tbuckley/cabot-search huggingface dataset:
Molecular Pathogenesis of Granulosa Cell Tumors of the Ovary
Authors: Stacey Jamieson, Peter J. Fuller
Journal: Endocrine Reviews (2012)

Granulosa cell tumors of the ovary (GCT) comprise a distinct subset of ovarian cancers that account for approximately 5% of all ovarian malignancies. They are thought to arise from normal proliferating granulosa cells of the late preovulatory follicle and exhibit many morphological and biochemical features of these cells. GCT are distinct from other ovarian carcinomas in their hormonal activity; their ability to secrete estrogen, inhibin, and Müllerian inhibiting substance accounts for some of the clinical manifestations of the disease and also provides useful tumor markers for disease surveillance. Although considered to be of low malignant potential, GCT are commonly associated with slow, indolent disease progression, and frequent yet long delays to tumor recurrence are characteristic of this disease. Unlike the more intensely investigated epithelial ovarian tumors, relatively little is known about the molecular and genetic changes that give rise to GCT. To date, many investigations have centered around pathways known to be involved in normal granulosa cell proliferation, including those activated by FSH receptor stimulation. Most recently, the finding that approximately 97% of adult GCT harbor a somatic missense mutation in the FOXL2 gene (c.402C→G; p.C134W) represents an exciting advancement in the field of GCT research. The high frequency with which the mutation occurs in adult GCT, along with its absence from juvenile GCT and other human malignancies is suggestive of an oncogenic or gain-of-function mutation and, indeed, that the mutation is pathognomonic for adult GCT. In this review, we explore the implications of this finding and the most recent work characterizing molecular pathways of potential pathogenetic significance in GCT.
Central nervous system occurrence in elderly patients with aggressive lymphoma and a long-term follow-up
Authors: M. Björkholm, H. Hagberg, H. Holte, S. Kvaloy, L. Teerenhovi, H. Anderson, E. Cavallin-Ståhl, J. Myhre, H. Pertovaara, Å Öst, B. Nilsson, E. Ösby
Journal: Annals of Oncology (2007)
P202 Impact study of 243 indirect bronchial provocation tests with mannitol in the diagnosis and management of asthma
Authors: I. A. Du Rand, L. O'Reilly, D. Wilson
Journal: Thorax (2011)

<h3>Introduction and Objective</h3> Our lung investigation unit introduced indirect bronchial provocation challenge tests with mannitol to replace direct bronchial provocation tests with Methacholine. Mannitol challenge tests have practical and safety profile advantages. The sensitivity and specificity for PC<sub>20</sub> Methacholine are 91% (84.2%–97.8%) and 90% (76.9%–100%) respectively.1 The specificity of PD<sub>15</sub> Mannitol compares well to Methacholine at 98.4% (96.2%–99.4%), but the sensitivity of PD<sub>15</sub> Mannitol is lower at 58.8% (50.7%–62.6%).2 The aim of the study was to review the clinical interpretation of mannitol challenge test results in the diagnosis of asthma. <h3>Methods</h3> Data were collected on all Mannitol challenge tests performed between July 2008 and January 2011. A retrospective analysis of case notes was performed to assess the indication for the test, the interpretation of results and any subsequent changes in management. <h3>Results</h3> 243 tests were performed and 240 sets of data analysed, 3 sets of case notes could not be obtained. 147 (61%) patients presented with wheeze and dyspnoea with a possible diagnosis of asthma, 48/134 (36%) tests were positive confirming the diagnosis and 13 (8.8%) patients were unable to perform the test. 89 (37%) patients presented with cough, 20/86 (23.3%) tests were positive and three patients were unable to perform the test. 68/69 (99%) of the positive mannitol tests were interpreted as confirmation of the diagnosis of asthma. The 155 negative tests were interpreted as false negative in 20 (13%) patients. In 87 (56%) cases additional tests were subsequently performed and an alternative diagnosis was made and in 48 (31%) cases the result was interpreted as true negative. Three of these patients (6%) re-presented and were subsequently diagnosed with asthma. <h3>Conclusion</h3> Mannitol challenge tests are useful in confirming the diagnosis of asthma in patients with high pre-test probability of the disease. Physicians need to recognise the risk of false negative mannitol test results and perform additional tests when the diagnosis is uncertain and clinical suspicion remains high.
Home based tuberculosis (TB) care program
Authors: Armen Hayrapetyan, Hayk Davtyan, Karapet Davtyan, Vahe Khachadourian
Journal: European Respiratory Journal (2014)

