tbuckley/cabot-search huggingface dataset:
Origins of cardiac dysfunction in cirrhosis
Authors: W Jimenez
Journal: Gut (2003)

Neurogenesis is essential to brain development, and plays a central role in the response to brain injury. Stroke and head trauma stimulate proliferation of endogenous neural stem cells (NSC). However, the survival of young neurons is sharply reduced by post-injury inflammation. Cellular mitochondria are critical to successful neurogenesis and are a major target of inflammatory injury. Mitochondrial protection was shown to improve survival of young neurons. This study tested whether reducing cellular microRNA-210 (miR-210) would enhance mitochondrial function and improve survival of young murine neurons under inflammatory conditions. Several studies have demonstrated the potential of miR-210 inhibition to enhance and protect mitochondrial function through upregulation of mitochondrial proteins. Here miR-210 inhibition significantly increased neuronal survival and protected the activity of mitochondrial enzymes cytochrome c oxidase and aconitase in differentiating NSC cultures exposed to inflammatory mediators. Unexpectedly, we found that reducing miR-210 significantly attenuated NSC proliferation upon induction of differentiation. Further investigation revealed that increased mitochondrial function suppresses the shift to primarily glycolytic metabolism and reduced mitochondrial length characteristic of dividing cells. Activation of AMPK-retinoblastoma signaling is important in NSC proliferation, and the reduction of this activation observed by miR-210 inhibition is one mechanism contributing to the reduced proliferation. Post-injury neurogenesis occurs as a burst of proliferation that peaks in days followed by migration and differentiation over weeks. Our studies suggest that mitochondrial protective miR-210 inhibition should be delayed until after the initial burst of proliferation, but could be beneficial during the prolonged differentiation stage. <b>Significance Statement:</b> Increasing the success of endogenous neurogenesis after brain injury holds therapeutic promise. Post-injury inflammation markedly reduces newborn neuron survival. This study found that enhancement of mitochondrial function by reducing microRNA-210 (miR-210) levels could improve survival of young neurons under inflammatory conditions. MiR-210 inhibition protected the activity of mitochondrial enzymes cytochrome c oxidase and aconitase. On the other hand, we observed decreased precursor cell proliferation likely due to suppression of the AMPK/retinoblastoma axis with miR-210 inhibition. Thus mitochondrial protection is a double-edged sword: early inhibition reduces proliferation, but inhibition later significantly increases neuroblast survival. This in part explains contradictory published reports of the effects of miR-210 on neurogenesis.
British Society of Gastroenterology guidelines for ulcerative colitis surveillance: creating consensus or confusion?
Authors: B Hudson
Journal: Gut (2006)

Absence of grade A evidence combined with discrepancies between retrospective studies in reported survival benefit has led to controversy surrounding the colonoscopic surveillance of ulcerative colitis (UC) patients. Such controversy was demonstrated in 2000 by an audit which revealed widespread variations in surveillance practice.1 Following the introduction of British Society of Gastroenterology (BSG) guidelines in 2002,2 concern was expressed regarding the medicolegal implications posed by national recommendations based on inconclusive evidence and lacking multicentre consensus.3 Three years after the publication of the guidelines, a questionnaire survey has indicated that widespread disparities in opinion and practice still exist.

Questionnaires were distributed to all consultants and specialist registrars in gastroenterology within the Wales deanery. A 45.1% (23/51) response rate was achieved. Although a significant majority (73.9% …
Effect of Cholesterol Depletion On Interleukin-8 Production in Human Respiratory Epithelial Cells
Authors: Min Jung Kim, Jung Yeon Hong, Kyung Eun Lee, Hwan Soo Kim, Yoon Ki Han, Hye Mi Jee, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim
Journal: Journal of Allergy and Clinical Immunology (2013)
An Essential Role for Tumor Necrosis Factor in Natural Killer Cell–mediated Tumor Rejection in the Peritoneum
Authors: Mark J. Smyth, Janice M. Kelly, Alan G. Baxter, Heinrich Körner, Jonathon D. Sedgwick
Journal: The Journal of Experimental Medicine (1998)

