bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated fluorescent in situ hybridization (FISH) analysis of t(9;22)(q34;q11) in interphase nuclei
Authors: Kajtár Béla , Méhes Gábor , Lörch Thomas , Deák Linda , Kneifné Marika , Alpár Donát , Pajor László
Published: April 2006

Background:

For chronic myeloid leukemia, the FISH detection of t(9;22)(q34;q11) in interphase nuclei of peripheral leukocytes is an alternative method to bone marrow karyotyping for monitoring treatment. With automation, several drawbacks of manual analysis may be circumvented. In this article, the capabilities of a commercially available automated image acquisition and analysis system were determined by detecting t(9;22)(q34;q11) in interphase nuclei of peripheral leukocytes.

Methods:

Three peripheral blood samples of normal adults, 21 samples of CML patients, and one sample of a t(9;22)(q34;q11) positive cell‐line were used.

Results:

Single nuclei with correctly detected signals amounted to 99.6% of nuclei analyzed after exclusion of overlapping nuclei and nuclei with incorrect signal detection. A cut‐off value of 0.84 μm was defined to discriminate between translocation positive and negative nuclei based on the shortest distance between signals. Using this value, the false positive rate of the automated analysis for negative samples was 7.0%, whereas that of the manual analysis was 5.8%. Automated and manual results showed strong correlation (R2 = 0.985), the mean difference of results was only 3.7%.

Conclusions:

A reliable and objective automated analysis of large numbers of cells is possible, avoiding interobserver variability and producing statistically more accurate results than manual evaluation. © 2006 International Society for Analytical Cytology
Unconventional detection methods for microfluidic devices
Authors: Viskari Pertti J. , Landers James P.
Published: April 2006

The direction of modern analytical techniques is to push for lower detection limits, improved selectivity and sensitivity, faster analysis time, higher throughput, and more inexpensive analysis systems with ever‐decreasing sample volumes. These very ambitious goals are exacerbated by the need to reduce the overall size of the device and the instrumentation – the quest for functional micrototal analysis systems epitomizes this. Microfluidic devices fabricated in glass, and more recently, in a variety of polymers, brings us a step closer to being able to achieve these stringent goals and to realize the economical fabrication of sophisticated instrumentation. However, this places a significant burden on the detection systems associated with microchip‐based analysis systems. There is a need for a universal detector that can efficiently detect sample analytes in real time and with minimal sample manipulation steps, such as lengthy labeling protocols. This review highlights the advances in uncommon or less frequently used detection methods associated with microfluidic devices. As a result, the three most common methods – LIF, electrochemical, and mass spectrometric techniques – are omitted in order to focus on the more esoteric detection methods reported in the literature over the last 2 years.
Functionalized magnetic micro‐ and nanoparticles: Optimization and application to μ‐chip tryptic digestion
Authors: Bílková Zuzana , Slováková Marcela , Minc Nicolas , Fütterer Claus , Cecal Roxana , Horák Daniel , Beneš Milan , le Potier Isabelle , Křenková Jana , Przybylski Michael , Viovy Jean‐Louis
Published: April 2006

The preparation of an easily replaceable protease microreactor for μ‐chip application is described. Magnetic particles coated with poly(N‐isopropylacrylamide), polystyrene, poly(2‐hydroxyethyl methacrylate‐co‐ethylene dimethacrylate), poly(glycidyl methacrylate), [(2‐amino‐ethyl)hydroxymethylen]biphosphonic acid, or alginic acid with immobilized trypsin were utilized for heterogeneous digestion. The properties were optimized, with the constraint of allowing immobilization in a microchannel by a magnetic field gradient. To obtain the highest digestion efficiency, sub‐micrometer spheres were organized by an inhomogeneous external magnetic field perpendicularly to the direction of the channel. Kinetic parameters of the enzyme reactor immobilized in μ‐chip capillary (μ‐chip immobilized magnetic enzyme reactor (IMER)) were determined. The capability of the proteolytic reactor was demonstrated by five model (glyco)proteins ranging in molecular mass from 4.3 to 150 kDa. Digestion efficiency of proteins in various conformations was investigated using SDS‐PAGE, HPCE, RP‐HPLC, and MS. The compatibility of the μ‐chip IMER system with total and limited proteolysis of high‐molecular‐weight (glyco)proteins was confirmed. It opens the route to automated, high‐throughput proteomic μ‐chip devices.
Analysis of arsenic compounds by capillary electrophoresis using indirect UV and mass spectrometric detections
Authors: Kitagawa Fumihiko , Shiomi Kazutaka , Otsuka Koji
Published: April 2006

CE with indirect UV and mass‐spectrometric detection was used for the simultaneous determination of arsenic acid (As(V)), arsenous acid (As(III)), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), trimethylarsine oxide (TMAO), tetramethylarsonium ion (TMA+), arsenobetaine (AB), and arsenocholine (AC). In the CE‐indirect UV analysis, a baseline separation of arsenic species was successfully achieved by using a basic background solution (BGS) for anions and an acidic BGS for cations, respectively. The LOD values in CE‐indirect UV for the individual analytes were 7.8, 12.5, 7.8, 12.5, 62.5, 125, 250, and 62.5 ppm, respectively. To achieve sensitive and selective analysis, CE coupled with ESI‐MS was applied to the determination of arsenic compounds. The organic arsenic species were successfully separated with a higher sensitivity by CE‐MS using the acidic BGS. The LODs in CE‐MS for MMA, DMA, TMAO, TMA+, AB, and AC were 1.0, 0.1, 0.01, 0.1, 0.01, and 0.01 ppm, respectively. In contrast, the analysis of inorganic arsenic species (As(V) and As(III)) resulted in a lower detectability in CE‐MS compared to that obtained with the CE‐indirect UV analysis. However, the speciation of eight arsenics by CE‐MS was successfully achieved in a single run by switching the ESI polarity during MS detection.
Rapid detection of Staphylococcus aureus by a combination of monoclonal antibody‐coated latex and capillary electrophoresis
Authors: Gao Peng , Xu Guowang , Shi Xianzhe , Yuan Kailong , Tian Jing
Published: April 2006

