Observation of a Nuclear Recoil Peak at the 100 eV Scale Induced by Neutron Capture.

Coherent elastic neutrino-nucleus scattering and low-mass dark matter detectors rely crucially on the understanding of their response to nuclear recoils. We report the first observation of a nuclear recoil peak at around 112 eV induced by neutron capture. The measurement was performed with a CaWO_{4} cryogenic detector from the NUCLEUS experiment exposed to a ^{252}Cf source placed in a compact moderator. We identify the expected peak structure from the single-γ de-excitation of ^{183}W with 3σ and its origin by neutron capture with 6σ significance. This result demonstrates a new method for precise, in situ, and nonintrusive calibration of low-threshold experiments.

N-terminal region of human chemokine receptor CXCR3: Structural analysis of CXCR3(1-48) by experimental and computational studies.

Our study on the highly charged N-terminal peptide of the human chemokine receptor CXCR3 by spectroscopic methods in solution and by means of molecular dynamics simulations showed that the charge content modulates the intrinsic structural preference of its flexible backbone. Collectively, our findings suggest that the structural organization of a protein should be seen as a part of a continuum in which the ratio between electrostatic and hydrophobic interactions and the intrinsic flexibility are important properties used to optimize the folding. When this ratio changes and the structure is intrinsically flexible, the structural organization of the system moves along the continuum of the possible conformational states. By all this combined information, one can describe the structure of CXCR3(1-48) as an ensemble of conformations. In fact, the peptide shows stretches of negative charges embedded in a flexible sequence which can be used to maximize promiscuous interactions relevant to molecular recognition but globally the peptide appears as a poly-structured globule-like ensemble that is dynamically stabilized by H-bonds. We have approached the study of the most populated ensembles with subset selection to explain our experimental data also by evidencing that the changes into the fraction of charged residues discriminate between dynamically poly-structured states, conceivably because of small free energy barriers existing between the different conformations of CXCR3(1-48). Therefore, the overlap of a highly flexible backbone, negatively charged residues and sites which can be modified by post-translational modifications represent the structural organization that controls the molecular mechanisms underlying the biological functions carried out by CXCR3(1-48).

Functional and structural features of adipokine family.

In the mid-1990s, the interest in adipose tissue was revived by the discovery of leptin. Since then numerous other hormones have been isolated from white adipose tissue that has no longer considered an inert tissue mainly devoted to energy storage but emerged as an active participant in regulating physiologic and pathologic processes, including immunity and inflammation. Adipose tissue produces and releases a variety of proinflammatory and anti-inflammatory factors, including the adipokines, as well as cytokines and chemokines. Proinflammatory molecules produced by adipose tissue have been implicated as active participants in the development of insulin resistance and the increased risk of cardiovascular disease associated with obesity. In contrast, reduced leptin levels might predispose to increased susceptibility to infection caused by reduced T-cell responses in malnourished individuals. Altered adipokine levels have been observed in a variety of inflammatory conditions, although their pathogenic role has not been completely clarified. In this paper we want to review: (i) the role of adipose tissue in different biological processes, (ii) the functional and structural description of all the known adipokines subdivided in different subfamilies, (iii) the adipokine involvement in obesity and cancers, and (iv) the adipokine interactome.

Small bowel obstruction caused by mesh migration. Case report.

INTRODUCTION: Endoscopic hernia repair methods have become increasingly popular over the past 15 years. Nonetheless, there is no consensus regarding an optimal fixation method. Transabdominal sutures and titanium tacks or staples are the most traditional ones. CASE REPORT: We present a case of mechanic small bowel obstruction due to mesh migration occurring one year and a half after incisional hernia repair with polytetrafluoroethylene mesh fixed by spiral tacks. DISCUSSION: Titanium spiral tacks are dangerous because of their sharp components, which can damage organs such as the small intestine, by causing microperforations. The type of prosthesis used has also contributed to the intraluminal migration, since polytetrafluoroethylene mesh is very flexible and poorly integrates in the abdominal wall. CONCLUSION: A prosthesis of a different material combined with a different fixation system such as absorbable tacks, biological glue, or mechanical tacks without sharp components, would have obviated mesh migration.

Changes in the gene expression profile of gastric cancer cells in response to ibuprofen: a gene pathway analysis.

