tbuckley/cabot-search huggingface dataset:
Isolation and Characterization of Broad and Ultrapotent Human Monoclonal Antibodies with Therapeutic Activity against Chikungunya Virus
Authors: Scott A. Smith, Laurie A. Silva, Julie M. Fox, Andrew I. Flyak, Nurgun Kose, Gopal Sapparapu, Solomiia Khomandiak, Alison W. Ashbrook, Kristen M. Kahle, Rachel H. Fong, Sherri Swayne, Benjamin J. Doranz, Charles E. McGee, Mark T. Heise, Pankaj Pal, James D. Brien, S. Kyle Austin, Michael S. Diamond, Terence S. Dermody, James E. Crowe
Journal: Cell Host & Microbe (2015)
Mutational analyses in Gitelman syndrome
Authors: L.P.W.J. van den Heuvel, H.H. Lemmink, P.E.M. Tachner, R. Vargas, P. Niaudet, L.M. GuayWoodford, P. Goodyer, L. Monnens, S.C. Hebert, N.V.A.M. Knoers
Journal: Journal of the American Society of Nephrology (1996)
Abstract 2782: The effect of ERRFI1 as a novel AKT regulator on cell proliferation and response to therapy is cell context dependent
Authors: Junmei Hou, Kaustubh N. Bhinge, Liewei Wang
Journal: Cancer Research (2014)

Abstract ERRFI1, a negative regulator of the EGFR family, is known to inhibit EGFR activation along with downstream of EGFR signaling. It is recognized as a tumor suppressor. However, ERRFI1 has multiple functions, and here, we present a novel function of ERRFI1. We found that it can directly interact with AKT and positively regulate AKT activity through regulation of AKT473 site by inhibiting PHLPP, the phosphatase access to AKT. The effect of this regulation on cell proliferation and on response to chemotherapy is cell context dependent, e.g. EGFR levels. We hypothesize that in cancer cells with high EGFR expression, down regulation of ERRFI1 enhances EGFR signaling, while on the other hand, increases AKT dephosphorylation. The strength of these two opposing signals will determine the eventual cellular phenotypes. In cancer cells with low EGFR expression, the direct effect of ERRFI1 on AKT is dominant, resulting in activation of AKT. To test these hypotheses, we knockdown ERRFI1 in multiple human cancer cell lines with different EGFR levels. Knockdown of ERRFI1 in high EGFR expressing cells resulted in an increase of cell proliferation and resistance to gemcitabine treatment, and this effect was due to the dominant negative effect of ERRFI1on EGFR, which was confirmed by increased EGFR signaling. Knockdown of ERRFI1 in cell lines with moderate level of EGFR also increased cell proliferation and resistance to gemcitabine, although biochemically, down regulation of ERRFI1 reduced AKT pS473 levels, but increased ERK/MAPK signaling. The addition of EGFR inhibitor, gefitinib, overcame gemcitabine resistance due to downregualtion of ERRFI1. In contrary, in cell lines with low level of EGFR, ERRFI1 positively regulated AKT signaling via directly binding to AKT and blocking PHLPP access to AKT. Therefore, down-regulation of ERRFI1 inhibited cell proliferation and sensitized cells to gemcitabine. In summary, we identified a novel function of ERRFI1 as a positive AKT regulator and its effect on cell proliferation and response to therapy is cell context dependent, e.g. EGFR levels. These results provide us insights into the dual roles of ERRFI1 in regulation of EGFR and AKT pathway and would help us to better individualize cancer therapy. Citation Format: Junmei Hou, Kaustubh N. Bhinge, Liewei Wang. The effect of ERRFI1 as a novel AKT regulator on cell proliferation and response to therapy is cell context dependent. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2782. doi:10.1158/1538-7445.AM2014-2782
HYDROXYSTEROID DEHYDROGENASE ACTIVTTY IN HUMAN SKIN.
Authors: A. V. MUIR, K. C. CALMAN, J. THOMSON, M. P. MACSWEEN, J. A. MILNE, J. CHAKRABORTY, J. K. GRANT
Journal: British Journal of Dermatology (1968)

