tbuckley/cabot-search huggingface dataset:
Polythiazide and Chlorothiazide
Authors: James H. Currens
Journal: JAMA (1963)

<h3>To the Editor:</h3> —The editorial, "Clinical Evaluation of New Drugs" (<b>184:</b>233 [April 20] 1963), and the article by Dr. Spiekerman and his colleagues in the same issue ofThe Journal(p 191) were read with interest. I am surprised that more attention was not devoted to the duration of action of chlorothiazide as compared with polythiazide, since this is rather elementary in the pharmacology of these two drugs. Chlorothiazide has an action of about 6 hours, so that there would be about 12 hours of each day when the patient would have little or no thiazide effect. Polythiazide, on the other hand, has a duration of action of 24 to 36 hours, so that the patient would have continuous effect from polythiazide on daily dosage. In my experience with polythiazide, because of this prolonged action, it has been necessary to use only a 2-mg dosage administered every second day.
Notch3 Functions as a Tumor Suppressor by Controlling Cellular Senescence
Authors: Hang Cui, Yahui Kong, Mei Xu, Hong Zhang
Journal: Cancer Research (2013)

Abstract Notch signaling regulates a broad spectrum of cell fate decisions and differentiation. Both oncogenic and tumor suppressor functions have been shown for Notch signaling. However, little is known about the underlying mechanisms of its tumor suppressor function. Here, we report that expression of Notch3, a member of Notch family transmembrane receptors, was elevated in human cells during senescence activated by various senescence-inducing stimuli. This upregulation of Notch3 was required for the induction of p21 expression in senescent cells. Downregulation of Notch3 led to a delayed onset of senescence and extended replicative lifespan, whereas adventitious expression of Notch3 was sufficient to activate senescence and p21 expression. The ability of Notch3 to induce senescence and p21 expression was dependent on the canonical Notch singling. Deletion of p21 in cells significantly attenuated Notch3-induced senescence. Furthermore, a significant decrease in Notch3 expression was observed in human tumor cell lines as well as primary human breast cancer and melanoma samples compared with normal tissues. Restoration of Notch3 expression in human tumor cells resulted in inhibition of cell proliferation and activation of senescence. Collectively, our results reveal a novel function of Notch3 in senescence regulation and tumor suppression. Cancer Res; 73(11); 3451–9. ©2013 AACR.
The Posterior Cerebral Radionuclide Angiogram for the Detection of Carotid Artery Disease
Authors: RENATO ARMAS, J ROBERT KIRKWOOD, SAID ZUBI
Journal: Clinical Nuclear Medicine (1981)

To determine the accuracy of the posterior cerebral radionuclide angiogram (CRAG) in the detection of carotid occlusive disease, a retrospective study of 186 patients who underwent both CRAG and contrast cerebral angiography within a period of 30 days was carried out. Asymmetry of neck activity was highly specific (97%) but insensitive (27%) for detection of carotid disease. When asymmetry of cerebral perfusion was also considered, the sensitivity rose to 61%, but the specificity fell to 77%. For the entire group, including carotid and intracerebral disease, the sensitivity of the posterior CRAG was 49% and the specificity 89%. From these data and a review of the literature, we conclude that the CRAG is too insensitive to be used as a screening test for carotid occlusive disease.
Genotype linked to long QT syndrome
Authors: D. Josefson
Journal: BMJ (1998)

The clinical course of the congenital long QT syndrome, a hereditary arrhythmic disorder, can be predicted through genotypic analysis, according to researchers from the University of Rochester researchers (New England Journal of Medicine , 1998;339:960-5).

This is the first research that has found a link between variations in genotype and differential clinical disease expression, and the finding may allow doctors to tailor the treatment of patients who have the syndrome according to their genotype.

The long QT syndrome is caused by defective ventricular repolarisation leading to abnormally long pauses between heart beats. The prolonged pauses can cause …
Medicine Over There
Authors: Alister Brass
Journal: JAMA (1970)

