bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colorectal carcinomas with microsatellite instability display a different pattern of target gene mutations according to large bowel site of origin
Authors: Pinheiro Manuela , Ahlquist Terje , Danielsen Stine A , Lind Guro E , Veiga Isabel , Pinto Carla , Costa Vera , Afonso Luís , Sousa Olga , Fragoso Maria , Santos Lúcio , Henrique Rui , Lopes Paula , Lopes Carlos , Lothe Ragnhild A , Teixeira Manuel R 
Published: November 2010

Abstract

Background
Only a few studies have addressed the molecular pathways specifically involved in carcinogenesis of the distal colon and rectum. We aimed to identify potential differences among genetic alterations in distal colon and rectal carcinomas as compared to cancers arising elsewhere in the large bowel.

Methods
Constitutional and tumor DNA from a test series of 37 patients with rectal and 25 patients with sigmoid carcinomas, previously analyzed for microsatellite instability (MSI), was studied for BAX, IGF2R, TGFBR2, MSH3, and MSH6 microsatellite sequence alterations, BRAF and KRAS mutations, and MLH1 promoter methylation. The findings were then compared with those of an independent validation series consisting of 36 MSI-H carcinomas with origin from each of the large bowel regions. Immunohistochemical and germline mutation analyses of the mismatch repair system were performed when appropriate.

Results
In the test series, IGFR2 and BAX mutations were present in one and two out of the six distal MSI-H carcinomas, respectively, and no mutations were detected in TGFBR2, MSH3, and MSH6. We confirmed these findings in the validation series, with TGFBR2 and MSH3 microsatellite mutations occurring less frequently in MSI-H rectal and sigmoid carcinomas than in MSI-H colon carcinomas elsewhere (P = 0.00005 and P = 0.0000005, respectively, when considering all MSI-carcinomas of both series). No MLH1 promoter methylation was observed in the MSI-H rectal and sigmoid carcinomas of both series, as compared to 53% found in MSI-H carcinomas from other locations (P = 0.004). KRAS and BRAF mutational frequencies were 19% and 43% in proximal carcinomas and 25% and 17% in rectal/sigmoid carcinomas, respectively.

Conclusion
The mechanism and the pattern of genetic changes driving MSI-H carcinogenesis in distal colon and rectum appears to differ from that occurring elsewhere in the colon and further investigation is warranted both in patients with sporadic or hereditary disease.
Neck dissection and post-operative chemotherapy with dimethyl triazeno imidazole carboxamide and cisplatin protocol are useful for oral mucosal melanoma
Authors: Yang Xi , Ren Guo-xin , Zhang Chen-ping , Zhou Guo-yu , Hu Yong-jie , Yang Wen-jun , Guo Wei , Li Jiang , Zhong Lai-ping 
Published: November 2010

Abstract

Background
Oral mucosal melanoma (OMM) is a clinically rare disease with poor prognosis. Various treatment methods have been investigated with the aim of improving the prognosis. This study aimed to analyze the data of a single institution in the management of OMM.

Methods
A total of 78 consecutive OMM patients were included in this retrospective study. The intraoral lesion was treated either by cryotherapy, surgery or both; the neck was treated by neck dissection or observation; post-operative chemotherapy with dimethyl triazeno imidazole carboxamide and cisplatin was performed in some patients. The Kaplan-Meier method was used for statistical analysis.

Results
Among the 78 patients, there were 50 males and 28 females with an average age of 53.8 years (ranging from 27 to 85 years). The most common sites of OMM were the hard palate and gingiva. The main cause of death in OMM was distant metastasis. No significant difference was found between the intraoral/cervical lesion recurrence/post-operative distant metastasis and the intraoral lesion site/biopsy method/treatment method. The metastasis rate of cervical lymph node was high in the OMM patients, even in the patients with clinically negative necks. Cervical lesion recurrence was correlated with N stage and intraoral lesion recurrence. The survival period was longer in the patients with T3 staging, clinical stage III disease, with post-operative chemotherapy and without post-operative distant metastasis when compared to those patients with T4a staging, clinical stage IV disease, without post-operative chemotherapy and with post-operative distant metastasis.

