tbuckley/cabot-search huggingface dataset:
Human prion protein sequence elements impede cross-species chronic wasting disease transmission
Authors: Timothy D. Kurt, Lin Jiang, Natalia Fernández-Borges, Cyrus Bett, Jun Liu, Tom Yang, Terry R. Spraker, Joaquín Castilla, David Eisenberg, Qingzhong Kong, Christina J. Sigurdson
Journal: Journal of Clinical Investigation (2015)

Chronic wasting disease (CWD) is a fatal prion disease of North American deer and elk and poses an unclear risk for transmission to humans. Human exposure to CWD occurs through hunting activities and consumption of venison from prion-infected animals. Although the amino acid residues of the prion protein (PrP) that prevent or permit human CWD infection are unknown, NMR-based structural studies suggest that the β2-α2 loop (residues 165-175) may impact species barriers. Here we sought to define PrP sequence determinants that affect CWD transmission to humans. We engineered transgenic mice that express human PrP with four amino acid substitutions that result in expression of PrP with a β2-α2 loop (residues 165-175) that exactly matches that of elk PrP. Compared with transgenic mice expressing unaltered human PrP, mice expressing the human-elk chimeric PrP were highly susceptible to elk and deer CWD prions but were concurrently less susceptible to human Creutzfeldt-Jakob disease prions. A systematic in vitro survey of amino acid differences between humans and cervids identified two additional residues that impacted CWD conversion of human PrP. This work identifies amino acids that constitute a substantial structural barrier for CWD transmission to humans and helps illuminate the molecular requirements for cross-species prion transmission.
Management of Adult Acute Myelogenous Leukaemia
Authors: D. Crowther, R. L. Powles, C. J. T. Bateman, M. E. J. Beard, C. L. Gauci, P. F. M. Wrigley, J. S. Malpas, G. H. Fairley, R. B. Scott
Journal: BMJ (1973)

Consecutive adult patients admitted to St. Bartholomew's Hospital with acute myelogenous leukaemia have been treated with a remission induction drug schedule consisting of daunorubicin and cytosine arabinoside. Intermittent five-day courses were used in 72 patients, and a complete remission was obtained in 39 patients (54%). An alternative drug schedule in 22 patients resulted in fewer remissions but this may have been due to age differences in the two groups. Age and initial platelet count were found to be important factors in determining the success of remission induction therapy; the older patients and those with low platelet counts responded less well.A series of 23 patients who achieved remissions was divided into two groups; one received intermittent combination chemotherapy as the only form of maintenance, and the other was given weekly immunotherapy in addition to the chemotherapy. The immunotherapy consisted of irradiated allogeneic leukaemic cells and B.C.G. Eight of the 10 patients on chemotherapy alone have already relapsed compared with five out of 13 patients in the immunotherapy group. It is hoped that these promising initial results with this form of maintenance will be confirmed as more patients enter the maintenance trials.
The Appearance of Amebic Abscess of Liver on ln-111-Leukocyte Scan
Authors: I ROSS McDOUGALL
Journal: Clinical Nuclear Medicine (1981)

A 25-year-old man had clinical features suggesting a diagnosis of amebic abscess of the liver. Ultrasound examination showed an encapsulated lesion in the right lobe of the liver consistent with amebic or pyogenic abscess, ln-111-leukocyte scan of the liver showed a rim of increased activity surrounding a photopenic “cavity”; Tc-99m-sulfur colloid scan showed a larger defect. The combined appearance of the scans was thought to be typical of those expected for amebic abscess. Metronidazole therapy was started and the patient made a good recovery.
Reproducibility of Ventilation Studies
Authors: H SUSSKIND, H L ATKINS, J F KLOPPER, A N ANSARI
Journal: Clinical Nuclear Medicine (1978)

Differences in ventilation patterns were observed in several instances in two consecutive ventilation studies with 127Xe and 133Xe gas involving a group of 20 patients with COPD and other pulmonary disorders. Included were differences in the distribution of a tracer gas bolus during the initial inspiration, the distribution of gas tracer after equilibration and during gas washout, artifacts external to the lung, and variations in the half-time for gas washout. These observed discrepancies are clinically significant and could lead to erroneous or ambiguous diagnoses.
Topotecan/Cisplatin Compared with Cisplatin/Etoposide as First-Line Treatment for Patients with Extensive Disease Small-Cell Lung Cancer: Final Results of a Randomized Phase III Trial
Authors: Thomas H. Fink, Rudolf M. Huber, David F. Heigener, Corrina Eschbach, Cornelius Waller, Ernst U. Steinhauer, Johann C. Virchow, Frank Eberhardt, Hans Schweisfurth, Michael Schroeder, Thomas Ittel, Simone Hummler, Norbert Banik, Thomas Bogenrieder, Thomas Acker, Martin Wolf
Journal: Journal of Thoracic Oncology (2012)
Administrative Reorganization of Municipal Health Services — The Boston Experience
Authors: Robert H. Hamlin, Arnold I. Kisch, H. Jack Geiger
Journal: New England Journal of Medicine (1965)

