bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropathologic and neuroinflammatory activities of HIV‐1‐infected human astrocytes in murine brain
Authors: Dou Huanyu , Morehead Justin , Bradley Jennifer , Gorantla Santhi , Ellison Brent , Kingsley Jeff , Smith Lynette M. , Chao Wei , Bentsman Galina , Volsky David J. , Gendelman Howard E.
Published: May 2006

The balance between astrocyte and microglia neuroprotection and neurotoxicity defines the tempo of neuronal dysfunction during HIV‐1‐associated dementia (HAD). Astrocytes maintain brain homeostasis and respond actively to brain damage by providing functional and nutritive neuronal support. In HAD, low‐level, continuous infection of astrocytes occurs, but the functional consequences of thisinfection are poorly understood. To this end, human fetal astrocytes (HFA) and monocyte‐derived macrophages (MDM) were infected with HIV‐1DJV and HIV‐1NL4‐3 (neurotropic and lymphotropic strains respectively) and a pseudotyped Vesicular Stomatitis Virus (VSV/HIV‐1NL4‐3) prior to intracranial injection into the basal ganglia of severe combined immunodeficient mice. Neuropathological and immunohistochemical comparisons for inflammatory and neurotoxic activities were performed amongst the infected cell types at 7 or 14 days. HIV‐1‐infected MDM induced significant increases in Mac‐1, glial fibrillary acidic protein, ionized calcium‐binding adapter molecule 1, and proinflammatory cytokine RNA and/or protein expression when compared with HSV/HIV‐1‐ and HIV‐1‐infected HFA and sham‐operated mice. Levels of neuron‐specific nuclear protein, microtubule‐associated protein 2, and neurofilament antigens were reduced significantly in the brain regions injected with human MDM infected with HIV‐1DJV or VSV/HIV‐1. We conclude that HIV‐1 infection of astrocytes leads to limited neurodegeneration, underscoring the early and active role of macrophage‐driven neurotoxicity in disease. © 2006 Wiley‐Liss, Inc.
Tobacco smoking, NAT2 acetylation genotype and breast cancer risk
Authors: Lissowska Jolanta , Brinton Louise A. , Zatonski Witold , Blair Aaron , Bardin‐Mikolajczak Alicja , Peplonska Beata , Sherman Mark E. , Szeszenia‐Da̧browska Neonila , Chanock Stephen , García‐Closas Montserrat
Published: May 2006

The role of active and passive cigarette smoking in breast cancer etiology remains controversial. Using data from a large population‐based case‐control study in Poland (2386 cases, 2502 controls) conducted during 2000–2003, we examined the associations between active and passive smoking overall and for different age categories. We also evaluated differences in risk by estrogen receptor (ER) and progesterone receptor (PR) status in tumors, and the potential modification of the smoking association by N‐acetyl transferase 2 (NAT2) genotype. Women ever exposed to passive smoking at home or at work had a risk of breast cancer similar to those never exposed to active or passive smoking (OR (95%CI) = 1.11 (0.85–1.46), and no trends were observed with increasing hours/day‐years of passive smoking exposure. Active smoking was associated with a significant increase in risk only among women younger than 45 years of age (OR (95%CI) = 1.95 (1.38–2.76); 1.15 (0.93–1.40); 0.91 (0.77–1.09) for <45, 45–55 and >55 years of age, respectively; p‐heterogeneity <0.001 for <45 vs. >55 years) and prevailed for both ER+ and ER− tumors. The smoking association among women <45 years was stronger for current than former smokers, and a significant trend was observed with duration of smoking (p = 0.04). NAT2 slow vs. rapid/intermediate acetylation genotype was not related to breast cancer risk (0.99 (0.87–1.13)), and did not significantly modify the smoking relationships. In conclusion, our data indicate that passive smoking is not associated with breast cancer risk; however, active smoking might be associated with an increased risk for early onset breast cancers. © 2006 Wiley‐Liss, Inc.
Mutations within Wnt pathway genes in sporadic colorectal cancers and cell lines
Authors: Suraweera Nirosha , Robinson James , Volikos Emmanuoil , Guenther Thomas , Talbot Ian , Tomlinson Ian , Silver Andrew
Published: May 2006

Wnt signaling pathway activation via mutation of genetic components, commonly adenomatous polyposis coli (APC), has a major role in colorectal cancer (CRC). Most components have not been assessed for mutation in sporadic CRC. We have analyzed AXIN2, CK1α, DKK1, GSK‐3β, SOX17, LRP6 and PPP2R1B, β‐catenin and APC in a collection of sporadic CRCs (n = 47) and CRC cell lines (CLs; n = 26). The CRC set was enriched for microsatellite unstable cancers (MSI+, 30%, 14/47). Somatic mutation was not found in CK1α, DKK1, LRP6, β‐catenin or GSK‐3β; but heterozygous frame‐shift mutations, and an in‐frame deletion mutation were detected in exon 7 of AXIN2 (CRCs, 11%, 5/47; CLs, 8%, 2/26). Our data refute a previous suggestion that a CRC‐related mutational hot‐spot occurred in the Huntington elongation A subunit TOR (HEAT) repeat 2 of PPP2R1B; this “hotspot” is, more likely, a rare germline polymorphism. An early investigation proposing a high mutational frequency in HEAT repeat 13 was not substantiated. A heterozygous SOX17 mutation (L194P) was also found in a cell line. APC gene mutations were identified in 64% (30/47) of cancers and 7% of these (2/30) had an additional mutation in another Wnt gene. Overall, 70% (33/47) of CRCs had a somatic mutation in a Wnt pathway gene. The number of tumors containing such a mutation was not significantly higher in MSI+ (57%, 8/14) compared to MSI− (76%, 25/33) cancers (p = 0.3, Fisher's exact test); APC mutation was significantly increased in the MSI− subgroup (p = 0.02, Fisher's exact test). Further, mutational screening of other Wnt pathway genes is warranted. © 2006 Wiley‐Liss, Inc.
Enhanced antitumor effect against human telomerase reverse transcriptase (hTERT) by vaccination with chemotactic‐hTERT gene‐modified tumor cell and the combination with anti‐4‐1BB monoclonal antibodies
Authors: Lin Xiaoyan , Zhou Chunxia , Wang Shengdian , Wang Dongmei , Ma Wenbo , Liang Xiao , Lin Chen , Wang Zheng , Li Jie , Guo Sujuan , Zhang Youhui , Zhang Shuren
Published: May 2006

