tbuckley/cabot-search huggingface dataset:
Modulation of Gene Expression and Tumor Cell Growth by Redox Modification of STAT3
Authors: Li Li, Shing-hu Cheung, Emma L. Evans, Peter E. Shaw
Journal: Cancer Research (2010)

Reactive oxygen species (ROS) promote tumor cell proliferation and survival by directly modulating growth-regulatory molecules and key transcription factors. The signal transducer and activator of transcription 3 (STAT3) is constitutively active in a variety of tumor cell types, where the effect of ROS on the Janus kinase/STAT pathway has been examined. We report here that STAT3 is directly sensitive to intracellular oxidants. Oxidation of conserved cysteines by peroxide decreased STAT3 binding to consensus serum-inducible elements (SIE) in vitro and in vivo and diminished interleukin (IL)-6-mediated reporter expression. Inhibitory effects produced by cysteine oxidation in STAT3 were negated in redox-insensitive STAT3 mutants. In contrast, ROS had no effect on IL-6-induced STAT3 recruitment to the c-myc P2 promoter. Expression of a redox-insensitive STAT3 in breast carcinoma cells accelerated their proliferation while reducing resistance to oxidative stress. Our results implicate STAT3 in coupling intracellular redox homeostasis to cell proliferation and survival.
Down-regulation of Integrin α2 Surface Expression by Mutant Epidermal Growth Factor Receptor (EGFRvIII) Induces Aberrant Cell Spreading and Focal Adhesion Formation
Authors: Yan Ning, Reema Zeineldin, Yueying Liu, Martina Rosenberg, M. Sharon Stack, Laurie G. Hudson
Journal: Cancer Research (2005)

Abstract Elevated expression or activity of the epidermal growth factor receptor (EGFR) is common in ovarian cancer and is associated with poor patient prognosis. A naturally occurring EGFR mutation termed variant III (EGFRvIII) has been detected in many human tumors, including those of the ovary. This mutant receptor does not bind EGF; however, it is constitutively active as detected by receptor dimerization, autophosphorylation, and stimulation of signal transduction cascades. To identify the consequences of EGFRvIII expression in ovarian tumor cells, we introduced EGFRvIII into the epithelial ovarian cancer cell line OVCA 433. The EGFRvIII-transfected cells displayed a motile phenotype, defects in cell spreading, and decreased integrin α2 protein expression as detected by Western blot analysis and flow cytometry. Inhibition of EGFRvIII catalytic activity using the EGFR-selective tyrphostin AG1478 restored integrin α2 expression within 4 to 8 hours after treatment. The modulation of integrin α2 expression corresponded to marked changes in the actin cytoskeleton as detected by redistribution of filamentous-actin. Furthermore, focal adhesions were evident only when EGFRvIII activity was inhibited. Together, these findings suggest that expression of the constitutively active mutant EGFRvIII promotes changes in cell shape and focal adhesion formation, mediated in part through specific modulation of integrin α2 expression and function. We conclude that EGFR-activating mutations, such as EGFRvIII, in ovarian cancer may contribute to a more aggressive disease.
Increased Leukotrienes in Exhaled Breath Condensate in Childhood Asthma
Authors: Zsuzsanna Csoma, Sergei A. Kharitonov, Beatrix Balint, Andrew Bush, Nicola M. Wilson, Peter J. Barnes
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Cysteinyl leukotrienes (cys-LTs; LTC4, LTD4, and LTE4) are generated predominantly by mast cells and eosinophils and induce airway smooth muscle contraction, microvascular leakage, and mucous hypersecretion whereas leukotriene B4 (LTB4) is a potent chemoattractant of neutrophils. We measured cys-LTs and LTB4 in exhaled breath condensate from children aged 7–14 years including healthy nonatopic children (n = 11) and children with mild intermittent asthma (steroid naive, n = 11), mild persistent asthma (low-dose inhaled steroid treatment, n = 13), or moderate to severe persistent asthma (high-dose inhaled steroid treatment, n = 13). Exhaled LTB4 levels were increased in patients with mild and moderate to severe persistent asthma compared with patients with mild intermittent asthma (126.0 ± 8.8 and 131.9 ± 7.1 versus 52.7 ± 3.8 pg/ml, p < 0.001 and p < 0.0001) and normal subjects (126.0 ± 8.8 and 131.9 ± 7.1 versus 47.9 ± 4.1 pg/ml, p < 0.0001). Elevated exhaled cys-LT levels were found in patients with mild and moderate to severe persistent asthma compared with normal subjects (27.9 ± 2.8 and 31.5 ± 4.5 versus 18.5 ± 0.5 pg/ml, p < 0.01 and p < 0.05). There was an inverse correlation between exhaled cys-LTs and LTB4 in patients with mild persistent asthma. We conclude that exhaled cys-LTs and LTB4 may be noninvasive markers of airway inflammation in pediatric asthma.
Dutch doctors oppose new euthanasia proposals
Authors: T. Sheldon
Journal: BMJ (1996)

