bluuebunny/crossref_metadata_2025 huggingface dataset:
The theoretical basis of cancer‐stem‐cell‐based therapeutics of cancer: can it be put into practice?
Authors: Sánchez‐García Isidro , Vicente‐Dueñas Carolina , Cobaleda César
Published: November 2007

In spite of the advances in our knowledge of cancer biology, most cancers remain not curable with present therapies. Current treatments consider cancer as resulting from uncontrolled proliferation and are non‐specific. Although they can reduce tumour burden, relapse occurs in most cases. This was long attributed to incomplete tumour elimination, but recent developments indicate that different types of cells contribute to the tumour structure, and that the tumour's cellular organization would be analogous to that of a normal tissue, with a main mass of differentiating cells sensitive to anti proliferative agents, together with a small percentage of quiescent, resistant stem cells responsible for replenishing the tumour: the Cancer Stem Cells (CSCs). Anti‐CSCs targeted therapeutic agents would prevent tumour regeneration. New mouse models tailored to exploit this novel concept will be critical to develop CSC‐based anti‐cancer therapies. Here we review the biological basis and the therapeutic implications of the stem‐cell model of cancer. BioEssays 29:1269–1280, 2007. © 2007 Wiley Periodicals, Inc.
Solubility Correlations. Part 1
Authors: Battino Rubin , Seybold Paul G.
Published: November 2007

A method is described for estimating solubility by fitting both solute and solvent properties in a single equation. The method is illustrated by examining the solubilities of five rare gases (He, Ne, Ar, Kr, Xe) and five ‘permanent’ gases (O2, N2, CH4, CF4, SF6) in either n‐alkane (C5H12 to C16H34) or alkan‐1‐ol (CH3OH to C11H23OH) solvents. Generally, the correlation (R2) values of the fits achieved were significantly better than 0.9. It is suggested that similar methods can be used for estimating other physico‐chemical properties such as excess molar volumes and enthalpies of solution.
Genomic Analyses and the Origin of the Eukaryotes
Authors: Rivera Maria C.
Published: November 2007

The availability of whole‐genome data has created the extraordinary opportunity to reconstruct in fine details the ‘tree of life’. The application of such comprehensive effort promises to unravel the enigmatic evolutionary relationships between prokaryotes and eukaryotes. Traditionally, biologists have represented the evolutionary relationships of all organisms by a bifurcating phylogenetic tree. But recent analyses of completely sequenced genomes using conditioned reconstruction (CR), a newly developed gene‐content algorithm, suggest that a cycle graph or ‘ring’ rather than a ‘tree’ is a better representation of the evolutionary relationships between prokaryotes and eukaryotes. CR is the first phylogenetic‐reconstruction method to provide precise evidence about the origin of the eukaryotes. This review summarizes how the CR analyses of complete genomes provide evidence for a fusion origin of the eukaryotes.
Measurable Notions of Complexity and Their Relationship to Biological Complexity
Authors: Brooks J. Paul
Published: November 2007

Complexity is often invoked as a motivation for a systems approach to biology. We review three measurable notions of complexity from the areas of computation and data analysis. These measures have each led to mathematical theory and to further insight on the complexity of objects, demonstrating the benefits of having a well‐defined measure of complexity. Each measure is applicable in the study of particular biological systems; however, none is satisfactory to serve as a universal measure of biological complexity. The study of biological systems will likely require numerous measures of complexity, each appropriate for analysis in specific settings.
The association between N‐acetyltransferase 2 gene polymorphisms and pancreatic cancer
Authors: Ayaz Lokman , Ercan Bahadır , Dirlik Musa , Atik Uğur , Tamer Lülüfer
Published: November 2007

Pancreatic cancer has been linked with exposure to environmental chemicals, which generally require metabolic activation to highly reactive toxic or carcinogenic intermediates. N‐acetyltransferase 1 (NAT1) and N‐acetyltransferase 2 (NAT2) are expressed primarily in extrahepatic and hepatic tissues, respectively. Both enzymes catalyze N‐ and O‐acetylation of aromatic and heterocyclic amines. It is believed that these compounds are activated via O‐acetylation and detoxified by N‐acetylation. Several polymorphisms of these two genes have been associated with an increased risk of cancer. Twenty‐seven cases of pancreatic cancer and 104 controls were included in this study. Blood was collected in EDTA‐containing tubes, and genomic DNA was extracted from the white blood cells by using a high pure PCR template preparation kit. Genotyping of NAT2 polymorphisms was detected by a real time PCR instrument. There was a significant difference in the distribution of the NAT2*6A acetylators phenotype between cases and the controls. The odds ratio of pancreatic cancer for the NAT2*6A slow phenotype was 5.7 (95% CI = 1.27–25.55; p = 0.023) compared with the fast type. Our results suggest that slow acetylators have higher risk of developing pancreatic cancer than fast acetylators. NAT2 gene polymorphisms may be associated with genetic susceptibility to pancreatic cancer. Copyright © 2007 John Wiley & Sons, Ltd.
Technique for ipsilateral rescue embolization of common femoral side branch vessel injury
Authors: Bates Mark C. , E. Campbell John
Published: November 2007

We report a novel double wire technique for ipsilateral access of the external iliac/common femoral artery transition side‐branches in a patient with active extravasation. The case is noteworthy in that asymptomatic extravasation was noted in both the inferior epigastric and deep circumflex iliac branches on femoral angiography prior to intraaortic balloon pump insertion following emergent diagnostic left heart cathetrization. We speculate the side branch injury was related to the J‐wire and describe how this complication may be best treated by the ipsilateral technique reported herein. © 2007 Wiley‐Liss, Inc.
Successful percutaneous repair of perivalvular prosthetic regurgitation
Authors: Sorajja Paul , Cabalka Allison K. , Hagler Donald J. , Reeder Guy S. , Chandrasekaran Krishnawamy , Cetta Frank , Rihal Charanjit S.
Published: November 2007

Objective:

To examine the feasibility and outcome of percutaneous transcatheter repair of perivalvular regurgitation.

