bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of Clinical, Histological, and Cytokeratin Profiles of Squamous Cell Carcinoma of the Oral Tongue With Prognosis
Authors: Dantas da Silveira Ericka Janine , Pina Godoy Gustavo , AlvesUchôa Lins Ruthinéia Diógenes , Silva Arruda Maria de Lourdes , Formiga Ramos Carlos Cesar , de Almeida Freitas Roseana , Guedes Queiroz Lélia Maria
Published: October 2007

The aim of the present study was to clinically, morphologically, and immunohistochemically correlate the expression of cytokeratins (CKs) 7, 10, 13, 14, 16, and 19 in 30 cases of tongue squamous cell carcinoma (SCC) with disease outcome, metastases, clinical stage (tumor, node, metastasis [TNM]), and histological grade of malignancy proposed by Bryne. Statistical analysis (χ2 test) showed that only histological grading was not significantly correlated with the clinical variables. CK expression varied in the samples analyzed. CK 10 expression was significantly correlated with the presence of metastases, and the expression of CK 16 was related to disease outcome and also to TNM stages III and IV. These results indicate that metastases and TNM are effective prognostic indicators. The histological grading proposed by Bryne did not reflect the biological behavior of the tongue SCC cases studied. Analysis of some intermediate CK filaments can reflect the biological behavior and aggressiveness of some tongue SCCs.
. . . And the Olive Said to the Cerebellum: Organization and Functional Significance of the Olivo-Cerebellar System
Authors: Ausim Azizi S.
Published: October 2007

What is the role of the olive in cerebellar operations? And what is the role of the cerebellum in the sensory and motor functioning of the nervous system? It is clear that the olivo-cerebellar network plays a key role in the managing of vertebrate motor control, as lesions in this network cause motor deficits in humans and animals. However, it is increasingly becoming clear that the olivo-cerebellar system is involved in the control of more than simple motor behaviors. The elegant and almost geometric organization of the olivocerebellar network lends itself to performing these complex operations. In this review, the salient anatomical, physiological, and clinical features of this system are discussed. A computer-assisted visualization system is used to illustrate some of the anatomical points. The idea that the cerebellum and the olivo-cerebellar networks are perhaps in the upper echelons of the hierarchy of brain functioning, if such a hierarchy indeed exists, is discussed. NEUROSCIENTIST 13(6):616—625, 2007. DOI: 10.1177/1073858407299286
Late-Onset Epileptogenesis and Seizure Genesis: Lessons From Models of Cerebral Ischemia
Authors: Epsztein Jérôme , Ben-Ari Yehezkel , Represa Alfonso , Crépel Valérie
Published: October 2007

Patients surviving ischemic stroke often express delayed epileptic syndromes. Late poststroke seizures occur after a latency period lasting from several months to years after the insult. These seizures might result from ischemia-induced neuronal death and associated morphological and physiological changes that are only partly elucidated. This review summarizes the long-term morphofunctional alterations observed in animal models of both focal and global ischemia that could explain late-onset seizures and epileptogenesis. In particular, this review emphasizes the change in GABAergic and glutamatergic signaling leading to hyperexcitability and seizure genesis. NEUROSCIENTIST 14(1):78—90, 2008.
The Role of the Right Temporoparietal Junction in Social Interaction: How Low-Level Computational Processes Contribute to Meta-Cognition
Authors: Decety Jean , Lamm Claus
Published: October 2007

Accumulating evidence from cognitive neuroscience indicates that the right inferior parietal cortex, at the junction with the posterior temporal cortex, plays a critical role in various aspects of social cognition such as theory of mind and empathy. With a quantitative meta-analysis of 70 functional neuroimaging studies, the authors demonstrate that this area is also engaged in lower-level (bottom-up) computational processes associated with the sense of agency and reorienting attention to salient stimuli. It is argued that this domain-general computational mechanism is crucial for higher level social cognitive processing. NEUROSCIENTIST 13(6): 580—593, 2007. DOI: 10.1177/1073858407304654
The Endoplasmic Reticulum as an Integrator of Multiple Dendritic Events
Authors: Myoung Kyu Park  , Yu Mi Choi  , Yun Kyung Kang  , Petersen Ole H.
Published: October 2007

Dendrites are integrating elements that receive numerous subsets of heterogeneous synaptic inputs, which generate temporally and spatially distinct changes in membrane potential and intracellular Ca2+ levels in local domains. The ubiquitously distributed endoplasmic reticulum (ER) in dendrites is luminally connected to the bulk ER in the soma, constituting a huge interconnected intracellular network that allows rapid Ca2+ diffusion and equilibration. The ER is an excitable organelle that can elicit or terminate cytosolic Ca2+ signals in local or global domains. The absolute level or changes in the Ca2+ concentration in the ER lumen are also very important for the synthesis and maturation of proteins, regulation of gene expression, mitochondrial functions, neuronal excitability, and synaptic plasticity. Through the connected lumen of the ER, information from multiple dendritic events in neurons appears to be delivered into the bulk ER in the soma. Therefore, the ER network in neurons is emerging as a conveyor and integrator of signals. In this article, we will discuss the various roles of the ER and the functional and structural organization of the ER network in neurons. NEUROSCIENTIST 14(1):68—77, 2008.
Functional Anatomic Models of Language: Assembling the Pieces
Authors: Ben Shalom Dorit , Poeppel David
Published: October 2007