Nonsteroidal anti-inflammatory drugs possess antiproliferative activities that can affect cancer cells. The aim of this study was to examine the antiproliferative effects of ibuprofen on the MKN-45 cell line. Cells were treated with ibuprofen for 24, 48 or 72 h, and cell proliferation was evaluated by cell counting and [(3)H]-thymidine incorporation. Using microarray technology, we studied changes in the gene expression profiles over time after ibuprofen treatment. Ibuprofen induced a dose- and time-dependent reduction in cell number without altering cell viability. Genes involved in the 'biological oxidation' and 'G(1)/S checkpoint' pathways were the most significantly represented at 24 h, whereas genes involved in the 'cell cycle' and 'DNA replication' pathways were represented at 48 and 72 h. Genes associated with the 'apoptosis' pathway were also significantly represented at 72 h. Modulation of the expression of p53 and p53-induced genes (CDKN1A/p21 and GADD45), which are involved in the G(1)/S transition, suggested an effect of ibuprofen on cell-cycle progression. Using flow cytometry, we observed an early block in the G(1) phase of the cell cycle after ibuprofen treatment. In addition, P450 family transcripts were upregulated and intracellular reactive oxygen species (ROS) was increased following 12 h of ibuprofen treatment. Ibuprofen induced ROS, which resulted in cellular alterations that promoted a p53-dependent G(1) blockade. These findings suggest that ibuprofen exerts its antiproliferative actions through cell-cycle control and the induction of apoptosis. Both of these mechanisms appear to be independent of ibuprofen's anti-inflammatory effects.

Simultaneous evaluation of the circulating levels of both Th1 and Th2 chemokines in patients with autoimmune Addison's disease.

BACKGROUND: Chemokines play a key role in the recruitment of the immune cells into the autoimmune process. Thus, the simultaneous evaluation of circulating levels of Th1-related chemokines, such as CX chemokine ligand 10 (CXCL10) and macrophage inflammatory proteins 1α (CCL3/MIP-1α), and Th2-related chemokines, such as macrophage inflammatory proteins 1 ß (CCL4/MIP-1ß) could be useful in the approach to some autoimmune diseases, including autoimmune Addison's disease (AAD). AIM: To evaluate plasmatic levels of MIP-1α, MIP-1ß, CXCL10 and adrenocortical antibodies in patients with AAD under treatment with corticosteroids. PATIENTS AND METHODS: Twelve women and 5 men (group 1) were divided in 2 subgroups: 9 subjects with isolated AAD (group 1a) and 8 with AAD associated with chronic autoimmune thyroiditis (group 1b). MIP-1α, MIP- 1ß and CXCL10 were evaluated in the serum of all patients and in 20 healthy controls, using a system for microarray suspension. RESULTS: The levels of MIP-1α, MIP-1ß and CXCL10 resulted significantly increased vs controls (p<0.001). An inverse significant correlation between the serum levels of MIP- 1ß and the duration of the disease was observed. CONCLUSION: High levels of MIP-1α and MIP-1ß associated with increased levels of CXCL10 in AAD seem to indicate a role of these chemokines in the autoimmune pathology of adrenal gland through the recruitment in loco of Th1 and Th2 cells. The simultaneous measurement of Th1-related chemokines (CXCL10 and MIP-1α) and of Th2-related chemokine MIP-1ß in the serum of patients with AAD would sustain a novel preliminary hypothesis on the immune microenvironment of chronic autoimmune inflammation within adrenal glands.

Laparoscopic pancreaticoduodenectomy for tumors of the head of pancreas; 10 cases for a single center experience.

