tbuckley/cabot-search huggingface dataset:
The uses of ethnography in the science of cultural evolution
Authors: Jamshid Tehrani
Journal: Behavioral and Brain Sciences (2006)

There is considerable scope for developing a more explicit role for ethnography within the research program proposed in the article. Ethnographic studies of cultural micro-evolution would complement experimental approaches by providing insights into the “natural” settings in which cultural behaviours occur. Ethnography can also contribute to the study of cultural macro-evolution by shedding light on the conditions that generate and maintain cultural lineages.
Surgical treatment of spinal cord compression from epidural metastasis.
Authors: N Sundaresan, V P Sachdev, J F Holland, F Moore, M Sung, P A Paciucci, L T Wu, K Kelligher, L Hough
Journal: Journal of Clinical Oncology (1995)

PURPOSE A retrospective study of the results of neoplastic cord compression was undertaken to determine the effectiveness of surgical treatment and to assess quality of life in patients undergoing extensive procedures with potential morbidity. PATIENTS AND METHODS Over a 5-year period (1989 to 1993), a total of 110 patients underwent surgery. Fifty-five patients (50%) had undergone prior treatment, including 47 (43%) who had failed to respond to prior irradiation (RT). Before surgery, 48 patients (44%) were nonambulatory, with severe paresis being present in 20. Surgery included staged anterior-posterior resections in 53 patients (48%), anterior resections in 33 (30%), and posterior resection in six (5%), all of whom required spinal instrumentation for reconstruction; only 18 patients underwent resection without instrumentation. RESULTS Postoperatively, 90 patients (82%) were improved, both in terms of pain relief and ambulatory status. Fifty-three patients (48%) experienced postoperative complications, related statistically to the following three factors: age over 65 years, prior treatment, and presence of paraparesis. The overall median survival duration was 16 months, with 46% alive at 2 years. Apart from primary tumor, the presence of preoperative paraparesis had the most significant impact on survival. CONCLUSION Our data suggest that the effective surgical treatment of neoplastic compression requires anterior-posterior resection in most patients to achieve the goal of total tumor resection, with the majority requiring instrumentation. Long-term survival is feasible in a subset of patients with this aggressive surgical approach.
Predictors of Recurrence in Patients With T2 and Early T3, N0 Adenocarcinoma of the Rectum Treated by Surgery Alone
Authors: Aviram Nissan, Alexander Stojadinovic, Jinru Shia, Axel Hoos, Jose G. Guillem, David Klimstra, Alfred M. Cohen, Bruce D. Minsky, Philip B. Paty, W. Douglas Wong
Journal: Journal of Clinical Oncology (2006)

Treatment of rectal cancer with neoadjuvant radiotherapy has been shown to reduce local recurrence and improve overall survival. The role of chemoradiotherapy in patients with T2, N0 and early T3, N0 rectal cancer, treated by radical surgery with total mesorectal excision, remains controversial. The aim of this study was to identify predictors of recurrence in this group of patients to enhance treatment selection.One hundred patients with primary T2-3, N0 adenocarcinoma of the rectum, uniformly treated by surgery alone, were studied. The pathology slides available for 97 patients were rereviewed. Three patients with incomplete data sets were excluded. Clinical and survival data were obtained from a prospective computerized database and updated from hospital and office charts. The study end points were disease-free survival, disease-specific survival (DSS), time to pelvic recurrence (PR), and distant recurrence.Complete follow-up was available for all study patients. Median follow-up was 79.5 months (range, 57.7 to 105.9 months). During this time period 30 patients (31.9%) died as a result of disease and 64 patients (68.1%) remained alive and disease free. Five-year DSS was 73%. The cumulative risk for PR was 8% at 5 years and 10% at 8 years. Lymphovascular invasion, preoperative serum carcinoembryonic antigen (CEA > 5 ng/mL) level, and age older than 70 years were all associated with adverse outcome. CONCLUSION Patients with T2-3, N0 rectal cancers and either lymphovascular invasion or elevated CEA levels have reduced survival and a higher incidence of PR, and should be considered for future randomized trials.
Mucosal healing in inflammatory bowel diseases: a systematic review
Authors: Markus F Neurath, Simon P L Travis
Journal: Gut (2012)

