bluuebunny/crossref_metadata_2025_split huggingface dataset:
The human cationic host defense peptide LL-37 mediates contrasting effects on apoptotic pathways in different primary cells of the innate immune system
Authors: Barlow Peter G , Li Yuexin , Wilkinson Thomas S , Bowdish Dawn M E , Lau Y Elaine , Cosseau Celine , Haslett Christopher , Simpson A John , Hancock Robert E W , Davidson Donald J 
Published: June 2006

Abstract
The human cathelicidin LL-37 is a cationic host defense peptide (antimicrobial peptide) expressed primarily by neutrophils and epithelial cells. This peptide, up-regulated under conditions of inflammation, has immunomodulatory and antimicrobial functions. We demonstrate that LL-37 is a potent inhibitor of human neutrophil apoptosis, signaling through P2X7 receptors and G-protein-coupled receptors other than the formyl peptide receptor-like-1 molecule. This process involved modulation of Mcl-1 expression, inhibition of BID and procaspase-3 cleavage, and the activation of phosphatidylinositol-3 kinase but not the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway. In contrast to the inhibition of neutrophil apoptosis, LL-37 induced apoptosis in primary airway epithelial cells, demonstrating alternate consequences of LL-37-mediated modulation of apoptotic pathways in different human primary cells. We propose that these novel immunomodulatory properties of LL-37 contribute to peptide-mediated enhancement of innate host defenses against acute infection and are of considerable significance in the development of such peptides and their synthetic analogs as potential therapeutics for use against multiple antibiotic-resistant infectious diseases.
Mucosal IL-8 and TGF-β recruit blood monocytes: evidence for cross-talk between the lamina propria stroma and myeloid cells
Authors: Smythies Lesley E , Maheshwari Akhil , Clements Ronald , Eckhoff Devin , Novak Lea , Vu Huong L , Mosteller-Barnum L Meg , Sellers Marty , Smith Phillip D 
Published: June 2006

Abstract
The lamina propria of the gastrointestinal mucosa contains the largest population of mononuclear phagocytes in the body, yet little is known about the cellular mechanisms that regulate mononuclear cell recruitment to noninflamed and inflamed intestinal mucosa. Here, we show that intestinal macrophages do not proliferate. We also show that a substantial proportion of intestinal macrophages express chemokine receptors for interleukin (IL)-8 and transforming growth factor-β (TGF-β), and a smaller proportion expresses receptors for N-formylmethionyl-leucyl-phenylalanine and C5a, but, surprisingly, they do not migrate to the corresponding ligands. In contrast, autologous blood monocytes, which express the same receptors, do migrate to the ligands. Blood monocytes also migrate to conditioned medium (CM) derived from lamina propria extracellular matrix, which we show contains IL-8 and TGF-β that are produced by epithelial cells and lamina propria mast cells. This migration is specific to IL-8 and TGF-β, as preincubation of the stroma-CM with antibodies to IL-8 and TGF-β significantly blocked monocyte chemotaxis to the stromal products. Together, these findings indicate that blood monocytes are the exclusive source of macrophages in the intestinal mucosa and underscore the central role of newly recruited blood monocytes in maintaining the macrophage population in noninflamed mucosa and in serving as the exclusive source of macrophages in inflamed mucosa.
Moderate antiangiogenic activity by local, transgenic expression of endostatin in Rip1Tag2 transgenic mice
Authors: Schaffhauser Birgit , Veikkola Tanja , Strittmatter Karin , Antoniadis Helena , Alitalo Kari , Christofori Gerhard 
Published: June 2006

Abstract
Many previous reports have demonstrated that systemic administration of endostatin (ES), a proteolytic cleavage product of collagen type XVIII and an endogenous angiogenesis inhibitor, represses tumor angiogenesis in different preclinical tumor models with varying efficacy. For example, systemic delivery of recombinant ES to rat insulin promoter 1 (Rip1)T-antigen 2 (Tag2)-transgenic mice, a mouse model of pancreatic β-cell carcinogenesis, has repressed tumor angiogenesis efficiently and with it, tumor growth. Here, we report that the transgenic expression of ES in Rip1ES-transgenic mice only interferes moderately with tumor growth in Rip1Tag2;Rip1ES double-transgenic mice. Tumor incidence is not reduced by the local expression of ES, and tumor outgrowth and progression to tumor malignancy are only retarded slightly. A significant effect of local ES expression on tumor angiogenesis is only apparent during the early stages of tumor development, where less angiogenic hyperplastic lesions are observed. Although efficiently produced and secreted by transgenic β cells, locally expressed ES appears to be sequestered in the microenvironment, and its systemic levels are not increased. The results indicate that the antiangiogenic functions of ES critically depend on the mode of delivery and the site of expression: although its systemic application represses tumor angiogenesis and tumor growth efficiently, locally expressed ES appears to be less effective, and hence, additional mechanisms of solubilization or activation of latent ES seem to be required. These results have important implications about the modes of delivery used in antiangiogenic, therapeutic strategies, which are based on the antiangiogenic activities of ES.
Tumor and lymph node lymphangiogenesis—impact on cancer metastasis
Authors: Tobler Nadja E , Detmar Michael 
Published: June 2006

