The functional characterization of interleukin-10 receptor expression on human natural killer cells

Human natural killer (NK) cells are large granular lymphocytes that constitutively express functional forms of the interleukin-2 receptor (IL-2R) and lyse tumor and virally infected cells without prior sensitization. NK cells with high density expression of CD56 (CD56bright) express the high affinity IL-2R and proliferate in response to low (picomolar) concentrations of IL-2. CD56dim NK cells express the intermediate affinity IL-2R and demonstrate enhanced cytotoxic activity without proliferation in response to high (nanomolar) concentrations of IL-2. In the present study, we characterized IL-10R expression on human NK cells and the functional consequences of IL-10 binding directly to highly purified subsets of CD56bright and CD56dim NK cells. Binding studies using 125I-IL-10 indicated that resting human NK cells constitutively express the IL-10 receptor protein at a surface density of approximately 90 receptor sites per cell, with a kd of approximately 1 nmol/L. Alone, IL-10 did not induce proliferation of CD56bright or CD56dim NK cell subsets. However, at low concentrations (0.5 to 5 ng/mL), IL-10 significantly augmented IL-2-induced proliferation of the CD56bright NK cell subset mediated via the high-affinity IL-2R. In the absence of IL-2, IL-10 was able to induce significant NK cytotoxic activity against NK-resistant tumor cell targets in both subsets of NK cells in a dose-dependent fashion. Furthermore, the combination of IL-10 and IL-2 had an additive effect on NK cytotoxic activity, whereas that of IL-10 and IL-12 did not. Production of interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor by IL-2-activated NK cells was also significantly enhanced by IL-10. Neither resting nor activated human NK cells appear to produce human IL-10 protein. In summary, NK cells constitutively express the IL-10R protein in low density, and the functional consequences of IL-10 binding directly to human NK cell subsets appear to be stimulatory and dose-dependent. In contrast to its direct effects on human T cells and monocytes/macrophages, IL-10 potentiates cytokine production by human NK cells.     

Effects of a High Dose,Aglycone-Rich Soy Extract on Prostate-Specific Antigen and Serum Isoflavone Concentrations in Men With Localized Prostate Cancer

The efficacy and safety of consuming high-dose isoflavone supplements for prostate cancer is not clear. A double-blind, placebo controlled, randomized trial was conducted in 53 men with prostate cancer enrolled in an active surveillance program. The treatment group consumed a supplement containing 450 mg genistein, 300 mg daidzein, and other isoflavones daily for 6 mo. Prostate-specific antigen (PSA) was measured in both groups at baseline, 3 mo, and 6 mo, and serum concentrations of genistein, daidzein, and equol were assessed at baseline and 6 mo in the treatment group. Following the completion of the 6-mo double-blind study, men were enrolled in a 6-mo open label trial with the same isoflavone-rich supplement, and PSA was measured at 3 and 6 mo. PSA concentrations did not change in either group after 6 mo or after 12 mo when the open-label study was included. The 6 mo serum concentrations of genistein and daidzein (39.85 and 45.59 μmol/l, respectively) were significantly greater than baseline values and substantially higher than levels previously reported in other studies. Equol levels did not change. Although high amounts of aglycone isoflavones may result in significantly elevated serum concentrations of genistein and daidzein, these dietary supplements alone did not lower PSA levels in men with low-volume prostate cancer.     

Influence of maternal labor time on delta-aminolevulinate dehydratase enzyme activity and markers of oxidative stress in newborns

Abstract

The purpose is to determine markers of oxidative stress related to the longer and shorter duration of labor (DOL) of pregnant women in the umbilical cord blood of neonates, not yet studied. Blood samples from the umbilical cord were collected from pregnant women with normal delivery and classified according to DOL in two groups: a group with DOL less than 310?min (n?=?33) and a group with DOL greater than or equal to 310?min (n?=?35). The oxidative stress parameters were analyzed by the quantification of thiobarbituric acid reactive substances (TBARS), nitrate/nitrite (NOx), protein thiol groups (P-SH) and non-protein (NP-SH), vitamin C and plasma iron reduction capacity (FRAP), in addition to the activity of the enzyme delta-aminolevulinate dehydratase (δ-ALA-D). The activity of the δ-ALA-D enzyme was shown to be decreased in longer DOL, however, the oxidant parameters and antioxidants were higher in the longer DOL, with the exception of NP-SH that was lower. The longer maternal DOL time is related to the alteration of δ-ALA-D enzyme activity and other parameters in neonates, suggesting an increase in the passage of maternal oxidative markers by umbilical cord blood.     

Conduire les premières consultations pour obésité en médecine générale. De l’analyse d’une demande à une proposition d’un suivi pour obésité: points forts et pièges à éviter

The quality of healthcare support about obese patients needs to customize rightly the basics of the healthcare plan. The challenges of the first consultations, for the general practitioner and his/her patient are even more important as they engage usually on a long term relationship. The therapeutic management of obese patients cannot be summed up as an energy imbalance between inputs and expenditures. The involved elements in this process are multiple and subtle. There are errors to avoid in order keeping off an impairment of the care relationship for a long time.     

长梗南五味子化学成分的研究

从长梗南五味子(Kadsura longepedunculata)根中分离出一个新化合物,经光谱和化学方法证明为南五内酯酸(kadsulactoneacid,I),同时还分离得到5个已知化合物:南五内酯(I)、(+)-安五脂素(II)、二氢愈疮木脂素(IV)、d-表加巴辛(V)和β-谷甾醇(VI)。     

Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques [see comments]

Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro.     

Two cases of Kallmann syndrome associated with empty sella

Kallmann syndrome (KS) is a developmental disease characterized by the association of isolated hypogonadotropic hypogonadism and anosmia/hyposmia. We report an unusual presentation of two females with KS and empty sella. These females, aged at 20 and 29-year-old, presented primary amenorrhea with prepubertal estradiol and low gonadotropin levels. No other significant clinical signs were observed. Empty sella was observed on MRI in both cases. Sequencing of FGFR1 gene, recently implicated in autosomal form of KS, was performed and one splicing mutation (IVS14 + 1G > A) was identified in one patient.