Conclusions
Radical surgery including wide intraoral resection and neck dissection is recommended for OMM patients. Post-operative chemotherapy may also be beneficial for both primary and recurrent OMM patients.
Soluble ephrin a1 is necessary for the growth of HeLa and SK-BR3 cells
Authors: Alford Spencer , Watson-Hurthig Adam , Scott Nadia , Carette Amanda , Lorimer Heather , Bazowski Jessa , Howard Perry L 
Published: November 2010

AbstractBackgroundEphrin A1 (EFNA1) is a member of the A-type ephrin family of cell surface proteins that function as ligands for the A-type Eph receptor tyrosine kinase family. In malignancy, the precise role of EFNA1 and its preferred receptor, EPHA2, is controversial. Several studies have found that EFNA1 may suppress EPHA2-mediated oncogenesis, or enhance it, depending on cell type and context. However, little is known about the conditions that influence whether EFNA1 promotes or suppresses tumorigenicity. EFNA1 exists in a soluble form as well as a glycophosphatidylinositol (GPI) membrane attached form. We investigated whether the contradictory roles of EFNA1 in malignancy might in part be related to the existence of both soluble and membrane attached forms of EFNA1 and potential differences in the manner in which they interact with EPHA2.ResultsUsing a RNAi strategy to reduce the expression of endogenous EFNA1 and EPHA2, we found that both EFNA1 and EPHA2 are required for growth of HeLa and SK-BR3 cells. The growth defects could be rescued by conditioned media from cells overexpressing soluble EFNA1. Interestingly, we found that overexpression of the membrane attached form of EFNA1 suppresses growth of HeLa cells in 3D but not 2D. Knockdown of endogenous EFNA1, or overexpression of full-length EFNA1, resulted in relocalization of EPHA2 from the cell surface to sites of cell-cell contact. Overexpression of soluble EFNA1 however resulted in more EPHA2 distributed on the cell surface, away from cell-cell contacts, and promoted the growth of HeLa cells.ConclusionsWe conclude that soluble EFNA1 is necessary for the transformation of HeLa and SK-BR3 cells and participates in the relocalization of EPHA2 away from sites of cell-cell contact during transformation.
Supernumerary, ectopic tooth in the maxillary antrum presenting with recurrent haemoptysis
Authors: Saleem Taimur , Khalid Umair , Hameed Anam , Ghaffar Shehzad 
Published: November 2010

Abstract

Background
Ectopic eruption of teeth in non-dental sites is a rare phenomenon and can present in a variety of ways such as chronic or recurrent sinusitis, sepsis, nasolacrimal duct obstruction, headaches, ostiomeatal complex disease and facial numbness. However, presentation of such patients with recurrent haemoptysis has not been described in the literature so far. We have described a case of an ectopic, supernumerary molar tooth in the maxillary antrum in a patient who initially presented with haemoptysis.

Case presentation
A 45-year-old male presented with a 2-month history of episodic haemoptysis. A pedunculated growth from the inferior nasal turbinate was seen with fibre-optic visualization. Although the patient was empirically started on antibiotic and anti-allergic therapy, there was no improvement after a few weeks and the patient had recurrent episodes of haemoptysis. Fibre-optic visualization was repeated showing bilateral osteomeatal erythema. Computed tomography scan of the paranasal sinuses demonstrated complete opacification of the left maxillary antrum along with a focal area of density comparable to bone. An ectopic, supernumerary molar tooth was found in the left maxillary antrum on endoscopic examination and subsequently removed. In addition, copious purulent discharge was seen. Post-operatively, the patient was treated with a 10-day course of oral amoxicillin-clavulanate. On follow-up, he reported resolution of symptoms.

