tbuckley/cabot-search huggingface dataset:
EXPERIMENTAL STUDIES ON DIABETES
Authors: Frederick M. Allen
Journal: The Journal of Experimental Medicine (1920)

1. The injurious effects of excessive carbohydrate diet are demon strable in partially depancreatized dogs, in the same manner as in human patients. With severe diabetes there is rapid progress of emaciation and weakness and early death. 2. With milder diabetes, there is frequently a transitional state following operation, when the fate depends on the diet. If the tolerance is spared for a time, recovery sometimes occurs to such extent that diabetes cannot be produced by any kind or quantity of feeding, but only by removal of a small additional fragment of pancreatic tissue. The proper degree of carbohydrate overfeeding is important in this early period for producing the most useful type of diabetic animals; namely, those having good digestion and general health combined with a permanent lowering of assimilative power, like the condition of human patients. 3. In the early stage, glucose is more powerful than starch in producing diabetes, and animals which are progressing toward complete recovery on starch diet can be sent into hopeless diabetes by admix ture of glucose. The difference seems to be merely of the rate of absorption, and indicates that a rapid flood of carbohydrate is more injurious to the pancreatic function than a slow absorption. When ever permanent diabetes is present, so that complete recovery is impossible, starch brings on glycosuria more slowly than sugar, but just as surely. The difference in time in different cases amounts to days, weeks, or months. The clinical lesson from such experiments is that even if a patient becomes free from glycosuria on withdrawal of sugar only, nevertheless other foods should also be limited. 4. No significant differences were observed between the assimilation of different starches, or any extreme lowering of the carbohydrate tolerance by proteins, such as alleged by certain writers in connection with the "oatmeal cure." 5. Repair of traumatic inflammation and hypertrophy of the pancreas remnant have been mentioned incidentally as the basis of the early tendency to recovery, and also hydropic degeneration of Lang erhans islands as an accompaniment of the lowering of tolerance by excessive diet. These are believed to have their parallels in human cases, and are to be described more fully hereafter.
Parvovirus arthropathy masquerading as the arthritis of Behcet's disease
Authors: H J LONGHURST
Journal: Annals of the Rheumatic Diseases (2001)

Parvovirus B19 is common, with 50–75% of UK adults having evidence of previous infection. Complications, such as arthritis, occur in a small minority. We report a case of parvovirus associated arthritis causing diagnostic confusion in a patient known to have Behcet's disease.

### CASE REPORT

A 34 year old white woman presented with a small joint polyarthritis, low back discomfort, severe heel pain, and patchy sensory disturbance, after a febrile illness with a rash. She had had Behcet's disease since the age of 3 years, manifest by arthralgia, mouth, nasal and genital ulcers, conjunctivitis, facial swelling, and livedo reticularis. Before her presentation, her Behcet's disease had been relatively well …
A phase II study of palonosetron combined with dexamethasone to prevent nausea and vomiting induced by highly emetogenic chemotherapy
Authors: M. Maemondo, N. Masuda, I. Sekine, K. Kubota, Y. Segawa, M. Shibuya, F. Imamura, N. Katakami, T. Hida, S. Takeo
Journal: Annals of Oncology (2009)
Genetic Evidence for Unequal Effective Population Sizes of Human Females and Males
Authors: J. A. Wilder
Journal: Molecular Biology and Evolution (2004)

The time to the most recent common ancestor (TMRCA) of the human mitochondria (mtDNA) is estimated to be older than that of the nonrecombining portion of the Y chromosome (NRY). Surveys of variation in globally distributed humans typically result in mtDNA TMRCA values just under 200 thousand years ago (kya), whereas those for the NRY range between 46 and 110 kya. A favored hypothesis for this finding is that natural selection has acted on the NRY, leading to a recent selective sweep. An alternate hypothesis is that sex-biased demographic processes are responsible. Here, we re-examine the disparity between NRY and mtDNA TMRCAs using data collected from individual human populations—a sampling strategy that minimizes the confounding influence of population subdivision in global data sets. We survey variation at 782 bp of the mitochondrial cytochrome c oxidase subunit 3 gene as well as at 26.5 kb of noncoding DNA from the NRY in a sample of 25 Khoisan, 24 Mongolians, and 24 Papua New Guineans. Data from both loci in all populations are best described by a model of constant population size, with the exception of Mongolian mtDNA, which appears to be experiencing rapid population growth. Taking these demographic models into account, we estimate the TMRCAs for each locus in each population. A pattern that is remarkably consistent across all three populations is an approximately twofold deeper coalescence for mtDNA than for the NRY. The oldest TMRCAs are observed for the Khoisan (73.6 kya for the NRY and 176.5 kya for mtDNA), whereas those in the non-African populations are consistently lower (averaging 47.7 kya for the NRY and 92.8 kya for mtDNA). Our data do not suggest that differential natural selection is the cause of this difference in TMRCAs. Rather, these results are most consistent with a higher female effective population size.
Placebo-Controlled Phase III Trial of Immunologic Therapy with Sipuleucel-T (APC8015) in Patients with Metastatic, Asymptomatic Hormone Refractory Prostate Cancer
Authors: Eric J. Small, Paul F. Schellhammer, Celestia S. Higano, Charles H. Redfern, John J. Nemunaitis, Frank H. Valone, Suleman S. Verjee, Lori A. Jones, Robert M. Hershberg
Journal: Journal of Clinical Oncology (2006)

