tbuckley/cabot-search huggingface dataset:
Neutral endopeptidase in the heart. Neutral endopeptidase inhibition prevents isoproterenol-induced myocardial hypoperfusion in rats by reducing bradykinin degradation.
Authors: G Piedimonte, J A Nadel, C S Long, J I Hoffman
Journal: Circulation Research (1994)

Peptide mediators may play a role in the control of myocardial perfusion. We found immunohistochemical evidence of the peptide-degrading enzyme neutral endopeptidase (NEP) in cultured rat myocytes. Therefore, we examined the effect of an NEP inhibitor, phosphoramidon, on myocardial perfusion in rats after (1) stimulating sensory nerves with capsaicin and (2) inducing myocardial hypoperfusion with isoproterenol, with or without pretreatment with selective antagonists of the substance P (NK1) and bradykinin (B2) receptors. Three to five sequential determinations of myocardial blood flow were made in anesthetized rats by injecting 100,000 radionuclide-labeled microspheres suspended in 70% dextrose into the left ventricle. Phosphoramidon doubled coronary blood flow in response to a dose of capsaicin that was ineffective in the absence of the inhibitor. Isoproterenol (50 mg/kg IP) caused an immediate fall in blood pressure and coronary blood flow; after 20 minutes, flow had returned to normal but pressure was still subnormal. Administration of phosphoramidon reduced the recovery of blood pressure but greatly increased coronary blood flow. These changes were not altered by a substance P NK1 receptor blocker but were completely abolished by a selective bradykinin B2 receptor blocker. Our data indicate that (1) NEP is present in the rat myocardium, (2) sensory nerve-induced coronary vasodilation is markedly potentiated by NEP inhibition, (3) isoproterenol-induced myocardial hypoperfusion is prevented by NEP inhibition, and (4) this effect of NEP inhibition is due to reduced degradation of bradykinin.
[87] EFFICACY OF ANTIVIRAL THERAPY ON DISEASE PROGRESSION IN HEPATITIS C RECURRENCE AFTER LIVER TRANSPLANTATION: A RANDOMIZED CONTROLLED STUDY
Authors: J.A. Carrion, M. Navasa, M. Garcia-Retortillo, J.C. Garcia-Pagan, G. Crespo, M. Bruguera, J. Bosch, X. Forns
Journal: Journal of Hepatology (2007)
Energy Drinks and Caffeine-Related Adverse Effects
Authors: Kent A. Sepkowitz
Journal: JAMA (2012)

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
POLYMORPHONUCLEAR LEUKOCYTES IN IMMUNOLOGIC REACTIONS
Authors: Charles G. Cochrane, Barbara S. Aikin
Journal: The Journal of Experimental Medicine (1966)

Vascular basement membrane was disrupted in the presence of polymorphonuclear leukocytes (PMN's) during two immunologic reactions: The Arthus phenomenon and the reaction to locally injected antibody to vascular basement membrane. This disruption was evidenced by (a) the inability of the basement membrane to retain circulating carbon, by (b) loss of antigenic constituents, and by (c) electron microscopic observation showing actual gaps in the structure of the vascular basement membrane. The factors within PMN's responsible for damage to isolated glomerular basement membrane in vitro were found by isolation procedures to be cathepsins D and E. Cationic proteins of PMN's were separable from the cathepsins. While inducing vascular permeability upon injection, these basic proteins failed to inflict the severe damage to the basement membrane observed in Arthus and antibasement membrane reactions. It is concluded that the full expression of these immunologic lesions requires destruction of the basement membrane possibly brought about by cathepsins D and E. Some of the physicochemical properties of these pathologically active leukocytic factors are given.
Distinctive clinical phenotype and treatment outcome of type 1 autoimmune hepatitis in the elderly
Authors: Albert J. Czaja, Herschel A. Carpenter
Journal: Hepatology (2006)

