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PubMed2000

Elevation of soluble Fas and soluble Fas ligand in reactive macrophage activation syndromes.

Derailed T-cell activation can give rise to life-threatening macrophage activation, the final common pathway of the different forms of reactive macrophage activation syndromes (rMAS). Besides inappropriate activation of the immune system, impaired termination of immune responses might be another mechanism leading to rMAS. The Fas (CD95)/Fas ligand (CD95 ligand) system functions in turning off immune responses by executing activation-induced cell death (AICD). Soluble Fas (sFas) and Fas ligand (sFasL) can interfere with their corresponding membrane-bound counterparts, qualifying them as potential parameters of impaired immune termination. Hence, sFas and sFasL were analyzed in sera of rMAS patients. We show that soluble Fas/CD95 (sFas) is elevated >2 SD over the mean of controls in all 8 rMAS episodes studied (mean 12.08 +/- 6.12 ng/mL, range 3.7-20.2; controls 2.46 +/- 0.49, range 1.5-2.9). sFasL was detected during five rMAS episodes (0.70 +/- 0.49 ng/mL, range 0.16-1.28; controls all below the limit of detection of 0.1). In addition, both parameters decrease during convalescence, reflecting clinical evolution. In conclusion, sFas seems to be consistently elevated during acute rMAS. sFasL is detected only in a subgroup of our adult rMAS patients extending the recent finding of sFasL elevation in a majority of children with macrophage activation syndromes (Hasegawa et al. Blood 1998;91(8):2793-2799). By interfering with AICD, sFas and sFasL might contribute to the pathogenesis of at least a subset of rMAS.

Adult↗

PubMed1997

Soluble Fas (APO-1, CD95) and soluble Fas ligand in rheumatic diseases.

OBJECTIVE: To assess levels of soluble Fas (sFas) and soluble Fas ligand (sFas-L) in sera from patients with various rheumatic diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), mixed connective tissue disease (MCTD), and Sjogren's syndrome (SS). METHODS: Levels of sFas and sFas-L were determined by a sandwich enzyme-linked immunosorbent assay. RESULTS: In SLE, PM/DM, MCTD, and SS, sFas levels were significantly higher compared with normal controls. Levels of sFas in the SLE patients were significantly higher than in patients with other rheumatic diseases. Levels of sFas-L were significantly increased in SS patients. SLE and RA patients with high levels sFas-L tended to have high levels of sFas, while sFas and sFasL levels did not correlate in patients with other diseases. In some of the SLE patients, sFas and sFas-L levels decreased following steroid therapy. CONCLUSION: Serum sFas and sFas-L levels were significantly higher in some rheumatic disease patients. Since these changes are complex in these rheumatic diseases, it may be difficult to directly relate sFas and sFasL to their pathogenesis.

Adolescent↗

PubMed1996

A functional analysis of recombinant soluble CD46 in vivo and a comparison with recombinant soluble forms of CD55 and CD35 in vitro.

The human cell surface complement regulatory proteins CD46 (MCP), CD55 (DAF) and CD35 (CR1) protect autologous cells from complement-mediated damage by inhibiting C3 and C5 convertases. This regulatory potential has previously been exploited in the treatment of some models of inflammatory injury by the generation of recombinant soluble (rs) proteins, such as rsCD55 and rsCD35 . More recently, we have shown that rsCD46 inhibits complement activation in the fluid phase. In this report, the ability of rsCD46, rsD55 and rsCD35 to regulate human complement activation mediated by the classical pathway in vitro was clearly demonstrated by all three soluble proteins; however, rsCD35 was a more effective inhibitor than either rsCD46 or rsCD55. A combination of rsCD46+ rsCD55 was more potent than either of these proteins alone. Cell lysis via alternative pathway activation in vitro was efficiently regulated by rsCD46 and rsCD35 to a similar extent, whereas rsCD55 was not effective. Assays of rsCD46 in vivo have previously not been possible due to difficulties in expressing sufficient quantities of protein. This limitation has been overcome and now we report the ability of rsCD46 to inhibit immune complex-mediated inflammation in a rat using the reverse passive Arthus reaction model. Administration of rsCD46 significantly reduced the size of lesion, and histological examination showed a reduction in inflammatory infiltrate and edema. These data suggest that rsCD46, in addition to rsCd55 and rsCD35, may be useful a therapeutic agent.

Animals↗

PubMed2002

Increased incidence rate of colorectal tumors due to the intake of a soluble dietary fiber in rat chemical carcinogenesis can be suppressed by substituting partially an insoluble dietary fiber for the soluble one.

