tbuckley/cabot-search huggingface dataset:
Induction and maintenance of mucosal enterokinase activity in proximal small intestine by a genetically determined response to mediated sodium transport
Authors: N J Bett, D A W Grant, A I Magee, J Hermon-Taylor
Journal: Gut (1981)

Mucosal enterokinase activity was established at intervals throughout the small intestine in guinea-pigs; maximum activity was present in the duodenum and proximal jejunum in new born as well as adult animals. Transposition of 5 cm lengths of small gut from the high enterokinase containing proximal region to the distal intestine and <i>vice versa</i> showed that mucosal enterokinase activity in the transposed segments was little changed after several weeks of healthy life. Isolation of proximal jejunal loops from luminal continuity resulted in the fall of mucosal enterokinase activity to minimal levels within 16 hours. Low levels of mucosal enterokinase activity were identified in loops of both proximal and distal jejunum 12 weeks after isolation. Luminal perfusion studies <i>in vivo</i> in proximal jejunal loops 24 hours after isolation showed that mucosal enterokinase activity could be restored to near normal levels within four to six hours by luminal sodium in the presence of active pancreatic endopeptidases, oligopeptides, L-amino acids, or D-glucose but not D-amino acids or D-fructose. Near normal mucosal enterokinase activity persisted in the loops for as long as luminal perfusion with 144 mM sodium and L-lysine or trypsin was maintained (24 hours). The time course of the restoration of mucosal enterokinase activity was compatible with an initial precursor activation as well as biosynthesis. The requirement for luminal sodium appeared to be absolute regardless of the co-substrate and supports the conclusion that mucosal enterokinase activity is dependent on mediated sodium transport. The ability of proximal intestinal enterocytes to respond to sodium flux with an increase in enterokinase activity is a property determined in intrauterine life: distal intestinal enterocytes may have functioning structural genes for enterokinase but appear to be unable to respond.
Cortical morphology in children and adolescents with different apolipoprotein E gene polymorphisms: an observational study
Authors: Philip Shaw, Jason P Lerch, Jens C Pruessner, Kristin N Taylor, A Blythe Rose, Deanna Greenstein, Liv Clasen, Alan Evans, Judith L Rapoport, Jay N Giedd
Journal: The Lancet Neurology (2007)
VEGF and c-Met Blockade Amplify Angiogenesis Inhibition in Pancreatic Islet Cancer
Authors: Weon-Kyoo You, Barbara Sennino, Casey W. Williamson, Beverly Falcón, Hiroya Hashizume, Li-Chin Yao, Dana T. Aftab, Donald M. McDonald
Journal: Cancer Research (2011)