OBJECTIVE: The tumors of the head of the pancreas are one of the leading causes of cancer-related death in Western countries. The current gold standard for these tumors is a Whipple procedure. This procedure did not change in its surgical steps since when it was initially introduced in 1935. More recently, a laparoscopic approach with similar outcomes has been described. The aim of this paper is to describe the laparoscopic surgical technique performed in our unit, reporting single center postoperative outcomes. PATIENTS AND METHODS: From the 1st January 2013 to the 31st December 2015 a database was created. Data about patients who underwent a laparoscopic pancreaticoduodenectomy (LPD) were collected prospectively. All patients were preoperatively assessed with blood samples, tumor markers, CT chest abdomen and pelvis and/or MRI pancreas. Only patients with specific characteristics were considered eligible for an LPD: performance status 0, body mass index (BMI) less than 30 kg/m2, a small neoplastic lesion (< 3.5 cm) confined to the pancreas, the absence of infiltrated organs and/or blood vessels (T1 or T2). Postoperative data and complications were recorded and described according to the Clavien-Dindo classification and the international study group of pancreatic surgery definitions. RESULTS: In a time interval of 36 months, 31 patients with an initially considered resectable pancreatic cancer were referred. 11 patients were found to have metastasis during the preoperative workout. Only 10 patients were considered eligible for a LPD. Six of them were men (60%). The mean BMI was 25.01 kg/m2 (19.6-29.8). 5 patients, who underwent to LPD did not have any comorbidities. An overall 50% of all patients were jaundice at the time of diagnosis with a mean bilirubin level of 181.3 µmol/L (119.7-307.8). All patients with a direct bilirubin greater than 250 µmol/L underwent a preoperative percutaneous biliary drainage. In the majority of the LPD performed (50%), the histology reported a pancreatic adenocarcinoma. Other postoperative histology described were: IPMN (20%), ampullar neoplasia (20%) and neuroendocrine tumor (10%). Neo-adjuvant chemotherapy was never considered indicated. The reported postoperative complications were: 1 anastomotic bleeding, 2 pancreatic fistula, 1 infected intra-abdominal collection and 1 delay gastric emptying. The pancreatic fistulas were considered grade A and grade B. One fatality after LPD occurred because of an uncontrollable, diffuse severe hemorrhagic gastritis associated with a GJ anastomosis bleeding in the POD 25. The mean hospital stay was 12.3 days (8-25). The mean operative time was 224 min (170-310). There were no intraoperative complications. The main intraoperative blood loss was 220 ml (180-400) and intraoperative blood transfusions were not required. The resection margins were negative (R0) in 100% of cases and the mean lymph nodes harvested were 24 (18-40). The LPD is still a not common practice. Our results are comparable with those reported in literature about the open technique. These remarkable surgical outcomes are probably related to the extremely careful preoperative patient selection performed. The indication for a laparoscopic vs. an open pancreaticoduodenectomy was based on a CT scan pancreas performed less than 30 days before the planned date of surgery and a careful preoperative assessment. A low complication rate and a relative short stay in hospital were associated to a good quality of life in the early postoperative period and an early referral for postoperative chemotherapy. Good clinical outcomes were associated with outstanding oncological results. CONCLUSIONS: Laparoscopic pancreaticoduodenectomy is a feasible surgical procedure. Remarkable oncological and surgical outcomes can be achieved with a morbidity and mortality rate in line with the data reported by the large series of open procedures.

Eritrodisestesia palmoplantar tras tratamiento perioperatorio con quimioterapia / Palmoplantar erythrodysesthesia after perioperative treatment with chemotherapy

La eritrodisestesia palmoplantar es una reacción adversa que se asocia a la administración de docetaxel y fluoropirimidinas. La actividad de la enzima dihidropirimidina deshidrogenasa (DPD) determina la tasa de catabolismo del 5-Fluorouracilo (5-FU) y está sujeta a variabilidad interindividual y polimorfismo genético. Por tanto, los pacientes con deficiencia de DPD presentan un mayor riesgo de toxicidad. Presentamos el caso de un paciente tratado con docetaxel, oxaliplatino y 5-FU (esquema FLOT) que presentó toxicidad cutánea moderada y del que se sospechó deficiencia de DPD.(AU)

Palmoplantar erythrodysesthesia is an adverse event associated with the administration of docetaxel and fluoropyrimidines. The activity of the enzyme dihydropyrimidine dehydrogenase (DPD) determines the rate of catabolism of 5-Fluorouracil (5-FU) and is subject to interindividual variability and genetic polymorphism. Therefore, patients with DPD deficiency present an increased risk of toxicity. We present the case of a patient treated with docetaxel, oxaliplatin and 5-FU (FLOT scheme) who presented moderate skin toxicity and who was suspected of DPD deficiency.(AU)

Classification and comparison of capillary columns by determination of the solution enthalpy of polar and non polar probes.

The behaviour and separation characteristics of capillary columns containing different stationary phases (bonded methyl- and methylphenylsiloxanes and polyglycols, and carbon layer and porous polymer) were classified and compared by measuring the values of the solution enthalpy DeltaHs of n-alkanes and 1-alcohols at various temperatures. The difference in DeltaHs values between straight-chain 1-alcohols and n-alkanes with the same number of carbon atom (DeltaDeltaHs) does not change with changing temperature when gas-liquid partition stationary phases are used, but depends on the column composition and polarity and therefore permits to evaluate the influence of polarity on the solute-solvent interaction. The trend of the DeltaDeltaHs values is correlated with that of the DeltaC parameter and with the McReynolds' polarity constants.

