tbuckley/cabot-search huggingface dataset:
Selective Visualization of Cyclooxygenase-2 in Inflammation and Cancer by Targeted Fluorescent Imaging Agents
Authors: Md. Jashim Uddin, Brenda C. Crews, Anna L. Blobaum, Philip J. Kingsley, D. Lee Gorden, J. Oliver McIntyre, Lynn M. Matrisian, Kotha Subbaramaiah, Andrew J. Dannenberg, David W. Piston, Lawrence J. Marnett
Journal: Cancer Research (2010)

Abstract Effective diagnosis of inflammation and cancer by molecular imaging is challenging because of interference from nonselective accumulation of the contrast agents in normal tissues. Here, we report a series of novel fluorescence imaging agents that efficiently target cyclooxygenase-2 (COX-2), which is normally absent from cells, but is found at high levels in inflammatory lesions and in many premalignant and malignant tumors. After either i.p. or i.v. injection, these reagents become highly enriched in inflamed or tumor tissue compared with normal tissue and this accumulation provides sufficient signal for in vivo fluorescence imaging. Further, we show that only the intact parent compound is found in the region of interest. COX-2–specific delivery was unambiguously confirmed using animals bearing targeted deletions of COX-2 and by blocking the COX-2 active site with high-affinity inhibitors in both in vitro and in vivo models. Because of their high specificity, contrast, and detectability, these fluorocoxibs are ideal candidates for detection of inflammatory lesions or early-stage COX-2–expressing human cancers, such as those in the esophagus, oropharynx, and colon. Cancer Res; 70(9); 3618–27. ©2010 AACR.
The Role of Nuclear Imaging in the Management of the First Total Artificial Heart Recipient
Authors: ANDREW TAYLOR, WALTER MILTON, PAUL E. CHRISTIAN, FREDERICK L. DATZ, LYLE JOYCE, WILLIAM C. DeVRIES
Journal: Clinical Nuclear Medicine (1985)

On December 2,1982, a permanent total artificial heart was implanted into the chest of a 61-year-old man with a progressive and irreversible cardiomyopathy. During the ensuing four-month hospitalization, a number of nuclear medicine procedures were obtained to assist in patient management. These procedures included gated cardiac radionuclide ventriculography, an I-123 iodoamphetamine scan for cerebral perfusion, and ln-111 labeled leukocyte imaging. These radionuclide studies demonstrate the advantages of being able to monitor physiologic changes noninvasively and illustrate a potential role for nuclear cardiology in managing patients with a total artificial heart.
Selective ablation of insulin receptor substrate-1 decreases cardiac contractility in vivo without attenuating PAI-1 expression or perivascular fibrosis
Authors: Satoshi Fujii, Tomoo Furumoto, Hisao Onozuka, Taisei Mikami, Daisuke Goto, Tarikuz Zaman, Taeko Sugawara, Yasuo Terauchi, Takashi Kadowaki, Burton E. Sobel, Akira Kitabatake
Journal: Journal of the American College of Cardiology (2003)
Novel IL-12 family members shed light on the orchestration of Th1 responses
Authors: Frank Brombacher, Robert A. Kastelein, Gottfried Alber
Journal: Trends in Immunology (2003)

Interleukin-12 (IL-12), which is composed of a p35 and a p40 subunit, is a proinflammatory natural-killer (NK) cell-stimulating, Th1-inducing and Th1-maintaining cytokine, which promotes cell-mediated immunity. On activation, heterodimeric IL-12 is found in small amounts, whereas free p40 is produced in excess. Besides IL-12, other p40-dependent molecules exist that orchestrate Th1 responses. Homodimeric p40 can act as an IL-12 antagonist by competing for its receptor. Recent data also reveal potential immunostimulatory functions of p40. In addition, p40 can be covalently linked to a p35-related protein p19. This heterodimer is known as IL-23 and has activities on memory T cells. Finally, IL-27, the latest addition to this family, is a heterodimer composed of the p40-related protein EBI3 (Epstein–Barr virus-induced gene 3) and the p35-related protein p28. IL-27 is involved in early Th1 initiation.
Effect of Rotavirus Vaccination on Death from Childhood Diarrhea in Mexico
Authors: Vesta Richardson, Joselito Hernandez-Pichardo, Manjari Quintanar-Solares, Marcelino Esparza-Aguilar, Brian Johnson, Cesar Misael Gomez-Altamirano, Umesh Parashar, Manish Patel
Journal: New England Journal of Medicine (2010)

