tbuckley/cabot-search huggingface dataset:
Defining topological similarities among ion transport proteins with anti-amiloride antibodies
Authors: Thomas Kieber-Emmons, Chaomei Lin, Katherine V. Prammer, Annabelle Villalobos, Farhad Kosari, Thomas R. Kleyman
Journal: Kidney International (1995)

The structural features of amiloride binding sites on amiloride-sensitive transport proteins have received limited characterization. An antibody that recognizes limited regions of amiloride and can mimic, in binding specificity, certain amiloride-sensitive transport proteins was used as a model to elucidate potential amino acid residue relationships that might define putative amiloride contact sites. Analysis of the structure of this antibody has allowed us to identify sequence relationships among several Na+ selective transport proteins. A structure-based relational database was employed to re-examine sequence homologies among these ion transport proteins. A search of the protein sequence databank identified representative amino acid tracts among amiloride sensitive proteins involving planar residues that might be involved in interacting with amiloride. Computer models of sites within transmembrane domains of NHE1 and NHE2 isoforms of the Na+/H+ exchanger reflective of these planar tracts indicate that amiloride probably spans two helices for interaction with the Na+/H+ exchanger. Structural analysis of this monoclonal anti-amiloride antibody appears to mimic some of the salient features of amiloride binding sites on these proteins.
Small Ubiquitin-Related Modifier Pathway Is a Major Determinant of Doxorubicin Cytotoxicity in <i>Saccharomyces cerevisiae</i>
Authors: Ruea-Yea Huang, David Kowalski, Hans Minderman, Nishant Gandhi, Erica S. Johnson
Journal: Cancer Research (2007)

Abstract Development of drug resistance is a major challenge in cancer chemotherapy using doxorubicin. By screening the collection of Saccharomyces cerevisiae deletion strains to identify doxorubicin-resistant mutants, we have discovered that the small ubiquitin-related modifier (SUMO) pathway is a major determinant of doxorubicin cytotoxicity in yeast. Mutants lacking UBA2 (SUMO activating enzyme; E1), UBC9 (conjugating enzyme; E2), and ULP1 and ULP2 (desumoylation peptidases) are all doxorubicin resistant, as are mutants lacking MLP1, UIP3, and NUP60, which all interact with ULP1. Most informatively, mutants lacking the SUMO E3 ligase Siz1 are strongly doxorubicin resistant, whereas mutants of other SUMO ligases are either weakly resistant (siz2) or hypersensitive (mms21) to doxorubicin. These results suggest that doxorubicin cytotoxicity is regulated by Siz1-dependent sumoylation of specific proteins. Eliminating SUMO attachment to proliferating cell nuclear antigen or topoisomerase II does not affect doxorubicin cytotoxicity, whereas reducing SUMO attachment to the bud neck–associated septin proteins has a modest effect. Consistent with these results, doxorubicin resistance in the siz1Δ strain does not seem to involve an effect on DNA repair. Instead, siz1Δ cells accumulate lower intracellular levels of doxorubicin than wild-type (WT) cells, suggesting that they are defective in doxorubicin retention. Although siz1Δ cells are cross-resistant to daunorubicin, they are hypersensitive to cisplatin and show near WT sensitivity to other drugs, suggesting that the siz1Δ mutation does not cause a general multidrug resistance phenotype. Cumulatively, these results reveal that SUMO modification of proteins mediates the doxorubicin cytotoxicity in yeast, at least partially, by modification of septins and of proteins that control the intracellular drug concentration. [Cancer Res 2007;67(2):765–72]
Connective tissue biology and hepatic fibrosis: Report of a conference
Authors: Montgomery D. Bissell, Scott L. Friedman, Jacquelyn J. Maher, Joseph F. Roll
Journal: Hepatology (1990)

The past 15 years have seen major advances in the characterization of extracellular matrix proteins and structure of matrix. As a by-product of this work, investigators now have an array of molecular and immunological reagents for monitoring matrix metabolism. Progress in the isolation and culture of individual cell types from liver has made possible direct measurement of matrix protein production and also has opened the way to studies of matrix degradation. The expanding knowledge of soluble mediators of inflammation is being applied to the regulation of matrix protein synthesis and degradation. Finally, experimental models of fibrosis in vivo are available for defining the complexity of matrix metabolism in the intact tissue and for validating the findings from cell culture and in vitro systems.
Regulation of the α2(I) collagen gene transcription in fat-storing cells derived from a cirrhotic liver
Authors: Yutaka Inagaki, Sharada Truter, Patricia Greenwel, Marcos Rojkind, Masashi Unoura, Kenichi Kobayashi, Francesco Ramirez
Journal: Hepatology (1995)

