bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a highly metastatic model that reveals a crucial role of fibronectin in lung cancer cell migration and invasion
Authors: Jia Deshui , Yan Mingxia , Wang Xiaomin , Hao Xiangfang , Liang Linhui , Liu Lei , Kong Hanwei , He Xianghuo , Li Jinjun , Yao Ming 
Published: July 2010

AbstractBackgroundThe formation of metastasis is the most common cause of death in patients with lung cancer. A major implement to understand the molecular mechanisms involved in lung cancer metastasis has been the lack of suitable models to address it. In this study, we aimed at establishing a highly metastatic model of human lung cancer and characterizing its metastatic properties and underlying mechanisms.MethodsThe human lung adeno-carcinoma SPC-A-1 cell line was used as parental cells for developing of highly metastatic cells byin vivoselection in NOD/SCID mice. After three rounds of selection, a new SPC-A-1sci cell line was established from pulmonary metastatic lesions. Subsequently, the metastatic properties of this cell line were analyzed, including optical imaging ofin vivometastasis, immunofluorescence and immunohistochemical analysis of several epithelial mesenchymal transition (EMT) makers and trans-well migration and invasion assays. Finally, the functional roles of fibronectin in the invasive and metastatic potentials of SPC-A-1sci cells were determined by shRNA analysis.ResultsA spontaneously pulmonary metastatic model of human lung adeno-carcinoma was established in NOD/SCID mice, from which a new lung cancer cell line, designated SPC-A-1sci, was isolated. Initially, the highly metastatic behavior of this cell line was validated by optical imaging in mice models. Further analyses showed that this cell line exhibit phenotypic and molecular alterations consistent with EMT. Compared with its parent cell line SPC-A-1, SPC-A-1sci was more aggressivein vitro, including increased potentials for cell spreading, migration and invasion. Importantly, fibronectin, a mesenchymal maker of EMT, was found to be highly expressed in SPC-A-1sci cells and down-regulation of it can decrease thein vitroandin vivometastatic abilities of this cell line.ConclusionsWe have successfully established a new human lung cancer cell line with highly metastatic potentials, which is subject to EMT and possibly mediated by increased fibronectin expression. This cell line and its reproducibles.c. mouse model can further be used to identify underlying mechanisms of lung cancer metastasis.
Association of the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio and concentrations of plasma lipids with high-density lipoprotein subclass distribution in the Chinese population
Authors: Tian Li , Liu Yinghui , Qin Yang , Long Shiyin , Xu Yanhua , Fu Mingde 
Published: July 2010

Abstract

Background
To evaluate the relationship between the low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio and HDL subclass distribution and to further examine and discuss the potential impact of LDL-C and HDL-C together with TG on HDL subclass metabolism.

Results
Small-sized preβ1-HDL, HDL3b and HDL3a increased significantly while large-sized HDL2a and HDL2b decreased significantly as the LDL-C/HDL-C ratio increased. The subjects in low HDL-C level (< 1.03 mmol/L) who had an elevation of the LDL-C/HDL-C ratio and a reduction of HDL2b/preβ1-HDL regardless of an undesirable or high LDL-C level. At desirable LDL-C levels (< 3.34 mmol/L), the HDL2b/preβ1-HDL ratio was 5.4 for the subjects with a high HDL-C concentration (≥ 1.55 mmol/L); however, at high LDL-C levels (≥ 3.36 mmol/L), the ratio of LDL-C/HDL-C was 2.8 in subjects, and an extremely low HDL2b/preβ1-HDL value although with high HDL-C concentration.

Conclusion
With increase of the LDL-C/HDL-C ratio, there was a general shift toward smaller-sized HDL particles, which implied that the maturation process of HDL was blocked. High HDL-C concentrations can regulate the HDL subclass distribution at desirable and borderline LDL-C levels but cannot counteract the influence of high LDL-C levels on HDL subclass distribution.
Copy number variation of the SELENBP1 gene in schizophrenia
Authors: Amar Shirly , Ovadia Ofer , Maier Wolfgang , Ebstein Richard , Belmaker RH , Mishmar Dan , Agam Galila 
Published: July 2010

Abstract

Background
Schizophrenia is associated with rare copy-number (CN) mutations. Screening for such alleles genome-wide, though comprehensive, cannot study in-depth the causality of particular loci, therefore cannot provide the functional interpretation for the disease etiology. We hypothesized that CN mutations in the SELENBP1 locus could associate with the disorder and that these mutations could alter the gene product's activity in patients.