Autoimmune hepatitis is classically a disease of young women. Our aims were to determine its occurrence, clinical phenotype, and outcome in elderly patients and contrast findings to young adults. Two-hundred-and-five white North American adults with definite type 1 autoimmune hepatitis were grouped according to age at presentation and the groups compared. Forty-seven patients (23%) were aged > or = 60 years (median age, 68 years), and 31 patients (15%) were aged < or = 30 years (median age, 25 years). The patients > or = 60 years had a higher frequency of cirrhosis at presentation than the patients < or = 30 years (33% versus 10%, P = .03). They also had thyroid or rheumatic diseases more commonly (42% vs. 13%, P = .006). HLA DR3 occurred more frequently in the patients < or = 30 years than in those > or = 60 years (58% vs. 23%, P = .004), and HLA DR4 occurred more often in the patients > or = 60 years (47% vs. 13%, P = .003). Patients aged > or = 60 years failed corticosteroid treatment less commonly than those aged < or = 30 years (5% vs. 24%, P = .03). Autoimmune hepatitis occurred in patients aged 18-30 years (15%), 31-39 years (15%), 40-49 years (21%), 50-59 years (25%), and > or = 60 years (23%). Differences in age distribution, HLA frequencies, and treatment outcome occurred after age > or = 40 years. In conclusion, elderly patients have a greater frequency of cirrhosis at presentation and HLA DR4 than patients < or = 30 years, and they have a lower occurrence of treatment failure. Transitions in clinical and genetic phenotypes occur after age > or = 40 years. Genetic susceptibilities may favor etiologic factors that are age-related.
Quantity and location of stone compounds, not the mere presence in small amounts within the stone fabric, are important factors for the correct classification of gallstones and a better knowledge of their pathogenesis
Authors: F Cetta, F Lombardo, M Giubbolini, C Baldi, A Cariati
Journal: Hepatology (1996)

Familial Prevalence of Gallstones in First-Degree Relatives of Patients With Gallstones patients should always be screened for gallstone occur-To the Editor: rence.''Why?The most likely consequence is that their asymptomatic gallstones will be removed, exposing We write in response to the recent article by Shiv et them to immediate postsurgical complications, late al., ''High Familial Prevalence of Gallstones in the postcholecystectomy diarrhea, or gastroduodenal re-First-Degree Relatives of Gallstone Patients.'' 1 Flaws flux.The authors themselves state that of the ''eleven in the study design may have easily biased the results, of . . .51 (21.6%) relatives'' who ''had symptoms of leading to costly recommendations without adequate upper abdominal discomfort and dyspepsia . . .these evidence.symptoms were not characteristic of gallstone disease.''With regard to study design, a high degree of selec-We find the endorsement of expensive and possibly deltion bias was present from the outset.For example, eterious recommendations frightening, especially only subjects with gallstones who had two living firstwhen based on the results of a single study.degree relatives willing to participate in the study were To be clear, we are not dismissing the possibility that included.It is easy to conceive that subjects whose famcertain families are at higher risk for the development of ily members did not welcome a familial trend toward cholelithiasis.However, this study, because of design ercholelithiasis had negative personal interests in the rors, cannot be relied upon to provide the correct answer.project and would be less likely to enroll (or vice versa).In addition, which first-degree family members partici-YVONNE ROMERO, M.D. pated was also a nonrandom, self-selection process.Gastroenterology Fellow Overall, the study design favors enrollment of family members with gastrointestinal symptoms or those SIDNEY F. PHILLIPS, M.D. members who were curious to their gallstone status.Professor of Medicine The control group was selected specifically for ''not Gastroenterology Research Unit having any family history of gallstones or any systemic Mayo Clinic disease known to predispose to gallstone formation.''Rochester, MN With the intentional exclusion of control families who REFERENCE may have had a trend toward cholelithiasis, is it really
Comment on: Boronat et al. Differences in Cardiovascular Risk Profile of Diabetic Subjects Discordantly Classified by Diagnostic Criteria Based on Glycated Hemoglobin and Oral Glucose Tolerance Test. Diabetes Care 2010;33:2671–2673
Authors: Caroline K. Kramer, Maria Rosario Araneta
Journal: Diabetes Care (2011)