A phased introduction of a monovalent rotavirus vaccine occurred in Mexico from February 2006 through May 2007. We assessed the effect of vaccination on deaths from diarrhea in Mexican children in 2008 and 2009.We obtained data on deaths from diarrhea, regardless of cause, from January 2003 through May 2009 in Mexican children under 5 years of age. We compared diarrhea-related mortality in 2008 and during the 2008 and 2009 rotavirus seasons with the mortality at baseline (2003-2006), before the introduction of the rotavirus vaccine. Vaccine coverage was estimated from administrative data.By December 2007, an estimated 74% of children who were 11 months of age or younger had received one dose of rotavirus vaccine. In 2008, there were 1118 diarrhea-related deaths among children younger than 5 years of age, a reduction of 675 from the annual median of 1793 deaths during the 2003-2006 period. Diarrhea-related mortality fell from an annual median of 18.1 deaths per 100,000 children at baseline to 11.8 per 100,000 children in 2008 (rate reduction, 35%; 95% confidence interval [CI], 29 to 39; P<0.001). Among infants who were 11 months of age or younger, diarrhea-related mortality fell from 61.5 deaths per 100,000 children at baseline to 36.0 per 100,000 children in 2008 (rate reduction, 41%; 95% CI, 36 to 47; P<0.001). As compared with baseline, diarrhea-related mortality was 29% lower for children between the ages of 12 and 23 months, few of whom were age-eligible for vaccination. Mortality among unvaccinated children between the ages of 24 and 59 months was not significantly reduced. The reduction in the number of diarrhea-related deaths persisted through two full rotavirus seasons (2008 and 2009).After the introduction of a rotavirus vaccine, a significant decline in diarrhea-related deaths among Mexican children was observed, suggesting a potential benefit from rotavirus vaccination.
P4-10-06: Evaluation of BRCAPro Risk Assessment Model in Patients with Ductal Carcinoma In Situ.
Authors: KI Muse, N Elsayegh, AM Gutierrez-Barrera, H Kuerer, V Valero, JK Litton, GN Hortobagyi, BK Arun
Journal: Cancer Research (2011)

