bluuebunny/crossref_metadata_2025 huggingface dataset:
Quali aree protette nella mondializzazione? Riflessioni a partire dai paesaggi agro-pastorali del Parco nazionale della Maiella
Authors: Zanolin Giacomo
Published: January 2024

Abstract What Protected Areas in Globalisation? Reflections from the Agro-Pastoral Landscapes of the Maiella National Park This paper aims to reflect on a possible interpretation of the role that protected areas could play in the globalization. Starting from the example of the Maiella National Park (Italy), the paper aims to highlight the role of anthropic action as a key factor that throughout history has contributed to the generation of the current forms of ecosystems, characterized in this context by high levels of biodiversity, especially from the botanical point of view. All this provides an opportunity to reflect on the constructive role played by humankind in ecological dynamics, and so to develop a critical discussion of the significance of protected areas as peculiar places of globalization, capable of conveying crucial ethical values.
Long-term Hematopoietic Transfer of the Anti-Cancer and Lifespan-Extending Capabilities of A Genetically Engineered Blood System by Transplantation of Bone Marrow Mononuclear Cells
Authors: Wang Jing-Ping , Hung Chun-Hao , Liou Yao-Huei , Liu Ching-Chen , Yeh Kun-Hai , Wang Keh-Yang , Lai Zheng-Sheng , Chatterjee Biswanath , Hsu Tzu-Chi , Lee Tung-Liang , Shyu Yu-Chiau , Hsiao Pei-Wen , Chen Liuh-Yow , Chuang Trees-Juen , Yu Chen-Hsin Albert , Liao Nah-Shih , Shen Che-Kun James
Published: January 2024

A causal relationship exists among the aging process, organ decay and dis-function, and the occurrence of various diseases including cancer. A genetically engineered mouse model, termed
Eklf
K74R/K74R
or
Eklf
(K74R), carrying mutation on the well-conserved sumoylation site of the hematopoietic transcription factor KLF1/ EKLF has been generated that possesses extended lifespan and healthy characteristics including cancer resistance. We show that the healthy longevity characteristics of the
Eklf
(K74R) mice, as exemplified by their higher anti-cancer capability, are likely gender-, age- and genetic background-independent. Significantly, the anti-cancer capability, in particular that against melanoma as well as hepatocellular carcinoma, and lifespan-extending property of
Eklf
(K74R) mice could be transferred to wild-type mice via transplantation of their bone marrow mononuclear cells at young age of the latter. Furthermore, NK(K74R) cells carry higher
in vitro
cancer cell-killing ability than wild type NK cells. Targeted/global gene expression profiling analysis has identified changes of the expression of specific proteins, including the immune checkpoint factors PD-1 and PD-L1, and cellular pathways in the leukocytes of the
Eklf
(K74R) that are in the directions of anti-cancer and/or anti-aging. This study demonstrates the feasibility of developing a transferable hematopoietic/ blood system for long-term anti-cancer and, potentially, for anti-aging.
Assessment of Learning Styles Using Kolb’s Learning Style Inventory among Medical College Students: A Cross-sectional Study
Authors: Vemuri Veena Rani , Rao Kiran Arun
Published: January 2024

Introduction: Technology has become increasingly integral in medical education, especially with the implementation of newer Competency Based Medical Education (CBME) curricula. Blending conventional methods with e-learning and ensuring its effectiveness in supporting student learning requires effort and consideration. In this regard, Kolb’s learning styles, introduced in 1984, can be helpful in identifying different types of learners within the student population and tailoring teaching methods accordingly to enhance student outcomes. Aim: To assess the learning styles of medical students using Kolb’s Learning Style Inventory, version 3.1, and to compare the learning styles with the year of study. Materials and Methods: A cross-sectional, questionnairebased study was conducted in the Department of Pharmacology, Terna Medical College, Navi Mumbai, Maharashtra, India. on 194 first and second Bachelor of Medicine and Bachelor of Surgery (MBBS) students. The study included students who were present when the questionnaire was administered. The learning styles were assessed using Kolb’s Learning Style Inventory, version 3.1. Descriptive statistics were applied. Results: The total strength of both the first and second-year batches combined was 254. Out of these, 194 students were present when the questionnaire was administered, resulting in a response rate of 76.38%. Seven incorrectly answered questionnaires were excluded from the analysis. Among the 194 valid questionnaires received, 55 students (29.41%) had convergent as their learning style, making it the most common learning style. The next most common learning style was accommodative, with 52 students (27.81%) exhibiting this style. Specifically, among the first-year MBBS students, 35 out of 108 (32.41%) had a convergent learning style, while among the second-year MBBS students, 24 out of 79 (30.38%) had an accommodative learning style. There was a statistically significant difference observed in the learning styles between the first and second-year MBBS students (p-value <0.05). Conclusion: In present study, it was observed that the convergent learning style was dominant among the medical students in the first and second years combined, with the first year being predominantly convergent and the second year being predominantly accommodative.
Impact of Tense Instruction on Narrative Composition Writing in Senior Secondary Students
Authors: Shiolbial Noel D. , Gowon Rahila P.
Published: January 2024