Can any good thing come out of Indochina except half a million Americans on their way home? Ironically, yes: advances in medical knowledge and, for those physicians who have spent time there, a world of experience they could never have gained at home. This paradox is brought out in two fine new books<sup>1,2</sup>by physicians who are Vietnam veterans. But though Dr. Bourne and Dr. Eccles Smith both write as medical specialists— Bourne as a psychiatrist with a team studying stress from the Walter Reed Army Institute of Research, Eccles Smith the surgeon in charge of a civilian hospital in a battered coastal province—the scope of their reporting goes beyond the clinical. Their stories will give scant comfort to those who believe that the "battle for the hearts and minds" of the Vietnamese is being won by the government of the South and its allies, and that without peace
[452] CHRONIC HEPATITIS C IS CHARACTERISED BY AN
Authors: C. Liaskos, D.P. Bogdanos, N. Gatselis, M. Homer, Z. Shums, D. Murphy, E.I. Rigopoulou, H. Smith, D. Vergani, G.L. Norman, G.N. Dalekos
Journal: Journal of Hepatology (2007)
ORTHOPEDIC OPERATIONS ON THE HAND
Authors: ARTHUR STEINDLER
Journal: JAMA (1918)

Unusual as the opportunities are for reconstruction work on the upper extremity, they are counterbalanced by an adequate amount of technical difficulties. To overcome these, investigation into numerous questions of a theoretical as well as a technical nature becomes necessary. Some detail work has been devoted to the solution of surgical problems; much less attention has been given to the study of the principles of a mechanical or a physiologic nature. Yet it would seem that mechanical and physiologic analysis is as essential for systematic progress in this field as it is in other fields of surgery. Conditions existing in the wrist and hand compare favorably with those of the foot and ankle for several reasons: The muscle supply is more abundant; there is, as shall be shown presently, a greater possibility of detaching muscles of the hand and forearm for the purpose of transplantation, by virtue of certain anatomic
Myeloperoxidase Deficiency
Authors: MICHAEL F. PARRY
Journal: Annals of Internal Medicine (1981)

Leukocyte differential counting by flow cytochemistry has shown 28 subjects with partial or complete neutrophil myeloperoxidase (MPO) deficiency in a population of about 60 000 patients screened at a general hospital. Partial (13 patients) or complete (13 patients) MPO deficiency was confirmed by examination of cytochemical stains in 26, biochemical measurement of total enzymatic activity in eight, and flow cytometry in six patients. None had apparent hematologic disorders. Only four patients had infections; of these, two had major systemic infections (one, candidiasis; one, bacteremia). In assays of leukocyte function only minor defects in killing of Staphylococcus aureus by MPO-deficient cells were noted whereas killing of Candida albicans was much more impaired. Family studies in eight patients have shown various degrees of partial or complete MPO deficiency in first-degree relatives of six. The findings indicate that the incidence of MPO deficiency is much higher than previously suspected. Although MPO appears to be necessary for killing of Candida species by neutrophils, the importance of its role in normal antibacterial defense must be re-evaluated.
PVA hydrogel sheet macroencapsulation for the bioartificial pancreas
Authors: Meirigeng Qi, Yuanjun Gu, Naoaki Sakata, Dohoon Kim, Yasumasa Shirouzu, Chizuru Yamamoto, Akihito Hiura, Shoichiro Sumi, Kazutomo Inoue
Journal: Biomaterials (2004)
Detection of Metastatic Involvement of the Pericardium on F-18 FDG-PET/CT Imaging
Authors: Anastasios Douroukas, Vincenzo Arena, Ettore Pelosi
Journal: Clinical Nuclear Medicine (2008)

This is the case of a 46-year-old man with non-small cell lung cancer (NSCLC). The patient was initially studied with a conventional contrast enhanced CT scan that revealed a lung nodule in the lower right lobe, pathologic lymph nodes, and a pericardial effusion.1 The whole body PET/CT study with F-18 FDG showed 2 sites of pathologic uptakes in the right lung, in multiple lymph nodes in the right pulmonary hilum, mediastinum, and supraclavicular regions and in the pericardium.2–4 The transaxial PET/CT images showed diffuse involvement and a massive effusion of the pericardium.5 Based on the PET findings, the patient underwent a pericardial biopsy, which proved the presence of metastases.6–8
Evaluation of Glutathione Metabolic Genes on Outcomes in Advanced Non-small Cell Lung Cancer Patients after Initial Treatment with Platinum-Based Chemotherapy: An NCCTG-97-24-51 Based Study
Authors: Ping Yang, Sumithra J. Mandrekar, Shauna H. Hillman, Katie L. Allen Ziegler, Zhifu Sun, Jason A. Wampfler, Julie M. Cunningham, Jeff A. Sloan, Alex A. Adjei, Edith Perez, James R. Jett
Journal: Journal of Thoracic Oncology (2009)
Extrahepatic deposition and cytotoxicity of lithocholic acid: Studies in two hamster models of hepatic failure and in cultured human fibroblasts
Authors: Susan Ceryak, Bernard Bouscarel, Mauro Malavolti, Hans Fromm
Journal: Hepatology (1998)

