tbuckley/cabot-search huggingface dataset:
Abstract 1075: Molecular determinants of colon and renal cancers' immune contextures
Authors: Etienne Becht, Nicolas A. Giraldo, Romain Remark, Aurelien de Reynies, Laetitia Lacroix, Diane Damotte, Catherine Sautès-Fridman, Wolf-Herman Fridman
Journal: Cancer Research (2014)

Abstract In the vast majority of cancer types, as demonstrated and exemplified in colorectal cancer (CRC), a high density of CD8+ T cells in the tumor microenvironment correlates with a good prognosis for the patient. However, an opposite correlation has been reported in primary clear cell renal cell carcinoma (RCC) tumors. Our team studied the immune infiltrates of pulmonary metastases from CRC and RCC. We reported that despite the advanced stage of the disease in these patients, the immune infiltrate of pulmonary metastases remained a prognostic factor. As in the primary tumors, a high density of CD8+ T cells correlated with good prognosis for CRC metastases while it correlated with a bad prognosis for RCC metastases. These results suggest that the identity of the tumor cell is critical in shaping the immune contexture of a given tumor. We therefore investigated the molecular characteristics of the tumor cells which could be responsible for this opposite clinical impact in RCC versus CRC. First, we assessed the prognostic value associated with the expression of genes specific for different immune populations in several cohorts of primary CRC (n=177) and RCC tumors (n=72 and n=479), and confirmed the opposite impact of infiltrating lymphocyte densities on patient survival. In addition, RCC tumors showed a higher expression of genes related to inflammation, immunosuppression and angiogenesis. By comparing transcriptomic data from RCC and CRC cell lines, we observed that RCC tumor cells also expressed a significantly higher amount of these transcripts when compared to CRC tumor cells. Altogether, these results support the hypothesis that RCC malignant cells produce factors which are able to modify and determine the functional orientation of their immune microenvironment. Identifying which factors and pathways are critical for the RCC-related detrimental impact of CD8+ T cells on prognosis will be a major breakthrough, enabling the identification of new immunomodulatory drug targets and guide researchers and clinicians in immunotherapy protocols. Citation Format: Etienne Becht, Nicolas A. Giraldo, Romain Remark, Aurelien de Reynies, Laetitia Lacroix, Diane Damotte, Catherine Sautès-Fridman, Wolf-Herman Fridman. Molecular determinants of colon and renal cancers' immune contextures. [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 1075. doi:10.1158/1538-7445.AM2014-1075
Decreased leukocyte recruitment in the mesenteric microcirculation of rats with cirrhosis is partially restored by treatment with peginterferon: An in vivo study
Authors: Anja M. Geerts, Kin-Jip Cheung, Hans Van Vlierberghe, An S. De Vriese, Siska Mortier, Eline Vanheule, Norbert Lameire, Martine De Vos, Isabelle Colle
Journal: Journal of Hepatology (2006)
Appearance of Specific Colostrum Antibodies after Clinical Infection with Salmonella Typhimurium
Authors: R. A. Allardyce, D. J. C. Shearman, D. B. L. McClelland, K. Marwick, A. J. Simpson, R. B. Laidlaw
Journal: BMJ (1974)

Colostrum and serum antibodies to <i>Salmonella typhimurium</i> have been found in three patients after clinical gastrointestinal infection during pregnancy. High levels of colostrum IgA agglutinins were directed specifically against both the flagellar and somatic antigens of the infective organism. The levels of colostrum agglutinating activity exceeded those found in the patients sera, while control colostrum gave negative results.
Hyperprolactinemia and depression
Authors: D. F. Merritt
Journal: JAMA (1991)

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 Journals 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
Determinants of Diabetes Mellitus in the Pima Indians
Authors: William C Knowler, Mohammed F Saad, David J Pettitt, Robert G Nelson, Peter H Bennett
Journal: Diabetes Care (1993)