In the past few years, a series of influential review articles have summarized the state of the art with respect to cortical models of language organization. The present article is a mini-review and conceptual meta-analysis of several of the most prominent recent contributions. Based on the models, the authors extract some generalizations to arrive at a more robust model that 1) does justice to the range of neurological data, 2) is more connected to research in linguistics and psycholinguistics, and 3) stimulates hypothesis-driven research in this domain. In particular, the article attempts to unify a few of the current large-scale models of the functional neuroanatomy of language in a more principled manner. First, the authors argue that the relevant type of processing in a given cortical area, that is, memorizing (temporal cortex) versus analyzing (parietal) versus synthesizing (frontal), lies at the basis of local neuronal structure and function. Second, from an anatomic perspective, more dorsal regions within each of these (temporal, parietal, and frontal) systems specialize more in phonological processing, middle areas in syntactic processing, and more ventral areas in semantic processing. NEUROSCIENTIST 14(1):119—127, 2008.
Reviews: BDNF and Memory Formation and Storage
Authors: Bekinschtein Pedro , Cammarota Martin , Izquierdo Ivan , Medina Jorge H.
Published: October 2007

During the past decade, a large body of evidence has implicated BDNF in synaptic plasticity. In this review, we focus on the newer experiments that involve BDNF in different aspects of learning and memory processing—in particular, in memory persistence and storage. NEUROSCIENTIST 14(2):147—156, 2008. DOI: 10.1177/1073858407305850
Similarity and Diversity in Visual Cortex: Is There a Unifying Theory of Cortical Computation?
Authors: Van Hooser Stephen D.
Published: October 2007

The cerebral cortex, with its conserved 6-layer structure, has inspired many unifying models of function. However, recent comparative studies of primary visual cortex have revealed considerable structural diversity, raising doubts about the possibility of an all-encompassing theory. This review examines similarities and differences in V1 across mammals. Gross laminar interconnections are relatively conserved. Major functional response classes are found universally or nearly universally. Orientation and spatial frequency tuning bandwidths are quite similar despite an enormous range of visual resolution across species, and orientation tuning is contrast-invariant. Nevertheless, there is considerable diversity in the abundance of different cell classes, laminar organization, functional architecture, and functional connectivity. Orientation-selective responses arise in different layers in different species. Some mammals have elaborate columnar architecture like orientation maps and ocular dominance bands, but others lack this organization with no apparent impact on single cell properties. Finally, local functional connectivity varies according to map structure: similar cells are connected in smooth map regions but dissimilar cells are linked in animals without maps. If there is a single structure/function relation for cortex, it must accommodate significant variations in cortical circuitry. Alternatively, natural selection may craft unique circuits that function differently in each species. NEURO-SCIENTIST 13(6):639—656, 2007. DOI: 10.1177/1073858407306597
Mitochondrial Dynamics and Peripheral Neuropathy
Authors: Baloh Robert H.
Published: October 2007

Peripheral neuropathy is perhaps the archetypal disease of axonal degeneration, characteristically involving degeneration of the longest axons in the body. Evidence from both inherited and acquired forms of peripheral neuropathy strongly supports that the primary pathology is in the axons themselves and points to disruption of axonal transport as an important disease mechanism. Recent studies in human genetics have further identified abnormalities in mitochondrial dynamics—the fusion, fission, and movement of mitochondria— as a player in the pathogenesis of inherited peripheral neuropathy. This review provides an update on the mechanisms of mitochondrial trafficking in axons and the emerging relationship between the disruption of mitochondrial dynamics and axonal degeneration. Evidence suggests mitochondria are a “critical cargo” whose transport is necessary for proper axonal and synaptic function. Importantly, understanding the regulation of mitochondrial movement and the consequences of decreased axonal mitochondrial function may define new paths for therapeutic agents in peripheral neuropathy and other neurodegenerative diseases. NEUROSCIENTIST 14(1):12—18, 2008. DOI: 10.1177/1073858407307354
Urachal Abnormalities: An Incidental Finding and What It Can Mean for Your Patient
Authors: Johnson Laura
Published: October 2007

Urachal abnormalities are rare, especially in adults, and are usually incidentally detected with sonography or by computed tomography. When discovered, they may help to explain patient symptoms. The author reports an incidental finding of urachal diverticula in an adult male. In addition, this report reviews different types of urachal abnormalities, etiology, associated pathology, and treatment.
Sonographic Evaluation of Venous Insufficiency and Sonography-Guided Radiofrequency Ablation of the Great Saphenous Vein
Authors: Garrison Kassandra L.
Published: October 2007

Venous insufficiency (VI) is a pathology that is underappreciated and commonly missed sonographically. When performed correctly, a sonographic evaluation lends information that can provide a minimally invasive treatment option for the patient. The purpose of this case study is to provide an overview of the essential steps in the sonographic evaluation for VI, highlighting components specific to radiofrequency ablation of the great saphenous vein.
Systematic Review of Sonographic Measurements of the Ulnar Nerve at the Elbow
Authors: Thoirs Kerry , Williams Marie A. , Phillips Maureen
Published: October 2007