Introduction   High TB treatment success rate is essential to a successful TB program. One of the reasons for poor TB treatment is the inability of some TB patients to visit TB outpatient centers to take their medications. A pilot program was implemented in Armenia to provide home based TB treatment to patients who were unable to visit TB outpatient centers to receive their routine treatment. The pilot program aimed at improving TB treatment adherence and the treatment success rate among TB patients in Armenia.   Methods   The program waslaunched in 2013 involving TB patients according to specific eligibility criteria. The inclusion of the patients was based on the decision of responsible physician and the corresponding TB specialist working at the National TB Program (NTP). The treatment course was also controlled and monitored through weekly report forms.   Results   Out of 57 TB patients included in the program, 12 (21%) were included involved for only a part of their treatment course (temporary) while 45 (79%) for their entire treatment course (full treatment).Among the 23 patients who completed the full home based treatment 21 (91%) have had successful treatment outcome, and 2 (9%) died due to non TB reasons. After improvement in health condition of TB patient in temporary TB home based program, their TB management and treatment were transferred to TB outpatient centers.   Conclusions   Such high rate of treatment success among patients with serious morbidity is an evidence for effectiveness of home based TB care program. The program contributed to a higher adherence to treatment and consequently a better TB treatment outcome. Evaluation of the project suggested scaling up the program to cover all eligible TB patients in Armenia.
Effects of vitamin A deficiency and repletion on rat insulin secretion in vivo and in vitro from isolated islets.
Authors: B S Chertow, W S Blaner, N G Baranetsky, W I Sivitz, M B Cordle, D Thompson, P Meda
Journal: Journal of Clinical Investigation (1987)

We studied the effects of vitamin A deficiency and repletion on rat insulin release and islet cellular retinol binding protein (CRBP) and cellular retinoic acid binding protein (CRABP). Biphasic insulin release from vitamin A-deficient perifused islets was markedly impaired. Release remained impaired with retinoic acid (RA) repletion, 2 micrograms/g diet compared to release from islets of rats repleted with retinol in the form of retinyl palmitate, 4 micrograms/g diet. Release normalized with RA, 8 micrograms/g diet. Vitamin A deficiency did not affect islet insulin content, cell size, number or structure. In vivo, vitamin A-deficient rats had impaired glucose-induced acute insulin release and glucose intolerance, which improved with repletion. Normal islets had greater concentrations of CRBP than CRABP; vitamin A deficiency reduced CRBP but not CRABP levels. We conclude retinol is required for normal insulin secretion. Retinoic acid may substitute for retinol in this function.
Elevated Plasma Vitamin B12 Levels as a Marker for Cancer: A Population-Based Cohort Study
Authors: Johan Frederik Berg Arendt, Lars Pedersen, Ebba Nexo, Henrik Toft Sørensen
Journal: JNCI Journal of the National Cancer Institute (2013)

A substantial proportion of patients referred for plasma vitamin B12 (cobalamin [Cbl]) measurement present with high Cbl levels, which have been reported in patients with different cancer types. However, the cancer risk among patients with newly diagnosed high Cbl levels has not been adequately examined. We conducted this cohort study using population-based Danish medical registries. Patients referred for Cbl measurement with levels greater than the lower reference limit (≥200 pmol/L) were identified from the population of Northern Denmark during the period of 1998 to 2009 using a database of laboratory test results covering the entire population. Data on cancer incidence (follow-up 1998–2010), Cbl treatment, and prior diagnoses were obtained from medical registries. Patients receiving Cbl treatment were excluded. Cancer risks were calculated as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs), stratified by plasma Cbl levels. All statistical tests were two-sided. We identified 333 667 persons without prevalent cancer and not receiving Cbl treatment. Six percent had Cbl levels greater than the upper reference limit (≥601 pmol/L). Cancer risk increased with higher Cbl levels and was highest during the first year of follow-up (Cbl 601–800 pmol/L: SIR = 3.44, 95% CI = 3.14 to 3.76; Cbl >800 pmol/L: SIR = 6.27, 95% CI = 5.70 to 6.88; both P < .001). The risks were particularly elevated for hematological and smoking- and alcohol-related cancers for persons with high Cbl levels. High Cbl levels were associated with the risk of subsequently diagnosed cancer, mostly within the first year of follow-up. This may have clinical implications for the interpretation of high Cbl levels.
Clinical and Safety Outcomes Associated With Treatment of Acute Venous Thromboembolism
Authors: Lana A. Castellucci, Chris Cameron, Grégoire Le Gal, Marc A. Rodger, Doug Coyle, Philip S. Wells, Tammy Clifford, Esteban Gandara, George Wells, Marc Carrier
Journal: JAMA (2014)

