tbuckley/cabot-search huggingface dataset:
Deep Hypothermia and Surgical Treatment of Intracranial Aneurysms
Authors: Alfred Uihlein
Journal: JAMA (1966)

Sixty-six patients having 67 intracranial aneurysms underwent operation by induced deep hypothermia and extracorporeal circulation by either the open-chest or the closed-chest method at the Mayo Clinic in a five-year period, 1960 to 1965. One patient was killed by her demented husband and 15 patients died of unsuccessful operation. Factors unrelated to the extracorporeal circulation technique per se contributed to death in more than half of the cases. Deletion of these reduced the overall mortality to about 14.5%. The increased operating time required by deep hypothermia and circulatory arrest did not appear to increase the postoperative complications. Alteration in blood-clotting characteristics constituted the major deterrent to deep hypothermia. The closed-chest method of perfusion is preferable.
Estrogenic Regulation of Growth and Polypeptide Growth Factor Secretion in Human Breast Carcinoma
Authors: ROBERT B. DICKSON, MARC E. LIPPMAN
Journal: Endocrine Reviews (1987)

HORMONAL influences on cancer cell proliferation have recently received much attention with the proposal of autocrine or self-stimulating polypeptide growth factors (1). The growth of several types of cancer has long been known to be under endocrine control by steroid hormones: leukemia, prostate carcinoma, endometrial carcinoma, and breast carcinoma. The present article will summarize what is known at present concerning the possible interaction of steroidal endocrine and polypeptide autocrine and paracrine regulators in control of human breast cancer growth. Breast cancer is notable among the above mentioned cancers in that its growth is dependent upon estrogenic hormones in about one-third of clinical cases and can be inhibited by antiestrogenic antagonists (2). The frequency of breast cancer in women who never had functional ovaries is only 1% that in women with intact ovaries. Thus estrogens are involved, at least initially, in nearly all breast cancers.
Asteatotic eczema (‘eczema craquelé’) with histopathological interface dermatitis: a new cutaneous reaction following pemetrexed
Authors: E. Frouin, G. Sebille, S. Freudenberger, B. Menecier, E. Quoix, B. Cribier, D. Lipsker
Journal: British Journal of Dermatology (2011)
Stimulation of human neutrophils by soluble and insoluble immunoglobulin aggregates. Secretion of granule constituents and increased oxidation of glucose.
Authors: P M Henson, Z G Oades
Journal: Journal of Clinical Investigation (1975)

Reaction of human neutrophils with aggregated immunoglobulin on nonphagocytosable surfaces results in secretion of granule enzymes (exocytosis of granules) and stimulation of glucose oxidation by the nexose monophosphate pathway (HMP). The role of HMP stimulation in the enzyme secretion and some requirements for the two neutrophil activities have been examined. It was found that (a) HMP stimulation could be selectively inhibited under conditions where release of granule enzymes remained unchanged or was enhanced, for example, by reduced glucose concentration or by 2-deoxyglucose. (b) Removal of Ca++ and addition of agents which increased the intracellular levels of cyclic AMP (cAMP), however, prevented both activities, while colchicine had greater inhibitory activity on HMP stimulation than upon secretion. (c) Neutrophils incubated in suspension with particulate aggregated gamma-globulin phagocytosed the particles and exhibited a stimulated HMP and released granule enzymes. In contrast, incubation in suspension with soluble aggregated gamma-globulin resulted in the stimulated HMP only. Granule evzymes were not liberated. 300-fold less soluble aggregates bound to a surface, however readily induced exocytosis of granules from adherent neutrophils. This demonstrates the importance of surface effects in the induction of secretion from neutrophils. Aggregated immunoglobulin reacting with neutrophil Fc receptors thus induces both degranulation (exocytosis) and increased HMP activity. The pathways leading to these events are separable although apparently sharing some common steps, including the initiating events.
Cancer: tilting at windmills?
Authors: Prakash Kulkarni, Takumi Shiraishi, Rahul V Kulkarni
Journal: Molecular Cancer (2013)

