tbuckley/cabot-search huggingface dataset:
Ovarian antral folliculogenesis during the human menstrual cycle: a review
Authors: Angela R. Baerwald, Gregg P. Adams, Roger A. Pierson
Journal: Human Reproduction Update (2011)

Ovarian follicles undergo dynamic morphologic and endocrinologic changes during the human menstrual cycle. The physiologic mechanisms underlying recruitment and selection of antral follicles in women are not fully elucidated. A comprehensive review of >200 studies was conducted using PubMed. The objective was to compare and contrast different perspectives on human antral folliculogenesis. Antral folliculogenesis has been studied using histologic, endocrinologic and/or ultrasonographic techniques. Different theories of antral follicle recruitment include: (i) continuous recruitment throughout the menstrual cycle; (ii) recruitment of a 'cohort' of antral follicles once in the late-luteal phase or early-follicular phase of each cycle and (iii) recruitment of two or three 'cohorts' or 'waves' during each cycle. Generally, a single dominant follicle is selected in the mid-follicular phase of each cycle and this follicle ovulates at mid-cycle. However, a dominant follicle may also be selected during anovulatory waves that precede the ovulatory wave in some women. There is increasing evidence to indicate that multiple waves of antral follicles develop during the human menstrual cycle. Ovarian follicular waves in women are comparable with those documented in several animal species; however, species-specific differences exist. Enhancing our understanding of the endocrine and paracrine mechanisms underlying antral follicular wave dynamics has clinical implications for understanding age-related changes in reproductive function, optimizing hormonal contraceptive and ovarian stimulation regimens and identifying non-invasive markers of the physiologic status of follicles which are predictive of oocyte competence and assisted reproduction outcomes.
Lysinuric protein intolerance. Basolateral transport defect in renal tubuli.
Authors: J Rajantie, O Simell, J Perheentupa
Journal: Journal of Clinical Investigation (1981)

In patients with an autosomal recessive diamino acid transport disorder, lysinuric protein intolerance (LPI), we measured plasma and urinary amino acids basally, and during intravenous infusion of citrulline at two rates. Compared with controls, the patients' plasma citrulline concentrations rose similarly, but urinary citrulline excretion increased excessively. Their plasma arginine and ornithine levels rose subnormally, but massive argininuria and moderate ornithinuria appeared. The excretion rates of the third diamino acid lysine and other amino acids remained practically unaltered, thus excluding mutual competition as the cause for the increases. The results suggest that (a) in the normal kidney reabsorption involves partial conversion of citrulline to arginine and ornithine (metabolic run-out), (b) in LPI, the diamino acid transport defect is located at the basolateral cell membrane of the renal tubules; this inhibits the efflux of arginine and ornithine, increasing their cellular concentration, which in turn inhibits the metabolic disposal of citrulline, and causes leakage of arginine, ornithine, and citrulline into the tubular lumen.
A Risk Prediction Model for the Assessment and Triage of Women with Hypertensive Disorders of Pregnancy in Low-Resourced Settings: The miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) Multi-country Prospective Cohort Study
Authors: Beth A. Payne, Jennifer A. Hutcheon, J. Mark Ansermino, David R. Hall, Zulfiqar A. Bhutta, Shereen Z. Bhutta, Christine Biryabarema, William A. Grobman, Henk Groen, Farizah Haniff, Jing Li, Laura A. Magee, Mario Merialdi, Annettee Nakimuli, Ziguang Qu, Rozina Sikandar, Nelson Sass, Diane Sawchuck, D. Wilhelm Steyn, Mariana Widmer, Jian Zhou, Peter von Dadelszen
Journal: PLoS Medicine (2014)

Beth Payne and colleagues use a risk prediction model, the Pre-eclampsia Integrated Estimate of RiSk (miniPIERS) to help inform the clinical assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings. Please see later in the article for the Editors' Summary
Novel Targeted Therapies for Eosinophil-Associated Diseases and Allergy
Authors: Susanne Radonjic-Hoesli, Peter Valent, Amy D. Klion, Michael E. Wechsler, Hans-Uwe Simon
Journal: The Annual Review of Pharmacology and Toxicology (2014)

