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At least 19 recordsLinked to original sources
PubMed1991

Evaluation of HIV P24 antigen, beta 2-microglobulin, neopterin, soluble CD4, soluble CD8, and soluble interleukin-2 receptor levels in patients with AIDS or AIDS-related complex treated with 2',3'-dideoxyinosine (ddI).

Circulating HIV P24 antigen, beta 2-microglobulin, neopterin, soluble CD4, soluble CD8, and soluble interleukin-2 receptor were measured in 13 zidovudine-intolerant patients (8 with ARC and 5 with AIDS) treated with dideoxyinosine (ddI). Measurements were made at baseline and at several intervals during therapy. Mean levels of HIV P24 antigen decreased early and significantly (P less than 0.01) after 2 weeks of ddI administration and remained low at weeks 8 and 12. In addition, mean SCD8 levels decreased late and significantly (P less than 0.02) after 16 weeks of ddI treatment and remained low at 24 weeks. In contrast, ddI administration had no substantial effect on mean levels of beta 2-microglobulin, neopterin, soluble CD4, and soluble interleukin-2 receptor. ddI administration appears to have been associated with early reduction of HIV P24 antigen levels and later reduction of SCD8 mean levels in these patients.

AIDS-Related Complex↗
PubMed1990

Soluble forms of tumor necrosis factor receptors (TNF-Rs). The cDNA for the type I TNF-R, cloned using amino acid sequence data of its soluble form, encodes both the cell surface and a soluble form of the receptor.

Two proteins which specifically bind tumor necrosis factor (TNF) have recently been isolated from human urine in our laboratory. The two proteins cross-react immunologically with two species of cell surface TNF receptors (TNF-R). Antibodies against one of the two TNF binding proteins (TBPI) were found to have effects characteristic of TNF, including stimulating phosphorylation of specific cellular proteins. Oligonucleotide probes designed on the basis of the NH2-terminal amino acid sequence of TBPI were used to clone the cDNA for the structurally related cell surface type 1 TNF-R. It is notable that although this receptor can signal the phosphorylation of cellular proteins, it appears from its amino acid sequence to be devoid of intrinsic protein kinase activity. The extracellular domain of the receptor is composed of four internal cysteine-rich repeats, homologous to structures repeated four times in the extracellular domains of the nerve growth factor receptor and the B lymphocytes surface antigen CDw40. The amino acid composition and size of the extracellular domain of the type I TNF-R closely resemble those of TBPI. The COOH-terminal amino acid sequence of the four cysteine rich repeats within the extracellular domain of the type I TNF-R matches the COOH-terminal sequence of TBPI. Amino acid sequences in the extracellular domain also fully match other sequences found in TBPI. On the other hand, amino acid sequences in the soluble form of the type II TNF-R (TBPII), while indicating a marked homology of structure, did not suggest any identity between this protein and the extracellular domain of the type I TNF-R. CHO cells transfected with type I TNF-R cDNA produced both cell surface and soluble forms of the receptor. The receptor produced by CHO cells was recognized by several monoclonal antibodies against TBPI, reacting with several distinct epitopes in this molecule. These data suggest that the soluble forms of the TNF-Rs are structurally identical to the extracellular cytokine binding domains of these receptors and are consistent with the notion that the soluble forms are, at least partly, derived from the same transcripts that encode the cell surface receptors.

Amino Acid Sequence↗
PubMed1991

Activation of T lymphocytes in dengue virus infections. High levels of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferon-gamma in sera of children with dengue.

