tbuckley/cabot-search huggingface dataset:
Mammalian Target of Rapamycin Regulates Vascular Endothelial Growth Factor–Dependent Liver Cyst Growth in Polycystin-2–Defective Mice
Authors: Carlo Spirli, Stefano Okolicsanyi, Romina Fiorotto, Luca Fabris, Massimiliano Cadamuro, Silvia Lecchi, Xin Tian, Stefan Somlo, Mario Strazzabosco
Journal: Hepatology (2009)

Polycystic liver disease may complicate autosomal dominant polycystic kidney disease (ADPKD), a disease caused by mutations in polycystins, which are proteins that regulate signaling, morphogenesis, and differentiation in epithelial cells. The cystic biliary epithelium [liver cystic epithelium (LCE)] secretes vascular endothelial growth factor (VEGF), which promotes liver cyst growth via autocrine and paracrine mechanisms. The expression of insulin-like growth factor 1 (IGF1), insulin-like growth factor 1 receptor (IGF1R), and phosphorylated mammalian target of rapamycin (p-mTOR) and the protein kinase A (PKA)–dependent phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) are also up-regulated in LCE. We have hypothesized that mammalian target of rapamycin (mTOR) represents a common pathway for the regulation of hypoxia-inducible factor 1 alpha (HIF1α)–dependent VEGF secretion by IGF1 and ERK1/2. Conditional polycystin-2–knockout (Pkd2KO) mice were used for in vivo studies and to isolate cystic cholangiocytes [liver cystic epithelial cells (LCECs)]. The expression of p-mTOR, VEGF, cleaved caspase 3 (CC3), proliferating cell nuclear antigen (PCNA), IGF1, IGF1R, phosphorylated extracellular signal-regulated kinase, p-P70S6K, HIF1α, and VEGF in LCE, LCECs, and wild-type cholangiocytes was studied with immunohistochemistry, western blotting, or enzyme-linked immunosorbent assays. The cystic area was measured by computer-assisted morphometry of pancytokeratin-stained sections. Cell proliferation in vitro was studied with 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H -tetrazolium and bromodeoxyuridine assays. The treatment of Pkd2KO mice with the mTOR inhibitor rapamycin significantly reduced the liver cyst area, liver/body weight ratio, pericystic microvascular density, and PCNA expression while increasing expression of CC3. Rapamycin inhibited IGF1-stimulated HIF1α accumulation and VEGF secretion in LCECs. IGF1-stimulated LCEC proliferation was inhibited by rapamycin and SU5416 (a vascular endothelial growth factor receptor 2 inhibitor). Phosphorylation of the mTOR-dependent kinase P70S6K was significantly reduced by PKA inhibitor 14-22 amide and by the mitogen signal-regulated kinase inhibitor U1026. Conclusion: These data demonstrate that PKA-dependent up-regulation of mTOR has a central role in the proliferative, antiapoptotic, and pro-angiogenic effects of IGF1 and VEGF in polycystin-2–defective mice. This study also highlights a mechanistic link between PKA, ERK, mTOR, and HIF1α-mediated VEGF secretion and provides a proof of concept for the potential use of mTOR inhibitors in ADPKD and conditions with aberrant cholangiocyte proliferation. (Hepatology 2010.)
Endocrine disrupters and human health
Authors: P. T C Harrison
Journal: BMJ (2001)

Infertility is an emotive issue, and having children is a recognised “right,” so any implication that environmental pollution affects reproduction has to be taken seriously. When the putative causative agents might also be responsible for various cancers and other diseases, then the level of interest that the issue attracts is unsurprising—hence the calls in the early 1990s for action in line with the “precautionary principle.”1 In men hypospadias, cryptorchidism, cancer of the prostate, testicular cancer, and semen quality and in women breast cancer, cystic ovaries, and endometriosis have all been suggested as indicators of adverse trends in reproductive health.2 The idea that these trends are real and are connected with environmental pollution is gaining credence internationally. The effect on human health of environmental chemicals that are mediated through the endocrine system—endocrine disrupters—has generated huge interest and investment. Why is this, and what is the evidence for the assumed association?

