tbuckley/cabot-search huggingface dataset:
Effects of taurodihydrofusidate, a bile salt analogue, on bile formation and biliary lipid secretion in the rhesus monkey.
Authors: M Beaudoin, M C Carey, D M Small
Journal: Journal of Clinical Investigation (1975)

Bile salts play a major role in bile formation and biliary lipid secretion. Sodium taurodihydrofusidate (TDHF), a derivative of the antibiotic fusidic acid, closely resembles bile salts in terms of structure, micellar characteristics, and capacity ot solubilize otherwise insolbule lipids. We have therefore studied the biliary secretion of this bile salt analogue and its influence on bile formation and biliary lipid secretion in primates. Alert, unanesthetized female rhesus monkeys prepared with a total biliary fistula were allowed to reach a steady bile salt secretion rate before each study. In three animals (group I),[14C]TDHF was infused intravenously. Most of the compound was secreted rapidly in bile chemically unchanged. The biliary secretion of this drug produced a twofold increase in bile flow; however, the bile salt output was markedly reduced during the infusion. In spite of this reduction, the phospholipid output remained essentially unchanged whereas the cholesterol output increased almost twofold. In five other animals (group II), the effect of TDHF on the bile salt secretion was further investigated by an intravenous infusion of [14C]taurocholate followed by a combined infusion of [14C]taurocholate and TDHF. When TDHF was added to the infusate, a reduction in the [14C]taurocholate output and a progressive rise in the plasma [14C]taurocholate concentration were observed in each animal. An analysis of the data in both groups indicates that (a) the most likely explanation to account for the decreased bile salt output is that the bile salt analogue, TDHF, interfered with bile salt secretion into the biliary canaliculi; (b) TDHF induces a greater secretion of biliary water than was observed with bile salts, an effect consistent with a stimulation of the bile salt-independent canalicular flow; (c) at similar 3alpha-hydroxysteroid secretion rates TDHF caused a significant increase in cholesterol secretion compared to that induced by bile salt. This finding suggests that TDHF affects cholesterol metabolism or secretion in a way distinct from bile salts. Thus, the solubilization of biliary lipids in mixed micelles, although essential, is only one of the factors which determine their secretion into bile.
Abstract 1220: Enigma blocks Cbl-c-mediated RET ubiquitination and degradation
Authors: Stephen C. Kales, Stanley Lipkowitz
Journal: Cancer Research (2011)

Abstract RET (rearranged during transfection) is an RTK that is activated by glial cell-derived neurotrophic factors (GDNF) and is critical to neuronal and kidney development. RET mutations causing loss of function are associated with Hirschsprung's disease, while gain of function mutations are associated with thyroid carcinomas and mutiple endocrine neoplasias (MEN2A&amp;B). Cbl proteins are a family of ubiquitin protein ligases that mediate RTK degradation and thereby serve as negative regulators of RTK signaling. Cbl-c (a.k.a. Cbl-3), the most recently identified of the human Cbl proteins, is restricted to epithelial cells and most resembles the Cbl proteins found in lower organisms. Cbl-c can ubiquitinate and downregulate RTKs including activated RET and EGFR. Through yeast two-hybrid screening, we identified the LIM protein Enigma (a.k.a. PDLIM7) as a Cbl-c interacting protein. Enigma is an adapter protein for kinase anchoring to the cytoskeleton and is required for the mitogenic signaling of the RET/PTC2 oncogene. The interaction was confirmed in mammalian cells through co-immunoprecipitation of transfected and endogenous Cbl-c and Enigma. Enigma did not co-immunoprecipitate with c-Cbl or Cbl-b indicating that this interaction is specific to Cbl-c. Cbl-c can ubiquitinate and downregulate an activated form of RET, RET-MEN2A and we show that Enigma prevents Cbl-c-mediated RET ubiquitination and downregulation. This effect is specific to RET as EGFR ubiquitination was unaffected by the presence of Enigma. An Enigma mutant, lacking the RET binding site, does not block Cbl-c recruitment and subsequent ubiquitination and downregulation of RET. Our data suggest that Enigma blocks Cbl-c binding to the RET receptor and prevents its ubiquitination. This is further supported by microscopy data which demonstrates maintained surface expression of RET in the presence of Enigma. Together these data demonstrate a novel interaction between a positive and negative regulator or RET signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1220. doi:10.1158/1538-7445.AM2011-1220
The NHS programme for information technology
Authors: Justin Keen
Journal: BMJ (2006)

