tbuckley/cabot-search huggingface dataset:
Therapy for HDV!
Authors: John M. Taylor
Journal: Hepatology (2003)

Hepatitis delta virus (HDV) can dramatically worsen liver disease in patients coinfected with hepatitis B virus (HBV). No effective medical therapy exists for HDV. The HDV envelope requires HBV surface antigen proteins provided by HBV. Once inside a cell, however, HDV can replicate its genome in the absence of any HBV gene products. In vitro, HDV virion assembly is critically dependent on prenyl lipid modification, or prenylation, of its nucleocapsid–like protein large delta antigen. To overcome limitations of current animal models and to test the hypothesis that pharmacologic prenylation inhibition can prevent the production of HDV virions in vivo, we established a convenient mouse–based model of HDV infection capable of yielding viremia. Such mice were then treated with the prenylation inhibitors FTI–277 and FTI–2153. Both agents were highly effective at clearing HDV viremia. As expected, HDV inhibition exhibited duration–of–treatment dependence. These results provide the first preclinical data supporting the in vivo efficacy of prenylation inhibition as a novel antiviral therapy with potential application to HDV and a wide variety of other viruses.
The transcription factor Erg regulates expression of histone deacetylase 6 and multiple pathways involved in endothelial cell migration and angiogenesis
Authors: Graeme M. Birdsey, Nicola H. Dryden, Aarti V. Shah, Rebecca Hannah, Matthew D. Hall, Dorian O. Haskard, Maddy Parsons, Justin C. Mason, Marketa Zvelebil, Berthold Gottgens, Anne J. Ridley, Anna M. Randi
Journal: Blood (2011)
TARTAR EMETIC IN KALA-AZAR
Authors: P. Mackie
Journal: BMJ (1915)

51NDOLJO_A2. The site of maximumiin intensity ancd the line of con- dluction of the miiurmur.These do not usually coincide with what is foundw -itls sinmilar miturmnurs of organic origin.3. The conidition of the lunt.s.With doubtful ape.murmiul'urs evidence of pulmnoinary engorgemoient is stronogly in favour of organic valve disease, as that condition is almost invariably absen, in thze reftlx of anaemia.4. The effect of change of position upon tlle sound.It i.s essceitial to examinn??e erery casc of susp)ected valve disease both in th7e standivq and rCclcolblent positio?.
What care is 'essential'? What services are 'basic'?
Authors: D. M. Eddy
Journal: JAMA (1991)

The concept of essential health care postulates that there is a set of basic services that should be available to all who need care, with more services obtainable by those who want and can afford to purchase them. Eddy discusses the difficulties with putting the concept of a basic level of care into practice: the lack of operational definitions for 'essential care' and 'basic services', and the need to appoint decision makers who will determine if a particular treatment is essential. He argues for the need to decide about benefits, harms, and costs when determining an intervention's essentialness, and for the importance of having these decisions made by patients. Eddy identifies methodological issues that need resolution, and offers observations on the ethical implications of providing different levels of care for different persons, and of having health care policies decided by a small group of people.
A Phase I Trial of an IV-Administered Vascular Endothelial Growth Factor Trap for Treatment in Patients with Choroidal Neovascularization due to Age-Related Macular Degeneration
Authors: Q NGUYEN, S SHAH, G HAFIZ, E QUINLAN, J SUNG, K CHU, J CEDARBAUM, P CAMPOCHIARO
Journal: Ophthalmology (2006)
Half a million Americans use methamphetamine every week
Authors: Bob Roehr
Journal: BMJ (2005)

An estimated 12.3 million Americans, or 5% of the adult population, have used methamphetamine at least once, claims a US expert on substance misuse. He also says an estimated 600 000 people are weekly users of the drug. Alex Kral, of the non-profit scientific research and development group RTI International, was speaking at the first US national conference on methamphetamine, HIV, and hepatitis, held in Salt Lake City, Utah, last month. The conference brought together medical providers, social services, and law enforcement agencies in a bid to address the widespread misuse of the drug.
Medical problems of adults who were sexually abused in childhood.
Authors: R P Arnold, D Rogers, D A Cook
Journal: BMJ (1990)

