tbuckley/cabot-search huggingface dataset:
An elusive role for glycosylation in the structure and function of reproductive hormones
Authors: K. Willey
Journal: Human Reproduction Update (1999)

The crescendo of events leading first to ovulation and subsequently to birth is orchestrated by a broad repertoire of hormones. The major hormones of the ovulatory cycle are representatives of four hormone classes: neurotransmitters, releasing factors, trophic hormones acting on target tissues, and steroid-like molecules released by the target tissues. The punctuate and staccato rhythm of the neurotransmitters and releasing hormones relentlessly drive the swelling and protracted wave of activity by the luteotrophic and steroid hormones. Carbohydrates alone are notably absent as hormones and the predominant role for glycosylation appears to be the conferment of increased solubility to endocrine molecules, either during their manufacture or by modulating circulatory half-life. Rarely considered examples of the importance of glycosylation in reproductive hormones include adenosine, important for spermatozoan activity, and the hormone-binding globulins, which ensure the aqueous transport of hydrophobic steroids. The archetype glycoprotein hormones, especially human chorionic gonadotrophin (HCG), are discussed more extensively, as the structural and functional roles of carbohydrate in these hormones have been studied exhaustively. Conversely, the direct involvement of HCG and the importance of its carbohydrate for autonomous growth, in both placental invasion and tumorigenesis, has received little attention in the literature.
Bleeding massive gastric ulcer on diflunisal (Dolobid)
Authors: B Scott
Journal: BMJ (1979)

hypnotised and trained in autohypnosis to avert an attack.This can be perfected so that it is effective in a fraction of the time for chemotherapy, without any side effects, without any need for "sleeping away" the illness, and without the incapacity.Hypnosis is more time consuming than writing a prescription, but far less so than most physicians realise; and it has the added merit of permanent remission in appreciable numbers of sufferers.
Pneumonic Plague in an Untreated Plague-Vaccinated Individual
Authors: Richard J. Cohen
Journal: JAMA (1967)

A 50-year old American immunization technician in South Vietnam was discovered to have pneumonic plague eight days after the onset of fever, chills, pleuretic chest pain, and a cough productive of large amounts of bloody sputum. His survival, untreated, for that period of time with a disease renowned for its rapid lethality suggests that prior immunizations with killed and living vaccines significantly altered the natural course of the disease.
Dynamic sets of potentially interchangeable connotations: A theory of mental objects
Authors: Alexandre Linhares
Journal: Behavioral and Brain Sciences (2008)

Abstract Analogy-making is an ability with which we can abstract from surface similarities and perceive deep, meaningful similarities between different mental objects and situations. I propose that mental objects are dynamically changing sets of potentially interchangeable connotations. Unfortunately, most models of analogy seem devoid of both semantics and relevance-extraction, postulating analogy as a one-to-one mapping devoid of connotation transfer.
<b> <i>In vivo</i> </b> Near-Infrared Fluorescence Imaging of Integrin αvβ3 in Brain Tumor Xenografts
Authors: Xiaoyuan Chen, Peter S. Conti, Rex A. Moats
Journal: Cancer Research (2004)

Abstract Noninvasive visualization of cell adhesion molecule αvβ3 integrin expression in vivo has been well studied by using the radionuclide imaging modalities in various preclinical tumor models. A literature survey indicated no previous use of cyanine dyes as contrast agents for in vivo optical detection of tumor integrin. Herein, we report the integrin receptor specificity of novel peptide-dye conjugate arginine-glycine-aspartic acid (RGD)-Cy5.5 as a contrast agent in vitro, in vivo, and ex vivo. The RGD-Cy5.5 exhibited intermediate affinity for αvβ3 integrin (IC50 = 58.1 ± 5.6 nmol/L). The conjugate led to elevated cell-associated fluorescence on integrin-expressing tumor cells and endothelial cells and produced minimal cell fluorescence when coincubated with c(RGDyK). In vivo imaging with a prototype three-dimensional small-animal imaging system visualized subcutaneous U87MG glioblastoma xenograft with a broad range of concentrations of fluorescent probe administered via the tail vein. The intermediate dose (0.5 nmol) produces better tumor contrast than high dose (3 nmol) and low dose (0.1 nmol) during 30 minutes to 24 hours postinjection, because of partial self-inhibition of receptor-specific tumor uptake at high dose and the presence of significant amount of background fluorescence at low dose, respectively. The tumor contrast was also dependent on the mouse viewing angles. Tumor uptake of RGD-Cy5.5 was blocked by unlabeled c(RGDyK). This study suggests that the combination of the specificity of RGD peptide/integrin interaction with near-infrared fluorescence detection may be applied to noninvasive imaging of integrin expression and monitoring anti-integrin treatment efficacy providing near real-time measurements.
Clinical presentation, management and outcomes in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF)
Authors: F. Follath, M. B. Yilmaz, J. F. Delgado, J. T. Parissis, R. Porcher, E. Gayat, Nigel Burrows, A. Mclean, F. Vilas-Boas, A. Mebazaa
Journal: Intensive Care Medicine (2011)
Asymmetric Chromatid Segregation in Cardiac Progenitor Cells Is Enhanced by Pim-1 Kinase
Authors: Balaji Sundararaman, Daniele Avitabile, Mathias H. Konstandin, Christopher T. Cottage, Natalie Gude, Mark A. Sussman
Journal: Circulation Research (2012)

