tbuckley/cabot-search huggingface dataset:
Mechanistic link between the anti-HCV effect of interferon gamma and control of viral replication by a ras-MAPK signaling cascade
Authors: Ying Huang, Xinyi Cynthia Chen, Madhavi Konduri, Nadejda Fomina, Jin Lu, Ling Jin, Alexander Kolykhalov, Seng‐Lai Tan
Journal: Hepatology (2005)

Interferon-gamma (IFN-gamma) exerts potent antiviral activity in the hepatitis C virus (HCV) replicon systems. However, the mechanisms underlying the direct antiviral effect have not been determined. We found that the type II transcriptional response to IFN-gamma could be suppressed by inhibition of MEK1/2 kinase activity by MEK1/2 inhibitor U0126 in the hepatoma cell line Huh-7. Using a bicistronic HCV replicon system expressing a luciferase reporter gene in Huh-7 cells (RLuc-replicon), we showed that inhibition of MEK1/2 kinase activity is sufficient to counteract the antiviral activity of IFN-gamma. Expression of a constitutive active form of Ras inhibited the luciferase activity of RLuc-replicon, whereas a dominant-negative mutant of Ras enhanced the reporter activity, indicating that the Ras-MAPK pathway has a role in limiting replication of the viral RNA. Consistent with the involvement of the Ras-MAPK pathway, treatment with epidermal growth factor suppressed HCV protein expression in the RLuc-replicon cells, an effect that could be abolished by U0126. Inhibition of MEK1/2 kinase activity correlated with reduced phosphorylation of the HCV NS5A protein and enhanced RLuc-replicon luciferase reporter activity, in line with recent reports that phosphorylation of NS5A negatively modulates HCV RNA replication. Finally, genetic deletion analysis in yeast supported the role of a MEK-like kinase(s) in the regulation of NS5A phosphorylation. In conclusion, the direct anti-HCV effect of IFN-gamma in cell culture is, at least in part, mediated through the Ras-MAPK signaling pathway, which possibly involves a direct or indirect modulation of NS5A protein phosphorylation.
Cortical Necrosis of Kidneys in an Infant
Authors: M. Y. Ali
Journal: BMJ (1956)

Bilateral cortical necrosis of the kidneys is very un- common, and is particularly rare in infants.The con- dition has been typically described by various authors in association with pregnancy.Where the disease was not associated with pregnancy the age distribution in reported cases covered a very wide range, but only a few cases were recorded in children below the age of 3 months.Since the 9-weeks-old case reported by Campbell and Henderson in 1949, only two cases have been published (Zuelzer et al., 1951).Those two cases occurred in infants aged 5 days and 12 hours respectively.In the three above-mentioned cases some essential features were different from those found in the follow- ing case, both clinically and in the gross pathological appearance.The rapid clinical course, the rarity of the condition in this age group, and the gross anatomical appearance of the kidneys justify the recording of this case. Case RecordA 3-weeks-old male infant was admitted to the Springfield City Hospital, Ohio, on January 25, 1954, with respiratory difficulty.The mother stated that he refused feedings.The infant was born in the Springfield City Hospital on December 31, 1953.The mother, a 1-gravida, was delivered after the 35th week of gestation.The infant, although weighing 5 lb.1I+ oz. (2.6 kg.), was considered premature.The
Identification and Characterization of Enhancers Controlling the Inflammatory Gene Expression Program in Macrophages
Authors: Serena Ghisletti, Iros Barozzi, Flore Mietton, Sara Polletti, Francesca De Santa, Elisa Venturini, Lorna Gregory, Lorne Lonie, Adeline Chew, Chia-Lin Wei, Jiannis Ragoussis, Gioacchino Natoli
Journal: Immunity (2010)
VALUE OF QRS SCORE AT PRESENTATION IN PREDICTING INFARCT SIZE AND MORTALITY IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Hiroki Shiomi, Masami Kosuge, Takeshi Morimoto, Hiroki Watanabe, Tomohiko Taniguchi, Kenji Nakatsuma, Toshiaki Toyota, Erika Yamamoto, Yutaka Furukawa, Yoshihisa Nakagawa, Minoru Horie, Kazuo Kimura, Takeshi Kimura
Journal: Journal of the American College of Cardiology (2015)
Leptospirosis complicated by fatal intracerebral haemorrhage.
Authors: M A Forwell, P J Redding, M J Brodie, D D Gentleman
Journal: BMJ (1984)

