tbuckley/cabot-search huggingface dataset:
Techniques for cryopreservation of individual or small numbers of human spermatozoa: a systematic review
Authors: F. AbdelHafez, M. Bedaiwy, S. A. El-Nashar, E. Sabanegh, N. Desai
Journal: Human Reproduction Update (2008)

Despite interest in cryopreservation of individual or small number of human spermatozoa, to date, little data is available as regards its effectiveness. We systematically reviewed the outcome after cryopreservation of individual or small numbers of human spermatozoa in patients with severe male factor of infertility. We searched the MEDLINE, EMBASE, Cochrane Systematic Reviews, CENTRAL, Web of Science, Scopus databases for relevant studies up to June of 2008. The search used terms referring to cryopreservation of small amount of sperm. Included studies were limited to human studies with no language restrictions. We identified 30 reports including 9 carriers used for cryopreservation of small quantities/numbers of human spermatozoa (7 non-biological and 2 biological carriers). A wide variety of cryopreservation vehicles were reported. The recovery rate of spermatozoa cryopreserved in a known small number varied widely from 59 to 100%. Fertilization rates were in the range of 18–67%. Frozen–thawed spermatozoa, using this method, were subsequently used for intracytoplasmic sperm injection in only five studies, with few pregnancies reported so far. To date, there remains no consensus as to the ideal carrier for cryopreservation of small number of spermatozoa for clinical purposes. Cryopreservation of individual or small numbers of human spermatozoa may replace the need for repeated surgical sperm retrieval. A controlled multicenter trial with sufficient follow-up would provide valid evidence of the potential benefit of this approach.
Competency-Based Education and Training in Internal Medicine
Authors: Steven E. Weinberger
Journal: Annals of Internal Medicine (2010)

Recent efforts to improve medical education include adopting a new framework based on 6 broad competencies defined by the Accreditation Council for Graduate Medical Education. In this article, the Alliance for Academic Internal Medicine Education Redesign Task Force II examines the advantages and challenges of a competency-based educational framework for medical residents. Efforts to refine specific competencies by developing detailed milestones are described, and examples of training program initiatives using a competency-based approach are presented. Meeting the challenges of a competency-based framework and supporting these educational innovations require a robust faculty development program. Challenges to competency-based education include teaching and evaluating the competencies related to practice-based learning and improvement and systems-based practice, as well as implementing a flexible time frame to achieve competencies. However, the Alliance for Academic Internal Medicine Education Redesign Task Force II does not favor reducing internal medicine training to less than 36 months as part of competency-based education. Rather, the 36-month time frame should allow for remediation to address deficiencies in achieving competencies and for diverse enrichment experiences in such areas as quality of care and practice improvement for residents who have demonstrated skills in all required competencies.
AT <sub>2</sub> Receptor Activation Induces Natriuresis and Lowers Blood Pressure
Authors: Brandon A. Kemp, Nancy L. Howell, John J. Gildea, Susanna R. Keller, Shetal H. Padia, Robert M. Carey
Journal: Circulation Research (2014)