One of the striking characteristics of cancer cells is their phenotypic diversity and ability to switch phenotypes in response to environmental fluctuations. Such phenotypic changes (e.g. from drug-sensitive to drug-resistant), which are critical for survival and proliferation, are widely believed to arise due to mutations in the cancer cell's genome. However, there is growing concern that such a deterministic view is not entirely consistent with multiple lines of evidence which indicate that cancer can arise in the absence of mutations and can even be reversed to normalcy despite the mutations. In this Commentary, we wish to present an alternate view that highlights how stochasticity in protein interaction networks (PINs) may play a key role in cancer initiation and progression. We highlight the potential role of intrinsically disordered proteins (IDPs) and submit that targeting IDPs can lead to new insights and treatment protocols for cancer.
Early Trough Levels and Antibodies to Infliximab Predict Safety and Success of Reinitiation of Infliximab Therapy
Authors: Filip Baert, David Drobne, Ann Gils, Niels Vande Casteele, Scott Hauenstein, Sharat Singh, Steve Lockton, Paul Rutgeerts, Séverine Vermeire
Journal: Clinical Gastroenterology and Hepatology (2014)
Survival of trauma patients who have prehospital tracheal intubation without anaesthesia or muscle relaxants: observational study
Authors: D. Lockey, G. Davies, T. Coats
Journal: BMJ (2001)

In the United Kingdom, it is current practice for paramedics to perform tracheal intubation on trauma patients when the airway is compromised and basic airway manoeuvres have failed.Paramedics in Britain never use anaesthetic drugs or muscle relaxants to achieve intubation.Anecdotal experience shows that patients who can be intubated without the use of drugs have a poor prognosis.We investigated mortality in a population of trauma patients who were intubated before reaching hospital without anaesthetic drugs being used.
LOW-MOLECULAR-WEIGHT HEPARIN IN EXTRACORPOREAL CIRCULATION
Authors: S. Massonnet-Castel, E. Pelissier, G. Dreyfus, A. Deloche, B. Abry, P. Guibourt, E. Terrier, J. Passelecq, B. Jaulmes, A. Carpentier
Journal: The Lancet (1984)
Angiotensin II downregulates the fatty acid oxidation pathway in adult rat cardiomyocytes via release of tumour necrosis factor-α
Authors: Corinne Pellieux, Christophe Montessuit, Irène Papageorgiou, René Lerch
Journal: Cardiovascular Research (2009)

Advanced heart failure is often associated with reduced myocardial fatty acid oxidation capacity. We have previously observed that failing hearts of mice with overexpression of angiotensinogen in the myocardium exhibit marked reduction of key regulatory proteins of fatty acid oxidation. In the present study, we determined whether exposure of adult rat cardiac (ARC) myocytes to angiotensin II (Ang II) influences expression of fatty acid translocase, muscle-type carnitine palmitoyl transferase-I, and medium-chain acyl-CoA dehydrogenase.Ang II reduced mRNA expression of the three regulatory proteins in ARC myocytes during the entire 14-days culture period. However, protein expression and palmitate oxidation rate remained unaltered for 7 days, but subsequently markedly decreased. The decrease of protein expression and of fatty acid oxidation coincided with the onset of increased protein expression of tumour necrosis factor-alpha (TNF-alpha). The effect of Ang II was completely abolished by either blocking TNF-alpha formation through inhibition of reactive oxygen species-mediated activation of nuclear factor-kappaB or by neutralizing TNF-alpha with a specific antibody. Activation of peroxisome proliferator-activated receptor-alpha (PPARalpha) and PPARbeta/delta counteracted Ang II-mediated reduction of the fatty acid oxidation pathway.Prolonged exposure of cardiac myocytes to Ang II elicits downregulation of the fatty acid oxidation pathway mediated by enhanced synthesis of TNF-alpha.
Intraperitoneal Chemotherapy With Cisplatin and Melphalan
Authors: M. J. Piccart, J. Abrams, P. F. Dodion, N. Crespeigne, J. P. Sculier, J. C. Pector, C. Finet, C. Nouwijnck, H. Bondue, G. Atassi, Y. Kenis
Journal: JNCI Journal of the National Cancer Institute (1988)