This massive natural experiment needs evaluating and regulating 

T he NHS National Programme for IT in England is one of the largest information technology programmes in the world.1 The programme has been subjected to hostile media coverage in its four year history, and it has been difficult to know how much of this is justified. The publication of the National Audit Office report on the programme gives both supporters and critics food for thought.2 The audit office finds that elements of the programme are progressing well, but also points to key challenges over the next few years—in ensuring that the promised systems are delivered and that NHS staff are engaged with the programme.3

The report contains a wealth of detail, but doctors should pay particular attention to two issues. Firstly, the report notes that the Department of Health has failed to show benefits of the programme that will justify its …
THE FORM OF THE STOOL AS A CRITERION OF LAXATION
Authors: GEORGE R. COWGILL
Journal: JAMA (1933)

It has been well established that one of the important functions of the large intestine is to dehydrate the food residues received from the small bowel in preparation for elimination by the act of defecation. Burnett<sup>1</sup>has made this the basis of a test for what he calls intestinal indigestion and has suggested that the ability to form a hard stool made up of numerous smaller parts called<i>fecal units</i>indicates that the large intestine is in excellent condition; cases were described in which the shape of the stool was changed by dietary means from a "soft and formless" type to a "unit basis" with concomitant improvement of health. He also reported on the rate of passage of food residues through the alimentary tract, his method being to study the time required for practically all of a 50 cc. quantity of millet seed to be eliminated. As a result
Abstract 5546: Screening the <i>RbBP6</i> gene for abnormal alternative splicing in colon cancer
Authors: Zodwa Dlamini, Zukile Mbita
Journal: Cancer Research (2011)

Abstract Cancer arises after a series of mutations that result in uncontrolled cellular differentiation and growth. These result because the genes required for normal cell growth and apoptotic processes are abnormally regulated and thus the progression of cancer and survival is favoured. The RbBP6 gene is amongst the genes which are down-regulated in cancerous cells. RbBP6 is a gene that has been shown to regulate cell cycle control and apoptosis. RbBP6 isoform 3 has been shown to regulate G2/M cell cycle checkpoint while the alternatively spliced RbBP6 transcript 1 product has been implicated in apoptosis regulation and cancer. Expression and regulation of the gene in colon cancer was examined by amplifying cDNA of RNA extracted from three colon adenocarcinoma cell lines obtained from different stages of colon cancer, using RT-PCR with the RbBP6 exon 16 primers and confirmation of the 2 splice variants by NCBI BLAST. Two bands appeared on a 1% Agarose gel, the ratio of the intensity of the two bands was found to be 1:1 in the primary cell line compared to down-regulation in grade II cell line while these alternatively spliced products could hardly be amplified in grade III cell line. RbBP6 has two splice isoforms which are regulated by alternative splicing in colon cancer. The expression of these splice variants was found to be indirectly proportional to colon cancer progression. The primary colon cancer cell line showed more expression of these alternatively spliced products, which decreased significantly in grade II and III. This suggests that RbBP6 alternatively spliced products could be anti-carcinogenic but are de-regulated in favour of carcinogenesis and this further suggests that RbBP6 gene might be somehow involved in the development and progression of colon adenocarcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5546. doi:10.1158/1538-7445.AM2011-5546
Hyperamylasaemia: not the usual suspects: Fig 2
Authors: Rajeev Srivastava, Callum Fraser, Douglas Gentleman, Lynne A Jamieson, Michael J Murphy
Journal: BMJ (2005)

Interpretation of abnormally high serum amylase activity is not always straightforward.Sometimes, as here, patients are erroneously labelled as having pancreatitis despite the absence of clinical features to support this diagnosis.Such assumptions may affect the interpretation of investigations.
Determinant of psychological markers of physical activity habituation among 10-12 years old children
Authors: N A Wahat, M N Jawis, H A Hashim, N S Bistamam
Journal: British Journal of Sports Medicine (2010)