Angiogenesis inhibitors that block VEGF receptor (VEGFR) signaling slow the growth of many types of tumors, but eventually the disease progresses. Multiple strategies are being explored to improve efficacy by concurrent inhibition of other functionally relevant receptor tyrosine kinases (RTK). XL880 (foretinib, GSK1363089) and XL184 (cabozantinib) are small-molecule inhibitors that potently block multiple RTKs, including VEGFR and the receptor of hepatocyte growth factor c-Met, which can drive tumor invasion and metastasis. This study compared the cellular effects of XL880 and XL184 with those of an RTK inhibitor (XL999) that blocks VEGFR but not c-Met. Treatment of RIP-Tag2 mice with XL999 resulted in 43% reduction in vascularity of spontaneous pancreatic islet tumors over 7 days, but treatment with XL880 or XL184 eliminated approximately 80% of the tumor vasculature, reduced pericytes and empty basement membrane sleeves, caused widespread intratumoral hypoxia and tumor cell apoptosis, and slowed regrowth of the tumor vasculature after drug withdrawal. Importantly, XL880 and XL184 also decreased invasiveness of primary tumors and reduced metastasis. Overall, these findings indicate that inhibition of c-Met and functionally related kinases amplifies the effects of VEGFR blockade and leads to rapid, robust, and progressive regression of tumor vasculature, increased intratumoral hypoxia and apoptosis, and reduced tumor invasiveness and metastasis.
Noninvasive Prenatal Testing and Detection of Maternal Cancer
Authors: Roberto Romero, Maurice J. Mahoney
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Active Smoking, Household Passive Smoking, and Breast Cancer: Evidence From the California Teachers Study
Authors: P. Reynolds, S. Hurley, D. E. Goldberg, H. Anton-Culver, L. Bernstein, D. Deapen, P. L. Horn-Ross, D. Peel, R. Pinder, R. K. Ross, D. West, W. E. Wright, A. Ziogas
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: There is great interest in whether exposure to tobacco smoke, a substance containing human carcinogens, may contribute to a woman's risk of developing breast cancer. To date, literature addressing this question has been mixed, and the question has seldom been examined in large prospective study designs. Methods: In a 1995 baseline survey, 116 544 members of the California Teachers Study (CTS) cohort, with no previous breast cancer diagnosis and living in the state at initial contact, reported their smoking status. From entry into the cohort through 2000, 2005 study participants were newly diagnosed with invasive breast cancer. We estimated hazard ratios (HRs) for breast cancer associated with several active smoking and household passive smoking variables using Cox proportional hazards models. Results: Irrespective of whether we included passive smokers in the reference category, the incidence of breast cancer among current smokers was higher than that among never smokers (HR = 1.32, 95% confidence interval [CI] = 1.10 to 1.57 relative to all never smokers; HR = 1.25, 95% CI = 1.02 to 1.53 relative to only those never smokers who were unexposed to household passive smoking). Among active smokers, breast cancer risks were statistically significantly increased, compared with all never smokers, among women who started smoking at a younger age, who began smoking at least 5 years before their first full-term pregnancy, or who had longer duration or greater intensity of smoking. Current smoking was associated with increased breast cancer risk relative to all nonsmokers in women without a family history of breast cancer but not among women with such a family history. Breast cancer risks among never smokers reporting household passive smoking exposure were not greater than those among never smokers reporting no such exposure. Conclusion: Our study provides evidence that active smoking may play a role in breast cancer etiology and suggests that further research into the connection is warranted, especially with respect to genetic susceptibilities.
Association of Protein C and Type 1 Plasminogen Activator Inhibitor with Primary Graft Dysfunction
Authors: Jason D. Christie, Nancy Robinson, Lorraine B. Ware, Michael Plotnick, Joao De Andrade, Vibha Lama, Aaron Milstone, Jonathan Orens, Ann Weinacker, Ejigayehu Demissie, Scarlett Bellamy, Steven M. Kawut
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Acute lung injury is characterized by hypercoagulability and impaired fibrinolysis. We hypothesized that lower protein C and higher type 1 plasminogen activator inhibitor (PAI-1) levels in plasma would be associated with primary graft dysfunction (PGD) after lung transplantation.Prospective, multicenter cohort study.We measured plasma levels of protein C and PAI-1 before lung transplantation and 6, 24, 48, and 72 h after allograft reperfusion in 128 lung transplant recipients at six centers. The primary outcome was grade 3 PGD (Pa(O(2))/Fi(O(2)) < 200 with alveolar infiltrates) 72 h after transplantation. Biomarker profiles were evaluated using logistic regression and generalized estimating equations.Patients who developed PGD had lower protein C levels 24 h posttransplantation than did patients without PGD (mean +/- SD [relative to control]: 64 +/- 27 vs. 92 +/- 41%, respectively; p = 0.002). Patients with PGD also had PAI-1 levels that were almost double those of patients without PGD at 24 h (213 +/- 144 vs. 117 +/- 89 ng/ml, respectively; p < 0.001). Throughout the 72-h postoperative period, protein C levels were significantly lower (p = 0.007) and PAI-1 levels were higher (p = 0.026) in subjects with PGD than in others. These differences persisted despite adjustment for potential confounders in multivariate analyses. Higher recipient pulmonary artery pressures, measured immediately pretransplantation, were associated with higher PAI-1 levels and increased risk of PGD.Lower postoperative protein C and higher PAI-1 plasma levels are associated with PGD after lung transplantation. Impaired fibrinolysis and enhanced coagulation may be important in PGD pathogenesis.
Ultrasonic Fetal Cephalometry
Authors: P. Davies
Journal: BMJ (1972)

