tbuckley/cabot-search huggingface dataset:
Large-Scale mtDNA Screening Reveals a Surprising Matrilineal Complexity in East Asia and Its Implications to the Peopling of the Region
Authors: Q.-P. Kong, C. Sun, H.-W. Wang, M. Zhao, W.-Z. Wang, L. Zhong, X.-D. Hao, H. Pan, S.-Y. Wang, Y.-T. Cheng, C.-L. Zhu, S.-F. Wu, L.-N. Liu, J.-Q. Jin, Y.-G. Yao, Y.-P. Zhang
Journal: Molecular Biology and Evolution (2010)

In order to achieve a thorough coverage of the basal lineages in the Chinese matrilineal pool, we have sequenced the mitochondrial DNA (mtDNA) control region and partial coding region segments of 6,093 mtDNAs sampled from 84 populations across China. By comparing with the available complete mtDNA sequences, 194 of those mtDNAs could not be firmly assigned into the available haplogroups. Completely sequencing 51 representatives selected from these unclassified mtDNAs identified a number of novel lineages, including five novel basal haplogroups that directly emanate from the Eurasian founder nodes (M and N). No matrilineal contribution from the archaic hominid was observed. Subsequent analyses suggested that these newly identified basal lineages likely represent the genetic relics of modern humans initially peopling East Asia instead of being the results of gene flow from the neighboring regions. The observation that most of the newly recognized mtDNA lineages have already differentiated and show the highest genetic diversity in southern China provided additional evidence in support of the Southern Route peopling hypothesis of East Asians. Specifically, the enrichment of most of the basal lineages in southern China and their rather ancient ages in Late Pleistocene further suggested that this region was likely the genetic reservoir of modern humans after they entered East Asia.
Ammonia metabolism in chronic obstructive pulmonary disease with special reference to congestive right ventricular failure
Authors: A. Valero, G. Alroy, B. Eisenkraft, J. Itskovitch
Journal: Thorax (1974)

<b>Valero, A., Alroy, G., Eisenkraft, B., and Itskovitch, J. (1974).</b><i>Thorax</i>, <b>29</b>, 703-709. <b>Ammonia metabolism in chronic obstructive pulmonary disease with special reference to congestive right ventricular failure.</b> A study of 36 patients was undertaken to evaluate the role of raised blood and CSF ammonia in the production of central nervous manifestations in chronic obstructive pulmonary disease (COPD) with special reference to congestive right ventricular failure (CRVF). The patient material comprised five categories: 11 controls, seven mentally alert patients with COPD, eight with COPD and CRVF, four with primary cardiac disease and CRVF, and eight with cirrhosis of the liver. Each patient was examined clinically especially for neurological manifestations such as asterixis, confusion, and drowsiness. Each patient also had measurement of venous pressure, bromsulphthalein, ECG, chest radiograph, and spirometry. The mean values of CSF-glutamine, CSF and arterial blood-ammonia, pH, <i>P</i>co<sub>2</sub>, and <i>P</i>o<sub>2</sub> for each group were compared and statistically analysed. The results indicate that no correlation existed between central nervous manifestations acid-base balance or <i>P</i>o<sub>2</sub>. Ammonia-glutamine levels were found to relate to hepatic congestion whether it was caused by primary cardiac or pulmonary heart disease.
Secondary Failure of Metformin Monotherapy in Clinical Practice
Authors: Jonathan B. Brown, Christopher Conner, Gregory A. Nichols
Journal: Diabetes Care (2009)

