bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effects of hypoxia on etoposide-induced apoptosis according to the cancer cell lines
Authors: Cosse Jean-Philippe , Sermeus Audrey , Vannuvel Kayleen , Ninane Noelle , Raes Martine , Michiels Carine 
Published: September 2007

Abstract

Background
It is more and more recognized that hypoxia plays a role in the resistance of cancer cells to chemotherapy. However, the mechanisms underlying this resistance still need deeper understanding. The aim of this study was to investigate the effect of hypoxia on this process since hypoxia is one of the hallmarks of tumor environment.

Results
The effect of hypoxia on the apoptosis induced by etoposide, one drug commonly used in chemotherapy, was investigated using three different cancer cell lines. Gene expression changes were also studied in order to delineate the mechanisms responsible for the hypoxia-induced chemoresistance. We observed that hypoxia differentially influenced etoposide-induced cell death according to the cancer cell type. While hypoxia inhibited apoptosis in hepatoma HepG2 cells, it had no influence in lung carcinoma A549 cells and further enhanced it in breast cancer MCF-7 cells. Etoposide increased p53 activity in all cell lines while hypoxia alone decreased it only in HepG2 cells. Hypoxia had no influence on the etoposide-induced p53 activity in A549, increased p53 abundance in MCF-7 cells but markedly decreased p53 activity in HepG2 cells. Using low density DNA arrays to detect the expression of genes involved in the regulation of apoptosis, etoposide and hypoxia were shown to each influence the expression of numerous genes, many of the ones influenced by etoposide being p53 target genes. Again, the influence of hypoxia on the etoposide-induced changes was different according to the cell type.

Conclusion
These results evidenced that there was a striking parallelism between the effect of hypoxia on the etoposide-induced p53 stabilization as well as p53 target gene expression and its effect on the etoposide-induced apoptosis according to the cell type. They are very interesting not only because they provide one possible mechanism for the induction of chemoresistance under hypoxic conditions in cells like HepG2 but also because they indicate that not all cell types respond the same way. This knowledge is of importance in designing adequate treatment according to the type of tumors.
Induction of cystine/glutamate transporter in bacterial lipopolysaccharide induced endotoxemia in mice
Authors: Taguchi Kumiko , Tamba Michiko , Bannai Shiro , Sato Hideyo 
Published: September 2007

Abstract

Background
Cystine/glutamate transporter, system xc-, contributes to the maintenance of intracellular glutathione levels and the redox balance in the extracellular space. The main component of the transporter, xCT, is known to be strongly induced by various stimuli like oxidative stress in mammalian cultured cells. We examined the expression of xCT mRNA in vivo in the experimental endotoxemia.

Methods
Northern blot analysis and in situ hybridization were used to investigate the expression of xCT mRNA in the tissues of the mice exposed to bacterial lipopolysaccharide (LPS).

Results
Northern blot analysis revealed that xCT mRNA was constitutively expressed in the brain, thymus, and spleen, and that the expression of xCT mRNA was strongly up-regulated in thymus and spleen by the administration of a sublethal dose of LPS. In addition to brain, thymus, and spleen, xCT mRNA was detected also in the bronchiolar epithelium of the lung by the administration of the lethal dose of LPS.

Conclusion
xCT is induced in some specific tissues by the administration of LPS. The results suggest that cystine/glutamate transporter plays an important role under the inflammatory conditions.
Characterization of EN-1078D, a poorly differentiated human endometrial carcinoma cell line: a novel tool to study endometrial invasion in vitro
Authors: Dery Marie-Claude , Van Themsche Celine , Provencher Diane , Mes-Masson Anne-Marie , Asselin Eric 
Published: September 2007

Abstract

Background
To date, tools to study metastasis in endometrial cancers are insufficiently developed. The aim of this study was to characterize the cell line EN-1078D, a new endometrial carcinoma cell line derived from a metastasis to the ovary.