Cardiac progenitor cells (CPCs) in the adult heart are used for cell-based treatment of myocardial damage, but factors determining stemness, self-renewal, and lineage commitment are poorly understood. Immortal DNA strands inherited through asymmetric chromatid segregation correlate with self-renewal of adult stem cells, but the capacity of CPCs for asymmetric segregation to retain immortal strands is unknown. Cardioprotective kinase Pim-1 increases asymmetric cell division in vivo, but the ability of Pim-1 to enhance asymmetric chromatid segregation is unknown.We aimed to demonstrate immortal strand segregation in CPCs and the enhancement of asymmetric chromatid distribution by Pim-1 kinase.Asymmetric segregation is tracked by incorporation of bromodeoxyuridine. The CPC DNA was labeled for several generations and then blocked in second cytokinesis during chase to determine distribution of immortal versus newly synthesized strands. Intensity ratios of binucleated CPCs with bromodeoxyuridine of ≥70:30 between daughter nuclei indicative of asymmetric chromatid segregation occur with a frequency of 4.57, and asymmetric chromatid segregation is demonstrated at late mitotic phases. Asymmetric chromatid segregation is significantly enhanced by Pim-1 overexpression in CPCs (9.19 versus 4.79 in eGFP-expressing cells; P=0.006).Asymmetric segregation of chromatids in CPCs is increased nearly two-fold with Pim-1 kinase overexpression, indicating that Pim-1 promotes self-renewal of stem cells.
Accelerated Evolution of PAK3- and PIM1-like Kinase Gene Families in the Zebra Finch, Taeniopygia guttata
Authors: L. Kong, P. V. Lovell, A. Heger, C. V. Mello, C. P. Ponting
Journal: Molecular Biology and Evolution (2010)

Genes encoding protein kinases tend to evolve slowly over evolutionary time, and only rarely do they appear as recent duplications in sequenced vertebrate genomes. Consequently, it was a surprise to find two families of kinase genes that have greatly and recently expanded in the zebra finch (Taeniopygia guttata) lineage. In contrast to other amniotic genomes (including chicken) that harbor only single copies of p21-activated serine/threonine kinase 3 (PAK3) and proviral integration site 1 (PIM1) genes, the zebra finch genome appeared at first to additionally contain 67 PAK3-like (PAK3L) and 51 PIM1-like (PIM1L) protein kinase genes. An exhaustive analysis of these gene models, however, revealed most to be incomplete, owing to the absence of terminal exons. After reprediction, 31 PAK3L genes and 10 PIM1L genes remain, and all but three are predicted, from the retention of functional sites and open reading frames, to be enzymatically active. PAK3L, but not PIM1L, gene sequences show evidence of recurrent episodes of positive selection, concentrated within structures spatially adjacent to N- and C-terminal protein regions that have been discarded from zebra finch PAK3L genes. At least seven zebra finch PAK3L genes were observed to be expressed in testis, whereas two sequences were found transcribed in the brain, one broadly including the song nuclei and the other in the ventricular zone and in cells resembling Bergmann's glia in the cerebellar Purkinje cell layer. Two PIM1L sequences were also observed to be expressed with broad distributions in the zebra finch brain, one in both the ventricular zone and the cerebellum and apparently associated with glial cells and the other showing neuronal cell expression and marked enrichment in midbrain/thalamic nuclei. These expression patterns do not correlate with zebra finch-specific features such as vocal learning. Nevertheless, our results show how ancient and conserved intracellular signaling molecules can be co-opted, following duplication, thereby resulting in lineage-specific functions, presumably affecting the zebra finch testis and brain.
Cocaine Dependence With and Without PTSD Among Subjects in the National Institute on Drug Abuse Collaborative Cocaine Treatment Study
Authors: L M Najavits, D R Gastfriend, J P Barber, S Reif, L R Muenz, J Blaine, A Frank, P Crits-Christoph, M Thase, R D Weiss
Journal: American Journal of Psychiatry (1998)