A systematic review was performed to identify studies reporting summary data (mean, standard deviation) of sonographic cross-sectional measurements of the ulnar nerve at the elbow. Comparisons of measurements were performed to determine whether statistical differences existed between groups of individuals symptomatic and asymptomatic of ulnar nerve entrapment at the elbow (UNE). Across the four studies meeting the selection criteria of the search, five sample groups were identified and compared: three asymptomatic of UNE and two symptomatic of UNE. There were significant differences between measurements of people with and without UNE ( P < .0001—.041). Significant differences also existed between the two symptomatic populations ( P < .0001—.0062) and between the three asymptomatic populations ( P < .0001—.41). This systematic review demonstrates that significant differences exist between sonographic measurements of ulnar nerve dimension between people with and without UNE, confirming that these measurements are potential discriminators of UNE. The demonstration of significant differences between measurements of ulnar nerve size within sample populations with similar symptomatic status suggests that further studies are required to confirm the effect of ulnar nerve pathologies, measurement protocols, and anthropometric factors.
Unexpected Doppler Waveform Patterns in the Lower Extremity Arteries
Authors: Viduetsky Alexander
Published: October 2007

Unexpected Doppler findings in the arteries of the lower extremity may be found during a routine noninvasive vascular examination. Low-resistive Doppler arterial waveforms in the external iliac and femoral arteries are abnormal and often indicators of proximal high-grade stenosis. Occasionally, other medical conditions could also cause anomalous low-resistive arterial waveforms in the arteries of lower extremities. Detailed knowledge of vascular anatomy, careful sonographic scanning, and meticulous analysis of Doppler waveforms in all examined vessels are paramount for adequate examination and reporting. Vascular sonographers should consider different clinical scenarios whenever abnormal Doppler waveforms are detected.
Constriction Rings and Congenital Amputations of the Fingers and Toes in a Mild Case of Amniotic Band Syndrome
Authors: Allen Lisa M. , Silverman Robert K. , Nosovitch John T. , Lohnes Tammy M. , Williams Kathleen D.
Published: October 2007

Amniotic band syndrome (ABS) may result in fetal anomalies that vary in severity from minor to lethal. Although numerous conditions have been grouped with this diagnosis, a subset of this population will have no other intrauterine abnormalities other than isolated defects of the extremities. ABS may present as constriction rings and congenital amputation affecting the limbs and digits. Routine sonographic evaluation of the fetus in the second trimester can identify the major defects associated with ABS. Detailed evaluation of the fetal extremities, including views of the hands and feet, will increase the detection of minor defects.
Uterus Didelphys and Dicavitary Twin Pregnancy
Authors: Allegrezza Danielle M.
Published: October 2007

Uterus didelphys, also known as a duplicated uterus, is an embryological abnormality resulting from the failure of fusion of the Mullerian ducts, causing full uterine development to erroneously occur bilaterally. The occurrence of uterus didelphys is very low in the general population and often predisposes women to a variety of gynecological difficulties. There appears to be a high association with obstetrical complications, such as spontaneous abortion, preterm labor, cervical incompetence, and malpresentation. Uterus didelphys is also associated with urinary tract abnormalities. Presented is a case of a woman with a didelphys uterus and a twin pregnancy.
Sonographic Assessment of Axillary Lymph Nodes After a Mammographically Recommended Breast Sonogram for Women 55 Years and Older: A Feasibility Study
Authors: Evans Kevin D. , Li Xiaobai , Robertson Suzanne R. , Boyd Ashley M. , Knopp Michael
Published: October 2007

Sonographic guidelines have been provided for assessing lymph nodes both in the axilla and other areas of the body. The objective of this study was to determine the feasibility of using sonography and Doppler to provide diagnostic nodal information for women 55 years and older. The authors conducted a retrospective longitudinal study of a group of women 55 years and older who provided their prior health histories, mammography, and sonogram results, as well as eventual pathology reports, to help establish the value of Doppler measurements, nodal dimensions, and subjective assessment data collected at the time of the breast sonogram. Each patient consented to allow 15 minutes of scanning of her axilla to evaluate three lymph nodes. Fifty-two women provided data points that were captured and compared to published guidelines, such as longitudinal/diameter (L/D) ratio, resistive index (RI), and Stavros's subjective grading scale. The longitudinal axis compared to the diameter of a node (L/D ratio), shape, and RI was statistically correlated with published guidelines. Sonographic measures and Doppler assessment of axillary lymph nodes are feasible, and continued research could result in a reliable set of parameters that could be used as an economical, noninvasive imaging technique for possible staging of women 55 years and older.
Sonographic Evaluation of a Testicular Fracture
Authors: Guthrie Joy D.
Published: October 2007

Testicular fracture with or without rupture is a rare but serious complication of scrotal trauma. Sonography is well established as the gold standard for testicular injury in an acute setting. The normal testicular parenchymal pattern is homogeneous by gray-scale sonography and free of internal irregularities. The sonographic findings in testicular fracture include a distinct or indistinct fracture line coursing through the testicle. This case study demonstrates an acute testicular fracture with associated hematocele. The fracture line in this examination was seen dissecting the left testicle without scrotal wall rupture and sustained flow to the superior half of the testicle. Prompt evaluation by gray scale and color and spectral Doppler revealed adequate flow to the superior portion of the testicle. Sonography proved helpful in guiding the surgical treatment that resulted in salvage of the upper half of the traumatized testicle instead of the customary orchiectomy (removal of the testicle).
Microvascular endothelial cells express a phosphatidylserine receptor: a functionally active receptor for phosphatidylserine-positive erythrocytes
Authors: Setty B. N. Yamaja , Betal Suhita Gayen
Published: October 2007

