tbuckley/cabot-search huggingface dataset:
Inactivating cholecystokinin-2 receptor inhibits progastrin-dependent colonic crypt fission, proliferation, and colorectal cancer in mice
Authors: Guangchun Jin, Vigneshwaran Ramanathan, Michael Quante, Gwang Ho Baik, Xiangdong Yang, Sophie S.W. Wang, Shuiping Tu, Shanisha A.K. Gordon, David Mark Pritchard, Andrea Varro, Arthur Shulkes, Timothy C. Wang
Journal: Journal of Clinical Investigation (2009)

Hyperproliferation of the colonic epithelium, leading to expansion of colonic crypt progenitors, is a recognized risk factor for colorectal cancer. Overexpression of progastrin, a nonamidated and incompletely processed product of the gastrin gene, has been shown to induce colonic hyperproliferation and promote colorectal cancer in mice, but the mechanism of pathogenesis has not been defined. Cholecystokinin-2 receptor (CCK2R) is the primary receptor for cholecystokinin (CCK) and amidated gastrin. Here, we show that Cck2r was expressed in murine colonic crypts and upregulated in the transgenic mice that overexpress human progastrin. Murine deletion of Cck2r abrogated progastrin-dependent increases in colonic proliferation, mucosal thickness, and β-catenin and CD44 expression in the colon tumor. In addition, either deletion or antagonism of Cck2r resulted in the inhibition of progastrin-dependent increases in progenitors expressing doublecortin and CaM kinase–like-1 (DCAMKL1), stem cells expressing leucine rich repeat–containing G protein–coupled receptor 5 (LgR5), and colonic crypt fission. Furthermore, in the azoxymethane mouse model of colorectal carcinogenesis, Cck2r deletion in human progastrin–overexpressing mice resulted in markedly decreased aberrant crypt foci formation and substantially reduced tumor size and multiplicity. Taken together, these observations indicate that progastrin induces proliferative effects, primarily in colonic progenitor cells, through a CCK2R-dependent pathway. Moreover, our data suggest that CCK2R may be a potential target in the treatment or prevention of colorectal cancer.
Steady-State Serum Concentration of Alpha Tocopherol Not Altered by Supplementation With Oral Beta Carotene
Authors: D. W. Nierenberg, T. A. Stukel, L. A. Mott, E. R. Greenberg
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Steady-State Serum Concentration of Alpha Tocopherol Not Altered by Supplementation With Oral Beta Carotene Get access David W. Nierenberg, David W. Nierenberg Departments of Medicine and Pharmacology/Toxicology, Dartmouth-Hitchcock Medical CenterLebanon, N.H. Correspondence to : David W. Nierenberg, M.D., Department of Medicine, Dartmouth-Hitchcock Medical Center, Hinman Box 7506, Lebanon, NH 03756. Search for other works by this author on: Oxford Academic PubMed Google Scholar Therese A. Stukel, Therese A. Stukel Community and Family Medicine, Dartmouth-Hitchcock Medical CenterLebanon, N.H. Search for other works by this author on: Oxford Academic PubMed Google Scholar Leila A. Mott, Leila A. Mott Community and Family Medicine, Dartmouth-Hitchcock Medical CenterLebanon, N.H. Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Robert Greenberg E. Robert Greenberg Community and Family Medicine, Dartmouth-Hitchcock Medical CenterLebanon, N.H. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 2, 19 January 1994, Pages 117–120, https://doi.org/10.1093/jnci/86.2.117 Published: 19 January 1994 Article history Received: 10 August 1993 Accepted: 27 October 1993 Published: 19 January 1994
Undesirable Side-effects from Decamethonium Iodide
Authors: S. M. Guerrier, J. C. Mason
Journal: BMJ (1952)