Background:

Perivalvular prosthetic regurgitation causes significant morbidity, and is associated with high perioperative mortality if open surgical repair is required.

Methods:

Percutaneous repair of perivalvular regurgitation was attempted in 16 patients with heart failure or hemolytic anemia. All patients were either not candidates or were high‐risk for open surgical repair (Parsonnet score, 39 ± 7). Regurgitant lesions were perimitral in 14 patients (2 had multiple defects) and peri‐aortic in 2 patients. Under echocardiographic and fluoroscopic guidance, patients underwent implantation of either the Amplatzer Septal Occluder or Duct Occluder.

Results:

Successful percutaneous closure with mild or no residual regurgitation was achieved in 17 of 21 attempts (81%). In one patient, an occluder could not be deployed. There were no procedural deaths, strokes, or myocardial infarctions, and no prosthetic obstruction from device deployment. NYHA functional class improved from 3.1 ± 0.6 to 2.0 ± 1.0 at follow‐up (mean, 3.1 mos; P = 0.0001 vs. baseline). One patient with heart failure had symptom resolution but died suddenly 4 weeks after the procedure. One subsequent noncardiac death and two late deaths from progressive heart failure also occurred.

Conclusions:

Percutaneous repair of perivalvular prosthetic regurgitation is a feasible alternative to open surgical correction, and may be preferred in patients at significant perioperative risk. Further experience with careful attention to patient selection, late morbidity, and mortality is required in this high risk patient subset. © 2007 Wiley‐Liss, Inc.
Rheolytic thrombectomy in patient with massive pulmonary embolism: A case report and review of literature
Authors: Brahmbhatt Tejas , Tutton Sean , Mannebach Patrick , Cinquegrani Michael
Published: November 2007

Objective:

Despite advances in management with thrombolytic therapy or open embolectomy, the mortality rate remains high in patients with massive pulmonary embolism (MPE).

Background:

We present a case of 51‐year‐female patient who collapsed while jogging and was brought to the Emergency Department. Upon arrival, she was found to have marked hypotension and hypoxia. EKG showed marked ST T abnormalities suggestive of anterior and lateral ischemia. Blood was drawn for labs. Patient received aspirin, heparin, and was transferred to cardiac catheterization laboratory.

Methods:

Coronary angiogram revealed normal epicardial coronaries. A pigtail catheter was inserted through right femoral vein and pulmonary angiogram was performed. It revealed bilateral MPE. Tissue plasminogen activator was initiated as per standard protocol. A 7‐French aspiration catheter (Export, Medtronic Vascular, Santa Rosa, CA) was used without any success. Rheolytic thrombectomy (RT) (AngioJet, Possis, Minneapolis, MN) was performed successfully with adjunctive local and systemic thrombolytic therapy. Immediate pulmonary angiogram showed increased perfusion through right pulmonary artery. Her hemodynamic status improved significantly. Patient was discharged home after 8 days of hospitalization. Patient remains on lifelong anticoagulation therapy and she continues to remain stable at 20 months follow up.

Conclusions:

RT with adjunctive localized and systematic thrombolytic therapy was performed successfully in this patient with MPE and significant hemodynamic compromise. In our patient who was very unstable from cardio‐respiratory perspective with maximized hemodynamic support, RT device use was life saving. RT has an advantage of not dispersing emboli particles to the distal pulmonary circulation. © 2007 Wiley‐Liss, Inc.
Statin use and risk of breast cancer
Authors: Pocobelli Gaia , Newcomb Polly A. , Trentham‐Dietz Amy , Titus‐Ernstoff Linda , Hampton John M. , Egan Kathleen M.
Published: November 2007

BACKGROUND.

Findings that statins inhibited the proliferation of breast cancer cells in vitro and in rodents have raised interest in whether the use of statins might decrease a woman's risk of developing breast cancer. We analyzed data from a population‐based case‐control study to evaluate the association between the use of statins and breast cancer risk.

METHODS.

Cases of incident invasive breast cancer in women 50 years of age or older and diagnosed from 1995–2001 were identified from population‐based cancer registries in Wisconsin, Massachusetts, and New Hampshire. Controls were randomly selected, within each state, from lists of licensed drivers and Medicare beneficiaries. Information on the use of statins and other breast cancer risk factors was ascertained from structured telephone interviews.

RESULTS.

Overall, breast cancer cases were not more likely than controls to have ever used statins. Ever use of lipophilic statins as a group (simvastatin, lovastatin, and fluvastatin) and ever use of the hydrophilic statin pravastatin were also not associated with breast cancer risk. Ever use of fluvastatin was associated with a decreased risk of breast cancer (odds ratio [OR], 0.5; 95% confidence interval, 0.3–0.8) but the magnitude of the ORs did not vary across categories of duration of use.

CONCLUSIONS.

The use of statins overall was not associated with breast cancer risk. Cancer 2008. © 2007 American Cancer Society.
The bone morphogenetic protein pathway is active in human colon adenomas and inactivated in colorectal cancer
Authors: Kodach Liudmila L. , Bleuming Sylvia A. , Musler Alex R. , Peppelenbosch Maikel P. , Hommes Daniel W. , van den Brink Gijs R. , van Noesel Carel J. M. , Offerhaus G. Johan A. , Hardwick James C. H.
Published: November 2007

BACKGROUND.

