tbuckley/cabot-search huggingface dataset:
Final “Perspectives on the News”
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2011)

### Genomics and diabetes

At a plenary session of the American Association of Clinical Endocrinology (AACE) Annual Meeting in April 2011, Eric Topol, La Jolla, California, discussed the concept that genomics can be used to create “a revolution in medicine” for diabetes prevention and management. Although the decoding of the human genome was greeted with much fanfare in 2000, this information “has failed so far to produce medical miracles.” There has, however, been remarkable progress in the use of the human genome to understand the underpinning of many common diseases. We are progressing from genome-wide association studies (GWASs), involving 106 single nucleotide polymorphisms (SNPs) and providing insight into common gene variations with population frequency >5%, to whole-exon sequencing of 1.5% of the genome, finding rare and low frequency elements, to whole genome sequencing, allowing an understanding of regulatory as well as coding sequences. More than one thousand GWASs have been carried out, identifying several hundred traits tracking with important diseases. The discovery of a variant of transcription factor 7-like 2 (TCF7L2) associated with diabetes may lead to the greatest understanding of its pathogenesis, and a number of other polymorphisms have been found to be related to diabetes.

A meta-analysis of GWAS data from over 100,00 individuals confirms 38 gene loci (1), and a recent review cites 67 loci for nonautoimmune diabetes (2), suggesting that there are many different genetic pathways to its development. Topol suggested that diabetes risk is associated with “a combination of lower variants below the 5% threshold … down to <1%” (3). He reviewed a number of interesting candidates, including regions of the genome that do not appear to code for specific peptides but, rather, regulate transcription of other genes (4). Another potential cause is variation in the melatonin receptor 1b, which, like TCF7L2, is associated with impairment in insulin …
Is closure of large mucosal defects after endoscopic mucosal resection and endoscopic submucosal dissection truly needed?
Authors: M. Matsushita, N. Danbara, M. Omiya, K. Uchida, A. Nishio, K. Okazaki
Journal: Endoscopy (2008)

We read with interest the article by Sakamoto et al. [1] on closure of large mucosal defects after endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for the prevention of complications. Because closure of large mucosal defects is quite difficult with conventional clips, they designed a new closure device, a “loop clip”, which consists of a metal clip attached to a loop of nylon string. After a loop clip was connected to the mid edges of a large mucosal defect, conventional clips were placed to achieve complete closure in three lesions. With a figure-of-8-shaped ring (8-ring) and clips [2], and with an endoloop and clips [3], other endoscopic closure techniques for post-EMR large mucosal defects were also described. We believe that these techniques have some drawbacks, and furthermore, we doubt whether the prophylactic closure could effectively prevent delayed bleeding.
Computer analysis of ventilation-perfusion scans for detection and assessment of lung disease.
Authors: G H Burton, W A Seed, P Vernon
Journal: Thorax (1985)

A previously reported computer analysis has been used to provide numerical ventilation-perfusion lung scan data, for comparison with tests of airways function and results of arterial blood gas analysis in 11 patients with pulmonary embolism, 18 with asthma, and 37 with chronic obstructive lung disease. In pulmonary embolism an index of underperfusion showed high sensitivity, and an index of ventilation-perfusion mismatching correlated well with severity (hypoxaemia). In asthma an index of underventilation was sensitive and correlated well with severity of airways obstruction. In chronic obstructive lung disease the same index was sensitive but correlated poorly with severity. This was attributed to heterogeneity of the lung disease (airways obstruction plus emphysema) in chronic obstructive lung disease. Ventilation-perfusion mismatching was frequently present in airways disease, and was often of great severity in chronic obstructive lung disease. Discrimination between pulmonary embolism and either type of airways disease was possible by using a combination of underfusion and underventilation indices. The technique offers the prospect of increasing the information derived from lung scans and of automating the reporting of scans.
A neurophysioiogical account of working memory limits: Between-item segregation and within-chunk integration
Authors: Antonino Raffone, Gezinus Wolters, Jacob M. Murre
Journal: Behavioral and Brain Sciences (2001)

We suggest a neurophysiological account of the short-term memory capacity limit based on a model of visual working memory (Raffone &amp; Wolters, in press). Simulations have revealed a critical capacity limit of about four independent patterns. The model mechanisms may be applicable to working memory in general and they allow a reinterpretation of some of the issues discussed by Cowan.
Preconditioning in Cardiomyocytes Protects by Attenuating Oxidant Stress at Reperfusion
Authors: Terry L. Vanden Hoek, Lance B. Becker, Zuo-Hui Shao, Chang-Qing Li, Paul T. Schumacker
Journal: Circulation Research (2000)