In epidemiologic studies on human colorectal tumors, results on the relative protective effect of soluble and insoluble fibers are not consistent. We studied in this work the effect in rats of feeding guar gum or guar gum together with cellulose on the incidence of colorectal tumors induced by 1,2-dimethylhydrazine. The results were as follows: (i) The enhancement of tumor formation by feeding solely guar gum (guar gum group) was suppressed completely when two-thirds of the guar gum was replaced with cellulose (cellulose-guar gum group). The odds ratio for tumor formation was 0.075 (95% CI 0.006-0.936, p = 0.044) for guar gum group vs. no fiber control and 0.833 (0.134-5.167, p = 0.83) for cellulose-guar gum group vs. the control. (ii) In both groups, serum cholesterol and triglyceride levels decreased significantly compared to the no fiber control group, and fecal excretion of total bile acids almost doubled. (iii) In guar gum group rats, the deconjugation activity (beta-glucuronidase, beta-glucosidase) was higher than the control or cellulose-guar gum group rats. (iv) The amount of cecal short-chain fatty acids was almost double in guar gum group rats compared to the cellulose-guar gum group or the control rats, and pH of the cecal content of the guar gum group rats had a tendency to be lower. (v) The concentration of fecal secondary bile acids was extremely low in the younger rats of the guar gum group. From these results, it seemed significant to study the cancer preventive effect of the mixed feeding to experimental animals of water-soluble and insoluble fibers instead of the singular feeding.

Animals↗

PubMed2002

Prediction of the aqueous solubility: comparison of the general solubility equation and the method using an amended solvation energy relationship.

An Amended Solvation Energy Relationship (ASER) was recently reported to successfully predict the aqueous solubilities of a set of 664 organic compounds. The average absolute error and root mean square error are 0.43 and 0.62 log units, respectively. When the General Solubility Equation (GSE) is applied to the same set of compounds, it gives an average absolute error of 0.45 log units and a root mean square error of 0.62 log units. These results are similar to those of the ASER method. The advantages and disadvantages of each method are discussed. It is shown that when the two methods agree with each other, they also agree with the experimentally determined values.

Forecasting↗

PubMed1980

Solubility and partitioning I: Solubility of nonelectrolytes in water.

On the basis of a semiempirical analysis, an equation was obtained that enables the estimation of the aqueous solubility of either liquid or crystalline organic nonelectrolytes: (see formula in text) where log PC and delta Sf are estimated from the chemical structure and MP is either known or experimentally determined. Analysis of this equation provides a means of assessing the role of crystal structure [as reflected by the melting point (MP) and the entropy of fusion (delta Sf)] and of the activity coefficient [as reflected by the octanol-water partition coefficient (PC)] in controlling the aqueous solubility of a drug. Techniques are also provided for estimating the entropy of fusion of organic compounds.

Alcohols↗

PubMed1987

Solubility properties in biological media 9: prediction of solubility and partition of organic nonelectrolytes in blood and tissues from solvatochromic parameters.

Solubilities in and partition among human blood, brain, lung, kidney, muscle, and fat tissue are well correlated by linear solvation energy relationships of the form: XYZ = XYZo + mVI/100 + s pi + b beta m where XYZ is the logarithm of the solubility property, VI is the intrinsic (van der Waals') molar volume, pi and beta are the solvatochromic parameters that measure solute dipolarity/polarizability and hydrogen-bond acceptor basicity, respectively, and the subscript m indicates that for self-associating compounds, the parameter applies to the non-self-associated "monomer" solute. The equation for log K(brain--blood) indicates that increasing molar volume favors, whereas increasing dipolarity and hydrogen-bond acceptor basicity oppose, solute transfer from blood into brain.

Chemical Phenomena↗

PubMed2003

Soluble Fas (sFas) and soluble Fas ligand (sFas-L) balance in laryngeal carcinoma before and after surgical treatment.

BACKGROUND AND OBJECTIVES: Fas and its specific ligand (Fas-L), both of which are involved in apoptosis, exist in membrane-bound and soluble forms. The soluble forms (sFas and sFas-L) have been observed in various tumours, but their clinical significance has not yet been clarified. The aim of this study was to assess serum sFas and sFas-L levels in patients with laryngeal squamous cell carcinoma (LSCC) and their possible correlations with surgical treatment. METHODS: Serum sFas and sFas-L levels were determined by ELISA in samples taken from 26 LSCC patients on the day before surgery (T0), and 2 weeks (T1) and 6 months after surgery (T2), and in samples taken from 35 healthy volunteers. RESULTS: The mean serum sFas levels in the 35 healthy volunteers and the 26 LSCC patients at T0 were respectively 5941 +/- 411 pg/ml and 6290 +/- 652 pg/ml (P = 0.63), and the mean serum sFas-L levels were 0.1 +/- 0.05 ng/ml and 2.95 +/- 0.8 ng/ml (P < 0.0001). After surgery, there was a statistically significant decrease in sFas at both T1 (P < 0.05) and T2 (P < 0.01), and in sFas-L at T2 (P < 0.01). CONCLUSIONS: The decrease in sFas and sFas-L levels after surgery suggest that they may be produced by or closely linked to tumour cells. Larger prospective clinical studies of patients with LSCC will be needed to establish the clinical significance of sFas and sFas-L, as reported for other neoplasms.