SUMMARY.— The effects of various factors on the histochemical demonstration of 3β-hydroxysteroid dehydrogenase activity in human skin were examined by a semiquantitative technique of granule counting. The optimum concentration of DHA was found to be 0·1 mg./ml. and of NAD 0·3 mg./ml. Vitamin K and nicotinamide enhanced the histochemical demonstration of the enzyme whereas cyproterone and cyproterone acetate inhibited the reaction.
Dietary fiber in prophylaxis and therapy of disease. A review: DietaryProgress in Biochemistry and Pharmacology, volume 24 Z. Madar and H.S. Odes, eds. Basel, Karger, 1990, $89.50, SFr. 134.-, DM 160.-, $55.90 (viii + 144 pp), ISBN 3-805-55043-X
Authors: Frank J. Repka
Journal: Trends in Endocrinology and Metabolism (1991)
Antidepressant Prevention of Postnatal Depression
Authors: Louise M Howard, Elizabeth Boath, Carol Henshaw
Journal: PLoS Medicine (2006)

Postnatal depression (PND) occurs in 10 to 15 percent of mothers [1] and is therefore the commonest complication of childbearing. The morbidity of PND for the mother and its potentially negative associations with neonatal and child development and on other family members are well established [2–4]. In theory, the antenatal period and early puerperium are opportune times to implement interventions to prevent PND because mothers are in frequent contact with health professionals. It is also increasingly recognised that some women who are diagnosed with depression postnatally have been depressed during the antenatal period [5,6], so it is important to detect and treat symptoms of depression antenatally to reduce the incidence of PND. We have therefore recently carried out a Cochrane review of antidepressant prevention of postnatal depression (see Text S1).
MONOCYTIC LEUKEMIA, AN UNCOMMON CAUSE OF RENAL FAILURE
Authors: R D TAYLOR, R BIRCHALL, I H PAGE
Journal: Annals of Internal Medicine (1950)

Case Reports1 June 1950MONOCYTIC LEUKEMIA, AN UNCOMMON CAUSE OF RENAL FAILURER. D. TAYLOR, M.D., ROBERT BIRCHALL, M.D., IRVINE H. PAGE, M.D., F.A.C.P.R. D. TAYLOR, M.D.Search for more papers by this author, ROBERT BIRCHALL, M.D.Search for more papers by this author, IRVINE H. PAGE, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-32-6-1197 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMost causes of renal failure are easily recognized. However, the record of the patient reported here presents an example of death due to renal insufficiency, the mechanism of which was not clear until autopsy had been performed. The kidneys were found to be almost completely replaced by leukemic tissue. Such infiltration of kidneys to a degree great enough to cause uremia is uncommon.CASE REPORTA 50 year old Jewess was admitted to the Research Division of Cleveland Clinic Hospital because of progressive anasarca and weakness of short duration. She had been examined as an out-patient in the Clinic three...Bibliography1. UngerleiderClark HECP: A study of the transverse diameter of the heart silhouette with prediction table based on the teleroentgenogram, Am. Heart J. 17: 92-102, 1939. CrossrefGoogle Scholar2. WatkinsHall CHBE: Monocytic leukemia of the Naegeli and Schilling types, Am. J. Clin. Path. 10: 387, 1940. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication April 4, 1947. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTHE NATURAL HISTORY OF UNTREATED ACUTE LEUKEMIA 1 June 1950Volume 32, Issue 6Page: 1197-1202KeywordsAutopsyEdemaHospitalsKidneysOutpatientsRenal failure ePublished: 1 December 2008 Issue Published: 1 June 1950 PDF downloadLoading ...
Lesson of the week: Haemochromatosis and exercise related joint pains
Authors: I. McCurdie, J D. Perry
Journal: BMJ (1999)

Idiopathic haemochromatosis is an inherited disorder of iron metabolism in which excess iron absorption leads to tissue damage associated with a characteristic arthropathy. It is an uncommon but important cause of joint pains in middle age, and early diagnosis and treatment can reduce the long term illnesses and premature death associated with other complications of the disease.1 We describe two cases of haemochromatosis in patients who presented with exercise related joint pains that were initially attributed to their running but were subsequently found to be the presenting symptoms of haemochromatosis. Earlier diagnosis might have prevented their subsequent irreversible joint damage.

