tbuckley/cabot-search huggingface dataset:
Transferrin and transferrin receptor gene expression and iron uptake in hepatocellular carcinoma in the rat
Authors: Rosa Maria Pascale, Maria Rosaria De Miglio, Maria Rosaria Muroni, Maria Maddalena Simile, Lucia Daino, Maria Antonietta Seddaiu, Stefano Pusceddu, Leonardo Gaspa, Diego Calvisi, Giacomo Manenti, Francesco Feo
Journal: Hepatology (1998)

Iron plays an important role in cell growth and metabolism. In preneoplastic liver nodules, a rise in the number of transferrin receptors (Tf-R) is associated with decreased endocytosis of the Fe2-Tf/Tf-R complex. Because nodules are precursors of hepatocellular carcinoma (HCC), the question arises whether changes in iron uptake by nodules persist in HCC. Current work showed up-regulation of Tf messenger RNA (mRNA) production in preneoplastic nodules, 12 to 37 weeks after initiation, and down-regulation in atypical nodules (at 45 and 50 weeks) and HCCs, induced in rats by the "resistant hepatocyte" model. Tf-R gene expression increased in nodules and HCCs. Tf-R numbers increased, without changes in affinity constant, in HCC. Iron uptake was higher in HCC than in normal liver, 5 to 40 minutes after injection of 59Fe2-Tf, with preferential accumulation in cytosol of tumor cells and in microsomes of normal liver. Purification through Percoll gradient of mitochondria plus lysosomes allowed the identification in liver and HCC of an endosomal compartment sequestering injected 125I-Tf. This subfraction was not seen when 59Fe2-Tf was injected into rats, and 59Fe was found in particulate material of both tissues. Liver and HCC exhibited comparable basal activities of plasma membrane NADH oxidase, an enzyme involved in iron uptake and cell growth. Stimulation of this activity by Fe2-Tf was higher in HCC than in normal liver. These results indicate that Tf expression may be a marker of preneoplastic liver progression to malignancy. Differently from nodules, HCC may sequester relatively high iron amounts, necessary for fast growth, both through the endocytic pathway and the reduced form of nicotinamide adenine dinucleotide (NADH) oxidase system.
Improvement of chronic idiopathic urticaria with <scp>l</scp>‐thyroxine: a new TSH role in immune response?
Authors: M. Aversano, P. Caiazzo, G. Iorio, L. Ponticiello, B. Laganá, F. Leccese
Journal: Allergy (2005)

The association between chronic idiopathic urticaria (CIU) and autoimmune thyroiditis (AT) is known, as well as major prevalence of antithyroid antibodies in the allergical subjects and other autoimmune diseases. We have evaluated the effects of l-thyroxine on clinical symptoms of CIU in AT patients suggesting the hypothesis of a new thyroid-stimulating hormone (TSH) role in immune system.In 20 female patients with CIU + AT, both hypothyroid and euthyroid, we have investigated the therapeutic effects of l-thyroxine dosed to suppress the TSH. Free-T3, Free-T4, TSH, antithyroperoxidase and antithyroglobulin antibodies, total immunoglobulin (Ig)E, Rheuma test and eritro-sedimentation rate were monitored during treatment.In 16 patients a strong decrease of urticaria symptoms has happened after 12 weeks. The TPO Ab and HTG Ab clearly decreased in 14 patients. Furthermore, in two patients with rheumatoid arthritis and in two patients with pollen allergy a strong decrease of rheuma test titer and total IgE has happened.The reason of AT is associated to CIU and others allergical and autoimmune diseases is poorly known. The exclusive hormonal therapy reduces the symptoms of CIU and inflammatory response in many chronic diseases associated to AT. We suggest a stimulatory effect of TSH able to produce considerable changes of the immune response and immune tolerance in patients with AT causing target organs damage. The causal mechanism involves immune, nervous and endocrine system, sharing a common set of hormones, cytokines and receptors, in a unique totally integrated loop (the neuro-immuno-endocrine axis).
Effective management of health.
Authors: R F Logan, R E Klein, J S Ashley
Journal: BMJ (1971)