Transforming growth factor β (TGFβ) is important in colorectal cancer (CRC) progression. Bone morphogenetic proteins (BMPs), a subgroup within the TGFβ superfamily, recently also have been implicated in CRC, but their precise role in CRC has yet to be investigated.

METHODS.

The authors used a tissue microarray and immunohistochemistry of BMP receptors and signal transduction elements in adenomas and CRC specimens to elucidate the role of BMP signaling in CRC carcinogenesis.

RESULTS.

The adenoma specimens expressed all 3 BMP receptors (BMPRs) (BMPR type 1a [BMPR1a], BMPR1b, and BMPR2) and expressed SMAD family member 4 (SMAD4); and 20 of 22 adenomas (90.9%) exhibited active BMP signaling, as determined by nuclear phosphorylated SMAD1,5,8 (pSMAD1,5,8) expression. In contrast, pSMAD1,5,8 nuclear staining was present in 5 CRC specimens (22.7%) but was lost in 17 CRC specimens (77.3%; cancer vs adenoma; P < .0001). The earliest loss of pSMAD1,5,8 nuclear staining was detected in regions of high‐grade dysplasia/carcinoma in situ within adenomas. CRCs showed frequent loss of BMPR2 (P < .0001) and SMAD4 (P < .01) compared with adenomas. Negative expression of BMPR2 was observed more frequently in earlier stage cancers (Dukes stage B) than in advanced cancers (Dukes stage C; P < .05).

CONCLUSIONS.

Taken together, the current results indicated that loss of BMP signaling correlates tightly with progression of adenomas to cancer and occurs relatively early during cancer progression. Cancer 2008. © 2007 American Cancer Society.
Multiple biomarkers improve prediction of bladder cancer recurrence and mortality in patients undergoing cystectomy
Authors: Shariat Shahrokh F. , Karakiewicz Pierre I. , Ashfaq Raheela , Lerner Seth P. , Palapattu Ganesh S. , Cote Richard J. , Sagalowsky Arthur I. , Lotan Yair
Published: November 2007

BACKGROUND.

Tested was whether the assessment of 5 established bladder cancer biomarkers (p53, pRB, p21, p27, and cyclin E1) could improve the ability to predict disease recurrence and cancer‐specific survival after radical cystectomy in patients with pTa‐3N0M0 urothelial carcinoma of the bladder (UCB).

METHODS.

The study comprised 191 patients with pTa‐3N0M0 UCB treated with radical cystectomy and bilateral lymphadenectomy (median follow‐up, 3.1 years). Biomarker expression was assayed on serial tissue microarray slides using quantitative immunohistochemistry using advanced cell imaging and color detection software. Predictive accuracy was quantified using the concordance index and 200‐bootstrap resamples were used to reduce overfit bias. Bootstrap‐adjusted predictive accuracy estimates were compared using the Mantel‐Haenszel test.

RESULTS.

UCB recurred in 36 (18.8%) patients and 30 (15.7%) died of bladder cancer; 157 (82.2%) patients had altered expression of at least 1 biomarker. In univariate analyses the number of altered biomarkers had the highest predictive accuracy for both disease recurrence (76.8%, P < .001) and cancer‐specific mortality (78.3%, P < .001). Addition of the number of altered biomarkers increased the predictive accuracy of nomograms based on the TNM staging system for disease recurrence and cancer‐specific mortality by 10.9% (83.4% vs 72.5%, P < .001) and 8.6% (86.9% vs 78.3, P < .001), respectively.

CONCLUSIONS.

Assessment of the number of altered biomarkers in the cystectomy specimen improves the prediction of bladder cancer recurrence and survival in patients with pTa‐3N0M0 disease. Prospective evaluation of alteration in these biomarkers can help identify patients who would benefit from adjuvant treatment after radical cystectomy. Cancer 2008. © 2007 American Cancer Society.
Late recurrence from salivary gland cancer
Authors: Chen Allen M. , Garcia Joaquin , Granchi Phillip J. , Johnson Jessica , Eisele David W.
Published: November 2007

BACKGROUND.

The purpose of the current study was to determine the incidence of late recurrences, which were defined as those occurring ≥5 years after initial therapy, among patients treated for salivary gland cancer.

METHODS.

Between 1960 and 2000, 145 patients underwent definitive therapy for localized carcinomas of the salivary glands and were clinically without evidence of disease at 5 years of follow‐up. Cumulative probabilities for developing a subsequent late recurrence were estimated using the Kaplan‐Meier method.

RESULTS.

The 10‐year and 15‐year cumulative probabilities of late recurrence in patients who were free of disease at 5 years were 13% and 18%, respectively. The crude rates of late recurrence by histologic subtype were adenoid cystic carcinoma (26%), mixed malignant tumor (25%), mucoepidermoid carcinoma (17%), adenocarcinoma (10%), and acinic cell carcinoma (8%). Sites of late recurrence included distant metastasis (17 patients), local recurrence (8 patients), and regional recurrence (2 patients). The median time to late recurrence was 7.1 years (range, 5.2–23.1 years) from the date of initial surgery. Salvage treatment varied according to location of disease recurrence and initial treatment characteristics. The 15‐year estimate of overall survival was 39% for patients who experienced a late recurrence compared with 71% for those who remained free of disease (P = .001).

CONCLUSIONS.

A significant proportion of patients who are presumed to be cured of their disease at 5 years after initial treatment for salivary gland cancer will be found to develop late disease recurrence with additional follow‐up. Cancer 2008. © 2007 American Cancer Society.
Increased inducible nitric oxide synthase in lung carcinoma of smokers
Authors: Chen George G. , Lee Tak Wai , Xu Hu , Yip Johnson H. Y. , Li Mingyue , Mok Tony S. K. , Yim Anthony P. C.
Published: November 2007

BACKGROUND.