Human telomerase reverse transcriptase (hTERT) represents an attractive target for cancer immunotherapy because hTERT is reactivated in most human tumors. In an attempt to develop an effective vaccine against most human cancers, we constructed chemotactic‐hTERT vaccine. Two hTERT fragments encoding multiple cytotoxic T lymphocyte and T helper cell epitopes were fused as a tumor antigen (named Te). The plasmid based DNA vaccine (pCCL21‐Te‐Fc) was constructed by linking human CCL21 and IgG Fc gene sequences to each end of Te. In poorly immunogenic B16F10 mouse melanoma model, DNA (pCCL21‐Te‐Fc) vaccination significantly inhibited tumor growth and all of the mice were dead by day 52. The immunization with pCCL21‐Te‐Fc‐modified tumor cells (B16/CCL21‐Te‐Fc) resulted in a higher antitumor effect than DNA vaccination and 25% of tumor‐bearing mice achieved long‐term survival (>120 days). The combined therapy of B16/CCL21‐Te‐Fc plus anti‐4‐1BB MAbs further enhanced the immune response, resulting in 75% of tumor‐bearing mice achieved long‐term survival (>120 days) in subcutaneous model and few lung nodules in pulmonary metastasis model. Rechallenge experiment showed that a persistent memory response was successfully induced by the combined therapy. In vivo depletion of lymphocytes indicated that CD8+ T cells were essential in the antitumor activity induced by B16/CCL21‐Te‐Fc plus anti‐4‐1BB MAbs, whereas NK cells and CD4+ T cells played substantial roles. The CTL activity induced by pCCL21‐Te‐Fc‐transfected PBMCs specifically lysed a variety of human leukocyte antigen‐matched and hTERT‐positive human tumor cells, suggesting pCCL21‐Te‐Fc could serve as a vaccine against most human cancers. © 2006 Wiley‐Liss, Inc.
Epigenetic inactivation of the SFRP genes is associated with drinking, smoking and HPV in head and neck squamous cell carcinoma
Authors: Marsit Carmen J. , McClean Michael D. , Furniss Constance Sloane , Kelsey Karl T.
Published: May 2006

The soluble frizzled receptor protein (SFRP) family encodes antagonists of the WNT pathway, and silencing of these genes, through promoter hypermethylation, leads to constitutive WNT signaling. In bladder cancers, hypermethylation of the SFRP genes occurs more often in current and former smokers and is a strong predictor of poor patient survival. Hence, we examined methylation of these genes in another tobacco‐related epithelial cancer, head and neck squamous cell carcinoma (HNSCC), to determine if the pattern of tobacco exposure again predicts the epigenetic alteration of these genes. Using methylation‐specific PCR, the prevalence of methylation of SFRP1, SFRP2, SFRP4 and SFRP5 was 35, 32, 35 and 29%, respectively among 350 HNSCC cases. Promoter methylation of SFRP1 occurred more often in both heavy (OR 3.5, 95% CI 0.9–13.7) and light drinkers (OR 3.7, 95% CI 1.0–14.3) compared to nondrinkers. SFRP4 promoter methylation, on the other hand, occurred at a higher prevalence in never smokers and former smokers than in current smokers, and also was independently associated with HPV16 viral DNA. A joint effects model of SFRP4 promoter methylation demonstrated that smoking status and HPV virus significantly interacted (p < 0.04) such that never smokers with HPV16 had an OR of SFRP4 methylation of 9.0 (95% CI 2.1–38.6). These results suggest that epigenetic alterations of the SFRP genes are highly prevalent in HNSCC, and that the clonal selection for these alterations is complex and may be related to the carcinogenic exposures that are known risk factors for this disease. © 2006 Wiley‐Liss, Inc.
Association of vitamin D receptor FokI polymorphism with prostate cancer risk, clinicopathological features and recurrence of prostate specific antigen after radical prostatectomy
Authors: Huang Shu‐Pin , Huang Chao‐Yuan , Wu Wen‐Jeng , Pu Yeong‐Shiau , Chen Jun , Chen Yun‐Yun , Yu Chia‐Cheng , Wu Tony T. , Wang Jyh‐Seng , Lee Ying‐Huei , Huang Jong‐Khing , Huang Chun‐Hsiung , Wu Ming‐Tsang
Published: May 2006