THE plight of the cities — "urban blight," the flight to the suburbs, the downward spiral of tax bases and the upward spiral of costs, and the difficulties of local governments in coping with regional problems — has commanded widespread attention in the United States in recent years. It is less widely recognized that municipal health services similarly have come under new and increased pressures and face profound tasks of readjustment and reorganization.Within the general complex of urban problems, a number of special factors contribute to the pressures on health services. The cities share in the overall national trend . . .
Mr. Bottomly's Cases of Hernia and Spontaneous Gangrene
Authors: G. Bottomly
Journal: BMJ (1840)

ISO CASES BY MR.BOTTOMLY.- tumor, constituted the treatment, but without the slightest benefit.On visiting the infant the next morning at ten, I was informed it had passed a restless night, with frequent yomiting.Under these circumstances, the operation was the only chance of saving its life; and I confess it was withi some reluctance I resolved on it, but the symptoms being so urgent, the duty was imperative.I operated without any more delay, forty-four hours after the hernia was
Potential Relief for Refractory Angina
Authors: Christopher B. Granger, Bernard J. Gersh
Journal: New England Journal of Medicine (2015)

Physicians who practice primarily in outpatient settings are faced with a large and growing population of patients with chronic, stable, but refractory angina,1,2 as a consequence of an aging population and our ability to prolong the lives of patients with coronary disease. The mortality among patients with refractory angina is surprisingly low,3 but the effect of persistent, recurrent, and frequent symptoms on quality of life is substantial and emphasizes the need for alternative therapeutic options.The newest drug in this therapeutic area, ivabradine, which is approved in Europe, has been shown to reduce angina and improve exercise time in . . .
A CASE OF WIDELY-DISTRIBUTED SUPERFICIAL TELANGIECTATIC NAEVUS (CAPILLARY HAEMANGIECTATIC NAEVUS) ASSOCIATED WITH AREAS OF NAEVUS ANAEMICU—INDICATIONS THAT A PORTION OF THE CEREBRAL MENINGES ARE SIMILARLY INVOLVED
Authors: F. PARKES WEBER, KENNETH E. HARRIS
Journal: British Journal of Dermatology (1932)

Journal Article A CASE OF WIDELY‐DISTRIBUTED SUPERFICIAL TELANGIECTATIC NÆVUS (CAPILLARY HÆMANGIECTATIC NÆVUS) ASSOCIATED WITH AREAS OF NÆVUS ANÆMICU—INDICATIONS THAT A PORTION OF THE CEREBRAL MENINGES ARE SIMILARLY INVOLVED Get access F. PARKES WEBER, M.D., F. PARKES WEBER, M.D. Search for other works by this author on: Oxford Academic Google Scholar KENNETH E. HARRIS, M.D. KENNETH E. HARRIS, M.D. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 44, Issue 2, 1 February 1932, Pages 77–83, https://doi.org/10.1111/j.1365-2133.1932.tb09573.x Published: 01 February 1932
Abstract LB-182: Serum amyloid A is elevated in serum of lung cancer patients with poor prognosis
Authors: William Chi Shing Cho, Wai-wai Cheng, Tai-tong Yip, Joseph SK Au
Journal: Cancer Research (2010)

Abstract Discussion Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-182.
One, two, or many mechanisms? The brain's processing of complex words
Authors: Thomas F. M&uuml;nte, Antoni Rodriguez-Fornells, Marta Kutas
Journal: Behavioral and Brain Sciences (1999)

The heated debate over whether there is only a single mechanism or two mechanisms for morphology has diverted valuable research energy away from the more critical questions about the neural computations involved in the comprehension and production of morphologically complex forms. Cognitive neuroscience data implicate many brain areas. All extant models, whether they rely on a connectionist network or espouse two mechanisms, are too underspecified to explain why more than a few brain areas differ in their activity during the processing of regular and irregular forms. No one doubts that the brain treats regular and irregular words differently, but brain data indicate that a simplistic account will not do. It is time for us to search for the critical factors free from theoretical blinders.
SECRETION AND EXUDATION CONSIDERED AS A FACTOR IN DISEASES OF THE EYE.
Authors: JOHN W. WRIGHT
Journal: JAMA (1899)

