tbuckley/cabot-search huggingface dataset:
IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac disease–associated inflammation and lymphomagenesis
Authors: Georgia Malamut, Raja El Machhour, Nicolas Montcuquet, Séverine Martin-Lannerée, Isabelle Dusanter-Fourt, Virginie Verkarre, Jean-Jacques Mention, Gabriel Rahmi, Hiroshi Kiyono, Eric A. Butz, Nicole Brousse, Christophe Cellier, Nadine Cerf-Bensussan, Bertrand Meresse
Journal: Journal of Clinical Investigation (2010)

Enteropathy-associated T cell lymphoma is a severe complication of celiac disease (CD). One mechanism suggested to underlie its development is chronic exposure of intraepithelial lymphocytes (IELs) to potent antiapoptotic signals initiated by IL-15, a cytokine overexpressed in the enterocytes of individuals with CD. However, the signaling pathway by which IL-15 transmits these antiapoptotic signals has not been firmly established. Here we show that the survival signals delivered by IL-15 to freshly isolated human IELs and to human IEL cell lines derived from CD patients with type II refractory CD (RCDII) - a clinicopathological entity considered an intermediary step between CD and enteropathy-associated T cell lymphoma - depend on the antiapoptotic factors Bcl-2 and/or Bcl-xL. The signals also required IL-15Rbeta, Jak3, and STAT5, but were independent of PI3K, ERK, and STAT3. Consistent with these data, IELs from patients with active CD and RCDII contained increased amounts of Bcl-xL, phospho-Jak3, and phospho-STAT5. Furthermore, incubation of patient duodenal biopsies with a fully humanized human IL-15-specific Ab effectively blocked Jak3 and STAT5 phosphorylation. In addition, treatment with this Ab induced IEL apoptosis and wiped out the massive IEL accumulation in mice overexpressing human IL-15 in their gut epithelium. Together, our results delineate the IL-15-driven survival pathway in human IELs and demonstrate that IL-15 and its downstream effectors are meaningful therapeutic targets in RCDII.
Report of an infant with GM1 gangliosidosis type I and extensive and unusual mongolian spots
Authors: MARC WEISSBLUTH, NANCY B. ESTERLY, WILLIAM A. CARO
Journal: British Journal of Dermatology (1981)

An infant with GM1 gangliosidosis was found to have an eruption at birth consisting of extensive and unusual slate blue macules resembling mongolian spots. All areas of skin were involved except face, scalp, palms, and soles. A biopsy of a macule obtained at 5 months of age demonstrated melanocytic cells in the dermis consistent with monogolian spot but also a perivascular histiocytic infiltrate. At 8 months of age, absence of beta-galactosidase activity was documented in both peripheral leukocytes and skin fibroblasts confirming the diagnosis of GM1 gangliosidosis. The dermal histiocytic cells noted on skin biopsy were interpreted as a manifestation of this storage disease. The coexistence of the hyperpigmented lesions and the heritable enzyme defect was believed to be coincidental.
Operative Strategies in Inflammatory Bowel Disease
Authors: N MORTENSEN
Journal: Gut (2000)

Operative Strategies in Inflammatory Bowel Disease . Edited by Michelassi F, Milsom JW. (Pp 515; illustrated; £114.50.) New York: Springer-Verlag, 1999. ISBN 0 387 94966 6.

I enjoyed looking at this book. The editors' intention is that “at a moment's notice any surgeon may open …
Case of Enterectomy in which Murphy's Button was Used
Authors: D. D. Day
Journal: BMJ (1895)

April 4th.Since the above was written the patient has gained strength and has left the hospital.He is very emaciated and the malignant growth is rapidly increasing, but he has no abdominal pain and no sickness, and takes ordinary food.The: button has probably dropped back into the disused portion of the intestine.
Oncology As a Subspecialty?
Authors: RANDALL N. FAIREY
Journal: Annals of Internal Medicine (1971)