The study examined the effect of tenses instruction on sentence construction, paragraphing, and editing in senior secondary students' narrative composition writing achievements in Shendam Local Government Area, Plateau State, Nigeria. The study investigated three research questions and three hypotheses. The study adopted a quasi-experimental (non-randomised control group) research design. The study's population included all 959 senior secondary II English students in Shendam Local Government Area, Plateau State, Nigeria, and a sample of 90 students from two intact classes (Experimental group 50, control group 40) participated in the study. Students in the experimental group received six weeks of training on tenses instruction, while those in the control group received standard conventional instruction. The researchers used the Narrative Composition Achievement Test for obtaining baseline and after the intervention data. A reliability of 0.80 was calculated using the Pearson product moment correlation coefficient, which was satisfactory. Data were examined using descriptive statistics (means and SDI) and analysis of covariance ANCOVA. At baseline, students revealed inadequate abilities in sentence construction, paragraphing, and editing on the narrative composition accomplishment test. Students' ability to form sentences, generate paragraphs, and edit narrative composition writing was also significantly improved by tenses instruction. The study concluded that tenses instruction has significant effects on sentence construction, paragraphing, and editing in the achievement test for narrative composition.
Identifying the Learning Style of Students Using Machine Learning Techniques: An Approach of Felder Silverman Learning Style Model (FSLSM)
Authors: WAAM Wanniarachchi, , HKS Premadasa,
Published: January 2024

Identification of the learning style of the students in the teaching and learning environment plays a significant importance in improving both teaching and learning perspectives. The intension of the research was to investigate about applying the Machine Learning Techniques for identification of the Learning style of the students in online learning environment based on the Felder Silverman Learning Style (FSLSM) identification model. The significance of this experiment is that the proposed methodology considers the combination of access frequency (f) of course materials and total time (T) students spent on each course activity. For data collection process, it was designed reusable plugin for the Moodle for time tracking. Real-time dataset was prepared using three course modules designed according to the features of FSLSM model and the features for analyzing the students according to the FSLSM, it was selected seven criteria, and the features were validated using Pearson Correlation Coefficient method. These course modules were enrolled 150 students per each module. Once the data set was prepared, the data set was preprocessed and applied Five Supervised Classification Machine learning algorithms as Decision Tree, Logistic Regression, Random Forest, Support Vector Machine and K-Nearest Neighbors algorithm. The models were evaluated using Accuracy, Precision, Recall and F1 values. Over the five algorithms the Decision Tree classifier algorithm performed with best average accuracy with 93.5% for Input, 86% for Perception, 89.5 for Processing and 94% for Understanding dimension. The models were validated using the K-fold Cross validation and Standard Deviation values. Mean Squared Error, Bias and Variance values were considered the evaluation of underfitting or overfitting context of the model. To parameter optimization, the Grid Search Methodology was applied to find the best combination of criterion for the model. Finally, an application was developed for Identifying the Learning Style of the Students using the designed Machine learning model. The Consistency of the ML Model based on the Decision Tree classifier algorithm were evaluated using the results generated through developed application and the results suggested that consistency for taught machine learning algorithms is often between 85% to 95%, which is an acceptable range. The results generated by the application for identification of the learning style suggested the combination of learning style for particular students sample as Global-Mild, Visual- Strong, Sensing- Moderate and Reflective-Strong. Identification of these combination of learning style assist for teachers by giving an insight which components of the learning contents should be improved in course designing process.
Emergency and Urgent Care Network: Analysis of the Stroke Care Line According to Care Times and Outcomes
Authors: Leite Karina Fonseca de Souza , Andrade Rubia Laine de Paula , Faria Mariana Gaspar Botelho Funari de , Isaac Igor Simões da Silva , Ferreira Kamila Santos , Remigio Juan Lacalle , Camilo Millene Rodrigues , Neto Octavio Marques Pontes , Monroe Aline Aparecida
Published: January 2024

Background: Given the importance of acute stroke care for public health in terms of its burden and consequences like disability and death, evidence-based practice has directed the development of clinical protocols and operational guidelines to care of the populations affected by this pathology.

Aim: To evaluate the impact of implementing the stroke care line in the Urgency and Emergency Care Network of a large Brazilian municipality.

Methods: This is a retrospective study, conducted between 2014 and 2019 in public health services in Ribeirao Preto, SP, a large municipality of Brazil. Data was collected through secondary sources. A total of 403 patients were included in the study, of which: 172 were treated between 2014 and 2016 and 231 between 2017 and 2019; 118 were served by the mobile pre-hospital care services and 285 by the fixed pre-hospital care services. Data comprise clinical, epidemiological characteristics and severity of cases, as well as stroke care times and outcomes and were analyzed using descriptive techniques, Mann-Whitney and Chi-squared tests.

Results: First care provided by a mobile pre-hospital care unit increased from 16.9% to 38.5%. The service times for people undergoing thrombolysis were shorter in the period from 2017 to 2019 compared to 2014 to 2016 in the door-to-needle, stroke onset-to-call, stroke onset-to-ambulance dispatch and regulation-to-door times. Stroke victims treated first by a mobile (ambulance) unit had shorter care times when compared to those who received care in a fixed unit, except in ambulance dispatch-to-door time. No difference was identified in the percentage of outcomes studied in the period from 2017 to 2019 compared to the period from 2014 to 2016. There was a higher craniectomy occurrence in people treated at home than in those attended in health services. The percentage of unfavorable stroke outcomes increased depending on the case severity.