Cisplatin and melphalan given ip exert a synergistic therapeutic effect against ascitic P388 leukemia in mice and have different dose-limiting toxic effects as well as favorable pharmacokinetic characteristics in ip phase I studies. We gave a total of 98 courses of cisplatin (escalated from 40 to 120 mg/m2) and melphalan (escalated from 12 to 30 mg/m2) to 30 patients with ip tumors, most of whom had residual ovarian cancer following iv cisplatin-containing regimens. Treatment was delivered in 2 L of 0.9% NaCl through a Tenckhoff catheter with or without a Port-a-Cath system every 28 days for one to nine cycles. Myelosuppression was dose-related and leukopenia was dose-limiting. The maximum tolerated dose was 120 mg of cisplatin/m2 and 20 mg of melphalan/m2. With the exception of treatment-induced nausea and vomiting, nonhematologic toxic effects were mild and no (or very little) local toxicity occurred. Pharmacokinetic analyses showed that the areas under the peritoneal concentration versus time curve averaged 16-fold and 17-fold more than the area under the plasma curve for cisplatin and melphalan, respectively. Objective responses were documented by third-look laparotomy in ovarian cancer patients with minimal (less than 2 cm) residual disease.
<i>DR5</i> Receptor Mediates Anoikis in Human Colorectal Carcinoma Cell Lines
Authors: Luciana M. Laguinge, Raed N. Samara, Wenge Wang, Wafik S. El-Deiry, Georgia Corner, Leonard Augenlicht, Lopa Mishra, J. Milburn Jessup
Journal: Cancer Research (2008)

Abstract As human colorectal cancer (CRC) cells metastasize to distant sites, they are susceptible to detachment-induced cell death or anoikis — a form of apoptosis that occurs when anchorage-dependent CRC cells go into suspension. Our goal was to identify whether tumor necrosis factor receptor apoptosis-inducing ligand (TRAIL) receptors mediate anoikis in human CRC cells. First, we assessed whether caspases of the extrinsic (caspase-8) or intrinsic (caspase-9) death pathways were involved. Caspase-8 was cleaved during exposure to suspension culture in four CRC lines, and cell death was inhibited by caspase-3 and caspase-8 inhibitors but not by a caspase-9 inhibitor. Gene transcripts in macrophage inflammatory protein-101 (MIP-110), a weakly metastatic human CRC, were increased at least 2-fold for TRAIL-R2 (DR5) and TRAIL after 24 h of suspension culture compared with cells in monolayer culture. The increased expression of DR5 was confirmed at the protein level at 24 h, and exposure of MIP-101 cells to an antagonistic antibody to DR5 decreased caspase-8 activation. The antagonistic antibody to DR5 inhibited anoikis in four human CRC lines. Treatment with an antagonistic DR4 antibody or a neutralizing antibody to TRAIL ligand did not reduce anoikis consistently. Knockdown of DR5 or TRAIL also inhibited anoikis, whereas exogenous TRAIL or FasL did not consistently increase anoikis. In summary, DR5 receptor mediates death signals for anoikis in human CRC cells through the extrinsic apoptotic pathway. [Cancer Res 2008;68(3):909–17]
Intramural distribution of regulatory peptides in the sigmoid-recto-anal region of the human gut.
Authors: G L Ferri, T E Adrian, J M Allen, L Soimero, A Cancellieri, J C Yeats, M Blank, J M Polak, S R Bloom
Journal: Gut (1988)