Natural killer (NK) cells are thought to provide the first line of defence against tumors, particularly major histocompatibility complex (MHC) class I− variants. We have confirmed in C57BL/6 (B6) mice lacking perforin that peritoneal growth of MHC class I− RMA-S tumor cells in unprimed mice is controlled by perforin-dependent cytotoxicity mediated by CD3− NK1.1+ cells. Furthermore, we demonstrate that B6 mice lacking tumor necrosis factor (TNF) are also significantly defective in their rejection of RMA-S, despite the fact that RMA-S is insensitive to TNF in vitro and that spleen NK cells from B6 and TNF-deficient mice are equally lytic towards RMA-S. NK cell recruitment into the peritoneum was abrogated in TNF-deficient mice challenged with RMA-S or RM-1, a B6 MHC class I− prostate carcinoma, compared with B6 or perforin-deficient mice. The reduced NK cell migration to the peritoneum of TNF-deficient mice correlated with the defective NK cell response to tumor in these mice. By contrast, a lack of TNF did not affect peptide-specific cytotoxic T lymphocyte–mediated rejection of tumor from the peritoneum of preimmunized mice. Overall, these data show that NK cells delivering perforin are the major effectors of class I− tumor rejection in the peritoneum, and that TNF is specifically critical for their recruitment to the peritoneum.
Metabolic syndrome and arterial stiffness: The Health 2000 Survey
Authors: Kalle Sipilä, Teemu Koivistoinen, Leena Moilanen, Tuomo Nieminen, Antti Reunanen, Antti Jula, Veikko Salomaa, Risto Kaaja, Tiit Kööbi, Katriina Kukkonen-Harjula, Silja Majahalme, Mika Kähönen
Journal: Metabolism (2007)
Effect of alpha interferon on the altered t‐b‐cell immunoregulation in patients with thalassemia major
Authors: Patricia Nualart, Maria E. Estevez, Isidro J. Ballart, Susana A. De Miani, Jorge Peñalver, Luisa Sen
Journal: American Journal of Hematology (1987)

Abstract We studied the ability of B‐lymphocytes to differentiate to immunoglobulin‐producing cells in 14 patients with thalassemia major, 11 parents of the patients, and 86 normal subjects. In comparison with the parents of the patients and with the normal individuals, the patients were found to have 1) an increased number of cells spontaneously secreting immunoglobulin; 2) a decreased number of plaque‐forming cells (PFC) when induced with pokeweed mitogen (PWM) and a deficient helper T‐cell function for the induction of B‐cell differentiation; 3) an increase in the number of PFC after the addition of alpha interferon (100 IU/ml) to the cell cultures with PWM. Previous incubation of non‐T‐cells with alpha interferon for 1 hr and subsequent coculture with T‐cells from the same patients or from normal subjects in the presence of PWM increased the number of PFC. On the contrary, previous incubation of T‐cells with alpha interferon followed by coculture with normal non‐T‐cells or cells from the same patient did not modify the number of PFC. These results suggest that patients with thalassemia major possess hyperreactive spontaneous B‐cell responses and that these B‐cells are unable to differentiate to immunoglobulin‐secreting cells in the presence of PWM. This would be due to a T‐helper‐cell deficiency with an inability to produce lymphokines (interferon being one of them), while the B‐cell function seems to remain intrinsically intact.
Diabetes Patients and Their Physicians—All Eager for Knowledge From the West
Authors: Leona V Miller
Journal: Diabetes Care (1993)

During my flight to Moscow recently, I read John Steinbeck's Russian Journal. My daughter had given me the book, thinking, perhaps, that it might inspire me to keep a similar record. I have never been a journal keeper, although I often have wished that I had recorded impressions of situations and people I had encountered on my travels. I didn't keep a journal, but it did make me compare the differences and similarities of my impressions with Steinbeck's. The differences are not surprising, for he wrote of his visit to the Soviet Union shortly after World War II. He observed that the nation had many shortages of farming equipment and other types of machinery, but that the people were tremendously optimistic. They had won the war, and they were then ready to turn their efforts to supplying the needs of a peace-time population.
Brain Tumor Cells in Circulation Are Enriched for Mesenchymal Gene Expression
Authors: James P. Sullivan, Brian V. Nahed, Marissa W. Madden, Samantha M. Oliveira, Simeon Springer, Deepak Bhere, Andrew S. Chi, Hiroaki Wakimoto, S. Michael Rothenberg, Lecia V. Sequist, Ravi Kapur, Khalid Shah, A. John Iafrate, William T. Curry, Jay S. Loeffler, Tracy T. Batchelor, David N. Louis, Mehmet Toner, Shyamala Maheswaran, Daniel A. Haber
Journal: Cancer Discovery (2014)

