tbuckley/cabot-search huggingface dataset:
The Meaning of Translational Research and Why It Matters
Authors: Steven H. Woolf
Journal: JAMA (2008)

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
Inactivation of Kupffer cells prevents early alcohol-induced liver injury
Authors: Yukito Adachi, Blair U. Bradford, Wenshi Gao, Heidi K. Bojes, Ronald G. Thurman
Journal: Hepatology (1994)

It is well recognized that consumption of alcohol leads to liver disease in a dose-dependent manner; however, the exact mechanisms remain unclear. Hypoxia subsequent to a hypermetabolic state may be involved; therefore, when it was observed recently that inactivation of Kupffer cells prevented stimulation of hepatic oxygen uptake by alcohol, the idea that Kupffer cells participate in early events that ultimately lead to alcohol-induced liver disease became a real possibility. The purpose of this study was to test that hypothesis. Male Wistar rats were exposed to ethanol continuously by means of intragastric feeding for up to 4 weeks using the model developed by Tsukamoto and French. In this model, ethanol causes fatty liver, necrosis and inflammation--changes characteristic of alcohol-induced liver disease in human beings. Kupffer cells were inactivated by twice weekly treatment with gadolinium chloride (GdCl3), a selective Kupffer cell toxicant. AST levels were elevated to 192 +/- 13 and 244 +/- 56 IU/L in rats exposed to ethanol for 2 and 4 wk, respectively (control value, 88 +/- 7). This injury was prevented almost completely by GdCl3 treatment. Fatty changes, inflammation and necrosis were also all reduced dramatically by GdCl3 treatment. The average hepatic pathological score of rats treated with ethanol for 4 wk was 4.3 +/- 0.6, which was reduced significantly in ethanol- and GdCl3-treated rats to 1.8 +/- 0.5 (p < 0.05). Rates of ethanol elimination were elevated 2- to 3-fold in rats exposed to ethanol for 2 to 4 wk. This elevation was blocked by GdCl3 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacokinetics of contraceptive steroids in patients with cystic fibrosis.
Authors: R J Stead, S F Grimmer, S M Rogers, D J Back, M L Orme, M E Hodson, J C Batten
Journal: Thorax (1987)

The pharmacokinetics of the commonly used contraceptive steroids ethinyloestradiol and levonorgestrel were investigated after oral and intravenous administration in six women with cystic fibrosis. The results were compared with data obtained from healthy women of similar age. The total body clearance of ethinyloestradiol was significantly higher in the patients with cystic fibrosis (0.61 (SD 0.19) l/h/kg) than in control women (0.32 (0.16) l/h/kg; p less than 0.02). In addition, the oral bioavailability of ethinyloestradiol was greater in women with cystic fibrosis than in controls (76.9% (11.7%) compared with 47.3% (7.5%); p less than 0.001). As a result of these two changes, the area under the plasma concentration--time curve after an oral dose of ethinyloestradiol was similar in patients and controls. The pharmacokinetics of levonorgestrel did not differ significantly between patients with cystic fibrosis and healthy women. The data suggest that women with cystic fibrosis will receive similar contraceptive protection from these steroids as do healthy women.
Unifying Screening Processes Within the PROSPR Consortium: A Conceptual Model for Breast, Cervical, and Colorectal Cancer Screening
Authors: E. F. Beaber, J. J. Kim, M. M. Schapira, A. N. A. Tosteson, A. G. Zauber, A. M. Geiger, A. Kamineni, D. L. Weaver, J. A. Tiro
Journal: JNCI Journal of the National Cancer Institute (2015)