breaking down communication barriers.If this is a desirable end in itself then creation of more or less water-tight general- practitioner units within district general hospitals should be viewed with reservation.The isolated unit may be a geographical necessity in many areas, but problems of communication will rcmain unsolved unless frequent visits by specialists can be arranged. SHORTCOMINGSShortcomings in the delivery of health care in the U.S.A. derive from irregular distribution of resources-manpower and hospital-inherent in a system governed by the economic laws of supply and demand.Where facilities exist their utilization is efficient.Local over-provision, with corresponding deprivation in poor rural and urban ghetto areas, can be corrected only by federal government action.Together with the increasing and paralysing individual cost of care in hospital there are major problems requiring solution at political level.In Britain a relatively even distribution of care has been achieved, but at the cost of widespread mediocrity, so that it is necessary to strike a warning note in conclusion.A British graduate in medicine now enters a world market for his services.Probably clinical satisfaction is his main requirement after qualification and financial considerations are of secondary importance.The higher standards of vocational training now being implemented are going to raise the graduate's requirement for full facilities for investigation and treatment of his patients rather than otherwise.8These facilities are available only within hospital.The North American general practitioner enjoys them to the full, whereas his British opposite number is at present unlikely to have more than a limited access to them.In addition, the American general practitioner's income and standard of living arc appreciably higher than that of his British counterpart.Together these advantages exert a compelling influence on many of our most capable young doctors.It is beyond our power to remedy the financial differential, but to alter the British general practitioner's clinical opportunities by inte- grating him fully with the hospital service would cost nothing.It may demand faith, courage, and submission to an unwonted degree of discipline on his part.At its best in North America such integration produces some of the finest possible medical care.After 22 years of experimentation there is now no reason for the British National Health Service to aim at anything less.
A framework for the unification of the behavioral sciences
Authors: Herbert Gintis
Journal: Behavioral and Brain Sciences (2007)

The various behavioral disciplines model human behavior in distinct and incompatible ways. Yet, recent theoretical and empirical developments have created the conditions for rendering coherent the areas of overlap of the various behavioral disciplines. The analytical tools deployed in this task incorporate core principles from several behavioral disciplines. The proposed framework recognizes evolutionary theory, covering both genetic and cultural evolution, as the integrating principle of behavioral science. Moreover, if decision theory and game theory are broadened to encompass other-regarding preferences, they become capable of modeling all aspects of decision making, including those normally considered “psychological,” “sociological,” or “anthropological.” The mind as a decision-making organ then becomes the organizing principle of psychology.
Cost-Effective Diagnostic Imaging: The Clinician's Guide
Authors: Prentiss Taylor
Journal: JAMA (1995)

This handy little book is the work of experienced clinical radiologists from five institutions in New York State and Philadelphia. They guide the reader through discussion of the relative advantages and disadvantages of imaging study options in a diagnostic workup. Cost analysis is provided, using a national database with median costs that span different types of institutions, from the academic medical center to the rural community hospital. The authors thoughtfully provide total costs data that
Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet
Authors: Naoto Matsuzawa, Toshinari Takamura, Seiichiro Kurita, Hirofumi Misu, Tsuguhito Ota, Hitoshi Ando, Masayoshi Yokoyama, Masao Honda, Yoh Zen, Yasuni Nakanuma, Ken-ichi Miyamoto, Shuichi Kaneko
Journal: Hepatology (2007)