Rationale : Compound 21 (C-21) is a highly selective nonpeptide AT 2 receptor (AT 2 R) agonist. Objective : To test the hypothesis that renal proximal tubule AT 2 Rs induce natriuresis and lower blood pressure in Sprague-Dawley rats and mice. Methods and Results : In rats, AT 2 R activation with intravenous C-21 increased urinary sodium excretion by 10-fold ( P &lt;0.0001); this natriuresis was abolished by direct renal interstitial infusion of specific AT 2 R antagonist PD-123319. C-21 increased fractional excretion of Na + ( P &lt;0.05) and lithium ( P &lt;0.01) without altering renal hemodynamic function. AT 2 R activation increased renal proximal tubule cell apical membrane AT 2 R protein ( P &lt;0.001) without changing total AT 2 R expression and internalized/inactivated Na + -H + exchanger-3 and Na + /K + ATPase. C-21–induced natriuresis was accompanied by an increase in renal interstitial cGMP ( P &lt;0.01); C-21–induced increases in urinary sodium excretion and renal interstitial cGMP were abolished by renal interstitial nitric oxide synthase inhibitor l -N 6 -nitroarginine methyl ester or bradykinin B 2 receptor antagonist icatibant. Renal AT 2 R activation with C-21 prevented Na + retention and lowered blood pressure in the angiotensin II infusion model of experimental hypertension. Conclusions : AT 2 R activation initiates its translocation to the renal proximal tubule cell apical membrane and the internalization of Na + -H + exchanger-3 and Na + /K + ATPase, inducing natriuresis in a bradykinin-nitric oxide-cGMP–dependent manner. Intrarenal AT 2 R activation prevents Na + retention and lowers blood pressure in angiotensin II–dependent hypertension. AT 2 R activation holds promise as a renal proximal tubule natriuretic/diuretic target for the treatment of fluid-retaining states and hypertension.
Reactions Associated With Ampicillin Therapy
Authors: C. Warren Bierman
Journal: JAMA (1972)

Fifty patients who had had adverse reactions to therapy with ampicillin trihydrate were studied immunologically to determine the role of allergy in these reactions. Thirty-four of the 50 patients had only a maculopapular rash. They all had negative skin test reactions and had no reaction to readministration of ampicillin. Sixteen patients had urticarial reactions, and of these, six had positive skin test results. Ten tolerated readministration, two were not challenged because of positive immediate skin test reactions, and urticaria developed in four—three of whom had delayed skin reactions. We conclude that the common maculopapular rash related to ampicillin is not an allergic reaction. Furthermore, both immediate and delayed skin reactions should be tested for in patients with urticaria to rule out ampicillin allergy.
Increased Prevalence of<i>EGFR</i>-Mutant Lung Cancer in Women and in East Asian Populations: Analysis of Estrogen-Related Polymorphisms
Authors: Daphne W. Bell, Brian W. Brannigan, Keitaro Matsuo, Dianne M. Finkelstein, Raffaella Sordella, Jeff Settleman, Tetsuya Mitsudomi, Daniel A. Haber
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Somatic mutations in the epidermal growth factor receptor (EGFR) gene occur in a subset of non–small-cell lung cancer (NSCLC) and are highly predictive of the clinical response to selective EGFR kinase inhibitors. The prevalence of EGFR-mutant NSCLC is appreciably higher in females than in males and in East Asian than in Caucasian populations. We hypothesized that these disparate frequencies may be attributable to underlying genetic modifiers. Given the coincident differences in sex and ethnic origin, we tested allozymatic variants of enzymes involved in estrogen biosynthesis and metabolism, encoded by polymorphic alleles known to differ in frequency between Caucasian and Asian populations, as modifying alleles. Experimental Design: We genotyped nine polymorphisms in the CYP1A1, CYP17A1, CYP19, HSD17B1, COMT, GSTM1, and GSTT1 genes, in a series of 100 Japanese NSCLCs, selected for equal representation of EGFR wild-type (wt) and EGFR-mutant cases, as well as male and female cases. Associations between polymorphic variants and the EGFR genotype and sex of NSCLC cases were examined using Fisher's exact test of significance. Results: Only CYP1A1*2C showed a difference in allele frequency that approached statistical significance. Heterozygotes were underrepresented among EGFR-mutant cases compared with EGFR-wt cases (27% versus 47%, P = 0.08), with a concurrent trend toward overrepresentation of CYP1A1*2CIle/Ile homozygotes among EGFR-mutant cases as compared with EGFR-wt cases (69% versus 51%, P = 0.13). Conclusion: Within the power of this study, our findings suggest that the selected polymorphic variants in the estrogen biosynthesis and metabolism pathways are unlikely to be major genetic modifiers of the prevalence of EGFR-mutant NSCLC.
Inhibition of Glioma Growth in Vivo by Selective Activation of the CB2 Cannabinoid Receptor
Authors: Cristina Sánchez, María L. de Ceballos, Teresa Gómez del Pulgar, Daniel Rueda, César Corbacho, Guillermo Velasco, Ismael Galve-Roperh, John W. Huffman, Santiago Ramón y Cajal, Manuel Guzmán
Journal: Cancer Research (2001)