Letters and Comments1 March 1971Oncology As a Subspecialty?RANDALL N. FAIREY, B. SC., M.D.RANDALL N. FAIREY, B. SC., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-3-447_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In an era of increasing corporate medical effort in the treatment of disease, I find it difficult to support the view expressed by Dr. B. J. Kennedy in "Oncology in Medicine" (Ann Intern Med73:637-639, 1970). With skill, and certainly some bias, he has attempted to justify medical oncology as a subspecialty of internal medicine. The picture of the "broadly trained internist with aptitudes in all its subspecialties," the physician with a background in molecular biology and biochemistry, the "expert in the pharmacology of chemotherapeutic drugs and use of isotopes," the internist involved in psychiatric care, and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByMEDICAL ONCOLOGY 1 March 1971Volume 74, Issue 3Page: 447-448KeywordsBiochemistryDrugsMolecular biologyPharmacologySub-specialty care Issue Published: 1 March 1971 PDF DownloadLoading ...
The fragility of the locality assumption: Comparative evidence
Authors: Philip J. Benson
Journal: Behavioral and Brain Sciences (1997)

The locality assumption (LA) seems rather awkward, especially when one considers centres of neuronal specialisation as defined by observed CNS activity. It is clear from electrophysiology that extra-striate functional compartmentalisation (modularity) is rather less well-defined than first thought; neuropsychological assessment attaching significance to varieties of preserved behaviour also reveals that some basic flaws must be inherent in current reasoning supporting LA.
Initiation of Sustained Rhythmic Activity by Single Propagated Action Potentials in Canine Cardiac Purkinje Fibers Exposed to Sodium-Free Solution or to Ouabain
Authors: PAUL F. CRANEFIELD, RONALD S. ARONSON
Journal: Circulation Research (1974)

Canine cardiac Purkinje fibers were exposed to sodium-free solutions containing 128 mM tetraethylammonium chloride and 16.2 mM calcium. Some fibers exposed to these solutions were spontaneously active. Other fibers were quiescent, but they could be thrown into sustained rhythmic activity by a single driven action potential; the sustained activity resulted from the depolarizing phase of an oscillatory after-potential. Premature action potentials often showed prolonged plateaus, and their repolarization continued to a more negative level than that seen during the regular sustained activity. This condition caused a temporary slowing of rhythm and, on rare occasions, a cessation of spontaneous activity. Other canine cardiac Purkinje fibers were exposed to normal Tyrode's solution containing 0.125 mg ouabain/liter. In such fibers driven activity caused progressive loss of resting potential. Concomitant with that loss of resting potential, oscillatory after-potentials appeared. These oscillatory after-potentials sometimes grew into sustained rhythmic activity that occurred at a level of resting potential at which the normal sodium-dependent upstroke was presumably inactivated.
White Phosphorus Dermal Burns
Authors: Johnathan C Conner, Vikhyat S Bebarta
Journal: New England Journal of Medicine (2007)

A 19-year-old man presented with painful burns on his posterior scalp after exposure to an incendiary agent. Smoke emanated from the wounds on removal of the dressing that had been applied during prehospital treatment. The wounds appeared waxy and yellow under natural light (Panel A) and fluorescent under ultraviolet light (i.e., Wood's lamp) (Panel B), consistent with a white phosphorus burn. Remaining particles were brushed off the wound, and the burns were irrigated with copious saline. His pain diminished, but the persistent presence of white phosphorus on examination under ultraviolet light required surgical debridement. White phosphorus is an incendiary agent . . .
Disruption of inhibitory G-proteins mediates a reduction in atrial β-adrenergic signaling by enhancing eNOS expression
Authors: E DANSON, Y ZHANG, C SEARS, A EDWARDS, B CASADEI, D PATERSON
Journal: Cardiovascular Research (2005)

Objective: Cardiac parasympathetic nerve activity is reduced in most cardiovascular disease states, and this may contribute to enhanced cardiac sympathetic responsiveness. Disruption of inhibitory G-proteins (Gi) ablates the cholinergic pathway and increases cardiac endothelial nitric oxide (NO) synthase (eNOS) expression, suggesting that NO may offset the impaired attenuation of β-adrenergic regulation of supraventricular excitability. To test this, we investigated the role of endogenous NO production on β-adrenergic regulation of rate (HR), contraction (CR) and calcium (Ca2+) handling in atria following blockade of Gi-coupled muscarinic receptors.
Abstract 4208: Post-translational modification of E2F1 in malignant melanoma
Authors: Peng Meng, Rita Ghosh
Journal: Cancer Research (2012)