OBJECTIVE We sought to document the secondary failure rate of metformin monotherapy in a clinical practice setting and to explore factors that predict therapeutic failure. RESEARCH DESIGN AND METHODS We studied 1,799 type 2 diabetic patients who, between 2004 and 2006, lowered their A1C to &amp;lt;7% after initiating metformin monotherapy as their first-ever anti-hyperglycemic drug. We examined all A1C values recorded through 31 December 2008 (2–5 years of follow-up), defining secondary failure as a subsequent A1C ≥7.5% or the addition or substitution of another anti-hyperglycemic agent. We used logistic regression to identify factors associated with the probability of secondary failure. RESULTS Of the 1,799 patients studied, 42% (n = 748) experienced secondary failure; the mean failure rate was 17% per year. However, patients who initiated metformin within 3 months of diabetes diagnosis failed at an age-and A1C-adjusted rate of 12.2% (10.5–14.4%) per year, and patients who initiated while A1C was &amp;lt;7% failed at an adjusted rate of 12.3% per year. An interaction term between duration of diagnosed diabetes and A1C was not significant. Age, duration, and A1C at initiation were the only factors that predicted secondary failure. CONCLUSIONS Although metformin failure may occur more rapidly in clinical practice than in clinical trails, initiating it soon after diabetes diagnosis and while A1C is low might preserve β-cell function, prolong the effectiveness of metformin, reduce lifetime glycemic burden, and prevent diabetes complications. Our findings support the current treatment algorithm for hyperglycemia management that recommends metformin initiation when diabetes is first diagnosed.
Effect of using an interactive booklet about childhood respiratory tract infections in primary care consultations on reconsulting and antibiotic prescribing: a cluster randomised controlled trial
Authors: N. A Francis, C. C Butler, K. Hood, S. Simpson, F. Wood, J. Nuttall
Journal: BMJ (2009)

To establish whether an interactive booklet on respiratory tract infections in children reduces reconsultation for the same illness episode, reduces antibiotic use, and affects future consulting intentions, while maintaining parental satisfaction with care.
Phase I/II Study of Sequential Dose-Intensified Ifosfamide, Cisplatin, and Etoposide Plus Paclitaxel As Induction Chemotherapy for Poor Prognosis Germ Cell Tumors by the German Testicular Cancer Study Group
Authors: Jörg T. Hartmann, Thomas Gauler, Bernd Metzner, Arthur Gerl, Jochen Casper, Oliver Rick, Marius Horger, Jan Schleicher, Günter Derigs, Regine Mayer-Steinacker, Jörg Beyer, Markus A. Kuczyk, Carsten Bokemeyer
Journal: Journal of Clinical Oncology (2007)

To evaluate the feasibility and the toxicity of sequential, dose-intensified chemotherapy combined with paclitaxel plus peripheral blood-derived hematopoietic stem-cell support (PBSC) for patients with untreated metastatic germ cell tumors (GCTs) who have poor International Germ Cell Consensus Cancer Group prognostic features.Paclitaxel was added to high-dose (HD) etoposide, ifosfamide, and cisplatin (VIP; etoposide 1,500 mg/m2, ifosfamide 10,000 mg/m2, and cisplatin 100 mg/m2; cumulative dose; days -6 through -2 per cycle) at three dose levels (135, 175, and 225 mg/m2) applied on day -6. Cycles were supported by PBSC and granulocyte colony-stimulating factor. One cycle of standard VIP was administered before start of HD-VIP plus paclitaxel cycles to collect autologous PBSC.Fifty-two of 53 patients receiving 152 cycles were assessable. As expected, myelosuppression was the major adverse effect. Median durations of leukocytes less than 1,000/microL and thrombocytes less than 25,000/microL were 6 and 4 days, respectively, independently of the dose of paclitaxel applied. WHO grade 2 neurotoxicity and grade 3 encephalopathy were observed in 5% of patients each. Other main adverse effects observed were stomatitis, diarrhea, and obstipation. Seventy-nine percent of patients achieved a favorable response to chemotherapy plus secondary surgery. After a median follow-up time of 41 months in surviving patients, the calculated 2- and 5-year survival rates were 77.6% (95% CI, 65.4% to 89.9%) and 75.2% (95% CI, 62.5% to 87.8%), respectively.Dose-intensive, sequential HD-VIP plus paclitaxel up to a dose of 225 mg/m2 in patients with poor prognosis GCT is a feasible approach. The regimen warrants investigation for its therapeutic potential in an expanded cohort of poor prognosis GCT patients.
Cyclosporine inhibits catabolism of low-density lipoproteins in HepG2 cells by about 25%
Authors: O A Rayyes, A Wallmark, C Florén
Journal: Hepatology (1996)