Numbers of studies has been done to determine physiological effect of physical activity (PA) on children's health throughout the life. However, few studies were done to determine psychological effects and markers towards PA specifically among Malaysian children. It is important to determine the motivational cues in performing the exercise behaviour among children, therefore help to sustain their PA throughout the life. The aim of this study was to investigate the psychological correlates of PA and to provide evidence of psychological markers of PA habituation among children. Three hundred and eighty children (age 10.5 ± 0.5 years old) were randomly recruited from district of Kota Bharu, Kelantan, Malaysia primary schools. Subject's height and weight (BMI) followed by PA-Q was obtained during the test visits. Results indicated that physical education enjoyment showed positive correlations with intention (r = 0.47, p &lt; 0.01), attitude (r = 0.44, p &lt; 0.01), subjective norms (r = 0.48, p &lt; 0.01), behavioural control (r = 0.47, p &lt; 0.01), habit strength (r = 0.49, p &lt; 0.01) and the sustainability of doing PA outside the school (r = 0.23, p &lt; 0.01). These data suggest that children PA is positively correlates with enjoyment experienced during physical education lesson during the school. Moreover, intention to perform exercise was positively correlates with attitude, subjective norm and behavioural control. Therefore, it can lead to the automaticity to perform the exercise behaviour regularly and increase the sustainability to carry it out throughout the life.
L1 (LINE-1) Retrotransposon Evolution and Amplification in Recent Human History
Authors: Stéphane Boissinot, Pascale Chevret, Anthony V. Furano
Journal: Molecular Biology and Evolution (2000)

L1 (LINE-1) elements constitute a large family of mammalian retrotransposons that have been replicating and evolving in mammals for more than 100 Myr and now compose 20% or more of the DNA of some mammals. Here, we investigated the evolutionary dynamics of the active human Ta L1 family and found that it arose approximately 4 MYA and subsequently differentiated into two major subfamilies, Ta-0 and Ta-1, each of which contain additional subsets. Ta-1, which has not heretofore been described, is younger than Ta-0 and now accounts for at least 50% of the Ta family. Although Ta-0 contains some active elements, the Ta-1 subfamily has replaced it as the replicatively dominant subfamily in humans; 69% of the loci that contain Ta-1 inserts are polymorphic for the presence or absence of the insert in human populations, as compared with 29% of the loci that contain Ta-0 inserts. This value is 90% for loci that contain Ta-1d inserts, which are the youngest subset of Ta-1 and now account for about two thirds of the Ta-1 subfamily. The successive emergence and amplification of distinct Ta L1 subfamilies shows that L1 evolution has been as active in recent human history as it has been found to be for rodent L1 families. In addition, Ta-1 elements have been accumulating in humans at about the same rate per generation as recently evolved active rodent L1 subfamilies.
Abdominal bruits. Clinical and angiographic correlation
Authors: M. J. McLoughlin
Journal: JAMA (1975)

The results of abdominal auscultation were correlated with abdominal angiograms in 503 patients. Bruits were heard in 106 (21%). The majority of bruits were in the epigastrium, mainly because of a high incidence of celiac artery stenosis usually of the extrinsic compression type. Sixty-seven patients had stenoses or occlusions of one or more renal arteries and 27 (40%) had bruits. Most of these patients, however, had other possible causes for their bruits, usually related to atherosclerosis of coincidental celiac compression. Collateral channels were considered to be the cause of epigastric bruits in eight of ten patients with complete occlusion of the celiac artery and in two patients with splenic artery occlusions. Collateral channels may be partly responsible for bruits in many patients with celiac artery stenosis. (<i>JAMA</i>232:1238-1242, 1975)
Lack of association of HLA class I genes and TNF <i>α</i>‐308 polymorphism in toluene diisocyanate‐induced asthma
Authors: B. Beghé, M. Padoan, C. T. Moss, S. J. Barton, J. W. Holloway, S. T. Holgate, W. M. Howell, C. E. Mapp
Journal: Allergy (2003)

