bluuebunny/crossref_metadata_2025_split huggingface dataset:
The C‐terminal domain of focal adhesion kinase reduces the tumor cell invasiveness in chondrosarcoma cell lines
Authors: Lee Jin Woo , Kim Yun Hee , Park Hee Boong , Xu Li‐Hui , Cance William G. , Block Joel A. , Scully Sean P. 
Published: May 2003

AbstractHuman chondrosarcoma is a malignancy that has no effective systemic therapy, making the interruption of the metastatic cascade critical to enhance patient survival. The processes of local invasion and metastases share similar mechanisms at a cellular level. Focal adhesion kinase (FAK) has been implicated in local invasion of malignant tumor cells. In the current manuscript we examine the effect of FAK inhibition on cell attachment to extracellular matrix (ECM) and in vitro invasion. Bovine articular chondrocytes and two human chondrosarcoma cell lines were utilized to examine FAK activity in tumor cell invasiveness. Endogenous FAK activity was inhibited by adenoviral transfection with the C‐terminal domain of FAK. This inhibition resulted from decreased FAK phosphorylation, while FAK expression remained unchanged. Inhibition of FAK phosphorylation and hence its activity lead to decreased cell adhesion to Type II collagen and decreased cell invasiveness. These effects were not due to changes in integrin expression, indicating that the inhibition was the result of disruption of outside: in signaling. There are three important aspects to these results. The first is that interruption of transmembrane signaling can affect cell attachment. The second is that in chondrosarcoma, cell differentiation correlates with FAK expression and metastatic potential. Thirdly, that cell invasiveness correlates with FAK activity and implies a mechanistic role for this molecular complex in local invasion and metastasis. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Relationship of demethylation processes to veratric acid concentration and cell density in cultures of Rhodococcus erythropolis
Authors: Paździoch‐Czochra Marzanna , Malarczyk Elżbieta , Sielewiesiuk Jan 
Published: June 2003

AbstractThe aim of this study was to investigate the correlation between veratrate degradation, veratric acid concentration and cell density in Rhodococcus erythropolis cultures. The optimum culture conditions for veratrate demethylation proved to be a cell density of A
660=1 and a concentration of 0.02% veratrate. All the products of demethylation (i.e. vanillic and protocatechuic acids) were found to be present and correlated with the appearance of high levels of free radicals and formaldehyde after contact of the cells with veratrate. Demethylation was accompanied by oscillatory changes in the levels of endogenous oxygen uptake and phenolic products. Changes in veratrate concentration and cell density caused a disturbance in the demethylation process and also in the efficiency of phenolics, formaldehyde and reactive oxygen species.
Runx transcription factors and the developmental balance between cell proliferation and differentiation
Authors: Coffman James A. 
Published: June 2003

AbstractThe runt box (Runx) is a highly conserved DNA binding and protein—protein interaction domain that defines a family of heterodimeric transcription factors with essential roles in metazoan development. The first member of this family to be identified was the Drosophila regulatory gene runt, which was named by virtue of its function in establishing segmentation patterns during embryogenesis, and subsequently discovered to have additional functions in sex determination and neurogenesis. A second Drosophila Runx gene, lozenge, is required for cell patterning in the eye and for hematopoiesis. The genome project has revealed the existence of two additional Drosophila Runx genes, which to date have not been functionally characterized. Other invertebrate species with well‐characterized Runx transcription factors include the nematode Caenorhabditis elegans and the sea urchin Strongylocentrotus purpuratus, each of which apparently contains only a single Runx gene.There are three Runx genes in mammals; Runx1 is required for definitive hematopoiesis and is a frequently mutated gene in human leukemia, Runx2 is required for osteogenesis and is associated with cleidocranial dysplasia, and Runx3 controls neurogenesis in the dorsal root ganglia and cell proliferation in the gastric epithelium, and is frequently deleted or silenced in human gastric cancer. Studies using mammalian systems and sea urchins indicate that Runx proteins have essential functions in both cell proliferation and differentiation, and in mammals they are both proto‐oncogenes and tumor suppressors. Thus, a central question concerning the cell biology of Runx proteins is how are the opposing functions of this class of transcription factors regulated during development? Here I review current knowledge of Runx protein structure, function and regulation, and outline directions for future research aimed at understanding how Runx protein function is modulated during the transition from cell proliferation to differentiation in animal development.
Treatment‐latency and previous episodes: relationships to pretreatment morbidity and response to maintenance treatment in bipolar I and II disorders
Authors: Baldessarini Ross J , Tondo Leonardo , Hennen John 
Published: May 2003