The rapid detection of pathogenic bacteria is extremely important in biotechnology and clinical diagnosis. CE has been utilized in the field of bacterial analysis for many years, but to some extent, simultaneous separation and identification of certain microbes from complex samples by CE coupled with UV detector is still a challenge. In this paper, we propose a new strategy for rapid separation and identification of Staphylococcus aureus (S. aureus) in bacterial mixtures by means of specific mAb‐coated latex coupled with CZE. An appropriate set of conditions that selectively isolated S. aureus from the microorganisms Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae were established. S. aureus could be differentiated from the others by unique peaks in the electropherograms. The validity was also confirmed by LIF with antibodies specific to both the latex and the microbial cells. The LOD is as low as 9.0×105 colony forming unit/mL. We have also utilized this technology to identify S. aureus in a stool sample coming from a healthy volunteer spiked successfully with S. aureus. This CZE‐UV technique can be applied to rapid diagnosis of enteritis caused by S. aureus or other bacterial control‐related fields needing rapid identification of target pathogens from microbial mixtures. In theory, this method is suitable for the detection of any bacterium as long as corresponding bacterium‐specific antibody‐coated latex is available.
Analysis of polymerase chain reaction amplifications through phosphate detection using an enzyme–based microbiosensor in a microfluidic device
Authors: Shiddiky Muhammad J. A. , Rahman Md. Aminur , Park Jang‐Su , Shim Yoon‐Bo
Published: April 2006

An electrochemical method was developed for analyzing PCR amplification through the detection of inorganic phosphates (Pi). This method coupled a microchip to a nanoparticle comprising poly‐5,2'‐5',2''‐terthiophene‐3'‐carboxylic acid (poly‐TTCA)/pyruvate oxidase (PyO) modified microbiosensor. It detects Pi produced from the pyrophosphate (PPi), which is released as a byproduct of PCR. After completion of PCR, PPi is hydrolyzed to Pi by inorganic pyrophosphatase. On the microbiosensor surface, pyruvate was converted to H2O2 by PyO in the presence of Pi and oxygen, and subsequently, the anodic current of enzymatically generated H2O2 was detected at +0.5 V versus Ag/AgCl. The CE‐EC analysis was completed within 2 min in a coated channel with 75.0 mm separation length at the field strength of −200 V/cm. Excellent operation stability of poly‐TTCA/PyO was observed for a long period of analysis. The reproducibility of the analysis yielded an RSD of 3.4% (n = 22) for the peak areas and 1.8% (n = 22) for the migration times. The sensitivity of the analysis was 0.59 ± 0.01 nA/cycle with a regression coefficient of 0.971.
Life cycle evaluation of CO2 recovery and mineral sequestration alternatives
Authors: Khoo Hsien H. , Tan Reginald B.H.
Published: April 2006

CO2 fixation technologies such as mineral sequestration—that is, the storage of CO2 as carbonate rocks—are beginning to emerge as means to mitigate global climatic change. In this study, the Life Cycle Assessment (LCA) approach is applied to quantify the effective systemwide environmental impacts of CO2 sequestration in mineral rocks. Five alternative processes for mineral sequestration are compared in combination with various CO2 recovery technologies. SimaPro's Eco‐indicator '99 (“Hierarchist‐Average” version) is used for generating the impact assessment results and sensitivity analysis was carried out to compare the results with other possible weighting options. Finally, the sequestration effectiveness parameter was calculated for the various combinations of CO2 recovery and mineral sequestration options. © 2006 American Institute of Chemical Engineers Environ Prog, 2006
High incidence of t(7;12)(q36;p13) in infant AML but not in infant ALL, with a dismal outcome and ectopic expression of HLXB9
Authors: von Bergh Anne R. M. , van Drunen Ellen , van Wering Elisabeth R. , van Zutven Laura J. C. M. , Hainmann Ina , Lönnerholm Gudmar , Meijerink Jules P. , Pieters Rob , Beverloo H. Berna
Published: April 2006

The t(7;12)(q36;p13) is a recurrent translocation involving the ETV6/TEL gene (12p13) and a heterogeneous breakpoint at 7q36. A fusion transcript between HLXB9 and ETV6 in AML with t(7;12) is occasionally found. To study the incidence of t(7;12) in infant and childhood acute leukemia, we screened 320 cases <36 months using FISH. Additionally, 28 pediatric cases >36 months with cytogenetic breakpoints at 12p and 7q were investigated. We studied the presence of an HXLB9‐ETV6 fusion transcript and quantified the expression of various genes located in the 7q36 breakpoint region. In total, six AML patients carried the t(7;12) of which five were infants and one child of 18 months. Only one out of 99 infant ALL patients harbored the t(7;12). No t(7;12) was found in older children with AML or ALL. AML patients carrying a t(7;12) had a poor outcome with a 3‐year EFS of 0%. A fusion of HLXB9 to ETV6 was found in four AML cases with t(7;12). The 7q36 genes NOM1, LMBR1, RNF32, and SHH were equally expressed among t(7;12)‐positive AML versus t(7;12)‐negative AML, t(7;12)‐negative ALL, or normal bone marrow. However, the HLXB9 expression was highly increased in t(7;12)‐positive cases, including those with an HLXB9‐ETV6 fusion. We conclude that the t(7;12) is almost exclusively present in infant AML and covers 30% of infant AML, while it is extremely rare in infant ALL and older children. The t(7;12) is associated with a poor outcome and an ectopic expression of HLXB9 is commonly involved in this genetic subtype of leukemia. © 2006 Wiley‐Liss, Inc.
The Nutrition, Aging, and Memory in Elders (NAME) study: design and methods for a study of micronutrients and cognitive function in a homebound elderly population
Authors: Scott Tammy M. , Peter Inga , Tucker Katherine L. , Arsenault Lisa , Bergethon Peter , Bhadelia Rafeeque , Buell Jennifer , Collins Lauren , Dashe John F. , Griffith John , Hibberd Patricia , Leins Drew , Liu Timothy , Ordovas Jose M. , Patz Samuel , Price Lori Lyn , Qiu Wei Qiao , Sarnak Mark , Selhub Jacob , Smaldone Lauren , Wagner Carey , Wang Lixia , Weiner Daniel , Yee Jacqueline , Rosenberg Irwin , Folstein Marshal
Published: April 2006