Decamethonium iodide (CIO) is a cheap and easily pre- pared compound.The short duration of muscular relaxation which it produces and the apparent absence of undesirable side-effects (Hewer et al., 1949; Organe, 1949; Davies and Lewis, 1949; -Bailey and Murphy, 1951) led us to suppose that this drug could be employed -usefully in surgical procedures requiring relaxation for short periods.It was also used in repeated doses to produce relaxation for longer periods. Present InvestigationIn a series of 233 administrations of CIO to subjects between the ages of 16 and 75 (see Table ) we have noted one case of cumulative action similar to those reported by Gray (1950) and Barry et al. (1951).We also had four cases which exhibited cardiovascular abnormalities.Analysis of 233 Administrations of CIO Operation Appendicectomy
The C282Y mutation in the haemochromatosis gene (HFE) and hepatitis C virus infection are independent cofactors for porphyria cutanea tarda in Australian patients
Authors: Katherine A. Stuart, Frances Busfield, Elizabeth C. Jazwinska, Peter Gibson, Lesley A. Butterworth, W.Graham Cooksley, Lawrie W. Powell, Darrell H.G. Crawford
Journal: Journal of Hepatology (1998)
[476] PREVALENCE OF HBV GENOTYPES IN CENTRAL AND EASTERN EUROPE
Authors: K. Deterding, I. Constantinescu, J. Gervain, V. Nemecek, K.P. Bielawski, M. Zalewska, T. Bock, A. Ambrozaitis, J. Stanczak, M. Takacs, J. Slusarczyk, M. Drazdakova, J. Wiegand, M.P. Manns, H. Wedemeyer
Journal: Journal of Hepatology (2007)
Correction: Author's Reply
Authors: Amir Attaran
Journal: PLoS Medicine (2006)

In PLoS Medicine, volume 2, issue 11: DOI: 10.1371/journal.pmed.0020405

Reference 3 [United Nations (2005) Data availability analysis. New York: United Nations. Available: http://unstats.un.org/unsd/mi/techgroup/January2005/Series%20update%20status%20query_FC.xls. Accessed 13 October 2005] was publicly accessible at the time of publication of Amir Attaran's article, but is no longer publicly accessible. This file can now be found as Dataset S1. 

Dataset S1Millennium Indicators Database: 
(41.5 KB XLS).

Click here for additional data file.(42K, xls)
18F-FDG PET Findings of a Parathyroid Cancer With Cortical Skeletal Demineralization
Authors: Hye-kyung Shim, Bom Sahn Kim
Journal: Clinical Nuclear Medicine (2012)

A 57-year-old man with the incidental finding of hypercalcemia visited our hospital. On radiographic evaluation, an extrathyroid mass and a thyroid isthmic nodule, which showed accumulation of 99mTc-methoxyisobutylisonitrile, was observed. Suspecting parathyroid cancer, an FDG PET was performed. FDG accumulation was noted in both lesions, with diffuse skeletal hypermetabolism. The extrathyroid mass and isthmic nodule were confirmed to be a parathyroid carcinoma and nodular goiter, respectively. The skeletal metabolism was nearly normalized postoperatively. We report a case of parathyroid cancer with skeletal demineralization, which is identified rarely on FDG PET.
Biochemical and Allergenic Properties of the House Dust Mite Extract, <i>Dermatophagoides pteronyssinus</i>
Authors: Akika Ishii, Hiroshi Shimomura, Junichi Hashiguchi, Yasuhiro Kabasawa
Journal: Allergy (1982)

A Further study has been made on the house dust mite extract, Dermatophagoides pteronyssinus , with emphasis on gel‐filtrated fraction 2 (F 2 ). The crude mite extract showed at least nine discs on polyacrylamide disc electrophoresis and contained less than 0.25 % sialic acid and less than 0.5 mM hexosamine and no detectable uronic acid. From gel filtration of the crude extract a No. 2 fraction (F 2 ) with allergenic activity showed at least five components on SDS disc electrophoresis covering a molecular weight range of between 15,000 and 70,000. The major allergenic activity of F 2 dissolved in pH 7–8 and 4–5 on an isoelectric focusing column. Affinity chromatography of lectins showed that allergenic activity did not relate to structures of N ‐acetyl‐D‐glucosamine or N ‐acetyl‐D‐galactosamine. Allergenic activity of the crude extract was not affected by peptic digestion and the mite digest prepared by trypsin and pronase showed a similar fraction‐action and activity profile as crude extract.
Experimentation in Children
Authors: William J. Curran
Journal: JAMA (1969)

Reexamination of legal and ethical principles in the United States and England yields suggestions concerning standards for the use of children in clinical investigation. Where the research is therapeutic, a minor may be included if informed consent is obtained from the parents or guardian. Where the research is not therapeutic, minors may be included if 14 years of age or older and if intelligent and mature enough to give informed consent. Parental consent is also required with discernible risks or hazards. For tissue and organ donation, the donor should be 14 years old or older and intelligent and mature enough to give informed consent and have parental or guardian consent also. Donations should be restricted to relatives or close friends. Also children under 14 may participate in clinical investigation which is not for their direct benefit where the studies are sound, promise important new knowledge for mankind, and there is no discernible risk.
Monoclonal antibodies in the management of acute leukemia
Authors: Jean C. Y. Wang, Patrice Beauregard, Praniti Soamboonsrup, Peter B. Neame
Journal: American Journal of Hematology (1995)

