bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mactinin treatment promotes wound‐healing‐associated inflammation in urokinase knockout mice
Authors: Luikart Sharon D. , Levay‐Young Brett , Hinkel Tim , Shearer Jeffry , Mills Charles , Caldwell Michael D. , Gyetko Margaret R. , Oegema Theodore R. 
Published: April 2006

ABSTRACTMactinin, a 31 kDa fragment from the amino‐terminal end of α‐actinin, is chemotactic for monocytes and can promote monocyte/macrophage maturation. Macrophages are essential for wound healing, in which they play key roles in debridement, angiogenesis, fibroblast proliferation, and collagen metabolism. We have previously determined that urokinase is necessary to form mactinin from extracellular α‐actinin, which may be present at sites of inflammation as a result of cell movement. Thus, urokinase knockout mice are unable to form mactinin and therefore are an ideal model to study mactinin's effects on wound healing. Saline‐ and mactinin‐treated wounds were analyzed in a subcutaneous sponge wound model in both wild‐type and urokinase knockout mice. The wounded urokinase knockout mice had markedly decreased leukocyte infiltration compared with wounded wild‐type mice. In addition, production of the proinflammatory cytokine, interleukin‐12, and of collagen was also decreased in knockouts. Treatment of knockout mice with mactinin resulted in leukocyte infiltration numbers, interleukin‐12 levels, and hydroxyproline measurements similar to those in wild‐type mice. The results suggest that impaired wound healing in urokinase‐deficient mice can be restored by administration of mactinin.
Use of an in vitro model of tissue‐engineered human skin to study keratinocyte attachment and migration in the process of reepithelialization
Authors: Harrison Caroline A. , Heaton Martin J. , Layton Christopher M. , Mac Neil Sheila 
Published: April 2006

ABSTRACTTo produce a stable epidermis, keratinocytes need to be firmly attached to the basement membrane. However, following wounding, keratinocytes are required to develop a migratory phenotype in order to reepithelialize the wound. To investigate some of the issues underlying reepithelialization, we have developed a three‐dimensional in vitro model of tissue‐engineered skin, comprising sterilized human dermis seeded with human keratinocytes and dermal fibroblasts. Using this model, we have shown that the inclusion of fibroblasts within the model increases the stability of keratinocyte attachment. We have also demonstrated that keratinocyte migration occurs most effectively in the absence of a basement membrane and following the inclusion of fibroblasts in the model. In addition, subjecting the keratinocyte layer to mechanical trauma induces a migratory phenotype. We conclude that this three‐dimensional in vitro wound model can be used to increase our understanding of the factors that enhance keratinocyte migration and hence wound healing in vivo.
Effect of Vacuum Assisted Closure® Therapy on early systemic cytokine levels in a swine model
Authors: Kilpadi Deepak V. , Bower Curtis E. , Reade Clifton C. , Robinson Penni J. , Sun You Su , Zeri Richard , Nifong L. Wiley , Wooden William A. 
Published: April 2006

ABSTRACTVacuum Assisted Closure® (V.A.C.®) Therapy has previously been shown to facilitate healing of wounds. However, the physiological mechanism(s) of this treatment modality and its systemic effects require further investigations. The goal of this porcine study was to investigate the effect of V.A.C.® Therapy on the systemic distribution of the inflammatory cytokines interleukin (IL)‐6, IL‐8, IL‐10, and transforming growth factor‐β1. Twelve pigs were each given one full‐thickness excisional wound, using electrocautery. Six of the pigs were treated with V.A.C.® Therapy and six with saline‐moistened gauze. Serum samples were collected immediately after wound creation, and hourly for 4 hours. Samples were analyzed using commercially available enzyme‐linked immunosorbent assay kits. During the initial 4 hours of treatment, V.A.C.® Therapy resulted in earlier and greater peaking of IL‐10 and maintenance of IL‐6 levels compared with saline‐moistened gauze controls, which showed decreased IL‐6 values over the first hour (both at p<0.05). No other treatment‐based differences were detected.
Platelet-Activating Factor-Acetylhydrolase Can Monodeacylate and Inactivate Lipoteichoic Acid
Authors: Seo Ho Seong , Kim Je Hak , Nahm Moon H. 
Published: April 2006

