tbuckley/cabot-search huggingface dataset:
Cardiovascular Disease in Type 2 Diabetes From Population to Man to Mechanisms
Authors: Markku Laakso
Journal: Diabetes Care (2010)

Epidemic of diabetes, affecting about 3–5% of Western populations, is one of the main threats to human health in the 21st century (1). Changes in the human environment, behavior, and lifestyle have resulted in a dramatic increase in the incidence and prevalence of diabetes in people with genetic susceptibility to diabetes. The global number of people with diabetes was 151 million in 2000, and it is projected to increase to 221 million in 2010 (an increase of 46%) both in developed and developing countries (2).

Chronic hyperglycemia leads to many long-term complications in the eyes, kidneys, nerves, heart, and blood vessels. Individuals with pre-diabetes, undiagnosed type 2 diabetes, and long-lasting type 2 diabetes are at high risk of all complications of macrovascular disease, coronary heart disease (CHD), stroke, and peripheral vascular disease. More than 70% of patients with type 2 diabetes die of cardiovascular causes (3). Therefore, the epidemic of type 2 diabetes will be followed by an epidemic of diabetes-related cardiovascular disease (CVD).

Over the years, epidemiological studies have produced important information on the prevalence and incidence of diabetes complications in different populations. They have also given important information on different risk factors determining susceptibility to diabetes complications (Fig. 1). This information is crucial for mechanistic studies in physiology at the tissue level and for molecular biology studies at the cellular level. A good example is glycated hemoglobin. Several studies have indicated that glycated hemoglobin is associated with diabetes complications in prospective epidemiological studies. That information has been crucial for the planning of clinical trials to test the hypothesis that the treatment of chronic hyperglycemia leads to reduction in long-term diabetes complications. Moreover, information from epidemiology has led to several mechanistic studies and the elucidation of molecular level insights how insulin resistance and hyperglycemia lead to diabetes complications. …
The diagnostic value of mucosubstances in rectal biopsies from patients with ulcerative colitis and Crohn's disease
Authors: M. I. Filipe, I. Dawson
Journal: Gut (1970)

Sixty-two biopsies from 36 patients with ulcerative colitis and 29 biopsies from 15 patients with Crohn9s disease were studied with special reference to the content of neutral, acid non-sulphated and sulphated mucosubstances. A marked decrease was found in mucosubstance in patients with active ulcerative colitis and was related to the intensity of inflammation in the lamina propria but not to the duration of the disease. In patients with active Crohn9s disease there was no corresponding decrease. Techniques for mucosubstances appear to be of value in differentiating between the two diseases in rectal biopsies.
SOME CLINICAL OBSERVATIONS OF MENINGEAL COMPLICATIONS, FOLLOWED BY DEATH AND POSTMORTEM EXAMINATIONS.
Authors: SAMUEL BELL
Journal: JAMA (1897)

The dura mater, histologically speaking, is composed of two distinct membranes, the external being a dense fibrous membrane lining closely the interior of the calvarium; the inner surface is smooth, lined with epithelium and is a serous membrane. The dura mater is therefore a fibro-serous membrane; externally fibrous, internally serous. The latter is more intimately connected with the brain structure. In keeping with these anatomic facts each layer is subject to somewhat different pathologic conditions. The inner layer of the dura is far less frequently diseased than the outer; a chronic, simple inflammation of the latter may exist for an indefinite period prior to death. It is frequently observed, as in case number one, in making autopsies, that it is difficult or impossible to remove the calvarium without considerable force, and often laceration of the dura is the result. In these cases the dura is firmly adherent to the calvarium
Critical Role of Interferon Regulatory Factor-1 in Murine Liver Transplant Ischemia Reperfusion Injury
Authors: Shinya Ueki, Rajeev Dhupar, Jon Cardinal, Allan Tsung, Junichi Yoshida, Kikumi S. Ozaki, John R. Klune, Noriko Murase, David A. Geller
Journal: Hepatology (2009)

Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates gene expression during immunity. We hypothesized that IRF-1 plays a pivotal role in liver transplant (LTx) ischemia/reperfusion (I/R) injury. Mouse orthotopic LTx was conducted after 24 hours cold storage in University of Wisconsin (UW) solution in wildtype (WT) C57BL/6 and IRF-1 knockout (KO) mice. IRF-1 deficiency in liver grafts, but not in recipients, resulted in significant reduction of hepatocyte apoptosis and liver injury, as well as improved survival. IRF-1 mRNA up-regulation was typically seen in graft hepatocytes in WT→WT LTx. Deficiency of IRF-1 signaling in graft resulted in significantly reduced messenger RNA (mRNA) levels for death ligands and death receptors in hepatocytes, as well as decreased caspase-8 activities, indicating that IRF-1 mediates death ligand-induced hepatocyte death. Further, a smaller but significant IRF-1 mRNA up-regulation was seen in WT graft nonparenchymal cells (NPC) and associated with interferon gamma (IFN-γ) mRNA up-regulation exclusively in NPC. IFN-γ mRNA was significantly reduced in IRF-1 KO graft. Thus, IRF-1 in graft hepatocytes and NPC has distinct effects in hepatic I/R injury. However, LTx with chimeric liver grafts showed that grafts lacking hepatocellular IRF-1 had better protection compared with those lacking IRF-1 in NPC. The study identifies a critical role for IRF-1 in liver transplant I/R injury. (Hepatology 2010.)
N-terminally cleaved Bcl-xL mediates ischemia-induced neuronal death
Authors: Dimitry Ofengeim, Ying-bei Chen, Takahiro Miyawaki, Hongmei Li, Silvio Sacchetti, Richard J Flannery, Kambiz N Alavian, Fabrizio Pontarelli, Brian A Roelofs, John A Hickman, J Marie Hardwick, R Suzanne Zukin, Elizabeth A Jonas
Journal: Nature Neuroscience (2012)
THE HUMAN ANTIBODY RESPONSE TO SIMULTANEOUS INJECTION OF SIX SPECIFIC POLYSACCHARIDES OF PNEUMOCOCCUS
Authors: Michael Heidelberger, Colin M. MacLeod, Marie M. Di Lapi
Journal: The Journal of Experimental Medicine (1948)

A new experimental procedure for the production of arteriosclerosis in the bird is described. The subcutaneous implantation of diethylstilbestrol by means of which a sustained increase in the concentration of cholesterol, phospholipid, and neutral fat can be readily established, is shown to induce atherosclerosis of the aorta. The atherosclerosis has been compared with that artificially induced in the bird by the prolonged feeding of cholesterol and also with that occurring spontaneously. The stilbestrol-induced lesion more closely resembled the spontaneously occurring one in the bird than did that produced by cholesterol feeding. But all 3 lesions were fundamentally similar, differing only in the amounts and proportions of the various lipid constituents present. The concentrations of cholesterol in plasma of the stilbestrol-treated and cholesterol-fed birds were of the same order. Yet cholesterol constituted a greater proportion of the lipids deposited in the arterial wall of the cholesterol-fed than in that of the stilbestrol-treated birds. This finding suggests that the cholesterol content of the vascular lesion depends not only on the absolute concentration of cholesterol in plasma, but also on the proportion of cholesterol to other lipid constituents in plasma.
Allelic Association of Human Dopamine D2 Receptor Gene in Alcoholism
Authors: Leonard S. Rubin
Journal: JAMA (1990)

To the Editor.—  Blum and colleagues 1 report a strong relationship between an allele of the dopamine D 2 receptor and alcoholism. After controlling for the confounding effects of race and sex (matching and statistical control), a contingency table basic to their conclusion was constructed. Of 35 nonalcoholics, the A 1 allele was found to be present in seven subjects and absent in 28. Of 35 alcoholics, the A1 allele was present in 24 subjects and absent in 11. A calculated χ of 14.8 ( df = 1, P  1 allele.  To further evaluate the import of the reported finding, statistical analyses were performed to determine the predictive value of the presence or absence of the A, allele for medical diagnosis. The sensitivity of the A 1 allele test was calculated from the authors data to be 0.686 (24/35).
The American College of Physicians Award Lecture: The Development of the Defibrillator.
Authors: William B. Kouwenhoven
Journal: Annals of Internal Medicine (1969)