Background: Toluene diisocyanate (TDI)‐induced asthma is a common cause of occupational asthma and it affects 5–15% of the exposed population suggesting an underlying genetic susceptibility. Methods: To investigate the role of genetic factors in the development of TDI‐induced asthma, we analyzed the distribution of human leukocyte antigen (HLA) class I genes and of tumor necrosis factor (TNF)‐ α A‐308G polymorphism in 142 patients with TDI‐induced asthma and in 50 asymptomatic exposed subjects. Results: Neither the distribution of HLA class I antigens nor the distribution of TNF‐ α A‐308G polymorphism was different between patients with TDI‐induced asthma and asymptomatic exposed subjects. Conclusions: These results suggest that HLA class I antigens and TNF‐ α A‐308G are not associated with susceptibility or resistance to the development of TDI‐induced asthma.
Acute Aortic Dissections
Authors: Leslie W. Ottinger
Journal: JAMA (1975)

The objective of this monograph is to review current information on dissections and to present an organized approach to therapy. The book includes sections on the embryology, anatomy, histology, and biophysics of the aorta; basic considerations related to pathology; incidence and classification of dissections; diagnostic and clinical considerations; and surgical and medical therapy. The organization is excellent, the style direct and economical, the references extensive, and the index adequate. Though it makes interesting reading for those whose contact with dissections is peripheral, the book's primary appeal will be to cardiologists and surgeons who must determine, provide, and evaluate treatment. A new classification to serve as a framework for these steps is proposed that should not only simplify and systematize these decisions but should also facilitate comparison of such factors as time of intervention and type of therapy. The book is the very model of a splendid monograph, summarizing what is
Plasma B-Type Natriuretic Peptide Levels in Ambulatory Patients With Established Chronic Symptomatic Systolic Heart Failure
Authors: W.H. Wilson Tang, John P. Girod, Michael J. Lee, Randall C. Starling, James B. Young, Frederick Van Lente, Gary S. Francis
Journal: Circulation (2003)

Background— The diagnostic and prognostic values of plasma B-type natriuretic peptide (BNP) testing are established. However, the range of plasma BNP levels present in the setting of chronic, stable systolic heart failure (HF) is unclear. Methods and Results— We followed up 558 consecutive ambulatory patients with chronic, stable systolic HF (left ventricular ejection fraction &lt;50%) treated at a specialized outpatient HF clinic between November 2001 and February 2003. Retrospective chart review was performed to determine clinical and functional data at the time of BNP testing (Biosite Triage). The clinical characteristics of patients with plasma BNP levels &lt;100 pg/mL and those with ≥100 pg/mL were compared. In our cohort, 60 patients were considered asymptomatic, and their plasma BNP levels ranged from 5 to 572 pg/mL (median, 147 pg/mL). Of the remaining 498 symptomatic (NYHA functional class II–III) patients, 106 (21.3%) had plasma BNP levels in the “normal” diagnostic range (&lt;100 pg/mL). Patients in this “normal BNP” subgroup were more likely to be younger, to be female, to have nonischemic pathogenesis, and to have better-preserved cardiac and renal function and less likely to have atrial fibrillation. Conclusions— In the ambulatory care setting, both symptomatic and asymptomatic patients with chronic, stable systolic HF may present with a wide range of plasma BNP levels. In a subset of symptomatic patients (up to 21% in our cohort), plasma BNP levels are below what would be considered “diagnostic” (&lt;100 pg/mL).
Abstract 5743: Positron emission tomography (PET) imaging analogs of glutamine: Development and evaluation as probes for cancer imaging
Authors: Jason R. Buck, Sam Saleh, Matthew R. Hight, Mike L. Nickels, H. Charles Manning
Journal: Cancer Research (2012)