Doctors in the Netherlands fear that proposals to write an acceptance of euthanasia into Dutch law and to relax the current strict criteria that doctors must follow could lead to increased opportunities for euthanasia.

The proposals come from the influential Dutch Association for Voluntary Euthanasia, which has 82000 members. It hopes to stimulate public debate before government research on current euthanasia policy is published …
Biphasic amyloidosis: link between macular and lichenoid forms*
Authors: MARTIN H. BROWNSTEIN, KEN HASHIMOTO, GERALD GREENWALD
Journal: British Journal of Dermatology (2006)

A woman manifested lichen amyloidosus of the right lower limb and macular amyloidosis of her left leg with congenitally impaired cutaneous sensation. Another patient had bilateral lichenoid amyloidosis of her legs. Unilateral triamcinolone injections produced the picture of macular amyloidosis in the treated leg. Light and electron microscopic studies of biopsies from both patients showed similar amyloid deposits in the papillae; the significant difference was epidermal hyperplasia in the lichenoid lesions. We suggest the term biophasic for the existence of both macular and lichenoid amyloidosis in the same patient.
Coevolution of Solid Stress and Interstitial Fluid Pressure in Tumors During Progression: Implications for Vascular Collapse
Authors: Triantafyllos Stylianopoulos, John D. Martin, Matija Snuderl, Fotios Mpekris, Saloni R. Jain, Rakesh K. Jain
Journal: Cancer Research (2013)

The stress harbored by the solid phase of tumors is known as solid stress. Solid stress can be either applied externally by the surrounding normal tissue or induced by the tumor itself due to its growth. Fluid pressure is the isotropic stress exerted by the fluid phase. We recently showed that growth-induced solid stress is on the order of 1.3 to 13.0 kPa (10-100 mmHg)--high enough to cause compression of fragile blood vessels, resulting in poor perfusion and hypoxia. However, the evolution of growth-induced stress with tumor progression and its effect on cancer cell proliferation in vivo is not understood. To this end, we developed a mathematical model for tumor growth that takes into account all three types of stresses: growth-induced stress, externally applied stress, and fluid pressure. First, we conducted in vivo experiments and found that growth-induced stress is related to tumor volume through a biexponential relationship. Then, we incorporated this information into our mathematical model and showed that due to the evolution of growth-induced stress, total solid stress levels are higher in the tumor interior and lower in the periphery. Elevated compressive solid stress in the interior of the tumor is sufficient to cause the collapse of blood vessels and results in a lower growth rate of cancer cells compared with the periphery, independently from that caused by the lack of nutrients due to vessel collapse. Furthermore, solid stress in the periphery of the tumor causes blood vessels in the surrounding normal tissue to deform to elliptical shapes. We present histologic sections of human cancers that show such vessel deformations. Finally, we found that fluid pressure increases with tumor growth due to increased vascular permeability and lymphatic impairment, and is governed by the microvascular pressure. Crucially, fluid pressure does not cause vessel compression of tumor vessels.
Rosiglitazone Evaluated for Cardiovascular Outcomes — An Interim Analysis
Authors: Philip D. Home, Stuart J. Pocock, Henning Beck-Nielsen, Ramón Gomis, Markolf Hanefeld, Nigel P. Jones, Michel Komajda, John J.V. McMurray
Journal: New England Journal of Medicine (2007)

