tbuckley/cabot-search huggingface dataset:
Abstract 3372: Constraints-based metabolic flux analysis approach links tumor stage to metabolic adaptations and survival in cancer cells
Authors: Abhinav Achreja, Lifeng Yang, Hongyun Zhao, Juan Marini, Deepak Nagrath
Journal: Cancer Research (2014)

Abstract The Warburg effect has been observed in many cancers and their high glycolytic capacity has signified their dependence on glucose. More recently, glutamine has emerged not only as an important nutrient for many cancers, but also necessary for their elevated energetic requirements. Due to these high energetic demands, certain cancer cells become addicted to glutamine to maintain viability. We postulate that distinct metabolic reconfigurations of certain cancers define their dependence or independence on glutamine for survival while maintaining their proliferative propensity and redox status. An intricate picture of the metabolic profiles is to be drawn from estimating intracellular fluxes, by combining stable isotope tracer measurements and experimental metabolomics data from different cancer cell lines, which have been observed to be glutamine dependent and independent. To this extent, we describe an approach that utilizes a redox-balanced model incorporating the electron transport chain and comprehensive amino-acid metabolic reactions to elucidate the importance of oxidative phosphorylation, often overlooked in classical approaches. Diving deeper into the foray of metabolic reprogramming, we perform in silico experiments using a constraint-based multi-objective modeling approach. This methodology elucidates the switching of metabolic pathways in glutamine-dependent and -independent cancers under nutrient-available and nutrient-deprived conditions. Our approach assumes that cancer cells operate at optimal levels, maintaining multiple objectives under certain environmental conditions. Constraining the proliferative phenotype from a maximal to minimal levels of the cells under different nutrient conditions emulates the observed behavior of glutamine-dependent cells under deprivation conditions and contrasts their metabolic reprogramming against that of glutamine-independent cells. We corroborated our simulations with experimentally derived metabolic fluxes and found that glutamine anabolism over catabolism dictates adaptations and survival in invasive cancers. Our results will lead to identification of potential targets for inducing nutrient-sensitivity and enhance current therapeutic approaches. Citation Format: Abhinav Achreja, Lifeng Yang, Hongyun Zhao, Juan Marini, Deepak Nagrath. Constraints-based metabolic flux analysis approach links tumor stage to metabolic adaptations and survival in cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3372. doi:10.1158/1538-7445.AM2014-3372
On Certain Complications of the Nervous System, as Sequelae of Fevers
Authors: J. W. Ogle
Journal: BMJ (1867)

swelling which appeared in his thigh.It involved all this part of the limb; and arose from some cause evidently below the fascia; in fact, it so much re- sembled at first sight, and upon manipulation, a limb affected with acute necrosis of the bone, with separa- tion of the periosteum and effusion underneath it, that I quite thought that this had taken place.A few days, however, disclosed the following very unusual state.The thigh was full of pus, suddenly produced by the bursting of the great reservoir of matter in the knee-joint.The swelling of the knee subsided a little; but the pain was as bad as ever.As the hole in the capsule of the knee-joint gave vent to the pus under cover of the muscles, there was but little chance of the pointing of the abscess;and in a short time I let out three pints of thick well- formed pus, by an incision a little above the knee through the vastus externus muscle.
Estrogen and Postmenopausal Osteoporosis
Authors: Gilbert S. Gordan
Journal: Annals of Internal Medicine (1993)