Methods
We analyzed SELENBP1 CN variation (CNV) in blood DNA from 49 schizophrenia patients and 49 controls (cohort A). Since CN of genes may vary among tissues, we investigated SELENBP1 CN in age- sex- and postmortem interval-matched cerebellar DNA samples from 14 patients and 14 controls (cohort B). Since CNV may either be de-novo or inherited we analyzed CNV of the SELENBP1 locus in blood DNA from 26 trios of schizophrenia probands and their healthy parents (cohort C). SELENBP1 mRNA levels were measured by real-time PCR.

Results
In cohort A reduced CN of the SELENBP1 locus was found in four patients but in none of the controls. In cohort B we found reduced CN of the SELENBP1 locus in two patients but in none of the controls. In cohort C three patients exhibited drastic CN reduction, not present in their parents, indicating de-novo mutation. A reduction in SELENBP1 mRNA levels in the postmortem cerebellar samples of schizophrenia patients was found.

Conclusions
We report a focused study of CN mutations in the selenium binding-protein1 (SELENBP1) locus previously linked with schizophrenia. We provide evidence for recurrence of decreased CN of the SELENBP1 locus in three unrelated patients' cohorts but not in controls, raising the possibility of functional involvement of these mutations in the etiology of the disease.
SHIP2, a factor associated with diet-induced obesity and insulin sensitivity, attenuates FGF signaling in vivo
Authors: Jurynec Michael J. , Grunwald David Jonah 
Published: July 2010

SUMMARYSH2-domain-containing inositol phosphatase 2 (SHIP2) belongs to a small family of phosphoinositide 5-phosphatases that help terminate intracellular signaling initiated by activated receptor tyrosine kinases. Mammalian SHIP2 is viewed primarily as an attenuator of insulin signaling and has become a prominent candidate target for therapeutic agents that are designed to augment insulin signaling. Despite this view, no signaling pathway has yet been demonstrated as being affected directly by SHIP2 function in vivo, and in vitro studies indicate that the protein may function in multiple signaling pathways. Here, we analyze the role of a SHIP2 family member in the early zebrafish embryo where developmental and gene expression defects can be used to assay specific signaling pathways. The zebrafish ship2a transcript is maternally supplied, and inhibiting the expression of its protein product results in the expansion of dorsal tissue fates at the expense of ventral ones. We show that the developmental defects are the result of perturbation of fibroblast growth factor (FGF) signaling in the early embryo. Loss of Ship2a leads to an increased and expanded expression of outputs of FGF-mediated signaling, including FGF-dependent gene expression and activated mitogen-activated protein kinase (MAPK) signaling. Our findings demonstrate that Ship2a attenuates the FGF signaling pathway in vivo and functions in the establishment of normal tissue patterning in the early embryo. We suggest that modulation of FGF signaling may be a principal function of SHIP2 in mammals.
Rgs16 and Rgs8 in embryonic endocrine pancreas and mouse models of diabetes
Authors: Villasenor Alethia , Wang Zhao V. , Rivera Lee B. , Ocal Ozhan , Asterholm Ingrid Wernstedt , Scherer Philipp E. , Brekken Rolf A. , Cleaver Ondine , Wilkie Thomas M. 
Published: July 2010

SUMMARYDiabetes is characterized by the loss, or gradual dysfunction, of insulin-producing pancreatic β-cells. Although β-cells can replicate in younger adults, the available diabetes therapies do not specifically target β-cell regeneration. Novel approaches are needed to discover new therapeutics and to understand the contributions of endocrine progenitors and β-cell regeneration during islet expansion. Here, we show that the regulators of G protein signaling Rgs16 and Rgs8 are expressed in pancreatic progenitor and endocrine cells during development, then extinguished in adults, but reactivated in models of both type 1 and type 2 diabetes. Exendin-4, a glucagon-like peptide 1 (Glp-1)/incretin mimetic that stimulates β-cell expansion, insulin secretion and normalization of blood glucose levels in diabetics, also promoted re-expression of Rgs16::GFP within a few days in pancreatic ductal-associated cells and islet β-cells. These findings show that Rgs16::GFP and Rgs8::GFP are novel and early reporters of G protein-coupled receptor (GPCR)-stimulated β-cell expansion after therapeutic treatment and in diabetes models. Rgs16 and Rgs8 are likely to control aspects of islet progenitor cell activation, differentiation and β-cell expansion in embryos and metabolically stressed adults.
Staged carotid endarterectomy under local anaesthetic in patients requiring cardiac surgery
Authors: Birchley David , Villaquiran Jaime , Akowuah Enoch , Lewis Terence , Ashley Simon 
Published: July 2010