Cigarette smoking is well known to play an important role in the development of lung cancer. Inducible nitric oxide synthase (iNOS) can either promote or inhibit cell proliferation and growth, which makes its role in the development of malignant tumors controversial. The relation between cigarette smoking and iNOS in human lung cancer is unknown.

METHODS.

The study examined the levels of iNOS/NO in nonsmall‐cell lung cancer (NSCLC) tissues of smokers and nonsmokers and in NSCLC cells (NCI‐H23) treated by 4‐(N‐Methyl‐N‐nitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK), a potent tobacco‐specific carcinogen.

RESULTS.

The level of iNOS/NO was significantly higher in lung cancer tissues of smokers than that of nonsmokers. Unlike iNOS/NO, the activity of caspase‐3 was reduced in the former compared with the latter. The expression of the cleaved caspase‐3 was deceased in NCI‐H23 cells treated with S‐Nitroso‐N‐acetylpenicillamine (SNAP), an NO donor, whereas treatment with NG‐methyl‐L‐arginine (NMA), an NO inhibitor, caused an increase in cleaved caspase‐3. Consistent with the change in caspase‐3, SNAP treatment inhibited cell death induced by UCN01, a potent cell death‐inducer. NMA treatment greatly enhanced the sensitivity of the cells to UCN01. Further, the cells treated by NNK showed an increase in iNOS protein, accompanied by an elevation of cell proliferation.

CONCLUSIONS.

The study demonstrates that cigarette smoking promotes the level of iNOS/NO but suppresses the activity of caspase‐3, which may lead to the proliferation and growth of lung cancer cells. Cancer 2008. © 2007 American Cancer Society.
Ablation of CdTe with 100 µs Nd:YAG laser pulses: dependence on target preparation method
Authors: Rzeszutek J. , Oszwaldowski M. , Savchuk V.
Published: November 2007

The results of experimental studies of the ablation of CdTe with a pulsed Nd:YAG laser (wavelength 1064 nm) performed with 100 µs pulses and repetition time of 35 Hz are presented for the pulse energy range from 0.13 to 0.25 J. The main goal is to elucidate the dependence of the ablation process on the target preparation method. The investigation of the vapour stream intensity and chemical composition and their evolution with time are performed with a quadrupole mass spectrometer synchronized with the laser pulses. These studies are performed for three kinds of targets: a target made of CdTe bulk crystal (BC target), a target made of CdTe fine powder pressed under the pressure of 700 atm (PP target), and a target made of loose CdTe powder (N‐PP target). The applicability of these targets for obtaining high quality CdTe thin films is determined. The best chemical composition of the vapour stream can be obtained with the BC target. A major drawback of this target is the energetic threshold for ablation with Nd:YAG laser and resulting delay in the ablation process above the threshold. The advantage of powder targets over BC target is the lack of any ablation threshold or delay. Weaker angular dependence of the particle emission (associated with the surface roughness), if confirmed in further experiments, can be the most important advantage of PP and N‐PP targets. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Growth of ultra‐high purity PbI2 single crystal: (1) Preparation of high purity PbI2
Authors: Hayashi T. , Kinpara M. , Wang J. F. , Mimura K. , Isshiki M.
Published: November 2007

In order to prepare high purity lead iodide (PbI2) single crystals, the starting material‐iodine (I) has been purified by the sublimation method, and the PbI2 polycrystalline by the normal freezing method. The purification effect of these methods has been confirmed by evaluating the impurity concentration in ingot by glow discharge mass spectrometry (GDMS) analysis. By comparing the purity of three different starting materials, non‐purified iodine+6N‐Pb, purified iodine+6N‐Pb and commercial 6N‐PbI2, PbI2 synthesized by purified iodine in the present experiment has the highest purity. This indicates that these purification methods are suitable. The present research results are expected to prepare high‐resistivity PbI2 used in radiation detector. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Structure determination of two asymmetrically substituted oxadiazoles from powder diffraction data
Authors: Emmerling F. , Reck G. , Kraus W. , Orgzall I. , Schulz B.
Published: November 2007

The crystal structures of the 1,3,4 oxadiazole compounds N,N‐dimethyl‐N‐[4‐(1,3,4‐oxadiazol‐2‐yl)phenyl]amine (1) and 2‐methyl‐5‐phenyl‐1,3,4‐oxadiazole (2) have been determined. In case of 1 no adequate crystals were available; therefore the structure was solved at room temperature from X‐ray powder diffraction data using the method of simulated annealing. This solution is compared to a second one obtained by applying the molecular replacement method. Subsequent Rietveld refinements combined with the so called two stage method based on the data collected to 1.6 Å resolution yielded an Rwp value of 7.27% for 1. Compound 1 crystallizes in the orthorhombic space group P212121 with lattice parameters of a = 7.599(4) Å, b = 6.004(2) Å, c = 21.736(3) Å. The crystal structure of 2 was solved by means of single crystal structure analysis (monoclinic space group P21/c, a = 8.010(3) Å, b = 10.783(4) Å, c = 19.234(7) Å, β = 90.794(9)°). (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Affecting Kt/V: An Analysis of Staff Interventions
Authors: Henning Michael R.
Published: November 2007

This article examines current and past literature on the use of Kt/V to determine dialysis adequacy and the staff‐dependent factors that influence this measurement of dialysis adequacy. The variance in Kt/V values between centers and between regions of the United States has been noted as a limitation in the interpretation of much evidence‐based research and the topic of several studies. It is important for the dialysis staff, nurses in particular, to take a leading role in managing patient care in order to maximize Kt/V values, which are linked to morbidity and mortality. Although some believe that Kt/V is an inadequate measure of adequacy, it seems to be the value most associated with dialysis patients. Dialysis nurses are an essential link in managing a patient's dialysis prescription, central venous catheter management, and patient and staff education—the latter of critical importance in maximizing dialysis adequacy.
The usefulness of detecting thyroglobulin in fine‐needle aspirates from patients with neck lesions using a sensitive thyroglobulin assay
Authors: Sigstad E. , Heilo A. , Paus E. , Holgersen K. , Grøholt K. K. , Jørgensen L. H. , Bogsrud T. V. , Berner A. , Bjøro T.
Published: November 2007

The aim of this study was to assess the diagnostic utility of thyroglobulin (Tg) in fine needle aspirates (Tg‐FNAB) of nonthyroidal neck masses using a sensitive in‐house method for detecting Tg in washout specimens.

