tbuckley/cabot-search huggingface dataset:
Training in advanced trauma life support is unnecessary for all senior house officers in accident and emergency
Authors: J W. S Tice
Journal: BMJ (1998)

EDITOR—Price and Hughes's proposition that all senior house officers should be trained in advanced trauma life support before working in accident and emergency1 fails to tackle the fundamental problems in trauma care in the United Kingdom. Of course senior house officers in accident and emergency must be familiar with advanced trauma life support and be capable of initiating the management of a multiply injured patient, but they cannot and should not be expected to be an expert …
Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS: Results from the nordic NMDSG08A phase II trial
Authors: M Tobiasson, I Dybedahl, M S Holm, M Karimi, L Brandefors, H Garelius, M Grövdal, I Högh-Dufva, K Grønbæk, M Jansson, C Marcher, L Nilsson, A O Kittang, A Porwit, L Saft, L Möllgård, E Hellström-Lindberg
Journal: Blood Cancer Journal (2014)

This prospective phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for >8 weeks and a transfusion need of 4 units over 8 weeks were included. Aza 75 mg m(-2) d(-1), 5/28 days, was given for six cycles; non-responding patients received another three cycles combined with Epo 60 000 units per week. Primary end point was transfusion independence (TI). All patients underwent targeted mutational screen for 42 candidate genes. Thirty enrolled patients received one cycle of Aza. Ten patients discontinued the study early, 7 due to adverse events including 2 deaths. Thirty-eight serious adverse events were reported, the most common being infection. Five patients achieved TI after six cycles and one after Aza+Epo, giving a total response rate of 20%. Mutational screening revealed a high frequency of recurrent mutations. Although no single mutation predicted for response, SF3A1 (n=3) and DNMT3A (n=4) were only observed in non-responders. We conclude that Aza can induce TI in severely anemic MDS patients, but efficacy is limited, toxicity substantial and most responses of short duration. This treatment cannot be generally recommended in lower-risk MDS. Mutational screening revealed a high frequency of mutations.
Intensive chemotherapy with cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation for relapsed Hodgkin's disease.
Authors: D E Reece, M J Barnett, J M Connors, R N Fairey, J W Fay, J P Greer, G P Herzig, R H Herzig, H G Klingemann, C F LeMaistre
Journal: Journal of Clinical Oncology (1991)

Fifty-six consecutive patients with advanced Hodgkin's disease considered incurable with further conventional chemotherapy were entered into a protocol that included high-dose cyclophosphamide (7.2 g/m2), carmustine (BCNU; 0.6 g/m2), and etoposide (VP16-213; 2.4 g/m2) (CBV) followed by autologous bone marrow transplantation (BMT). Prior combination chemotherapy had failed in all the patients, and all but five had been previously treated with both mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and doxorubicin, bleomycin, and vinblastine with or without dacarbazine (ABV[D]). Thirty-four eligible patients received short-course conventional chemotherapy and/or involved-field radiotherapy before CBV. However, formal restaging was not performed after these conventional therapies; ie, the therapies were not used to select responding patients for transplantation, and all who received such therapy subsequently received CBV and autologous marrow grafts. Forty-four patients (80%; 95% confidence interval [CI], 69% to 91%) achieved a complete response after CBV and BMT. Performance status at protocol entry and the use of conventional cytoreduction therapy before CBV correlated with response. Median follow-up is now 3.5 years (range, 2.5 to 5.0 years). Kaplan-Meier estimates for overall and event-free survival 5 years after transplant are 53% (95% CI, 37% to 67%) and 47% (95% CI, 33% to 60%), respectively. In a univariate analysis, patients with a normal performance status and those without constitutional ("B") symptoms at protocol entry had an improved overall and event-free survival. In a multivariate analysis, only a normal performance status remained significant. Disease progression occurred in 17 patients at an actuarial rate of 39% (95% CI; 26% to 56%) and occurred at previous sites of active disease in all but one patient; our analysis did not identify prognostic factors for progression. Toxic deaths, caused by either neutropenic sepsis or interstitial pneumonitis (IP), occurred in 12 patients (21%; 95% CI, 10% to 32%). CBV with autologous marrow support can produce durable remissions in a substantial number of patients with Hodgkin's disease considered incurable with conventional measures. Regimen refinements may even further improve the therapeutic index of BMT in this malignancy.
A Quantitative Trait Locus (LSq-1) on Mouse Chromosome 7 Is Linked to the Absence of Tissue Loss After Surgical Hindlimb Ischemia
Authors: Ayotunde O. Dokun, Sehoon Keum, Surovi Hazarika, Yongjun Li, Gregory M. Lamonte, Ferrin Wheeler, Douglas A. Marchuk, Brian H. Annex
Journal: Circulation (2008)

