tbuckley/cabot-search huggingface dataset:
Integration of genomic analysis and in vivo transfection to identify sprouty 2 as a candidate tumor suppressor in liver cancer
Authors: Susie A. Lee, Coral Ho, Ritu Roy, Cynthia Kosinski, Mohini A. Patil, Aaron D. Tward, Jane Fridlyand, Xin Chen
Journal: Hepatology (2008)

Hepatocellular carcinoma (HCC) is 1 of the leading causes of cancer-related deaths worldwide, yet the molecular genetics underlying this malignancy are still poorly understood. In our study, we applied statistical methods to correlate human HCC gene expression data obtained from complementary DNA (cDNA) microarrays and corresponding DNA copy number variation data obtained from array-based comparative genomic hybridization. We have thus identified 76 genes that are up-regulated and show frequent DNA copy number gain, and 37 genes that are down-regulated and show frequent DNA copy loss in human HCC samples. Among these down-regulated genes is Sprouty2 (Spry2), a known inhibitor of receptor tyrosine kinases. We investigated the potential role of Spry2 in HCC by expressing dominant negative Spry2 (Spry2Y55F) and activated β-catenin (ΔN90-β-catenin) in the mouse liver through hydrodynamic injection and sleeping beauty–mediated somatic integration. When stably expressed in mouse hepatocytes, Spry2Y55F cooperates with ΔN90-β-catenin to confer a neoplastic phenotype in mice. Tumor cells show high levels of expression of phospho-extracellular signal-regulated kinase (ERK), as well as deregulation of genes involved in cell proliferation, apoptosis, and angiogenesis. Conclusion: We identified a set of candidate oncogenes and tumor suppressor genes for human HCC. Our study provides evidence that inhibition of Spry activity cooperates with other oncogenes to promote liver cancer in mouse models, and Spry2 may function as a candidate tumor suppressor for HCC development in vivo. In addition, we demonstrate that the integration of genomic analysis and in vivo transfection is a powerful tool to identify genes that are important during hepatic carcinogenesis. (HEPATOLOGY 2008.)
Infection with Animal Helminths as a Factor in Causing Poliomyelitis and Epilepsy
Authors: A. W. Woodruff, B. Bisseru, J. C. Bowe
Journal: BMJ (1966)

Staphylococcal Colonization in Newborn-Barrie BtRnau contact, or by contaminated objects.According to Jellard (1957), the main reservoirs of this organism are (a) open lesions in the mothers, babies, or staff ; (b) adult skin and nasal carriers; and (c) the babies themselves, the umbilical cord being one of the principal sites.More than 80% of hospital-born infants are said to develop umbilical colonization by staphylococci at the fourth day (Fairchild, Graber, Vogel, and Ingersoll, 1958).In this respect the presence of the organism in the babies' stools has not been emphasized.Since staphylococci were cultured from the stools in nearly 50% of babies by the eighth day, the stools must be regarded as a potential reservoir of infection to which appropriate action must be directed during nursery outbreaks of staphylococcal sepsis. SummaryRectal colonization by Staph.aureus occurred in 48 % of 92 normal newborn infants by the eighth day, and was not asso- ciated with any gastro-intestinal disturbance.The finding of Staph.aureus in stool cultures from infants with diarrhoea should be regarded as incidental, unless shown to be caused by an epidemic strain.However, the prevalence of this organism in the stools may be a significant reservoir of staphylococcal spread in nursery infections.
Tachycardia short-circuited with intracardiac shock
Authors: J. Maurice
Journal: JAMA (1983)

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
A microRNA upregulated in asthma airway T cells promotes TH2 cytokine production
Authors: Laura J Simpson, Sana Patel, Nirav R Bhakta, David F Choy, Hans D Brightbill, Xin Ren, Yanli Wang, Heather H Pua, Dirk Baumjohann, Misty M Montoya, Marisella Panduro, Kelly A Remedios, Xiaozhu Huang, John V Fahy, Joseph R Arron, Prescott G Woodruff, K Mark Ansel
Journal: Nature Immunology (2014)
Analgesic Nephropathy in 1981: Which Drug Is Responsible?
Authors: Martin Goldberg
Journal: JAMA (1982)

