tbuckley/cabot-search huggingface dataset:
The Brief MAST: A Shortened Version of the Michigan Alcoholism Screening Test
Authors: ALEX D. POKORNY, BYRON A. MILLER, HOWARD B. KAPLAN
Journal: American Journal of Psychiatry (1972)

The authors report an abbreviated version of the Michigan Alcoholism Screening Test (MAST). They hypothesized, on the basis of previously published data, that scores based on ten of the questions of the MAST would be as effective in discriminating between alcoholics and nonalcoholics as scores based on all 25 questions. The responses of 60 alcoholic and 62 nonalcoholic psychiatric patients supported their hypothesis.
Intestinal absorption under the influence of vasopressin: studies in unanaesthetised rats.
Authors: R Dennhardt, B Lingelbach, F J Haberich
Journal: Gut (1979)

Experiments were carried out in different segments of the intestine of unanaesthetised rats to assess the effect of vasopressin on intestinal absorptive processes. The following data were observed. (1) Within a physiological range of doses (Aziz, 1969), ADH diminished the net sodium absorption mainly by reducing the unidirectional sodium influx, whereas the behaviour of the efflux was not uniform. (2) The unidirectional volume fluxes showed the same behaviour as did the sodium fluxes. (3) ADH produced an oral-aboral gradient (jejunum greater than ileum greater than colon). (4) ADH did not significantly change the transfer of actively transported sugars; it did influence, however, passively transported substances. (5) During the intravenous application of ADH, a substance was secreted into the perfusion solution which diminished the absorption of volume and electrolytes. (6) Cyclic AMP acted on intestinal absorption in the same way as did ADH. In view of these results two mutually independent transport pathways for sodium and water are supposed, one of which is influenced by ADH or cAMP. Based on a two membrane model, an ADH mechanism is discussed: the permeability of the luminal membrane system is enhanced in the presence of vasopressin.
Effects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activity
Authors: Alan Dresner, Didier Laurent, Melissa Marcucci, Margaret E. Griffin, Sylvie Dufour, Gary W. Cline, Lori A. Slezak, Dana K. Andersen, Ripudaman S. Hundal, Douglas L. Rothman, Kitt Falk Petersen, Gerald I. Shulman
Journal: Journal of Clinical Investigation (1999)

To examine the mechanism by which free fatty acids (FFA) induce insulin resistance in human skeletal muscle, glycogen, glucose-6-phosphate, and intracellular glucose concentrations were measured using carbon-13 and phosphorous-31 nuclear magnetic resonance spectroscopy in seven healthy subjects before and after a hyperinsulinemic-euglycemic clamp following a five-hour infusion of either lipid/heparin or glycerol/heparin. IRS-1–associated phosphatidylinositol 3-kinase (PI 3-kinase) activity was also measured in muscle biopsy samples obtained from seven additional subjects before and after an identical protocol. Rates of insulin stimulated whole-body glucose uptake. Glucose oxidation and muscle glycogen synthesis were 50%–60% lower following the lipid infusion compared with the glycerol infusion and were associated with a ∼90% decrease in the increment in intramuscular glucose-6-phosphate concentration, implying diminished glucose transport or phosphorylation activity. To distinguish between these two possibilities, intracellular glucose concentration was measured and found to be significantly lower in the lipid infusion studies, implying that glucose transport is the rate-controlling step. Insulin stimulation, during the glycerol infusion, resulted in a fourfold increase in PI 3-kinase activity over basal that was abolished during the lipid infusion. Taken together, these data suggest that increased concentrations of plasma FFA induce insulin resistance in humans through inhibition of glucose transport activity; this may be a consequence of decreased IRS-1–associated PI 3-kinase activity.
Progressive Pseudogenization: Vitamin C Synthesis and Its Loss in Bats
Authors: Jie Cui, Yi-Hsuan Pan, Yijian Zhang, Gareth Jones, Shuyi Zhang
Journal: Molecular Biology and Evolution (2010)

