tbuckley/cabot-search huggingface dataset:
STAT3 is a critical cell-intrinsic regulator of human unconventional T cell numbers and function
Authors: Robert P. Wilson, Megan L. Ives, Geetha Rao, Anthony Lau, Kathryn Payne, Masao Kobayashi, Peter D. Arkwright, Jane Peake, Melanie Wong, Stephen Adelstein, Joanne M. Smart, Martyn A. French, David A. Fulcher, Capucine Picard, Jacinta Bustamante, Stephanie Boisson-Dupuis, Paul Gray, Polina Stepensky, Klaus Warnatz, Alexandra F. Freeman, Jamie Rossjohn, James McCluskey, Steven M. Holland, Jean-Laurent Casanova, Gulbu Uzel, Cindy S. Ma, Stuart G. Tangye, Elissa K. Deenick
Journal: The Journal of Experimental Medicine (2015)

Unconventional T cells such as γδ T cells, natural killer T cells (NKT cells) and mucosal-associated invariant T cells (MAIT cells) are a major component of the immune system; however, the cytokine signaling pathways that control their development and function in humans are unknown. Primary immunodeficiencies caused by single gene mutations provide a unique opportunity to investigate the role of specific molecules in regulating human lymphocyte development and function. We found that individuals with loss-of-function mutations in STAT3 had reduced numbers of peripheral blood MAIT and NKT but not γδ T cells. Analysis of STAT3 mosaic individuals revealed that this effect was cell intrinsic. Surprisingly, the residual STAT3-deficient MAIT cells expressed normal levels of the transcription factor RORγt. Despite this, they displayed a deficiency in secretion of IL-17A and IL-17F, but were able to secrete normal levels of cytokines such as IFNγ and TNF. The deficiency in MAIT and NKT cells in STAT3-deficient patients was mirrored by loss-of-function mutations in IL12RB1 and IL21R, respectively. Thus, these results reveal for the first time the essential role of STAT3 signaling downstream of IL-23R and IL-21R in controlling human MAIT and NKT cell numbers.
Spontaneous atrial fibrillation in a freestyle skier
Authors: G Whyte, N Stephens, S Sharma, R Shave, R Budgett, W J McKenna
Journal: British Journal of Sports Medicine (2004)

A male freestyle skier was found to have atrial fibrillation during a routine physiological assessment. This was found to be associated with the consumption of an unusually large amount of alcohol. Athletes should be counselled about the potential dangers of alcohol consumption before exhaustive exercise.
Presence of high-risk mucosal human papillomavirus genotypes in primary melanoma and in acquired dysplastic melanocytic naevi
Authors: M. La Placa, S. Ambretti, F. Bonvicini, S. Venturoli, T. Bianchi, C. Varotti, M. Zerbini, M. Musiani
Journal: British Journal of Dermatology (2005)

Some studies have shown that cutaneous and mucosal melanoma biopsy specimens harbour human papillomavirus (HPV), suggesting that this virus may play a role in development and progression of the tumour.To investigate the presence of HPV DNA and the prevalence of different high-risk mucosal HPV genotypes in primary melanoma (PM) and in acquired dysplastic melanocytic naevi (ADMN).Fifty-one PMs from 18 men and 33 women (median age 55.5 years), 33 ADMN from 15 men and 18 women (median age 35.1 years) and 20 control skin samples from nine men and 11 women (median age 43.5 years) were studied. All diagnoses were made after histological analysis. HPV DNA analysis was made using two different polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA) methods, namely MY-PCR and GP-PCR.Using GP-PCR, mucosal HPVs were detected in 14 PMs (27%; P = 0.0166) and eight ADMN (24%; P = 0.0367), while with MY-PCR, mucosal HPVs were found in 11 PMs (22%; P = 0.04) and five ADMN (15%; P not significant). All control skin samples were negative for mucosal HPVs with both DNA amplification procedures.Using our PCR-ELISA methods, the detection of mucosal high-risk HPV genotypes in 24% of precursor lesions (ADMN) and in 27% of PMs adds to the body of evidence indicating a colocalization of mucosal HPV and tumoral melanocytic pathologies.
Community Factors in the Development of Antibiotic Resistance
Authors: Elaine Larson
Journal: Annual Review of Public Health (2006)

