tbuckley/cabot-search huggingface dataset:
Revisiting gonadotrophin-releasing hormone agonist protocols and management of poor ovarian responses to gonadotrophins
Authors: J-N Hugues
Journal: Human Reproduction Update (1998)

Within the past decade, gonadotrophin-releasing hormone (GnRH) agonists have contributed greatly to the success of cycles programmed for in-vitro fertilization and embryo transfer. However, apart from a preventive effect on the luteinizing hormone (LH) surge, most of the beneficial effects of these molecules are still only partly known. A precise analysis of regimens using GnRH agonists for ovarian stimulation shows that many parameters may interfere with the outcome of long-term and short-term protocols. The great variability between these protocols hampers our comprehension of the mechanisms involved in the overall clinical improvement seen with this therapy. The hypothyseal desensitization induced by GnRH agonists is greatly dependent on the dose and duration of their administration, but the residual gonadotrophin secretion is imperfectly estimated by hormonal measurements using radio-immunometric assays. Moreover, the specific role of GnRH agonist-induced ovarian quiescence on subsequent ovarian responsiveness to gonadotrophins and on endometrial receptivity deserves further investigation. Finally, a direct ovarian action of GnRH agonists on steroidogenesis, folliculogenesis and embryo quality is still controversial in humans. These putative deleterious effects of GnRH agonists have led some authors to recommend a reduction of both dose and duration of GnRH agonist administration for women identified by a poor response to gonadotrophins. Using this approach, a few reports have recently shown some clinical advantages for ovarian responsiveness but no convincing evidence for any improvement in pregnancy rate. It thus appears that the overall impact of GnRH agonists on reproductive function is still partly misunderstood. Keywords:GnRH agonist/gonadotrophins/hypophysis/ovary
Plasma Fatty Acid–Binding Protein 4, Nonesterified Fatty Acids, and Incident Diabetes in Older Adults
Authors: Luc Djoussé, Owais Khawaja, Traci M. Bartz, Mary L. Biggs, Joachim H. Ix, Susan J. Zieman, Jorge R. Kizer, Russell P. Tracy, David S. Siscovick, Kenneth J. Mukamal
Journal: Diabetes Care (2012)

To examine the relation of fatty acid-binding protein (FABP)4 and nonesterified fatty acids (NEFAs) to diabetes in older adults.We ascertained incident diabetes among 3,740 Cardiovascular Health Study participants (1992-2007) based on the use of hypoglycemic medications, fasting glucose ≥ 126 mg/dL, or nonfasting glucose ≥ 200 mg/dL. FABP4 and NEFA were measured on specimens collected between 1992 and 1993.Mean age of the 3,740 subjects studied was 74.8 years. For each SD increase in log FABP4, hazard ratios (HRs) for diabetes were 1.35 (95% CI 1.10-1.65) for women and 1.45 (1.13-1.85) for men controlling for age, race, education, physical activity, cystatin C, alcohol intake, smoking, self-reported health status, and estrogen use for women (P for sex-FABP4 interaction 0.10). BMI modified the FABP4-diabetes relation (P = 0.009 overall; 0.02 for women and 0.135 for men), in that statistically significant higher risk of diabetes was mainly seen in men with BMI <25 kg/m(2) (HR per SD: 1.78 [95% CI 1.13-2.81]). There was a modest and nonsignificant association of NEFA with diabetes (P(trend) = 0.21). However, when restricted to the first 5 years of follow-up, multivariable-adjusted HRs for diabetes were 1.0 (ref.), 1.68 (95% CI 1.12-2.53), and 1.63 (1.07-2.50) across consecutive tertiles of NEFA (P(trend) = 0.03).Plasma FABP4 was positively associated with incident diabetes in older adults, and such association was statistically significant in lean men only. A significant positive association between plasma NEFA and incident diabetes was observed during the first 5 years of follow-up.
Cases of Generalised Septic Infection Treated with Antistreptococcus Serum
Authors: F. P. Mackie
Journal: BMJ (1899)