This study examined the prevalence of lifetime traumatic events and current symptoms of posttraumatic stress disorder (PTSD) among treatment-seeking cocaine-dependent outpatients and compared patients with and without PTSD on current substance use, psychopathology, and sociodemographic characteristics.The subjects were 122 adult cocaine-dependent outpatients participating in a treatment outcome study of psychosocial therapy. In addition to standard self-report and interview measures of psychopathology and substance use, the subjects completed the Trauma History Questionnaire and the PTSD Checklist before entering treatment.These patients experienced a large number of lifetime traumatic events (mean = 5.7); men experienced more general disasters and crime-related traumas than women, and women experienced more physical and sexual abuse than men. According to self-report measures, 20.5% of the subjects currently met the DSM-III-R criteria for PTSD; the rate of PTSD was 30.2% among women and 15.2% among men. Patients with PTSD had significantly higher rates of co-occurring axis I and axis II disorders, interpersonal problems, medical problems, resistance to treatment, and psychopathology symptoms than patients without PTSD. Psychopathology symptoms represented the most consistent difference between the two groups and provided the best prediction of PTSD status in a logistic regression. However, the groups did not differ significantly in current substance use or sociodemographic characteristics.These findings underscore the value of screening substance abusers for PTSD, because it can identify a small but substantial number who might require additional treatment. Further studies of the relationship between PTSD and substance abuse appear warranted.
PD-L1 marks a subset of melanomas with a shorter overall survival and distinct genetic and morphological characteristics
Authors: D. Massi, D. Brusa, B. Merelli, M. Ciano, V. Audrito, S. Serra, R. Buonincontri, G. Baroni, R. Nassini, D. Minocci, L. Cattaneo, E. Tamborini, A. Carobbio, E. Rulli, S. Deaglio, M. Mandalà
Journal: Annals of Oncology (2014)
Deriving Ethnic-Specific BMI Cutoff Points for Assessing Diabetes Risk
Authors: Maria Chiu, Peter C. Austin, Douglas G. Manuel, Baiju R. Shah, Jack V. Tu
Journal: Diabetes Care (2011)

OBJECTIVE The definition of obesity (BMI ≥30 kg/m2), a key risk factor of diabetes, is widely used in white populations; however, its appropriateness in nonwhite populations has been questioned. We compared the incidence rates of diabetes across white, South Asian, Chinese, and black populations and identified equivalent ethnic-specific BMI cutoff values for assessing diabetes risk. RESEARCH DESIGN AND METHODS We conducted a multiethnic cohort study of 59,824 nondiabetic adults aged ≥30 years living in Ontario, Canada. Subjects were identified from Statistics Canada’s population health surveys and followed for up to 12.8 years for diabetes incidence using record linkages to multiple health administrative databases. RESULTS The median duration of follow-up was 6 years. After adjusting for age, sex, sociodemographic characteristics, and BMI, the risk of diabetes was significantly higher among South Asian (hazard ratio 3.40, P &amp;lt; 0.001), black (1.99, P &amp;lt; 0.001), and Chinese (1.87, P = 0.002) subjects than among white subjects. The median age at diagnosis was lowest among South Asian (aged 49 years) subjects, followed by Chinese (aged 55 years), black (aged 57 years), and white (aged 58 years) subjects. For the equivalent incidence rate of diabetes at a BMI of 30 kg/m2 in white subjects, the BMI cutoff value was 24 kg/m2 in South Asian, 25 kg/m2 in Chinese, and 26 kg/m2 in black subjects. CONCLUSIONS South Asian, Chinese, and black subjects developed diabetes at a higher rate, at an earlier age, and at lower ranges of BMI than their white counterparts. Our findings highlight the need for designing ethnically tailored prevention strategies and for lowering current targets for ideal body weight for nonwhite populations.
Leukotriene D<sub>4</sub>-induced hypoxaemia in asthma is mediated by the cys-leukotriene<sub>1</sub>receptor
Authors: A. Casas, F. P. Gómez, B. Dahlén, J. Roca, J. A. Barberà, S-E. Dahlén, R. Rodríguez-Roisin
Journal: European Respiratory Journal (2005)

