tbuckley/cabot-search huggingface dataset:
Salivary Transcriptome Diagnostics for Oral Cancer Detection
Authors: Yang Li, Maie A. R. St. John, Xiaofeng Zhou, Yong Kim, Uttam Sinha, Richard C. K. Jordan, David Eisele, Elliot Abemayor, David Elashoff, No-Hee Park, David T. Wong
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Oral fluid (saliva) meets the demand for noninvasive, accessible, and highly efficient diagnostic medium. Recent discovery that a large panel of human RNA can be reliably detected in saliva gives rise to a novel clinical approach, salivary transcriptome diagnostics. The purpose of this study is to evaluate the diagnostic value of this new approach by using oral squamous cell carcinoma (OSCC) as the proof-of-principle disease. Experimental Design: Unstimulated saliva was collected from patients (n = 32) with primary T1/T2 OSCC and normal subjects (n = 32) with matched age, gender, and smoking history. RNA isolation was done from the saliva supernatant, followed by two-round linear amplification with T7 RNA polymerase. Human Genome U133A microarrays were applied for profiling human salivary transcriptome. The different gene expression patterns were analyzed by combining a t test comparison and a fold-change analysis on 10 matched cancer patients and controls. Quantitative polymerase chain reaction (qPCR) was used to validate the selected genes that showed significant difference (P &amp;lt; 0.01) by microarray. The predictive power of these salivary mRNA biomarkers was analyzed by receiver operating characteristic curve and classification models. Results: Microarray analysis showed there are 1,679 genes exhibited significantly different expression level in saliva between cancer patients and controls (P &amp;lt; 0.05). Seven cancer-related mRNA biomarkers that exhibited at least a 3.5-fold elevation in OSCC saliva (P &amp;lt; 0.01) were consistently validated by qPCR on saliva samples from OSCC patients (n = 32) and controls (n = 32). These potential salivary RNA biomarkers are transcripts of IL8, IL1B, DUSP1, HA3, OAZ1, S100P, and SAT. The combinations of these biomarkers yielded sensitivity (91%) and specificity (91%) in distinguishing OSCC from the controls. Conclusions: The utility of salivary transcriptome diagnostics is successfully demonstrated in this study for oral cancer detection. This novel clinical approach could be exploited to a robust, high-throughput, and reproducible tool for early cancer detection. Salivary transcriptome profiling can be applied to evaluate its usefulness for other major disease applications as well as for normal health surveillance.
Coupling erythropoietin secretion to mesenchymal stromal cells enhances their regenerative properties
Authors: Ian B. Copland, E. Marc Jolicoeur, Marc-Antoine Gillis, Jessica Cuerquis, Nicoletta Eliopoulos, Borhane Annabi, Angelo Calderone, Jean-Francois Tanguay, Anique Ducharme, Jacques Galipeau
Journal: Cardiovascular Research (2008)