As<i>secretion, exudation</i>and<i>infiltration</i>are so much concerned in the diseases of the eye, I ask your attention, in a general way, to these subjects, not that anything new is offered, but as an introduction to the topic under consideration. Secretion is a physiologic process, and consists in the elaboration from the blood, or other sources, of material which is discharged on the external or internal surfaces of the body. The material so separated and discharged is a secretion. Many of the secretions have special uses, which do not involve their discharge from the body. Others have no office to perform, but are separated from the blood to be discharged from the body; such may be termed excretions. Most secretions in a healthy body consist of certain well-known combinations, but when these combinations vary, or when new materials enter into their construction, the secretion may be considered abnormal. Exudation
Abstract 3172: Role of miRNA-211in melanocytes and melanoma
Authors: Nityanand Maddodi, Shajil Madhavan, Sulochana Devi, Ashika Jayanthy, Vijayasaradhi Setaluri
Journal: Cancer Research (2012)

Abstract MicroRNAs (miRNAs) are small non-coding regulatory RNAs that regulate gene expression. Evidence is accumulating that miRNAs are involved in almost all aspects of tumor biology including tumor cell survival, proliferation and migration. Here, we report that miRNA-211, which maps to the sixth intron of TRPM1 gene (a suppressor of melanoma metastasis), is highly expressed in primary melanocytes and its expression is reduced in primary and metastatic melanoma cell lines. Expression of miRNA-211 correlates with expression of TRPM1, a transient receptor potential family member calcium channel protein that we showed to be involved in regulation of melanocyte calcium homeostasis and melanin pigmentation. Inhibition of miRNA-211 expression by anti-miR211 inhibited intercellular Ca+2 update and the growth of rapidly growing melanocytes. Ectopic expression of miRNA-211in melanoma cells inhibit growth and reduced their migration. Regulation of miRNA-211 and its function in melanocytes and melanoma have not been well understood. We show that ectopic expression of p53 (a tumor suppressor) in melanocytes increase miRNA-211 expression and decrease TRPM1 expression. Inhibition of miRNA-211 did not change TPRM1 expression in melanocytes. Additionally, we show that 1.4 kb intron 6 genomic region of TRPM1 which contain miRNA-211 region is sufficient to activate miRNA-211 expression. And 1.4 kb of 6th intron luciferase reporter plasmid transfection followed by luciferase assay showed increase in promoter driven luciferase activity. These data suggests that the presence of putative promoter region of miRNA-211 in the sixth intron of TRPM1 gene. We propose that activation of endogenous miRNA-211 expression or targeted delivery of miR-211 in melanoma is a potential therapeutic option for treatment of cutaneous melanoma. 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 3172. doi:1538-7445.AM2012-3172
THE MECHANISM OF WATER BINDING IN STRATUM CORNEUM
Authors: J. D. MIDDLETON
Journal: British Journal of Dermatology (1968)

SUMMARY.— The results presented in this paper confirm the published observations by others that the hygroscopic water-soluble substances within the corneum are responsible for much of the water binding ability of the horny layer. The ability of corneum to bind water is reduced when it is extracted with solvents, which remove lipid, and then with water, which removes the water-soluble substances. Our interpretation of this is that the water-soluble substances are retained within the corneum by a lipid-containing semipermeable membrane system which allows these substances to take up water by osmosis and protects them from dissolution when the intact corneum is immersed in water. Our experiments show that isolated corneum from guinea-pig footpads and from human palms, soles and abdomen can take up and lose water by osmosis. Powdering the corneum allows water to extract the water-soluble substances without a prior solvent extraction. The powdering procedure ruptures the cell walls of the corneum cells and we propose that it is the cell walls which make up the lipid containing semi permeable membrane system. A method for measuring extensibility of isolated strips of corneum in a humid atmosphere has been developed. Using this technique it has been shown that it is the water held by the water-soluble substances that is responsible for most of the extensibility of corneum.
A Cl- channel activated by parathyroid hormone in rabbit renal proximal tubule cells.
Authors: M Suzuki, T Morita, K Hanaoka, Y Kawaguchi, O Sakai
Journal: Journal of Clinical Investigation (1991)