Leptospirosis complicated by fatal intracerebral haemorrhageLeptospirosis is a potentially fatal bacterial disease that has tradi- tionally been associated with occupations such as mining and farming, in which the risk of contact with contaminated rodent urine is fairly high.'We describe a patient who contracted leptospirosis while on a walking holiday in the inner Hebrides.Despite early diagnosis and apparently successful initial treatment he died after a spontaneous intracerebral haemorrhage.
866 DUCTULAR REACTION IS AN INDEPENDENT PREDICTOR OF ADVANCED FIBROSIS IN NAFLD
Authors: G. Svegliati-Baroni, I. Pierantonelli, E. Vanni, M. Guido, S. Saccomanno, E. Gentilcore, G. Faraci, A. Benedetti, M. Rizzetto, G. Marchesini, E. Bugianesi
Journal: Journal of Hepatology (2011)
Prolonged Δ <sup>4</sup> -Cholestenone Feeding in Birds
Authors: C. W. NICHOLS, S. LINDSAY, D. D. CHAPMAN, I. L. CHAIKOFF
Journal: Circulation Research (1960)

The pathologic changes in the aorta, liver, and adrenal glands, and the changes in sterols of plasma and liver induced in birds by the prolonged feeding of a diet containing 0.5 per cent Δ 4 -cholestenone are described. Lesions were found in the media of thoracic aortas and intima of the abdominal aortas of the sterol-fed birds and evidence is presented to show that the crystalline material in the abdominal plaques is not cholesterol. There was enlargement of both liver and adrenal glands with a pronounced deposition of total digitonin-precipitable sterols which could not be accounted for by Liebermann-Burchard reacting sterols (LBRS). In the Δ 4 -cholestenone-fed birds the level of LBRS in plasma, fell to about 50 per cent of that in control birds, whereas the levels of total digitonin-precipitable sterols (TDPS) rose to values of 200 mg. per 100 ml. The fraction of the TDPS present as non-LBRS was quite constant in the plasma of the sterol-fed birds (63-69 per cent). By means of isotope dilution procedures the non-LBRS in the livers of sterol-fed birds was identified as dihydrocholesterol.
Abstract 814: A systemic miRNA signature predictive of early breast cancer
Authors: Helen M. Heneghan, Nicola Miller, Ronan Kelly, Mary Nugent, Michael J. Kerin
Journal: Cancer Research (2010)

Abstract Background: The potential of miRNAs as novel tumor markers has been the focus of much recent attention due to their tissue specificity and unique ability to predict clinicopathological parameters with superior accuracy to mRNA expression profiling. Recent reports have documented altered serum or plasma miRNAs in a variety of cancers including prostate, colon, lung and breast. However it is unknown whether the specific miRNAs reported to be altered in these studies are tumor specific or a general cancer phenomenon. We wished to determine whether a panel of 9 circulating ‘oncomirs’ were tumor specific or similarly expressed in all cancers, and thus identify systemic miRNA signatures predictive of specific cancers. Methods: Using a real-time quantitative PCR approach, expression levels of a panel of 9 oncogenic miRNAs were quantified in blood specimens from 163 cancer patients (breast, colon, renal, prostate and melanoma) and 44 age-matched disease free control individuals. Advanced QBase Plus software and SPSS were used for biostatistical analysis of the data, and correlation with clinicopathological variables. Results: Our panel of circulating miRNAs were detectable at various levels in the circulation of all cancer patients. Expression of general oncomirs such as let 7a and miR-21 were similarly expressed in all cancers. However other specific miRNAs were remarkably different between cancer types. MiR-10b and miR-145 were significantly decreased in the circulation of colon cancer patients compared to other cancers (p=0.000 and p=0.017 respectively). MiR-195, miR-342 and miR-181c were found to be breast cancer specific; elevated levels of these three miRNAs could reliably differentiate breast cancer patients from healthy controls and from patients with other malignancies with high sensitivities (area under curve by ROC analysis: 0.941, 0.963, and 0.926 respectively). Furthermore, systemic miR-195 was detectable in patients with in-situ disease, levels increased progressively as stage of disease advanced, and decreased significantly post curative tumor resection to levels comparable with controls (p=0.001). Conclusion: These findings suggest that individual malignancies, in particular breast cancers, display specific systemic miRNAs profiles, which could aid in early diagnosis and in discriminating one cancer from another. This is of major clinical importance as it illustrates the potential for systemic miRNAs as sensitive and specific yet non-invasive cancer biomarkers. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 814.
MISE EN EVIDENCE DU RÔLE DES FACTEURS IRRITATIFS ET DES TRAUMATISMES DANS LA LOCALISATION ÉLÉCT1VE DES ANTICORPS DANS LES ORGANES DE CHOC<sup>1</sup>
Authors: B. N. HALPERN, G. BIOZZI, B. BENACERRAF
Journal: Allergy (1955)
Local treatment with antithrombotic drugs can prevent thrombus formation: An angioscopic and angiographic study
Authors: Takanobu Tomaru, Fumitaka Nakamura, Yoshiharu Fujimori, Masao Omata, Sachio Kawai, Ryozo Okada, Yaeko Murata, Yasumi Uchida
Journal: Journal of the American College of Cardiology (1995)
Enhanced bioavailability of rebamipide nanocrystal tablets: Formulation and in vitro/in vivo evaluation
Authors: Yu Guo, Yongjun Wang, Lu Xu
Journal: Asian Journal of Pharmaceutical Sciences (2014)

