bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in the incidence of cancer in Qidong, China, 1978–2002
Authors: Chen Jian‐Guo , Zhu Jian , Parkin Donald Maxwell , Zhang Yong‐Hui , Lu Jian‐Hua , Zhu Yuan‐Rong , Chen Tao‐Yang
Published: April 2006

A population‐based cancer registry was established in Qidong, Jiangsu Province, China, in 1972, and the trends in incidence rates of the major cancer sites have been analyzed for a 25‐year period, 1978–2002. Five‐year age‐specific rates, crude incidence rates, world age‐standardized rates (ASR), percent change (PC) and annual percent change (APC) were calculated using annual data on population size, and estimates of its age structure. The indices of histological verification of diagnosis, death certificate only and proportion of mortality to incidence were employed for assessing the registration quality. A total of 51,933 incident cases of cancer were registered in Qidong from years 1978 to 2002, with a male‐to‐female sex ratio of 1.9:1. Crude incidence increased markedly over the 25‐year period (PC and APC of +55.6% and +2.1%, respectively), but ASR showed a slight decrease (−0.4% in males, and −0.3% in females), indicating that the major part of this is due to population ageing. The leading cancer sites in rank were liver (average ASR = 50.8 per 100,000), stomach (26.7), lung (22.7), colon‐rectum (8.9), oesophagus (7.4) and breast (5.4). Cancers of liver, lung, colon‐rectum and female breast all showed increases in incidence during the study period, with APCs (ASR) of +0.1%, +1.7% and +1.4% for males, and +0.2%, +0.9%, +1.9% and +1.1% for females, while the cancers of stomach (APC: −3.2% in male, and −2.4% in female) and cervix (APC: −4.7%) showed notable declines. Examination of age‐specific rates showed declining trends in the younger generations for liver cancer, but increases for cervix cancer. The results underline the increasing importance of cancer as a cause of mortality and morbidity in a population that is ageing and undergoing profound changes in socioeconomic development and lifestyle. The cancers of high lethality that have been common in the Chinese population (liver, stomach, oesophagus) are showing some evidence of decline, at least in younger generations, but they remain major problems. At the same time, the cancers associated with economically “developed” societies—lung, colon‐rectum and female breast—are showing increases. The population‐based cancer registry is an indispensable tool for providing data for planning and evaluation of programmes for cancer control in all societies. © 2006 Wiley‐Liss, Inc.
UDP‐N‐acetyl‐D‐galactosamine:polypeptide N‐acetylgalactosaminyltransferase 6 (ppGalNAc‐T6) mRNA as a potential new marker for detection of bone marrow‐disseminated breast cancer cells
Authors: Freire Teresa , Berois Nora , Sóñora Cecilia , Varangot Mario , Barrios Enrique , Osinaga Eduardo
Published: April 2006

The evaluation of disseminated epithelial tumor cells in patients with early stages of breast cancer has generated considerable interest because of its potential association with poor clinical outcome. Considering that O‐glycosylation pathways are frequently altered in breast cancer, we performed this work to evaluate the potential usefulness of UDP‐N‐acetyl‐D‐galactosamine:polypeptide N‐acetylgalactosaminyltransferases (ppGalNAc‐Ts) (a family of glycosyltransferases which catalyze the first key step of mucin‐type O‐glycosylation) to detect disseminated cells in bone marrow samples from patients with operable breast cancer. Using RT‐PCR assays, we studied the gene expression of 9 enzymes (ppGalNAc‐T1–T9). Among the ppGalNAc‐Ts expressed by breast tumors (‐T1, ‐T2, ‐T3, ‐T6 and ‐T7), the best specificity (negative results on all PBMN cell samples from healthy donors) was shown for ppGalNAc‐T6. Thus, we selected this enzyme as a target gene for further evaluation. ppGalNAc‐T6 mRNA was found in 22/25 (88%) breast cancer samples, in all 3 human breast cancer cell lines evaluated (MCF‐7, ZR75‐1 and T47D), in 1/30 (3%) PBMN cells and 0/19 bone marrow samples obtained from patients without cancer. Using this method, 22/61 (36%) patients with breast cancer, who underwent curative surgery, showed positive ppGalNAc‐T6 mRNA in bone marrow aspirates obtained prior to surgery, including 11/34 patients with stage‐I or ‐II, without histopathological lymph node involvement. In a preliminary follow‐up evaluation, 19/61 patients experienced recurrence of the disease. ppGalNAc‐T6 was positive in 11/19 (57.9%) of these patients. Interestingly, in the group of patients without lymph node involvement, disease recurrence was observed in 54.5% of patients who showed ppGalNAc‐T6 mRNA‐positive bone marrow aspirates and only in 4.3% of patients when ppGalNAc‐T6 was negative (p = 0.014). These results indicate that ppGalNAc‐T6 mRNA could be a specific marker applicable to the molecular diagnosis of breast cancer cells dissemination. © 2006 Wiley‐Liss, Inc.
Durability of a cardiac valve leaflet made of calf pericardium: Fatigue and energy consumption
Authors: Páez J.M. García , Sanmartín A. Carrera , Herrero E. Jorge , Millán I. , Cordon A. , Rocha A. , Maestro M. , Burgos R. , Téllez G. , Castillo‐Olivares J.L.
Published: April 2006