To investigate the effect of vitamin D receptor (VDR) FokI polymorphism on susceptibility to prostate cancer and the outcome of the disease in a Taiwanese population, we genotyped a total of 416 prostate cancer patients, 502 age‐matched male controls and 189 non age‐matched symptomatic benign prostatic hyperplasia. Although we did not find a significant association between VDR FokI genotypes and overall prostate cancer risk, we found that in men aged less than or equal to the median age of 73 years with VDR FokI F allele specifically had an increased risk of prostate cancer with a marginal significant trend (OR, 2.08; 95% CI, 1.00–4.34, p for trend = 0.056). The FF genotype was also highly associated with more aggressive prostate cancer (Gleason score 8–10) (OR, 2.47; 95% CI, 1.20–5.08) than did the Ff and ff genotypes. After adjusting other covariates, we found that in patients who had localized prostate cancer for which a radical prostatectomy was performed (n = 131), the VDR FokI FF genotype was associated with worse prostate‐specific antigen (PSA) recurrence‐free survival (hazard ratio = 3.25, 95% CI = 1.32–8.00, p = 0.010). Our findings suggest that the VDR FF genotype may increase the risk of early‐onset prostate cancer and is associated with more aggressive disease. Furthermore, the VDR polymorphism could be used as a prognostic marker for localized prostate cancer after radical prostatectomy. © 2006 Wiley‐Liss, Inc.
Mobility and integration sites of a murine C57BL/6 melanoma endogenous retrovirus involved in tumor progression in vivo
Authors: Pothlichet Julien , Mangeney Marianne , Heidmann Thierry
Published: May 2006

Tumor development is a multistep process in which both genetic and epigenetic events cooperate for the emergence of a malignant clone with metastatic properties. The possibility that endogenous retroviruses promote the expansion of a neoplastic clone by subverting immunosurveillance has been proposed and recently demonstrated in the case of the B16 murine melanoma, which spontaneously express the melanoma‐associated retrovirus (MelARV). Indeed, knocking down, by RNA interference, this endogenous retrovirus resulted in the rejection of the tumor cells in immunocompetent mice, without any alteration of their transformed phenotype. Here, we characterize the MelARV proviruses present in the B16 melanoma. Complete sequencing of the viral genomic RNA and characterization of the integration sites within both the B16 tumor cells and a subline selected in vivo for increased metastatic activity disclosed mobility of the element with new proviral insertions targeting critical genes and altering their transcriptional profile. The results show that MelARV can act both at the genetic level, inducing mutations by insertion, and at the epigenetic level, promoting immunosuppression of the host. These properties may as well be relevant to human tumors, such as germline tumors and melanoma, where endogenous retroviruses are active. © 2006 Wiley‐Liss, Inc.
Interspecies in vitro metabolism of the phosphodiesterase‐4 (PDE4) inhibitor L‐454,560
Authors: Bateman Kevin P. , Trimble Laird , Chauret Nathalie , Silva Jose , Day Stephen , Macdonald Dwight , Dube Daniel , Gallant Michel , Mastracchio Anthony , Perrier Helene , Girard Yves , Nicoll‐Griffith Deborah
Published: May 2006

L‐454,560 is a potent phospodiesterase 4 (PDE4) inhibitor which was identified as a development candidate for the treatment of asthma and chronic obstructive pulmonary disease (COPD). As part of the discovery of this compound, interspecies in vitro metabolism data was generated using liver microsomes and hepatocytes in order to understand the metabolic fate of the compound. In microsomes, metabolism of the 3‐methyl‐1,2,4‐oxadiazole ring was the predominant pathway observed, including ring cleavage. In rat hepatocytes, hydroxylation of the methyl group on the oxadiazole ring and double‐bond isomerization were the most abundant metabolites observed. No major species differences were found in terms of microsomal metabolite profiles. The use of LC with UV and MS detection is highlighted, as well as information from tandem mass spectrometry and NMR. Copyright © 2006 John Wiley & Sons, Ltd.
A validated method for the determination of nicotine, cotinine, trans‐3′‐hydroxycotinine, and norcotinine in human plasma using solid‐phase extraction and liquid chromatography‐atmospheric pressure chemical ionization‐mass spectrometry
Authors: Kim Insook , Huestis Marilyn A.
Published: May 2006

A liquid chromatographic‐mass spectrometric method for the simultaneous determination of nicotine, cotinine, trans‐3′‐hydroxycotinine, and norcotinine in human plasma was developed and validated. Analytes and deuterated internal standards were extracted from human plasma using solid‐phase extraction and analyzed by liquid chromatography/atmospheric pressure chemical ionization‐mass spectrometric detection with selected ion monitoring (SIM). Limits of detection and quantification were 1.0 and 2.5 ng/ml, respectively, for all analytes. Linearity ranged from 2.5 to 500 ng/ml of human plasma using a weighting factor of 1/x; correlation coefficients for the calibration curves were > 0.99. Intra‐ and inter‐assay precision and accuracy were < 15.0%. Recoveries were 108.2–110.8% nicotine, 95.8–108.7% cotinine, 90.5–99.5% trans‐3′‐hydroxycotinine, and 99.5–109.5% norcotinine. The method was also partially validated in bovine serum, owing to the difficulty of obtaining nicotine‐free human plasma for the preparation of calibrators and quality control (QC) samples. This method proved to be robust and accurate for the quantification of nicotine, cotinine, trans‐3′‐hydroxycotinine, and norcotinine in human plasma collected in clinical studies of acute nicotine effects on brain activity and on the development of neonates of maternal smokers. Copyright © 2006 John Wiley & Sons, Ltd.
An investigation into the effect of number of trials during proprioceptive testing in patients with patellofemoral pain syndrome
Authors: Selfe James , Callaghan Michael , McHenry Alec , Richards Jim , Oldham Jackie
Published: May 2006

