tbuckley/cabot-search huggingface dataset:
The burden of stomach cancer in indigenous populations: a systematic review and global assessment
Authors: Melina Arnold, Suzanne P Moore, Sven Hassler, Lis Ellison-Loschmann, David Forman, Freddie Bray
Journal: Gut (2013)

<h3>Objective</h3> Stomach cancer is a leading cause of cancer death, especially in developing countries. Incidence has been associated with poverty and is also reported to disproportionately affect indigenous peoples, many of whom live in poor socioeconomic circumstances and experience lower standards of health. In this comprehensive assessment, we explore the burden of stomach cancer among indigenous peoples globally. <h3>Design</h3> The literature was searched systematically for studies on stomach cancer incidence, mortality and survival in indigenous populations, including Indigenous Australians, Maori in New Zealand, indigenous peoples from the circumpolar region, native Americans and Alaska natives in the USA, and the Mapuche peoples in Chile. Data from the New Zealand Health Information Service and the Surveillance Epidemiology and End Results (SEER) Program were used to estimate trends in incidence. <h3>Results</h3> Elevated rates of stomach cancer incidence and mortality were found in almost all indigenous peoples relative to corresponding non-indigenous populations in the same regions or countries. This was particularly evident among Inuit residing in the circumpolar region (standardised incidence ratios (SIR) males: 3.9, females: 3.6) and in Maori (SIR males: 2.2, females: 3.2). Increasing trends in incidence were found for some groups. <h3>Conclusions</h3> We found a higher burden of stomach cancer in indigenous populations globally, and rising incidence in some indigenous groups, in stark contrast to the decreasing global trends. This is of major public health concern requiring close surveillance and further research of potential risk factors. Given evidence that improving nutrition and housing sanitation, and <i>Helicobacter pylori</i> eradication programmes could reduce stomach cancer rates, policies which address these initiatives could reduce inequalities in stomach cancer burden for indigenous peoples.
Genome-Wide Epigenetic Regulation of miRNAs in Cancer
Authors: Constance Baer, Rainer Claus, Christoph Plass
Journal: Cancer Research (2013)

Abstract Aberrant microRNA (miRNA) expression contributes to tumorigenesis and cancer progression. Although the number of reported deregulated miRNAs in various cancer types is growing fast, the underlying mechanisms of aberrant miRNA regulation are still poorly studied. Epigenetic alterations including aberrant DNA methylation deregulate miRNA expression, which was first shown by reexpression of miRNAs upon pharmacologic DNA demethylation. However, studying the influence of DNA methylation on miRNA transcription on a genome-wide level was hampered by poor miRNA promoter annotation. Putative miRNA promoters were identified on a genome-wide level by using common promoter surrogate markers (e.g., histone modifications) and were later validated as such in different tumor entities. Integrating promoter datasets and global DNA methylation analysis revealed an extensive influence of DNA hyper- as well as hypomethylation on miRNA regulation. In this review, we summarize the current knowledge of the field and discuss recent efforts to map miRNA promoter sequences and to determine the contribution of epigenetic mechanisms to the regulation of miRNA expression. We discuss examples of tumor suppressive and oncogenic miRNAs such as the miR-34 and miR-21 family, respectively, which highlight the complexity and consequences of epigenetic miRNA deregulation. Cancer Res; 73(2); 473–7. ©2012 AACR.
AUTO- AND ISOTRANSPLANTATION, IN DOGS, OF THE PARATHYROID GLANDULES
Authors: W. S. Halsted
Journal: The Journal of Experimental Medicine (1909)

1. The autotransplantation of parathyroid glandules into the thyroid gland and behind the musculus rectus abdominis has been successful in sixty-one per cent. of the cases in which a deficiency greater than one-half has been created. 2. In no instance has the autotransplantation succeeded without the creation of such deficiency. 3. Isotransplantation has been uniformly unsuccessful. 4. Parathyroid tissue transplanted in excess of what is urgently required by the organism has not lived. 5. One parathyroid autograft may suffice to maintain the animal in good health and spirits for many months and possibly for years. 6. Excised or deprived of their blood supply in the course of operation upon the human subject, parathyroid glands should, in the present state of our knowledge, be grafted, and probably into the thyroid gland. 7. Complete excision of the thyroid lobes in dogs may be well borne for a year or more. The myxoedema which usually has manifested itself within a few weeks has not increased after the first few months. May it subsequently diminish with the hypertrophy of accessory thyroids? 8. Parathyroid tissue is essential to the life of dogs, as has been conclusively proved by the result of excision of the sole, sustaining graft. There may be found, perhaps, in our experiments, explanation of the fact observed by others (Enderlen, Payr) that, when transplanted, thyroid preserves its integrity less well than parathyroid tissue. In the instances recorded the amount of thyroid gland excised may have been insufficient to make possible the fullest success of the transplantation; and particularly so when we consider the extent of the hypertrophy of which the thyroid gland seems capable.
Physiology of IgD. VI. Transfer of the immunoaugmenting effect of IgD with T delta-containing helper cell populations.
Authors: R F Coico, B Xue, D Wallace, G W Siskind, G J Thorbecke
Journal: The Journal of Experimental Medicine (1985)