LJAN. 2r, IS9 three pairs of sterilised thread gloves in the tin containing the gauze mops and make my unknown assistant and nurse wear them, I feel that the risk of wound contamination is very greatly diminished because the deterrent effect of the gloved hand upon the unsurgical mind and hand is most marked and salutary, as their unfortunate owner does not feel impelled to feel the patient's pulse or open a door ur window during the trying vicissitudes of any long operation in private practice.
Massive hepatic apoptosis associated with TGF-β1 activation after Fas ligand treatment of IGF binding protein-1–deficient mice
Authors: Julia I. Leu, Mary Ann S. Crissey, Rebecca Taub
Journal: Journal of Clinical Investigation (2003)

Acute liver failure caused by viral hepatitis or toxic damage involves both apoptotic and necrotic pathways. IGF binding protein-1 (IGFBP-1), a hepatocyte-derived secreted protein, is required for normal liver regeneration. To determine whether IGFBP-1 could prevent liver injury that entails direct stimulation of hepatocyte apoptosis, IGFBP-1–/– mice, IGFBP-1+/+ mice, and mice pretreated with Ab’s against IGFBP-1 were treated with a normally sublethal dose of Fas agonist. IGFBP-1 deficiency was associated with massive hepatocyte apoptosis and caspase activation within 3 hours of Fas agonist treatment, which could be corrected by pretreatment with IGFBP-1. IGFBP-1–deficient livers had enhanced signaling via the integrin receptor at early times (0.5 to 1 hour) after Fas agonist treatment accompanied by elevated activated matrix metalloproteinase-9 (MMP-9), a known target of fibronectin signaling and activator of TGF-β. Within 3 hours of Fas agonist treatment, elevated expression of active TGF-β1, a hepatocyte apoptogen, was observed in IGFBP-1–deficient livers that correlated with the appearance of the apoptotic process. Both MMP-9 and TGF-β1 expression were suppressed by IGFBP-1 treatment, supporting their role in the apoptotic process. IGFBP-1–/– mice also displayed increased injury in a toxic hepatic injury model caused by CCl4. These findings indicate that IGFBP-1 functions as a critical hepatic survival factor in the liver by reducing the level of proapoptotic signals.
Stressing the obvious? Cell stress and cell stress proteins in cardiovascular disease
Authors: A SHAMAEITOUSI, J HALCOX, B HENDERSON
Journal: Cardiovascular Research (2006)

It is only some forty years since the discovery of the heat shock or cell stress response and just over twenty years since the heat shock/cell stress response was linked to protein misfolding. The plethora of intracellular proteins which promote correct protein folding in the cell, variously termed molecular chaperones, heat shock proteins, or cell stress proteins, have only been identified in the last fifteen years. During this period it has also been discovered that: (i) molecular chaperones are potent immunogens with immunomodulatory activity and (ii) they can be secreted by cells and exhibit intercellular signaling actions. These various functions of molecular chaperones are increasingly being linked to the pathology of the cardiovascular system. Molecular chaperones within cells can exhibit cardioprotection if their levels are artificially elevated, suggesting that these proteins may have therapeutic activity. In contrast, there is evidence that atherogenesis may be linked to immunity to one specific molecular chaperone, Hsp60. This may offer the possibility of treating atherosclerosis by vaccination. However, there is also growing evidence that secreted molecular chaperones have pro- or anti-inflammatory actions that are relevant to cardiovascular pathology. This review brings these various strands of research together to provide an overview of the role of molecular chaperones in cardiovascular disease.
Viewpoint: untoward effects of beta-adrenoceptor agonists in asthma
Authors: J Morley, S Sanjar, C Newth
Journal: European Respiratory Journal (1990)