Sipuleucel-T (APC8015) is an investigational immunotherapy product designed to stimulate T-cell immunity against prostatic acid phosphatase. A phase III study was undertaken to evaluate the safety and efficacy of sipuleucel-T in a placebo-controlled study.A total of 127 patients with asymptomatic metastatic hormone refractory prostate cancer (HRPC) were randomly assigned in a 2:1 ratio to receive three infusions of sipuleucel-T (n = 82) or placebo (n = 45) every 2 weeks. On disease progression, placebo patients could receive APC8015F, a product made with frozen leukapheresis cells.Of the 127 patients, 115 patients had progressive disease at the time of data analysis, and all patients were followed for survival for 36 months. The median for time to disease progression (TTP) for sipuleucel-T was 11.7 weeks compared with 10.0 weeks for placebo (P = .052, log-rank; hazard ratio [HR], 1.45; 95%CI, 0.99 to 2.11). Median survival was 25.9 months for sipuleucel-T and 21.4 months for placebo (P = .01, log-rank; HR, 1.70; 95%CI, 1.13 to 2.56). Treatment remained a strong independent predictor of overall survival after adjusting for prognostic factors using a Cox multivariable regression model (P = .002, Wald test; HR, 2.12; 95%CI, 1.31 to 3.44). The median ratio of T-cell stimulation at 8 weeks to pretreatment was eight-fold higher in sipuleucel-T-treated patients (16.9 v 1.99; P < .001). Sipuleucel-T therapy was well tolerated.While the improvement in the primary end point TTP did not achieve statistical significance, this study suggests that sipuleucel-T may provide a survival advantage to asymptomatic HRPC patients. Supportive studies are underway.
Altered Myocardial Microvascular 3D Architecture in Experimental Hypercholesterolemia
Authors: Martin Rodriguez-Porcel, Amir Lerman, Erik L. Ritman, Stephanie H. Wilson, Patricia J. M. Best, Lilach O. Lerman
Journal: Circulation (2000)

Background —Experimental hypercholesterolemia (HC) impairs intramyocardial microvascular function. However, whether this is associated with alterations in microvascular architecture remained unknown. Using a novel 3D micro-CT scanner, we tested the hypothesis that HC is associated with an alteration in the microvascular architecture. Methods and Results —Pigs were euthanized after 12 weeks of either normal (n=6) or 2% HC (n=6) diet. The hearts were excised and the coronary arteries injected with a radiopaque contrast material. Myocardial samples were scanned with micro-CT, and 3D images were reconstructed with 21-μm cubic voxels. The myocardium was tomographically subdivided into subepicardium and subendocardium, and microvessels (&lt;500 μm in diameter) were counted in situ within each region. In the subendocardium of HC pigs, the intramyocardial density of microvessels was significantly higher than in normal animals (1221.4±199.7 versus 758.3±90.8 vessels/cm 3 , P &lt;0.05) because of an increase in the number of microvessels &lt;200 μm in diameter (1214.4±199.7 versus 746.6±101.5 vessels/cm 3 , P &lt;0.05). The subepicardial vascular density was similar in both groups. Conclusions —HC has differential effects on the spatial density of the subendocardial microvasculature that may play a role in regulation and/or spatial distribution of myocardial blood flow. This study also demonstrates the feasibility of studying myocardial microvascular architecture with micro-CT in pathophysiological states.
<i>S100P</i> Is an Early Developmental Marker of Pancreatic Carcinogenesis
Authors: Kenoki Ohuchida, Kazuhiro Mizumoto, Takuya Egami, Hiroshi Yamaguchi, Kei Fujii, Hiroyuki Konomi, Eishi Nagai, Koji Yamaguchi, Masazumi Tsuneyoshi, Masao Tanaka
Journal: Clinical Cancer Research (2006)