Letters15 January 1993Estrogen and Postmenopausal OsteoporosisGilbert S. Gordan, MDGilbert S. Gordan, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-2-199301150-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:As one of Fuller Albright's students, I was gratified to read in the 1 July Annals [1, 2] that the value of estrogen replacement therapy for postmenopausal osteoporosis, first reported by him to the Association of American Physicians over half a century ago [3] has been finally recognized. In 1973, we reported that estrogen reduced fractures in women with advanced osteoporosis as shown by roentgenographic and height measurements [4]. Androgens and anabolic steroids were less effective. A number of other beliefs about osteoporosis and hormone replacement therapy need to be clarified, such as the belief that only ...References1. Lufkin EG, et al. Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med. 1992; 117:1-9. Google Scholar2. Ott SA. Estrogen therapy for osteoporosis—even in the elderly (Editorial). Ann Intern Med. 1992; 117:85-6. Google Scholar3. Albright F, et al. Post-menopausal osteoporosis. Trans Assoc Am Physicians. 1940; 55:298-305. Google Scholar4. Gordan GS, et al. Antifracture efficacy of long-term estrogens for osteoporosis. Trans Assoc Am Physicians. 1973; 86:326-32. Google Scholar5. Stampfer MJ, et al. Postmenopausal estrogen therapy and cardiovascular disease: ten year follow-up from the Nurses' Health Study. N Engl J Med. 1991; 325:756-62. Google Scholar Author, Article, and Disclosure InformationAuthors: Gilbert S. Gordan, MD PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byBone turnover alterations across the menopausal transition in south-eastern Chinese women 15 January 1993Volume 118, Issue 2Page: 155-156KeywordsEstrogen replacement therapyEstrogensHormone replacement therapyLipid metabolismMedical risk factorsMenopauseOsteoporosisProgesteroneStable coronary artery diseaseSteroids ePublished: 15 August 2000 Issue Published: 15 January 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Urea stimulation of KCl cotransport induces abnormal volume reduction in sickle reticulocytes
Authors: Clinton H. Joiner, R. Kirk Rettig, Maorong Jiang, Mary Risinger, Robert S. Franco
Journal: Blood (2006)

Abstract KCl cotransport (KCC) activity contributes to pathologic dehydration in sickle (SS) red blood cells (RBCs). KCC activation by urea was measured in SS and normal (AA) RBCs as Cl-dependent Rb influx. KCC-mediated volume reduction was assessed by measuring reticulocyte cellular hemoglobin concentration (CHC) cytometrically. Urea activated KCC fluxes in fresh RBCs to levels seen in swollen cells, although SS RBCs required lower urea concentrations than did normal (AA) RBCs. Little additional KCC stimulation by urea occurred in swollen AA or SS RBCs. The pH dependence of KCC in “euvolemic” SS RBCs treated with urea was similar to that in swollen cells. Urea triggered volume reduction in SS and AA reticulocytes, establishing a higher CHC. Volume reduction was Cl dependent and was limited by the KCC inhibitor, dihydro-indenyl-oxyalkanoic acid. Final CHC depended on urea concentration, but not on initial CHC. Under all activation conditions, volume reduction was exaggerated in SS reticulocytes and produced higher CHCs than in AA reticulocytes. The sulfhydryl-reducing agent, dithiothreitol, normalized the sensitivity of KCC activation to urea in SS RBCs and mitigated the urea-stimulated volume decrease in SS reticulocytes, suggesting that the dysfunctional activity of KCC in SS RBCs was due in part to reversible sulfhydryl oxidation.
Serum Transaminase Elevations and Other Hepatic Abnormalities in Patients Receiving Isoniazid
Authors: LAWRENCE SCHARER
Journal: Annals of Internal Medicine (1969)

Elevations of serum transaminase levels, both serum glutamic-oxalacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT), were observed in 10% of asymptomatic patients during the first 2 months of isoniazid (INH) administration. Reactions occurred both in hospitalized tuberculosis patients and in healthy hospital employees receiving INH chemoprophylaxis. Hospitalized patients in whom the drug was interrupted showed a prompt return of the enzyme levels to normal. Liver biopsy performed in five of eight patients showed hepatocellular damage during the reaction. Resumption of INH therapy without transaminase elevation was later effected in all of these patients. Isoniazid was not interrupted in seven of nine healthy subjects who showed asymptomatic serum enzyme abnormalities during INH chemoprophylaxis. This reaction was self-limited with return of SGOT and SGPT levels to normal over a variable period of time. In one patient with sustained elevations liver biopsy showed hepatocellular damage. Further study is required to evaluate the possibility of occult liver damage due to isoniazid.
Endocrine Aspects of Cancer Gene Therapy
Authors: Luisa Barzon, Marco Boscaro, Giorgio Palù
Journal: Endocrine Reviews (2004)

