IgE-mediated histamine release from nasal mucosa is inhibited by SLPI (secretory leukocyte protease inhibitor) to the level of spontaneous release.

The secretory leukocyte protease inhibitor (SLPI) is a low-molecular-weight inhibitor of proteases, such as elastase and cathepsin G which are released from leukocytes during phagocytosis. The purpose of this study was to determine whether or not SLPI is able to inhibit IgE-mediated histamine release. Nasal mucosa from 11 test subjects without atopic disposition was used for this in vitro study. We found that SLPI inhibited histamine release in a dose-dependent way but was without influence on the spontaneous release

Secretory leukocyte protease inhibitor in punch biopsies from human colonic mucosa.

Secretory leukocyte protease inhibitor (SLPI) is a well-known protease inhibitor. Its function is thought to be protease/protease-inhibitor balance. Free proteolytic activity, mainly pancreatic elastase, anionic trypsin and granulocytic elastase, has been demonstrated in faecal extracts from patients with ulcerative colitis. We wanted to verify that SLPI is actually secreted from normal human colonic mucosa. Also, we wanted to ascertain whether studies of SLPI secretion based on punch biopsies were dependent on biopsy area or on biopsy circumference. Normal colonic mucosa was sampled during surgery for colonic cancer. A total of 36 samples from four patients were used. Mucosa preparation was carried out using a punch biopsy technique, and samples of 3, 4 and 6 mm diameter were used. All media contained SLPI at varying concentrations. When expressed in terms of the sample area, the secretion per millimetre-squared seemed to decrease with increasing area. When calculated as secretion per circumference, secretion seemed to be constant. In conclusion, SLPI was secreted from normal human colonic mucosa. The SLPI secretion seemed dependent on the circumference of the biopsy rather than on the area of the biopsy

The presence of elafin, SLPI, IL1-RA and STNFalpha RI in head and neck squamous cell carcinomas and their relation to the degree of tumour differentiation.

Biopsy samples of head and neck carcinomas were investigated with regard to elafin, secretory leukocyte protease inhibitor (SLPI), interleukin 1-receptor antagonist [(IL)1-RA] and soluble tumour necrosis factor alpha receptor antagonist (STNFalpha RI). SLPI and elafin are serine protease inhibitors produced in the serous cells of the upper respiratory airways and in the keratinocytes, respectively. We have now found the presence of elafin and SLPI in squamous cell carcinomas of the upper respiratory tract (tonsillar, hypopharyngeal, tongue, mouth floor, gingival and laryngeal cancer). Significantly higher amounts of SLPI and elafin are present in well-differentiated and moderately differentiated tumours than in poorly differentiated tumours (p < 0.0001 and p < 0.0015). Tumour necrosis factor-alpha and IL-1beta have been shown to stimulate the production of SLPI and elafin. Since these cytokines can both be difficult to detect, we chose to study their inhibitors, STNFalpha RI and IL1-RA, instead. IL1-RA was expressed in highly differentiated tumours as well as in poorly differentiated ones. No significant difference was seen between the groups. STNFalpha RI was only found in very small amounts, sparsely distributed in the tumours, and was not related to the degree of differentiation

