tbuckley/cabot-search huggingface dataset:
Clinical significance of worsening versus stable preradiographic MRI lesions in a cohort study of persons at higher risk for knee osteoarthritis
Authors: Leena Sharma, Michael Nevitt, Marc Hochberg, Ali Guermazi, Frank W Roemer, Michel Crema, Charles Eaton, Rebecca Jackson, Kent Kwoh, Jane Cauley, Orit Almagor, Joan S Chmiel
Journal: Annals of the Rheumatic Diseases (2015)

Background Whether preradiographic lesions in knees at risk for osteoarthritis are incidental versus disease is unclear. We hypothesised, in persons without but at higher risk for knee osteoarthritis, that: 12–48 month MRI lesion status worsening is associated with 12–48 month incident radiographic osteoarthritis (objective component of clinical definition of knee osteoarthritis) and 48–84 month persistent symptoms. Methods In 849 Osteoarthritis Initiative participants Kellgren/Lawrence (KL) 0 in both knees, we assessed cartilage damage, bone marrow lesions (BMLs), and menisci on 12 month (baseline) and 48 month MRIs. Multivariable logistic regression was used to evaluate associations between 12–48 month worsening versus stable status and outcome (12–48 month incident KL ≥1 and KL ≥2, and 48–84 month persistent symptoms defined as frequent symptoms or medication use most days of ≥1 month in past 12 month, at consecutive visits 48–84 months), adjusting for age, gender, body mass index (BMI), injury and surgery. Results Mean age was 59.6 (8.8), BMI 26.7 (4.2) and 55.9% were women. 12–48 month status worsening of cartilage damage, meniscal tear, meniscal extrusion, and BMLs was associated with 12–48 month incident radiographic outcomes, and worsening of cartilage damage and BMLs with 48–84 month persistent symptoms. There was a dose-response association for magnitude of worsening of cartilage damage, meniscal tear, meniscal extrusion, and BMLs and radiographic outcomes, and cartilage damage and BMLs and persistent symptoms. Conclusions In persons at higher risk, worsening MRI lesion status was associated with concurrent incident radiographic osteoarthritis and subsequent persistent symptoms. These findings suggest that such lesions represent early osteoarthritis, and add support for a paradigm shift towards investigation of intervention effectiveness at this stage.
Sensory Evoked Potentials in Clinical Disorders of the Nervous System
Authors: A Starr
Journal: Annual Review of Neuroscience (1978)

Ann. Rev, Neurosci. 1978. 13103-27 Copyright (C3 1978 by Annual Review; Inc. All rightr reserved SENSORY EVOKED 011505 POTENTIALS IN CLINICAL DISORDERS OF THE NERVOUS SYSTEM A. Starr Department of Neurology, University of California Irvine Medical Center, Orange, California 92668 INTRODUCTION The diagnostic tools presently used by clinicians in the field of neuroscience provide useful information about the structure of the nervous system, but fall short with respect to providing insights into function. For this, the clinician must still rely on history, physical examination, and the patient’s own description of the experience of his disorder. The search for relatively noninvasive, simple tests of brain function has stimulated the recent development of sensory evoked potentials recorded from the scalp as low-risk, clinically applicable procedures capable of providing new and objective information about a variety of nervous system functions. In this review I summarize the various applications of auditory, visual, and somatosensory evoked potentials to the study of clinical neurological disorders in man, beginning with a brief description of the stimuli employed, normal patterns of evoked potentials, stimulus and subject variables that inﬂuence these potentials, and their probable neural generators. Clinical applications are analyzed with reference to each sensory system rather than according to disease states. Table 1 contains a listing of the various types of auditory, visual, and somatosensory evoked potentials based on their presumed sites of origin from along the sensory pathway. The evoked potential wave forms are included in the ﬁgures and the technical details of their recording are in Table 2. Sensory evoked potentials were among the earliest measures used to study the functions of the brain (Lindsley 1969, Davis 1976, Bergamini & Bergamasco 1967). While techniques for quantifying intracellular and single neuronal activity now predominate in the study of other animals, interest in evoked potentials persists particularly for the analysis of human brain functions. Moreover, the development 103 0147-006X/78/0325-0l03$01.00
Pulmonary macrophages: key players in the innate defence of the airways
Authors: Adam J Byrne, Sara A Mathie, Lisa G Gregory, Clare M Lloyd
Journal: Thorax (2015)