A recent meta-analysis raised concern regarding an increased risk of myocardial infarction and death from cardiovascular causes associated with rosiglitazone treatment of type 2 diabetes.We conducted an unplanned interim analysis of a randomized, multicenter, open-label, noninferiority trial involving 4447 patients with type 2 diabetes who had inadequate glycemic control while receiving metformin or sulfonylurea, in which 2220 patients were assigned to receive add-on rosiglitazone (rosiglitazone group), and 2227 to receive a combination of metformin plus sulfonylurea (control group). The primary end point was hospitalization or death from cardiovascular causes.Because the mean follow-up was only 3.75 years, our interim analysis had limited statistical power to detect treatment differences. A total of 217 patients in the rosiglitazone group and 202 patients in the control group had the adjudicated primary end point (hazard ratio, 1.08; 95% confidence interval [CI], 0.89 to 1.31). After the inclusion of end points pending adjudication, the hazard ratio was 1.11 (95% CI, 0.93 to 1.32). There were no statistically significant differences between the rosiglitazone group and the control group regarding myocardial infarction and death from cardiovascular causes or any cause. There were more patients with heart failure in the rosiglitazone group than in the control group (hazard ratio, 2.15; 95% CI, 1.30 to 3.57).Our interim findings from this ongoing study were inconclusive regarding the effect of rosiglitazone on the overall risk of hospitalization or death from cardiovascular causes. There was no evidence of any increase in death from either cardiovascular causes or all causes. Rosiglitazone was associated with an increased risk of heart failure. The data were insufficient to determine whether the drug was associated with an increase in the risk of myocardial infarction. (ClinicalTrials.gov number, NCT00379769 [ClinicalTrials.gov].).
<i>In utero</i> and perinatal complications preceding asthma
Authors: I. Annesi‐Maesano, D. Moreau, D. Strachan
Journal: Allergy (2001)

Background: It has been suggested that pregnancy and early life may influence the development of asthma in the offspring, but published studies have not carefully controlled for potential biases. Methods: In a large British birth cohort of 4065 natural children of 2583 mothers, we investigated whether in utero and perinatal influences contribute to the development and the severity of asthma in childhood, allowing for possible confounders of the relationship, and considering the nonindependence of familial data. Results: Child asthma (10.1%) was more frequently reported by mothers when there had been health complications during pregnancy (prevalence=14.3%; adjusted odds ratio [OR adj ]=2.01; 95% confidence interval, 1.52–2.67), labor, or delivery (19.3%, OR adj =1.35, 1.01–1.81); child illness or health complications during the first week of life (22.6%, OR adj =1.35, 1.01–1.82); and birth weight of &lt;2.5 kg (7.0%, OR adj =1.57, 1.10–2.25). Specific causes of health complications during pregnancy which significantly related to asthma were early or threatened labor ( ICD : 644) (4.8%, OR adj =1.58, 1.03–2.40) and the malposition or malpresentation of the fetus ( ICD : 652) (1.6%, OR adj =3.63, 1.47–8.91). Conclusions: The results provide further evidence that in utero and perinatal factors may increase the risk of developing asthma.
Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils.
Authors: D Campanelli, M Melchior, Y Fu, M Nakata, H Shuman, C Nathan, J E Gabay
Journal: The Journal of Experimental Medicine (1990)

Closely similar but nonidentical NH2-terminal amino acid sequences have been reported for a protein or proteins in human neutrophils whose bioactivities is/are diverse (as a serine protease, antibiotic, and Wegener's granulomatosis autoantigen) but that share(s) several features: localization in the azurophil granules, a molecular mass of approximately 29 kD, reactivity with diisopropylfluorophosphate, and the ability to degrade elastin. We previously purified one such entity, termed p29b. Using a monospecific antibody, we have cloned from human bone marrow a cDNA encoding the complete p29b protein in its mature form, along with pre- and pro-sequences. The predicted amino acid sequence agrees closely with the NH2-terminal sequence obtained previously from purified p29b, as well as with sequences newly obtained from CNBr fragments. The primary structure is highly homologous to elastase, cathepsin G, T cell granzymes, and other serine proteases, and shares both the catalytic triad and substrate binding pocket of elastase. Hybridization of the full-length cDNA with restriction enzyme digests of human genomic DNA revealed only one fragment. This suggests that the closely related species described previously are the same, and can be subsumed by the term used for the first-described activity, proteinase 3. Proteinase 3 is more abundant in neutrophils than elastase and has a similar proteolytic profile and specific activity. Thus, proteinase 3 may share the role previously attributed to neutrophil elastase in tissue damage, and has the potential to function as an antimicrobial agent.
THE CHOICE AND USE OF MEDICAL LITERATURE.
Authors: Hugh T Patrick
Journal: JAMA (1904)

