tbuckley/cabot-search huggingface dataset:
Psychosurgery: Damaging the Brain to Save the Mind
Authors: Thomas H. Lewis
Journal: JAMA (1993)

Joann Rodgers is an accomplished magazine and newspaper journalist. She here offers her review of a complex medical and ethical issue. When she was invited by an editor to popularize modern psychosurgery, the task seemed at first to involve reviving a bleak and defunct story long relegated to psychiatry's past (dogging a fled horse?). Psychosurgery, after all, is burdened with a gruesome reputation. It has been condemned by ethical thinkers and rejected for its reliance upon faith and conviction rather than upon a plausible scientific base. And it has a reputation for wretched excesses. Still, proponents feel that all this may be brushed aside. The author has collected information and interviews which suggest that a rehearing is in order. The main arguments for the new psychosurgery are several. First, there is an urgent need for effective surgical procedures for psychiatric and social problems (see especially Breggin, PR, "The Return of
Targeting caspase-1 by inhalation-therapy: effects of Ac-YVAD-CHO on IL-1β, IL-18 and downstream proinflammatory parameters as detected in rat endotoxaemia
Authors: Kim A. Boost, Sandra Hoegl, Christian Hofstetter, Michael Flondor, Klaus Stegewerth, Ilka Platacis, Josef Pfeilschifter, Heiko Muhl, Bernhard Zwissler
Journal: Intensive Care Medicine (2007)
Abstract 4679: Betulinic acid inhibits deubiquitinases to increase the degradation of pro-survival proteins and enhance prostate cancer-specific apoptosis
Authors: Teresita Reiner, Ricardo Parrondo, Alicia de las Pozas, Deanna Palenzuela, Carlos Perez-Stable
Journal: Cancer Research (2012)

Abstract Inhibition of the ubiquitin proteasome (UPS) pathway is a valid anti-cancer target but the alternative strategy to increase activity in order to degrade pro-survival proteins is much less developed. Betulinic acid (BA) is a naturally occurring small molecule with multiple mechanisms for increasing apoptosis in cancer cells, making it an attractive anti-prostate cancer agent. There is evidence that BA can activate the UPS pathway to degrade multiple pro-survival proteins such as androgen receptor (AR), but the mechanism is not clear. Our western blot data in prostate cancer (PC) cells indicates that 10 μM BA decreases the levels of multiple pro-survival proteins including AR, cyclins, and cyclin-dependent kinases. Inhibition of the UPS pathway with 1 μM MG132 blocks the BA-mediated decrease of AR and AKT proteins and lowers cell death, suggesting a dependence on the UPS pathway. In TRAMP transgenic mice, BA treatment (10 mg/kg) inhibits tumor growth, increases apoptosis, decreases angiogenesis and proliferation, and lowers AR and cyclin D1 protein levels (immunohistochemistry) without toxic side effects to normal tissues. However, BA does not increase UPS activity (Proteasome-Glo Chymotrypsin-like Cell-Based Assay; Promega) in LNCaP PC cells suggesting an alternative mechanism for increasing protein degradation. BA-mediated inhibition of deubiquitinase (DUB) activity, as determined by DUB-Glo Protease Assay (Promega) and DUB labeling with HA-ubiquitin vinyl sulfone, results in the accumulation of poly-ubiquitinated (Ub) proteins that are recognized by the UPS pathway and degraded. The cyclin D1 T286A mutant that cannot be degraded by the UPS pathway is resistant to BA-mediated degradation. In non-cancer BJ fibroblast, however, BA does not inhibit DUB activity nor increases total poly-Ub proteins and this is associated with no effect on cell death. Our data suggests that BA-mediated inhibition of DUBs and induction of apoptotic cell death specifically in PC but not in non-cancer cells will provide an effective non-toxic and clinically selective agent. 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 4679. doi:1538-7445.AM2012-4679
The Role of Chitin and TNF-Alpha in Airway Inflammation Induced By House Dust Mite in Murine Model
Authors: Sang Min Lee, Joon Pyo Choi, Young Min Kim, Seung Jin Choi, Hyun Taek Park, Sang Pyo Lee, Sang Heon Cho, Yoon-Keun Kim
Journal: Journal of Allergy and Clinical Immunology (2014)
Cytotoxicity of a factor from normal and abnormal human spleens for allogenic leukemia cells
Authors: Bismarck B. Lozzio, Carmen B. Lozzio, Elena G. Bamberger
Journal: American Journal of Hematology (1978)