For the past 50 years, it was believed that all bats, like humans and guinea pigs, did not synthesize vitamin C (Vc) because they lacked activity of L-gulonolactone oxidase (GULO) in their livers. Humans and guinea pigs lack the activity due to pseudogenization of GULO in their genomes, but there is no genetic evidence to show whether such loss in bats is caused by pseudogenization. Unexpectedly, our successful molecular cloning in one frugivorous bat (Rousettus leschenaultii) and one insectivorous bat (Hipposideros armiger) ascertains that no pseudogenization occurs in these species. Furthermore, we find normal GULO protein expression using bat-specific anti-GULO polyclonal antibodies in bats, evaluated by Western blotting. Most surprisingly, GULO activity assays reveal that these two bat species have retained the ability to synthesize Vc, but at low levels compared with the mouse. It is known that bats in the genus Pteropus have lost GULO activity. We then found that functional constraints acting on the GULO of Pteropus vampyrus (which lost its function) are relaxed. These results imply that the ability to synthesize Vc in bats has not been lost completely in species as previously thought. We also suggest that the evolution of bat GULO genes can be a good model to study genetic processes associated with loss-of-function.
Somatic Mutations in Cerebral Cortical Malformations
Authors: Saumya S. Jamuar, Anh-Thu N. Lam, Martin Kircher, Alissa M. D’Gama, Jian Wang, Brenda J. Barry, Xiaochang Zhang, Robert Sean Hill, Jennifer N. Partlow, Aldo Rozzo, Sarah Servattalab, Bhaven K. Mehta, Meral Topcu, Dina Amrom, Eva Andermann, Bernard Dan, Elena Parrini, Renzo Guerrini, Ingrid E. Scheffer, Samuel F. Berkovic, Richard J. Leventer, Yiping Shen, Bai Lin Wu, A. James Barkovich, Mustafa Sahin, Bernard S. Chang, Michael Bamshad, Deborah A. Nickerson, Jay Shendure, Annapurna Poduri, Timothy W. Yu, Christopher A. Walsh
Journal: New England Journal of Medicine (2014)

Although there is increasing recognition of the role of somatic mutations in genetic disorders, the prevalence of somatic mutations in neurodevelopmental disease and the optimal techniques to detect somatic mosaicism have not been systematically evaluated.Using a customized panel of known and candidate genes associated with brain malformations, we applied targeted high-coverage sequencing (depth, ≥200×) to leukocyte-derived DNA samples from 158 persons with brain malformations, including the double-cortex syndrome (subcortical band heterotopia, 30 persons), polymicrogyria with megalencephaly (20), periventricular nodular heterotopia (61), and pachygyria (47). We validated candidate mutations with the use of Sanger sequencing and, for variants present at unequal read depths, subcloning followed by colony sequencing.Validated, causal mutations were found in 27 persons (17%; range, 10 to 30% for each phenotype). Mutations were somatic in 8 of the 27 (30%), predominantly in persons with the double-cortex syndrome (in whom we found mutations in DCX and LIS1), persons with periventricular nodular heterotopia (FLNA), and persons with pachygyria (TUBB2B). Of the somatic mutations we detected, 5 (63%) were undetectable with the use of traditional Sanger sequencing but were validated through subcloning and subsequent sequencing of the subcloned DNA. We found potentially causal mutations in the candidate genes DYNC1H1, KIF5C, and other kinesin genes in persons with pachygyria.Targeted sequencing was found to be useful for detecting somatic mutations in patients with brain malformations. High-coverage sequencing panels provide an important complement to whole-exome and whole-genome sequencing in the evaluation of somatic mutations in neuropsychiatric disease. (Funded by the National Institute of Neurological Disorders and Stroke and others.).
Primary Sjogren syndrome
Authors: M. Ramos-Casals, P. Brito-Zeron, A. Siso-Almirall, X. Bosch
Journal: BMJ (2012)