To review the research findings on the determinants of diabetes mellitus in Pima Indians.Pima Indians in Arizona have participated in a longitudinal diabetes study that has provided data on and hypotheses about the development of NIDDM. Findings from this study are reviewed and updated.Frequency distributions of plasma glucose and HbA1 are bimodal in Pima adults, and substantial risk of the specific vascular complications of diabetes is confined to those in the higher components of these distributions. These findings contributed to the adoption of internationally recognized criteria for classification of glucose tolerance. Diabetes in the Pimas is strongly familial, and probably of genetic origin, although the precise nature of the gene or genes involved remains unknown. Obesity, which is at least in part environmentally determined, is a major factor interacting with the presumed genetic susceptibility to result in diabetes. The incidence of diabetes in the Pimas has increased during the last several decades, providing further evidence for environmental-genetic interaction. Longitudinal studies suggest that the progression from normal to diabetes can be considered to involve two stages. The first, primarily attributable to insulin resistance, leads to impaired glucose tolerance, and the second, which depends on insulin secretory failure, leads to worsening hyperglycemia and overt diabetes.The Pimas and many other American Indian populations suffer from a high incidence of diabetes and its characteristic disabling or fatal complications, and would benefit from continued research on the pathogenesis and prevention of the disease.
Low molecular weight heparin in prevention of restenosis after angioplasty. Results of Enoxaparin Restenosis (ERA) Trial.
Authors: D P Faxon, T E Spiro, S Minor, G Coté, J Douglas, R Gottlieb, R Califf, K Dorosti, E Topol, J B Gordon
Journal: Circulation (1994)

Heparin, an anticoagulant, possesses antiproliferative effects and has been shown to reduce neointimal proliferation and restenosis following vascular injury in experimental studies.The primary aim of this double-blind multicenter study was to determine if 40 mg Enoxaparin, a low molecular weight heparin, administered subcutaneously once daily for 1 month after successful angioplasty would reduce the incidence of restenosis. Four hundred fifty-eight patients were randomized at nine clinical centers (231 to placebo and 227 to Enoxaparin). The primary end point was angiographic or clinical restenosis. Angiographic restenosis was defined as a loss of 50% of the initial gain as measured by quantitative coronary angiography (QCA) at a core laboratory. In the absence of QCA, clinical evidence of restenosis was defined as death, myocardial infarction, repeat revascularization, or worsening angina. Using the intention-to-treat analysis for all patients, restenosis occurred in 51% of the placebo group and 52% of the Enoxaparin group (relative risk, 1.07, P = .625). Likewise, no difference in restenosis was evident when the change in minimal lumen diameter or other angiographic definitions of restenosis were used. Adverse clinical events were infrequent and did not differ between the groups with the exception of minor bleeding complications, which were more common in the Enoxaparin group.Enoxaparin (40 mg/d SC for 1 month) following successful angioplasty did not reduce the incidence of angiographic restenosis or the occurrence of clinical events over 6 months. The treatment was well tolerated, although in-hospital minor bleeding was more common with active treatment.
THE SERUM-ALDEHYDE TEST APPLIED TO TRYPANOSOMIASIS: OBSERVATIONS ON CAMELS
Authors: W. C. Spackman
Journal: BMJ (1923)

Physical Signs.-Pupils:right greater thani left; left shows no reaction to light, right sluggish.Lingual anld labial tremors.Knee-jerks and ankle-jerks absent; Rombergism present.Wasser- mann reaction: blood positive; cerebro-spiinal fluid, 10 cells per cubic millimetre.Globulin and Wassermann reactions positive.Colloidal gold test positive; paretic curve.Pr-esent Condition (three months after malarial treatment).-Mental condition shows a remarkable inmprovement.No seizures have occurred.Speech is practically normal, and there is no evidence of hallucinations.Has now started light mechanical work at a garage.CASE III.J. G., aged 30; general paralysis of the insane.Had syphilis in 1914 and was inadequately treated.In October, 1922, he " lost his speech " momentarily; this recurred every month or so until a few weeks ago, when he became speechless for twenty-four hours and also suffered from transient hemiplegia.For the past few weeks he has been quite unable to carry on his work as " decora- tive artist."Mentally he was somewhat elated, unduly inquisitive, and slow in replying to questions.His wife stated that he frequently talked "nonsense."Physical Signs.-Pupils:right greater than left; Argyll Robert- son; slight lingual
A Palpatory Sign of Dissecting Aneurysm
Authors: John Storer
Journal: JAMA (1965)