We show that the IgD-induced augmentation of the immune response to trinitrophenylated keyhole limpet hemocyanin can be transferred to syngeneic mice with spleen cells from IgD-injected donors. The augmenting activity is present in the Lyt-1+2-, L3T4+ T cell population and is absent from B cells. The ability of transferred T cells to augment the immune response correlates with the presence of a high frequency of Lyt-1+2- T cells that form rosettes with IgD-coated sheep erythrocytes (T delta cells). Such rosette-forming cells can also be induced by incubation of spleen cells from normal donors in IgD-coated petri dishes. Injection of normal spleen cells exposed to IgD-coated petri dishes together with antigen also augments the immune response of recipients. The existence of a regulatory circuit based upon interactions between T delta cells, antigen, B cell surface IgD, and serum IgD, is proposed.
Role of renin isoelectric heterogeneity in renal storage and secretion of renin.
Authors: J A Opsahl, P A Abraham, J G Shake, S A Katz
Journal: Journal of the American Society of Nephrology (1993)

Renin is a glycoprotein that is heterogeneous with respect to carbohydrate content and net charge. In an attempt to clarify the role of renin isoelectric heterogeneity in renal renin storage and secretion, the isoelectric profile of renal renin, secreted renin, and circulating renin were directly assessed and compared under basal and stimulated conditions by the use of an in vivo blood perfused rabbit kidney preparation. Under basal conditions, the kidney preferentially stored and secreted the relatively basic isoelectric forms of renin. Acute stimulation of renin secretion (reduced renal perfusion pressure and angiotensin-converting enzyme inhibition) significantly increased the secretion of the relatively basic isoelectric forms but had very little effect on the secretion of the relatively acidic renin forms. Circulating renin was composed primarily of relatively basic forms, which increased disproportionately after stimulation of renin secretion. These findings suggest that the isoelectric heterogeneity of renin is important in the cellular processing of renin and can be explained by a two-pool model in which the relatively acidic isoelectric forms of renin are constitutively secreted (and not stored) and the relatively basic isoelectric forms represent a regulated pathway in which they are stored and rapidly released in response to acute secretory stimuli. Preferential hepatic extraction of the more basic isoelectric forms has previously been described. Data from this study suggest that the disproportionate increase in circulating basic forms of renin observed after acute stimulation reflects the net effect of preferential renal the more basic renin isoelectric forms. The disproportionate increase in relatively basic circulating renin forms after acute secretory stimulation results in an overall circulating renin activity with a shorter half-life.
Quantifying Ascertainment Bias and Species-Specific Length Differences in Human and Chimpanzee Microsatellites Using Genome Sequences
Authors: Edward J. Vowles, William Amos
Journal: Molecular Biology and Evolution (2005)

