor concentrations did not depend on the type of anticoagulant used or the time delay between sampling and processing. Soluble interleukin 2 receptor concentrations were not influenced by time delay before centrifugation, but concentrations were increased 10-fold in EDTA plasma exclusively when EDTA had contact with blood cells. Soluble transferrin receptor concentrations rose progressively with storage time before centrifugation. Contact of EDTA to whole blood or serum resulted in the same increase of soluble transferrin receptor concentration. The results suggest that standardization of the use of anticoagulant and time delay before centrifugation and serum or plasma separation is necessary for soluble interleukin 2 receptor and soluble transferrin receptor.

Anticoagulants↗

PubMed1997

The Effect of Sodium Dodecyl Sulfate and M-alpha-Cyclodextrin on the Solubility and Partitioning of Xylenes in Aqueous Solutions

The solubility and the partitioning of p- and o-xylene in aqueous solutions containing M-alpha-CD, a partially methylated alpha-cyclodextrin, and the anionic surfactant sodium dodecyl sulfate (SDS) were studied by extraction experiments to evaluate the applicability of liquid membrane permeation for the separation of xylene isomeres. Experiments were carried out with the pure xylenes and 1:1 mixtures of o- and p-xylene. The interactions of M-alpha-CD and SDS and their effects on the solubility and partitioning of xylenes were investigated. M-alpha-CD was found to form 1:1 complexes with p- and o-xylene. Formation constants were determined as 141 M-1 for p-xylene and 48 M-1 for o-xylene, respectively, which are higher than those reported with nonmethylated alpha-CD. This can be explained by additional hydrophobic interactions with the methyl groups of the cyclodextrin. In contrast to the solubility in CD solutions, o-xylene was found to be more soluble than p-xylene in aqueous solutions of SDS. At constant concentrations of M-alpha-CD the addition of SDS led to the displacement of p-xylene from the cyclodextrin cavity, which resulted in a decrease in its solubility. This decrease lasted until micelles were formed. Due to the solubilization of p-xylene in the micelles, further addition of SDS resulted in a linear increase in the solubility of p-xylene. However, at constant CD concentrations the solubility of o-xylene increased with the addition of SDS until about 5 mmol/liter SDS. This might be attributed to the formation of a ternary complex consisting of cyclodextrin, o-xylene, and SDS. At SDS concentrations greater than 5 mmol/liter, the solubility of o-xylene decreased, which was probably due to the formation of a more stable complex between SDS and M-alpha-CD. An addition of SDS beyond a critical concentration (CMC), where micelles are formed, resulted again in a linear increase of o-xylene solubility. The CMC was found to depend linearly on the concentration of M-alpha-CD in aqueous solution. Extraction experiments with a 1:1 mixture of o- and p-xylene showed that the two xylenes and SDS are in competition for M-alpha-CD. Since surfactants are always present when using emulsion liquid membranes and due to the complex interactions between SDS, the xylenes, and M-alpha-CD, no sufficient selectivity for the separation of the xylenes by liquid membrane permeation could be achieved.

Journal Article↗

PubMed1997

Prediction of Solubility of Nonpolar Gases in Micellar Solutions of Ionic Surfactants

The solubilities of methane, carbon dioxide, ethane, and propane have been determined experimentally at 1 atm partial pressure and 25°C in aqueous solutions of sodium dodecyl sulfate and cetyltrimethylammonium bromide. For this purpose a specially developed apparatus is used, which is relatively simple compared to those reported in the literature hitherto. Above the CMC, the solubility of each gas increases linearly with surfactant concentration indicating micellar solubilization. The degree of solubilization is greatest for propane and decreases in the order propane > ethane > carbon dioxide > methane. Both the length of the alkyl chain and the properties of the head-group region (i.e., the micelle-water interfacial tension) are observed to determine the intramicellar solubility. A method for estimating the solubilities is also proposed based on the rationale that the micellar phase may be represented by a droplet of a "model solvent" into which the solubilizate molecule dissolves as it would in a bulk solvent. The mixture of the solute species and the model solvent is assumed to behave as a regular solution. Accordingly, a characteristic solubility parameter is estimated for the model solvent from the interaction potential between two adjacent surfactant molecules in a micelle. The solubility computed using the regular solution approximation is further corrected for the Laplace pressure that acts across the curved micelle-water interface and generally reduces the intramicellar solubility. It is concluded that for small nonpolar solutes, micellar solubilities may be reasonably well predicted by assuming that the model solvent has a solubilizing capacity (i.e., solubility parameter) close to that of a bulk equivalent alkane. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗

PubMed2000

Hazard identification and dose response of inhaled nickel-soluble salts.

A substantial body of occupational epidemiology data has shown that exposure to mixed soluble and insoluble nickel causes the development of lung and nasal cancer. However, due to coexposure of these populations to soluble and insoluble forms of nickel, and limitations in exposure measurements, the contribution of soluble nickel is difficult to determine. Soluble nickel was negative in an NTP inhalation bioassay, while there was some evidence for tumorigenicity in rats for less soluble nickel oxide, and there was clear evidence for tumorigenicity of insoluble nickel subsulfide in rats. Results of parenteral assays follow a similar pattern, but provide evidence of weak carcinogenicity of soluble nickel. Kinetic factors also indicate that exposure to soluble nickel alone has a low carcinogenic potential. Overall, we conclude that the carcinogenic activity of insoluble nickel compounds should not be used to predict the carcinogenic potential of water-soluble nickel salts. The overall data suggest a nonlinear dose-response relationship for carcinogenicity, but the data are insufficient to determine the doses at which such nonlinearities occur. Under the U.S. EPA's 1996 proposed "Guidelines for Carcinogen Risk Assessment," inhaled soluble nickel compounds would be classified as "cannot be determined," because the existing evidence is composed of conflicting data. A reference concentration of 2 x 10(-4) mg Ni/cu x m was calculated, based on lung fibrosis in male rats observed in the NTP study.

Administration, Inhalation↗

PubMed1998

Increased release of the soluble form of the adhesion molecules L-selectin and ICAM-1 but not E-selectin during attacks of angina pectoris.

Myocardial ischemia leads to the activation of neutrophils as well as endothelial cells. The interaction between these cells is dependent on certain adhesion glycoproteins which are expressed on their surface. Adhesion of neutrophils to endothelium, mediated by adhesion molecules, has been shown to result in coronary capillary plugging and impairment of coronary blood flow. In certain conditions, upon cell activation, adhesion proteins may be released in soluble form into the circulating blood. The purpose of our study was to verify whether myocardial ischemia occurring during angina episodes results in the release of the soluble adhesion molecules, L-selectin, E-selectin, and intracellular adhesion molecule-1 (ICAM-1), into the circulation. Plasma samples were collected by venepuncture from 15 patients admitted to the emergency room with chest pain caused by attacks of angina pectoris and 15 patients with noncardiac chest pain. To confirm the diagnosis, all patients underwent an exercise stress test and, if not conclusive, 99mTc MIBI SPECT or coronary arteriography. Another set of plasma samples were taken from each patient in the absence of chest pain. In addition, blood for analysis was obtained from 15 sex-and age-matched healthy subjects. Soluble adhesion molecules plasma levels were measured by standard enzyme-linked immunosorbent assay. In patients with angina pectoris, plasma levels of soluble L-selectin estimated during chest pain were significantly higher than in the control group and decreased in the absence of chest pain. Similarly, the mean concentration of soluble ICAM-1 at the time of angina onset was significantly elevated in the patients in comparison with the control group and remained higher, although not significantly, in the absence of chest pain. In patients with noncardiac chest pain, plasma levels of soluble L-selectin did not differ significantly from those observed in control subjects. In this group of patients, the plasma levels of soluble ICAM-1 estimated during pain onset and in the absence of this symptom were not significantly elevated. On the contrary, the mean values of soluble E-selectin in the patients with ischemic cardiac pain during chest pain and in the absence of this symptom, as well as those in the patients with noncardiac chest pain during or without symptoms, remained unchanged in comparison with the control group. During attacks of angina pectoris an increase in the plasma levels of the soluble adhesion molecules, ICAM-1 and L-selectin, was noted, possibly reflecting activation of neutrophils and endothelial cells during myocardial ischemia. However, E-selectin plasma levels remained unchanged in response to myocardial ischemia.