<h3>To the Editor:—</h3> Since effective surgical measures have been developed to manage the patient with dissecting aortic aneurysm, it is no longer a lesion of mere academic interest. However, definitive surgery depends upon accurate and speedy diagnosis, and this is frequently difficult to achieve. An aneurysm arising in the proximal aorta may present classical findings by producing aortic insufficiency and changes in the character of the head and arm vessels. Physical findings in the patient with an aneurysm at or beyond the origin of the left subclavian artery may be scanty and obscure. Nor are aortography or other x-ray techniques exclusively and consistently of diagnostic value. There is need for a single, sure, diagnostic method. The sign hereinafter described is not offered as a<i>sine qua non</i>of dissecting aneurysm. However, since its chance discovery some ten years ago it has been observed in every patient (12) seen by the
Intussusceptive Angiogenesis
Authors: V. Djonov, M. Schmid, S. A. Tschanz, P. H. Burri
Journal: Circulation Research (2000)

Abstract —Intussusceptive angiogenesis is a novel mode of blood vessel formation and remodeling, which occurs by internal division of the preexisting capillary plexus without sprouting. In this study, the process is demonstrated in developing chicken eye vasculature and in the chorioallantoic membrane by methylmethacrylate (Mercox) casting, transmission electron microscopy, and in vivo observation. In a first step of intussusceptive angiogenesis, the capillary plexus expands by insertion of numerous transcapillary tissue pillars, ie, by intussusceptive microvascular growth. In a subsequent step, a vascular tree arises from the primitive capillary plexus as a result of intussusceptive pillar formation and pillar fusions, a process we termed “intussusceptive arborization.” On the basis of the morphological observations, a 4-step model for intussusceptive arborization is proposed, as follows: phase I, numerous circular pillars are formed in rows, thus demarcating future vessels; phase II, formation of narrow tissue septa by pillar reshaping and pillar fusions; phase III, delineation, segregation, growth, and extraction of the new vascular entity by merging of septa; and phase IV, formation of new branching generations by successively repeating the process, complemented by growth and maturation of all components. In contrast to sprouting, intussusceptive angiogenesis does not require intense local endothelial cell proliferation; it is implemented primarily by rearrangement and attenuation of the endothelial cell plates. In summary, transcapillary pillar formation, ie, intussusception, is a central and probably widespread process, which plays a role not only in capillary network growth and expansion (intussusceptive microvascular growth), but also in vascular plexus remodeling and tree formation (intussusceptive arborization).
ABC of sleep disorders. Recreational drugs and sleep.
Authors: J R Stradling
Journal: BMJ (1993)

Alcohol, nicotine, and caffeine can all alter sleep, both separately and in combination Alcohol, nicotine, and caffeine are all powerful drugs that are commonly used during recreation.They all alter sleep (either initiation or maintenance), and in combination their effects can differ from their individual actions.Anyone who complains of poor sleep, therefore, should be asked how much ofthese drugs they consume.In many cases such people may have other causes for their insomnia -for example, anxiety or depression.Trials of abstinence may need to last for several weeks before any benefit can be seen because of the length of time that any well established aberrant sleep pattern can take to improve.Smoking and nicotine _ , ~n .. ...v.The effect of smoking on sleep may be compounded by other variables.
Evolution of the Volume-Outcome Relation for Hospitals Performing Coronary Angioplasty
Authors: Vivian Ho
Journal: Circulation (2000)