Sjögren syndrome is a systemic autoimmune disease causing secretory gland dysfunction.This leads to dryness of the main mucosal surfaces such as the mouth, eyes, nose, pharynx, larynx, and vagina. 1 Sjögren syndrome may be a serious disease, with excess mortality caused by haematological cancer. 2The cause of Sjögren syndrome is unknown, but factors postulated to play a role are both genetic and environmental. 1 The disease overwhelmingly affects middle aged women but may also affect children, men, and elderly people.When sicca symptoms appear in a previously healthy person, the syndrome is classified as primary Sjögren syndrome.Sjögren syndrome associated with another underlying systemic autoimmune disorder, such as systemic lupus erythematosus, rheumatoid arthritis, or scleroderma is known as secondary or, increasingly, associated Sjögren syndrome.Sicca symptoms (dry mouth and eyes) are among the most common oral and ocular complaints seen by general practitioners, but even so the disease is often underdiagnosed or misdiagnosed. 3 4Although incidence data in primary care are scarce, preliminary reports suggest it may be around two per 1000 patients per year, 5 with an overall prevalence in Europe of nearly 0.1%. 6 7Patients with Sjögren syndrome require a health spend double that of the mean for primary care patients and similar to that for patients with rheumatoid arthritis.
Therapeutic activity of a combination of immunostimulatory monoclonal antibodies (anti-B7-H1, CD137 and OX40) on a c-myc-driven spontaneous transgenic model of hepatocellular carcinoma
Authors: Aizea Morales-Kastresana, Sanmamed F Miguel, Inmaculada Rodriguez, Asis Palazon, Ivan Martinez-Forero, Sara Labiano, Sandra Hervas-Stubbs, Bruno Sangro, Carmen Ochoa, Ana Rouzaut, Arantza Azpilikueta, Elixabet Bolaños, Maria Jure-Kunkel, Ines Gutgemann, Ignacio Melero
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Several immunostimulatory monoclonal antibodies (ISmAbs) that derepress and unleash antitumor immune responses are showing efficacy in cancer clinical trials. MAbs anti-B7-H1 (PD-L1) block a critical inhibitory pathway for T cells, while antibodies anti-CD137 and OX40 provide
Gastric freezing in the rat.
Authors: R Buchan, C G Clark
Journal: Gut (1965)

EDITORIAL SYNOPSIS This study reports the effects of gastric freezing on gastric secretion in the rat.The criteria necessary to induce achlorhydria are defined and secretory studies, performed at monthly intervals after freezing, recorded.The results show that gastric freezing can induce achlorhydria in the rat, so that freezing have may some therapeutic value if the technical problems in man can be overcome.The treatment of chronic duodenal ulceration by gastric freezing, introduced by Wangensteen, Peter, Nicoloff, Walder, Sosin, and Bernstein (1962), was based on experimental studies which showed that achlorhydria, resistant to insulin, peptone, and submaximal histamine stimulation, could be induced in gastric pouches in the dog.Bernstein, Goodale, McFee, Madsen, Allcock, and Wangensteen (1964) reported enthusiastically on the therapeutic effects in man, but noted that a single freeze failed to induce prolonged secretory depression in the dog and is either slight or short-lived (Berg and Nanson, 1963; Clapp, Gilat, Tayao, Creemers, and Sherlock, 1963; Fores, Mitchell, and Weldon, 1964; Macleod, 1964).Similarly, in man the reduction in acid secretion after maximum histamine stimulation is frequently unsatisfactory (Nabseth, Seletz, Gentin, Gottlieb, and Zamcheck, 1964; Lawrie, Smith, Goodall, Pitman, and Forrest, 1964; Karacadag and Klotz, 1964) or recovery occurs within six to eight weeks (Hitchcock, Bitter, and Sutherland, 1964).In the only two reports of controlled clinical trials of gastric freezing for duodenal ulcer in man, one showed no benefit (Perry, Dunphy, Fruin, and Littman, 1964) while the other showed improvement in 75 % of cases after six months, compared with 25 % of controls (Rose, Fordtran, Harrell, and Friedman, 1964).In both cases, the numbers were small and the period of observations short.Gastric freezing appears an attractive alternative to surgery, but several observations raised doubt about its therapeutic potential.Therefore it is essential to re-examine the experimental basis of this procedure and this paper reports our experience of gastric freezing in the rat.This animal was chosen partly because of the ease with which gastric freezing can be induced and observed, and partly because tests of gastric function are well established.
Phase I Clinical Trial of Mafosfamide in Infants and Children Aged 3 Years or Younger With Newly Diagnosed Embryonal Tumors: A Pediatric Brain Tumor Consortium Study (PBTC-001)
Authors: Susan M. Blaney, James Boyett, Henry Friedman, Amar Gajjar, Russ Geyer, Marc Horowtiz, Daniel Hunt, Mark Kieran, Larry Kun, Roger Packer, Peter Phillips, Ian F. Pollack, Michael Prados, Richard Heideman
Journal: Journal of Clinical Oncology (2005)