Phosphatidylserine (PS)–positive erythrocytes adhere to endothelium and subendothelial matrix components. While thrombospondin mediates these inter-actions, it is unknown whether PS-associated erythrocyte-endothelial adhesion occurs in the absence of plasma ligands. Using ionophore-treated PS-expressing control HbAA erythrocytes, we demonstrate that PS-positive erythrocytes adhered to human lung microendothelial cells in the absence of plasma ligands, that this adhesion was enhanced following endothelial activation with IL-1α, TNF-α, LPS, hypoxia, and heme, and that this adhesive interaction was selective to erythrocyte PS. We next explored whether microendothelial cells express an adhesion receptor that recognizes cell surface–expressed PS (PSR) similar to that expressed on activated macrophages. We demonstrate constitutive expression of both PSR mRNA and protein that were up-regulated in a time-dependent manner following endothelial activation. While minimal PSR expression was noted on unstimulated cells, endothelial activation up-regulated PSR surface expression. In antibody-blocking studies, using PS-positive erythrocytes generated either artificially via ionophore treatment of control erythrocytes or from patients with sickle cell disease, we demonstrate that PSR was functional, supporting PS-mediated erythrocyte adhesion to activated endothelium. Our results demonstrate the existence of a novel functional adhesion receptor for PS on the microendothelium that is up-regulated by such pathologically relevant agonists as hypoxia, cytokines, and heme.
ALK5- and TGFBR2-independent role of ALK1 in the pathogenesis of hereditary hemorrhagic telangiectasia type 2
Authors: Park Sung O. , Lee Young Jae , Seki Tsugio , Hong Kwon-Ho , Fliess Naime , Jiang Zhigang , Park Alice , Wu Xiaofang , Kaartinen Vesa , Roman Beth L. , Oh S. Paul
Published: October 2007

ALK1 belongs to the type I receptor family for transforming growth factor-β family ligands. Heterozygous ALK1 mutations cause hereditary hemorrhagic telangiectasia type 2 (HHT2), a multisystemic vascular disorder. Based largely on in vitro studies, TGF-β1 has been considered as the most likely ALK1 ligand related to HHT, yet the identity of the physiologic ALK1 ligand remains controversial. In cultured endothelial cells, ALK1 and another TGF-β type I receptor, ALK5, regulate angiogenesis by controlling TGF-β signal transduction, and ALK5 is required for ALK1 signaling. However, the extent to which such interactions between these 2 receptors play a role in pathogenesis of HHT is unknown. We directly addressed these issues in vivo by comparing the phenotypes of mice in which the Alk1, Alk5, or Tgfbr2 gene was conditionally deleted in restricted vascular endothelia using a novel endothelial Cre transgenic line. Alk1-conditional deletion resulted in severe vascular malformations mimicking all pathologic features of HHT. Yet Alk5- or Tgfbr2-conditional deletion in mice, or Alk5 inhibition in zebrafish, did not affect vessel morphogenesis. These data indicate that neither ALK5 nor TGFBR2 is required for ALK1 signaling pertinent to the pathogenesis of HHT and suggest that HHT might not be a TGF-β subfamily disease.
Program of active aging in a rural Mexican community: a qualitative approach
Authors: de la Luz Martínez-Maldonado María , Correa-Muñoz Elsa , Mendoza-Núñez Víctor Manuel
Published: October 2007

Background

Education is one of the key elements in the promotion of a thorough paradigm for active aging. The aim of this study is to analyze factors that contribute the empowerment of older adults in a rural Mexican community and, thus, promote active aging.

Methods

The study was conducted in a rural Mexican community (Valle del Mezquital), based on an action-research paradigm. One hundred and fifty-five elderly subjects with elementary school education participated in a formal training program promoting gerontological development and health education. Participants in turn became coordinators of mutual-help groups (gerontological nucleus) in Mexico. In-depth interviews were carried out to assess the empowerment after training for active aging.

Results

It was found that there was an increasing feeling of empowerment, creativity and self-fulfillment among participants. Among the main factors that positively influenced training of the elderly toward active aging were the teaching of gerontology topics themselves; besides, their motivation, the self-esteem, the increased undertaking of responsibility, the feeling of belonging to the group, and the sharing of information based on personal experience and on gerontological knowledge.

Conclusion

The main factors that contribute to empowerment of older adults in a rural Mexican community for participate in active aging programs are the training and teaching of gerontology topics themselves; besides, their interest, experience and involvement.
A study of the efficacy and cost-effectiveness of MRSA screening and monitoring on surgical wards using a new, rapid molecular test (EMMS)
Authors: Hardy Katherine J , Szczepura Ala , Davies Ruth , Bradbury Andrew , Stallard Nigel , Gossain Savita , Walley Paul , Hawkey Peter M
Published: October 2007

Background

MRSA is a significant contributor to prolonged hospital stay, poor clinical outcome and increased healthcare costs amongst surgical patients. A PCR test has been developed for rapid detection of MRSA in nasal swabs. The aims of this study are (1) to estimate the effectiveness of screening using this rapid PCR tests vs culture in reducing MRSA cross-infection rates; (2) to compare the cost of each testing strategy, including subsequent health care costs; and (3) to model different policies for the early identification and control of MRSA infection in surgical patients.