Hospitals performing more surgical procedures tend to yield better outcomes. This study examines the evolution of this volume-outcome relation over time.The relation between the number of percutaneous transluminal coronary angioplasty (PTCA) procedures performed at hospitals (volume) and in-hospital bypass surgery and death for 353 488 patients treated in California between 1984 and 1996 was examined. Descriptive statistics and logistic regression were used to compare outcomes for 3 periods: 1984 to 1987, 1988 to 1992, and 1993 to 1996. The in-hospital mortality rate was 2.5% for hospitals performing <200 PTCA procedures per year but only 1.3% for hospitals performing >400 procedures per year in 1984 to 1987. By 1993 to 1996, mortality rates in these 2 volume categories narrowed to 1.7% and 1.3%, respectively. Bypass surgery rates also narrowed and fell in low-volume (<200 procedures) versus high-volume (>400 procedures) hospitals from 12.4% versus 6.9% in 1984 to 1987 to 4.6% versus 3.3% in 1993 to 1996. In a logistic regression, PTCA procedures significantly predicted in-hospital mortality and bypass surgery rates in all 3 time periods. However, coefficient estimates indicate that improvements over time in outcomes for hospitals performing <200 procedures were comparable to the predicted benefits of increasing volume above 400 procedures within time periods.Over time, the disparity in outcomes between low- and high-volume hospitals has narrowed, and outcomes have improved significantly for all hospitals. Given these improvements, lower minimum volume standards may be advisable in less populated areas, where the alternative is no angioplasty at all.
The Evolution of Reproductive Systems and Sex-Determining Mechanisms Within Rumex (Polygonaceae) Inferred from Nuclear and Chloroplastidial Sequence Data
Authors: Rafael Navajas-Pérez, Roberto de la Herrán, Ginés López González, Manuel Jamilena, Rafael Lozano, Carmelo Ruiz Rejón, Manuel Ruiz Rejón, Manuel A. Garrido-Ramos
Journal: Molecular Biology and Evolution (2005)

The genus Rumex includes hermaphroditic, polygamous, gynodioecious, monoecious, and dioecious species, with the dioecious species being represented by different sex-determining mechanisms and sex-chromosome systems. Therefore, this genus represents an exceptional case study to test several hypotheses concerning the evolution of both mating systems and the genetic control of sex determination in plants. Here, we compare nuclear intergenic transcribed spacers and chloroplast intergenic sequences of 31 species of Rumex. Our phylogenetic analysis supports a systematic classification of the genus, which differs from that currently accepted. In contrast to the current view, this new phylogeny suggests a common origin for all Eurasian and American dioecious species of Rumex, with gynodioecy as an intermediate state on the way to dioecy. Our results support the contention that sex determination based on the balance between the number of X chromosomes and the number of autosomes (X/A balance) has evolved secondarily from male-determining Y mechanisms and that multiple sex-chromosome systems, XX/XY1Y2, were derived twice from an XX/XY system. The resulting phylogeny is consistent with a classification of Rumex species according to their basic chromosome number, implying that the evolution of Rumex species might have followed a process of chromosomal reduction from x = 10 toward x = 7 through intermediate stages (x = 9 and x = 8).
The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients
Authors: Anne Joutel, Fréderic Andreux, Swann Gaulis, Valérie Domenga, Michaelle Cecillon, Nicole Battail, Nadia Piga, Françoise Chapon, Catherine Godfrain, Elisabeth Tournier-Lasserve
Journal: Journal of Clinical Investigation (2000)

Mutations in Notch3 cause CADASIL (cerebral autosomal dominant adult onset arteriopathy), which leads to stroke and dementia in humans. CADASIL arteriopathy is characterized by major alterations of vascular smooth muscle cells and the presence of specific granular osmiophilic deposits. Patients carry highly stereotyped mutations that lead to an odd number of cysteine residues within EGF-like repeats of the Notch3 receptor extracellular domain. Such mutations may alter the processing or the trafficking of this receptor, or may favor its oligomerization. In this study, we examined the Notch3 expression pattern in normal tissues and investigated the consequences of mutations on Notch3 expression in transfected cells and CADASIL brains. In normal tissues, Notch3 expression is restricted to vascular smooth muscle cells. Notch3 undergoes a proteolytic cleavage leading to a 210-kDa extracellular fragment and a 97-kDa intracellular fragment. In CADASIL brains, we found evidence of a dramatic and selective accumulation of the 210-kDa Notch3 cleavage product. Notch3 accumulates at the cytoplasmic membrane of vascular smooth muscle cells, in close vicinity to but not within the granular osmiophilic material. These results strongly suggest that CADASIL mutations specifically impair the clearance of the Notch3 ectodomain, but not the cytosolic domain, from the cell surface.
Pulling through or pegging out
Authors: G. Mercurio
Journal: BMJ (1995)