Objective: To clarify relationships of treatment delay and pretreatment episode count with pretreatment morbidity and responses to maintenance treatments in bipolar disorders.Methods: In 450 DSM‐IV bipolar I (n = 293) or II (n = 157) patients (280 women, 170 men), we evaluated correlations of latency from illness‐onset to starting maintenance treatment and pretreatment episode counts with pretreatment morbidity and treatment response. We considered morbidity measures before and during treatment, and their differences.Results: Latency averaged 7.8 years, with 9.0 episodes per patient, before various maintenance treatments started. Morbidity (percentage of time‐ill, episodes per year, first wellness‐interval, or proportion of subjects hospitalized or having no recurrences) during maintenance treatment averaging 4.2 years was unrelated to treatment latency or pretreatment episode count. However, pretreatment morbidity was greater with shorter latency, resulting in larger relative reduction of morbidity after earlier treatment.Conclusions: Greater treatment latency and pretreatment episode count were not followed by greater morbidity during treatment, although longer delay yielded smaller during‐versus‐before treatment reduction in morbidity. Predictions that longer treatment delay or more pretreatment episodes lead to poorer responses to various maintenance treatments in bipolar I or II disorder were not supported.
One‐week triple therapy with esomeprazole, clarithromycin and metronidazole provides effective eradication of Helicobacter pylori infection
Authors: Veldhuyzen Van Zanten S. , Machado S. , Lee J. 
Published: June 2003

SummaryAim: To compare the eradication rates of treatment with esomeprazole, metronidazole and clarithromycin (EMC) vs. omeprazole, metronidazole and clarithromycin (OMC), given for 7 days. OMC treatment was followed by 3 weeks of treatment with 20 mg omeprazole alone; the EMC group received placebo.Methods: A randomized, double‐blind, controlled study was conducted in 36 Canadian centres. Patients had a minimum 3‐month history of dyspepsia, with or without a previous history of peptic ulcer disease, and were Helicobacter pylori positive by urea breath test. The eradication of H. pylori was determined by two negative breath tests performed at least 4 and 8 weeks following the completion of treatment.Results: The intention‐to‐treat and per protocol populations consisted of 379 and 339 patients, respectively. The success rates of EMC/placebo were 76% (144/190) by intention‐to‐treat and 80% (138/172) by per protocol analysis; for OMC/omeprazole, the rates were 72% (137/189) and 75% (125/167), respectively. The difference between the two treatment groups was not significant. Treatment was well tolerated.Conclusions: A 7‐day regimen of esomeprazole, metronidazole and clarithromycin is effective and well tolerated for the eradication of H. pylori infection.
Review article: the treatment of refractory Helicobacter pylori infection
Authors: Mégraud F. , Lamouliatte H. 
Published: June 2003

SummaryThe occurrence of refractory Helicobacter pylori infection is increasing. When the bacteria are not eradicated it means that the antibiotics have not reached the gastric mucosa at a sufficient concentration and over a sufficient time lapse to kill them. The main reasons for this are poor patient compliance, resistant bacteria, low gastric pH and a high bacterial load. Therefore, when administering a new treatment, it is important to choose antibiotics which do not face resistance problems and which increase the dosage of antisecretory drugs and the duration of treatment and, if possible, to add a topical agent such as bismuth salt.The recommended empirical strategy is to prescribe quadruple therapy or, alternatively, 2‐week triple therapy including amoxicillin–metronidazole, tetracycline–metronidazole or amoxicillin–rifabutin. However, when H. pylori is susceptible, clarithromycin can still be used. In the case of a high level of metronidazole resistance, furazolidone can be employed. In each case, it is important to ensure good patient compliance, and counselling is helpful in this regard. However, the best approach remains the prevention of refractory H. pylori infection and, for this purpose, antimicrobial susceptibility testing before first‐line therapy is important and should be encouraged.
Impact of structural and autocyclic basin‐floor topography on the depositional evolution of the deep‐water Valparaiso forearc basin, central Chile
Authors: Laursen Jane , Normark William R. 
Published: May 2003