Abstract This report reviews the diagnostic significance of immune markers, their relationship to patient outcome, and the therapeutic uses of monoclonal antibodies (MoAbs) in acute leukemia. Immunophenotyping allows for rapid and reproducible diagnosis in the majority of cases of acute leukemia. It is of particular importance in recognizing the major immunologic subclasses of acute lymphoblastic leukemia (ALL), and in identifying subtypes of acute myeloblastic leukemia (AML) which cannot be differentiated by morphology and cytochemistry alone, such as FAB M0 or M7. Immune marker analysis has been used to detect minimal residual disease in patients' bone marrow and CSF after treatment. However, the presence of leukemia‐associated phenotypes on small numbers of normal ceils may reduce the sensitivity of detection in some cases. The prognostic value of immune markers in AML is limited. In ALL, the prognostic significance of the different immunophenotypic subtypes has been lessened by modern treatment protocols. The relationship of mixed‐lineage or biphenotypic antigen expression to patient outcome in both AML and ALL is unclear. Therapeutic applications of MoAbs in acute leukemia include immunologic techniques for purging malignant cells from autografts prior to transplantation, T‐lymphocyte depletion from allografts as a strategy to reduce graft‐versus‐host disease, and the use of flow cytometry to monitor the timing and extent of leukapheresis in peripheral stem cell transplantation. MoAbs have also enabled the recent development of transplantation protocols using positively‐selected CD34 + stem cells.
Activated murine macrophages secrete a metabolite of arginine with the bioactivity of endothelium-derived relaxing factor and the chemical reactivity of nitric oxide.
Authors: D J Stuehr, S S Gross, I Sakuma, R Levi, C F Nathan
Journal: The Journal of Experimental Medicine (1989)

L-arginine-dependent synthesis of nitrite (NO2-) and nitrate (NO3-) by macrophages correlates with and is required for their execution of nonspecific cytotoxicity toward some tumor cells and microbes. However, the bioactive L-arginine metabolites responsible for cytotoxicity are unknown. Mammalian endothelial cells have recently been shown to release nitric oxide (NO.); we therefore determined if this reactive metabolite was synthesized by activated murine macrophages. Macrophage-derived NO. was detected by two independent methods: a bioassay for NO.-mediated relaxation of preconstricted rings of rabbit aorta; and a spectroscopic measurement of the reaction of NO. with clostridial ferredoxin, an Fe-S protein. After activation with IFN-gamma and LPS, macrophages continuously secreted a substance that relaxed rabbit aortic rings denuded of endothelium. Production of the vasorelaxant was enhanced by 0.5 mM L-arginine and inhibited reversibly by NG-methylated L-arginine analogs that block macrophage NO2-/NO3- synthesis. The vasorelaxant was scavenged by ferrous myoglobin, was labile, and was neither NO2- nor a cyclooxygenase metabolite. Activated M phi also secreted a substance that bleached Fd, a reaction carried out by NO. and NO2, but not NO2-. Macrophage bleaching of Fd correlated directly with time, cell number, and concomitant NO2-/NO3- production, required L-arginine, and was independent of reactive oxygen intermediates. Thus, activated murine M phi release NO. and/or a closely related, highly reactive nitrogen oxide such as NO2, during their conversion of L-arginine to NO2-/NO3-. NO. and NO2 may mediate L-arginine-dependent pathologic effects of M phi, as well as physiologic effects not previously considered for this widely distributed cell type.
Exercise Testing as a Long-Term Predictor of the Development of Microalbuminuria in Normoalbuminuric IDDM Patients
Authors: Sheila F O'Brien, Gerald F Watts, Jake K Powrie, Kenneth M Shaw
Journal: Diabetes Care (1995)