IMPORTANCE Many anticoagulant strategies are available for the treatment of acute venous thromboembolism, yet little guidance exists regarding which drug is most effective and safe.OBJECTIVE To summarize and compare the efficacy and safety outcomes associated with 8 anticoagulation options (unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], or fondaparinux in combination with vitamin K antagonists); LMWH with dabigatran or edoxaban; rivaroxaban; apixaban; and LMWH alone) for treatment of venous thromboembolism.DATA SOURCES A systematic literature search was conducted using MEDLINE, EMBASE, and the evidence-based medicine reviews from inception through February 28, 2014.STUDY SELECTION Eligible studies were randomized trials reporting rates of recurrent venous thromboembolism and major bleeding in patients with acute venous thromboembolism.Of the 1197 studies identified, 45 trials including 44 989 patients were included in the analyses.DATA EXTRACTION AND SYNTHESIS Two reviewers independently extracted trial-level data including number of patients, duration of follow-up, and outcomes.The data were pooled using network meta-analysis. MAIN OUTCOMES AND MEASURESThe primary clinical and safety outcomes were recurrent venous thromboembolism and major bleeding, respectively.RESULTS Compared with the LMWH-vitamin K antagonist combination, a treatment strategy using the UFH-vitamin K antagonist combination was associated with an increased risk of recurrent venous thromboembolism (hazard ratio [HR], 1.42; 95% credible interval [CrI], 1.15-1.79).The proportion of patients experiencing recurrent venous thromboembolism during 3 months of treatment were 1.84% (95% CrI, 1.33%-2.51%)for the UFH-vitamin K antagonist combination and 1.30% (95% CrI, 1.02%-1.62%)for the LMWH-vitamin K antagonist combination.Rivaroxaban (HR, 0.55; 95% CrI, 0.35-0.89)and apixaban (HR, 0.31; 95% CrI, 0.15-0.62)were associated with a lower risk of bleeding than was the LMWH-vitamin K antagonist combination, with a lower proportion of patients experiencing a major bleeding event during 3 months of anticoagulation: 0.49% (95% CrI, 0.29%-0.85%)for rivaroxaban, 0.28% (95% CrI, 0.14%-0.50%)for apixaban, and 0.89% (95% CrI, 0.66%-1.16%)for the LMWH-vitamin K antagonist combination.CONCLUSIONS AND RELEVANCE Using meta-analytic pooling, there were no statistically significant differences for efficacy and safety associated with most treatment strategies used to treat acute venous thromboembolism compared with the LMWH-vitamin K antagonist combination.However, findings suggest that the UFH-vitamin K antagonist combination is associated with the least effective strategy and that rivaroxaban and apixaban may be associated with the lowest risk for bleeding.
Abstract 5539: A predominant serrated pathway in hyperplastic polyposis syndrome generates microsatellite-stable and -unstable colorectal cancers
Authors: Carel V. Noesel
Journal: Cancer Research (2011)

Abstract Background and aims: Hyperplastic polyposis syndrome (HPS) is characterized by the presence of multiple colorectal serrated polyps and is associated with an increased colorectal cancer (CRC) risk. The mixture of distinct precursor lesion types and malignancies provides a unique model to study the canonical pathway and a proposed serrated CRC-pathway in humans. Methods: To establish which CRC-pathways play a role in HPS and particularly to obtain new support for the serrated CRC pathway, we analyzed the molecular characteristics of polyps (n=84) and CRCs (n=19) in 17 HPS patients as compared to control groups of various sporadic polyps(n=59) and sporadic microsatellite-stable CRCs(n=16). Results: In both HPS and sporadic polyps, APC mutations were exclusively identified in adenomas whereas BRAF mutations were confined to serrated polyps. Six of 19(32%) HPS CRCs were identified within a serrated polyp. Mutation analysis performed in both the CRC and the serrated component of these lesions showed identical BRAF mutations. One HPS CRC was located within an adenoma, both components harboring an identical APC mutation. Overall, 10/19(53%) HPS CRCs carried a BRAF mutation, compared to none in control group CRCs (p=0.001). Six of the BRAF-mutated HPS CRCs were microsatellite-unstable (MSI-high) due to MLH1 methylation. Conclusion: Our findings provide novel supporting evidence for the existence of a serrated CRC pathway which predominates over the classical Wnt pathway of carcinogenesis in HPS. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5539. doi:10.1158/1538-7445.AM2011-5539
The functional and structural changes of the glomerulus throughout the course of murine lupus nephritis.
Authors: B A Kiberd
Journal: Journal of the American Society of Nephrology (1992)