AbstractThe Valparaiso Basin constitutes a unique and prominent deep‐water forearc basin underlying a 40‐km by 60‐km mid‐slope terrace at 2.5‐km water depth on the central Chile margin. Seismic‐reflection data, collected as part of the CONDOR investigation, image a 3–3.5‐km thick sediment succession that fills a smoothly sagged, margin‐parallel, elongated trough at the base of the upper slope. In response to underthrusting of the Juan Fernández Ridge on the Nazca plate, the basin fill is increasingly deformed in the seaward direction above seaward‐vergent outer forearc compressional highs. Syn‐depositional growth of a large margin‐parallel monoclinal high in conjunction with sagging of the inner trough of the basin created stratal geometries similar to those observed in forearc basins bordered by large accretionary prisms. Margin‐parallel compressional ridges diverted turbidity currents along the basin axis and exerted a direct control on sediment depositional processes. As structural depressions became buried, transverse input from point sources on the adjacent upper slope formed complex fan systems with sediment waves characterising the overbank environment, common on many Pleistocene turbidite systems. Mass failure as a result of local topographic inversion formed a prominent mass‐flow deposit, and ultimately resulted in canyon formation and hence a new focused point source feeding the basin.The Valparaiso Basin is presently filled to the spill point of the outer forearc highs, causing headward erosion of incipient canyons into the basin fill and allowing bypass of sediment to the Chile Trench. Age estimates that are constrained by subduction‐related syn‐depositional deformation of the upper 700–800 m of the basin fill suggest that glacio‐eustatic sea‐level lowstands, in conjunction with accelerated denudation rates, within the past 350 ka may have contributed to the increase in simultaneously active point sources along the upper slope as well as an increased complexity of proximal depositional facies.
Bone mineral density outcomes following long‐term treatment with subcutaneous testosterone pellet implants in male hypogonadism
Authors: Zacharin Margaret R. , Pua Joseph , Kanumakala Shankar 
Published: June 2003

Summarybackground Osteoporosis is a common complication of untreated male hypogonadism. Even mild hypogonadism due to suboptimal testosterone replacement may result in decreased bone mineralization and osteoporosis.objective To assess bone mineral density in hypogonadal men following long‐term long‐acting subcutaneous testosterone pellet implants as replacement therapy.patients A cross‐sectional study of 37 patients with primary or secondary hypogonadism receiving long‐term (mean 6·6 years) subcutaneous testosterone pellet implants as replacement therapy.measurements Bone mineral density was measured in all patients using dual energy X‐ray absorptiometry. Serum testosterone 3–4 months after insertion of pellets was measured in all patients to assess adequacy of replacement therapy.results Mean areal bone mineral density were 1·02 (SD 0·14) g/cm2 with a mean Z score of −0·64 (SD 1·3) and 0·87 (SD 0·13) g/cm2 with a mean Z score of −0·72 (SD 1·2) at lumbar spine and neck of femur, respectively. Mean serum testosterone 3–4 months after pellets insertion was 15·45 nmol/l (SD 4·2 nmol/l). There was no significant correlation between bone mineral density and patient's age at start or duration of testosterone therapy.conclusions Bone mineral density in long‐term regularly treated hypogonadal men was not different from the age‐matched reference range for normal men. Long‐acting subcutaneous testosterone pellet implants as replacement therapy in male hypogonadism are safe, acceptable to the patient, result in adequate bone mass accumulation and maintenance of normal bone mineral density. By provision of sustained physiological levels of testosterone they may contribute to increased androgen effect at the receptor level.
Hereditary corticosteroid‐binding globulin deficiency due to a missense mutation (Asp367Asn, CBG Lyon) in a Brazilian kindred
Authors: Brunner Elisa , Baima Jader , Vieira Teresa C. , Vieira José G. H. , Abucham Julio 
Published: June 2003

