bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth Hormone and Insulin-Like Growth Factor I Insensitivity of Fibroblasts Isolated from a Patient with an IκBα Mutation
Authors: Wu Shufang , Walenkamp Marie J. , Lankester Arjan , Bidlingmaier Martin , Wit Jan M. , De Luca Francesco 
Published: January 2010

Abstract
Context: NF-κB is a family of transcription factors involved in cell proliferation, differentiation, and apoptosis.
Objective: We have recently demonstrated that NF-κB is expressed in the growth plate and it mediates the growth-promoting effects of IGF-I on chondrogenesis and longitudinal bone growth. Humans with defects of the NF-κB pathway exhibit growth failure, which suggests a possible regulatory role for NF-κB in statural growth. We have previously reported a child with ectodermal dysplasia, immunodeficiency, and growth retardation, harboring a heterozygous mutation of IκBα, an essential component of the NF-κB pathway. Since he was found with low IGF-l and IGFBP-3, and elevated GH secretion, an IGF-l generation test was carried out: baseline IGF-l was low and only responded to a high dose of GH. Thus, the diagnosis of GH resistance was made.
Results: To assess the underlying mechanisms of his GH resistance, we cultured the patient’s skin fibroblasts with GH and/or IGF-I. While both GH and IGF-l induced cell proliferation and NF-κB activity in controls’ fibroblasts, they had no effect on the patient’s fibroblasts. In the fibroblasts of the patient’s father (who displays mosaicism for the IκBα mutation), GH and IGF-l elicited an attenuated stimulatory effect. In addition, GH stimulated STAT5 phosphorylation and IGF-l mRNA expression in controls ’ and the father’s fibroblasts, while IGF-l induced PI3K activity and mRNA and protein expression of TDAG51, a target gene for IGF-I. In contrast, none of these effects was elicited by GH or IGF-l in the patient’s fibroblasts.
Conclusion: Our findings suggest that this patient’s IκBα mutation caused GH and IGF-l resistance which, in turn, contributed to his growth failure.
Delayed Remission after Transsphenoidal Surgery in Patients with Cushing’s Disease
Authors: Valassi Elena , Biller Beverly M. K. , Swearingen Brooke , Pecori Giraldi Francesca , Losa Marco , Mortini Pietro , Hayden Douglas , Cavagnini Francesco , Klibanski Anne 
Published: January 2010

Abstract
Background: Transsphenoidal surgery (TSS) is the treatment of choice for Cushing’s disease (CD). Postoperative hypercortisolemia mandates further therapy.
Objective: The aim of the study was to characterize patients without immediate postoperative remission who have a delayed decrease to normal or low cortisol levels without further therapy.
Design and Setting: A retrospective case series was conducted at three tertiary care centers.
Patients and Intervention: We reviewed the records of 620 patients (512 females, 108 males; mean age, 38 ± 13 yr) who underwent transsphenoidal pituitary surgery for CD between 1982 and 2007.
Results: Outcomes were classified into the following three groups based upon the postoperative pattern of cortisol testing: group IC (immediate control) included 437 of the 620 patients (70.5%) with hypocortisolism and/or cortisol normalization throughout the postoperative follow-up; group NC (no control) included 148 of 620 patients (23.9%) with persistent hypercortisolism; and group DC (delayed control) included 35 of 620 patients (5.6%) who had early elevated or normal UFC levels and developed a delayed and persistent cortisol decrease after an average of 38 ± 50 postoperative days. The total rate of recurrence was 13% at a median follow-up time of 66 months after TSS; the cumulative rate of recurrence at 4.5 yr was significantly higher in group DC vs. group IC (43 vs. 14%; P = 0.02).
Conclusions: Hormonal assessment in the immediate postoperative period after TSS for CD may be misleading because delayed remission can occur in a subset of patients. Expectant management and retesting may spare some patients from unnecessary further treatment. Optimal timing to determine the need for further therapy after TSS remains to be determined.
Impact of Growth Hormone Therapy on Quality of Life in Adults with Turner Syndrome
Authors: Amundson Emily , Boman Ulla Wide , Barrenäs Marie-Louise , Bryman Inger , Landin-Wilhelmsen Kerstin 
Published: January 2010