Methods and Results
Cells were characterized using cytology, transmission electron microscopy, karyotyping and morphological appearance in culture. Molecular features were determined by RT-PCR, Western Blot, FISH and sequencing. MTT proliferation assays were performed to investigate the sensitivity of EN-1078D to anticancer agents such as cisplatin and doxorubicin. Also, subcutaneous and intravenous injections in nude mice were done to test the tumorigenic and metastatic properties of EN-1078D cells. Our results indicate that EN-1078D cells express both oestrogen receptors isoforms (ER alpha and ER beta) and also low levels of progesterone receptor B (PR-B). In addition, this cell line expresses high levels of MMP-2 and MMP-14 mRNA, low levels of TIMP-1 and TIMP-2 transcripts and no detectable levels of MMP-9 mRNA. Moreover, all nude mice developed tumors by subcutaneous injections and cell invasion was observed in vitro in response to TGF-beta 3. Her-2/neu was not overamplified but mutations in the C-2 domain of PTEN gene as well as codon 12 of the K-Ras gene were found. Finally, EN-1078D shows sensitivity to drugs commonly used in chemotherapy such as cisplatin and doxorubicin: IC50 of 2.8 μM of cisplatin after 72 hours of exposure and 0.54 μM of doxorubicin after 48 hours.

Conclusion
Taken together, these results suggest that EN-1078D will be an excellent tool to study the properties of metastatic endometrial cancer cells in vitro and their regulation by sex steroids.
Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice
Authors: Verhoeff Joost JC , Stalpers Lukas JA , Coumou Annet W , Koedooder Kees , Lavini Cristina , Van Noorden Cornelis JF , Haveman Jaap , Vandertop William P , van Furth Wouter R 
Published: September 2007

Abstract

Background
High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models– high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a stereotactic brachytherapy mouse model for high-dose focal irradiation of experimental intracerebral (orthotopic) brain tumors.

Methods
Twenty-one nude mice received a hollow guide-screw implanted in the skull. After three weeks, 5 × 105 U251-NG2 human glioblastoma cells were injected. Five days later, a 2 mCi iodine-125 brachytherapy seed was inserted through the guide-screw in 11 randomly selected mice; 10 mice received a sham seed. Mice were euthanized when severe neurological or physical symptoms occurred. The cumulative irradiation dose 5 mm below the active iodine-125 seeds was 23.0 Gy after 13 weeks (BEDtumor = 30.6 Gy).

Results
In the sham group, 9/10 animals (90%) showed signs of lethal tumor progression within 6 weeks. In the experimental group, 2/11 mice (18%) died of tumor progression within 13 weeks. Acute side effects in terms of weight loss or neurological symptoms were not observed in the irradiated animals.

Conclusion
The intracerebral implantation of an iodine-125 brachytherapy seed through a stereotactic guide-screw in the skull of mice with implanted brain tumors resulted in a significantly prolonged survival, caused by high-dose irradiation of the brain tumor that is biologically comparable to high-dose fractionated radiotherapy– without fatal irradiation toxicity. This is an excellent mouse model for testing orthotopic brain tumor therapies in combination with radiation therapy.
Distinct roles of Hoxa2 and Krox20in the development of rhythmic neural networks controlling inspiratory depth, respiratory frequency, and jaw opening
Authors: Chatonnet Fabrice , Wrobel Ludovic J , Mézières Valérie , Pasqualetti Massimo , Ducret Sébastien , Taillebourg Emmanuel , Charnay Patrick , Rijli Filippo M , Champagnat Jean 
Published: September 2007

Abstract
Background
Little is known about the involvement of molecular determinants of segmental patterning of rhombomeres (r) in the development of rhythmic neural networks in the mouse hindbrain. Here, we compare the phenotypes of mice carrying targeted inactivations of Hoxa2, the only Hox gene expressed up to r2, and of Krox20, expressed in r3 and r5. We investigated the impact of such mutations on the neural circuits controlling jaw opening and breathing in newborn mice, compatible with Hoxa2-dependent trigeminal defects and direct regulation of Hoxa2 by Krox20 in r3.