Surveys of variability of homologous microsatellite loci among species reveal an ascertainment bias for microsatellite length where microsatellite loci isolated in one species tend to be longer than homologous loci in related species. Here, we take advantage of the availability of aligned human and chimpanzee genome sequences to compare length difference of homologous microsatellites for loci identified in humans to length difference for loci identified in chimpanzees. We are able to quantify ascertainment bias for a range of motifs and microsatellite lengths. Because ascertainment bias should not exist if a microsatellite selected in one species is as likely to be longer as it is to be shorter than its homologue, we propose that the nature of ascertainment bias can provide evidence for understanding how microsatellites evolve. We show that bias is greater for longer microsatellites but also that many long microsatellites have short homologues. These results are consistent with the notion that growth of long microsatellites is constrained by an upper length boundary that, when reached, sometimes results in large deletions. By evaluating ascertainment bias separately for interrupted and uninterrupted repeats we also show that long microsatellites tend to become interrupted, thereby contributing a second component of ascertainment bias. Having accounted for ascertainment bias, in agreement with results published elsewhere, we find that microsatellites in humans are longer on average than those in chimpanzees. This length difference is similar among repeat motifs but surprisingly comprises two roughly equal components, one associated with the repeats themselves and one with the flanking sequences. The differences we find can only be explained if microsatellites are both evolving directionally under a biased mutation process and are doing so at different rates in different closely related species.
Protection of Human Lung Cells against Hyperoxia Using the DNA Base Excision Repair Genes hOgg1 and Fpg
Authors: Min Wu, Ying-Hui He, Masayoshi Kobune, Yi Xu, Mark R. Kelley, William J. Martin
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Hyperoxia causes pulmonary toxicity in part by injuring alveolar epithelial cells. Previous studies have shown that toxic oxygen-derived species damage DNA and this damage is recognized and repaired by either human enzyme 8-oxoguanine DNA glycosylase (hOgg1) or Escherichia coli enzyme formamidopyrimidine DNA glycosylase (Fpg). To determine whether these DNA repair proteins can reduce O2-mediated DNA damage in lung cells, A549 lung epithelial cells were transduced with either hOgg1 or Fpg using a retroviral vector containing enhanced green fluorescent protein. Expression of each gene in the transduced cells was confirmed by fluorescent microscopy, Northern blotting, Western blotting, and an enzymatic oligonucleotide cleavage assay. A549 cells expressing either hOgg1 or Fpg were protected from hyperoxia as evidenced by a decrease in DNA damage and a corresponding increase in cell survival. Further, we determined that overexpression of hOgg1 or Fpg partially mitigated the toxic effects of hydrogen peroxide in lung cells. Our data suggest that increased expression of DNA base excision repair genes might represent a new approach for protecting critical lung cells from the toxic effects of hyperoxia.
Effects of Continuous Positive Airway Pressure on Cardiac Volumes in Patients with Ischemic and Dilated Cardiomyopathy
Authors: SANGEETA MEHTA, PETER P. LIU, FABIA S. FITZGERALD, YASMIN K. ALLIDINA, T. DOUGLAS BRADLEY
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The effects of continuous positive airway pressure (CPAP) on left (LV) and right ventricular (RV) volumes in patients with congestive heart failure (CHF) have not been studied. We hypothesized that CPAP would cause greater reductions in cardiac volumes in CHF patients with idiopathic dilated cardiomyopathy (IDC) than in those with ischemic cardiomyopathy (IsC), because their ventricles are more compliant. The effects of a 30-min CPAP application at 10 cm H2O on RV and LV end-diastolic (EDV) and end-systolic volumes (ESV), determined by radionuclide angiography, were therefore tested in 22 patients with CHF due to IsC (n = 13) or IDC (n = 9). CPAP-induced reductions in LVEDV, LVESV, RVEDV, and RVESV were significantly greater (p < 0.05) in the IDC than in the IsC group. Whereas in the IsC group CPAP caused no significant changes in LV or RV volumes, in the IDC group it induced significant reductions in RVEDV (527 ± 77 ml to 354 ± 50 ml, p = 0.03) and RVESV (400 ± 78 ml to 272 ± 54 ml, p = 0.04) that were greater than any reductions in LVEDV and LVESV. We conclude that CPAP causes greater short-term reductions in RV and LV volumes in CHF patients with IDC than in those with IsC, and that among patients with IDC, CPAP causes greater reductions in RV than in LV volumes. Mehta S, Liu PP, Fitzgerald FS, Allidina YK, Bradley TD. Effects of continuous positive airway pressure on cardiac volumes in patients with ischemic and dilated cardiomyopathy.
Sphingosine 1-Phosphate Reduces Vascular Leak in Murine and Canine Models of Acute Lung Injury
Authors: Bryan J. McVerry, Xinqi Peng, Paul M. Hassoun, Saad Sammani, Brett A. Simon, Joe G. N. Garcia
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Excessive mechanical stress is a key component of ventilator-associated lung injury, resulting in profound vascular leak and an intense inflammatory response. To extend our in vitro observations concerning the barrier-protective effects of the lipid growth factor sphingosine 1-phosphate (Sph 1-P), we assessed the ability of Sph 1-P to prevent regional pulmonary edema accumulation in clinically relevant rodent and canine models of acute lung injury induced by combined intrabronchial endotoxin administration and high tidal volume mechanical ventilation. Intravenously delivered Sph 1-P significantly attenuated both alveolar and vascular barrier dysfunction while significantly reducing shunt formation associated with lung injury. Whole lung computed tomographic image analysis demonstrated the capability of Sph 1-P to abrogate significantly the accumulation of extravascular lung water evoked by 6-hour exposure to endotoxin. Axial density profiles and vertical density gradients localized the Sph 1-P response to transitional zones between aerated and consolidated lung regions. Together, these results indicate that Sph 1-P represents a novel therapeutic intervention for the prevention of pulmonary edema related to inflammatory injury and increased vascular permeability.
Role of interferon alpha in promoting T helper cell type 1 responses in the small intestine in coeliac disease
Authors: G Monteleone
Journal: Gut (2001)