The pilot episode of ER is a rollercoaster ride through Chicago County General's emergency room, which lurches from one resuscitation to another and pauses for character moments or patient vignettes. Creator Michael Crichton, author of Jurassic Park, based ER on his experiences as a medical student, and the product has energy, humour, and charismatic characters. Chief resident Dr Mark Green—played by “Goose” from the film Top Gun—is, we are told, “the best.” We were spared seeing him with a patient with rhinitis caseosa and reporting, “Maverick, there are bogeys all over me.” Paediatrician Dr Douglas Ross was established as a heavy drinking heart throb by the subtle device of showing him drunk and bragging about his conquests; surgeon Dr Peter Benton was repeatedly described as a git, and Sherry Stringfield, …
Abstract DDT02-03: Discovery of GDC-0994, a potent and selective ERK1/2 inhibitor in early clinical development
Authors: Kirk Robarge, Jacob Schwarz, Jim Blake, Michael Burkard, Jocelyn Chan, Huifen Chen, Kang-Jye Chou, Dolores Diaz, John Gaudino, Stephen Gould, Jonas Grina, Xin Linghu, Lichuan Liu, Matthew Martinson, David A. Moreno, Christine Orr, Patricia Pacheco, Ann Qin, Kevin Rasor, Li Ren, Sheerin Shahidi-Latham, Jeffrey Stults, Francis Sullivan, Weiru Wang, Peter Yin, Aihe Zhou, Marcia Belvin, Mark Merchant, John G. Moffat
Journal: Cancer Research (2014)

Abstract The extracellular-signal-regulated kinases (ERK1 and ERK2) represent an essential node within the RAS/RAF/MEK/ERK signaling cascade that commonly is activated by oncogenic mutations in BRAF or RAS or by upstream oncogenic signaling, such as receptor tyrosine kinase (RTK) activation. While targeting upstream nodes with RAF and MEK inhibitors has proven effective clinically, resistance frequently develops through reactivation of the pathway. Simultaneous targeting of multiple nodes in the pathway, such as MEK and ERK, offers the prospect of enhanced efficacy as well as reduced potential for acquired resistance. Here, we present the discovery and characterization of GDC-0994, an orally bioavailable, small molecule inhibitor of ERK kinase activity. GDC-0994 is highly selective for ERK1 and ERK2, with biochemical potency of 1.1 nM and 0.3 nM, respectively. Daily, oral dosing of GDC-0994 results in significant single-agent activity in multiple in vivo cancer models, including KRAS-mutant and BRAF-mutant human xenograft tumors in mice. PD biomarker inhibition of phospho-p90RSK in these tumors correlates with potency in vitro and in vivo. In contrast to other published ERK inhibitors, GDC-0994 neither increases nor decreases phospho-ERK, suggesting that different ERK inhibitors have alternative mechanisms of action with respect to feedback signaling. Furthermore, we demonstrate a novel approach for targeting the oncogenic signaling through the RAS pathway by combining ERK and MEK inhibitors. GDC-0994 is currently in Phase I clinical development. Citation Format: Kirk Robarge, Jacob Schwarz, Jim Blake, Michael Burkard, Jocelyn Chan, Huifen Chen, Kang-Jye Chou, Dolores Diaz, John Gaudino, Stephen Gould, Jonas Grina, Xin Linghu, Lichuan Liu, Matthew Martinson, David A. Moreno, Christine Orr, Patricia Pacheco, Ann Qin, Kevin Rasor, Li Ren, Sheerin Shahidi-Latham, Jeffrey Stults, Francis Sullivan, Weiru Wang, Peter Yin, Aihe Zhou, Marcia Belvin, Mark Merchant, John G. Moffat. Discovery of GDC-0994, a potent and selective ERK1/2 inhibitor in early clinical development. [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 DDT02-03. doi:10.1158/1538-7445.AM2014-DDT02-03