Abstract Background: The BRCAPRo model is used to predict a patient's likelihood to possess a BRCA1 or BRCA2 gene mutation based upon personal and family history. Ductal carcinoma in situ (DCIS) is considered a non-invasive condition which can progress to an invasive breast cancer if left untreated. Currently, DCIS is not specifically accounted for in the BRCAPro model, thereby causing DCIS to be weighted in the same manner as an invasive breast cancer diagnosis. Historically, a diagnosis of DCIS has been entered as having developed into an invasive breast cancer ten years later. However, there are no standard guidelines of how DCIS should be entered. We sought to determine if there were any differences in how DCIS was treated in the BRCAPro model to predict the more effective method in calculating the BRCAPro. Methods: Women with pure DCIS, who were referred for genetic counseling and underwent genetic testing, were included in the study. The likelihood of carrying a BRCA mutation was calculated using the BRCAPRO model (Version 5.1). Patient characteristics which were entered into the BRCAPro model include: tumor markers (estrogen receptor-ER and progesterone receptor-PR), history of oophorectomy prior to diagnosis, family history of 1st and 2nd degree relatives with breast and ovarian cancer, race and Ashkenazi Jewish ancestry. Each patient's BRCAPro risk estimate was calculated and compared by entering DCIS at the presenting age of diagnosis and by adding 10 years to the age of diagnosis. Descriptive statistics and a student's t-test were used to compare BRCAPro estimates between the two groups. Results: Ninety-five patients with pure DCIS underwent genetic counseling and testing. The average age of DCIS diagnosis was 45 years (range 26–65). Of the 95 DCIS patients included in the study 21% (n=20) tested positive for a BRCA gene mutation (8 BRCA1 and 12 BRCA2), 77% (n=74) test negative and 0.01% (n=1) had a variant of uncertain significance. Overall, DCIS patients who tested positive for a BRCA mutation had a higher BRCAPro (40%) than patients who tested negative (12%) when presenting age of diagnosis was assessed. When 10 years was added, the BRCAPro estimate was still higher amongst BRCA positive patients (28%) than BRCA negative patients (8%). The mean BRCAPro probability when DCIS was entered at presenting age of diagnosis was 18% (0.1−95.4) versus 12% (0.1−89.9) when calculated 10 years later. Conclusion: In our cohort there was no significant difference in BRCAPro probability whether DCIS was entered at the presenting age of diagnosis or 10 years later (p=0.1). However, future studies are needed to determine the most effective method to incorporate DCIS into the BRCAPro model in order to determine those individuals who may or may not be at increase risk to possess a BRCA gene mutation. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-06.
A Combination of Oral Sildenafil and Beraprost Ameliorates Pulmonary Hypertension in Rats
Authors: Takefumi Itoh, Noritoshi Nagaya, Takafumi Fujii, Takashi Iwase, Norifumi Nakanishi, Kaoru Hamada, Kenji Kangawa, Hiroshi Kimura
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Sildenafil, an oral phosphodiesterase type-5 inhibitor, has vasodilatory effects through a cyclic guanosine 3', 5'-monophosphate-dependent mechanism, whereas beraprost, an oral prostacyclin analog, induces vasorelaxation through a cAMP-dependent mechanism. We investigated whether the combination of oral sildenafil and beraprost is superior to each drug alone in the treatment of pulmonary hypertension. Rats were randomized to receive repeated administration of saline, sildenafil, beraprost, or both of these drugs twice a day for 3 weeks. Three weeks after monocrotaline (MCT) injection, there was significant development of pulmonary hypertension. The increases in right ventricular systolic pressure and ratio of right ventricular weight to body weight were significantly attenuated in the Sildenafil and Beraprost groups. Combination therapy with sildenafil and beraprost had additive effects on increases in plasma cAMP and cyclic guanosine 3', 5'-monophosphate levels, resulting in further improvement in pulmonary hemodynamics compared with treatment with each drug alone. Unlike MCT rats given saline, sildenafil, or beraprost alone, all rats treated with both drugs remained alive during 6-week follow-up. These results suggest that combination therapy with oral sildenafil and beraprost attenuates the development of MCT-induced pulmonary hypertension compared with treatment with each drug alone.
THE RELATION OF INFLAMMATION TO THE MOLECULAR STRUCTURE OF CARBON COMPOUNDS SOLUBLE IN THE FLUIDS OF THE BODY
Authors: Eugene L. Opie
Journal: The Journal of Experimental Medicine (1965)