It has been reported that the severe complication of dengue virus infection, dengue hemorrhagic fever (DHF) is much more commonly observed during secondary dengue virus infections than primary infections. In order to elucidate the role of T lymphocytes in the pathogenesis of DHF, we attempted to determine whether T lymphocytes are activated in vivo during dengue virus infections, by examining the levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4), soluble CD8 (sCD8), interleukin-2 (IL-2) and interferon-gamma (IFN gamma) in the sera of 59 patients with DHF and 41 patients with dengue fever (DF). The levels of sIL-2R, sCD4, sCD8, IL-2, and IFN gamma were significantly higher in the acute sera of patients with DHF than in the sera of healthy children (P less than 0.001 for all markers). The acute sera of patients with DF contained higher levels of sIL-2R, sCD4, IL-2, and IFN gamma than the sera of healthy children (P less than 0.001 for sIL-2R, IL-2, and IFN gamma; P less than 0.05 for sCD4), but did not have elevated levels of sCD8. The levels of sIL-2R (P less than 0.05), sCD4 (P less than 0.001), and sCD8 (P less than 0.001) were higher in DHF than in DF on days 3-4 after the onset of fever. The levels of IL-2 and IFN gamma in patients with DHF were highest 1 d before defervescence. There were no significant differences in the levels of sIL-2R, sCD4, sCD8, IL-2, and IFN gamma among grades 1, 2, and 3 of DHF. These results indicate (a) T lymphocytes are activated and produce IL-2 and IFN gamma in vivo during DHF and DF, (b) CD4+ T lymphocytes are activated in DHF and DF, and the level of activation is higher in DHF than in DF, and (c) activation of CD8+ T lymphocytes is evident in DHF, but not in DF.

Adolescent↗
PubMed1992

Association of recombinant soluble IL-6-signal transducer, gp130, with a complex of IL 6 and soluble IL-6 receptor, and establishment of an ELISA for soluble gp130.

IL-6 mediates its pleiotropic functions through two membrane proteins, a ligand-binding molecule (IL-6 receptor, IL-6R) and a non-ligand-binding signal transducer (gp130). Starting with a previously isolated cDNA clone encoding human gp130, recombinant soluble gp130 (sgp130) lacking the transmembrane and cytoplasmic regions was expressed in COS7 cells or CHO cells. sgp130 could associate with a complex of IL-6 and soluble IL-6R (sIL-6R), also lacking transmembrane and cytoplasmic regions. This indicated that extracellular region of gp130 was responsible for the association with IL-6R which was occupied by IL-6. An enzyme-linked immunosorbent assay (ELISA) for the quantitation of sgp130 was established, which was based on the interaction of sgp130 with the complex of IL-6 and sIL-6R and could detect sgp130 as low as 1 ng/ml.

Animals↗
PubMed1991

17 Beta-hydroxysteroid dehydrogenases in human breast tissues: purification and characterization of soluble enzymes and the distribution of particulate and soluble forms in adipose, non-adipose and tumour tissues.

17 Beta-Hydroxysteroid dehydrogenase (17 beta-HSD) is present in multiple forms in human breast tissue. One soluble form, with a molecular weight of approximately 35 kDa, was purified to near homogeneity from whole normal breast tissue. This form catalysed the oxidation of oestradiol and the reduction of oestrone, with NADP+ and NADPH as the preferred coenzymes. Three other soluble forms with higher molecular weights (in the range 50-80 kDa) were isolated. They catalysed the oxidation of oestradiol but not the reduction of oestrone, and all of them had properties very different from those of the low molecular weight enzyme. Activities of 17 beta-HSD were measured in particulate and soluble fractions from normal breast adipose and non-adipose tissues, and from breast tumours obtained from post-menopausal women, in the oxidative direction with NAD+ and NADP+ as coenzymes and in the reductive direction with NADH and NADPH as coenzymes. Particulate fractions from tumours had much higher oxidative and reductive activities than those from normal tissues. Soluble fractions from tumours had higher oxidative activities than those from the normal tissues but similar reductive activities. The major soluble form of 17 beta-HSD in adipose tissue was the 35 kDa enzyme which had both oxidative and reductive activities. In contrast, the majority of the soluble activity in non-adipose tissue was due to enzymes, with molecular weights in the range 50-80 kDa, which had oxidative activity only. The soluble fractions of tumours, like those of non-adipose tissue, contained enzymes with molecular weights in the range 50-80 kDa. In addition, they contained a 35 kDa enzyme with properties different from those of the enzyme with the same molecular weight present in adipose tissue.

17-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Different daily blood glucose control and free insulin levels during treatment with mixtures of soluble and lente or soluble and NPH semisynthetic human insulins.