Abstract
Context: GH and/or oxandrolone are used to promote growth in Turner syndrome (TS).
Objective: The aim of this study was to compare quality of life (QoL) in TS women with controls and determine the impact of growth promoting therapy on QoL in TS women.
Design: This was a cross-sectional, case-control study.
Setting: The study was conducted at an outpatient clinic at Sahlgrenska University Hospital, Göteborg, Sweden.
Patients: Patients included 111 TS women (age range 18–59 yr) and 111 randomly selected, age-matched women (25–54 yr) from the World Health Organization Monitoring Trends and Determinants for Cardiovascular Disease project (Göteborg, Sweden) served as controls.
Main Outcome Measures: QoL was estimated by the Psychological General Well-Being scale (anxiety, depressed mood, positive well-being, self-control, general health and vitality) and the Nottingham Health Profile (physical mobility, pain, sleep, energy, social isolation, and emotional reactions).
Results: TS women reported more social isolation than controls (P &lt; 0.001). After age adjustment, significantly less pain (&lt;0.05) was reported attributable to GH treatment within TS. No significant difference in any other subscales used could be shown. In TS, QoL was negatively affected by higher current age and age at diagnosis and positively affected by better body balance, fine motor function, and higher bone mineral density.
Conclusions: Social isolation was more commonly reported in the whole TS cohort than in the population. Except for less pain, no significant impact on QoL attributable to GH treatment could be found, despite the mean +5.1 cm final height.
Change in Amniotic Fluid Levels of Multiple Anti-Angiogenic Proteins before Development of Preeclampsia and Intrauterine Growth Restriction
Authors: Wang Chao-Nin , Chang Shuenn-Dyh , Peng Hsiu-Huei , Lee Yun-Shien , Chang Yao-Lung , Cheng Po-Jen , Chao An-Shine , Wang Tzu-Hao , Wang Hsin-Shih 
Published: January 2010

AbstractContext: The cause of preeclampsia remains unknown. Excessive antiangiogenic proteins have been proposed to play a pathogenic role in preeclampsia.Objective: Our objective was to determine the differences in soluble endoglin (sEndoglin), soluble fms-like tyrosine kinase receptor-1 (sFLT1), leptin, adiponectin, and endothelin 1 concentrations between normal and preeclampsia amniotic fluid (AF). Such results may help us understand the pathophysiology of preeclampsia.Methods: We performed a nested case-control study. Seventy-one women with preeclampsia were matched to 71 normotensive controls. The preeclamptic women were broken into two subgroups according to the association with fetal intrauterine growth restriction (IUGR). AF concentrations of sEndoglin, sFLT1, leptin, adiponectin, and endothelin 1 were measured by ELISA. Receiver-operating characteristics curve analysis was used to compare the discriminative values of these potential biomarkers. Functional network analysis was performed using MetaCore to reveal the common functions of the interacting proteins.Results: Increased AF concentrations of sFLT1, sEndoglin, endothelin 1, and leptin were found in women who later developed preeclampsia. sFLT1, sEndoglin, leptin, and adiponectin were significantly higher in the preeclampsia with IUGR than those without IUGR. Leptin has the largest area under the curve (0.753). Network analysis revealed that elevated amniotic proteins are involved in the inflammatory process of the human placenta.Conclusions: Significant elevation of leptin can be detected in AF 2 months earlier than the appearance of symptoms; thus, it may be used as a predictive marker for preeclampsia. The increase of these antiangiogenic proteins supports the roles of inflammation and oxidative stress in pathogenesis of preeclampsia.
A Link between mir-100 and FRAP1/mTOR in Clear Cell Ovarian Cancer
Authors: Nagaraja Ankur K. , Creighton Chad J. , Yu Zhifeng , Zhu Huifeng , Gunaratne Preethi H. , Reid Jeffrey G. , Olokpa Emuejevoke , Itamochi Hiroaki , Ueno Naoto T. , Hawkins Shannon M. , Anderson Matthew L. , Matzuk Martin M. 
Published: January 2010

Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that direct gene regulation through translational repression and degradation of complementary mRNA. Although miRNAs have been implicated as oncogenes and tumor suppressors in a variety of human cancers, functional roles for individual miRNAs have not been described in clear cell ovarian carcinoma, an aggressive and chemoresistant subtype of ovarian cancer. We performed deep sequencing to comprehensively profile miRNA expression in 10 human clear cell ovarian cancer cell lines compared with normal ovarian surface epithelial cultures and discovered 54 miRNAs that were aberrantly expressed. Because of the critical roles of the phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog 1/mammalian target of rapamycin (mTOR) pathway in clear cell ovarian cancer, we focused on mir-100, a putative tumor suppressor that was the most down-regulated miRNA in our cancer cell lines, and its up-regulated target, FRAP1/mTOR. Overexpression of mir-100 inhibited mTOR signaling and enhanced sensitivity to the rapamycin analog RAD001 (everolimus), confirming the key relationship between mir-100 and the mTOR pathway. Furthermore, overexpression of the putative tumor suppressor mir-22 repressed the EVI1 oncogene, which is known to suppress apoptosis by stimulating phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog 1 signaling. In addition to these specific effects, reversing the expression of mir-22 and the putative oncogene mir-182 had widespread effects on target and nontarget gene populations that ultimately caused a global shift in the cancer gene signature toward a more normal state. Our experiments have revealed strong candidate miRNAs and their target genes that may contribute to the pathogenesis of clear cell ovarian cancer, thereby highlighting alternative therapeutic strategies for the treatment of this deadly cancer.
Contamination with E1A-Positive Wild-Type Adenovirus Accounts for Species-Specific Stimulation of Islet Cell Proliferation by CCK: A Cautionary Note
Authors: Lavine Jeremy A. , Raess Philipp W. , Davis Dawn B. , Rabaglia Mary E. , Presley Brent K. , Keller Mark P. , Beinfeld Margery C. , Kopin Alan S. , Newgard Christopher B. , Attie Alan D. 
Published: January 2010

AbstractWe have previously reported that adenovirus-mediated expression of preprocholecystokin (CCK) stimulates human and mouse islet cell proliferation. In follow-up studies, we became concerned that the CCK adenovirus might have been contaminated with a wild-type E1A-containing adenovirus. Here we show conclusively that the proliferative effects reported in the original paper in mouse and human islets were not due to CCK expression but rather to a contaminating E1A-expressing wild-type adenovirus. We also show, however, that CCK expression does have a proliferative effect in rat islets. We hope that our report of the steps taken to detect the wild-type virus contamination, and purification of the contributing viral stocks, will be helpful to other investigators, and that our experience will serve as a cautionary tale for use of adenovirus vectors, especially for studies on cellular replication.
On the tribo-cryogenic characteristics of titanium alloys
Authors: El-Tayeb N S M , Yap T C , Brevern P V 
Published: January 2010

Friction and wear behaviours of Ti-6Al-4V (Ti64) and Ti-5Al-4V-0.6Mo-0.4Fe (Ti54) alloys sliding against a tungsten carbide wheel under dry and cryogenic sliding conditions were investigated at different sliding speeds, loads, and distances. Mathematical models utilizing response surface methodology were developed as a function of sliding conditions for predicting the friction and wear characteristics of both titanium alloys. The controlling variables were determined by utilizing design of experiments. The developed models are able to predict the measured friction coefficient and wear volume with reasonable degree of accuracy for both titanium alloys within the ranges of studied parameters. Results showed no substantial difference between tribo-characteristics of both titanium alloys. Under cryogenic sliding condition, tribo-characteristics were lower than those obtained under dry sliding, except at higher load, cryogenic sliding surprisingly gave higher friction coefficient. Analyses of worn surfaces and wear debris by using scanning electron microscopy and energy-dispersive spectroscopy revealed that the role of cryogenic conditions at the sliding interface was partially attributed to changing material properties and possible hydrodynamic effect. Under dry sliding, the main wear modes were adhesion and delamination, while under cryogenic sliding, in addition to delamination, abrasion wear mode dominated.
Combining Targeted Therapies: Practical Issues to Consider at the Bench and Bedside
Authors: Rodon Jordi , Perez Jose , Kurzrock Razelle 
Published: January 2010