The choice and the use of medical literature depend first on what the physician tries to be; not on what he would like to be, not on what his ideal may be, but on what he thoughtfully, consistently, persistently strives to be. <h3>KINDS OF PHYSICIANS.</h3> Our day-dreams of attainment are much the same, but the daily walk of physicians varies greatly. Most of us have met a physician who may be called the family factotum. He hobnobs with fussy mothers and puttering fathers. He is greatly interested in grandma's cough, knows just how to wash the baby, has his special poultice, and can take off warts. Dropping in to ask about Aunt Em's backache, he stays an hour visiting with the folks. He is a gentle and kindly soul, but his mind is occupied with the trivialities of medicine and domestic chit-chat. Then, there is our old friend who in
9/11 Study on Cancer Risk May Be Premature
Authors: M. Goozner
Journal: JNCI Journal of the National Cancer Institute (2011)

N E W Snonexposed colleagues, and that uncorrected number was statistically signifi cant.Elevated rates emerged for prostate and thyroid cancer, melanoma, non-Hodgkins lymphoma, multiple myeloma, and leukemia.With the prevalence of cancer in the general population, at least some of the increases were probably an artifact of the intensifi ed screenings that 9/11 fi rst responders in the study received.Screening can turn up tumors that may remain undetected and subclinical in nonscreened groups, the researchers said.Most fi refi ghters who worked at the site were enrolled in an ongoing health monitoring program and receive comprehensive blood screening every 12 -18 months.That may help account for the 21% increase in prostate cancer among the exposed fi refi ghters compared with the general population.The exposed group also receives routine chest x-rays and follow-up CT scans if they have asthma or other respiratory ailments, which were the major health problems documented among the police and fi refi ghters in the wake of 9/11.More than two-thirds of fi rst responders reported new or worsened breathing problems, according to a December 2006 study in Environmental Health Perspec tives , and the disproportionate number of CT scans given to that group may have detected the increases in thyroid cancers and lymphoma that the study found.
Cytokines and Late Preconditioning
Authors: D BUXTON
Journal: Cardiovascular Research (2004)

See article by Dawn et al.  [7]  (pages 61–71) in this issue .

It is now almost two decades since the first reports of ischemic preconditioning, the induction of cardiac tolerance to ischemic stress by a sublethal period of ischemia [1]. In the early 1990s, these findings were extended to show that preconditioning is a biphasic phenomenon; an early phase of preconditioning develops within minutes and lasts for 2 to 3 h, while a late phase is delayed until 12–24 h after the ischemic stress and lasts for 3 to 4 days [2,3]. In contrast to the early or “classic” phase of preconditioning, the heart is also protected against stunning during the late phase [4].

The late or delayed phase of ischemic preconditioning has attracted considerable attention because it holds the promise of clinically relevant manipulations that could be cardioprotective in patients with chronic ischemic heart disease. A large body of work has contributed to unraveling many of the mechanistic secrets that underlie late preconditioning. Stress signals, both ischemic and non-ischemic, activate signaling pathways that in turn lead to the activation of transcription factors. Transcriptional activation results in the synthesis of a number of protein effectors of late preconditioning, including inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX 2), aldose reductase, and mitochondrial manganese superoxide dismutase (Mn-SOD) [4,5]. Late preconditioning requires the parallel induction of multiple effectors, and blockade of synthesis of any of the … 

*Tel.: +1 301 435 0516; fax: +1 301 480 1454. E-mail address: db225a{at}nih.gov
Insulin Lipoatrophy-Reply
Authors: Thomas H. Whitley
Journal: JAMA (1976)

<h3>In Reply.—</h3> Drs Sachson and Feld make a valid point in that numerous examples of insulin lipoatrophy disappearing with direct injection of single-peak insulin have appeared. However, this phenomenon is not as straightforward as they seem to suggest. Several points appear worthy of consideration in this regard. First, lipoatrophy developed in our patient during the administration of single-peak insulin. In the reference cited by Drs Sachson and Feld, it is not clear what proportion of these patients were initially using single-peak insulin. Second, (in this report) 16 of 21 lipoatrophic areas were resolved, four showed improvement, and "several children reported that when injections were discontinued the reaccumulated fat had a tendency to disappear again." Third, since avoiding injections at a lipoatrophic site is the time-honored approach to this problem and since we (like Drs Ferland and Ehrlich?) instructed that injections be made around the edge of the atrophic area, one
Endoscopic Ultrasound and Endoscopic Ultrasound-Guided Fine-Needle Biopsy for the Diagnosis of Malignant Submucosal Tumors
Authors: M. Polkowski
Journal: Endoscopy (2005)