Background

Micronutrient status can affect cognitive function in the elderly; however, there is much to learn about the precise effects. Understanding mediating factors by which micronutrient status affects cognitive function would contribute to elders' quality of life and their ability to remain in the home.

Objectives

The Nutrition, Aging, and Memory in Elders (NAME) Study is designed to advance the current level of knowledge by investigating potential mediating factors by which micronutrient status contributes to cognitive impairment and central nervous system abnormalities in the elderly. NAME targets homebound elders because they are understudied and particularly at risk for poor nutritional status.

Methods

Subjects are community‐based elders aged 60 and older, recruited through area Aging Services Access Points. The NAME core data include demographics; neuropsychological testing and activities of daily living measures; food frequency, health and behavioral questionnaires; anthropometrics; gene status; plasma micronutrients, homocysteine, and other blood determinants. A neurological examination, psychiatric examination, and brain MRI and volumetric measurements are obtained from a sub‐sample.

Results

Preliminary data from first 300 subjects are reported. These data show that the NAME protocol is feasible and that the enrolled subjects are racially diverse, at‐risk, and had similar basic demographics to the population from which they were drawn.

Conclusion

The goal of the NAME study is to evaluate novel relationships between nutritional factors and cognitive impairment. These data may provide important information on potential new therapeutic strategies and supplementation standards for the elderly to maintain cognitive function and potentially reduce the public health costs of dementia. Copyright © 2006 John Wiley & Sons, Ltd.
CYP2D6 genotype and venlafaxine‐XR concentrations in depressed elderly
Authors: Whyte Ellen M. , Romkes Marjorie , Mulsant Benoit H. , Kirshne Margaret A. , Begley Amy E. , Reynolds Charles F. , Pollock Bruce G.
Published: April 2006

Introduction

The elderly are at increased risk for medication‐related adverse events. Recent reports indicate that venlafaxine may put the elderly at increased risk of cardio‐ and cerebrovascular adverse events. We investigated the relationship between theCYP2D6polymorphism and steady‐state plasma concentration of venlafaxine (VEN) and its primary metabolite o‐desmethylvenlafaxine (ODV) in elderly participants receiving venlafaxine‐XR for major depression in order to explore the contribution of pharmacogenetics to medication tolerability.

Methods

Forty‐six elderly participants received venlafaxine‐XR for the treatment of major depression.CYP2D6genotype and steady‐state plasma levels of VEN and ODV were determined.

Results

Sixty‐five percent of participants were homozygous of the wild type (WT) allele, whereas 35% carried one or more variant alleles associated with intermediate and poor 2D6 metabolizer status. VEN concentration per unit dose was significantly higher and ODV concentration per unit dose was significantly lower in participants who carried one or more variant alleles compared to participants who were homozygous for the WT allele. The VEN and ODV concentrations per unit dose were also correlated with creatinine clearance.CYP2D6genotype was not associated with medication associated side‐effects.

Conclusions

Plasma dose‐corrected concentrations of VEN and ODV correlated with genetically determinedCYP2D6enzymatic activity in depressed elders treated with venlafaxine‐XR. This relationship was not masked by the effects of age‐related illness or polypharmacy. Future clinical application of pharmacogenetics to examine 2D6‐dependent medications may help reduce the incidence of medication adverse events particularly in those elders at higher risk for medication adverse events due to impaired renal or cardiac function. Copyright © 2006 John Wiley & Sons, Ltd.
Angiotensin converting enzyme (ACE) inhibitors modulate the rate of progression of amnestic mild cognitive impairment
Authors: Rozzini Luca , Chilovi Barbara Vicini , Bertoletti Erik , Conti Marta , Rio Ilenia Del , Trabucchi Marco , Padovani Alessandro
Published: April 2006

Background

Predictors of progression to dementia in individuals with mild cognitive impairment (MCI) define different groups with higher risks of progression. To date, efforts to differentiate those who will progress to dementia from those who will not have proved inconclusive, and while grades of risk have been identified, their generalizability is not clear.

Aim

To examine the clinical and socio‐demographical risk factors for progression of memory decline in a sample of subjects with referred memory complaints who met criteria for amnestic MCI.

Methods and materials

Seventy‐four subjects consecutively recruited who met the operational criteria for amnestic MCI. They underwent multidimensional assessment and a neuropsychological battery at baseline and at follow‐up, after one year. Memory decline was defined using the short story mean score change (at follow‐up and at baseline). Subjects showing memory decline, with or without conversion to AD over time, were classified as havingprogressiveMCI; subjects that remained unchanged or improved during follow‐up were considered as havingstableMCI.