ABSTRACT

Bacterial lipoteichoic acid (LTA) shares a structural motif with platelet-activating factor (PAF). Both molecules are strong inflammatory agents and have a glycerol backbone with two lipid chains at the
sn
-1 and
sn
-2 positions. PAF is normally inactivated by PAF-acetylhydrolase (PAF-AH), a phospholipase A2 (PLA2), which removes a short acyl group at the
sn
-2 position. To investigate whether PAF-AH can similarly degrade LTA, we studied the effects of porcine PLA2, bee venom PLA2, and recombinant human PAF-AH on pneumococcal LTA (PnLTA) and staphylococcal LTA (StLTA). After incubation with a porcine or bee venom PLA2, a large fraction of PnLTA lost 264 Da, which corresponds to the mass of the oleic acid group at the
sn
-2 position. After incubation with recombinant human PAF-AH, PnLTA lost 264 Da; the reduction did not occur when PAF-AH was exposed to Pefabloc SC, an irreversible inhibitor of the PAF-AH active site. Following PAF-AH treatment, PnLTA and StLTA were not able to stimulate mouse RAW 264.7 cells to produce tumor necrosis factor alpha but could stimulate CHO cells expressing human TLR2. This stimulation pattern has been observed with monoacyl PnLTA prepared by mild alkali hydrolysis (22). Taking these data together, we conclude that PAF-AH can remove one acyl chain at the
sn
-2 position of LTA and produce a monoacyl-LTA that is inactive against mouse cells.
Increased Levels ofCandida albicansMannan-Specific T-Cell-Derived Antigen Binding Molecules in Patients with Invasive Candidiasis
Authors: Kosonen Jan , Rantala Arto , Little Colin H. , Lintu Päivi , Harjamäki Pirjo-Riitta , Georgiou George M. , Cone Robert E. , Savolainen Johannes 
Published: April 2006

ABSTRACTIn addition to cytokines, CD4+T cells have been found to secrete soluble, T-cell-derived antigen binding molecules (TABMs). These antigen-specific immunoproteins are thought to have immunoregulatory properties in the suppression of cell-mediated immunity (CMI) because they often associate with interleukin-10 (IL-10) and transforming growth factor beta. Decreased CMI causes susceptibility to infections caused by organisms which are normally nonpathogenic. In this situation, e.g.,Candida albicanssaprophytism may develop into invasive candidiasis. The difficult diagnosis of invasive candidiasis is based on the findings obtained from blood cultures and with tissue biopsy specimens, with some additional diagnostic value gained by the detection ofCandida albicansmannan antigenemia and antimannan antibodies. In the present study,Candida albicansmannan-specific TABM (CAM-TABM) levels in the sera of patients with invasive candidiasis (n= 11),Candidacolonization (n= 11) and noncolonization (n= 10), recurrent vulvovaginal candidiasis (n= 30), and atopic eczema dermatitis syndrome (n= 59) and healthy controls (n= 30) were analyzed. For 14 participants, the effect of mannan stimulation on TABM production and gamma interferon (IFN-γ) and IL-4 mRNA expression by peripheral blood lymphocytes was also studied. It was demonstrated that CAM-TABM production was the highest in patients with invasive candidiasis and that CAM-TABM levels could distinguishCandida-colonized patients from noncolonized patients. In addition, the CAM-TABM level was directly related to mRNA expression for IL-4 but not IFN-γ. These results reinforce the view that TABMs are associated with decreased CMI, immunoregulation, and the T-helper cell 2-type immune response.
One-Step Immunochromatography Assay Kit for Detecting Antibodies to Canine Parvovirus
Authors: Oh Jin-Sik , Ha Gun-Woo , Cho Young-Shik , Kim Min-Jae , An Dong-Jun , Hwang Kyu-Kye , Lim Yoon-Kyu , Park Bong-Kyun , Kang BoKyu , Song Dae-Sub 
Published: April 2006