The development of new therapeutic strategies is essential for the management of gliomas, one of the most malignant forms of cancer. We have shown previously that the growth of the rat glioma C6 cell line is inhibited by psychoactive cannabinoids (I. Galve-Roperh et al., Nat. Med., 6: 313-319, 2000). These compounds act on the brain and some other organs through the widely expressed CB(1) receptor. By contrast, the other cannabinoid receptor subtype, the CB(2) receptor, shows a much more restricted distribution and is absent from normal brain. Here we show that local administration of the selective CB(2) agonist JWH-133 at 50 microg/day to Rag-2(-/-) mice induced a considerable regression of malignant tumors generated by inoculation of C6 glioma cells. The selective involvement of the CB(2) receptor in this action was evidenced by: (a) the prevention by the CB(2) antagonist SR144528 but not the CB(1) antagonist SR141716; (b) the down-regulation of the CB(2) receptor but not the CB(1) receptor in the tumors; and (c) the absence of typical CB(1)-mediated psychotropic side effects. Cannabinoid receptor expression was subsequently examined in biopsies from human astrocytomas. A full 70% (26 of 37) of the human astrocytomas analyzed expressed significant levels of cannabinoid receptors. Of interest, the extent of CB(2) receptor expression was directly related with tumor malignancy. In addition, the growth of grade IV human astrocytoma cells in Rag-2(-/-) mice was completely blocked by JWH-133 administration at 50 microg/day. Experiments carried out with C6 glioma cells in culture evidenced the internalization of the CB(2) but not the CB(1) receptor upon JWH-133 challenge and showed that selective activation of the CB(2) receptor signaled apoptosis via enhanced ceramide synthesis de novo. These results support a therapeutic approach for the treatment of malignant gliomas devoid of psychotropic side effects.
Chaetoglobosin A preferentially induces apoptosis in chronic lymphocytic leukemia cells by targeting the cytoskeleton
Authors: P B Knudsen, B Hanna, S Ohl, L Sellner, T Zenz, H Döhner, S Stilgenbauer, T O Larsen, P Lichter, M Seiffert
Journal: Leukemia (2013)
ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients
Authors: O.A. Cornely, M. Bassetti, T. Calandra, J. Garbino, B.J. Kullberg, O. Lortholary, W. Meersseman, M. Akova, M.C. Arendrup, S. Arikan-Akdagli, J. Bille, E. Castagnola, M. Cuenca-Estrella, J.P. Donnelly, A.H. Groll, R. Herbrecht, W.W. Hope, H.E. Jensen, C. Lass-Florl, G. Petrikkos, M.D. Richardson, E. Roilides, P.E. Verweij, C. Viscoli, A.J. Ullmann
Journal: Clinical Microbiology and Infection (2012)
Genomic Changes in Chromosomes 10, 16, and X in Malignant Peripheral Nerve Sheath Tumors Identify a High-Risk Patient Group
Authors: Helge R. Brekke, Franclim R. Ribeiro, Matthias Kolberg, Trude H. Ågesen, Guro E. Lind, Mette Eknæs, Kirsten S. Hall, Bodil Bjerkehagen, Eva van den Berg, Manuel R. Teixeira, Nils Mandahl, Sigbjørn Smeland, Fredrik Mertens, Rolf I. Skotheim, Ragnhild A. Lothe
Journal: Journal of Clinical Oncology (2010)