Abstract Malignant melanoma has the highest fatality among all skin cancers. No current treatment significantly enhances survival once metastasis is established. Previous studies have shown that E2F1, a transcription factor, is over-expressed in melanoma cells. However, the mechanism through which E2F1 is elevated remains unknown. E2F1 is known to be involved in many important biological processes, including cell cycle progression, DNA damage, DNA repair, differentiation, development, autophagy and apoptosis. This underscores the importance of E2F1 in carcinogenesis. Normally in late S phase, E2F1 is recognized by the E3 ligase p45 SKP2 and undergoes ubiquitination and finally degradation in 26S proteasome. Our overall hypothesis is that E2F1 escapes proteasomal degradation in melanoma cells due to changes in post-translational modification. In this study we have used melanoma cells of increasing disease progression. Our results show that although the primary melanoma cells have high level of E2F1 message and protein, it is unstable. On the other hand the more metastatic melanoma cells have low levels of E2F1 which is however very stable. Consistent with this result, post-translational modification of E2F1 including the phosphorylation at Serine 337 and the acetylation at Lysine 117 increase with melanoma progression, which suggests that these post-translational modification sites might play an important role in stabilization of E2F1 and keep it functionally active in the more metastatic cell lines. E2F1 knockdown data also shows that E2F1 KD can inhibit cell proliferation in early stage melanoma cells but not in the more metastatic cells, which also suggest that inhibition of post-translational modifications and stability of E2F1 may be a more effective way to inhibit melanoma progression to more advanced stages. Abrogation of acetylation is expected to cause E2F1 protein instability. On the other hand, if acetylation is potentiated, the stabilized E2F1 will continue to promote progression through the cell cycle. We are currently testing whether the ectopic expression of the continuously acetylated E2F1 protein can rescue proliferation inhibition caused by E2F1 down-regulation, and drive metastasis and a mutant E2F1 with abrogated acetylation can block rescue of the proliferation inhibition in the E2F1 down-regulated melanoma cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4208. doi:1538-7445.AM2012-4208
Morphological changes in isolated perfused dog lungs after acute hydrostatic edema.
Authors: D O DeFouw, P B Berendsen
Journal: Circulation Research (1978)

Morphometric data from stable (nonedematous) isolated dog lungs, perfused with nearly cell-free perfusates, were compared to similar stereological evaluations of isolated dog lungs after induction of severe acute hydrostatic edema. In the edematous lungs, capillary surface and volume densities were substantially increased. Alveolar surface density was also increased. Thicknesses of the endothelial and type I epithelial cellular compartments of the air-blood barrier were unchanged. Thickness of the interstitial compartmemt of the air-blood barrier was substantially increased and this, in turn, caused an overall increase in mean thickness of the barrier. Volume densities of the nonparenchymal connective tissue spaces surrounding the extra-alveolar vessels and airways were also increased. In both the endothelial and type I epithelial cells cytoplasmic volume densities of pinocytotic vesicles were increased. In addition, the number of vesicles opening onto the luminal and albuminal cellular surfaces increased signficantly. Transendothelial vesicular passage may contribute to interstitial edema formation, and transepithelial vesicular transport may contribute to alveolar flooding in isolated perfused dog lungs.
Health experts should have higher profile in climate change talks, say campaigners
Authors: R. Watson
Journal: BMJ (2009)

The impact of climate change on human health should be given a higher priority as governments prepare for crucial international negotiations at the end of the year, according to two non-governmental organisations.

The Health and Environment Alliance and Healthcare Without Harm want the European Union to include senior health experts in its delegation to the Copenhagen talks in December.

Pendo Maro, the …
How not to give a presentation
Authors: R. Smith
Journal: BMJ (2000)

that a comparison of apples and oranges is impossible.At first glance, some papers seemed to have addressedthe important topic of a real comparison of apples and oranges.Table 3 reveals the truth.This article, certain to become the classic in the field, clearly demonstrates that apples and oranges are not only comparable; indeed they are quite similar.The admonition "Let's not compare apples with oranges" should be replaced immediately with a more appropriate expression such as "Let's not compare walnuts with elephants" or "Let's not compare tumour necrosis factor with linguini."
STRAIN-RATE BY TISSUE STRAIN IMAGING IS POWERFUL TOOL TO EVALUATE ISCHEMIC DIASTOLIC STUNNING COURSE AFTER REPERFUSED ST-ELEVATION ACUTE CORONARY SYNDROME
Authors: Noriaki Iwahashi, Masami Kosuge, Jun Okuda, Kengo Tsukahara, Yoshio Tahara, Kiyoshi Hibi, Toshiaki Ebina, Shinichi Sumita, Kazuaki Uchino, Toshiyuki Ishikawa, Satoshi Umemura, Kazuo Kimura
Journal: Journal of the American College of Cardiology (2010)
Unusual Case of Adrenal and Renal Metastases From Papillary Carcinoma of Thyroid
Authors: Gaurav Malhotra, Trupti S. Upadhye, Epari Sridhar, Ramesh V. Asopa, Parul S. Garde, Sachin Gawde, Venkatesh Rangarajan
Journal: Clinical Nuclear Medicine (2010)