ABSTRACT
This study was performed to determine the feasibility of using whole serum to detect antibodies to canine parvovirus (CPV) under nonlaboratory conditions and to evaluate the performance characteristics of an immunochromatography assay kit. Precise detection of levels of antibody against CPV in puppies can be used to determine a vaccination schedule, because maternal antibodies frequently result in the failure of protective vaccination, and can also be used to determine the antibody levels of infected puppies. Several methods for the titration of CPV antibodies have been reported, including the hemagglutination inhibition (HI) assay, which is considered the “gold standard.” These methods, however, require intricate and time-consuming procedures. In this study, a total of 386 serum specimens were tested. Compared to the HI assay, the rapid assay had a 97.1% sensitivity and a 76.6% specificity (with a cutoff HI titer of 1:80). This single-step assay could be performed rapidly and easily without special equipment. The kit provides a reliable method for detection of anti-CPV antibody where laboratory support and personnel are limited.
ESAT-6 Peptide Recognition by Bovine CD8
+
Lymphocytes of Naturally Infected Cows in Herds from Southern Italy
Authors: Vitale Fabrizio , Reale Stefano , Petrotta Enrico , Caracappa Santo , Barera Annalisa , La Manna Marco Pio , Macaluso Pasquale , Caccamo Nadia , Dieli Francesco , Vordermeier Hans Martin , Sireci Guido , Salerno Alfredo 
Published: April 2006

ABSTRACT

The aim of this study was to define epitopes of
Mycobacterium bovis
from ESAT-6 (early secretory antigen of 6 kDa) recognized by CD8
+
T lymphocytes from cows naturally infected with
Mycobacterium bovis
. We found that bovine CD8
+
T cells recognized 10 out of 11 ESAT-6 peptides tested.
Occupational exposure to eight organic dusts and respiratory cancer among Finns
Authors: Laakkonen A , Kyyrönen P , Kauppinen T , Pukkala E I 
Published: April 2006

Background:There is inconclusive evidence concerning cancer risks of organic dusts.Aim:The carcinogenic exposures are mainly inhalatory and the authors therefore studied associations between occupational exposure to eight different organic dusts and respiratory cancers in Finland.Methods:The authors followed up a cohort of all economically active Finns born between 1906 and 1945 for 30 million person-years during 1971–95. Incident cases of nasal, laryngeal, and lung cancer and mesotheliomas were identified through a record linkage with the Finnish Cancer Registry. Occupations from the population census in 1970 were converted to exposures to eight organic dusts with a job-exposure matrix (FINJEM). Cumulative exposure (CE) was calculated as a product of prevalence, level, and estimated duration of exposure. Standardised incidence ratios (SIR) and 95% confidence intervals (CI) adjusted for age, period, and social class were calculated for each organic dust using the economically active population as the reference.Results:A total of 20 426 incident cases of respiratory cancer were observed. Slightly increased risk was observed among men exposed to wood dust for nasal cancer (SIR 1.42, 95% CI 0.79 to 2.44). For laryngeal cancer, men exposed to plant dust (mainly grain millers) had a raised SIR in the high exposure class (SIR 3.55, 95% CI 1.30 to 7.72). Men exposed to wood dust had a raised SIR for lung cancer, but only in the low exposure class (SIR 1.11, 95% CI 1.04 to 1.18). Women exposed to wood dust showed an increased SIR for mesotheliomas in the low exposure class (SIR 4.57, 95% CI 1.25 to 11.7) and some excess in the medium exposure category.Conclusions:Exposure to organic dusts is unlikely to be a major risk factor of respiratory cancer. Even exposure to wood dust which is a major exposure in Finland seems to have minor effect for nasal cancer. The authors found suggestive evidence that exposure to grain dust may increase the risk of laryngeal cancer, and some support to the hypothesis that exposure to textile dust, and to plant and animal dust (agricultural dusts) may decrease the risk of lung cancer.
Effects of low-calcium reperfusion and adenosine on diastolic behavior during the transitory systolic overshoot of the stunned myocardium in the rabbit
Authors: González Germán E. , Rodríguez Manuel , Donato Martín , Palleiro Jimena , D'Annunzio Verónica , Morales Celina , Gelpi Ricardo J. 
Published: April 2006