The glomerular functional and structural changes in a murine model (MRL-lpr/lpr) of progressive lupus nephritis were studied. Animals were grouped into three age categories. (I, 14 wk; II, 20 wk; and III, 26 wk). GFR fell with age (257 +/- 43, 178 +/- 50, and 150 +/- 40 microL/min for Groups I through III, respectively). Similarly, the ultrafiltration coefficient (Kf) measured on isolated glomeruli fell with time (0.030 +/- 0.006, 0.023 +/- 0.006, and 0.013 +/- 0.002 nL/s/mm Hg, respectively). Both indomethacin and a selective thromboxane receptor antagonist L-670,596 significantly improved GFR in Group II animals to values seen in Group I animals. Neither agent had any effect to increase GFR in older group III animals. L-670,596 had no effect on Kf in Group II or III animals. Glomerular morphometric evaluation demonstrated a progressive rise in glomerular tuft volume, mesangial matrix expansion, proliferation in cells, and a reduction in open capillary loops and epithelial filtration slits with age. However, because of the increase in glomerular volume, calculated surface area remained well preserved over the three respective groups (61 +/- 18, 76 +/- 15, and 71 +/- 13 microns2 x 10(3)). Therefore, the fall in Kf is likely due to a fall in hydraulic permeability (Lp). The ultrastructural component of the glomerular capillary wall that correlated best with Lp was the epithelial filtration slit number per micrometer of glomerular basement length (r = 0.73; P < 0.0001), which suggests that the structural correlate Kf is in the filtration slit length (FSL). Despite the cell proliferation and mesangial matrix expansion in early disease (Group II), the overall FSL remains stable because of a slight increase in filtration surface area and a slight reduction in epithelial slits per micrometer of glomerular basement membrane. The fall in GFR appears to be hemodynamically mediated by thromboxane A2. In older Group III animals, the fall in GFR appears to be due to a 40% reduction in FSL rather than being hemodynamically based. Thus, the early improvement in function with pharmacological agents is deceptive because considerable disease may be present because of adaptive structural changes. Eventually, with disease progression, compensating hemodynamic and structural factors fail to maintain GFR within normal limits.
DETERMINATION OF HUMAN PLATELET SURVIVAL UTILIZING C14-LABELED SEROTONIN*
Authors: Robert M. Heyssel
Journal: Journal of Clinical Investigation (1961)

All of the methods available for estimation of platelet survival have certain disadvantages.Iso- lation and considerable manipulation of platelets in vitro are necessary with the Cr51 technique (1, 2).The p32 (3), diisopropylfluorophosphate32 (DFP32) (4), or S35 (5) methods are all in vivo labeling procedures.Studies with p32 or S35 re- quire special subjects for study (patients with polycythemia vera or leukemia).Finally, both autologous and homologous platelet survival can- not be studied with facility.The use of serotonin [5-hydroxytryptamine (5- HTA)] as a platelet label appeared to have cer- tain advantages.It is preferentially concentrated by blood platelets in vivo and in vitro (6).Iso- lation of platelets is not required to achieve an in vitro label, and in vivo labeling of platelets can be accomplished without labeling their precursors.We have used radioactive labeled (C14) serotonin to study platelet survival. MATERIALS AND METHODSC14-labeled 5-hydroxytryptamine.1 C14-labeled 5-HTA [5-hydroxy-3-indolyl-(ethyl-2-amino-1 -C14)] creatinine sulfate monohydrate complex (specific activity 6.87 mc per mmole) was made up in sterile, pyrogen-free, iso- tonic saline solution in concentration of 2.5 /zc per ml.Each milliliter of solution contained approximately 64 lzg of 5-HTA.After filtration through a cellulose bac- teriological 2 filter and bacterial culture, the solution was stored in a refrigerator at 40 C in a multi-dose vial.Paper chromatography of the material as originally received confirmed that greater than 95 per cent of C1' activity was associated with 5-HTA.Deterioration of the substance was noted on prolonged storage.
Regulation of Vascular Smooth Muscle Cell Turnover by Endothelial Cell–Secreted MicroRNA-126
Authors: Jing Zhou, Yi-Shuan Li, Phu Nguyen, Kuei-Chun Wang, Anna Weiss, Yi-Chun Kuo, Jeng-Jiann Chiu, John Y. Shyy, Shu Chien
Journal: Circulation Research (2013)