In 1953, Spühler and Zollinger from Switzerland described a group of patients with chronic interstitial nephritis in whom there appeared to be an association between the renal disease and the ingestion of large quantities of certain analgesic drugs. This report was followed by several others from other countries in Europe and, ultimately, from South Africa, Australasia, and North America supporting this proposed drug-disease association. In the 1950s and 1960s there raged in the literature (also manifest at international medical congresses) debate and controversy concerning the possible relationships between "over-the-counter" pain-relieving medication and kidney disease. The major issues under discussion were (1) Was there, indeed, a causal relationship between analgesic drugs and renal disease, or was there merely a coincidental association between certain types of renal disease and the desire to consume analgesics (eg, some proposed that the renal disease was no different from chronic bacterial pyelonephritis)? (2) If there was
Effect of overdose of trazodone.
Authors: E. Baughan, S. S. Jawad
Journal: BMJ (1992)

examination.Infants cannot describe their complaints and often resent abdominal palpation.Stringer and colleagues confirm that among children with intussusception only a minority have the traditional triad of symptoms.It is natural for trainees in general practice to try to reach an accurate diagnosis, but in these difficult
Histone Deacetylation Inhibition in Pulmonary Hypertension
Authors: Lan Zhao, Chien-Nien Chen, Nabil Hajji, Eduardo Oliver, Emanuele Cotroneo, John Wharton, Daren Wang, Min Li, Timothy A. McKinsey, Kurt R. Stenmark, Martin R. Wilkins
Journal: Circulation (2012)

Background— Epigenetic programming, dynamically regulated by histone acetylation, is a key mechanism regulating cell proliferation and survival. Little is known about the contribution of histone deacetylase (HDAC) activity to the development of pulmonary arterial hypertension, a condition characterized by profound structural remodeling of pulmonary arteries and arterioles. Methods and Results— HDAC1 and HDAC5 protein levels were elevated in lungs from human idiopathic pulmonary arterial hypertension and in lungs and right ventricles from rats exposed to hypoxia. Immunohistochemistry localized increased expression to remodeled vessels in the lung. Both valproic acid, a class I HDAC inhibitor, and suberoylanilide hydroxamic acid (vorinostat), an inhibitor of class I, II, and IV HDACs, mitigated the development of and reduced established hypoxia-induced pulmonary hypertension in the rat. Both valproic acid and suberoylanilide hydroxamic acid inhibited the imprinted highly proliferative phenotype of fibroblasts and R-cells from pulmonary hypertensive bovine vessels and platelet-derived growth factor–stimulated growth of human vascular smooth muscle cells in culture. Exposure to valproic acid and suberoylanilide hydroxamic acid was associated with increased levels of p21 and FOXO3 and reduced expression of survivin. The significantly higher levels of expression of cKIT, monocyte chemoattractant protein-1, interleukin-6, stromal-derived factor-1, platelet-derived growth factor-b, and S100A4 in R-cells were downregulated by valproic acid and suberoylanilide hydroxamic acid treatment. Conclusions— Increased HDAC activity contributes to the vascular pathology of pulmonary hypertension. The effectiveness of HDAC inhibitors, valproic acid, and suberoylanilide hydroxamic acid, in models of pulmonary arterial hypertension supports a therapeutic strategy based on HDAC inhibition in pulmonary arterial hypertension.
ANGEIOMATA IN VALVES OF HEART OF A NEWLY BORN CHILD
Authors: Joseph L. Nichols
Journal: The Journal of Experimental Medicine (1908)

The following pathological condition was found in the heart and bladder of a male child eighteen days old, who came to autopsy at the Johns Hopkins Hospital in August, I898 , and is, on account of its rarity, w6rthy of a brief description.The mother of the child gave a normal history, and the present pregnancy, her first, was brought to a successful issue in the obstetrical ward of this hospital, without interference or complications, except a few mild epileptiform convulsions before and after delivery.The child, however, never did well, grew progressively thinner and weaker, and succumbed at the end of eighteen days to constant vomiting and diarrhoea.The weight at birth was 2,8oo gm., at death 2,o95 gm.Nothing abnormal was noted about the heart sounds in the obstetrical ward.At autopsy, the body was that of an undersized, newly born, male child, showing nmch emaciation and considerable livor mortis.There were no special marks upon the external surface.The intestines showed a considerable degree of follicular enteritis.With the exception of the heart and bladder, the other organs presented no apparent pathological alterations.In the heart the aortic and pulmonic valves were normal; the foramen ovale was still patent by a small opening a few millimeters in diameter.On the tricuspid and mitral valves, however, strung along their upper or auricular surfaces, were from eight to ten minute, dark purplish red globules, varying in size from a pin's point to one, on the tricuspid valve, as large as a pin's head.All of these protruded more or less from the valvular surface, while the larger ones were distinctly pedunculated.They were quite hard
Systemic Administration of Micro-dystrophin Restores Cardiac Geometry and Prevents Dobutamine-induced Cardiac Pump Failure
Authors: DeWayne Townsend, Michael J Blankinship, James M Allen, Paul Gregorevic, Jeffrey S Chamberlain, Joseph M Metzger
Journal: Molecular Therapy (2007)

