tbuckley/cabot-search huggingface dataset:
Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults
Authors: Edward S Chambers, Alexander Viardot, Arianna Psichas, Douglas J Morrison, Kevin G Murphy, Sagen E K Zac-Varghese, Kenneth MacDougall, Tom Preston, Catriona Tedford, Graham S Finlayson, John E Blundell, Jimmy D Bell, E Louise Thomas, Shahrul Mt-Isa, Deborah Ashby, Glen R Gibson, Sofia Kolida, Waljit S Dhillo, Stephen R Bloom, Wayne Morley, Stuart Clegg, Gary Frost
Journal: Gut (2014)

The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults.
Myocardial energy provision is preserved by increased utilization of glucose and ketone bodies in CD36 knockout mice
Authors: Kazuhiro Nakatani, Tadashi Watabe, Daisaku Masuda, Masao Imaizumi, Eku Shimosegawa, Takuya Kobayashi, Masami Sairyo, Yinghong Zhu, Takeshi Okada, Ryota Kawase, Hajime Nakaoka, Atsuhiko Naito, Tohru Ohama, Masahiro Koseki, Toru Oka, Hiroshi Akazawa, Makoto Nishida, Issei Komuro, Yasushi Sakata, Jun Hatazawa, Shizuya Yamashita
Journal: Metabolism (2015)
Safety and efficacy of recombinant hirudin (CGP 39 393) versus heparin in patients with stable angina undergoing coronary angioplasty.
Authors: A A van den Bos, J W Deckers, G R Heyndrickx, G J Laarman, H Suryapranata, F Zijlstra, P Close, J J Rijnierse, H R Buller, P W Serruys
Journal: Circulation (1993)

BACKGROUND Enhanced thrombin activity has been associated with acute and long-term complications following balloon angioplasty (percutaneous transluminal coronary angioplasty (PTCA). We evaluated, in a 2-to-1 randomized, double-blind trial, the effects of recombinant hirudin, CGP 39 393, relative to unfractionated sodium heparin on periprocedural events, bleeding, early angiographic outcome, and coagulation in 113 patients with stable angina undergoing PTCA. METHODS AND RESULTS Prior to PTCA, 20 mg CGP 39 393 was administered as a bolus, followed by continuous infusion at a rate of 0.16 mg.kg-1 x h-1, or 10,000 IU sodium heparin was administered as a bolus and continued at a rate of 12 IU.kg-1 x h-1 for 24 hours. Infusion was adjusted to activated partial thromboplastin time (APTT) levels. ST segment was monitored for 24 hours, and angiograms were analyzed with quantitative technique (QCA). In 74 CGP 39 393- and 39 heparin-treated patients, 132 lesions were dilated. Myocardial infarction and/or emergency coronary bypass surgery occurred in 1 (1.4%) CGP 39 393 patient compared with 4 (10.3%) heparin patients (relative risk, 7.6; 95% confidence interval, 0.9, 65.6). At 24 hours, complete perfusion was present in 91% heparin and 100% CGP 39 393 patients. Significant ST segment displacement was found in 11% of heparin versus 4% of CGP 39 393 subjects. Bleeding occurred only at the puncture site in 4 CGP 39 393-treated patients. QCA did not reveal significant differences between the groups. APTT values were more often in the target range and more stable in CGP 39 393 patients. Levels of thrombin-antithrombin III complexes, prothrombin fragment F1+2, and fibrinopeptide A indicated that CGP 39 393 was an effective inhibitor of thrombin activity. CONCLUSIONS CGP 39 393 can safely be administered to patients undergoing elective PTCA for stable anginal symptoms and may have a more favorable anticoagulant profile than heparin.
A MOST MEMORABLE PATIENT
Authors: A M. Barr
Journal: BMJ (1996)

In 1960, two years after qualifying, I joined my father's general practice in Perth, Western Australia. Soon afterwards, wrongly assessing my level of competence, he took my mother off on their first trip to Europe and left me to it. Of the many interesting patients in his singlehanded practice, several were ex-servicemen who had suffered badly in Japanese …
Sulfonylurea receptor 1 gene variants are associated with gestational diabetes and type 2 diabetes but not with altered secretion of insulin.
Authors: J Rissanen, A Markkanen, P Kärkkäinen, J Pihlajamäki, P Kekäläinen, L Mykkänen, J Kuusisto, P Karhapää, L Niskanen, M Laakso
Journal: Diabetes Care (2000)