### Case 1

A 51 year old woman who was a recreational runner presented with a five year history of pain in the middle of both feet. An acute ankle sprain 10 years before had not responded to conservative treatment, and she had not been given a clear diagnosis for her ongoing functional instability and persistent exercise related pain. At presentation to the sports clinic she gave a more recent history of back pain, pain in both sides of her hip, and pain in both metacarpals; she had had increasing difficulty with her grip over the previous two years because of aching and stiffness of her second and third metacarpals. Her brother also had similar symptoms which had not been investigated; he was later confirmed as having haemochromatosis. The patient had no other symptoms or signs of chronic liver disease or endocrine disturbance. She did, however, have soft tissue swelling over the affected metacarpals, some reduction in internal rotation of both hips, and painful, stiff subtalar joints.

The pattern of affected joints and the family history prompted further investigation. She had a serum ferritin concentration of 1087 =B5g/l, with normal results in liver function tests and a normal glucose concentration, full blood …
Fas Signaling in Macrophages Promotes Chronicity in K/BxN Serum–Induced Arthritis
Authors: Qi‐Quan Huang, Robert Birkett, Renee E. Koessler, Carla M. Cuda, G. Kenneth Haines, Jian‐Ping Jin, Harris Perlman, Richard M. Pope
Journal: Arthritis & Rheumatology (2013)

A nonapoptotic role of Fas signaling has been implicated in the regulation of inflammation and innate immunity. This study was undertaken to elucidate the contribution of Fas signaling in macrophages to the development of arthritis.K/BxN serum-transfer arthritis was induced in a mouse line in which Fas was conditionally deleted in the myeloid lineage (Cre(LysM) Fas(flox/flox) mice). The arthritis was assessed clinically and histologically. Expression of interleukin-1β (IL-1β), CXCL5, IL-10, IL-6, and gp96 was determined by enzyme-linked immunosorbent assay. Bone marrow-derived macrophages were activated with IL-1β and gp96. Cell phenotype and apoptosis were analyzed by flow cytometry.Arthritis onset in Cre(LysM) Fas(flox/flox) mice was comparable with that observed in control mice; however, resolution was accelerated during the chronic phase. The attenuated arthritis was associated with reduced articular expression of the endogenous Toll-like receptor 2 (TLR-2) ligand gp96 and the neutrophil chemotactic chemokine CXCL5, and enhanced expression of IL-10. Activation with IL-1β or gp96 induced increased IL-10 expression in Fas-deficient murine macrophages compared with control macrophages. IL-10 suppressed IL-6 and CXCL5 expression induced by IL-1β plus gp96. IL-1β-mediated activation of ERK, which regulates IL-10 expression, was increased in Fas-deficient mouse macrophages.Taken together, our findings indicate that impaired Fas signaling results in enhanced expression of antiinflammatory IL-10 and reduced expression of gp96, and these effects are associated with accelerated resolution of inflammation during the chronic phase of arthritis. These observations suggest that strategies to reduce endogenous TLR ligands and increase IL-10 may be beneficial in the treatment of rheumatoid arthritis.
The Effect of Thyroidectomy and Thyroid-stimulating Hormone on a Transplanted Acute Leukemia in the Fischer Rat
Authors: David M. Morris
Journal: Cancer Research (1960)

Since the role of the thyroid in leukemogenesis has not been clearly established, the following experiments were designed to study the effect of thyroidectomy and increased titers of thyroid-stimulating hormone on leukemia development in the Fischer rat under carefully controlled nutritional conditions. In two separate experiments, neither thyroidectomy alone nor thyroidectomy plus TSH injections prior to tumor implantation influenced the course of leukemia development as measured by survival time, rate of tumor growth, and development of a leukemic blood picture. Food consumption was controlled so that the growth rate of both experimental and control animals was the same throughout the experiment.
440. The Multidrug Resistant Phenotype in Tumor Cells Facilitates Adenoviral Replication: New Concepts for Oncolytic Vector Development
Authors: Eunhee Kim, Taeyoung Koo, Dong Hyun Ko, Yoon A. Kang, Joo-Hang Kim, Chae-Ok Yun
Journal: Molecular Therapy (2004)