Abstract
The extent of lymph node (LN) metastasis is a major determinant for the staging and the prognosis of most human malignancies and often guides therapeutic decisions. Although the clinical significance of LN involvement is well documented, little has been known about the molecular mechanisms that promote tumor spread via lymphatic vessels to sentinel and distal LN and beyond. However, recent discoveries have identified novel lymphatic-specific markers, and the newly discovered lymphangiogenesis factors vascular endothelial growth factor-C (VEGF-C) and VEGF-D were found to promote tumor-associated lymphatic vessel growth in mouse tumor models, leading to enhanced tumor spread to sentinel LN. Our recent findings indicate that VEGF-A also acts as a potent tumor lymphangiogenesis factor that promotes lymphatic tumor spread. VEGF-A overexpressing primary tumors induced sentinel LN lymphangiogenesis even before metastasizing and maintained their lymphangiogenic activity after metastasis to draining LN. Our recent studies showed that primary human melanomas that later metastasized were characterized by increased lymphangiogenesis and that the degree of tumor lymphangiogenesis can serve as a novel predictor of LN metastasis and overall patient survival, independently of tumor thickness. Tumor lymphangiogenesis also significantly predicted the presence of sentinel LN metastases at the time of surgical excision of the primary melanoma. Together, these findings suggest that tumor lymphangiogenesis actively contributes to cancer dissemination, that blockade of lymphatic vessel growth might inhibit tumor metastasis to LN, and that the extent of tumor-associated lymphangiogenesis could serve as a novel, prognostic parameter for the metastatic risk of human cancers.
The source of APRIL up-regulation in human solid tumor lesions
Authors: Mhawech-Fauceglia P , Kaya G , Sauter G , McKee T , Donze O , Schwaller J , Huard B 
Published: June 2006

Abstract
Abundant mRNA expression for a proliferation-inducing ligand (APRIL) from tumor necrosis factor (TNF) family is observed in many solid tumors. Here, we analyzed in situ the cellular source of APRIL in human solid tumors with anti-APRIL antibodies. In most cases, neutrophils present in the tumor stroma constituted the main source of APRIL. In cutaneous lesions such as melanoma or basal cell carcinoma, tumor-adjacent keratinocytes also produced APRIL. APRIL production by tumor cells themselves was a rare event, only observed in urothelial bladder cancer and squamous cell carcinoma. Detailed analysis revealed that APRIL dissociated from producing cells, and secreted APRIL was retained in the tumor lesions. A direct binding onto tumor cells via heparan sulfate proteoglycans (HSPG) was observed in in vitro experiments and confirmed in situ. Taken together, our analysis indicates a potential role for HSPG/APRIL interactions in the development of solid tumors.
The use of hydroxyapatite-coated CAD-CAM femoral components in adolescents and young adults with inflammatory polyarthropathy
Authors: McCullough C. J. , Remedios D. , Tytherleigh-Strong G. , Hua J. , Walker P. S. 
Published: June 2006

Between June 1991 and January 1995, 42 hydroxyapatite-coated CAD-CAM femoral components were inserted in 25 patients with inflammatory polyarthropathy, 21 of whom had juvenile idiopathic arthritis. Their mean age was 21 years (11 to 35). All the patients were reviewed clinically and radiologically at one, three and five years. At the final review at a mean of 11.2 years (8 to 13) 37 hips in 23 patients were available for assessment. A total of four femoral components (9.5%) had failed, of which two were radiologically loose and two were revised. The four failed components were in patients aged 16 years or less at the time of surgery. Hydroxyapatite-coated customised femoral components give excellent medium- to long-term results in skeletally-mature young adults with inflammatory polyarthropathy. Patients aged less than 16 years at the time of surgery have a risk of 28.5% of failure of the femoral component at approximately ten years.
The incidence of deep prosthetic infections in a specialist orthopaedic hospital
Authors: Phillips J. E. , Crane T. P. , Noy M. , Elliott T. S. J. , Grimer R. J. 
Published: June 2006