The peritoneal, like the pleural cavity, gives opportunity to measure with adequate accuracy the activity of inflammatory reactions defined by movement of fluid within the cavity, by migration of leucocytes into it, and by exudation of proteins from the plasma. The activity of inflammatory reactions caused by saccharides or by alcohols that were tested varied in accord with their molecular weight, the osmotic pressure maintained by solutions of corresponding concentration, their boiling point, or by other colligative properties. Blood serum or globulin in the concentration with which it occurs in blood serum injected into the peritoneal cavity caused changes which differed little from those caused by physiological salt solution. Protein with molecular weight as low as that of cytochrome C (12,000) or ovalbumin (45,000) when in dilute solution (1 per cent) were rapidly absorbed, whereas trypsin and chymotrypsin under the same conditions caused very active inflammatory reactions because they set free amino acids and perhaps polypeptides with amino acids in short chains. The activity of inflammatory reactions caused by carbon compounds soluble in body fluids varied in accord with their colligative properties.
1185 A MULTICENTRIC STUDY REGARDING THE QUALITY OF TISSUE SAMPLES AT PERCUTANEOUS LIVER BIOPSY
Authors: I. Sporea, A. Popescu, M. Curescu, I. Rogoveanu, L. Sandulescu, C. Brise, C. Cijevschi Prelipcean, C. Mihai, D. Gherhardt, R. Sirli, M. Cornianu, S. Bota
Journal: Journal of Hepatology (2011)
The scandal of poor medical research: Sloppy use of literature often to blame
Authors: R Jones, J Scouller, F Grainer, M Lachlan, S Evans, N Torrance, R C Tallis, N A Matheson, J A Morris, T E J Ind, H Dudley, A Sykes, G R Masterson, S G Ashcroft, J P W Bell, H Goodare
Journal: BMJ (1994)

The scandal ofpoor medical research Sloppy use ofliterature often to blame EDrroR,-Douglas G Altman highlights the need for improvement in research studies and publications.'Editors of the BMJ have been active in trying to tighten the standards of published articles,23 and formal statistical appraisal is now part of the peer review process.However, four papers chosen haphazardly from last year's BMJ provide examples of sloppy use of the literature, which could be tackled by explicit guidelines and perhaps formal appraisal of the literature.The BMJ's current instructions to authors include guidance only on referencing style.We suggest three guidelines for discussion.
Abnormal Communication between the Aorta and Left Ventricle
Authors: ROBERT N. COOLEY, LEONARD C. HARRIS, ALVIN E. RODIN
Journal: Circulation (1965)

A case is presented of a 16-month-old white boy with a communication or tunnel between the right sinus of Valsalva and the outflow tract of the left ventricle. The presence of a murmur at birth and the subsequent clinical course suggest that the tunnel was congenital. The physical, electrocardiographic, phonocardiographic, and aortographic findings were quite similar to those of "aortico-left ventricular tunnel" as described by Levy et al. 1 The tunnel was occluded surgically, but failure to appreciate the presence of severe aortic stenosis contributed to a fatal outcome. Postmortem study was carried out, and the relationship of the findings of aortico-left ventricular tunnel to aneurysm of the sinuses of Valsalva and the Marfan syndrome is briefly discussed.
8;21 translocation and multilineage involvement
Authors: Y. L. Kwong, L. M. Ching, H. W. Liu, C. P. Lee, A. Pollock, L. C. Chan
Journal: American Journal of Hematology (1993)

Abstract The translocation (8;21)(q22;q22) is commonly associated with acute myeloid leukemia (AML) M2 according to the French‐American‐British (FAB) classification. We describe 11 cases of t(8;21) diagnosed by strict FAB criteria. Six cases were diagnosed as AML M2, 3 cases as AML M4, 1 case as refractory anemia with excess of blasts in transformation, and 1 case as Philadelphia chromosome negative chronic myeloid leukemia in acceleration. Translocation (8;21) could thus occur in a wider variety of hematological abnormalities. Accordingly, we propose that t(8;21) may involve different hemopoietic lineages.
Influence of Apolipoproteins on the Association Between Lipids and Insulin Sensitivity
Authors: Simona Baldi, Fabrice Bonnet, Martine Laville, Cecilia Morgantini, Lucilla Monti, Kurt Hojlund, Ele Ferrannini, Andrea Natali
Journal: Diabetes Care (2013)