The aim of the study was to see whether adults who had been sexually abused in childhood were vulnerable to physical symptoms and therefore investigation and intervention. The case histories of seven patients who were aged 22-39, were under the care of three consultant psychiatrists, had experienced childhood sexual abuse, and had a history of medical or surgical intervention were surveyed. The patients had had a mean of 18 contacts with non-psychiatric consultant teams and a mean of eight operations, with a high rate (66-70%) of normal findings. They had experienced many somatic symptoms, which led to investigations and interventions in the specialties of gynaecology, obstetrics, gastroenterology, urology, rheumatology, haematology, orthopaedics, neurology, and neuropsychiatry. The history of childhood sexual abuse was recognised only in the later stages of this medical and surgical intervention. The possibility of childhood sexual abuse should be considered earlier in such cases to prevent further unnecessary intervention.
Metastatic Breast Cancer
Authors: Larry Norton
Journal: New England Journal of Medicine (1991)

WITHIN the young discipline of medical oncology, the systemic therapy of metastatic breast cancer has a long history. Bilateral oophorectomy, which was noted in the 19th century to cause the regression of advanced disease, was the first effective treatment for any disseminated human cancer.1 Breast cancer was also one of the first cancers found to respond to chemotherapy, and was a proving ground for principles of combination chemotherapy that are now almost universally applied.2 In subsequent years improved methods of diagnosis and monitoring, new drugs, and better means of alleviating drug toxicity have expanded the arsenal of the medical oncologist. . . .
Detecting the risks of osteoporotic fractures in coeliac disease
Authors: J R F Walters
Journal: Gut (2003)

The recent report by Thomason and colleagues ( Gut 2003; 52 :518–22) which failed to detect a significant increase in fractures experienced by treated coeliacs might reassure many patients and physicians. However, this study, and the accompanying commentary by Compston ( Gut 2003; 52 :459), need full and critical assessment before changes in practice are adopted and coeliacs are no longer targeted to be screened for osteoporosis.

It is not surprising that no significant increase in fracture could be detected in this population of well treated coeliacs, given previous findings. The American Gastroenterology Association recently reviewed studies of osteoporosis in gastrointestinal diseases, including coeliac disease, according to standard levels of evidence.1 All such studies have shown low mean bone mineral density (BMD) around the …
Protein kinase C delta: a master regulator of apoptosis in neointimal thickening?
Authors: J. W. Fischer
Journal: Cardiovascular Research (2009)

Smooth muscle cell (SMC)-driven neointimal hyperplasia is a key mechanism that reduces the long-term benefit of vascular interventions such as stenting, balloon angioplasty, and by-pass grafting. Furthermore, neointimal hyperplasia contributes significantly to the progression of atherosclerotic lesions. In response to arterial injury, neointimal hyperplasia develops rapidly—within a couple of months—as opposed to atherosclerotic lesions, which progress over decades. In general, the contribution of SMC to neointimal thickening can be attributed to increased SMC migration, proliferation, reduced apoptosis, and increased extracellular matrix accumulation. In addition, the recruitment of vascular progenitor cells and constrictive remodelling contribute to lesion formation and luminal narrowing.1,2 All of these mechanisms hold promise for the development of therapeutic interventions, and an impressive body of work has identified numerous potential targets. Unfortunately, many of these interventions were effective in rodent models but failed in human disease. However, in the recent past extensive clinical experience has been collected using drug-eluting stents (DES) for local delivery of antiproliferative drugs. Although highly efficient in inhibiting stent restenosis, sirolimus- and paclitaxel-eluting stents reduce endothelial re-growth and require long-term dual anti-platelet therapy.3 Therefore, new strategies that efficiently inhibit restenosis may still be of clinical … 

*Corresponding author. Tel: +49 201 723 3460; Fax: +49 201 723 5968. E-mail address : j.fischer{at}uk-essen.de
Rim of FDG Uptake Around a Pulmonary Infarct on PET/CT in a Patient With Unsuspected Pulmonary Embolism
Authors: Aref Badr, Judith M. Joyce, Janet Durick
Journal: Clinical Nuclear Medicine (2009)