Conclusion: The care flow organization with defined responsibilities for each care point through the creation of a care line and the use of pre-established protocols reduced pre- and in-hospital care times; however, they did not have a significative influence on the case outcomes.
Mechanisms of stroke protection by physical activity
Authors: Endres Matthias , Gertz Karen , Lindauer Ute , Katchanov Juri , Schultze Jörg , Schröck Helmut , Nickenig Georg , Kuschinsky Wolfgang , Dirnagl Ulrich , Laufs Ulrich
Published: October 2003

Regular physical activity is associated with a decrease of cerebrovascular and cardiovascular events, which may relate to enhanced endothelium‐dependent vasodilation. Here, we provide evidence that physical activity protects against ischemic stroke via mechanisms related to the upregulation of endothelial nitric oxide synthase (eNOS) in the vasculature. Voluntary training on running wheels or exercise on a treadmill apparatus for 3 weeks, respectively, reduced cerebral infarct size and functional deficits, improved endothelium‐dependent vasorelaxation, and augmented cerebral blood flow in wild‐type mice. The neuroprotective effects of physical training were completely absent in eNOS‐deficient mice, indicating that the enhanced eNOS activity by physical training was the predominant mechanism by which this modality protects against cerebral injury. Our results suggest that physical activity not only decreases stroke risk, but also provides a prophylactic treatment strategy for increasing blood flow and reducing brain injury during cerebral ischemia.
On symptomatic heterozygous alpha‐sarcoglycan gene mutation carriers
Authors: Fischer Dirk , Aurino Stefania , Nigro Vincenzo , Schröder Rolf
Published: October 2003

Mutations in the human alpha‐sarcoglycan gene on chromosome 17q21.2 have been shown to cause a severe childhood autosomal recessive muscular dystrophy, a less severe limb girdle muscular dystrophy, exercise intolerance, or asymptomatic hyperCKemia. Here, we describe the clinical findings in a German family harboring a 371 T > C (Ile124Thr) missense mutation in the alpha‐sarcoglycan gene. Whereas our index patient, an 11‐year‐old girl homozygous for this mutation, presented with a severe Duchenne‐like phenotype, 7 out of 12 heterozygous mutation carriers from three generations showed mild to moderate scapular winging. In analogy to symptomatic female dystrophinopathy carriers, our results suggest that heterozygous alpha‐sarcoglycan gene mutation carriers can be symptomatic with selective muscle weakness. This finding may be attributed to an additional negative variation in a yet unknown modifier gene essential to the function of the sarcoglycan complex in shoulder girdle muscles.
Preliminary screening study of reproductive outcomes after exposure to yarrow in the pregnant rat
Authors: Boswell‐Ruys Claire L. , Ritchie Helen E. , Brown‐Woodman Patricia D.
Published: October 2003

BACKGROUND: Yarrow (Achillea millefolium) is used for the treatment of diarrhea, as a urinary antiseptic, hypotensive, and diuretic. Yarrow also has traditionally been used as an abortifacient, emmenagogue, contraceptive, and for stimulating uterine contractions. For this reason, it is contra‐indicated for use in pregnancy. There has, however, been little scientific research carried out to either confirm or refute this recommendation. METHODS: Female rats were dosed, orally by gavage using 56 times the human dose of yarrow daily on either gestation days (GD) 1–8 or GD 8–15. Two groups of controls were included; the first received water and the second received an equivalent dose of ethanol to that found in the yarrow preparation over the two gestation periods. On GD 20, rats were sacrificed, placentae were weighed, and corpora lutea counted. The fetuses were weighed and examined for signs of external, internal or skeletal malformations.RESULTS: The dose used was not materno‐toxic. There was no increase in pre‐ or post‐implantation losses suggesting that yarrow was neither an abortifacient nor a contraceptive. Placental weights were increased in rats treated with yarrow on GD 8–15 compared to water and ethanol controls and on GD 1–8 compared to water control fetuses. Body weight was reduced in fetuses exposed to yarrow on GD 8–15 compared to water control fetuses. There was no difference in incidence of external or internal malformations.CONCLUSIONS: In the present study it was found that yarrow, when administered to rats at 56 times the human dose, was associated with reduced fetal weight and increased placental weight. In the absence of a no observable effect level for these variables it must be concluded that the consumption of yarrow is contraindicated during pregnancy until further investigations have been carried out. Birth Defects Res B 68:416–420, 2003. © 2003 Wiley‐Liss, Inc.
Docetaxel and ketoconazole in advanced hormone‐refractory prostate carcinoma
Authors: Van Veldhuizen Peter J. , Reed Gregory , Aggarwal Arvind , Baranda Joaquina , Zulfiqar Muhammad , Williamson Stephen
Published: October 2003

BACKGROUND

Docetaxel has significant single‐agent activity in patients with prostate carcinoma, and ketoconazole has activity as a second‐line hormonal agent. In vitro, ketoconazole exhibits synergy with several chemotherapeutic agents. A potential drug interaction exists, however, because both docetaxel and ketoconazole are metabolized hepatically by the cytochrome p450 system (CYP3A4). The authors performed a Phase I study and a pharmacokinetic study evaluating the both tolerability of a docetaxel/ketoconazole combination as well as this potential drug interaction.

METHODS

For all initial patients, docetaxel was administered intravenously at a dose of 55 mg/m2 over 1 hour every 21 days. Starting on Day 8 after their first docetaxel dose, cohorts of at least 3–5 new patients were enrolled to receive escalating doses of ketoconazole. When the maximally tolerated dose (MTD) of ketoconazole was reached, the subsequent cohort of patients received an escalating dose of docetaxel. Pharmacokinetic studies were performed after docetaxel infusions on Day 1 (prior to ketoconazole) and Day 22 (after starting ketoconazole).

RESULTS

Twenty‐six patients were enrolled and completed at least 2 cycles of treatment. The MTD was ketoconazole 400 mg twice daily and docetaxel 55 mg/m2. Dose‐limiting toxicities included neutropenia and fatigue. Ketoconazole did not cause a consistent effect on docetaxel pharmacokinetics, although there was significant intrapatient and interpatient variability in serum levels.

