tbuckley/cabot-search huggingface dataset:
A Developmental Taxonomy of Glioblastoma Defined and Maintained by MicroRNAs
Authors: Tae-Min Kim, Wei Huang, Richard Park, Peter J. Park, Mark D. Johnson
Journal: Cancer Research (2011)

mRNA expression profiling has suggested the existence of multiple glioblastoma subclasses, but their number and characteristics vary among studies and the etiology underlying their development is unclear. In this study, we analyzed 261 microRNA expression profiles from The Cancer Genome Atlas (TCGA), identifying five clinically and genetically distinct subclasses of glioblastoma that each related to a different neural precursor cell type. These microRNA-based glioblastoma subclasses displayed microRNA and mRNA expression signatures resembling those of radial glia, oligoneuronal precursors, neuronal precursors, neuroepithelial/neural crest precursors, or astrocyte precursors. Each subclass was determined to be genetically distinct, based on the significant differences they displayed in terms of patient race, age, treatment response, and survival. We also identified several microRNAs as potent regulators of subclass-specific gene expression networks in glioblastoma. Foremost among these is miR-9, which suppresses mesenchymal differentiation in glioblastoma by downregulating expression of JAK kinases and inhibiting activation of STAT3. Our findings suggest that microRNAs are important determinants of glioblastoma subclasses through their ability to regulate developmental growth and differentiation programs in several transformed neural precursor cell types. Taken together, our results define developmental microRNA expression signatures that both characterize and contribute to the phenotypic diversity of glioblastoma subclasses, thereby providing an expanded framework for understanding the pathogenesis of glioblastoma in a human neurodevelopmental context.
The value of Doppler US in the study of hepatic hemodynamics
Authors: L. Barbara, K. Okuda, K.J.W. Taylor, R.J. Groszmann, L. Barbara, L. Bolondi, P.N. Burns, S. Gaiani, J. Bosch, A. Braillon, P.N. Burns, M. Dauzat, R.J. Groszmann, M. Lafortune, D. Lebrec, F. Moriyasu, K. Okuda, L. Pagliaro, E. Pisi, G. Pomier-Layrargues, C.C. Sieber, K.J.W. Taylor, G. Verme, P.N.T. Wells, R. Williams
Journal: Journal of Hepatology (1990)
Identification of a novel pneumococcal vaccine antigen preferentially expressed during meningitis in mice
Authors: Layla K. Mahdi, Hui Wang, Mark B. Van der Hoek, James C. Paton, Abiodun D. Ogunniyi
Journal: Journal of Clinical Investigation (2012)

Streptococcus pneumoniae is the most common cause of severe bacterial meningitis in children, the elderly, and immunocompromised individuals. To identify virulence factors preferentially expressed during meningitis, we conducted niche-specific genome-wide in vivo transcriptomic analysis after intranasal infection of mice with serotype 4 or 6A pneumococci. The expression of 34 bacterial genes was substantially altered in brain tissue of mice infected with either of the 2 strains. Ten upregulated genes were common to both strains, 7 of which were evaluated for their role in the development of meningitis. One previously uncharacterized protein, α-glycerophosphate oxidase (GlpO), was cytotoxic for human brain microvascular endothelial cells (HBMECs) via generation of H(2)O(2). A glpO deletion mutant was defective in adherence to HBMECs in vitro as well as in progression from the blood to the brain in vivo. Mutant bacteria also induced markedly reduced meningeal inflammation and brain pathology compared with wild type, despite similar levels of bacteremia. Immunization of mice with GlpO protected against invasive pneumococcal disease and provided additive protection when formulated with pneumolysin toxoid. Our results provide the basis of a strategy that can be adapted to identify genes that contribute to the development of meningitis caused by other pathogens.
Girls' Sports Injuries in High School Athletics
Authors: James G. Garrick
Journal: JAMA (1978)

Because of appreciable increases in the number of participants, injuries resulting from girls' interscholastic athletic activities have become a concern for school administrators and medical care providers. Four girls' high school athletic programs were prospectively studied for two years. Specially trained athletic trainers placed at each school examined each injured athlete and collected epidemiologic data. The 870 participant-seasons in nine sports resulted in 192 injuries. Three times more injuries occurred in practices than in competitive events. Although more than one third required a physician's services, the majority (59%) had returned to full athletic activity within a week of injury. Strains and sprains accounted for nearly two thirds of the injuries. Generally, the type and frequency of injuries were comparable with those seen in noncontact boys' interscholastic sports.
Abstract 2706: Discovery of predictive biomarkers based on differential chemosensitivity of colorectal cell lines
Authors: Florian T. Unger, Markus Meyer, Agnieszka Harasym, Jörg Spangenberg, Kevin Sullivan, Hartmut Juhl, Kerstin A. David
Journal: Cancer Research (2010)