Recently, nonalcoholic steatohepatitis (NASH) was found to be correlated with cardiovascular disease events independently of the metabolic syndrome. The aim of this study was to investigate whether an atherogenic (Ath) diet induces the pathology of steatohepatitis necessary for the diagnosis of human NASH and how cholesterol and triglyceride alter the hepatic gene expression profiles responsible for oxidative stress. We investigated the liver pathology and plasma and hepatic lipids of mice fed the Ath diet. The hepatic gene expression profile was examined with microarrays and real-time polymerase chain reactions. The Ath diet induced dyslipidemia, lipid peroxidation, and stellate cell activation in the liver and finally caused precirrhotic steatohepatitis after 24 weeks. Cellular ballooning, a necessary histological feature defining human NASH, was observed in contrast to existing animal models. The addition of a high-fat component to the Ath diet caused hepatic insulin resistance and further accelerated the pathology of steatohepatitis. A global gene expression analysis revealed that the Ath diet up-regulated the hepatic expression levels of genes for fatty acid synthesis, oxidative stress, inflammation, and fibrogenesis, which were further accelerated by the addition of a high-fat component. Conversely, the high-fat component down-regulated the hepatic gene expression of antioxidant enzymes and might have increased oxidative stress. Conclusion: The Ath diet induces oxidative stress and steatohepatitis with cellular ballooning. The high-fat component induces insulin resistance, down-regulates genes for antioxidant enzymes, and further aggravates the steatohepatitis. This model suggests the critical role of lipids in causing oxidative stress and insulin resistance leading to steatohepatitis.
Abstract 16: Involvement of BH4 domain of bcl-2 in the regulation of HIF-1-mediated VEGF expression in hypoxic tumor cells
Authors: Chiara Gabellini, Daniela Trisciuoglio, Marianna desideri, Ylenia Ragazzoni, Teresa De Luca, Donatella Del Bufalo
Journal: Cancer Research (2011)

Abstract In addition to act as an antiapoptotic protein, bcl-2 can also promote tumor angiogenesis. In this context, we have previously demonstrated that under hypoxia bcl-2 promotes hypoxia inducible factor 1 (HIF-1) -mediated vascular endothelial growth factor (VEGF) expression in melanoma and breast carcinoma. Here, we report on the role of the BH4 domain in bcl-2 functions, by showing that removal of or mutations at the BH4 domain abrogates the ability of bcl-2 to induce VEGF protein expression and transcriptional activity under hypoxia in human melanoma cells. We have also extended this observation to other human tumor histotypes such as colon, ovarian and lung carcinomas. The involvement of BH4 on HIF-1α protein expression, stability, ubiquitination and HIF-1 transcriptional activity was also demonstrated in melanoma experimental model. Moreover, we validated the role of the BH4 domain of bcl-2 in the regulation of HIF-1/VEGF axis, demonstrating that BH4 peptide is sufficient to increase HIF-1α protein half-life impairing HIF-1α protein ubiquitination, and to enhance VEGF secretion in melanoma cells exposed to hypoxia. Finally we found that the mechanism by which bcl-2 regulates HIF-1-mediated VEGF expression does not require BH1 and BH2 domains, and it is independent of antiapoptotic and prosurvival function of bcl-2. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 16. doi:10.1158/1538-7445.AM2011-16
Is Medical School the Right Place to Choose a Specialty?
Authors: Sean Schafer, William Shore, Norman Hearst
Journal: JAMA (2001)