We read with interest the article by Boronat et al. (1). In that article, individuals with discordant diabetes status by A1C and oral glucose tolerance test (OGTT) had their cardiovascular risk profile evaluated. Those who fulfilled the A1C-based criterion presented greater measures of BMI and waist circumference and lower values for HDL cholesterol than individuals with diabetic OGTT but A1C <6.5% (1). Both elevated A1C (2) and diabetes by OGTT (3) are associated with risks of cardiovascular disease and death compared with fasting glucose in observational studies. To further evaluate the findings by Boronat et al., we analyzed the risk profile of 693 participants (mean age 71.6 years; 39.5% men) from the Rancho Bernardo cohort who were categorized discordantly by …
The cell cycle regulator CDC25A is a target for JAK2V617F oncogene
Authors: Emilie-Fleur Gautier, Muriel Picard, Camille Laurent, Caroline Marty, Jean-Luc Villeval, Cécile Demur, François Delhommeau, Elizabeth Hexner, Stéphane Giraudier, Nicolas Bonnevialle, Bernard Ducommun, Christian Récher, Guy Laurent, Stéphane Manenti, Véronique Mansat-De Mas
Journal: Blood (2011)
Critical issues in air pollution epidemiology.
Authors: M Lippmann, P J Lioy
Journal: Environmental Health Perspectives (1985)

The epidemiological studies which have had significant impact on the setting of National Ambient Air Quality Standards (NAAQSs) were performed more than twenty years ago. Most of the more recent studies have been seriously flawed in their design and/or execution because they neglected to account for important variables such as: pollutant exposures other than those from ambient air; the influence of personal activity on pollutant uptake; host responsiveness; and the separate contributions of recent transient peak exposures and long-term chronic exposures on the effects endpoints. For particulate pollutants, the influence of composition and size distribution has also received too little consideration. In order to address these deficiencies, research and methods development are needed on: indices for particulate exposures; identification of exposures relevant to the effects; improved indices of effects; acquisition of response data; identification of exposed populations; and identification of susceptible subgroups. Approaches to these needs are discussed, along with brief reviews of several recent studies that have focused on critical issues of concern, made the necessary efforts to characterize the relevant exposures of the populations being studied, and demonstrated human responses to ambient pollutants at current exposure levels.
The columnar lined oesophagus: a riddle wrapped in a mystery inside an enigma
Authors: STUART JON SPECHLER
Journal: Gut (1997)

See article on page585 

Just a few years ago, the definition and pathogenesis of Barrett’s oesophagus seemed straightforward. Barrett’s oesophagus was the condition in which metaplastic columnar epithelium replaced oesophageal squamous mucosa that had been damaged by exposure to refluxed gastric juice. The condition was sought primarily in patients with gastro-oesophageal reflux disease (GORD), and was identified when endoscopic examination revealed long segments of columnar epithelium extending well up the oesophagus. Biopsy specimens taken from the oesophageal columnar lining usually showed a peculiar form of intestinal metaplasia called specialised columnar epithelium or specialised intestinal metaplasia. In patients who developed adenocarcinomas in Barrett’s oesophagus, the columnar epithelium surrounding the oesophageal tumour invariably contained specialised intestinal metaplasia that often exhibited dysplastic changes. Eventually, Barrett’s oesophagus with specialised intestinal metaplasia became recognised as the major risk factor for adenocarcinoma of the oesophagus and oesophagogastric junction.1 

Over the past two decades, the incidence of adenocarcinoma of the oesophagus and oesophagogastric junction has been rising dramatically in the United …
Immunological regulation of synaptic transmission in isolated guinea pig autonomic ganglia.
Authors: D Weinreich, B J Undem
Journal: Journal of Clinical Investigation (1987)

We have attempted to identify a role for mast cells in autonomic ganglia by examining the effects of antigen challenge on mast cell-associated mediator release and synaptic transmission through the superior cervical ganglion isolated from ovalbumin-sensitized guinea pigs. Ovalbumin induced the release of 7.9 ng of histamine, 40 pg of immunoreactive sulfidopeptide-leukotriene, and 140 pg of immunoreactive-PgD2 per ganglion. Ovalbumin produced long-lasting potentiation (51 +/- 4%, mean +/- SEM, n = 66) of synaptic transmission, the protracted nature of which could not be mimicked by exogenous histamine (10(-5) M). Selective histamine H1 antagonists inhibited the antigen-induced potentiation, but did not reverse it when added any time after antigen exposure. These results indicate that immunologic activation of mast cells can directly potentiate neurotransmission in sympathetic ganglia. Histamine appears to be a mediator involved in the induction of antigen-induced potentiation of synaptic transmission, but alone cannot account for the long term nature of this phenomenon.
Moses Judah Folkman
Authors: Jeanne Lenzer
Journal: BMJ (2008)

Judah Folkman spent his life in dogged pursuit of a cure for cancer. For most of his career he was ridiculed and called a charlatan. But his discoveries were eventually hailed world wide and launched a new field of study: angiogenesis. Over 1000 laboratories are now studying angiogenesis, and more than 1.2m patients are taking antiangiogenic drugs for cancer and other diseases.