Recent studies have identified mucosal healing on endoscopy as a key prognostic parameter in the management of inflammatory bowel diseases (IBD), thus highlighting the role of endoscopy for monitoring of disease activity in IBD. In fact, mucosal healing has emerged as a key treatment goal in IBD that predicts sustained clinical remission and resection-free survival of patients. The structural basis of mucosal healing is an intact barrier function of the gut epithelium that prevents translocation of commensal bacteria into the mucosa and submucosa with subsequent immune cell activation. Thus, mucosal healing should be considered as an initial event in the suppression of inflammation of deeper layers of the bowel wall, rather than as a sign of complete healing of gut inflammation. In this systematic review, the clinical studies on mucosal healing are summarised and the effects of anti-inflammatory or immunosuppressive drugs such as 5-aminosalicylates, corticosteroids, azathioprine, ciclosporin and anti-TNF antibodies (adalimumab, certolizumab pegol, infliximab) on mucosal healing are discussed. Finally, the implications of mucosal healing for subsequent clinical management in patients with IBD are highlighted.
A scoring system for mucosal disease severity with special reference to oral lichen planus
Authors: M. Escudier, N. Ahmed, P. Shirlaw, J. Setterfield, A. Tappuni, M.M. Black, S.J. Challacombe
Journal: British Journal of Dermatology (2007)

Background To date, there is only weak evidence for the superiority of any interventions over placebo for the palliation of symptomatic oral lichen planus (LP). Further research involving large placebo-controlled, randomized clinical trials is needed. These will require carefully selected and standardized outcome measures. Objectives To formulate a scoring system for intraoral LP. Methods One hundred and fifty-six patients with biopsy-confirmed LP were scored at the first and subsequent visits according to (i) extent of site involvement, (ii) disease activity at each site and (iii) an overall pain score as reported by the patient. Overall differences between clinical variants of LP were analysed using the Kruskal–Wallis test and pairwise differences by the Mann–Whitney U-test. Clinical sensitivity (Wilcoxon signed-rank test) was assessed by scoring patients before and after treatment (n = 23). Results Reticular LP (n = 48) was the commonest single type of clinical presentation, followed by ulcerative (n = 30), atrophic (n = 22), desquamative (n = 18) and plaque (n = 1). The median severity and activity scores were 13/6 (reticular), 39/20 (ulcerative), 20/9 (atrophic) and 23/11 (desquamative). Two or more clinical variants were seen in 37 cases. Statistical significance was observed for differences between clinical variants (P < 0·0001) and variation in scores (P < 0·01) when ulcerative LP was compared with all other types. Clinical sensitivity was statistically significant (P < 0·01), while reproducibility was high and allowed the response to therapy to be easily assessed. Conclusions It is suggested that this scoring system is easy to use, reproducible and sensitive enough to detect clinical responses to therapy.
Enhanced Na <sup>+</sup> Channel Intermediate Inactivation in Brugada Syndrome
Authors: Dao W. Wang, Naomasa Makita, Akira Kitabatake, Jeffrey R. Balser, Alfred L. George
Journal: Circulation Research (2000)