The global impact of antibiotic resistance is potentially devastating, threatening to set back progress against certain infectious diseases to the pre-antibiotic era. Although most antibiotic-resistant bacteria originally emerged in hospitals, drug-resistant strains are becoming more common in the community. Factors that facilitate the development of resistance within the community can be categorized as behavioral or environmental/policy. Behavioral factors include inappropriate use of antibiotics and ineffective infection control and hygiene practices. Environmental/policy factors include the continued use of antibiotics in agriculture and the lack of new drug development. A multifaceted approach that includes behavioral strategies in the community and the political will to make difficult regulatory decisions will help to minimize the problem of antimicrobial resistance globally.
Adjuvant Chemotherapy in Older and Younger Women With Lymph Node–Positive Breast Cancer
Authors: Hyman B. Muss, Susan Woolf, Donald Berry, Constance Cirrincione, Raymond B. Weiss, Daniel Budman, William C. Wood, I. Craig Henderson, Clifford Hudis, Eric Winer, Harvey Cohen, Judith Wheeler, Larry Norton
Journal: JAMA (2005)

Adjuvant chemotherapy improves survival for patients with local-regional breast cancer, but healthy older patients at high risk of recurrence are frequently not offered adjuvant chemotherapy, and the benefit of adjuvant chemotherapy in older patients is uncertain.To compare the benefits and toxic effects of adjuvant chemotherapy among breast cancer patients in age groups of 50 years or younger, 51 to 64 years, and 65 years or older.Retrospective review of data from 4 randomized trials that accrued patients from academic and community medical centers between 1975 and 1999. Median follow-up for all patients was 9.6 years. All trials randomized patients to different regimens, doses, schedules, and durations of chemotherapy and all had a treatment arm with doses or schedules that were regarded to be "high" and potentially more toxic.A total of 6487 women with lymph node-positive breast cancer; 542 (8%) patients were 65 years or older and 159 (2%) were 70 years or older.Comparison of disease-free survival, overall survival, and treatment-related mortality among different age groups.Multivariate analysis showed that smaller tumor size, fewer positive lymph nodes, more chemotherapy, and tamoxifen use were all significantly (P<.001) related to longer disease-free and overall survival. There was no association between age and disease-free survival. Overall survival was significantly (P<.001) worse for patients aged 65 or older because of death from causes other than breast cancer. Thirty-three deaths (0.5% of all patients) were attributed to treatment, and older women had higher treatment-related mortality. Older women and younger women derived similar reductions in breast cancer mortality and recurrence from regimens containing more chemotherapy.Age alone should not be a contraindication to the use of optimal chemotherapy regimens in older women who are in good general health.
Understanding the Value of Continuity in the 21st Century
Authors: S. Ryan Greysen, Allan S. Detsky
Journal: JAMA Internal Medicine (2015)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Renal tubular transport of 3H-digoxin in saline diuresis in rats.
Authors: R J Roman, M L Kauker
Journal: Circulation Research (1976)

We evaluated urinary excretion and tubular transport of 3H-digoxin by three different methods in anesthetized rats made diuretic by infusion of 2.5% saline. In one group small volumes of 3H-digoxin and 14C-inulin were injected simultaneously into surface proximal convolutions, and urine was collected serially from both ureters. Digoxin recovery was lower after early (62.1 +/- 5.3%) than after late (86.9 +/- 7.7%) proximal administration but inulin recovery was complete (99.6 +/- 2.7%) after all injections. Most of the digoxin was excreted simultaneously with inulin. Delayed recovery was low. In another group of rats digoxin and inulin were applied directly to the capsule of the left kidney. Two-thirds of the recovered digoxin appeared from the left ureter and one-third from the right. The difference (41.9 +/- 7.4%) is an estimate of transtubular digoxin influx. Digoxin excretion preceded inulin only on the left. Digoxin to inulin concentration ratios were 6 times higher from the left than the right, whereas inulin recoveries from the two sides were similar. In a third group of rats tubular fluid was collected from surface convolutions of proximal and distal tubule. In the accessible segment of the proximal tubule 35.9% of the filtered digoxin was reabsorbed. In the more distal nephron, drug was added into the lumen; this resulted in a net urinary excretion of 80.2 +/- 18.2%. These findings are compatible with free filtration of digoxin at the glomerulus followed by passive proximal tubular reabsorption and an influx against a concentration gradient in the distal nephron.
A Mechanism of Sudden Death in Chlorpromazine Therapy
Authors: ROBERT CANCRO, RUSSELL WILDER
Journal: American Journal of Psychiatry (1970)