The field of cancer gene therapy is in continuous expansion, and technology is quickly moving ahead as far as gene targeting and regulation of gene expression are concerned. This review focuses on the endocrine aspects of gene therapy, including the possibility to exploit hormone and hormone receptor functions for regulating therapeutic gene expression, the use of endocrine-specific genes as new therapeutic tools, the effects of viral vector delivery and transgene expression on the endocrine system, and the endocrine response to viral vector delivery. Present ethical concerns of gene therapy and the risk of germ cell transduction are also discussed, along with potential lines of innovation to improve cell and gene targeting.
1-123 MIBG Scintigraphy in Adults
Authors: ABDELHAMID H. ELGAZZAR, MICHAEL J. GELFAND, LEE C. WASHBURN, JAMES CLARK, NIRMALA NAGARAJ, DWIGHT CUMMINGS, JUDY HUGHES, HARRY R. MAXON
Journal: Clinical Nuclear Medicine (1995)

Thirty-one adult patients with clinical findings suggestive of pheochromocytoma were studied with I-123 MIBG. All patients had images obtained at 24 and 48 hours. Five patients had abnormal uptake proved to be because of H23 MIBG avid tumors. The remaining 26 patients had no proven tumors and showed physiologic uptake in various organs. The 24-hour images were of high quality. In all cases, the 48-hour images contributed no significant additional information. Only in 1 patient did the 48-hour image add some certainty. Physiologic uptake was seen in the salivary glands, liver, G.I. tract, and urinary bladder in all patients (100%). Uptake was also observed in the lung and heart (90%), normal adrenal glands (32%), thyroid (29%), spleen (23%) uterus (13%), and neck muscles (6%). The authors' experience indicates that I-123 MIBG gives superior images compared to the previously used I-131 MIBG, that the optimum imaging time for adults is 18–24 hours, and that normal distribution patterns including uterine and neck muscle uptake should be familiar to physicians interpreting the studies.
Are New Zealand's new primary health organisations fit for purpose?
Authors: Robin Gauld, Nicholas Mays
Journal: BMJ (2006)

Attempts to make New Zealand's health care more equitable have resulted in rapid change.But the reforms are largely untested and their effects difficult to predict Evidence is growing that primary care has a crucial role in healthcare systems. 1 Governments therefore need to ensure that they get any reforms right.In the United Kingdom, attempts to improve primary care through competition between existing general practices and new corporate entrants have been suggested to undermine some of its strengths: quality, efficiency, and equity. 2The New Zealand government has also pursued a bold strategy for improving primary care.Irrespective of its merits in principle, the strategy has produced a wide variety of organisations of varying capability and complex funding arrangements.We assess the changes and their likely effects.
Menarche and Puberty in Daughters of Amenorrheic Women
Authors: Zion Ben-Rafael
Journal: JAMA (1983)

Twenty-six daughters born to amenorrheic women after gonadotropin-induced ovulation were studied at 10 to 16 years of age. The aim of the study was to assess whether the mothers' condition, namely, amenorrhea and infertility followed by the pharmacologic induction of ovulation, had any effect on their female offspring in terms of endocrine disorders at puberty. The daughters were found to have normal onset of puberty as well as normal physical and mental development. The mean age at menarche, body weight, and height were similar to those of the general female population in Israel. A functioning hypothalamic-pituitary-ovarian axis was evidenced by the appearance of menarche followed by regular cycles. These data form a reassuring sample for the clinicians, the treated mothers, and their offspring.
A National Study of Ethics Committees
Authors: Glenn McGee, Joshua P. Spanogle, Arthur L. Caplan, David A. Asch
Journal: The American Journal of Bioethics (2001)

Conceived as a solution to clinical dilemmas, and now required by organizations for hospital accreditation, ethics committees have been subject only to small-scale studies. The wide use of ethics committees and the diverse roles they have played compel study. In 1999 the University of Pennsylvania Ethics Committee Research Group (ECRG) completed the first national survey of the presence, composition, and activities of U.S. healthcare ethics committees (HECs). Ethics committees are relatively young, on average seven years in operation. Eighty-six percent of ethics committees report that they played a role in ongoing clinical decision making through clinical ethics consultation. All are engaged in developing institutional clinical policy. Although 4.5% of HECs write policy on managed care, 50% of HEC chairs feel inadequately prepared to address managed care. The power and activity of ethics committees parallels the composition of those committees and the relationship of members to their institutions. The role of ethics committees across the nation in making policies about clinical care is greater than was known, and ethics committees will likely continue to play an important role in the debate and resolution of clinical cases and clinical policies.
Positional effect of cis/trans alpha globin gene deletions on the formation of “H” bodies
Authors: C. C. Thompson, M. A. M. Ali, S. Boyadjian, M. Vacovsky
Journal: American Journal of Hematology (1989)