The purpose of this study was to investigate the effect of increasing the number of test trials in the assessment of knee joint position sense, in a group of patellofemoral patients, and second, to investigate the effects of joint angle and type of test. Thirty‐two patients with a diagnosis of patellofemoral pain syndrome were admitted to this study. Knee joint position sense was measured by performing an ipsilateral matching activity at target angles of 20° and 60° using two techniques; Passive Angle Reproduction (PAR), and Active Angle Reproduction (AAR). The results show that five repetitions are required for AAR and six for PAR. A two‐way repeated‐measures ANOVA showed that there was no significant difference (p = 0.559) in the accuracy of angle reproduction for the two angles (60° and 20°); however, there was a significant difference (p = 0.001) between the two types of test (AAR and PAR). The results of this study have implications for clinicians and researchers who examine knee joint proprioception as part of functional assessment in a variety of knee joint pathologies including PFPS. A “quick” one‐off assessment of knee joint position sense may give erroneous data; subjects need to have several trials before a true picture of their proprioceptive status emerges. Type of testing performed, active or passive, is also important, although the angle of testing may not be relevant. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1218–1224, 2006
Longitudinal quantitative evaluation of lesion size change in femoral head osteonecrosis using three‐dimensional magnetic resonance imaging and image registration
Authors: Takao Masaki , Sugano Nobuhiko , Nishii Takashi , Miki Hidenobu , Sato Yoshinobu , Tamura Shinichi , Yoshikawa Hideki
Published: May 2006

It remains controversial whether some lesions of femoral head osteonecrosis regress during the natural course of the disease. With image registration, accurately matched image sets of the same subject can be acquired at different times. We applied image registration to evaluate lesion size change and assessed accuracy and usefulness compared to volume measurements and a conventional method. We also investigated whether lesions regress with this technique and with volume measurements. Baseline and 1 year minimum follow‐up scans were conducted on 25 patients (31 hips) without radiological evidence of collapse. A three‐dimensional (3D) spoiled gradient recalled echo sequence was used in the coronal direction (slice thickness = 2 mm; slice pitch = 1 mm). Size change was evaluated on all contiguous pairs of matched images after image registration. As a conventional method, coronal images (slice thickness = 5 mm) were reconstructed, and size change was evaluated on the five representative coronal slices. Evaluation with the conventional method identified eight lesions with apparent reduction; assessments using image registration and volume measurements identified three lesions, all within a year of initial steroid treatment and remaining at ARCO stage I at follow up. Evaluation of lesion size change using image registration was comparable to volume measurements. Inaccurate estimation of lesion size change due to mismatching of slice planes can be excluded. We demonstrated that some early lesions detected less than a year after initial steroid treatment can show size reduction with image registration as well as with volume measurements. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1231–1239, 2006
Alterations in surface geometry in retrieved polyethylene glenoid component
Authors: Braman Jonathan P. , Falicov Alexis , Boorman Richard , Matsen Frederick A.
Published: May 2006

This study characterized and quantified the changes found in retrieved glenoid polyethylene components found at revision total shoulder arthroplasty (TSA). Twenty components obtained at revision TSA were evaluated, all from a system (Global, DePuy, Warsaw, IN) with a glenoid radius of curvature 3 mm greater than that of the humeral head. Laser surface scanning provided three‐dimensional analysis of the surface of the glenoid component. Scans of unused components of similar sizes enabled determination of the changes occurring after implantation. Alterations in radius of curvature were noted in every glenoid. All showed loss of the balance stability angle (BSA, the maximal angle that the net humeral joint reaction force can make with the glenoid center line before the humeral head would dislocate) of at least 5° in one or more directions. Increase in BSA in one direction was seen in 11 of the components. In five of these, the increase was associated with a reduction of the local radius to match that of the humeral component. Glenoid surface morphology and stability can be changed by in vivo use. While correlation with clinical instability in the patients from whom the implants were obtained was not possible, many of the observed changes in surface morphology are of sufficient magnitude to compromise the contribution of the glenoid surface to shoulder stability. Three patterns of wear were identified: “humeral” that showed loss of the mismatch between the humeral and glenoid radii of curvature (5 of 20 components), “diffuse” that showed broad surface irregularity (18 of 20), and “rim” wear with loss of the polyethylene rim of the component (14 of 20). More than one type of wear was possible within a single glenoid. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1249–1260, 2006
Nerve endings of the wrist joint: A preliminary report of the dorsal radiocarpal ligament
Authors: Lin Yu‐Te , Berger Richard A. , Berger Evelyn J. , Tomita Kazunari , Jew Jean Y. , Yang Chao , An Kai‐Nan
Published: May 2006

As part of an investigation of the articular nerve ending populations in the wrist joint capsule associated with the anterior and posterior interosseous nerves, this study addresses the nerve ending population in the dorsal radiocarpal ligament. The ligaments were harvested from four wrists of two fresh cadavers within 12 h of death. Tissues were fixed, cryostat sectioned, and processed for fluorescence immunohistochemistry using antibody to protein gene product 9.5 (PGP 9.5), a general or pan neuronal marker, and a secondary antibody conjugated to a fluorescent tag (Alexa Fluor 488). The sections were evaluated with a confocal laser microscope and an image analyzer. Labeled nerve endings were mapped, measured, and categorized. Type I (Ruffini‐like ending), Type III (Golgi‐like tendon organ) and Type IV (noncorpuscular) nerve endings could be identified in all four DRC ligaments, with Types I and IV dominating. These receptors were distributed primarily over the superficial two thirds of the ligament (>80%), and near the bony attachments (>70%). The dorsal radiocarpal ligament has a rich sensory innervation from the posterior interosseous nerve terminating in nerve endings located in the superficial two‐thirds of the ligaments, primarily near bony attachment sites. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1225–1230, 2006
Doxorubicin induces cell senescence preferentially over apoptosis in the FU‐SY‐1 synovial sarcoma cell line
Authors: Joyner David E. , Bastar Jeffrey D. , Randall R. Lor
Published: May 2006