The distribution of regulatory peptides was studied in the separated mucosa, submucosa and muscularis externa taken at 10 sampling sites encompassing the whole human sigmoid colon (five sites), rectum (two sites), and anal canal (three sites). Consistently high concentrations of VIP were measured in the muscle layer at most sites (proximal sigmoid: 286 (16) pmol/g, upper rectum: 269 (17), a moderate decrease being found in the distal smooth sphincter (151 (30) pmol/g). Values are expressed as mean (SE). Conversely, substance P concentrations showed an obvious decline in the recto-anal muscle (mid sigmoid: 19 (2.0) pmol/g, distal rectum: 7.1 (1.3), upper anal canal: 1.6 (0.6)). Somatostatin was mainly present in the sigmoid mucosa and submucosa (37 (9.3) and 15 (3.5) pmol/g, respectively) and showed low, but consistent concentrations in the muscle (mid sigmoid: 2.2 (0.7) pmol/g, upper anal canal: 1.5 (0.8]. Starting in the distal sigmoid colon, a distinct peak of tissue NPY was revealed, which was most striking in the muscle (of mid sigmoid: 16 (3.9) pmol/g, upper rectum: 47 (7.8), anal sphincter: 58 (14)). Peptide YY was confined to the mucosa and showed an earlier peak (upper sigmoid: 709 (186) pmol/g, mid-distal sigmoid: 1965 (484)). A clear differential distribution of regulatory peptides was thus shown in the region studied. A possible role is suggested for NPY and VIP containing nerves in the effector control of the human internal anal sphincter.
Natural Killer Cell-Mediated Killing of Freshly Isolated Neuroblastoma Cells
Authors: Roberta Castriconi, Alessandra Dondero, Maria Valeria Corrias, Edoardo Lanino, Daniela Pende, Lorenzo Moretta, Cristina Bottino, Alessandro Moretta
Journal: Cancer Research (2004)

Abstract In the present study, we assessed the susceptibility of freshly isolated neuroblastoma cells to killing mediated by normal human natural killer (NK) cells and analyzed the receptor–ligand interactions that regulate this event. We show that killing of freshly isolated neuroblasts, similar to neuroblastoma cell lines, involves NKp46 and NKp30 (natural cytotoxicity receptors). However, freshly isolated neuroblasts were generally more resistant to NK-mediated lysis than conventional neuroblastoma cell lines. Moreover, a significant heterogeneity in susceptibility to lysis existed among neuroblastomas derived from different patients. Remarkably, susceptibility to lysis directly correlated with the surface expression, on neuroblasts, of poliovirus receptor [PVR (CD155)], a ligand for the DNAX accessory molecule-1 [DNAM-1 (CD226)] triggering receptor expressed by NK cells. Indeed, PVR-expressing neuroblastomas were efficiently killed by NK cells. Moreover, monoclonal antibody-mediated masking of either DNAM-1 (on NK cells) or PVR (on neuroblasts) resulted in strong inhibition of tumor cell lysis. Thus, assessment of the PVR surface levels may represent a novel useful criterion to predict the susceptibility/resistance of neuroblastomas to NK-mediated killing.
Inhibition of H3K27 histone trimethylation activates fibroblasts and induces fibrosis
Authors: Marlene Krämer, Clara Dees, Jingang Huang, Inga Schlottmann, Katrin Palumbo-Zerr, Pawel Zerr, Kolja Gelse, Christian Beyer, Alfiya Distler, Victor E Marquez, Oliver Distler, Georg Schett, Jörg H W Distler
Journal: Annals of the Rheumatic Diseases (2012)

