tbuckley/cabot-search huggingface dataset:
Abstract IA06: Epigenetic regulation and heterogeneity in cancer
Authors: Bradley E. Bernstein
Journal: Cancer Research (2013)

Abstract We are using emerging technologies to characterize chromatin state and regulation in human cells. Chromatin maps for diverse normal tissues and cells reveal the locations and cell type-specificities of distal regulatory elements and facilitate the interpretation of genetic variants associated with complex human diseases. Analogous studies of malignant tumors reveal regulatory programs that drive proliferation, while also emphasizing the importance of epigenetic heterogeneity in cancer biology and therapeutic resistance. I will highlight representative studies in these areas and touch on new technological approaches for the study of tumor heterogeneity. Citation Format: Bradley E. Bernstein. Epigenetic regulation and heterogeneity in cancer. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr IA06.
Organic and Inorganic Mercury in Neonatal Rat Brain after Prenatal Exposure to Methylmercury and Mercury Vapor
Authors: Hiromi Ishitobi, Sander Stern, Sally W. Thurston, Grazyna Zareba, Margaret Langdon, Robert Gelein, Bernard Weiss
Journal: Environmental Health Perspectives (2009)

Many populations are exposed to multiple species of mercury (Hg), predominantly organic Hg as methylmercury (MeHg) from fish, and inorganic Hg as Hg vapor from dental amalgams. Most of our knowledge of the neurotoxicity of Hg is based on research devoted to studying only one form at a time, mostly MeHg.In this study we investigated the effects of prenatal exposure to MeHg and Hg vapor on Hg concentrations in the brain of neonatal rats.Female Long-Evans hooded rats were exposed to MeHg (0, 3, 6, or 9 ppm as drinking solution), Hg vapor (0, 300, or 1,000 microg/m3 for 2 hr/day), or the combination of both, from 30 days before breeding through gestational day 18. On postnatal day 4, whole brains were taken from one male and one female from each of four litters in each treatment group to assess organic and inorganic Hg in the brain by cold vapor atomic absorption spectrometry.Statistical analysis using linear mixed effects models showed that MeHg dose was the primary determinant of both organic and inorganic brain Hg levels. For both outcomes, we also found significant interactions between MeHg and Hg vapor exposure. These interactions were driven by the fact that among animals not exposed to MeHg, animals exposed to Hg vapor had significantly greater organic and inorganic brain Hg levels than did unexposed animals.This interaction, heretofore not reported, suggests that coexposure to MeHg and Hg vapor at levels relevant to human exposure might elevate neurotoxic risks.
Severe Hypoglycemia in Children With IDDM: A prospective population study, 1992–1994
Authors: Sam Nordfeldt, Johnny Ludvigsson
Journal: Diabetes Care (1997)

OBJECTIVE Is an increased incidence of severe hypoglycemia an unavoidable effect of improved metabolic control? And, if so, to what extent? RESEARCH DESIGN AND METHODS In 1992–1994, severe hypoglycemia was prospectively registered in our intensively treated IDDM population, 146 children 1–18 years of age with &amp;gt; 90% of the patients on ≥ 4 insulin injections per day. The two categories, “severe hypoglycemia with unconsciousness” (U hypoglycemia) and “severe hypoglycemia without unconsciousness but needing the assistance of another person” (NU hypoglycemia), were analyzed in relation to yearly mean HbA1c levels, insulin doses and proportion of short-acting insulin, age at onset, duration of diabetes, age, sex, and weight-to-height ratio. RESULTS Yearly mean HbA1c levels improved from 8.1 ± 1.6% in 1992 to 6.9 ± 1.3% in 1994. The yearly incidence of U hypoglycemia was 0.15–0.19 events per patient-year, seen in 10–16% of patients, showing no significant increase from 1992–1994. For NU hypoglycemia, slightly increasing figures from 1.01 to 1.26 events per patient-year, seen in 27–38% of patients yearly, were reported. There was no significant correlation between severe (U or NU) hypoglycemia and HbA1c, but still an association was seen in certain calculations. In multiple regression analysis, U hypoglycemia was not related to any factor, but the square root of the rate of NU hypoglycemia was related to lower HbA1c levels (P = 0.0003), higher insulin doses (IU · kg−1 · 24 h−1) (P = 0.0024), and a lower proportion of short-acting insulin out of the total daily insulin dose (P = 0.031). CONCLUSIONS Multiple-dose insulin therapy with rather low yearly mean HbA1c values causes a slight increase of NU hypoglycemia but no increase of U hypoglycemia in our population of children with IDDM. Near physiological HbA1c levels may be achieved without any pronounced risk of increasing the incidence of severe hypoglycemia when multiple-injection insulin therapy is combined with adequate self-control based on psychosocial support and active education.
Near-Ultraviolet Mutagenesis in Superoxide Dismutase-deficient Strains of Escherichia coli.
Authors: RL Knowles, A Eisenstark
Journal: Environmental Health Perspectives (1994)