Peripheral arterial disease (PAD) caused by occlusive atherosclerosis of the lower extremity has 2 major clinical manifestations. Critical limb ischemia is characterized by rest pain and/or tissue loss and has a > or = 40% risk of death and major amputation. Intermittent claudication causes pain on walking, has no tissue loss, and has amputation plus mortality rates of 2% to 4% per year. Progression from claudication to limb ischemia is infrequent. Risk factors in most PAD patients overlap. Thus, we hypothesized that genetic variations may be linked to presence or absence of tissue loss in PAD.Hindlimb ischemia (murine model of PAD) was induced in C57BL/6, BALB/c, C57BL/6 x BALB/c (F1), F1 x BALB/c (N2), A/J, and C57BL/6J-Chr7(A/J)/NaJ chromosome substitution strains. Mice were monitored for perfusion recovery and tissue necrosis. Genome-wide scanning with polymorphic markers across the 19 murine autosomes was performed on the N2 mice. Greater tissue loss and poorer perfusion recovery occurred in BALB/c than in the C57BL/6 strain. Analysis of 105 N2 progeny identified a single quantitative trait locus on chromosome 7 that exhibited significant linkage to both tissue necrosis and extent of perfusion recovery. Using the appropriate chromosome substitution strain, we demonstrate that C57BL/6-derived chromosome 7 is required for tissue preservation.We have identified a quantitative trait locus on murine chromosome 7 (LSq-1) that is associated with the absence of tissue loss in a preclinical model of PAD and may be useful in identifying gene(s) that influence PAD in humans.
Polymorphism in anti-phosphocholine antibodies reflecting evolution of immunoglobulin families.
Authors: S H Clarke, J L Claflin, M Potter, S Rudikoff
Journal: The Journal of Experimental Medicine (1983)

Complete variable (V) region amino acid sequences were determined for four heavy (H) and one light (L) chain from C57BL phosphocholine (PC)-binding monoclonal antibodies. Additional NH2-terminal sequences were obtained from H and L chains of C57BL and CBA/J origin. When these V regions were compared with previously reported anti-PC sequences, a number of observations could be made regarding the function and evolution of L and H chain segments used in these antibodies. (a) L and H chain V segments are remarkably conserved in these inbred strains, although there has been an accumulation of point mutations identifying apparently allelic forms of VK and VH. (b) Mice of each genotype use the same three VK segments in combination with a single VH segment to produce most anti-PC antibodies. An exception has been noted that indicates the occasional use of a second VH gene segment. (c) Multiple, different DH regions are used by mice of each strain, which suggests that the DH segment sequence plays no critical role in either antigen binding or VH-VL pairing. Furthermore, the DH segments and their corresponding gene families appear to be highly conserved in the inbred strains studied. (d) Most PC-binding antibodies use the JH1 joining segment. All JH1 sequences from C57BL mice differ from the BALB/c JH1 at position 105, which identifies allelic forms of the JH1 region. These studies are a first assessment of the nature of mutational events associated with the evolution of specific multigene immunoglobulin families and indicate that homologous VH, DH, JH, VK, and JK genes are similarly assembled and expressed in PC antibodies from three diverse genotypes.
SALICYLIC IONIZATION IN ACUTE PERICARDITIS
Authors: J. S. Mackintosh
Journal: BMJ (1913)