There has been an increasing number of sudden deaths in psychotic patients taking phenothiazines. The authors present a case report that they believe offers some insight into why such deaths occur. They feel that the combination of vasodilatation with the hypotensive effects of phenothiazines might explain some of the unexpected deaths.
Complete identification of endocrine cells in the gastrointestinal tract using semithin-thin sections to identify motilin cells in human and animal intestine.
Authors: J M Polak, A G Pearse, C M Heath
Journal: Gut (1975)

The present (Wiesbaden) classification of gut endocrine cells relies mainly on ultrastructure and the results of silver impregnation. Correlation with hormone production requires parallel immunology but conventional immune cytochemistry is, in most cases, difficult or at present impossible. The serial, semithin-thin-section technique offers an alternative, which provides absolute correlation between cell type and hormone production. The successful use of the technique is illustrated here by localization of motilin in the enterochromaffin cells of the small intestine.
Systemic delivery of siRNA to tumors using a lipid nanoparticle containing a tumor-specific cleavable PEG-lipid
Authors: Hiroto Hatakeyama, Hidetaka Akita, Erika Ito, Yasuhiro Hayashi, Motoi Oishi, Yukio Nagasaki, Radostin Danev, Kuniaki Nagayama, Noritada Kaji, Hiroshi Kikuchi, Yoshinobu Baba, Hideyoshi Harashima
Journal: Biomaterials (2011)
Krüppel-like factor 15 regulates BMPER in endothelial cells
Authors: Thomas Helbing, Franziska Volkmar, Ulrich Goebel, Jennifer Heinke, Philipp Diehl, Heike L. Pahl, Christoph Bode, Cam Patterson, Martin Moser
Journal: Cardiovascular Research (2009)

Bone morphogenetic proteins (BMPs) are involved in embryonic and adult blood vessel formation in health and disease. Previous studies have shown that BMP endothelial cell precursor-derived regulator (BMPER) plays an important role in endothelial cell function and blood vessel formation. BMPER is a key regulator of BMP4 activity and a prerequisite for BMP pathway activation by BMP4 in endothelial cells. Here, we characterize the BMPER promoter and elucidate mechanisms of BMPER regulation.To investigate transcriptional mechanisms of BMPER expression, the murine BMPER promoter was cloned and characterized. A series of 5' deletions of the BMPER promoter revealed that the proximal promoter contains activating cis-elements. By overexpression or siRNA-based knockdown, we demonstrate that BMPER expression is activated by Krüppel-like factor (KLF) 15. As determined by gelshift analyses, KLF15 binds directly to a predicted KLF-binding element at -284 bp within the BMPER promoter. Co-expression experiments show that Sp1 acts as an antagonist for KLF15-induced promoter activation. Endothelin-1 was identified as a potent inhibitor of KLF15 and BMPER expression in endothelial cells, suggesting that KLF15 is a transducer of endothelin-1 activity on BMPER expression. The selective ET(B) endothelin receptor antagonist BQ788 abolished the downregulation of BMPER expression by endothelin-1.Mechanistically, we found that KLF15 is a strong and direct activator of the BMPER expression. BMPER is downregulated by endothelin-1 in a dose-dependent fashion and in parallel to KLF15. As KLF15 deficiency is accompanied by a vascular phenotype and BMPER is necessary for proper blood vessel formation, we suggest a chain of events in which the effects of endothelin-1 on BMPER are mediated by KLF15.
Statins Activate Peroxisome Proliferator-Activated Receptor γ Through Extracellular Signal-Regulated Kinase 1/2 and p38 Mitogen-Activated Protein Kinase–Dependent Cyclooxygenase-2 Expression in Macrophages
Authors: Miyuki Yano, Takeshi Matsumura, Takafumi Senokuchi, Norio Ishii, Yusuke Murata, Kayo Taketa, Hiroyuki Motoshima, Tetsuya Taguchi, Kazuhiro Sonoda, Daisuke Kukidome, Yoh Takuwa, Teruo Kawada, Michael Brownlee, Takeshi Nishikawa, Eiichi Araki
Journal: Circulation Research (2007)