To compare daily blood glucose and free-insulin profiles after the administration of two different mixtures of semisynthetic human insulins (soluble + lente or soluble + NPH), 8 well-controlled insulin-dependent diabetic patients with identical basal blood glucose levels were studied. At the beginning of the first daily period of study, each subject was connected to an Artificial Pancreas to achieve a standard blood glucose (100 mg/dl); after at least 4 hours of normoglycemia, feed-back control was interrupted and the insulin mixture injected, at 8 p.m. and 8 a.m., at the dose previously optimised but always in the ratio 1:2 (1/3 rapid-acting + 2/3 intermediate-acting insulin). Blood glucose and free-insulin were then monitored for a 24-hour period, starting from 8 p.m. The same observation was repeated for each patient a few days later, only changing the intermediate-acting insulin. After dinner (8.30 p.m.) and after breakfast (8.30 a.m.) mean blood glucose was lower with soluble + NPH mixture, while early in the morning and in the late afternoon better glycaemic control was achieved with soluble + lente. F-IRI showed an almost specular behaviour: lower values soon after mixture injection and higher levels 8-12 hours later were observed with soluble + lente than with soluble + NPH. These data indicate that, at the ratio 1:2, the mixture of short-acting with lente HM insulin differs from the one with NPH not only for a lower activity of soluble insulin but also for a stronger and more prolonged effect of the intermediate preparation. This difference should be carefully taken into account in clinical practice.

Adult↗
PubMed1990

Identification of soluble interleukin-1 binding protein in cell-free supernatants. Evidence for soluble interleukin-1 receptor.

This study describes the identification and characterization of a soluble interleukin-1 (IL-1) binding protein in the conditioned media from Raji human B-lymphoma cells. The soluble IL-1 binding material was isolated by IL-1 affinity chromatography, and treatment with trypsin decreased its ability to bind to IL-1 demonstrating its protein nature. The soluble IL-1 binding protein was specific for IL-1 and was able to discriminate between Il-1 alpha and IL-1 beta in a manner analogous to the membrane-bound Raji IL-1 receptor. The specificity of the IL-1 binding protein was further established in two ways. 1) Cell-free supernatants from Raji "receptor-negative" cells did not contain any IL-1 binding protein, thus ruling out nonspecific interactions between IL-1 and a serum or other protein present in the conditioned medium; and 2) the soluble binding protein inhibited IL-1 binding to Raji cells in a dose-dependent manner. Scatchard analysis of IL-1 beta binding showed the dissociation constant (KD) to be 5.1 nM for the soluble IL-1 binding protein compared with 0.8 nM for the membrane-bound IL-1 receptor. Gel chromatography of the soluble binding protein yielded a major peak of IL-1 binding activity with a molecular mass of 35-45 kDa. The characteristics of the soluble IL-1 binding protein described above are consistent with those of the extracellular binding domain of the membrane-bound Raji IL-1 receptor.

Cell Line↗
PubMed1989

Solubility behavior of narcotic analgesics in aqueous media: solubilities and dissociation constants of morphine, fentanyl, and sufentanil.

The pH dependence of the aqueous solubility of morphine, fentanyl, and sufentanil was investigated at 35 degrees C. Dissociation constants and corresponding pKa' values of the drugs were obtained from measured free-base solubilities (determined at high pH's) and the concentrations of saturated solutions at intermediate pH's. Morphine, fentanyl, and sufentanil exhibited pKa' values of 8.08, 8.99, and 8.51, respectively. Over the pH range of 5 to 12.5 the apparent solubilities are determined by the intrinsic solubility of the free base plus the concentration of ionized drug necessary to satisfy the dissociation equilibrium at a given pH. Consequently, the drug concentrations of saturated aqueous solutions fall off precipitously as the pH is raised and ionization is suppressed. Further, at low pH's the aqueous solubility of morphine increased in a linear fashion with increases in the molar strength of citric acid which was added to acidify the medium, suggesting the formation of a soluble morphine-citrate complex.

Analgesics, Opioid↗
PubMed1992

Particulate and soluble bovine endothelial nitric oxide synthases are structurally similar proteins yet different from soluble brain nitric oxide synthase.

In cultured bovine aortic endothelial cells (BAECs), 95% of the total endothelial nitric oxide (NO) synthase (type III) activity was found in the particulate fraction and only 5% was found in the soluble fraction. The soluble and particulate endothelial NO synthase activities behaved similarly on anion-exchange and gel filtration chromatography, whereas the soluble brain NO synthase (type I) had chromatographic properties different from the type III endothelial NO synthases. We have purified the particulate endothelial NO synthase from cultured and native BAECs using affinity chromatography on 2',5'-ADP Sepharose followed by Superose 6 gel filtration chromatography. Subsequently, monoclonal antibodies were generated against the purified particulate endothelial NO synthase. In protein immunoblotting analyses, crude and partially purified samples of particulate and soluble type III endothelial NO synthase demonstrated a single band at a molecular mass of 135 kDa with monoclonal antibody (MAb) H32. Purified type I soluble brain NO synthase did not cross-react with MAb H32. These data indicate that the soluble and particulate endothelial NO synthase are structurally similar proteins and represent an isozyme that can be distinguished from the brain NO synthase.