Abstract —Cardiomyocyte death after ischemia/reperfusion correlates with oxidant stress, and antioxidants confer protection in that model. Preconditioning (PC) with hypoxia or adenosine also confers protection, leading us to hypothesize that PC protects by attenuating oxidant generation during subsequent ischemia/reperfusion. Chick cardiomyocytes were preconditioned with 10 minutes of hypoxia or adenosine (100 μmol/L), followed by 1 hour of simulated ischemia and 3 hours of reperfusion. Adenosine PC decreased cell death from 50±3% to 18±4% and enhanced the return of contractions during reperfusion, as observed previously with hypoxic PC. A transient burst of dichlorofluorescein (sensitive to H 2 O 2 ) oxidation that was significantly attenuated by PC initiated by hypoxia or adenosine was seen at reperfusion. The protein kinase C (PKC) inhibitor Go-6976 and the mitochondrial ATP-sensitive K + (K ATP ) channel inhibitor 5-hydroxydecanoate each abolished protection and abrogated the PC-induced attenuation of reperfusion oxidant stress. By contrast, when given only at reperfusion, the K + channel opener pinacidil or the antioxidants 2-mercaptopropionylglycine and 1,10-phenanthroline decreased oxidant stress at reperfusion and improved survival and return of contractions. Thus, PC protection is associated with an attenuation of the oxidant burst at reperfusion, regardless of the method by which PC is triggered. Loss of PC protection associated with PKC inhibition or K ATP channel inhibitors is associated with a restoration of that oxidant stress. These results suggest a mechanism for PC protection and reveal a functional link between PKC activation and K ATP channel activation in that pathway.
Methylation of a Panel of MicroRNA Genes Is a Novel Biomarker for Detection of Bladder Cancer
Authors: Takashi Shimizu, Hiromu Suzuki, Masanori Nojima, Hiroshi Kitamura, Eiichiro Yamamoto, Reo Maruyama, Masami Ashida, Tomo Hatahira, Masahiro Kai, Naoya Masumori, Takashi Tokino, Kohzoh Imai, Taiji Tsukamoto, Minoru Toyota
Journal: European Urology (2012)
Inhibition of biliary bicarbonate secretion in ethinyl estradiol-induced cholestasis is not associated with impaired activity of the Cl−/HCO3− exchanger in the rat
Authors: Domenico Alvaro, Alessandro Gigliozzi, Claudia Piat, Laura Carli, Flavia Fraioli, Rosamaria Romeo, Chiara Francia, Adolfo F. Attili, Livio Capocaccia
Journal: Journal of Hepatology (1997)
A phase III study of the safety and efficacy of viramidine versus ribavirin in treatment-naïve patients with chronic hepatitis C: ViSER1 results
Authors: Yves Benhamou, Nezam H. Afdhal, David R. Nelson, Mitchell L. Shiffman, Deanine G. Halliman, Jamie Heise, Eric Chun, Paul J. Pockros
Journal: Hepatology (2009)

Abstract Pegylated interferon (peg-IFN) and ribavirin (RBV) are effective in eradicating the hepatitis C virus in more than half of patients. However, anemia arising from RBV-induced hemolysis can prompt dose reductions and lower sustained virologic response (SVR) rates. In early clinical trials, Viramidine (VRD, renamed taribavirin), an RBV prodrug, was associated with less anemia and VRD given at 600 mg twice daily (BID) appeared to provide the best safety with comparable efficacy to RBV. The phase III Viramidine's Safety and Efficacy versus Ribavirin 1 (ViSER1) study randomized 972 treatment-naïve patients with chronic hepatitis C to fixed-dose VRD (600 mg BID) or weight-based RBV (1000 or 1200 mg/day), each given with peg-IFN alfa-2b at 1.5 μg/kg/week. The primary efficacy endpoint was SVR rate, and the primary safety endpoint was hemoglobin (Hb) event rate (percent of patients with Hb &lt; 10 g/dL or at least a 2.5-g/dL decrease from baseline). SVR rates were 37.7% with VRD (244/647) and 52.3% with RBV (170/325). Thus, the ViSER1 study failed to demonstrate the primary noninferiority efficacy endpoint. Significantly fewer patients had Hb events with VRD (353/647; 54.6%) compared to those with RBV (272/325; 83.7%) ( P &lt; 0.001), and significantly fewer developed anemia (Hb &lt; 10 g/dL) with VRD (34/647; 5.3%) compared to those with RBV (76/325; 23.5%) ( P &lt; 0.001). Conclusion: Fixed doses of VRD failed to demonstrate noninferiority to RBV in producing SVR rates. The incidence of anemia was approximately four-fold significantly lower with VRD than with RBV. These results suggest fixed-dose VRD given 600 mg BID is insufficient to treat patients with chronic hepatitis C; a weight-based dosing trial of viramidine is currently under way. (Hepatology 2009.)
Atrial natriuretic factor significantly contributes to the mineralocorticoid escape phenomenon. Evidence for a guanylate cyclase-mediated pathway.
Authors: N Yokota, B G Bruneau, M L Kuroski de Bold, A J de Bold
Journal: Journal of Clinical Investigation (1994)