Macrophages are the most numerous immune-cells present in the lung environment under homoeostatic conditions and are ideally positioned to dictate the innate defence of the airways. Pulmonary macrophage populations are heterogeneous and demonstrate remarkable plasticity, owing to variations in origin, tissue residency and environmental influences. Lung macrophage diversity facilitates considerable specialisation, aids efficient responses to environmental signals and allows rapid alterations in phenotype and physiology in response to a plethora of cytokines and microbial signals. This review describes pulmonary macrophage origins, phenotypes, roles in diseases of the airways and implications for the treatment of respiratory disease.
Homoharringtonine as a new antileukemic agent.
Authors: T Ohnuma, J F Holland
Journal: Journal of Clinical Oncology (1985)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1985.3.5.604 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3889228 Homoharringtonine as a new antileukemic agent. T OhnumaxT OhnumaSearch for articles by this author , J F HollandxJ F HollandSearch for articles by this author https://doi.org/10.1200/JCO.1985.3.5.604 First Page PDF © 1985 by American Society of Clinical Oncology
Abstract 2669: Chaetoglobosin K, an Akt pathway inhibitor, prevents proliferation and migration of prostate carcinoma cells
Authors: Amna Ali, Silvia Caggia, Diane F. Matesic, Shafiq A. Khan
Journal: Cancer Research (2015)

Abstract Chaetoglobosin K (ChK) is an indolylcytochalasin isolated from the fungus Diplodia macrospora that has shown anti-tumorigenic effects in multiple human lung and ovarian carcinoma cell lines. We have previously reported that ChK decreases Akt activation and modulates key downstream Akt/mTOR pathway effectors in tumorigenic cells. The down-regulation of Akt activation by ChK is independent of class I PI3K enzyme inhibition or the upstream mediators PDK1, PTEN, and mTORC2. The purpose of these studies was to investigate the effect of ChK on the proliferation and migration of prostate carcinoma cells of various metastatic potential and PTEN status. The activation of Akt was monitored to assess the ability of ChK to inhibit Akt in prostate carcinoma cells. In these studies, MTT assays were used to measure the number of viable PC3, DU145, and LNCaP cells treated with ChK. Scratch wound and transwell migration assays were utilized to examine the effect of ChK on cell migration. To assess Akt activation, western blot analysis was performed to measure changes in Akt phosphorylation at the ser473 and thr308 sites after cells were treated with ChK or vehicle. ChK was found to inhibit the number of viable PC3, DU145, and LNCaP cells with IC50 values in the 3-5μM range. ChK inhibited migration of PC3 cells into the wound space at 1μM by approximately 60% after 72 hours as compared to vehicle treated controls. ChK inhibited transwell migration of PC3 cells by greater than 90% compared to controls after 5 hours. Additionally, ChK treatment lowered Akt phosphorylation at key activation sites. In summary, ChK inhibits the proliferation, migration, and Akt activation of prostate carcinoma cells in vitro. Further mechanistic studies of ChK will substantiate its therapeutic potential in the treatment of prostate and other cancers. Citation Format: Amna Ali, Silvia Caggia, Diane F. Matesic, Shafiq A. Khan. Chaetoglobosin K, an Akt pathway inhibitor, prevents proliferation and migration of prostate carcinoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2669. doi:10.1158/1538-7445.AM2015-2669
Left Ventricular Function in Acute and Chronic Coronary Artery Disease
Authors: C E Rackley, R O Russell
Journal: Annual Review of Medicine (1975)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Part 12: Pediatric Advanced Life Support
Authors: Allan R. de Caen, Marc D. Berg, Leon Chameides, Cheryl K. Gooden, Robert W. Hickey, Halden F. Scott, Robert M. Sutton, Janice A. Tijssen, Alexis Topjian, Élise W. van der Jagt, Stephen M. Schexnayder, Ricardo A. Samson
Journal: Circulation (2015)
Bioactivation in Chemical Teratogenesis
Authors: M R Juchau
Journal: The Annual Review of Pharmacology and Toxicology (1989)