We report a rare case of adrenal and renal metastases from papillary thyroid carcinoma (PTC). A 30-year-old man underwent total thyroidectomy with left neck dissection for cytology proven nodal metastases from PTC. This was followed by high-dose radioiodine therapy with a dose of 265 mCi (9.805 GBq). Thereafter, patient was lost to follow-up. He presented 2 decades later with low backache radiating to both the lower limbs. Magnetic resonance imaging examination of spine detected left SI joint, dorsal and lumbar vertebral metastases. A whole-body radioiodine scan showed extensive iodine avid foci in thyroid bed, mediastinum, bilateral lungs, liver, bones, and in bilateral lumbar regions. An abdominal single photon emission computed tomography-computed tomography (CT) revealed the lumbar lesions to be within bilateral adrenal glands. Contrast-enhanced CT of abdomen revealed lesions in bilateral adrenals and renal regions suggestive of metastases. A CT-guided biopsy of left adrenal focus confirmed metastasis from the carcinoma of thyroid. A high degree of suspicion with further radiologic and cytologic correlation clinched the diagnosis of both adrenal and renal metastases from PTC, which has been rarely reported. Fortunately, radioiodine concentration in adrenal metastases made them amenable to high-dose radioiodine therapy. Therefore, 225 mCi (8.325 GBq) of radioiodine was administered to this patient. This case is a strong reminder of the fact that regular and long-term follow-up is imperative in the management of thyroid cancer patients.
Cytoprotection by fructose and other ketohexoses during bile salt-induced apoptosis of hepatocytes
Authors: I. M. Zeid, S. F. Bronk, P. J. Fesmier, G. J. Gores
Journal: Hepatology (1997)

Toxic bile salts cause hepatocyte necrosis at high concentrations and apoptosis at lower concentrations. Although fructose prevents bile salt– induced necrosis, the effect of fructose on bile salt–induced apoptosis is unclear. Our aim was to determine if fructose also protects against bile salt–induced apoptosis. Fructose inhibited glycochenodeoxycholate (GCDC)–induced apoptosis in a concentration–dependent manner with a maximum inhibition of 72% ± 10% at 10 mmol/L. First, we determined if fructose inhibited apoptosis by decreasing adenosine triphosphate (ATP) and intracellular pH (pHi). Although fructose decreased ATP to &lt;25% of basal values, oligomycin (an ATP synthase inhibitor) did not inhibit apoptosis despite decreasing ATP to similar values. Fructose (10 mmol/L) decreased intracellular pH (pHi) by 0.2 U. However, extracellular acidification (pH 6.8), which decreased hepatocyte pHi 0.35 U and is known to inhibit necrosis, actually potentiated apoptosis 1.6–fold. Fructose cytoprotection also could not be explained by induction of bcl–2 transcription or metal chelation. Because we could not attribute fructose cytoprotection to metabolic effects, alterations in the expression of bcl–2, or metal chelation, we next determined if the poorly metabolized ketohexoses, tagatose and sorbose, also inhibited apoptosis; unexpectedly, both ketohexoses inhibited apoptosis. Because bile salt–induced apoptosis and necrosis are inhibited by fructose, these data suggest that similar processes initiate bile salt–induced hepatocyte necrosis and apoptosis. In contrast, acidosis, which inhibits necrosis, potentiates apoptosis. Thus, ketohexose–sensitive pathways appear to initiate both bile salt–induced cell apoptosis and necrosis, whereas dissimilar, pH–sensitive, effector mechanisms execute these two different cell death processes.
Abstract 3142: Abnormal expression of the ALK protein in ovarian carcinoma is associated with low copy number amplification of the 2p23 locus
Authors: Patricia Merkel, Barbara Grubinska, Allison Drew, Stephen J. Szilvassy, Tibor Gyuris, Kim Merriam, Kim Tsui, James Rottman, Alex Parker, Rachael Brake
Journal: Cancer Research (2010)