THE OPPORTUNITY TO GAIN exposure to the various fields of medicine en route to selecting a specialty.Each spring, the residency match process lights a fire under senior medical students.Interviewing applicants and residencies evaluate and rank each other prior to final placement by the National Residency Matching Program (NRMP).At many schools, the culminating event is a Match Day ceremony, where seniors gather to learn whether their efforts have merited entry into their program of choice.The agony and ecstasy of medical school crystallize into a single moment as the seal is broken on the envelope holding each graduate's match outcome.The result is met with elation and relief for many, disappointment for some.Most feel satisfaction at advancing closer to a career, perhaps mingled with regret at leaving other options behind.Even amid the jubilation, an undercurrent of anticipation and trepidation is palpable at the prospect of assuming real responsibilities.In 2001, 93.7% of graduating allopathic US medical students matched into residency, accounting for 73.8% of the 18354 positions filled by the NRMP. 1 An additional 4215 positions were filled by US osteopathic applicants, US international medical graduates (IMGs) and non-US IMGs.Overall, available positions in primary and specialty care both showed an 89% fill rate, although entry into primary care was down 3.6% compared to 2000. 1 Residency training is a relatively new development in medical education. 2 In the early 1900s, medical school was considered adequate preparation for general practice.Expansion of information by the 1920s necessitated a "rounding out" year of internship.Specialty training (a privilege reserved for only the most promising candidates) was also launched around this time.Required to live on hospital grounds, these intrepid and typically unpaid souls were aptly dubbed "residents."Although much of their time was spent caring for patients, resident physicians also languished in laboratory and custodial work.The process could take many years, advancement was arbitrary, and attrition was high.Some physicians eschewed this pathway and sought specialty training abroad; others proclaimed themselves specialists after brief, unregulated study.The quality of postgraduate education varied widely.The lack of standardization was addressed in the 1930s with the establishment of many specialty boards.By the 1950s, residents exceeded medical students in number and specialist physicians exceeded generalists.A match plan (similar to today's) was established in 1951.Further refinements included salaries for residents and relaxation of rules pertaining to personal life.The 1970s saw merging of internship and residency as well as proliferation of subspecialty and fellowship training.Electronic application was recently introduced.How will the residency selection process continue to evolve?jms060601f1scan
Interrupting the sympathetic outflow in causalgia and reflex sympathetic dystrophy
Authors: G D Schott
Journal: BMJ (1998)

Causalgia and reflex sympathetic dystrophy are poorly understood disorders that most commonly follow trauma to a limb, although they are also seen in other medical conditions. Patients typically develop chronic burning pain, together with various combinations of sensory disturbances, swelling, and vasomotor, sudomotor, and trophic changes.1-3 Traditionally, the pain is treated by interrupting the sympathetic supply to the painful area. Is this an effective approach?

Periarterial sympathectomy was first used to treat causalgia, in which, by definition, major nerve injury occurs. Various forms of surgical sympathectomy have subsequently been carried out, 3 4 especially during war time, when controlled trials were not feasible, and so whether surgery was truly effective will never be known. Open surgical sympathectomy to relieve pain in causalgia and related conditions is rarely recommended now, not least because less invasive procedures—including endoscopic sympathectomy and percutaneous radiofrequency lesioning of the sympathetic trunk—have been developed, although critical evaluation of efficacy is awaited.4

For several decades, …
A piece of mind. Dit dit
Authors: M. L. Evans
Journal: JAMA (1990)

A mere pair of "dits" conveys a lot of meaning to an experienced ham radio operator. Superficially, they're the Morse code version of "shave and a haircut—six bits." At the end of a telegraphic contact, the first operator sends "dit di-di dit dit." The listening op replies, "dit dit." To hams, "dit dit" can mean myriad things—from "stand by, I'm looking for a pencil" to a shortened version of "hi hi" (the telegraphic "ha ha"). Say one operator gets a phone call. Hearing silence, the other op sends "?"—di-di dah dah di-dit. The ham on the phone casually reaches for the key and taps, "dit dit."<i>I'm here. No need to worry. The electricity didn't go out, I'm not having a heart attack. Dit dit. I'm still with you. You're not alone</i>. Close ham radio friends often make daily or weekly "skeds," or schedules, on a certain frequency at a
Abstract 3057: CDK5 modulates the cell cycle, apoptosis and paclitaxel sensitivity in human ovarian cancer cells with wild-type p53 function
Authors: Shu Zhang, Weiqun Mao, Ahmed A. Ahmed, Zong-Fang Li, Xiao-Feng Le, Robert C. Bast
Journal: Cancer Research (2012)