Abstract —Brugada syndrome is an inherited cardiac disease that causes sudden death related to idiopathic ventricular fibrillation in a structurally normal heart. The disease is characterized by ST-segment elevation in the right precordial ECG leads and is frequently accompanied by an apparent right bundle-branch block. The biophysical properties of the SCN5A mutation T1620M associated with Brugada syndrome were examined for defects in intermediate inactivation ( I M ), a gating process in Na + channels with kinetic features intermediate between fast and slow inactivation. Cultured mammalian cells expressing T1620M Na + channels in the presence of the human β 1 subunit exhibit enhanced intermediate inactivation at both 22°C and 32°C compared with wild-type recombinant human heart Na + channels (WT-hH1). Our findings support the hypothesis that Brugada syndrome is caused, in part, by functionally reduced Na + current in the myocardium due to an increased proportion of Na + channels that enter the I M state. This phenomenon may contribute significantly to arrhythmogenesis in patients with Brugada syndrome. The full text of this article is available at http://www.circresaha.org.
Nuclear factor κB essential modulator–deficient child with immunodeficiency yet without anhidrotic ectodermal dysplasia
Authors: Tim Niehues, Janine Reichenbach, Jennifer Neubert, Sonja Gudowius, Anne Puel, Gerd Horneff, Elke Lainka, Uta Dirksen, Horst Schroten, Rainer Döffinger, Jean Laurent Casanova, Volker Wahn
Journal: Journal of Allergy and Clinical Immunology (2004)
The Potential of Bone Marrow-Derived Cells to Differentiate to Glomerular Mesangial Cells
Authors: TOSHIYUKI IMASAWA, YASUNORI UTSUNOMIYA, TETSUYA KAWAMURA, YU ZHONG, RYUJI NAGASAWA, MASARU OKABE, NAOKI MARUYAMA, TATSUO HOSOYA, TSUNEYA OHNO
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Bone marrow stem cells (BMC) develop into hematopoietic and mesenchymal lineages but have not been known to differentiate into glomerular cells. To investigate whether such differentiation is possible, a search was made for donor glomerular cells in lethally irradiated C57BL/6j (B6) mice given transplants of BMC from syngeneic mice transgenic for green fluorescence protein (GFP) ([GFP→B6] mice). After the recipients of donor BMC manifested GFP-positive cells in their glomeruli, the numbers of such cells increased markedly, in a time-dependent manner, from 2 wk to 24 wk after bone marrow transplantation. Immunohistochemical analyses revealed that most GFP-positive cells in the glomeruli were neither macrophages nor T cells. With the use of a laser-scanning confocal microscope, GFP-positive cells were observed within the mesangium of [GFP→B6] mice. Furthermore, indirect immunofluorescence assays demonstrated that desmin-positive cells in the glomeruli of these chimeric mice were also positive for GFP. Among glomerular cells isolated from [GFP→B6] mice 24 wk after bone marrow transplantation and then cultured, the majority of cells (approximately 84%) stained for desmin and approximately 60% of the desmin-positive cells expressed GFP. In addition, these GFP-positive cells in the cultures contracted in response to angiotensin II stimulation. These results suggest that bone marrow-derived cells may have the potential to differentiate into glomerular mesangial cells.
Identification of Homozygous Hemochromatosis Subjects by Measurement of Hepatic Iron Index
Authors: Kim M. Summers, June W. Halliday, Lawrie W. Powell
Journal: Hepatology (1990)

The value of measurement of hepatic iron concentration and determination of the hepatic iron index in distinguishing homozygotes from heterozygotes for hemochromatosis was examined. The study group included 42 homozygotes with an unequivocal diagnosis of hemochromatosis and six individuals who had initial equivocal results but were established as homozygous after extensive follow–up. These were compared with 15 heterozygotes with no sign of increasing body iron stores who had undergone liver biopsy because of an initial suspicion of raised iron levels. In these subjects a hepatic iron concentration of greater than 75 μmol/gm dry weight was clearly indicative of homozygous hemochromatosis. Body iron accumulation was age–related both in homozygotes and in these heterozygotes with mild biochemical abnormalities (r = 0.476; p = 0.001 and r = 0.689; p = 0.01, respectively), with a rate of accretion of approximately 5 μmol/gm dry weight/year in homozygotes and 0.9 μmol/gm dry weight/year in heterozygotes. Thus, lower values in young subjects may be consistent with homozygosity, and higher values in older individuals are consistent with heterozygosity. To overcome this problem, the hepatic iron index (hepatic iron concentration divided by age in years) was analyzed and found to separate the two groups effectively, with no homozygote having an index of less than 1.9 and no heterozygote having an index of greater than 1.5. These results in a series of patients who have been followed for a median of 3 yr (range = 1 to 30 yr) validate the use of the hepatic iron index to discriminate hemochromatosis homozygotes from heterozygotes with raised levels of serum ferritin, transferrin saturation or both. (Hepatology 1990;12:20-25).
Genetic Approaches to Neural Circuits in the Mouse
Authors: Z. Josh Huang, Hongkui Zeng
Journal: Annual Review of Neuroscience (2013)