Evaluation of malignancies by positron emission tomography/computed tomography has revolutionized the noninvasive approach to cancer diagnosis and management. However, demonstration of fluorodeoxyglucose (FDG) avidity is not synonymous with a malignant finding since a wide variety of nonmalignant conditions have been reported which demonstrate FDG uptake. We report an asymptomatic patient with an atypical pattern of moderate FDG uptake along the border of a pleural based opacity at the lung base on positron emission tomography/computed tomography, suggesting the presence of a pulmonary infarct. Awareness of this appearance is important, since this pattern may indicate underlying pulmonary embolism, a potentially life-threatening condition.
Abstract 291: Vitamin D induces <i>KDM6B/JMJD3</i> histone demethylase gene in human colorectal cancer cells
Authors: Fábio Pereira, Antonio Barbáchano, Javier Silva, Félix Bonilla, Moray Campbell, Alberto Muñoz, María Jesús Larriba
Journal: Cancer Research (2012)

Abstract Epidemiological and preclinical studies have shown that the active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) has protective effects against colorectal cancer (CRC). Histone tails are subjected to a variety of post-translational modifications, including methylation, which play an important gene regulatory role in development and physiology. Misregulation of histone modifications alters gene expression and leads to perturbations of the cellular identity, which may contribute to cancer initiation, progression and/or metastasis. We have found that 1,25(OH)2D3 regulates the expression of JMJD3 gene (also known as KDM6B) that encodes for a histone H3 lysine 27 demethylase with an important gene regulatory role in development and physiology. 1,25(OH)2D3 induces JMJD3 RNA expression in a time- and dose-dependent manner, activates the JMJD3 gene promoter and increases the level of JMJD3 RNA in human cancer cells of colon, breast and skin origin. JMJD3 upregulation is strictly dependent on vitamin D receptor (VDR) expression and is abolished by the protein synthesis inhibitor cycloheximide. We have also shown that JMJD3 modulates the gene regulatory action of 1,25(OH)2D3. In SW480-ADH CRC cells, JMJD3 knockdown by short-hairpin RNA or expression of an inactive mutant JMJD3 fragment decreases the induction by 1,25(OH)2D3 of CYP24A1, CDH1/E-cadherin and CST5/cystatin D genes and of an epithelial adhesive phenotype. Moreover, JMJD3 knockdown upregulates the epithelial-mesenchymal transition inducers SNAI1, ZEB1 and ZEB2 and the mesenchymal markers FN1/fibronectin 1 and LEF1, while it downregulates the epithelial genes CDH1/E-cadherin, CLDN1/claudin-1 and CLDN7/claudin-7. Additionally, JMJD3 knockdown blunts the nuclear export of β-catenin and abolishes the inhibition of β-catenin transcriptional activity caused by 1,25(OH)2D3. In line with data in cultured cells, the expression level of JMJD3 RNA is lower in tumour than in normal tissue in 56% of the CRC patients studied and correlates directly with VDR and inversely with SNAI1 RNA expression. Together, our results indicate that an epigenetic gene coding for a histone demethylase such as JMJD3 is a VDR target that partially mediate the effects of 1,25(OH)2D3 on human CRC cells. 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 291. doi:1538-7445.AM2012-291
Visualization of Hypoxia in Microscopic Tumors by Immunofluorescent Microscopy
Authors: Xiao-Feng Li, Sean Carlin, Muneyasu Urano, James Russell, C. Clifton Ling, Joseph A. O'Donoghue
Journal: Cancer Research (2007)

Abstract Tumor hypoxia is commonly observed in primary solid malignancies but the hypoxic status of subclinical micrometastatic disease is largely unknown. The distribution of hypoxia in microscopic tumors was studied in animal models of disseminated peritoneal disease and intradermal (i.d.) growing tumors. Tumors derived from human colorectal adenocarcinoma cell lines HT29 and HCT-8 ranged in size from a few hundred microns to several millimeters in diameter. Hypoxia was detected by immunofluorescent visualization of pimonidazole and the hypoxia-regulated protein carbonic anhydrase 9. Tumor blood perfusion, cellular proliferation, and vascularity were visualized using Hoechst 33342, bromodeoxyuridine, and CD31 staining, respectively. In general, tumors of &amp;lt;1 mm diameter were intensely hypoxic, poorly perfused, and possessed little to no vasculature. Larger tumors (∼1–4 mm diameter) were well perfused with widespread vasculature and were not significantly hypoxic. Patterns of hypoxia in disseminated peritoneal tumors and i.d. tumors were similar. Levels of hypoxia in microscopic peritoneal tumors were reduced by carbogen breathing. Peritoneal and i.d. tumor models are suitable for studying hypoxia in microscopic tumors. If the patterns of tumor hypoxia in human patients are similar to those observed in these animal experiments, then the efficacy of systemic treatments of micrometastatic disease may be compromised by hypoxic resistance. [Cancer Res 2007;67(16):7646–52]
Imaging evidence for persistent subclinical fasciitis and arthritis in tumour necrosis factor receptor-associated periodic syndrome (TRAPS) between febrile attacks
Authors: N. Quillinan, A. Mohammad, G. Mannion, D. O'Keeffe, D. Bergin, R. Coughlan, M. F. McDermott, D. McGonagle
Journal: Annals of the Rheumatic Diseases (2009)