We studied the mechanical behavior of membranes of calf pericardium, similar to those employed in prosthetic valve leaflets, when subjected to tensile fatigue. The objective was to assess its durability, as a fundamental property of cardiac bioprosthesis, and analyze the energy consumption. For this purpose, the authors built a hydraulic simulator to subject a spherical valve leaflet made of calf pericardium to cyclic stress mimicking cardiac function. A total of 522 assays were performed in 40 samples, subjected to cyclic pressures greater than 6 atm, and 482 subjected to pressures ranging between 2 and 6 atm. The mathematical expression that establishes the relationship between the pressure exerted and the frequency was obtained. If we assume that the function is continuous, this equation provides the range of fatigue tolerated for a given number of cycles. Using the optimal values (the five highest values per series), the expression was found to be y = 9.95x−0 1214 (R2 = 0.955), where x represents the frequency in cycles per second and y the pressure in atmospheres. In addition, we established the mathematical relationship between the energy consumed and the frequency, which was a function of the pressure exerted, regardless of the region or zone from which the samples had been obtained. The methods of manual and morphology‐based selection employed produced widely dispersed results. When a mechanical criterion was included, the similarity in the energy consumed during fatigue testing markedly improved the correlation, with a coefficient of determination between paired samples of R2 = 0.7477. A mechanical criterion, such as energy consumption, can help to improve sample selection and produce more consistent results. Finally, we obtained the mathematical expression that relates the energy consumed to the pressure exerted and the number of cycles per second to which the valve leaflet was subjected. This procedure enables us to establish the limit to the energy that a biomaterial can consume over a period of time during which it is subjected to a working pressure and, thus, calculate more precisely its durability. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Cartilage tissue engineering using human auricular chondrocytes embedded in different hydrogel materials
Authors: Yamaoka Hisayo , Asato Hirotaka , Ogasawara Toru , Nishizawa Satoru , Takahashi Tsuguharu , Nakatsuka Takashi , Koshima Isao , Nakamura Kozo , Kawaguchi Hiroshi , Chung Ung‐il , Takato Tsuyoshi , Hoshi Kazuto
Published: April 2006

To seek a suitable scaffold for cartilage tissue engineering, we compared various hydrogel materials originating from animals, plants, or synthetic peptides. Human auricular chondrocytes were embedded in atelopeptide collagen, alginate, or PuraMatrix™, all of which are or will soon be clinically available. The chondrocytes in the atelopeptide collagen proliferated well, while the others showed no proliferation. A high‐cell density culture within each hydrogel enhanced the expression of collagen type II mRNA, when compared with that without hydrogel. By stimulation with insulin and BMP‐2, collagen type II and glycosaminoglycan were significantly accumulated within all hydrogels. Chondrocytes in the atelopeptide collagen showed high expression of β1 integrin, seemingly promoting cell–matrix signaling. The N‐cadherin expression was inhibited in the alginate, implying that decrease in cell‐to‐cell contacts may maintain chondrocyte activity. The matrix synthesis in PuraMatrix™ was less than that in others, while its Young's modulus was the lowest, suggesting a weakness in gelling ability and storage of cells and matrices. Considering biological effects and clinical availability, atelopeptide collagen may be accessible for clinical use. However, because synthetic peptides can control the risk of disease transmission and immunoreactivities, some improvement in gelling ability would provide a more useful hydrogel for ideal cartilage regeneration. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Nanoparticles of poly(D,L‐lactide)/methoxy poly(ethylene glycol)‐poly(D,L‐lactide) blends for controlled release of paclitaxel
Authors: Dong Yuancai , Feng Si‐Shen
Published: April 2006

Paclitaxel is one of the best antineoplastic drugs found in nature in the past decades, which has excellent therapeutic effects against a wide spectrum of cancers. Because of its high hydrophobicity, Cremophor EL has to be used as adjuvant in its clinical dosage form (Taxol®), which has been found to cause serious side effects. Nanoparticles of biodegradable polymers may provide an ideal solution. In this research, paclitaxel‐loaded nanoparticles of poly(D,L‐lactide)/methoxy poly(ethylene glycol)‐polylactide (PLA/MPEG‐PLA) blends of various blend ratio 100/0, 75/25, 50/50, 25/75, and 0/100 were formulated by the nanoprecipitation method for controlled release of paclitaxel. It was found that increasing the proportion of MPEG‐PLA component in the blend from 0 to 100% resulted in a progressive decrease of the particle size from 230.6 ± 11.1 nm to 74.8 ± 14.0 nm. The zeta potential of the drug‐loaded nanoparticles was increased accordingly from −19.60 ± 1.13 mV to a nearly neutral, that is, −0.33 ± 0.28 mV, which indicates the gradual enrichment of PEG segments on the particle surface. The findings were further confirmed by X‐Ray Photoelectron Spectroscopy (XPS) analysis. Differential scanning calorimetry (DSC) analysis showed that the glass transition temperature of PLA was significantly decreased from 58.7 to 52.1°C with an increase of MPEG‐PLA proportion from 0 to 75%, suggesting the miscibility of PLA and MPEG‐PLA. The pure PLA nanoparticles (100/0) exhibited the slowest drug‐release rate with 37.3% encapsulated drug released from the nanoparticles for 14 days while the MPEG‐PLA nanoparticles (0/100) achieved the fastest drug release with 95.9% drug release in the same period. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
A novel tool for high‐resolution transmission electron microscopy of intact interfaces between bone and metallic implants
Authors: Engqvist H. , Botton G. A. , Couillard M. , Mohammadi S. , Malmström J. , Emanuelsson L. , Hermansson L. , Phaneuf M. W. , Thomsen P.
Published: April 2006