Purpose The purpose of this study was to identify genetic aberrations contributing to clinical aggressiveness of malignant peripheral nerve sheath tumors (MPNSTs). Patients and Methods Samples from 48 MPNSTs and 10 neurofibromas were collected from 51 patients with (n = 31) or without (n = 20) neurofibromatosis type 1 (NF1). Genome-wide DNA copy number changes were assessed by chromosomal and array-based comparative genomic hybridization (CGH) and examined for prognostic significance. For a subset of 20 samples, RNA microarray data were integrated with the genome data to identify potential target genes. Results Forty-four (92%) MPNSTs displayed DNA copy number changes (median, 18 changes per tumor; range, 2 to 35 changes). Known frequent chromosomal gains at chromosome arms 8q (69%), 17q (67%), and 7p (52%) and losses from 9p (50%), 11q (48%), and 17p (44%) were confirmed. Additionally, gains at 16p or losses from 10q or Xq identified a high-risk group with only 11% 10-year disease-specific survival (P = .00005). Multivariate analyses including NF1 status, tumor location, size, grade, sex, complete remission, and initial metastatic status showed that the genomic high-risk group was the most significant predictor of poor survival. Several genes whose expression was affected by the DNA copy number aberrations were identified. Conclusion The presence of specific genetic aberrations was strongly associated with poor survival independent of known clinical risk factors. Conversely, within the total patient cohort with 34% 10-year disease-specific survival, a low-risk group was identified: without changes at chromosomes 10q, 16p, or Xq in their MPNSTs, the patients had 74% 10-year survival.
Differential synergy of Notch and T cell receptor signaling determines αβ versus γδ lineage fate
Authors: Annette I. Garbe, Andreas Krueger, Fotini Gounari, Juan Carlos Zúñiga-Pflücker, Harald von Boehmer
Journal: The Journal of Experimental Medicine (2006)

Thymic precursors expressing the pre–T cell receptor (TCR), the γδTCR, or the αβTCR can all enter the CD4+8+ αβ lineage, albeit with different efficacy. Here it is shown that proliferation and differentiation of precursors with the different TCRs into αβ lineage cells require Notch signaling at the DN3 stage of thymic development. At the DN4 stage, Notch signaling still significantly contributes to the generation of αβ T cells. In particular, in αβ lineage commitment, the pre-TCR synergizes more efficiently with Notch signals than the other two TCRs, whereas γδTCR-expressing cells can survive and expand in the absence of Notch signals, even though Notch signaling enhances their proliferation. These observations suggest a new model of αβ versus γδ lineage choice in which lineage fate is determined by the extent of synergy between TCR and Notch signaling and in which the evolutionarily recent advent of the cell-autonomously signaling pre-TCR increased the efficacy of αβ T cell generation.
P-Glycoprotein, CYP3A, and Plasma Carboxylesterase Determine Brain and Blood Disposition of the mTOR Inhibitor Everolimus (Afinitor) in Mice
Authors: Seng Chuan Tang, Rolf W. Sparidans, Ka Lei Cheung, Tatsuki Fukami, Selvi Durmus, Els Wagenaar, Tsuyoshi Yokoi, Bart J.M. van Vlijmen, Jos H. Beijnen, Alfred H. Schinkel
Journal: Clinical Cancer Research (2014)