T BI, TISH 1205 was not detected in the routinie examiinationi of the urine, aind the diagnosis was only made p)ost miorkite.Highl arterial tensioln and conlsequeent clhanlg-es in lhcart anid arteries lhave usually been present in tllese cases, aud lave been reaaided by soImie as constant.They were not recognizable in a case recorded recently, ancd in Cases I and II above tlhey -were not present to any appreciable deglree clinically, in spite of tlle fact that they were care- fully souglht for.There were somiie signs of retinal changes in Case i, and-microseopically the walls of the aLterioles of the kiidneys were distinctly tlhiclkened; but considerilng the extremiie degree of fibrosis of the kidneys alndl tfliir minuilte size, in conjuinction witlh tlle coini- paratively lona duration of the symptoms, any clhanges plCselst would seemi unaccountably slighit.Dr. Sawyer 4 suggests one year as ali average duration of symiiptolmis in simililar cases, and notes tlhree years in the exceptionally lolnger ones; buit this boy had obvious symiiptoms, whlich lhardly varied at all over a period of seven anid a lhalf years.
“Parallel architecture” as a variety of stratificationalism
Authors: David G. Lockwood
Journal: Behavioral and Brain Sciences (2003)

The model of parallel architecture for language presented by Jackendoff is a kind of stratificational model in the spirit of Sydney Lamb. It differs from the more usual stratificationalism most importantly in its clear commitment to nativism, though the variety of nativism is greatly modified from what is more usual among Chomskyans. The revised model presents a potential for fruitful discussion with proponents of stratificationalism, and the potential for enrichment via a relational implementation.
Deactivation by Benzodiazepine of the Basal Forebrain and Amygdala in Normal Humans During Sleep: A Placebo-Controlled [<sup>15</sup>O]H<sub>2</sub>O PET Study
Authors: Naofumi Kajimura, Masami Nishikawa, Makoto Uchiyama, Masaaki Kato, Tsuyoshi Watanabe, Toru Nakajima, Toru Hori, Tetsuo Nakabayashi, Masanori Sekimoto, Kenichi Ogawa, Harumasa Takano, Etsuko Imabayashi, Masahiko Hiroki, Takashi Onishi, Takeshi Uema, Yutaka Takayama, Hiroshi Matsuda, Masako Okawa, Kiyohisa Takahashi
Journal: American Journal of Psychiatry (2004)

The authors' goal was to identify differences in regional brain activity between physiological and benzodiazepine-induced sleep to clarify the brain structures involved in the drug's hypnotic effect.Using positron emission tomography, they compared regional cerebral blood flow during non-REM sleep in nine volunteers treated with placebo or triazolam, a short-acting benzodiazepine, in a double-blind, crossover design.Blood flow in the basal forebrain and amygdaloid complexes was lower during non-REM sleep when subjects were given triazolam than when they were given placebo.The hypnotic effect of the benzodiazepines may be mediated mainly by deactivation of the forebrain control system for wakefulness and also by the anxiolytic effect induced by deactivation of the emotional center.
Black Lung Benefits
Authors: W. Keith C. Morgan
Journal: JAMA (1973)

<h3>To the Editor.—</h3> On Sept 30, 1972, a new set of regulations for black lung benefits was published in the<i>Federal Register</i>. The regulations included some interim standards designed to facilitate the more rapid processing of black lung compensation claims. Since that time, the Appalachian Laboratory for Occupational Respiratory Diseases has repeatedly been asked by physicians in the field of industrial medicine and chest diseases what percentage of working miners are eligible to receive black lung benefits under the interim standards. At the present time and until 1973, a miner may qualify for black lung benefits if (1) his chest roentgenogram shows evidence of pneumoconiosis— either simple or complicated; (2) he has worked for 15 years in a coal mine and has sufficient ventilatory impairment to meet the criteria shown in the table published on page 20646 of the<i>Federal Register</i>; and (3) he has certain other respiratory impairments, such
The effect of oral activated charcoal on the course of congenital erythropoietic porphyria
Authors: R.J. HIFT, P.N. MEISSNER, R.E. KIRSCH
Journal: British Journal of Dermatology (1993)