Conclusion
Recurrent haemoptysis has not been described as a presentation for a supernumerary, ectopic tooth in literature before. We recommend that in patients with sinusitis-type of opacification of maxillary antrum and whose condition is refractory to conventional medical treatment, consideration should be given to the investigation of possible underlying anomalies as the cause of such symptoms. Presence of foreign bodies and ectopic teeth in paranasal sinuses can be reliably excluded with the use of appropriate radiological imaging and endoscopic examination.
Targeting the hotspots: investigating spatial and demographic variations in HIV infection in small communities in South Africa
Authors: Wand Handan , Ramjee Gita 
Published: November 2010

BackgroundIn South Africa, the severity of the HIV/AIDS epidemic varies according to geographical location; hence, localized monitoring of the epidemic would enable more effective prevention strategies. Our objectives were to assess the core areas of HIV infection in KwaZulu‐Natal, South Africa, using epidemiological data among sexually active women from localized communities.MethodsA total of 5753 women from urban, peri‐rural and rural communities in KwaZulu‐Natal were screened from 2002 to 2005. Each participant was geocoded using a global information system, based on residence at time of screening. The Spatial Scan Statistics programme was used to identify areas with disproportionate excesses in HIV prevalence and incidence.ResultsThis study identified three hotspots with excessively high HIV prevalence rates of 56%, 51% and 39%. A total of 458 sexually active women (19% of all cases) were included in these hotspots, and had been exclusively recruited by the Botha's Hill (west of Durban) and Umkomaas (south of Durban) clinic sites. Most of these women were Christian and Zulu‐speaking. They were also less likely to be married than women outside these areas (12% vs. 16%, p = 0.001) and more likely to have sex more than three times a week (27% vs. 20%, p < 0.001) and to have had more than three sexual partners (55% vs. 45%, p < 0.001). Diagnosis of genital herpes simplex virus type 2 was also more common in the hotspots. This study also identified areas of high HIV incidence, which were broadly consistent with those with high prevalence rates.ConclusionsGeographic excesses of HIV infections at rates among the highest in the world were detected in certain rural communities of Durban, South Africa. The results reinforce the inference that risk of HIV infection is associated with definable geographical areas. Localized monitoring of the epidemic is therefore essential for more effective prevention strategies ‐ and particularly urgent in a region such as KwaZulu‐Natal, where the epidemic is particularly rampant.
Regulation of Placental Growth by Aldosterone and Cortisol
Authors: Gennari-Moser Carine , Khankin Eliyahu V. , Schüller Simone , Escher Geneviève , Frey Brigitte M. , Portmann C.-Bettina , Baumann Marc U. , Lehmann Andrea D. , Surbek Daniel , Karumanchi S. Ananth , Frey Felix J. , Mohaupt Markus G. 
Published: November 2010

AbstractDuring pregnancy, trophoblasts grow to adapt the feto-maternal unit to fetal requirements. Aldosterone and cortisol levels increase, the latter being inactivated by a healthy placenta. By contrast, preeclamptic placental growth is reduced while aldosterone levels are low and placental cortisol tissue levels are high due to improper deactivation. Aldosterone acts as a growth factor in many tissues, whereas cortisol inhibits growth. We hypothesized that in preeclampsia low aldosterone and enhanced cortisol availability might mutually affect placental growth and function. Proliferation of cultured human trophoblasts was time- and dose-dependently increased with aldosterone (P &lt; 0.04 to P &lt; 0.0001) and inhibited by spironolactone and glucocorticoids (P &lt; 0.01). Mineralo- and glucocorticoid receptor expression and activation upon agonist stimulation was verified by visualization of nuclear translocation of the receptors. Functional aldosterone deficiency simulated in pregnant mice by spironolactone treatment (15 μg/g body weight/day) led to a reduced fetal umbilical blood flow (P &lt; 0.05). In rat (P &lt; 0.05; R2 = 0.2055) and human (X2 = 3.85; P = 0.0249) pregnancy, placental size was positively related to plasma aldosterone. Autocrine production of these steroid hormones was excluded functionally and via the absence of specific enzymatic transcripts for CYP11B2 and CYP11B1. In conclusion, activation of mineralocorticoid receptors by maternal aldosterone appears to be required for trophoblast growth and a normal feto-placental function. Thus, low aldosterone levels and enhanced cortisol availability may be one explanation for the reduced placental size in preeclampsia and related disorders.
A Treasure Trove of Hypothalamic Neurocircuitries Governing Body Weight Homeostasis
Authors: Vianna Claudia R. , Coppari Roberto 
Published: November 2010