Methods/Design

The study is a prospective two-period cross-over study set in 7 surgical wards covering different surgical specialities. A total of 10,000 patients > 18 years will be tested over 16 months. The only difference between the two study periods is the method used for the detection of MRSA in each ward (rapid v conventional culture), with all other infection control practices remaining consistent between the arms. The study has been designed to complement routine practice in the NHS. Outcomes are MRSA cross-infection rates (primary outcome) and need for antibiotic therapy and MRSA-related morbidity. Parallel economic and modelling studies are being conducted to aid in the interpretation of the results and to evaluate the cost-effectiveness of the rapid PCR screening strategy.

Discussion

This paper highlights the design, methods and operational aspects of a study evaluating rapid MRSA screening in the surgical ward setting.
Patients' satisfaction and opinions of their experiences during admission in a tertiary care hospital in Pakistan – a cross sectional study
Authors: Imam Sardar Zakariya , Syed Khezar Shahzada , Ali Syed Ahad , Ali Syed Umer , Fatima Kiran , Gill Marium , Hassan Muhammad Ovais , Hashmi Saad Hasan , Siddiqi Maham T , Khan Hadi Muhammad , Jameel Omar Farooq
Published: October 2007

Background

It is often felt that developing countries need to improve their quality of healthcare provision. This study hopes to generate data that can help managers and doctors to improve the standard of care they provide in line with the wishes of the patients.

Methods

It was a cross sectional study carried out at a major tertiary care hospital of Karachi. Patients between the ages of 18 and 80 years admitted to the hospital for at least one day were included. Patients in the maternity, psychiatry and chemotherapy wards and those in the ICU/CCU were excluded. A pretested, peer reviewed translation of a validated patient satisfaction scale developed by the Picker Institute of Europe was administered.

Results

A total of 173 patients (response rate: 78.6 %) filled the questionnaire. Patient satisfaction was at levels comparable to European surveys for most aspects of hospital care. However, nearly half the patients (48%) felt they had to wait too long to get a bed in the hospital after presenting to the ER. 68.6% of the patients said that they were never asked for views on the quality of care provided. 20% of the patients did not find anyone in the staff to talk to about their worries and fears while 27.6% felt that they were given emotional support to only some extent. Up to one third of the patients said they were not provided enough information regarding their operative procedures beforehand.

Conclusion

Although several components of patient care equal the quality levels of the west, many sections require considerable improvement in order to improve health care provision. The healthcare team needs to get more involved with the patients, providing them greater support and keeping them informed and involved with their medical treatment. Efforts should be made to get regular feedback from the patients.
Leiomyosarcoma of the Adrenal vein: a novel approach to surgical resection
Authors: Wang Tracy S , Ocal Idris Tolgay , Salem Ronald R , Elefteriades John , Sosa Julie A
Published: October 2007

Background

Leiomyosarcomas typically originate within smooth muscle cells. Leiomyosarcomas arising from the adrenal vein are rare malignancies associated with delayed diagnosis and poor prognosis. The most common vascular site of origin is the inferior vena cava.

Case presentation

This is a 64-year old woman who presented with a 13 × 6.5 × 6.6 cm heterogeneous mass arising in the region of the right adrenal gland and extending into the inferior vena cava (IVC) and the right atrium. Biochemical evaluation excluded a functional tumor of the adrenal gland, and multiple tumor markers were negative. We present the novel use of deep hypothermic circulatory arrest (DHCA) in the resection of an adrenal vein leiomyosarcoma extending into the right atrium. The patient remains free of disease ten months after surgery. DHCA afforded a bloodless operative field for optimal resection of disease from within the IVC.

Conclusion

The diagnosis of leiomyosarcomas of the adrenal vein is one of exclusion and involves preoperative radiological imaging and biochemical evaluation to exclude other functional tumors of the adrenal gland. Aggressive surgical resection is associated with improved survival and may be best achieved via collaboration among different surgical subspecialties.
A critical evaluation of loss of heterozygosity detected in tumor tissues, blood serum and bone marrow plasma from patients with breast cancer
Authors: Schwarzenbach Heidi , Müller Volkmar , Beeger Cord , Gottberg Miriam , Stahmann Nicole , Pantel Klaus
Published: October 2007

Introduction

The aim of the study was to perform a comparative analysis of LOH (loss of heterozygosity) in primary tumors as well as peripheral blood and bone marrow (BM) of patients with breast cancer (BCa).

Methods

Performing PCR-based fluorescence microsatellite analysis and using a panel of seven polymorphic microsatellite markers, we compared the profiles of LOH in primary tumors, peripheral blood and BM plasma from patients with primary BCa (n = 40, stage M0) as well as tumor tissues and blood serum from metastatic BCa patients (n = 48, stage M1). During the course of systemic treatment blood samplings from 12 M0 and 16 M1 patients were at least once repeated.