Coeliac disease (CD) is caused by a CD4 T helper cell type 1 (Th1) response in the small intestinal mucosa to dietary gluten. As the major Th1 inducing cytokine, interleukin 12, is undetectable in CD gut mucosa, the mechanism by which Th1 effector cells are generated remains unknown. Interferon (IFN) alpha, a cytokine capable of promoting IFN-gamma synthesis, has been implicated in the development of Th1 mediated immune diseases. Here we report a case of CD-like enteropathy in a patient receiving IFN-alpha for chronic myeloid leukaemia. Morphological assessment of duodenal biopsies taken from the patient showed total villous atrophy, crypt cell hyperplasia, and a high number of CD3+ intraepithelial lymphocytes. Both antigliadin antibodies and antiendomysial antibodies were positive. RNA analysis revealed pronounced expression of IFN-gamma. Withdrawal of gluten from the diet resulted in a patchy improvement in intestinal morphology, normalisation of laboratory parameters, and resolution of clinical symptoms. By western blot analysis, IFN-alpha protein was seen in the duodenal mucosa from untreated CD patients but not in controls. This was associated with marked expression of IFN-gamma protein in CD mucosa. Collectively, these results suggest a role for IFN-alpha in promoting Th1 responses to gluten.
Association between maternal sleep practices and risk of late stillbirth: a case-control study
Authors: T. Stacey, J. M. D. Thompson, E. A. Mitchell, A. J. Ekeroma, J. M. Zuccollo, L. M. E. McCowan
Journal: BMJ (2011)

To determine whether snoring, sleep position, and other sleep practices in pregnant women are associated with risk of late stillbirth.Prospective population based case-control study.Auckland, New Zealand155 women with a singleton late stillbirth (≥ 28 weeks' gestation) without congenital abnormality born between July 2006 and June 2009 and booked to deliver in Auckland.310 women with single ongoing pregnancies and gestation matched to that at which the stillbirth occurred. Multivariable logistic regression adjusted for known confounding factors.Maternal snoring, daytime sleepiness (measured with the Epworth sleepiness scale), and sleep position at the time of going to sleep and on waking (left side, right side, back, and other).The prevalence of late stillbirth in this study was 3.09/1000 births. No relation was found between snoring or daytime sleepiness and risk of late stillbirth. However, women who slept on their back or on their right side on the previous night (before stillbirth or interview) were more likely to experience a late stillbirth compared with women who slept on their left side (adjusted odds ratio for back sleeping 2.54 (95% CI 1.04 to 6.18), and for right side sleeping 1.74 (0.98 to 3.01)). The absolute risk of late stillbirth for women who went to sleep on their left was 1.96/1000 and was 3.93/1000 for women who did not go to sleep on their left. Women who got up to go to the toilet once or less on the last night were more likely to experience a late stillbirth compared with women who got up more frequently (adjusted odds ratio 2.28 (1.40 to 3.71)). Women who regularly slept during the day in the previous month were also more likely to experience a late stillbirth than those who did not (2.04 (1.26 to 3.27)).This is the first study to report maternal sleep related practices as risk factors for stillbirth, and these findings require urgent confirmation in further studies.
Janus Reveals Another Face: The Biologic Rationale for Targeting Janus Kinase 2 in Lymphoma
Authors: Ann Mullally, Benjamin L. Ebert
Journal: Journal of Clinical Oncology (2012)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2012.44.0347 Journal of Clinical Oncology - published online before print September 10, 2012 PMID: 22965959 Janus Reveals Another Face: The Biologic Rationale for Targeting Janus Kinase 2 in Lymphoma Ann MullallyxAnn MullallySearch for articles by this author , Benjamin L. EbertxBenjamin L. EbertSearch for articles by this author Show More Brigham and Women's Hospital, Harvard Medical School, Boston, MA https://doi.org/10.1200/JCO.2012.44.0347 First Page Full Text PDF Figures and Tables © 2012 by American Society of Clinical Oncology
ISOTOPIC LABELLING OF CUTANEOUS STRUCTURES* A PRELIMINARY COMPARISON OF LOCAL IN VIVO AND IN VITRO TECHNIQUES APPLIED TO HEALTHY AND PATHOLOGICAL HUMAN SKIN *
Authors: J. M. LACHAPELLE
Journal: British Journal of Dermatology (1969)