Abstract Anaplastic lymphoma kinase (ALK) is predominantly expressed in the brain and spinal cord during neonatal development and is subsequently down-regulated in the adult. In cancer, ALK is ectopically expressed as a consequence of one of several different cytogenetic translocations or inversions that lead to the expression of an oligomerized, constitutively active, intracellular tyrosine kinase. The resulting fusion protein has been identified in anaplastic large cell lymphomas, non small cell lung carcinomas and more recently breast and colorectal carcinomas. Preclinical data convincingly demonstrates that fusion transcripts can drive tumorigenesis and inhibition of ALK in vitro and in vivo leads to inhibition of cellular growth. Full length (fl) ALK is also expressed in a variety of other tumor types, and recent data suggest that at least in neuroblastoma, the flALK transcript contains activating point mutations in the tyrosine kinase domain. These data suggest that flALK may also be a therapeutic target in cancer. Here we demonstrate that a significant subset of ovarian carcinoma cell lines and biopsy specimens aberrantly express ALK. Gene expression analysis in 126 ovarian carcinoma samples demonstrated a prevalence of ALK expression of 19%. Analysis of the histological subtypes within this study, showed specific enrichment of ALK transcript in papillary ovarian carcinoma (15 of 42 samples). This subtype showed a range of ALK expression between 2 - 4 fold increase above normal ovarian tissue. We have also confirmed that in a subset of ovarian tumor cell lines and primary tumor samples that ALK transcript is converted into ALK protein. DNA sequence analysis has revealed that in these patient samples and cell lines, ALK is predominantly wild type. Single nucleotide polymorphism (SNP) analysis and fluorescent in situ hybridization (FISH) suggest that over expression may occur as a consequence of low copy number amplification. These preliminary findings suggest that ALK expression in cancer has now been observed in ovarian carcinomas by a mechanism distinct from cytogenetic translocations or inversions. Currently, we are attempting to correlate the aberrant expression of ALK with ovarian cancer prognosis as well as understand the value of inhibiting ALK expression in this cell type. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3142.
A Case of Sarcoma of the Brain Removed by Operation: Subsequent Operation for Removal of A Second Tumour: Recovery
Authors: J. M. Clarke, R. G. P. Lansdown
Journal: BMJ (1901)

History of Present Illnew.-Thepatient first presented herself for treatment in April, igoo.She was then suffering from a very severe attack of pain in the right hypochondrium, with much vomiting, cold perspiration, and general collapse.Her general condition was unmatisfactory, she was in failing health, she had lost considerably in weight, and there was swelling of the legs and abdomen.The skin was sallow, with a slight tinge of jaundice.Her condition of general debility was steadily getting worse.A physical examination showed the liver to be enlarged, and the gall bladder could be felt as a hard mass well defined, about 2 inches wide and 3 inches long, trending towards the umbilicus.The mass was tender on palpation, and painful after any exertion.In June and July the swelling gradually increased, and the mass extended over a larger area, approaching nearer to the umbilicus.A little later tlle tumnour gave a sensation of fluctuation, and became less definite in outline, but more obvious on inspection.The diagnosis arrived at by Dr.Fry wvas gall stones, with malignant disease of the gall bladder and surrouinding parts.His diagnosis was strengthened by the fact that the patient was steadily losing ground.About the middle of July there seeTned to be a sudden and considerable decrease in size of the tumour, with somle relief and temporary imnprovemiient.Dr. Fry then advised the patient to see Mr. Mayo Robson, with a view to operation.A namnesis.-Onexamination on July 28tlt, a very distinct tumour could be felt beneath the right costal margin adherent to the parietes, wliichl was thought to be the distended gall bladder acutely inflameid and suppurating.As it couild not be said definitely that there was malignant disease opelation was advised without delay.Since the stomach was dilated stenosis of the pylorus was thouglht to be present, due either to adlhesions or to independent growth.Operation.-OnAugust gth, a vertical incision tlhrough the upper part of the right rectus was imade down to the gall bladder, ;and a dense mass of adhesions was at once encountered.An abscess was found in the ohlieath of the rectus; this was cleared out anid purified as far as possible.The gall bladder, which was very much thickened and bound down to the liver, was opened, and some thick purulent discharge escaped, general soiliig of the peritoneum being prevented by packing sponges atll round the'site of operation.A large stone was removed from the gall bladdei and another from the cystic duct.A fistulalwas found betweenthe gall