We compared mutagenic spectra induced by polychromatic near-ultraviolet radiation (near-UV; 300-400 nm) with superoxide anion (O2-) -dependent mutagenesis using a set of Escherichia coli tester strains. Near-UV radiation produced increased frequencies of G:C to A:T transitions, G:C to T:A and A:T to T:A transversions, and small increases in frameshift mutations in wild-type cells. Tester strains lacking superoxide dismutase (SOD) activity (sodAsodB double mutants) demonstrated high spontaneous mutation frequencies and increased near-UV sensitivity. The double mutants also showed increased mutations induced by near-UV compared to either isogenic wild type, sodA or sodB single mutants. Futhermore, these mutants had an unusual spontaneous mutation spectrum, with a predominance of A:T to T:A transversions, followed by G:C to T:A transversions and frameshifts generated in runs of adenines in both the +1 and -1 direction. Other frameshifts were detected to a lesser degree. The oxygen dependency and the type of mutations spontaneously induced in SOD-deficient cells indicated that this mutagenic spectrum was caused by oxidative DNA damage. However, no apparent synergistic action between near-UV radiation and an increased flux of O2- could be detected. From the frequency and types of mutations induced by the two agents, we speculate that near-UV-induced mutagenesis and O2--dependent mutagenesis involve, in part, different lesion(s) and/or mechanism(s). The nature and possible mutagenic pathways of each are discussed.
A lymphokine regulates expression of alpha-1-proteinase inhibitor in human monocytes and macrophages.
Authors: S Takemura, T H Rossing, D H Perlmutter
Journal: Journal of Clinical Investigation (1986)

Biosynthesis and secretion of alpha-1-proteinase inhibitor (alpha 1 PI) has been demonstrated in primary cultures of human mononuclear phagocytes, making it possible to study regulation of alpha 1 PI in normal (PiMM) and homozygous-deficient (PiZZ) individuals. In this study, expression of alpha 1 PI by blood monocytes, bronchoalveolar, and breast milk macrophages decreased during 1 wk in culture whereas expression of other secreted proteins increased. The addition of crude supernatants from mitogen-stimulated peripheral blood mononuclear cells to confluent monolayers of mononuclear phagocytes after 1 wk in culture resulted in a 2- to 2.5-fold increase in alpha 1 PI expression. The increase in alpha 1 PI expression was dose- and time-dependent, and involved a mechanism acting at a pretranslational level as shown by an increase in specific messenger RNA content corresponding to the increase in synthesis and secretion of alpha 1 PI. Although alpha 1 PI was expressed in native form and in forms complexed with serine protease by monocytes early in culture, it was expressed in its native form alone when monocytes were incubated with the lymphokine after 1 wk in culture. The regulating factor had the characteristics of a polypeptide and was derived from T lymphocytes, but it was not interferon-alpha, -beta, -gamma, or interleukin 2. This lymphokine also stimulated synthesis of alpha 1 PI in monocytes of homozygous-deficient PiZZ individuals, but had minimal effect on secretion, thereby increasing the intracellular accumulation of the inhibitor and exaggerating the defect in secretion of alpha 1 PI in these individuals. Regulation of mononuclear phagocyte alpha 1 PI expression by a lymphokine provides a model for further analysis of the effect of enhanced synthesis on a defect in posttranslational processing/secretion and for analysis of differential regulation of protease and inhibitor expressed in the same cells.
Dietary fat clearance in normal subjects is regulated by genetic variation in apolipoprotein E.
Authors: M S Weintraub, S Eisenberg, J L Breslow
Journal: Journal of Clinical Investigation (1987)