Surgical resection coupled with adjuvant radiotherapy and/or doxorubicin based chemotherapy are the mainstays of synovial sarcoma (SS) treatment. Although effective as a SS adjuvant, the proposed mechanism of action of doxorubicin remains controversial. Current opinion supports DNA damage‐induced apoptosis. This in vitro study used cDNA gene expression profiling to investigate whether apoptosis, alone or in combination with cell senescence, is induced by doxorubicin in SS cells. Cell cultures of the FU‐SY‐1 SS, the pleomorphic SW982 sarcoma, and a primary dermal fibroblast (NHDF), were exposed to 500 nM doxorubicin, and then processed for cDNA microarray analysis. The one class response option of SAM (Significance Analysis of Microarrays) was used to test for significant overexpression of 15 apoptosis‐related genes and nine senescence‐related genes. Drug‐induced cell senescence was quantified by measuring β‐galactosidase activity. None of 15 apoptosis‐related genes and only two of nine senescence‐related genes were identified by SAM as significantly overexpressed in doxorubicin‐treated cultures. Drug‐induced senescence as reflected by β‐galactosidase activity was significantly increased (p < 0.05) only in FU‐SY‐1 SS cultures. Apoptosis does not appear to be a major determinant of doxorubicin‐induced mortality in FU‐SY‐1 SS or NHDF cultures, but may impact SW982 cells via the overexpression of BAX relative to Bcl‐2. Doxorubicin‐induced cell senescence was prominent in FU‐SY‐1 SS cultures, but negligible in SW982 and NHDF cultures. Likely, both apoptosis and cell senescence contribute to doxorubicin‐induced cell death in this synovial sarcoma cell line. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1163–1169, 2006
Moderate soft tissue trauma delays new bone formation only in the early phase of fracture healing
Authors: Claes Lutz , Maurer‐Klein Nikola , Henke Thomas , Gerngross Heinz , Melnyk Mark , Augat Peter
Published: May 2006

The aim of this study was to investigate the effect of a moderate soft tissue trauma to the course of fracture healing in a standardized animal model. Thirty‐eight Wistar rats were randomly divided into a fracture group (F, n = 19) and a group with a fracture and a soft tissue trauma (F + STT, n = 19). The fracture and the soft tissue trauma were created using an impact device with a standardized energy. All fractures were stabilized by two Kirschner wires. Three rats were measured for blood flow and sacrificed at days 1, 3, 7, and 14, and seven rats at day 28, from both groups. A three‐point bending test was performed on the healed tibia after 28 days. During the first 24 h there was a reduction in blood flow, which was more pronounced in the F + STT group than in the F group. From histological sections, the shape of the callus formation, as well as the tissue distribution of newly formed bone, fibrous cartilage and fibrous connective tissue were determined. Distinctly more periosteal new bone formed and a larger callus formed at days 3 and 7 in group F compared to group F + STT. However, by days 14 and 28, the ossification and overall callus size no longer showed differences between the two groups. A fast recovery of blood flow and callus formation took place in the F + STT group, which led to similar histological and biomechanical results in fracture healing observed after 28 days between the two groups. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1178–1185, 2006
Endochondral growth in growth plates of three species at two anatomical locations modulated by mechanical compression and tension
Authors: Stokes Ian A.F. , Aronsson David D. , Dimock Abigail N. , Cortright Valerie , Beck Samantha
Published: May 2006

Sustained mechanical loading alters longitudinal growth of bones, and this growth sensitivity to load has been implicated in progression of skeletal deformities during growth. The objective of this study was to quantify the relationship between altered growth and different magnitudes of sustained altered stress in a diverse set of nonhuman growth plates. The sensitivity of endochondral growth to differing magnitudes of sustained compression or distraction stress was measured in growth plates of three species of immature animals (rats, rabbits, calves) at two anatomical locations (caudal vertebra and proximal tibia) with two different ages of rats and rabbits. An external loading apparatus was applied for 8 days, and growth was measured as the distance between fluorescent markers administered 24 and 48 h prior to euthanasia. An apparently linear relationship between stress and percentage growth modulation (percent difference between loaded and control growth plates) was found, with distraction accelerating growth and compression slowing growth. The growth‐rate sensitivity to stress was between 9.2 and 23.9% per 0.1 MPa for different growth plates and averaged 17.1% per 0.1 MPa. The growth‐rate sensitivity to stress differed between vertebrae and the proximal tibia (15 and 18.6% per 0.1 MPa, respectively). The range of control growth rates of different growth plates was large (30 microns/day for rat vertebrae to 366 microns/day for rabbit proximal tibia). The relatively small differences in growth‐rate sensitivity to stress for a diverse set of growth plates suggest that these results might be generalized to other growth plates, including human. These data may be applicable to planning the management of progressive deformities in patients having residual growth. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1327–1334, 2006
Expression of survivin and correlation with PCNA in osteosarcoma
Authors: Wang Wenji , Luo Huiying , Wang Aiqin
Published: May 2006

Background and Objectives

Survivin is a new anti‐apoptosis gene with reported expression during fetal development and in cancer tissues. Proliferating cell nuclear antigen (PCNA) is essential for the replication of deoxyribonucleic acid (DNA). In this experiment, we examined the expression of survivin and PCNA in human osteosarcoma tissues and investigating whether survivin and PCNA expressions were correlated with histological grades, histological types, and patients' clinical characteristics.