Changes in the sexual morphology of fish exposed to sewage effluent have led some scientists to conjecture that humans also live in a “sea of oestrogens” and that the apparent increases in the incidence of certain reproductive conditions may be due …
Identification of Flt3+CD150− myeloid progenitors in adult mouse bone marrow that harbor T lymphoid developmental potential
Authors: Anthony W. S. Chi, Alejandro Chavez, Lanwei Xu, Brittany N. Weber, Olga Shestova, Andras Schaffer, Gerald Wertheim, Warren S. Pear, David Izon, Avinash Bhandoola
Journal: Blood (2011)
A dynamic duo: Emotion and development
Authors: Arlene S. Walker-Andrews, Jeannette Haviland-Jones
Journal: Behavioral and Brain Sciences (2005)

A dynamic systems (DS) approach uncovers important connections between emotion and neurophysiology. It is critical, however, to include a developmental perspective. Strides in the understanding of emotional development, as well as the present use of DS in developmental science, add significantly to the study of emotion. Examples include stranger fear during infancy, intermodal perception of emotion, and development of individual emotional systems.
Paricalcitol aggravates perivascular fibrosis in rats with renal insufficiency and low calcitriol
Authors: J.M. Repo, I.S. Rantala, T.T. Honkanen, J.T. Mustonen, P. Kööbi, A.M. Tahvanainen, O.J. Niemelä, I. Tikkanen, J.M. Rysä, H.J. Ruskoaho, I.H. Pörsti
Journal: Kidney International (2007)
Surgical Treatment of Left Ventricular Aneurysms
Authors: C. R. Lam, H. Gale, E. Drake
Journal: JAMA (1964)

Six patients with large postinfarction ventricular aneurysms have received surgical treatment. The aneurysms were excised during cardiopulmonary bypass with a pump oxygenator of the bubble type. There were two fatalities in patients with large areas of infarction involving the ventricular septum. The four surviving patients have returned to their normal activities. A review of the reported experience of other cardiac centers indicates that the prognosis following definitive surgical treatment of ventricular aneurysms is remarkably good.
Indication for temporary pace maker implantation in Lyme Borreliosis Carditis
Authors: Biljana Milentijevic, Zorana Vasiljevic, Igor Mrdovic, A. Karadzic, Predrag Mitrovic, Tanja Jozic, Gordana Matic, Dubravka Rajic, Nebojsa Radovanovic
Journal: European Journal of Heart Failure (2000)
Ionizing Radiation Enhances Matrix Metalloproteinase-2 Secretion and Invasion of Glioma Cells through Src/Epidermal Growth Factor Receptor–Mediated p38/Akt and Phosphatidylinositol 3-Kinase/Akt Signaling Pathways
Authors: Chang-Min Park, Myung-Jin Park, Hee-Jin Kwak, Hyung-Chahn Lee, Mi-Suk Kim, Seung-Hoon Lee, In-Chul Park, Chang Hun Rhee, Seok-Il Hong
Journal: Cancer Research (2006)

Abstract Glioblastoma is a severe type of primary brain tumor, and its highly invasive character is considered to be a major therapeutic obstacle. Several recent studies have reported that ionizing radiation (IR) enhances the invasion of tumor cells, but the mechanisms for this effect are not well understood. In this study, we investigated the possible signaling mechanisms involved in IR-induced invasion of glioma cells. IR increased the matrix metalloproteinase (MMP)-2 promoter activity, mRNA transcription, and protein secretion along with the invasiveness of glioma cells lacking functional PTEN (U87, U251, U373, and C6) but not those harboring wild-type (WT)-PTEN (LN18 and LN428). IR activated phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin, and blockade of these kinases by specific inhibitors (LY294002, Akt inhibitor IV, and rapamycin, respectively) and transfection of dominant-negative (DN) mutants (DN-p85 and DN-Akt) or WT-PTEN suppressed the IR-induced MMP-2 secretion in U251 and U373 cells. In addition, inhibitors of epidermal growth factor receptor (EGFR; AG490 and AG1478), Src (PP2), and p38 (SB203580), EGFR neutralizing antibody, and transfection of DN-Src and DN-p38 significantly blocked IR-induced Akt phosphorylation and MMP-2 secretion. IR-induced activation of EGFR was suppressed by PP2, whereas LY294002 and SB203580 did not affect the activations of p38 and PI3K, respectively. Finally, these kinase inhibitors significantly reduced the IR-induced invasiveness of these cells on Matrigel. Taken together, our findings suggest that IR induces Src-dependent EGFR activation, which triggers the p38/Akt and PI3K/Akt signaling pathways, leading to increased MMP-2 expression and heightened invasiveness of PTEN mutant glioma cells. (Cancer Res 2006; 66(17): 8511-9)
4,5-Diaryloxazole inhibitors of cyclooxygenase-2 (COX-2)
Authors: John J. Talley, Stephen R. Bertenshaw, David L. Brown, Jeffery S. Carter, Mathew J. Graneto, Carol M. Koboldt, Jaime L. Masferrer, Bryan H. Norman, D. Joseph Rogier, Ben S. Zweifel, Karen Seibert
Journal: Medicinal Research Reviews (1999)

