tbuckley/cabot-search huggingface dataset:
Experimental evaluation of vitellogenin as a predictive biomarker for reproductive disruption.
Authors: A O Cheek, T H Brouwer, S Carroll, S Manning, J A McLachlan, M Brouwer
Journal: Environmental Health Perspectives (2001)

Vitellogenin (VTG) synthesis in male oviparous vertebrates is used as an indicator of environmental estrogen exposure, but the relationship between elevated VTG levels and the effects of environmental estrogens on reproductive success are poorly understood. To examine whether altered VTG expression predicts reproductive impairment, we exposed medaka (Oryzias latipes) for 2 or 8 weeks posthatch to 0, 0.5, 1.0, 2.5, and 7.5 ppb of the environmental estrogen o,p'-DDT. Fish were sampled 2, 4, and 8 weeks after hatch to examine VTG expression and gonad development. After exposure, fish were transferred to clean water, grown to sexual maturity, and placed in mating pairs. We collected eggs for 7 days and scored them for fecundity (number of eggs), fertility (percent fertilized), and hatching success (percent hatched). DDT had no effect on VTG expression after a 2-week exposure, whereas all doses induced VTG after 8 weeks. At both exposure durations, the highest doses of DDT caused a female-skewed sex ratio in adults. Gonadal feminization appeared to be progressive: some ovotestes were observed after 2- or 4-week exposure to the two highest doses, but the proportion of ovaries increased after 8 weeks. Both 2- and 8-week exposures significantly reduced fertility and hatching success at all doses, with lower doses having a greater effect after longer exposure. Fertility and hatching success were more sensitive to estrogenic disruption than were gonad differentiation and vitellogenin expression. We suggest that VTG expression may be interpreted as a warning of reproductive consequences, but absence of expression cannot be interpreted as absence of consequences.
A Lecture on Cancer of the Tongue and its Removal
Authors: R. Barwell
Journal: BMJ (1889)

THus, Gentlemen, the various appearances I have shown you dur- ing the last few minutes are all the result of inflammation of the superficial structures of the tongue; but the point of chief in- terest to you, as family and general practitioners, is to know whither, when not cured, such diseases may lead.Now, whether the changes in the mucosa assume the form of nodules, plaques,
Functional domains of GABAA receptors
Authors: Geoffrey B. Smith, Richard W. Olsen
Journal: Trends in Pharmacological Sciences (1995)

The transmitter-gated ion channels mediate rapid synaptic transmission, for example, at the neuromuscular junction using acetylcholine and in the CNS using primarily the amino acids glutamate and GABA. GABAA-receptor Cl− channels share sequence homology with a superfamily of these channels including nicotinic acetylcholine receptor and inhibitory glycine receptor. In this article, Geoffrey Smith and Richard Olsen discuss recent affinity labelling and sitedirected mutagenesis studies on GABAA receptors that have identified amino acid residues essential for binding of agonists and allosteric modulators as well as the ion channel wall formation. The structural domains identified are consistent with results obtained with other members of the transmitter-gated ion channel superfamily and suggest that structural models for one member of the family may apply to the others as well.
Virginia Medical Society Proceedings.
Authors: Bittle C. Keister
Journal: JAMA (1903)

Roanoke, Va., Oct. 24, 1903. <h3>To the Editor:</h3> —I observe inThe Journal, October 3, that your reporter of the proceedings of the recent meeting of the State Medical Society of Virginia has got things a little mixed, and I hasten to make the correction: There were charges of various kinds preferred against "seven" of the Roanoke doctors, but it appears that not one of these charges was clearly sustained before the judiciary committee, and I can not understand why your reporter singled out my name and omitted the others. While it is true that when I located in this city three years ago I made a few professional announcements through a newspaper of my establishing a private sanitarium here, giving its location and objects, I fail to see wherein I violated in the least degree the true spirit of the Principles of Ethics, more especially since the Virginia State
P5-05-03: The Effect of Breastfeeding on Molecular Characteristics of Invasive Breast Cancer.
Authors: RE Ellsworth, AL Valente, JL Kane, CD Shriver
Journal: Cancer Research (2011)