Methods

Sixty‐eight osteosarcoma samples were divided into two groups based on the degree of tumor cell differentiation. Immunohistochemical staining was performed to analyze the expression of survinin and PCNA. Four histological types and patients' clinical characteristics were also recorded.

Results

There were abundant levels of survivin and PCNA immunoreactivity in the nucleus and/or cytoplasm of the osteosarcoma cells. All cells essentially revealed the cytoplasmic localization and the nuclear signals of survivin in same cases, while PCNA from the majority of cases predominantly showed nuclear expression. Scoring on the percentage of positive cells indicated that survivin expression was significantly associated with the PCNA‐labeling index (LI), which was correlated with the histological grades of osteosarcoma (χ2 = 17.86 and χ2 = 23.75, respectively).

Conclusions

The expression of survivin can be used as a useful indicator in grading the malignancy of osteosarcoma. J. Surg. Oncol. 2006;93:578–584. © 2006 Wiley‐Liss, Inc.
Can axillary dissection be avoided in patients with sentinel lymph node metastasis?
Authors: Katz Angela , Niemierko Andrzej , Gage Irene , Evans Sheila , Shaffer Margaret , Fleury Thomas , Smith Frederick P. , Petrucci Peter E. , Flax Richard , Drogula Cynthia , Magnant Colette
Published: May 2006

Background

Who should undergo a completion dissection following identification of a +sentinel lymph node (SLN) is controversial.

Methods

The records of 1,133 patients who underwent SLN mapping were reviewed. The association between patient, tumor, and treatment characteristics and the presence of +SLNs and +nonSLNs was analyzed using two‐way tables of frequency counts and Pearson χ2 test. Possible predictors of +SLNs and +nonSLNs were analyzed using simple and multiple logistic regression.

Results

One thousand one hundred forty‐eight SLN procedures were performed. 367 procedures (32%) yielded +SLNs. For patients with a +SLN, on multiple logistic regression analysis LVSI, increasing numbers of +SLNs, decreasing numbers of negative SLNs, and increasing size of the largest SLN metastasis were statistically significantly associated with increased likelihood of nonSLN involvement. No subgroup was identified that did not have a significant rate of nonSLN involvement on completion axillary dissection, except those who had a large number of negative SLNs (≥3) and small size of the largest SLN metastasis (<10 mm).

Conclusions

A definitive answer to the question of who needs a completion axillary dissection awaits the results of ongoing trials. In the interim, our data does not support eliminating dissection for any subgroup of patients with +SLNs. J. Surg. Oncol. 2006;93:550–558. © 2006 Wiley‐Liss, Inc.
Effectiveness of radical en‐bloc‐esophagectomy compared to transhiatal esophagectomy in squamous cell cancer of the esophagus is influenced by nodal micrometastases
Authors: Yekebas Emre F. , Schurr Paulus G. , Kaifi Jussuf T. , Link Bjoern C. , Kutup Asad , Mann Oliver , Wolfram Lars , Izbicki Jakob R.
Published: May 2006

Purpose

The appropriate surgery for curable squamous cell cancer (SCC) of the esophagus is discussed controversially.

Patients and Methods

Transthoracic esophagectomy (TTE) with radical en‐bloc‐lymphadenectomy was performed in 79/120 patients (66%). Due to severe comorbidity, 41/120 patients (34%) underwent less traumatizing transhiatal esophagectomy. Lymph nodes were stained using mAb BER‐Ep4.

Results

pN0 status was found in 54 patients (45%) and pN1 status in 66 patients (55%). In the pN0 subgroup, 30 out of 54 patients (55.6%) had occult tumor cells in lymph nodes detected with BER‐Ep4. pN1 patients had additional BER‐Ep4 positive cells in histopathologically negative lymph nodes in 41 out of 66 patients (59.2%). Median disease‐specific survival was 31.4 and 16.8 months for the transthoracic and transhiatal groups, respectively (P = 0.129). pN0 patients lived longer after transthoracic resection (P = 0.0349), and in the subgroup without lymph node micrometastases this effect was even stronger (P = 0.025). In contrast, in pN0 patients with nodal microinvolvement, TTE did not entail a survival benefit when compared with the transhiatal group (P = 0.333).

Conclusion

TTE results in improved outcome in the absence of lymph node micrometastases. Poor survival in patients with lymphatic micro‐dissemination indicates systemic disease and the need for adjuvant treatment. J. Surg. Oncol. 2006;93:541–549. © 2006 Wiley‐Liss, Inc.
A practical scoring system based upon ROC analysis for evaluating potential lymph nodes metastasis during gastric surgery
Authors: Wu Yulian , Chen Jian , Yu Junxiu , Gao Shunliang , Shen Hongwei
Published: May 2006

Background and Objectives

Current preoperative N staging does not offer an accurate estimation of lymph node involvement. We establish a new scoring system for predicting N stages to guide a rational lymphadenectomy for gastric cancer.

Methods

Variables correlated with N stages were selected by multivariate stepwise logistic regression analysis. Variables granted the different scores according to the odds ratio (OR). Receiver operating characteristic (ROC) analysis was used to generate scoring ranges from N0 to N3. The agreement between predicted N staging and actual pN classification was analyzed using kappa statistics.

Results

Tumor size, depth of invasion, and histological types were selected to establish the scoring system. Scores 0–4, 5–7, 8–9, and 10–13 were postulated to predict N0‐3, respectively. The predicted N stage has good agreement with the actual pN classifications. The negative predictive values for N0‐3 were 87.0, 86.4, 90.4, and 90.2%; the positive predictive values were 74.7, 62.8, 57.3, and 69.6%, respectively. The accuracy is 82% for N0‐1, and 83.7% for N2‐3.