A phase I trial of intrathecal (IT) mafosfamide was performed to determine the optimal dose, dose-limiting toxicities, and incidence and severity of other toxicities when administered in association with concomitant multiagent systemic chemotherapy to children younger than 3 years with newly diagnosed embryonal tumors.Twenty-five assessable patients received IT mafosfamide at one of six dose levels ranging from 5 mg to 17 mg. Patients were premedicated with dexamethasone (0.15 mg/kg) and morphine (0.1 mg/kg) before receiving IT mafosfamide. Serial samples of CSF for pharmacokinetic studies were obtained in a subset of patients with Ommaya reservoirs.Irritability, presumably secondary to pain or headache during mafosfamide administration, was dose limiting in two of three patients at the 17-mg dose level. The maximum-tolerated dose of IT mafosfamide following premedication with dexamethasone and morphine was 14 mg.The maximum tolerated dose and recommended phase II dose of IT mafosfamide in patients younger than 3 years with newly diagnosed embryonal CNS tumors is 14 mg. A trial to assess the efficacy of regional therapy with IT mafosfamide administered with intensive systemic chemotherapy in children younger than 3 years with primary intracranial embryonal tumors is now in progress.
MODE OF ACTION OF STREPTOMYCIN ON TYPE b H. INFLUENZAE
Authors: Hattie E. Alexander, Grace Leidy
Journal: The Journal of Experimental Medicine (1947)

1. Of fourteen patients with type b H. influenzae infections treated with streptomycin alone ten recovered promptly; in three of the four remaining cases failure was proved to be due to emergence of resistance of the organisms to streptomycin. 2. The rapid development of resistance to 1000 units of streptomycin per cc. during treatment argues against metabolic adaptation of the bacteria. 3. Careful study of large samples of initial bacterial populations shows resistant members in all ten strains examined. The incidence varies from 1 in 1.1 billion to 1 in 13.8 billion organisms. 4. The proportion of resistant members is not significantly higher, before treatment, in patients who do poorly than in those who respond promptly. 5. The results indicate that emergence of resistance is the result of a selective process; after elimination of sensitive members the very few resistant ones, apparently present in all strains, make up most or all of the population in the cultures taken after commencement of treatment. 6. The survival of organisms which can grow in high concentrations of streptomycin, either in patients or in vitro, is influenced more by the size of the bacterial population than by any other known factor. 7. Since the bacterial population is relatively small in those patients with mild or moderately severe infections the likelihood of a significant number of very resistant members being present is remote. 8. The traits responsible for resistance of the organisms are apparently inherited: (a) The resistant state of one strain has been transmitted in vitro without change in degree through over one hundred subcultures in the absence of streptomycin, (b) Persistence of resistant organisms in the nasopharynx of one patient during a one year period raises an important public health problem.
A Putative Vesicular Transporter Expressed in Drosophila Mushroom Bodies that Mediates Sexual Behavior May Define a Neurotransmitter System
Authors: Elizabeth S. Brooks, Christina L. Greer, Rafael Romero-Calderón, Christine N. Serway, Anna Grygoruk, Jasmine M. Haimovitz, Bac T. Nguyen, Rod Najibi, Christopher J. Tabone, J. Steven de Belle, David E. Krantz
Journal: Neuron (2011)
Multiple Robust Signatures for Detecting Lymph Node Metastasis in Head and Neck Cancer
Authors: Paul Roepman, Patrick Kemmeren, Lodewijk F.A. Wessels, Piet J. Slootweg, Frank C.P. Holstege
Journal: Cancer Research (2006)

