tbuckley/cabot-search huggingface dataset:
A novel influenza A virus mitochondrial protein that induces cell death
Authors: Weisan Chen, Paul A. Calvo, Daniela Malide, James Gibbs, Ulrich Schubert, Igor Bacik, Sameh Basta, Robert O'Neill, Jeanne Schickli, Peter Palese, Peter Henklein, Jack R. Bennink, Jonathan W. Yewdell
Journal: Nature Medicine (2001)
Metabolomics of human breast cancer: new approaches for tumor typing and biomarker discovery
Authors: Carsten Denkert, Elmar Bucher, Mika Hilvo, Reza Salek, Matej Orešič, Julian Griffin, Scarlet Brockmöller, Frederick Klauschen, Sibylle Loibl, Dinesh Kumar Barupal, Jan Budczies, Kristiina Iljin, Valentina Nekljudova, Oliver Fiehn
Journal: Genome Medicine (2012)

Breast cancer is the most common cancer in women worldwide, and the development of new technologies for better understanding of the molecular changes involved in breast cancer progression is essential. Metabolic changes precede overt phenotypic changes, because cellular regulation ultimately affects the use of small-molecule substrates for cell division, growth or environmental changes such as hypoxia. Differences in metabolism between normal cells and cancer cells have been identified. Because small alterations in enzyme concentrations or activities can cause large changes in overall metabolite levels, the metabolome can be regarded as the amplified output of a biological system. The metabolome coverage in human breast cancer tissues can be maximized by combining different technologies for metabolic profiling. Researchers are investigating alterations in the steady state concentrations of metabolites that reflect amplified changes in genetic control of metabolism. Metabolomic results can be used to classify breast cancer on the basis of tumor biology, to identify new prognostic and predictive markers and to discover new targets for future therapeutic interventions. Here, we examine recent results, including those from the European FP7 project METAcancer consortium, that show that integrated metabolomic analyses can provide information on the stage, subtype and grade of breast tumors and give mechanistic insights. We predict an intensified use of metabolomic screens in clinical and preclinical studies focusing on the onset and progression of tumor development.
Sympathoadrenal Activity in Fasting Pregnant Rats
Authors: James B. Young, Lewis Landsberg
Journal: Journal of Clinical Investigation (1979)

The pattern of urinary catecholamine excretion in fasting differs in pregnant and nonpregnant rats, which suggests that the sympathoadrenal response to fasting is altered by pregnancy. In fasting nonpregnant animals, urinary norepinephrine (NE) excretion decreases and epinephrine (E) excretion remains unchanged, whereas the excretion of both catecholamines rises significantly with refeeding. In contrast, fasting third-trimester pregnant rats exhibit a 420% increase in urinary E and a 345% increase in urinary NE, elevations which fall with refeeding. Specific evaluation of sympathoadrenal activity in fasting pregnant rats reveals stimulation of the adrenal medulla and suppression of sympathetic nerves. In fasting third-trimester rats the adrenal content of E is 37% lower in innervated adrenals as compared with contralateral denervated glands, which indicates the presence of neurally-mediated adrenal medullary activation. Adrenalectomy completely abolishes the fasting-induced rise in urinary E and NE in pregnant rats. Studies with 2-deoxy-D-glucose suggest that stimulation of the adrenal medulla results from hypoglycemia, which is present after 3 d of fasting in pregnant rats (plasma glucose 36.7 mg/dl). Sympathetic nervous system activity, as measured by [3H]NE turnover in the heart, decreases in fasting pregnant rats despite hypoglycemia, a response similar to that seen in fasting nonpregnant animals where plasma glucose is maintained above 50 mg/dl. The calculated NE turnover rate is 44% lower in 2-d fasted pregnant rats than in fed pregnant animals (17.6 ± 1.3 vs. 31.3 ± 1.8 ng NE/heart per h, respectively). Thus adrenal medullary and sympathetic nervous system responses in fasting pregnant rats appear to be dissociated, which suggests that diet-induced changes in sympathetic activity and stimulation of the adrenal medulla by hypoglycemia may be independently regulated.
The Janus kinases (Jaks)
Authors: Kunihiro Yamaoka, Pipsa Saharinen, Marko Pesu, Vance ET Holt, Olli Silvennoinen, John J O'Shea
Journal: Genome biology (2004)