Fat-storing cells (FSC) are the main producers of type I collagen in both normal and fibrotic livers. In order to elucidate the molecular mechanisms controlling collagen expression in FSC, we examined the transcription of the alpha 2(I) collagen gene (COL1A2) in two distinct FSC clones, CFSC-2G and CFSC-5H, derived from a single CCl4-induced cirrhotic liver. The phenotype of CFSC-2G resembles freshly isolated FSC, whereas that of CFSC-5H mimics activated myofibroblasts. Cell transfection experiments showed that the upstream sequence between nucleotides -378 and -183 is essential for COL1A2 transcription in both FSC clones. This is the same promoter region that is transcriptionally active and contains the binding site of a multimeric protein complex that mediates TGF-beta stimulation of COL1A2 expression in dermal fibroblasts. We therefore examined the relative levels of endogenous and transfected COL1A2 transcription and their response to TGF-beta treatment in the two FSC clones. The results showed that CFSC-5H expresses a significantly higher level of the COL1A2 mRNA than CFSC-2G. They also showed that TGF-beta treatment increases both endogenous and transfected COL1A2 transcription in CFSC-2G but not in CFSC-5H. Interestingly, nuclear proteins from both FSC clones bind to the TGF-beta-responsive element more strongly than those from dermal fibroblasts. Altogether, the data suggest that collagen production in CFSC-5H cells has been already activated by the autocrine stimulation of TGF-beta. In contrast, CFSC-2G cells are only partially activated but can be easily recruited to produce collagen when stimulated by exogenous TGF-beta.(ABSTRACT TRUNCATED AT 250 WORDS)
Genetic susceptibility to food allergy is linked to differential TH2-TH1 responses in C3H/HeJ and BALB/c mice
Authors: Vivian Morafo, Kamal Srivastava, Chih-Kang Huang, Gary Kleiner, Soo-Young Lee, Hugh A. Sampson, Xiu-Min Li
Journal: Journal of Allergy and Clinical Immunology (2003)
Demonstration of the production and physiological role of insulin-like growth factor II in rat thyroid follicular cells in culture.
Authors: R M Maciel, A C Moses, G Villone, D Tramontano, S H Ingbar
Journal: Journal of Clinical Investigation (1988)

Insulin-like growth factors (IGFs) are potent mitogens for FRTL5 rat thyroid follicular cells. IGFs also synergize the independent mitogenic effects of thyrotropin-stimulating hormone (TSH) and other agents that increase intracellular AMP concentration. We examined whether FRTL5 cells and M12 cells, a TSH-independent mutant cell line derived therefrom, secrete IGF that regulates the growth of rat thyroid follicular cells. Immunoreactive IGF-II, but not IGF-I, was found in media conditioned by FRTL5 cells; media from M12 cells contained four- to fivefold higher concentrations. Medium conditioned by FRTL5 and M12 both stimulated [3H]thymidine incorporation in FRTL5 and amplified the mitogenic effects of TSH. M12-conditioned medium was more potent than FRTL5-conditioned medium. Sm-1.2, a monoclonal antibody that recognizes IGF-I and IGF-II but not insulin, inhibited basal DNA synthesis in FRTL5 and M12 cells and the mitogenic effects in FRTL5 of agents that are synergized by IGF, such as TSH, forskolin, Bt2cAMP, and Graves'-IgG. Sm-1.2 did not inhibit the mitogenic response to insulin. Thus, rat insulin-like growth factor II (rIGF-II) is an autocrine growth factor that regulates FRTL5 growth, in part by amplifying the mitogenic response to TSH. Results with M12 cells raise the possibility that endogenous rIGF-II may partially mediate the TSH-independent growth of these cells.
Vagotomy and Pyloroplasty for Gastric Ulcer
Authors: R. J. Clarke, D. L. Lewis, J. A. Williams
Journal: BMJ (1972)