Abstract A search for an endogenous cytotoxic factor (ECF) was made by analyzing 103 spleens from normal humans and patients suffering from hematopoietic malignancies, solid tumors, inflammatory diseases, and congestive and hyperplastic splenomegalies. A highly purified ECF was obtained by a combination of gel filtration and ion‐exchange column chromatography. The factor is a low‐molecular‐weight (&lt; 2,000) substance and is probably a peptide or peptide‐nucleotide complex. The biologic activity of the ECF was assayed on myelogenous and lymphatic leukemia cells of human origin. The spleens from normal individuals produced and/or stored the largest quantity of the ECF. The amount of ECF extractable from the pathologic spleen was drastically diminished regardless of the disease or therapeutic regimen. The ECF was significantly more cytotoxic for lymphatic than for myelogenous leukemia cells.
Genotype-Specific Abnormalities in Mitochondrial Function Associate with Distinct Profiles of Energy Metabolism and Catecholamine Content in Pheochromocytoma and Paraganglioma
Authors: Jyotsna U. Rao, Udo F.H. Engelke, Richard J.T. Rodenburg, Ron A. Wevers, Karel Pacak, Graeme Eisenhofer, Nan Qin, Benno Kusters, Angelina G. Goudswaard, Jacques W.M. Lenders, Ad R.M.M. Hermus, Arjen R. Mensenkamp, Henricus P.M. Kunst, Fred C.G.J. Sweep, Henri J.L.M. Timmers
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Pheochromocytomas and paragangliomas (PGL) are neuroendocrine tumors of sympathetic and parasympathetic paraganglia. This study investigated the relationships between genotype-specific differences in mitochondrial function and catecholamine content in PGL tumors. Experimental Design: Respiratory chain enzyme assays and 1H-nuclear magnetic resonance (NMR) spectroscopy at 500 MHz were conducted on homogenates of 35 sporadic PGLs and 59 PGLs from patients with hereditary mutations in succinate dehydrogenase subunits B and D (SDHB, SDHD), succinate dehydrogenase assembly factor 2, von Hippel-Lindau (VHL), rearranged during transfection (RET), neurofibromatosis type 1 (NF1), and myc-associated factor X. Results: In SDHx-related PGLs, a significant decrease in complex II activity (P &amp;lt; 0.0001) and a significant increase in complex I, III, and IV enzyme activities were observed when compared to sporadic, RET, and NF1 tumors. Also, a significant increase in citrate synthase (P &amp;lt; 0.0001) enzyme activity was observed in SDHx-related PGLs when compared to sporadic-, VHL-, RET-, and NF1-related tumors. An increase in succinate accumulation (P &amp;lt; 0.001) and decrease in ATP/ADP/AMP accumulation (P &amp;lt; 0.001) was observed when compared to sporadic PGLs and PGLs of other genotypes. Positive correlations (P &amp;lt; 0.01) were observed between respiratory chain complex II activity and total catecholamine content and ATP/ADP/AMP and total catecholamine contents in tumor tissues. Conclusions: This study for the first time establishes a relationship between determinants of energy metabolism, like activity of respiratory chain enzyme complex II, ATP/ADP/AMP content, and catecholamine content in PGL tumors. Also, this study for the first time successfully uses NMR spectroscopy to detect catecholamines in PGL tumors and provides ex vivo evidence for the accumulation of succinate in PGL tumors with an SDHx mutation. Clin Cancer Res; 19(14); 3787–95. ©2013 AACR.
Scientific Aspects of Neurology
Authors: J. H. Talbott
Journal: JAMA (1961)