CONCLUSIONS

The recommended Phase II dose for this combination is ketoconazole 400 mg twice daily and docetaxel 55 mg/m2 every 21 days. Cancer 2003. Published 2003 by the American Cancer Society.
The analysis of immunophenotype of gastrin‐producing tumors of the pancreas and gastrointestinal tract
Authors: Gurevich Larissa , Kazantseva Irina , Isakov Vassili A. , Korsakova Nina , Egorov Alexey , Kubishkin Valeriy , Bulgakov Gennadiy
Published: October 2003

BACKGROUND

Gastrinomas are located more frequently in the pancreas, which normally has no cells that can produce gastrin. They have a more aggressive course than other pancreatic endocrine tumors and extrapancreatic gastrinomas associated with multiple endocrine neoplasia Type 1 syndrome. The current study analyzed immunophenotypes of gastrinomas and compared them with other pancreatic endocrine tumors.

METHODS

Twenty‐one formalin‐fixed, paraffin‐embedded specimens (15‐tumors in the pancreas, 1 in the duodenum, 1 in the stomach, 1 in the liver, and 3 of unknown primary location) accompanied by Zollinger—Ellison syndrome and 17 other pancreatic endocrine tumor specimens were investigated. They were stained immunohistochemically for gastrin, chromogranin A, synaptophysin, insulin, glucagon, somatostatin, pancreatic polypeptide, calcitonin, serotonin, chorionic gonadotropin, adrenocorticotropic hormone, carcinoembryonic antigen, epithelial membrane antigen, and cytokeratin 19.

RESULTS

Gastrinomas coexpressed neuroendocrine and exocrine markers, including chromogranin A, synaptophysin, carcinoembryonic antigen, cytokeratin 19, and epithelial membrane antigen. Carcinoembryonic antigen was found in all 17 gastrinomas (100%), cytokeratin 19 was found in 15 of 17 (88.2%) gastrinomas, and epithelial membrane antigen was found in 16 of 18 (88.9 %) gastrinomas. Cytokeratin 19, epithelial membrane antigen, and carcinoembryonic antigen were not found to be present in the pancreatic endocrine tumors, but chromogranin A and synaptophysin were. Chorionic gonadotropin was found in 16 gastrinomas (100%), but only in 2 of 17 other pancreatic endocrine tumors (11.8 %).

CONCLUSIONS

Pancreatic gastrinomas were characterized by the coexpression of neuroendocrine markers, exocrine markers, and chorionic gonadotropin. Therefore, pancreatic gastrinomas made a special intermediate group of tumors, which phenotypically combined features of neuroendocrine and exocrine neoplasms. These findings suggested that sporadic pancreatic gastrinomas and other pancreatic endocrine tumors are different phenotypically and are possibly of different origin. Cancer 2003. © 2003 American Cancer Society.
Estimation of an optimal radiotherapy utilization rate for breast carcinoma
Authors: Delaney Geoff , Barton Michael , Jacob Susannah
Published: October 2003

BACKGROUND

Radiotherapy utilization rates for breast carcinoma vary widely, both within and between countries. Current estimates of the proportion of patients with carcinoma who optimally should receive radiotherapy are based either on expert opinion or on the measurement of actual utilization rates, and not on the best scientific evidence.

METHODS

To develop an evidence‐based benchmark for radiotherapy utilization in patients with breast carcinoma, the authors undertook a systematic review of treatment guidelines on the use of radiotherapy for breast carcinoma. A decision tree was constructed, and the proportions of patients with clinical features that lead to a decision for radiotherapy were obtained from epidemiological data. This ideal utilization rate was compared with the utilization rates of radiotherapy over the last decade for breast carcinoma in Australia and internationally.

RESULTS

The proportion of patients with breast carcinoma in whom radiotherapy would be recommended according to the best available evidence was calculated at 83% (95% confidence interval, 82–85%) of all patients with breast carcinoma. A review of actual radiotherapy utilization rates for breast carcinoma revealed that, in clinical practice, actual utilization rates varied between 24% and 71%.

CONCLUSIONS

A substantial difference was found between the recommended optimal utilization of radiotherapy based on evidence and the actual rates reported in clinical practice. The reasons for these differences need to be examined, and a plan for addressing the suboptimal use of radiotherapy needs to be implemented. Cancer 2003. © 2003 American Cancer Society.
Molecular genetic alterations in the laser‐capture–microdissected stroma adjacent to bladder carcinoma
Authors: Paterson Ryan F. , Ulbright Thomas M. , MacLennan Gregory T. , Zhang Shaobo , Pan Chong‐Xian , Sweeney Christopher J. , Moore Curtiss R. , Foster Richard S. , Koch Michael O. , Eble John N. , Cheng Liang
Published: October 2003

BACKGROUND

Urothelial carcinoma commonly manifested loss of heterozygosity (LOH) at different regions of chromosomes 17p, 3p, and 9q. Recent studies suggested that bladder stromal cells may be implicated in the growth and progression of urothelial carcinoma. To better understand the genetic alterations in the stromal cells in patients with bladder carcinoma, the authors evaluated the prevalence of allelic loss at three microsatellite polymorphic markers on chromosomes 17p13 (TP53), 3p25‐26 (D3S3050), and 9q32‐33 (D9S177). In addition, the pattern of X‐chromosome inactivation of the stromal cells was evaluated by analyzing the DNA methylation pattern at a polymorphic site on the androgen receptor gene.