Abstract INTRODUCTION: Breastfeeding has been associated with an overall decreased risk of developing breast cancer and the protective effect of breastfeeding has been associated with decreased risk of triple negative and estrogen-responsive breast cancer. Although the mechanism by which breastfeeding provides a protective effect is not well-defined, physical changes in the mammary epithelium reflecting maximal differentiation, may be involved. METHODS: The database of the Clinical Breast Care Project was queried to identify all patients born between 1946 and 1964 (“baby boomers”) with invasive breast cancer who had given birth to at least one living child. Clinicopathologic characteristics were compared between patients who breastfed for at least six cumulative months and those who never breastfed using chi-square and Fisher's exact tests. RNA was isolated after laser-microdissection of 24 pairs of breastfeeding and non-breastfeeding tumors matched by stage, subtype and grade. Gene expression data was generated using HG U133A 2.0 microarrays and analyzed using the Partek Genomics Suite using a FDR&amp;lt;0.05, 2-fold expression difference to define significance. RESULTS: Of the 1,008 parous women with invasive breast cancer in the database, 325 (33%) breastfed at least 6 months, 165 (16%) breastfeed less than 6 months, and 518 (51%) never breastfed. Women who breastfed &amp;lt;6 months were not included in additional analyses. Age at menarche and first birth and number of children did not differ between groups; age at diagnosis was significantly (P&amp;lt;0.0001) lower (54.5 years) in women who breastfed compared to those who did not (61.0 years). No differences were detected between patients who breastfed and those who did not for ethnicity or for any tumor characteristics, including tumor stage, grade or size, hormone, HER2 or lymph node status, or subtype. At the molecular level, however, 21 probes representing 19 genes were differentially expressed between women who breastfed and those who did not. Eleven genes, including HAPLN1, had significantly higher and 8 genes, including LGALS7, had significantly lower expression in tumors from women who did not breastfeed. CONCLUSIONS: Despite the matching of tumor samples, and lack of differences in pathological characteristics between women who breastfed ≥6 months and those who did not breastfeed, differentially expressed genes were identified between tumors from the two groups. Many of the differentially expressed genes have been associated with prognosis, especially in ER negative breast tumors. These data suggest that breastfeeding does alter the underlying molecular characteristics of invasive breast tumors, and may reflect alterations in exposure to estrogen levels during breastfeeding. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-05-03.
Low-efficiency of percutaneous adenovirus-mediated arterial gene transfer in the atherosclerotic rabbit.
Authors: L J Feldman, P G Steg, L P Zheng, D Chen, M Kearney, S E McGarr, J J Barry, J F Dedieu, M Perricaudet, J M Isner
Journal: Journal of Clinical Investigation (1995)

Recombinant adenoviruses are the most efficient vectors with which to perform arterial gene transfer.Previous in vivo studies of adenovirus-mediated arterial transfection, however, have been performed using normal or endothe- lium-denuded arteries.It is unclear whether these results can be extended to atherosclerotic arteries.Accordingly, this study was designed to (a) assess the feasibility of adenovirus- mediated gene transfer to atherosclerotic lesions, and (b) compare the transfection efficiency, anatomic distribution of transfected cells, and duration of transgene expression achieved in normal versus atherosclerotic arteries.A recom- binant adenovirus including a nuclear-targeted (-galactosidase gene was percutaneously delivered to the iliac artery of normal (n = 25) and atherosclerotic (n = 25) rabbits.Transgene expression, assessed by morphometric as well as chemiluminescent analyses, was documented in all normal and atherosclerotic arteries between 3 and 14 d after gene transfer, but was undetectable at later time points.Transfected cells were identified as smooth muscle cells located in the media of normal arteries, and in the neointima and the vasa-vasora of atherosclerotic arteries.Two percent of medial cells, but only 0.2% of medial and neointimal cells expressed the transgene in normal and atherosclerotic arteries, respectively (P = 0.0001).Similarly, nuclear ,B-ga- lactosidase activity was higher in normal than in atheroscle- rotic arteries (3.2 vs. 0.8 mU/mg protein, P = 0.02).These findings indicate that atherosclerosis reduces the transfec- tion efficiency which can be achieved with adenoviral vec- tors, and thus constitutes a potential limitation to adenovi- rus-based, arterial gene therapy.(
Neonatal peptide exposure can prime T cells and, upon subsequent immunization, induce their immune deviation: implications for antibody vs. T cell-mediated autoimmunity.
Authors: R R Singh, B H Hahn, E E Sercarz
Journal: The Journal of Experimental Medicine (1996)