Beta-adrenoceptor agonists are potent and selective relaxants of airway smooth muscle. They produce symptomatic bronchodilatory effects and are the most widely used therapy in asthma. In patients with asthma, they usually effect a reduction of airway resistance, but there have been several reports of episodes of increased airway obstruction, arterial hypoxaemia and even death associated with such therapy. "Anomalous or paradoxical bronchospasm" are appropriate terminologies to describe this unexpected phenomenon. Five mechanisms have been proposed to account for anomalous responses to these substances: 1) reactive myogenic tone; 2) metabolic products with spasmogenic activity; 3) adrenoceptor tachyphylaxis; 4) increased inflammatory burden; and 5) induction of airway hyperreactivity. Following a review of the relative merits of each proposal, it is concluded that increased inflammatory burden and induction of airway hyperreactivity, alone or in combination, provide the most plausible explanation for paradoxical bronchospasm.
Jejuno-ileal bypass arthropathy: its clinical features and associations.
Authors: J P Delamere, R M Baddeley, K W Walton
Journal: Annals of the Rheumatic Diseases (1983)

Postoperative arthropathy has been reported in patients undergoing jejunoileal bypass for morbid obesity. The true frequency of this complication, and its independence from preexisting joint disease and from osteomalacia have not been clearly established. Of 107 patients who had undergone jejunoileal bypass, and in whom osteomalacia had been excluded, 38 developed a distinctive arthropathy. This consisted of episodic polyarthralgia, and occasionally arthritis, affecting both large and small joints. The articular symptom complex was independent of other major postoperative complications and unrelated to metabolic disturbances consequent upon rapid weight reduction. Preoperative joint symptoms had a similar incidence in those who did and in those who did not subsequently develop the postoperative arthropathy. Reversal of the intestinal bypass was always associated with an immediate, complete, and permanent remission of arthropathic symptoms.
Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
Authors: Bryony A Thompson, Amanda B Spurdle, John-Paul Plazzer, Marc S Greenblatt, Kiwamu Akagi, Fahd Al-Mulla, Bharati Bapat, Inge Bernstein, Gabriel Capellá, Johan T den Dunnen, Desiree du Sart, Aurelie Fabre, Michael P Farrell, Susan M Farrington, Ian M Frayling, Thierry Frebourg, David E Goldgar, Christopher D Heinen, Elke Holinski-Feder, Maija Kohonen-Corish, Kristina Lagerstedt Robinson, Suet Yi Leung, Alexandra Martins, Pal Moller, Monika Morak, Minna Nystrom, Paivi Peltomaki, Marta Pineda, Ming Qi, Rajkumar Ramesar, Lene Juel Rasmussen, Brigitte Royer-Pokora, Rodney J Scott, Rolf Sijmons, Sean V Tavtigian, Carli M Tops, Thomas Weber, Juul Wijnen, Michael O Woods, Finlay Macrae, Maurizio Genuardi
Journal: Nature Genetics (2013)
Clinicopathological features and prognostic significance of CXCL12 in blastic plasmacytoid dendritic cell neoplasm
Authors: Keiko Hashikawa, Daisuke Niino, Shinichiro Yasumoto, Takekuni Nakama, Junichi Kiyasu, Kensaku Sato, Yoshizo Kimura, Masanori Takeuchi, Yasuo Sugita, Takashi Hashimoto, Koichi Ohshima
Journal: Journal of the American Academy of Dermatology (2011)
Effect of Oral Sebacic Acid on Postprandial Glycemia, Insulinemia, and Glucose Rate of Appearance in Type 2 Diabetes
Authors: Amerigo Iaconelli, Amalia Gastaldelli, Chiara Chiellini, Donatella Gniuli, Angela Favuzzi, Christophe Binnert, Katherine Macé, Geltrude Mingrone
Journal: Diabetes Care (2010)