To investigate the possible association of the variants in the nucleotide binding fold regions of the sulfonylurea receptor 1 (SUR1) gene with gestational diabetes mellitus (GDM), type 2 diabetes, and altered insulin secretion in Finnish subjects.The nucleotide binding fold regions of the SUR1 gene were amplified with polymerase chain reaction and screened by the single-strand conformational polymorphism analysis in 42 subjects with GDM and 40 subjects with type 2 diabetes. Detected variants were further investigated in 377 normoglycemic subjects by restriction fragment-length polymorphism analysis. The effect of the variants of the SUR1 gene on first-phase insulin secretion was studied in 295 normoglycemic subjects.In subjects with GDM or type 2 diabetes, one amino acid change (S1369A), four silent substitutions (R1273R, L829L, T759T, and K649K), and three intron variants were identified in the nucleotide binding fold regions of the SUR1 gene. A tagGCC allele of exon 16 splice acceptor site was more frequent in subjects with GDM (0.55 allele frequency, n = 42) and type 2 diabetes (0.60, n = 40) than in normoglycemic subjects (0.43, n = 377) (P1 = 0.024 and P2 = 0.009, respectively). Similarly, an AGG allele of the R1273R polymorphism was more common in subjects with GDM (0.87) and type 2 diabetes (0.87) than in normoglycemic subjects (0.74) (P1 = 0.009 and P2 = 0.001, respectively). However, the S1369A, R1273R, and cagGCC-->tagGCC variants of the SUR1 gene were not associated with altered first-phase insulin secretion in 295 normoglycemic subjects.These results suggest that a functional variant that contributes to the risk of GDM and type 2 diabetes may locate close to the SUR1 gene.
The Role of Sunlight in the Cutaneous Production of Vitamin D3
Authors: A R Webb, M F Holick
Journal: Annual Review of Nutrition (1988)

INTRODUCTION .. .... . . . . . ...... . . . .... .   . . . . . ..... .   . . . . . ........ . . . . . 375 HISTORICAL REVIEW........ . . . . .   . .... . . . . . . . ....... . . .... . . . . . . . . ... . . . ......... . . . . . . 376 PHOTOCHEMISTRY OF PROVITAMIN D AND ITS PHOTOISOMERS ..... . ........ 377 FORMA nON OF VITAMIN D3 IN SKIN. . . .... . . .   . . . . . . ..... . ....... . . . . . . . . . . . . .. 378 Photobiology of Vitamin D3 . .. ..   . . . . . . ... .... . ........ . ...... . . . . . .   . . . . . . 378 Action Spectra for the Formation of Previtamin D3 and Its Photoisomers . . .. . . . . . .. 380 Factors that Regulate the Cutaneous Production of Vitamin D3. . . . . ........ . . . . . . . . . . . 382 Photodegradation of Vitamin D3.... . . . . . . . . . . . . .   . . . . . . . . . . . . . . . ....... . . . . . . . . . . ... 387 Artificial Light Sources and Vitamin D . . ....... . . . . . .. . . . . . . . . ..... . . . .. . . . . . . . . . .. . ....... . 387 EPIDEMIOLOGY OF VITAMIN D . . . . . ......... . . . . . . . . . . . . . . . . . ... . . ......... . . . . .   . . 388 Vitamin D Deficiency in Children and Adults ...... . . . . . . . . . . . . . . . .. . .... . . . . . . . . . . . . . . . . . . 388 Environmental Factors . . . . . . . .... . . . . . . . .. . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391 CONCLUSION . . . ....... .   . . ........ . . ..... . . . . . .   . . . . . . . .. . . . ...... . . . . . 393
The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells
Authors: Luigi Maddaluno, Sue Ellen Verbrugge, Chiara Martinoli, Gianluca Matteoli, Andrea Chiavelli, Yiping Zeng, Elizabeth D. Williams, Maria Rescigno, Ugo Cavallaro
Journal: The Journal of Experimental Medicine (2009)