Previous data suggested an active Cl- conductance in the renal proximal convoluted tubule, although single channel conductance and regulation were not found. We have investigated the presence and regulation of the Cl- channel in proximal convoluted tubules by patch clamp analysis. The current-voltage relationship of whole cells with 130 mM NaCl in the pipette was nonlinear. The addition of 1-34 PTH (10(-8) M), forskolin, or cAMP significantly increased whole cell Cl- conductance. We found a single Cl- channel in excised apical membranes possessing conductance of 33 picosiemens (pS) at positive and 22.5 pS at negative potential, which was blocked by 4,4'-diisothiocyanostilbene-2,2'- disulfonic acid (10(-4) M) and was selective to Cl- (Cl/Na = 10). The channel was activated by prolonged membrane depolarization, by a catalytic subunit of protein kinase A (PKA), or by purified kinase C (PKC), but not by Ca2+ (1 microM) inside the membrane. During cell-attached patch clamping, the channel was similarly activated by PTH, phorbol ester, or dibutyryl cAMP in a dose-dependent manner. To investigate second messenger contributions to the PTH-action, the PTH-evoked channels were modified further by the subsequent addition of several blockers of the second messengers. This suggested that PKA and PKC were involved in Cl- channel activation. We therefore conclude that renal proximal convoluted tubule cells possess an apical Cl- channel activated by PTH via the PKA and PKC pathways.
Adrenergic Nervous System in Sodium Metabolism
Authors: John R. Gill, Frederic C. Bartter
Journal: New England Journal of Medicine (1966)

WHEN dietary sodium is reduced to very low values the renal excretion of sodium normally decreases in three or four days to levels that approach zero. The mechanisms responsible for the renal adjustments to such a change in sodium intake are not entirely clear. Although a fall in the intake of sodium can increase the production of aldosterone, the decrease in urinary sodium may occur while aldosterone excretion (and presumably secretion) is still normal.1 Furthermore, when the intake of sodium is not restricted, large doses of aldosterone or other sodium-retaining steroids usually do not decrease urinary sodium to values as . . .
FOXL1, a Novel Candidate Tumor Suppressor, Inhibits Tumor Aggressiveness and Predicts Outcome in Human Pancreatic Cancer
Authors: Geng Zhang, Peijun He, Jochen Gaedcke, B. Michael Ghadimi, Thomas Ried, Harris G. Yfantis, Dong H. Lee, Nader Hanna, H. Richard Alexander, S. Perwez Hussain
Journal: Cancer Research (2013)

The forkhead box L1 (FOXL1) transcription factor regulates epithelial proliferation and development of gastrointestinal tract and has been implicated in gastrointestinal tumorigenesis in mouse models. However, the role of FOXL1 in pancreatic cancer development and progression remains to be elucidated. Here, we report that higher expression of FOXL1 is significantly associated with better clinical outcome in human pancreatic ductal adenocarcinoma (PDAC). A lower FOXL1 expression is correlated with metastasis and advanced pathologic stage of pancreatic cancer. Mechanistic analyses showed that overexpression of FOXL1 induces apoptosis and inhibits proliferation and invasion in pancreatic cancer cells, whereas silencing of FOXL1 by siRNA inhibits apoptosis and enhances tumor cell growth and invasion. Furthermore, FOXL1 overexpression significantly suppressed the growth of tumor xenografts in nude mice. FOXL1 promoted apoptosis partly through the induction of TNF-related apoptosis-inducing ligand (TRAIL) in pancreatic cancer cells. In addition, FOXL1 suppressed the transcription of zinc finger E-box-binding homeobox 1 (ZEB1), an activator of epithelial-mesenchymal transition, and the negative regulation of ZEB1 contributed to the inhibitory effect of FOXL1 on tumor cell invasion. Taken together, our findings suggest that FOXL1 expression is a candidate predictor of clinical outcome in patients with resected PDAC and it plays an inhibitory role in pancreatic tumor progression.
TET1 is a tumor suppressor of hematopoietic malignancy
Authors: Luisa Cimmino, Meelad M Dawlaty, Delphine Ndiaye-Lobry, Yoon Sing Yap, Sofia Bakogianni, Yiting Yu, Sanchari Bhattacharyya, Rita Shaknovich, Huimin Geng, Camille Lobry, Jasper Mullenders, Bryan King, Thomas Trimarchi, Beatriz Aranda-Orgilles, Cynthia Liu, Steven Shen, Amit K Verma, Rudolf Jaenisch, Iannis Aifantis
Journal: Nature Immunology (2015)
Misleading Steal Phenomenon of Ga-67 Uptake by the Spleen in a Patient With Sarcoidosis
Authors: Pinhas Stark, Idit Pazgal, Hanna Bernstine, Adam Steinmetz
Journal: Clinical Nuclear Medicine (2007)