s1 May 1969The American College of Physicians Award Lecture: The Development of the Defibrillator.William B. KouwenhovenWilliam B. KouwenhovenSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1059_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn 1928 I was chosen a member of a team to study the effects of electric shocks on human beings. In 1930 we were asked to investigate the statement of Prevost and Battelli in 1899 that they had been able to defibrillate the ventricular fibrillating dog's heart by applying an electric countershock directly to the myocardium. They had used direct cardiac massage to circulate oxygenated blood. We confirmed their statement and developed an open-chest defibrillator. Their method became a standard operating room procedure in fibrillation cases.We also found that the human heart could be defibrillated by placing the electrodes... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: William B. KouwenhovenAffiliations: Baltimore, Maryland PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1969Volume 70, Issue 5Page: 1059-1059KeywordsAtrial fibrillationBloodHeartMyocardiumShock ePublished: 1 December 2008 Issue Published: 1 May 1969 PDF downloadLoading ...
The Heart in Progressive Muscular Dystrophy
Authors: JACOB ZATUCHNI, ERNEST E. AEGERTER, LYNDALL MOLTHAN, CHARLES R. SHUMAN
Journal: Circulation (1951)

A case of progressive muscular dystrophy with cardiac involvement in a young Negro man is reported. The presenting problem was cardiomegaly and congestive heart failure. It was not until compensation was achieved that the underlying myopathy became apparent. Death was unexpected and presumably sudden. An unusual finding at the postmortem examination was the marked thickening of the endocardium. The literature in regard to the clinical and pathologic manifestations of cardiac involvement in this myopathy is reviewed.
Management of Patients With Peripheral Artery Disease (Compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations)
Authors: Jeffrey L. Anderson, Jonathan L. Halperin, Nancy Albert, Biykem Bozkurt, Ralph G. Brindis, Lesley H. Curtis, David DeMets, Robert A. Guyton, Judith S. Hochman, Richard J. Kovacs, E. Magnus Ohman, Susan J. Pressler, Frank W. Sellke, Win-Kuang Shen
Journal: Journal of the American College of Cardiology (2013)
Preventing Falls in Acute Care Hospitals
Authors: Terry P. Haines, Frances Healey
Journal: JAMA (2011)

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
Abstract 407: Angiotensin Converting Enzyme 2 (ACE2) Overexpression in Myocytes of Stroke Prone Spontaneously Hypertensive Rats (SHRSP) led to Cardiac Fibrosis
Authors: Rachel Masson, Stuart A Nicklin, Lorraine M Work, Kirsten Gilday, Paul Gregorevic, James M Allen, Jeffrey S Chamberlain, Delyth Graham, Anna F Dominiczak, Andrew H Baker
Journal: Circulation (2007)

Aim: Assess the effect of ACE2 overexpression in vivo on heart function and blood pressure. Identify an efficient cardiac gene delivery vector by comparison and optimisation of adeno-associated virus 6 (AAV6) and AAV9 mediated gene delivery to myocardium in vivo in SHRSPs. Methods: We administered a single intravenous injection of AAV6CMVlacZ or AAV9CMVlacZ at 3 doses (2x10 11 , 1.5x10 12 and 3x10 12 vp/rat) into 6 week old SHRSP. Animals were sacrificed 14 days post delivery and tissues stained for β-galactosidase (β-gal) expression which was confirmed by immunohistochemistry (IHC). Quantitative PCR compared the presence of lacZ containing genomes between tissues and animals. To assess the effect of ACE2 overexpression in SHRSP, 4 groups of animals (n = 6/group) were included in the study; PBS, Enalapril, AAV6-alkaline phosphatase (control reporter gene) and AAV6-ACE2. Blood pressure was monitored by tail cuff and cardiac function assessed by echocardiography (ECHO). Cardiac structure was assessed by haematoxylin and eosin (H&amp;E) staining and cardiac fibrosis evaluated by Masson’s trichrome and picrosirius red. Results: AAV6-mediated gene transfer was high in heart and skeletal muscle and a dose-dependent response was observed. β-gal staining and IHC confirmed transgene expression throughout the musculature but not within other tissues (kidney, liver, spleen and lung). Whilst AAV9 mediated approximately 10 fold (for highest dose) less gene transfer to the heart than AAV6, levels were comparable in skeletal muscle. However, the AAV9 vector accumulated in the kidneys. ACE2 was overexpressed selectively in the AAV6-ACE2-injected animals. ECHO showed substantial systolic dysfunction in ACE2-injected SHRSP’s compared to controls, and H&amp;E revealed abnormal cardiac structure. Masson’s trichrome and picrosirius red indicated severe cardiac fibrosis. Blood pressure was significantly lower (p&lt;0.001) in the ACE2 group in weeks 9, 10 and 11 post infusion compared to PBS and control vector infused animals. Conclusions: AAV6 exhibited a more favourable profile for cardiac gene delivery than AAV9, and represents a useful tool for studying mechanisms of cardiovascular disease. Overexpression of ACE2 in SHRSP myocardium led to severe cardiac fibrosis.
Diabetes Mellitus and Optic Atrophy in Two Siblings: A Report on a New Association and a Review of the Literature
Authors: Romesh Khardori, John W Stephens, Otto C Page, Robert S Dow
Journal: Diabetes Care (1983)