Abstract Chemoresistance is the main reason for therapeutic ineffectiveness and recurrence in colorectal cancer. Furthermore, the choice of optimal chemotherapy is complicated by an interpatient variability in drug response caused by the individual geno- and phenotype. To promote a more individualized therapy, predictive biomarkers which indicate individual drug response of patients are urgently needed. In this study, using a combination of HPLC and mass spectroscopy, we discovered differentially expressed proteins which might be linked to specific phenotypes of intrinsic chemoresistance in colorectal cancer cell lines. Several commercially available cell lines as well as primary mixed cultures and clonal cell lines established from colorectal cancer patients were treated with different drugs, such as 5-Fluorouracil, Oxaliplatin and drug combinations e.g. FOLFOX. Two different assays, the ATPliteTM-(Perkin Elmer) and FMC-assay (according to Larsson et al.) were used in parallel to measure cytotoxic and cytostatic drug effects. Both assays showed time and dose dependent drug responses which differed significantly among the 18 colorectal cell cultures. The analysis of obtained in vitro chemosensitivity data allowed us to cluster sensitive versus resistant cell lines by determining IC50-values. From all 18 cell cultures, differential protein expression was analyzed using a combination of reversed phase high performance liquid chromatography and matrix assisted laser desorption/ionization mass spectrometry (RP-HPLC MALDI MS) workflow. Up to 3500 m/z ion signals in the molecular mass range between 2500-35000 m/z were detected reflecting a complex pattern of small proteins and peptides. For protein identification, RP-HPLC fractionated samples were digested by trypsin and fragments of interest were subjected to MS/MS analysis in the TOF/TOF mode. The corresponding MS/MS spectra were used to search the NCBInr database using MASCOT software. Based on these data, we hope to gain more understanding of the biological processes of chemoresistance concerning important cellular drug responses (e.g. signal transduction pathways) and thereby obtain insight into new drug targets for future therapeutic intervention. 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 2706.
Pioglitazone treatment enhances the sympathetic nervous system response to oral carbohydrate load in obese individuals with metabolic syndrome
Authors: Nora E. Straznicky, Mariee T. Grima, Carolina I. Sari, Nina Eikelis, Gavin W. Lambert, Paul J. Nestel, Katrina Richards, John B. Dixon, Markus P. Schlaich, Elisabeth A. Lambert
Journal: Metabolism (2015)
Molecular Epidemiology of Cytomegalovirus Infections in Women and Their Infants
Authors: Eng-Shang Huang, Charles A. Alford, David W. Reynolds, Sergio Stagno, Robert F. Pass
Journal: New England Journal of Medicine (1980)

We studied cytomegaloviruses (CMV's) isolated from mothers and their children to determine whether recurrent infections and transmission to the fetus in immune women are due to reinfection or reactivaton of endogenous virus. Twenty-one strains of CMV from six mother-baby pairs, from two congenitally infected siblings, and from repeat isolates from four women were examined for genetic relatedness, by means of restriction endonuclease analysis of purified viral DNA. Although CMV's from unrelated persons were always different, strains from five to six congenitally infected babies were identical or very closely related to those from their mothers. Strains from congenitally infected siblings were also concordant, as were repeat isolates form three of four women. Major differences in viral DNA were detected in strains recovered from the same woman or from a mother-baby pair in only two cases. Endogenous CMV appears to be most frequent source of recurrent infection and intrauterine transmission in immune women; reinfection also occurs, but less commonly.
BONE MINERAL DENSITY IN YOUNG ADULT FEMALES WITH AND WITHOUT STRESS FRACTURES
Authors: R. A. Wyatt, A. Ramos-Gabatin
Journal: Clinical Nuclear Medicine (1992)

S: APRIL 9–12, 1992 San Antonio Convention Center & Hyatt Regency Hotel SAN ANTONIO, TEXAS Southwestern Chapter Society of Nuclear Medicine SPECT/PET Nuclear Cardiology Symposium and 37th Annual Meeting: PDF Only
Isotypic analysis of grass‐pollen‐specific antibodies in human plasma.
Authors: T. Batard, A. Laroze, B. David, G. Peltre, B. Basuyaux
Journal: Allergy (1996)