Abstract
Changes in physical activities and feeding habits have transformed the historically rare disease of obesity into a modern metabolic pandemic. Obesity occurs when energy intake exceeds energy expenditure over time. This energy imbalance significantly increases the risk for cardiovascular disease and type 2 diabetes mellitus and as such represents an enormous socioeconomic burden and health threat. To combat obesity, a better understanding of the molecular mechanisms and neurocircuitries underlying normal body weight homeostasis is required. In the 1940s, pioneering lesion experiments unveiled the importance of medial and lateral hypothalamic structures. In the 1980s and 1990s, several neuropeptides and peripheral hormones critical for appropriate feeding behavior, energy expenditure, and hence body weight homeostasis were identified. In the 2000s, results from metabolic analyses of genetically engineered mice bearing mutations only in selected neuronal groups greatly advanced our knowledge of the peripheral/brain feedback-loop modalities by which central neurons control energy balance. In this review, we will summarize these recent progresses with particular emphasis on the biochemical identities of hypothalamic neurons and molecular components underlying normal appetite, energy expenditure, and body weight homeostasis. We will also parse which of those neurons and molecules are critical components of homeostatic adaptive pathways against obesity induced by hypercaloric feeding.
Exercise Induces a Marked Increase in Plasma Follistatin: Evidence That Follistatin Is a Contraction-Induced Hepatokine
Authors: Hansen Jakob , Brandt Claus , Nielsen Anders R. , Hojman Pernille , Whitham Martin , Febbraio Mark A. , Pedersen Bente K. , Plomgaard Peter 
Published: November 2010

Abstract
Follistatin is a member of the TGF-β super family and inhibits the action of myostatin to regulate skeletal muscle growth. The regulation of follistatin during physical exercise is unclear but may be important because physical activity is a major intervention to prevent age-related sarcopenia. First, healthy subjects performed either bicycle or one-legged knee extensor exercise. Arterial-venous differences were assessed during the one-legged knee extensor experiment. Next, mice performed 1 h of swimming, and the expression of follistatin was examined in various tissues using quantitative PCR. Western blotting assessed follistatin protein content in the liver. IL-6 and epinephrine were investigated as drivers of follistatin secretion. After 3 h of bicycle exercise, plasma follistatin increased 3 h into recovery with a peak of 7-fold. No net release of follistatin could be detected from the exercising limb. In mice performing a bout of swimming exercise, increases in plasma follistatin as well as follistatin mRNA and protein expression in the liver were observed. IL-6 infusion to healthy young men did not affect the follistatin concentration in the circulation. When mice were stimulated with epinephrine, no increase in the hepatic mRNA of follistatin was observed. This is the first study to demonstrate that plasma follistatin is increased during exercise and most likely originates from the liver. These data introduce new perspectives regarding muscle-liver cross talk during exercise and during recovery from exercise.
Plasticity of the Reproductive Axis Caused by Social Status Change in an African Cichlid Fish: I. Pituitary Gonadotropins
Authors: Maruska Karen P. , Levavi-Sivan Berta , Biran Jakob , Fernald Russell D. 
Published: November 2010

AbstractSocial position in a dominance hierarchy is often tightly coupled with fertility. Consequently, an animal that can recognize and rapidly take advantage of an opportunity to rise in rank will have a reproductive advantage. Reproduction in all vertebrates is controlled by the brain-pituitary-gonad axis, and in males of the African cichlid fish Astatotilapia burtoni, GnRH1 neurons at the apex of this axis are under social control. However, little is known about how quickly social information is transformed into functional reproductive change, or about how socially controlled changes in GnRH1 neurons influence downstream actions of the brain-pituitary-gonad axis. We created an opportunity for reproductively suppressed males to ascend in status and then measured how quickly the perception of this opportunity caused changes in mRNA and protein levels of the pituitary gonadotropins. mRNA levels of the β-subunits of LH and FSH rose rapidly in the pituitary 30 min after suppressed males perceived an opportunity to ascend. In contrast, mRNA levels of GnRH receptor-1 remained unchanged during social transition but were higher in stable dominant compared with subordinate males. In the circulation, levels of both LH and FSH were also quickly elevated. There was a positive correlation between mRNA in the pituitary and circulating protein levels for LH and FSH, and both gonadotropins were positively correlated with plasma 11-ketotestosterone. Our results show that the pituitary is stimulated extremely rapidly after perception of social opportunity, probably to allow suppressed males to quickly achieve reproductive success in a dynamic social environment.
Development of severe skeletal defects in induced SHP-2-deficient adult mice: a model of skeletal malformation in humans with SHP-2 mutations
Authors: Bauler Timothy J. , Kamiya Nobuhiro , Lapinski Philip E. , Langewisch Eric , Mishina Yuji , Wilkinson John E. , Feng Gen-Sheng , King Philip D. 
Published: November 2010