Within the past decade, interest has increased markedly in the elucidation of mechanisms whereby drugs and other chemicals can alter the normal developmental pattern of the developing conceptus. This has, in large measure, been attributable to the recent availability of methods for the successful long-term culture of whole embryos as well as various embryonic tissues (e.g. limb buds). These preparations have enabled a more straightforward investigation of the direct effects of chemicals on the conceptus per se, without the complicating and frequently confounding participation of maternal factors. The demonstration that exogenous metabolic preparations could be incorporated into such culture systems has enabled investigators to pursue questions about the nature of proximate and ultimate chemical species responsible for producing abnormal morphogenesis. Demonstrations of the capacity of the early conceptus to effect profound dysmorphogenic bioactivation provide additional relevance to such questions. Elucidation of the identity of the chemical species represents a first and necessary step in unravelling the pathogenic mechanism. Control of their rates of generation and inactivation or elimination are probable major determinants of incidence/severity of chemically induced embryotoxicity. Future investigations of these phenomena promise to yield key contributions to the discovery of mechanisms in chemical teratogenesis.
Depressive Symptoms in Youth With Type 1 or Type 2 Diabetes: Results of the Pediatric Diabetes Consortium Screening Assessment of Depression in Diabetes Study
Authors: Janet Silverstein, Peiyao Cheng, Katrina J. Ruedy, Craig Kollman, Roy W. Beck, Georgeanna J. Klingensmith, Jamie R. Wood, Steven Willi, Fida Bacha, Joyce Lee, Eda Cengiz, Maria J. Redondo, William V. Tamborlane
Journal: Diabetes Care (2015)

OBJECTIVE To evaluate the frequency of depressive symptoms and the diagnosis and management of depression in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D) enrolled in the Pediatric Diabetes Consortium T1D and T2D registries. RESEARCH DESIGN AND METHODS The Children’s Depression Inventory (CDI) 2 Self-Report (Short) version was completed by 261 T1D and 339 T2D youth aged 10–17 years. RESULTS Symptoms of depression were identified in 13% of T1D and 22% of T2D (P = 0.007) participants; of these, only 4% of T1D and 9% of T2D youth were treated by a therapist within the prior 12 months. Depressive symptoms were associated with lower family income (P = 0.006) and obesity (P = 0.002) in T1D but not T2D youth. CONCLUSIONS Depressive symptoms are more frequent than diagnosed depression in youth with T1D or T2D. These results underscore the need for regular depression screening and appropriate referral for youth with diabetes.
Treatment during a vulnerable developmental period rescues a genetic epilepsy
Authors: Stephan Lawrence Marguet, Vu Thao Quyen Le-Schulte, Andrea Merseburg, Axel Neu, Ronny Eichler, Igor Jakovcevski, Anton Ivanov, Ileana Livia Hanganu-Opatz, Christophe Bernard, Fabio Morellini, Dirk Isbrandt
Journal: Nature Medicine (2015)
Safeguarding human health in the Anthropocene epoch: report of The Rockefeller Foundation – Lancet Commission on planetary health. Making the sustainable development goals operational through an urban agenda: perspectives from science
Authors: Sarah Whitmee, Andy Haines, Chris Beyrer, Frederick Boltz, Anthony G. Capon, Braulio Ferreira D.S Dias, Alex Ezeh, Howard Frumkin, Peng Gong, Peter Head, Richard Horton, Georgina M. Mace, Robert Marten, Samuel S. Myers, Sania Nishtar, Steven A. Osofsky, Subhrendu K. Pattanayak, Montira J. Pongsiri, Cristina Romanelli, Agnes Soucat, Jeanette Vega, Derek Yach
Journal: The Lancet (2015)
Genomic Characterization of a South American<i>Phytophthora</i>Hybrid Mandates Reassessment of the Geographic Origins of<i>Phytophthora infestans</i>
Authors: Michael D. Martin, Filipe G. Vieira, Simon Y.W. Ho, Nathan Wales, Mikkel Schubert, Andaine Seguin-Orlando, Jean B. Ristaino, M. Thomas P. Gilbert
Journal: Molecular Biology and Evolution (2015)