The adhesion molecule L1, which is extensively characterized in the nervous system, is also expressed in dendritic cells (DCs), but its function there has remained elusive. To address this issue, we ablated L1 expression in DCs of conditional knockout mice. L1-deficient DCs were impaired in adhesion to and transmigration through monolayers of either lymphatic or blood vessel endothelial cells, implicating L1 in transendothelial migration of DCs. In agreement with these findings, L1 was expressed in cutaneous DCs that migrated to draining lymph nodes, and its ablation reduced DC trafficking in vivo. Within the skin, L1 was found in Langerhans cells but not in dermal DCs, and L1 deficiency impaired Langerhans cell migration. Under inflammatory conditions, L1 also became expressed in vascular endothelium and enhanced transmigration of DCs, likely through L1 homophilic interactions. Our results implicate L1 in the regulation of DC trafficking and shed light on novel mechanisms underlying transendothelial migration of DCs. These observations might offer novel therapeutic perspectives for the treatment of certain immunological disorders.
Pharmacological Treatment of Parkinson Disease
Authors: Barbara S. Connolly, Anthony E. Lang
Journal: JAMA (2014)

Parkinson disease is the second most common neurodegenerative disease worldwide. Although no available therapies alter the underlying neurodegenerative process, symptomatic therapies can improve patient quality of life.To provide an evidence-based review of the initial pharmacological management of the classic motor symptoms of Parkinson disease; describe management of medication-related motor complications (such as motor fluctuations and dyskinesia), and other medication adverse effects (nausea, psychosis, and impulse control disorders and related behaviors); and discuss the management of selected nonmotor symptoms of Parkinson disease, including rapid eye movement sleep behavior disorder, cognitive impairment, depression, orthostatic hypotension, and sialorrhea.References were identified using searches of PubMed between January 1985 and February 2014 for English-language human studies and the full database of the Cochrane Library. The classification of studies by quality (classes I-IV) was assessed using the levels of evidence guidelines from the American Academy of Neurology and the highest-quality data for each topic.Although levodopa is the most effective medication available for treating the motor symptoms of Parkinson disease, in certain instances (eg, mild symptoms, tremor as the only or most prominent symptom, aged <60 years) other medications (eg, monoamine oxidase type B inhibitors [MAOBIs], amantadine, anticholinergics, β-blockers, or dopamine agonists) may be initiated first to avoid levodopa-related motor complications. Motor fluctuations may be managed by modifying the levodopa dosing regimen or by adding several other medications, such as MAOBIs, catechol-O-methyltransferase inhibitors, or dopamine agonists. Impulse control disorders are typically managed by reducing or withdrawing dopaminergic medication, particularly dopamine agonists. Evidence-based management of some nonmotor symptoms is limited by a paucity of high-quality positive studies.Strong evidence supports using levodopa and dopamine agonists for motor symptoms at all stages of Parkinson disease. Dopamine agonists and drugs that block dopamine metabolism are effective for motor fluctuations and clozapine is effective for hallucinations. Cholinesterase inhibitors may improve symptoms of dementia and antidepressants and pramipexole may improve depression. Evidence supporting other therapies for motor and nonmotor features is less well established.
The Roentgenographic Findings in Acute Pyelonephritis
Authors: R. Brent Harrison
Journal: JAMA (1979)

ACUTE pyelonephritis is a common disease the clinical signs and symptoms of which have been well known for many years. The roentgenographic findings, however, have been emphasized only relatively recently.<sup>1-5</sup>In two large series of acute pyelonephritis, about one fourth of the patients had abnormalities on the excretory urogram.<sup>2,3</sup>We believe that the high incidence of urologic abnormalities justifies a review of the roentgenographic findings in light of the limited information now available on the subject. <h3>Roentgenographic Findings</h3><h3>Ileus of the Ureter.—</h3> Gram-negative bacilli have the ability to impede or stop ureteral peristalsis.<sup>6</sup>Since most urinary tract infections are due to<i>Escherichia coli</i>,<sup>7</sup>it is not surprising that ileus of the ureter may be seen with acute pyelonephritis. Although the entire collecting system may be dilated, mimicking obstruction,<sup>1</sup>it is our experience that involvement is usually of the proximal portion of the infected ureter. This
Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals
Authors: Stein Emil Vollset, Robert Clarke, Sarah Lewington, Marta Ebbing, Jim Halsey, Eva Lonn, Jane Armitage, JoAnn E Manson, Graeme J Hankey, J David Spence, Pilar Galan, Kaare H Bønaa, Rex Jamison, J Michael Gaziano, Peter Guarino, John A Baron, Richard FA Logan, Edward L Giovannucci, Martin den Heijer, Per M Ueland, Derrick Bennett, Rory Collins, Richard Peto
Journal: The Lancet (2013)
Estrogen Receptor-α Phosphorylation at Serine 305, Nuclear p21-Activated Kinase 1 Expression, and Response to Tamoxifen in Postmenopausal Breast Cancer
Authors: Josefine Bostner, Lambert Skoog, Tommy Fornander, Bo Nordenskjöld, Olle Stål
Journal: Clinical Cancer Research (2010)