Effects of bile acids on tissues outside of the enterohepatic circulation may be of major pathophysiological significance under conditions of elevated serum bile acid concentrations, such as in hepatobiliary disease. Two hamster models of hepatic failure, namely functional hepatectomy (HepX), and 2-day bile duct ligation (BDL), as well as cultured human fibroblasts, were used to study the comparative tissue uptake, distribution, and cytotoxicity of lithocholic acid (LCA) in relation to various experimental conditions, such as binding of LCA to low-density lipoprotein (LDL) or albumin as protein carriers. Fifteen minutes after iv infusion of [24- 14 C]LCA, the majority of LCA in sham-operated control animals was recovered in liver, bile, and small intestine. After hepatectomy, a significant increase in LCA was found in blood, muscle, heart, brain, adrenals, and thymus. In bile duct-ligated animals, significantly more LCA was associated with blood and skin, and a greater than twofold increase in LCA was observed in the colon. In the hepatectomized model, the administration of LCA bound to LDL resulted in a significantly higher uptake in the kidneys and skin. The comparative time- and concentration-dependent uptake of [ 14 C]LCA, [ 14 C]chenodeoxycholic acid (CDCA), and [ 14 C]cholic acid (CA) in cultured human fibroblasts was nonsaturable and remained a function of concentration. Initial rates of uptake were significantly increased by approximately tenfold, with decreasing hydroxylation of the respective bile acid. After 1 hour of exposure of fibroblasts to LCA, there was a significant, dose-dependent decrease in mitochondrial dehydrogenase activity from 18% to 34% of the control, at LCA concentrations ranging from 1 to 20 μmol/L. At a respective concentration of 100 and 700 μmol/L, CDCA caused a 35% and 99% inhibition of mitochondrial dehydrogenase activity. None of the bile acids tested, with the exception of 700 μmol/L CDCA, caused a significant release of cytosolic lactate dehydrogenase into the medium. In conclusion, we show that bile acids selectively accumulate in nonhepatic tissues under two conditions of impaired liver function. Furthermore, the extrahepatic tissue distribution of bile acids during cholestasis may be affected by serum lipoprotein composition. At a respective concentration of 1 and 100 μmol/L, LCA and CDCA induced mitochondrial damage in human fibroblasts, after just 1 hour of exposure. Therefore, enhanced extrahepatic uptake of hydrophobic bile acids during liver dysfunction, or disorders of lipoprotein metabolism, may have important implications for bile-acid induced cytotoxic effects in tissues of the systemic circulation.
The modulation of lymphocyte functions by molecules secreted by macrophages. I. Description and partial biochemical analysis.
Authors: J Calderon, J M Kiely, J L Lefko, E R Unanue
Journal: The Journal of Experimental Medicine (1975)

Culture fluids of peritoneal exudate cells rich in macrophages stimulated DNA synthesis of thymocytes and, to lesser extent, of spleen cells. We also investigated the effects of culture fluids from macrophages on the in vitro response to a hapten-carrier protein (fluorescein-menocyanin) using spleen cells from immune mice. Macrophage culture fluids contained an activity that increased the plaque-forming cell response of both IgG and IgM class. This increase was observed in the absence of any added hapten protein to the culture. The helper function of T lymphocytes (as evidenced by challenging with the hapten on the homologous carrier) was also increased by the macrophage culture fluid. However, this enhancement was best observed in conditions of relatively low T-cell activity. Also, the macrophage fluid allowed spleen cells of nude athymic mice to make a plaque-forming cell response to sheep red blood cells of both the IgM and IgG class. The macrophage was the cell source of the stimulatory molecule since it was generated only in cultures of macrophages devoid of significant number of lymphocytes. Stimulatory activity was not found in cultures of lymphocytes, mouse embryo cells, or 3T3 cells. The thymocyte stimulatory molecule did not contain H-2 antigens, was resistant to diisopropylfluorophosphate treatment, eluted from Sephadex with a size ranging from 15,000 to 21,000 daltons, and was sensitive to chymotrypsin and pepsin.
The Tumor Lysis Syndrome
Authors: Michael A. Baumann
Journal: JAMA (1983)