Eosinophil-associated diseases often present with life-threatening manifestations and/or chronic organ damage. Currently available therapeutic options are limited to a few drugs that often have to be prescribed on a lifelong basis to keep eosinophil counts under control. In the past 10 years, treatment options and outcomes in patients with clonal eosinophilic and other eosinophilic disorders have improved substantially. Several new targeted therapies have emerged, addressing different aspects of eosinophil expansion and inflammation. In this review, we discuss available and currently tested agents as well as new strategies and drug targets relevant to both primary and secondary eosinophilic diseases, including allergic disorders.
Hormone Therapy Failure in Human Prostate Cancer: Analysis by Complementary DNA and Tissue Microarrays
Authors: L. Bubendorf, M. Kolmer, J. Kononen, P. Koivisto, S. Mousses, Y. Chen, E. Mahlamaki, P. Schraml, H. Moch, N. Willi, A. G. Elkahloun, T. G. Pretlow, T. C. Gasser, M. J. Mihatsch, G. Sauter, O.-P. Kallioniemi
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: The molecular mechanisms underlying the progression of prostate cancer during hormonal therapy have remained poorly understood. In this study, we developed a new strategy for the identification of differentially expressed genes in hormone-refractory human prostate cancer by use of a combination of complementary DNA (cDNA) and tissue microarray technologies. METHODS: Differences in gene expression between hormone-refractory CWR22R prostate cancer xenografts (human prostate cancer transplanted into nude mice) and a xenograft of the parental, hormone-sensitive CWR22 strain were analyzed by use of cDNA microarray technology. To validate the data from cDNA microarrays on clinical prostate cancer specimens, a tissue microarray of specimens from 26 prostates with benign prostatic hyperplasia, 208 primary prostate cancers, and 30 hormone-refractory local recurrences was constructed and used for immunohistochemical detection of protein expression. RESULTS: Among 5184 genes surveyed with cDNA microarray technology, expression of 37 (0.7%) was increased more than twofold in the hormone-refractory CWR22R xenografts compared with the CWR22 xenograft; expression of 135 (2.6%) genes was reduced by more than 50%. The genes encoding insulin-like growth factor-binding protein 2 (IGFBP2) and 27-kd heat-shock protein (HSP27) were among the most consistently overexpressed genes in the CWR22R tumors. Immunohistochemical analysis of tissue microarrays demonstrated high expression of IGFBP2 protein in 100% of the hormone-refractory clinical tumors, in 36% of the primary tumors, and in 0% of the benign prostatic specimens (two-sided P = .0001). Overexpression of HSP27 protein was demonstrated in 31% of the hormone-refractory tumors, in 5% of the primary tumors, and in 0% of the benign prostatic specimens (two-sided P = .0001). CONCLUSIONS: The combination of cDNA and tissue microarray technologies enables rapid identification of genes associated with progression of prostate cancer to the hormone-refractory state and may facilitate analysis of the role of the encoded gene products in the pathogenesis of human prostate cancer.
Early determinants of long-term T-cell reconstitution after hematopoietic stem cell transplantation for severe combined immunodeficiency
Authors: José A. Borghans, Robbert G. Bredius, Mette D. Hazenberg, Helene Roelofs, Els C. Jol-van der Zijde, Jeroen Heidt, Sigrid A. Otto, Taco W. Kuijpers, Willem E. Fibbe, Jaak M. Vossen, Frank Miedema, Maarten J. van Tol
Journal: Blood (2006)
Pulmonary veno-occlusive disease in a HIV-infected intravenous drug abuser
Authors: R Escamilla, C Hermant, J Berjaud, C Mazerolles, X Daussy
Journal: European Respiratory Journal (1995)