As the oomycete pathogen causing potato late blight disease, Phytophthora infestans triggered the famous 19th-century Irish potato famine and remains the leading cause of global commercial potato crop destruction. But the geographic origin of the genotype that caused this devastating initial outbreak remains disputed, as does the New World center of origin of the species itself. Both Mexico and South America have been proposed, generating considerable controversy. Here, we readdress the pathogen's origins using a genomic data set encompassing 71 globally sourced modern and historical samples of P. infestans and the hybrid species P. andina, a close relative known only from the Andean highlands. Previous studies have suggested that the nuclear DNA lineage behind the initial outbreaks in Europe in 1845 is now extinct. Analysis of P. andina's phased haplotypes recovered eight haploid genome sequences, four of which represent a previously unknown basal lineage of P. infestans closely related to the famine-era lineage. Our analyses further reveal that clonal lineages of both P. andina and historical P. infestans diverged earlier than modern Mexican lineages, casting doubt on recent claims of a Mexican center of origin. Finally, we use haplotype phasing to demonstrate that basal branches of the clade comprising Mexican samples are occupied by clonal isolates collected from wild Solanum hosts, suggesting that modern Mexican P. infestans diversified on Solanum tuberosum after a host jump from a wild species and that the origins of P. infestans are more complex than was previously thought.
Chlorophylls purified by a new large-scale method inhibit aflatoxin carcinogenesis in the rat
Authors: Carole Jubert, Mike Simonich, Bill Roebuck, Gayle Orner, Rod Dashwood, David Williams, George Bailey
Journal: Cancer Research (2006)

3928   Commercially available chlorophylls lack the purity or cost efficiency to be used in whole-animal cancer chemoprevention experiments. To circumvent this, a method was developed for large scale extraction, purification and separation of chlorophyll a and b from spinach. An initial extraction protocol was devised to circumvent the notorious sensitivity of chlorophylls to degradation by light, heat, oxygen, acids and bases. Further purification, and separation of chlorophyll a and b, was achieved using counter-current chromatography, a liquid-liquid extraction method that can offer minimal sample degradation and high sample recovery. Chlorophyll structures and purity were established by HPLC, FAB mass spectrometry and nuclear magnetic resonance. Purity was estimated to be >95% (100% by HPLC) compared to commercial chlorophyll a samples which were only 90-92% pure by HPLC. Typical yields from 30g of freeze-dried spinach were 300 mg of chlorophyll a and 100 mg of chlorophyll b. Chlorophylls a and b purified by this method were recombined to approximate their ratio in spinach, and used in the first known test of chlorophylls as chemopreventive agents in a whole-animal cancer model. Forty-two male F344 rats were arranged into 6 treatment groups. Experimental groups (N = 10 rats each) received either 250ug/kg body weight AFB1 in vehicle, 250 ug/kg AFB1 plus 250 mg/kg body weight CHL (as Cu-chlorin content) in vehicle, or 250ug/kg AFB1 plus 250 mg/kg Chla in vehicle. Control groups (N = 4 rats each) received only vehicle, CHL or Chla in vehicle. All treatments were administered by gavage 5 times per week for 2 weeks. At 18 weeks after treatment GST-P positive foci were evaluated in the livers and aberrant crypt foci (ACF) were evaluated in the colon. AFB1 exposure resulted in 9.1 ± 0.9 volume % of the liver occupied by GST-P positive foci. Inclusion of chlorophyll or chlorophyllin in AFB1 exposures significantly (P
Diagnosis and Management of Jaundice
Authors: M COHEN
Journal: JAMA (1963)

Although the problems of at least 80% of patients presenting with jaundice lend themselves to accurate diagnosis by conventional clinical and laboratory findings, the remainder present an ever-increasing problem. The widespread and often indiscriminate use of many drugs has made the diagnosis of jaundice more difficult. It is now well established that many of these substances may effect liver function in a very selective fashion, resulting in a pattern of laboratory findings similar to those usually associated with surgical lesions of the biliary tree.By reviewing the newer concepts of bilirubin metabolism, the physician is in a better position to avoid these pitfalls. Since 1953, when the role of the liver in conjugation of bilirubin with glucuronic acid was defined, considerable revision in our previous concepts of bilirubin metabolism has taken place. The enzymatic activity of glucuronyl transferase and the conditions which arise in the presence of a deficiency of this enzyme have now defined a whole series of previously poorly understood jaundiced states.The problem presented by the jaundiced newborn is discussed at some length. Similarly, jaundice of long standing in the elderly debilitated adult is also discussed. The author feels that laparotomy with liver biopsy and/or cholangiography are of definite value in the management of these problems.
Fewer infections, but maintained antitumor activity with lower-dose versus standard-dose cladribine in pretreated low-grade non-Hodgkin's lymphoma.
Authors: D C Betticher, A von Rohr, D Ratschiller, S F Schmitz, T Egger, T Sonderegger, R Herrmann, T Kroner, G B Zulian, F Cavalli, M F Fey, T Cerny
Journal: Journal of Clinical Oncology (1998)