The mechanism underlying the mineralocorticoid escape phenomenon remains unknown. To assess the possible contribution of natriuretic peptides to mineralocorticoid escape, rats were injected with 5 mg deoxycorticosterone acetate for 3 d. Plasma atrial natriuretic factor (ANF) rose to twice basal levels and atrial ANF content decreased significantly by 24 h of treatment. This coincided with renal escape and with a significant increase in urinary cGMP excretion. Plasma ANF remained elevated and atrial ANF content continued to decline by 48 and 72 h while atrial ANF mRNA levels increased significantly only at 72 h. Plasma brain natriuretic peptide did not increase during escape although atrial brain natriuretic peptide mRNA levels increased significantly. Chronically administered HS-142-1 (HS), a specific antagonist of the guanylate cyclase-coupled natriuretic peptide receptors, significantly and dose-dependently impaired the escape phenomenon. The highest dose of HS completely suppressed the increase in urinary cGMP. Despite the continued suppression, partial escape was observed by the end of the observation period. HS alone influenced neither plasma nor tissue or urine parameters. These findings show that despite activation of atrial ANF, blockade of the guanylate cyclase-coupled natriuretic peptide receptors impairs the ability of the kidney to escape the Na+ retaining effect of excess mineralocorticoid in a dose-dependent fashion. Later-acting, unknown mechanisms eventually come into play to mediate the escape phenomenon through a guanylate cyclase-independent pathway. Therefore, ANF of cardiac origin appears to be a major factor initiating mineralocorticoid escape through a guanylate cyclase-dependent pathway.
Progeria: Blood Samples Requested
Authors: MARC E. WEKSLER
Journal: Annals of Internal Medicine (1978)

Letters and Corrections1 September 1978Progeria: Blood Samples RequestedMARC E. WEKSLER, M.D.MARC E. WEKSLER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-89-3-431_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The New York Hospital-Cornell Medical Center and The Sloan-Kettering Institute are studying patients with progeria. These studies require a small sample of heparinized blood. We can transport such a sample from any area of the United States for study in our laboratories.If progeric patients cannot give a fresh blood sample or have died, a 2- to 3-ml serum specimen would be helpful.Please contact Dr. Weksler at the address below or call collect: (212)472-6794.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York Hospital—Cornell Medical Center 525 East 68th Street; New York, NY 10021 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1978Volume 89, Issue 3Page: 431-431KeywordsBlood ePublished: 1 December 2008 Issue Published: 1 September 1978 PDF downloadLoading ...
The tumor virus landscape of AIDS-related lymphomas
Authors: Aaron Arvey, Akinyemi I. Ojesina, Chandra Sekhar Pedamallu, Gianna Ballon, Joonil Jung, Fujiko Duke, Lorenzo Leoncini, Giulia De Falco, Eric Bressman, Wayne Tam, Amy Chadburn, Matthew Meyerson, Ethel Cesarman
Journal: Blood (2015)
Screening Asymptomatic Adults for Cardiac Risk Factors: The Serum Cholesterol Level
Authors: Alan M. Garber
Journal: Annals of Internal Medicine (1989)