In vitro, p21-activated kinase 1 (Pak1) phosphorylates the serine 305 residue of the estrogen receptor alpha (ERalpha) and influences the response of breast cancer cells to tamoxifen. We investigated the influence of Pak1 and pERalpha(ser305) on breast cancer prognosis and results of tamoxifen therapy.We examined Pak1 and pERalpha(ser305) protein by immunohistochemistry in a series of 912 tumors from node-negative breast cancer patients randomized to tamoxifen or no adjuvant endocrine treatment.Cytoplasmic Pak1 correlated to large tumors and ER negativity, whereas nuclear Pak1 and pERalpha(ser305) correlated to small tumors and ER positivity. Nuclear expression of Pak1 and pERalpha(ser305) predicted reduced response to tamoxifen in patients with ERalpha-positive tumors (tamoxifen versus no tamoxifen: hazard ratio (HR), 1.33; 95% confidence interval (95% CI), 0.42-4.2; P = 0.63), whereas patients lacking this combination benefitted significantly from tamoxifen (HR, 0.43; 95% CI, 0.30-0.62; P < 0.0001). Similar nonsignificant trends were detected in analyses of the proteins separately. Pak1 in the cytoplasm was an independent prognostic marker, indicating increased recurrence rate (HR, 1.79; 95% CI, 1.17-2.74; P = 0.0068) and breast cancer mortality (HR, 1.98; 95% CI, 1.14-3.46; P = 0.016) for patients randomized to no adjuvant treatment.Our results suggest that patients with tumors expressing Pak1 and pERalpha(ser305) in combination are a group in which tamoxifen treatment is insufficient. In addition, the pathway may be of interest as a drug target in breast cancer. Furthermore, the findings support previous studies showing that Pak1 has differential roles in the cytoplasm and the nucleus.
Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors Vandetanib (ZD6474) and AZD2171 in Lung Cancer
Authors: Emer O. Hanrahan, John V. Heymach
Journal: Clinical Cancer Research (2007)