The aims of the present study were to determine whether the transitory systolic overshoot (TSO) that occurs in the early reperfusion (R) of the stunned myocardium is accompanied by diastolic alterations, and to determine whether the R with low Ca2+ Krebs–Henseleit’s solution or with adenosine modifies these alterations. Isolated–isovolumic rabbit hearts were divided in 3 groups (G). G1 (n = 11) was perfused with Krebs–Henseleit's solution, subjected to 15 min of global ischemia and 30 min R; G2 (n = 10) was reperfused during the first 10 min with Krebs–Henseleit's solution [Ca2+] = 1 mmol/L, which was increased in the perfusate to 1.5 mmol/L up to 20 min R and at 2.5 mmol/L from 20 to 30 min R. G3 (n = 12) was perfused with Krebs–Henseleit's solution with adenosine (0.03 μg·kg–1·min –1) from 10 min before ischemia and during all R. Left ventricular (LV) +dP/dtmax (mmHg/s), LV end diastolic pressure (LVEDP, mmHg), and 1 relaxation index (t1/2) were measured in preischemic state, at 30, 50, 60, 70, 90, and 120 s R, and then at 5 and 30 min R. The +dP/dtmax recovered to 621 ± 77 mmHg/s (p > 0.05), 346 ± 31 mmHg/s (p < 0.05 vs. G1), and 533 ± 76 mmHg/s (p > 0.05) from preischemic value of 730 ± 39, 690 ± 32, and 758 ± 57 in G1, G2, and G3, respectively. The LVEDP in G1 and G3 increased early in the R, and it was negatively correlated with the +dP/dtmax (r = –0.63, p = 0.0369; and r = –0.71, p = 0.0090, respectively). The R with low Ca2+ abolished this correlation and attenuated the TSO phase. The correlation between LVEDP and +dP/dtmax in G1 and G3 and the lack of correlation in G2 suggests there are common mechanisms for the systolic and diastolic alterations during the TSO phase that are possibly related to Ca2+ overload but not with the vascular tone.
Dual X-ray absorptiometry model for characterizing water in the human forearm using multiple frequency bioimpedance analysis
Authors: Bartolini Miria E. , Wilson Kyle , Raja Mohan , Raymer Graydon H. , Thompson R. Terry , Webber Colin E. , Moran Gerald R. 
Published: April 2006

The purpose of this study was to develop a method for measuring intracellular (ICW) and extracellular water (ECW) in the human forearm using multiple frequency bioimpedance analysis (MFBIA). The approach was (i) to measure whole-body and forearm fat-free mass using dual X-ray absorptiometry (DXA); (ii) to use these measurements to estimate the fat-free mass (FFM) resistivity in both the forearm and in the whole body; and (iii) to use the ratio of these FFM resistivities to estimate the resistivity in the ICW and ECW compartments of the forearm. To first demonstrate the accuracy of the DXA software in differentiating lean body mass from fat and bone within a volume of tissue, ex-vivo bovine muscle tissue samples (n = 3) were used to approximate the physical properties of the human forearm. It was found that although the human whole-body software overestimates FFM, it was slightly underestimated by the small animal software. Using this technique, DXA measures of FFM were obtained from human volunteers (n = 11; age = 20 ± 5 years; height = 170 ± 12 cm; mass = 64 ± 16 kg). These measures were used in conjunction with MFBIA measures of impedance of the whole body and of the forearm to determine the resistivities of the ICW and ECW compartments of the forearm, namely 375.8 ± 25.2 Ωcm and 55.6 ± 3.7 Ωcm, respectively. These were used in MFBIA equations to calculate the ICW, ECW, and total arm water (TAW) volumes of the human forearm. The calculated TAW and the ECW (± SD) volume fraction (667.29 ± 200.15 mL and 0.169 ± 0.039 mL, respectively) were in agreement with literature values. MFBIA results were compared with those obtained using nuclear magnetic resonance relaxometry (NMRR). MFBIA was performed on 15 subjects before and after an intense maximal handgrip exercise to estimate changes in water volume in muscle. Following exercise, the total and intracellular water of the forearm increased on average by 8% ± 3% and 10% ± 4% (mean ± SD), respectively. In 5 healthy volunteers, MFBIA and NMRR were performed before and after a similar exercise of the forearm muscle. The changes with exercise of intracellular and total arm water volumes as measured by MFBIA were estimated. The percent increases in total water were found to be 9.4% ± 4.2% and 9.4% ± 2.6% and in intracellular water were found to be 10.6% ± 4.6% and 12.0% ± 2.8% (mean ± SD) for NMRR and MFBIA, respectively. The results show that the exercise-induced changes in ICW and TAW determined with the MFBIA model are consistent with those observed with NMRR and radiotracer literature.
A Novel Role of DNA Polymerase η in Modulating Cellular Sensitivity to Chemotherapeutic Agents
Authors: Chen Yih-wen , Cleaver James E. , Hanaoka Fumio , Chang Ching-fang , Chou Kai-ming 
Published: April 2006

