tbuckley/cabot-search huggingface dataset:
Abstract 4609: MEF2 plays a critical role in RENCA macrobead-induced tumor cell growth inhibition
Authors: Prithy C. Martis, Atira Dudley, Melissa A. Laramore, Barry H. Smith, Lawrence S. Gazda
Journal: Cancer Research (2014)

Abstract Regulation of cell proliferation and cell death is often dependent on the coupling of extracellular signals to the activation or repression of specific intracellular signaling pathways. We have previously demonstrated the capacity of mouse renal adenocarcinoma (RENCA) cells encapsulated in agarose macrobeads to form numerous small tumor colonies within the macrobeads over a period of several months. As the encapsulated tumor colonies mature and reach a maximum size, the macrobeads themselves, or conditioned media from cultured macrobeads, markedly inhibit the in vitro and in vivo growth of epithelial-derived tumor cells outside the macrobead microenvironment. Myocyte enhancer factor 2 (MEF2) is a family of four transcription factors that have been shown to play a central role in linking signaling pathways to the genes responsible for cell division, differentiation and death. In this study, we evaluated the expression and role of MEF2 in regulating cell proliferation in mouse (RENCA) and human cell lines (J82, MCF7) in response to RENCA macrobeads. Freely growing RENCA target cells transiently transfected with a MEF2 transcriptional response element and exposed to conditioned media from variously aged macrobeads demonstrated increased response element activation in parallel with the increasing age of the macrobeads. Similarly, growth inhibition of the freely growing RENCA cells increased with older macrobeads. Suppression of the expressed MEF2 isoforms in target RENCA cells, either individually (MEF2a, MEF2b, and MEF2d) or in combination (MEF2pool) using synthetic small interfering RNA (siRNA) markedly reduced the growth inhibitory effects of RENCA macrobeads. In J82 and MCF7 cell lines, MEF2D expression was responsive to replete media from RENCA macrobeads, increasing 2.0-fold and 2.7-fold respectively. Degradation of MEF2D mRNA transcripts in the human cell lines studied resulted in abatement of the growth inhibitory effect of the RENCA macrobeads. These findings reveal an essential role for MEF2 in RENCA macrobead-induced cancer cell growth inhibition and raise interesting questions about the molecular basis of this response. Citation Format: Prithy C. Martis, Atira Dudley, Melissa A. Laramore, Barry H. Smith, Lawrence S. Gazda. MEF2 plays a critical role in RENCA macrobead-induced tumor cell growth inhibition. [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 4609. doi:10.1158/1538-7445.AM2014-4609
Unemployment and child abuse.
Authors: L S Taitz, J M King, J Nicholson, M Kessel
Journal: BMJ (1987)

The employment state of men living in the homes of children at the time that child abuse was diagnosed was determined. The series included a wide range of abuse, including non-accidental injury, failure to thrive, neglect, and emotional deprivation. Two cohorts of children seen during 1974-9 and 1980-5 were compared; these periods were chosen because a large increase in unemployment began in Sheffield in 1980. Although the proportion of the men without work was significantly increased during the second period, this increase could not be ascribed to the rise in either long term or short term unemployment among those who had previously been in regular employment. It was accounted for by a rise in the proportions of single parent families and families in which the resident man had never had regular employment. This may reflect an increase in pregnancies among young mothers. There was no evidence to support the belief that the loss of a job in otherwise stable families leads to an increase in child abuse.
Influence of non-steroidal anti-inflammatory drugs on diuretic treatment of mild to moderate essential hypertension.
Authors: P P Koopmans, T Thien, F W Gribnau
Journal: BMJ (1984)