Bronchoprovocation with cysteinyl-leukotrienes (LTs) induces airflow obstruction and gas exchange abnormalities, namely ventilation-perfusion ratio (V'(A)/Q') imbalance. However, it is unknown which of the two different receptors for cysteinyl-LTs mediate these V'(A)/Q' disturbances. In a double-blinded, crossover design, 10 patients with mild asthma were randomised to receive an oral single dose of the selective cysteinyl-LT1 receptor antagonist montelukast (40 mg) or placebo before leukotriene (LT)D4 inhalation challenge. Gas exchange, including V'(A)/Q' descriptors were measured at baseline, 3 h after montelukast/placebo pretreatment and 5, 15 and 45 min after the LTD4 challenge. Compared with montelukast, inhalation of LTD(4) induced a marked fall in forced expiratory volume in one second (mean+/-se 33+/-2%) and profound V'(A)/Q' mismatching, reflected by a decreased arterial oxygen tension (from 100+/-4 to 75+/-3 mmHg) and an increased overall index of V'(A)/Q' heterogeneity dispersion of retention minus excretion inert gases corrected for dead space (from 4.9+/-1.2 to 8.4+/-1.1; normal< or =3.0; dimensionless), 5 min after placebo. Following montelukast, LTD4 produced no significant changes in any of the variables. In conclusion, these findings point to the view that leukotriene D4)-induced gas exchange disturbances and bronchoconstriction are both mediated by the cysteinyl-leukotriene1 receptor.
Antitumor Activity in Melanoma and Anti-Self Responses in a Phase I Trial With the Anti-Cytotoxic T Lymphocyte–Associated Antigen 4 Monoclonal Antibody CP-675,206
Authors: Antoni Ribas, Luis H. Camacho, Gabriel Lopez-Berestein, Dmitri Pavlov, Cecile A. Bulanhagui, Robert Millham, Begoña Comin-Anduix, James M. Reuben, Elisabeth Seja, Charla A. Parker, Amarnath Sharma, John A. Glaspy, Jesus Gomez-Navarro
Journal: Journal of Clinical Oncology (2005)

Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade with CP-675,206, a fully human anti-CTLA4 monoclonal antibody, may break peripheral immunologic tolerance leading to effective immune responses to cancer in humans. A phase I trial was conducted to test the safety of CP-675,206.Thirty-nine patients with solid malignancies (melanoma, n = 34; renal cell, n = 4; colon, n = 1) received an intravenous (IV) infusion of CP-675,206 at seven dose levels. The primary objective was to determine the maximum-tolerated dose and the recommended phase II dose.Dose-limiting toxicities and autoimmune phenomena included diarrhea, dermatitis, vitiligo, panhypopituitarism and hyperthyroidism. Two patients experienced complete responses (maintained for 34+ and 25+ months), and there were two partial responses (26+ and 25+ months) among 29 patients with measurable melanoma. There have been no relapses thus far after objective response to therapy. Four other patients had stable disease at end of study evaluation (16, 7, 7, and 4 months). Additionally, five patients had extended periods without disease progression (36+, 35+, 26+, 24+, and 23+ months) after local treatment of progressive metastases. Longer systemic exposure to CP-675,206 achieved in higher dose cohorts predicted for a higher probability of response.CP-675,206 can be administered safely to humans as a single IV dose up to 15 mg/kg, resulting in breaking of peripheral immune tolerance to self-tissues and antitumor activity in melanoma.
CSF 5-HIAA and Family History of Antisocial Personality Disorder in Newborns
Authors: J N Constantino, J A Morris, D L Murphy
Journal: American Journal of Psychiatry (1997)

The relationship between genetic liability for antisocial behavior and CSF 5-hydroxyindoleacetic acid (5-HIAA) in newborns was explored.The authors assayed 5-HIAA in "leftover" CSF from 193 neurologically normal newborns and obtained family psychiatric histories of the newborns' first- and second-degree relatives.Levels of 5-HIAA were significantly lower in the infants with family histories of antisocial personality disorder than in the newborns without such family histories.These findings support the possibility that serotonin mediates one component of genetic liability to antisocial outcome, but the magnitude of that component may be less than what has been inferred from previously published reports.
Herpes Zoster and Tofacitinib Therapy in Patients With Rheumatoid Arthritis
Authors: Kevin L. Winthrop, Hisashi Yamanaka, Hernan Valdez, Eric Mortensen, Robert Chew, Sriram Krishnaswami, Thomas Kawabata, Richard Riese
Journal: Arthritis & Rheumatology (2014)