Both statins and peroxisome proliferator-activated receptor (PPAR)γ ligands have been reported to protect against the progression of atherosclerosis. In the present study, we investigated the effects of statins on PPARγ activation in macrophages. Statins increased PPARγ activity, which was inhibited by mevalonate, farnesylpyrophosphate, or geranylgeranylpyrophosphate. Furthermore, a farnesyl transferase inhibitor and a geranylgeranyl transferase inhibitor mimicked the effects of statins. Statins inhibited the membrane translocations of Ras, RhoA, Rac, and Cdc42, and overexpression of dominant-negative mutants of RhoA (DN-RhoA) and Cdc42 (DN-Cdc42), but not of Ras or Rac, increased PPARγ activity. Statins induced extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) activation. However, DN-RhoA and DN-Cdc42 activated p38 MAPK, but not ERK1/2. ERK1/2- or p38 MAPK–specific inhibitors abrogated statin-induced PPARγ activation. Statins induced cyclooxygenase (COX)-2 expression and increased intracellular 15-deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ 2 ) levels through ERK1/2- and p38 MAPK–dependent pathways, and inhibitors or small interfering RNA of COX-2 inhibited statin-induced PPARγ activation. Statins also activate PPARα via COX-2–dependent increases in 15d-PGJ 2 levels. We further demonstrated that statins inhibited lipopolysaccharide-induced tumor necrosis factor α or monocyte chemoattractant protein-1 mRNA expression, and these effects by statins were abrogated by the PPARγ antagonist T0070907 or by small interfering RNA of PPARγ or PPARα. Statins also induced ATP-binding cassette protein A1 or CD36 mRNA expression, and these effects were suppressed by small interfering RNAs of PPARγ or PPARα. In conclusion, statins induce COX-2–dependent increase in 15d-PGJ 2 level through a RhoA- and Cdc42-dependent p38 MAPK pathway and a RhoA- and Cdc42-independent ERK1/2 pathway, thereby activating PPARγ. Statins also activate PPARα via COX-2–dependent pathway. These effects of statins may explain their antiatherogenic actions.
Diagnostic Accuracy of Computed Tomographic Colonography for the Detection of Advanced Neoplasia in Individuals at Increased Risk of Colorectal Cancer
Authors: Daniele Regge
Journal: JAMA (2009)