In an open triple crossover study in 10 patients with mild to moderate essential hypertension the influence was investigated of adding indomethacin 50 mg, naproxen 250 mg, or sulindac 200 mg, each twice daily for four weeks, to diuretic treatment with hydrochlorothiazide 50 mg a day. After two weeks9 treatment with indomethacin a slight increase in blood pressure was observed, whereas both sulindac and naproxen tended to enhance the antihypertensive effect of hydrochlorothiazide. After treatment for four weeks, however, the effects of all three drugs on blood pressure appeared to be blunted. Furthermore, body weight increased significantly during treatment with indomethacin but not during treatment with naproxen or sulindac. No significant changes were found for various biochemical variables, including concentrations of plasma electrolytes and serum creatinine and albumin, plasma renin activity, plasma aldosterone concentration, and 24 hour urinary excretion of sodium and potassium, with the exception, however, of an increase in plasma potassium concentration during treatment with indomethacin. These observations suggest that the interaction of indomethacin, naproxen, and sulindac with diuretic treatment in mild to moderate essential hypertension is transient and of minor clinical importance.
OD or Not OD?
Authors: R. A. P. Burt
Journal: JAMA (1988)

To the Editor.  —When I was a medical student, our professor of therapeutics warned us of the potency of modern drugs, describing them picturesquely and memorably as therapeutic thunderbolts of Jove. It is this warning, coupled with my involvement in the development of new drugs, that made me particularly conscious of the importance of ensuring that medication instructions are clear and unambiguous, while my training in anesthesia has made me aware of the dangers of miscommunication in drug therapy. Whereas the anesthesiologist personally administers drugs to patients, most physicians write a prescription but leave to a nurse the actual administration of the drug. As the prescriber usually is not present when the drug is given, clear instruction on dose and frequency of administration is paramount. The Latin abbreviations bid, tid, and qid are commonly used to indicate dosing frequency, and if more specific timing is required a mixture of Latin
Hepatitis Delta Virus Infection and Labrea Hepatitis
Authors: Edna Strauss
Journal: JAMA (1988)

<h3>To the Editor.</h3> —In an interesting article, Bensabath et al<sup>1</sup>suggest that delta virus infection is the preponderant cause of Labrea hepatitis. They declare that the clinical picture of the classic form of massive hepatic necrosis is indistinguishable from the fulminant steatosis observed in Labrea hepatitis. Among the 21 cases histologically examined they found 13 cases with morula cells (Labrea hepatitis), 84% of whom had delta infection. In the eight cases of extensive necrosis there was a 62% incidence of delta infection. The authors conclude that both forms of acute hepatic failure can be attributed to delta infection. There is no doubt that delta infection is prevalent in the region, but this argument is not sufficient to prove that it is the cause of Labrea hepatitis, particularly because delta hepatitis is a worldwide infection known to produce, on occasion, a classic fulminant hepatitis with massive necrosis. Why, then, do
Caring for the uninsured and underinsured. Another pound of cure
Authors: T. Harkin
Journal: JAMA (1991)

THE theme issue ofThe Journalon caring for the uninsured and underinsured<sup>1</sup>was thought-provoking and addressed the pressing need for improved access to health care for Americans. AlthoughThe Journalis to be commended for its bold initiative in presenting an array of views related to health care access, the failure to substantively address health promotion and the prevention of disease and disability in this context was conspicuous. Although the issue was devoted to access to health care for those with inadequate insurance coverage and necessarily focused on costs, the preoccupation with diagnostic and therapeutic interventions and the virtual neglect of prevention cut to the essence of the long-standing and growing health care problems facing our nation. Access to affordable and quality health care is a fundamental right that should be extended to and enjoyed by all Americans. As amply demonstrated by the recent flurry of proposals, there
T cell receptor ligation induces interleukin (IL) 2R beta chain expression in rat CD4,8 double positive thymocytes, initiating an IL-2-dependent differentiation pathway of CD8 alpha+/beta- T cells.
Authors: J H Park, R Mitnacht, N Torres-Nagel, T Hünig
Journal: The Journal of Experimental Medicine (1993)