The aim of this study was to elucidate the possible causes of elevated low–density lipoprotein (LDL)–cholesterol levels in transplanted patients treated with the immunosuppressant drug, cyclosporine. HepG2 cells, from a well–differentiated cell–line of hepatoma cells, were cultured and used as a model for in vitro hepatocytic LDL uptake. Different concentrations of cyclosporine, which were within the range of concentrations found in humans treated with cyclosporine, were added to tissue culture medium together with 125I–LDL. The results showed that cyclosporine reduced LDL uptake and degradation in HepG2 cells by about 25%. The cells were also pretreated with cyclosporine for 1 to 24 hours and then incubated with new medium containing labeled LDL for 2 hours at 4 degrees C in an LDL–binding assay. The data showed that cyclosporine reduced the subsequent LDL binding. Cyclosporine has no toxic effects on HepG2 cells, as shown by unchanged growth capacity of the cells. By means of a 50–fold excess of unlabeled LDL, a monoclonal anti–LDL receptor antibody, and dextran sulfate, we also evaluated if this inhibition of LDL binding occurred through the LDL receptor– mediated pathway, through non–LDL receptor–mediated pathways, or through both. The results show that cyclosporine reduces LDL binding and uptake by mainly inhibiting the LDL receptor–mediated pathway. We also studied the effect of the LDL–cyclosporine complex on the binding of labelled LDL. The presence of cyclosporine in the LDL particle does not influence the binding behaviour of LDL to its receptor. We also found that cyclosporine reduces the expression of the LDL receptor messenger RNA (mRNA) by about 40%. Thus, the interpretation of this study is that cyclosporine can cause an increase in LDL–cholesterol in the plasma of transplantation patients by reducing the catabolism of LDL in the liver by inhibiting mainly the LDL receptor–mediated catabolism through an effect on LDL receptor synthesis.
Increased production of superoxide anion by neonatal polymorphonuclear leukocytes stimulated with a chemotactic peptide
Authors: Munehiro Yamazaki, Takafumi Matsuoka, Kozo Yasui, Atsushi Komiyama, Taro Akabane
Journal: American Journal of Hematology (1988)

Abstract In order to assess the functional property of neonatal polymorphonuclear leukocytes (PMNs), we studied their chemoattractant‐stimulated superoxide anion (O 2 − ) production using a soluble chemotactic peptide N‐formyl‐methionyl‐leucyl‐phenylalanine (FMLP) as a PMN stimulus. O 2 − production by neonatal PMNs was increased: when stimulated with 10 −7 M FMLP, O 2 − values (nanomoles; mean ± SE) produced by 10 6 PMNs were 16.5 ± 1.3 for neonatal PMNs and 12.6 ± 0.6 for adult PMNs (p &lt; .02). When studied under various concentrations (10 −9 to 10 −6 M) of FMLP, neonatal PMNs produced more O 2 − than adult cells under the stimulation of a lower concentration (10 −8 M) as well as a higher concentration (10 −7 M) of FMLP. The increased O 2 − production by neonatal PMNs was also observed under their stimulation by phorbol myristate acetate. Neonatal and adult PMNs produced equal amounts of O 2 − when stimulated with a particulate stimulus of opsonized zymosan. To analyze further the mechanism for the increase in FMLP‐induced O 2 − production by neonatal PMNs, we next studied whether there was some abnormality in their FMLP receptors. Neonatal PMNs had normal numbers of FMLP receptors; the receptor numbers (mean) per cell were 54,000 in neonatal PMNs and 56,000 in adult cells. Additionally, the FMLP receptors had normal affinity for the peptide. These results demonstrate that the increased production of O 2 − by FMLP‐stimulated neonatal PMNs is not due to the abnormality of its binding to the receptors but is due to that of the subsequent events.
Disruption of Fas Receptor Signaling by Nitric Oxide in Eosinophils
Authors: Holger Hebestreit, Birgit Dibbert, Ivo Balatti, Doris Braun, Andreas Schapowal, Kurt Blaser, Hans-Uwe Simon
Journal: The Journal of Experimental Medicine (1998)