Sarcoidosis is a multisystemic granulomatous disease of unknown etiology. Most frequently, sarcoidosis presents with bilateral hilar lymphadenopathy and pulmonary infiltration. Histologically, the spleen is the second most commonly involved organ, but splenomegaly is uncommon and massive splenomegaly is rare. Ga-67 scintigraphy has been widely used in the clinical evaluation of sarcoidosis. We describe a patient with a clinical diagnosis of sarcoidosis, in whom Ga-67 scintigraphy showed intense uptake by the massively enlarged spleen, with no additional pathologic uptake, findings which were interpreted as splenic involvement by malignant lymphoma. However, diagnostic splenectomy revealed the diagnosis of splenic involvement by sarcoidosis. A follow-up Ga-67 scan revealed mediastinal, salivary and lacrimal gland uptake typical for sarcoidosis. The authors conclude that any unexpected Ga-67 uptake pattern should be interpreted cautiously in correlation with available clinical data.
Sequential oral contraception and clotting factors.
Authors: L. Poller, J. M. Thomson
Journal: BMJ (1969)

MEDBRITCISHOUNA is so narrow ?(Maximum in the one= £1,005 and in the other=F£1,172.)The career prospects in radiography are shown to be poor indeed when comparison is made with those of physiotherapists.In 1958 the scales were: physiotherapists top grade-£750 to £960; superintendent radiographer-£810 to £920.(Maximum £40 less for superintendent radiographer.)In 1969 the scales were: physiotherapists top grade-1,570 to £2,050; superinten- dent radiographer III-£1,286 to £1,668.(The £40 less for the superintendent radio- grapher in 1958 has now grown to £382 on the final increment.)What inducement really is there to seniors to stay in radiography-particularly the married men, whose skills are so often sought by industry ?These figures speak for them- selves and illustrate clearly the point which
Integration of Hepatitis B Virus DNA into the Genome of Liver Cells in Chronic Liver Disease and Hepatocellular Carcinoma
Authors: David A. Shafritz, Daniel Shouval, Howard I. Sherman, Stefanos J. Hadziyannis, Michael C. Kew
Journal: New England Journal of Medicine (1981)

We used recombinant-DNA technology and gel electrophoresis to find hepatitis B virus DNA (HBV-DNA) in liver and tumor tissue from patients with hepatocellular carcinoma and chronic liver disease, and to study the integration of HBV-DNA into the genome of these tissues' cells. In 12 patients with hepatocellular carcinoma who had hepatitis B surface antigen (HBsAg) in their serum, integrated HBV-DNA was identified in the tumors; it was also found in tumors from three of eight patients who were seronegative for HBsAg but positive for antibody to HBsAg. In some cases, integrated HBV-DNA was also present in nontumorous liver tissue that had the same hybridization pattern or one different from that of the tumor. In five carriers of HBsAg who had evidence of the carrier state and chronic liver disease for less than two years, HBV-DNA was present but not integrated in liver tissue. In the two patients who had carried HBsAg for more than eight years, HBV-DNA was integrated into the host genome. These data suggest that integration of HBV-DNA into hepatocytes occurs during the course of persistent HBV infection and precedes development of gross neoplasm. (N Engl J Med. 1981; 305:1067–73.)
Sustained hemodynamic and antianginal effect of high dose oral isosorbide dinitrate.
Authors: D T Danahy, D T Burwell, W S Aronow, R Prakash
Journal: Circulation (1977)

Twenty-one patients with documented coronary atherosclerotic heart disease were studied to determine the effect of high dose oral isosorbide dinitrate (ISDN) on heart rate, blood pressure, and exercise time until angina pectoris. Patients were tested in two phases, initially with 0.4 mg of sublingual nitroglycerin and with sublingual placebo, and then with oral ISDN, mean dose 29 mg, and oral placebo. Both phases of the study were conducted in a randomized, double-blind, crossover manner. After ISDN was compared to oral placebo, heart rate increased at 30 to 300 min (P less than 0.01) (peak increase 18 beats/min at 60 min), and systolic blood pressure decreased from 45 to 300 min (P less than 0.005) (peak decrease 18 mm Hg at 60 min). Exercise time at 2 min after sublingual nitroglycerin increased 51% as compared to oral placebo, exercise time increased 54% at 1 hr (P less than 0.005), 37% at 3 hr (P less than 0.01), and 12% at 5 hr (NS). Twelve of 21 patients (57%) improved their exercise time until angina larger than or equal to 25% at 1 hr after oral ISDN. The exercise response to sublingual nitroglycerin was a good predictor of this response to oral ISDN.