We evaluated whether the association of insulin sensitivity with HDL cholesterol (HDL) and triglycerides is influenced by major plasma apolipoproteins, as suggested by recent experimental evidence.This study included a cross-sectional analysis of the RISC Study, a multicenter European clinical investigation in 1,017 healthy volunteers balanced in sex (women 54%) and age strata (range 30-60 years). Insulin sensitivity (M/I in µmol ⋅ min(-1) ⋅ kgFFM(-1) ⋅ nM(-1)) was measured by the clamp technique and apolipoproteins (ApoB, -C3, -A1, and -E) by Multiplex Technology.The center-, sex-, and age-adjusted standardized regression coefficients (STDβ) with M/I were similar for HDL and triglycerides (+19.9 ± 1.9 vs. -20.0 ± 2.0, P < 0.0001). Further adjustment for triglycerides (or HDL), BMI, and adiponectin (or nonesterified fatty acid) attenuated the strength of the association of M/I with both HDL (STDβ +6.4 ± 2.3, P < 0.01) and triglycerides (-9.5 ± 2.1, P < 0.001). Neither ApoA1 nor ApoE and ApoB showed any association with M/I independent from plasma HDL cholesterol and triglycerides. ApoC3, in contrast, in both men and women, was positively associated with M/I independently of plasma lipids. A relative enrichment of plasma lipids with ApoC3 is associated with lower body fat percentage and lower plasma alanine amino transferase.Our results suggest that HDL cholesterol modulates insulin sensitivity through a mechanism that is partially mediated by BMI and adiponectin but not by ApoA1. Similarly, the influence of triglycerides on insulin sensitivity is in part mediated by BMI and is unrelated to ApoE or ApoB, but it is significantly modulated by ApoC3, which appears to protect from the negative effect of plasma lipids.
Comparative Effectiveness of Clopidogrel in Medically Managed Patients With Unstable Angina and Non–ST-Segment Elevation Myocardial Infarction
Authors: Matthew D. Solomon, Alan S. Go, David Shilane, Derek B. Boothroyd, Thomas K. Leong, Dhruv S. Kazi, Tara I. Chang, Mark A. Hlatky
Journal: Journal of the American College of Cardiology (2014)
Aerobic exercise training improves insulin sensitivity without changes in body weight, body fat, adiponectin, and inflammatory markers in overweight and obese girls
Authors: George P. Nassis, Katerina Papantakou, Katerina Skenderi, Maria Triandafillopoulou, Stavros A. Kavouras, Mary Yannakoulia, George P. Chrousos, Labros S. Sidossis
Journal: Metabolism (2005)
Cost-Effectiveness of a Vaccine To Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults
Authors: John Hornberger, Katherine Robertus
Journal: Annals of Internal Medicine (2006)

Background: The Shingles Prevention Study showed that a varicella-zoster virus (VZV) vaccine administered to adults 60 years of age or older reduced the incidence of herpes zoster from 11.12 to 5.42 cases per 1000 person-years. Median follow-up was 3.1 years, and relative risk reduction was 51.3% (95% CI, 44.2% to 57.6%). Objective: To assess the extent to which clinical and cost variables influence the cost-effectiveness of VZV vaccination for preventing herpes zoster in immunocompetent older adults. Design: Decision theoretical model. Data Sources: English-language data published to March 2006 identified from MEDLINE on herpes zoster rates, vaccine effectiveness, quality of life, medical resource use, and unit costs. Target Population: Immunocompetent adults 60 years of age or older with a history of VZV infection. Time Horizon: Lifetime. Perspective: U.S. societal. Interventions: Varicella-zoster virus vaccination versus no vaccination. Outcome Measures: Incremental quality-adjusted survival and cost per quality-adjusted life-year (QALY) gained. Results of Base-Case Analysis: By reducing incidence and severity of herpes zoster, vaccination can increase quality-adjusted survival by 0.6 day compared with no vaccination. One scenario in which vaccination costs less than $100 000 per QALY gained is when 1) the unit cost of vaccination is less than $200, 2) the age at vaccination is less than 70 years, and 3) the duration of vaccine efficacy is more than 30 years. Results of Sensitivity Analysis: Vaccination would be more cost-effective in "younger" older adults (age 60 to 64 years) than in "older" older adults (age ≥80 years). Longer life expectancy and a higher level of vaccine efficacy offset a lower risk for herpes zoster in the younger group. Other factors influencing cost-effectiveness include quality-of-life adjustments for acute zoster, unit cost of the vaccine, risk for herpes zoster, and duration of vaccine efficacy. Limitations: The effectiveness of VZV vaccination remains uncertain beyond the median 3.1-year duration of follow-up in the Shingles Prevention Study. Conclusions: Varicella-zoster virus vaccination to prevent herpes zoster in older adults would increase QALYs compared with no vaccination. Resolution of uncertainties about the average quality-of-life effects of acute zoster and the duration of vaccine efficacy is needed to better determine the cost-effectiveness of zoster vaccination in older adults.
Somatostatin Receptors as Markers for Endocrine Tumors
Authors: Jean-Claude Reubi
Journal: JAMA (1987)