METHODS

The authors studied 18 female patients who underwent either transurethral resection (n = 2) or radical cystectomy (n = 16) for high‐grade muscle‐invasive urothelial carcinoma of the urinary bladder. Genomic DNA samples from the stromal cells immediately adjacent to the tumor and the tumor itself were prepared from formalin‐fixed, paraffin‐processed tissues using laser‐assisted microdissection and LOH was determined.

RESULTS

The stromal cells showed a high frequency of LOH on chromosomes 17p13 (29%), 3p25‐26 (61%), and 9q32‐33 (47%) with no clear concordance with the adjacent tumor cells. Fourteen specimens (78%) showed LOH in the stroma in at least 1 of 3 markers examined. Nonrandom X‐chromosome inactivation was frequent in the stromal cells (50% of informative specimens).

CONCLUSIONS

The current study revealed that some of the genetic changes that commonly occur with invasive urothelial carcinoma were frequently found in the adjacent stroma and suggested that the stroma of urothelial carcinoma may play an important role in bladder carcinogenesis. Cancer 2003. © 2003 American Cancer Society.
A neurocomputational model for prostate carcinoma detection
Authors: Kalra Pankaj , Togami Joanna , Bansal B.S. Gaurav , Partin Alan W. , Brawer Michael K. , Babaian Richard J. , Ross Lawrence S. , Niederberger Craig S.
Published: October 2003

BACKGROUND

Current guidelines for prostate carcinoma screening rely primarily on the digital rectal examination (DRE) and prostate specific antigen (PSA). Well described patient risk factors for prostate carcinoma also include age, ethnicity, family history, and complexed PSA. However, due to the nonlinear relation of each of these variables with prostate carcinoma, it is difficult to predict reliably each patient's risk based on linear univariate analysis. The authors investigated a neural network to model the risk of prostate carcinoma by seven readily available clinical features.

METHODS

The database for the current study comprised 3268 men recently evaluated for the early detection of prostate carcinoma. The seven clinical features evaluated included age, race, family history, International Prostate Symptom Score (IPSS), DRE, and total and complexed PSA. Three hundred forty‐eight subjects in the dataset included men with determined prostate biopsy outcomes and for whom at least 6 of 7 features were available. The dataset was divided randomly into a training set (60%) and a test set (40%), with n1/n2 cross‐validation used to evaluate model accuracy, and was modeled with linear and quadratic discriminant function analysis and a neural computational system. After a model with acceptable goodness of fit was achieved, reverse regression analysis using Wilks's generalized likelihood ratio test was performed to evaluate the statistical significance of each input variable.

RESULTS

The receiving operating characteristic (ROC) area for the neural computational system in the test set was 0.825, whereas total PSA and complexed PSA alone had ROC areas of 0.678 and 0.697, respectively. The ROC area of logistic regression in the test set was 0.510, linear discriminant function analysis was 0.674, and quadratic discriminant function analysis was 0.011. All were significantly less than the ROC area of the neural computational model (all Ps < 0.002). Reverse regression based on Wilks's generalized likelihood ratio test demonstrated each input feature to be highly significant to the model (all Ps ≪ 0.000001).

CONCLUSIONS

The authors modeled a combination of well described patient risk factors for prostate carcinoma using a neural computational system with acceptable goodness of fit. They demonstrated that each of the seven variates on which the model was based was critically significant to model performance. The authors presented this model for clinical use and suggested that clinicians use it in deciding to perform prostate biopsy. Cancer 2003. © 2003 American Cancer Society.
Skull base and nonskull base chordomas
Authors: Naka Takahiko , Boltze Carsten , Samii Amir , Herold Christian , Ostertag Helmut , Iwamoto Yukihide , Oda Yoshinao , Tsuneyoshi Masazumi , Kuester Doerthe , Roessner Albert
Published: October 2003

BACKGROUND

To the authors' knowledge, little is known regarding the relation between the proliferative ability and clinicopathologic parameters in skull base chordomas (SBCs) and nonskull base chordomas (NSBCs).

METHODS

The authors investigated 122 conventional chordomas for their clinicopathologic parameters, proliferative ability (MIB‐1 labeling index [LI]) and clinical outcome.

RESULTS

Primary NSBCs were found to affect more elderly patients and demonstrated a higher MIB‐1 LI compared with primary SBCs. Mitosis was more commonly noted in recurrent NSBCs compared with primary NSBCs. Apoptosis was more frequent in elderly patients than in younger patients with regard to both SBCs and NSBCs. Apoptosis also was found to be correlated with necrosis in SBCs, suggesting a common factor for the two different types of cell death. Mucoid matrix was reported to be more abundant in NSBCs than in SBCs, and appeared to occur more often in elder NSBC patients compared with younger NSBC patients. This indicates that it is produced in the later stages of tumorigenesis. In SBCs, several clinicopathologic parameters were found to be correlated with MIB‐1 LI. Among them, increased age, recurrence, and nuclear pleomorphism were the only independent factors found to indicate a higher MIB‐1 LI. No such parameters were found in NSBCs. However, in these lesions, prognosis was significantly poorer in those cases with nuclear pleomorphism compared with those without.