Summaryobjective Abnormal corticosteroid‐binding globulin (CBG) is an extremely rare condition and only three mutations have been described in four families. The molecular basis of an abnormal CBG in a Brazilian family was studied and correlations between genotype and serum cortisol, cortisol binding capacity (CBC) and CBG levels were determined.subjects All 10 family members, comprising three generations, and nine healthy volunteers were studied.measurements Genomic DNA was extracted from white blood cells from all family members. The human cbg exons 2–5 were amplified by PCR, submitted to automatic sequencing. Cortisol and CBG levels in serum were measured by radioimmunoassay (RIA). CBC in serum was determined using tritiated cortisol and other cortisol binding parameters were calculated through Scatchard analysis.results A missense mutation in exon 5 of cbg (1254G → A; Asp367Asn), recently described as CBG Lyon, was found in all family members. The proband and one sister were homozygous whereas all other family members, including parents, were heterozygous for this mutation. Cortisol levels in the only two homozygotes were lower than in heterozygotes and both were significantly lower as compared to controls (69 and 182 nmol/l vs. 267 ± 129 nmol/l vs. 459 ± 195 nmol/l, respectively, P < 0·05). CBC was decreased in the two homozygotes as compared to heterozygotes and in both groups as compared to controls (< 90 and 114 nmol/l vs. 305·0 ± 81·4 nmol/l vs. 594·8 ± 59·5 nmol/l, respectively, P < 0·05). CBG levels were lower in homozygotes as compared to heterozygotes and in both as compared to controls (325 and 375 nmol/l vs. 496·75 ± 50·75 nmol/l vs. 647·25 ± 87·50 nmol/l, respectively, P < 0·05).conclusions An abnormal CBG resulting from a missense mutation and known as CBG Lyon was found in this Brazilian kindred. This abnormal CBG has decreased affinity for cortisol and results in low or low normal serum cortisol levels in homozygous and heterozygous subjects. Although relative hypotension and fatigue have recently been associated with CBG deficiency in a family with two CBG mutations (null and Lyon), the two homozygous subjects in this kindred were both normotensive and only the proband presented with fatigue.
Perturbations in adiponectin, leptin and resistin levels in acromegaly: lack of correlation with insulin resistance
Authors: Silha Josef V. , Krsek Michal , Hana Vaclav , Marek Josef , Jezkova Jana , Weiss Vladimir , Murphy Liam J. 
Published: June 2003

Summarybackground Insulin resistance, impaired glucose tolerance and type 2 diabetes are common in acromegalic subjects. The mechanism underlying this insulin resistance is unclear.design We investigated the levels of the adipocytokines, resistin, adiponectin and leptin in a group of 18 acromegalic subjects and 18 control subjects matched for age, gender and body mass index.results Here we demonstrate for the first time significant elevation in adiponectin levels in acromegalic subjects compared to control subjects 12·5 ± 1·2 vs. 8·97 ± 1·1 mg/l, P = 0·029. The resistin levels were similar in acromegalic subjects and controls; 20·65 ± 2·99 vs. 19·03 ± 4·72 µg/l. No evidence of a correlation between adiponectin and insulin resistance as calculated from HOMA‐R was found. No correlation was observed either between adiponectin or resistin levels and GH levels, total IGF‐I or free IGF‐I levels. Leptin levels were significantly reduced in acromegalic subjects, 8·22 ± 2·26 vs. 18·3 ± 4·1 µg/l, P = 0·004. In control subjects, significant correlations between leptin levels and HOMA‐R and between resistin levels and HOMA‐R were observed. These relationships were not apparent in acromegalic subjects.conclusion From these data we conclude that changes in resistin and adiponectin levels are unlikely to account for the insulin resistance of acromegaly.
Short‐term effects of prednisolone and dexamethasone on circulating concentrations of leptin and sex hormone‐binding globulin in children being treated for acute lymphoblastic leukaemia
Authors: Wallace A. M. , Tucker P. , Williams D. M. , Hughes I. A. , Ahmed S. F. 
Published: June 2003