Adult↗

PubMed2000

The clinicopathological significance of preoperative serum-soluble interleukin-2 receptor concentrations in operable non-small-cell lung cancer patients.

BACKGROUND: Serum-soluble interleukin-2 receptor (IL-2R) concentrations have been found to be elevated in cancer patients. However, the importance of this finding in patients with non-small-cell lung cancer (NSCLC) has not been previously established. METHODS: Preoperative serum-soluble IL-2R concentrations were determined in 65 consecutive patients with operable NSCLC. The correlation of preoperative serum-soluble IL-2R concentrations with various clinicopathological features of this cancer was evaluated to clarify the clinical significance of this parameter. RESULTS: Although serum-soluble IL-2R concentrations were not significantly higher in operable NSCLC patients than in normal controls (P = .1180), serum-soluble IL-2R concentrations were significantly higher in patients with stage IIIB or IV disease than in normal controls (P = .0001). The presence of intrapulmonary metastasis was the only clinicopathological feature that was significantly correlated to serum-soluble IL-2R concentration (P = .0004). The sensitivity of serum-soluble IL-2R concentration in identifying the presence of intrapulmonary metastasis was 87.5%; specificity was 75%. CONCLUSIONS: Elevated preoperative serum-soluble IL-2R concentrations in patients with operable NSCLC reflect the occurrence of intrapulmonary metastasis. Preoperative examination of serum-soluble IL-2R concentrations may be valuable in the detection of the intrapulmonary metastasis preoperatively.

Aged↗

PubMedDate not supplied

Relative susceptibility of cytoskeleton-associated and soluble neurofilament subunits to aluminum exposure in intact cells. A possible mechanism for reduction of neurofilament axonal transport during aluminum neurotoxicity.

Previous studies have demonstrated the appearance of phosphorylated neurofilament (NF) subunits within perikaryal cytoskeletons following aluminum exposure. In order to examine the mechanisms leading to this altered distribution of NF subunits, we carried out biochemical analyses of NF subunits in Triton-insoluble and -soluble fractions derived from aluminum-treated NB2a/d1 cells. In addition to increases in the Triton-insoluble cytoskeleton, increases in all three NF subunits were also detected within the Triton-soluble fraction of aluminum-treated cells. To address the nature of this increase in Triton-soluble subunits, aluminum-treated and untreated cultures were harvested in the absence of Triton and fractionated by established procedures to yield fractions greatly enriched for perikarya and neurites, respectively. Each of these subcellular fractions was then subjected to further homogenization in the presence of 1% Triton and centrifugation to yield Triton-insoluble cytoskeletons and Triton-soluble material derived from perikarya and axonal neurites, respectively. Resulting Triton-soluble fractions were "clarified" by high-speed centrifugation to eliminate oligomeric assemblies or soluble neurofilaments. Immunoblot analysis demonstrated quantitative recovery of the aluminum-induced increase in Triton-soluble NF subunits in the perikaryal fraction. Additional aluminum-treated and untreated cultures were pulse-chase radiolabeled with [35S]methionine and fractionated into Triton-insoluble and soluble fractions from isolated perikarya and axonal neurites. Autoradiographic analysis of immunoprecipitated NF subunits revealed that aluminum treatment delayed the translocation of newly synthesized subunits into neurites and resulted in the accumulation of radiolabeled subunits within the Triton-soluble fraction of perikarya. These findings suggest that aluminum may exert a relatively greater effect on NF subunits that have not yet undergone axonal transport and/or incorporation into Triton-insoluble structures vs those that have already deposited into axons. This possibility was supported by the observation that a higher concentration of aluminum was required to alter the electrophoretic migration of in vitro reassembled neurofilaments vs that required for unassembled NF subunits. These findings provide possible mechanisms for the accumulation of NF subunits in perikarya during aluminum intoxication.