CONCLUSIONS

The results of the current study suggest that nuclear pleomorphism is a prognostic indicator in NSBCs. The proliferative ability of SBCs appears to be closely associated with patient age, clinical status (recurrence), and nuclear pleomorphism. Cancer 2003. © 2003 American Cancer Society.
Extracellular inorganic phosphate regulates Gibbon ape leukemia virus receptor‐2/phosphate transporter mRNA expression in rat bone marrow stromal cells
Authors: Wada Keinoshin , Mizuno Morimichi , Komori Takahide , Tamura Masato
Published: October 2003

In mammalian cells, several observations indicate not only that phosphate transport probably regulates local inorganic phosphate (Pi) concentration, but also that Pi affects normal cellular metabolism, which in turn regulates apoptosis and the process of mineralization. To elucidate how extracellular Pi regulates cellular functions of pre‐osteoblastic cells, we investigated the expression of type III sodium (Na)‐dependent Pi transporters in rat bone marrow stromal cells and ROB‐C26 pre‐osteoblastic cells. The mRNA expression level of gibbon ape leukemia virus receptor (Glvr)‐2 was increased by the addition of Pi in rat bone marrow stromal cells, but not in ROB‐C26 or normal rat kidney (NRK) cells. In contrast, the level of Glvr‐1 mRNA was not altered by the addition of extracellular Pi in these cells. The induction of Glvr‐2 mRNA by Pi was inhibited in the presence of cycloheximide (CHX). Moreover, mitogen‐activated protein kinase (MEK) /extracellular‐signal‐regulated kinase (ERK) pathway inhibitors; U0126 (1.4‐diamino‐2, 3‐dicyano‐1, 4‐bis [2‐amino‐phenylthio] butadiene) and PD98059 (2′‐Amino‐3′‐methoxyflavone) inhibited inducible Glvr‐2 mRNA expression, but p38 MEK inhibitor SB203580 [4‐(4′‐fluorophenyl)‐2‐(4′‐methyl‐sulfinylphenyl)‐5‐(4′pyridyl) imidazole] did not inhibit the induction of Glvr‐2 mRNA expression, suggesting that extracellular Pi regulates de novo protein synthesis and MEK/ERK activity in rat bone marrow stromal cells, and through these, induction of Glvr‐2 mRNA. Although Pi also induced osteopontin mRNA expression in rat bone marrow stromal cells but not in ROB‐C26 and NRK cells, changes in cell viability with the addition of Pi were similar in both cell types. These data indicate that extracellular Pi regulates Glvr‐2 mRNA expression, provide insights into possible mechanisms whereby Pi may regulate protein phosphorylation, and suggest a potential role for the Pi transporter in rat bone marrow stromal cells. J. Cell. Physiol. 198: 40–47, 2004. © 2003 Wiley‐Liss, Inc.
Critical protein domains and amino acid residues for gating the KIR6.2 channel by intracellular ATP
Authors: Wu Jianping , Piao Hailan , Rojas Asheebo , Wang Runping , Wang Ying , Cui Ningren , Shi Yun , Chen Fuxue , Jiang Chun
Published: October 2003

KATP channels couple intermediary metabolism to cellular excitability. Such a property relies on the inherent ATP‐sensing mechanism known to be located in the Kir6 subunit. However, the molecular basis for the ATP sensitivity remains unclear. Here we showed evidence for protein domains and amino acid residues essential for the channel gating by intracellular ATP. Chimerical channels were constructed using protein domains of Kir6.2 and Kir1.1, expressed in HEK293 cells, and studied in inside‐out patches. The N and C termini, although important, were inadequate for channel gating by intracellular ATP. Full ATP sensitivity also required M1 and M2 helices. Cytosolic portions of the M1 and M2 sequences were crucial, in which six amino acid residues were identified, i.e., Thr76, Met77, Ala161, Iso162, Leu164, and Cys166. Site‐specific mutation of any of them reduced the ATP sensitivity. Construction of these residues together with the N/C termini produced ATP sensitivity identical to the wild‐type channels. The requirement for specific membrane helices suggests that the Kir6.2 gating by ATP is not shared by even two closest relatives in the K+ channel family, although the general gating mechanisms involving membrane helices appear to be conserved in all K+ channels. J. Cell. Physiol. 198: 73–81, 2004. © 2003 Wiley‐Liss, Inc.
EGF mediates protection against Fas‐induced apoptosis by depleting and oxidizing intracellular GSH stocks
Authors: Musallam Lina , Éthier Chantal , Haddad Pierre Selim , Bilodeau Marc
Published: October 2003

Several pieces of evidence have demonstrated the importance of reduction/oxidation (redox) signaling in biological processes, including sensitivity toward apoptosis. In parallel, it was recently reported that growth factors induce the generation of reactive oxygen species (ROS). Therefore, we tested the hypothesis that the anti‐apoptotic effect of epidermal growth factor (EGF) was mediated by changes in the redox state of hepatocytes through changes in GSH stocks. Isolated mouse hepatocytes were cultured and exposed to anti‐Fas stimulation in order to induce apoptosis. Cell death by apoptosis was assessed by Hoechst 33258 staining and by measuring caspase‐3 proteolysis activity. Cell treatment with EGF significantly decreased total (GSx) and reduced (GSH) glutathione levels in the presence and the absence of anti‐Fas. Furthermore, glutathione reductase activity was lower in EGF‐treated cultures (by 28%) as compared to untreated cultures which lead to a significant decline in GSH/GSx ratio. These effects were found to be EGF‐receptor tyrosine kinase activity dependent. Co‐stimulation of cells with anti‐Fas and EGF attenuated caspase‐3 activation and cell death by apoptosis by 70%. GSH monoethylester (GSHmee) significantly attenuated the effect of EGF on GSH and GSH/GSx ratio. It caused an increase in caspase‐3 activation and in the percentage of apoptotic cells in anti‐Fas + EGF‐treated cells, thus resulting in a 53% decline in the protective effect of EGF. In conclusion, EGF induces a significant and specific depletion and oxidization of intracellular GSH, paralleled by a protection against Fas‐induced apoptosis. GSH replenishment partly counteracted these effects suggesting that GSH depletion contributed to the protective effect of EGF against caspase‐3 activation and cell death by apoptosis. J. Cell. Physiol. 198: 62–72, 2004. © 2003 Wiley‐Liss, Inc.
Elevated interleukin‐9 receptor expression and response to interleukins‐9 and ‐7 in thymocytes during radiation‐induced T‐cell lymphomagenesis in B6C3F1 mice
Authors: Nishimura Mayumi , Kakinuma Shizuko , Yamamoto Daisuke , Kobayashi Yoshiro , Suzuki Gen , Sado Toshihiko , Shimada Yoshiya
Published: October 2003