Genome-wide mRNA expression measurements can identify molecular signatures of cancer and are anticipated to improve patient management. Such expression profiles are currently being critically evaluated based on an apparent instability in gene composition and the limited overlap between signatures from different studies. We have recently identified a primary tumor signature for detection of lymph node metastasis in head and neck squamous cell carcinomas. Before starting a large multicenter prospective validation, we have thoroughly evaluated the composition of this signature. A multiple training approach was used for validating the original set of predictive genes. Based on different combinations of training samples, multiple signatures were assessed for predictive accuracy and gene composition. The initial set of predictive genes is a subset of a larger group of 825 genes with predictive power. Many of the predictive genes are interchangeable because of a similar expression pattern across the tumor samples. The head and neck metastasis signature has a more stable gene composition than previous predictors. Exclusion of the strongest predictive genes could be compensated by raising the number of genes included in the signature. Multiple accurate predictive signatures can be designed using various subsets of predictive genes. The absence of genes with strong predictive power can be compensated by including more genes with lower predictive power. Lack of overlap between predictive signatures from different studies with the same goal may be explained by the fact that there are more predictive genes than required to design an accurate predictor.
Correlation of ERG Expression and DNA Methylation Biomarkers with Adverse Clinicopathologic Features of Prostate Cancer
Authors: Ken Kron, Liyang Liu, Dominique Trudel, Vaijayanti Pethe, John Trachtenberg, Neil Fleshner, Bharati Bapat, Theodorus van der Kwast
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Fusion of the TMPRSS2 gene with the ERG oncogene and aberrant DNA methylation patterns are commonly found in prostate cancer. The aim of this study was to analyze the relationship between ERG expression, DNA methylation of three biomarkers, and clinicopathologic features of prostate cancer. Experimental Design: Immunohistochemistry for ERG protein was conducted as a surrogate for TMPRSS2-ERG fusions. We analyzed methylation of CYP26A1, TBX15, and HOXD3 in 219 prostatectomy specimens by the quantitative MethyLight assay. DNA methylation was compared between ERG-positive and -negative cases and correlations of ERG and DNA methylation with clinicopathologic features were analyzed using χ2, Spearman correlation, logistic regression, and Cox regression. Results: ERG expression varied according to Gleason pattern (almost absent in pattern II, highest in pattern III, and lower in pattern IV/V) and showed a strong positive correlation with methylation levels of CYP26A1, TBX15, and HOXD3 (Spearman P &amp;lt; 0.005). TBX15 and HOXD3 methylation were significantly associated with pathologic stage, Gleason score, and Gleason pattern (P ≤ 0.015). In multivariate regression analysis, PSA, TBX15 high methylation, and HOXD3 high methylation were significantly associated with stage (P &amp;lt; 0.05), whereas ERG expression was negatively correlated with Gleason score (P = 0.003). In univariate time-to-recurrence analysis, a combination of HOXD3/TBX15 high methylation predicted recurrence in ERG-positive and -negative cases (P &amp;lt; 0.05). Conclusions: CYP26A1, TBX15, and HOXD3 are methylation markers of prostate cancer associated with ERG expression and clinicopathologic variables, suggesting that incorporation of these markers may be useful in a pre- and posttreatment clinical setting. Clin Cancer Res; 18(10); 2896–904. ©2012 AACR.
Signal transducer and activator of transcription 3 (STAT3) activation in prostate cancer: Direct STAT3 inhibition induces apoptosis in prostate cancer lines.
Authors: Paula M De Angelis, Katherine L Kravik, Siv H Tunheim, Terje Haug, Wenche H Reichelt
Journal: Molecular Cancer (2004)

Signal transducers and activators of transcription (STAT) were originally discovered as components of cytokine signal transduction pathways. Persistent activation of one STAT, STAT3, is a common feature of prostate cancer. Activated STAT3 was found in pathology specimens obtained from prostatectomy in the cancerous areas but not in the normal margins. Because the activation of STAT3 is mediated by the action of an upstream Janus kinase (JAK) kinase, usually JAK1 or JAK2, the activation step for STAT3 might itself be a target for therapy in prostate cancer. However, the redundancy of upstream kinases may make this strategy unreliable for therapy. To develop molecular targets for prostate cancer treatment, JAK kinase and STAT3 inhibition of two prostate cancer lines were compared. DU145 and NRP-154 cells were treated with JAK kinase inhibitors, analyzed for onset of apoptosis, and measured by annexin V binding and propidium iodide uptake. Activation of caspases in the cells was determined by measuring cleaved caspase-3 following treatment. For determining the effect on mitochondrial membrane depolarization that accompanies apoptosis, the fluorescent dye JC-1 was used. STAT3 was specifically inhibited by transfecting either a dominant-negative (DN) STAT3 plasmid or antisense STAT3 oligonucleotides into the cells. To look for reduction in STAT3 levels within cells, fixed and permeabilized prostate cancer cells were stained with antibody to STAT3. We found that more than one JAK kinase is involved in STAT3 activation in prostate cancer lines. AG490 (JAK2 specific) induced apoptosis in DU145 but not in NRP-154 prostate cancer lines, whereas piceatannol (JAK1 specific) induced apoptosis in NRP-154 but not in DU145 cells. Next, we demonstrated efficacy of specific STAT3 inhibitors in prostate cancer lines. Both induction of apoptosis and reduction in intracellular STAT3 protein were observed following treatment with antisense STAT3 oligonucleotides, while transfection of a DN-STAT3 plasmid into both prostate cancer cell lines resulted in loss of viability and onset of apoptosis. We conclude that STAT3-specific inhibitors, rather than JAK kinase-specific inhibitors, should be more useful therapeutically in treating androgen-resistant prostate cancer and that STAT3 is an appropriate target in the treatment of prostate cancer.