Our goal was to clarify the involvement and clinical significance of S100P in pancreatic carcinogenesis.We examined S100P expression in 45 bulk pancreatic tissues; in microdissected cells, including invasive ductal carcinoma (IDC) cells (20 sections), pancreatic intraepithelial neoplasia (PanIN) cells (12 sections), intraductal papillary mucinous neoplasm (IPMN) cells (19 sections), and normal epithelial cells (11 sections); and in pancreatic juice samples from 99 patients with pancreatic diseases (32 cancer, 35 IPMN, and 32 chronic pancreatitis samples). We used quantitative real-time reverse transcription-PCR with gene-specific priming to measure S100P in these various types of samples.In bulk tissue analyses, pancreatic cancer and IPMN expressed significantly higher levels of S100P than did nonneoplastic pancreas (P<0.017 and P=0.0013, respectively). Microdissection analyses revealed that IPMN expressed significantly higher levels of S100P than did IDC (P<0.0001) and PanIN (P=0.0031), although S100P expression did not differ between IDC and PanIN (P=0.077). In pancreatic juice analyses, cancer and IPMN juice expressed significantly higher levels of S100P than did pancreatitis juice (both P<0.0001). Receiver operating characteristic curve analyses revealed that measurement of S100P in pancreatic juice was useful for discriminating neoplastic disease from chronic pancreatitis (area under the curve=0.837; 95% confidence interval, 0.749-0.903).S100P may be an early developmental marker of pancreatic carcinogenesis, and measurement of S100P in pancreatic juice may be useful for early detection of pancreatic cancer or screening of early pancreatic carcinogenesis.
Low Estradiol Concentrations in Men With Subnormal Testosterone Concentrations and Type 2 Diabetes
Authors: Sandeep Dhindsa, Richard Furlanetto, Mehul Vora, Husam Ghanim, Ajay Chaudhuri, Paresh Dandona
Journal: Diabetes Care (2011)

It has been suggested that the high prevalence of subnormal free testosterone concentrations, along with low or inappropriately normal gonadotropins in men with type 2 diabetes, may be the result of an increase in plasma estradiol concentrations secondary to an increase in aromatase activity in the adipose tissue that leads to the suppression of the hypothalamo-hypophyseal-gonadal axis.To investigate this hypothesis, plasma estradiol, testosterone, leutinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin (SHBG) concentrations were measured in fasting blood samples of 240 men with type 2 diabetes. Free estradiol concentrations were either calculated (n = 198) using total estradiol and SHBG measured by immunoassay or directly measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and equilibrium dialysis (n = 102).The calculated free estradiol concentration in men with subnormal free testosterone concentrations was lower than that in men with normal free testosterone concentrations (median 0.047 vs. 0.063 ng/dL, P < 0.001). Directly measured (LC-MS/MS) free estradiol concentrations were also lower in men with subnormal free testosterone concentrations (median 0.025 vs. 0.045 ng/dL, P = 0.008). Free estradiol concentrations were directly related to free testosterone but not to BMI or age.These data show that the suppression of the hypothalamo-hypophyseal-gonadal axis in patients with subnormal free testosterone concentrations and type 2 diabetes is not associated with increased estradiol concentrations. The pathogenesis of subnormal free testosterone concentrations in type 2 diabetes needs to be investigated further.
Diverse Sources of <i>C. difficile</i> Infection Identified on Whole-Genome Sequencing
Authors: David W. Eyre, Madeleine L. Cule, Daniel J. Wilson, David Griffiths, Alison Vaughan, Lily O'Connor, Camilla L.C. Ip, Tanya Golubchik, Elizabeth M. Batty, John M. Finney, David H. Wyllie, Xavier Didelot, Paolo Piazza, Rory Bowden, Kate E. Dingle, Rosalind M. Harding, Derrick W. Crook, Mark H. Wilcox, Tim E.A. Peto, A. Sarah Walker
Journal: New England Journal of Medicine (2013)