Results

Subjects withprogressiveMCI (n = 39, 53%) were older (p = <0.001) and more educated (p = 0.01) compared tostableMCI (n = 35, 47%) and their global cognitive performances, at baseline, were more compromised when assessed by ADAS‐Cog (p = 0.05). Antihypertensive drug prescription was greater in thestableMCI compared toprogressiveMCI (p = 0.01) and significant higher levels of plasma total homocysteine were obeserved inprogressiveMCI (p = 0.03). When analyzed in a logistic regression model, the prescription of Angiotensin Converting Enzyme Inhibitors (ACE) was found to be independently associated to the stability of cognitive function, whereas older age, higher education, higher levels of plasma total homocysteine and total ADAS‐Cog basal score were independently associated with the progression of cognitive decline.

Conclusions

Older age, higher education, poor global cognitive performance, higher levels of plasma total homocysteine are independently associated with the progression of memory decline while the prescription of ACE Inhibitors is a protective factor for cognitive deterioration. Copyright © 2006 John Wiley & Sons, Ltd.
Multi‐target fluorescence in situ hybridization in bladder washings for prediction of recurrent bladder cancer
Authors: Zellweger Tobias , Benz Gabriel , Cathomas Gieri , Mihatsch Michael J. , Sulser Tullio , Gasser Thomas C. , Bubendorf Lukas
Published: April 2006

The objective of this study was to evaluate the diagnostic value of chromosomal analysis by fluorescence in situ hybridization (FISH) for predicting recurrence of urothelial carcinoma (UC) after transurethral resection. One hundred and thirty‐eight patients (median age 68.5 years) with a history of UC were eligible for this prospective study. FISH was applied to cytospin specimens prepared from bladder washings taken during a negative control cystoscopy. The multi‐target FISH test UroVysion® (Abbott/Vysis) containing probes to the centromeres of chromosomes 3, 7, 17 and the 9p21 locus was used. UC recurrence was defined as a positive biopsy during follow‐up. The median follow‐up time was 19.2 (4–52) months. FISH was positive in 50 (36%) patients and negative in 88 (64%) patients. A recurrence occurred in 39% of the patients with a positive FISH test and in 21% of patients with a negative FISH test. FISH positivity according to manufacturer's criteria, at the time of a negative cystoscopy, was not significantly associated with the risk of recurrence (p = 0.12). However, the sensitivity of the FISH test to predict recurrence was significantly improved by considering specimens with rare (≤10) tetraploid cells as negative (p < 0.006). In addition, presence of 9p21 deletion was significantly associated with recurrence (p < 0.01). Notably, positive standard cytology was an independent factor for subsequent recurrence in this study (p < 0.001). Taken together, multi‐target FISH may help to stratify the risk of recurrence of UC at the time of a negative follow‐up cystoscopy. Defining the optimal threshold for FISH positivity requires consideration of tetraploid pattern and 9p21 deletion. Our results also emphasize the paramount importance of conventional cytology for UC surveillance. © 2006 Wiley‐Liss, Inc.
High birth weight increases mammary tumorigenesis in rats
Authors: de Assis Sonia , Khan Galam , Hilakivi‐Clarke Leena
Published: April 2006

Epidemiological studies have investigated whether a high birth weight is associated with increased breast cancer risk, but the results remain inconclusive. This study was designed to determine whether high birth weight increases later susceptibility to carcinogen‐induced mammary tumorigenesis in an animal model and to determine mechanisms mediating this association. Pregnant female Sprague Dawley rats were fed either a control or a high‐fat diet during the extent of gestation. Maternal exposure to the high‐fat diet increased pregnancy leptin levels and offspring's birth weight, but had no effect on pregnancy estradiol or insulin‐like growth factor 1 levels. Changes in the offspring's mammary gland morphology and protein expression were assessed. The mammary epithelial tree of the high‐birth‐weight offspring was denser, contained more terminal end buds and exhibited higher number of proliferating cells. Further, their mammary glands expressed lower levels of ER‐α, but higher levels of activated MAPK. No alterations in apoptosis were noted. High‐birth‐weight rats developed 7,12‐dimethylbenz[a]anthracene‐induced mammary tumors significantly earlier, and tumors grew larger than in the controls. The tumors in this group expressed higher levels of leptin receptor and activated Akt, and contained fewer apoptotic cells than those in the controls. Our results indicate that high birth weight is related to shortened latency to develop mammary tumors—perhaps reflecting an increase in activated MAPK levels and increased tumor growth—perhaps caused by a lower apoptotic response due to higher leptin receptor and activated Akt levels in the tumors. © 2006 Wiley‐Liss, Inc.
Breast cancer risk in relation to abortion: Results from the EPIC study
Authors: Reeves Gillian K. , Kan Sau‐Wan , Key Tim , Tjønneland Anne , Olsen Anja , Overvad Kim , Peeters Petra H. , Clavel‐Chapelon Françoise , Paoletti Xavier , Berrino Franco , Krogh Vittorio , Palli Domenico , Tumino Rosario , Panico Salvatore , Vineis Paulo , Gonzalez Carlos A. , Ardanaz Eva , Martinez Carmen , Amiano Pilar , Quiros José R. , Tormo Maria R. , Khaw Kay‐Tee , Trichopoulou Antonia , Psaltopoulou Theodora , Kalapothaki Victoria , Nagel Gabriele , Chang‐Claude Jenny , Boeing Heiner , Lahmann Petra H. , Wirfält Elisabet , Kaaks Rudolf , Riboli Elio
Published: April 2006