Rationale: Endothelial microRNA-126 (miR-126) modulates vascular development and angiogenesis. However, its role in the regulation of smooth muscle cell (SMC) function is unknown. Objective: To elucidate the role of miR-126 secreted by endothelial cells (ECs) in regulating SMC turnover in vitro and in vivo, as well as the effects of shear stress on the regulation. Methods and Results: Coculture of SMCs with ECs or treatment of SMCs with conditioned media from static EC monoculture (EC-CM) increased SMC miR-126 level and SMC turnover; these effects were abolished by inhibition of endothelial miR-126 and by the application of laminar shear stress to ECs. SMC miR-126 did not increase when treated with EC-CM from ECs subjected to inhibition of miR biogenesis, or with CM from sheared ECs. Depletion of extracellular/secreted vesicles in EC-CM did not affect the increase of SMC miR-126 by EC-CM. Biotinylated miR-126 or FLAG (DYKDDDDK epitope)-tagged Argonaute2 transfected into ECs was detected in the cocultured or EC-CM–treated SMCs, indicating a direct EC-to-SMC transmission of miR-126 and Argonaute2. Endothelial miR-126 represses forkhead box O3, B-cell lymphoma 2, and insulin receptor substrate 1 mRNAs in the cocultured SMCs, suggesting the functional roles of the transmitted miR-126. Systemic depletion of miR-126 in mice inhibited neointimal lesion formation of carotid arteries induced by cessation of blood flow. Administration of EC-CM or miR-126 mitigated the inhibitory effect. Conclusions: Endothelial miR-126 acts as a key intercellular mediator to increase SMC turnover, and its release is reduced by atheroprotective laminar shear stress.
Rational Design of Antiviral Agents
Authors: M A McKinlay, M G Rossmann
Journal: The Annual Review of Pharmacology and Toxicology (1989)

Examining the change in the state of the art of antiviral drug discovery, from the discovery nearly 40 years ago of a smallpox drug (methisazone) of unknown mechanism of action to the analysis of an antiviral agent bound to a virus at atomic resolution, gives the reader an appreciation for the magnitude of the advances in the science of antiviral chemotherapy. The clinical success of amantadine, acyclovir, and azidothymidine have proved that antiviral chemotherapy is a reality. The next step will be to apply the new tools of x-ray crystallography and computational chemistry to the antiviral challenges that lie before us.
The relationship and epidemiology of acute terminal ileitis and Crohn's disease
Authors: J. Kewenter, L. Hulten, N. G. Kock
Journal: Gut (1974)

The frequency of admission for acute terminal ileitis, Crohn's disease, and acute mesenteric lymphadenitis has been compared from the years 1951 to 1970, and the long-term results of operation for acute terminal ileitis in 1951-1965 have been examined. Whereas the admission rates for both acute terminal ileitis and Crohn's disease rose during the review period, that for acute lymphadenitis tended to fall slightly. Sixty-eight of 72 patients operated upon by appendicectomy who had acute terminal ileitis were followed up. One of these, with small intestinal stenosis at the initial operation, proved to have histological evidence of Crohn's disease, and a further nine have since developed unequivocal evidence of the disease. A cutaneous fistula developed in only one patient after appendicectomy. It is concluded that appendicectomy can safely be performed in acute terminal ileitis provided that the caecum is not inflamed and that Crohn's disease seldom develops as a sequel.
STUDIES ON NON-PRECIPITATING ANTIBODY
Authors: Ludwig A. Sternberger, Samuel M. Feinberg, Martha E. Clarke
Journal: The Journal of Experimental Medicine (1956)

Brief exposure of serum to alkali in the cold seems to convert non-precipitating antibody to a precipitin-like material. This was disclosed by the following lines of evidence. 1. Immune sera, after addition of antigen and removal of the ensuing precipitates, yielded after alkali treatment more antibody-antigen complex than did sera to which no antigen was added. 2. When immune sera were depleted of precipitating antibody, treated by alkali, and antibody-antigen complex was allowed to precipitate, the resulting supernates formed additional prescipitates upon admixture of specific antigen. No precipitation occurred upon addition of non-specific protein to the treated supemates or the addition of specific antigen to depleted sera not treated by alkali. 3. Alkali-treated immune sera precipitated more antigen than untreated sera.