Duchenne muscular dystrophy (DMD) is a fatal disease of striated muscle deterioration resulting from the loss of the cytoskeletal protein dystrophin. Most patients develop significant cardiomyopathy, with heart failure being the second leading cause of death in DMD. Compared with the extensive studies on skeletal muscle defects and potential therapy in DMD, very little attention has been directed at the increasing incidence of heart failure in DMD. Here we show that a single systemic injection of recombinant adeno-associated virus (rAAV2/6) harboring micro-dystrophin leads to extensive cardiac transduction, with micro-dystrophin correctly localized at the periphery of the cardiac myocytes and functionally associated with the sarcolemmal membrane. Significantly, micro-dystrophin gene transfer corrected the baseline end-diastolic volume defect in the mdx mouse heart and prevented cardiac pump failure induced by dobutamine stress testing in vivo, although several parameters of systolic function were not corrected. These results demonstrate that systemic gene delivery of micro-dystrophin can restore ventricular distensibility and protect the mdx myocardium from pump dysfunction during adrenergic stimulation in vivo.
Serum Levels of Free and Total Prostate-Specific Antigen in Males with Liver Cirrhosis
Authors: Yoko Kubota, Isoji Sasagawa, Haruhide Sinzawa, Takuya Kunii, Keiichi Itoh, Hiroshi Miura, Kyoichi Imai, Teruhiro Nakada
Journal: European Urology (1999)
Evidence for accelerated colorectal adenoma–carcinoma progression in<i>MUTYH</i>-associated polyposis?
Authors: M H Nieuwenhuis, S Vogt, N Jones, M Nielsen, F J Hes, J R Sampson, S Aretz, H F A Vasen
Journal: Gut (2011)

MUTYH-associated polyposis (MAP) is an autosomal recessive inherited disorder characterised by the development of polyposis in the upper and lower gastrointestinal tract and a high risk of colorectal cancer (CRC). We evaluated the natural history of the disease and the outcome of colorectal surveillance and management.A large Western European dataset of biallelic MUTYH mutation carriers comprising 254 patients was used. Detailed information was collected on polyp and cancer development in the colorectum, and the outcome of surveillance and surgery. Survival methods were used to calculate the risk of CRC development.The mean follow-up was 9.8 years. Colorectal polyposis was diagnosed at a mean age of 44.8 years (range: 12-77 years). Most patients had <100 colorectal adenomas at diagnosis. CRC was diagnosed in 147 (58%) of the 254 patients (mean age at diagnosis: 48.5, range: 21-77 years). The cumulative lifetime risk of CRC was 63% at age 60 years. There was no correlation between the number of adenomas and the presence of CRC. The cumulative risk of CRC in patients presenting with polyps was 9% after 5 years of follow-up. Patients presenting with CRC had 11% risk of developing a metachronous CRC at 5 years after surgery. Thirty-seven per cent of patients with MAP with CRC who underwent partial colonic resection needed secondary surgery shortly afterwards.The high risk of developing CRC under surveillance in patients with MAP may suggest an accelerated carcinogenesis. Surveillance of these patients should therefore include colonoscopy at short intervals, for example, at 1-2-year intervals starting from the age of 18 to 20 years. If surgery for CRC is warranted, a (sub)total colectomy is recommended.
Heme regulates B-cell differentiation, antibody class switch, and heme oxygenase-1 expression in B cells as a ligand of Bach2
Authors: Miki Watanabe-Matsui, Akihiko Muto, Toshitaka Matsui, Ari Itoh-Nakadai, Osamu Nakajima, Kazutaka Murayama, Masayuki Yamamoto, Masao Ikeda-Saito, Kazuhiko Igarashi
Journal: Blood (2011)
Abstract P2-16-17: Characterization of response to everolimus (EVE) in BOLERO-2: A phase 3 trial of EVE plus exemestane (EXE) in postmenopausal women with HR+, HER2- advanced breast cancer
Authors: H Burris, M Gnant, G Hortobagyi, L Hart, DA Yardley, J Eakle, L Provencher, T Brechenmacher, S Saletan, T Taran, H Rugo
Journal: Cancer Research (2013)