The communications presented at the Leeds Neurological Sciences Colloquium, 1959-1960, encompass an interesting group of subjects by the leaders in this specialty from Scotland and England, plus one foreign guest. The titles are as penetrating as the discussions. A new technique for the selection of sites for muscle biopsy, based upon the zone of maximum electrical excitability of the muscle, is described in the chapter, The Diagnostic Value of Motor Point Muscle Biopsy. A biopsy, performed at the appropriate site, includes one or more motor end-plates, with a portion of the axon. Harriman studied several neurogenic and primary muscle disorders with this technique. Broca's contribution to aphasia was reviewed by Critchley a century later. The significance of Broca's area has suffered considerably in the intervening years, according to Critehley, due to the confusion between localization of lesions and localization of function. Broca was less to blame than some of his
<i>GSTP1</i> and <i>TNF</i> Gene Variants and Associations between Air Pollution and Incident Childhood Asthma: The Traffic, Asthma and Genetics (TAG) Study
Authors: Elaina A. MacIntyre, Michael Brauer, Erik Melén, Carl Peter Bauer, Mario Bauer, Dietrich Berdel, Anna Bergström, Bert Brunekreef, Moira Chan-Yeung, Claudia Klümper, Elaine Fuertes, Ulrike Gehring, Anna Gref, Joachim Heinrich, Olf Herbarth, Marjan Kerkhof, Gerard H. Koppelman, Anita L. Kozyrskyj, Göran Pershagen, Dirkje S. Postma, Elisabeth Thiering, Carla M.T. Tiesler, Christopher Carlsten
Journal: Environmental Health Perspectives (2014)

Genetics may partially explain observed heterogeneity in associations between traffic-related air pollution and incident asthma.Our aim was to investigate the impact of gene variants associated with oxidative stress and inflammation on associations between air pollution and incident childhood asthma.Traffic-related air pollution, asthma, wheeze, gene variant, and potential confounder data were pooled across six birth cohorts. Parents reported physician-diagnosed asthma and wheeze from birth to 7-8 years of age (confirmed by pediatric allergist in two cohorts). Individual estimates of annual average air pollution [nitrogen dioxide (NO2), particulate matter ≤ 2.5 μm (PM2.5), PM2.5 absorbance, ozone] were assigned to each child's birth address using land use regression, atmospheric modeling, and ambient monitoring data. Effect modification by variants in GSTP1 (rs1138272/Ala114Val and rs1695/IIe105Val) and TNF (rs1800629/G-308A) was investigated.Data on asthma, wheeze, potential confounders, at least one SNP of interest, and NO2 were available for 5,115 children. GSTP1 rs1138272 and TNF rs1800629 SNPs were associated with asthma and wheeze, respectively. In relation to air pollution exposure, children with one or more GSTP1 rs1138272 minor allele were at increased risk of current asthma [odds ratio (OR) = 2.59; 95% CI: 1.43, 4.68 per 10 μg/m3 NO2] and ever asthma (OR = 1.64; 95% CI: 1.06, 2.53) compared with homozygous major allele carriers (OR = 0.95; 95% CI: 0.68, 1.32 for current and OR = 1.20; 95% CI: 0.98, 1.48 for ever asthma; Bonferroni-corrected interaction p = 0.04 and 0.01, respectively). Similarly, for GSTP1 rs1695, associations between NO2 and current and ever asthma had ORs of 1.43 (95% CI: 1.03, 1.98) and 1.36 (95% CI: 1.08, 1.70), respectively, for minor allele carriers compared with ORs of 0.82 (95% CI: 0.52, 1.32) and 1.12 (95% CI: 0.84, 1.49) for homozygous major allele carriers (Bonferroni-corrected interaction p-values 0.48 and 0.09). There were no clear differences by TNF genotype.Children carrying GSTP1 rs1138272 or rs1695 minor alleles may constitute a susceptible population at increased risk of asthma associated with air pollution.
Low Level Her2 Overexpression Is Associated with Rapid Tumor Cell Proliferation and Poor Prognosis in Prostate Cancer
Authors: Sarah Minner, Birte Jessen, Lars Stiedenroth, Eike Burandt, Jens Köllermann, Martina Mirlacher, Andreas Erbersdobler, Christian Eichelberg, Margit Fisch, Tim Henrik Brümmendorf, Carsten Bokemeyer, Ronald Simon, Thomas Steuber, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm
Journal: Clinical Cancer Research (2010)