Objectives Epigenetic modifications such as DNA methylation and histone acetylation have been implicated in the pathogenesis of systemic sclerosis. However, histone methylation has not been investigated so far. We therefore aimed to evaluate the role of the trimethylation of histone H3 on lysine 27 (H3K27me3) on fibroblast activation and fibrosis. Methods H3K27me3 was inhibited by 3-deazaneplanocin A (DZNep) in cultured fibroblasts and in two murine models of dermal fibrosis. Fibrosis was analysed by assessment of the dermal thickening, determination of the hydroxyproline content and by quantification of the numbers of myofibroblasts. The expression of fos-related antigen 2 (fra-2) was assessed by real-time PCR, western blot and immunohistochemistry and modulated by siRNA. Results Inhibition of H3K27me3 stimulated the release of collagen in cultured fibroblasts in a time and dose-dependent manner. Treatment with DZNep exacerbated fibrosis induced by bleomycin or by overexpression of a constitutively active transforming growth factor β receptor type I. Moreover, treatment with DZNep alone was sufficient to induce fibrosis. Inhibition of H3K27me3 induced the expression of the profibrotic transcription factor fra-2 in vitro and in vivo. Knockdown of fra-2 completely prevented the profibrotic effects of DZNep. Conclusions These data demonstrate a novel role of H3 Lys27 histone methylation in fibrosis. In contrast to other epigenetic modifications such as DNA methylation and histone acetylation, H3 Lys27 histone methylation acts as a negative regulator of fibroblast activation in vitro and in vivo by repressing the expression of fra-2.
A phase II monocentric study of oxaliplatin in combination with gemcitabine (GEMOX) in patients with advanced/metastatic transitional cell carcinoma (TCC) of the urothelial tract
Authors: C. Theodore, F. Bidault, N. Bouvet-Forteau, M. Abdelatif, K. Fizazi, M. di Palma, P. Wibault, R. de Crevoisier, A. Laplanche
Journal: Annals of Oncology (2006)
Gene expression pattern of laser microdissected colonic crypts of adenomas with low grade dysplasia
Authors: S Lechner
Journal: Gut (2003)

<b>Background and aims:</b> Colorectal epithelial cells are prone to malignant transformation. Therefore, identification of differences in gene expression in the process from normal colonic crypts to adenomas with low grade dysplasia is essential for further insights into early tumorigenesis. To achieve this goal, a novel gene expression analysis strategy, screening for expressed transcripts in small histologically defined tissue samples, was performed. <b>Methods:</b> First, laser mediated microdissection was used to isolate normal and adenomatous crypts from colonic cryosections. Then, nested RNA arbitrarily primed polymerase chain reaction (RAP-PCR) for differential display was performed to screen mRNA populations and to generate hybridisation probes for cDNA expression arrays. After evaluation of cDNA expression arrays, differential expression was confirmed at the protein level by immunohistochemistry. <b>Results:</b> Evaluation of gene expression profiles of normal versus adenomatous colonic crypts of six different patients revealed, in general, dysregulation of up to 11% of all analysed genes (total number n=588): specifically, p21-rac1 was upregulated in four of six patients, mitogen activated protein kinase (MAPK) p38α in three of six patients, and interferon γ receptor in three of six patients. Conversely, FAST kinase was found to be downregulated in three of six patients, p53 in three of six patients, and thrombospondin 2 in three of six patients. <b>Conclusions:</b> For the first time, distinct gene expression profiles of dysplastic areas within colonic adenomas, using the combination of laser mediated microdissection with RAP-PCR and cDNA expression array, were shown. In these samples, upregulation of proliferation associated genes (ras-oncogene related p21-rac1 and MAPK p38α) as well as downregulation of apoptosis related genes (FAST kinase and p53) most likely reflects specific alterations in adenomas with low grade dysplasia. Based on upregulation of p21-rac1 and MAPK p38α, activation of the MAPK pathway appears to be an early event in colonic carcinogenesis.
Mimicry of Pre–B Cell Receptor Signaling by Activation of the Tyrosine Kinase Blk
Authors: Theresa Tretter, Ashley E. Ross, Dominic I. Dordai, Stephen Desiderio
Journal: The Journal of Experimental Medicine (2003)