INTRODUCTION There is no clear guidance as to the management of carotid stenotic disease prior to cardiac surgery. We aimed to review the results of a single centre performing carotid endarterectomy (CEA) under local anaesthesia prior to cardiac surgery. PATIENTS AND METHODS All patients referred for cardiac surgery in our tertiary referral unit between January 1998 and August 2008 were identified and data relating to those 100 undergoing CEA prior to cardiac surgery were reviewed. Eighty had coronary artery bypass grafting (CABG) alone, 15 combined valve surgery and CABG and three underwent isolated valve surgery. Two patients died prior to cardiac surgery. RESULTS One hundred patients were prospectively identified after screening by clinical features and carotid duplex scanning to require CEA from a total of 11,394. The stroke rate was 1% between CEA and cardiac surgery, 2% following cardiac surgery and 3% in total. Ninety-eight patients proceeded to cardiac surgery (two deaths post-CEA). The cumulative event rate (stroke, myocardial infarct [included in view of the nature of the patients in our cohort] and/or death) was 10.2% following all cardiac surgery (CABG and valve). In 80 patients undergoing CABG only, the cumulative event rate was 7.5% after CABG. Including the two deaths pre-cardiac surgery, the rates were 12% and 8%. The risk of peri-operative stroke and 30-day mortality were reduced to that of patients undergoing cardiac surgery without significant carotid arterial disease, 3% versus 3.3% and 5.1% versus 6.5%, respectively. CONCLUSIONS This study demonstrates that a policy of selective screening for significant carotid artery disease in cardiac surgical patients combined with a strategy of CEA under local anaesthesia prior to unselected cardiac surgery (CABG with or without valve surgery) leads to rates of peri-operative CVA, myocardial infarction and death comparable to rates published for CEA prior to isolated CABG surgery. Furthermore, it reduces the risk of peri-operative stroke and 30-day mortality to that observed in patients undergoing cardiac surgery without significant carotid arterial disease.
Leucocyte count and oral temperature are a useful guide to selecting women with right iliac fossa pain for diagnostic laparoscopy
Authors: Singh-Ranger D , Ogadegbe A 
Published: July 2010

INTRODUCTION In women, negative appendicectomy rates can be as high as 34%. A 5-fold reduction is possible with diagnostic laparoscopy. A selective policy is favoured as indiscriminate use may increase postoperative morbidity. Scoring systems are helpful but not used widely du to their complexity. The value of leucocyte count and temperature in selecting women with right iliac fossa pain for diagnostic laparoscopy is investigated. PATIENTS AND METHODS Over a 12-month period, admission leucocyte count and temperature data were obtained from women undergoing appendicectomy. Cohorts were sub-categorised by age (< 20, 21–40 and > 40 years) and the proportion of negative (normal appendix) and positive (inflamed, gangrenous or perforated appendix) appendicectomies compared. RESULTS In 100 women, 11% had leucocyte counts and temperature ≥ 11 × 109/l and 38°C, respectively; all had appendicitis. In 50%, leucocyte counts and temperature were ≥ 11 × 109/l and < 38°C; negative appendicectomies occurred in 13.8% < 20 years, 10% > 40 years (P < 0.01) and 27.3% aged 21–40 years (P = 0.086). In 39%, the negative appendicectomy rate was ≥ 36.8% when leucocyte count and temperature were < 11 × 109/l and 38°C (P = 0.1). CONCLUSION Diagnostic laparoscopy should be considered in all women when leucocyte counts and temperature are ≥ 11 × 109/l and 38°C and for females aged 21–40 years when these values are ≥ 11 × 109/l and < 38°C.
High incidence of absent nerve conduction in older patients with bilateral carpal tunnel syndrome
Authors: Povlsen BO 
Published: July 2010