Aluminum↗

PubMed1988

The aging of a brain soluble fraction modifies its effect on the activity of neuronal Na+, K+-ATPase.

In previous work we presented evidence showing that a brain soluble fraction was necessary to observe the stimulation of membrane Na+,K+-ATPase activity by catecholamines. Preliminary experiments suggested to us that the soluble fraction by itself was able to modify this enzyme activity. In the present study we have assayed the activity of synaptosomal Na+,K+-ATPase in the presence of a soluble fraction (aqueous supernatant after 100,000 g 30 min) prepared from rat cerebral cortex. The soluble fraction was used at different times after its preparation and different conditions in the incubation period previous to the enzyme assay were tested. It was observed that the enzyme activity increased 70% in the presence of a "0 min" soluble fraction. This effect was not found: a) in the presence of a "30 min" soluble fraction or b) when the membranes plus a "0 min" soluble fraction were incubated for 30 min (15 min at 37 degrees C + 15 min at 0 degree C) before the ATPase assay. In the presence of a "60 min" or "24 h" soluble fraction Na+,K+-ATPase activity was inhibited 50%. Results obtained indicate that Na+,K+-ATPase activity of synaptosomal membranes can be stimulated, inhibited or unchanged, depending on the aging of the soluble fraction.

Animals↗

PubMed2004

Soluble Fas and Fas ligand provide new information on metastasis and response to chemotherapy in SCLC patients.

BACKGROUND: The Fas/Fas ligand (FasL) system is a major regulator of apoptosis. Chemotherapeutic drugs have been shown to induce Fas expression on the surface of lung cancer cells, and cancer cell apoptosis. However, this mechanism is not considered to be associated with Fas expressed on lung cancer cells. Soluble Fas and FasL concentrations are reportedly elevated in the peripheral blood of patients with lung cancer, but the roles of circulating soluble Fas and FasL in that disease have not been clarified. MATERIALS AND METHODS: We measured the circulating soluble Fas and FasL levels in 21 patients with small cell lung cancer (SCLC), and 12 healthy matched controls, in order to examine whether such ligands could provide any important information and/or reveal any new clinical features of SCLC. RESULTS: In the CR patients, the neuronal specific enolase (NSE), soluble Fas and soluble FasL concentrations were 21.26+/-3.65 ng/ml, 3.58+/-0.19 ng/ml and 0.50+/-0.15 ng/ml, while in the partial response (PR)/no change (NC)/progressive disease (PD) group of patients they were 33.96+/-7.86 ng/ml, 5.29+/-0.29 ng/ml and 0.59+/-0.07 ng/ml, respectively. The NSE, soluble Fas and soluble FasL concentrations were all elevated in the PR/NC/PD patients, however, significant differences were only seen in Fas concentration between CR and PR/NC/PD patients and CR patients and the controls (p<0.001). CONCLUSIONS: Serum soluble Fas and FasL play important roles in the proliferation and metastasis of SCLC, as well as in the cytotoxic reaction and apoptosis induced by anticancer drugs in SCLC. Further study of the mechanisms and participation of circulating soluble Fas and FasL is necessary to develop treatment strategies for SCLC.

Aged↗

PubMed1997

Soluble E-selectin, ICAM-1 and VCAM-1 levels in systemic and coronary circulation in patients with variant angina.