In a series of 68 patients with gastric ulcer who were treated by vagotomy and pyloroplasty there were no operative deaths, though one patient who received massive transfusions died 14 weeks later from hepatic necrosis probably associated with serum hepatitis. Four patients developed recurrent peptic ulceration requiring further surgical treatment. The clinical condition of all but three of the remainder was satisfactory after an average follow-up period of three years and two months. Of the 14 patients who presented with an acutely bleeding gastric ulcer, one subsequently required gastrectomy for continued bleeding; in all the others the immediate and long-term results were satisfactory. Of 21 patients with a “high” ulcer and 29 with combined gastric and duodenal ulceration one (4·8%) and three (10%) respectively suffered recurrences. We conclude that vagotomy and pyloroplasty is a satisfactory form of treatment for a high or bleeding gastric ulcer, but that for all other gastric ulcers some form of gastric resection is preferable.
Risk Factors for Acute Leukemia in Children: A Review
Authors: Martin Belson, Beverely Kingsley, Adrianne Holmes
Journal: Environmental Health Perspectives (2006)

Although overall incidence is rare, leukemia is the most common type of childhood cancer. It accounts for 30% of all cancers diagnosed in children younger than 15 years. Within this population, acute lymphocytic leukemia (ALL) occurs approximately five times more frequently than acute myelogenous leukemia (AML) and accounts for approximately 78% of all childhood leukemia diagnoses. Epidemiologic studies of acute leukemias in children have examined possible risk factors, including genetic, infectious, and environmental, in an attempt to determine etiology. Only one environmental risk factor (ionizing radiation) has been significantly linked to ALL or AML. Most environmental risk factors have been found to be weakly and inconsistently associated with either form of acute childhood leukemia. Our review focuses on the demographics of childhood leukemia and the risk factors that have been associated with the development of childhood ALL or AML. The environmental risk factors discussed include ionizing radiation, non-ionizing radiation, hydrocarbons, pesticides, alcohol use, cigarette smoking, and illicit drug use. Knowledge of these particular risk factors can be used to support measures to reduce potentially harmful exposures and decrease the risk of disease. We also review genetic and infectious risk factors and other variables, including maternal reproductive history and birth characteristics.
In the Open: Diary of a Homeless Alcoholic
Authors: Donald W. Goodwin
Journal: JAMA (1997)

Organ of Corti, showing four rows of hair cells. Colored scanning electron micrograph, magnification X1830. From<b>Inside Information: Imaging the Human Body</b>, by William A. Ewing, 127 pp, with illus, paper, $23, ISBN 0-684-83108-2, New York, NY, Fireside Books, 1996. Reprinted by permission.<b>A Homeless Alcoholic</b> The author started keeping a diary to help him stop drinking. It didn't help. After a while he stopped the diary, thinking that might help. It didn't. Nothing helped except being broke, and this was always temporary, with money coming in from somewhere: a day labor office, an unemployment check, a small inheritance. This may explain why the entries in Timothy Donahue's<i>In the Open</i>move from topic to topic without connecting bridges, skipping around in time (from 1990 to 1994) as pointlessly as the writer hitchhikes around the country. The reader learns a lot about alcoholism and the homeless. Those who know all
Renal Complications of Small-Bowel Bypass Surgery
Authors: Samuel Vaisrub
Journal: JAMA (1976)

Gastroenterostomy—a disease! The exclamation, attributed to a famous French surgeon earlier in the century, can be readily extrapolated to other bypass operations, be they intestinal or vascular. They too give rise to worrisome complications, some of which may not become manifest for months, even years.  Jejunoileal bypass for the treatment of intractable obesity is no exception to this vulnerability. A number of reports attest to the occurrence of short-term, as well as long-range, sequelae. The most common and troublesome sequelae are diarrhea and psychiatric disorders which in some cases are severe enough to necessitate restitution of small-bowel continuity. Other complications—electrolyte disturbances, biliary stones, fatty infiltration of the liver (p 1248)—though less manifest, can also become serious. Hepatic steatosis, for instance, has occasionally progressed to cirrhosis.1,2  A less serious complication—or so it appeared until recently—is hyperoxaluria, which occasionally causes nephrolithiasis. The increased excretion of urinary oxalate is the result of
Viruses and Genetics
Authors: Mason G. Robertson
Journal: JAMA (1971)