Results

The overall incidences of LOH in tumor tissues, blood and BM samples were 27.5%, 9.0% and 5.0%, respectively. The marker D3S1255 was the only one in the panel that showed similar frequencies of LOH ranging from 19.0 to 24.5% in tumor, blood and BM samples. Both M0 blood serum and BM plasma samples displayed the same rate of 19.0%, whereas tumor and M1 serum showed a rate of 24.5% and 24.0%, respectively, at this locus. This marker also showed the highest frequency of LOH in serum and BM samples, whereas in tumor samples LOHs at the markers D13S218 (38%) and D17S855 (36%) were more frequent. Statistical analysis of the tumor samples showed that occurrence of LOH at the markers D3S1255 (P < 0.04), D9S171 (P < 0.05) and D17S855 (P < 0.03) correlated with undifferentiated nuclear grade. Additionally, significant associations of the number of LOH recorded at D17S250 with estrogen receptor (P < 0.02), progesterone receptor (P < 0.03) expression and high proliferation score (Ki-67 expression, P = 0.009) were observed. In blood serum samples a relationship between positive lymph node status and LOH at the marker D3S1255 was revealed (M0 stage, P = 0.05; M0+M1 stage, P = 0.004).

Conclusion

Our study demonstrates heterogeneous profiles and low rates of LOH, particularly on free DNA in BM and blood samples. However, the significant associations of LOH with some risk factors and the demonstrated possibility of monitoring free DNA in patients undergoing systemic therapy suggest that LOH analysis may be developed into a useful diagnostic tool.
Involvement of CCR9 at multiple stages of adult T lymphopoiesis
Authors: Svensson Marcus , Marsal Jan , Uronen-Hansson Heli , Cheng Min , Jenkinson William , Cilio Corrado , Jacobsen Sten Eirik W , Sitnicka Ewa , Anderson Graham , Agace William W
Published: October 2007

The chemokine CCL25 is constitutively expressed in the thymus, and its receptor CCR9 is expressed on subsets of developing thymocytes. Nevertheless, the function of CCL25/CCR9 in adult thymopoiesis remains unclear. Here, we demonstrate that purified CCR9−/− hematopoietic stem cells are deficient in their ability to generate all major thymocyte subsets including double-negative 1 (DN1) cells in competitive transfers. CCR9−/− bone marrow contained normal numbers of lineage− Sca-1+c-kit+, common lymphoid progenitors, and lymphoid-primed multipotent progenitors (LMPP), and CCR9−/− LMPP showed similar T cell potential as their wild-type (WT) counterparts when cultured on OP9–δ-like 1 stromal cells. In contrast, early thymic progenitor and DN2 thymocyte numbers were reduced in the thymus of adult CCR9−/− mice. In fetal thymic organ cultures (FTOC), CCR9−/− DN1 cells were as efficient as WT DN1 cells in generating double-positive (DP) thymocytes; however, under competitive FTOC, CCR9−/− DP cell numbers were reduced significantly. Similarly, following intrathymic injection into sublethally irradiated recipients, CCR9−/− DN cells were out-competed by WT DN cells in generating DP thymocytes. Finally, in competitive reaggregation thymic organ cultures, CCR9−/− preselection DP thymocytes were disadvantaged significantly in their ability to generate CD4 single-positive (SP) thymocytes, a finding that correlated with a reduced ability to form TCR-MHC-dependent conjugates with thymic epithelial cells. Together, these results highlight a role for CCR9 at several stages of adult thymopoiesis: in hematopoietic progenitor seeding of the thymus, in the DN-DP thymocyte transition, and in the generation of CD4 SP thymocytes.
Implications for Prostate Cancer of Insulin-Like Growth Factor-I (IGF-I) Genetic Variation and Circulating IGF-I Levels
Authors: Johansson Mattias , McKay James D. , Wiklund Fredrik , Rinaldi Sabina , Verheus Martijn , van Gils Carla H. , Hallmans Göran , Bälter Katarina , Adami Hans-Olov , Grönberg Henrik , Stattin Pär , Kaaks Rudolf
Published: October 2007

Background: Elevated levels of circulating IGF-I have consistently been associated with increased prostate cancer risk. We recently found a haplotype in the 3′ region of the IGF-I gene associated with increased risk of prostate cancer, and we hypothesized that the observed association is mediated by circulating IGF-I.

Materials and Methods: We analyzed haplotypes and three haplotype-tagging single nucleotide polymorphisms (htSNPs) in the 3′ region of the IGF-I gene in relation to circulating levels IGF-I in 698 control subjects from the CAncer Prostate in Sweden (CAPS) study and 575 cases and controls from the prospective Northern Sweden Health and Disease Cohort (NSHDC) study. We also performed a meta-analysis of these two and four other association studies on genetic variation in the 3′ region of the IGF-I gene in relation to circulating IGF-I levels.

Results: The IGF-I haplotype previously associated with prostate cancer risk, labeled “TCC,” was associated with elevated levels of IGF-I in the CAPS study (P = 0.02), but not in the NSHDC study. In contrast, two of the three IGF-I htSNPs tagging this haplotype, rs6220 and rs7136446, were associated with elevated levels of IGF-I in the NSHDC (P = 0.03 and P = 0.04, respectively), but not in the CAPS study. In the meta-analysis, the TCC haplotype and the rs6220 SNP were associated with elevated levels of circulating IGF-I (P = 0.001 and P < 0.0001, respectively).