To understand the organization and assembly of mammalian brain circuits, we need a comprehensive tool set that can address the challenges of cellular diversity, spatial complexity at synapse resolution, dynamic complexity of circuit operations, and multifaceted developmental processes rooted in the genome. Complementary to physics- and chemistry-based methods, genetic tools tap into intrinsic cellular and developmental mechanisms. Thus, they have the potential to achieve appropriate spatiotemporal resolution and the cellular-molecular specificity necessary for observing and probing the makings and inner workings of neurons and neuronal circuits. Furthermore, genetic analysis will be key to unraveling the intricate link from genes to circuits to systems, in part through systematic targeting and tracking of individual cellular components of neural circuits. Here we review recent progress in genetic tool development and advances in genetic analysis of neural circuits in the mouse. We also discuss future directions and implications for understanding brain disorders.
Genetic Mediators of Neurocognitive Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia
Authors: Kevin R. Krull, Deepa Bhojwani, Heather M. Conklin, Deqing Pei, Cheng Cheng, Wilburn E. Reddick, John T. Sandlund, Ching-Hon Pui
Journal: Journal of Clinical Oncology (2013)

Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) are at increased risk for neurocognitive problems, with significant interindividual variability in outcome. This study examined genetic polymorphisms associated with variability in neurocognitive outcome. Patients and Methods Neurocognitive outcomes were evaluated at the end of therapy in 243 survivors treated on an institutional protocol featuring risk-adapted chemotherapy without prophylactic cranial irradiation. Polymorphisms in genes related to pharmacokinetics or pharmacodynamics of antileukemic agents, drug metabolism, oxidative stress, and attention problems in noncancer populations were examined as predictors of outcome, using multiple general linear models and controlling for age at diagnosis, sex, race, and treatment intensity. Results Compared with national norms, the cohort demonstrated significantly higher rates of problems on direct assessment of sustained attention (P = .01) and on parent ratings of attention problems (P = .02). Children with the A2756G polymorphism in methionine synthase (MS) were more likely to demonstrate deficits in attentiveness (P = .03) and response speed (P = .02), whereas those with various polymorphisms in glutathione S-transferase demonstrated increased performance variability (P = .01) and reduced attentiveness (P = .003). Polymorphisms in monoamine oxidase (T1460CA) were associated with increased attention variability (P = .03). Parent-reported attention problems were more common in children with the Cys112Arg polymorphism in apoliopoprotein E4 (P = .01). Conclusion These results are consistent with our previous report of association between attention problems and MS in an independent cohort of long-term survivors of childhood ALL treated with chemotherapy only. The results also raise the possibility of an impact from genetic predispositions related to oxidative stress and CNS integrity.
Influence of the lonic Environment on Spontaneous Electrical and Mechanical Activity of the Rat Portal Vein
Authors: JOHANN AXELSSON, BO WAHLSTROöm, Börje JOHANSSON, OLOF JONSSON
Journal: Circulation Research (1967)

The effects of variations in external K + and Ca 2+ concentrations on electrical and mechanical activity of the isolated rat portal vein were studied using a sucrose-gap technique. Spontaneous activity in normal Krebs solution consists of bursts of action potentials accompanied by phasic contractions. Moderate reduction in [K+] o results in slight hyperpolarization with decreased discharge frequency. Greater reduction or total removal of extracellular K causes a temporary increase in burst frequency. Graded increases in [K+] o from 6 up to 128 mM cause depolarization with an increase in discharge frequency and in contraction amplitude until [K+] o reaches a level of 6 to 7 times normal when spike potentials are abolished and a contracture develops. The relationship between membrance potential and log [K + ] o indicates a relatively low permeability to K + . Increasing [Ca 2+ ] o causes slight hyperpolarization, decreased burst frequency, increased burst duration and increased contraction amplitude. Reducing [Ca 2+ ] o causes increased frequency of discharge and shortening of bursts, until single spikes appear, each preceded by a prepotential; thus the activity resembles that in cardiac pacemaker cells. In Ca 2+ -free solution, electrical and mechanical activity ceases within 10 to 15 min. Calcium is essential for activation of the contractile mechanism and for maintenance of spontaneous spike discharge.
The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels
Authors: Noboru Toda, Tomio Okamura
Journal: Pharmacological Reviews (2003)