A total of 256 samples from 145 patients were evaluated for Tg in washout specimen from FNAB and compared to corresponding cytological smear and histology of 46 surgical specimens. Tg was measured by a sensitive in‐house time‐resolved immunofluorometric assay.

The sensitivity for Tg‐FNAB alone or in combination with cytological findings was found to be 100% in both the follow‐up group and before primary surgery. In the follow‐up group the specificity of Tg‐FNAB was 100%.

Fifty‐nine of 60 follow‐up specimens with malignant cytology were Tg‐FNAB positive (n = 195). Histological examination of one lymph node with malignant cytology and negative Tg‐FNAB showed metastasis from carcinoma of the salivary gland. Tg‐FNAB was positive in 25 specimens with suspicious or cystic cytology. Tg‐FNAB values were high (median 4557 μg/l, range 122–37200 μg/l) in washout specimen from cystic metastasis from which cytology did not confirm malignancy. Of the 20 lymph nodes with histology confirming metastasis from differentiated thyroid carcinoma (DTC), the Tg‐FNAB was positive in 19 and intermediate in one. However, before primary surgery, two Tg‐FNABs were false positive compared to the histology of the lymph nodes. TgAb in serum did not interfere with FNAB‐Tg measurements.

Tg‐FNAB measurement is accurate with high sensitivity (100%) and of great importance in detecting cystic metastasis when cytology is not conclusive. Even metastases to small neck lymph nodes may be detected by using sensitive Tg‐assay. Serum thyroglobulin antibodies appear to have ignorable effect on the clinical performance of Tg‐FNAB. Diagn. Cytopathol. 2007;35:761–767. © 2007 Wiley‐Liss, Inc.
Case report and review of lupus erythematosus cells in cytology fluids
Authors: Park Jason Y. , Malik Aarti , Dumoff Kimberly L. , Gupta Prabodh K.
Published: November 2007

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease typically diagnosed by a combination of physical findings and clinical laboratory testing. Several decades ago, the diagnosis of lupus included the lupus erythematosus (LE) cell assay. Autoimmune serology techniques such as anti‐nuclear antibody staining have replaced the LE cell assay. However, as presented in this report and review of the literature, the in vivo finding of LE cells by cytopathology remains an important finding consistent with the diagnosis of SLE. Diagn. Cytopathol. 2007;35:806–809. © 2007 Wiley‐Liss, Inc.
Evidence for the involvement of lung‐specific γδ T cell subsets in local responses to Streptococcus pneumoniae infection
Authors: Kirby Alun C. , Newton Darren J. , Carding Simon R. , Kaye Paul M.
Published: November 2007

Although γδ T cells are involved in the response to many pathogens, the dynamics and heterogeneity of the local γδ T cell response remains poorly defined. We recently identified γδ T cells as regulators of macrophages and dendritic cells during the resolution of Streptococcus pneumoniae‐mediated lung inflammation. Here, using PCR, spectratype analysis and flow cytometry, we show that multiple γδ T cell subsets, including those bearing Vγ1, Vγ4 and Vγ6 TCR, increase in number in the lungs of infected mice, but not in associated lymphoid tissue. These γδ T cells displayed signs of activation, as defined by CD69 and CD25 expression. In vivo BrdU incorporation suggested that local expansion, rather than recruitment, was the principal mechanism underlying this increase in γδ T cells. This conclusion was supported by the finding that pulmonary γδ T cells, but not αβ T cells, isolated from mice that had resolved infection exhibited lung‐homing capacity in both naive and infected recipients. Together, these data provide novel insights into the origins of the heterogeneous γδ T cell response that accompanies lung infection, and the first evidence that inflammation‐associated γδ T cells may exhibit distinct tissue‐homing potential.
Therapy‐induced antitumor vaccination by targeting tumor necrosis factor‐α to tumor vessels in combination with melphalan
Authors: Mortara Lorenzo , Balza Enrica , Sassi Francesca , Castellani Patrizia , Carnemolla Barbara , De Lerma Barbaro Andrea , Fossati Sara , Tosi Giovanna , Accolla Roberto S. , Borsi Laura
Published: November 2007

Treatment of tumor‐bearing mice with mouse (m)TNF‐α, targeted to tumor vasculature by the anti‐ED‐B fibronectin domain antibody L19(scFv) and combined with melphalan, induces a therapeutic immune response. Upon treatment, a highly efficient priming of CD4+ T cells and consequent activation and maturation of CD8+ CTL effectors is generated, as demonstrated by in vivo depletion and adoptive cell transfer experiments. Immunohistochemical analysis of the tumor tissue demonstrated massive infiltration of CD4+ and CD8+ T cells 6 days after treatment and much earlier in the anamnestic response to tumor challenge in cured mice. In fact, the curative treatment with L19mTNF‐α and melphalan resulted in long‐lasting antitumor immune memory, accompanied by a mixed Th1/Th2‐type response and significant in vitro tumor‐specific cytolytic activity. Finally, the combined treatment reduced the percentage and absolute number of CD4+CD25+ regulatory T cells in the tumor‐draining lymph nodes of mice responding to therapy, and this was associated with the establishment of protective immunity. These findings pave the way for alternative therapeutic strategies based on the targeted delivery of biological and pharmacological cytotoxic compounds that not only kill most of the tumor cells but, more importantly, trigger an effective and long‐lasting antitumor adaptive immune response.
CD303 (BDCA‐2) signals in plasmacytoid dendritic cells via a BCR‐like signalosome involving Syk, Slp65 and PLCγ2
Authors: Röck Jürgen , Schneider Erik , Grün Joachim R. , Grützkau Andreas , Küppers Ralf , Schmitz Jürgen , Winkels Gregor
Published: November 2007