Mesenchymal stromal cells (MSCs) possess intrinsic features that identify them as useful for treating ischaemic syndromes. Poor in vivo survival/engraftment of MSCs, however, limits their overall effectiveness. In this work, we tested whether genetically engineering MSCs to secrete erythropoietin (Epo) could represent a better therapeutic platform than MSCs in their native form. MSCs from C57Bl/6 mice were retrovirally transduced with either an empty vector or one that causes the production of Epo and were then analysed for the alterations in angiogenic and survival potential. Using a mouse model of myocardial infarction (MI), the regenerative potential of null MSCs and Epo-overexpressing MSCs (Epo+MSCs) was assessed using serial echocardiogram and invasive haemodynamic measurements. Infarct size, capillary density and neutrophil influx were assessed using histologic techniques. Using in vitro assays coupled with an in vivo Matrigel plug assay, we demonstrate that engineering MSCs to express Epo does not alter their immunophenotype or plasticity. However, relative to mock-modified MSCs [wild-type (WT)-MSCs], Epo+MSCs are more resilient to apoptotic stimuli and initiate a more robust host-derived angiogenic response. We also identify and characterize the autocrine loop established on MSCs by having them secrete Epo. Furthermore, in a murine model of MI, animals receiving intracardiac injections of Epo+MSCs exhibited significantly enhanced cardiac function compared with WT-MSCs and saline-injected control animals post-MI, owing to the increased myocardial capillary density and the reduced neutrophilia. Epo overexpression enhances the cellular regenerative properties of MSCs by both autocrine and paracrine pathways.
Adjuvant Therapy of Stage III and IV Malignant Melanoma Using Granulocyte-Macrophage Colony-Stimulating Factor
Authors: Lynn E. Spitler, Michael L. Grossbard, Marc S. Ernstoff, Gary Silver, Mark Jacobs, F. Ann Hayes, Seng Jaw Soong
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To evaluate granulocyte-macrophage colony-stimulating factor (GM-CSF) as surgical adjuvant therapy in patients with malignant melanoma who are at high risk of recurrence. PATIENTS AND METHODS: Forty-eight assessable patients with stage III or IV melanoma were treated in a phase II trial with long-term, chronic, intermittent GM-CSF after surgical resection of disease. Patients with stage III disease were required to have more than four positive nodes or a more than 3-cm mass. All patients were rendered clinically disease-free by surgery before enrollment. The GM-CSF was administered subcutaneously in 28-day cycles, such that a dose of 125 μg/m 2 was delivered daily for 14 days followed by 14 days of rest. Treatment cycles continued for 1 year or until disease recurrence. Patients were evaluated for toxicity and disease-free and overall survival. RESULTS: Overall and disease-free survival were significantly prolonged in patients who received GM-CSF compared with matched historical controls. The median survival duration was 37.5 months in the study patients versus 12.2 months in the matched controls (P &lt; .001). GM-CSF was well tolerated; only one subject discontinued drug due to an adverse event (grade 2 injection site reaction). CONCLUSION: GM-CSF may provide an antitumor effect that prolongs survival and disease-free survival in patients with stage III and IV melanoma who are clinically disease-free. These results support institution of a prospective, randomized clinical trial to definitively determine the value of surgical adjuvant therapy with GM-CSF in such patients.
Cardiac function, coronary flow and MO2hypertrophy induced by pressure and volume overloading1
Authors: Asrar B. Malik, A. S. Geha
Journal: Cardiovascular Research (1977)

Journal Article Cardiac function, coronary flow and MO2hypertrophy induced by pressure and volume overloading Get access A. B. MALIK, A. B. MALIK 2 From the Department of Physiology, Albany Medical College, New York, and the Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 2Address for reprints: Dr A. B. Malik, Department of Physiology, Albany Medical College of Union University, 47 New Scotland Avenue, Albany, New York 12208, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar A. S. GEHA A. S. GEHA From the Department of Physiology, Albany Medical College, New York, and the Department of Surgery, Yale University School of Medicine, New Haven, Connecticut Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 11, Issue 4, July 1977, Pages 310–316, https://doi.org/10.1093/cvr/11.4.310 Published: 01 July 1977
Dynamic relation between myocardial contractility and energy metabolism during and following brief coronary occlusion in the pig.
Authors: G G Schwartz, S Schaefer, D J Meyerhoff, J Gober, P Fochler, B Massie, M W Weiner
Journal: Circulation Research (1990)

Changes in high-energy phosphate metabolism may be important in the regulation of myocardial contractile function during ischemia. This study sought to determine the dynamic relation between myocardial contractile function and high-energy phosphate metabolism during and following brief (24-second) coronary occlusion, when large and rapid changes in both parameters occur. Eight anesthetized, open-chest pigs were instrumented with a Doppler flow probe and occluder on the anterior descending coronary artery, segment length crystals in the anterior left ventricular wall, and a surface coil for phosphorus-31 nuclear magnetic resonance spectroscopy. Phosphorus-31 spectra were reconstructed with a 4.8-second time resolution by summing corresponding short blocks of data from multiple occlusions. Metabolic and functional parameters were unchanged during the first 4.8 seconds of occlusion. During the remainder of occlusion, phosphocreatine progressively declined to 66 +/- 3% of control, inorganic phosphate rose to 170 +/- 8% of control, and segment shortening fell to 25 +/- 9% of control. A strong linear correlation was found between dynamic changes in segment shortening and phosphocreatine (r2 = 0.97), inorganic phosphate (r2 = 0.96), and the ratio of phosphocreatine to inorganic phosphate (r2 = 0.98) during occlusion. At any level of the ratio between phosphocreatine and inorganic phosphate, segment shortening was greater during reflow than during occlusion. The close, dynamic relation between segment shortening and phosphorus metabolites supports the regulation of contractility by changes in energy metabolism or its by-products during ischemia. During reactive hyperemia, the high coronary flow rate may be an independent factor modulating contractility.
The respiratory health benefits of quitting cannabis use
Authors: Donald P. Tashkin
Journal: European Respiratory Journal (2015)