OBJECTIVE To determine the association between exercise-induced albuminuria and the development of microalbuminuria over 10 years in subjects with insulin-dependent diabetes mellitus (IDDM) who were initially normoalbuminuric. RESEARCH DESIGN AND METHODS Thirty-two patients with IDDM and a resting urinary albumin/creatinine ratio (UA/UC) &amp;lt;2.1 mg/mmol (&amp;lt; 15 μg/min) were exercised after water loading on a treadmill for 20 min at double their resting heart rate. UA/UC was determined before and after exercise. The exercise test was considered positive if the UA/UC was &amp;gt;4.3 mg/mmol (&amp;gt;30 μg/min). Results were compared with resting UA/UC after a 10-year follow-up. Persistent microalbuminuria was defined as a UA/UC &amp;gt;2.1 mg/mmol (&amp;gt; 15 μg/min) in each of two early-morning urine collections. RESULTS Five patients developed persistent microalbuminuria after 10 years, and four patients were predicted by a positive exercise test. Two patients with positive exercise tests did not develop persistent microalbuminuria. The sensitivity of the exercise test for the development of microalbuminuria was 80% (95% confidence interval [CI] 65.8–94.2%) and the specificity was 92.9% (95% CI 83.9–100%). The postexercise UA/UC was positively associated with the UA/UC after 10 years (P = 0.005, R2 = 0.31). This association was independent of HbA1, systolic blood pressure, body mass index, and duration of diabetes, but HbA1 remained an independent predictor (P = 0.02) of UA/UC at follow-up. CONCLUSIONS Exercise testing may be useful for identifying normoalbuminuric IDDM patients who are susceptible to the later development of microalbuminuria.
Combined Intraperitoneal and Intravenous Chemotherapy for Women With Optimally Debulked Ovarian Cancer: Results From an Intergroup Phase II Trial
Authors: Mace L. Rothenberg, P.Y. Liu, Patricia S. Braly, Sharon P. Wilczynski, Edward V. Hannigan, Scott Wadler, Gavin Stuart, Caroline Jiang, Maurie Markman, David S. Alberts
Journal: Journal of Clinical Oncology (2003)

The median survival time for women with optimally debulked adenocarcinoma of the ovary treated with intravenous (IV) chemotherapy is 41 to 52 months, and the 2-year survival rate is 65% to 70%. Recent studies evaluating intraperitoneal (IP) chemotherapy have reported a median survival time of 49 to 63 months and 2-year survival rates of 70% to 80%. This phase II trial was undertaken to evaluate the feasibility of and 2-year survival rate achieved by the combination of IP paclitaxel, IP cisplatin, and IV paclitaxel in women with optimally debulked, stage III ovarian cancer.Treatment consisted of paclitaxel 135 mg/m(2) IV over 24 hours on days 1 to 2, cisplatin 100 mg/m(2) IP on day 2, and paclitaxel 60 mg/m(2) IP on day 8 administered every 21 days for six cycles.In 68 assessable women with optimal stage III ovarian cancer, the 2-year survival rate was 91%, and the median survival time was 51 months. The 2-year disease-free survival rate was 66%, and median disease-free survival time was 33 months. Ninety-six percent of all patients experienced at least one grade 3 to 4 adverse event during therapy, with the most common events being neutropenia (79%), nausea (50%), vomiting (34%), and fatigue/malaise/lethargy (24%). Seventy-one percent of patients completed all six cycles of IV/IP therapy as planned.Combined IV and IP chemotherapy with cisplatin and paclitaxel is associated with a very promising 2-year survival rate in women with optimally debulked ovarian cancer. The ultimate impact of this approach on overall survival requires further evaluation in a randomized trial setting.
Medici Scrittori d'Europa e d'America
Authors: Guiseppe Draetta
Journal: JAMA (1992)

"The physician who writes" has always been a topic of interest for medical periodicals of different kinds (historical, scientific, and even popular). Perhaps no other profession among those whose culture is based on technology and whose method on experiment has offered so many famous examples. This may be the result not only of the human experience gained in practice but also of the humanistic education of many physicians. About ten years ago Arnaldo Cherubini published<i>I medici scrittori dal XV al XX secolo (Physicians and Writers From the 15th to the 20th Century</i>), which was a remarkable achievement in documenting and interpreting this phenomenon. Although some studies on particular authors of varying degrees of importance and some collections of different countries' literature were available, no one had attempted, at least in recent times, to compile a work of such broad scope. In this book European physicians who engaged in writing
Problems of tuberculosis in decline.
Authors: N W Horne
Journal: BMJ (1984)