Prediction of theoretical plate number in isothermal gas chromatographic analysis on capillary columns.

A method for the prediction of the efficiency of gas chromatographic analysis in isothermal conditions by using experimental data of 1-alcohols and n-alkanes measured on capillary columns filled with polar and non-polar stationary phases in isothermal and isobaric conditions is described. The theoretical plate height trend indicates the change of separation efficiency as a function of inlet pressure and column temperature. By evaluating the variation of the diffusion coefficients of the analysed compounds into the mobile and stationary phase it is possible to predict the column efficiency and the number of theoretical plates at any temperature.

Polymerase chain reaction-based detection of circulating melanoma cells as an effective marker of tumor progression. Melanoma Cooperative Group.

PURPOSE: Reverse transcriptase (RT) polymerase chain reaction (PCR) with multiple markers has been demonstrated to be highly sensitive in detecting circulating cells from patients with malignant melanoma (MM). We evaluated the clinical significance of the presence in peripheral blood of specific PCR-positive mRNA markers as an expression of circulating melanoma cells. PATIENTS AND METHODS: Total cellular RNA was obtained from the peripheral blood of 235 patients with either localized (n = 154) or metastatic (n = 81) melanoma. We performed RT-PCR using tyrosinase, p97, MUC18, and MelanA/MART1 as gene markers. The PCR products were analyzed by gel electrophoresis and Southern blot hybridization. In addition, 20 healthy subjects and 21 patients with nonmelanoma cancer were used as negative controls. RESULTS: Although detected at various levels among assessable patients, each mRNA marker was significantly correlated with disease stage. A significant correlation with disease stage was demonstrated for patients who were positive to all four markers (P < .0001) or to at least three markers (P < .001). Univariate analysis showed a significant correlation between risk of recurrence (evaluated in stage I, II, and III patients) and increasing number of PCR-positive markers (P = .0002). Logistic regression multivariate analysis indicated that each single marker (except tyrosinase) and, more especially, the presence of four PCR-positive markers remained statistically independent prognostic factors for tumor progression. CONCLUSION: Our data establish the existence of a significant correlation among clinical stages, tumor progression, and presence of circulating melanoma-associated antigens in peripheral blood of MM patients. Preliminary assessment of a subset of patients with a higher risk of recurrence needs longer follow-up and further studies to define the role of RT-PCR in monitoring MM patients.

Detection of occult melanoma cells in paraffin-embedded histologically negative sentinel lymph nodes using a reverse transcriptase polymerase chain reaction assay.

PURPOSE: Detection of occult metastasis before the development of clinical disease could allow more accurate staging, appropriate follow-up procedures, and adjuvant therapies in patients with malignant melanoma (MM). The sentinel lymph node (SLN) has been proposed as a reliable predictor of metastatic disease in the lymphatic basin draining the primary melanoma. In this study, we screened both paraffin-embedded SLNs and peripheral-blood (PB) samples from MM patients at various stage of disease using a multimarker reverse transcriptase polymerase chain reaction (RT-PCR) assay. The prognostic significance of the presence of PCR-positive markers was also evaluated. PATIENTS AND METHODS: Total RNA was obtained from paraffin-embedded SLN sections and PB samples of 75 MM patients. RT-PCR was performed using tyrosinase and MelanA/MART1 as melanoma-associated markers. Radiolabeled PCR products were analyzed on denaturing polyacrylamide gels. RESULTS: Good sensitivity of the RT-PCR assay on archival tissues was demonstrated after comparison of RT-PCR results on frozen and paraffin-embedded SLNs from 16 MM patients. Significant correlation between the disease stage and marker expression in both PB and SLN samples was observed; the highest value was for patients who were positive for both markers in SLN (P =.006). Progression of disease was significantly associated with the total number of PCR-positive markers in both PB (P =.034) and SLN (P =.001) samples. CONCLUSION: Although sensitivity is lowered by the use of paraffin-embedded specimens, our data indicate that RT-PCR analysis of serial sections from archival SLNs may be helpful in improving detection of occult micrometastases, thus improving staging of patients with melanoma.

Effect of injected sample amount on the shape of chromatographic peaks under condition of linear partition isotherm.

In a previous paper a model function was tested in order to approximate the peak shape obtained on non-polar column by injecting different compounds. The simulation of the symmetrical or non-symmetrical shape of gas chromatographic peaks was satisfactory. In this paper, the influence of the amount of injected substance was investigated at different values of inlet pressure and carrier gas velocity, in order to evaluate the relative contribution to the total peak area and shape of the symmetrical distribution due to partition phenomena and of the non-symmetrical and tailing distribution due to adsorption-desorption kinetics. The effect of the molecular mass and of the chain length of compounds belonging to the homologous series of 1-alcohols and n-alkanes on the adsorption phenomena was evaluated.