A key feature in the understanding of the mechanisms of integration versus rejection of implanted materials is a deepened understanding of the elemental and molecular compositions of the interface zone between the surface of the synthetic man‐made material and the biological components of tissue. Intact interfaces between metallic implants and tissues have not been able to image and analyse on the ultrastructural level with the common transmission electron microscopy (TEM) sample preparation techniques. By using focused ion beam microscopy for site‐specific preparation of TEM samples, intact interfaces between metal implants and calcified tissue were imaged for the first time. The interface's elemental and crystallographic compositions were determined using energy dispersive X‐ray mapping and electron diffraction. The developed technique fulfills a long‐sought‐for demand to correlate the surface properties of implanted metal prostheses with the fine structure and composition of preserved interfaces with tissues. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Bioactivation of a cobalt alloy by coating with wollastonite during investment casting
Authors: Almanza J.M. , Escobedo J.C. , Ortiz J.C. , Cortés D.A.
Published: April 2006

Cobalt alloy samples were bioactivated during investment casting. The cavities of the investment mold were previously coated with wollastonite. Additionally, before coating with wollastonite, some mold cavities were filled out with graphite rods to avoid a chemical reaction between the wollastonite powder and the investment material. Half of the cast samples were heat treated at 1220°C for 1 h. To perform the in vitro bioactivity assessment, the cast and heat‐treated samples were immersed in a simulated body fluid solution (SBF) for a period of 21 days. The surface of the samples before and after immersion in SBF was characterized by SEM, EDX, and XRD analyses. During the casting, particles of pseudowollastonite were embedded on the metallic surface. After immersion of the samples in SBF, a ceramic layer was formed on both the alloy obtained by using the investment mold and the alloy obtained by using the graphite‐filled cavity. The ceramic layer was thicker on the alloy cast in the investment mold. The layer was identified as hydroxyapatite by XRD analysis, in all the cases. The heat‐treated samples after immersion in SBF showed the formation of a thin homogeneous layer consisting of fine grains of apatite. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Hypoxia and DNA‐damaging agent bleomycin both increase the cellular level of the protein 4E‐BP
Authors: Le Bouffant Ronan , Cormier Patrick , Mulner‐Lorillon Odile , Bellé Robert
Published: April 2006

The 4E‐binding proteins (4E‐BPs) regulate the cap‐dependent eukaryotic initiation factor 4E (eIF4E). The level of 4E‐BP protein is regulated during early development of sea urchin embryos. Fertilization leads to the rapid disappearance of the protein that reappears later in development. We show that two important cellular stresses, hypoxia and bleomycin prolonged checkpoint mobilization provoked the overexpression of the protein 4E‐BP in developing sea urchin embryos. Hypoxia resulted after 1 h in a reversible gradual increase in the protein 4E‐BP level. At 20 h, the protein 4E‐BP had reached the level existing in the unfertilized eggs. Bleomycin used as a DNA‐damaging agent for checkpoint activation, provoked cell cycle inhibition and after prolonged exposure (20 h), induced the expression of the protein 4E‐BP. The effect of bleomycin on 4E‐BP protein overexpression was dose‐dependent between 0.4 and 1.2 mM. The role of the overexpression of the protein 4E‐BP is discussed in relation with cellular stress responses. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Identification of skeletal muscle autoantigens by expression library screening using sera from autoimmune rippling muscle disease (ARMD) patients
Authors: Watkins Thomas C. , Zelinka Lisa M. , Kesic Matt , Ansevin Carl F. , Walker Gary R.
Published: April 2006

Novel forms of contractile regulation observed in skeletal muscle are evident in neuromuscular diseases like rippling muscle disease (RMD). Previous studies of an autoimmune form of RMD (ARMD) identified a very high molecular weight skeletal muscle protein antigen recognized by ARMD patient antisera. This study utilized ARMD and myasthenia gravis (MG) patient antisera, to screen a human skeletal muscle cDNA library that subsequently identified proteins that could play a role in ARMD. Based on nucleotide sequence analysis, three distinct ARMD antigens were identified: titin Isoform N2A, ATP synthase 6, and PPP1R3 (protein phosphatase 1 regulatory subunit 3). The region of titin identified by ARMD antisera is distinct from the main immunogenic region (MIR) recognized by classical MG antibodies. Sera from classical MG patient identifies an expressed sequence corresponding to the titin MIR. Although the mechanism of antibody penetration is not known, previous studies have shown that rippling muscle antibodies affect the contractile machinery of myofibers resulting in mechanical sensitivity. Titin's role as a modulator of muscle contractility makes it a potential target in understanding muscle mechanosensitive regulation. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
In vitro toxicology evaluation of pharmaceuticals using Raman micro‐spectroscopy
Authors: Owen Chris A. , Selvakumaran Jamuna , Notingher Ioan , Jell Gavin , Hench Larry L. , Stevens Molly M.
Published: April 2006

Raman micro‐spectroscopy combined with multivariate analysis was employed to monitor real‐time biochemical changes induced in living cells in vitro following exposure to a pharmaceutical. The cancer drug etoposide (topoisomerase II inhibitor) was used to induce double‐strand DNA breaks in human type II pneumocyte‐like cells (A549 cell‐line). Raman spectra of A549 cells exposed to 100 µM etoposide were collected and classical least squares (CLS) analysis used to determine the relative concentrations of the main cellular components. It was found that the concentrations of DNA and RNA significantly (P < 0.05) decreased, whilst the concentration of lipids significantly (P < 0.05) increased with increasing etoposide exposure time as compared to control untreated A549 cells. The concentration of DNA decreased by 27.5 and 87.0% after 24 and 48 h exposure to etoposide respectively. Principal components analysis (PCA) successfully discriminated between treated and untreated cells, with the main variance between treatment groups attributed to changes in DNA and lipid. DNA fragmentation was confirmed by Western blot analysis of apoptosis regulator protein p53 and cell metabolic activity determined by MTT assay. The over‐expression of p53 protein in the etoposide treated cells indicated a significant level of DNA fragmentation and apoptosis. MTT tests confirmed that cellular metabolic activity decreased following exposure to etoposide by 29.4 and 61.2% after 24 and 48 h, respectively. Raman micro‐spectroscopy may find applications in the toxicology screening of other drugs, chemicals and new biomaterials, with a range of cell types. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Membrane proteinase 3 and its interactions within microdomains of neutrophil membranes
Authors: Fridlich Ram , David Alina , Aviram Irit
Published: April 2006