Conclusions: Genetic variation in the 3′ region of the IGF-I gene seems to influence circulating levels of IGF-I. This observation is consistent with the hypothesis that variation in the IGF-I gene plays a role in prostate cancer susceptibility by influencing circulating levels of IGF-I.
α6β4 integrin activates Rac-dependent p21-activated kinase 1 to drive NF-κB-dependent resistance to apoptosis in 3D mammary acini
Authors: Friedland Julie C. , Lakins Johnathon N. , Kazanietz Marcelo G. , Chernoff Jonathan , Boettiger David , Weaver Valerie M.
Published: October 2007

Malignant transformation and multidrug resistance are linked to resistance to apoptosis, yet the molecular mechanisms that mediate tumor survival remain poorly understood. Because the stroma can influence tumor behavior by regulating the tissue phenotype, we explored the role of extracellular matrix signaling and tissue organization in epithelial survival. We report that elevated (α6)β4 integrin-dependent Rac-Pak1 signaling supports resistance to apoptosis in mammary acini by permitting stress-dependent activation of the p65 subunit of NF-κB through Pak1. We found that inhibiting Pak1 through expression of N17Rac or PID compromises NF-κB activation and renders mammary acini sensitive to death, but that resistance to apoptosis could be restored to these structures by overexpressing wild-type NF-κB p65. We also observed that acini expressing elevated levels of Pak1 can activate p65 and survive death treatments, even in the absence of activated Rac, yet will die if activation of NF-κB is simultaneously inhibited through expression of IκBαM. Thus, mammary tissues can resist apoptotic stimuli by activating NF-κB through α6β4 integrin-dependent Rac-Pak1 signaling. Our data emphasize the importance of the extracellular matrix stroma in tissue survival and suggest that α6β4 integrin-dependent Rac stimulation of Pak1 could be an important mechanism mediating apoptosis-resistance in some breast tumors.
Design of a parallel crank-rocker flapping mechanism for insect-inspired micro air vehicles
Authors: Conn A T , Burgess S C , Ling C S
Published: October 2007

In the current paper, a novel micro air vehicle (MAV) flapping mechanism for replicating insect wing kinematics is presented. Insects flap their wings in a complex motion that enables them to generate several unsteady aerodynamic mechanisms, which are extremely beneficial for lift production. A flapping wing MAV that can reproduce these aerodynamic mechanisms in a controlled manner is likely to outperform alternative flight platforms such as rotary wing MAVs. A biomimetic design approach was undertaken to develop a novel flapping mechanism, the parallel crank-rocker (PCR). Unlike several existing flapping mechanisms (which are compared using an original classification method), the PCR mechanism has an integrated flapping and pitching output motion which is not constrained. This allows the wing angle of attack, a key kinematic parameter, to be adjusted and enables the MAV to enact manoeuvres and have flight stability. Testing of a near-MAV scale PCR prototype using a high-speed camera showed that the flapping angle and adjustable angle of attack both closely matched predicted values, proving the mechanism can replicate insect wing kinematics. A mean lift force of 3.35 g was measured with the prototype in a hovering orientation and flapping at 7.15 Hz.
Numerical modelling of electro-osmotically driven flow within the microthin liquid layer near an earthworm surface - a biomimetic approach
Authors: Yan Y Y , Zu Y Q , Ren L Q , Li J Q
Published: October 2007

The electro-osmotic flow near an earthworm body surface is a basic electrokinetic phenomenon that takes place when the earthworm moves in moist soil. The flow within a microthin liquid layer near earthworm's body surface is induced by the electric double layer (EDL) interaction. Such a microscale electro-osmotic flow plays a role of lubrication between the earthworm's body surface and the surrounding medium of moist soil and reduces surface adhesion. In the current paper, the electro-osmotic flow near earthworm surface is numerically simulated to further understand the mechanism of antisoil adhesion. A lattice Poisson method is first employed to solve electric potential and charge distributions in the EDL along an earthworm surface; the external electric field is then obtained by solving the Laplace equation. The motion of electro-osmotic flow controlled by Navier-Stokes equations is simulated by the lattice Boltzmann method. Typically, the simulation of electro-osmotic flow shows that moving vortices, which likely contribute to antisoil adhesion, can be formed near the earthworm body surface by the non-uniform and variational electrical force.
Technology trajectories, innovation, and the growth of biomimetics
Authors: Bonser R H C , Vincent J F V
Published: October 2007

Publication rate of patents can be a useful measure of innovation and productivity in science and technology. Patenting activity in new technological fields follows a sigmoid (S-shaped) path. Qualitative and quantitative models in management and economics literature explain why such patterns of productivity may occur.

TRIZ analysis suggests that patents are generated in bursts during the evolution of a product and that they are at different levels of inventiveness. The tendency is for the inventiveness to reduce as the product is more mature. This makes it possible to guess at the lifetime stage of a product and gauge its maturity and profitability.