General frameworks of the cancer screening process are available, but none directly compare the process in detail across different organ sites. This limits the ability of medical and public health professionals to develop and evaluate coordinated screening programs that apply resources and population management strategies available for one cancer site to other sites. We present a trans-organ conceptual model that incorporates a single screening episode for breast, cervical, and colorectal cancers into a unified framework based on clinical guidelines and protocols; the model concepts could be expanded to other organ sites. The model covers four types of care in the screening process: risk assessment, detection, diagnosis, and treatment. Interfaces between different provider teams (eg, primary care and specialty care), including communication and transfer of responsibility, may occur when transitioning between types of care. Our model highlights across each organ site similarities and differences in steps, interfaces, and transitions in the screening process and documents the conclusion of a screening episode. This model was developed within the National Cancer Institute–funded consortium Population-based Research Optimizing Screening through Personalized Regimens (PROSPR). PROSPR aims to optimize the screening process for breast, cervical, and colorectal cancer and includes seven research centers and a statistical coordinating center. Given current health care reform initiatives in the United States, this conceptual model can facilitate the development of comprehensive quality metrics for cancer screening and promote trans-organ comparative cancer screening research. PROSPR findings will support the design of interventions that improve screening outcomes across multiple cancer sites.
Genistein supplementation and estrogen replacement therapy improve endothelial dysfunction induced by ovariectomy in rats
Authors: F Squadrito
Journal: Cardiovascular Research (2000)

Background: We investigated the effect of genistein, a phytoestrogen derived from a soy diet with a flavonoid chemical structure, on endothelial dysfunction induced by estrogen deficiency in rats. Methods: Female mature Sprague–Dawley rats were subjected to a bilateral ovariectomy (OVX rats). Sham-operated animals (Sham OVX rats) were used as controls. Three weeks after surgery animals were randomized to the following treatments: genistein (0.2 mg/kg/day, s.c. for 4 weeks), 17β-estradiol (20 μg/kg/day, s.c. for 4 weeks) or their respective vehicles. Mean arterial blood pressure (MAP), heart rate (HR), total plasma cholesterol, plasma estradiol, plasma genistein levels and uterine weights were studied. Furthermore, we investigated acetylcholine (ACh 10 nM–10 μM) and sodium nitroprusside: (SN 15–30 nM) induced relaxation of aortic rings as well as NG-l-arginine (L-NMA: 10–100 μM) induced vasoconstriction in phenylephrine precontracted aortic segments and calcium-dependent nitric oxide synthase (cNOS) activity in homogenates of lungs taken from both sham OVX and OVX rats. Results: Untreated OVX rats had, compared with sham OVX animals, unchanged body weight, MAP, HR and plasma cholesterol. In contrast ovariectomy impaired endothelial responses, blunted L-NMA induced contraction (L-NMA 100 μM: Sham OVX=2.1±0.2 g/mg tissue; OVX=1.7±0.4 g/mg tissue) and reduced cNOS activity. Treatment with 17β-estradiol increased the hormone plasma levels, reverted the endothelial dysfunction and increased cNOS activity in lung homogenates. Genistein supplementation enhanced the circulating levels of the phytoestrogen and affected NOS activity and endothelial dysfunction to the same extent. Conclusions: Our data suggest that genistein and 17β-estradiol show overlapping effects on experimental endothelial dysfunction.
Association Between Helicopter vs Ground Emergency Medical Services and Survival for Adults With Major Trauma
Authors: Samuel M. Galvagno, Elliott R. Haut, S. Nabeel Zafar, Michael G. Millin, David T. Efron, George J. Koenig, Susan P. Baker, Stephen M. Bowman, Peter J. Pronovost, Adil H. Haider
Journal: JAMA (2012)

Helicopter emergency medical services and their possible effect on outcomes for traumatically injured patients remain a subject of debate. Because helicopter services are a limited and expensive resource, a methodologically rigorous investigation of its effectiveness compared with ground emergency medical services is warranted.
INFLUENZA-LIKE BACILLI ISOLATED FROM CATS
Authors: T. M. Rivers, Stanhope Bayne-Jones
Journal: The Journal of Experimental Medicine (1923)

Six strains of Gram-negative non-motile bacilli from cats have been described. They do not grow on ordinary media. They do grow, however, on a medium to which an autoclave-labile substance alone has been added as an accessory growth factor. These bacilli are similar to Bacillus parainfluenzaaeisolated from man. One strain of a Gram-negative non-motile bacillus more exacting than Bacillus influenzae in its food requirements was found and for convenience has been placed for the present in the parainfluenza group.
A mouse model of acute biliary pancreatitis induced by retrograde pancreatic duct infusion of Na-taurocholate
Authors: J. M Laukkarinen, G. J D Van Acker, E. R Weiss, M. L Steer, G. Perides
Journal: Gut (2007)