OBJECTIVE Dicarboxylic acids are natural products with the potential of being an alternate dietary source of energy. We aimed to evaluate the effect of sebacic acid (a 10-carbon dicarboxylic acid; C10) ingestion on postprandial glycemia and glucose rate of appearance (Ra) in healthy and type 2 diabetic subjects. Furthermore, the effect of C10 on insulin-mediated glucose uptake and on GLUT4 expression was assessed in L6 muscle cells in vitro. RESEARCH DESIGN AND METHODS Subjects ingested a mixed meal (50% carbohydrates, 15% proteins, and 35% lipids) containing 0 g (control) or 10 g C10 in addition to the meal or 23 g C10 as a substitute of fats. RESULTS In type 2 diabetic subjects, the incremental glucose area under the curve (AUC) decreased by 42% (P &amp;lt; 0.05) and 70% (P &amp;lt; 0.05) in the 10 g C10 and 23 g C10 groups, respectively. At the largest amounts used, C10 reduced the glucose AUC in healthy volunteers also. When fats were substituted with 23 g C10, AUC of Ra was significantly reduced on the order of 18% (P &amp;lt; 0.05) in both healthy and diabetic subjects. The insulin-dependent glucose uptake by L6 cells was increased in the presence of C10 (38.7 ± 10.3 vs. 11.4 ± 5.4%; P = 0.026). This increase was associated with a 1.7-fold raise of GLUT4. CONCLUSIONS Sebacic acid significantly reduced hyperglycemia after a meal in type 2 diabetic subjects. This beneficial effect was associated with a reduction in glucose Ra, probably due to lowered hepatic glucose output and increased peripheral glucose disposal.
Significance of lymphocytosis in bronchoalveolar lavage in suspected ocular sarcoidosis
Authors: T. Takahashi, A. Azuma, S. Abe, O. Kawanami, K. Ohara, S. Kudoh
Journal: European Respiratory Journal (2001)

Ocular sarcoidosis is frequent in Japan, but in many cases the condition remains undiagnosed in patients with suspected ocular sarcoidosis. Bronchoalveolar lavage (BAL) was performed in order to study the clinical implications of lymphocytosis of BAL fluid in such patients with characteristic ocular manifestations. The subjects included in this study were 39 patients with suspected ocular sarcoidosis. The patients were divided into four types based on high-resolution computed tomography (HRCT) findings; no lung involvement (HRCT-0), bilateral hilar lymphadenopathy (BHL) without lung involvement (HRCT-I), lung involvement and BHL (HRCT-II), and lung involvement and no BHL (HRCT-III). Transbronchial lung biopsy (TBLB) and BAL were conducted after examining serum angiotensin-converting enzyme and serum lysozyme values, skin test for purified protein derivative chest radiograph, HRCT, and gallium scintigram. Twenty patients were histologically diagnosed as having sarcoidosis, and 19 patients remained undiagnosed. Granuloma was identified by TBLB in 19 of 20 patients in type HRCT-II but in only one of 19 patients in types HRCT-0 and HRCT-I (p&lt;0.0001). Lymphocytosis in BAL (&gt;15%) was identified in all patients who showed lung field involvement (type HRCT-II) and in 16 of 19 patients without lung field involvement (types HRCT-0 and HRCT-I). There were 10 patients whose only relevant findings were lymphocytosis in BAL. Among these 10 patients, an increased CD4+/CD8+ ratio (&gt;3.5) in BAL was seen in 60%. The authors conclude that high-resolution computed tomography results yield the same degree of diagnostic accuracy as transbronchial lung biopsy in ocular sarcoidosis suspects. However, bronchoalveolar lavage revealed significant lymphocytosis in patients with negative high-resolution computed tomography results. It should be kept in mind that a diagnostic group of patients with sarcoidosis who manifest ocular involvement and lymphocytosis in bronchoalveolar lavage exists.
Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition
Authors: Alexandre Puissant, Stacey M. Frumm, Gabriela Alexe, Christopher F. Bassil, Jun Qi, Yvan H. Chanthery, Erin A. Nekritz, Rhamy Zeid, William Clay Gustafson, Patricia Greninger, Matthew J. Garnett, Ultan McDermott, Cyril H. Benes, Andrew L. Kung, William A. Weiss, James E. Bradner, Kimberly Stegmaier
Journal: Cancer Discovery (2013)