INTRODUCTION Carpal tunnel syndrome has been reported by some to have a less satisfactory outcome in older patients following surgery. However, this impression is not supported by other investigators but no objective explanation has been suggested for these differences. In our department, such patients are routinely treated with night wrist splints and, if this is unsatisfactory, they are investigated with nerve conduction studies prior to surgery. PATIENTS AND METHODS This paper reports the neurophysiological outcome in a young (< 40 years of age) and an older (> 60 years of age) group of patients with clinical bilateral carpal tunnel syndrome who did not benefit from splints. RESULTS The results showed that both the motor and sensory conduction speeds are significantly lower in the older age group. More importantly in the older group, half had one or more hands where the sensory conduction was absent. In four out of these 10 patients this finding was bilateral and three patients had unilateral absent motor conduction. In the younger group, no patient had absent conduction. CONCLUSIONS Poor surgical outcome in some older patients may be because of irreversibly damaged nerves prior to surgery and pre-operative neurophysiology is, therefore, recommended both for clinical and medicolegal reasons.
Amputation and the assessment of limb viability: perceptions of two hundred and thirty two orthopaedic trainees
Authors: Eardley WGP , Taylor DM , Parker PJ 
Published: July 2010

INTRODUCTION The management of complex extremity injury, which may require assessment of limb viability and performance of amputation, is a challenge to those involved in its emergent and definitive care. Concern exists regarding the exposure of orthopaedic trainees to such cases due both to changes in training and centralisation of trauma services. SUBJECTS AND METHODS This is a web-based observational study by survey, investigating the confidence and perceived adequacy of training of UK orthopaedic specialist trainees in the assessment of limb viability and amputation surgery. 222 responses from 888 trainees were required to achieve a < 5% error rate with 90% confidence; 232 surveys were completed. RESULTS Trainee confidence in dealing with the assessment of limb viability is high despite infrequent exposure to cases. The majority of trainees perceive their training in limb viability assessment as adequate. For performance of amputation, exposure is minimal, confidence is lower and 36% of trainees regard their training as inadequate. CONCLUSIONS Limb viability assessment is an area in which trainees feel confident and well trained. There is, however, a perceived training inadequacy in amputation surgery and a corresponding lack of confidence for many trainees, irrespective of training year. This is the first study to offer an insight into specific training experiences of junior orthopaedic surgeons at a national level and it should drive the development of opportunities for trainees to develop skills in amputation surgery.
Does the two-week rule pathway improve the diagnosis of soft tissue sarcoma? A retrospective review of referral patterns and outcomes over five years in a regional sarcoma centre
Authors: Pencavel Tim D , Strauss Dirk C , Thomas Greg P , Thomas J Meirion , Hayes Andrew J 
Published: July 2010

INTRODUCTION The NHS Cancer Plan was introduced in 2000 and included guidelines for the rapid assessment and referral of cases of suspected malignancy. We wished to assess the efficiency and appropriateness of patients referred under the Department of Health's general practitioner referral guidelines implemented for sarcomas in December 2000. PATIENTS AND METHODS A retrospective case-note review was performed of all patients referred to our regional soft tissue sarcoma unit between 1 January 2004 and 31 December 2008. Patients referred under the two-week guidelines and all patients referred routinely were analysed. The main outcome measures were the total number of patients referred on the basis of the two-week guidelines and the proportion they constitute of all referrals. The referring criteria were noted and compared to the observed criteria recorded. The final histo-logical diagnosis of patients referred on the basis of the two-week guidelines are documented. RESULTS A total of 2746 referrals for suspected sarcoma were made from January 2004 to December 2008. Of these, 154 referrals were made under the two-week rule of which 102 were referred purely on the clinical criteria for suspected soft tissue sarcoma. The remaining patients were referred after non-urgent special investigations indicated the possibility of sarcoma. Twelve patients referred under the two-week rule were proved to have sarcoma, nine after specific investigations including imaging or histological diagnosis. Of the 102 patients referred on clinical suspicion of a sarcoma, two patients had proven soft tissue sarcomas and one patient a cutaneous sarcoma. Between 2004 and 2008, the number of 2-week referrals rose 25-fold but accounted for an increase of less than 1% of the sarcomas treated in this unit. CONCLUSIONS The numbers of all referrals for suspected sarcoma are increasing; however, the rate of increase of 2-week referrals is increasing faster than routine referrals and will exceed it in 2012 if current trends continue. There has not been a commensurate rise in the detection of sarcoma or, more specifically, diagnosis of the deep sarcomas associated with worse prognosis. Current clinical guidelines have essentially had no impact on the early diagnosis and treatment of soft tissue sarcoma, and may negatively impact on the treatment of patients with proven sarcoma by delaying treatment within a regional centre because of redirection of a large number of patients with benign abnormalities to such centres.
The diagnosis and management of femoro-acetabular impingement
Authors: Macfarlane Robert J , Haddad Fares S 
Published: July 2010