Aged↗

PubMed1993

Elevated soluble CD8 antigen and soluble interleukin-2 receptors in the sera of patients with juvenile rheumatoid arthritis.

Activated T lymphocytes release various molecules including soluble CD8 (sCD8) antigen and soluble interleukin-2 receptor (sIL-2R). Elevated serum sCD8 antigen levels have been found in patients with viral infections, certain hematologic malignancies, and rheumatoid arthritis. On the other hand, elevated serum levels of sIL-2R have been found in various diseases including juvenile rheumatoid arthritis (JRA). We measured sCD8 antigen and sIL-2R levels using enzyme-linked immunosorbent assays in the sera of 49 afebrile patients with JRA (systemic 15, polyarticular 16, and pauciarticular 18) and 16 normal children. Disease activity was classified as mild, moderate, and severe. Sera from patients with severe JRA expressed statistically significant higher levels of both sCD8 and sIL-2R, whereas patients with mild disease had the lowest levels. There were no differences in the serum sCD8 and sIL-2R levels between the groups of patients with pauciarticular-, systemic-, and polyarticular-onset disease. Patients who were treated with prednisone had statistically nonsignificant higher serum levels of sCD8 and sIL-2R. A statistically significant positive correlation was found between sCD8 and sIL-2R levels, sCD8 levels and erythrocyte sedimentation rate (ESR), and sIL-2R levels and ESR. Our findings further suggest the presence of activated lymphocytes in patients with JRA and show that sCD8 antigen serum levels correlate with both serum levels of sIL-2R and ESR and thus may represent alternative indicators of disease activity.

Adolescent↗

PubMed1994

Increased concentrations of soluble tumor necrosis factor receptor 75 but not of soluble intercellular adhesion molecule-1 are associated with the decline of CD4+ lymphocytes in HIV infection.

Immune activation seems to be involved in the pathogenesis of human immunodeficiency virus (HIV) infection. The immune activation markers neopterin and beta 2-microglobulin can predict the future rate of the decrease in CD4+ T cells. In a longitudinal study, we assessed whether the decline in the CD4+ T-cell count is associated with increased concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble tumor necrosis factor receptor 75 (sTNFR 75), compared to increased concentrations of beta 2-microglobulin and urinary neopterin. Forty-seven individuals representing all stages of HIV infection were followed-up for a mean of 12.7 months (range, 8 to 16 months). The percentage of the change of the CD4+ T-cell count from study entry to study end ranged from -97 to +98%; the median was -33%. Concentrations of urinary neopterin, sTNFR 75, and beta 2-microglobulin correlated with the percentage of the change of the CD4+ T-cell count from study entry to study end (r = -0.45, confidence interval (CI) -0.65 to -0.19; r = -0.42, 95% CI -0.63 to -0.15; and r = -0.416, 95% CI -0.62 to -0.15), but those of sICAM-1 did not. This difference was found despite significant correlations between sICAM-1 and sTNFR 75 and beta 2-microglobulin. Levels of sICAM-1 obtained at study entry correlated with levels of sICAM-1 obtained at study end (r = 0.46, 95% CI 0.17 to 0.68). In a multivariate linear regression analysis, urinary neopterin and sTNFR 75 were jointly significant for the percentage of the change of the CD4+ T-cell count. These results suggest that sTNFR 75 is a useful marker to estimate disease progression in HIV infection, whereas sICAM-1 does not seem to provide any information related to the decline of the CD4+ T-cell count.

Adult↗

PubMed1995

Serum levels of tumor necrosis factor (TNF), soluble receptors for TNF (55- and 75-kDa sTNFr), and soluble CD14 (sCD14) in epithelial ovarian cancer.