Endocrine tumors of the gastrointestinal tract are relatively rare neoplasias that secrete large amounts of peptide hormones such as insulin, glucagon, gastrin, or vasoactive intestinal peptide (VIP). 1 These substances are usually responsible for the distinct clinical features observed in patients with such tumors, named specifically insulinomas, glucagonomas, gastrinomas, VIPomas, or carcinoids. Although most are relatively slow-growing tumors, they may lead in early stages to dramatic symptoms such as hypoglycemia, gastric ulcerations, or watery diarrhea. Unfortunately, they are often difficult to localize precisely at that stage. 2   Somatostatin, 3 a tetradecapeptide that inhibits peptide hormone release in various sites such as the pituitary, the pancreas, and the gastrointestinal tract, has been shown recently to have beneficial effects when given chronically in the form of a stable non-degradable octapeptide analogue (SMS 201-995) in such gastrointestinal endocrine tumors. 4,5 It is likely that its therapeutic effect is due in part to inhibition
The use and interpretation of tests for steroid impaired hypothalamic–pituitary–adrenocortical function
Authors: J. LANDON, E. SNITCHER, LESLEY REES
Journal: British Journal of Dermatology (1976)

Journal Article The use and interpretation of tests for steroid impaired hypothalamic–pituitary–adrenocortical function Get access J. LANDON, J. LANDON Department of Chemical Pathology, St Bartholomew's Hospital, London EC1 Search for other works by this author on: Oxford Academic Google Scholar E. SNITCHER, E. SNITCHER Department of Chemical Pathology, St Bartholomew's Hospital, London EC1 Search for other works by this author on: Oxford Academic Google Scholar LESLEY REES LESLEY REES Department of Chemical Pathology, St Bartholomew's Hospital, London EC1 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 94, Issue s12, 1 March 1976, Pages 61–65, https://doi.org/10.1111/j.1365-2133.1976.tb02271.x Published: 01 March 1976
Thinking the unthinkable!
Authors: Z. A. Bhutta
Journal: BMJ (2002)

Preparing for Armageddon in South Asia 

News p 1412 

The unthinkable has actually happened. Over a span of barely four years, the subcontinent and its military and political leadership seem to have moved seamlessly from an obtuse nuclear capability and a doctrine of nuclear deterrence to the present state of nuclear weaponisation.1 As a million soldiers face each other across the volatile line of control and the border between India and Pakistan, the arguments have shifted from no use of nuclear weapons to their potential use in the event of conventional war, to the current state of actual deployment. To a large extent the numerical superiority of the Indian army and air force translates into a no win situation for Pakistan in the event of a conventional conflict. Faced with the potential of humiliation and dismemberment in such a scenario, a nuclear first strike becomes a frighteningly real possibility.2

The debate and outcry on this reckless brinkmanship in South Asia has remained confined to the peace groups, and the vernacular press has largely been jingoistic and indifferent to the disastrous consequences of nuclear war. While …