Apolipoprotein E (apo E) plays an important role in receptor mediated clearance of lipoprotein particles from plasma. Common genetic variation in apo E exists with three alleles coding for proteins called E2, E3, and E4. In in vitro receptor binding assays, E2 binds poorly, whereas E3 and E4 function normally. Recently, the apo E phenotype has been shown to have an effect on low density lipoprotein (LDL) cholesterol levels with levels in subjects with E2 lower and E4 higher than E3. We have examined the effect of the apo E polymorphism on dietary fat clearance using the vitamin A-fat loading test, which specifically labels intestinally derived lipoproteins with retinyl palmitate (RP). 27 normal subjects were studied, 10 with E3/3, 9 with E3/2, 7 with E4/3, and 1 with E4/4. After a vitamin A-containing fatty meal, postprandial RP concentrations were measured in chylomicron (Sf greater than 1,000) and nonchylomicron (Sf less than 1,000) fractions for 14 h. Compared with E3/3 subjects, E3/2 subjects had a significantly higher nonchylomicron RP concentration (P less than 0.05) (peak heights and areas below the curves) indicating slower clearance and the E4/3, E4/4 group had a significantly lower nonchylomicron RP concentration (P less than 0.05) indicating faster clearance. The clearance in the latter group was twice that of E3/2 subjects (P less than 0.01). Thus, heterozygosity for the defective form of apo E, E2, delays, and the surprising presence of a functionally normal allele, E4, increases clearance. This apo E effect on exogenous fat clearance may explain the recently described effect of the apo E phenotypes on LDL cholesterol levels.
Die another day
Authors: Mary Mather
Journal: BMJ (2005)

Did you ever have so much passion that you thought you might burst into flames?Do you remember staying up all night putting the world to rights and raging against the conservative establishment?What happened?You are now bored stupid living in the suburbs, driving a Teutonic monster, and musing about private schools.Your "radicalism" is confined to wearing surf gear at the weekend and dreaming of buying a retreat in the Dordogne.Well, it's flashback time to an era when politics mattered to you.This book is about David Widgery, a father, general practitioner, writer, socialist, rock promoter, and a take-no-prisoners activist.In his short life he packed in more living than an entire nursing home.His willingness to speak out against injustice inspired many people of his generation.(Check out the celebrity endorsements.)He was a non-conformist and was expelled from school, only to attain his qualifications for medicine at night class.At university he skipped class to attend radical socialist meetings, write for an underground magazine, and demonstrate against the war in Vietnam.The lifestyle puritans would not have approved of his drinking at university.As if destined for greatness he duly failed his finals.All that was left to him was the rear end of medicine-inner city general practice-and his sentence was in the east end of London.Obscurity beckoned.David Widgery was unusual, for he had that rarest of gifts: passion.He had socialist ideals, but not the self obsessed "new" Thatcherite version that is peddled today.In the late 1970s and 1980s unemployment, strikes, poverty, and the destruction of many traditional communities scarred a generation.The social convulsions saw the emergence of the far right National Front touting a populist racist manifesto, which sparked race riots across Britain.The political left formed the Anti-Nazi League, which confronted the National Front in the streets, and Widgery was a founding figure.He wrote two influential books about the lives of his patients.These powerful testimonies countered the prevailing dogma that merely "getting on your bike" could emancipate the poor.In a regular column for the BMJ he articulated many of the untaught and unappreciated immeasurables of general practice.He had his own personal demons, and his struggle ended in 1992 at the age of 45.In the east end they have a name for his type: diamond geezer.
Abstract 5054: Inferring mutational chronology in breast cancer by deep-sequencing tumor subpopulations
Authors: Nicholas E. Navin, Yong Wang, Jill Waters, Ken Chen, Ira Hall, Ankit Malhotra, Aaron Quinlan
Journal: Cancer Research (2012)