<h3>To the Editor.—</h3> The recent report by Vogelzang et al (1983;249:513) of tumor lysis syndrome after chemotherapy for small-cell bronchogenic carcinoma was of great interest. We would like to report an additional case recently seen in our facility. <h3>Report of a Case.—</h3> A 78-year-old man was found to have small-cell carcinoma of the lung with multiple metastases to liver and bone. Pretreatment chemistries included the following values: potassium, 4.7 mEq/L; creatinine, 1.3 mg/dL; uric acid, 7.8 mg/dL; phosphorus, 2.7 mg/dL; calcium, 4.7 mEq/L; alkaline phosphatase, 475 units/L (reference range, 30 to 115 units/L); SGOT, 81 units/L (reference range, 0 to 41 units/L); lactate dehydrogenase (LDH), 496 units/L (reference range, 60 to 200 units/L); bilirubin, 1.1 mg/dL. Chemotherapy was initiated with doxorubicin (Adriamycin), 30 mg/sq m; cyclophosphamide, 900 mg/sq m; and vincristine, 2.0 mg—all intravenously on the same day. Seven days later, the patient had become oliguric, and repeated laboratory studies
Saying No Isn't NICE — The Travails of Britain's National Institute for Health and Clinical Excellence
Authors: Robert Steinbrook
Journal: New England Journal of Medicine (2008)

Britain's National Institute for Health and Clinical Excellence, known as NICE, is an independent, government-funded organization that advises the British National Health Service (NHS).1 Established in 1999, the institute has recommended coverage for hundreds of medicines. Since 2002, NHS organizations in England and Wales have been required to pay for medicines and treatments recommended in NICE “technology appraisals.” The NHS usually does not provide medicines or treatments that are not recommended by NICE — although exceptions are possible.NICE (www.nice.org.uk), however, has been criticized for the slow release of its appraisals, which has delayed the availability of some treatments that . . .
Remodeling of the extracellular matrix through overexpression of collagen VI contributes to cisplatin resistance in ovarian cancer cells
Authors: Cheryl A. Sherman-Baust, Ashani T. Weeraratna, Leticia B.A. Rangel, Ellen S. Pizer, Kathleen R. Cho, Donald R. Schwartz, Teresa Shock, Patrice J. Morin
Journal: Cancer Cell (2003)
[265] IMPROVED SURVIVAL OF PATIENTS WITH HEPATOCELLULAR CARCINOMA DETECTED BY RECENT INTENSIVE SURVEILLANCE
Authors: D.Y. Kim, K.-H. Han, S.H. Aim, H.W. Lee, Y.J. Yoon, J.K. Kim, Y.H. Paik, K.S. Lee, C.Y. Chon, Y.M. Moon
Journal: Journal of Hepatology (2007)
A lesson on sustainable living
Authors: Dilip Menon
Journal: BMJ (2004)

is to ensure that access is broadened through appropriate, supported public channels such as cancer information centres and public libraries. Limitations of studyThe interviews used in our analysis were collected for five individual projects for the DIPEx database, using the same interview methods and maximum variation sampling.The samples should not (individually or together) be interpreted as numerically representative of cancer patients, having been selected to represent the broadest practicable range of experience, as is appropriate to the aims of this qualitative study.Many important questions about the impact of the internet are beyond the scope of a qualitative interview study.These include what impact the internet has on the consultation, how it affects patients' participation in decisions, what effect it has on health outcomes, and, indeed, what the relevant outcomes are.This study prepares the ground for further qualitative and quanti-tative work by identifying the many different ways and stages at which information on the internet is used, as well as the meanings the internet has for patients and the implications for relationships in health care.We are grateful to all of our interview participants and the many nurse specialists, support groups, general practitioners, and consultants who helped us to recruit them.We also thank our internal referees,
How much energy does the breast fed infant consume and expend?
Authors: A Lucas, G Ewing, S B Roberts, W A Coward
Journal: BMJ (1987)

Energy intake in breast fed infants is uncertain. The doubly labelled water method was used to measure, simultaneously and non-invasively, energy expenditure, energy intake, milk volume intake, energy deposition, and the energy content of breast milk in 12 "free living" breast fed babies at 5 and 11 weeks of age. The validity of this new approach was assessed in a parallel study in 12 formula fed infants. The babies who were exclusively breast fed expended 1.28 and 1.68 MJ/day at five and 11 weeks and had intakes of 1.81 and 2.22 MJ/day; these intakes were associated with normal growth but were well below those recommended previously. At five and 11 weeks the calculated energy content of breast milk was 0.24 and 0.25 MJ/100 ml, which is substantially lower than that commonly reported in milk obtained unphysiologically by expression of the breast. These data cast doubt on the widely used published standards for infant feeding.
Cellular responses to steroids in the enhancement of Na+ transport by rat collecting duct cells in culture. Differences between glucocorticoid and mineralocorticoid hormones.
Authors: J R Laplace, R F Husted, J B Stokes
Journal: Journal of Clinical Investigation (1992)