Abstract Glioblastoma (GBM) is a highly aggressive brain cancer characterized by local invasion and angiogenic recruitment, yet metastatic dissemination is extremely rare. Here, we adapted a microfluidic device to deplete hematopoietic cells from blood specimens of patients with GBM, uncovering evidence of circulating brain tumor cells (CTC). Staining and scoring criteria for GBM CTCs were first established using orthotopic patient-derived xenografts (PDX), and then applied clinically: CTCs were identified in at least one blood specimen from 13 of 33 patients (39%; 26 of 87 samples). Single GBM CTCs isolated from both patients and mouse PDX models demonstrated enrichment for mesenchymal over neural differentiation markers compared with primary GBMs. Within primary GBMs, RNA in situ hybridization identified a subpopulation of highly migratory mesenchymal tumor cells, and in a rare patient with disseminated GBM, systemic lesions were exclusively mesenchymal. Thus, a mesenchymal subset of GBM cells invades the vasculature and may proliferate outside the brain. Significance: GBMs are locally invasive within the brain but rarely metastasize to distant organs, exemplifying the debate over “seed” versus “soil.” We demonstrate that GBMs shed CTCs with invasive mesenchymal characteristics into the circulation. Rare metastatic GBM lesions are primarily mesenchymal and show additional mutations absent in the primary tumor. Cancer Discov; 4(11); 1299–1309. ©2014 AACR. See related commentary by Seoane and De Mattos-Arruda, p. 1259 This article is highlighted in the In This Issue feature, p. 1243
Not All Hypertrophy Is Created Equal
Authors: Ronglih Liao, Thomas Force
Journal: Circulation Research (2007)

C ardiac hypertrophy is the natural response of myocardi- um to various stressors, including neurohormonal stimuli, hemodynamic overload, and injury.In the face of continued stress, pathological hypertrophy progresses to a loss of cardiomyocytes, the development of fibrosis, and, ultimately, heart failure.Emerging evidence has shown that glycogen synthase kinase-3␤ (GSK-3␤) is an important negative regulator of cardiomyocyte hypertrophy, yet inhibition of GSK-3␤ has been shown to reduce cell death after ischemia reperfusion.Therefore, it has been difficult to predict what the consequences of chronic inhibition of GSK-3 in the heart would be because it might be a balance between the potential for the aggravation of cardiac hypertrophy versus antiapoptotic effects.In this issue of Circulation Research, Hirotani and colleagues report that sustained inhibition of GSK-3␤ in postneonatal hearts results in well-compensated "physiologic" cardiac hypertrophy and, most intriguingly, exerts protective effects against the development of "pathological" hypertrophy and heart failure with pressure overload. 1Although there are a number of concerns that need to be addressed before targeting GSK-3 for the treatment of heart failure, this "best of both worlds" outcome provides an interesting and favorable rationale for such intervention.The GSK-3 family of protein kinases is encoded by 2 genes, ␣ and ␤.They are highly conserved throughout evolution and are critical to the regulation of diverse biological processes ranging from organ development to cell death, including cell growth, cell cycling, cytoskeletal organization, and metabolism. 2,3Furthermore, dysregulation of GSK-3␤ has been implicated in the pathogenesis of many human diseases including Alzheimer disease, diabetes, and tumorgenesis. 4 -8 GSK-3␣ (51 kDa) is the larger of the two and has a glycine-rich N terminus of unknown function.GSK-3␤ (47 kDa) and ␣ share significant sequence homology (97%) in their kinase domains, however the homology between the last 76 C-terminal resides is rather low (36%). 3Both isoforms are widely expressed, but the majority of prior investigations have focused on the role of GSK-3␤.This bias likely arose
Loss of Heterozygosity at 2q37 in Sporadic Wilms' Tumor: Putative Role for <i>miR-562</i>
Authors: Kylie M. Drake, E. Cristy Ruteshouser, Rachael Natrajan, Phyllis Harbor, Jenny Wegert, Manfred Gessler, Kathy Pritchard-Jones, Paul Grundy, Jeffrey Dome, Vicki Huff, Chris Jones, Micheala A. Aldred
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Wilms' tumor is a childhood cancer of the kidney with an incidence of ∼1 in 10,000. Cooccurrence of Wilms' tumor with 2q37 deletion syndrome, an uncommon constitutional chromosome abnormality, has been reported previously in three children. Given these are independently rare clinical entities, we hypothesized that 2q37 harbors a tumor suppressor gene important in Wilms' tumor pathogenesis. Experimental Design: To test this, we performed loss of heterozygosity analysis in a panel of 226 sporadic Wilms' tumor samples and mutation analysis of candidate genes. Results: Loss of heterozygosity was present in at least 4% of cases. Two tumors harbored homozygous deletions at 2q37.1, supporting the presence of a tumor suppressor gene that follows a classic two-hit model. However, no other evidence of second mutations was found, suggesting that heterozygous deletion alone may be sufficient to promote tumorigenesis in concert with other genomic abnormalities. We show that miR-562, a microRNA within the candidate region, is expressed only in kidney and colon and regulates EYA1, a critical gene for renal development. miR-562 expression is reduced in Wilms' tumor and may contribute to tumorigenesis by deregulating EYA1. Two other candidate regions were localized at 2q37.3 and 2qter, but available data from patients with constitutional deletions suggest that these probably do not confer a high risk for Wilms' tumor. Conclusions: Our data support the presence of a tumor suppressor gene at 2q37.1 and suggest that, in individuals with constitutional 2q37 deletions, any increased risk for developing Wilms' tumor likely correlates with deletions encompassing 2q37.1. (Clin Cancer Res 2009;15(19):5985–92)
Intestinal Epithelial Cells Synthesize Glucocorticoids and Regulate T Cell Activation
Authors: Igor Cima, Nadia Corazza, Bernhard Dick, Andrea Fuhrer, Simon Herren, Sabine Jakob, Erick Ayuni, Christoph Mueller, Thomas Brunner
Journal: The Journal of Experimental Medicine (2004)