Amino Acid Oxidoreductases↗
PubMed1979

Solubility determination of barely aqueous-soluble organic solids.

Solubility determination of organic molecules having very low solubilities is hampered by such problems as slow equilibration during measurement, influence of impurities, and inherent heterogeneity in the energetic content of the crystalline solid. Three approaches to meeting these problems are presented. The first approach involves enhancing the dissolution rate by the addition of a water-immiscible solvent in which the organic solute is more soluble, thereby increasing the surface area available for dissolution. The second method is a combination of experimental data with a group contribution approach that allows the estimation of extremely insoluble solids. This approach involves measurement of the solubility in an organic solvent and calculation of the aqueous solubility from the estimated partition coefficient and the organic solvent data. The third approach is based on using a large excess of the solid and a highly specific analytical determination of the main component. The first two approaches were explored in detail and tested using norethindrone, norethindrone acetate, methyltestosterone, and methyltestosterone acetate.

Kinetics↗
PubMed1989

Predicting the solubility of sulfamethoxypyridazine in individual solvents. I: Calculating partial solubility parameters.

Sulfamethoxypyridazine, a representative model of a drug molecule, is used to test the extended Hansen method for estimating partial solubility parameters of solid compounds. Solubilities are determined in polar and nonpolar solvents. The method provides reasonable partial parameters for the sulfonamide, and it may be useful in obtaining partial parameters for other drug molecules. A four-parameter extended Hansen approach involving proton donor and acceptor parameters is used in fitting the data to a theoretical model. A term, Wh, is introduced as an empirical measure of solute-solvent interactions due to hydrogen bonding. The use of the empirical term Wh allows the researcher to fit experimental solubilities and thus design regression models and equations which provide a reasonable prediction of solubilities of a polar drug in a number of very different solvents. A Flory-Huggins size correction term improves the prediction of sulfamethoxypyridazine solubilities in these irregular solutions.

Chemical Phenomena↗
PubMed1989

Predicting the solubility of sulfamethoxypyridazine in individual solvents. II: Relationship between solute-solvent interaction terms and partial solubility parameters.

In the first paper in the series, an expanded system of parameters was devised to account for orientation and induction effects, and the term Wh was introduced to replace delta 1h delta 2h of the extended Hansen solubility approach. In the present report, a new term, Kh = Wh/delta 1h delta 2h is observed to take on values larger or smaller than unity depending on whether the hydrogen bonded solute-solvent interaction is larger or smaller than predicted by the term delta 1h delta 2h. The acidic delta a and basic delta b solubility parameters are used to represent two parameters, sigma and tau, suggested by Small in his study of proton donor-acceptor properties. The Small equation, including a heat of mixing term for hydrogen bonded species, is shown to be capable of semiquantitative evaluation. A partial molar heat delta H2h of hydrogen bonding is calculated using delta h and Wh terms; delta H2h is found to be correlated with the logarithm of the residual activity coefficient, In alpha R, a term representing strong solute-solvent interaction. The terms Wh, delta H2h, and In alpha 2R may be used to test the deviation from the geometric mean assumed in regular solution theory, and to replace the hydrogen bonding terms of the extended Hansen three-parameter model. The solubility of sulfamethoxypyridazine in 30 solvents is used to test the semiempirical solubility equations. The results are interpreted in terms of partial solubility parameters and the proton donor-acceptor properties of the solvents.

Chemical Phenomena↗
PubMed1975

Improvement of solubility and dissolution rate of poorly water-soluble salicylic acid by a spray-drying technique.