Most mechanistic studies of pancreatitis in mice employ the secretagogue-induced model. The currently reported studies were designed to develop an alternative, and possibly more clinically relevant, mouse model of pancreatitis.Na-taurocholate (10-50 microl, 1-5%) in saline, or saline alone, was retrogradely infused into the mouse pancreatic duct. The animals were killed 6-24 hours later and the severity of pancreatitis in the pancreatic head and tail was examined by quantitating hyperamylasemia, pancreatic edema, acinar cell necrosis, and pancreatic inflammation. In addition, intrapancreatic activation of trypsinogen, generation of IL-6, intrapulmonary sequestration of neutrophils, and alterations in lung compliance were evaluated. The effects of Na-taurocholate on in-vitro acinar cell calcium transients, viability, and trypsinogen activation were examined.Little or no evidence of pancreatitis was observed in mice infused with saline alone or in the tail of pancreata removed from animals infused with Na-taurocholate. In the head of the pancreas, evidence of pancreatitis was observed 12-24 hours after infusion of 20-50 microl 2-5% Na-taurocholate and the earliest morphological changes involved terminal duct and acinar cells. Intrapancreatic trypsin activity was transiently elevated within 5 minutes of Na-taurocholate infusion and pancreatic IL-6 levels were elevated 24 hours later. Under in-vitro conditions, Na-taurocholate triggered pathological acinar cell calcium transients, cell death, and calcium-dependent trypsinogen activation.This clinically relevant model of acute biliary pancreatitis yields reproducible results and its severity can be easily manipulated. It is ideally suited for use in mechanistic studies employing genetically modified mouse strains.
Ribosomal DNA variation within and between species of rodents, with emphasis on the genus Onychomys.
Authors: M W Allard, R L Honeycutt
Journal: Molecular Biology and Evolution (1991)

Patterns of restriction-endonuclease site and length variation at the nuclear rDNA locus (18S + 28S rRNA gene complex) were examined in rodents. Of the 164 restriction sites mapped for seven species, 22 were conserved (mapping to the 18S, 28S, and 5.8S genes and ITS1) in all three Onychomys species as well as in Mus musculus and in three closely related peromyscine rodents, Peromyscus boylii, P. eremicus, and Reithrodontomys megalotis. The nontranscribed spacer (NTS) region revealed most of the variation among these taxa, with the patterns of variation grouping into the following categories, (1) intraindividual variation revealing as many as four site-specific repeat types within an individual, (2) intraspecific and interspecific site variation confined to the NTS, and (3) length variation in both the transcribed and NTS regions. Length variation in the 28S rRNA gene was also examined in 17 additional rodent species, and most size differences mapped to the divergent domain, D8, found in sequence comparisons between Mus and Rattus. The systematic implications of rDNA variation are discussed using the perspective gained from these rodent comparisons.
Job losses are likely as NHS staff reject offer of national pay freeze
Authors: A. O'Dowd
Journal: BMJ (2011)

NHS staff unions have rejected a pay offer from the body that negotiates pay and conditions for the government. The offer would have guaranteed jobs in return for a two year freeze on annual pay increments.

In December NHS Employers wrote to trade unions on the NHS Staff Council proposing that NHS organisations freeze annual incremental pay progression for all groups of staff in England in return for a guarantee of no compulsory redundancies for staff earning up to £34 200 (€40 650; $54 300)—around 80% of the NHS workforce.

This freeze would be irrespective of the fact that all public sector workers earning more than £21 000 a year …
Regulation of human gut B lymphocytes by T lymphocytes.
Authors: R Clancy, A Cripps, H Chipchase
Journal: Gut (1984)