The administration or oral activated charcoal to two patients with congenital erythropoietic porphyria has previously been reported to result in a marked reduction in plasma and urinary porphyrin concentrations and in one case, clinical remission. We describe an additional case in which the use of charcoal was associated with an apparent exacerbation of the biochemical activity of the disease following an initial period of remission. This result is unexpected, and currently unexplained. We conclude that charcoal therapy in porphyria may not be without risk, and should be used with caution.
Telomerase-Independent Telomere Length Maintenance in the Absence of Alternative Lengthening of Telomeres–Associated Promyelocytic Leukemia Bodies
Authors: Clare L. Fasching, Kylie Bower, Roger R. Reddel
Journal: Cancer Research (2005)

Abstract Immortal tumor cells and cell lines employ a telomere maintenance mechanism that allows them to escape the normal limits on proliferative potential. In the absence of telomerase, telomere length may be maintained by an alternative lengthening of telomeres (ALT) mechanism. All human ALT cell lines described thus far have nuclear domains of unknown function, termed ALT-associated promyelocytic leukemia bodies (APB), containing promyelocytic leukemia protein, telomeric DNA and telomere binding proteins. Here we describe telomerase-negative human cells with telomeres that contain a substantial proportion of nontelomeric DNA sequences (like telomerase-null Saccharomyces cerevisiae survivor type I cells) and that are maintained in the absence of APBs. In other respects, they resemble typical ALT cell lines: the telomeres are highly heterogeneous in length (ranging from very short to very long) and undergo rapid changes in length. In addition, these cells are capable of copying a targeted DNA tag from one telomere into other telomeres. These data show that APBs are not always essential for ALT-mediated telomere maintenance.
Expression of different combinations of interleukins by human T cell leukemic cell lines that are clonally related.
Authors: T Noma, H Nakakubo, M Sugita, S Kumagai, M Maeda, A Shimizu, T Honjo
Journal: The Journal of Experimental Medicine (1989)

We have analyzed expression patterns of 7 lymphokine mRNAs by Northern blot analyses in 19 different human T cell clones derived from patients with adult T cell leukemia. However, we were not able to reveal particular combinations of lymphokine production that allowed classification of human T cells. Especially, four clonally related leukemic lines that were established independently from the same patient with adult T cell leukemia expressed different combinations of lymphokine mRNAs, indicating that the expression of various lymphokines is not fixed but rather variable even among progenies of a single T cell clone.
Enhancer alterations in cancer: a source for a cell identity crisis
Authors: Ken J Kron, Swneke D Bailey, Mathieu Lupien
Journal: Genome Medicine (2014)

Enhancers are selectively utilized to orchestrate gene expression programs that first govern pluripotency and then proceed to highly specialized programs required for the process of cellular differentiation. Whereas gene-proximal promoters are typically active across numerous cell types, distal enhancer activation is cell-type-specific and central to cell fate determination, thereby accounting for cell identity. Recent studies have highlighted the diversity of enhancer usage, cataloguing millions of such elements in the human genome. The disruption of enhancer activity, through genetic or epigenetic alterations, can impact cell-type-specific functions, resulting in a wide range of pathologies. In cancer, these alterations can promote a 'cell identity crisis', in which enhancers associated with oncogenes and multipotentiality are activated, while those promoting cell fate commitment are inactivated. Overall, these alterations favor an undifferentiated cellular phenotype. Here, we review the current knowledge regarding the role of enhancers in normal cell function, and discuss how genetic and epigenetic changes in enhancer elements potentiate oncogenesis. In addition, we discuss how understanding the mechanisms regulating enhancer activity can inform therapeutic opportunities in cancer cells and highlight key challenges that remain in understanding enhancer biology as it relates to oncology.
Colorectal Cancer Survival Advantage in MUTYH-Associated Polyposis and Lynch Syndrome Families
Authors: H. T. Lynch, S. J. Lanspa
Journal: JNCI Journal of the National Cancer Institute (2010)