Glucocorticoids (GCs) are important steroid hormones with widespread activities in metabolism, development, and immune regulation. The adrenal glands are the major source of GCs and release these hormones in response to psychological and immunological stress. However, there is increasing evidence that GCs may also be synthesized by nonadrenal tissues. Here, we report that the intestinal mucosa expresses steroidogenic enzymes and releases the GC corticosterone in response to T cell activation. T cell activation causes an increase in the intestinal expression of the steroidogenic enzymes required for GC synthesis. In situ hybridization analysis revealed that these enzymes are confined to the crypt region of the intestinal epithelial layer. Surprisingly, in situ–produced GCs exhibit both an inhibitory and a costimulatory role on intestinal T cell activation. In the absence of intestinal GCs in vivo, activation by anti-CD3 injection resulted in reduced CD69 expression and interferon-γ production by intestinal T cells, whereas activation by viral infection led to increased T cell activation. We conclude that the intestinal mucosa is a potent source of immunoregulatory GCs.
Chromogranin A Polymorphisms Are Associated With Hypertensive Renal Disease
Authors: Rany M. Salem, Peter E. Cadman, Yuqing Chen, Fangwen Rao, Gen Wen, Bruce A. Hamilton, Brinda K. Rana, Douglas W. Smith, Mats Stridsberg, Harry J. Ward, Manjula Mahata, Sushil K. Mahata, Donald W. Bowden, Pamela J. Hicks, Barry I. Freedman, Nicholas J. Schork, Daniel T. O'Connor
Journal: Journal of the American Society of Nephrology (2008)

Chromogranin A is released together with epinephrine and norepinephrine from catecholaminergic cells. Specific endopeptidases cleave chromogranin A into biologically active peptide fragments, including catestatin, which inhibits catecholamine release. Previous studies have suggested that a deficit in this sympathetic "braking" system might be an early event in the pathogenesis of human hypertension. Whether chromogranin A (CHGA) polymorphisms predict end-organ complications of hypertension, such as end-stage renal disease, is unknown. Among blacks, we studied common genetic variants spanning the CHGA locus in 2 independent case-control studies of hypertensive ESRD. Two haplotypes were significantly more frequent among subjects with hypertensive ESRD: 1) in the promoter (5') region, G-462A-->T-415C-->C-89A, haplotype ATC (adjusted odds ratio = 2.65; P = 0.037), and 2) at the 3'-end, C11825T (3'-UTR, C+87T)-->G12602C, haplotype TC (adjusted odds ratio = 2.73, P = 0.0196). Circulating levels of catestatin were lower among those with hypertensive ESRD than controls, an unexpected finding given that peptide levels are usually elevated in ESRD because of reduced renal elimination. We found that the 3'-UTR + 87T variant decreased reporter gene expression, providing a possible mechanistic explanation for diminished catestatin. In summary, common variants in chromogranin A associate with the risk of hypertensive ESRD in blacks.
Cardiac Arrhythmias in Patients With Acute Cerebrovascular Accidents
Authors: J. Ronald Mikolich
Journal: JAMA (1981)