Bromodomain inhibition comprises a promising therapeutic strategy in cancer, particularly for hematologic malignancies. To date, however, genomic biomarkers to direct clinical translation have been lacking. We conducted a cell-based screen of genetically defined cancer cell lines using a prototypical inhibitor of BET bromodomains. Integration of genetic features with chemosensitivity data revealed a robust correlation between MYCN amplification and sensitivity to bromodomain inhibition. We characterized the mechanistic and translational significance of this finding in neuroblastoma, a childhood cancer with frequent amplification of MYCN. Genome-wide expression analysis showed downregulation of the MYCN transcriptional program accompanied by suppression of MYCN transcription. Functionally, bromodomain-mediated inhibition of MYCN impaired growth and induced apoptosis in neuroblastoma. BRD4 knockdown phenocopied these effects, establishing BET bromodomains as transcriptional regulators of MYCN. BET inhibition conferred a significant survival advantage in 3 in vivo neuroblastoma models, providing a compelling rationale for developing BET bromodomain inhibitors in patients with neuroblastoma.
<i>INF2</i>Mutations in Charcot–Marie–Tooth Disease with Glomerulopathy
Authors: Olivia Boyer, Fabien Nevo, Emmanuelle Plaisier, Benoit Funalot, Olivier Gribouval, Geneviève Benoit, Evelyne Huynh Cong, Christelle Arrondel, Marie-Josèphe Tête, Rodrick Montjean, Laurence Richard, Alexandre Karras, Claire Pouteil-Noble, Leila Balafrej, Alain Bonnardeaux, Guillaume Canaud, Christophe Charasse, Jacques Dantal, Georges Deschenes, Patrice Deteix, Odile Dubourg, Philippe Petiot, Dominique Pouthier, Eric Leguern, Anne Guiochon-Mantel, Isabelle Broutin, Marie-Claire Gubler, Sophie Saunier, Pierre Ronco, Jean-Michel Vallat, Miguel Angel Alonso, Corinne Antignac, Géraldine Mollet
Journal: New England Journal of Medicine (2011)

Charcot–Marie–Tooth neuropathy has been reported to be associated with renal diseases, mostly focal segmental glomerulosclerosis (FSGS). However, the common mechanisms underlying the neuropathy and FSGS remain unknown. Mutations in INF2 were recently identified in patients with autosomal dominant FSGS. INF2 encodes a formin protein that interacts with the Rho-GTPase CDC42 and myelin and lymphocyte protein (MAL) that are implicated in essential steps of myelination and myelin maintenance. We therefore hypothesized that INF2 may be responsible for cases of Charcot–Marie–Tooth neuropathy associated with FSGS.
Quality Measures for Symptoms and Advance Care Planning in Cancer: A Systematic Review
Authors: Karl A. Lorenz, Joanne Lynn, Sydney Dy, Anne Wilkinson, Richard A. Mularski, Lisa R. Shugarman, Rhonda Hughes, Steven M. Asch, Cony Rolon, Afshin Rastegar, Paul G. Shekelle
Journal: Journal of Clinical Oncology (2006)

Measuring quality of care for symptom management and ascertaining patient goals offers an important step toward improving palliative cancer management. This study was designed to identify systematically the quality measures and the evidence to support their use in pain, dyspnea, depression, and advance care planning (ACP), and to identify research gaps.
A Network of High-Mobility Group Box Transcription Factors Programs Innate Interleukin-17 Production
Authors: Nidhi Malhotra, Kavitha Narayan, Ok Hyun Cho, Katelyn E. Sylvia, Catherine Yin, Heather Melichar, Mehdi Rashighi, Veronique Lefebvre, John E. Harris, Leslie J. Berg, Joonsoo Kang
Journal: Immunity (2013)
Mortality among displaced former UNITA members and their families in Angola: a retrospective cluster survey
Authors: T. Grein
Journal: BMJ (2003)