OBJECTIVE: The purpose of this study was to assess whether the plasma levels of soluble adhesion molecules including E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are elevated in patients with variant angina and whether they are released in the coronary circulation. METHODS: Antecubital venous plasma samples were collected from 33 patients with variant angina, 22 patients with stable effort angina and 20 control subjects. Samples were also collected from the aortic root (AO) and the coronary sinus (CS) in 18 patients with variant angina before and after left coronary spasm induced by intracoronary injection of acetylcholine. The soluble adhesion molecules were assayed by enzyme immunoassay. RESULTS: Antecubital venous plasma soluble E-selectin (P < .05), ICAM-1 (P < .01) and VCAM-1 (NS) levels were higher in the variant angina group than in the control group, respectively. The plasma soluble ICAM-1 level was also higher (P < .01) in the variant angina group than in the stable effort angina group. In the variant angina group, both soluble ICAM-1 (P < .05) and VCAM-1 (P < .01) levels were significantly lower in CS than AO at baseline. In contrast, after the spasm the plasma soluble ICAM-1 level was (P < .05) higher in CS than AO and the CS-AO differences of soluble ICAM-1 (P < .05) and VCAM-1 (P < .05) increased as compared with the baseline, respectively. These values were remained unchanged in the stable effort angina group after rapid atrial pacing and in the control group after administration of acetylcholine. CONCLUSIONS: Circulating plasma levels of both soluble E-selectin and ICAM-1 were elevated in patients with variant angina, indicating an association of an inflammatory reaction with coronary spasm. Both soluble ICAM-1 and VCAM-1 appeared to be trapped in the coronary circulation at baseline and released into the coronary circulation following coronary spasm and reperfusion in the patients.

Acetylcholine↗

PubMed2003

Aggregation and solubility behavior of asphaltenes and their subfractions.

Asphaltenes from four different crude oils (Arab Heavy, B6, Canadon Seco, and Hondo) were fractionated in mixtures of heptane and toluene and analyzed chemically, by vapor pressure osmometry (VPO), and by small angle neutron scattering (SANS). Solubility profiles of the asphaltenes and their subfractions indicated strong cooperative asphaltene interactions of a particular subfraction that is polar and hydrogen bonding. This subfraction had lower H/C ratios and modestly higher N, V, Ni, and Fe contents than the less polar and more soluble subfraction of asphaltenes. VPO and SANS studies indicated that the less soluble subfractions formed aggregates that were considerably larger than the more soluble subfractions. In general, asphaltene aggregate size increased with decreasing solvent aromaticity up to the solubility limit, beyond which the aggregate size decreased with heptane addition. The presence of a low wavevector Q feature in the scattering curves at 25 degrees C indicated that the individual aggregates were flocculating; however, the intensity of the feature was diminished upon heating of the samples to 80 degrees C. The solubility mechanism for Canadon Seco asphaltenes, the largest aggregate formers, appears to be dominated by aromatic pi-bonding interactions due to their low H/C ratio and low nitrogen content. B6 and Hondo asphaltenes formed similar-sized aggregates in heptol and the solubility mechanism is most likely driven by polar interactions due to their relatively high H/C ratios and high nitrogen contents. Arab Heavy, the least polar asphaltene, had a H/C ratio similar to Canadon Seco but formed the smallest aggregates in heptol. The enhancement in polar and pi-bonding interactions for the less soluble subfraction indicated by elemental analysis is reflected by the aggregate size from SANS. The less soluble asphaltenes contribute the majority of species responsible for aggregation and likely cause many petroleum production problems such as pipeline deposition and water-in-oil emulsion stabilization.

Journal Article↗

PubMed2000

Serum soluble Fas levels in ovarian cancer.