The role of interleukin (IL)2 in intrathymic T cell development is highly controversial, and nothing is known about IL-2R expression on thymocytes of the T cell receptor (TCR) alpha/beta lineage undergoing TCR-driven differentiation events. We analyze here IL-2R alpha and beta mRNA expression in an in vitro system where newly generated rat CD4,8 double positive (DP) thymocytes respond to TCR ligation plus IL-2 (but not to either stimulus alone) with rapid differentiation to functional CD8 single positive T cells (Hünig, T., and R. Mitnacht. 1991. J. Exp. Med. 173:561). TCR ligation induced expression of IL-2R beta (but not alpha) chain mRNA in DP thymocytes. Addition of IL-2 then lead to functional maturation and expression of the IL-2R alpha chain. To investigate if the CD8 T cells generated via this IL-2R beta-driven pathway in vitro correspond to the bulk of CD8 T cells seeding peripheral lymphoid organs in vivo, we compared their phenotype to that of lymph node CD8 T cells. Surprisingly, analysis of CD8 cell surface expression using a novel anti-CD8 monoclonal antibody specific for the alpha/beta heterodimeric isoform, and of CD8 alpha and beta chain mRNA revealed that T cells generated by TCR ligation plus IL-2 resemble thymus-independent rather than thymus-derived CD8 cells in that they express CD8 alpha without beta chains. These findings demonstrate that TCR crosslinking induces functional IL-2R on immature DP rat thymocytes. In addition, they show that at least in vitro, CD8 alpha/alpha T cells are generated from TCR-stimulated DP thymocytes (which express the CD8 alpha/beta in the heterodimeric isoform) along an IL-2-driven pathway of T cell differentiation.
Temporal Clustering of Exacerbations in Chronic Obstructive Pulmonary Disease
Authors: John R. Hurst, Gavin C. Donaldson, Jennifer K. Quint, James J. P. Goldring, Ramin Baghai-Ravary, Jadwiga A. Wedzicha
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Exacerbations are important events in chronic obstructive pulmonary disease. Preventing exacerbations is a key treatment goal. Observational data suggest that after a first exacerbation, patients may be at increased risk of a second exacerbation, but this has not been specifically studied. We hypothesized that exacerbations may cluster together in time, a finding that would have important implications for targeting preventative interventions and the analysis of clinical trial data.To assess whether exacerbations are random events, or cluster in time.A total of 297 patients in the London chronic obstructive pulmonary disease cohort recorded daily symptoms and were assessed for a total of 904 patient-years. The observed timing of second exacerbations after an initial exacerbation was compared with that expected should exacerbations occur randomly.The observed timing distribution of second exacerbations differed significantly (P < 0.001) from the expected exponential function (shape parameter of the fitted Weibull function, 0.966 [95% confidence interval, 0.948-0.985]), suggesting that more second exacerbations occurred sooner than later and that exacerbations cluster together in time. Twenty-seven percent of first exacerbations were followed by a second recurrent event within 8 weeks. Approximately one third of exacerbations were recurrent exacerbations. Although initial exacerbations were milder than isolated events, they were not less likely to receive treatment, and under-treatment of initial events is not a plausible explanation for exacerbation recurrence. Recurrent exacerbations contribute significantly to overall exacerbation frequency (rho = 0.81; P < 0.0001).Exacerbations are not random events but cluster together in time such that there is a high-risk period for recurrent exacerbation in the 8-week period after an initial excerbation.
Service Excellence in Health Care
Authors: Thom Mayer
Journal: JAMA (1999)

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
Inferring Cortical Function From the Patient's Job: He Made Grass Trimmer, But Could He Have Made Vice President?-Reply
Authors: Patrick A. Murphy
Journal: JAMA (1989)

In Reply.—  I disagree with Dr Roberts' suggestion that a patient's job provides no information about mental status. The patient had a Mini Mental State score of 23 or 24 on repeated tests, which is clearly abnormal and required explanation. We determined that there was no evidence of mass lesions in the brain by computed tomographic scan and no abnormality on lumbar puncture. However, since he was going to be treated only with ketoconazole, there was a good deal of angst among the house officers about whether we were missing subclinical central nervous system blastomycosis, which would require amphotericin B therapy.  The history of severe head injury at age 9 years was clearly relevant, but since head injury does not necessarily impair cortical function we sought further reassurance. The patient did not graduate from high school, although this information was edited out of the manuscript. He had the kind of
Renal cell carcinoma–derived gangliosides suppress nuclear factor-κB activation in T cells
Authors: Robert G. Uzzo, Patricia Rayman, Vladimir Kolenko, Peter E. Clark, Martha K. Cathcart, Tracy Bloom, Andrew C. Novick, Ronald M. Bukowski, Thomas Hamilton, James H. Finke
Journal: Journal of Clinical Investigation (1999)