Results
We found that Hoxa2 mutants displayed an impaired oro-buccal reflex, similarly to Krox20 mutants. In contrast, while Krox20 is required for the development of the rhythm-promoting parafacial respiratory group (pFRG) modulating respiratory frequency, Hoxa2 inactivation did not affect neonatal breathing frequency. Instead, we found that Hoxa2-/- but not Krox20-/- mutation leads to the elimination of a transient control of the inspiratory amplitude normally occurring during the first hours following birth. Tracing of r2-specific progenies of Hoxa2 expressing cells indicated that the control of inspiratory activity resides in rostral pontine areas and required an intact r2-derived territory.

Conclusion
Thus, inspiratory shaping and respiratory frequency are under the control of distinct Hox-dependent segmental cues in the mammalian brain. Moreover, these data point to the importance of rhombomere-specific genetic control in the development of modular neural networks in the mammalian hindbrain.
A case-control study of rheumatoid arthritis identifies an associated single nucleotide polymorphism in the NCF4 gene, supporting a role for the NADPH-oxidase complex in autoimmunity
Authors: Olsson Lina M , Lindqvist Anna-Karin , Källberg Henrik , Padyukov Leonid , Burkhardt Harald , Alfredsson Lars , Klareskog Lars , Holmdahl Rikard 
Published: September 2007

AbstractRheumatoid arthritis (RA) is a chronic inflammatory disease with a heritability of 60%. Genetic contributions to RA are made by multiple genes, but only a few gene associations have yet been confirmed. By studying animal models, reduced capacity of the NADPH-oxidase (NOX) complex, caused by a single nucleotide polymorphism (SNP) in one of its components (the NCF1 gene), has been found to increase severity of arthritis. To our knowledge, however, no studies investigating the potential role played by reduced reactive oxygen species production in human RA have yet been reported. In order to examine the role played by the NOX complex in RA, we investigated the association of 51 SNPs in five genes of the NOX complex (CYBB, CYBA, NCF4, NCF2, and RAC2) in a Swedish case-control cohort consisting of 1,842 RA cases and 1,038 control individuals. Several SNPs were found to be mildly associated in men in NCF4 (rs729749, P = 0.001), NCF2 (rs789181, P = 0.02) and RAC2 (rs1476002, P = 0.05). No associations were detected in CYBA or CYBB. By stratifying for autoantibody status, we identified a strong association for rs729749 (in NCF4) in autoantibody negative disease, with the strongest association detected in rheumatoid factor negative men (CT genotype versus CC genotype: odds ratio 0.34, 95% confidence interval 0.2 to 0.6; P = 0.0001). To our knowledge, this is the first genetic association identified between RA and the NOX complex, and it supports previous findings from animal models of the importance of reactive oxygen species production capacity to the development of arthritis.
Incidence and predictors of mental ill-health in adults with intellectual disabilities
Authors: Smiley Elita , Cooper Sally-Ann , Finlayson Janet , Jackson Alison , Allan Linda , Mantry Dipali , McGrother Catherine , McConnachie Alex , Morrison Jillian 
Published: October 2007

BackgroundThe point prevalence of mental ill-health among adults with intellectual disabilities is 40.9%, but its incidence is unknown.AimsTo determine the incidence and possible predictors of mental ill-health.MethodProspective cohort study to measure mental ill-health in adults with mild to profound intellectual disabilities.ResultsCohort retention was 70% (n=651). The 2-year incidence of mental ill-health was 16.3% (12.6% excluding problem behaviours, and 4.6% for problem behaviours) and the standardised incidence ratio was 1.87 (95%CI1.51 2.28). Factors related to incident mental ill-health have some similarities with those in the general population, but also important differences. Type of accommodation and support, previous mental ill-health, urinary incontinence, not having impaired mobility, more severe intellectual disabilities, adult abuse, parental divorce in childhood and preceding life events predicted incident ill-health; however, deprivation, other childhood abuse or adversity, daytime occupation, and marital and smoking status did not.ConclusionsThis is a first step towards intervention trials, and identifying sub-populations for more proactive measures. Public health strategy and policy that is appropriate for this population should be developed.
Neurokinin-1 receptor antagonists as novel antidepressants: trials and tribulations
Authors: Hafizi Sepehr , Chandra Prakash , Cowen Philip J. 
Published: October 2007