Prognostic value of serum biological markers in patients with hepatocellular carcinoma.

PURPOSE: Prognosis of patients with hepatocellular carcinoma (HCC) is assessed by using indexes based on clinical and instrumental parameters. The Cancer of the Liver Italian Program (CLIP) staging system combines the Child-Pugh classification with tumor size, portal invasion, and alpha-fetoprotein and predicts the outcome of HCC patients more precisely than the Okuda staging system. Serum levels of a number of biological variables have been found to be increased in patients with HCC and are associated with different outcomes. Our aims in this study were to test the prognostic role of the serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble interleukin-2 receptor (sIL-2R), interleukin 6 (IL-6), and anti-p53 and to assess whether the addition of any of the above serum markers could further improve the predictive ability of the CLIP score. EXPERIMENTAL DESIGN: Serum levels of sICAM-1, sIL-2R, IL-6, and anti-p53 were assayed in 80 patients with HCC and correlated with their outcomes. Nonparametric procedures were applied to test correlations between serum sICAM-1, sIL-2R, IL-6, anti-p53, and other prognostic factors. For survival analyses, the product-limit method, log-rank test, and Cox proportional hazards model were applied. RESULTS: Only serum levels of sIL-2R correlated with survival, which was longer for patients with lower values (< or =950 units/ml). However, with multivariate analysis sIL-2R did not confirm its predictive role when tested with the CLIP score as a covariate, with a hazard of death of 1.51 (95% confidence interval, 0.76-3.01). CONCLUSIONS: Serum levels of sICAM-1, sIL-2R, IL-6, and anti-p53 are not useful as prognostic factors for HCC in clinical practice. They do not improve the predictive ability of the CLIP score.

Azidothymidine and interferon-alpha in vitro effects on hematopoiesis: protective in vitro activity of IL-1 and GM-CSF.

Preclinical and clinical studies with an azidothymidine (AZT)/interferon-alpha (IFN-alpha) combination resulted in a marked and synergistic antiretroviral activity. The administration of the two drugs in HIV-seropositive patients affected with Kaposi's sarcoma, however, induced neutropenia, thrombocytopenia, and, in some cases, anemia. A possible means to improve the therapeutic index of AZT and/or IFN-alpha in AIDS patients could be the addition of hematopoietic growth factors. In vitro activity of cytokines on the hematotoxicity of the AZT-IFN-alpha association has not yet been studied. We have performed an in vitro study to evaluate the toxicity of AZT, IFN-alpha, or both on peripheral blood hematopoietic progenitors (CFU-GM and BFU-E) and to assess the activity of interleukin 1 (IL-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), or both in modifying AZT-IFN-alpha hematotoxicity. Results indicate that AZT, IFN-alpha, and combinations of the two have a dose-dependent inhibitory effect on the in vitro growth of peripheral blood hematopoietic progenitors. Combinations of AZT and IFN-alpha inhibited CFU-GM and BFU-E proliferation in an additive manner. Neither IL-1 nor GM-CSF alone was able to induce a significant reduction of AZT-induced damage. Only the addition to the cultures of both cytokines partially curbed the antiproliferative activity of AZT at low dosages.

Serum erythropoietin increase in patients receiving adjuvant therapy with 5-fluorouracil and leucovorin.

High-dose anticancer drugs have been shown to induce an increase in serum erythropoietin (sEpo) levels not mediated by hypoxia. In this study, sEpo was assessed in seven patients who had been administered a course of 5-day leucovorin-modulated 5-fluorouracil (5-FU-LV) as an adjuvant therapy after the removal of colon cancer. During this study, the mean hemoglobin (Hb) concentration stayed at a constant level, peripheral blood (PB) reticulocytes showed an early, sharp decline, and sEpo levels progressively increased for 15 days after the start of chemotherapy. These results appear to indicate that the increase in sEpo, which was not related to anemia, may have followed from the administration of a cytotoxic drug at doses used in routine, clinical practice.

In vitro synergistic inhibition of human bone marrow hemopoietic progenitor growth by a 3'-azido-3'-deoxy-thymidine, 2',3'-dideoxycytidine combination.