Top of pageAbstract
Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase functions to stabilize telomere length during chromosomal replication. Previous studies have shown that hTERT promoter is highly active in most tumor and immortal cell lines but inactive in normal somatic cell types. The use of wild type hTERT promoter however, may be limited by its inability to direct high level and cancer cell-specific expression necessary for effective targeted gene therapy. To improve cancer cell-specificity and strength of the hTERT promoter, a modified hTERT, m-hTERT promoter was generated in which additional copies of c-Myc and Sp1 binding sites were incorporated adjacent to the promoter. As assessed using relative LacZ expression, hTERT and m-hTERT promoter activity was significantly upregulated in cancer cells but not in normal cells; and within this upregulated cancer cells, m-hTERT promoter strength was substantially higher than that of the wild type hTERT. Next, to restrict viral replication to tumor cells, a conditional replication-competent adenoviruses, Ad-TERT-Δ19 and Ad-mTERT-Δ19 were generated in which E1A gene that is essential for viral replication was placed under the control of the hTERT and m-hTERT promoter, respectively. While the wild type Ad-TERT-Δ19 replicated in and induced cytopathic effect in cancer and in some normal cell lines, Ad-mTERT-Δ19 enhanced viral replication and cytopathic effect in cancer cells only. Finally, the growth of established human cervical carcinoma in nude mice was significantly suppressed by intra-tumoral injection of Ad-mTERT-Δ19. Taken together, present results strongly suggest that the use of m-hTERT promoter is not only useful in the regulation of therapeutic gene expression but also that replication-competent oncolytic adenovirus under the control of m-hTERT promoter may be a new promising tool for the treatment of human malignancies.
Abstract 9192: Genetic Ancestry is Associated with Left Ventricular Mass Among Hispanic Subgroups: The Multi-Ethnic Study of Atherosclerosis
Authors: Carlos J Rodriguez, William C Stewart, David A Bluemke, Esteban González-Burchard, Joao A Lima, Donna K Arnett
Journal: Circulation (2011)

Hispanics represent a recently admixed population of European, Native American and African parental populations. Hispanics have higher left ventricular mass (LVM) than non-Hispanic whites, and this relationship persists across Hispanic subgroups. However, the contribution of genetic ancestry to LVM across Hispanic subgroups is not known. Methods - We examined 705 Hispanic participants. Percent genetic ancestry for each Hispanic subgroup was estimated with 199 ancestry informative markers using the population genetics analysis program STRUCTURE. LVM from cardiac MRI was evaluated as a continuous measurement, with allometric methods that model height and weight in a regression analysis. Associations between ancestry and LVM were evaluated through linear regression models consisting of age, gender, both highest education level and annual income, and diabetes treatment, hypertension, physical activity, and body mass index. Results - Mexicans along with Central Americans had the highest Native American (74%) ancestry. Caribbean-Hispanics (Dominicans, Puerto Ricans and Cubans) had the highest African (35%) ancestry. Among Caribbean Hispanics (in age and gender adjusted analysis), each SD increase in African ancestry was associated with a 3.4 unit increase in LVM (p &lt; 0.03). Among Mexican-origin Hispanics, each SD increase in Native American ancestry was associated with a 2.4 unit increase in LVM (p = 0.06). These relationships were not attributable to differences in socioeconomic status or clinical factors. In Caribbean-Hispanics, African ancestry explains 9.6% of the total variance in LVM in fully adjusted models. In Mexican-origin Hispanics, Native American ancestry explains 13.0% of the total variance in fully adjusted models. There was insufficient evidence in these data to detect an association between genetic ancestry and LVM in Central/South Americans. Conclusion - African and Native American ancestry was significantly associated with increasing LVM among Caribbean-Hispanics and Mexican-origin Hispanics, respectively. The findings persisted after accounting for LVM risk factors. These results highlight the heterogeneity of the Hispanic population and the relative importance of genetic ancestry in assessing LVM risk.
Abstract P281: Cardiovascular Health Correlates of Physical Activity and Sedentary Behavior Patterns in American Adults
Authors: Sydney A Jones, Amy H Herring, Feng Wen, Kelly R Evenson
Journal: Circulation (2015)

Background: Latent class analysis, a data reduction tool, can be used to group people according to the patterns of physical activity in which they engage. Patterns of physical activity may be differentially associated with cardiovascular health measures. We explored the cross-sectional correlation of patterns in objectively measured physical activity and sedentary behavior with cardiovascular health measures.