It has been thought that Clostridium difficile infection is transmitted predominantly within health care settings. However, endemic spread has hampered identification of precise sources of infection and the assessment of the efficacy of interventions.
Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia
Authors: Hubert Schrezenmeier, Jakob R. Passweg, Judith C. W. Marsh, Andrea Bacigalupo, Christopher N. Bredeson, Eduardo Bullorsky, Bruce M. Camitta, Richard E. Champlin, Robert Peter Gale, Monika Fuhrer, John P. Klein, Anna Locasciulli, Rosi Oneto, Antonius V. M. B. Schattenberg, Gerard Socie, Mary Eapen
Journal: Blood (2007)
Synthesis and distribution of H-2 antigens in preimplantation mouse embryos.
Authors: C G Webb, W E Gall, G M Edelman
Journal: The Journal of Experimental Medicine (1977)

Synthesis of H-2 antigens by preimplantation mouse embryos is first detectable at the late blastocyst stage. These antigens were detected using immune precipitation assays of extracts of embryos labeled by incorporation of radioactive amino acids but not by surface iodination. Experiments using isolated inner cell massess and trophoblast vesicles indicate that it is the cells of the inner cell mass that synthesize these antigens. H-2 antigens were not detected in either early blastocysts or at earlier cleavage stages.
Genomic and Clinical Analysis of Amplification of the 13q31 Chromosomal Region in Alveolar Rhabdomyosarcoma: A Report from the Children's Oncology Group
Authors: Jennifer L. Reichek, Fenghai Duan, Lynette M. Smith, Donna M. Gustafson, Roddy S. O'Connor, Chune Zhang, Mandy J. Dunlevy, Julie M. Gastier-Foster, Frederic G. Barr
Journal: Clinical Cancer Research (2011)

Abstract Purpose: This study determined the molecular characteristics and clinical significance of amplification of the 13q31 chromosomal region in alveolar rhabdomyosarcoma (ARMS), an aggressive pediatric cancer with frequent PAX3-FOXO1 and PAX7-FOXO1 gene fusions. Experimental Design: The 13q31 amplicon was localized in an initial panel of ARMS cases using oligonucleotide arrays. A fluorescence in situ hybridization assay for this localized region was designed, and applied to more ARMS cases to determine the frequency and distribution of amplification. Quantitative reverse transcription-PCR assays were applied to measure gene expression. The clinical significance of copy number and expression was determined with Kaplan–Meier and Cox proportional hazard models. Results: We localized the 13q31 amplicon to a 0.15 Mb region containing the MIR17HG gene encoding the polycistronic microRNA cluster, miR-17–92. This amplicon is present in 23% of ARMS cases with a marked preference for PAX7-FOXO1-positive cases. In tumors with 13q31 amplification, there is significantly increased expression of 5 of 6 microRNA's within the miR-17–92 cluster (miR-17, miR-19a, miR-19b, miR-20a, and miR-92a). In addition, a subset of nonamplified tumors with copy number-independent overexpression of all 6 microRNA's was identified. In clinical analyses, there was a significantly worse outcome associated with increased expression of the 5 microRNA's described above in 13q31-amplified cases when compared to nonamplified cases. There was also an improved outcome in 13q31-amplified cases with lower expression of these microRNA's. Conclusions: 13q31 amplification and expression of the miR-17–92 cluster provide novel markers for identifying good and poor prognostic subsets of PAX7-FOXO1-positive ARMS. Clin Cancer Res; 17(6); 1463–73. ©2011 AACR.
Identification of PP2A Complexes and Pathways Involved in Cell Transformation
Authors: Anna A. Sablina, Melissa Hector, Nathalie Colpaert, William C. Hahn
Journal: Cancer Research (2010)

Abstract The simian virus 40 small t (SV40ST) oncoprotein interacts with protein phosphatase 2A (PP2A), an abundantly expressed family of serine–threonine phosphatases. This interaction is essential for the transformation of human cells by SV40, and several PP2A subunits have been implicated as tumor suppressor genes. However, the pathways controlled by specific PP2A complexes involved in cell transformation remain incompletely understood. Using a comprehensive loss-of-function approach, we identified 4 PP2A regulatory subunits [B56α, B56γ, PR72/PR130, and PTPA (protein phosphatase 2A activator)], which when suppressed replaced the expression of SV40ST in human cell transformation. We found that manipulation of complexes containing PP2A B56α, B56γ, and PR72/PR130 activates the pathways regulated by c-Myc, Wnt, and PI3K (phosphoinositide 3-kinase)/Akt in a manner that depends on their specific phosphatase activity. In contrast, suppression of PTPA disrupts the assembly of PP2A heterotrimeric complexes, which leads to the activation of these same oncogenic pathways. These observations delineate the PP2A family members and pathways perturbed by SV40ST during human cell transformation. Cancer Res; 70(24); 10474–84. ©2010 AACR.
Low Diagnostic Yield of Elective Coronary Angiography
Authors: Manesh R. Patel, Eric D. Peterson, David Dai, J. Matthew Brennan, Rita F. Redberg, H. Vernon Anderson, Ralph G. Brindis, Pamela S. Douglas
Journal: New England Journal of Medicine (2010)