The son of a rabbi and a social worker, Folkman’s interest in medicine was sparked as a young boy when his father took him on visits to his congregants who were in hospital. Folkman told his father that he too wanted to help patients but he wanted to do it as a doctor. He entered Harvard Medical School at the age of 19.

Folkman’s first discoveries came early in his career. In 1961 he was drafted into military service aboard a naval vessel. He was given the task of finding out whether blood could be dried and reconstituted. To test the experimental blood, Folkman bathed a cultured rabbit thyroid in the blood. The gland thrived. But Folkman went one step further, he wanted to see if the blood could support new growth, so he injected the thyroid with cancer cells, the fastest growing cells he could think of. What he observed would fascinate and drive him for the rest of his career: the cancer cells grew into tiny tumours, but they all stopped growing at about 1 mm in size, something that doesn’t happen normally in living …
Dual role of tumor necrosis factor-? in hepatic ischemia-reperfusion injury: Studies in tumor necrosis factor-? gene knockout mice
Authors: Narci Teoh, Jacqueline Field, Jaim Sutton, Geoffrey Farrell
Journal: Hepatology (2004)

Although hepatic ischemia-reperfusion (IR) injury is partially mediated by tumor necrosis factor-α (TNF), we recently found that low-dose TNF before IR is hepatoprotective. We examined the seemingly conflicting roles of TNF in mediating liver injury in a partial hepatic IR model using TNF gene knockout (TNF ko) mice to allow TNF replacement at specified times. Compared with wild-type mice, TNF ko mice exhibit minimal alanine aminotransferase release and few hepatonecrotic lesions during the early (time, 2 hours) and late (time, 24 hours) phases of IR. TNF ko mice differed from wild-type mice in that TNF ko mice exhibited no activation or induction of nuclear factor-κ B, p38, cyclin D1, or proliferating cell nuclear antigen after IR. A single low-dose TNF injection 1 minute before the onset of hepatic ischemia restored hepatic IR injury in TNF ko mice. To clarify the importance of TNF for hepatoprotection, preconditioning (10 minutes of ischemia and 10 minutes of reperfusion) was performed before the onset of IR for TNF ko mice whose capacity to undergo IR injury had been restored by TNF replacement. Ischemic preconditioning failed to protect these mice from TNF-augmented IR injury; however, following the administration of intravenous TNF (1 μg per kg body weight, which mimics the early increase in hepatic and plasma TNF levels that is mobilized by ischemic preconditioning), significant hepatoprotection against both the early and late phases of TNF-augmented IR injury was observed. In conclusion, TNF appears to mediate both the early and late phases of liver injury in hepatic IR, but it also is an essential mediator of hepatoprotective effects brought about by ischemic preconditioning. (HEPATOLOGY 2004;39:412–421.)
The Mood-Elevating Effects of Sleep Deprivation in Depression-Reply
Authors: Thomas A. Wehr
Journal: JAMA (1992)

In Reply.  —In depressed patients, it is clear that sleep deprivation alters both their physiological and psychological states. Biological models assume that changes in the former mediate effects of sleep deprivation on the latter. Dr Germine makes a parallel assumption when he talks about medication playing the role of preventing resurfacing of painful affects. Psychodynamic constructs, like those proposed by Germine, are intuitively easier to link to the subjective changes experienced by depressed patients after sleep deprivation, but they are not easily accessible to experimental testing.  Biological mechanisms are more accessible, and for this reason, they have been the principal focus of experimental investigation in recent years. This is why I emphasized the biological component of the sleep deprivation response in my brief and selective review.  Some biological explanations, such as increased triiodothyronine secretion and rapid eye movement sleep deprivation, seem cogent, because they link sleep deprivation with other established
Chronic metabolic acidosis enhances NHE-3 protein abundance and transport activity in the rat thick ascending limb by increasing NHE-3 mRNA.
Authors: K Laghmani, P Borensztein, P Ambühl, M Froissart, M Bichara, O W Moe, R J Alpern, M Paillard
Journal: Journal of Clinical Investigation (1997)