Two siblings with diabetes mellitus and optic atrophy (Wolfram syndrome) are described. As often noted, they also had atonic urinary bladders. Only one of the siblings had some impairment of hearing. Other findings not previously reported that appeared in each subject were esophageal dysphagia and vertigo. An autopsy in one revealed brain stem hypoplasia and thinning and flattening of the optic nerves with atrophy of the lateral geniculate bodies.
Intrathecal Alcohol for Relief of Pain
Authors: C. Ottley
Journal: BMJ (1938)

<h3>Objective</h3> The primary objective was to assess the characteristics and prognosis of pyogenic spondylodiscitis (PS) in patients with infective endocarditis (IE). The secondary objectives were to assess the factors associated with occurrence of PS. <h3>Methods</h3> Prospective case–control bi-centre study of 1755 patients with definite IE with (n=150) or without (n=1605) PS. Clinical, microbiological and prognostic variables were recorded. <h3>Results</h3> Patients with PS were older (mean age 69.7±18 vs 66.2±14; p=0.004) and had more arterial hypertension (48% vs 34.5%; p&lt;0.001) and autoimmune disease (5% vs 2%; p=0.03) than patients without PS. The lumbar vertebrae were the most frequently involved (84 patients, 66%), especially L4–L5. Neurological symptoms were observed in 59% of patients. Enterococci and <i>Streptococcus gallolyticus</i> were more frequent (24% vs 12% and 24% vs 11%; p&lt;0001, respectively) in the PS group. The diagnosis of PS was based on contrast-enhanced MRI in 92 patients, bone CT in 88 patients and <sup>18</sup>F-FDG PET/CT in 56 patients. In-hospital (16% vs 13.5%, p=0.38) and 1-year (21% vs 22%, p=0.82) mortalities did not differ between patients with or without PS. <h3>Conclusions</h3> PS is a frequent complication of IE (8.5% of IE), is observed in older hypertensive patients with enterococcal or <i>S. gallolyticus</i> IE, and has a similar prognosis than other forms of IE. Since PS is associated with specific management, multimodality imaging including MRI, CT and PET/CT should be used for early diagnosis of this complication of endocarditis.
Depressive Symptoms and Physical Activity During 3 Decades in Adult Life
Authors: Snehal M. Pinto Pereira, Marie-Claude Geoffroy, Christine Power
Journal: JAMA Psychiatry (2014)