The preoperative serum levels of tumor necrosis factor (TNF), soluble receptors for TNF (55- and 75-kDa sTNFr), and soluble CD14 (sCD14) were retrospectively measured in 66 patients with epithelial ovarian cancer and in 59 patients with benign ovarian masses. The preoperative serum TNF and sCD14 levels were higher in patients with epithelial ovarian cancer than in those with benign ovarian disease (P = 0.001 and P < 0.0001, respectively). Among patients with advanced malignancy, preoperative serum TNF and sCD14 correlated with neither the common prognostic variables nor the clinical outcome of patients. The preoperative serum 55- and 75-kDa sTNFr levels were higher in patients with epithelial ovarian cancer than in those with benign ovarian disease (P < 0.0001 and P = 0.02, respectively). Among patients with advanced malignancy, preoperative serum 55- and 75-kDa sTNFr correlated with FIGO stage (IV vs III, P = 0.008 and P = 0.01, respectively) and with the clinical outcome of patients. Among patients followed after surgery and chemotherapy for advanced epithelial ovarian cancer, 55- and 75-kDa sTNFr levels were significantly higher in the samples drawn from patients with clinical evidence of disease when compared to those from patients without clinical evidence of disease; conversely, TNF and sCD14 levels were similar in the two groups. In conclusion, the preoperative serum levels of TNF, 55- and 75-kDa sTNFr, and sCD14 were significantly higher in patients with epithelial ovarian cancer than in those with benign ovarian disease. The measurement of serum TNF and sCD14 seemed to be of limited clinical value for the management of patients with advanced epithelial ovarian cancer. Conversely, the assay of serum 55- and 75-kDa sTNFr might have a potential clinical relevance, for both prognostic purposes and assessment of disease status.

Adult↗

PubMed1991

Effects of base-soluble proteins and methanol-soluble polysaccharides from corn on mycelial growth of Aspergillus flavus.

The antifungal activity of base-soluble proteins (BSP) and methanol-soluble polysaccharides (PS) from A. flavus resistant (Yellow Creole) and susceptible (Huffman) genotypes of corn were investigated by in vitro studies. Bioassays of fungal growth inhibition in agar media showed antifungal activity by proteins and polysaccharides only from the Huffman genotype. Microgramme quantities of protein and polysaccharides were required to retard fungal growth. The polysaccharides have molecular weights greater than 3.5 kilodaltons. Cathodic PAGE of native protein from the two genotypes showed six protein bands with differences in staining intensity of individual components. SDS-PAGE showed four distinct bands in Yellow Creole that were absent in Huffman. Both of the protein samples contained traces of carbohydrate. Analysis of hydrolyzed polysaccharide from the two genotypes showed different proportions of mannose and glucose.

Aspergillus flavus↗

PubMed1987

Soluble minerals in chemical evolution. II. Characterization of the adsorption of 5'-AMP and 5'-CMP on a variety of soluble mineral salts.

The adsorption of 5'-AMP and 5'-CMP was studied in saturated solutions of several soluble mineral salts (NaCl, Na2SO4, MgCl2 X 6H2O, MgSO4 X 7H2O, CaCl2 X 2H2O, CaSO4 X 2H2O, SrCl2 X 6H2O, SrSO4, and ZnSO4 X 7H2O) as a function of pH, ionic strength, and surface area of the solid salt. The adsorption shows a pH dependence; this can be correlated with the charge on the nucleotide molecule which is determined by the state of protonation of the N-1 nitrogen of 5'-AMP or N-3 nitrogen of 5'-CMP and the phosphate oxygens. The adsorption which results from the binding between the nucleotide molecule and the salt surface is proposed as being due to electrostatic forces. It was concluded that the adsorption was reversible in nature. The adsorption shows a strong dependence upon ionic strength and decreases with increasing ionic strength. Surface area is shown to be an important factor in evaluating and comparing the magnitude of adsorption of nucleotides onto various mineral salts. The implications of the results of the study are discussed in terms of the importance of soluble mineral salts as adsorption sites in the characterization of the adsorption reactions of an adsorbed template in biogeochemical cycles.

Adenosine Monophosphate↗

PubMed2006

Soluble MICB in malignant diseases: analysis of diagnostic significance and correlation with soluble MICA.