Abstract
Genetic defects in polymerase η (pol η; hRad30a gene) result in xeroderma pigmentosum variant syndrome (XP-V), and XP-V patients are sensitive to sunlight and highly prone to cancer development. Here, we show that pol η plays a significant role in modulating cellular sensitivity to DNA-targeting anticancer agents. When compared with normal human fibroblast cells, pol η–deficient cells derived from XP-V patients were 3-fold more sensitive to β-d-arabinofuranosylcytosine, gemcitabine, or cis-diamminedichloroplatinum (cisplatin) single-agent treatments and at least 10-fold more sensitive to the gemcitabine/cisplatin combination treatment, a commonly used clinical regimen for treating a wide spectrum of cancers. Cellular and biochemical analyses strongly suggested that the higher sensitivity of XP-V cells to these agents was due to the inability of pol η–deficient cells to help resume the DNA replication process paused by the gemcitabine/cisplatin-introduced DNA lesions. These results indicated that pol η can play an important role in determining the cellular sensitivity to therapeutic agents. The findings not only illuminate pol η as a potential pharmacologic target for developing new anticancer agents but also provide new directions for improving future chemotherapy regimen design considering the use of nucleoside analogues and cisplatin derivatives. (Mol Cancer Res 2006;4(4):257–65)
Frequent IGF2/H19 Domain Epigenetic Alterations and Elevated IGF2 Expression in Epithelial Ovarian Cancer
Authors: Murphy Susan K. , Huang Zhiqing , Wen Yaqing , Spillman Monique A. , Whitaker Regina S. , Simel Lauren R. , Nichols Teresa D. , Marks Jeffrey R. , Berchuck Andrew 
Published: April 2006