To clarify the role of ABCB1, ABCG2, and CYP3A in blood and brain exposure of everolimus using knockout mouse models.We used wild-type, Abcb1a/1b(-/-), Abcg2(-/-), Abcb1a/1b;Abcg2(-/-), and Cyp3a(-/-) mice to study everolimus oral bioavailability and brain accumulation.Following everolimus administration, brain concentrations and brain-to-liver ratios were substantially increased in Abcb1a/1b(-/-)and Abcb1a/1b;Abcg2(-/-), but not Abcg2(-/-)mice. The fraction of everolimus located in the plasma compartment was highly increased in all knockout strains. In vitro, everolimus was rapidly degraded in wild-type but not knockout plasma. Carboxylesterase 1c (Ces1c), a plasma carboxylesterase gene, was highly upregulated (∼80-fold) in the liver of knockout mice relative to wild-type mice, and plasma Ces1c likely protected everolimus from degradation by binding and stabilizing it. This binding was prevented by preincubation with the carboxylesterase inhibitor BNPP. In vivo knockdown experiments confirmed the involvement of Ces1c in everolimus stabilization. Everolimus also markedly inhibited the hydrolysis of irinotecan and p-nitrophenyl acetate by mouse plasma carboxylesterase and recombinant human CES2, respectively. After correcting for carboxylesterase binding, Cyp3a(-/-), but not Abcb1a/1b(-/-), Abcg2(-/-), or Abcb1a/1b;Abcg2(-/-)mice, displayed highly (>5-fold) increased oral availability of everolimus.Brain accumulation of everolimus was restricted by Abcb1, but not Abcg2, suggesting the use of coadministered ABCB1 inhibitors to improve brain tumor treatment. Cyp3a, but not Abcb1a/1b, restricted everolimus oral availability, underscoring drug-drug interaction risks via CYP3A. Upregulated Ces1c likely mediated the tight binding and stabilization of everolimus, causing higher plasma retention in knockout strains. This Ces upregulation might confound other pharmacologic studies.
Effect of oral theophylline on resting energy expenditure in normal volunteers.
Authors: A Dash, A Agrawal, N Venkat, J Moxham, J Ponte
Journal: Thorax (1994)

BACKGROUND--The aim of this study was to investigate the contribution of regular treatment with oral theophylline to the increase in resting oxygen consumption observed in patients with chronic airflow limitation who are receiving bronchodilator therapy. METHODS--Resting oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured in 10 normal subjects (six men, age 21-48 years, weight 50-85 kg) before and after 11 days of treatment with either placebo or theophylline in a double blind manner, in twice daily oral doses ensuring trough serum concentrations between 8.4 and 13.5 mg/l. An open canopy method was used to measure VO2 and VCO2 and in all test conditions this was extended for 60 minutes after an inhalation of 800 micrograms of salbutamol super-imposed on the background placebo or theophylline treatment. RESULTS--Resting VO2 and heart rate were increased during theophylline treatment compared with placebo by 6.5% and 8.4% respectively. Salbutamol inhalation transiently increased VO2, VCO2, and heart rate in all tests but this was not modified by background theophylline treatment. CONCLUSION--Oral theophylline treatment causes a sustained increase in resting oxygen consumption and heart rate but does not modify the metabolic response to acutely inhaled salbutamol.
Sympathetic nervous system inhibition increases hepatic progenitors and reduces liver injury
Authors: Jude A. Oben, Tania Roskams, Shiqi Yang, Huizhi Lin, Nicoletta Sinelli, Zhiping Li, Michael Torbenson, Jiawen Huang, Paul Guarino, Michel Kafrouni, Anna Mae Diehl
Journal: Hepatology (2003)

Recovery from liver damage might be enhanced by encouraging repopulation of the liver by endogenous hepatic progenitor cells. Oval cells are resident hepatic stem cells that promote liver regeneration and repair. Little is known about the mediators that regulate the accumulation of these cells in the liver. Parasympathetic nervous system inhibition reduces the number of oval cells in injured livers. The effect of sympathetic nervous system (SNS) inhibition on oval cell number is not known. Adrenergic inhibition mobilizes hematopoietic precursors into the circulation and has also been shown to promote liver regeneration. Thus, we hypothesized that SNS inhibition would promote hepatic accumulation of oval cells and reduce liver damage in mice fed antioxidant–depleted diets to induce liver injury. Our results confirm this hypothesis. Compared with control mice that were fed only the antioxidant–depleted diets, mice fed the same diets with prazosin (PRZ, an α–1 adrenoceptor antagonist) or 6–hydroxydopamine (6–OHDA, an agent that induces chemical sympathectomy) had significantly increased numbers of oval cells. Increased oval cell accumulation was accompanied by less hepatic necrosis and steatosis, lower serum aminotransferases, and greater liver and whole body weights. Neither PRZ nor 6–OHDA affected the expression of cytokines, growth factors, or growth factor receptors that are known to regulate progenitor cells. In conclusion, stress–related sympathetic activity modulates progenitor cell accumulation in damaged livers and SNS blockade with α–adrenoceptor antagonists enhances hepatic progenitor cell accumulation.
Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17 cells in graft-versus-host disease
Authors: Tangsheng Yi, Ying Chen, Lin Wang, Gong Du, Daniel Huang, Dongchang Zhao, Heather Johnston, James Young, Ivan Todorov, Dale T. Umetsu, Lieping Chen, Yoichiro Iwakura, Fouad Kandeel, Stephen Forman, Defu Zeng
Journal: Blood (2009)
Nutritional deficiencies in iron overloaded patients with hemoglobinopathies
Authors: Susan Claster, John C. Wood, Leila Noetzli, Susan M. Carson, Thomas C. Hofstra, Rachna Khanna, Thomas D. Coates
Journal: American Journal of Hematology (2009)