Dysregulation of cytokine receptor expression and responsiveness to cytokines is hypothesized to play an important role in the development and expansion of preneoplastic cells or progression of neoplastic cells during the early and late stages of leukemogenesis. To determine the crucial changes in initiated cells that confer significant growth during the early stage of radiation‐induced lymphomagenesis, we examined both the expression of receptors for thymus‐derived cytokines and thymocyte response to cytokines before the onset of T cell lymphomas in B6C3F1 mice after split‐dose irradiation. After irradiation, thymic T cell subsets underwent delayed regeneration consisting of two phases as determined by receptor expression. The first phase occurred within 1 week post‐irradiation and was accompanied by transient expansion of T cell subsets strongly expressing receptor genes for IL‐1, IL‐2, IL‐6, IL‐7, IL‐15, and TNFα. The second phase occurred 12 weeks after irradiation and was characterized by increased expression of IL‐9Rα. Thymocytes from non‐irradiated control mice were unresponsive to IL‐9. However, IL‐9 acted synergistically with IL‐7 and PHA to stimulate the proliferation of irradiated cells during the second post‐irradiation phase. Moreover, these cells showed hyper‐responsiveness to IL‐7 or PHA alone compared to age‐matched non‐irradiated control thymocytes. These results suggest that the unusual expression of IL‐9 receptors and/or increased responsiveness of thymocytes to cytokines are key processes in the development of radiation‐induced T cell lymphomas. J. Cell. Physiol. 198: 82–90, 2004. © 2003 Wiley‐Liss, Inc.
Gonadotropin and steroid hormones stimulate proliferation of the rat ovarian surface epithelium
Authors: Stewart Sherri L. , Querec Troy D. , Gruver Briana N. , O'Hare Brendan , Babb James S. , Patriotis Christos
Published: October 2003

The ovarian surface epithelium (OSE) is a single layer of flattened or cuboidal cells covering the ovary. Ninety percent of all human ovarian malignancies arise from this layer of cells. Incessant ovulation, hyperovulation induced by infertility treatment, and hormone replacement therapy have been suggested as risk factors for ovarian cancer. In this study, two groups of rats, with and without surgically induced injury to the ovary, were treated with 17β‐estradiol, pregnant mare's serum gonadotropin (PMSG), human chorionic gonadotropin (hCG), or the combination PMSG/hCG, and the proliferative response of the OSE cells was measured using bromodeoxyuridne (BrdU) and 3H‐thymidine. All hormones, alone or in combination with ovarian surgery, were found to increase significantly the rate of proliferation of the rat OSE. These data demonstrate that hormones associated with infertility treatments and hormone replacement therapy, as well as injury‐ or ovulation‐induced rupture of the ovarian surface, stimulate the rat OSE, and hence could have a role in the development of ovarian cancer via proliferation‐associated mutagenesis, or alternatively, by promoting the rapid selection of OSE cells with accumulated mutations. J. Cell. Physiol. 198: 119–124, 2004. © 2003 Wiley‐Liss, Inc.
Anatomy of the crocodilian spinal vein
Authors: Zippel Kevin C. , Lillywhite Harvey B. , Mladinich Christopher R.J.
Published: October 2003

The crocodilian spinal vein is remarkably robust yet historically overlooked. Using corrosion casting, we describe the anatomy of this vessel and its connections with the caval and hepatic venous systems in representatives from four crocodilian genera. The spinal vein arises from an enlarged occipital sinus over the medulla and extends the entire length of the vertebral column. Unlike in squamate reptiles, the spinal vein is single (nonplexiform), voluminous, and situated dorsal to the spinal cord, and plexi lateral to the cord span between emerging intercostal veins. The connections with the other venous systems are otherwise similar to those in other tetrapods. The overall anatomy of this vessel and its abundant connections with the other venous systems indicate it likely plays a primary role in returning blood to the heart from all parts of the body. Preliminary studies of function suggest that this vessel could also play an adaptive role during basking and diving. J. Morphol. 258:327–335, 2003. © 2003 Wiley‐Liss, Inc.
Mechanisms of internalization of apoptotic and necrotic L929 cells by a macrophage cell line studied by electron microscopy
Authors: Krysko Dmitri V. , Brouckaert Greet , Kalai Michael , Vandenabeele Peter , D'Herde Katharina
Published: October 2003