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension. Its origin remains unknown but in some cases a viral aetiology has been suggested. Recently primary pulmonary hypertension has been increasingly observed in patients with human immunodeficiency virus (HIV) infection, but only one case of pulmonary veno-occlusive disease has so far been described. We report the case of a 27 year old male intravenous drug abuser with HIV infection and pulmonary hypertension. Open lung biopsy led to the diagnosis of pulmonary veno-occlusive disease. This second case of pulmonary veno-occlusive disease raises the question of a relationship between HIV infection and lesions involving the pulmonary veins. However, the pathogenesis of vascular changes remains to be elucidated.
Recognizing features that are dissimilar in male and female breast cancer: expression of p21Waf1 and p27Kip1 using an immunohistochemical assay
Authors: G. Curigliano, M. Colleoni, G. Renne, G. Mazzarol, R. Gennari, G. Peruzzotti, F. de Braud, C. Robertson, E. Maiorano, P. Veronesi, F. Nolè, M. Mandalà, G. Ferretti, G. Viale, A. Goldhirsch
Journal: Annals of Oncology (2002)
US Congress debates stemcell research
Authors: J. Ciment
Journal: BMJ (1999)

The controversy surrounding the recent harvesting and culture of human embryonic stem cells—the cells that form within days after fertilisation and transform into all other forms of human cells as a fetus develops—was debated last week by the US Congress.

The ban on federal funding for research using human embryos should be lifted, argued Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania. He was giving …
Niclosamide: An Established Antihelminthic Drug as a Potential Therapy Against S100A4-Mediated Metastatic Colon Tumors
Authors: D. M. Helfman
Journal: JNCI Journal of the National Cancer Institute (2011)

Progression of cancers because of the ability of primary tumor cells to grow outside their local environment and spread to distant sites (metastasize) is a major problem and a major cause of death from cancers. Patients with non-metastatic local stage I tumor have a 5-year survival rate of 90%, which drops to approximately 10% in patients with distant metastasis at the time of diagnosis. Therefore, it is important to identify genes that mediate metastasis and develop effective therapies against these potential targets.
Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer: a retrospective analysis
Authors: Wilko Weichert, Annika Röske, Volker Gekeler, Thomas Beckers, Matthias PA Ebert, Matthias Pross, Manfred Dietel, Carsten Denkert, Christoph Röcken
Journal: The Lancet Oncology (2008)
Sulfonylureas, ATP-sensitive K+ channels, and cellular K+ loss during hypoxia, ischemia, and metabolic inhibition in mammalian ventricle.
Authors: N Venkatesh, S T Lamp, J N Weiss
Journal: Circulation Research (1991)

Sulfonylurea derivatives glibenclamide and tolbutamide are selective blockers of ATP-sensitive K+ (KATP) channels. However, their ability to prevent cellular K+ loss and shortening of action potential duration during ischemia or hypoxia in the intact heart is modest compared with their efficacy at blocking KATP channels in excised membrane patches. In the isolated arterially perfused rabbit interventricular septum, the increase in unidirectional K+ efflux and shortening of action potential duration during substrate-free hypoxia were effectively blocked by glibenclamide, but only by very high concentrations (100 microM); during hypoxia with glucose present, glibenclamide was only partially effective at reducing K+ loss. During total global ischemia (10 minutes), up to 100 microM glibenclamide or 1 mM tolbutamide attenuated shortening of action potential duration but only reduced [K+]0 accumulation by a maximum of 32 +/- 6%. In isolated patch-clamped guinea pig ventricular myocytes in which the whole-cell ATP-sensitive K+ current was activated by exposure to the metabolic inhibitors, glibenclamide (up to 100 microM) and tolbutamide (10 mM) were only partially effective at blocking the whole-cell ATP-sensitive K+ current (maximum block, 51 +/- 10% and 50 +/- 9%, respectively), especially when ADP was included in the patch electrode solution. In inside-out membrane patches excised from these myocytes, glibenclamide blocked unitary currents through KATP channels with a Kd of 0.5 microM and a Hill coefficient of 0.5 in the absence of ADP at the cytosolic membrane surface, but block was incomplete when 100 microM ADP (+2 mM free Mg2+) was present. ADP had a similar effect on block of KATP channels by tolbutamide. These findings suggest that free cytosolic [ADP], which rises rapidly to the 100 microM range during early myocardial ischemia and hypoxia, may account for the limited efficacy of sulfonylureas at blocking ischemic and hypoxic cellular K+ loss under these conditions.
An Autoimmune Response Signature Associated with the Development of Triple-Negative Breast Cancer Reflects Disease Pathogenesis
Authors: Hiroyuki Katayama, Clayton Boldt, Jon J. Ladd, Melissa M. Johnson, Timothy Chao, Michela Capello, Jinfeng Suo, Jianning Mao, JoAnn E. Manson, Ross Prentice, Francisco Esteva, Hong Wang, Mary L. Disis, Samir Hanash
Journal: Cancer Research (2015)