Guidelines for triaging patients for cardiac catheterization recommend a risk assessment and noninvasive testing. We determined patterns of noninvasive testing and the diagnostic yield of catheterization among patients with suspected coronary artery disease in a contemporary national sample.From January 2004 through April 2008, at 663 hospitals in the American College of Cardiology National Cardiovascular Data Registry, we identified patients without known coronary artery disease who were undergoing elective catheterization. The patients' demographic characteristics, risk factors, and symptoms and the results of noninvasive testing were correlated with the presence of obstructive coronary artery disease, which was defined as stenosis of 50% or more of the diameter of the left main coronary artery or stenosis of 70% or more of the diameter of a major epicardial vessel.A total of 398,978 patients were included in the study. The median age was 61 years; 52.7% of the patients were men, 26.0% had diabetes, and 69.6% had hypertension. Noninvasive testing was performed in 83.9% of the patients. At catheterization, 149,739 patients (37.6%) had obstructive coronary artery disease. No coronary artery disease (defined as <20% stenosis in all vessels) was reported in 39.2% of the patients. Independent predictors of obstructive coronary artery disease included male sex (odds ratio, 2.70; 95% confidence interval [CI], 2.64 to 2.76), older age (odds ratio per 5-year increment, 1.29; 95% CI, 1.28 to 1.30), presence of insulin-dependent diabetes (odds ratio, 2.14; 95% CI, 2.07 to 2.21), and presence of dyslipidemia (odds ratio, 1.62; 95% CI, 1.57 to 1.67). Patients with a positive result on a noninvasive test were moderately more likely to have obstructive coronary artery disease than those who did not undergo any testing (41.0% vs. 35.0%; P<0.001; adjusted odds ratio, 1.28; 95% CI, 1.19 to 1.37).In this study, slightly more than one third of patients without known disease who underwent elective cardiac catheterization had obstructive coronary artery disease. Better strategies for risk stratification are needed to inform decisions and to increase the diagnostic yield of cardiac catheterization in routine clinical practice.
Validation of a Cheyne-Stokes respiration (CSR) detection algorithm for a CPAP device
Authors: Dinesh Ramanan, Peter Bateman, Holger Woehrle, Glenn Richards, Jeff Armitstead
Journal: European Respiratory Journal (2014)

Introduction:  CSR is a periodic breathing pattern characterized by a waxing-and-waning of ventilation, primarily during sleep. CSR is very common in heart failure (HF) and can also occur during continuous positive airway pressure (CPAP) therapy initiation for obstructive sleep apnoea (OSA) or during ongoing therapy. Persistent CSR on CPAP therapy can be associated with persisting symptoms as well as a worse prognosis in patients with HF. CSR pattern recognition has been established analyzing a qualitative nasal flow signal using a diagnostic device (Weinreich,G et al. Sleep. 2009;32:553-7). We investigated if CSR detection could also be used while monitoring CPAP therapy through the airflow measured by the PAP device.  Objective:  To assess the accuracy of an algorithm for CSR detection, running on a CPAP device to provide a clinically relevant measure of CSR.  Methods:  Phase 1: Algorithm efficacy was determined by processing 69 diagnostic nasal flow records (27 OSA, 20 CSR, 11 CSR+OSA & 11 normals) using software simulation. Phase 2: 25 nasal flow records (selected from 150 serially recorded auto-cpap studies) with a Apnea-Hypopnea index ≥ 5. These records were replayed by a lung simulator to a PAP device running the new algorithm. In both phases, results were compared to scoring by an expert blinded to the algorithm results.  Results:  Phase 1 achieved sensitivity, specificity, accuracy (with 95% CI) of 80%(63%,90%), 90%(76%,96%), 86%(73%90%) for detecting any CSR period. Phase 2 achieved 100%(51%,100%), 81%(60%,93%), 84%(70%,98%).  Conclusion:  Our study shows that a novel algorithm for detecting CSR breathing on a PAP device is highly accurate and can be a useful tool for monitoring therapy.