Abstract Introduction: The BOLERO-2 trial demonstrated that combining the oral mammalian target of rapamycin (mTOR) inhibitor, EVE, with the steroidal aromatase inhibitor, EXE, more than doubled median progression-free survival (PFS) compared with placebo (PBO) plus EXE in postmenopausal women with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2−) breast cancer (BC) who relapsed or progressed following a nonsteroidal aromatase inhibitor (NSAI). Patients also achieved responses per Response Evaluation Criteria in Solid Tumors (RECIST) during treatment with EVE+EXE. Methods: The phase 3, double-blind, BOLERO-2 trial randomized postmenopausal women with HR+ BC progressing or recurring after NSAIs in a 2:1 manner to EVE 10 mg once daily plus EXE 25 mg once daily (EVE+EXE; n = 485) or placebo (PBO) plus EXE (PBO+EXE; n = 239). The primary endpoint was PFS by local assessment. Overall response rate (ORR; complete + partial response per investigator assessment based on RECIST 1.0) and duration of overall response were secondary endpoints. In addition, best percentage change from baseline in sum of longest diameters of target lesions was assessed. Results: At the time of final PFS analyses at 18 months’ median follow-up, ORR was significantly higher in the EVE+EXE arm compared with the PBO+EXE arm (12.6% vs 1.7%, respectively, by local assessment; P&amp;lt;.0001). Among patients with measurable disease at baseline, 71% in the EVE+EXE arm had a decrease in the sum of longest diameters of target lesions compared with baseline vs 30% in the PBO+EXE arm. Median duration of overall response was 10.5 months (95% confidence interval [CI]: 8.2, 21.9 months) for EVE+EXE and 6.9 months (95% CI: 4.2, 6.9 months) for PBO+EXE. Of note, only 4 patients in the PBO+EXE arm had an objective response to treatment. Conclusions: In addition to PFS, the combination of EVE plus EXE significantly improved ORR vs PBO+EXE in patients with HR+, HER2− advanced BC progressing during or after NSAI therapy. Furthermore, greater than two-thirds of patients treated with EVE+EXE experienced tumor shrinkage during treatment. These results further support the rationale for combining EVE with EXE to improve clinical outcomes in HR+, HER2− advanced BC progressing after NSAI therapy. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-17.
Strategy for rheumatology: hospital versus community.
Authors: C Cooper, J R Kirwan
Journal: Annals of the Rheumatic Diseases (1990)

Strategy for rheumatology: hospital versus community How can our system of providing rheumatological services be made more effective and more efficient?The answer to this question entails careful consideration of five issues: (a) the health burden posed by rheumatic diseases, (b) the services currently provided by the specialty, (c) measure- ment of the shortfalls between need and provision, (d) evaluating alternative strategies of provision, and (e) incor- porating successful strategies into the altered structural framework which has recently been laid down for the health service as a whole.Although much more information is required about each of these five issues before the question posed above can be fully answered, some inroads have been made recently.
ING5 Is a Tip60 Cofactor That Acetylates p53 in Response to DNA Damage
Authors: Nansong Liu, Jiadong Wang, Jifeng Wang, Rukai Wang, Zhongle Liu, Yao Yu, Hong Lu
Journal: Cancer Research (2013)