Spray drying techniques have been applied to improve the solubility and dissolution rate of poorly water-soluble salicylic acid. Spray drying of the acid dispersed in acacia solutions resulted in as much as a 50% improvement in the solubility of the product. Solubility improvement was closely related not only to the concentration of acacia but also the amount of amorphous material in the spray-dried products. The heat of solution was inversely related to these parameters. The dissolution rate of spray-dried product was almost instantaneous being about 60 times faster than that of the original powder. A great improvement in the wettability of the spray-dried material seemed to be mainly responsible for the increase of dissolution rate.

Diffusion↗
PubMed1989

Enhancement of the dissolution rates of poorly water-soluble drugs by water-soluble gelatin.

The dissolution behavior of several acidic and basic drugs from kneaded mixtures with water-soluble gelatin have been studied in comparison with that of the drug alone. The results revealed a significant increase of dissolution rate of drugs from kneaded mixtures. The water-soluble gelatin showed little interaction with any of the drugs in solution or in the solid state. Interestingly, the contact angle of the kneaded mixture was remarkably decreased compared with that of the drug powder and was found to be almost the same as that of water-soluble gelatin powder. Thus, the enhanced dissolution rate of the drug caused by water-soluble gelatin was explained by the improvement of wettability of the drug by water.

Chemistry, Pharmaceutical↗
PubMed1989

Resistance of cytolytic lymphocytes to perforin-mediated killing. Murine cytotoxic T lymphocytes and human natural killer cells do not contain functional soluble homologous restriction factor or other specific soluble protective factors.

CTL and NK cells produce a cytolytic pore-forming protein (perforin, cytolysin) localized in their cytoplasmic granules. These cytotoxic cells are resistant to killing mediated by other lymphocytes and by purified perforin. A membrane factor, known as homologous restriction factor (HRF), has been suggested to confer protection to different cell types against both C- and perforin-mediated lysis. The granules of human large granular lymphocytes have been reported to contain, in addition to perforin, a soluble HRF activity that can be eluted from anion-exchange columns at 115 mM NaCl. Here, we report that a soluble HRF activity is absent in the granules or the cytosol of murine CTL and human NK cells. Our data indicate that the inhibition attributed to HRF could be explained by exogenous EDTA added during granule fractionation. EDTA was shown to bind to Mono Q and to elute at 90 to 120 mM NaCl. A second perforin-inhibitory activity was also eluted from such a column. However, it was present in preparations obtained not only from CTL and NK cells, but also from some perforin-susceptible tumor cell lines, indicating that it has nonrestricted distribution and suggesting that it is probably irrelevant to the perforin-protection mechanism. Our results argue against a role for soluble granule HRF or other soluble factors in mediating resistance of cytotoxic lymphocytes against perforin-mediated lysis.

Animals↗
PubMed1992

Increased soluble CD4 and decreased soluble CD8 molecules in patients with Sjögren's syndrome.

PURPOSE: A new enzyme-linked immunosorbent assay for soluble CD4 (sCD4) and soluble CD8 (sCD8) molecules has been developed. We estimated the concentrations of these molecules in patients with Sjögren's syndrome and in patients with systemic lupus erythematosus (SLE) serving as a control population for non-Sjögren's inflammatory disease, since several findings suggestive of an aberration of immunocompetent cells have been reported in these autoimmune diseases. PATIENTS AND METHODS: The study population consisted of 41 patients with Sjögren's syndrome (28 cases of the primary form and 13 cases of the secondary form), 66 patients with SLE, and 43 normal individuals. Serum samples and clinical and laboratory data were collected from each patient and control. Assays of the sCD4 and sCD8 molecules were performed using an enzyme-linked immunosorbent kit developed by T Cell Science Inc., Cambridge, MA. RESULTS: The concentration of sCD4 was significantly increased in patients with both primary and secondary Sjögren's syndrome as compared with that in the control subjects. In contrast, sCD8 was significantly decreased in patients with primary disease but not in patients with secondary disease. A low or high concentration of sCD8 was significantly correlated with the presence of anti-SS-A antibody or hypocomplementemia, respectively. A similar significant correlation was noted between an increased sCD4 concentration and increased serum IgG level. In patients with SLE, the levels of both sCD4 and sCD8 were significantly increased. CONCLUSION: These observations represent the first evidence of an increased level of the sCD4 molecule and a decreased level of the sCD8 molecule and an association with immunologic abnormalities in Sjögren's syndrome. The increased and decreased levels of these soluble molecules observed may play a pathologic role in patients with Sjögren's syndrome.

Adult↗