The cardinal features of colorectal cancer in patients with the MUTYH-associated polyposis syndrome, featured in this editorial, are of very recent discovery and remain under review as new clinical phenotypes for these patients are still being identified. Importantly, its phenotype results from homozygosity of the MUTYH gene and, therefore, is inherited in an autosomal recessive pattern. In a more intensively studied hereditary colorectal cancer syndrome, namely Lynch syndrome, the cardinal features have been shown to result from an autosomal dominantly inherited pattern and includes earlier average age of cancer onset, when compared with the general population (45 years for Lynch syndrome colorectal cancer and 64 years for patients with colorectal cancer in the general population), accelerated carcinogenesis, high risk for metachronous colorectal cancers, specific pathology features for Lynch syndrome colorectal cancers that are more often poorly differentiated and have an excess of Colorectal Cancer Survival Advantage in MUTYH-Associated Polyposis and Lynch Syndrome Families
Guanylyl Cyclases as a Family of Putative Odorant Receptors
Authors: Angelia D. Gibson, David L. Garbers
Journal: Annual Review of Neuroscience (2000)

Mammals can discriminate among a large number (&gt;10,000) of unique odorants. The most highly supported explanation for this ability is that olfactory neurons express a large number of seven transmembrane receptors that are not spatially organized at the level of the olfactory epithelium, but whose axonal projections form a distinct pattern within the olfactory bulb. The odor-induced signaling pathway in olfactory neurons includes a G s -like protein (G olf ) that activates a specific adenylyl cyclase (type III) isoform, resulting in elevations of cyclic AMP and subsequent activation of a cyclic nucleotide-gated channel. The channel also can be regulated by cyclic GMP. Recently, an olfactory neuron-specific guanylyl cyclase was discovered in rodents, and subsequently a large family of sensory neuronal guanylyl cyclases was identified in nematodes. These guanylyl cyclases are concentrated in the plasma membrane of the dendritic cilia and contain extracellular domains that retain many of the primary sequence characteristics of guanylyl cyclases known to be receptors for various peptides. Thus, the guanylyl cyclases appear to represent a second family of odorant/pheromone receptors.
New Strategies in Ovarian Cancer: Translating the Molecular Complexity of Ovarian Cancer into Treatment Advances
Authors: Joyce Liu, Ursula A. Matulonis
Journal: Clinical Cancer Research (2014)

Abstract An improved understanding of the genomics of ovarian cancer and the separation of ovarian cancer into histologically and molecularly defined subgroups have affected drug development and clinical trial design in ovarian cancer. Active therapies that have been tested in ovarian cancer include agents that inhibit angiogenesis and poly (ADP-ribose) polymerase inhibitors (PARPi). However, no FDA drug approvals for ovarian cancer have been granted since 2006, and overall survival improvements have been difficult to achieve with new agents. The genomic complexity of ovarian cancer and modest single-agent activity of many biologic agents in this disease have led to testing of biologic agent combinations. In this article, we review recent advances in the understanding of the molecular diversity of ovarian cancer as well as emerging therapeutic strategies such as new agents and biologic combinations that attempt to target multiple aberrant pathways in this cancer. Clin Cancer Res; 20(20); 5150–6. ©2014 AACR.
Preferential migration of effector CD8+ T cells into the interstitium of the normal lung
Authors: E. Galkina
Journal: Journal of Clinical Investigation (2005)

The respiratory tract is a primary site of infection and exposure to environmental antigens and an important site of memory T cell localization. We analyzed the migration and retention of naive and activated CD8+ T cells within the noninflamed lungs and quantitated the partitioning of adoptively transferred T cells between the pulmonary vascular and interstitial compartments. Activated but not naive T cells were retained within the lungs for a prolonged period. Effector CD8+ T cells preferentially egressed from the pulmonary vascular compartment into the noninflamed pulmonary interstitium. T cell retention within the lung vasculature was leukocyte function antigen-1 dependent, while the egress of effector T cells from the vascular to the interstitium functions through a pertussis toxin–sensitive (PTX-sensitive) mechanism driven in part by constitutive CC chemokine ligand 5 expression in the lungs. These results document a novel mechanism of adhesion receptor– and pulmonary chemokine–dependent regulation of the migration of activated CD8+ T cells into an important nonlymphoid peripheral site (i.e., the normal/noninflamed lung).