The Janus kinase (Jak) family is one of ten recognized families of non-receptor tyrosine kinases. Mammals have four members of this family, Jak1, Jak2, Jak3 and Tyrosine kinase 2 (Tyk2). Birds, fish and insects also have Jaks. Each protein has a kinase domain and a catalytically inactive pseudo-kinase domain, and they each bind cytokine receptors through amino-terminal FERM (Band-4.1, ezrin, radixin, moesin) domains. Upon binding of cytokines to their receptors, Jaks are activated and phosphorylate the receptors, creating docking sites for signaling molecules, especially members of the signal transducer and activator of transcription (Stat) family. Mutations of the Drosophila Jak (Hopscotch) have revealed developmental defects, and constitutive activation of Jaks in flies and humans is associated with leukemia-like syndromes. Through the generation of Jak-deficient cell lines and gene-targeted mice, the essential, nonredundant functions of Jaks in cytokine signaling have been established. Importantly, deficiency of Jak3 is the basis of human autosomal recessive severe combined immunodeficiency (SCID); accordingly, a selective Jak3 inhibitor has been developed, forming a new class of immunosuppressive drugs.
Tracking Medical Errors
Authors: Bridget M. Kuehn
Journal: JAMA (2005)

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
IL-21 enhances natural killer cell activation in response to antibody-coated tumor cells
Authors: Julie M. Roda, Robin Parihar, Susheela Tridandapani, William E. Carson
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

633 

Natural killer (NK) cells are innate immune cells that are unique due to their constitutive expression of an activating receptor for the Fc portion of IgG (FcγRIIIa). FcR-activated NK cells have been shown to secrete interferon (IFN)-γ and other immune modulatory cytokines, and are also able to mediate antibody-dependant cellular cytotoxicity (ADCC) against antibody (Ab)-coated targets. Interleukin (IL)-21 is a recently discovered cytokine that has been shown to enhance NK cell IFN-γ secretion and lytic activity. The present study investigated NK cell activity in response to dual stimulation by IL-21 and Ab-coated targets. Purified human NK cells cultured with IL-21 and immobilized IgG or human breast cancer cells coated with a therapeutic monoclonal Ab (trastuzumab) secreted > 5-fold higher levels of IFN-γ as compared to NK cells stimulated with either mAb-coated tumor cells or IL-21 alone. Enhanced secretion of TNF-α and the T cell-recruiting chemokines IL-8, MIP-1α, IP-10, MIG, and RANTES was also observed in response to co-stimulation. Supernatants derived from NK cells that had been stimulated with IL-21 and monoclonal Ab (mAb)-coated breast cancer cells were able to drive the migration of both naive and activated T cells in an in vitro chemotaxis assay. NK cell production of IFN-γ in response to mAb-coated tumor cells and IL-21 was dependent on activation of the signal transducer and activator of transcription (STAT)-1 and the p44/p42 mitogen-activated protein kinase (MAPK), as IFN-γ production was not observed from NK cells from STAT-1 knockout mice or NK cells that had been pre-treated with a specific chemical inhibitor of the p44/p42 MAPK. In contrast, IFN-γ production by co-stimulated NK cells was not dependent on activation of Akt or the MAPK family members p38 and Jnk. In addition, the p44/p42 MAPK was activated following FcγRIIIa ligation in STAT1-knockout NK cells, and STAT-1 was activated in response to IL-21 in NK cells pre-treated with the p44/p42 MAPK inhibitor. These results suggested that NK cell IFN-γ production in response to IL-21 and mAb-coated tumor cells was dependent on distinct and non-interacting signals mediated by the IL-21 receptor (STAT-1) and the FcR (p44/p42 MAPK) on the surface of NK cells. IL-21 also enhanced NK cell lytic activity against trastuzumab-coated human breast cancer cells and rituxan-coated B cell lymphomas. Co-administration of IL-21 and mAb-coated tumor cells to immunocompetent mice led to enhanced production of IFN-γ by NK cells. Furthermore, the administration of IL-21 significantly enhanced the effects of an anti-HER2/ neu mAb in a murine solid tumor model. These findings suggest that administration of IL-21 could enhance the innate immune response to anti-tumor mAbs in patients with cancer.
Use of “progressive disease” according to Rustin interpretation of serum CEA and CA19-9 to identify patients with a poor outcome in advanced colorectal cancer.
Authors: S. M. Crawford, L. C. Barker, A. J. Scally
Journal: Journal of Clinical Oncology (2010)