Cannabis is the second most widely smoked substance besides tobacco. Moreover, its use in some societies has increased over the past several years [1], possibly due to changing perceptions regarding its potentially deleterious effects on health and its putative health benefits [2], as reflected by decriminalisation and legalisation for medicinal or recreational use by some regulatory authorities. A limited number of observational studies have examined the effects of cannabis on respiratory health [3–9]. These have nearly uniformly demonstrated an association between cannabis use and symptoms of chronic bronchitis [3–7, 9], particularly chronic cough and sputum production, with more variable effects on wheezing and generally negative effects on breathlessness. In addition, there is some evidence of an association with acute bronchitic episodes [3] and increased healthcare utilisation for acute respiratory illness [10]. Findings from a couple of these studies have also suggested additive effects of cannabis and tobacco smoking on symptoms of chronic bronchitis [4, 8]. Quitting cannabis smoking and the effects on respiratory symptoms <http://ow.ly/MTU6R>
Bisphosphonates for osteoarthritis prevention: "Holy Grail" or not?
Authors: K. G Saag
Journal: Annals of the Rheumatic Diseases (2008)

The search for effective disease modifying osteoarthritis (OA) agents has been a long and winding road with much unrealised promise. While a debate persists about whether OA is predominately a disease of bone, cartilage, or both, there has been interest in the possible OA disease modifying effects of bone antiresorptive agents including oestrogens, selective oestrogen receptor modulators, calcitonin and bisphosphonates.1 Bisphosphonates, the most commonly used therapeutic agents for osteoporosis prevention and treatment, hold OA treatment appeal based on their known pharmacology of altering bone remodelling through a direct inhibitory effect on the osteoclast. Such effects could retard subchondral bone remodelling, believed important by some in osteophyte formation and subchondral sclerosis. Also of potential benefit in OA, bisphosphonates have effects beyond the osteoclast and may be slightly immunomodulating via inhibition of pro-inflammatory cytokines.2 In vitro, etidronate binds to human cartilage3 and can modestly inhibit matrix metalloproteinases.4 Neridronate stimulated osteoblasts to produce osteocalcin in an OA model, providing yet another potential pathway for bisphosphonate activity in OA.5 Animal data supports a possible reduction in osteophyte progression and a suppression in subchondral bone resorption with bisphosphonates. Rabbits treated with zoledronic acid6 and rats receiving alendronate7 experienced chondroprotection. Bisphosphonates may also stimulate collagen and proteoglycan synthesis.8 9 …
STUDIES ON THE INTERACTION BETWEEN PHAGOCYTES AND TUBERCLE BACILLI
Authors: Hartmann Stähelin, Manfred L. Karnovsky, Ann E. Farnham, Emanuel Suter
Journal: The Journal of Experimental Medicine (1957)

In continuing studies concerning the interactions between phagocytes and tubercle bacilli the effect of tuberculous infection on respiration and glucose utilization was investigated in guinea pigs. Peritoneal exudates rich in polymorphonuclear leucocytes, derived from guinea pigs infected with tubercle bacilli, had a significantly higher rate of respiration than the same cells from normal animals. The difference between cells from normal and infected animals was greater when the animals were infected with a virulent strain (Vallée) than when infected with an attenuated one (R1Rv or BCG). By the use of glucose labelled with C(14) at position 1 or 6, or uniformly labelled glucose, it was established that this difference in oxygen uptake between normal and infected cells was probably not caused by a difference in the pathway of glucose utilization. Similarly, the respiration of liver and kidney slices from normal and infected guinea pigs was compared and it was found that liver slices showed differences similar to those shown by leucocytes, but that the kidney slices did not. The possibility has not been ruled out that the difference in rate of respiration of liver slices due to infection might be caused by tuberculous lesions in the livers of infected animals. The mononuclear cells which invade the liver have a higher rate of oxygen uptake than liver cells. The rate of glucose utilization and the total amount of CO(2) produced was also determined in intact guinea pigs. Both functions were found not to differ significantly in normal and infected animals. The rate of production of CO(2) from C(1) and C(6) of glucose was the same in both groups of animals. The ratio of the rate of production of C(14)O(2) from C(1) and C(6) of glucose by the whole animal was found to be about 1.35. It was found to be much higher with polymorphonuclear leucocytes (C(1)/C(6) = 8 in the absence of serum). During the process of phagocytosis this ratio increased from about 25 to about 130 (in the presence of 2 per cent serum) indicating an increase in the direct oxidative pathway of glucose utilization during stimulated cellular activity.
Clinical management of concurrent diabetes and tuberculosis and the implications for patient services
Authors: Anca Lelia Riza, Fiona Pearson, Cesar Ugarte-Gil, Bachti Alisjahbana, Steven van de Vijver, Nicolae M Panduru, Philip C Hill, Rovina Ruslami, David Moore, Rob Aarnoutse, Julia A Critchley, Reinout van Crevel
Journal: The Lancet Diabetes & Endocrinology (2014)
Plastic architecture of bacterial genome revealed by comparative genomics of Photorhabdus variants
Authors: Sophie Gaudriault, Sylvie Pages, Anne Lanois, Christine Laroui, Corinne Teyssier, Estelle Jumas-Bilak, Alain Givaudan
Journal: Genome biology (2008)