Abstract
Numerous practical issues must be considered when combining targeted therapies in early clinical drug development. These include tumor resistance mechanisms, the existence of multiple, redundant signaling pathways, and the failure of single-agent therapies to achieve cures. The strategies adopted to examine combinatorial therapy include the goal of hitting more than one target by specifically inhibiting signal transduction cascades and suppressing specific mechanisms of action with the use of multitargeted kinase inhibitors made possible by high-throughput screening techniques, combinatorial chemistry, and chemoinformatics. Two complex considerations are: which agents to combine given the heterogeneity of tumors and their various underlying perturbations, including secondary mutations and feedback loops, and how to translate findings from the bench to the bedside or directly from the bedside. Another consideration is: When is there enough information to provide a rationale for instituting a phase I trial? Various strategies have been used in combining molecules, including targeting diverse pathways, inhibiting upstream and downstream signals, and adopting a synthetic lethality paradigm. Other issues are: determining appropriate target populations for treatment, how to combine therapeutics with diagnostics, and the frequency of targets in patients referred to clinical trials. Here, we review these issues and we propose various novel trial designs that are logical for determining the efficacy of a drug or drug combination for personalized treatment. A difficult issue that must be answered is how many and which drugs to combine. Recent technologies, such as multiplexed assay platforms and bioinformatics, will shape the future of clinical trials and help answer these questions surrounding combinatorial treatment.
Therapeutic Usefulness of Postoperative Adjuvant Chemotherapy with Tegafur–Uracil (UFT) in Patients with Breast Cancer: Focus on the Results of Clinical Studies in Japan
Authors: Nakayama Takahiro , Noguchi Shinzaburo 
Published: January 2010

Abstract
In Japan, the history of postoperative chemotherapy for breast cancer started with 5-fluorouracil (5-FU), launched in the 1980s. Currently, oral fluoropyrimidine–based regimens indicated for the treatment of breast cancer in Japan include tegafur plus uracil (UFT); tegafur, gimeracil, and oteracil (TS-1); doxifluridine; and capecitabine. In particular, UFT represents an important option for long-term treatment because of minimal adverse events and the potential for long-term maintenance of effective plasma concentrations of 5-FU to inhibit micrometastasis after surgery. Therefore, various clinical studies of postoperative adjuvant chemotherapy with UFT have been conducted in patients with completely resected tumors. Recent studies have shown that UFT prolongs survival after tumor resection in patients with gastric cancer, colorectal cancer, and lung cancer. In patients with breast cancer, large clinical trials of UFT-based postoperative chemotherapy conducted in Japan have shown that UFT is useful for the treatment of intermediate-risk patients with no lymph node metastasis. This paper reviews the results of clinical studies of UFT conducted in Japan to assess the therapeutic usefulness of this oral 5-FU. The types of patients most likely to benefit from UFT are discussed on the basis of currently available evidence and a global consensus of treatment recommendations. The optimal timing of endocrine therapy and strategies for postoperative adjuvant chemotherapy with UFT in patients with breast cancer are also discussed.
HP/HT Well Intervention by Coil Tubing—East Coast Case Histories
Authors: Mohammad Haidher Syed 
Published: January 2010

Abstract
Coil tubing is a single string of pipe, which can intervene into wells and perform specific jobs without mobilizing a rig. The basic applications are cleaning wellbore/perforations, stimulating selective zones, controlling wells, milling/drilling cement/tools/fish downhole, conveying tools in deviated/horizontal wells, gas lifting, setting cement plugs below production packer, and many other applications.
Operating coiled tubing units in HPHT and ultra HPHT wells requires conformance of specific parameters for safety and successful operations. Challenges of the operations and treatment design are exacerbated considering the environment downhole. The conditions become more severe in ultra HPHT environment if the well is deviated or approaches horizontal.
Intervention and treatment in ultra HPHT and in highly deviated or in horizontal wells requires special procedures, techniques and tools. The requirements include modified procedures as well as equipment and products to withstand the BHST temperatures for the entire operation.
As an example of complications in HPHT wells, on the east coast of India, bottomhole static temperatures could go as high as 507°F and mud weight could vary between 14 and 19 ppg in deviated wells. Experience has shown that conventionally calculated bottomhole circulating temperature alone is inadequate to determine the working temperature downhole. However, with the help of computer-aided temperature simulation and all the above techniques, many successful CTU operations have been executed under these difficult conditions.
Using case histories for illustration, this paper will share best practices developed from 4 years of successful interventions in HPHT and ultra-HPHT wells. These practices will include HPHT coil tubing intervention considerations, modified procedures, special techniques and product choices.
Feasibility of Air Injection in a Light Oil Field of Western India
Authors: Mitra Sujit , Bhushan B. V. , Raju P. V. , Kumar Subir , Sur Sidhartha , Mehta S. A. , Moore R. G. 
Published: January 2010