<h3>To the Editor.—</h3> The item discussing herpesvirus transforming cells by passing on genes (<b>216</b>:2078, 1971) evokes thoughts on an old philosophical question concerning genetics. The question is, of course, "How does the currently accepted theory of genetics allow for acquired characteristics?" At present, we accept only various types of haphazard "mutations," generally radiation or chemical damage to chromosomes. Survival of the mutation in turn depends on natural selection. The question can be turned around. "How does an acquired characteristic come to be shared by a variety of species?" Example: The variety of mammalian species in Australia which share the marsupial characteristic. Is it possible that viruses afford the "missing link" in our theories? Can genetically unrelated species under certain circumstances be "infected" with the same genetic material? Is it further possible that, under certain circumstances, higher organisms are capable of "shedding" some of their genetic material in the form
Lower Ventral Striatal Activation During Reward Anticipation in Adolescent Smokers
Authors: Jan Peters, Uli Bromberg, Sophia Schneider, Stefanie Brassen, Mareike Menz, Tobias Banaschewski, Patricia J. Conrod, Herta Flor, Jürgen Gallinat, Hugh Garavan, Andreas Heinz, Bernd Itterman, Mark Lathrop, Jean-Luc Martinot, Tomas Paus, Jean-Baptiste Poline, Trevor W. Robbins, Marcella Rietschel, Michael Smolka, Andreas Ströhle, Maren Struve, Eva Loth, Gunter Schumann, Christian Büchel
Journal: American Journal of Psychiatry (2011)

Objective: Adolescents are particularly vulnerable to addiction, and in the case of smoking, this often leads to long-lasting nicotine dependence. The authors investigated a possible neural mechanism underlying this vulnerability. Method: Functional MRI was performed during reward anticipation in 43 adolescent smokers and 43 subjects matched on age, gender, and IQ. The authors also assessed group differences in novelty seeking, impulsivity, and reward delay discounting. Results: In relation to the comparison subjects, the adolescent smokers showed greater reward delay discounting and higher scores for novelty seeking. Neural responses in the ventral striatum during reward anticipation were significantly lower in the smokers than in the comparison subjects, and in the smokers this response was correlated with smoking frequency. Notably, the lower response to reward anticipation in the ventral striatum was also observed in smokers (N=14) who had smoked on fewer than 10 occasions. Conclusions: The present findings suggest that a lower response to reward anticipation in the ventral striatum may be a vulnerability factor for the development of early nicotine use.
Staining Methods: Histologic and Histochemical
Authors: H. R. Catchpole
Journal: JAMA (1962)

McManus and Mowry's text is an upto-date (1957-1958) laboratory book of methodology. More inclusive than Gomori, less technical than Pearse, and not too different in scope and size from Lillie, the stated objective is to provide a text for use in routine work and research by pathologists, histochemists, cytologists, and their technical assistants. In point of fact, its coverage and appeal would appear to be limited rather to the first and last of these categories. There is a good deal of the "instinctive" minutiae that one associates with the experienced technician. Major sections deal with special methods for individual constituents or groups of constituents of cells and tissues and with the study of special cells, tissues, and organs. These divisions seem reasonable. The topics are briefly introduced and the methods summarily presented in the text, making the book rather easier to use than Pearse. Reference to such topics as electron
Book: Holding Health Care Accountable: Law and the New Medical Marketplace
Authors: J. Murphy
Journal: BMJ (2001)

E Haavi Morreim Oxford University Press, £39.50, pp 320 ISBN 0 19 514132 6 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> This book provides a most informative guide to how drastic funding cuts have affected healthcare delivery. It looks at how cuts have changed both the ethos behind healthcare delivery and the suitability of the traditional contract and tort doctrines as mechanisms of legal accountability. The book focuses on the legal and practical implications of resource shortages and it highlights the transition from an age of “if it may help, try it” to one of “don't do it unless it definitely will help.” In this sense its interest to British readers is obvious, even though it is written on the … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
CAROTID ATHEROSCLEROSIS IN BRAZILIAN WOMEN WITH LOW FRAMINGHAM RISK SCORE
Authors: Isly Lucena de Barros, Laura Costa, Ana Paula Tavares Souza, Pedro Veras, Daniela Fantato, Bento Bezerra, Natanael Morais, Moacir Novaes, Jos&eacute; Carlos Nicolau
Journal: Journal of the American College of Cardiology (2012)
A novel, unstable DNA mutation cracks decades-old clinical enigma
Authors: T. Randall
Journal: JAMA (1993)