The Control of Infection Committee at a specialist orthopaedic hospital prospectively collected data on all episodes of bacteriologically-proven deep infection arising after primary hip and knee replacements over a 15-year period from 1987 to 2001. There were 10 735 patients who underwent primary hip or knee replacement. In 34 of 5947 hip replacements (0.57%) and 41 of 4788 knee replacements (0.86%) a deep infection developed. The most common infecting micro-organism was coagulase-negative staphylococcus, followed by Staphylococcus aureus, enterococci and streptococci. Of the infecting organisms, 72% were sensitive to routine prophylactic antimicrobial agents. Of the infections, 29% (22) arose in the first three months following surgery, 35% between three months and one year (26), and 36% (27) after one year. Most cases were detected early and treated aggressively, with eradication of the infection in 96% (72). There was no significant change in the infection rate or type of infecting micro-organism over the course of this study. These results set a benchmark, and importantly emphasise that only 64% of peri-prosthetic infections arise within one year of surgery. These results also illustrate the advantages of conducting joint replacement surgery in the isolation of a specialist hospital.
Low tibial osteotomy for varus-type osteoarthritis of the ankle
Authors: Tanaka Y. , Takakura Y. , Hayashi K. , Taniguchi A. , Kumai T. , Sugimoto K. 
Published: June 2006

In this retrospective study we have assessed the results of low tibial valgus osteotomy for varus-type osteoarthritis of the ankle and its indications. We performed an opening wedge osteotomy in 25 women (26 ankles). The mean follow-up was for eight years and three months (2 years 3 months to 17 years 11 months). Of the 26 ankles, 19 showed excellent or good clinical results. Their mean scores for pain, walking, and activities of daily living were significantly improved but there was no change in the range of movement. In the ankles which were classified radiologically as stage 2 according to our own grading system, with narrowing of the medial joint space, and in 11 as stage 3a, with obliteration of the joint space at the medial malleolus only, the joint space recovered. In contrast, such recovery was seen in only two of 12 ankles classified as stage 3b, with obliteration of the joint space advancing to the upper surface of the dome of the talus. Low tibial osteotomy is indicated for varus-type osteoarthritis of stage 2 or stage 3a.
Computer navigation of the acetabular component
Authors: Spencer J. M. F. , Day R. E. , Sloan K. E. , Beaver R. J. 
Published: June 2006

Our aim was to assess the intra- and inter-observer reliability in the establishment of the anterior pelvic plane used in imageless computer-assisted navigation. From this we determined the subsequent effects on version and inclination of the acetabular component. A cadaver model was developed with a specifically-designed rod which held the component tracker at a fixed orientation to the pelvis, leaving the anterior pelvic plane as the only variable. Eight surgeons determined the anterior pelvic plane by palpating and registering the bony landmarks as reference points. The exact anterior pelvic plane was then established by using anatomically-placed bone screws as reference points. The difference between the surgeons was found to be highly significant (p < 0.001). The variation was significantly larger for anteversion (sd 9.6°) than for inclination (sd 6.3°). The present method for registering pelvic landmarks shows significant inaccuracy, which highlights the need for improved methods of registration before this technique is considered to be safe.
Arthrodesis versus Mayo resection
Authors: Grondal L. , Broström E. , Wretenberg P. , Stark A. 
Published: June 2006

In a prospective randomised study 31 patients were allocated to either arthrodesis or Mayo resection of the first metatarsophalangeal joint as part of a total reconstruction of the rheumatoid forefoot. Of these, 29 were re-examined after a mean of 72 months (57 to 80), the Foot Function Index was scored and any deformity measured. Load distribution was analysed using a Fscan mat in 14 cases, and time and distance were measured in 12 of these patients using a 3D Motion system. We found excellent patient satisfaction and a significant, lasting reduction of the Foot Function Index, with no statistically significant differences between the groups. There were no significant differences in recurrence of the deformity, the need for special shoes, gait velocity, step length, plantar moment, mean pressure or the position of the centre of force under the forefoot. The cadence was higher and the stance phase shorter in the fusion group. These results suggest that a Mayo resection may be an equally good option for managing the first metatarsophalangeal joint in reconstruction of the rheumatoid forefoot.
Management of complex tibial and femoral nonunion using the Ilizarov technique, and its cost implications
Authors: Patil S. , Montgomery R. 
Published: June 2006