The role of spontaneous and induced abortion on breast cancer risk is examined among 267,361 women recruited into the European Prospective Investigation into Cancer and nutrition between 1992 and 2000. The data were collected from 20 centers, across 9 countries, and included information on a total of 4,805 women with breast cancer, of whom 1,657 reported having ever had any type of abortion. Overall, the relative risk of breast cancer in women who reported ever having had a spontaneous abortion was not significantly elevated when compared with women who reported never having had such an abortion (RR = 1.07, 95% CI = 0.99–1.14). However, there was some evidence of a slight increase in the risk of breast cancer among women who reported having had 2 or more spontaneous abortions (1.20, 1.07–1.35). The relative risk of breast cancer among women who reported ever having had an induced abortion when compared to women who reported never having had an induced abortion was 0.95 (0.87–1.03). Overall, the findings provide further unbiased evidence of the lack of an adverse effect of induced abortion on breast cancer risk. © 2006 Wiley‐Liss, Inc.
Genetic polymorphisms of the XPG and XPD nucleotide excision repair genes in sarcoma patients
Authors: Le Morvan Valérie , Longy Michel , Bonaïti‐Pellié Catherine , Bui Binh , Houédé Nadine , Coindre Jean‐Michel , Robert Jacques , Pourquier Philippe
Published: April 2006

There are more than 50 subtypes of soft tissue sarcomas, among which 30% are associated with specific genetic alterations, including translocations. Several studies have reported associations between cancer risk and polymorphisms of DNA repair genes from the nucleotide excision repair (NER) pathway. NER involves more than 20 proteins whose inactivation leads to xeroderma pigmentosum (XP) or cockayne syndrome (CS), among which XPD, a helicase allowing DNA strand excision by the endonuclease XPG. DNA from 93 patients with synovial sarcomas, myxoid liposarcomas, dermatofibrosarcomas protuberans (DFSP), malignant fibrous histiocytomas and leiomyosarcomas were genotyped for both XPD Lys751Gln and XPG Asp1104His polymorphisms. Departure from Hardy‐Weinberg was highly significant for the XPG polymorphism with an excess of heterozygotes in synovial sarcomas (p = 1.5 × 10−5), myxoid liposarcomas (p = 1.5 × 10−4) and to a lesser extent in DFSP (p = 0.028). In the case of XPD, a significant deviation was observed in synovial sarcomas (p = 3 × 10−6) and DFSP (p = 0.0014). When tumors were pooled according to their genetic alterations, the proportion of carriers of the variant XPG allele was significantly increased in sarcomas with specific translocations as compared to sarcomas with complex genetics (p < 10−9). No difference was found for XPD. Genotyping of the tumor samples in synovial sarcomas and myxoid liposarcomas revealed frequent loss of heterozygosity for XPG, mostly due to the loss of the frequent allele. For XPD, both alleles were lost with a similar frequency. Our results raise the potential implication of the XPG Asp1104His polymorphism in the occurrence of chromosomal translocations associated with specific subtypes of sarcomas. © 2006 Wiley‐Liss, Inc.
Time to clearance of human papillomavirus infection by type and human immunodeficiency virus serostatus
Authors: Koshiol Jill E. , Schroeder Jane C. , Jamieson Denise J. , Marshall Stephen W. , Duerr Ann , Heilig Charles M. , Shah Keerti V. , Klein Robert S. , Cu‐Uvin Susan , Schuman Paula , Celentano David , Smith Jennifer S.
Published: April 2006

Persistent infection with high‐risk human papillomavirus (HPV) is central to cervical carcinogenesis. Certain high‐risk types, such as HPV16, may be more persistent than other HPV types, and type‐specific HPV persistence may differ by HIV serostatus. This study evaluated the association between HPV type and clearance of HPV infections in 522 HIV‐seropositive and 279 HIV‐seronegative participants in the HIV Epidemiology Research Study (HERS, United States, 1993–2000). Type‐specific HPV infections were detected using MY09/MY11/HMB01‐based PCR and 26 HPV type‐specific probes. The estimated duration of type‐specific infections was measured from the first HPV‐positive visit to the first of two consecutive negative visits. Hazard ratios (HRs) and 95% confidence intervals (CIs) for HPV clearance were calculated using Cox models adjusted for study site and risk behavior (sexual or injection drugs). A total of 1,800 HPV infections were detected in 801 women with 4.4 years median follow‐up. HRs for clearance of HPV16 and related types versus low‐risk HPV types were 0.79 (95% CI: 0.64–0.97) in HIV‐positive women and 0.86 (95% CI: 0.59–1.27) in HIV‐negative women. HRs for HPV18 versus low‐risk types were 0.80 (95% CI: 0.56–1.16) and 0.57 (95% CI: 0.22–1.45) for HIV‐positive and ‐negative women, respectively. HPV types within the high‐risk category had low estimated clearance rates relative to low‐risk types, but HRs were not substantially modified by HIV serostatus. © 2006 Wiley‐Liss, Inc.
Benign ovarian cysts and breast cancer risk
Authors: Bosetti Cristina , Scotti Lorenza , Negri Eva , Talamini Renato , Levi Fabio , Franceschi Silvia , Montella Maurizio , Giacosa Attilio , Vecchia Carlo La
Published: April 2006