Since it has been shown that autoanti‐IgE may be mistaken for antiallergen antibodies, thus appearing as pseudo‐allergen‐specific antibodies, it is crucial to separate true‐ from pseudo‐allergen‐specific antibodies and to determine to what extent autoanti‐IgE appeared as pseudo‐allergen‐specific antibodies. For this purpose, human Ig pools were affinity‐purified successively on a grass‐pollen column and then on an antihuman‐IgE column. IgG 1–4, IgA, and IgM antibodies that were eluted from the grass‐pollen column separated into pseudo‐ (˜30–40%) and true‐allergen‐specific antibodies that were coretained and not coretained, respectively, with the IgE on the anti‐IgE column. Levels of autoanti‐IgE were determined in individual plasma samples by surface plasmon resonance and statistically compared to the concentrations of allergen‐specific antibodies obtained previously in the same plasma samples. A positive correlation between IgM autoanti‐IgE levels and grass‐pollen‐“specific” IgM concentrations (P&lt; 0.0002), and negative correlations between IgA autoanti‐IgE and both IgE anti‐grass pollen and IgG2 autoanti‐IgE levels (P&lt;0.03, in both cases) were observed for the first time. This supports the contentions that: (1) autoanti‐IgE antibodies appeared as pseudo‐grass‐pollen‐specific antibodies (2) they hid IgE antibodies when the latter were measured, and (3) they compete with one another in binCling IgE. Lastly, a model of large Ig complexes is discussed.
NHS could save 1bn by adopting green strategies used in kidney units
Authors: M. Limb
Journal: BMJ (2013)

Tryptophan hydroxylase (TPH) activity was measured in various rat brain regions after administering large doses of methamphetamine (METH). After four sequential doses of METH (15 mg/kg), given every 6 hr, TPH activity was decreased (to approximately 10% of control) in both the neostriatum and hippocampus. The depression of enzyme activity persisted for at least 30 days. When compared with the depression of neostriatal tyrosine hydroxylase activity, the depression of neostriatal and hippocampal TPH activity occurred sooner and was more pronounced. The depression of TPH activity was dependent on the number of doses and the amount of drug administered. Five days after one to two doses of METH, a transient recovery was observed but when four doses were given, the enzyme was depressed. No decrease in TPH activity was observed in brain areas containing serotonergic cell bodies. Agents which prevent the METH-induced decrease of neostriatal tyrosine hydroxylase activity, i.e., haloperidol, alpha-methyl-p-tyrosine and gamma-aminobutyric acid transaminase inhibitors also prevented the decrease in TPH activity caused by METH. In addition, fluoxetine, an inhibitor of 5-hydroxytryptamine re-uptake, prevented the METH-induced decrease in neostriatal and hippocampal TPH activity but did not alter the decrease in nenostriatal tyrosine hydroxylase activity.
Partnering with patients
Authors: F. Godlee
Journal: BMJ (2013)

Last month we published a plea from Dave deBronkart (also known as e-Patient Dave) to “let patients help.” As a survivor of stage IV, grade 4 renal cell carcinoma, he described how the online patient community helped save his life ( BMJ 2013;346:f1990). His aim is nothing less than to revolutionise the relationship between patients and healthcare providers. “Please,” he wrote, “let patients help improve healthcare. Let patients help steer our decisions, strategic and practical. Let patients help define what value in medicine is.”

This week we hear from another e-Patient, Kelly Young, who tells us why she became “a rheumatoid arthritis warrior” (doi:10.1136/bmj.f2901). Her blog, rawarrior.com, was …
BMA leaders accused of weak opposition to the government
Authors: Annabel Ferriman
Journal: BMJ (2006)

The BMA leadership was accused at its annual meeting this week of having failed patients, doctors, and the country by not actively opposing the current wave of organisational and financial reforms of the health service. 