Plasmacytoid dendritic cells (PDC) are the main type I interferon (IFN‐I) producers and play a central role in innate and adaptive immunity. CD303 (BDCA‐2) is a type II c‐type lectin specifically expressed by human PDC. CD303 signaling induces tyrosine phosphorylation and Src kinase dependent calcium influx. Cross‐linking CD303 results in the inhibition of IFN‐I production in stimulated PDC. Here, we demonstrate that PDC express a signalosome similar to the BCR signalosome, consisting of Lyn, Syk, Btk, Slp65 (Blnk) and PLCγ2. CD303 associates with the signaling adapter FcR γ‐chain. Triggering CD303 leads to tyrosine phosphorylation of Syk, Slp65, PLCγ2 and cytoskeletal proteins. Analogous to BCR signaling, CD303 signaling is likely linked with its internalization by clathrin‐mediated endocytosis. Furthermore, CD303 signaling leads to reduced levels of transcripts for IFN‐I genes and IFN‐I‐responsive genes, indicating that the inhibition of IFN‐I production by stimulated PDC is at least partially regulated at the transcriptional level. These results support a possible therapeutic value of an anti‐CD303 mAb strategy, since the production of IFN‐I by PDC is considered to be a major pathophysiological factor in systemic lupus erythematosus patients.

See accompanying commentary at http://dx.doi.org/10.1002/eji200737944
Effect of chronic azathioprine treatment on germ‐line transmission ofHprtmutation in mice
Authors: Bendre Sachin V. , Shaddock Joseph G. , Dobrovolsky Vasily N. , Albertini Richard J. , Heflich Robert H.
Published: November 2007

Azathioprine (Aza), a prodrug of 6‐mercaptopurine, is used in human medicine to prevent transplant rejection and for the treatment of autoimmune diseases. Extremely highHPRTlymphocyte mutant frequencies (MFs) are found in humans and mice chronically treated with Aza, and these elevated MFs appear to be caused by selection and amplification of pre‐existingHPRTmutant lymphocytes. In the present study, we investigated if in vivo selection by Aza also promotes the germ‐line transmission ofHprtmutants. Fifty‐five male C57BL/6 mice were treated with 10 mg/kg Aza three times/week for 24 weeks; 10 control mice were treated with the vehicle. Each of these males then was bred to unexposed females for a total of 8 weeks. Analysis of the Aza‐treated males after the breeding period indicated that 12 had highly elevatedHprtlymphocyte MFs (1 × 10−4–2.5 × 10−1vs. normal MFs of <1 × 10−5), indicating that the Aza treatment successfully selected somatic cell mutants. The female offspring from the breeding were sacrificed at 28 days of age andHprtMFs were measured in spleen lymphocytes. Most of the 364 female offspring (332 from Aza‐treated fathers) hadHprtMFs of 0–6 × 10−6, but seven of the offspring had moderately elevated MFs of 16 × 10−6–55 × 10−6. Since one of these mice was fathered by a control male, these relatively high MFs appear to be part of the normal variation in lymphocyteHprtMF. The present results provide no evidence that long‐term Aza treatment promotes high levels of germ‐lineHprtmutation transmission in mice. Environ. Mol. Mutagen., 2007. Published 2007 Wiley‐Liss, Inc.
A preliminary investigation of the reliability and validity of the Brief Assessment Schedule Depression Cards and the Beck Depression Inventory‐Fast Screen to screen for depression in older stroke survivors
Authors: Healey A. K. , Kneebone I. I. , Carroll M. , Anderson S. J.
Published: November 2007

Objective

To conduct an initial assessment of the reliability and validity of the Brief Assessment Schedule Depression Cards (BASDEC) and the Beck Depression Inventory‐Fast Screen (BDI‐FS) to screen for depression in older stroke survivors.

Methods

Participants from four inpatient rehabilitation units completed the BASDEC and the BDI‐FS together with the Hospital Anxiety and Depression Scale (HADS) for comparison. The Structured Clinical Interview for DSM‐IV Axis 1 Disorders (SCID) was then completed with all participants to ascertain a criterion depression diagnosis. The BASDEC and BDI‐FS were subsequently completed for a second time.

Results

Forty‐nine stroke survivors (M = 78.80, SD = 6.79 years) were included. The BASDEC and BDI‐FS demonstrated acceptable internal consistency and test–retest reliability. The BASDEC (cut‐off ≥7) resulted in a sensitivity of 1.0 and specificity of 0.95 for detecting major depression whereas the BDI‐FS (cut‐off ≥4) had a sensitivity of 0.71 and specificity of 0.74. When participants with minor depression were included in analyses, sensitivity lowered to 0.69 (specificity = 0.97) for the BASDEC and 0.62 (specificity = 0.78) for the BDI‐FS.