Abstract Heterogeneous breast carcinomas often contain nuclei with multiple distributions of ploidy, each representing a distinct genomic subpopulation. We present an approach called Ploidy-Seq that combines flow-sorting and next-generation sequencing to isolate tumor subpopulations and deep-sequence the nuclei at high coverage (80-100X) to identify somatic mutations. We applied Ploidy-Seq to a triple-negative (ER-, PR-, Her2-) ductal carcinoma that showed three major tumor subpopulations and one stromal subpopulation. In order to distinguish germline from somatic mutations, we first identified all of the SNPs in the 2N stromal cells. We then studied the evolution of different molecular clocks within the breast tumor, including single nucleotide variations (SNVs), indels, structural rearrangements, copy number changes and translocations. By applying set theory operations, we compared the three tumor subpopulations to identify early mutations (present in all subpopulations), intermediate events (shared between two subpopulations) and late mutations (exclusive to each subpopulation). Overall we identified 101 nonsynonymous point mutations of which 31 had occurred early and were present in all tumor subpopulations. Many of the early mutations occurred in cancer genes including THSD7B involved in TGFβ signaling, the CDH26 cadherin-like 26 gene, and the kinesin gene KIF2B. Early mutations were further studied by single-cell sequencing, which showed evidence of clonal expansions within the tumor, suggesting that they provided a major selective advantage. These early mutations are of considerable interest for therapeutic targeting since they are present in all of the tumor subpopulations, and are likely to be driving the growth of the cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5054. doi:1538-7445.AM2012-5054
Inhaled Steroid Use and Glaucoma
Authors: Evan Benjamin Dreyer
Journal: New England Journal of Medicine (1993)

To the Editor: Inhaled steroids are commonly used in the treatment of chronic asthma, partly because of their diminished systemic side effects as compared with systemic steroids1. Irrespective of the route of administration, however, steroid use has been associated with both glaucoma and cataract formation2. A substantial number of people have elevated intraocular pressure when treated with long-term topical or systemic glucocorticoids3. Although glaucoma is more common in certain populations (e.g., African Americans, Northern Europeans, and first-degree relatives of patients with glaucoma), it can also develop in people without risk factors3. We have evaluated three patients . . .
Relationship between hepatocyte proliferative activity and liver functional reserve in human cirrhosis
Authors: M Delhaye
Journal: Hepatology (1996)

Hepatocyte proliferative activity is elevated in cirrhotic patients who develop hepatocellular carcinoma (HCC) and decreased in alcohol-induced hepatitis patients with poor outcome. Hepatocyte proliferative activity has not been evaluated in an unselected population of cirrhotic patients regarding the severity of the disease. Forty-six cirrhotic patients (21 alcoholic, 20 viral, and 5 other) were prospectively analyzed by proliferating cell nuclear antigen (PCNA) immunostaining on methanol-fixed, paraffin-embedded liver biopsy specimens. In these conditions, the PCNA-labeling index (PCNA-LI) measures the number of cells in the S-phase and assesses tissue proliferation. The median value of the PCNA-LI for all samples was 4.3% (range, 0%-20.2%). It declined with worsening Child-Pugh score: 9.15% (range, 3.3%-20.2%), 5.3% (range, 1.2%-18%), and 2.4% (range, 0%-4.4%) in Child classes A, B, and C, respectively (P < .05). Using the best cutoff PCNA-LI value to divide cirrhosis into slowly and rapidly proliferating tissue subsets, the PCNA index was independently associated with serum albumin. The probability of survival in patients with a high PCNA-LI ( > 4.4%) was significantly higher than in those with a lower PCNA-LI (0.93 vs. 0.53, at a median follow-up of 153 days; P = .01). In all 6 patients undergoing placement of a transjugular intrahepatic portosystemic shunt (TIPS), the PCNA-LI decreased after the procedure. This early impairment of hepatocyte proliferative activity after TIPS placement might reflect the functional alterations induced by this treatment. In conclusion, hepatocyte proliferative activity assessed by PCNA-LI is increased in cirrhotic patients and decreases with worsening of the disease.
FDG-PET Evaluation of Chondromyxoid Fibroma of Left Ilium
Authors: Kenichiro Hamada, Yasuhiko Tomita, Eiichi Konishi, Tetsuho Fujimoto, Yu Fen Jin, Hidetatsu Outani, Hironari Tamiya, Norifumi Naka, Nobuhito Araki
Journal: Clinical Nuclear Medicine (2008)