Abstract Background The phenotypic consequences of large genomic architecture modifications within a clonal bacterial population are rarely evaluated because of the difficulties associated with using molecular approaches in a mixed population. Bacterial variants frequently arise among Photorhabdus luminescens , a nematode-symbiotic and insect-pathogenic bacterium. We therefore studied genome plasticity within Photorhabdus variants. Results We used a combination of macrorestriction and DNA microarray experiments to perform a comparative genomic study of different P. luminescens TT01 variants. Prolonged culturing of TT01 strain and a genomic variant, collected from the laboratory-maintained symbiotic nematode, generated bacterial lineages composed of primary and secondary phenotypic variants and colonial variants. The primary phenotypic variants exhibit several characteristics that are absent from the secondary forms. We identify substantial plasticity of the genome architecture of some variants, mediated mainly by deletions in the 'flexible' gene pool of the TT01 reference genome and also by genomic amplification. We show that the primary or secondary phenotypic variant status is independent from global genomic architecture and that the bacterial lineages are genomic lineages. We focused on two unusual genomic changes: a deletion at a new recombination hotspot composed of long approximate repeats; and a 275 kilobase single block duplication belonging to a new class of genomic duplications. Conclusion Our findings demonstrate that major genomic variations occur in Photorhabdus clonal populations. The phenotypic consequences of these genomic changes are cryptic. This study provides insight into the field of bacterial genome architecture and further elucidates the role played by clonal genomic variation in bacterial genome evolution.
Chromosomal Changes of Similar Nature in Seven Established Cell Lines Derived From the Peripheral Blood of Patients With Leukemia&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Harald zur Hausen
Journal: JNCI Journal of the National Cancer Institute (1967)

Seven cell lines derived from the peripheral blood of leukemic patients were examined cytogenetically. All strains had predominantly diploid chromosome numbers. In a few metaphases, incomplete condensation of single chromosomes involved chiefly chromosomes that were affected by secondary constrictions. In anaphase preparations the uncoiled material failed to move in step with the divided chromosomes and was easily detected. Autoradiography with tritiated thymidine revealed DNA synthesis of incompletely condensed material during the G2 period; this indicated a disturbed DNA replication pattern of the involved chromosomes. The implications of these findings are discussed.
An Open, Randomized, Parallel-Group Study to Compare the Efficacy and Safety Profile of Inhaled Human Insulin (Exubera) With Glibenclamide as Adjunctive Therapy in Patients With Type 2 Diabetes Poorly Controlled on Metformin
Authors: Anthony H. Barnett, Manfred Dreyer, Peter Lange, Marjana Serdarevic-Pehar
Journal: Diabetes Care (2007)

We thank Kanna and Abreu-Pacheco (1) for their comments on our study (2). As Kanna and Abreu-Pacheco point out, overweight and obesity are strongly linked to the development of type 2 diabetes and can complicate its management. While most patients with type 2 diabetes are overweight (3), this study (2) included individuals with a range of BMI values typical of those seen in clinical practice; mean BMI in …
Heme Oxygenase-1 Regulates Myeloid Cell Trafficking in AKI
Authors: Travis D. Hull, Ahmed I. Kamal, Ravindra Boddu, Subhashini Bolisetty, Lingling Guo, Cornelia C. Tisher, Sunil Rangarajan, Bo Chen, Lisa M. Curtis, James F. George, Anupam Agarwal
Journal: Journal of the American Society of Nephrology (2015)