Conclusions

The BASDEC and BDI‐FS were found to have acceptable reliability. The BASDEC demonstrated some advantage in criterion validity over the BDI‐FS at the examined cut‐offs. Copyright © 2007 John Wiley & Sons, Ltd.
Matrix metalloproteinase inhibition protects rat livers from prolonged cold ischemia–warm reperfusion injury
Authors: Defamie Virginie , Laurens Marina , Patrono Damiano , Devel Laurent , Brault Antoine , Saint-Paul Marie-Christine , Yiotakis Athanasios , Barbry Pascal , Gugenheim Jean , Crenesse Dominique , Dive Vincent , Huet Pierre-Michel , Mari Bernard
Published: November 2007

Matrix metalloproteinases (MMPs) have been implicated in the hepatic injury induced after cold ischemia–warm reperfusion (CI-WR), by altering the extracellular matrix (ECM), but their precise role remains unknown. The hepatic MMP expression was evaluated after 2 conditions of CI (4°C for 24 and 42 hours: viable and nonviable livers) followed by different periods of WR, using isolated perfused rat livers. CI-WR induced moderate changes in hepatic MMP transcript levels not influenced by CI duration, whereas gelatinase activities accumulated in liver effluents. Therefore, the protective effect of a new phosphinic MMP inhibitor, RXP409, was tested after prolonged CI. RXP409 (10 μM) was added to the University of Wisconsin solution, and livers were preserved for 42 hours (4°C), then reperfused for 1 hour in Krebs solution (37°C), containing 20% erythrocytes. Liver viability parameters were recorded, and the extent of cell necrosis was evaluated on liver biopsies, using trypan blue nuclear uptake. Treatment with RXP409 significantly improved liver function (transaminase release and bile secretion) and liver injury. In particular, the MMP inhibitor significantly modified the extent of cell death from large clusters of necrotic hepatocytes as found in control livers (2%–60% of liver biopsies; mean, 26% ± 9%) to isolated necrotic hepatocytes as found in treated livers (0.2%–12%; mean, 3% ± 2%) (

P

< 0.05).

Conclusion:

These data demonstrate that MMPs, by altering the ECM, play a major role in liver CI-WR injury leading to extensive hepatocyte necrosis and that their inhibition might prove to be a new strategy in improving preservation solutions. (Hepatology 2007.)
Synthesis of Enantiomerically Pure 1,5,5‐Trideuterated cis‐ and trans‐2,4‐Dioxa‐3‐phosphadecalins. 31P‐NMR Evidence of Covalent‐Bond Formation and the Stereochemical Implications in the Course of the Inhibition of δ‐Chymotrypsin
Authors: Stöckli Markus J. , Rüedi Peter
Published: November 2007

The irreversible inhibition of δ‐chymotrypsin with the enantiomerically pure, P(3)‐axially and P(3)‐equatorially X‐substituted cis‐ and trans‐configurated 2,4‐dioxa‐3‐phospha(1,5,5‐2H3)bicyclo[4.4.0]decane 3‐oxides (X=F, 2,4‐dinitrophenoxy) was monitored by 31P‐NMR spectroscopy. 1H‐Correlated 31P{2H}‐NMR spectra enabled the direct observation of the vicinal coupling (3J) between the P‐atom of the inhibitor and the CH2O moiety of Ser195 (=‘Ser195’(CH2O)), thus establishing the covalent nature of the ‘Ser195’(CH2OP) bond in the inhibited enzyme. The stereochemical course of the phosphorylation is dependent on the structure of the inhibitor, and neat inversion, both inversion and retention, as well as neat retention of the configuration at the P‐atom was found.
Vanadium(III) Chloride (VCl3): Efficient Reagent for the Introduction of Tetrahydrofuran‐Based Acetal Protecting Groups for Alcohols
Authors: Das Biswanath , Krishnaiah Maddeboina , Reddy Vtukuri Saidi , Laxminarayana Keetha
Published: November 2007

Treatment of different types of alcohols with tetrahydrofuran (THF) in the presence of VCl3 and CCl4 smoothly afforded the corresponding THF‐based acetals in excellent yields. The reaction is fast at room temperature, and several functional groups are tolerated, with no racemization being observed. A radical mechanism, based on Cl3C. as the active species, is proposed for this novel kind of transformation, which complements the classical tetrahydro‐2H‐pyran‐2‐yl (THP) protocol.
New Eremophilenolactones from Senecio nemorensis
Authors: Meng Fan‐Jun , Zhao Hong , Xie Wei‐Dong , Zhao Rui‐Jian , Lai Peng‐Xiang , Zhou Yan‐Xia , Miao Yan‐Li
Published: November 2007

Three new eremophilane sesquiterpenes were isolated from the MeOH extract of the roots of Senecio nemorensis. Their structures were identified as 8α‐hydroxy‐6β‐(isobutanoyloxy)‐1‐oxoeremophila‐7(11),9‐dieno‐12,8β‐lactone (1), 6β,8β‐dimethoxy‐1‐oxoeremophila‐7(11),9‐dieno‐12,8α‐lactone (2), and 10α‐hydroxy‐6β‐(isobutanoyloxy)‐1‐oxoeremophila‐7(11),8‐dieno‐12,8‐lactone (3), respectively, based on spectroscopic data, including IR, EI‐MS, HR‐ESI‐MS, and 1D‐ and 2D‐NMR data.
Three Cyclized Isoprenylated Flavonoids from the Roots and Rhizomes of Sophora tonkinensis
Authors: Ding Peilan , Chen Daofeng
Published: November 2007

Two new flavanones, tonkinochromanes D (1) and E (2), and a new chalcone, tonkinochromane F (3), were isolated from the roots and rhizomes of Sophora tonkinensis. Their structures were elucidated by spectroscopic methods, including 2D‐NMR and circular‐dichroism (CD) techniques, in combination with HR‐MS analysis. Compounds 1–3, as well the previously reported tonkinochromanes A–C, were shown by LC‐MS analysis to be ‘artifacts’ resulting from acid‐catalyzed electrophilic cyclization of isoprenyl side chains during extraction.
Four New Lanostane Triterpenoids from Euphorbia humifusa
Authors: Lu Zhi‐Qiang , Chen Guang‐Tong , Zhang Jin‐Qiang , Huang Hui‐Lian , Guan Shu‐Hong , Guo De‐An
Published: November 2007