e14041 Background: Serum tumour markers have an established role in the monitoring of systemic treatment for trophoblastic, prostatic, epithelial ovarian and germ cell tumours but their use in other common cancers is less well defined. We have retrospectively assessed the information gained from a rising concentration of CEA and CA19-9 in colorectal cancer categorised according to Rustin's criteria. Methods: Patients (Pts) had marker measurements scheduled before each cycle of chemotherapy and weekly when inpatients. Their records were assessed for these data. Progression (P) and response (R) was as defined by Rustin with the addition of progression from normal values of the marker. The overall survival of Pts was analysed using a Cox proportional hazards model incorporating each marker individually and a composite 'pessimistic' categorisation where Pts were categorised as P if either marker showed this pattern irrespective of the other. Results: 150 Pts were available for analysis, 143 by both markers. For CEA, the hazard ratio for progression, compared to response, was 2.51 (95% CI: 1.51, 4.17; p < 0.001) and for CA19-9 it was 1.82 (95% CI: 0.90, 3.66; p = 0.09). Using the pessimistic categorisation, the hazard ratio increased to 4.03 (95% CI: 1.71, 9.50; p = 0.001). Conclusions: P was strongly associated with short survival and the pessimistic composite marker showed a tendency to be superior in identifying patients destined to have a short survival time. Since continuing systemic treatment in Pts who are not benefiting is deleterious to quality of life and unnecessarily costly, tumour marker monitoring has a clear potential in refining patient management. It may also provide an objective definition of progression free survival in clinical trials. It warrants formal evaluation in prospective studies. No significant financial relationships to disclose.
In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus
Authors: Neeta Singh Roy, Su Wang, Li Jiang, Jian Kang, Abdellatif Benraiss, Catherine Harrison-Restelli, Richard A. R. Fraser, William T. Couldwell, Ayano Kawaguchi, Hideyuki Okano, Maiken Nedergaard, Steven A. Goldman
Journal: Nature Medicine (2000)
Abstract 603: Combinatorial Effect of Statins and JNK Inhibitor on Proinflammatory Signaling in Human Abdominal Aortic Aneurysm Tissue
Authors: Koichi Yoshimura, Hiroki Aoki, Masahiko Onoda, Yasuhiro Ikeda, Hidekazu Aoyama, Noriyasu Morikage, Akira Furutani, Kimikazu Hamano, Masunori Matsuzaki
Journal: Circulation (2007)

Recent studies suggested that statins attenuate the growth of human abdominal aortic aneurysm (AAA), which is a common and life-threatening disease. We and others reported that c-Jun N-terminal kin...
Antimicrobial Prophylaxis for Children with Vesicoureteral Reflux
Authors: Ian Hewitt, Roberto Dall'Amico, Giovanni Montini
Journal: New England Journal of Medicine (2014)

This is a multi-centric randomized controlled trial [1] comparing cotrimoxazole prophylaxis versus no prophylaxis in children (<6 years old) with vesicoureteral reflux (VUR) detected after a first or second episode of urinary tract infection (UTI). The trial was designed to determine efficacy in preventing recurrence of UTI and renal scarring, as well as antibiotic resistance patterns. It was conducted across 19 sites in the United States, recruiting subjects over nearly five years, with follow-up for at least two years. Among 86% children who completed the study, the investigators observed lower recurrence of UTI in the intervention group (14.8%) in comparison to controls (27.4%). Intention-totreat analysis showed similar results but lesser magnitude of difference (25.5% vs 37.4%). However, there was no difference in the incidence of renal scarring (new scarring or worsening of pre-existing scarring); 11.9% and 10.2% in the intervention and control groups, respectively. The prevalence of antibiotic resistance increased significantly with prophylaxis. The investigators concluded that antibiotic prophylaxis is useful to prevent repeat episodes of UTI in children with VUR.
Abstract 12306: Changes of Metabolomic Profiling Are Associated With Reduced Exercise Capacity in Patients With Heart Failure
Authors: Masaya Tsuda, Shintaro Kinugawa, Arata Fukushima, Shoji Matsushima, Takaaki Furihata, Shingo Takada, Tomoyasu Kadoguchi, Masato Kudo, Junichi Matsumoto, Takashi Yokota, Koichi Okita, Hiroyuki Tsutsui
Journal: Circulation (2014)