Benign ovarian cysts have been suggested to influence breast cancer risk. To provide a comprehensive picture of the relation between ovarian cysts and breast cancer, we analyzed the data of 3 case‐control studies conducted in northern Italy and the Swiss Canton of Vaud between 1983 and 2001. These studies included 6,315 incident, histologically confirmed breast cancer cases and 6,038 hospital‐based controls. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models, including terms for sociodemographic, menstrual and reproductive factors. Overall, 4.9% of breast cancer cases and 6.6% of controls reported a history of ovarian cysts, with a multivariate OR of 0.72 (95% CI 0.62–0.85). The inverse association between ovarian cysts and breast cancer was consistent in separate strata of age at menarche, parity, age at menopause status and family history of breast cancer. No meaningful differences were also found across strata of menstrual cycle length, oral contraceptive use, history of oophorectomy and body mass index. Thus, the inverse relation between ovarian cysts and breast cancer risk was not accounted for by earlier menopause, or by any difference in reproductive and menstrual characteristics. Although some hormonal correlates of ovarian cysts may have a role on breast cancer risk, a biological explanation of this inverse association is still unclear. © 2006 Wiley‐Liss, Inc.
Chemotherapy pretreatment sensitizes solid tumor‐derived cell lines to Vα24+ NKT cell‐mediated cytotoxicity
Authors: Mattarollo Stephen R. , Kenna Tony , Nieda Mie , Nicol Andrew J.
Published: April 2006

There is an increasing awareness of the therapeutic potential for combining immune‐based therapies with chemotherapy in the treatment of malignant diseases, but few published studies evaluate possible cytotoxic synergies between chemotherapy and cytotoxic immune cells. Human Vα24+/Vβ11+ NKT cells are being evaluated for use in cell‐based immunotherapy of malignancy because of their immune regulatory functions and potent cytotoxic potential. In this study, we evaluated the cytotoxicity of combinations of chemotherapy and NKT cells to determine whether there is a potential to combine these treatment modalities for human cancer therapy. The cytotoxicity of NKT cells was tested against solid‐tumor derived cell lines NCI‐H358, DLD‐1, HT‐29, DU‐145, TSU‐Pr1 and MDA‐MB231, with or without prior treatment of these target cells, with a range of chemotherapy agents. Low concentrations of chemotherapeutic agents led to sensitization of cell lines to NKT‐mediated cytotoxicity, with the greatest effect being observed for prostate cancer cells. Synergistic cytotoxicity occurred in an NKT cell in a dose‐dependent manner. Chemotherapy agents induced upregulation of cell surface TRAIL‐R2 (DR5) and Fas (CD95) expression, increasing the capacity for NKT cells to recognize and kill via TRAIL‐ and FasL‐mediated pathways. We conclude that administration of cytotoxic immune cells after chemotherapy may increase antitumor activities in comparison with the use of either treatment alone. © 2006 Wiley‐Liss, Inc.
Risk factors for prostate cancer: A national case‐control study
Authors: Cox Brian , Sneyd Mary J. , Paul Charlotte , Skegg David C. G.
Published: April 2006

Statutory notification of cancer in New Zealand provided an opportunity to investigate risk factors for prostate cancer in a large national population‐based case‐control study. We analyzed data obtained from telephone interviews with 923 cases and 1,224 controls. For inclusion in the study, all subjects had to have been married at some time. We found an increased risk of prostate cancer among those with a history of prostate cancer in first degree relatives (RR 2.6; 95% CI, 1.9–3.7) and an increased risk of prostate cancer with length of marriage among men married only once and still married at interview. For a consecutive subgroup of 550 cases and 819 controls, data on height and weight at age 20 and at 5 years before interview were collected. Men less than or equal to 1.7 m in height at age 20 years had a lower risk of prostate cancer than men taller at that age. There was no association between weight or body mass index and risk of prostate cancer. © 2006 Wiley‐Liss, Inc.
Docosahexaenoic acid in combination with celecoxib modulates HSP70 and p53 proteins in prostate cancer cells
Authors: Narayanan Narayanan K. , Narayanan Bhagavathi A. , Bosland Maarten , Condon Mark S. , Nargi Dominick
Published: April 2006

The role of cyclooxygenase‐2 (COX‐2) and the mechanism by which it influences the development and behavior of prostate cancer is unclear. Selective COX‐2 inhibitors may be effective against prostate cancer via COX‐2‐independent mechanisms. But administration of high doses of COX‐2 inhibitors over longer period of time may not be devoid of side effects. There is increasing interest in using COX‐2 inhibitors in combination with other chemopreventive agents to overcome the issue of toxicity. However, the molecular mechanisms underlying their combined actions are not well understood. Therefore, the present study was designed to determine the effects of low doses of docosahexaenoic acid (DHA) in combination with celecoxib on the molecular targets at the proteins level in rat prostate cancer cells. Two‐dimensional gel electrophoresis, in combination with mass spectrometry analysis, was used for protein identification. Western blot analysis confirmed the proteins identified. Paraffin‐embedded tissue sections from the rat prostate tumor were used to detect base level expression of heat shock protein 70 (HSP70) and p53. The rate of cancer cell growth was inhibited more effectively (p < 0.01) by DHA in combination with celecoxib at lower doses (2.5 μM each). A total number of twelve proteins were differentially expressed by the combined action of DHA and celecoxib at low doses. It was interesting to note that these agents activated both HSP70 and p53 proteins. Activation of HSP70 by the combined actions of DHA and celecoxib in the presence of wild‐type p53 reveals a unique COX‐2 independent mode of action against prostate cancer. © 2006 Wiley‐Liss, Inc.
Serum concentrations of Dickkopf‐1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation
Authors: Politou Marianna C. , Heath Deborah J. , Rahemtulla Amin , Szydlo Richard , Anagnostopoulos Athanasios , Dimopoulos Meletios A. , Croucher Peter I. , Terpos Evangelos
Published: April 2006