We reviewed 78 femoral and tibial nonunions treated between January 1992 and December 2003. Of these, we classified 41 in 40 patients as complex cases because of infection (22), bone loss (6) or failed previous surgery (13). The complex cases were all treated with Ilizarov frames. At a mean time of 14.1 months (4 to 38), 39 had healed successfully. Using the Association for the Study and Application of the Methods of Ilizarov scoring system we obtained 17 excellent, 14 good, four fair and six poor bone results. The functional results were excellent in 14 patients, good in 14, fair in two and poor in two. A total of six patients were lost to follow-up and two had amputations so were not evaluated for final functional assessment. All but two patients were very satisfied with the results. The average cost of treatment to the treating hospital was approximately £30 000 per patient. We suggest that early referral to a tertiary centre could reduce the morbidity and prolonged time off work for these patients. The results justify the expense, but the National Health Service needs to make financial provision for the reconstruction of this type of complex nonunion.
Gold-Labeled Nanoparticle-Based Immunoresonance Scattering Spectral Assay for Trace Apolipoprotein AI and Apolipoprotein B
Authors: Jiang Zhiliang , Sun Shuangjiao , Liang Aihui , Huang Wenxin , Qin Aimiao 
Published: June 2006

AbstractBackground: Apolipoprotein AI (ApoAI) and ApoB are risk indicators of cardiovascular disease. We describe the use of immunoresonance scattering to measure the ApoAI and ApoB in serum.Methods: We used a trisodium citrate method to prepare 9.0-nm gold nanoparticles labeled with goat anti-human ApoAI and ApoB antibodies. The immune reaction between gold-labeled antibodies and antigens took place in Na2HPO4-NaH2PO4 buffer solution (pH 6.4 for ApoAI and pH 6.0 for ApoB) in the presence of 75 g/L polyethylene glycol (PEG). We used a transmission electron microscope to observe the shape of the gold nanoparticles. Results were compared with those obtained by immunoturbidimetric methods. Twenty-five human serum samples were assayed by the immunoresonance scattering assay preset with the data indicated and by an immunoturbidimetric assay.Results: The presence of PEG greatly enhanced the intensity of resonance-scattering peaks at 560 nm. The intensity (ΔI) was proportional to concentration at 0.00833–0.3333 mg/L ApoAI and 0.00197–0.1972 mg/L ApoB. The detection limits were 2.04 and 0.96 μg/L for ApoAI and ApoB, respectively. The results for human serum samples were in agreement with those obtained with an immunoturbidimetric method. Linear regression analysis revealed a correlation coefficient, slope, and intercept of 0.915, 0.966, and 68.53 mg/L, respectively, for ApoAI and 0.919, 0.996, and 15.46 mg/L for ApoB.Conclusion: This method showed high sensitivity and good selectivity for quantitative determination of ApoAI and ApoB in human serum, with satisfactory results.
Calculation of Bioavailable and Free Testosterone in Men: A Comparison of 5 Published Algorithms
Authors: de Ronde Willem , van der Schouw Yvonne T , Pols Huibert AP , Gooren Louis JG , Muller Majon , Grobbee Diederick E , de Jong Frank H 
Published: June 2006