INTRODUCTION Femoro-acetabular impingement (FAI) was first described in 1999 as abnormal abutment between the acetab-ulum and the femoral head and neck. Since then, it has been shown to be responsible for many acetabular labral tears and is implicated in the aetiology of osteoarthritis of the hip. This review introduces the concept of FAI and reports the key aspects of its diagnosis and management. MATERIALS AND METHODS A comprehensive search of the literature was conducted using the Pubmed database. Articles relating to the aetiology, pathophysiology, clinical features, diagnosis and treatment of FAI were reviewed. Search terms included femoro-acetabular impingement, arthroscopic treatment, open treatment, aetiology, pathophysiology. The search was limited to articles published in English. All articles were read in full by the authors and selected for inclusion based on relevance to the article. RESULTS An increasing number of studies relating to FAI have been produced in the 10 years since its recognition. A range of clinical and radiological features have been described. Surgical management can be performed using a number of techniques, with promising results from various studies. Early treatment with open surgery has paved the way for less invasive and arthroscopic approaches, with short-to-medium term data demonstrating favourable functional results for arthroscopic treatment of FAI. CONCLUSIONS A greater awareness of the diagnostic features of FAI, and the various management options available, will allow timely diagnosis and treatment of a relatively newly recognised syndrome. Early treatment may then help to prevent progression to end-stage osteoarthritis of the hip.
Splenic torsion: a case report
Authors: Hussain M , Deshpande R , Bailey STR 
Published: July 2010

Introduction Torsion of the spleen is a rare cause of abdominal pain. Predisposition occurs following abnormal development of splenic suspensory ligaments. We report a case of splenic torsion in a spleen sited in a normal anatomical position and discuss the latest treatment options. To the best of our knowledge, this has not been reported in the literature to date. Case Presentation A 73-year-old Caucasian woman presented to our department with sudden onset, severe, left-upper abdominal pain. An enhanced computed tomography revealed an unenhancing spleen. She underwent an urgent laparotomy and splenectomy for 360° torsion of her spleen. Conclusions Splenic torsion in a wandering spleen has been described with an incidence of < 0.2%. Symptoms vary from asymptomatic to an acute surgical abdomen. Diagnosis is commonly made using colour Doppler sonography or enhanced computed tomography. Surgery is guided by clinical setting, with preservation of the spleen as the goal.
Upregulation of CDKN2A and suppression of cyclin D1 gene expressions in ACTH-secreting pituitary adenomas
Authors: Tani Yuji , Inoshita Naoko , Sugiyama Toru , Kato Masako , Yamada Shozo , Shichiri Masayoshi , Hirata Yukio 
Published: July 2010

ObjectiveCushing's disease (CD) is usually caused by ACTH-secreting pituitary microadenomas, while silent corticotroph adenomas (SCA) are macroadenomas without Cushingoid features. However, the molecular mechanism(s) underlying their different tumor growth remains unknown. The aim of the current study was to evaluate and compare the gene expression profile of cell cycle regulators and cell growth-related transcription factors in CD, SCA, and non-functioning adenomas (NFA).Design and methodsTumor tissue specimens resected from 43 pituitary tumors were studied: CD (n=10), SCA (n=11), and NFA (n=22). The absolute transcript numbers of the following genes were quantified with real-time quantitative PCR assays: CDKN2A (or p16INK4a), cyclin family (A1, B1, D1, and E1), E2F1, RB1, BUB1, BUBR1, ETS1, and ETS2. Protein expressions of p16 and cyclin D1 were semi-quantitatively evaluated by immunohistochemical study.Results and conclusionCDKN2A gene expression was about fourfold greater in CD than in SCA and NFA. The gene expressions of cyclins D1, E1, and B1, but not of A1, in CD were significantly suppressed than those in NFA. Cyclin D1 gene expression positively correlated with cyclins B1 and E1. The gene expressions of E2F1, RB1, BUB1, BUBR1, ETS1, and ETS2 did not differ between each group. Positive immunostaining for p16 and negative immunostaining for cyclin D1 were more frequent in CD than in NFA; there were positive correlations between mRNA and protein expressions of p16 and cyclin D1. Thus, it is suggested that upregulated CDKN2A with the concomitant downregulated cyclin gene family is partly involved in the small size of ACTH-secreting adenoma.