It has been suggested that Fas ligand–Fas receptor interactions are involved in the regulation of eosinophil apoptosis and that dysfunctions in this system could contribute to the accumulation of these cells in allergic and asthmatic diseases. Here, we demonstrate that nitric oxide (NO) specifically prevents Fas receptor–mediated apoptosis in freshly isolated human eosinophils. In contrast, rapid acceleration of eosinophil apoptosis by activation of the Fas receptor occurs in the presence of eosinophil hematopoietins. Analysis of the intracellular mechanisms revealed that NO disrupts Fas receptor–mediated signaling events at the level of, or proximal to, Jun kinase (JNK), but distal to sphingomyelinase (SMase) activation and ceramide generation. In addition, activation of SMase occurs downstream of an interleukin 1 converting enzyme–like (ICE-like) protease(s) that is not blocked by NO. However, NO prevents activation of a protease that targets lamin B1. These findings suggest a role for an additional NO-sensitive apoptotic signaling pathway that amplifies the proteolytic cascade initialized by activation of the Fas receptor. Therefore, NO concentrations within allergic inflammatory sites may be important in determining whether an eosinophil survives or undergoes apoptosis upon Fas ligand stimulation.
Validation of Contrast-Enhanced Magnetic Resonance Imaging to Monitor Regenerative Efficacy After Cell Therapy in a Porcine Model of Convalescent Myocardial Infarction
Authors: Konstantinos Malliaras, Rachel R. Smith, Hideaki Kanazawa, Kristine Yee, Jeffrey Seinfeld, Eleni Tseliou, James F. Dawkins, Michelle Kreke, Ke Cheng, Daniel Luthringer, Chak-Sum Ho, Agnieszka Blusztajn, Ileana Valle, Supurna Chowdhury, Raj R. Makkar, Rohan Dharmakumar, Debiao Li, Linda Marbán, Eduardo Marbán
Journal: Circulation (2013)

Magnetic resonance imaging (MRI) in the CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) trial revealed that cardiosphere-derived cells (CDCs) decrease scar size and increase viable myocardium after myocardial infarction (MI), but MRI has not been validated as an index of regeneration after cell therapy. We tested the validity of contrast-enhanced MRI in quantifying scarred and viable myocardium after cell therapy in a porcine model of convalescent MI.
Meta-analysis, power analysis, and the null-hypothesis significance-test procedure
Authors: Joseph S. Rossi
Journal: Behavioral and Brain Sciences (1998)

Chow's (1996) defense of the null-hypothesis significance-test procedure (NHSTP) is thoughtful and compelling in many respects. Nevertheless, techniques such as meta-analysis, power analysis, effect size estimation, and confidence intervals can be useful supplements to NHSTP in furthering the cumulative nature of behavioral research, as illustrated by the history of research on the spontaneous recovery of verbal learning.
Randomized Phase III Trial of Weekly Compared With Every-3-Weeks Paclitaxel for Metastatic Breast Cancer, With Trastuzumab for all HER-2 Overexpressors and Random Assignment to Trastuzumab or Not in HER-2 Nonoverexpressors: Final Results of Cancer and Leukemia Group B Protocol 9840
Authors: Andrew D. Seidman, Donald Berry, Constance Cirrincione, Lyndsay Harris, Hyman Muss, P. Kelly Marcom, Grandella Gipson, Harold Burstein, Diana Lake, Charles L. Shapiro, Peter Ungaro, Larry Norton, Eric Winer, Clifford Hudis
Journal: Journal of Clinical Oncology (2008)