In vitro growth of human normal bone marrow granulocyte-macrophage colony forming units (CFU-GMs) and erythroid burst forming units (BFU-Es) was dose-dependently inhibited by 3'-azido-3'deoxythymidine (AZT) (from 0.1 microM to 4 microM) and 2',3'-dideoxycytidine (ddC) (from 0.01 microM to 1.0 microM). These ranges included minimum in vitro inhibitory concentrations to HIV-1 and concentrations corresponding to plasma level achievable in vivo. A synergistic inhibitory effect, statistically highly significant, was observed when combinations of the two drugs were added to cultures. This severe in vitro toxicity of ddC and the synergistic toxicity of AZT-ddC combinations on hemopoietic progenitor cells should be considered when the two drugs are administered in concurrent or alternating regimens.

GPX4 and GPX7 over-expression in human hepatocellular carcinoma tissues.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is still one of the most fatal cancers. Hence, it needs to identify always new putative markers to improve its diagnosis and prognosis. The selenium is an essential trace mineral implicated as a key factor in the early stage of cancer and exerts its biological function through the selenoproteins. In the last years our group has been studying the involvement of some selenoproteins in HCC. However, no many data are reported in literature about the correlation between HCC and the glutathione peroxidases (GPXs), both selenium and non selenium-containing GPXs. In this paper we have evaluated the GPX4 and GPX7 expression in some paraffin-embedded tissues from liver biopsy of patients with hepatitis C virus (HCV)-related cirrhosis and HCC by immunohistochemistry and RT-qPCR analysis. Our results evidenced that i) GPX4 and GPX7 had a statistically significant over-expression in HCC tissues compared to cirrhotic counterparts used as non tumor tissues, and ii) their expression was higher in grade III HCC tissues with respect to grade I-II samples. Therefore, we propose to use GPX4 and GPX7 as possible markers for improving HCC diagnosis/prognosis.

S1P-induced airway smooth muscle hyperresponsiveness and lung inflammation in vivo: molecular and cellular mechanisms.

BACKGROUND AND PURPOSE: Sphingosine-1-phosphate (S1P) has been shown to be involved in the asthmatic disease as well in preclinical mouse experimental models of this disease. The aim of this study was to understand the mechanism(s) underlying S1P effects on the lung. EXPERIMENTAL APPROACH: BALB/c, mast cell-deficient and Nude mice were injected with S1P (s.c.) on days 0 and 7. Functional, molecular and cellular studies were performed. KEY RESULTS: S1P administration to BALB/c mice increased airway smooth muscle reactivity, mucus production, PGD2 , IgE, IL-4 and IL-13 release. These features were associated to a higher recruitment of mast cells to the lung. Mast cell-deficient Kit (W) (-sh/) (W) (-sh) mice injected with S1P did not display airway smooth muscle hyper-reactivity. However, lung inflammation and IgE production were still present. Treatment in vivo with the anti-CD23 antibody B3B4, which blocks IgE production, inhibited both S1P-induced airway smooth muscle reactivity in vitro and lung inflammation. S1P administration to Nude mice did not elicit airway smooth muscle hyper-reactivity and lung inflammation. Naïve (untreated) mice subjected to the adoptive transfer of CD4+ T-cells harvested from S1P-treated mice presented all the features elicited by S1P in the lung. CONCLUSIONS AND IMPLICATIONS: S1P triggers a cascade of events that sequentially involves T-cells, IgE and mast cells reproducing several asthma-like features. This model may represent a useful tool for defining the role of S1P in the mechanism of action of currently-used drugs as well as in the development of new therapeutic approaches for asthma-like diseases.

Interferon-alpha inhibits CFU-GM mobilization following chemotherapy and G-CSF administration.

Changes in routine hematologic data and in circulating granulocyte-macrophage colony-forming units (CFU-GM) during granulocyte colony-stimulating factor (G-CSF) administration were evaluated in non-small cell lung carcinoma (NSCLC) patients treated with a combination of 5-fluorouracil (5-FU) and cisplatin (DDP) with and without the addition of interferon-alpha (IFN-alpha). The patterns of leukocyte changes following chemotherapy plus G-CSF were similar in both the IFN-alpha-inclusive and the IFN-alpha-devoid courses. However, the twofold increase in CFU-GM observed in patients receiving chemotherapy plus G-CSF was completely absent following the course including IFN-alpha. The activity of G-CSF on the hematologic pattern is seemingly affected by its combination with IFN-alpha treatment. Mechanisms of the possible in vivo interaction among IFNs and hematopoietic growth factors remain to be elucidated.