A series of methysulfonyl or sulfonamido substituted 4,5-diaryloxazole were prepared and evaluated for their ability to inhibit the inducible form of cyclooxygenase (COX-2) in vitro and in vivo. Several unique substitution patterns were identified that led to potent and selective inhibitors of COX-2. In general, 2-trifluoromethly-4,5-diaryloxazoles substituted with a methylsulfonyl or sulfonamido group were particularly potent inhibitors. One of the more potent compounds with a selectivity for COX-2 of about 800 fold was 4b (SC-299). SC-299, a highly fluorescent molecule, may be useful for spectroscopic studies on preferential inhibitor binding to COX-2. © 1999 John Wiley & Sons, Inc. Med Res Rev, 19, No. 3, 199–208, 1999.
Unusual Cause of Gastric Bleeding: Cronkhite-Canada Polyposis
Authors: J. Armengol-Miró, J. Pedreira, J. Guardia
Journal: Endoscopy (1977)

A 39-year-old male presented with melena and sideropenic anemia. Gastric barium meal showed multiple feeling defects and gastric endoscopy showed in the antrum several polypoid lesions that histopathologically were consistent with Cronkhite-Canada polyposis. Studies on intestinal absorption were within normal limits.
EXERCISE AS A MODE OF TREATING DISEASES OF THE HEART.
Authors: N. S. DAVIS
Journal: JAMA (1903)

Our knowledge of diseases of the heart is of comparatively recent date. It is true that Vesalius did much to make known the anatomy of the organ and that Harvey demonstrated its purpose or function. This much was learned in the sixteenth century, and during the following centuries contributions were made slowly to a knowledge of its pathology; but methods of physical diagnosis by which its pathologic states could be recognized during life were not discovered until the end of the eighteenth and first quarter of the nineteenth centuries. The opinions of former generations of medical men have not yet been outgrown by laymen, and many of the latter think that a permanent anatomic defect in the heart means sudden death, death which is especially apt to be caused by physical exertion. The fact that overexertion, either mental or physical, can cause dilatation, and, perhaps, fatal weakness, of the
Synchronized DC Precordial Shock for Arrhythmias
Authors: Thomas Killip
Journal: JAMA (1963)

Synchronized precordial direct current shock has been applied in the treatment of sustained arrhythmia 84 times in 62 patients. Sinus rhythm was restored in 90% of the patients in 85% of the attempts. Single and multiple shocks were tolerated without significant electrocardiographic abnormality, aside from change in rhythm, or transaminase rise. No pulmonary or systemic emboli occurred during 71 reversions to sinus rhythm although anticoagulants had been withheld in more than half the patients. Complications were limited to the development of other arrhythmias in three patients. Synchronized direct current precordial shock is a safe, simple, and effective therapy of ectopic arrhythmia which may be utilized on an elective or emergency basis. The results are immediately apparent.
Children need international formulary to guarantee rational use of drugs
Authors: M. Bonati
Journal: BMJ (2004)

Diagnosis of autism Adequate funding is needed for assessment services2][3] One important additional reason for such provision, which their review does not emphasise, is that well coordinated, multiagency assessment teams for autism spectrum disorders have a better chance of accurately not giving a diagnosis of it.Our multiagency assessment service for autism spectrum disorders has seen 57 patients in the past two years.We request baseline speech and language therapy and (where applicable) educational psychology assessments on the likelihood of autism spectrum disorder in all cases before patients are seen by our team, so as to ensure best use of clinical resources.Despite this approach only 26 patients (46%) deemed to be likely cases of autism spectrum disorder received a positive diagnosis.This is not due to overzealous interpretation of ICD-10 diagnostic criteria (which are increasingly recognised as being in urgent need of review), as we tend, if anything, to err in favour of diagnosis, even if ICD-10 (or DSM-IV) criteria, are not strictly fulfilled.Relevant agencies must receive adequate funding for implementing the national autism plan for children. 3This is to benefit not only the children and their families who are struggling with the often devastating impact of this disorder but also the depressingly high number of children whom, we suspect, will be wrongly, or inaccurately, given diagnoses, if assessment services for autism spectrum disorders do not improve.
NONINVASIVE IDENTIFICATION OF LEFT MAIN AND TRIPLE-VESSEL CORONARY ARTERY DISEASE IN PATIENTS WITH PRIOR MYOCARDIAL INFARCTION
Authors: Alnoor Abdulla, Jamshid Maddahl, Deborah Barbour, Ernest Garcia, H. J.C. Swan, Alan D. Waxman, Daniel S. Berman
Journal: Clinical Nuclear Medicine (1981)