Expression of ligands of the immunoreceptor NKG2D such as MICA and MICB has been proposed to play an important role in the immunosurveillance of tumors. Proteolytic shedding of NKG2D ligands from cancer cells therefore constitutes an immune escape mechanism impairing anti-tumor reactivity by NKG2D-bearing cytotoxic lymphocytes. Serum levels of sMICA have been shown to be of diagnostic significance in malignant diseases of various origins. Here, we investigated the potential of soluble MICB, the sister molecule of MICA, as a marker in cancer and its correlation with soluble MICA. Analysis of MICB in sera of 512 individuals revealed slightly higher MICB levels in patients with various malignancies (N = 296; 95th percentile 216 pg/ml; P = 0.069) than in healthy individuals (N = 62; 95th percentile 51 pg/ml). Patients with benign diseases (N = 154; 95th percentile 198 pg/ml) exhibited intermediate MICB levels. In cancer patients, elevated MICB levels correlated significantly with cancer stage and metastasis (P = 0.007 and 0.007, respectively). Between MICB and MICA levels, only a weak correlation was found (r = 0.24). Combination of both markers resulted only in a slightly higher diagnostic power in the high specificity range. The reduction of MICA and MICB surface expression on cells by shedding and the effects of sMICA and sMICB in serum on host lymphocyte NKG2D expression might play a role in late stages of tumor progression by overcoming the confining effect of NK cells and CD8 T cells. While MICB levels are not suited for the diagnosis of cancer in early stages, they may provide additional information for the staging of cancer disease.

Biomarkers, Tumor↗

PubMed2005

Soluble Fas receptor and soluble Fas ligand in the serum of women with uterine tumors.

It is commonly accepted that apoptosis plays an important role in the death of normal and neoplastic cells. Related proteins and their receptors on cell surfaces regulate apoptosis. One of the best-characterized systems is the Fas-Fas ligand system. The aim of the study was to examine the concentrations of soluble Fas receptor (sFas) and the soluble ligand for the Fas receptor (sFasL) in serum of women with uterine tumors. The study included 42 women with uterine tumors. As a normal control, sera were obtained from 20 healthy female volunteers. The concentrations of sFas and sFasL in serum were measured by enzyme-linked immunosorbent assay ELISA. Significant increases of the mean value of sFas and sFasL were found in the serum of women with uterine tumor compared to the control group (p < 0.0001). The mean levels of these parameters increased in consecutive stages of the clinical extent of the uterine cancer (I-III). The lowest concentration was observed in women with stage I and the highest in women with stage III of clinical extent according to FIGO. Apoptosis that appears to occur in the cancerous cells of malignant uterine tumors is associated with high levels of sFas and sFasL in serum.

Adult↗

PubMed2005

Recent advances in GFP folding reporter and split-GFP solubility reporter technologies. Application to improving the folding and solubility of recalcitrant proteins from Mycobacterium tuberculosis.

We have improved our green fluorescent protein (GFP) folding reporter technology [Waldo et al., (1999) Nat. Biotechnol. 17, 691-695] to evolve recalcitrant proteins from Mycobacterium tuberculosis. The target protein is inserted into the scaffolding of the GFP, eliminating false-positive artifacts caused by expression of truncated protein variants from internal cryptic ribosome binding sites in the target RNA. In parallel, we have developed a new quantitative fluorescent protein tagging and detection system based on micro-domains of GFP. This split-GFP system, which works both in vivo and in vitro, is amenable to high-throughput assays of protein expression and solubility [Cabantous et al., (2005) Nat. Biotechnol. 23, 102-107]. Together, the GFP folding reporter and split-GFP technologies offer a comprehensive system for manipulating and improving protein folding and solubility.

Bacterial Proteins↗

PubMed1992

The determination of epsilon-amino groups in soluble and poorly soluble proteinaceous materials by a spectrophotometric method using trinitrobenzenesulfonic acid.

A procedure using 2,4,6-trinitrobenzenesulfonic acid (TNBS) for the determination of epsilon-amino groups in soluble and poorly soluble proteinaceous materials is presented. The major modification from previous procedures is an extended TNBS reaction time to allow a stoichiometric reaction with amino groups. In addition, autoclave hydrolysis is used to assure sample dissolution for spectrophotometric measurements. The assay accuracy was evaluated by determining epsilon-amino groups of insulin and bovine albumin. The determinations differed from literature values by < or = 3.3%. The epsilon-amino group content of Type B gelatin was found to be 33.0 mol/gelatin molecule of 1000 residues and is in agreement with similar source gelatins and collagen. The coefficient of variation for determinations on all three materials was < or = 5.3%. The assay should be applicable to a broad range of proteinaceous materials.

Albumins↗

PubMed1983

Interactions of antibodies against soluble phosphofructokinase with the soluble and particulate enzymes from yeast.

Antibodies obtained from rabbits against soluble yeast phosphofructokinase also react with the particulate yeast phosphofructokinase. Their effects on the activity of the soluble enzyme recognized as inactivation or slight activation depend on the specific immune response of an individual animal yielding antisera with different proportions of inactivating and activating antibodies. The availability of particulate phosphofructokinase to complex inactivating antibodies specifically allows a separation of activating and inactivating antibodies from each other by a simple extraction procedure.

Animals↗