Methods: Accelerometer data from National Health and Nutrition Examination Survey (NHANES) adult participants in 2003-2006 were used to derive latent classes describing patterns of physical activity and sedentary behavior. Latent classes were defined for both accelerometer measures: percent of wear time in moderate-to-vigorous physical activity [MVPA] and percent of wear time in sedentary behavior.

Obesity (body mass index ≥30 kg/m2), low- (LDL) and high-density lipoprotein cholesterol (HDL), triglycerides, and blood pressure were measured. Hypertension was defined as blood pressure >140/80 mmHg or treatment. Dyslipidemia was LDL ≥190 mg/dL or triglycerides ≥500 mg/dL. History of cardiovascular disease (CVD), diabetes, smoking status, and alcohol consumption (≥12 drinks/year) were self-reported.

We included participants ≥20 years with adherent accelerometer data for ≥8 hours/day on ≥3 days. Associations between latent classes and cardiovascular health measures were evaluated using Chi-square tests. Weights were used to account for the NHANES sampling design.

Results: Participants (N=7236) were more likely female (53%) and non-Hispanic white (73%), with a mean age of 47 years. The prevalence of obesity was 33%, hypertension 39%, and diabetes 11%. Twenty-three percent were current smokers and 9% had a history of CVD. Five latent classes were identified for MVPA and five for sedentary behavior.

Compared to the most active MVPA class (N=62), the least active MVPA class (N=5117) included more individuals with obesity (38 vs. 12%), hypertension (46 vs. 23%), diabetes (14 vs. 1%), and a history of CVD (12 vs. 0%). Former smokers and non-alcohol drinkers also were overrepresented in the least compared to most active class (27 vs. 20% and 31 vs. 21%, respectively). MVPA patterns were similar by dyslipidemia status.

Diabetics comprised 25% of the most sedentary class (N=641), compared to 5% of the least sedentary class (N=542). Those with obesity (40 vs. 27%) and hypertension (64 vs. 25%) also were overrepresented in the most compared to least sedentary class. Current smokers comprised 17% of the most and 31% of the least sedentary class, while formers smokers made up 40% of the most and 24% of the least sedentary class.

Conclusion: Measures of poor cardiovascular health were associated with less MVPA and more sedentary behavior. Understanding the correlates of physical activity and sedentary behavior patterns may help to inform interventions.
Ultrasound biomicroscopy as a tool for detecting and localizing occult foreign bodies after ocular trauma11The authors have no financial interest in ultrasound biomicroscopy or Humphrey Instruments.
Authors: Vincent A Deramo, Gaurav K Shah, Caroline R Baumal, Mitchell S Fineman, Zélia M Corrêa, William E Benson, Christopher J Rapuano, Elisabeth J Cohen, James J Augsburger
Journal: Ophthalmology (1999)
Portrait of a Negro
Authors: M. Therese Southgate
Journal: JAMA (2002)

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Improvements in antibiotic prescribing by community paediatricians in the Czech Republic
Authors: V Jindrák, J Marek, V Vaniš, P Urbaskova, J Vlček, L Janiga, V Marešová
Journal: Eurosurveillance (2008)

Repeated surveys among primary care paediatricians were performed annually from 1998 to 2002 in the Czech Republic. The task was to assess the prescription of antibiotics in treatment of respiratory infections in children. The results were evaluated in the light of existing guidelines and conclusions were used in a number of interventions aimed at reducing the inadequate use of antibiotics and hence preventing the potential increase of the antibiotic resistant bacteria. In addition, data on overall consumption of antibiotics in outpatient care and trends in the prevalence of resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes are discussed.