SummaryBased upon animal experiments and early clinical trials, neurokinin-1 receptor antagonists showed promise as novel antidepressants. Subsequently, however, more extensive clinical trials did not reveal evidence of efficacy in depression. The development of novel antidepressants will require a better understanding of the neural basis of antidepressant action in humans.
Characterizing Emergency Department Discussions about Depression
Authors: Rhodes Karin V. , Kushner Hallie M. , Bisgaier Joanna , Prenoveau Elizabeth 
Published: September 2007

Background: The reality of emergency health care in the United States today requires new approaches to mental health in the emergency department (ED). Major depression is a disabling condition that disproportionately affects women.Objectives: To characterize ED provider–patient discussions about depression.Methods: This was a secondary analysis of a database of audiotaped ED visits with women patients collected during a clinical trial of computer screening for domestic violence and other psychosocial risks. Nonemergent female patients, ages 18–65 years, were enrolled from two socioeconomically diverse academic EDs. All audio files with two or more relevant comments were identified as “significant depression discussions” and independently coded using a structured coding form.Results: Of 871 audiorecorded ED visits, 70 (8%) included discussions containing any reference to depression and 20 (2%) constituted significant depression discussions. Qualitative analysis of the 20 significant discussions found that 16 (80%) required less than 90 seconds to complete. Ten included less than optimal provider communication characteristics. Despite the brevity or quality of the communication, 15 of the 20 yielded high patient satisfaction with their ED treatment.Conclusions: ED providers rarely addressed depression. Qualitative analysis of significant patient–provider interactions regarding depression found that screening for depression in the ED can be accomplished with minimal expenditure of provider time and effort. Attention to psychosocial risk factors has the potential to improve the quality of ED care and patient satisfaction.
Testicular Adrenal Rest Tumors and Leydig and Sertoli Cell Function in Boys with Classical Congenital Adrenal Hyperplasia
Authors: Martinez-Aguayo A. , Rocha A. , Rojas N. , García C. , Parra R. , Lagos M. , Valdivia L. , Poggi H. , Cattani A. 
Published: September 2007

Abstract
Context: Infertility observed in adult males with congenital adrenal hyperplasia (CAH) has been associated with testicular adrenal rest tumors (TART) that may originate during childhood.
Objective: Our objective was to describe the prevalence of TART and Sertoli and Leydig cell function in a group of boys aged 2–10 yr with CAH and to compare prevalence with that of a control group.
Design: From August 2005 to January 2007, 19 patients with classical CAH (CAH group) were referred from seven endocrinology centers.
Methods: We studied 19 subjects in the CAH group and, as a control group, 13 boys from the community that did not have testicular diseases. A complete physical exam was performed. High-resolution ultrasound was used to determine TART prevalence. Inhibin B and anti-Müllerian hormone were used as Sertoli cell markers. The ratio between basal testosterone levels and testosterone levels 72 h after β-human chorionic gonadotropin (5000 U/m2) treatment [(T72− T0)/T0] was used to evaluate Leydig cell response.
Results: CAH and control groups were comparable in chronological age (5.9 vs. 5.6 yr; P = 0.67) and bone age/chronological age ratio (1.09 vs. 1.03; P = 0.09). TART prevalence was four of 19 (21%) in the CAH group. Lower values for inhibin B (49.2. vs. 65.2 pg/ml; P = 0.018), anti-Müllerian hormone (70.1 vs. 94.2 ng/ml; P = 0.002), and (T72− T0)/T0 (5.6 vs. 13.6; P &lt; 0.01) were observed in the CAH group.
Conclusion: TART in prepubertal males with classic CAH could be found during childhood. We also report differences in markers of gonadal function in a subgroup of patients, especially in those with inadequate control.
Radium in Engineering Practice
Authors: Pullin V. E. 
Published: October 2007