Computed tomographic (CT) colonography has been recognized as an alternative for colorectal cancer (CRC) screening in average-risk individuals, but less information is available on its performance in individuals at increased risk of CRC.To assess the accuracy of CT colonography in detecting advanced colorectal neoplasia in asymptomatic individuals at increased risk of CRC using unblinded colonoscopy as the reference standard.This was a multicenter, cross-sectional study. Individuals at increased risk of CRC due to either family history of advanced neoplasia in first-degree relatives, personal history of colorectal adenomas, or positive results from fecal occult blood tests (FOBTs) were recruited in 11 Italian centers and 1 Belgian center between December 2004 and May 2007. Each participant underwent CT colonography followed by colonoscopy on the same day.Sensitivity and specificity of CT colonography in detecting individuals with advanced neoplasia (ie, advanced adenoma or CRC) 6 mm or larger.Of 1103 participants, 937 were included in the final analysis: 373 cases in the family-history group, 343 in the group with personal history of adenomas, and 221 in the FOBT-positive group. Overall, CT colonography identified 151 of 177 participants with advanced neoplasia 6 mm or larger (sensitivity, 85.3%; 95% confidence interval [CI], 79.0%-90.0%) and correctly classified results as negative for 667 of 760 participants without such lesions (specificity, 87.8%; 95% CI, 85.2%-90.0%). The positive and negative predictive values were 61.9% (95% CI, 55.4%-68.0%) and 96.3% (95% CI, 94.6%-97.5%), respectively; after group stratification, a significantly lower negative predictive value was found for the FOBT-positive group (84.9%; 95% CI, 76.2%-91.3%; P < .001).In a group of persons at increased risk for CRC, CT colonography compared with colonoscopy resulted in a negative predictive value of 96.3% overall. When limited to FOBT-positive persons, the negative predictive value was 84.9%.
Computed Tomographic Imaging in the Diagnosis of Recurrent Ventral Hernia
Authors: Melissa Anne Mallory, Stanley W. Ashley
Journal: JAMA Surgery (2015)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Surgery journal
Liver biopsy in chronic hepatitis: 1968-78.
Authors: P J Scheuer
Journal: Gut (1978)

The classification of chronic hepatitis introduced in 1968 is still current, but has been modified. The concept of bridging hepatic necrosis has been incorporated, and is recognised as an important feature of both acute and chronic aggressive (active) hepatitis (CAH). In the pathogenesis of the latter, piecemeal necrosis is, however, thought to be the more important factor. The histological picture of CAH varies widely. Several causes of CAH have been identified, including hepatitis B virus. Recognition of surface and core components of the virus in tissue sections has facilitated study of the relationship between host response and pathological lesion in chronic hepatitis. CAH and primary biliary cirrhosis share histological features, and a mixed form has been postulated. Staining for copper sometimes helps to distinguish the two lesions. A third histological category, chronic lobular hepatitis, comprises patients with histological lesions like those of acute hepatitis, but with a chronic or recurrent course.
Statins?is there no end to their usefulness?
Authors: C WAINWRIGHT
Journal: Cardiovascular Research (2004)

See also article by Birnbaum et al.  [15]  (pages 345–355) in this issue .

Ever since the data from the West of Scotland Coronary Prevention (WOSCOP) Study demonstrated an unequivocal beneficial effect in patients at risk from coronary events [1], statins have become a standard addition to the therapeutic management of this group of the population. As inhibitors of HMG-CoA reductase, the primary pharmacodynamic effect of the statins is to inhibit the synthesis of cholesterol by the liver, thereby increasing hepatic cholesterol uptake and reducing circulating lipid levels–or is it? While lipid lowering is more than likely to underpin the clinical observations of a deceleration of atherosclerotic lesion formation and induction of regression and stabilisation of plaques, evidence is growing that the pleiotropic effects of statins (i.e. their effects beyond lipid lowering) may also contribute to their beneficial effects in this setting and may imply an earlier initiation of treatment. The pleiotropic effects of statins include an improvement in endothelial dysfunction and bioavailability of nitric oxide (NO), antioxidant potential, and anti-inflammatory properties. These properties immediately widen the scope for this increasingly versatile group of drugs. With respect to cardiovascular pathologies, statins have been shown to inhibit atrial myocardial remodelling [2,3], prevent atrial fibrillation [4], to conserve NO production in heart failure [5], to reduce the activity of small G-proteins in cardiac hypertrophy [6], and to contribute to post-ischaemic myocardial repair through mobilisation of endothelial progenitor cells [7]. A further potential use for statins is their ability to protect the myocardium from ischaemia/reperfusion injury.

The infarct-limiting effects of statins have been observed with a number of different statins, including simvastatin, [8,9], pravastatin [10,11], and cerivastatin [12], in a range of experimental models. … 

*Tel.: +44 1224 262450; fax: +44 1224 262555. Email address: c.wainwright{at}rgu.ac.uk