The aims of this study were first, to assess whether or not immunoglobulin secretion from human gut mucosal B lymphocytes can be modified by T lymphocytes, and second whether human gut mucosal T lymphocytes are capable of regulating mucosal B lymphocyte function. T and B lymphocyte enriched cell populations were isolated from gut mucosa and co-cultured in varying proportions. Addition of T lymphocytes to B enriched mucosal cell populations (ratio B:T = 2:1) showed that mucosal B lymphocytes were responsive to T cell 9help9. Addition of more T cells (ratio B:T = 2:10) suppressed immunoglobulin synthesis.
Treatment of Patients with Advanced Gastric Cancer -Single Center Experience from Tata Memorial Center (Tmc)
Authors: Sirohi Bhawna, Dawood Shaheenah, Ostwal Vikas, Talole Sanjay, Ramadwar Mukta, Shetty Nitin, Goel Mahesh, Shrikhande Shailesh
Journal: Annals of Oncology (2014)
Effect of digitalis glycosides on norepinephrine release in the heart. Dual mechanism of action.
Authors: R Kranzhöfer, M Haass, T Kurz, G Richardt, A Schömig
Journal: Circulation Research (1991)

The effect of ouabain on exocytotic and nonexocytotic norepinephrine release was investigated in perfused rat and guinea pig hearts. The overflow of endogenous norepinephrine and its neuronal metabolite 3,4-dihydroxyphenylethyleneglycol (DOPEG) was determined by high-pressure liquid chromatography. DOPEG served as the indicator of free axoplasmic norepinephrine concentrations. The overflow of the norepinephrine cotransmitter neuropeptide Y (NPY) was determined by radioimmunoassay and NPY was used as marker for exocytotic release. Electrical stimulation of the left stellate ganglion resulted in exocytotic norepinephrine release in rat and guinea pig hearts. Ouabain caused an increase in stimulation-induced norepinephrine overflow from rat and guinea pig hearts by 40%. However, overflow of NPY was decreased by 40%, indicating a reduced exocytosis rate. Ouabain increased both norepinephrine and NPY overflow, suggesting enhancement of exocytosis, when neuronal catecholamine uptake (uptake1) was blocked by desipramine or when presynaptic alpha 2-adrenoceptors were inhibited by yohimbine. The results demonstrate an interaction of ouabain with both calcium-dependent exocytosis and uptake1 of norepinephrine. Under calcium-free conditions, ouabain or potassium-free perfusate resulted in norepinephrine release from hearts when the axoplasmic norepinephrine concentration was elevated by the reserpinelike agent Ro 4-1284. This release was independent from neural activity, not accompanied by NPY overflow, and suppressed by the uptake1 blocker desipramine. These findings are in keeping with carrier-mediated nonexocytotic norepinephrine release that is caused by reversal of the transport direction of the uptake1 carrier. During myocardial ischemia nonexocytotic norepinephrine release was accelerated and enhanced by inhibition of Na+,K(+)-ATPase before ischemia. This study demonstrates the potential of digitalis glycosides to interact both with transmitter exocytosis and with the neuronal catecholamine transport system by Na+,K(+)-ATPase inhibition. Interaction with the catecholamine transport system involves both inhibition of norepinephrine inward transport and induction of norepinephrine outward transport, resulting in nonexocytotic norepinephrine release.
The Association of Aspirin Use With Age-Related Macular Degeneration
Authors: Gerald Liew, Paul Mitchell, Tien Yin Wong, Elena Rochtchina, Jie Jin Wang
Journal: JAMA Internal Medicine (2013)

<h3>Objective</h3>To determine whether regular aspirin use is associated with a higher risk for developing age-related macular degeneration (AMD) by using analyzed data from a 15-year prospective cohort.<h3>Methods</h3>A prospective analysis was conducted of data from an Australian population-based cohort with 4 examinations during a 15-year period (1992-1994 to 2007-2009). Participants completed a detailed questionnaire at baseline assessing aspirin use, cardiovascular disease status, and AMD risk factors. Age-related macular degeneration was graded side-by-side from retinal photographs taken at each study visit to assess the incidence of neovascular (wet) AMD and geographic atrophy (dry AMD) according to the international AMD classification.<h3>Results</h3>Of 2389 baseline participants with follow-up data available, 257 individuals (10.8%) were regular aspirin users and 63 of the 2389 developed neovascular AMD. Persons who were regular aspirin users were more likely to have incident neovascular AMD: the 15-year cumulative incidence was 9.3% in users and 3.7% in nonusers. After adjustment for age, sex, smoking, history of cardiovascular disease, systolic blood pressure, and body mass index, persons who were regular aspirin users had a higher risk of developing neovascular AMD (odds ratio [OR], 2.46; 95% CI, 1.25-4.83). The association showed a dose-response effect (multivariate-adjusted P = .01 for trend). Aspirin use was not associated with the incidence of geographic atrophy (multivariate-adjusted OR, 0.99; 95% CI, 0.59-1.65).<h3>Conclusion</h3>Regular aspirin use is associated with increased risk of incident neovascular AMD, independent of a history of cardiovascular disease and smoking.
Disparities in Adverse Childhood Experiences Among Individuals With a History of Military Service
Authors: John R. Blosnich, Melissa E. Dichter, Catherine Cerulli, Sonja V. Batten, Robert M. Bossarte
Journal: JAMA Psychiatry (2014)