The HER2 oncogene is involved in the biology of many different tumor types and serves as a prognostic marker and a therapeutic target in breast cancer. In contrast to breast cancer, studies on Her2 overexpression and gene amplification in prostate cancer have yielded different results. The purpose of this study was to learn more on the prevalence and clinical significance of HER2 amplification and overexpression in prostate cancer.A tissue microarray containing >2,000 prostate cancers with follow-up data was used. Tissue microarray sections were analyzed on protein and DNA level using two different antibodies (HercepTest, DAKO; Novocastra NCL-CB11) and fluorescence in situ hybridization.Immunohistochemical analyses showed highly similar results for both antibodies. Detectable Her2 immunostaining was observed in 17.2% for the HercepTest and in 22.5% for the Novocastra antibody with the vast majority of cases showing 1+ or 2+ staining. For both antibodies (HercepTest/Novocastra), significant associations were found between positive staining and high Gleason grade (P < 0.0001, both), advanced pT stage (P < 0.0001/P = 0.0015), rapid tumor cell proliferation (P = 0.0004/P = 0.0071), and tumor recurrence (P < 0.0001, both). HER2 amplification was only found in 1 of 2,525 analyzable cases (0.04%).Low-level Her2 overexpression occurs at relevant frequency in prostate cancer and in the absence of gene amplification. Increased Her2 expression may potentially lead to an aggressive behavior of tumor cells through the stimulation of tumor cell proliferation because Her2 staining was shown to be significantly associated with Ki67 labeling index. These data argue for reconsidering anti-Her2 therapy, possibly with modified approaches.
Patients in acute surgical wards: a survey in Glasgow.
Authors: I W Strang, F A Boddy, B Jennett
Journal: BMJ (1977)

A survey was made of all patients in general surgical, urological, and orthopaedic and accident wards in Glasgow on one day in June 1975. Its purpose was to define features of acute surgical practice of relevance to the future planning of resources, particularly bed numbers. Over 40% of the patients in both surgical and orthopaedic wards were over 65 years. Most patients had serious conditions and could not have been treated other than by admission to an acute surgical ward. But a substantial minority no longer needed such facilities and could have been transferred to second-line beds, although many still required skilled nursing care. Delay in the discharge of elderly patients from acute surgical wards as a consequence of non-surgical (often medical or social) problems results in a proportion of acute surgical beds fulfilling a second-line function. Unless arrangements for the earlier discharge of these patients are made any reduction in acute surgical beds is likely to restrict elective surgery, especially in orthopaedics.
Use of automated telephone disease management calls in an ethnically diverse sample of low-income patients with diabetes.
Authors: J D Piette, S J McPhee, M Weinberger, C A Mah, F B Kraemer
Journal: Diabetes Care (1999)

OBJECTIVE: We examined whether low-income patients with diabetes were able and willing to use automated telephone disease management (ATDM) calls to provide health status information that could improve the quality of their care. RESEARCH DESIGN AND METHODS: A total of 252 adults with diabetes, 30 of whom spoke Spanish as their primary language, were enrolled at the time of clinic visits in a Department of Veterans Affairs health care system (n = 132) or a county health care system (n = 120). Patients received ATDM calls for 12 months and responded to queries using their touch-tone telephones. We examined 1) whether patients completed ATDM assessments consistently over the year and used the calls to report their self-monitored blood glucose (SMBG) levels, 2) the characteristics of patients most likely to use the system frequently, 3) whether patients responded consistently within ATDM assessments, and 4) whether ATDM assessments differentiated among groups of patients with different clinical profiles at baseline. RESULTS: Half of all patients completed at least 77% of their attempted assessments, and one-fourth completed at least 91%. Half of all patients reported SMBG levels during at least 86% of their assessments. Patients completed assessments and reported glucose levels consistently over the year. Health status indicators were the most important determinants of assessment completion rates, while socioeconomic factors were more strongly associated with patients' likelihood of reporting SMBG data during assessments. Patients' responses within assessments were consistent, and the information they provided during their initial assessments identified groups with poor glycemic control and other health problems. CONCLUSIONS: Most low-income patients with diabetes can and will use ATDM calls as part of their care. The information they provide is reliable and has clinical significance. ATDM calls could improve the information base for diabetes management while relieving some of the pressures of delivering diabetes care under cost constraints.
Early BCG vaccination is unrelated to pulmonary immunity against<i>Mycobacterium tuberculosis</i>in adults
Authors: Christian Herzmann, Giovanni Sotgiu, Tom Schaberg, Martin Ernst, Steffen Stenger, Christoph Lange
Journal: European Respiratory Journal (2014)

In summary, we present data from the largest cohort reported, to our knowledge, of healthy adult contacts of tuberculosis patients evaluated by bronchoscopy for pulmonary immune responses against M. tuberculosis and M. bovis BCG.In support of previous epidemiological data, we were unable to find a protective effect of M. bovis BCG vaccination against the development of latent infection with M. tuberculosis by adulthood [2].The results underline the importance of the analysis of functional M. tuberculosis-specific immune responses from human lung cells for the assessment of correlates of immunity in future tuberculosis vaccine trials.
Serendipitous Detection of an Errant Central Venous Catheter
Authors: JOSEPH A. ORZEL, KENNETH ROMDALL, ROBERT GRIEP
Journal: Clinical Nuclear Medicine (1985)