Abstract Normal individuals have four AaL‐globin genes, two on each member of the chromosome 16 pair (αα/αα). The α‐thalassemia trait phenotype associated with deletions of two α‐genes can be either on the same chromosome, the cis type (αα/—), or on opposite chromosomes, the trans type (α‐/α‐). Traditionally, the observation on vitally stained smears of occasional cells containing “H” bodies has been used as an important diagnostic criterion for α‐thalassemia trait. These “H” bodies are thought to be precipitated β tetramers because of the presence of excess β‐globin chains. Our study in patients with various α‐genotypes indicates that normal subjects (αα/αα) and patients with silent α‐thalassemia trait (αα/α‐) generally have no “H” bodies. However, patients with the two‐gene deletion of the cis type α‐thalassemia (αα/—) show the occasional “H” body, and those with Hb “H” disease (α‐/—or α cs ‐/—) show many such bodies. On the other hand, patients with two‐gene deletion of the trans type (α‐/α‐) do not show “H” bodies. The number of “H” bodies found does not appear to correlate directly with the degree of imbalance in α‐ and β‐chain production among the various α‐genotypes examined. The chemical nature of “H” bodies is discussed, and an alternative hypothesis that embryonic ζ chains expressed in the cis type but not in the trans type of α‐thalassemia are involved in the formation of “H” bodies is proposed.
Detection by Competitive Enzyme-Linked Immunosorbent Assay of a Bovine Serum Albumin Peptide (ABBOS) in Infant Formulas Based on Hydrolyzed Cow's Milk Protein
Authors: Emerentia C H Van Beresteijn, Ron J G M Meijer
Journal: Diabetes Care (1996)

Our aim was to determine whether currently available products based on hydrolyzed milk protein and a small peptide (ABBOS) in bovine serum albumin (BSA) (positions 126-144) share common antigenic sites. The commercial products are primarily developed to reduce cow's milk protein-associated allergenicity, but whether they also could be used in intervention trials to elucidate the role of BSA in the etiology of IDDM is not known.A sensitive competitive enzyme-linked immunosorbent assay (ELISA) using a rabbit polyclonal antibody raised against the ABBOS peptide in BSA was developed. With this method, we determined cross-reactivity between the ABBOS peptide and commercially available products: four milk protein hydrolysates and eight infant formulas based on hydrolyzed milk protein. The products were further characterized by physicochemical techniques.Hydrolyzed milk protein products are found to inhibit competitively the binding of ABBOS peptide to antibody. The number of residual reactive sites varied considerably among products and was not strongly related to the degree of hydrolysis (DH) or the molecular mass distribution of the hydrolysates.The presence of possible immunoreactive peptides in infant formulas based on hydrolyzed cow's milk protein cannot be adequately predicted by the DH or molecular mass distribution of the hydrolysates. Its specific determination is needed to ensure infant formulas free of cross-reactive ABBOS antibody binding sites for use in ongoing and forthcoming intervention trials to elucidate the role of BSA as a possible environmental triggering agent of IDDM.
MICRORNA-20A RESTORES CARDIAC FUNCTION IN P300 HYPERTROPHIC HEARTS BY TARGETING P300 AND P300-DRIVEN ANGIOGENIC PROGRAM IN CARDIAC MYOCYTES AND CARDIAC PROGENITOR CELLS
Authors: Lina A. Shehadeh, Salil Sharma, JianQin Wei, Monica Pessanha, Claudia Rodrigues, Huijun Yuan, Michaela Scherr, Robert Duerr, Jing Liu, Nicholas Tsinoremas, Nanette Bishopric
Journal: Journal of the American College of Cardiology (2011)
Acute Intrahepatic Biliary Obstruction Caused by Hydatid Cysts Correlation Between Various Imaging Techniques
Authors: R. H. BAHAR, S. H. AL-MOHANNADI, I. WAFAI, A. R. AL-SUHAILI, H. M. ABDEL-DAYEM
Journal: Clinical Nuclear Medicine (1988)