Proteinase 3 (PR3) is a serine protease of neutrophil granules released to the medium or into the phagocytic vesicle upon neutrophil stimulation. A fraction of the enzyme is thought to associate with the cell membrane yielding membrane PR3 (mPR3). In autoimmune disorders characterized by the presence of antineutrophil cytoplasmic antibodies (ANCA), the reaction of the latter with their target antigen mPR3 activates the cell inflicting injuries on the surrounding tissues. In a previous communication we provided evidence for the presence of mPR3 in lipid rafts obtained by lysis of neutrophils in Triton X‐100 and for the mediation of PR3 binding to the membrane by a glycosylphosphatidylinositol (GPI)‐anchored neutrophil protein, possibly FcγRIIIb. In the current study we employed the mild detergent Brij 58 to isolate high molecular weight (HMW) protein complexes in the void volume of a Sepharose 4B gel filtration minicolumn. HMW complexes of unstimulated neutrophils comprised PR3, FcγRIIIb, the β2 integrin CD11b/CD18 as well as the membrane and cytosolic subunits of the NADPH oxidase, p22phox and p47phox/p67phox. Treatment of neutrophils with phosphatidylinositol‐specific phospholipase C (PI‐PLC) reduced amounts of PR3 and FcγRIIIb in HMW complexes isolated from the treated cells, supporting our previous suggestion that FcγRIIIb acts as a membrane adaptor for PR3. FcγRIIIb of HMW fractions co‐immunoprecipitated with PR3, indicating their presence in the same protein complex. Since HMW fractions contained also the majority of biotinylated proteins obtained by the reaction of neutrophils with a membrane impermeable biotinylating agent Sulfo‐NHS‐biotin, it was concluded that HMW proteins were derived from cell membranes. Lipid rafts isolated from Brij 58‐lysed neutrophils were similar in their protein composition to the HMW complexes but not identical. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
17β‐estradiol (E2) induces cdc25A gene expression in breast cancer cells by genomic and non‐genomic pathways
Authors: Ru Lee Wan , Chen Chien‐Cheng , Liu Shengxi , Safe Stephen
Published: April 2006

Cdc25A is a potent tyrosine phosphatase that catalyzes specific dephosphorylation of cyclin/cyclin‐dependent kinase (cdk) complexes to regulate G1 to S‐phase cell cycle progression. Cdc25A mRNA levels are induced by 17β‐estradiol (E2) in ZR‐75 breast cancer cells, and deletion analysis of the cdc25A promoter identified the −151 to −12 region as the minimal E2‐responsive sequence. Subsequent mutation/deletion analysis showed that at least three different cis‐elements were involved in activation of cdc25A by E2, namely, GC‐rich Sp1 binding sites, CCAAT motifs that bind NF‐Y, and E2F sites that bind DP/E2F1 proteins. Studies with inhibitors and dominant negative expression plasmids show that E2 activates cdc25A expression through activation of genomic ERα/Sp1 and E2F1 and cAMP‐dependent activation of NF‐YA. Thus, both genomic and non‐genomic pathways of estrogen action are involved in induction of cdc25A in breast cancer cells. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
The status of hospital medicine groups in the United States
Authors: Kralovec Peter D. , Miller Joseph A. , Wellikson Laurence , Huddleston Jeanne M.
Published: April 2006

BACKGROUND

Hospitalists, defined as hospital‐based physicians who take responsibility for managing the medical needs of inpatients, represent a significant trend in physician specialization. However, only limited anecdotal data quantifying the status of hospital medicine groups around the country is available.

OBJECTIVE

To better understand the extent and nature of the hospitalist movement, utilizing data from the 2003 Annual Survey of the American Hospital Association (AHA).

STUDY POPULATION

4895 acute care hospitals in the United States.

MEASUREMENTS

Number and percentage of hospitals with hospital medicine groups; mean number of hospitalists per group; hospitalists per average daily census (ADC) of 100 patients; distribution of groups by employment model.

DESCRIPTIVE VARIABLES

Census region; rural/urban status; number of beds; organizational control; teaching status.

RESULTS

There are approximately 1415 hospital medicine groups and 11 159 hospitalists in the United States. The overall penetration of hospital medicine groups at hospitals is 29% (55% at hospitals with 200 or more beds), and the in‐hospital impact at hospitals with hospital medicine groups is 3.93 hospitalists per 100 ADC. The average hospital medicine group has 7.9 hospitalists. There is a fairly equal distribution among the 3 major employment models for hospital medicine groups: hospital employees, independent provider groups, and physician groups. All these measures can vary substantially, depending on the characteristics of individual hospitals.