An analysis of patenting activity and other measures of inventiveness in the emerging field of biomimetics was presented, and future trends in biologically-inspired innovation was discussed.
A woodpecker hammer
Authors: Vincent J F V , Sahinkaya M N , O'Shea W
Published: October 2007

Woodpecker can be modelled as a low-inertia hammer. It uses the angular momentum of its body, generated by contraction of its leg muscles, to accelerate its head towards the tree, which it is pecking. It appears to peck at a resonant frequency.
Synovial joint lubrication — does nature teach more effective engineering lubrication strategies?
Authors: Neville A , Morina A , Liskiewicz T , Yan Y
Published: October 2007

Nature shows numerous examples of systems which show energy efficiency, elegance in their design and optimum use of materials. Biomimetics is an emerging field of research in engineering and successes have been documented in the diverse fields of robotics, mechanics, materials engineering, and many more. To date little biomimetics research has been directed towards tribology in terms of transferring technologies from biological systems into engineering applications. The potential for biomimicry has been recognized in terms of replicating natural lubricants but this system reviews the potential for mimicking the synovial joint as an efficient and durable tribological system for potential engineering systems. The use of materials and the integration of materials technology and fluid/surface interactions are central to the discussion.
Serotonin Transporter Phosphorylation by cGMP-Dependent Protein Kinase Is Altered by a Mutation Associated with Obsessive–Compulsive Disorder
Authors: Zhang Yuan-Wei , Gesmonde Joan , Ramamoorthy Sammanda , Rudnick Gary
Published: October 2007

Human serotonin transporter (hSERT) activity expressed in HeLa cells was stimulated by agents that release nitric oxide, stimulate soluble guanylyl cyclase, or activate cGMP-dependent protein kinase (PKG). This stimulation was blocked by a PKG inhibitor. A naturally occurring mutation, I425V, associated with obsessive–compulsive disorder and other neuropsychiatric disorders, activated hSERT and eliminated stimulation via the PKG pathway. Inhibitors of soluble guanylyl cyclase or PKG decreased activity of the I425V mutant, but not wild type, indicating that both wild-type and mutant transporters could exist in both high and low activity forms. Mutation of Thr-276 in the fifth transmembrane domain (TM5) to alanine or aspartate prevented activation of wild-type hSERT through the PKG pathway and also blocked the inhibition of I425V activity by inhibitors of the pathway. The accessibility of positions in TM5 near Thr-276 was modified in T276D, but not in I425V. These results are consistent with the hypothesis that PKG phosphorylates hSERT at Thr-276 and increases its activity by modifying the substrate permeation pathway formed, in part, by TM5. The effect of the I425V mutation may shift the balance of hSERT toward the phosphorylated form, possibly by interfering with the action of a phosphatase. However, association of hSERT with protein phosphatase 2A was not decreased in the I425V mutant.
Extracellular Signal-Regulated Kinase 2 (ERK2) Knockdown Mice Show Deficits in Long-Term Memory; ERK2 Has a Specific Function in Learning and Memory
Authors: Satoh Yasushi , Endo Shogo , Ikeda Toshio , Yamada Kazuyuki , Ito Masataka , Kuroki Masahiko , Hiramoto Takeshi , Imamura Osamu , Kobayashi Yasushi , Watanabe Yasuhiro , Itohara Shigeyoshi , Takishima Kunio
Published: October 2007

The extracellular signal-regulated kinase (ERK) 1 and 2 are important signaling components implicated in learning and memory. These isoforms display a high degree of sequence homology and share a similar substrate profile. However, recent findings suggest that these isoforms may have distinct roles: whereas ERK1 seems to be not so important for associative learning, ERK2 might be critically involved in learning and memory. Thus, the individual role of ERK2 has received considerable attention, although it is yet to be understood. Here, we have generated a series of mice in which ERK2 expression decreased in an allele dose-dependent manner. Null ERK2 knock-out mice were embryonic lethal, and the heterozygous mice were anatomically impaired. To gain a better understanding of the influence of ERK2 on learning and memory, we also generated knockdown mice in which ERK2 expression was partially (20–40%) reduced. These mutant mice were viable and fertile with normal appearance. The mutant mice showed a deficit in long-term memory in classical fear conditioning, whereas short-term memory was normal. The mice also showed learning deficit in the water maze and the eight-arm radial maze. The ERK1 expression level of the knockdown mice was comparable with the wild-type control. Together, our results indicate a noncompensable role of ERK2-dependent signal transduction in learning and memory.
Neural Correlates of Tactile Detection: A Combined Magnetoencephalography and Biophysically Based Computational Modeling Study
Authors: Jones Stephanie R. , Pritchett Dominique L. , Stufflebeam Steven M. , Hämäläinen Matti , Moore Christopher I.
Published: October 2007

Previous reports conflict as to the role of primary somatosensory neocortex (SI) in tactile detection. We addressed this question in normal human subjects using whole-head magnetoencephalography (MEG) recording. We found that the evoked signal (0–175 ms) showed a prominent equivalent current dipole that localized to the anterior bank of the postcentral gyrus, area 3b of SI. The magnitude and timing of peaks in the SI waveform were stimulus amplitude dependent and predicted perception beginning at ∼70 ms after stimulus. To make a direct and principled connection between the SI waveform and underlying neural dynamics, we developed a biophysically realistic computational SI model that contained excitatory and inhibitory neurons in supragranular and infragranular layers. The SI evoked response was successfully reproduced from the intracellular currents in pyramidal neurons driven by a sequence of lamina-specific excitatory input, consisting of output from the granular layer (∼25 ms), exogenous input to the supragranular layers (∼70 ms), and a second wave of granular output (∼135 ms). The model also predicted that SI correlates of perception reflect stronger and shorter-latency supragranular and late granular drive during perceived trials. These findings strongly support the view that signatures of tactile detection are present in human SI and are mediated by local neural dynamics induced by lamina-specific synaptic drive. Furthermore, our model provides a biophysically realistic solution to the MEG signal and can predict the electrophysiological correlates of human perception.