Background: Exercise intolerance is a major clinical manifestation, and closely related to poor prognosis in heart failure (HF) patients. Metabolic derangements have been shown to play an important role in this phenomenon. Recent metabolomic investigations have highlighted several novel biochemical pathways in HF, however, metabolic profiling associated with exercise capacity has not been elucidated. We thus investigated the metabolites associated with exercise capacity by using global metabolomic analysis of plasma samples in HF patients. Methods: Ten consecutive HF patients with reduced ejection fraction (57 ± 12 years old, New York Heart Association class II - III) and 5 age-matched healthy subjects as controls (56 ± 3 years old) were studied. Charged metabolites in plasma samples were measured by capillary electrophoresis mass spectrometry. Peak oxygen uptake (peak VO 2 ) and VE/VCO 2 slope were measured by cardiopulmonary exercise test. Results: A total of 233 charged metabolites were identified and quantified absolutely using standard chemicals for each metabolite. Significant increases in arginine methylation, phospholipid metabolites, and urea cycle metabolites were observed in HF patients compared to controls (Figure). Peak VO 2 was negatively correlated with methylarginine including asymmetric dimethylarginine (ADMA) (r=-0.77, P&lt;0.001) and symmetric dimethylarginine (SDMA) (r=-0.65, P=0.040) levels, and phospholipid metabolites including choline (r=-0.63, P=0.049) and N,N -dimethylglycine (r=-0.75, P=0.011) levels in HF patients. VE/VCO 2 slope was positively correlated with N,N -dimethylglycine (r=0.72, P=0.026) and Urea (r=0.82, P=0.006) levels. Conclusions: Increases in metabolites of arginine methylation, phospholipid metabolism, and urea cycle were associated with exercise intolerance in HF. These results provide mechanistic insights into exercise intolerance associated with HF.
Office-Based Treatment for Opioid Addiction Achieving Goals
Authors: Bridget M Kuehn
Journal: JAMA (2005)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
New Howard Hughes Investigators Named
Authors: Tracy Hampton
Journal: JAMA (2005)

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
Lesson of the Week: Subarachnoid haemorrhage presenting as head injury
Authors: D. E Sakas, L. S Dias, D. Beale
Journal: BMJ (1995)

Headache, nausea, vomiting, and transient loss of consciousness occur in two thirds of people who experience subarachnoid haemorrhage.'Loss of con- sciousness may result in an abrupt fall and trauma to the head immediately after the haemorrhage.The distinction between subarachnoid haemorrhage and head injury may therefore be blurred sometimes, with the spontaneous subarachnoid haemorrhage remaining unrecognised.We believe that this clinical problem has not been properly addressed.We report on four patients with head injury, in whom a spontaneous subarachnoid haemorrhage preceded the trauma, and suggest guidelines for investigating and managing such patients. Case reports CASE 1A 45 year old man became unconscious after he fell 6 m from scaffolding.On admission he was convulsing, with pupils of equal size and reacting to light.He had a laceration of the scalp and an orbital fracture.Computed tomography showed a small amount of subarachnoid blood, which was attributed to the injury.The possibility of a spontaneous cerebro- vascular haemorrhagic event as the cause of the fall was raised.Cerebral angiography showed a giant aneurysm in the right middle cerebral artery.At surgery, widespread subarachnoid haemorrhage and substantial recent clotting in the area surrounding the aneurysm confirmed that the aneurysm had recently bled.Despite successful clipping of the aneurysm the patient died three days later.CASE 2A 54 year old male engineer fell 6 m from a ladder and hit his head on a concrete surface.On admission he was localising and opening his eyes to painful stimuli,
Varieties of aggressive behavior in temporal lobe epilepsy
Authors: O Devinsky, D Bear
Journal: American Journal of Psychiatry (1984)

While an increase in aggression has frequently been reported in association with temporal lobe epilepsy, the validity of this behavioral observation and the relationship of specific aggressive behavior to electrophysiologic abnormality in the human limbic system remain unclear. Case reports of five patients document the clinical importance of aggressive behavior, especially during the interictal period, in patients with temporal lobe epilepsy. Aggressiveness was often encountered together with other deepened emotions and changes in behavior previously described as an interictal behavior syndrome. Variations among the individual patients may clarify the neuroanatomical mechanisms leading to aggression and suggest specific therapeutic interventions.
Cocktails with the headmaster
Authors: Kevin Barraclough
Journal: BMJ (2001)

We circled each other warily, clutching our canapes to ward off evil. My wife and I had been summoned to a party at our daughter's new school. We were there to swell the numbers and generally enhance the sense of collective smugness that would tempt other parents into stumping up the fees. We drifted, largely ignored, in a sea of the moneyed middle class. We were, I suppose, semi-interesting flotsam buffeted in the heavy …