Summaryobjective Disturbances in body weight regulation are often encountered during glucocorticoid treatment and are associated with increased insulin resistance and truncal fat accumulation. Children were investigated who were receiving glucocorticoid treatment for acute lymphoblastic leukaemia (ALL). They were randomized to receive either prednisolone or dexamethasone as part of induction of remission. This randomization process provided a suitable opportunity to compare the effects of these two administered steroid on surrogate markers of adipocyte activity (leptin) and hyperinsulinaemia/insulin resistance (SHBG).design and patients Prospective study over 16 weeks of children randomized to receive prednisolone (40 mg/m2) or dexamethasone (6·5 mg/m2) as part of the MRC‐ALL97/99 induction chemotherapy for ALL. Nineteen children (8 male, 11 female) with a median age 5·9 years (range 2·6–13 years) were recruited into the study. Main outcome measures were body mass index (BMI), serum leptin and sex hormone binding globulin (SHBG).results Glucocorticoid administration for 5 weeks resulted in significant (P < 0·05) increases in BMI, leptin (corrected for BMI) and the leptin : SHBG ratio and lowering of SHBG. Dose for dose, dexamethasone was significantly more potent than prednisolone in altering these parameters.conclusions Short‐term glucocorticoid treatment has significant effects on BMI, leptin and SHBG. The leptin : SHBG ratio increase indicates that this may be a novel and sensitive biochemical marker of metabolic change. Our results suggest that glucocorticoid treatment regimens should be kept as short as possible to avoid possible detrimental effects associated with increased adiposity and insulin resistance.
Mothers' involvement in caring for their premature infants: an historical overview
Authors: Davis Leigh , Mohay Heather , Edwards Helen 
Published: June 2003

Background. Advances in technology have resulted in increasing survival rates even for extremely premature infants. While sophisticated medical management is vital to infant survival, research has found that social factors and care giving processes are important predictors of infants' later outcome. Consequently, evidence is accumulating to demonstrate the fundamental role of mothers and families to the optimal developmental outcome of premature infants. Aim. The aim of the work reported here was to undertake an historical overview of premature infant care practices to increase neonatal nurse's knowledge of the crucial role of mothers and families in the care of their premature infants. Understanding past practice and current trends can provide neonatal nurses with critical insight which will assist in formulating current and future care. Method. Research and historical articles focusing on maternal involvement in preterm infant care from the development of the incubator to the present time were examined. A search of the literature between 1960 and 2002 was conducted using the MEDLINE, CINAHL and PSYCLIT databases. The search terms were premature infant, neonatal intensive care, history, and maternal care. Findings. Three major themes were identified which reflect the development of neonatal care. Firstly, over the last century advances in medical and public health practice saw a decline in mortality rates for mothers and infants. Secondly, the application of this new knowledge resulted in the institutionalization and professionalization of obstetric and neonatal care which, in turn, resulted in the isolation of infants from their mothers. Finally, concurrent advances in infant research emphasized the importance of mother–infant relationships to infants' developmental outcome, resulting in greater flexibility in hospital practices regarding parental contact with their infants. Conclusion. As biomedical advances in technology continue to help smaller, sicker premature infants to survive, neonatal nurses are strategically placed to promote positive outcomes for infants and their families through the integration of social science and behavioural research into nursing practice.
Identifying cancer nursing research priorities using the Delphi technique
Authors: Mcilfatrick Sonja J. , Keeney Sinaed 
Published: June 2003

Background. Nursing research is an integral component of improving the care of people with cancer. However, for research to be successfully integrated and applied to practice, ownership and identification must come from those in practice. The need for local and national strategies for cancer nursing research and the importance of establishing priorities for cancer nursing research have been repeatedly acknowledged. Study aim. The aim of the study was to facilitate a strategic approach to cancer nursing research by identifying the research priorities of cancer nurses. Research method. A three‐round Delphi survey was administered to nurses (n = 112) attending a cancer nursing research conference in Northern Ireland. Participants were asked to identify five research questions that they considered a high priority for cancer nursing. A response rate of 54% (60 delegates) was obtained for round one and this generated 117 statements. These statements were content analysed. Two subsequent quantitative rounds followed this. Results. The top priority areas identified were psychosocial issues, for example communication and information needs; professional issues relating to nurse burnout, stress and nurse‐led care; and context of care issues including continuity of care. Limitations. A potential limitation of the study is the use of conference delegates. However, it is argued that these are the people we wanted to target as they could be considered as experts who already had an interest and clinical background in both cancer research and practice. Conclusion. These priorities have helped to provide both direction and focus for the development of a cancer nursing research strategy for Northern Ireland. It is recommended that future research questions should be focused around the highest ranked priorities.