Activation of the transcription factor nuclear factor-κB (NFκB) is impaired in T cells from patients with renal cell carcinomas (RCCs). In circulating T cells from a subset of patients with RCCs, the suppression of NFκB binding activity is downstream from the stimulus-induced degradation of the cytoplasmic factor IκBα. Tumor-derived soluble products from cultured RCC explants inhibit NFκB activity in T cells from healthy volunteers, despite a normal level of stimulus-induced IκBα degradation in these cells. The inhibitory agent has several features characteristic of a ganglioside, including sensitivity to neuraminidase but not protease treatment; hydrophobicity; and molecular weight less than 3 kDa. Indeed, we detected gangliosides in supernatants from RCC explants and not from adjacent normal kidney tissue. Gangliosides prepared from RCC supernatants, as well as the purified bovine gangliosides Gm1 and Gd1a, suppressed NFκB binding activity in T cells and reduced expression of the cytokines IL-2 and IFN-γ. Taken together, our findings suggest that tumor-derived gangliosides may blunt antitumor immune responses in patients with RCCs.
THE PHOTODYNAMIC ACTION OF EOSIN AND ERYTHROSIN UPON SNAKE VENOM
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1906)

Since the haemolysins of the several venoms respond differently to photodynamic action, they may be regarded as possessing different chemical constitutions. As regards stability, cobra haemolysin ranks first, daboia second, and Crotalus third. The toxicity of all the venoms is more or less diminished by eosin and erythrosin in sunlight. This reduction in toxicity depends upon chemical changes, of more or less profound nature, taking place in certain of the active principles of the venom. The more stabile the predominant active principles the less the reduction in toxicity, and vice versa. Venom-neurotoxins are highly resistant to photodynamic action, venom-haemolysins are less resistant, while the haemorrhagin and thrombokinase of Crotalus and daboia venoms exhibit weak powers of resistance to their action. Hence it follows that while cobra venom remained almost unaltered, rattlesnake and daboia venoms were greatly reduced in toxicity when mixed with the fluorescent dyes and exposed to sunlight. There is an interesting parallel between the action of eosin and erythrosin upon the different venoms and their reactions to other injurious agencies. For example, the haemolysins of cobra and daboia venoms are more heat resistant than the haemolysin of Crotalus venom, and the former are less injured by the dyes than the latter. The neurotoxin of the former venoms is also more heat stabile than that of the rattlesnake, and the same relative degree of resistance holds for this substance and the anilines. Just as the haemorrhagin of rattlesnake venom and the thrombokinase of daboia venom are destroyed by a temperature of 75 degrees C., so are they readily inactivated by the photo dynamic substances employed. The globulin-precipitating and blood corpuscle-protecting principle of cobra venom is relatively thermostabile and in contradistinction to the immunity-precipitins it is also unaffected by eosin and erythrosin. This study of the action of photodynamic substances upon snake venoms serves again to bring out the fact of their highly complex nature, and while enlarging somewhat the field in which photodynamic activity is known to operate, it also proves that this form of destructive activity is affected by the same conditions of resistance as confront the action of the usual physical and chemical agents.
TIPS for gastric varices
Authors: B M Ryan
Journal: Gut (2003)

We recently read with interest the study by Tripathi and colleagues1 investigating the outcome of TIPS in patients with gastric (GV) compared to oesophageal varices (OV). This study confirmed the previous finding of lower mean portosystemic pressure gradient (PPG) in patients with GV bleeding relative to those with a history of OV bleeding.2 Indeed in this study 35% (14/40) of GV patients compared to only 8% (20/2320 of OV patients had a PPG <12 mm Hg.