Abstract Emerging evidence suggests that nutrient uptake in cancer cells is controlled by oncogenic signaling pathways. The natural amino acid glutamine is an essential nutrient for cell growth and proliferation. Glutamine also participates in protein synthesis and is a nitrogen source for the production of select nucleotides and amino acids. Consequently, quantitative measures of glutamine uptake may reflect critical processes in oncology. Recently, a fluorinated glutamine analog for positron emission tomography (PET) was shown to possess both highly specific cellular uptake in glioma cell lines and in vivo tumor localization (J Am Chem Soc 2011;133:1122-1133). Synthetic methodology leading to this agent, an optically pure 4-fluoro-glutamine derivative, was also reported. Though effective, this convergent synthesis requires multiple steps, extensive chromatographic separation, and nearly a week of reaction time. Employing a chiral auxiliary Schiff base and microwave-assisted organic synthesis, we have significantly improved the synthesis of this and similar agents, drastically reducing the number of synthetic steps (from ten to four) and the overall reaction time (from seven days to two hours). While the radiochemistry relies upon traditional box methods, we are also currently employing high-throughput microfluidic radiolabeling strategies to expedite probe production and labeling efficiency. Finally, using optically pure [18F]4-FGln (2S,4R) synthesized by our improved synthesis, we report preclinical PET images of models of human colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5743. doi:1538-7445.AM2012-5743
Ectopic ACTH Production with Autoantibody Formation in a Patient with Acute Myeloblastic Leukemia
Authors: Karl-Heinz Pflüger, Margarethe Gramse, Claus Gropp, Klaus Havemann
Journal: New England Journal of Medicine (1981)

A NUMBER of human cancers are associated with ectopic hormone generation.1 2 3 4 5 Ectopic hormone production, which is usually restricted to polypeptide hormones, is secretion by a tissue that does not normally produce that hormone. The tumors frequently associated with this phenomenon are small-cell bronchogenic carcinoma and gastrointestinal tumors. Reports of ectopic hormone production in leukemia and lymphoma are very rare. Hypoglycemia,6 7 8 probably caused by insulin-like activity, and hypercalcemia,9 10 11 12 13 caused by elevated parathyroid hormone levels, have been described in hemoblastosis in some instances. Only calcitonin seems to be elevated more frequently in these tumors, as reported recently.14 , 15 We describe a patient with . . .
Monocyte chemoattractant protein-1 in human atheromatous plaques.
Authors: N A Nelken, S R Coughlin, D Gordon, J N Wilcox
Journal: Journal of Clinical Investigation (1991)

Monocytes appear to be central to atherogenesis both as the progenitors of foam cells and as a potential source of growth factors mediating intimal hyperplasia, but the chemical messages which stimulate the influx of monocytes into human atheroma remain unknown. Monocyte chemoattractant protein-1 (MCP-1) is a recently described molecule with powerful monocyte chemotactic activity expressed by monocytes, vascular endothelial cells, and smooth muscle cells in culture. To begin to address the role of MCP-1 in vivo, we examined 10 normal arteries and 14 diseased human arteries for MCP-1 expression by in situ hybridization. MCP-1 mRNA was detected in 16% of 10,768 cells counted in human carotid endarterectomy specimens with highest expression seen in organizing thrombi (33%) and in macrophage rich areas bordering the necrotic lipid core (24%) as compared to the fibrous cap (8%) and the necrotic lipid core itself (5%). Based on immunohistochemical staining of serial sections and on cell morphology, MCP-1 mRNA appeared to be expressed by vascular smooth muscle cells (VSMC), mesenchymal appearing intimal cells (MICs), and macrophages. By contrast, few cells expressing MCP-1 mRNA were found in normal arteries (less than 0.1%). These data suggest a potential role for MCP-1 in mediating monocytic infiltration of the artery wall.
Bread From Bolted Flour and From Entire Wheat Flour
Authors: Packard Horace
Journal: JAMA (1913)

<h3>To the Editor:</h3> —I have admired very much the high stand whichThe Journalhas taken relative to pure foods and pure drugs, and its high standard in everything relating to the medical profession. I am writing now to call your attention to the injury which has been done through a recent editorial (Jan. 4, 1913, p. 50) relating to the use of bolted wheat Hour for food purposes and giving quasi-approval of it as an article of food. This has been seized on by the flour-millers in the Middle West and they are making use of it to their business advantage. I will admit that if one has the opportunity of reading your editorial all through, the last part rather annuls the first part and leaves the question "astride the fence." I have been trying through writings and lecturing and such influence as I have