Adverse childhood experiences (ACEs) are associated with several adulthood health problems, such as self-directed violence. For some individuals, enlistment in the military may be an instrumental act to escape adverse household environments; however, to our knowledge prevalence of ACEs among persons with a history of military service has not been documented in the United States using population-based data.To compare the prevalence of ACEs among individuals with and without a history of military service.Data are from the 2010 Behavioral Risk Factor Surveillance System. Computer-assisted telephone interviews were conducted with population-based samples of noninstitutionalized US adults from January 1 through December 31, 2010. Analyses were limited to respondents who received the ACE module (n = 60,598). Participants were categorized by history of military service and whether a respondent was 18 years of age in 1973.History of military service was defined by active duty service, veteran status, or training for the Reserves or National Guard. The ACE inventory assessed 11 negative experiences before the age of 18 years. Weighted χ2 tests and multiple logistic regression analyses were used to examine differences in ACEs by history of military service, era of service, and sex.Those with military experience had greater odds of any difference in prevalence of ACEs. In the all-volunteer era, men with military service had a higher prevalence of ACEs in all 11 categories than men without military service. Notably, in the all-volunteer era, men with military service had twice the odds of reporting forced sex before the age of 18 years (odds ratio, 2.19; 95% CI, 1.34-3.57) compared with men without military service. In the draft era, the only difference among men was household drug use, in which men with a history of military service had a significantly lower prevalence than men without a history of military service (2.1% vs. 3.3%; P = .003). Fewer differences were observed among women in the all-volunteer and draft eras.Differences in ACEs by era and sex lend preliminary support that enlistment may serve as an escape from adversity for some individuals, at least among men. Further research is needed to understand how best to support service members and veterans who may have experienced ACEs.
Risk of primary intracerebral haemorrhage associated with aspirin and non-steroidal anti-inflammatory drugs: case-control study
Authors: A. G Thrift, J. J McNeil, A. Forbes, G. A Donnan
Journal: BMJ (1999)

To examine the association between use of aspirin or other non-steroidal anti-inflammatory drugs and intracerebral haemorrhage.Case-control study.13 major city hospitals in the Melbourne and metropolitan area.331 consecutive cases of stroke verified by computed tomography or postmortem examination, and 331 age (+/- 5 years) and sex matched controls who were community based neighbours.Questionnaire administered to all subjects either directly or by proxy with the next of kin. Drug use was validated by reviewing prescribing records held by the participants' doctors.Previous use of aspirin or other non-steroidal anti-inflammatory drugs.Univariate analysis showed no increased risk of intracerebral haemorrhage with low dose aspirin use in the preceding 2 weeks. Using multiple logistic regression to control for possible confounding factors, the odds ratio associated with the use of aspirin was 1.00 (95% confidence interval 0.60 to 1. 66, P=0.998) and the odds ratio associated with the use of other non-steroidal anti-inflammatory drugs was 0.85 (0.45 to 1.61, P=0. 611) compared with respective non-users in the preceding fortnight. Moderate to high doses of aspirin (>1225 mg/week spread over at least three doses) yielded an odds ratio of 3.05 (1.02 to 9.14, P=0. 047). There was no evidence of an increased risk among subgroups defined by age, sex, blood pressure status, alcohol intake, smoking, and the presence or absence of previous cardiovascular disease.No increase in risk of intracerebral haemorrhage was found among aspirin users overall or among those who took low doses of the drug or other non-steroidal anti-inflammatory drugs. These data provide evidence that doses of aspirin usually used for prophylaxis against vascular disease produce no substantial increase in risk of intracerebral haemorrhage.