Dickkopf‐1 (DKK‐1) protein, a soluble inhibitor of Wnt signalling, has been implicated in the pathogenesis of myeloma bone disease through the suppression of osteoblast differentiation. In this study, serum concentrations of DKK‐1 were measured in 50 myeloma patients (32 at diagnosis and 18 before and after autologous stem cell transplantation (ASCT), 18 patients with monoclonal gammopathy of undetermined significance (MGUS), and 22 healthy controls. Serum DKK‐1 levels were increased in MM at diagnosis compared with MGUS (mean ± SD: 67 ± 54 ng/mL vs. 38 ± 13 ng/mL; p = 0.006) and controls (31 ± 11 ng/mL; p = 0.02), while there was no difference between MGUS patients and controls. Although patients with stage 2 and 3 myeloma had higher DKK‐1 values than stage 1 patients (79 ± 63 vs. 40 ± 13; p = 0.005), no significant correlation between serum DKK‐1 and myeloma bone disease was observed. Myeloma patients before ASCT also had increased levels of DKK‐1 (63 ± 77 ng/mL; p = 0.03) compared with controls, supporting the notion that DKK‐1 may be responsible for the suppressed osteoblast activity even in patients with low tumor burden. After ASCT, there was a sustained decrease in DKK‐1 levels over time, while bone formation markers elevated, suggesting that the reduction of DKK‐1 levels after ASCT may correlate with the normalization of osteoblast function. These results could provide the basis for developing agents that block DKK‐1, thus restoring osteoblast function and counteracting the increased osteoclastogenesis observed in myeloma. © 2006 Wiley‐Liss, Inc.
Biocompatibility of elastin‐like polymer poly(VPAVG) microparticles: in vitro and in vivo studies
Authors: Rincón A.C. , Molina‐Martinez I. T. , de las Heras B. , Alonso M. , Baílez C. , Rodríguez‐Cabello J.C. , Herrero‐Vanrell R.
Published: April 2006

Poly(L‐valine–L‐proline–L‐alanine–L‐valine–L‐glycine) (VPAVG) is a new kind of proteinaceous polymer belonging to the Elastin‐like family. These polymers are based on the recurrence of certain short peptide monomers that are considered as “building blocks” in the natural elastin. This smart thermoresponsive polymer has the ability to self‐associate at physiological temperature to form aggregates with about 60% in water. This ability can be harnessed to prepare microparticles loaded with an active substance. The aim of this report is to evaluate, from the results of the experiment conducted, the biocompatibility of microparticles prepared from poly(VPAVG). We have studied the cytotoxic effects of microparticles, edema formation after subcutaneous injection (1 and 2.5 mg) in rats (n = 6), and also intraocular tolerance after the intravitreal injection of 2.5 mg of poly(VPAVG) microparticles into pigmented rabbits (n = 12). The polymer did not induce any cytotoxicity or nonspecific depression of cellular respiration on macrophages under the range of polymer concentrations investigated in this study (20, 30, 40, and 60 mg/mL). We observed no inflammatory response to microparticles after subcutaneous injection in the hind‐paw of rats, with no significant differences between the control group (PBS) and experimental groups. Anterior and posterior segment signs were evaluated after intraocular injection of poly(VPAVG) microparticles. Only a few eyes (2/11) of the experimental group presented inflammation signs at day 28 postinjection. Nevertheless, 45% (5/11) of the eyes receiving microparticles showed tractional retinal detachment. The results observed in this work suggested certain fibroblastic activity induced by poly(VPAVG) microparticles after their intraocular injection. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Silicon addition to hydroxyapatite increases nanoscale electrostatic, van der Waals, and adhesive interactions
Authors: Vandiver Jennifer , Dean Delphine , Patel Nelesh , Botelho Claudia , Best Serena , Santos José D. , Lopes Maria A. , Bonfield William , Ortiz Christine
Published: April 2006

The normal intersurface forces between nanosized probe tips functionalized with COO−‐terminated alkanethiol self‐assembling monolayers and dense, polycrystalline silicon‐substituted synthetic hydroxyapatite (SiHA) and phase pure hydroxyapatite (HA) were measured via a nanomechanical technique called chemically specific high‐resolution force spectroscopy. A significantly larger van der Waals interaction was observed for the SiHA compared to HA; Hamaker constants (A) were found to be ASiHA = 35 ± 27 zJ and AHA = 13 ± 12 zJ. Using the Derjaguin–Landau–Verwey–Overbeek approximation, which assumes linear additivity of the electrostatic double layer and van der Waals components, and the nonlinear Poisson–Boltzmann surface charge model for electrostatic double‐layer forces, the surface charge per unit area, σ (C/m2), was calculated as a function of position for specific nanosized areas within individual grains. SiHA was observed to be more negatively charged than HA with σSiHA = −0.024 ± 0.013 C/m2, two times greater than σHA = −0.011 ± 0.006 C/m2. Additionally, SiHA was found to have increased surface adhesion (0.7 ± 0.3 nN) compared to HA (0.5 ± 0.3 nN). The characterization of the nanoscale variations in surface forces of SiHA and HA will enable an improved understanding of the initial stages of bone–biomaterial bonding. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Effect of arachidonic and eicosapentaenoic acid metabolism on RAW 264.7 macrophage proliferation
Authors: Nieves Diana , Moreno Juan José
Published: April 2006