The purpose of this study was to formulate rebamipide nanocrystal tablets (REB-NTs) by wet-milling technique to enhance its dissolution rate and oral bioavailability. The formulation and preparation technology were screened by single factor tests with particle size and distribution as indicators. Rebamipide nanocrystals (REB-NSs) was then achieved by freeze-dry from the prepared nanosuspensions which were characterized by differential scanning calorimetry (DSC) and x-ray powder diffraction (XRD), while the vitro dissolution and the plasma drug concentration of the nanocrystal tablets were investigated. The results indicated that the prepared nanosuspensions got an average particle size of 286 nm, PI of 0.173 and the average Zeta potential of −18.2 mv. The average particle size of obtained REB-NSs' redispersibility was 278 nm, and the crystalline of REB-NSs was the same as the rebamipide bulk drug as shown by DSC and XRD. The drug dissolution rate of self-made nanocrystal tablets in different dissolutions was slightly faster than that from the reference tablets, REB-MTs (Mucosta®), while the Cmax and AUC0–24 of REB-NTs were 1 and 1.57 times higher than that of REB-MTs, which means the nanotechnology could significantly improve the oral bioavailability of rebamipide.
Clinical Applications of Cardiopulmonary Physiology
Authors: David W. Cugell
Journal: JAMA (1961)

The rapid expansion of physiological knowledge has brought with it a new type of specialist—the clinical physiologist. In the cardiac and pulmonary fields great strides have been made by those capable of applying physiological principles and techniques to clinical problems. Proper clinical management demands a deep understanding of physiological principles. Dr. Williams has  set out to provide us with an explanation of basic physiologic principles as they apply to heart and lung function, how they become deranged in disease, and also to explain the physiological bases for some of the more common and important symptoms. I say bravely because it is inevitable that the author of such a textbook will incur the adverse criticism of both physiologist and clinician for what both probably consider a cursory and inadequate approach to the subject. Such criticism is grossly unfair. This is a textbook in another field entirely—clinical cardiopulmonary physiology—in which there
COCATS 4 Task Force 1: Training in Ambulatory, Consultative, and Longitudinal Cardiovascular Care
Authors: Valentin Fuster, Jonathan L. Halperin, Eric S. Williams, Nancy R. Cho, William F. Iobst, Debabrata Mukherjee, Prashant Vaishnava
Journal: Journal of the American College of Cardiology (2015)
Comparison of minimal residual disease as outcome predictor for AML patients in first complete remission undergoing myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation
Authors: R B Walter, B Gyurkocza, B E Storer, C D Godwin, J M Pagel, S A Buckley, M L Sorror, B L Wood, R Storb, F R Appelbaum, B M Sandmaier
Journal: Leukemia (2014)
Precautions When Lightning Strikes During the Monsoon: The Effect of Ozone on Condoms
Authors: Richard F. Baker
Journal: JAMA (1988)

<h3>To the Editor.—</h3> In the acquired immunodeficiency syndrome crisis, condoms have come into prominence in reducing the spread of human immunodeficiency virus infection. Recent recalls of several condom lots<sup>1</sup>have increased concern about condom dependability. Despite quality control during production, after the condoms leave the manufacturer problems may occur that affect the integrity of the condom. Environmental factors may play a significant role. Condoms deteriorate significantly when exposed to ultraviolet light<sup>2</sup>or when stored at length under hot and humid conditions.<sup>2</sup> Ozone is one of the major components of smog and also is produced during lightning storms. Since some condoms are sold in bulk packs and circulated without packaging, we tested unpack-aged condoms in this study of ozone effects. Partially (80% to 90%) unrolled condoms (N = 20) were fitted loosely over inverted 25×200-mm pyrex test tubes and exposed for 72 hours at 21°C in a controlled environmental
Decline in cardiovascular mortality in North Karelia and other parts of Finland.
Authors: J Tuomilehto, J Geboers, J T Salonen, A Nissinen, K Kuulasmaa, P Puska
Journal: BMJ (1986)