Neonatal exposure to antigen is believed to result in T cell clonal inactivation or deletion. Here we report that, contrary to this notion, neonatal injection of BALB/c mice with a hen egg lysozyme peptide 106-116 in putative "tolergenic" doses induced a T cell proliferative and an immunoglobulin G (IgG) antibody (Ab) response of both T helper cell 1 (Th1)- (IgG2a, IgG2b, and IgG 3) and Th2-dependent (IgG1) isotopes. Upon subsequent challenge with the peptide in complete Freund's adjuvant in adult life, although this neonatal regimen suppressed proliferation and the production of Th1 cytokines (interleukin[IL]-2 and interferon gamma), Th2 cytokine (IL-5, IL-4, and IL-10) secretion was increased, and the serum levels of Th1- and Th2-dependent isotypes of peptide-specific Ab remained elevated. The in vitro proliferative unresponsiveness in Th1 cells could be reversed by Abs to Th2 cytokines (IL-4 and IL-10). Thus, neonatal treatment with a peptide antigen induces T cell priming including production of IgG Abs of both Th1- and Th2-dependent isotypes. Upon subsequent peptide exposure, the peptide-specific T cell responses undergo an effective class switch in the direction of Th2, resulting in T cell proliferative unresponsiveness. Accordingly, this shift towards increased Ab production to autoantigen could be deleterious in individuals prone to antibody-mediated diseases. Indeed, neonatal treatment with a self-autoantigenic peptide from an anti-DNA monoclonal Ab (A6H 58-69) significantly increased the IgG anti-double-stranded DNA Ab levels in lupus-prone NZB/NZW F1 mice, despite suppressing peptide-specific T cell proliferation. This adverse clinical response is in sharp contrast to the beneficial outcome of neonatal treatment with autoantigens in Th1-mediated autoimmune diseases, such as autoimmune encephalomyelitis, as reported by others. A Th1 to Th2 immune deviation can explain the discordant biological responses after the presumed induction of neonatal tolerance in autoantibody- vs. Th-1 mediated autoimmune diseases.
EFFECTS PRODUCED BY THE INTRAVENOUS INJECTION IN MAN OF A TOXIC ANTIGENIC MATERIAL DERIVED FROM EBERTHELLA TYPHOSA: CLINICAL, HEMATOLOGICAL, CHEMICAL AND SEROLOGICAL STUDIES
Authors: Grant O. Favorite, Herbert R. Morgan
Journal: Journal of Clinical Investigation (1942)

The preparation of purified antigenic materials from cultures of Eberthella typhosa (1, 2) has demonstrated that substances of relative purity, and high antigenic and toxic activity, may be iso- lated for study.In investigations utilizing a syn- thetic medium for the culture of E. typhosa (3), which eliminates the possibility of non-specific contaminating materials (derived from the culture medium), a toxic, antigenic material has been isolated which has been extensively studied.This material acts as a complete antigen, giving rise to the formation of agglutinins (4), precipitins (4), bactericidal antibodies (5), and mouse-protective antibody (6).Possessing marked toxicity, it kills mice, rabbits, and guinea pigs with relatively small doses (4).A study of the tissues obtained from animals receiving intravascular injections of the material has shown pathological changes in- volving the heart muscle, lung, liver, spleen, bone marrow, and vascular bed (7).On intravenous injection in rabbits, the material induces a pro- nounced leukopenia and a marked temperature rise (4).Because of these properties it was de- sired to determine, insofar as possible, whether the material might exhibit similar effects following intravenous injection into patients for the purpose of inducing therapeutic febrile reactions. MATERIALS AND METHODSPreparation of antigen Following the technique previously described (3, 4) involving repeated precipitations with alcohol and resus- pension in water, an antigenic material was obtained from cultures of E. typhosa grown in a liquid medium which consisted only of ingredients removable by dialysis (3).The material which contained the 0 and Vi antigens possessed all the properties exhibited by that previously studied (4).The stock solution of antigen was made up 'John Ware Memorial Student Research Fellow.in distilled water and stored in the refrigerator for over a year.During this time no loss of.activity was ob- served.From this stock solution containing 1 mgm.per cc. of the antigen, successive dilutions were prepared in physiologic saline for intravenous administration.
Apolipoprotein A-I, B-100, and B-48 metabolism in subjects with chronic kidney disease, obesity, and the metabolic syndrome
Authors: Marcelo C. Batista, Francine K. Welty, Margaret R. Diffenderfer, Mark J. Sarnak, Ernst J. Schaefer, Stefania Lamon-Fava, Bela F. Asztalos, Gregory G. Dolnikowski, Margaret E. Brousseau, Julian B. Marsh
Journal: Metabolism (2004)
Congenital rubella affecting an infant whose mother had rubella antibodies before conception.
Authors: J W Partridge, T H Flewett, J E Whitehead
Journal: BMJ (1981)