An 18-year-old male was evaluated for recurrent attacks of right abdominal pain and intermittent jaundice caused by hydatid cysts of the liver. The case illustrates the value of dynamic functional information provided by Tc-99m-HIDA imaging over noninvasive modalities that demonstrate structural changes, such as ultrasound, computed tomography, and tin colloid liver imaging.
Pointing the way to a unified theory of action and perception
Authors: Mel Goodale
Journal: Behavioral and Brain Sciences (1997)

Deictic coding offers a useful model for understanding the interactions between the dorsal and ventral streams of visual processing in the cerebral cortex. By extending Ballard et al.'s ideas on teleassistance, I show how dedicated low-level visuomotor processes in the dorsal stream might be engaged for the services of high-level cognitive operations in the ventral stream.
Nonenzymatically Galactosylated Serum Albumin in a Galactosemic Infant
Authors: Joseph C. Urbanowski, Menashi A. Cohenford, Harvey L. Levy, John D. Crawford, Joel A. Dain
Journal: New England Journal of Medicine (1982)

Galactosemia is a molecular disease of genetic origin that is characterized by a deficiency of galactose-1-phosphate uridyltransferase.1 , 2 The resulting severe impairment of galactose metabolism has been recognized for over half a century, and the frequency of this disorder is estimated to be one to four in 100,000 births.3 , 4 Generally, the biochemical phenotype includes elevated concentrations of galactose, galactose-1-phosphate, and galactitol in tissue and body fluids.2 In neonates the clinical sequelae consist of vomiting, jaundice, hepatosplenomegaly, and death, and in surviving infants cirrhosis of the liver, mental retardation, and cataracts occur as chronic complications if dietary galactose is not restricted. 2 , 3 , 5 Sepsis . . .
THE CHALLENGE OF TENDON PAIN
Authors: B Vicenzino
Journal: British Journal of Sports Medicine (2013)

Most patients with tendinopathy report pain interfering with their physical capacity to perform to expectation, either at sport, recreation or work. Tendinopathy is a diagnosis associated with collagen disruption, increased tenocytes and ground substance, and neovessels. The relationship between these local tendon changes and patients' reported pain and disability is not a direct one, which necessitates the clinician to use clinical reasoning skills in interpreting the presenting signs and symptoms in light of the best available evidence. At this clinician-patient interface, a salient adage with which most would be familiar is: ‘Treat the patient not the disease (diagnostic image/diagnosis/pathology test result)’. For example, arthritic changes on x-ray do not match patient symptoms and level of disability. The mismatch between the pathology and presenting patient's pain and disability is particularly applicable for tendon, given that studies have shown that there is not a direct relationship between pathological findings on diagnostic imaging with reported pain and disability. Understanding pain and its underlying processes/mechanisms is imperative, if management approaches are to be advanced/optimised. Recent findings of local pathological changes in the tendon of the non-exercised/injured limb in experimental animal models of tendinopathy have further increased the imperative to better understand the pain and disability associated with tendon problems. These bilateral changes in unilateral injured tendons are paralleled by recent findings from quantitative sensory testing in human studies, which I propose serves as an impetus for better understanding tendon pain and disability. Quantitative sensory testing has shown that mechanical hyperalgesia is a characteristic of tendinopathy, not only locally at the site of the presenting condition (in unilateral cases) but also in the contralateral tendon site, as well as remotely (eg, at the tibialis anterior muscle for lateral epicondylalgia). It has been proposed that this widespread mechanical hyperalgesia is indicative of sensitisation of the central nervous system. Further work has shown that there is heightened spinal cord excitability to a noxious stimulus (that is, nociceptive flexor reflex) and a reduction in efficacy of endogenous pain modulation (inhibition) to a conditioning noxious stimulus, both of which imply abnormal endogenous pain inhibition mechanisms. These studies are cross sectional and thus it remains unknown if the central nervous system changes precede or follow the onset of tendinopathy. Nevertheless they contribute further to our understanding of tendon pain. Improved understanding of the mechanisms underlying tendon pain will better enable the clinician to treat the patient not the disease.