haematoma formation and no long-term sequelae.We wish to make two points.Firstly, the technique of insertion of the cannula is very important in avoiding trauma to the artery.We feel the Grandjean cannula (which uses a semirigid steel stilette) is a very significant advance.On the great majority of occasions the puncture is "first time" and through the anterior wall of the artery only.Secondly, the continuous flush technique removes problems of thrombosis at the catheter tip.Since using the Grandjean catheter we failed only once to insert the cannula at the first attempt.We have had no significant haema- toma formation at insertion or following re- moval.We do make a special point of form- ally examining the artery after insertion, at 12 hours, on removal at 24 hours, and at outpatient follow-up one month later.We have had no instances of arterial thrombosis, or pulse diminution, or splinter haemorrhages and, despite careful observation, no patients have developed forearm claudication after microcannulation, though, like others, we have certainly seen this after routine cardiac catheterization.We have our- selves had repeated arterial cannulation by this method.Obviously no invasive pro- cedure is entirely foolproof but we feel arterial microcannulation by this method is a safe procedure.-Weare, etc.,
Homozygous Missense Mutation in<i>IL36RN</i>in Generalized Pustular Dermatosis With Intraoral Involvement Compatible With Both AGEP and Generalized Pustular Psoriasis
Authors: Alexander A. Navarini, Michael A. Simpson, Luca Borradori, Nikhil Yawalkar, Christoph Schlapbach
Journal: JAMA Dermatology (2014)
A Retrospective Analysis of Dacarbazine Monotherapy for Recurrent or Metastatic Mucosal Melanoma
Authors: Meiko Nishimura, Naomi Kiyota, Masanori Toyoda, Naoko Chayahara, Kei Takenaka, Kiyoaki Uryu, Yoshinori Imamura, Yohei Funakoshi, Toru Mukohara, Hironobu Minami
Journal: Annals of Oncology (2014)
Parathyroid Hormone Stimulates Extracellular Signal-Regulated Kinase (ERK) Activity Through Two Independent Signal Transduction Pathways
Authors: ELEANOR D. LEDERER, SAMEET S. SOHI, KENNETH R. MCLEISH
Journal: Journal of the American Society of Nephrology (2000)

Parathyroid hormone (PTH), a major physiologic regulator of proximal renal tubule cell sodium-phosphate cotransport, stimulates several signal transduction pathways including extracellular signal-regulated kinases (ERK). The physiologic role of PTH-stimulated ERK is unknown. The purpose of the present study was to identify signaling components involved in PTH-stimulated ERK activity and to determine the role of PTH-stimulated ERK activity in regulation of phosphate transport. PTH-stimulated ERK activity was measured in opossum kidney (OK) cell lysates as phosphorylation of myelin basic protein by an in vitro kinase assay. PTH stimulated a dose-dependent increase in ERK activity with a peak at 10-7 M. The time course was biphasic with an early peak at 10 min and a later peak at 20 min. Pretreatment of OK cells with the nonreceptor tyrosine kinase inhibitors genistein and herbimycin A or with the phosphatidylinositol 3-kinase (PI-3K) inhibitors wortmannin and LY294002 blocked the early and late peaks of PTH-stimulated ERK activity. Pretreatment with the protein kinase C inhibitor calphostin C blocked only the later phase of PTH-stimulated ERK. To determine the role of ERK in regulation of phosphate transport, PTH inhibition of phosphate uptake and PTH regulation of sodium-phosphate cotransporter (NaPi-4) expression were measured in OK cells pretreated with the MEK inhibitor PD098059. PD098059 significantly attenuated PTH inhibition of phosphate uptake but did not prevent PTH downregulation of NaPi-4. It is concluded that PTH stimulates ERK through two signal transduction pathways: an early pathway dependent on tyrosine kinase and PI-3K and a late pathway dependent on protein kinase C. PTH-stimulated ERK regulates phosphate transport by a mechanism other than downregulation of NaPi-4 expression.
The emerging role of MIR-146A in the control of hematopoiesis, immune function and cancer
Authors: Catherine Labbaye, Ugo Testa
Journal: Journal of Hematology & Oncology (2012)