AS GENETICISTS have located the mutations that cause one disease after another in recent years, the novelty of such discoveries has perhaps worn thin. As expected, most of the mutations have fit comfortably within the paradigm of classical genetics. Without diminishing the importance of these achievements, observers draw the parallel that even a moon landing loses its luster after several successes.  It is remarkable then, that a newly discovered mutation can rock the genetics community as it did recently at the annual meeting of the American Society of Human Genetics in San Francisco, Calif.  Causing such excitement were not only the diseases that share this mutation—fragile X syndrome, myotonic dystrophy, and Kennedy disease—but the mutation itself, which is completely novel and, until it was sequenced, beyond the imagination of geneticists. It is neither an insertion, deletion, or point mutation, and its discovery is as surprising as expecting moon rocks and
Military Physicians of 12 Nations Cooperate in Haiti
Authors: Andrew A. Skolnick
Journal: JAMA (1995)

HELPING REBUILD the country's devastated health care system is not the only extraordinary part of the US military medical mission in Haiti. More than at any time in history, US Army medical personnel are working closely with the medical units of other armed forces. If the United States participates in future United Nations (UN) peacekeeping missions, such joint military medical operations may become routine. When the US-led multinational force occupied Haiti in September 1994 for the purpose of removing the military dictatorship and restoring democracy, they brought with them one of the most sophisticated, transportable health care systems in the world. When the UN took over the mission in March 1995, the United States assumed the responsibility of providing most of the health care for the entire operation, a job that requires working closely with military contingents from 11 other nations. "The US military is the only organization in the
Effect of a community oriented problem based learning curriculum on quality of primary care delivered by graduates: historical cohort comparison study
Authors: Robyn Tamblyn, Michal Abrahamowicz, Dale Dauphinee, Nadyne Girard, Gillian Bartlett, Paul Grand'Maison, Carlos Brailovsky
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To assess whether the transition from a traditional curriculum to a community oriented problem based learning curriculum at Sherbrooke University is associated with the expected improvements in preventive care and continuity of care without a decline in diagnosis and management of disease. <b>Design</b> Historical cohort comparison study. <b>Setting</b> Sherbrooke University and three traditional medical schools in Quebec, Canada. <b>Participants</b> 751 doctors from four graduation cohorts (1988-91); three before the transition to community based problem based learning (n = 600) and one after the transition (n = 151). <b>Outcome measures</b> Annual performance in preventive care (mammography screening rate), continuity of care, diagnosis (difference in prescribing rates for specific diseases and relief of symptoms), and management (prescribing rate for contraindicated drugs) assessed using provincial health databases for the first 4-7 years of practice. <b>Results</b> After transition to a community oriented problem based learning curriculum, graduates of Sherbrooke University showed a statistically significant improvement in mammography screening rates (55 more women screened per 1000, 95% confidence interval 10.6 to 99.3) and continuity of care (3.3% more visits coordinated by the doctor, 0.9% to 5.8%) compared with graduates of a traditional medical curriculum. Indicators of diagnostic and management performance did not show the hypothesised decline. Sherbrooke graduates showed a significant fourfold increase in disease specific prescribing rates compared with prescribing for symptom relief after the transition. <b>Conclusion</b> Transition to a community oriented problem based learning curriculum was associated with significant improvements in preventive care and continuity of care and an improvement in indicators of diagnostic performance.
Meningeal Irritation, Hemoptysis, and Eosinophilia—A Case of Human Dirofilariasis?
Authors: Robert G. Feldman
Journal: JAMA (1974)

There is no evidence that<i>Dirofilaria</i>can complete a life cycle and produce microfilaremia in humans. Our patient raises an interesting question. How frequently might dog owners develop otherwise unexplained eosinophilia, Löffler syndrome, and symptoms of meningeal irritation with pleocytosis due to dirofilarial infestations? Dirofilarial infestation as a cause of "coin lesion" on chest x-ray film has been emphasized, but other more subtle symptoms, signs, and serologic evidence alone make a definite diagnosis of human dirofilariasis difficult. (<i>JAMA</i>228:1018-1019, 1974)