Tumour necrosis factor receptor-associated periodic syndrome (TRAPS),1 formerly known as familial Hibernian fever,2 3 is an archetypal hereditary periodic fever syndrome and is an autosomal dominant condition characterised by mutations in the TNFRSF1A gene.4 5 Periodicity of fevers is typical of TRAPS, with peritonitis, arthritis and fasciitis. It is also well recognised that some patients continue to feel unwell between attacks. That subclinical TRAPS is still ongoing in such circumstances is supported by persistent acute phase response.6 7 There are no specific features to localise a site for this persistent inflammatory response and, to date, no studies have been done to investigate this interesting observation.

Whole body MRI has recently been introduced for the assessment of various skeletal pathologies including malignancy, myositis and arthritis.8,–,12 MRI …
THE NEW NEUROGLIA STAIN OF CARL WEIGERT
Authors: M. N. Voldeng
Journal: American Journal of Psychiatry (1896)

1st. The method is an elective one; that is to say: Nothing but neuroglia tissue is stained, unless the contrast stain is also employed. 2d. The method is sure and reliable in the main, though not absolutely so as yet. 3d. Rapidity of hardening or fixing without making the tissues brittle. 4th. It is believed that sections prepared in this manner are not likely to be durable. 5th. After the tissue has been subjected to the fixing process it is also well adapted for other staining methods, namely: Marchi, Golgi, Van Gieson, Nissl, hæmatoxylin, and carmine. This is of great advantage, inasmuch as it is always desirable to employ a number of different stains for the same tissue.
Response to requests for genetic testing is not based on age alone
Authors: P. S Harper, R. Glew, R. Harper
Journal: BMJ (1999)

EDITOR—Dickenson's article on genetic testing for adult onset disorders in young people raises an important issue,1 but her statement that “many clinical genetics units operate a bar at 18” suggests a lack of familiarity with current practice in clinical genetics and the way it has evolved since genetic testing for adult onset disorders became feasible.

She is right to distinguish the situation of adolescents requesting testing from that of parental …
Transitional Care Interventions to Prevent Readmissions for Persons With Heart Failure
Authors: Cynthia K Feltner, Christine D. Jones, Crystal Wiley Wiley Cene, Zhi Jie Zheng, Carla A Sueta, Emmanuel J.L. Coker-Schwimmer, Marina Arvanitis, Kathleen N. Lohr, Jennifer C. Middleton, Daniel E Jonas
Journal: Annals of Internal Medicine (2014)

Nearly 25% of patients hospitalized with heart failure (HF) are readmitted within 30 days.To assess the efficacy, comparative effectiveness, and harms of transitional care interventions to reduce readmission and mortality rates for adults hospitalized with HF.MEDLINE, Cochrane Library, CINAHL, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (1 January 1990 to late October 2013).Two reviewers independently selected randomized, controlled trials published in English reporting a readmission or mortality rate within 6 months of an index hospitalization.One reviewer extracted data, and another checked accuracy. Two reviewers assessed risk of bias and graded strength of evidence (SOE).Forty-seven trials were included. Most enrolled adults with moderate to severe HF and a mean age of 70 years. Few trials reported 30-day readmission rates. At 30 days, a high-intensity home-visiting program reduced all-cause readmission and the composite end point (all-cause readmission or death; low SOE). Over 3 to 6 months, home-visiting programs and multidisciplinary heart failure (MDS-HF) clinic interventions reduced all-cause readmission (high SOE). Home-visiting programs reduced HF-specific readmission and the composite end point (moderate SOE). Structured telephone support (STS) interventions reduced HF-specific readmission (high SOE) but not all-cause readmissions (moderate SOE). Home-visiting programs, MDS-HF clinics, and STS interventions produced a mortality benefit. Neither telemonitoring nor primarily educational interventions reduced readmission or mortality rates.Few trials reported 30-day readmission rates. Usual care was heterogeneous and sometimes not adequately described.Home-visiting programs and MDS-HF clinics reduced all-cause readmission and mortality; STS reduced HF-specific readmission and mortality. These interventions should receive the greatest consideration by systems or providers seeking to implement transitional care interventions for persons with HF.Agency for Healthcare Research and Quality.
Aspirin Dose for the Prevention of Cardiovascular Disease
Authors: Charles L. Campbell, Susan Smyth, Gilles Montalescot, Steven R. Steinhubl
Journal: JAMA (2007)