Abstract
Overexpression of the imprinted insulin-like growth factor-II (IGF2) is a prominent characteristic of gynecologic malignancies. The purpose of this study was to determine whether IGF2 loss of imprinting (LOI), aberrant H19 expression, and/or epigenetic deregulation of the IGF2/H19 imprinted domain contributes to elevated IGF2 expression in serous epithelial ovarian tumors. IGF2 LOI was observed in 5 of 23 informative serous epithelial ovarian cancers, but this did not correlate with elevated expression of IGF2 H19 RNA expression levels were also found not to correlate with IGF2 transcript levels. However, we identified positive correlations between elevated IGF2 expression and hypermethylation of CCCTC transcription factor binding sites 1 and 6 at the H19 proximal imprint center (P = 0.05 and 0.02, respectively). Hypermethylation of CCCTC transcription factor sites 1 and 6 was observed more frequently in cancer DNA compared with lymphocyte DNA obtained from women without malignancy (P &lt; 0.0001 for both sites 1 and 6). Ovarian cancers were also more likely to exhibit maternal allele-specific hypomethylation upstream of the imprinted IGF2 promoters when compared with normal lymphocyte DNA (P = 0.004). This is the same region shown previously to be hypomethylated in colon cancers with IGF2 LOI, but this was not associated with LOI in ovarian cancers. Elevated IGF2 expression is a frequent event in serous ovarian cancer and this occurs in the absence of IGF2 LOI. These data indicate that the epigenetic changes observed in these cancers at the imprint center may contribute to IGF2 overexpression in a novel mechanistic manner. (Mol Cancer Res 2006;4(4):283–92)
Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia
Authors: Del Principe Maria Ilaria , Del Poeta Giovanni , Buccisano Francesco , Maurillo Luca , Venditti Adriano , Zucchetto Antonella , Marini Rita , Niscola Pasquale , Consalvo Maria Antonietta Irno , Mazzone Carla , Ottaviani Licia , Panetta Paola , Bruno Antonio , Bomben Riccardo , Suppo Giovanna , Degan Massimo , Gattei Valter , de Fabritiis Paolo , Cantonetti Maria , Lo Coco Francesco , Del Principe Domenico , Amadori Sergio 
Published: April 2006

AbstractThe clinical course of B-cell chronic lymphocytic leukemia (B-CLL) is variable, and novel biologic parameters need to be added to the clinical staging systems to predict an indolent or aggressive outcome. We investigated the 70-kDa zeta-associated protein (ZAP-70), CD38, soluble CD23 (sCD23), and cytogenetics in 289 patients with B-CLL. Both a shorter progression-free survival (PFS) and overall survival (OS) were observed in ZAP-70+ (P < .001), in CD38+ (P < .001) and in sCD23+ patients (P < .001 and P = .013, respectively). ZAP-70+CD38+ or ZAP-70+ patients with an unmutated IgVH status showed both a shorter PFS (P < .001) and OS (P < .001 and P < .001, respectively) as compared with ZAP-70–/CD38– or ZAP-70– patients with mutated IgVH genes. Discordant patients showed an intermediate outcome. Note, ZAP-70+ patients even if CD38– or mutated showed a shorter PFS, whereas ZAP-70– patients even if CD38+ or unmutated had a longer PFS. Furthermore, ZAP-70 positivity was associated with a shorter PFS both within normal karyotype (P < .001) and within the poor-risk cytogenetic subset (P = .02). The predictive value of ZAP-70 expression was confirmed in multivariate analysis. Thus, ZAP-70 protein determined by flow cytometry improves the prognostic significance of cytogenetics and appears to be a better predictor of outcomes than IgVH gene mutational status. On this line, we recommend and are also interested in conducting a prospective randomized trial of early intervention versus observation for ZAP-70+ patients.
The Wingless homolog WNT5A and its receptor Frizzled-5 regulate inflammatory responses of human mononuclear cells induced by microbial stimulation
Authors: Blumenthal Antje , Ehlers Stefan , Lauber Jörg , Buer Jan , Lange Christoph , Goldmann Torsten , Heine Holger , Brandt Ernst , Reiling Norbert 
Published: April 2006

AbstractMicroarray - assisted gene - expression screens of human macrophages revealed WNT5A, a homolog of Wingless, a key regulator of Drosophila melanogaster embryonic segmentation and patterning, to be consistently up-regulated following stimulation with different mycobacterial species and conserved bacterial structures. The expression of WNT5A required Toll-like receptor signaling and NF-κB activation, which identifies a novel induction pathway for a Wingless homolog. We show that human peripheral-blood mononuclear cells express the WNT5A receptor Frizzled-5 (FZD5). Both WNT5A and FZD5 also were detected in granulomatous lesions in the lungs of Mycobacterium tuberculosis–infected patients. Functional studies showed that WNT5A and FZD5 regulate the microbially induced interleukin-12 response of antigen-presenting cells and interferon-γ production by mycobacterial antigenstimulated T cells. Our findings implicate the evolutionarily conserved WNT/Frizzled signaling system in bridging innate and adaptive immunity to infections.