Unanticipated, novel hypothesis on nitric oxide (NO) radical, an inorganic, labile, gaseous molecule, as a neurotransmitter first appeared in late 1989 and into the early 1990s, and solid evidences supporting this idea have been accumulated during the last decade of the 20th century. The discovery of nitrergic innervation of vascular smooth muscle has led to a new understanding of the neurogenic control of vascular function. Physiological roles of the nitrergic nerve in vascular smooth muscle include the dominant vasodilator control of cerebral and ocular arteries, the reciprocal regulation with the adrenergic vasoconstrictor nerve in other arteries and veins, and in the initiation and maintenance of penile erection in association with smooth muscle relaxation of the corpus cavernosum. The discovery of autonomic efferent nerves in which NO plays key roles as a neurotransmitter in blood vessels, the physiological roles of this nerve in the control of smooth muscle tone of the artery, vein, and corpus cavernosum, and pharmacological and pathological implications of neurogenic NO have been reviewed. This nerve is a postganglionic parasympathetic nerve. Mechanical responses to stimulation of the nerve, mainly mediated by NO, clearly differ from those to cholinergic nerve stimulation. The naming "nitrergic or nitroxidergic" is therefore proposed to avoid confusion of the term "cholinergic nerve", from which acetylcholine is released as a major neurotransmitter. By establishing functional roles of nitrergic, cholinergic, adrenergic, and other autonomic efferent nerves in the regulation of vascular tone and the interactions of these nerves in vivo, especially in humans, progress in the understanding of cardiovascular dysfunctions and the development of pharmacotherapeutic strategies would be expected in the future.
Superior vena cava obstruction caused by radiation induced venous fibrosis
Authors: J W G Van Putten
Journal: Thorax (2000)

Superior vena cava syndrome is most often caused by lung carcinoma. Two cases are described in whom venous obstruction in the superior mediastinum was caused by local vascular fibrosis due to radiotherapy five and seven years earlier. The development of radiation injury to greater vessels is discussed, together with the possibilities for treatment of superior vena cava syndrome.
Impact of a donor source on adult Philadelphia chromosome-negative acute lymphoblastic leukemia: a retrospective analysis from the Adult Acute Lymphoblastic Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation
Authors: S. Nishiwaki, K. Miyamura, K. Ohashi, M. Kurokawa, S. Taniguchi, T. Fukuda, K. Ikegame, S. Takahashi, T. Mori, K. Imai, H. Iida, M. Hidaka, H. Sakamaki, Y. Morishima, K. Kato, R. Suzuki, J. Tanaka
Journal: Annals of Oncology (2013)
Phenylbutyrate and Phenylacetate Induce Differentiation and Inhibit Proliferation of Human Medulloblastoma Cells
Authors: Xiao-Nan Li, Suhag Parikh, Qin Shu, Hye-Lim Jung, Chi-Wan Chow, Laszlo Perlaky, Hon-Chiu Eastwood Leung, Jack Su, Susan Blaney, Ching C. Lau
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Phenylbutyrate (PB) and phenylacetate (PA) have antiproliferative and differentiation-inducing effects in malignant tumors, and had been evaluated in Phase I/II clinical trials. This study was undertaken to evaluate their antitumor activities in medulloblastomas. Experimental Design: The biological effects of PB and PA, ranging from 0.1 mm to 3 mm, on two medulloblastoma cell lines (DAOY and D283-MED) were examined using various long-term in vitro and in vivo assays for morphology, proliferation, differentiation, anchorage-independent growth, apoptosis, and tumorigenicity. Results: PB and PA can both induce morphological changes and suppress proliferation in a time- and dose-dependent manner. These effects were more pronounced with PB and became irreversible in D283-MED cells after continuous exposure to 3 mm PB for 28 days. Both PB and PA were able to increase expression of glial marker glial fibriliary acidic protein and neuronal marker synaptophysin in two cell lines. For anchorage-independent growth, PB showed a more significant suppression than PA in D283-MED cells. PB caused more pronounced cell cycle arrest and remarkably reduced tumorigenicity in D283-MED cells than in DAOY cells. Apoptosis was readily induced in D283-MED cells with either low dose of PB or short-term treatment. In contrast, much higher concentrations of PB or longer treatment were required to achieve similar effect with DAOY cells. PB induced increased histones H3 acetylation in both cell lines, but histone H4 acetylation was only observed in D283-MED cells. Conclusions: PB, through induction of hyperacetylation of histone H3 and H4, is a much more potent antitumor agent than PA. 283-MED cells are more responsive to PB than DAOY cells, which may be dependent on their original state of differentiation as well as the changes of histone H4 acetylation status.