Phase II trials suggested that weekly paclitaxel might be more effective and less toxic than every-3-weeks administration for metastatic breast cancer (MBC). Cancer and Leukemia Group B (CALGB) protocol 9840 was initiated to address this question. Subsequently trastuzumab was demonstrated to improve outcomes of paclitaxel therapy for human epidermal growth factor receptor-2 (HER-2)-positive patients, and was therefore incorporated. Because inhibition of HER-family signaling had potential efficacy even without HER-2 overexpression, we randomly assigned for trastuzumab in this population.Patients were randomly assigned to paclitaxel 175 mg/m(2) every 3 weeks or 80 mg/m(2) weekly. After the first 171 patients, all HER-2-positive patients received trastuzumab; HER-2 nonoverexpressors were randomly assigned for trastuzumab, in addition to paclitaxel schedule. A total of 577 patients were treated on 9840. An additional 158 patients were included in analyses, for combined sample of 735. The primary end point was response rate (RR); secondary end points were time to progression (TTP), overall survival, and toxicity. Primary comparisons were between weekly versus every-3-weeks paclitaxel, and trastuzumab versus no trastuzumab in HER-2 nonoverexpressors.In the combined sample, weekly paclitaxel was superior to every-3-weeks administration: RR (42% v 29%, unadjusted odds ratio [OR] = 1.75; P = .0004), TTP (median, 9 v 5 months; adjusted HR = 1.43; P < .0001), and survival (median, 24 v 12 months; adjusted HR = 1.28; P = .0092). For HER-2 nonoverexpressors, trastuzumab did not improve efficacy. Grade 3 neuropathy was more common with weekly dosing (24% v 12%; P = .0003).Weekly paclitaxel is more effective than every-3-weeks administration for MBC. Trastuzumab did not improve efficacy for HER-2 nonoverexpressors. Neurotoxicity is a treatment-limiting toxicity for weekly paclitaxel.
Neuroendocrine Tumor Markers and Enterochromaffin-Like Cell Hyper/Dysplasia in Type 1 Diabetes
Authors: Christophe E.M. De Block, Gert Colpin, Kristof Thielemans, Willy Coopmans, Johannes J.P.M. Bogers, Paul A. Pelckmans, Eric A.E. Van Marck, Viviane Van Hoof, Manou Martin, Ivo H. De Leeuw, Roger Bouillon, Luc F. Van Gaal
Journal: Diabetes Care (2004)

OBJECTIVE—Parietal cell antibodies (PCAs) are found in 20% of type 1 diabetic patients, denoting autoimmune gastritis and pernicious anemia, which may predispose to enterochromaffin-like (ECL) cell hyper/dysplasia and gastric carcinoid tumors. We evaluated whether chromogranin A (CgA), 5-hydroxyindole acetic acid (5-HIAA), and neuron-specific enolase (NSE) contribute to screening for ECL cell hyper/dysplasia. RESEARCH DESIGN AND METHODS—Sera from 93 type 1 diabetic patients (53 men and 40 women, 31 PCA+ and 62 PCA−, aged 45 ± 13 years) were analyzed for PCAs by indirect immunofluorescence and for CgA, NSE, and gastrin by radioimmunoassay. Urinary 5-HIAA was tested by high-performance liquid chromatography. Corpus atrophy and ECL cell proliferation were assessed in gastric biopsies. RESULTS—PCA+ patients had higher gastrin (P &amp;lt; 0.0001) and CgA levels (P = 0.003) and were more prone to autoimmune gastritis (odds ratio [OR] 17, P &amp;lt; 0.0001) and ECL cell hyper/dysplasia (OR = 23, P = 0.005) than PCA− subjects. ECL cell hyper/dysplasia was present in seven PCA+ patients who showed higher CgA levels (P &amp;lt; 0.0001) than subjects without ECL cell hyper/dysplasia, but NSE and 5-HIAA levels were similar. CgA levels correlated with gastrinemia (r = 0.50, P &amp;lt; 0.0001), PCA titer (r = 0.42, P = 0.001), and 5-HIAA levels (r = 0.38, P = 0.012). Logistic regression identified the CgA level (β = 0.01, P = 0.027) as an independent risk factor for ECL cell hyper/dysplasia when PCA, CgA, 5-HIAA, NSE, gastrin, sex, and age were tested. Multivariate linear regression demonstrated that CgA level was determined by ECL cell density (r = 0.59, P &amp;lt; 0.0001) and gastrin level (r = 0.67, P = 0.02). One PCA+ patient with elevated gastrin, CgA, and 5-HIAA levels had a gastric carcinoid tumor. CONCLUSIONS—PCA+ patients, particularly those with high gastrin and CgA levels, risk developing ECL cell hyper/dysplasia. The determination of CgA, but not NSE and 5-HIAA, may complement histology in evaluating ECL cell mass.
Managing common breastfeeding problems in the community
Authors: L. H. Amir
Journal: BMJ (2014)