Posttranslational modification of p53 is a critical event in regulating the expression of its target genes. p53 is acetylated at lysine 120 (K120) by acetyltranferases Tip60 (KAT5) and hMOF (KAT8) in response to DNA damage. Identification of cofactors for these two enzymes will shed light on the mechanism by which cells make a choice between cell-cycle arrest and apoptosis. It has been reported that ING5, a member of the inhibitor of growth (ING) family, is involved in p53-dependent pathways, but its exact role is unknown. In this study, we found that ING5 expression was significantly increased and that ING5 assisted Tip60, but not hMOF, in acetylating p53 at K120 in response to DNA damage. ING5 had no effect on acetylation of p53 at K373/382, but it formed a complex with p53 and Tip60. ING5 was required for acetylation of p53 at K120, and p53 acetylated at K120 subsequently bound to the promoters of its target apoptotic genes, BAX and GADD45, to promote their expression and lead to apoptosis. Mutation of K120 to K120R abolished the effects of ING5 on p53-induced gene expression. Thus, we conclude that ING5 functions as a cofactor of Tip60 in the acetylation of p53 at K120 in response to DNA damage.
Abstract LB-306: The Ras exchange factor RasGRP1 opposes proliferative EGFR-SOS1 Ras signals and restricts intestinal epithelial cell growth
Authors: Philippe Depeille, Linda M. Henricks, Robert van de Ven, Ed Lemmens, Mary Matli, Kevin M. Haigis, David Donner, Robert Warren, Jeroen P. Roose
Journal: Cancer Research (2014)

Abstract The character of EGFR signals can influence cell fate. Anti-EGFR treatment has been successful as cancer therapy but not in colorectal cancer (CRC) where activating somatic KRAS mutations (KRASMUT) are prevalent. While relevant to CRC, intestinal EGFR signaling is poorly understood, particularly in the context of KRASMUT. Here we show that two distinct Ras nucleotide exchange factors, RasGRP1 and SOS1, lie downstream of the EGFR but act in functional opposition to one another in the context of KRASMUT. RasGRP1 creates a negative feedback loop that limits EGFR-SOS1-Ras signals and restricts CRC growth. Genetic Rasgrp1 depletion from KRasMUT mice exacerbates intestinal epithelial cell growth and dysplasia, leading to a highly serrated colonic epithelium. Furthermore, low RasGRP1 expression in CRC patient specimens correlates with poor clinical outcome. The unexpected inhibitory role of EGFR-RasGRP1 signals in KRASMUT gastrointestinal malignancies reveals an intricacy of EGFR signaling that should be considered for future molecular therapeutics. Citation Format: Philippe Depeille, Linda M. Henricks, Robert van de Ven, Ed Lemmens, Mary Matli, Kevin M. Haigis, David Donner, Robert Warren, Jeroen P. Roose. The Ras exchange factor RasGRP1 opposes proliferative EGFR-SOS1 Ras signals and restricts intestinal epithelial cell growth. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-306. doi:10.1158/1538-7445.AM2014-LB-306
The kinase Jnk2 promotes stress-induced mitophagy by targeting the small mitochondrial form of the tumor suppressor ARF for degradation
Authors: Qiao Zhang, Hong Kuang, Cong Chen, Jie Yan, Hanh Chi Do-Umehara, Xin-yuan Liu, Laura Dada, Karen M Ridge, Navdeep S Chandel, Jing Liu
Journal: Nature Immunology (2015)
HUMAN FOOD LAWS.
Authors: ROBERT W. HASTINGS
Journal: JAMA (1898)

"The comfort, energy, usefulness and moral character of a man depend largely upon his digestion, and this in turn depends largely upon what it has to act upon, viz., food." (Wm. Pepper.) In view of this it is strange how little interest man has taken in the regulation of the quality of that food. First and last, in one place or another, mankind has eaten nearly everything which by mastication could be made small enough to pass down his throat. But the great mass of humanity always has and does still subsist upon a few abundant, nutritious and easily obtainable foods. Such are found in fruits, grains and vegetables. Different peoples and races have made use of quite different kinds of foods. But with the more intimate knowledge of others' tastes, each of the so-called civilized nations has adopted certain of the customs and habits of others, and among them
Haemolytic anaemia in pregnancy in Nigerians.
Authors: F I Konotey-Ahulu
Journal: BMJ (1970)

unteers on the off-chance that their organs might one day be suitable for transplanta- tion.It would have been more appropriate if the subcommittee had directed attention to the main ethical dilemma of organ trans- plantation-namely, the fact that only some 10% of the 2,000-3,000 young people -needing treatment for terminal renal disease are being helped, the rest being allowed to die, despite the established fact that many of them would be provided with worthwhile therapy if more donor kidneys were avail- able.A change in the law with provision for "contracting out" is the only way in which there can be a solution to the shortage of donor organs.