Renal ischemia-reperfusion injury is mediated by a complex cascade of events, including the immune response, that occur secondary to injury to renal epithelial cells. We tested the hypothesis that heme oxygenase-1 (HO-1) expression, which is protective in ischemia-reperfusion injury, regulates trafficking of myeloid-derived immune cells in the kidney. Age-matched male wild-type (HO-1(+/+)), HO-1-knockout (HO-1(-/-)), and humanized HO-1-overexpressing (HBAC) mice underwent bilateral renal ischemia for 10 minutes. Ischemia-reperfusion injury resulted in significantly worse renal structure and function and increased mortality in HO-1(-/-) mice. In addition, there were more macrophages (CD45(+) CD11b(hi)F4/80(lo)) and neutrophils (CD45(+) CD11b(hi) MHCII(-) Gr-1(hi)) in HO-1(-/-) kidneys than in sham and HO-1(+/+) control kidneys subjected to ischemia-reperfusion. However, ischemic injury resulted in a significant decrease in the intrarenal resident dendritic cell (DC; CD45(+)MHCII(+)CD11b(lo)F4/80(hi)) population in HO-1(-/-) kidneys compared with controls. Syngeneic transplant experiments utilizing green fluorescent protein-positive HO-1(+/+) or HO-1(-/-) donor kidneys and green fluorescent protein-negative HO-1(+/+) recipients confirmed increased migration of the resident DC population from HO-1(-/-) donor kidneys, compared to HO-1(+/+) donor kidneys, to the peripheral lymphoid organs. This effect on renal DC migration was corroborated in myeloid-specific HO-1(-/-) mice subjected to bilateral ischemia. These mice also displayed impaired renal recovery and increased fibrosis at day 7 after injury. These results highlight an important role for HO-1 in orchestrating the trafficking of myeloid cells in AKI, which may represent a key pathway for therapeutic intervention.
Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial
Authors: Lucia Del Mastro, Sabino De Placido, Paolo Bruzzi, Michele De Laurentiis, Corrado Boni, Giovanna Cavazzini, Antonio Durando, Anna Turletti, Cecilia Nisticò, Enrichetta Valle, Ornella Garrone, Fabio Puglisi, Filippo Montemurro, Sandro Barni, Andrea Ardizzoni, Teresa Gamucci, Giuseppe Colantuoni, Mario Giuliano, Adriano Gravina, Paola Papaldo, Claudia Bighin, Giancarlo Bisagni, Valeria Forestieri, Francesco Cognetti
Journal: The Lancet (2015)
The McLean-Harvard First-Episode Mania Study: Prediction of Recovery and First Recurrence
Authors: Mauricio Tohen, Carlos A. Zarate, John Hennen, Hari-Mandir Kaur Khalsa, Stephen M. Strakowski, Priscilla Gebre-Medhin, Paola Salvatore, Ross J. Baldessarini
Journal: American Journal of Psychiatry (2003)

Since improved prediction of illness course early in bipolar disorder is required to guide treatment planning, the authors evaluated recovery, first recurrence, and new illness onset following first hospitalization for mania.Bipolar disorder patients (N=166) were followed 2-4 years after their first hospitalization for a manic or mixed episode to assess timing and predictors of outcomes. Three aspects of recovery were measured: syndromal (DSM-IV criteria for disorder no longer met), symptomatic (Young Mania Rating Scale score </=5 and Hamilton Depression Rating Scale score </=8), and functional (regaining of premorbid occupational and residential status). Rates of remission (syndromal recovery sustained >/=8 weeks), switching (onset of new dissimilar illness before recovery), relapse (new episode of mania within 8 weeks of syndromal recovery), and recurrence (new episode postremission) were also assessed.By 2 years, most subjects achieved syndromal recovery (98%, with 50% achieving recovery by 5.4 weeks); 72% achieved symptomatic recovery. Factors associated with a shorter time to syndromal recovery for 50% of the subjects were female sex, shorter index hospitalization, and lower initial depression ratings. Only 43% achieved functional recovery; these subjects were more often older and had shorter index hospitalizations. Within 2 years of syndromal recovery, 40% experienced a new episode of mania (20%) or depression (20%), and 19% switched phases without recovery. Predictors of mania recurrence were initial mood-congruent psychosis, lower premorbid occupational status, and initial manic presentation. Predictors of depression onset were higher occupational status, initial mixed presentation, and any comorbidity. Antidepressant treatment was marginally related to longer time to recovery and earlier relapse.Within 2-4 years of first lifetime hospitalization for mania, all but 2% of patients experienced syndromal recovery, but 28% remained symptomatic, only 43% achieved functional recovery, and 57% switched or had new illness episodes. Risks of new manic and depressive episodes were similar but were predicted by contrasting factors.