Abdulla, Alnoor; Maddahl, Jamshid; Barbour, Deborah; Garcia, Ernest; Swan, H. J.C.; Waxman, Alan D.; Berman, Daniel S. Author Information
Should a fixed external reference system be used to analyze left ventricular wall motion?
Authors: P D Clayton, G M Jeppson, S C Klausner
Journal: Circulation (1982)

To investigate whether a fixed external reference system should be used to most accurately describe regional left ventricular wall motion, we used vectors to analyze a simple model of ventricular contraction. If measured in a fixed external reference system, motion of implanted radiopaque midwall markers may contain translational as well as contractile components. Therefore, comparisons of different reference systems that use marker motion measured in a fixed reference system as a standard will be biased unless proper corrections are included. We conclude that evidence to data does not indicate that the use of a fixed reference system is superior to other methods for analyzing regional ventricular wall motion.
Fatal<i>N</i>-Butyl-2-Cyanoacrylate Pulmonary Embolism after Sclerotherapy for Variceal Bleeding
Authors: A. P. van Beek, K. J. van Erpecum
Journal: Endoscopy (2005)

A 30-year-old man presented with hematemesis. Five years earlier, he had been diagnosed with Escherichia coli liver abscesses, without a clear underlying cause being identified. Although he recovered with antibiotic treatment, extensive thrombosis of the portal, splenic, and superior mesenteric veins remained. The patient received prophylactic propanolol for a large fundic varix, and oral anticoagulants during the first year as well. Endoscopic evaluation during the current admission revealed bleeding from the fundic varix, and an injection of 1 ml N-butyl-2-cyanoacrylate (enbucrilate, Histoacryl), 0.5/0.8 (v/v) diluted with Lipiodol, was administered. Although the hemorrhage was temporarily stopped, repeated cyanoacrylate injections (two injections of 1 ml) and subsequent placement of a Sengstaken-Blakemore tube had to be carried out due to recurrent severe bleeding.
The Flexner Report and the Standardization of American Medical Education
Authors: A. H. Beck
Journal: JAMA (2004)

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18F-FDG Uptake in Multiple Splenic Foci on PET/CT
Authors: Glenna M. Gibson, Colin Arnold, Aravind S. Ravi Kumar
Journal: Clinical Nuclear Medicine (2014)

A previously well 48-year-old male patient presented with several months of weight loss, fever, massive hepatosplenomegaly, and pancytopenia. A provisional diagnosis of lymphoma could not be confirmed on blind lymph node or bone marrow biopsies. Referral for 18F-FDG PET was made to identify an appropriate biopsy site. Focal uptake in multiple splenic lesions was seen, with normal FDG uptake elsewhere in the body. Splenectomy was then performed and histology revealed leishmaniasis, with no evidence of lymphoma. Focally FDG avid splenic deposits have never been reported in leishmaniasis and were likely due to nodular red pulp expansion.
LTP is neither a memory trace nor an ultimate mechanism for its formation: The beginning of the end of the synaptic theory of neural memory
Authors: Lev P. Latash
Journal: Behavioral and Brain Sciences (1997)

The problem of neural memory storage is discussed, based on the results of studies of memory impairment after hippocampal lesions, motor learning, and electrophysiological research on “spinal memory.” I support Shors &amp; Matzel's major statements. The absence of reliable evidence on the LTP memory storage function and other data cast doubt on the synaptic theory of memory.
Diagnostic tests 4: likelihood ratios
Authors: Jonathan J Deeks, Douglas G Altman
Journal: BMJ (2004)

The properties of a diagnostic or screening test are often described using sensitivity and specificity or predictive values, as described in previous Notes.1 2 Likelihood ratios are alternative statistics for summarising diagnostic accuracy, which have several particularly powerful properties that make them more useful clinically than other statistics.3

Each test result has its own likelihood ratio, which summarises how many times more (or less) likely patients with the disease are to have that particular result than patients without the disease. More formally, it is the ratio of the probability of the specific test result in people who do have the disease to the probability in people who do not.