The trends in mortality from ischaemic heart disease, cerebrovascular stroke, and all cardiovascular diseases were analysed for the province of North Karelia and for the rest of Finland. Linear trends in mortality were computed for the population aged 35 to 64 for the period from 1969 to 1982, and changes in mortality between the three year means of 1969-71 and 1980-2 were calculated. In North Karelia, where a community based preventive programme has been carried out since 1972, the annual decline in mortality from ischaemic heart disease in men was on average 2.9%, whereas in the rest of Finland it was 2.0%. For women the respective average annual declines in mortality were 4.9% and 3.0%. The net decline from 1969-71 to 1980-2 in North Karelia was 100 deaths/100,000 men. The annual mortality from all cardiovascular disease in men decreased by 2.9% in North Karelia and by 2.6% in the rest of Finland; in women the decreases were 6.0% and 5.0% a year, respectively. The net decline in North Karelia was 71 deaths/100,000 men. The decline in mortality from all causes was also appreciable in both sexes in North Karelia, but it did not differ significantly from national trends.
Evaluation of Poliomyelitis Vaccination in Massachusetts
Authors: Alton S. Pope, Roy F. Feemster, David E. Rosengard, Florence R. B. Hopkins, Boris Vanadzin, Edgar W. Pattison
Journal: New England Journal of Medicine (1956)

IT is ironic that Massachusetts should have had its largest epidemic of poliomyelitis just before the time when poliomyelitis vaccine was to become available in sufficient quantities to protect the whole of the younger population. However, this furnished an unprecedented opportunity to evaluate the effectiveness of the vaccine in an epidemic situation. At the suggestion and with the financial assistance of the National Foundation for Infantile Paralysis, a special study was undertaken. Since the regular personnel of the Department were devoting their entire time to matters connected with the epidemic itself, it was necessary to obtain special field and office . . .
SENSITIVITY TO SULFATHIAZOLE
Authors: Paul R. Stalnaker
Journal: JAMA (1941)

<h3>To the Editor:—</h3> Continuing the report of Dr. Merritt H. Stiles of Philadelphia on the hypersensitivity to sulfathiazole, which appeared inThe Journal, October 18, page 1378, I would like to join him in reporting symptoms at variance with the statement of Wein and Lieberthal (The Journal, September 6, page 850), in which they report only nausea and vomiting following the administration of sulfathiazole. In checking my records on the last 50 patients to whom this drug has been given in the standard dosage of different drug houses of 7.7 grain (0.5 Gm.) tablets varying from 3 to 10 tablets in twenty-four hours, I find that 6 of the patients in addition to nausea and vomiting had temperatures ranging from 102 to 104 F. and 3 of these also had a distinct cutaneous rash. These symptoms appeared after the drug had been stopped for a few days and resumed again.
Salbutamol and Isoproterenol
Authors: Anne E. Tattersfield, Martin W. McNicol
Journal: New England Journal of Medicine (1969)

In a double-blind crossover trial in patients with asthma, similar initial bronchodilator activity was achieved with inhalations of salbutamol (100 μg), a new beta-adrenergic receptor-stimulating drug, and isoproterenol (500 μg), but the duration of action was longer with salbutamol. Heart rate did not increase with salbutamol but showed a small rise with isoproterenol. Normal subjects were given five times this dose of each drug. Salbutamol produced a small mean increase in heart rate (4 beats a minute) and no palpitation, whereas isoproterenol produced a large mean increase in heart rate (33 beats a minute) and pronounced palpitation. For comparable bronchodilator activity salbutamol appears to cause much less cardiovascular beta-receptor stimulation than isoproterenol, and it may prove to be more useful in the treatment of asthma.
Identification and Treatment of a Pineal Region Tumor in an Adolescent With Prodromal Psychotic Symptoms
Authors: Vijay A. Mittal, Katherine Karlsgodt, Jamie Zinberg, Tyrone D. Cannon, Carrie E. Bearden
Journal: American Journal of Psychiatry (2010)