<h3>Importance</h3> Associations have been documented between physical activity and depressive symptoms, but the direction of this association is unclear. <h3>Objective</h3> To examine whether depressive symptoms are concurrent with physical activity and to examine the direction of the relationship from 23 to 50 years of age. <h3>Design, Setting, and Participants</h3> Participants included members of the 1958 British Birth Cohort, a general population sample of all persons born in England, Scotland, and Wales in a single week in March 1958 who were followed up to 50 years of age (2008). We included approximately 11 000 cohort members with information on depressive symptoms or frequency of physical activity at 23, 33, 42, or 50 years of age. <h3>Exposures</h3> Depressive symptoms were measured using the Psychological subscale of the Malaise Inventory; frequency of physical activity, by questionnaire. <h3>Main Outcomes and Measures</h3> Number of depressive symptoms (on a scale of 0 to 15 items), depression (defined as being in the top 10% for symptoms at 23, 33, 42, or 50 years of age), and frequency of physical activity (times per week). <h3>Results</h3> At most ages, we found a trend of fewer depressive symptoms with more frequent activity; for example, per higher frequency of activity per week at 50 years of age, the mean number of symptoms was lower by 0.06 (95% CI, −0.09 to −0.04). In longitudinal analyses, activity was associated with fewer symptoms from 23 to 50 years of age (per higher frequency of activity per week, symptoms were lower by 0.06 [95% CI, −0.07 to −0.05]), and the magnitude of association did not vary with age (<i>P</i> = .21 for interaction). Those who were inactive at 23 years of age and remained inactive 5 years later showed no change in symptom level (mean difference, −0.01 [95% CI, −0.04 to 0.02]); those increasing activity to 3 times/wk had a lower mean number of symptoms (mean difference, −0.18 [95% CI, −0.22 to −0.15]). Such differences equate to estimated reductions in odds of depression by 19%. A longitudinal relationship observed between symptoms and activity weakened with age (<i>P</i> &lt; .001 for interaction). Mean activity among those with no symptoms at 23 years of age and 5 years later was higher by 0.60 (95% CI, 0.57-0.64) times/wk; in those with 1 additional depressive symptom, 0.53 (95% CI, 0.49-0.56) times/wk. Activity frequency did not differ among those with no symptoms at 43 years of age who subsequently had 0 or 1 symptom at 48 years of age. Associations for depression were generally similar to those for the full symptom spectrum. <h3>Conclusions and Relevance</h3> The relationship between activity and depressive symptoms was bidirectional, albeit more persistent during adult life in the direction from activity to depressive symptoms. Findings suggest that activity may alleviate depressive symptoms in the general population and, in turn, depressive symptoms in early adulthood may be a barrier to activity.
Transmitting biological information using oxygen: Reactive oxygen species as signalling molecules in cardiovascular pathophysiology
Authors: A SHAH, H SAUER
Journal: Cardiovascular Research (2006)

The involvement of reactive oxygen species (ROS) in deleterious processes such as DNA damage and reperfusion injury has long been recognized. More recently, however, it has been appreciated that ROS can specifically modulate diverse intracellular signalling pathways through covalent modifications of target molecules (“redox signalling”), thereby inducing distinct changes in cell phenotype that are important in many physiological and pathophysiological processes [1]. Indeed, some ROS such as H2O2 may be ideally suited to serve as signalling molecules in that they are small, highly diffusible, and rapidly generated and degraded. Despite an exponentially growing amount of information on the sources and mechanisms of ROS generation as well as their degradation by the antioxidant defence system, we are just starting to learn how ROS signalling may function within cells and in a coordinated way within tissues and organs.

The numerous sources of ROS generation, which include the mitochondrial respiratory chain and enzymes such as the NADPH oxidases (Noxs), xanthine oxidase, uncoupled nitric oxide (NO) synthases, 5-lipooxygenase, and cyclooxygenases, are counterbalanced by a large number of endogenous antioxidants and antioxidant enzymes. This raises the question of how individual ROS could specifically govern diverse signalling events and thereby regulate, in the cardiovascular system, physiological processes such as endothelial migration, vascular smooth muscle proliferation, and angiogenesis, as well as initiate pathophysiological modifications of tissue and organs, resulting in atherosclerosis, hypertension, cardiac hypertrophy, and cardiac and vascular remodelling. One possible answer could be the cell type-specific and subcellular localization of ROS sources and sinks which may allow spatial targeting of ROS to protein adaptor molecules which, after redox modification and subsequent structural change, could then further transmit the redox signal downstream. Indeed, distinct subcellular localization of Nox isoforms has recently been suggested to occur in vascular smooth muscle cells with differential compartmentalization … 

* Corresponding author. Tel.: +44 207 346 3865; fax: +44 207 346 4771. Email address: ajay.shah{at}kcl.ac.uk heinrich.sauer{at}physiologie.med.uni-giessen.de