PURPOSE To study the efficacy and the safety of cladribine (2-chlorodeoxyadenosine [2-CDA]) administered at two different dosages. PATIENTS AND METHODS In this two-cohort study, patients with low-grade refractory/relapsing non-Hodgkin's lymphoma (NHL) received 2-CDA at a dose of 0.7 mg/kg per cycle as a continuous intravenous (i.v.) infusion (group 1, n = 44) or at a reduced dose of 0.5 mg/kg per cycle as a subcutaneous (s.c.) bolus injection (group 2, n = 60). Three 2-CDA cycles at &gt; or = 4-week intervals were planned, then treatment could be pursued until six cycles. RESULTS A total of 300 cycles were administered (group 1, 114 cycles; group 2, 186). Patient characteristics in both groups were comparable. The median dose-intensities were 0.17 mg/kg/wk and 0.13 mg/kg/wk for groups 1 and 2, respectively (P &lt; or = .0001). The overall response rate for all 104 patients was 54% (95% confidence interval [CI], 45% to 66%; 15% complete response [CR] and 39% partial response [PR]). Response was similar in both patient groups (57% in group 1 and 53% in group 2; P = .72), and no association between 2-CDA dose-intensity and response rate was found (P = .35). Median remission duration was 7 and 12 months in groups 1 and 2, respectively (P = .21). Toxicity, in particular opportunistic infections (&gt; or = grade 2, 30% in group 1 v 7% in group 2; P = .003) and myelosuppression (&gt; or = grade 3 neutropenia, 33% v 8% of 2-CDA cycles, P &lt; .0001), were more frequent in group 1. Multiple logistic regression analysis showed that the infection risk (grade &gt; or = 2) was decreased by 81% with 2-CDA dose reduction in group 2 after adjusting for number of pretreatment regimens and time since diagnosis (P = .01). CONCLUSION When administered as a s.c. bolus injection, 2-CDA at 0.5 mg/kg per cycle is safe and this dose level should not be exceeded in this patient population.
Pregnancy Complications and Cardiovascular Disease Death
Authors: Piera M. Cirillo, Barbara A. Cohn
Journal: Circulation (2015)

Background— Few studies have investigated the combination of pregnancy complications that predict risk for cardiovascular disease (CVD) death and how risk changes with age. This report presents a comprehensive investigation of the relation of the occurrence of multiple pregnancy complications to CVD death over 5 decades in a large pregnancy cohort. Methods and Results— We examined pregnancy events (1959–1967) and CVD death through 2011 in 14 062 women from the Child Health and Development Studies. CVD death was determined by linkage to California Vital Statistics and National Death Index. Women were a median age of 26 years at enrollment and 66 years in 2011. Preexisting hypertension (hazard ratio, 3.5; 95% confidence interval, 2.4–5.1); glycosuria (hazard ratio, 4.2; confidence interval, 1.3–13.1); late-onset preeclampsia (after week 34, hazard ratio, 2.0; confidence interval, 1.2–3.5); and hemoglobin decline over the second and third trimesters (hazard ratio, 1.7; confidence interval, 1.2–2.7) predicted CVD death. Delivery of a small-for-gestation or preterm infant and early-onset preeclampsia (by week 34) significantly predicted premature CVD death ( P &lt;0.05 for age dependence). Preterm birth combined with hemorrhage, gestational hypertension, or preexisting hypertension identified women with a 4- to 7-fold increased risk of CVD death. Preeclampsia in combination with preexisting hypertension conferred a significant nearly 6-fold risk in comparison with a 4-fold risk for preexisting hypertension alone. Conclusions— We observed combinations of pregnancy complications that predict high risk of death and 2 new risk markers, glycosuria and hemoglobin decline. Obstetricians serve as primary care physicians for many young women and can readily use these complications to identify high-risk women to implement early prevention.