Prostaglandins (PGs) and leukotrienes (LTs) derived from arachidonic acid (AA) are potent mediators of inflammation and cell proliferation. Dietary intake of eicosapentaenoic acid (EPA) appears beneficial to both inflammatory processes and cell proliferation. However, there is no clear mechanism explaining these effects. In this study, we investigated the effect of EPA on the AA incorporation in phospholipid membranes, on AA release and metabolism, and consequently, on PG synthesis. Our results showed not only that [3H]AA and [14C]EPA were similar incorporated into RAW 264.7 macrophage membranes, but also that the redistribution pattern between phospholipids was alike. [3H]AA or [14C]EPA release was induced by fetal bovine serum (FBS) in a similar fashion with AA metabolizing 3‐fold more than EPA. In this way, we observed that AA could be metabolized by cyclooxygenase (COX)‐1, COX‐2 and 5‐lipoxygenase (5‐LOX) whereas EPA was metabolized by COX‐2 and 5‐LOX pathways. Moreover, both fatty acids were able to induce COX‐2 expression. When we incubated [3H]AA labeled cells with exogenous EPA, we observed that EPA did not modify FBS‐induced [3H]AA release but that the presence of EPA decreased [3H]AA metabolism and therefore PGE2 synthesis. Moreover, we studied the effect of AA and EPA metabolites on macrophage proliferation. Our results showed that PGE3 stimulated cell growth with a potency similar to that of PGE2, whereas LTB5 was less effective than LTB4. These data suggest that the effects of EPA on cell growth might be attributable, at least in part, to the marked decrease of eicosanoid release. J. Cell. Physiol. 208: 428–434, 2006. © 2006 Wiley‐Liss, Inc.
Degradation of C/EBPβ in cultured myotubes is calpain‐dependent
Authors: Wei Wei , Yang Hongmei , Cao Peirang , Menconi Michael , Chamberlain Chester , Petkova Victoria , Hasselgren Per‐Olof
Published: April 2006

Members of the C/EBP transcription factor family regulate cell differentiation and multiple other cellular functions. The cellular levels of C/EBPα, γ, δ, ε, and Gadd153/CHOP are regulated in part by proteasome‐dependent degradation. In contrast, mechanisms regulating the degradation of C/EBPβ are poorly understood. We tested the hypothesis that the degradation of C/EBPβ is calpain‐dependent. Studies were performed in cultured L6 myotubes (a rat skeletal muscle cell line) because we have found previously that C/EBPβ may be involved in the regulation of muscle proteolysis. Treatment of cultured L6 myotubes with the calpain inhibitors calpeptin and Calpain Inhibitor I and II resulted in increased C/EBPβ concentrations but did not influence cellular levels of the other C/EBP transcription factor family members. Transfection of myoblasts with a plasmid expressing the endogenous calpain inhibitor calpastatin resulted in increased cellular levels of C/EBPβ whereas the opposite result was observed in myoblasts overexpressing µ‐ or m‐calpain. Co‐immunoprecipitation provided evidence for protein–protein interaction between C/EBPβ and µ‐ and m‐calpain suggesting that C/EBPβ may be a calpain substrate. This notion was supported by experiments in which immunoprecipitated C/EBPβ was incubated with purified µ‐calpain in a cell‐free system. The increase in C/EBPβ levels caused by inhibition of calpain activity was accompanied by increased C/EBPβ DNA‐binding and gene activation. The present results suggest that C/EBPβ is degraded by a calpain‐dependent mechanism in skeletal muscle cells and that the role of calpains is specific for C/EBPβ among different members of the C/EBP transcription factor family. J. Cell. Physiol. 208: 386–398, 2006. © 2006 Wiley‐Liss, Inc.
HRTEM of dislocation cores and thin‐foil effects in metals and intermetallic compounds
Authors: Mills M.J. , Baluc N.L. , Sarosi P.M.
Published: April 2006

Examples of the observation and analysis of dislocation cores and dislocation fine structure in metals and intermetallics using high resolution transmission electron microscopy are discussed. Specific examples include the 60° dislocations in aluminum, a〈011〉 edge dislocations in NiAl, and screw dislocations in Ni3Al. The effect of the thin TEM foils on the structure and imaging of these dislocations is discussed in light of embedded atom method calculations for several configurations and coupled with image simulations. Some generalizations based on these calculations are discussed. These analyses enables determination of the spreading or decomposition of the edge component of the cores, both in and out of the glide plane, which can have significant implications for the modeling of macroscopic behavior. Microsc. Res. Tech. 69:317–329, 2006. © 2006 Wiley‐Liss, Inc.
Defect analysis in crystals using X‐ray topography
Authors: Raghothamachar Balaji , Dhanaraj Govindhan , Bai Jie , Dudley Michael
Published: April 2006

A brief review of X‐ray topography—a nondestructive method for direct observation and characterization of defects in single crystals—is presented here. The origin and development of this characterization method and the different techniques derived from it are described. Emphasis is placed on synchrotron X‐ray topography and its application in studying various crystal imperfections. Mechanisms of contrast formation on X‐ray topographs are discussed, with emphasis on contrast associated with dislocations. Determination of Burgers vectors and line directions of dislocations from analysis of X‐ray topographs is explained. Contrast from inclusions is illustrated, and their differentiation from dislocations is demonstrated with the aid of simulated topographs. Contrast arising from the deformation fields associated with cracks is also briefly covered. Microsc. Res. Tech. 69:343–358, 2006. © 2006 Wiley‐Liss, Inc.
AFM study of the plastic deformation of polysynthetically‐twinned (PST) TiAI crystals in soft orientation
Authors: Chen Yali , Pope David P.
Published: April 2006

PST TiAl samples with a nominal composition of Ti52Al48 were deformed at room temperature with compression axis inclined to the lamellar interfaces by 45° and one of the side surface normal directions set to be 〈11$\bar{2}$〉. The deformation structures on the free surfaces of the deformed samples were investigated using Atomic Force Microscope (AFM). It was found that in‐plane shear (shear in planes parallel to lamellar interfaces) is the dominant deformation mode in all γ domains and most of the deformation traces on the free surfaces are parallel to lamellar interfaces. Out‐of‐plane shear (shear in planes inclined to lamellar interfaces) also occurs but contributes much less to the macroscopic strain. This selective activation of deformation modes leads to a highly anisotropic deformation behavior in PST crystals with this orientation. Microsc. Res. Tech. 69:366–373, 2006. © 2006 Wiley‐Liss, Inc.