OBJECTIVE: To determine the value of serum soluble Fas levels as a prognostic marker for survival of women with ovarian cancer and as a discriminator between benign and malignant adnexal masses. METHODS: Serum soluble Fas levels were measured with an enzyme-linked immunosorbent assay in 52 women with ovarian cancer, 30 women with benign ovarian cysts, and 35 healthy women. RESULTS: Median serum soluble Fas levels in women with ovarian cancer, women with benign ovarian cysts, and healthy women were 3.7 (range 1.6-14.5), 2.3 (range 1.3-4.1), and 1.5 ng/mL (range 0.1-5.6), respectively (P <. 001). A univariate logistic regression model showed a significant influence of serum soluble Fas and CA 125 levels on the odds of presenting with ovarian cancer versus benign cysts (P <.001 and P =. 001, respectively). In a multivariable logistic regression model for soluble Fas and CA 125, both markers showed a statistically significant influence on the odds of presenting with ovarian cancer versus benign cysts (P =.01 and P =.01, respectively). Increased pretreatment serum soluble Fas levels were associated with shortened disease-free and overall survival (P =.002 and P =.001, respectively). A multivariable Cox regression model identified serum soluble Fas levels as a significant prognostic factor for disease-free and overall survival, independent of tumor stage (P =. 04 and P =.03, respectively). CONCLUSION: Soluble Fas levels might be useful as a discriminator between benign ovarian cysts and ovarian cancer, adding to the information obtained with the use of the established tumor marker CA 125. Pretreatment serum soluble Fas levels also might be an independent prognostic factor for disease-free and overall survival.

Adenocarcinoma, Mucinous↗

PubMed1994

Circulating soluble IL-2 receptor levels are low in patients with hypothyroid autoimmune thyroiditis.

In hypothyroid patients serum soluble IL-2 receptor levels showed scattered and conflicting results. In our report we studied circulating soluble interleukin 2 receptors in 22 patients with hypothyroid autoimmune thyroiditis before L-thyroxine treatment and when the patients became euthyroid. The mean of soluble Interleukin 2 receptor levels in the hypothyroid state was 48.6 pmol/l (95% confidence interval, 45.6-51.5) statistically lower than in the controls (95% confidence interval, 86.4 pmol/l, 83.3-89.4) (p < 0.0001). When the patients became euthyroid during L-thyroxine treatment, soluble Interleukin 2 receptor levels increased, showing mean values comparable to the controls. A positive high correlation (p < 0.001) was observed between soluble Interleukin 2 receptor levels and thyroxine free levels in the hypothyroid as well as in the euthyroid state and between soluble Interleukin 2 receptors and the mean weekly L-thyroxine dose. Our study confirmed that in the hypothyroid state, the behaviour of soluble Interleukin 2 receptors is anomalous as compared to other autoimmune diseases. In fact a strict relationship exists between the levels of thyroid hormones and soluble Interleukin 2 receptors but not between the latter and antithyroid antibodies. These results agree with those supporting a role for thyroid hormones in the regulation of the immune system. They also suggest that the measurement of soluble Interleukin 2 receptors could be used as a marker of the peripheral action of thyroid hormones.

Adolescent↗

PubMed2003

Soluble CD40 ligand in acute coronary syndromes.

BACKGROUND: CD40 ligand is expressed on platelets and released from them on activation. We investigated the predictive value of soluble CD40 ligand as a marker for clinical outcome and the therapeutic effect of glycoprotein IIb/IIIa receptor inhibition in patients with acute coronary syndromes. METHODS: Serum levels of soluble CD40 ligand were measured in 1088 patients with acute coronary syndromes who had previously been enrolled in a randomized trial comparing abciximab with placebo before coronary angioplasty and in 626 patients with acute chest pain. RESULTS: The levels of soluble CD40 ligand were elevated (above 5.0 microg per liter) in 221 patients with acute coronary syndromes (40.6 percent). Among patients receiving placebo, elevated soluble CD40 ligand levels indicated a significantly increased risk of death or nonfatal myocardial infarction during six months of follow-up (adjusted hazard ratio as compared with patients with low levels of the ligand [< or =5.0 microg per liter], 2.71; 95 percent confidence interval, 1.51 to 5.35; P=0.001). The prognostic value of this marker was validated in the patients with chest pain, among whom elevated soluble CD40 ligand levels identified those with acute coronary syndromes who were at high risk for death or nonfatal myocardial infarction (adjusted hazard ratio as compared with those with low levels of the ligand, 6.65; 95 percent confidence interval, 3.18 to 13.89; P<0.001). The increased risk in patients with elevated soluble CD40 ligand levels was significantly reduced by treatment with abciximab (adjusted hazard ratio as compared with those receiving placebo, 0.37; 95 percent confidence interval, 0.20 to 0.68; P=0.001), whereas there was no significant treatment effect of abciximab in patients with low levels of soluble CD40 ligand. CONCLUSIONS: In patients with unstable coronary artery disease, elevation of soluble CD40 ligand levels indicated an increased risk of cardiovascular events. Elevation of soluble CD40 ligand identifies a subgroup of patients at high risk who are likely to benefit from antiplatelet treatment with abciximab.