A likelihood ratio greater than 1 indicates that the test result is associated with the presence of the disease, whereas a likelihood ratio less than 1 indicates that the test result is associated with the absence of disease. The further likelihood ratios are from 1 the stronger the evidence for the presence or absence of disease. Likelihood ratios above 10 and below 0.1 are considered …
Influence of Conventional Cardiovascular Risk Factors and Lifestyle Characteristics on Cardiovascular Disease After Hematopoietic Cell Transplantation
Authors: Eric J. Chow, K. Scott Baker, Stephanie J. Lee, Mary E.D. Flowers, Kara L. Cushing-Haugen, Yoshihiro Inamoto, Nandita Khera, Wendy M. Leisenring, Karen L. Syrjala, Paul J. Martin
Journal: Journal of Clinical Oncology (2013)

To determine the influence of modifiable lifestyle factors on the risk of cardiovascular disease after hematopoietic cell transplantation (HCT).HCT survivors of ≥ 1 year treated from 1970 to 2010 (n = 3,833) were surveyed from 2010 to 2011 on current cardiovascular health and related lifestyle factors (smoking, diet, recreational physical activity). Responses (n = 2,362) were compared with those from a matched general population sample (National Health and Nutrition Examination Survey [NHANES]; n = 1,192).Compared with NHANES participants, HCT survivors (median age, 55.9 years; median 10.8 years since HCT; 71.3% allogeneic) had higher rates of cardiomyopathy (4.0% v 2.6%), stroke (4.8% v 3.3%), dyslipidemia (33.9% v 22.3%), and diabetes (14.3% v 11.7%; P < .05 for all comparisons). Prevalence of hypertension was similar (27.9% v 30.0%), and survivors were less likely to have ischemic heart disease (6.1% v 8.9%; P < .01). Among HCT survivors, hypertension, dyslipidemia, and diabetes were independent risk factors for ischemic heart disease and cardiomyopathy, and smoking was associated with ischemic heart disease and diabetes (odds ratios [ORs], 1.8 to 2.1; P = .02). Obesity was a risk factor for post-transplantation hypertension, dyslipidemia, and diabetes (ORs ≥ 2.0; P < .001). In contrast, lower fruit/vegetable intake was associated with greater risk of dyslipidemia and diabetes (ORs, 1.4 to 1.8; P ≤ .01), and lower physical activity level was associated with greater risk of hypertension and diabetes (ORs, 1.4 to 1.5; P < .05). Healthier lifestyle characteristics among HCT survivors attenuated risk of all cardiovascular conditions assessed.Attention of clinicians to conventional cardiovascular risk factors and modifiable lifestyle characteristics offers hope of reducing serious cardiovascular morbidity after HCT.
ROENTGEN-RAY TREATMENT OF TUMORS OF THE BRAIN
Authors: E. B. TOWNE
Journal: JAMA (1925)

The majority of intracranial tumors, excluding pituitary new growths, are infiltrating gliomas which can rarely be completely removed, but which sometimes progress favorably after palliative decompression. Those which undergo cystic degeneration are especially likely to do well. The meningiomas or dural endotheliomas, which compress but do not invade the brain, are purely surgical problems, because they do not recur after removal. Eighth nerve tumors are also benign, but a partial intracapsular enucleation must be done in order to save the seventh nerve. Roentgen-ray treatment of benign tumors has not given good results.<sup>1</sup> I believe that roentgen-ray therapy should be used only after the diagnosis of glioma has been made. The tumor should be localized and exploration should be done, so that encapsulated tumors will not be overlooked. If a benign tumor is not found, the diagnosis of glioma should be verified, if possible, by exposure of an infiltrating tumor,
The Statins in Preventive Cardiology
Authors: Daniel Steinberg
Journal: New England Journal of Medicine (2008)

The discovery of the statins by Akira Endo and colleagues in 1976 opened the door to a new era in preventive cardiology.1 The importance of this discovery was recently underscored by Endo's receipt of the 2008 Albert Lasker Clinical Medical Research Award. By inhibiting the biosynthesis of endogenous cholesterol, the statin drugs lower elevated blood cholesterol levels much more effectively than any of the dietary or drug regimens that were available before Endo's discovery. Moreover, they have proved to be remarkably free of serious side effects.The hypothesis that elevated blood cholesterol levels represent an important cause of atherosclerosis and . . .