SUMMARY
SHP-2 (encoded by PTPN11) is a ubiquitously expressed protein tyrosine phosphatase required for signal transduction by multiple different cell surface receptors. Humans with germline SHP-2 mutations develop Noonan syndrome or LEOPARD syndrome, which are characterized by cardiovascular, neurological and skeletal abnormalities. To study how SHP-2 regulates tissue homeostasis in normal adults, we used a conditional SHP-2 mouse mutant in which loss of expression of SHP-2 was induced in multiple tissues in response to drug administration. Induced deletion of SHP-2 resulted in impaired hematopoiesis, weight loss and lethality. Most strikingly, induced SHP-2-deficient mice developed severe skeletal abnormalities, including kyphoses and scolioses of the spine. Skeletal malformations were associated with alterations in cartilage and a marked increase in trabecular bone mass. Osteoclasts were essentially absent from the bones of SHP-2-deficient mice, thus accounting for the osteopetrotic phenotype. Studies in vitro revealed that osteoclastogenesis that was stimulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL) was defective in SHP-2-deficient mice. At least in part, this was explained by a requirement for SHP-2 in M-CSF-induced activation of the pro-survival protein kinase AKT in hematopoietic precursor cells. These findings illustrate an essential role for SHP-2 in skeletal growth and remodeling in adults, and reveal some of the cellular and molecular mechanisms involved. The model is predicted to be of further use in understanding how SHP-2 regulates skeletal morphogenesis, which could lead to the development of novel therapies for the treatment of skeletal malformations in human patients with SHP-2 mutations.
Self-generated Motion of Droplets Induced by Korteweg Force
Authors: Ban Takahiko , Aoyama Ai , Matsumoto Takuya 
Published: November 2010

Abstract
Phase-separating droplets exhibit self-generated motion depending on the composition of the constituent solution of a biocompatible material, aqueous two phase system. For higher concentrations than the equilibrium concentration, a droplet moved unidirectionally even in a homogeneous concentration field. For lower concentrations, the droplets hardly moved. The translational motion we observed is an effect of convection caused by Korteweg force.
Blocking Oxidation of Al Surfaces with Organic Thiol Monolayers Cured by Electron Beam
Authors: Nomura Shuhei , Yamada Taro , Kawai Maki 
Published: November 2010

Abstract
In order to expand the processing utility of metallic aluminum as a material for nanometer-scale fabrication, we attempted to block oxidation of Al(111) surface in O2 gas up to 1000 Torr, by predeposited organic monolayers. A full monolayer of biphenyl-4-thiol (BPT), appropriately treated by electron-beam irradiation, exhibited a significantly enhanced robustness against oxidation, compared to clean Al(111).
Thermal Properties of Alkali (Fluorosulfonyl)(trifluoromethylsulfonyl)amides
Authors: Kubota Keigo , Nohira Toshiyuki , Hagiwara Rika , Matsumoto Hajime 
Published: November 2010

Abstract
An asymmetric perfluorosulfonylamide anion, [(FSO2)(CF3SO2)N]− (C0C1−), has a significant ability to lower the melting temperatures of alkali salts down to around 373 K. Among alkali salts which have melting temperatures around 373 K, they have comparatively high decomposition temperature. The melting point of LiC0C1 is the lowest among the lithium salts of perfluoroalkyl- or fluorosulfonylamide anions of this kind.