A woman who had had high titres of rubella antibodies some months before she became pregnant gave birth to an infant in whom congenital rubella was confirmed at 4 months. Rubella haemagglutination inhibition tests, complement fixation tests, and immunofluorescence tests with anti-human IgG were carried out on sera from the mother. Rubella antibody titres in sera obtained in March 1971, seven and a half months before conception, were equivalent to 400 units, which is usually taken as indicating good immunity. Rubella virus was isolated from the baby9s nose and throat in July 1973 but was not isolated from a cervical swab taken from the mother in December 1973; tests of her immunological competence did not show any definite abnormality. The presence of high levels of rubella haemagglutination inhibition antibodies does not invariably confer immunity or exclude the possibility of congenital rubella in a subsequent pregnancy.
"BREVITY IS THE SOUL OF WIT"
Authors: W. H. Haupt
Journal: JAMA (1918)

the 70 per cent, of lives needlessly sacrificed, that might be saved as breadwinners in industrial pursuits.In an address delivered before the International Congress of Military Surgeons in 1904, after my return from the Russo- Japanese War, I said: "Perhaps the day is not distant when another summons will come to join the Army of the Republic, when the first call may be, not as in the Civil War for 75,000 men, nor as in the Spanish War for 250,000, but when, more likely it will be for a round half million, to be followed possibly by another of equal number.And the question will be asked by the young patriot of that day, not who the enemy is he is to meet-No, the American boy is not buijt that way-but he will demand to know what measures have been taken to insure him against the silent enemy who kills the 80 per cent.And when he learns the same prehistoric regulations as to sanitation and protection against this foe are in force as they were in 1904, will he respond to his country's call ?Yes, he will, for that is tV.e way the American boy is built.And he will follow, as did his forebears, in their footsteps, and he will fall by the way¬ side as they did before.And history will record another crime."We see by the light of thousands of years, And the knowledge of millions of men, The lessons they learned through blood and in tears Are ours for the reading, and then We sneer at their errors and follies and dreams, Their frail idols of mind and of stone, And call ourselves wiser, forgetting, it seems, That the future may laugh at our own.
ELECTROGALVANIC LESIONS OF THE ORAL CAVITY PRODUCED BY METALLIC DENTURES
Authors: EVERETT S. LAIN
Journal: JAMA (1933)

In a previous communication I<sup>1</sup>discussed lesions of the oral cavity caused by electrogalvanic discharges between dissimilar metallic dentures and reported thirty consecutive cases measured for electric current. Since that time I have been privileged to make a careful study of more than 300 additional cases which contained various dissimilar metallic dentures. From this study, I feel justified in forming certain definite conclusions. I have confirmed, by repeated experiments, that human saliva, whether acid, alkaline or neutral, makes a good electrolyte through which metallic electrons freely circulate from a higher to a lower electropotentiality. Thus, within every oral cavity which contains dentures such as plates, bridges, crowns, or fillings of dissimilar elemental consistency, there is constituted a complete galvanic battery. This newly discovered oral cavity phenomenon is in keeping with a fundamental law of electrophysics discovered by Galvani in 1786—later verified by Volta— which declares that when dissimilar metals
Abstract 2036: Overcoming platinum-resistance in ovarian cancer via targeting basonuclin1 (BNC1).
Authors: Sherry Y. Wu, Anna K. Unruh, Rajesha Rupaimoole, Cristina Ivan, Dennis Ruder, Sunila Pradeep, Vasudha Sehgal, Cristian Rodriguez-Aguayo, Chad Pecot, Takahito Miyake, Gabriel Lopez-Berestein, Prahlad Ram, Keith A. Baggerly, Anil K. Sood
Journal: Cancer Research (2013)