CONCLUSIONS

Hospital medicine appears to have become part of the mainstream delivery of health care in the United States. No employment model of hospital medicine group appears to dominate this specialty. We expect there will continue to be growth and diversity in the implementation of hospital medicine groups. Journal of Hospital Medicine 2006;1:75–80. © 2006 Society of Hospital Medicine.
Magnetic resonance imaging measures of brain atrophy in multiple sclerosis
Authors: Anderson Valerie M. , Fox Nick C. , Miller David H.
Published: April 2006

Magnetic resonance imaging (MRI) has been widely used to diagnose and monitor multiple sclerosis (MS). Although MRI‐visible lesions are a key feature of MS, they are thought to correlate poorly with clinical progression. Neurodegeneration is increasingly being recognized as an important factor in the pathogenesis of MS, and MRI measures of brain atrophy have been suggested as surrogate markers of neuroaxonal loss and disease progression. This pathology may be more relevant to the progression of disability than focal inflammation. A number of MRI‐based methods have been developed for the measurement of global and regional brain atrophy. Natural‐history studies of MS and clinically isolated syndromes suggestive of MS have observed atrophy in these subjects above that seen in controls, over periods ranging from three months to years. Brain atrophy has also been incorporated as an outcome measure in therapeutic trials of disease‐modifying treatments. This paper considers neuroaxonal loss and the pathological basis of brain atrophy, methods developed to quantify brain atrophy, the findings of natural‐history and therapeutic studies, the relationship of brain atrophy to disability and cognition, and the future research directions and clinical applications of brain atrophy measurements. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
In vivo three‐dimensional motion analysis of the forearm with radioulnar synostosis treated by the kanaya procedure
Authors: Oka Kunihiro , Doi Kazuteru , Suzuki Koichi , Murase Tsuyoshi , Goto Akira , Yoshikawa Hideki , Sugamoto Kazuomi , Moritomo Hisao
Published: April 2006

Attempts to separate congenital radioulnar synostosis and restore forearm rotation had been disappointing until a new mobilization technique was developed by Kanaya and colleagues using free vascularized fascio‐fat graft interposition. This technique provides a functional rotation arc, but postoperative forearm motion is difficult to evaluate given the inaccuracies in determining the range of motion and rotational axis using conventional x‐rays or computed tomography. This study represents an attempt to analyze in vivo three‐dimensional motion of the forearm with radioulnar synostosis treated by Kanaya's operation using a markerless bone registration technique. Six patients with seven postoperative forearms (six with congenital and one with posttraumatic radioulnar synostosis) underwent 3D computed tomography with the forearm in neutral, fully pronated, and fully supinated positions. Range of motion according to this method was 30 ± 18°, significantly smaller than the 82 ± 29° from manual examination. Improvements in range of motion were significantly greater in cases without dislocation of the radial head (46 ± 13°) than in cases with dislocation (19 ± 10°). Dislocation of the radial head was also significantly correlated with an abnormal axis of rotation of the forearm. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Investigation of in vivo 6DOF total knee arthoplasty kinematics using a dual orthogonal fluoroscopic system
Authors: Hanson George R. , Suggs Jeremy F. , Freiberg Andrew A. , Durbhakula Sridar , Li Guoan
Published: April 2006

Fluoroscopic techniques have been recently used to detect in vivo knee joint kinematics. This article presents a technique that uses two fluoroscopes to form a dual orthogonal fluoroscopic system for accurately measuring in vivo 6DOF total knee arthoplasty (TKA) kinematics. The system was rigorously validated and used to investigate in vivo kinematics of 12 patients after cruciate‐retaining TKA. In a repeatability study, the pose of two different TKA components was reproduced with standard deviations (SD) of 0.17 mm and 0.57° about all three axes. In an accuracy study, the reproduced component positions were compared to the known component positions. Position and rotation mean errors were all within 0.11 mm and 0.24°, with SD within 0.11 mm and 0.48°, respectively. The results of this study show that the matching process of the imaging system is able to accurately reproduce the spatial positions and orientations of both the femoral and tibial components. For CR TKA patients, a consistent anterior femoral translation was observed with flexion through 45° of flexion, and thereafter, the femur translated posteriorly with further flexion. The medial–lateral translation was measured to be less than 2 mm throughout the entire flexion range. Internal tibial rotation steadily increased through maximum flexion by approximately 6°. Varus rotation was also measured with flexion but had a mean magnitude less than 2.0°. In conclusion, the dual orthogonal fluoroscopic system accurately detects TKA kinematics and is applicable towards other joints of the musculoskeletal system, including the wrist, elbow, shoulder, ankle, and spine. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
On double Veronese embeddings in the Grassmannian 𝔾(1, N )
Authors: Sierra José Carlos , Ugaglia Luca
Published: April 2006

We classify all the embeddings of ℙn in a Grassmannian of lines 𝔾(1, N ) such that the composition with Plücker is given by a linear system of quadrics of ℙn . (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Analysis of 14 LRRK2 mutations in Parkinson's plus syndromes and late‐onset Parkinson's disease
Authors: Tan E.K. , Skipper Lisa , Chua Eva , Wong Meng‐Cheong , Pavanni Ratnagopal , Bonnard Carine , Kolatkar Prasanna , Liu Jian‐Jun
Published: April 2006