The Homogeneity of Interstellar Oxygen in the Galactic Disk

We present an analysis of high resolution HST Space Telescope Imaging Spectrograph (STIS) observations of O I 1356 and H I Lyman-alpha absorption in 36 sight lines that probe a variety of Galactic disk environments and include paths that range over nearly 4 orders of magnitude in f(H_2), over 2 orders of magnitude in mean sight line density, and that extend up to 6.5 kpc in length. Consequently, we have undertaken the study of gas-phase O/H abundance ratio homogeneity using the current sample and previously published Goddard High-Resolution Spectrograph (GHRS) results. Two distinct trends are identified in the 56 sight line sample: an apparent decrease in gas-phase oxygen abundance with increasing mean sight line density and a gap between the mean O/H ratio for sight lines shorter and longer than about 800 pc. The first effect is a smooth transition between two depletion levels associated with large mean density intervals; it is centered near a density of 1.5 cm^-3 and is similar to trends evident in gas-phase abundances of other elements. Paths less dense than the central value exhibit a mean O/H ratio of log_10 (O/H) = -3.41+/-0.01 (or 390+/-10 ppm), which is consistent with averages determined for several long, low-density paths observed by STIS (Andre et al. 2003) and short low-density paths observed by FUSE (Moos et al. 2002). Sight lines of higher mean density exhibit an average O/H value of log_10 (O/H) = -3.55+/-0.02 (284+/-12 ppm). The datapoints for low-density paths are scattered more widely than those for denser sight lines, due to O/H ratios for paths shorter than 800 pc that are generally about 0.10 dex lower than the values for longer ones.Comment: 33 pages, including 8 figures and 4 tables; accepted for publication in ApJ, tentatively in Oct 200

A GLIMPSE into the Nature of Galactic Mid-IR Excesses

We investigate the nature of the mid-IR excess for 31 intermediate-mass stars that exhibit an 8 micron excess in either the Galactic Legacy Infrared Mid-Plane Survey Extraordinaire or the Mid-Course Space Experiment using high resolution optical spectra to identify stars surrounded by warm circumstellar dust. From these data we determine projected stellar rotational velocities and estimate stellar effective temperatures for the sample. We estimate stellar ages from these temperatures, parallactic distances, and evolutionary models. Using MIPS [24] measurements and stellar parameters we determine the nature of the infrared excess for 19 GLIMPSE stars. We find that 15 stars exhibit Halpha emission and four exhibit Halpha absorption. Assuming that the mid-IR excesses arise in circumstellar disks, we use the Halpha fluxes to model and estimate the relative contributions of dust and free-free emission. Six stars exhibit Halpha fluxes that imply free-free emission can plausibly explain the infrared excess at [24]. These stars are candidate classical Be stars. Nine stars exhibit Halpha emission, but their Halpha fluxes are insufficient to explain the infrared excesses at [24], suggesting the presence of a circumstellar dust component. After the removal of the free-free component in these sources, we determine probable disk dust temperatures of Tdisk~300-800 K and fractional infrared luminosities of L(IR)/L(*)~10^-3. These nine stars may be pre-main-sequence stars with transitional disks undergoing disk clearing. Three of the four sources showing Halpha absorption exhibit circumstellar disk temperatures ~300-400 K, L(IR)/L(*)~10^-3, IR colors K-[24]< 3.3, and are warm debris disk candidates. One of the four Halpha absorption sources has K-[24]> 3.3 implying an optically thick outer disk and is a transition disk candidate.Comment: 17 figures. Accepted for publication in Ap

Interferon (IFN)-γ-Inducible Protein-10: Association with Histological Results, Viral Kinetics, and Outcome during Treatment with Pegylated IFN-α2a and Ribavirin for Chronic Hepatitis C Virus Infection

BackgroundWe investigated associations between interferon (IFN)-γ-inducible protein (IP)-10 and liver histological results, viral kinetic response, and treatment outcome in patients infected with hepatitis C virus (HCV) genotypes 1-4 MethodsPlasma IP-10 was monitored before, during, and after treatment with pegylated IFN-α2a and ribavirin in 265 HCV-infected patients ResultsIn univariate analyses, a low baseline IP-10 level was significantly associated with low baseline viral load, rapid viral response (RVR), a sustained viral response (SVR), body mass index <25 kg/m2, and less-pronounced fibrosis, inflammation, and steatosis (for HCV genotypes other than 3). When the results of the univariate analyses were included in multivariate analyses, a low plasma IP-10 level, low baseline viral load, and genotype 2 or 3 infection were independent predictors of an RVR and SVR. IP-10 levels decreased 6 weeks into treatment and remained low in patients with an SVR. By contrast, plasma levels of IP-10 rebounded in patients who had detectable HCV RNA after the completion of treatment. Using cutoff IP-10 levels of 150 and 600 pg/mL for predicting an SVR in patients infected with HCV genotype 1 yielded a specificity and sensitivity of 81% and 95%, respectively ConclusionBaseline IP-10 levels are predictive of the response to HCV treatmen

IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection

Plasma from 173 patients with HCV genotype 1 infection was analyzed for IP-10 levels prior to treatment with pegylated interferon-α-2a and ribavirin. Significantly lower IP-10 levels were observed in patients achieving a rapid viral response (RVR) (P &lt; .0001), even in those with body mass index (BMI) ≥ 25 kg/m2 (P = .004) and with baseline viral load ≥ 2 million IU/mL (P = .001). Similarly, significantly lower IP-10 levels were observed in patients obtaining a sustained viral response (SVR) (P = .0002), including those having higher BMI (P &lt; .05), higher viral load (P = .0005), and both higher BMI and viral load (P &lt; .03). In multivariate logistic regression analyses, a low IP-10 value was independently predictive of both RVR and SVR. A baseline cutoff IP-10 value of 600 pg/mL yielded a negative predictive value (NPV) of 79% (19/24) for all genotype 1-infected patients, which was comparable with that observed using a reduction in HCY-RNA by at least 2 logs after 12 weeks of therapy (NPV 86%; 19/22); by combining the two, 30 of 38 patients (NPV 79%) potentially could have been spared unnecessary therapy. In patients having both higher BMI and viral load, cut-off levels of 150 and 600 pg/mL yielded a positive predictive value (PPV) of 71% and NPV of 100%, respectively. In conclusion, pretreatment IP-10 levels predict RVR and SVR in patients infected with HCV genotype 1, even in those with higher BMI and viral load. A substantial proportion of the latter patients may achieve SVR in spite of unfavorable baseline characteristics if their pretreatment IP-10 level is low. Thus, pretreatment IP-10 analysis may prove helpful in decision-making regarding pharmaceutical intervention.</p

IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection

Plasma from 173 patients with HCV genotype 1 infection was analyzed for IP-10 levels prior to treatment with pegylated interferon-α-2a and ribavirin. Significantly lower IP-10 levels were observed in patients achieving a rapid viral response (RVR) (P &lt; .0001), even in those with body mass index (BMI) ≥ 25 kg/m2 (P = .004) and with baseline viral load ≥ 2 million IU/mL (P = .001). Similarly, significantly lower IP-10 levels were observed in patients obtaining a sustained viral response (SVR) (P = .0002), including those having higher BMI (P &lt; .05), higher viral load (P = .0005), and both higher BMI and viral load (P &lt; .03). In multivariate logistic regression analyses, a low IP-10 value was independently predictive of both RVR and SVR. A baseline cutoff IP-10 value of 600 pg/mL yielded a negative predictive value (NPV) of 79% (19/24) for all genotype 1-infected patients, which was comparable with that observed using a reduction in HCY-RNA by at least 2 logs after 12 weeks of therapy (NPV 86%; 19/22); by combining the two, 30 of 38 patients (NPV 79%) potentially could have been spared unnecessary therapy. In patients having both higher BMI and viral load, cut-off levels of 150 and 600 pg/mL yielded a positive predictive value (PPV) of 71% and NPV of 100%, respectively. In conclusion, pretreatment IP-10 levels predict RVR and SVR in patients infected with HCV genotype 1, even in those with higher BMI and viral load. A substantial proportion of the latter patients may achieve SVR in spite of unfavorable baseline characteristics if their pretreatment IP-10 level is low. Thus, pretreatment IP-10 analysis may prove helpful in decision-making regarding pharmaceutical intervention.</p

PHASED VARIANTS IMPROVE DLBCL MINIMAL RESIDUAL DISEASE DETECTION AT THE END OF THERAPY

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