Abciximab↗

PubMed1998

Interleukin (IL)-6 and its soluble receptor induce TIMP-1 expression in synoviocytes and chondrocytes, and block IL-1-induced collagenolytic activity.

To define the potential role of interleukin-6 (IL-6) and its soluble receptor alpha in cartilage metabolism, we analyzed their effects on tissue inhibitor of metalloproteases (TIMP) synthesis by synoviocytes and chondrocytes. TIMP-1 production by isolated human articular synovial fibroblasts and chondrocytes, stimulated by IL-6 and/or its soluble receptor, was first assayed by specific enzyme-linked immunosorbent assay; the slight stimulatory effect of IL-6 on TIMP-1 production by both types of cells was markedly amplified by the addition of soluble receptor, the maximal secretion being observed only at 96 h. TIMP-1 mRNA expression, determined by ribonuclease protection assay, was induced by IL-6 together with its soluble receptor, but TIMP-2 and -3 mRNAs were not affected by these factors. A specific neutralizing antibody abolished the effects of the soluble receptor. Finally, supernatant from synoviocytes stimulated by IL-6 plus its soluble receptor blocked almost completely the collagenolytic activity of supernatant from IL-1-induced synoviocytes. These observations indicate that IL-6 and its soluble receptor have a protective role in the metabolism of cartilage. Given the high levels of soluble receptor in synovial fluid and the marked induction of IL-6 by IL-1 or TNF-alpha, it is likely that IL-6 and its soluble receptor are critical in controlling the catabolic effects of pro-inflammatory cytokines.

Cartilage, Articular↗

PubMed1975

Solubility and net exchange of calcium, magnesium and phosphorus in digesta flowing along the gut of the sheep.

1. The changes in the solubility of calcium, magnesium and phosphorus in digesta flowing along the intestinal tract and the net movement across the intestinal wall of these elements were determined in six rams, each equipped with three T-shaped cannulas; cannulas were placed in a total of six different sites of the small intestine. Cr2O3 was used as a marker substance to measure the rate of flow of the digesta. 2. The concentrations of soluble Ca, Mg and P decreased as digesta moved along the intestine. TheMgreatest fall in soluble Ca occurred after the first 3 m of the intestine, while a significant decrease in soluble Mg was found only at 15 and 25 m from the pylorus. The concentration of soluble P in digesta decreased until the 7 m site and then remained stable. In the faeces, the level of soluble Mg was approximately 4 times higher than, and that of Ca equal to, the levels of Mg and Ca found in digesta flowing through the upper intestine. Unlike Ca and Mg, a very low concentration of soluble P was found in the faeces. 3. In the duodenum, 84, 78 and 62% of the total Ca, Mg and P respectively were soluble, whereas in the digesta flowing through the terminal ileum the corresponding values were 3-2, 7-2 and 19% for Ca, Mg and P respectively. 4. The forestomachs and the colon were found to be the main sites of g net absorption; 1-12 mmol/h was apparently absorbed from the stomach and 1-05 mmol/h from the colon. The supper small intestine (1-3 m from the pylorus) appeared to be the major site of Ca and P absorption. 5. In the last 10 m of the small intestine, considerable amounts of minerals were secreted; 4-70, 0-96 and 1-85 mmol Ca, Mg and P/h respectively were added to the digesta flowing between 15 and 25 m from the pylorus. The effect of the increase in the pH of digesta along the small intestine on the solubility of these minerals is discussed.

Animals↗