Chronic metabolic acidosis (CMA) is associated with an adaptive increase in the bicarbonate absorptive capacity of the rat medullary thick ascending limb (MTAL). To specify whether NHE-3, the apical MTAL Na/H exchanger, is involved in this adaptation, NHE-3 mRNA was quantified by a competitive RT-PCR using an internal standard which differed from the wild-type NHE-3 mRNA by an 80-bp deletion. CMA increased NHE-3 mRNA from 0.025+/-0.003 to 0.042+/-0.009 amol/ng total RNA (P < 0.005). NHE-3 transport activity was measured as the initial proton flux rate calculated from the Na-dependent cell pH recovery of Na-depleted acidified MTAL cells in the presence of 50 microM HOE694 which specifically blocks NHE-1, the basolateral MTAL NHE isoform. CMA caused a 68% increase in NHE-3 transport activity (P < 0.001). In addition, CMA was associated with a 71% increase in NHE-3 protein abundance (P < 0.05) as determined by Western blot analysis on MTAL membranes using a polyclonal antiserum directed against a cytoplasmic epitope of rat NHE-3. Thus, NHE-3 adapts to CMA in the rat MTAL via an increase in the mRNA transcript that enhances NHE-3 protein abundance and transport activity.
Annual health check of NHS trusts in England shows room for improvement
Authors: S. Mayor
Journal: BMJ (2008)

More NHS trusts in England are fully meeting the core standards set for their performance, but one in three are still failing in some areas, particularly infection control, according to the latest annual health check by the Healthcare Commission.

Overall, the annual assessment of English NHS trusts against the government’s 24 core standards, including safety and cleanliness, infection control, and dignity, showed that only 64% (251/391) had fully met these standards in 2007-8. This represented a 9% rise compared with the previous year. 

However, one in four trusts (114) failed to meet one or more of the three core standards that relate to infection control, representing a small rise from the previous year. And only 52% of acute trusts met the target to reduce rates of meticillin resistant Staphylococcus aureus (MRSA) by at least 60% over three years.

Mental health trusts showed particular improvement in meeting core standards, with 80% fully meeting them, a 13% rise compared …
Minimum price for alcohol is proposed for England and Wales
Authors: N. Hawkes
Journal: BMJ (2012)

The government has announced a consultation on setting a minimum price for alcohol of 45p (€0.55; $0.72) a unit, a move welcomed by the BMA and other members of the Alcohol Health Alliance. 

The figure chosen is more than the 40p backed by the prime minister earlier this year but less than the 50p a unit proposed in Scotland, and the proposal could yet be blocked by the European Union, which says that setting minimum prices is disproportionate and in breach of EU rules.

The consultation, launched today by the home secretary, Theresa May, aims to outlaw sales of cut price alcohol by supermarkets, which is blamed for encouraging binge drinking. The effect of a 45p minimum price would be felt most strongly among “own brand” spirits, which can sell for less than £10 for a 0.7 L bottle. This would increase to almost £12. The cheapest 0.75 L bottle of wine with alcohol content of 13% would be around £4.40. Cheap ciders would see big price rises.

Campaigners believe that raising the prices would cut consumption and reduce the harms caused by alcohol misuse, including crime and damage to health. The Alcohol Health Alliance welcomed the decision to launch the consultation, saying that it backed a 50p minimum price, as it would prevent more than 3000 alcohol related deaths and 40 000 crimes in England each year.

The consultation also suggests banning multibuy offers, proposes a …
EFFECT OF PROTON PUMP INHIBITORS ON OUTCOME OF PATIENTS DISCHARGED ON DUAL ANTIPLATELET THERAPY AFTER PERCUTANEOUS CORONARY INTERVENTION AND STENT IMPLANTATION
Authors: Ioannis Tentzeris, Rudolf Jarai, Serdar Farhan, Ivan Brosovic, Peter Smetana, Alexander Geppert, Jolanta Siller-Matula, Kurt Huber
Journal: Journal of the American College of Cardiology (2010)