It has recently been discovered that both mineralocorticoid (MC) and glucocorticoid (GC) hormones can stimulate electrogenic Na+ absorption by mammalian collecting duct cells in culture. In primary cultures of rat inner medullary collecting duct (IMCD) cells, 24-h incubation with either MC or GC agonist stimulates Na+ transport approximately threefold. We have now determined that the effects were not additive, but the time courses were different. As aldosterone is known to stimulate citrate synthase, Na+/K+ ATPase activity, and ouabain binding in cortical collecting duct principal cells, we determined the effects of steroids on these parameters in IMCD cells. MC and GC agonists both produced a small increase in citrate synthase activity. There was no increase in Na+/K+ ATPase activity but specific ouabain binding was increased more than two-fold by either agonist. To determine the role of apical Na+ entry in the steroid-induced effects, the Na+ channel inhibitor, benzamil, was used. Benzamil did not alter the stimulation of citrate synthase activity by either steroid. In contrast, GC stimulation of ouabain binding was prevented by benzamil, whereas MC stimulation was not. We conclude that there are differences in the way that MC and GC hormones produce an increased Na+ transport. Both appear to produce translocation (or activation) of pumps into the basolateral membrane. GC stimulation of pump translocation requires increased Na+ entry whereas MC stimulation does not.
Science, medicine, and the future : malaria
Authors: S Krishna
Journal: BMJ (1997)

Sixteen years ago, when I was a medical student interested in malaria, my professor of medicine asked me what the chances were of developing a malaria vaccine.So far, a successful vaccine is still being sought, but recent advances in the molecular biology of malaria suggest that one may become available soon, along with better diagnostic, preventive, and treatment strategies.Malaria is a huge and growing problem, especially in Africa: it kills one to two million children each year, causes disease in a further 400 million individuals, and accounts for 25-50% of all hospital admissions.Moreover, mortality associated with cerebral malaria (caused by infection with Plasmodium falciparum) has not improved in the past 30 years. 1 P falciparum is now virtually untreatable with chloroquine in most parts of the world, and many strains of P vivax are also resistant.Although quinine is often the antimalarial drug of choice for chloroquine resistant strains, it is poorly tolerated and compliance is therefore low.Newer antimalarials such as mefloquine are both expensive and not always effective.Some parasites are now resistant to most antimalarials.This drug resistance makes choice of chemoprophylaxis for travellers difficult as well.In the past 15 years research has expanded considerably from preventive strategies and development of vaccines to include better understanding of the pathophysiology of disease, both clinically and at the cellular and molecular level. 2A recent review of malaria research by the Wellcome Trust highlights some of these achievements and points to important directions for future study. 3In this article I review some of these advances in laboratory studies of malaria and discuss how they may affect future control measures and clinical management.
Runt-Related Transcription Factor RUNX3 Is a Target of MDM2-Mediated Ubiquitination
Authors: Xin-Zi Chi, Jiyeon Kim, Yong-Hee Lee, Jung-Won Lee, Kyeong-Sook Lee, Heejun Wee, Wun-Jae Kim, Woo-Yoon Park, Byung-Chul Oh, Gary S. Stein, Yoshiaki Ito, Andre J. van Wijnen, Suk-Chul Bae
Journal: Cancer Research (2009)

The p14(ARF)-MDM2-p53 pathway constitutes an effective mechanism for protecting cells from oncogenic stimuli such as activated Ras and Myc. Importantly, Ras activation induces p14(ARF) and often occurs earlier than p53 inactivation during cancer development. Here, we show that RUNX3, a tumor suppressor in various tumors including stomach, bladder, colon, and lung, is stabilized by Ras activation through the p14(ARF)-MDM2 signaling pathway. RUNX3 directly binds MDM2 through its Runt-related DNA-binding domain. MDM2 blocks RUNX3 transcriptional activity by interacting with RUNX3 through an acidic domain adjacent to the p53-binding domain of MDM2 and ubiquitinates RUNX3 on key lysine residues to mediate nuclear export and proteasomal degradation. Our data indicate that the lineage-specific tumor suppressor RUNX3 and the ubiquitous p53 protein are both principal responders of the p14(ARF)-MDM2 cell surveillance pathway that prevents pathologic consequences of abnormal oncogene activation.