The inappropriate placement of a patient's central venous catheter in the pleural space by the serendipitous injection of Tc-99m labeled red blood cells through the catheter during a Gl bleeding study was discovered. Position and patency of central venous lines can be incidentally evaluated by using existing central venous catheters for administration of radiopharmaceuticals during radionuclide imaging studies.
Effect of ingestion of fat on ileostomy effluent.
Authors: S E Higham, N W Read
Journal: Gut (1990)

Infusion of fat into the ileum slows small bowel transit and increases absorption of a carbohydrate meal. Paired studies were undertaken to investigate the effect of adding fat to the diet on gastrointestinal transit and absorption in eight people with terminal ileostomies. Each subject ate a daily diet that contained either low or high levels of fat but equivalent amounts of carbohydrate, protein, and fibre. Solid and liquid markers were added to the food to measure transit times. The ileostomy outputs after the meals were analysed for protein, fat, carbohydrate, polyethylene glycol, and the delivery of solid markers. All subjects produced more ileal effluent while taking the high fat diet compared with the low fat diet. Fat and protein outputs were significantly higher on the high fat days, but a greater proportion of the fat was absorbed during the high fat diet compared with the low fat diet. The output of carbohydrate on the two diets was not significantly different. The incorporation of fat in the diet produced no significant differences in the transit times of the first marker, but a slight prolongation of the transit time of the second marker. Increasing the fat content of the diet did not slow small bowel transit or increase nutrient absorption. The increase in protein and water output could be explained by an increased secretion of pancreatic enzymes.
Reproductive failure and reduced blood pressure in mice lacking the EP2 prostaglandin E2 receptor
Authors: Stephen L. Tilley, Laurent P. Audoly, Elizabeth H. Hicks, Hyung-Suk Kim, Patrick J. Flannery, Thomas M. Coffman, Beverly H. Koller
Journal: Journal of Clinical Investigation (1999)

Prostaglandins (PGs) are bioactive lipids that modulate a broad spectrum of biologic processes including reproduction and circulatory homeostasis. Although reproductive functions of mammals are influenced by PGs at numerous levels, including ovulation, fertilization, implantation, and decidualization, it is not clear which PGs are involved and whether a single mechanism affects all reproductive functions. Using mice deficient in 1 of 4 prostaglandin E2 (PGE2) receptors — specifically, the EP2 receptor — we show that Ep2–/– females are infertile secondary to failure of the released ovum to become fertilized in vivo. Ep2–/– ova could be fertilized in vitro, suggesting that in addition to previously defined roles, PGs may contribute to the microenvironment in which fertilization takes place. In addition to its effects on reproduction, PGE2 regulates regional blood flow in various vascular beds. However, its role in systemic blood pressure homeostasis is not clear. Mice deficient in the EP2 PGE2 receptor displayed resting systolic blood pressure that was significantly lower than in wild-type controls. Blood pressure increased in these animals when they were placed on a high-salt diet, suggesting that the EP2 receptor may be involved in sodium handling by the kidney. These studies demonstrate that PGE2, acting through the EP2 receptor, exerts potent regulatory effects on two major physiologic processes: blood pressure homeostasis and in vivo fertilization of the ovum.
Paramediastinal Inflammatory Changes After Chemoradiation Detected on FDG PET-CT Imaging
Authors: Olivier Gheysens, Kristof Baete, Christophe M. Deroose, Felix M. Mottaghy
Journal: Clinical Nuclear Medicine (2010)

A 56-year-old man with cT3N1M0 esophageal spinocellular epithelioma underwent FDG-PET/CT 4 and 8 months after chemoradiation because of progressive dysphagia. The initial FDG-PET/CT solely revealed the hypermetabolic tumor and a small adjacent lymph node at the upper thoracic esophagus. The second FDG-PET/CT showed slightly increased paramediastinal FDG-uptake due to inflammation. The third FDG-PET/CT showed a hypermetabolic focus at the thoracic esophagus (local recurrence), the left vocal cord, and in the paramediastinal area. The latter was consistent with chemoradiation-induced changes. This case illustrates that inflammatory changes after chemoradiation may take a long time to develop or subside and have to be appropriately recognized.