Abstract
Overall field settings like dip of 80, partial water drive, permeability of less than 50md and with 350 API oil make Field - A in Western India an ideal choice for gas injection. Non-availability of hydrocarbon / non-hydrocarbon gas makes air injection a preferred alternative. Viability of air injection process in laboratory was established through displacement tests in 1.83m long & 100mm diameter combustion tube using synthetic and natural core at IRS, ONGC.
In view of limitations of laboratory generated oil reactivity data for carrying out prediction in STARS, following workflow was adopted to estimate recovery from air injection.
Predicting recovery by immiscible gas injection – Pressure maintenance and Immiscible displacement Predicting Volumetric Sweep Efficiency – From miscible Gas Injection. It is felt that Miscible process mimics closely air injection as both these processes have displacement efficiency of more than 90% Predicting Recovery by Air Injection – Integrating immiscible flue gas with Nelson & McNeil derived profile after considering volumetric sweep from miscible gas displacement process. Air injection has the potential to enhance recovery from 19% to 62%.
Ways to Obtain Optimum Power Efficiency of Artificial Lift Installations
Authors: Takacs Gabor 
Published: January 2010

Abstract
Worldwide more than two thirds of the oil wells are placed on some kind of artificial lift, mostly on sucker-rod pumping, ESP, or gas lift. Because of the great number of installations it is extremely important that they operate under optimum conditions. Even small changes in operational efficiencies can significantly increase operational expenditures, so optimization of the energy efficiency has a great impact on profitability of oil production. The presentation deals with establishing the most energy-efficient operation of artificial lift installations. The aim of the optimization is finding the minimum operational costs while producing a prescribed liquid rate from the well, i.e. attaining the maximum power efficiency. Three forms of artificial lifting are studied: sucker-rod pumping, ESP, and gas lifting.
The power efficiency of any artificial lift system is defined by the relation of the useful power used for fluid lifting and the total input power. The useful hydraulic power is defined by the change of potential energy of the produced fluid, while the total input power can be calculated. Analysis of the power flow in rod pumped wells shows that maximum efficiency is reached with the proper combination of pump size, polished rod stroke length, and pumping speed. The installation's power efficiency is primarily determined by the choice of the pumping mode. The power efficiency of ESP installations is shown to reach a maximum when using a motor and a pump with the maximum efficiency while minimizing the power losses in the electric cable. Optimum design of continuous flow gas lift installations involves NODAL analyses and finds the combination of tubing size, injection and wellhead pressures, and flowline size that ensures the minimum compressor power requirements.
Getting the Most Out of Reservoir Surveillance: A Field Case Study
Authors: Ismadi D. , Suthichoti P. , Kabir C. S. 
Published: January 2010

Abstract
This study presents an inception-to-maturity data acquisition philosophy and deriving value from such surveillance. We show that wellhead pressures can be translated to bottomhole condition for many reservoir-engineering calculations during the flow period. While conversion of WHP to BHP is feasible during a flow test, measurements showed that shut-in tests do not lend themselves for such treatment because of rapid heat dissipation of a low-heat-capacity fluid, such as gas. Therefore, we relied upon flow-after-flow tests that were embedded in monthly variable-rate production measurements to obtain average-reservoir pressure and absolute open-flow potential. These average pressures enriched those that were obtained with downhole gauges from shut-in tests for the material-balance analysis. The resultant time-dependent inflow-performance relationship (IPR) and absolute-open-flow potential helped understand well performance. Indeed, evolution of declining IPR slope led to the identification of gradual wellbore blockage in one of the wells completed openhole. Downhole video recording confirmed mechanical issues in two openhole completions.
Production logging showed preferential flow from the upper section of the thick carbonate interval in two wells. However, residual doubts remained about possible flow up the annulus in the openhole/slotted-liner completions. Analytic modeling confirmed that the notion of preferential flow up the annulus is untenable.