From our review of the epidemiologic and clinical literature, we have developed recommendations for using the serum cholesterol test as a component of strategies to prevent coronary heart disease in asymptomatic adults. Total cholesterol, high-density lipoprotein, and low-density lipoprotein levels are risk factors for coronary disease and early mortality in middle-aged men. Weaker evidence suggests that hypercholesterolemia increases the risk for coronary disease in women or elderly men, or that hypertriglyceridemia increases the risk in men or women. A reduction in cholesterol levels lowers the incidence of and the mortality from coronary disease in asymptomatic, hypercholesterolemic, middle-aged men, but has not been shown to reduce overall mortality. The efficacy of treatment in women and elderly persons has not been studied. Screening and treatment plans should be individualized; a 5-year period between tests is adequate for asymptomatic, low-risk men, whereas more frequent testing is appropriate for high-risk men. Screening is optional for women and elderly persons.
Iron and the sudden infant death syndrome.
Authors: M. Murphy, J. Nicholl, A. O'Cathain
Journal: BMJ (1989)

Mechanical ventilation at homeSIR,-We support Dr M A Branthwaite's succinct case for a nationally coordinated home ventilation service in Britain' Such a system would help smaller centres such as our own, which historically lacks the designated funding.At present we experience much difficulty in obtaining financial agreement for ventilators and associated equipment from patients' home districts, which prolongs their stay in hospital.The current impetus arises from the greater understanding of the treatability of nocturnal hypoxaemia associated with sleep apnoea or chronic pulmonary disease; numerically, these groups account for a large fraction of the total
Relationship of isoniazid resistance to human immunodeficiency virus infection in patients with tuberculosis.
Authors: S Asch, L Knowles, A Rai, B E Jones, J Pogoda, P F Barnes
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

To investigate the relationship between isoniazid resistance and HIV infection in patients with tuberculosis, we evaluated data in the Los Angeles County tuberculosis registry on 1,506 patients for whom drug susceptibility results were available. Among 235 HIV-infected patients, isoniazid resistance was less common than in 1,271 patients who were HIV-seronegative or who had not been tested for HIV, with an unadjusted odds ratio of 0.3. After adjustment for other factors that affect drug resistance (ethnicity, country of birth, prior diagnosis of tuberculosis, and cavitation), the frequency if isoniazid resistance remained lower than that in patients without HIV infection, with an odds ratio of 0.4 (95% confidence interval, 0.2 to 0.8; p = 0.02). We conclude that in Los Angeles, a setting where there is no ongoing outbreak of drug-resistant tuberculosis, isoniazid-resistant tuberculosis is not more common in HIV-infected patients.
THE CULTURE OF WHOLE ORGANS
Authors: Harald Okkels
Journal: The Journal of Experimental Medicine (1937)

1. During the 1st and 2nd day of cultivation of the whole thyroid gland in the Lindbergh apparatus, perfused by a medium containing 20 or 40 per cent homologous serum diluted with glucose-Tyrode, the state of the thyroid epithelium remains histologically normal and even the most delicate cytological details retain their normal aspect. 2. Cultivation over a period up to 6 days need not cause any serious histological alteration of the gland; but cytological examination reveals an increasingly damaged condition of the mitochondria and the Golgi apparatus. These changes seem not to interfere with the life of the cells, however; epithelial culture from the perfused organs yields positive results. 3. The process of cultivation is liable to cause a slight morphological reaction in the thyroid epithelium, which resembles a feeble stimulation of the tissue. 4. Addition of the thyro-stimulating factor from the anterior pituitary to the perfusion fluid causes a stimulation of the cultivated thyroid epithelium which is comparable to, but not so marked as, the corresponding reaction in the living animal.
Sprouting a warfarin interaction
Authors: L. R. Kidd, D. H. Hanumantharaya
Journal: BMJ (2010)

A 70 year old woman was admitted with increasing shortness of breath and feeling generally unwell. The onset of these symptoms had coincided with a mild worsening of her angina. 

Her medical history included recurrent pulmonary emboli for which she was on lifelong warfarin (15 mg/day, international normalised ratio (INR) stable and therapeutic), an episode of severe pneumonia that necessitated admission to intensive care, and exertional angina for which she used a glyceryl trinitrate spray. She was on no additional medication, and described herself as being “very healthy,” taking great pride in maintaining a nourishing diet rich in fruit and vegetables.

On examination the patient was alert and orientated. Respiratory rate was mildly increased, but blood pressure and oxygen saturations were normal. She had right sided bronchial breathing, and plain film radiographs showed right perihilar consolidation. She was treated for community acquired pneumonia with intravenous cefuroxime and oral doxycycline, as per local hospital trust guidelines.

Two days after admission the patient showed clinical and subjective improvement. The haematology laboratory then phoned the doctor on call to say that the patient’s INR was greater than 15. There was no evidence of active bleeding. Following advice from a haematologist, the patient was treated with vitamin K. Over the next few days the INR decreased until the patient was deemed fit for discharge.