Abstract Cyclin-dependent kinase 5 (CDK5) is a ubiquitously expressed serine/threonine kinase that was initially identified in bovine brain extracts and plays an important role in normal neuron development and neurodegenerative diseases. This molecule has recently been shown to possess many cellular functions in non-neuronal tissues as well. Using a kinome siRNA screen, we identified CDK5 as a kinase that modulates paclitaxel sensitivity in human ovarian cancer cells. The aim of this report is to identify mechanisms by which CDK5 regulates paclitaxel sensitivity in human ovarian cancer cells. Despite nucleotide sequence homology with human CDK1, a role of CDK5 in regulating the cell cycle remains unclear. Here we demonstrate dual roles of CDK5 in regulating the cell cycle and apoptosis. We have found that knockdown of CDK5 with multiple siRNAs markedly inhibits cell proliferation and increases paclitaxel sensitivity in several p53 wild type ovarian cancer cell lines using assays for cell viability and clonogenic growth. CDK5 knockdown with or without paclitaxel treatment induces G1 arrest of the cell cycle and apoptotic cell death linked to a significant induction of p53, p21Cip1 and p27Kip1 proteins. Induction of G1 arrest following CDK5 knockdown depends on induction of p21Cip1 and p27Kip1, since silencing p21Cip1 and/or p27Kip1 dramatically reduces CDK5 knockdown-induced G1 arrest. A CDK5 knockdown-induced increase of p53 expression contributes both to CDK5 knockdown-induced G1 arrest and to apoptosis, as silencing p53 markedly diminishes CDK5 knockdown-induced G1 arrest and apoptosis. As expected, a CDK5 knockdown-induced increase in p21Cip1 expression depends on p53-mediated transcriptional activation demonstrated by QRT-PCR and reporter luciferase assays. CDK5 knockdown activates caspase-3 and a pan-caspase inhibitor completely blocks CDK5 knockdown-induced apoptosis. Significant Inhibition of Bcl-2 expression is found in CDK5 knockdown-induced apoptosis and additional inhibition of Bcl-2 expression is found with combined CDK5 and paclitaxel treatment. Taken together, these data suggest that CDK5 can modulate paclitaxel sensitivity through regulating both the cell cycle and apoptosis. CDK5 inhibition can potentiate paclitaxel activity in human ovarian cancer cells with wild-type p53 function, providing a novel approach for enhancing the efficacies of paclitaxel-based regimens for low grade ovarian cancer in the clinic. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3057. doi:1538-7445.AM2012-3057
Risks of Postmenopausal Hormone Replacement
Authors: Beverley E. Pearson Murphy
Journal: JAMA (2002)

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Physiology of the Retina and Visual Pathway
Authors: William F. Hoyt
Journal: JAMA (1971)

Professor Brindley, an acknowledged English expert on visual physiology, has revised his little book that appeared first in 1960. The format is essentially unchanged: more than half of the book is still devoted to the author's particular interest in the psychophysiology of vision. In the preface, the author acknowledges that he has purposely stressed his own contributions in order to satisfy his "obligation" to the reader, even if intentional omission of certain contributions by others appears "idiosyncratic." The first three chapters summarize photochemical processes in the retina, new findings on the origin of the ERG (electroretinogram) in vertebrates, and the function of retinal cells, particularly horizontal and amacrine cells, as described several years ago in<i>Necturus</i>(the mud puppy) by Dowling and co-workers. The fourth chapter, "The Central Pathways of Vision," devotes as much space to discussions of cortically evoked phosphenes in man as it does to the exciting findings
Synergism of platelet-aggregating agents. Role of elevation of cytoplasmic calcium.
Authors: J A Ware, M Smith, E W Salzman
Journal: Journal of Clinical Investigation (1987)

When a pair of platelet agonists, each in subthreshold concentration, is added together or in sequence to a platelet suspension, the platelet response is enhanced. Addition of two agonists to platelets loaded with aequorin also enhanced the observed rise in cytoplasmic ionized calcium ([Ca2+]i) in response to the second agonist if the agonists were added within 20 s of each other. Enhancement of aggregation and secretion required that an increase in [Ca2+]i (as indicated by aequorin but not necessarily indo-1) followed the first agonist, but not that the [Ca2+]i remain elevated until addition of the second agonist. Enhancement was not prevented by aspirin, ADP scavengers, or chelators of extracellular Ca2+. We conclude that a rise in [Ca2+]i induced by a first agonist "primes" platelets for an augmented functional response to a second agonist, which is not, however, determined by the [Ca2+]i at the time of addition of the second agonist.