Considerable advances have recently been made in nondestructive testing, and a new transportable X-ray laboratory is illustrated in the paper to show that X-rays have achieved a definite, if limited, function in this field. The paper is mainly devoted to a discussion of the properties of radium as a radiographic agent to show how it compares in value with the older X-ray method. The disintegration theory of radioactive materials is outlined and the relative wavelengths of various components of the so-called electromagnetic spectrum, used roughly to indicate their penetrating power, are given. The method of preparing radon is described as it has the great advantage that its use would afford an approximation to a point source of radiation. When employing one of the radium salts, the radium must be removed an appreciable distance from the sensitized film to obtain good definition, thus increasing the exposure time. Careful directions are given for the safe handling and storage of the element. The exposure camera in use in the Research Department, Woolwich, is described and curves are given indicating safe working distances for operators. Many experimental refinements making for clear radiography are mentioned. In the case of X-rays the effect of scattered radiation militates seriously against good results, whereas in gamma-ray photography there is practically no such harmful effect. Hence heavy irregular specimens may be radiographed by radium in perhaps one exposure. Exposure curves for radium, based upon experimental data obtained in the author's laboratory, are given. Owing to the general employment of photographic intensifying screens to shorten exposures, it is not possible to rely on calculations based on the inverse square law. The uses of X-rays and radium are compared and the particular advantages of radium illustrated by a large number of radiographs. X-rays have overwhelming advantages in the examination of metallic structures up to a thickness of about 3 inches. Radium, on the other hand, may be employed in the investigation of metals up to 8 inches or more in thickness.
The Stresses in Fusion Joints
Authors: Coker E. G. , Levi R. , Russell R. 
Published: October 2007

Modern use of fusion joints instead of riveted or bolted connexions has produced a variety of new forms which offer numerous fields of inquiry covering a great range of problems. One set of problems relates to stress distribution directed more especially to the determination of the maximum stresses in fusion joints. This is almost entirely an experimental matter, since nearly all such joints have discontinuities imposed by practical necessities which render them insoluble by theoretical analysis, while little or no help can be gained from our existing knowledge and long experience of riveted and bolted joints on account of their essentially different nature. The present inquiry deals with problems of plane stress distribution in which models are used for measuring the stress at any point required by photo-elastic means, and in the first instance some typical butt welds of an unsymmetrical type are analysed experimentally. Other ways of connecting plates in line are then considered in which a joint is made by a lenticular section of weld metal on one side and a cover plate on the other, the ends of the latter being joined to the main plates by triangular sections of fusion metal. When the gap between the two main plates is sufficient the lenticular section of metal may be replaced by a pair of triangular fillets binding the inner ends of the plates to the cover strap, and this form is also dealt with. The effects of triangular fillets of lesser height than the butt straps and of corresponding fillets of curved quadrantal form are also examined with reference to a double butt strap joint. The paper concludes with a brief summary of the main results afforded by the experimental analysis.
Heat Liberation and Transmission in Large Steam-Generating Plants
Authors: Robey E. W. , Harlow W. F. 
Published: October 2007

The demand for heavier duties and exacting guarantees of performance which has accompanied recent developments in steam-raising plants, has necessitated closer inquiry into the fundamental principles on which their performance depends. The authors present their views on certain aspects of the subject. These have been formed as a result of experience, combined with a consideration of the work of laboratory investigators. It would appear that important facts revealed by laboratory research do not always receive the attention due to them, and frequently erroneous ideas persist for years without question. The paper discusses the function of the chain grate mechanical stoker with particular reference to the subject of furnace design and secondary air application. It deals with the effect on the size and cost of equipment generally, which would result from a closer observance of the laws of heat transfer and frictional loss in flowing gases, and discusses particularly the phenomenon of delayed heat release in flue gases and the effect of this in boiler plant performance. The cause and prevention of air heater corrosion is dealt with, and the results of investigations into the dew point temperature of flue gases are given.