Abstract Purpose This study aims to interrogate if basonuclin1 (BNC1), a key gene identified through integrative TCGA-based functional genomic analysis, is a relevant target for overcoming chemo-resistance in high-grade serous ovarian cancer (HGS-OvCa). BNC1 is a transcription factor which can regulate ribosomal biogenesis and cell proliferation. Methods TCGA mRNA expression and clinical response data were used to systematically identify genes associated with chemo-resistance in patients with HGS-OvCa. Gene-specific effects were subsequently studied for selected targets in vitro. BNC1 targeted siRNA was used to study the functional role of BNC1 in chemo-resistance. Apoptosis and cell cycle analyses were carried out following BNC1 silencing in ovarian cancer cell lines with or without the presence of cisplatin. The in vivo effects of silencing BNC1 on the chemosensitivity were tested using an orthotopic mouse model (A2780CP20) of ovarian cancer. Results The expression of BNC1 was found to be increased by more than two-fold (Agilent platform; p&amp;lt;0.001) in chemo-resistant tumors in the TCGA dataset. A 5-fold increase in its expression level was also observed in cisplatin-resistant A2780-CP20 and IGROV-CP20 cells compared to parental cell lines. BNC1 silencing increased the sensitivity of A2780CP20 cells to cisplatin treatment (IC50) with a 30% increase in the percentage of apoptotic cells present at 72 hours following cisplatin treatment, when compared to cells treated with control siRNA. Profound G2-cell cycle arrest was also noted following combined siBNC1 and cisplatin (IC30) treatment (68% vs. 28%; siBNC1 plus cisplatin vs. siControl plus cisplatin; p&amp;lt;0.0001). Importantly, combinational treatment of siBNC1 and cisplatin resulted in a 90% reduction in tumor burden in chemo-resistant A2780CP20 orthotopic mouse model when compared to control siRNA plus cisplatin treatment group (p&amp;lt;0.01). Conclusion Collectively, BNC1 represents an important target for enhancing chemosensitivity in ovarian tumors and its down-regulation could lead to better clinical outcome. Citation Format: Sherry Y. Wu, Anna K. Unruh, Rajesha Rupaimoole, Cristina Ivan, Dennis Ruder, Sunila Pradeep, Vasudha Sehgal, Cristian Rodriguez-Aguayo, Chad Pecot, Takahito Miyake, Gabriel Lopez-Berestein, Prahlad Ram, Keith A. Baggerly, Anil K. Sood. Overcoming platinum-resistance in ovarian cancer via targeting basonuclin1 (BNC1). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2036. doi:10.1158/1538-7445.AM2013-2036
Plasticity of integrin expression by nerve-derived connective tissue cells. Human Schwann cells, perineurial cells, and fibroblasts express markedly different patterns of beta 1 integrins during nerve development, neoplasia, and in vitro.
Authors: L L Hsiao, J Peltonen, S Jaakkola, H Gralnick, J Uitto
Journal: Journal of Clinical Investigation (1991)

Strikingly selective expression patterns of beta 1, alpha 2, alpha 3, and alpha 5 integrin subunits were revealed in endoneurium, perineurium, and epineurium of fetal and adult human peripheral nerve by immunostaining with specific antibodies. The alpha 2 subunit was expressed only on Schwann cells both in fetal and adult nerve, whereas the alpha 3 epitopes were expressed exclusively in the adult tissue and were primarily present on perineurial cells. The alpha 5 epitopes were expressed only on the innermost cell layer of perineurium of fetal and adult nerve. The tumor cells within schwannomas and cutaneous neurofibromas expressed both alpha 2 and alpha 3 subunits, indicating that Schwann cells have the potential to express also the alpha 3 subunit in vivo. Cell cultures established from human fetal nerve and neurofibromas revealed expression of the alpha 2 and alpha 5 epitopes on Schwann cells, perineurial cells, and fibroblasts, whereas only Schwann cells contained the alpha 3 epitopes which were occasionally concentrated on the adjacent Schwann cells at cell-cell contacts. Our findings emphasize that nerve connective tissue cells change their profiles for expression of extracellular matrix receptors under conditions which have different regulatory control signals exerted by, for example, axons, humoral factors, or the extracellular matrix of the peripheral nerve. This plasticity may play an important role during nerve development and in neoplastic processes affecting the connective tissue compartments of peripheral nerve.