<h3>Objectives</h3> This study tested the concurrent validity of the systemic lupus erythematosus responder index (SRI) in assessing improvement in juvenile-onset systemic lupus erythematosus (jSLE). <h3>Methods</h3> The SRI considers changes in the SELENA–SLEDAI, BILAG and a 3-cm visual analogue scale of physician-rated disease activity (PGA) to determine patient improvement. Using prospectively collected data from 760 unique follow-up visit intervals of 274 jSLE patients, we assessed the sensitivity and specificity of the SRI using these external standards: physician-rated improvement (MD-change), patient/parent-rated major improvement of wellbeing (patient-change) and decrease in prescribed systemic corticosteroids (steroid-change). Modifications of the SRI that considered different thresholds for the SELENA–SLEDAI, BILAG and 10-cm PGA were explored and agreement with the American College of Rheumatology/PRINTO provisional criteria for improvement of jSLE (PCI) was examined. <h3>Results</h3> The sensitivity/specificity in capturing major improvement by the MD-change were 78%/76% for the SRI and 83%/78% for the PCI, respectively. There was fair agreement between the SRI and PCI (kappa=0.35, 95% CI 0.02 to 0.73) in capturing major improvement by the MD-change. Select modified versions of the SRI had improved accuracy overall. All improvement criteria tested had lower sensitivity when considering patient-change and steroid-change as external standards compared to MD-change. <h3>Conclusions</h3> The SRI and its modified versions based on meaningful changes in jSLE have high specificity but at most modest sensitivity for capturing jSLE improvement. When used as an endpoint of clinical trials in jSLE, the SRI will provide a conservative estimate regarding the efficacy of the therapeutic agent under investigation.
Combined Administration of Rituximab and ON 013105 Induces Apoptosis in Mantle Cell Lymphoma Cells and Reduces Tumor Burden in a Mouse Model of Mantle Cell Lymphoma
Authors: Anil Prasad, Ashutosh Shrivastava, Evangelos Papadopoulos, Paula M. Kuzontkoski, M.V. Ramana Reddy, Amanda M. Gillum, Ramesh Kumar, E. Premkumar Reddy, Jerome E. Groopman
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Mantle cell lymphoma (MCL) is an incurable B-cell lymphoma, and new therapeutic strategies are urgently needed. Experimental Design: The effects of ON 013105, a novel benzylstyryl sulfone kinase inhibitor, alone or with doxorubicin or rituximab, were examined in Granta 519 and Z138C cells. For in vivo studies, CB17/SCID mice were implanted subcutaneously with Z138C cells and treated with various combinations of ON 013105, doxorubicin, and rituximab. Tumor burden and body weight were monitored for 28 days. Results: ON 013105 induced mitochondria-mediated apoptosis in MCL cells. Death was preceded by translocation of tBid to the mitochondria and cytochrome c release. In addition, ON 013105–treated cells exhibited reduced levels of cyclin D1, c-Myc, Mcl-1, and Bcl-xL. Using nuclear magnetic resonance (NMR) spectroscopy, we showed specific binding of ON 013105 to eIF4E, a critical factor for the initiation of protein translation. We proffer that this drug–protein interaction preferentially prevents the translation of the aforementioned proteins and may be the mechanism by which ON 013105 induces apoptosis in MCL cells. Efficacy studies in a mouse xenograft model showed that ON 013105 inhibited MCL tumor growth and that combining ON 013105 with rituximab reduced tumor burden further with negligible unwanted effects. Conclusions: Our findings suggest that ON 013105, alone or in combination with rituximab, may be a potent therapeutic agent to treat MCLs. Clin Cancer Res; 19(1); 85–95. ©2012 AACR.