One of the hallmarks of both sickle cell disease (SCD) and thalassemia major (TM) is accelerated oxidative damage. Decreased antioxidant levels and increased oxidant stress biomarkers are found in both diseases. Although isolated vitamin deficiencies have been reported in TM and nontransfused SCD patients, a comprehensive evaluation of vitamin and trace mineral levels has never been performed in chronically transfused SCD or TM patients. As vitamins and trace minerals may be consumed as a result of chronic oxidative stress; we hypothesized that levels of these compounds would correlate with surrogates of iron overload, hemolysis, and inflammation in chronically transfused patients. Using a convenience sample of our group of chronically transfused patients we studied 43 patients with SCD (17 male, 26 female) and 24 patients with TM (13 male and 11 female). The age range for our patients varied from 1.5 to 31.4 years. Levels of vitamins A, thiamin, B6, B12, C, D, E as well as selenium, zinc, copper, and ceruloplasmin were measured. We found that 40-75% of the patients were deficient in A, C, D and selenium and 28-38% of the patients had low levels of B vitamins and folate. There was little association with iron overload, hemolysis, or inflammation. Although the precise mechanism of these deficiencies is unclear, they may contribute to the morbidity of chronically transfused hemoglobinopathy patients.
OTX2 Represses Myogenic and Neuronal Differentiation in Medulloblastoma Cells
Authors: Ren-Yuan Bai, Verena Staedtke, Hart G. Lidov, Charles G. Eberhart, Gregory J. Riggins
Journal: Cancer Research (2012)

Abstract The brain development transcription factor OTX2 is overexpressed and/or genomically amplified in most medulloblastomas, but the mechanistic basis for its contributions in this setting are not understood. In this study, we identified OTX2 as a transcriptional repressor and a gatekeeper of myogenic and neuronal differentiation in medulloblastoma cells. OTX2 binds to the MyoD1 core enhancer through its homeobox domain, and the remarkable repressor activity exhibited by the homeobox domain renders OTX2 transcriptionally repressive. RNA interference–mediated attenuation of OTX2 expression triggered myogenic and neuronal differentiation in vitro and prolonged the survival in an orthotopic medulloblastoma mouse model. Conversely, inducing myogenic conversion of medulloblastoma cells led to the loss of OTX2 expression. In medullomyoblastoma, a medulloblastoma subtype containing muscle elements, myogenic cells share cytogenetic signatures with the primitive tumor cells and OTX2 expression was lost in the differentiated myogenic cells. Thus, OTX2 functions via its homeobox domain as a suppressor of differentiation, and the loss of OTX2 expression is linked to the myogenesis in medullomyoblastoma. Together, our findings illustrate the origin of muscle cells in medullomyoblastomas and the oncogenic mechanism of OTX2 as a repressor of diverse differentiating potential. Cancer Res; 72(22); 5988–6001. ©2012 AACR.