The pleomorphic pathology of postmortem LRRK2‐positive patients and the frequent association with late‐onset Parkinson's disease (LOPD) symptoms suggest that LRRK2 mutations may play a role in Parkinson's Plus disorders and LOPD. Published studies primarily focus on the common G2019S mutation. Analysis of a spectrum of LRRK2 mutations in Parkinson's Plus disorders has yet to be reported. We investigated 14 leucine‐rich repeat kinase 2 (LRRK2) mutations in a cohort of Parkinson's Plus disorders and LOPD. A total of 458 patients with progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal ganglionic degeneration (CBGD), atypical Parkinsonism (AP), and LOPD were screened for 14 mutations that span exons 19 to 41 of the LRRK2 gene. Among the LOPD cases, 1 patient was found to harbor the R1441C mutation. He presented with typical features of PD at age of 58 years old and responded well to levodopa. We did not detect any of the 14 mutations in PSP, MSA, CBGD, and AP patients. We highlight the first case of LRRK2 R1441C mutation in late onset sporadic PD of non‐European ancestry. Furthermore, extensive mutational screen found LRRK2 mutations to be rare among patients who presented with PSP, MSA, CBGD, and AP. © 2006 Movement Disorder Society
Perception of heaviness in Parkinson's disease
Authors: Maschke Matthias , Tuite Paul J. , Krawczewski Kim , Pickett Kristen , Konczak Jürgen
Published: April 2006

The present study investigated whether a specific aspect of proprioception, the sense of heaviness or weight is affected in PD. We determined detection thresholds for the perception of a gravito‐inertial load in 10 PD patients and 11 age‐matched control subjects. A gradually increasing weight was applied to the index finger by means of two slings of different width (low vs. high skin pressure). For the controls, mean detection thresholds were 31.3 g at skin high pressure and 33.0 g under low pressure. PD patients revealed significantly higher thresholds than the control group in both pressure conditions (mean high pressure,47.7 g; mean low pressure, 52.3 g; group effect, P = 0.001). Thresholds of PD patients tended to increase with disease severity as measured by the Unified Parkinson's Disease Rating Scale Motor score (r = 0.55) but did not correlate significantly with levodopa equivalent dosage. The results demonstrate that the perception of heaviness or weight is already affected in the early stages of PD. These findings underline the growing evidence that proprioceptive and possibly haptic dysfunction is a common feature of PD. © 2006 Movement Disorder Society
Concepts of nerve regeneration and repair applied to brachial plexus reconstruction
Authors: Bertelli Jayme Augusto , Ghizoni Marcos Flávio
Published: April 2006

Brachial plexus injury is a serious condition that usually affects young adults. Progress in brachial plexus repair is intimately related to peripheral nerve surgery, and depends on clinical and experimental studies. We review the rat brachial plexus as an experimental model, together with its behavioral evaluation. Techniques to repair nerves, such as neurolysis, nerve coaptation, nerve grafting, nerve transfer, fascicular transfer, direct muscle neurotization, and end‐to‐side neurorraphy, are discussed in light of the authors' experimental studies. Intradural repair of the brachial plexus by graft implants into the spinal cord and motor rootlet transfer offer new possibilities in brachial plexus reconstruction. The clinical experience of intradural repair is presented. Surgical planning in root rupture or avulsion is proposed. In total avulsion, the authors are in favor of the reconstruction of thoraco‐brachial and abdomino‐antebrachial grasping, and on the transfer of the brachialis muscle to the wrist extensors if it is reinnervated. Surgical treatment of painful conditions and new drugs are also discussed. © 2006 Wiley‐Liss, Inc. Microsurgery, 2006.
Surgical treatment for spinal accessory nerve injury
Authors: Okajima Seiichiro , Tamai Kazuo , Fujiwara Hiroyoshi , Kobashi Hiroaki , Hirata Miyuki , Kubo Toshikazu
Published: April 2006

We report on the surgical results of spinal accessory nerve injuries between 1992–2003. We operated on 10 patients (9 female, and 1 male) who had injuries of the spinal accessory nerve. All injuries were iatrogenic. The mean age of patients was 39.2 years (range, 20–57 years). The average interval between date of injury and surgery was 7 months (range, 4–12 months). All patients had stiffness and pain in the shoulder girdle. The average active abduction of the shoulder joint was 79.5° (range, 60–100°) before surgery. End‐to‐end repairs were performed in 7 cases, and graft repairs were indicated in 3 cases. The mean follow‐up period was 18.4 months (range, 8–36 months). The average active abduction of the shoulder joint was 171° (range, 140–180°) at time of final follow‐up. © 2006 Wiley‐Liss, Inc. Microsurgery, 2006.
Evaluation of electrospray‐tandem mass spectrometry for the detection of phenylketonuria and other rare disorders
Authors: Lukacs Zoltan , Santer René
Published: April 2006

Since a few years ESI‐MS/MS has been employed for the simultaneous detection of a wide range of inborn errors of metabolism. The screening center North at the Hamburg University Medical Center processes 40–50 000 samples per year. To assess current developments in neonatal screening, the Northern German Working Group on Neonatal Screening consisting of health care providers, metabolic centers, and screening laboratories was founded. Based on current literature and experience four categories of diseases were established. The first three categories were recommended for screening under constant scientific evaluation, while glutaric aciduria II, β‐ketothiolase deficiency, short‐chain acylCoA dehydrogenase deficiency, and homocystinuria were not included in the screening program. In contrast, general screening for phenylketonuria (PKU) remains undisputed and MS/MS screening reduced false positives by simultaneously detecting phenylalanine and tyrosine. Recently, (6R)‐L‐erythro‐5,6,7,8‐tetrahydrobiopterin (BH4)‐sensitive PKU has been discovered. We were able to demonstrate that BH4 treatment without dietary restrictions may be sufficient for certain BH4‐responsive PKU patients. In general, MS/MS provides a potential to rapidly screen for a wide variety of rare metabolic disorders but a close cooperation between scientists and metabolic doctors is required to constantly evaluate results in terms of improving the outcome of patients.
Genotoxicity of glycidamide in comparison to (±)‐anti‐benzo[a]pyrene‐7,8‐dihydrodiol‐9,10‐epoxide and α‐acetoxy‐N‐nitroso‐diethanolamine in human blood and in mammalian V79‐cells
Authors: Thielen Silke , Baum Matthias , Hoffmann Michelle , Loeppky Richard N. , Eisenbrand Gerhard
Published: April 2006