### 1 What is the mechanism of action of warfarin?

#### Short answer

Warfarin inhibits the enzyme vitamin K epoxide reductase and thus prevents recycling of oxidised vitamin K. This lowers the amount of reduced vitamin K available, which, in turn, prevents carboxylation and activation of clotting factors dependent on vitamin K …
Ethnic Differences in Correlates of Microalbuminuria in NIDDM: The role of the acute-phase response
Authors: Niaz Islam, Fahrat Kazmi, Gary D Chusney, Martin B Mattock, A Zaini, John C Pickup
Journal: Diabetes Care (1998)

To investigate whether microalbuminuria is associated with markers of the acute-phase response in NIDDM and whether there are ethnic differences in this association among the three main racial groups in Malaysia.NIDDM patients of Chinese, Indian, and Malay origin attending a diabetic clinic in Kuala Lumpur, Malaysia, were matched for age, sex, diabetes duration, and glycemic control (n = 34 in each group). Urinary albumin-to-creatinine ratio was measured in an early morning urine sample. Biochemical measurements included markers of the acute-phase response: serum sialic acid, triglyceride, and (lowered) HDL cholesterol.The frequency of microalbuminuria did not differ among the Chinese, Indian, and Malay patients (44, 41, and 47%, respectively). In Chinese patients, those with microalbuminuria had evidence of an augmented acute-phase response, with higher serum sialic acid and triglyceride and lower HDL cholesterol levels; and urinary albumin-to-creatinine ratio was correlated with serum sialic acid and triglyceride. The acute-phase response markers were not different in Indians, with microalbuminuria being high in even the normoalbuminuric Indians; only the mean arterial blood pressure was correlated with urinary albumin-to-creatinine ratio in the Indians. Malay NIDDM subjects had an association of microalbuminuria with acute-phase markers, but this was weaker than in the Chinese subjects.Microalbuminuria is associated with an acute-phase response in Chinese NIDDM patients in Malaysia, as previously found in Caucasian NIDDM subjects. Elevated urinary albumin excretion has different correlates in other racial groups, such as those originating from the Indian subcontinent. The acute-phase response may have an etiological role in microalbuminuria.
Molecular characterization and phylogenetic relationships of a protein with potential oxygen-binding capabilities in the grasshopper embryo. A hemocyanin in insects?
Authors: D. Sanchez, M. D. Ganfornina, G. Gutierrez, M. J. Bastiani
Journal: Molecular Biology and Evolution (1998)

Arthropodan hemocyanins, prophenoloxidases (PPOs), and insect hexamerins form a superfamily of hemolymph proteins that we propose to call the AHPH superfamily. The evolutionary and functional relationships of these proteins are illuminated by a new embryonic hemolymph protein (EHP) that is expressed during early stages of development in the grasshopper embryo. EHP is a 78-kDa soluble protein present initially in the yolk sac content, and later in the embryonic hemolymph. Protein purification and peptide sequencing were used to identify an embryonic cDNA clone coding for EHP. In situ hybridization identifies hemocytes as EHP-expressing cells. As deduced from the cDNA clone, EHP is a secreted protein with two potential glycosylation sites. Sequence analysis defines EHP as a member of the AHPH superfamily. Phylogenetic analyses with all the currently available AHPH proteins, including EHP, were performed to ascertain the evolutionary history of this protein superfamily. We used both the entire protein sequence and each of the three domains present in the AHPH proteins. The phylogenies inferred for each of the domains suggest a mosaic evolution of these protein modules. Phylogenetic and multivariate analyses consistently group EHP with crustacean hemocyanins and, less closely, with insect hexamerins, relative to cheliceratan hemocyanins and PPOs. The grasshopper protein rigorously preserves the residues involved in oxygen binding, oligomerization, and allosteric regulation of the oxygen transport proteins. Although insects were thought not to have hemocyanins, we propose that EHP functions as an oxygen transport or storage protein during embryonic development.
Relationship between Left Ventricular Ejection Fraction and Number of Fragmented QRS Complex Derivations on Standard 12-Lead Electrocardiogram in Acute ST-Elevated Myocardial Infarction Patients
Authors: Ersin Yıldırım, Denizhan Karaçimen, Ceyhan Türkkan, Damirbek Osmonov, Kazım Serhan Özcan, Servet Altay, Ufuk Sadık Ceylan, Murat Uğur, Mehmet Bozbay, İzzet Erdinler
Journal: Journal of the American College of Cardiology (2013)