The representatives voted by 58% to 42% in support of a motion saying that the current policy of exposing defects in policy was not powerful enough and insisted that it be replaced by …
Potential Pitfalls of the Nuclear Stethoscope
Authors: MICHAEL J. ZEMA, BERNARD RESTIVO, DOUGLAS MUNSEY, BENILDA BARISO
Journal: Clinical Nuclear Medicine (1980)

Eleven patients (three with coronary artery disease, one with mitral valve prolapse, one with atrial septal defect, two with rheumatic mitral valve disease, one with rheumatic aortic valve disease, and three normal individuals) underwent determination of global left ventricular ejection fraction (LVEF) by 1) nuclear stethoscope (cardiac probe), 2) Tc-99m-labeled-erythrocyte gated nuclear angiocardiographic gamma cameracomputer techniques, and 3) single plane RAO contrast left ventriculography—all within a 6-hour period without concurrent drug intervention. In addition, global right ventricular ejection fraction (RVEF) was determined by a similar gated technique with gamma cameracomputer techniques. LVEF as determined by camera-computer techniques correlated well with that of contrast ventriculography (r = 0.95) in this heterogenous group of subjects. LVEF as determined by cardiac probe correlated somewhat less well with that of contrast ventriculography (r = 0.59). Two cases are described in which, although cardiac probe data were highly reproducible, gross overestimation of the true global LVEF was thought to occur due to malpositioning of the probe over either the right ventricle or the most contractile portion of the left ventricle in patients with coronary artery disease.
Acquired Autoimmune Polyglandular Syndrome, Thymoma, and an AIRE Defect
Authors: Mickie H. Cheng, Una Fan, Navdeep Grewal, Michael Barnes, Anand Mehta, Steven Taylor, Eystein S. Husebye, Elizabeth J. Murphy, Mark S. Anderson
Journal: New England Journal of Medicine (2010)

To the Editor: Paraneoplastic autoimmunity frequently accompanies thymoma. Because thymic tumors can support thymocyte development, aberrant T-cell generation has been suggested as a cause.1 The au...
Violence in Geriatric Patients
Authors: William M. Petrie
Journal: JAMA (1982)

Two hundred twenty-two patients admitted to a geriatric psychiatry unit were surveyed for the commission of acts dangerous to others. Eighteen of these patients had used either guns or knives in acts of violence. Organic illness accounted for a minority of such acts, the majority having been perpetrated by patients with functional diagnoses of late paraphrenia, schizophrenia, or mania. The most dangerous patients were those who, in a clear sensorium, experienced paranoid delusions, hallucinations, or both, and believed that they were in danger of being attacked. One hundred twenty-one aggressive patients who did not use weapons against others were also identified. This group, which included a larger percentage of patients suffering from dementia, posed a much less serious threat to others than the violent group.
Differential responses of osteoblast lineage cells to nanotopographically-modified, microroughened titanium–aluminum–vanadium alloy surfaces
Authors: Rolando A. Gittens, Rene Olivares-Navarrete, Taylor McLachlan, Ye Cai, Sharon L. Hyzy, Jennifer M. Schneider, Zvi Schwartz, Kenneth H. Sandhage, Barbara D. Boyan
Journal: Biomaterials (2012)
Neuropeptide and neuronal marker studies in vitiligo
Authors: M.S.K. AL'ABADIE, H.J. SENIOR, S.S. BLEEHEN, D.J. GAWKRODGER
Journal: British Journal of Dermatology (2006)

Neuropeptide and neuronal marker immunoreactivity was studied in skin biopsies from lesional and marginal areas in 12 patients with vitiligo, and in seven normal controls. The vitiligo was active in seven, static in two, and of unknown activity in three. Antibodies against general neuronal marker PGP 9.5 (PGP 9.5), substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY), were used. The epidermis, dermo-epidermal junction, papillary and reticular dermis, and appendages, were assessed semiquantitatively for reactivity with each antibody. Staining with PGP 9.5 in the upper dermis was assessed quantitatively by image analysis. An increase in reactivity against NPY antibody was seen in five of 10 cases (three with active vitiligo) in the marginal areas, and in three of 12 subjects (all with active vitiligo) in the lesional vitiligo areas. VIP antibody reactivity showed a minimal increase in the marginal and lesional vitiligo areas (in two cases each, both of whom had active vitiligo), SP and CGRP reactivities did not differ from normal. PGP 9.5 staining was minimally increased at the dermo-epidermal junction and lower Malpighian layer in biopsies from marginal areas in three of 10 subjects (all with active vitiligo). Quantitative analysis of PGP 9.5 reactivity in the upper dermis showed no difference between vitiligo and normal biopsies. These findings support the concept of neuronal or neuropeptide involvement in vitiligo, and in particular suggest that NPY may have a role in the pathogenesis of the disease.
Abstract 5207: miR-491 and miR-218: Two possible tools to reduce FOXP3 expression in breast carcinomas
Authors: Martina D. Modica, Tiziana Triulzi, Viola Regondi, Marilena V. Iorio, Andrea Balsari, Elda Tagliabue, Patrizia Casalini
Journal: Cancer Research (2014)