More than 50 million US adults take aspirin regularly for long-term prevention of cardiovascular disease, typically either 81 mg/d or 325 mg/d. Controversy remains regarding the most appropriate long-term daily dose.To review the mechanism of action of aspirin and the clinical literature for relationships among aspirin dosage, efficacy, and safety.A systematic review of the English-language literature was undertaken using MEDLINE and EMBASE (searched through February 2007) and the search term aspirin or acetylsalicylic acid and dose. The search was limited to clinical trials and was extended by a review of bibliographies of pertinent reports of original data and review articles. Published prospective studies using different aspirin dosages in the setting of cardiovascular disease were included.Although pharmacodynamic data demonstrate that long-term aspirin dosages as low as 30 mg/d are adequate to fully inhibit platelet thromboxane production, dosages as high as 1300 mg/d are approved for use. In the United States, 81 mg/d of aspirin is prescribed most commonly (60%), followed by 325 mg/d (35%). The available evidence, predominantly from secondary-prevention observational studies, supports that dosages greater than 75 to 81 mg/d do not enhance efficacy, whereas larger dosages are associated with an increased incidence of bleeding events, primarily related to gastrointestinal tract toxicity.Currently available clinical data do not support the routine, long-term use of aspirin dosages greater than 75 to 81 mg/d in the setting of cardiovascular disease prevention. Higher dosages, which may be commonly prescribed, do not better prevent events but are associated with increased risks of gastrointestinal bleeding.
DNA Methylation Maintains Allele-specific <i>KIR</i> Gene Expression in Human Natural Killer Cells
Authors: Huei-Wei Chan, Zoya B. Kurago, C. Andrew Stewart, Michael J. Wilson, Maureen P. Martin, Brian E. Mace, Mary Carrington, John Trowsdale, Charles T. Lutz
Journal: The Journal of Experimental Medicine (2003)

Killer immunoglobulin-like receptors (KIR) bind self-major histocompatibility complex class I molecules, allowing natural killer (NK) cells to recognize aberrant cells that have down-regulated class I. NK cells express variable numbers and combinations of highly homologous clonally restricted KIR genes, but uniformly express KIR2DL4. We show that NK clones express both 2DL4 alleles and either one or both alleles of the clonally restricted KIR 3DL1 and 3DL2 genes. Despite allele-independent expression, 3DL1 alleles differed in the core promoter by only one or two nucleotides. Allele-specific 3DL1 gene expression correlated with promoter and 5' gene DNA hypomethylation in NK cells in vitro and in vivo. The DNA methylase inhibitor, 5-aza-2'-deoxycytidine, induced KIR DNA hypomethylation and heterogeneous expression of multiple KIR genes. Thus, NK cells use DNA methylation to maintain clonally restricted expression of highly homologous KIR genes and alleles.
Nonsynaptic Glycine Receptor Activation during Early Neocortical Development
Authors: Alexander C Flint, Xiaolin Liu, Arnold R Kriegstein
Journal: Neuron (1998)

Glycine receptors (GlyRs) contribute to fast inhibitory synaptic transmission in the brain stem and spinal cord. GlyR subunits are expressed in the developing neocortex, but a neurotransmitter system involving cortical GlyRs has yet to be demonstrated. Here, we show that GlyRs in immature neocortex are excitatory and activated by a nonsynaptically released endogenous ligand. Of the potential ligands for cortical GlyRs, taurine is by far the most abundant in the developing neocortex. We found that taurine is stored in immature cortical neurons and that manipulations known to elevate extracellular taurine cause GlyR activation. These data indicate that nonsynaptically released taurine activates GlyRs during neocortical development. As fetal taurine deprivation can cause cortical dysgenesis, it is possible that taurine influences neocortical development by activating GlyRs.