Epidemiological data are scant and imprecise, but approximately one in every 300 routine endoscopies reveals a bulging of the gastrointestinal wall covered by smooth mucosa of normal appearance [1] (Figure [1]). Such a finding, though usually incidental, raises questions of clinical significance: Does the bulging represent a pathology that is real or only a figment of the endoscopist's imagination? Does it result from pressure on the wall from the outside, and if so, what is the compressing structure? Or is there a tumor deep in the wall, under the smooth surface of the overlying mucosa, a so-called submucosal tumor (SMT)? Finally, and most importantly, what is the risk that the lesion in question is malignant and requires treatment?
Safety of thalidomide
Authors: C L Crawford
Journal: BMJ (1994)

Organisation's projections suggest that 1 in every 1000 people in India will be infected by 2000.2An Indian news magazine recently highlighted the problem of cross border trafficking by prostitutes from Nepal.' Commercial sex is an important route of transmission of HIV in Asian countries.At the heart of this problem is the complacency shown by the central government in New Delhi.It is astonishing that, while the numbers of cases of HIV infection and AIDS are rising, the programme budget remains underspent.'There is no coherent national strategy on conducting safe sex campaigns.Government departments shy away from giving explicit information about the spread of HIV.Campaigns through leaflets will have no role in rural areas owing to low literacy rates.But it is not too late to reverse the rising number of cases.Satellite television is now reaching the most remote parts of India.Both the government and voluntary organisations should be keen on using this in their fight against HIV infection and AIDS.
Incidence of Breast-feeding
Authors: G. McLintock
Journal: BMJ (1942)

<h3>Objective</h3> Mental health problems are prevalent in youth with rheumatologic disease. Gaps in knowledge exist regarding their effect, as well as strategies for detection and effective treatment. To address these gaps, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Mental Health Workgroup developed and prioritized an agenda of research topics. <h3>Methods</h3> We systematically reviewed the literature and identified 5 major research domains in further need of study: (A) mental health burden and relationship to pediatric rheumatologic disease, (B) effect of mental health disorders on outcomes, (C) mental health awareness and education, (D) mental health screening, and (E) mental health treatment. Research topics within these areas were developed by workgroup leaders and refined by the workgroup. Members were surveyed to prioritize the topics by importance, feasibility of study, and actionability. <h3>Results</h3> Fifty-nine members (57%) completed the survey. Among the proposed research topics, 31/33 were rated as highly important and 4/33 were rated highly for importance, feasibility, and actionability. Topics rated most important related to (A) mental health burden and relationship to rheumatologic disease, and (B) the effect of mental health on outcomes. Topics rated most feasible and actionable were related to (D) mental health screening. <h3>Conclusion</h3> Addressing gaps in knowledge regarding mental health in youth with rheumatologic disease is essential for improving care. We have identified high priority research topics regarding mental health of pediatric rheumatology patients in need of further investigation that are feasible to study and believed to lead to actionable results in patient care.
Inhibition of Chickenpox Lesions by Measles and Measles Rash by Chickenpox
Authors: Vernon Knight
Journal: JAMA (1973)

It has been noted on occasion that chickenpox and measles may occur together or one may precede the other by a few days. Artenstein and Weinstein<sup>1</sup>estimated that about 15 such cases occurred in the state of Massachusetts in 1961. On the other hand, Merigan et al<sup>2</sup>noted the occurrence of both diseases within a few weeks in seven of 18 children who were admitted to a youth guidance center. It is probable that double infections are more likely to occur when the patients are young and when opportunity for intense exposure to both agents is present. The most remarkable thing about these cases of double infection is the finding that the first infection may diminish the severity of the rash of the second infection. Evidence for interference with measles rash by chickenpox is based on the finding of clear zones of normal skin encircling healing chickenpox crusts
Impact of adjuvant therapy on quality of life in women with node-positive operable breast cancer
Authors: C. Hürny, J. Bernhard, M. Castiglione-Gertsch, A.S. Coates, H.F. Peterson, R.D. Gelber, J.F. Forbes, C-M. Rudenstam, E. Simoncini, D. Crivellari, A. Goldhirsch, H-J. Senn
Journal: The Lancet (1996)