Abstract The Forkhead box P3 (FOXP3) gene is a member of the forkhead/winged-helix family of transcription factors implicated in the regulation of immune system development and function. However, FOXP3 is also expressed in human epithelial cancers, where it has been reported to be associated with poor prognosis and in particular with metastasis. Aim of our work is to identify microRNAs able to regulate FOXP3 expression in breast tumors. To discover microRNAs able to regulate FOXP3 expression in breast cancer cells, an in silico analysis has been performed. Among microRNAs harboring FOXP3 seed regions, we focused our attention on miR-218 and miR-491, described to have oncosuppressive properties. Indeed, it has been reported that miR-218 expression stimulates activation of tumor suppressor genes and miR-491 expression inversely correlates with migratory potential in HCC cell lines and in vivo with metastatic potential. We therefore evaluated the ability of these microRNAs to act as oncosuppressors by targeting FOXP3 in a breast cancer model. After transient co-transfection either of miR-218 or miR-491 with FOXP3 in MDA-MB-231 cells, a significant decrease in FOXP3 expression at protein level by WB was found. To perform functional studies both in vitro and in vivo, we generated a breast cancer cell model by stable transfection of MDA-MB-231 with inducible Tet-off plasmid encoding for FOXP3 encompassing 3′UTR region, thus maintaining microRNA-mediated regulation. We demonstrated that FOXP3 expressing clones display an increased migration capacity as compared with their respective non-induced cells. Also in these stable clones a reduction of FOXP3 expression after transfection of miR-491 and miR-218 has been demonstrated by WB. Moreover, FOXP3 was confirmed to be a direct target of both microRNAs by luciferase reporter assay. We also found an inverse correlation between miR-491 levels and FOXP3 expression in human breast carcinoma specimens. Overall, these preliminary results demonstrate that microRNAs can regulate FOXP3 expression, and encourage to further investigate the biological and functional consequences of this targeting, and to exploit microRNAs as a potential therapeutic tool for FOXP3 expressing breast carcinomas. Citation Format: Martina Di Modica, Tiziana Triulzi, Viola Regondi, Marilena V. Iorio, Andrea Balsari, Elda Tagliabue, Patrizia Casalini. miR-491 and miR-218: Two possible tools to reduce FOXP3 expression in breast carcinomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5207. doi:10.1158/1538-7445.AM2014-5207
Should a patient with primary intracerebral haemorrhage receive antiplatelet or anticoagulant therapy?
Authors: Mushtaq Wani, Emma Nga, Ranjini Navaratnasingham
Journal: BMJ (2005)

Patients with primary intracranial haemorrhage may have risk factors for future thromboembolic events. Such a situation presents a therapeutic dilemma, as illustrated by the following case. A 55 year old man was admitted with right sided weakness. His history included hypertension that was difficult to control, type 2 diabetes, angina, and hyperlipidaemia. He had also had a minor stroke affecting his right side about 10 years previously. He was taking medication: aspirin 75 mg, atorvastatin 10 mg, bendroflumethiazide 2.5 mg, ramipril 2.5 mg, amlodipine 5 mg, isosorbide mononitrate modified release 60 mg, pioglitazone 15 mg (all once a day); hydralazine 50 mg twice a day; and metformin 850 mg and methyldopa 250 mg three times a day. He had smoked 20-30 cigarettes a day most of his adult life until 10 yeas previously, and he drank alcohol in moderation.

Examination confirmed grade 4/5 weakness of his right arm and leg and dysarthria. He was rather obese, with a body mass index of 36. Blood pressure on admission was 200/125 mm Hg, which settled very quickly, however, at about 140/80 mm Hg once the dose of amlodipine was increased to 10 mg once daily.

Electrocardiography showed sinus rhythm and mild left ventricular hypertrophy (voltage criteria). A computed tomogram of the head about 90 hours after the onset of symptoms showed a deep left basal ganglia haematoma (fig 1).



Fig 1 
Computed tomogram of the head showing left basal ganglia haematoma (arrowed) 



This case raised an important question which is often ignored in practice. Should a patient who seems to have a high thromboembolic risk but is recovering from a potentially fatal intracranial haemorrhage receive antiplatelet agents to prevent future ischaemic (cerebrovascular and other vascular) events? Is there any evidence in favour of or against such therapy?

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