Four new lanostane triterpenoids, namely (3β)‐3‐hydroxy‐24‐methylenelanost‐8‐ene‐7,11‐dione (1), (3β)‐3‐hydroxylanosta‐8,24‐diene‐7,11‐dione (2), (3β,7α)‐3,7‐dihydroxylanosta‐8,24‐dien‐11‐one (3), and (3β,11β)‐3,11‐dihydroxylanosta‐8,24‐dien‐7‐one (4) were isolated from Euphorbia humifusa, together with 2 known compounds. The structures of these new compounds were elucidated on the basis of extensive spectroscopic analysis and comparison with the related known compounds.
Hydro‐climatic impacts on the ice cover of the lower Peace River
Authors: Beltaos Spyros
Published: November 2007

Since the late 1960s, a paucity of ice‐jam flooding in the lower Peace River has resulted in prolonged dry periods and considerable reduction in the area covered by lakes and ponds that provide habitat for aquatic life in the Peace–Athabasca Delta (PAD) region. Though major ice jams occur at breakup, antecedent conditions play a significant role in their frequency and severity. These conditions are partly defined by the mode of freezeup and the maximum thickness that is attained during the winter, shortly before the onset of spring and development of positive net heat fluxes to the ice cover. Data from hydrometric gauge records and from field surveys are utilized herein to study these conditions. It is shown that freezeup flows are considerably larger at the present time than before regulation, and may be responsible for more frequent formation of porous accumulation covers. Despite a concomitant rise in winter temperatures, solid‐ice thickness has increased since the 1960s. Using a simple ice growth model, specifically developed for the study area, it is shown that porous accumulation covers enhance winter ice growth via accelerated freezing into the porous accumulation. Coupled with a reduction in winter snowfall, this effect can not only negate, but reverse, the effect of warmer winters on ice thickness, thus explaining present conditions. The present model is also shown to be a useful prediction tool, especially for extrapolating incomplete data to the end of the winter. Copyright © 2007 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.
Early life events and conditions and breast cancer risk: From epidemiology to etiology
Authors: Trichopoulos Dimitrios , Adami Hans‐Olov , Ekbom Anders , Hsieh Chung‐Cheng , Lagiou Pagona
Published: November 2007

Risk factors for breast cancer—documented by intensive epidemiological investigations and viewed in the context of general principles of carcinogenesis—can be integrated to an etiologic model comprising 3 principal components: the likelihood of breast cancer occurrence depends on the number of mammary tissue‐specific stem cells, which is determined in early life; all growth‐enhancing mammotropic hormones affect the rate of expansion of initiated clones; and while a pregnancy stimulates the replication of already initiated cells, it conveys long‐term protection through differentiation of mammary tissue‐specific stem cells. This perspective accommodates much of what is known about the epidemiology and natural history of breast cancer and highlights the role of early life in the origin of this cancer. © 2007 Wiley‐Liss, Inc.
Fatigue strength of human cortical bone: Age, physical, and material heterogeneity effects
Authors: Zioupos P. , Gresle M. , Winwood K.
Published: November 2007

Human bone is highly heterogeneous at the microscale and this heterogeneity has been thought to relate to some fracture scenarios. The fatigue strength of cortical bone has been shown to relate to its inner architecture (osteonal or fibrolamellar) and some physical characteristics in the past, but never to the heterogeneity of its microstructure. The present study examines for the first time, the fatigue strength of human bone for six individuals of various ages in three main modes (tension, compression, and shear), the salient physical characteristics of these same specimens and the elastic mismatch that is present at a microstructural level by performing microhardness measurements on osteons and their surrounding matrix areas. The results showed that the ratio of hardness values in osteons and interstitial areas adversely affects fatigue strength with an effect more potent if not equal to the other usual factors such as “age” or features, material density, porosity, and mineral content, which are measured in a homogenized (averaged over a cross section) manner at a macrostructural (large scale) level. It has been known that fatigue microcracks localize in regions between osteons and interstitial matrix and in hypermineralized matrix areas. The present results indicate that, perhaps, heterogeneity not only influences the initiation of microcracks, but also their eventual growth and coalescence into larger cracks, which are detrimental for the integrity of the material. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Characterization and dynamic mechanical analysis of selective laser sintered hydroxyapatite‐filled polymeric composites
Authors: Zhang Y. , Hao L. , Savalani M. M. , Harris R. A. , Tanner K. E.
Published: November 2007

Selective laser sintering (SLS) is a manufacturing technique which enables the final product to be made directly and rapidly, without tooling or additional machining. For biomedical applications, SLS permits the fabrication of implants and scaffolds with complex geometry accurately and economically. In this study, hydroxyapatite‐reinforced polyethylene and polyamide composites were fabricated using SLS. The SLS samples were characterized in terms of their internal structure, morphology, and porosity. The mechanical properties were examined by dynamic mechanical analysis. The effects of SLS processing conditions, including particle size and laser power, were investigated, and the results were compared with conventional compression‐molded and machined specimens. The internal structure of sintered samples was porous, with open interconnected pores, and the pore size was up to 200 μm. Particle size and laser energy play a key role in the final density and mechanical properties of the sintered components. In the parameter range used, the use of smaller particles produced higher density and stiffness, and the laser‐induced energy could also be varied to optimize the manufacturing process. This study demonstrated that high‐HA‐content reinforced polymer composite can be successfully manufactured by SLS with controlled porosity features. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008