Conclusions

The new scoring system can predict the N stage of gastric cancer. With its good negative predictive value, it is possible to minimize the potential hazards of applying a more extensive lymph node dissection than necessary. J. Surg. Oncol. 2006;93:534–540. © 2006 Wiley‐Liss, Inc.
Adjuvant aromatase inhibitor therapy for early breast cancer: A review of the most recent data
Authors: Grana G.
Published: May 2006

Tamoxifen is the established adjuvant treatment for postmenopausal women with hormone‐sensitive early breast cancer. However, the side‐effects associated with tamoxifen therapy have prompted a search for safer and potentially more effective endocrine agents. Results from randomized trials of the third‐generation aromatase inhibitors, anastrozole, letrozole and exemestane, demonstrating improved efficacy compared with tamoxifen and favorable tolerability profiles, are discussed in this review. J. Surg. Oncol. 2006;93:585–592. © 2006 Wiley‐Liss, Inc.
Affinity liquid chromatography and capillary electrophoresis of seminal plasma proteins
Authors: Vařilová Tereza , Seménková Hana , Horák Pavel , Maděra Milan , Pacáková Vera , Tichá Marie , Štulík Karel
Published: May 2006

Interactions of boar, bull, and human seminal plasma proteins with heparin and phosphorylcholine were studied by affinity LC using heparin immobilized to a Toyopearl support. A step gradient elution from 0.15 to 1.50 M NaCl was employed to elute the seminal plasma proteins. Relative amounts of the heparin‐binding fraction of seminal plasma proteins (H+) in seminal plasma of three species were determined. Further on, the fraction of seminal plasma proteins interacting with phosphorylcholine‐binding proteins (P+) was evaluated. P+ proteins were not found in human seminal plasma and their highest amount was present in bull seminal plasma. A CE method was developed for separation of seminal plasma proteins. Various capillaries and separation conditions were tested; the best resolution was obtained in a bare‐silica capillary, with a micellar system consisting of a 0.02 M borate buffer and 0.05 M SDS pH 10.0. The optimized conditions were applied to the identification of the components in boar plasma.
A model of flow‐through pore formation in methacrylate ester‐based monolithic columns
Authors: Urban Jiří , Moravcová Dana , Jandera Pavel
Published: May 2006

The main factors affecting the porosity of methacrylate‐ester based monolithic columns were investigated. We prepared 23 monolithic capillary columns with porosity controlled by varying the proportions of butyl methacrylate and ethylene dimethacrylate monomers and of 1,4‐butanediol and 1‐propanol as the porogen solvent in the polymerization mixtures by thermally initiatedin‐situpolymerization in fused‐silica capillaries. Using mixture design software, we systematically varied the composition of the polymerisation mixtures to find significant factors affecting flow‐through pore formation. Multivariate analysis of the experimental data obtained for the fabricated columns yielded a model for prediction of the flow‐through porosity in monolithic beds as a function of the composition of the polymerization mixture used to prepare polymethacrylate monolithic capillary columns. The mean error of prediction was lower than 8% for eight columns prepared independently of the original set of 15 columns used to derive the flow‐through model. The flow‐through porosity increases with increasing concentration of the binary porogen solvent mixture, the concentration of 1,4‐butanediol being the main factor enhancing flow‐through pore formation. On the other hand, increasing concentrations of the hydrophobic monomer butyl methacrylate and increasing concentrations of 1‐propanol have a negative effect on flow‐through pore formation. The capillary columns prepared with a high proportion of flow‐through pores and a minimum amount of mesopores can be used for fast gradient separations of both low‐molecular weight compounds and biopolymers.
Spatial evaluation of soil erosion risk in the West Usambara Mountains, Tanzania
Authors: Vrieling A. , Sterk G. , Vigiak O.
Published: May 2006

Effective soil and water conservation programmes require the concentration of resources on limited areas. For that purpose regional‐scale assessments of erosion risk are required. However, availability of good‐quality spatial data for such assessments is often poor, especially in regions like sub‐Saharan Africa. This study was conducted to evaluate the potential of analysing regional erosion risk using a limited amount of readily available data. The analysis was executed for the 70‐km2 Baga watershed in the West Usambara Mountains, Tanzania. Principal data sources were a Landsat image and an SRTM DEM. Two qualitative mapping methods resulting in five erosion risk classes were evaluated against field‐based erosion risk estimates. The first method derived slope classes from the DEM and fractional vegetation cover (FVC) classes from the Landsat image and FVC field estimates. Data integration was achieved with a decision tree. The second method did not apply field data for the map construction, but combined five equally sized NDVI classes and five slope classes using the minimum‐operator. Resulting maps showed a high and comparable accuracy, 80 per cent for Method 1, and 81 per cent for Method 2, when allowing a maximum difference of one class with field erosion risk estimates. Spatial patterns of erosion risk were well represented by both methods and high erosion risk areas can be properly identified within the Baga watershed. Due to the limited data requirement of Method 2, it has a high potential for quick identification of erosion risk in other areas of the East African Highlands. Copyright © 2006 John Wiley & Sons, Ltd.
Performance of some under‐explored crops under saline irrigation in a semiarid climate in Northwest India
Authors: Dagar J. C. , Tomar O. S. , Kumar Y. , Bhagwan H. , Yadav R. K. , Tyagi N. K.
Published: May 2006