Abstract The repertoire of antigens associated with the development of an autoimmune response in breast cancer has relevance to detection and treatment strategies. We have investigated the occurrence of autoantibodies associated with the development of triple-negative breast cancer (TNBC) in the before diagnosis setting and in samples collected at the time of diagnosis of TNBC. Lysate arrays containing protein fractions from the TNBC MDA-MB-231 cell line were hybridized with TNBC plasmas from the Women's Health Initiative cohort, collected before clinical diagnosis and with plasmas from matched controls. An immune response directed against spliceosome and glycolysis proteins was observed with case plasmas as previously reported in estrogen receptor+ breast cancer. Importantly, autoantibodies directed against networks involving BRCA1, TP53, and cytokeratin proteins associated with a mesenchymal/basal phenotype were distinct to TNBC before diagnosis samples. Concordant autoantibody findings were observed with mouse plasma samples collected before occurrence of palpable tumors from a C3(1)-T triple negative mouse model. Plasma samples collected at the time of diagnosis of stage II TNBC and from matched healthy controls were subjected to proteomic analysis by mass spectrometry to identify Ig-bound proteins yielding a predominance of cytokeratins, including several associated with a mesenchymal/basal phenotype among cases compared with controls. Our data provide evidence indicative of a dynamic repertoire of antigens associated with a humoral immune response reflecting disease pathogenesis in TNBC. Cancer Res; 75(16); 3246–54. ©2015 AACR.
Src-like Adaptor Protein (Slap) Is a Negative Regulator of T Cell Receptor Signaling
Authors: Tomasz Sosinowski, Akhilesh Pandey, Vishva M. Dixit, Arthur Weiss
Journal: The Journal of Experimental Medicine (2000)

Initiation of T cell antigen receptor (TCR) signaling is dependent on Lck, a Src family kinase. The Src-like adaptor protein (SLAP) contains Src homology (SH)3 and SH2 domains, which are highly homologous to those of Lck and other Src family members. Because of the structural similarity between Lck and SLAP, we studied its potential role in TCR signaling. Here, we show that SLAP is expressed in T cells, and that when expressed in Jurkat T cells it can specifically inhibit TCR signaling leading to nuclear factor of activated T cells (NFAT)-, activator protein 1 (AP-1)–, and interleukin 2–dependent transcription. The SH3 and SH2 domains of SLAP are required for maximal attenuation of TCR signaling. This inhibitory activity can be bypassed by the combination of phorbol myristate acetate (PMA) and ionomycin, suggesting that SLAP acts proximally in the TCR signaling pathway. SLAP colocalizes with endosomes in Jurkat and in HeLa cells, and is insoluble in mild detergents. In stimulated Jurkat cells, SLAP associates with a molecular signaling complex containing CD3ζ, ZAP-70, SH2 domain–containing leukocyte protein of 76 kD (SLP-76), Vav, and possibly linker for activation of T cells (LAT). These results suggest that SLAP is a negative regulator of TCR signaling.
Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin
Authors: Lilian I. Plotkin, Robert S. Weinstein, A. Michael Parfitt, Paula K. Roberson, Stavros C. Manolagas, Teresita Bellido
Journal: Journal of Clinical Investigation (1999)