Rapid and efficient phagocytic removal of dying cells is a key feature of apoptosis. In necrotic caspase‐independent modes of death, the role and extent of phagocytosis is not well documented. To address this issue, we studied at the ultrastructural level the phagocytic response to dying cells in an in vitro phagocytosis assay with a mouse macrophage cell line (Mf4/4). As target cells, murine L929sAhFas cells were induced to die by TNFR1‐mediated necrosis or by Fas‐mediated apoptosis. Apoptotic L929sAhFas cells are taken up by complete engulfment of apoptotic bodies as single entities forming a tight‐fitting phagosome, thus resembling the “zipper”‐like mechanism of internalization. In contrast, primary and secondary necrotic cells were internalized by a macropinocytotic mechanism with formation of multiple ruffles by the ingesting macrophage. Ingestion of necrotic cellular material was invariably taking place after the integrity of the cell membrane was lost and did not occur as discrete particles, in contrast to apoptotic material that is surrounded by an intact membrane. Although nuclei of necrotic cells have been observed in the vicinity of macrophages, no uptake of necrotic nuclei was observed. The present report provides a basis for future studies aimed at discovering molecular pathways that precede these diverse mechanisms of uptake. J. Morphol. 258:336–345, 2003. © 2003 Wiley‐Liss, Inc.
Conversations about the moon with prospective teachers in Japan
Authors: Suzuki Mariko
Published: October 2003

As an instructor in courses for prospective teachers, I am interested in my students' ideas and ways in which they reconstruct their ideas in conversations about science. In the case study presented here, I reflect upon (a) ways in which I engaged prospective teachers in thinking together about their observations of a natural phenomenon, the changing phases of the moon, and (b) the ideas that they expressed. The case study examines ways in which prospective teachers developed understandings of the sun–earth–moon system from two perspectives: as viewed from the earth and from outside the solar system. © 2003 Wiley Periodicals, Inc.Sci Ed87:892–910, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.10082
From universal system of social policy to particularistic? The case of the Baltic States
Authors: Aidukaite Jolanta
Published: October 2003

This paper compares the system of social maintenance and insurance in the Soviet Union, which was in force in the three Baltic countries before their independence, with the currently existing social security systems. The aim of the paper is to highlight the forces that have influenced social policy transformation from its former highly universal, however authoritarian form, to the less universal, social insurance-based systems of present day Lithuania, Latvia and Estonia.

It will be demonstrated that the welfare–economy nexus is not the only important factor in the development of social programs. Rather, social policy should be studied as if embedded in the political, historical and cultural aspects of a given society. The people’s attitude towards distributive justice will be highlighted as being one of the most important factors for either social policy shortcomings or expansion.

This paper takes steps to combine quantitative and qualitative data.
Credit card rates and consumer search
Authors: Berlin Mitchell , Mester Loretta J.
Published: October 2003

Credit card rates have tended to be higher and stickier than other loan rates but have fallen over the past decade. Some argue this decline is due to a reduction in consumer search costs. Our evidence suggests search costs are not the best explanation for the decline. We test whether consumer search models explained credit card pricing in the 1980s when search costs were thought to be significant. We find that the distributions of rates were inconsistent with those derived from many models of search. Proposals for stricter disclosure requirements may have less effect on equilibrium credit card rates than intended.
Relationship between intramolecular hydrogen bonding and solvent accessibility of side‐chain donors and acceptors in proteins
Authors: Efimov Alexander V , Brazhnikov Evgenii V
Published: October 2003

This study shows that intramolecular hydrogen bonding in proteins depends on the accessibility of donors and acceptors to water molecules. The frequency of occurrence of H‐bonded side chains in proteins is inversely proportional to the solvent accessibility of their donors and acceptors. Estimates of the notional free energy of hydrogen bonding suggest that intramolecular hydrogen‐bonding interactions of buried and half‐buried donors and acceptors can contribute favorably to the stability of a protein, whereas those of solvent‐exposed polar atoms become less favorable or unfavorable.
Selectivity and conductance among the glycerol and water conducting aquaporin family of channels
Authors: Stroud Robert M. , Savage David , Miercke Larry J.W. , Lee John K. , Khademi Shahram , Harries William
Published: October 2003

The atomic structures of a transmembrane water plus glycerol conducting channel (GlpF), and now of aquaporin Z (AqpZ) from the same species, Escherichia coli, bring the total to three atomic resolution structures in the aquaporin (AQP) family. Members of the AQP family each assemble as tetramers of four channels. Common helical axes support a wider channel in the glycerol plus water channel paradigm, GlpF. Water molecules form a single hydrogen bonded file throughout the 28 Å long channel in AqpZ. The basis for absolute exclusion of proton or hydronium ion conductance through the line of water is explored using simulations.
Extracellular alkalosis activates ERK mitogen‐activated protein kinase of vascular smooth muscle cells through NADPH‐mediated formation of reactive oxygen species
Authors: Susa Shinji , Wakabayashi Ichiro
Published: October 2003

Extracellular alkalosis induced phosphorylation of extracellular signal‐regulated kinase (ERK) and enhanced serum‐induced ERK phosphorylation in cultured rat aortic smooth muscle cells. While extracellular alkalinization increased verapamil‐sensitive 45Ca2+ uptake into the cells, ERK phosphorylation induced by extracellular alkalosis was not affected by verapamil. On the other hand, probes for oxidant signaling, such as superoxide dismutase, 4,5‐dihydroxy‐1,3‐benzene‐disulfonic acid, a cell‐permeable antioxidant, and diphenyliodonium, a NADPH oxidase inhibitor, inhibited extracellular alkalosis‐induced phosphorylation of ERK. These results suggest that activation of ERK induced by extracellular alkalosis is not dependent on transplasmalemmal Ca2+ entry but is caused by reactive oxygen species derived from an activation of NADPH oxidase.