Problems of tuberculosis in declineProvided that the present momentum is maintained, tuber- culosis should be virtually eradicated from most of the developed countries within 50 years.Nevertheless, apathy on the part of doctors or administrators might appreciably delay this; moreover, some recent publications have shown some of the problems which will occur during the decline of the disease.The death rate from tuberculosis has fallen from about 25 to about one per 100 000 in the past 30 years.This welcome
Coronary Arteriography Standards of Excellence for the Community Hospital
Authors: Jack C. Manley
Journal: JAMA (1976)

The article by Weaver and co-workers (p 819) is a good article, demonstrating again that a very useful but potentially dangerous procedure can be well done at a low risk in a nonuniversity hospital. It also contains an excellent review of the literature. There is, however, no discussion in the article regarding the quality of angiography being performed at their community hospital and whether any of the angiography had to be repeated at the institution where the coronary bypass surgery was performed. Furthermore, from my own experience and that of my colleagues, some of their conclusions appear to differ from ours.<sup>1-3</sup> Our experience at St Luke's Hospital (Milwaukee) (a community hospital with university affiliation) has recently undergone review for the years 1973 to 1974 (more than 3,200 consecutive coronary angiograms). Our experience began most intensively seven years ago with our preoperative and postoperative assessment of patients undergoing bypass revascularization
The Urban Doctors Program
Authors: John T. Daugirdas
Journal: JAMA (1971)

Our goal in setting up the I Urban Doctors Program was to train physicians from and for the poverty communities of the Chicago area. We wanted to produce physicians who might practice in these communities not because they were "incentivated" to do so, either monetarily or otherwise, but because they saw this form of practice in their own neighborhoods as personally and professionally rewarding. We believed that there were two variables we could affect at the medical school level to improve the chances of producing this type of community-oriented physician. For the sake of discussion, let us call these "input" and "process." First, we examined the backgrounds of medical students at Northwestern University and at urban medical schools in general. We found that few students at these schools came from poverty communities in the area. We realized that a commitment by a medical school to train people from these communities
Government announces end of NHS IT programme--for second time
Authors: M. Cross
Journal: BMJ (2011)

For the second time in a year the UK government has announced the end of the £12bn (€13.7bn; $18.5bn) programme to computerise the NHS in England. 

However, the announcement offers no detail on how the Department of Health will extricate itself from troubled information technology (IT) contracts. It also implies that large parts of the programme will remain intact.

In a statement apparently leaked to daily newspapers the department said that the government “had announced an acceleration of the dismantling” of the NHS National Programme for IT. It noted that the programme “was created in 2002 under the last government” and that a review by the Cabinet Office’s new Major Projects Authority had concluded that the programme is “not fit to provide the modern IT services that the NHS needs.”

The review was launched after a devastating report by the National Audit Office into the most …
Cyclic adenosine 3′,5′-monophosphate in human lymphocytes. Alterations after phytohemagglutinin stimulation
Authors: Jay W. Smith, Alton L. Steiner, W. Marcus Newberry, Charles W. Parker
Journal: Journal of Clinical Investigation (1971)

We have studied cyclic adenosine 3',5'-monophosphate (cyclic AMP) concentrations in human peripheral blood lymphocytes after stimulation with phytohemagglutinin (PHA), isoproterenol, prostaglandins, and aminophylline. Purified lymphocytes were obtained by nylon fiber chromatography, and low speed centrifugation to remove platelets. Cyclic AMP levels were determined by a highly sensitive radioimmunoassay. At concentrations of 0.1-1.0 mmoles/liter isoproterenol and aminophylline produced moderate increases in cyclic AMP concentrations, whereas prostaglandins produced marked elevations. High concentrations of PHA produced 25-300% increases in cyclic AMP levels, alterations being demonstrated within 1-2 min. The early changes in cyclic AMP concentration appear to precede previously reported metabolic changes in PHA-stimulated cells. After 6 hr cyclic AMP levels in PHA-stimulated cells had usually fallen to the levels of control cells. After 24 hr the level in PHA-stimulated cells was characteristically below that of the control cells. Adenyl cyclase, the enzyme which converts ATP to cyclic AMP, was measured in lymphocyte homogenates. Adenyl cyclase activity was rapidly stimulated by fluoride, isoproterenol, prostaglandins, and PHA. Since adenyl cyclase is characteristically localized in external cell membranes, our results are consistent with an initial action of PHA at this level.