Genotoxic activity of glycidamide (GA) was investigated in comparison to that of the known carcinogens (±)‐anti‐benzo[a]pyrene‐7,8‐dihydrodiol‐9,10‐epoxide ((±)‐BPDE) and α‐acetoxy‐N‐nitroso‐diethanolamine (α‐A‐NDELA), using the hypoxanthine‐phosphoribosyl‐transferase (hPRT) gene mutation assay with V79 mammalian cells and modified alkaline single cell gel electrophoresis (alkaline comet assay with and without treatment of cells with formamido‐pyrimidine‐DNA‐glycosylase (FPG)) in lymphocytes from human whole blood. As shown earlier, GA induced significant DNA damage in lymphocytes from treated whole blood at ⪈300 μM (4 h) (Baum et al., Mutat. Res. 2005, 580, 61–69). In the present study, using the alkaline comet assay with FPG treatment, increased formation of DNA strand breaks was observed in lymphocytes treated with GA (10 μM; 4 h). α‐A‐NDELA and (±)‐BPDE were genotoxic at 10–30 μM (1 h). Genotoxic activity of these compounds was not enhanced after FPG treatment. FPG treatment thus offers an enhanced sensitivity of DNA damage detection for genotoxic compounds with preference for N7‐ resp. N3‐purine alkylation. In the hPRT assay with V79 cells, mutagenic activity of (±)‐BPDE became significant at ⪈3 μM (24 h). For α‐A‐NDELA significant activity was observed at ⪈10 μM (24 h). As previously observed, GA was considerably less effective, inducing significant mutagenicity roughly at about 80–300‐fold higher concentrations (800 μM; 24 h) (Baum et al., Mutat. Res. 2005, 580, 61–69).
A new oleanane glycoside from the roots of Astragalus caprinus
Authors: Mitaine‐Offer Anne‐Claire , Miyamoto Tomofumi , Semmar Nabil , Jay Maurice , Lacaille‐Dubois Marie‐Aleth
Published: April 2006

A novel oleanane‐type triterpene saponin (1) together with two known molecules, soyasapogenol B and astragaloside VIII were isolated from the roots of Astragalus caprinus. Their structural elucidation was performed mainly by 2D NMR techniques (COSY, TOCSY, NOESY, HSQC, HMBC) and mass spectrometry. Compound 1 was determined as 3‐O‐[α‐L‐rhamnopyranosyl‐(1 → 2)‐β‐D‐glucuronopyranosyl]‐22‐O‐β‐D‐apiofuranosyl‐soyasapogenol B. Copyright © 2006 John Wiley & Sons, Ltd.
A novel maternally transcribed homeobox gene, Eso‐1, is preferentially expressed in oocytes and regulated by cytoplasmic polyadenylation
Authors: Li Hung , Tsai Ming‐Shiun , Chen Chun‐Ying , Lian Wei‐Cheng , Chiu Yung‐Tsung , Chen Gin‐Den , Wang Sue‐Hong
Published: April 2006

The homeobox gene families play important roles in the transcriptional regulation of gene expression prior to and during embryo development. To identify novel homeobox genes expressed in early embryonic development, we conducted a degenerated oligonucleotide polymerase chain reaction (PCR) to screen a mouse embryonic stem (ES) cell cDNA library. A novel homeobox‐containing gene, Eso‐1, which is preferentially expressed in ES cells and ovaries, was identified. The full‐length Eso‐1 cDNA was found to be 1,710 bp with a predicted homeodomain that has no significant homology to previously reported homeodomain proteins. Eso‐1 was mapped to chromosome 14A3. Reverse transcription‐polymerase chain reaction (RT‐PCR) analyses showed that Eso‐1 was expressed through oogenesis and continuing to be expressed through to the blastocyst stage. De novo expression of Eso‐1 started at 13.5 days postcoitum in the ovaries, which coincides with the initiation of oogenesis. Northern blot analyses demonstrated that Eso‐1 is preferentially expressed in both ovaries and ES cells as a 1.7‐kb transcript. Results from whole mount in situ hybridization revealed that Eso‐1 in oocytes showed increased expression from primordial to antral follicles. The 3′‐untranslated region of Eso‐1 transcripts contained cytoplasmic polyadenylation sequences while the length of poly (A) tails changed during oocyte maturation, indicating that Eso‐1 expression is controlled by time‐dependent translational activation. We suggest that the novel homeodomain protein, Eso‐1, plays a role during oocyte maturation and early embryonic development. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Expression of a carboxy terminally truncated Stat5 with no transactivation domain in the mammary glands of transgenic mice inhibits cell proliferation during pregnancy, delays onset of milk secretion, and induces apoptosis upon involution
Authors: Iavnilovitch Elena , Eilon Tali , Groner Bernd , Barash Itamar
Published: April 2006