Abstract
Background: Estimation of serum concentrations of free testosterone (FT) and bioavailable testosterone (bioT) by calculation is an inexpensive and uncomplicated method. We compared results obtained with 5 different algorithms.
Methods: We used 5 different published algorithms [described by Sodergard et al. (bioTS and FTS), Vermeulen et al. (bioTV and FTV), Emadi-Konjin et al. (bioTE), Morris et al. (bioTM), and Ly et al. (FTL)] to estimate bioT and FT concentrations in samples obtained from 399 independently living men (ages 40–80 years) participating in a cross-sectional, single-center study.
Results: Mean bioT was highest for bioTS (10.4 nmol/L) and lowest for bioTE (3.87 nmol/L). Mean FT was highest for FTS (0.41 nmol/L), followed by FTV (0.35 nmol/L), and FTL (0.29 nmol/L). For bioT concentrations, the Pearson correlation coefficient was highest for the association between bioTS and bioTV (r = 0.98) and lowest between bioTM and bioTE (r = 0.66). FTL was significantly associated with both FTS (r = 0.96) and FTV (r = 0.88). The Pearson correlation coefficient for the association between FTL and bioTM almost reached 1.0. Bland-Altman analysis showed large differences between the results of different algorithms. BioTM, bioTE, bioTV, and FTL were all significantly associated with sex hormone binding globulin (SHBG) concentrations.
Conclusion: Algorithms to calculate FT and bioT must be revalidated in the local setting, otherwise over- or underestimation of FT and bioT concentrations can occur. Additionally, confounding of the results by SHBG concentrations may be introduced.
Repair of Infarcted Myocardium by an Extract of Geum japonicum with Dual Effects on Angiogenesis and Myogenesis
Authors: Li Ming , Yu Cheuk Man , Cheng Lei , Wang Mei , Gu Xuemei , Lee Ka Ho , Wang Tian , Sung Yn Tz , Sanderson John E 
Published: June 2006

Abstract
Background: It has become apparent recently that cardiac myocytes can divide after myocardial infarction, a circumstance that challenges the orthodox view that myocytes may be terminally differentiated. Replacement of the necrosed heart tissue by newly regenerated functional myocardium is a therapeutic ideal, but attempts to reconstitute functional myocardia and coronary vessels have been less successful.
Methods: We isolated a fraction containing 5 compounds from the Chinese herb Geum japonicum, which stimulates the processes of angiogenesis and cardiomyogenesis. We investigated these dual properties in both ex vivo and in vivo systems.
Results: We observed that this bioactive fraction displayed favorable dual actions on early angiogenesis and cardiomyogenesis in acute myocardial infarction in an animal model. Our results demonstrated that application of this bioactive fraction showed pronounced effects on limiting infarct size by 35%–45%, stimulating early development of new blood vessels in 24 h, and regenerating myocardium, replacing ∼49% of the total infarction volume after 2 weeks. Echocardiographic studies demonstrated marked improvement of left ventricular function within 2 days after infarction, and the improvement was sustained for &gt;1 month.
Conclusions: The properties of this bioactive fraction appear to be entirely novel and represent a new approach for the treatment of ischemic heart disease.
Genomic Rearrangements at the BRCA1 Locus in Spanish Families with Breast/Ovarian Cancer
Authors: de la Hoya Miguel , Gutiérrez-Enríquez Sara , Velasco Eladio , Osorio Ana , de Abajo Ana Sanchez , Vega Ana , Salazar Raquel , Esteban Eva , Llort Gemma , Gonzalez-Sarmiento Rogelio , Carracedo Angel , Benítez Javier , Miner Cristina , Díez Orland , Díaz-Rubio Eduardo , Caldes Trinidad 
Published: June 2006

Abstract
Background: Large genomic rearrangements (LGRs) account for a substantial proportion of the BRCA1 disease-causing changes, or variations, identified in families with hereditary breast/ovarian cancer [HB(O)C]. Great differences in the spectrum and prevalence of BRCA1 LGR have been observed among populations. Here we report the first comprehensive analysis of BRCA1 LGRs conducted in Spain.
Methods: We used multiplex ligation-dependent probe amplification (MLPA) to screen for BRCA1 LGRs in the index case individuals of 384 HB(O)C families who previously tested negative for BRCA1 and BRCA2 point variations, small insertions, and deletions. An alternative set of MLPA probes, long-range PCR, and real-time PCR were used to confirm positive results.
Results: We have identified 8 different BRCA1 rearrangements (del exon 1–24, del exon 8–13, del exon 11–15, del exon 14, dup exon 19–20, dup exon 20, exon 21–22 amplification, and del exon 23–24). With the exception of del exon 8–13, they are novel alterations. Overall, BRCA1 LGRs explain 1.4% of the Spanish HB(O)C families, and they account for 8.2% of all BRCA1 pathogenic variations identified in our study population. BRCA1 genetic variants affecting hybridization of commercially available MLPA probes are very rare in our population.
Conclusions: Screening for BRCA1 LGRs should be mandatory in Spanish HB(O)C families. A high proportion of country-specific rearrangements are scattered along the gene. MLPA is a robust method to screen for LGRs in our population. MLPA analysis of positive samples with an alternative set of probes, together with long-range PCR and real-time PCR, is a feasible approach to confirm results in cases in which LGR breakpoints have not been characterized.