Growing salt‐tolerant under‐explored crops utilizing saline ground water can provide for an economic use of abandoned semiarid lands. Field trials were conducted between 1999 and 2003 on a calcareous soil in a semiarid region of northwest India. Woody perennials were planted at the sill of furrows and irrigated with water of high salinity (EC 10–28 dS m−1), low salinity (EC 5–9 dS m−1) and alternately with these two waters. Woody species includedAzadirachta indica, Cordia rothii, Salvadora persica, Jatropha curcas, J. gossipifolia, Ricinus communis, Catharanthus roseus, Adhatoda vasicaandAloe barbadensis. Most of these could be grown successfully butS. persica—a highly salt‐tolerant halophyte—though it produced huge biomass, could not yield mature fruit due to frost injury. The salinity build up in the soil was greater during low‐rainfall years, but a good rainfall year, e.g. 714 mm in 2001, helped to leach out the accumulated salts. The uptake of Na+in plants was greater when irrigated with water of high salinity, while K+accumulation was greater with water of low salinity. Na+accumulation was higher in roots as compared to other parts except inJatrophaandSalvadora, while K+accumulation was greater in leaves. There was a negative correlation between Na+and K+accumulation and a positive correlation between Ca2+and Mg2+. Thus, saline water (ECiw 12 dS m−1) can successfully be used for growing several under‐explored crops of high economic value. Copyright © 2006 John Wiley & Sons, Ltd.
Soil erosion assessment of Lake Alemaya catchment, Ethiopia
Authors: Muleta S. , Yohannes F. , Rashid S.M.
Published: May 2006

Land degradation due to soil erosion is the major problem facing Ethiopia today. In the Lake Alemaya catchment soil erosion is caused by the intense rainfall, steep topography, and poor vegetation cover coupled with cultivation of steep lands, and inadequate conservation practices. Sediment from the catchment has affected the storage capacity of Lake Alemaya. This study has integrated the Agricultural Non‐point Source Pollution Model (AGNPS) and the technique of the Gographic Information System (GIS) to quantify soil erosion in the Lake Alemaya catchment. After application of the AGNPS, it appears that 66 per cent of the catchment has a soil erosion rate of 10 to more than 80 t ha−1 y−1. The annual soil loss is estimated at 31 t ha−1, which is more than the permissible value of 1–16 t ha−1 for different agro‐ecological zones of Ethiopia. The sediment yield of the catchment is about 10 148 ton with a delivery ratio of 6·82 per cent. Therefore, an effective management plan is needed for the conservation and rehabilitation of the catchment and to maintain the storage capacity of Lake Alemaya. Copyright © 2006 John Wiley & Sons, Ltd.
The impact of changing olive cultivation practices on the ground flora of olive groves in the Messara and Psiloritis regions, Crete, Greece
Authors: Allen H. D. , Randall R. E. , Amable G. S. , Devereux B. J.
Published: May 2006

This paper examines the impact that different olive cultivation practices have on the nature of the ground flora of olive groves in the region of the Psiloritis massif and Messara Plain in central and southern Crete, Greece. In lower, flatter areas there are areas of both traditional and intensive forms of olive cultivation. In more marginal, upland areas there are traditional terraced olive groves, some of which are being abandoned. The relationship between the vegetation composition of the ground flora and environmental variables was established, by means of TWINSPAN® and ordination analysis, using survey data from nineteen sites across the region. Four vegetation communities are identified: olive with herbaceous taxa; olive with sclerophyllous shrub taxa; and two forms of sclerophyllous shrub communities. Ordination results indicate that environmental variables, such as soil characteristics, slope aspect and slope angle, explain about 60 per cent of the species–environment relationships. The remaining variation in species composition is interpreted to be the result of different cultivation practices. The implications for land degradation are examined, in particular the changes in vegetation diversity of both intensive and semi‐abandoned olive groves, the potential for increased soil erosion, and the risk of fire as a result of increased fuel loading as flammable shrubs invade abandoned terraces. Intensification of olive cultivation in Crete, and across the Mediterranean, has been encouraged by subsidies from the European Union leading to rapid landscape change. Thus there is a need to monitor changes in olive cultivation practices both at the local scale, by means of ground‐based fieldwork, and at landscape and regional scales, by means of remote sensing. Copyright © 2006 John Wiley & Sons, Ltd.
Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells
Authors: Konstantakopoulos N. , Montgomery K.G. , Chamberlain N. , Quinn M.A. , Baker M.S. , Rice G.E. , Georgiou H.M. , Campbell I.G.
Published: May 2006

The incidence of hormone‐related diseases such as prostatic, breast, ovarian, and endometrial cancer is lower in Asian populations compared to Western countries. High consumption of soybean products that are rich in phytoestrogens, predominantly genistein, is postulated to be responsible for the lower incidence of hormone‐related disease, although the mechanism through which this effect might be mediated is unclear. In this study, microarray analysis was used to identify the changes in gene expression elicited by treatment of the human endometrial cancer cell line, Ishikawa, with genistein at both physiologically achievable and supraphysiological concentrations. Genistein treatment at 5 µM concentration induced multiple changes in gene expression including some implicated in oncogenesis. In contrast, treatment with a supraphysiological concentration of genistein predominantly activated stress response genes and showed very limited overlap with the genes regulated at lower concentrations. Of the genes regulated by genistein, 9.3% were also regulated by 17β‐estradiol suggesting that genistein exerts its response via the estrogen pathway. These results indicate that at physiological concentrations, genistein is able to elicit pleiotropic effects on a variety of pathways believed to be involved in tumorigenesis. Supraphysiological concentrations of genistein, such as those used in many previous studies, elicit changes in gene expression that are unlikely to occur in vivo. © 2006 Wiley‐Liss, Inc.