An adolescent male patient originally presented to a prodromal clinical research program with severe obsessive-compulsive behaviors and subthreshold symptoms of psychosis, which eventually developed into first-rank psychotic symptoms. The patient was followed over a 2-year period. His symptoms did not respond to psychotherapy or pharmacotherapy. However, when a pineal region tumor was discovered and treated with chemotherapy and autologous stem cell rescue, both psychotic symptoms and psychosocial functioning reverted toward baseline. Although subcortical brain structures have been implicated in the pathophysiology of idiopathic psychosis, reports of psychiatric sequelae of treatment of subcortical tumors are rare. Etiological pathways that may have played a role in symptom development are of particular interest, as understanding these mechanisms may shed light on the pathophysiology of psychotic disorders more generally.
Mutations of E3 Ubiquitin Ligase <i>Cbl</i> Family Members Constitute a Novel Common Pathogenic Lesion in Myeloid Malignancies
Authors: Hideki Makishima, Heather Cazzolli, Hadrian Szpurka, Andrew Dunbar, Ramon Tiu, Jungwon Huh, Hideki Muramatsu, Christine O'Keefe, Eric Hsi, Ronald L. Paquette, Seiji Kojima, Alan F. List, Mikkael A. Sekeres, Michael A. McDevitt, Jaroslaw P. Maciejewski
Journal: Journal of Clinical Oncology (2009)

Acquired somatic uniparental disomy (UPD) is commonly observed in myelodysplastic syndromes (MDS), myelodysplastic/myeloproliferative neoplasms (MDS/MPN), or secondary acute myelogenous leukemia (sAML) and may point toward genes harboring mutations. Recurrent UPD11q led to identification of homozygous mutations in c-Cbl, an E3 ubiquitin ligase involved in attenuation of proliferative signals transduced by activated receptor tyrosine kinases. We examined the role and frequency of Cbl gene family mutations in MPN and related conditions.We applied high-density SNP-A karyotyping to identify loss of heterozygosity of 11q in 442 patients with MDS, MDS/MPN, MPN, sAML evolved from these conditions, and primary AML. We sequenced c-Cbl, Cbl-b, and Cbl-c in patients with or without corresponding UPD or deletions and correlated mutational status with clinical features and outcomes.We identified c-Cbl mutations in 5% and 9% of patients with chronic myelomonocytic leukemia (CMML) and sAML, and also in CML blast crisis and juvenile myelomonocytic leukemia (JMML). Most mutations were homozygous and affected c-Cbl; mutations in Cbl-b were also found in patients with similar clinical features. Patients with Cbl family mutations showed poor prognosis, with a median survival of 5 months. Pathomorphologic features included monocytosis, monocytoid blasts, aberrant expression of phosphoSTAT5, and c-kit overexpression. Serial studies showed acquisition of c-Cbl mutations during malignant evolution.Mutations in the Cbl family RING finger domain or linker sequence constitute important pathogenic lesions associated with not only preleukemic CMML, JMML, and other MPN, but also progression to AML, suggesting that impairment of degradation of activated tyrosine kinases constitutes an important cancer mechanism.
Expression of allograft inflammatory factor-1 and CD68 in haemangioma: implication in the progression of haemangioma
Authors: J. Jia, Y. Bai, K. Fu, Z-J. Sun, X-M. Chen, Y-F. Zhao
Journal: British Journal of Dermatology (2008)

Recent studies revealed that immune and immune-mediated inflammatory events may contribute to the pathogenesis of haemangioma. As a modulator of immune responses, the allograft inflammatory factor-1 (AIF-1) is involved in immune dysfunction and macrophage activation.To investigate the possible role of AIF-1 in the progression of haemangioma.In a retrospective study of haemangiomas in the oral and facial regions, we assessed lesional immunoreactivities for AIF-1, CD68 and Ki67. Negative controls were similarly confirmed, including 24 pyogenic granulomas, 26 vascular malformations, five samples of normal skin, 10 squamous cell carcinomas of the tongue and three placentas. Immunostaining for each antigen in the haemangiomas was compared with control tissues.Out of all the samples, intense immunoreactivity for AIF-1 was detected in 17 of 19 (89%) haemangioma specimens, with a specific location in the endothelial cells. The intensity of AIF-1 immunostaining did not show remarkable difference among proliferating, involuting and involuted haemangiomas. CD68-positive endothelial cells were found in the neovessels of haemangiomas, as well as in pyogenic granulomas and squamous cell carcinoma.The exclusive expression of AIF-1 on endothelial cells of haemangiomas suggests that it may play a significant role in the pathophysiology and progression of haemangiomas. AIF-1 can be used as an additional biomarker for infantile haemangiomas. CD68-positive cells participate in the neovessel formation during proliferative haemangioma and contribute to the promotion of haemangioma growth.
The miR-126–VEGFR2 axis controls the innate response to pathogen-associated nucleic acids
Authors: Judith Agudo, Albert Ruzo, Navpreet Tung, Hélène Salmon, Marylène Leboeuf, Daigo Hashimoto, Christian Becker, Lee-Ann Garrett-Sinha, Alessia Baccarini, Miriam Merad, Brian D Brown
Journal: Nature Immunology (2013)