Objective Patients with rheumatoid arthritis (RA) are at increased risk for herpes zoster (HZ) (i.e., shingles). The aim of this study was to determine whether treatment with tofacitinib increases the risk of HZ in patients with RA. Methods HZ cases were identified as those reported by trial investigators from the databases of the phase II, phase III, and long‐term extension (LTE) clinical trials in the Tofacitinib RA Development Program. Crude incidence rates (IRs) of HZ per 100 patient‐years (with 95% confidence intervals [95% CIs]) were calculated by exposure group. Logistic regression analyses were performed to evaluate potential risk factors for HZ (e.g., age, prednisone use). Results Among 4,789 participants, 239 were identified as having tofacitinib‐associated HZ during the phase II, phase III, and LTE trials, of whom 208 (87%) were female and whose median age was 57 years (range 21–75 years). One HZ case (0.4%) was multidermatomal; none of the cases involved visceral dissemination or death. Twenty‐four patients with HZ (10%) permanently discontinued treatment with tofacitinib, and 16 (7%) were either hospitalized or received intravenous antiviral drugs. The crude HZ IR across the development program was 4.4 per 100 patient‐years (95% CI 3.8–4.9), but the IR was substantially higher within Asia (7.7 per 100 patient‐years, 95% CI 6.4–9.3). Older age was associated with HZ (odds ratio 1.9, 95% CI 1.5–2.6), and IRs for HZ were similar between patients receiving 5 mg tofacitinib twice daily (4.4 per 100 patient‐years, 95% CI 3.2–6.0) and those receiving 10 mg twice daily (4.2 per 100 patient‐years, 95% CI 3.1–5.8). In the phase III trials among placebo recipients, the incidence of HZ was 1.5 per 100 patient‐years (95% CI 0.5–4.6). Conclusion In the Tofacitinib RA Development Program, increased rates of HZ were observed in patients treated with tofacitinib compared with those receiving placebo, particularly among patients within Asia. Complicated HZ among tofacitinib‐treated patients was rare.
Selective Na+/H+ exchange inhibition by cariporide reduces liver fibrosis in the rat
Authors: Antonio Di Sario, Emanuele Bendia, Silvia Taffetani, Marco Marzioni, Cinzia Candelaresi, Paola Pigini, Ursula Schindler, Heinz-Werner Kleemann, Luciano Trozzi, Giampiero Macarri, Antonio Benedetti
Journal: Hepatology (2003)

The aim of this study was to evaluate the effect of cariporide, a selective Na + /H + exchange inhibitor, on isolated and cultured hepatic stellate cells (HSCs) and in 2 in vivo models of rat liver fibrosis. Platelet-derived growth factor (PDGF)-induced HSC proliferation, evaluated by measuring the percentage of bromodeoxyuridine-positive cells, was significantly inhibited by cariporide, with a maximal effect at 10 μmol/L. Incubation with cariporide did not inhibit PDGF-induced extracellular-regulated kinase 1/2 (ERK1/2), Akt (a downstream component of the phosphatidylinositol [PI]-3 kinase pathway), and protein kinase C (PKC) activation but reduced PDGF-induced activation of the Na + /H + exchanger, with a maximal effect at 10 μmol/L. Rats treated with dimethylnitrosamine (DMN; 10 mg/kg) for 1 and 5 weeks received a diet with or without 6 ppm cariporide. Treatment with cariporide reduced the degree of liver injury, as determined by alanine aminotransferase (ALT) values, also when administered after the induction of hepatic damage. This was associated with reduced HSC activation and proliferation and reduced collagen deposition, as determined by morphometric evaluation of α-smooth muscle actin (SMA)/proliferating cell nuclear antigen-positive cells and percentage of Sirius red-positive parenchyma, respectively. Moreover, cariporide was also able to reduce α(1)I procollagen messenger RNA (mRNA) expression. Similar effects were observed in bile duct-ligated (BDL) rats. In conclusion, selective inhibition of the Na + /H + exchanger by cariporide may represent an effective therapeutic strategy in the treatment of hepatic fibrosis. (Hepatology 2003;37:256-266.)
Rooting the Ribosomal Tree of Life
Authors: G. P. Fournier, J. P. Gogarten
Journal: Molecular Biology and Evolution (2010)

The origin of the genetic code and the rooting of the tree of life (ToL) are two of the most challenging problems in the study of life's early evolution. Although both have been the focus of numerous investigations utilizing a variety of methods, until now, each problem has been addressed independently. Typically, attempts to root the ToL have relied on phylogenies of genes with ancient duplications, which are subject to artifacts of tree reconstruction and horizontal gene transfer, or specific physiological characters believed to be primitive, which are often based on subjective criteria. Here, we demonstrate a unique method for rooting based on the identification of amino acid usage biases comprising the residual signature of a more primitive genetic code. Using a phylogenetic tree of concatenated ribosomal proteins, our analysis of amino acid compositional bias detects a strong and unique signal associated with the early expansion of the genetic code, placing the root of the translation machinery along the bacterial branch.