The group of patients who bleed at PPG <12 mm Hg (group 1) is particularly intriguing. As mentioned by the authors, low PPG in GV patients has been shown to correlate with the presence and size of a spontaneous gastrorenal shunt (GRS) which is present in up to 85% of GV patients but present in only about 20% of OV patients.3 Previously, Sanyal et al found that 50% (6/12) of patients who underwent TIPS for prevention of GV re-bleeding failed to decompress the varices as documented by endoscopy. 4/6 of these patients had a large GRS and a PPG <12 …
Detection of c-Ki-ras gene codon 12 mutations from pancreatic duct brushings in the diagnosis of pancreatic tumours.
Authors: J L Van Laethem, P Vertongen, J Deviere, J Van Rampelbergh, F Rickaert, M Cremer, P Robberecht
Journal: Gut (1995)

Differential diagnosis of pancreatic cancer and chronic pancreatitis is sometimes difficult and cytological examination of brushings or aspirated material collected during endoscopic retrograde cholangiopancreatography (ERCP) remains disappointing. As point mutations in codon 12 of the c-Ki-ras 2 gene are found in most pancreatic adenocarcinoma and not in chronic pancreatitis, this study analysed prospectively the presence of these mutations in brushing samples collected during ERCP in 45 patients (26 males, 19 females) showing a dominant stricture of the main pancreatic duct at pancreatography: 24 with pancreatic adenocarcinoma, 16 with chronic pancreatitis, and five intraductal mucin hypersecreting neoplasms. Twenty of 45 patients presented equivocal ERCP findings that did not permit a definite diagnosis. Ki-ras mutations at codon 12 were detected using a rapid and sensitive method based on polymerase chain reaction mediated restriction fragment length polymorphism analysis and confirmed by direct sequencing of polymerase chain reaction products. Results were compared with those provided by routine brush cytology. A definitive diagnosis was established for each patient. Mutations were detected in 20 of 24 patients with pancreatic adenocarcinoma (83%), but in none of the chronic pancreatitis patients and intraductal mucin hypersecreting neoplasms, irrespective of their location. By contrast, only 13 of 24 pancreatic adenocarcinoma (54%) were detected by conventional cytological examination, which yielded four false negative and seven non-contributive results. Sensitivity, specificity, and accuracy of molecular biological and cytological methods were 83%-76%, 100-83%, and 90%-58%, respectively. Notably the mutations could be detected in six patients with small tumour size (&lt; or = 2 cm). In conclusion, Ki-ras analysis performed on pancreatic brushing samples is an efficient procedure, more accurate than cytology in the diagnosis of pancreatic adenocarcinoma, and highly specific in the differentiation between neoplastic and chronic inflammatory ductal changes, especially in patients showing inconclusive ERCP findings.
South Western Branch. The Preliminary Education of Medical Students
Authors: P. Q. Karkeek
Journal: BMJ (1900)

IMEDICAL JOURNALI4-which caused adhesions, the long delay before operation was most adverse in the same manner: which delay had its origin in the universal timidity surgeons entertained with regard to tampering with the peritoneum.For tthis reason the smallest incision possible, from 2 to 4 inches, was in vogue in ovariotomy, necessitating greater violence in extraction, and precluding examination of the abdominal contents.Extraperitoneal treatment of the pedicle by clamp retarded year after year all progress in this branch ot surgery.Nothing was known as to the method of dealing with adhe- sions, which it was the custom to strip off the surface of the tumour before .evacuating the contents, so conducing to hanmorrhage.It was not known how many layers of the abdominal wall to suture, and in fact it was quite haphazard as to this.Not that surgeons were careless in those days, for according to their lights they took as much pains as men do at the present -day.Thus the temperature of the operating room was scrupulously regu- lated, being made very warm with steam kettles going, and the patient was kept in strict privacy before, during, and after the operation; those at- tending it were limited in number, and care was taken that no one present Oiad been in attendance on any contagious or infectious disorder.We now know that many of these precautions are unnecessary, some of our best results being obtained in the general operating theatre and wards of our hospitals.