Glucocorticoid-induced osteoporosis may be due, in part, to increased apoptosis of osteocytes and osteoblasts, and bisphosphonates (BPs) are effective in the management of this condition. We have tested the hypothesis that BPs suppress apoptosis in these cell types. Etidronate, alendronate, pamidronate, olpadronate, or amino-olpadronate (IG9402, a bisphosphonate that lacks antiresorptive activity) at 10–9 to 10–6 M prevented apoptosis of murine osteocytic MLO-Y4 cells, whether it was induced by etoposide, TNF-α, or the synthetic glucocorticoid dexamethasone. BPs also inhibited apoptosis of primary murine osteoblastic cells isolated from calvaria. Similar antiapoptotic effects on MLO-Y4 and osteoblastic cells were seen with nanomolar concentrations of the peptide hormone calcitonin. The antiapoptotic effect of BPs and calcitonin was associated with a rapid increase in the phosphorylated fraction of extracellular signal regulated kinases (ERKs) and was blocked by specific inhibitors of ERK activation. Consistent with these in vitro results, alendronate abolished the increased prevalence of apoptosis in vertebral cancellous bone osteocytes and osteoblasts that follows prednisolone administration to mice. These results suggest that the therapeutic efficacy of BPs or calcitonin in diseases such as glucocorticoid-induced osteoporosis may be due, in part, to their ability to prevent osteocyte and osteoblast apoptosis.
The Impact of the Organization of High-Dependency Care on Acute Hospital Mortality and Patient Flow for Critically Ill Patients
Authors: Hannah Wunsch, David A. Harrison, Andrew Jones, Kathryn Rowan
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: Little is known about the utility of provision of high-dependency care (HDC) that is in a geographically separate location from a primary intensive care unit (ICU).Objectives: To determine whether the availability of HDC in a geographically separate unit affects patient flow or mortality for critically ill patients.Methods: Admissions to ICUs in the United Kingdom, from 2009 to 2011, who received Level 3 intensive care in the first 24 hours after admission and subsequently Level 2 HDC. We compared differences in patient flow and outcomes for patients treated in hospitals providing some HDC in a geographically separate unit (dual HDC) with patients treated in hospitals providing all HDC in the same unit as intensive care (integrated HDC) using multilevel mixed effects models.Measurements and Main Results: In 192 adult general ICUs, 21.4% provided dual HDC. Acute hospital mortality was no different for patients cared for in ICUs with dual HDC versus those with integrated HDC (adjusted odds ratio, 0.94 [0.86–1.03]; P = 0.16). Dual HDC was associated with a decreased likelihood of a delayed discharge from the primary unit. However, total duration of critical care and the likelihood of discharge from the primary unit at night were increased with dual HDC.Conclusions: Availability of HDC in a geographically separate unit does not impact acute hospital mortality. The potential benefit of decreasing delays in discharge should be weighed against the increased total duration of critical care and greater likelihood of a transfer out of the primary unit at night.
The art of medicine in treating osteoarthritis: I will please
Authors: J W J Bijlsma, P M J Welsing
Journal: Annals of the Rheumatic Diseases (2008)

The Latin word placebo literally means, “I will please”. Until 1945 the placebo was a “morally” useful but innocuous management tool without curative or symptomatic consequences. When in the 1950s the double-blind randomised controlled trial (RCT) began to establish itself, the placebo was imbued with powerful therapeutic effects and its ethical use in clinical practice was being questioned.1 In a few years the placebo changed from what was called the “humble humbug” (a means of reinforcing a patient’s confidence in his recovery) to an entity with occult-like powers that could mimic potent drugs.

Nowadays placebo is primarily used within the RCT setting; use in clinical practice is generally considered unethical. In the current literature placebo is described as “inert”, “inactive” or “non-specific” and as “dummy” or “sham” treatment in the context of a RCT. An “active” treatment not expected to be useful for the complaints at hand, however, might work on the same principal. When we ask experienced doctors for their opinion on observed placebo effect we receive quite some contradictory responses. Conflicting explanations such as expectation, anxiety relief, faith, patient–doctor relationship, self-perceptions, classic conditioning, symbolic processes, holistic approach, fraud and tricking patients are mentioned among others.

Some of these feelings became apparent in the recent discussion of treatment of osteoarthritis (OA) with glucosamin. A long awaited “definite” trial, the GAIT (Glucosamin/chondroitin Arthritis Intervention Trial) had some remarkable results.2 In this study, patients with symptomatic (with more then half also radiological) knee OA were randomised to five treatment groups: glucosamin, chondroitin sulphate, a combination of glucosamin and chondroitin sulphate, celecoxib and placebo. Primary outcome was a decrease of at least 20% in pain measured by the Western Ontario and McMaster Universities (WOMAC) score. This outcome was reached in 64% of the glucosamin group, 65% of the chondroitin sulphate …