During B lymphoid ontogeny, assembly of the pre–B cell receptor (BCR) is a principal developmental checkpoint at which several Src-related kinases may play redundant roles. Here the Src-related kinase Blk is shown to effect functions associated with the pre-BCR. B lymphoid expression of an active Blk mutant caused proliferation of B progenitor cells and enhanced responsiveness of these cells to interleukin 7. In mice lacking a functional pre-BCR, active Blk supported maturation beyond the pro–B cell stage, suppressed VH to DJH rearrangement, relieved selection for productive heavy chain rearrangement, and stimulated κ rearrangement. These alterations were accompanied by tyrosine phosphorylation of immunoglobulin β and Syk, as well as changes in gene expression consistent with developmental maturation. Thus, sustained activation of Blk induces responses normally associated with the pre-BCR.
Spontaneous preterm birth and small for gestational age infants in women who stop smoking early in pregnancy: prospective cohort study
Authors: L. M E McCowan, G. A Dekker, E. Chan, A. Stewart, L. C Chappell, M. Hunter, R. Moss-Morris, R. A North
Journal: BMJ (2009)

<b>Objectives</b> To compare pregnancy outcomes between women who stopped smoking in early pregnancy and those who either did not smoke in pregnancy or continued to smoke. <b>Design</b> Prospective cohort study. <b>Setting</b> Auckland, New Zealand and Adelaide, Australia. <b>Participants</b> 2504 nulliparous women participating in the Screening for Pregnancy Endpoints (SCOPE) study grouped by maternal smoking status at 15 (±1) week’s gestation. <b>Main outcome measures</b> Spontaneous preterm birth and small for gestational age infants (birth weight &lt;10th customised centile). We compared odds of these outcomes between stopped smokers and non-smokers, and between current smokers and stopped smokers, using logistic regression, adjusting for demographic and clinical risk factors. <b>Results</b> 80% (n=1992) of women were non-smokers, 10% (n=261) had stopped smoking, and 10% (n=251) were current smokers. We noted no differences in rates of spontaneous preterm birth (4%, n=88 <i>v</i> 4%, n=10; adjusted odds ratio 1.03, 95% confidence interval l0.49 to 2.18; P=0.66) or small for gestational age infants (10%, n=195 <i>v</i> 10%, n=27; 1.06, 0.67 to 1.68; P=0.8) between non-smokers and stopped smokers. Current smokers had higher rates of spontaneous preterm birth (10%, n=25 <i>v</i> 4%, n=10; 3.21, 1.42 to 7.23; P=0.006) and small for gestational age infants (17%, n=42 <i>v</i> 10%, n=27; 1.76, 1.03 to 3.02; P=0.03) than stopped smokers. <b>Conclusion</b> In women who stopped smoking before 15 weeks’ gestation, rates of spontaneous preterm birth and small for gestational age infants did not differ from those in non-smokers, indicating that these severe adverse effects of smoking may be reversible if smoking is stopped early in pregnancy.
Detecting non-neutral heterogeneity across a region of DNA sequence in the ratio of polymorphism to divergence
Authors: J. H. McDonald
Journal: Molecular Biology and Evolution (1996)

Natural selection, in the form of balancing selection or selective sweeps, can result in a decoupling of the amounts of molecular polymorphism and divergence. Thus natural selection can cause some areas of DNA sequence to have greater silent polymorphism, relative to divergence between species, than other areas. It would be useful to have a statistical test for heterogeneity in the polymorphism to divergence ratio across a region of DNA sequence, one that could identify heterogeneity greater than that expected from the neutral processes of mutation, drift, and recombination. The only currently available test requires that a region be arbitrarily divided into sections that are compared with each other, and the subjectivity of this division could be problematic. Here a test is proposed in which runs of polymorphic and fixed sites are counted, where a "run" is a set of one or more sites of one type preceded and followed by the other type. The number of runs is smaller than otherwise expected if polymorphisms are clumped together. By simulating neutral evolution and comparing the observed number of runs to the simulations, a statistical test is possible which does not require any a priori decisions about subdivision.