Vascular endothelial growth factor (VEGF) is a rational target for advanced non-small cell lung cancer (NSCLC), a hypothesis validated by the recent Eastern Cooperative Oncology Group E4599 trial showing that the addition of the VEGF monoclonal antibody bevacizumab to chemotherapy prolongs overall survival. Several new tyrosine kinase inhibitors targeting the VEGF pathway are currently in advanced clinical development for NSCLC and offer several possible advantages compared with monoclonal antibodies, including oral administration, more flexible dosing, a broader spectrum of target inhibition, and different toxicity profiles. Among these agents, vandetanib (ZD6474), an inhibitor of the VEGF receptor (VEGFR)-2 and epidermal growth factor receptor tyrosine kinase, has been the most extensively studied. In a randomized phase II study of patients with platinum-refractory NSCLC, including squamous histology, vandetanib prolonged progression-free survival compared with gefitinib. In another phase II trial, an improvement in progression-free survival was observed for vandetanib in combination with docetaxel compared with docetaxel alone. AZD2171 is an inhibitor of VEGFR-1, VEGFR-2, and VEGFR-3 and other tyrosine kinases that has shown clinical activity in NSCLC in combination with carboplatin and paclitaxel. Several phase III trials are under way testing these agents either as monotherapy or in combination with chemotherapy in patients with lung cancer. Early results with these agents, and others being tested, raise the possibility that there will eventually be multiple VEGF-targeted therapies available in the clinic that can potentially benefit a broader range of patients with advanced-stage NSCLC.
Atorvastatin Pretreatment Improves Outcomes in Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Coronary Intervention
Authors: Giuseppe Patti, Vincenzo Pasceri, Giuseppe Colonna, Marco Miglionico, Dionigi Fischetti, Gennaro Sardella, Antonio Montinaro, Germano Di Sciascio
Journal: Journal of the American College of Cardiology (2007)
Legislation for smoke-free workplaces and health of bar workers in Ireland: before and after study
Authors: Shane Allwright, Gillian Paul, Birgit Greiner, Bernie J Mullally, Lisa Pursell, Alan Kelly, Brendan Bonner, Maureen D'Eath, Bill McConnell, James P McLaughlin, Diarmuid O'Donovan, Eamon O'Kane, Ivan J Perry
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To compare exposure to secondhand smoke and respiratory health in bar staff in the Republic of Ireland and Northern Ireland before and after the introduction of legislation for smoke-free workplaces in the Republic. <b>Design</b> Comparisons before and after the legislation in intervention and control regions. <b>Setting</b> Public houses in three areas in the Republic (intervention) and one area in Northern Ireland (control). <b>Participants</b> 329 bar staff enrolled in baseline survey; 249 (76%) followed up one year later. Of these, 158 were non-smokers both at baseline and follow-up. <b>Main outcome measures</b> Salivary cotinine concentration, self reported exposure to secondhand smoke, and respiratory and sensory irritation symptoms. <b>Results</b> In bar staff in the Republic who did not themselves smoke, salivary cotinine concentrations dropped by 80% after the smoke-free law (from median 29.0 nmol/l (95% confidence interval 18.2 to 43.2 nmol/l)) to 5.1 nmol/l (2.8 to 13.1 nmol/l) in contrast with a 20% decline in Northern Ireland over the same period (from median 25.3 nmol/l (10.4 to 59.2 nmol/l) to 20.4 nmol/l (13.2 to 33.8 nmol/l)). Changes in self reported exposure to secondhand smoke were consistent with the changes in cotinine concentrations. Reporting any respiratory symptom declined significantly in the Republic (down 16.7%, −26.1% to −7.3%) but not in Northern Ireland (0% difference, −32.7% to 32.7%). After adjustment for confounding, respiratory symptoms declined significantly more in the Republic than in Northern Ireland and the decline in cotinine concentration was twice as great. <b>Conclusion</b> The smoke-free law in the Republic of Ireland protects non-smoking bar workers from exposure to secondhand smoke.
A Prospective Study of Plasma Adiponectin and Pancreatic Cancer Risk in Five US Cohorts
Authors: Ying Bao, Edward L. Giovannucci, Peter Kraft, Meir J. Stampfer, Shuji Ogino, Jing Ma, Julie E. Buring, Howard D. Sesso, I-Min Lee, John Michael Gaziano, Nader Rifai, Michael N. Pollak, Barbara B. Cochrane, Virginia Kaklamani, Jennifer H. Lin, JoAnn E. Manson, Charles S. Fuchs, Brian M. Wolpin
Journal: JNCI Journal of the National Cancer Institute (2012)

The adipocyte-secreted hormone adiponectin has insulin-sensitizing and anti-inflammatory properties. Although development of pancreatic cancer is associated with states of insulin resistance and chronic inflammation, the mechanistic basis of the associations is poorly understood.To determine whether prediagnostic plasma levels of adiponectin are associated with risk of pancreatic cancer, we conducted a nested case-control study of 468 pancreatic cancer case subjects and 1080 matched control subjects from five prospective US cohorts: Health Professionals Follow-up Study, Nurses' Health Study, Physicians' Health Study, Women's Health Initiative, and Women's Health Study. Control subjects were matched to case subjects by prospective cohort, year of birth, smoking status, fasting status, and month of blood draw. All samples for plasma adiponectin were handled identically in a single batch. Odds ratios were calculated with conditional logistic regression, and linearity of the association between adiponectin and pancreatic cancer was modeled with restricted cubic spline regression. All statistical tests were two-sided.Median plasma adiponectin was lower in case subjects versus control subjects (6.2 vs 6.8 µg/mL, P = .009). Plasma adiponectin was inversely associated with pancreatic cancer risk, which was consistent across the five prospective cohorts (P (heterogeneity) = .49) and independent of other markers of insulin resistance (eg, diabetes, body mass index, physical activity, plasma C-peptide). Compared with the lowest quintile of adiponectin, individuals in quintiles 2 to 5 had multivariable odds ratios ([ORs] 95% confidence intervals [CIs]) of OR = 0.61 (95% CI = 0.43 to 0.86), OR = 0.58 (95% CI = 0.41 to 0.84), OR = 0.59 (95% CI = 0.40 to 0.87), and OR = 0.66 (95% CI = 0.44 to 0.97), respectively (P (trend) = .04). Restricted cubic spline regression confirmed a nonlinear association (P (nonlinearity) < .01). The association was not modified by sex, smoking, body mass index, physical activity, or C-peptide (all P (interaction) > .10).In this pooled analysis, low prediagnostic levels of circulating adiponectin were associated with an elevated risk of pancreatic cancer.