MicroRNA (miRs) represent a class of small non-coding regulatory RNAs playing a major role in the control of gene expression by repressing protein synthesis at the post-transcriptional level. Studies carried out during the last years have shown that some miRNAs plays a key role in the control of normal and malignant hgematopoiesis. In this review we focus on recent progress in analyzing the functional role of miR-146a in the control of normal and malignant hematopoiesis. On the other hand, this miRNA has shown to impact in the control of innate immune responses. Finally, many recent studies indicate a deregulation of miR-146 in many solid tumors and gene knockout studies indicate a role for this miRNA as a tumor suppressor.
Abnormal vasomotor changes early after coronary angioplasty. A quantitative arteriographic study of their time course.
Authors: H el-Tamimi, G J Davies, D Hackett, P Sritara, O Bertrand, F Crea, A Maseri
Journal: Circulation (1991)

To study the impact of percutaneous transluminal coronary angioplasty (PTCA) on coronary vasomotion, we prospectively analyzed spontaneous changes in coronary diameter and the response to the cold pressor test and intracoronary nitroglycerin in 11 patients subjected to successful single-vessel PTCA.All antianginal medications were stopped 48 hours before each study. The minimum diameter of the PTCA segment and the diameter of a distal segment in the angioplastied vessel and of a segment in a control vessel not manipulated by the balloon catheter or guide wire were measured by computerized edge detection immediately before PTCA and 5 minutes after, 4 hours after, and 8 days after PTCA. At 4 hours, PTCA and distal segments were constricted by 38 +/- 9% and 16 +/- 5%, respectively, compared with the values at 5 minutes (p less than 0.01). Before angioplasty, the cold pressor test caused vasoconstriction of PTCA and distal segments by 23 +/- 6% (p less than 0.0001) and 15 +/- 4% (p less than 0.008), respectively, but no constrictor response was elicited at 5 minutes or 4 hours after angioplasty. Eight days after PTCA, the basal coronary diameters were similar to those observed 5 minutes after PTCA and the response to the cold pressor test was similar to that observed before PTCA. All segments dilated significantly with nitroglycerin at all times, and no vasoconstriction changes were found in the control segments.Four hours after PTCA, transient spontaneous vasoconstriction of the PTCA and distal segments occurs, which is so intense that the cold pressor test does not cause any further constriction. These abnormalities resolve within 8 days of PTCA.
THE METABOLISM OF DESMOSTEROL IN HUMAN SUBJECTS DURING TRIPARANOL ADMINISTRATION*
Authors: DeWitt S. Goodman, Joel Avigan, Hildegard Wilson
Journal: Journal of Clinical Investigation (1962)

Recent studies with triparanol (1-[p-,3-diethylaminoethoxyphenyl ]-1-(p-tolyl) -2-(p-chloro- phenyl)ethanol) have demonstrated that this compound inhibits cholesterol biosynthesis by blocking the reduction of 24-dehydrocholesterol (desmos- terol) to cholesterol (2-4).Administration of triparanol to laboratory animals and to man re- sults in the accumulation of desmosterol in the plasma and tissues, usually with some concom- itant lowering of the plasma total sterol concen- tration (2, 5).In studies with human subjects it was observed that after about 2 weeks the desmosterol concentration tended to plateau at an average level of 27 per cent of the total circulating sterols (5).The ratios of desmosterol to cho- lesterol in animal tissues (2) differed somewhat from the ratios in plasma.In addition, injection of the cholesterol precursor 2-C14-mevalonic acid dur- ing triparanol administration resulted in the rapid appearance of labeled desmosterol in blood, while no significant radioactivity appeared in cholesterol in the first few days (5).The object of the present experiments was to study the metabolism of desmosterol in patients receiving triparanol.Since cholesterol serves as the biosynthetic precursor for several physiologi- cally important compounds, including bile acids and steroid hormones, the question arose whether desmosterol could also function as a precursor for these compounds without first being transformed into cholesterol.The studies reported herein dem- onstrate the direct conversion of desmosterol to both bile acids and to steroid hormones, and also provide information about the over-all metabolism of this sterol in the triparanol-treated man.EXPERIMENTAL Clinical material.Both of the patients studied were hospitalized on a metabolic ward of the Clinical Center.
Genetic Changes of Wnt Pathway Genes Are Common Events in Metaplastic Carcinomas of the Breast
Authors: Michael J. Hayes, Dafydd Thomas, Agnieszka Emmons, Thomas J. Giordano, Celina G. Kleer
Journal: Clinical Cancer Research (2008)