To assess the incidence and severity of cardiac arrhythmias in the acute period following a cerebrovascular accident (CVA), 30 patients with a CVA in a stroke intensive care unit had 24 hours of dynamic ECG recordings. Twenty consecutive patients electively admitted for cataract surgery served as a control group and also had recordings. Fifteen (50%) of 30 CVA patients had serious ventricular ectopy, compared with only three (15%) of the 20 control subjects. Among the patients with CVA, two had ventricular tachycardia, two had complete atrioventricular block, and two had asystole, all occurring in CVAs involving the anterior circulation. None of the control subjects experienced these arrhythmias. Cardiac arrhythmias are common in patients with acute CVAs, especially those involving the anterior circulation. Dynamic ECG recordings may detect such arrhythmias and provide data for therapeutic consideration.
Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice
Authors: Taku Okazaki, Yoshimasa Tanaka, Ryosuke Nishio, Tamotsu Mitsuiye, Akira Mizoguchi, Jian Wang, Masayoshi Ishida, Hiroshi Hiai, Akira Matsumori, Nagahiro Minato, Tasuku Honjo
Journal: Nature Medicine (2003)
Antibody Immunity to the p53 Oncogenic Protein Is a Prognostic Indicator in Ovarian Cancer
Authors: Vivian Goodell, Lupe G. Salazar, Nicole Urban, Charles W. Drescher, Heidi Gray, Ron E. Swensen, Martin W. McIntosh, Mary L. Disis
Journal: Journal of Clinical Oncology (2006)

Presence of intratumoral T-cell infiltration has been linked to improved survival in ovarian cancer patients. We questioned whether antibody immunity specific for ovarian cancer tumor antigens would predict disease outcome. We evaluated humoral immune responses against ovarian cancer antigens p53, HER-2/neu, and topoisomerase IIalpha.Serum was collected from 104 women (median age, 59 years; range, 34 to 89 years) at the time of their initial definitive surgery for ovarian cancer. Serum was analyzed by enzyme-linked immunosorbent assay for antibodies to p53, HER-2/neu, and topoisomerase IIalpha proteins. Antibody immunity to tetanus toxoid was assessed as a control. The incidence of humoral immunity at the time of diagnosis to any of these three antigens was tabulated. For patients with advanced-stage disease (III/IV), correlation was made between the presence of tumor-specific immunity at the time of diagnosis and overall survival. Patients were followed for a median of 1.8 years.Multivariate analysis showed the presence of p53 antibodies to be an independent variable for prediction of overall survival in advanced-stage patients. Overall survival was significantly higher for patients with antibodies to p53 when compared with patients without p53 antibodies (P = .01). The median survival for p53 antibody-positive patients was 51 months (95% CI, 23.5 to 60.5 months) compared with 24 months (95% CI, 19.4 to 28.6 months) for patients without antibodies to p53.Data presented here demonstrate that advanced stage ovarian cancer patients can have detectable tumor-specific antibody immunity and that immunity to p53 may predict improved overall survival in patients with advanced-stage disease.
Time course of right ventricular stroke volume and output in obstructive sleep apneas.
Authors: M R Bonsignore, O Marrone, S Romano, D Pieri
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Because the behavior of right ventricular stroke volume (RVSV) in the obstructive sleep apnea syndrome (OSAS) is undefined, we studied the time course of RVSV by right heart catheterization during sleep in five OSAS patients. In 55 obstructive apneas, heart rate (HR) and RVSV were calculated beat-by-beat. RVSV was estimated by integrating the area under the pulmonary arterial (PA) blood velocity signal obtained by a velocity sensor-/micromanometer-tipped catheter. Compared with preapnea, mean RVSV did not change significantly during apnea, but decreased by 15% during postapnea. Analysis of RVSV in the respiratory cycle showed that postapneic RVSV was mostly reduced at maximal inspiration, suggesting a role of increased lung volume in decreasing RVSV. As for HR, it decreased significantly during apnea in four out of five patients. In all patients, HR returned to preapneic values during postapnea. Therefore, right ventricular output decreased slightly in most patients during late apnea because of decreased HR, whereas it decreased in all patients during postapnea because of decreased RVSV. These results, together with the known finding that PA pressure increases towards the end of apneas and remains elevated in the immediate postapnea, suggest that the most relevant changes in the pulmonary circulation occur at the resumption of ventilation, not during the apneic phase.
Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms
Authors: Luca Malcovati, Elli Papaemmanuil, David T. Bowen, Jacqueline Boultwood, Matteo G. Della Porta, Cristiana Pascutto, Erica Travaglino, Michael J. Groves, Anna L. Godfrey, Ilaria Ambaglio, Anna Gallì, Matteo C. Da Vià, Simona Conte, Sudhir Tauro, Norene Keenan, Ann Hyslop, Jonathan Hinton, Laura J. Mudie, James S. Wainscoat, P. Andrew Futreal, Michael R. Stratton, Peter J. Campbell, Eva Hellström-Lindberg, Mario Cazzola
Journal: Blood (2011)