Signal transducer and activator of transcription (Stat5) is a transcription factor, which transduces extracellular cytokine and growth‐factor signals to the nuclei of mammalian cells. As a major mediator of prolactin action, it is involved in the regulation of the development, function, and survival of mammary epithelial cells. The carboxyl terminal of Stat5 encodes a transactivation domain (TAD), which interacts with coactivators and is crucial for the transcriptional induction of Stat5 target genes. To study the role of the Stat5 TAD in mediating Stat5 functions, a carboxy terminally truncated Stat5 variant (Stat5Δ750) was directed for expression in the mammary glands of transgenic mice by regulatory sequences of the β‐lactoglobulin (BLG) gene. Expression of Stat5Δ750 in mammary tissue reduced the rates of cell proliferation at mid and late pregnancy. Subsequently, morphological signs of milk secretion upon parturition were delayed. In double‐transgenic mice, expression of Stat5Δ750 drastically decreased BLG/luciferase activity during lactation, but did not affect the expression and secretion of the endogenous β‐casein or α‐lactalbumin into the milk. Expression of Stat5Δ750 also caused an increase in the number of apoptotic cells during mammary involution by a factor of 3 relative to control glands. Our data established a role for the Stat5 TAD in mediating the effects of Stat5 on mammary development, regulation of milk protein gene activity, and cell survival. The full effects of Stat5Δ750 may be partially buffered by the expression of endogenous wild‐type Stat5 and the formation of truncated and wild‐type heterodimers. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Regulation of conceptus adhesion by endometrial CXC chemokines during the implantation period in sheep
Authors: Imakawa Kazuhiko , Imai Misa , Sakai Akiharu , Suzuki Masako , Nagaoka Kentaro , Sakai Senkiti , Lee Sang‐Rae , Chang Kyu‐Tae , Echternkamp Sherrill E. , Christenson Ronald K.
Published: April 2006

To gain a better understanding of biochemical mechanisms of conceptus adhesion to the maternal endometrium in ruminant ungulates, the present study was performed to clarify roles of chemokines and extracellular matrix (ECM) components in the regulation of ovine blastocyst attachment to the endometrium. In addition to the chemokine, interferon‐γ inducible protein 10 kDa (IP‐10, CXCL10), the chemokine receptor, CXCR3, also recognizes two other chemokines; monokine induced by IFN‐γ (MIG, CXCL9) and IFN‐inducible T cell α chemoattractant (I‐TAC, CXCL11). Similar to CXCL10, CXCL9, and CXCL11 were expressed in the uterus during the peri‐implantation period, and CXCL9 mRNA expression was stimulated in endometrial explants from day 14 cyclic ewes by the addition of IFN‐τ or IFN‐γ. Without ECM components, conceptus cell adhesion was low on day 14 of gestation and exhibited a 2.5‐fold increase on day 17; adhesiveness on day 20 was 1/10 of that on day 14. Among various ECM components examined, trophoblast adhesion was greatest when fibronectin was used. Although day 14 conceptuses did not show much adhesive activity to fibronectin, day 17 trophoblast, and day 20 chorionic membrane exhibited 2.3‐fold and 50‐fold increase, respectively, which was enhanced by treatment with CXCL9 or CXCL10. These results indicate that through endometrial fibronectin and chemokines, ovine conceptus cells gain the ability to attach to the endometrium during pre‐implantation period; however, elucidation of molecular mechanisms by which the conceptus acquires the adhesive ability during this time period awaits further investigation. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Further steps toward direct magnetic resonance (MR) imaging detection of neural action currents: Optimization of MR sensitivity to transient and weak currents in a conductor
Authors: Pell Gaby S. , Abbott David F. , Fleming Steven W. , Prichard James W. , Jackson Graeme D.
Published: April 2006

The characteristics of an MRI technique that could be used for direct detection of neuronal activity are investigated. It was shown that magnitude imaging using echo planar imaging can detect transient local currents. The sensitivity of this method was thoroughly investigated. A partial k‐space EPI acquisition with homodyne reconstruction was found to increase the signal change. A unique sensitivity to the position of the current pulse within the imaging sequence was demonstrated with the greatest signal change occurring when the current pulse coincides with the acquisition of the center lines of k‐space. The signal change was shown to be highly sensitive to the spatial position of the current conductor relative to the voxel. Furthermore, with the use of optimization of spatial and temporal placement of the current pulse, the level of signal change obtained at this lower limit of current detectability was considerably magnified. It was possible to detect a current of 1.7 μA applied for 20 ms with an imaging time of 1.8 min. The level of sensitivity observed in our study brings us closer to that theoretically required for the detection of action currents in nerves. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Unaliasing lipid contamination for MR spectroscopic imaging of gliomas at 3T using sensitivity encoding (SENSE)
Authors: Ozturk‐Isik Esin , Crane Jason C. , Cha Soonmee , Chang Susan M. , Berger Mitchel S. , Nelson Sarah J.
Published: April 2006

3D magnetic resonance spectroscopic imaging (MRSI) has been successfully employed to extract information about brain tumor metabolism, such as cell membrane breakdown, cellular energetics, and neuronal integrity, through its ability to differentiate signals coming from choline (Cho), creatine (Cr), and N‐acetyl aspartate (NAA) molecules. The additional presence of lipids within subregions of the tumor may indicate cellular membrane breakdown due to cell death. Another potential source of lipids is subcutaneous fat, which may be excited with point‐resolved spectroscopy (PRESS) volume selection and aliased into the spectral field of view (FOV) due to the chemical shift artifact and the low bandwidth of the selection pulses. The purpose of our study was to employ a postprocessing method for unaliasing lipid resonances originating from in‐slice subcutaneous lipids from the 3D MRSI of gliomas at 3T, using an eight‐channel phased‐array coil and sensitivity encoding (SENSE). Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.