Chondromyxoid fibroma is a rare benign tumor, which is composed of immature myxoid mesenchymal tissue with features of early primitive cartilaginous differentiation, accounting for less than 1% of all primary bone tumors. Chondromyxoid fibromas arising from the ilium are relatively rare. Reports on fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging for chondromyxoid fibroma are limited. We present a case of a chondromyxoid fibroma of the left ilium with fluorodeoxyglucose-positron emission tomography (FDG-PET) findings, which showed increased accumulation of fluorodeoxyglucose in spite of its characteristic benign pathology. The maximum standardized uptake value (SUV) of the mass was 3.20.
Solitary Pulmonary Granulomatous Pneumocystosis
Authors: Mukesh Bhatt
Journal: Annals of Internal Medicine (1988)

Letters and Corrections15 August 1988Solitary Pulmonary Granulomatous PneumocystosisMukesh Bhatt, MD, Michael Muller, MD, Maria Sabatini, MDMukesh Bhatt, MDSearch for more papers by this author, Michael Muller, MDSearch for more papers by this author, Maria Sabatini, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-109-4-343_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:We describe a patient withPneumocystis cariniipneumonia who presented with a solitary pulmonary nodule. A 29-year-old homosexual man was hospitalized because of a 12-month history of fever and weight loss. A gallium scan had shown increased uptake in the left upper lobe 6 months earlier. Significant findings were oral thrush, axillary lymphadenopathy, and an erythrocyte sedimentation rate of 88 mm/h. A chest roentgenogram showed a left upper lobe nodular infiltrate without hilar lymphadenopathy. Because of a negative evaluation during a previous admission, an excision biopsy of the nodule was done. The resected specimen measured 3 X...References1. CrossSteigbigel AR. Pneumocystis carinii pneumonia presenting as localized nodular densities. N Engl J Med. 1974;291:831-2. CrossrefMedlineGoogle Scholar2. Cruishank B. Pulmonary granulomatous pneumocystosis following renal transplantation. Am J Clin Pathol. 1985;63:384-90. CrossrefGoogle Scholar3. BurkeGood BR. Pneumocystis carinii infection. Medicine (Baltimore). 1973;52:23-51. CrossrefMedlineGoogle Scholar4. HartzGeisingerScharjMuss JKMH. Granulomatous pneumocystosis presenting as a solitary pulmonary nodule. Arch Pathol Lab Med. 1985;109:466-9. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cabrini Medical Center New York, NY 10003 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHigh-resolution CT, histopathologic, and clinical features of granulomatous pneumocystis jiroveci pneumoniaImaging Features of Pneumocystis carinii PneumoniaIntroduction to AIDS PathologyHypercalcemia in a Patient With AIDS and Pneumocystis Carinii Pneumonia 15 August 1988Volume 109, Issue 4Page: 343-344KeywordsBiopsyErythrocyte sedimentation rateFeversGallium scanHomosexualsPneumocystis carinii pneumoniaThoraxWeight loss Issue Published: 15 August 1988 PDF downloadLoading ...