<h3>Abstract</h3> The regulation of transcription requires the coordination of numerous activities on DNA, yet it remains poorly understood how transcription factors facilitate these multiple functions. Here we use lattice light-sheet microscopy to integrate single-molecule and high-speed 4D imaging in developing <i>Drosophila</i> embryos to study the nuclear organization and interactions of the key patterning factors Zelda and Bicoid. In contrast to previous studies suggesting stable, cooperative binding, we show that both factors interact with DNA with surprisingly high off-rates. We find that both factors form dynamic subnuclear hubs, and that Bicoid binding is enriched within Zelda hubs. Remarkably, these hubs are both short lived and interact only transiently with sites of active Bicoid dependent transcription. Based on our observations we hypothesize that, beyond simply forming bridges between DNA and the transcription machinery, transcription factors can organize other proteins into hubs that transiently drive multiple activities at their gene targets.
Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma: A Weighty Connection
Authors: Brad Q. Starley, Christopher J. Calcagno, Stephen A. Harrison
Journal: Hepatology (2010)

Hepatocellular carcinoma (HCC) is a common and deadly malignancy that is increasing in incidence in developed countries. The emergence of hepatitis C virus (HCV) accounts for about half of this increase in HCC, although the etiology of HCC in 15%-50% of new HCC cases remains unclear. The most common form of chronic liver disease in developed countries is nonalcoholic fatty liver disease (NAFLD), which encompasses a broad spectrum of histopathology. The prevalence of NAFLD, including the more aggressive nonalcoholic steatohepatitis (NASH), is increasing with the growing epidemics of diabetes and obesity. NASH can progress to cirrhosis and its related complications. Growing evidence suggests that NASH accounts for a large proportion of idiopathic or cryptogenic cirrhosis, which is associated with the typical risk factors for NASH. HCC is a rare, although important complication of NAFLD. Diabetes and obesity have been established as independent risk factors for the development of HCC. New evidence also suggests that hepatic iron deposition increases the risk of HCC in NASH-derived cirrhosis. Multiple case reports and case reviews of HCC in the setting of NASH support the associations of diabetes and obesity with the risk of HCC, as well as suggest age and advanced fibrosis as significant risks. Insulin resistance and its subsequent inflammatory cascade that is associated with the development of NASH appear to play a significant role in the carcinogenesis of HCC. The complications of NASH, including cirrhosis and HCC, are expected to increase with the growing epidemic of diabetes and obesity. (Hepatology 2010;51:1820–1832)
Endobronchial lesions in a non-AIDS patient with disseminated Mycobacterium avium-intracellulare infection
Authors: JY Shih, HC Wang, IP Chiang, PC Yang, KT Luh
Journal: European Respiratory Journal (1997)

A 34 year old female developed Mycobacterium avium-intracellulare infection with generalized lymphadenopathy, hepatosplenomegaly, pulmonary infiltration, pleural effusion and endobronchial polypoid lesions. M. avium-intracellulare was identified by means of sputum cultures, pleural effusion culture and lymph node culture. The anti-human immunodeficiency virus (HIV) antibody was negative. The CD4+ cell count was normal. Bronchoscopic examination revealed multiple polypoid lesions, which had nearly occluded the right main bronchus, right middle lobe and left lower lobe bronchi. Neodymium yttrium aluminium garnet (Nd-YAG) laser and antimycobacterial therapy were used effectively to relieve the airway obstruction. The clinical symptoms and signs responded favourably to antimycobacterial therapy.