Metaplastic carcinomas are distinct invasive breast carcinomas with aberrant nonglandular differentiation, which may be spindle, squamous, or chondroid. The limited effective treatments result from the lack of knowledge of its molecular etiology. Given the role of the Wnt pathway in cell fate and in the development of breast cancer, we hypothesized that defects in this pathway may contribute to the development of metaplastic carcinomas.In 36 primary metaplastic carcinomas, we comprehensively determined the prevalence of and mechanism underlying beta-catenin and Wnt pathway deregulation using immunohistochemistry for beta-catenin expression and localization and mutational analysis for CTNNB1 (encoding beta-catenin), APC, WISP3, AXIN1, and AXIN2 genes. By immunohistochemistry, normal beta-catenin was seen as membrane staining, and it was aberrant when >5% of tumor cells had nuclear or cytoplasmic accumulation or reduced membrane staining.By immunohistochemistry, aberrant beta-catenin was present in 33 of 36 (92%) cases, revealing deregulation of the Wnt pathway. CTNNB1 missense mutations were detected in 7 of 27 (25.9%) tumors available for mutation analyses. All mutations affected the NH(2)-terminal domain of beta-catenin, presumably rendering the mutant protein resistant to degradation. Two of 27 (7.4%) tumors had mutations of APC, and 5 (18.5%) carried a frame shift mutation of WISP3. No AXIN1 or AXIN2 mutations were found.Activation of the Wnt signaling pathway is common in this specific subtype of breast carcinoma. The discovery of CTNNB1, APC, and WISP3 mutations may result in new treatments for patients with metaplastic carcinomas of the breast.
OBSERVATIONS AND EXPERIMENTS ON THE SO-CALLED THYROID CARCINOMA OF BROOK TROUT (SALVELINUS FONTINALIS) AND ITS RELATION TO ORDINARY GOITRE
Authors: David Marine, C. H. Lenhart
Journal: The Journal of Experimental Medicine (1910)

Is this thyroid hyperplasia true carcinoma? In view of the facts that young fish are more affected than old fish, that iodin stops the hyperplasia and causes it to return to the colloid state, that removal of the fish from the ponds to the open brook also affects a cure, that the clinical incidence of tumors is directly related to the water supply, and that the severity of the disease as determined by histological examination is likewise directly related to the water supply, we cannot accept the prevailing opinion that the disease is true cancer. On the other hand, we believe that the disease as studied by us is an extreme illustration of endemic goitre, the end stage of which is cretinism. The opinion that it is cancer is based purely on anatomical studies-the essential fact being that the growing thyroid invades bone, muscle, etc. Such findings in mammalian tissues are strong evidence of malignancy, but this standard cannot be applied to fish thyroids for the reason that any growth of a widely and loosely distributed nonencapsulated gland would give the histological appearance of invasion of the surrounding tissues. The general views as to the cause of the disease may be divided into two groups: (I) infectious and (2) metabolic. Taking up the infectious theory, there are abundant grounds for such a view when one considers the flora of the tank. The very careful histological examinations by Hofer, Bonnet and Pick have yielded uniformly negative results. Direct infection cannot be excluded, but the fact that fish placed in the tail-race recover spontaneously, although living in the theoretically most polluted water, is not in harmony with our present conception of water-borne infection. Taking up the metabolic theory, the three factors of overfeeding, overcrowding and limited proportional water supply together with the many possibilities into which they are divisible seem to us to be in some way, still obscure, directly concerned with the development of the disease. It is not probable that a single substance, whether the result of food decomposition or of excretory products, excites the thyroid to its activity but rather that the thyroid reaction is the result of the activity of a great variety of these products.