SUMMARY. The methods for isotopic labelling of cutaneous structures in man are described, and in vivo and in vitro techniques are discussed. A preliminary report is presented of tritiated thymidine labelling of normal and pathological human skin.
Taxol Resistance in Breast Cancer Cells Is Mediated by the Hippo Pathway Component TAZ and Its Downstream Transcriptional Targets<i>Cyr61</i>and<i>CTGF</i>
Authors: Dulcie Lai, King Ching Ho, Yawei Hao, Xiaolong Yang
Journal: Cancer Research (2011)

Taxol (paclitaxel) resistance represents a major challenge in breast cancer treatment. The TAZ (transcriptional co-activator with PDZ-binding motif) oncogene is a major component of the novel Hippo-LATS signaling pathway and a transcriptional coactivator that interacts with and activates multiple transcription factors to regulate various biological processes. Here, we report that elevated levels of TAZ found in human breast cancer cells are responsible for their resistance to Taxol. DNA microarray analysis identified the oncogenes Cyr61 and CTGF as downstream transcriptional targets of TAZ. Short hairpin RNA-mediated knockdown of both Cyr61 and CTGF reversed TAZ-induced Taxol resistance in breast cancer cells. Interaction of TAZ with the TEAD family of transcription factors was essential for TAZ to activate the Cyr61/CTGF promoters and to induce Taxol resistance. Our findings define the TAZ-TEAD-Cyr61/CTGF signaling pathway as an important modifier of the Taxol response in breast cancer cells, as well as highlighting it as a novel therapeutic target to treat drug-resistant breast cancers that arise commonly at advanced stages of disease.
Ubiquitous Elevation of Matrix Metalloproteinase-2 Expression in the Vasculature of Patients With Abdominal Aneurysms
Authors: Stephen Goodall, Mat Crowther, David M. Hemingway, Peter R. Bell, Matt M. Thompson
Journal: Circulation (2001)

Background Patients with abdominal aortic aneurysms (AAAs) exhibit arterial dilation and altered matrix composition throughout the vasculature. Matrix metalloproteinase-2 (MMP-2) is the dominant elastase in small AAAs, and overexpression of MMP-2 in vascular smooth muscle cells (SMCs) may be a primary etiological event in aneurysm genesis. The aim of this study was to investigate MMP-2 production in vascular tissue remote from the abdominal aorta. Methods and Results Inferior mesenteric vein (IMV) was harvested from patients undergoing aneurysm repair (n=21) or colectomy for diverticular disease (n=13, control). Matrix composition of the vessels was determined by stereological techniques. MMPs were extracted from tissue homogenates and quantified by gelatin zymography and ELISA. MMP-2, membrane type-1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinases type 2 (TIMP-2) expression were determined by Northern analysis. SMCs were isolated from IMV, and the production and expression of MMP-2 and TIMP-2 in the SMC lines were quantified. Tissue homogenates and isolated inferior mesenteric SMCs from patients with aneurysms demonstrated significantly elevated MMP-2 levels, with no difference in TIMP-2 or MT1-MMP. These differences were a result of increased MMP-2 expression. Histological examination revealed fragmentation of elastin fibers within venous tissue obtained from patients with AAA and a significant depletion of the elastin within the media. In situ zymography localized elastolysis to medial SMCs. Conclusions Patients with AAA have elevated MMP-2 levels in the vasculature remote from the aorta. This finding is due to increased MMP-2 expression from SMCs, a characteristic maintained in tissue culture. These data support both the systemic nature of aneurysmal disease and a primary role of MMP-2 in aneurysm formation.