tbuckley/cabot-search huggingface dataset:
Transformation of BALB/c-3T3 cells: III. Development of a co-culture clonal survival assay for quantification of chemical cytotoxicity in high-density cell cultures.
Authors: E J Matthews
Journal: Environmental Health Perspectives (1993)

A co-culture clonal survival assay was developed to measure the cytotoxicity of test chemical treatments to BALB/c-3T3 cells because the standard clonal survival assay using 200 wild type (WT) cells frequently overestimates chemical cytotoxicity when compared with identical treatment doses in high-density cultures. The assay used co-cultures of 3.2 x 10(4) WT cells, the same seeding density used in the transformation assay, and 200 ouabain resistant (OUAr) cells. After a 48-hr test chemical treatment, co-cultured cells were fed with culture medium containing 4 mM ouabain. The test chemical was cytotoxic to an equal percentage of WT and OUAr cells. Ouabain treatments killed the remaining WT cells. Thus, OUAr cells surviving the test chemical treatment measured the relative cloning efficiency (RCE) of all treated cells in the high-density cell co-culture. The co-culture assay succeeded because metabolic cooperation at the OUAr locus was not detected in BALB/c-3T3 cells. Five chemicals induced comparable cytotoxic responses in both assays, including actinomycin D, 5-bromo-2'-deoxyuridine, N'-methyl-N-nitro-N'-nitrosoguanidine, dimethyl sulfoxide and sodium chloride. In contrast, chemical cytotoxic responses detected in the standard and co-culture assays differed by &gt; or = 10-fold for 11-aminoundecanoic acid, benzo[a]pyrene, cytosine arabinoside, and 3-methyl-cholanthrene and differed by &gt; 2-fold for 2-acetylaminofluorene and dimethylnitrosamine. Detection of 11-aminoundecanoic acid-induced transformation was shown to be dependent on selecting treatment doses from the co-culture assay data. Thus, this method permits more accurate assessment of both chemical-induced cytotoxicity and transformation.
The Incidence of Cervical and Vaginal Dysplasia After Exposure to DES-Reply
Authors: Stanley J. Robboy
Journal: JAMA (1986)

In Reply.—  Dr Richart asserts that advances in our knowledge about the morphological appearances of HPV could have led to bias in the National Collaborative Diethylstilbestrol Adenosis Project study, in which tissue slides have been analyzed since 1976. 1 Although some bias is possible, we believe it to be minimal since the slides disclosing dysplasia were reviewed by all pathologists and cytologists, and many slides were rereviewed periodically over a period of years as part of quality-control procedures.  A major problem facing all pathologists and cytologists today is in fact the diagnostic criteria distinguishing HPV lesions from dysplasia and carcinoma in situ (collectively, Richart's CIN). Do lesions exhibiting both koilocytosis and marked nuclear atypia represent one disease state or both simultaneously? We have demonstrated that such lesions may have HPV demonstrable by immunoperoxidase stains while also demonstrating aneuploidy by microspectrophotometric analysis of Feulgen-stained slides. 2 We believe that many lesions
Quantitative and functional analysis of PDC-E2–specific autoreactive cytotoxic T lymphocytes in primary biliary cirrhosis
Authors: Hiroto Kita, Shuji Matsumura, Xiao-Song He, Aftab A. Ansari, Zhe-Xiong Lian, Judy Van de Water, Ross L. Coppel, Marshall M. Kaplan, M. Eric Gershwin
Journal: Journal of Clinical Investigation (2002)

While the pathologic mechanisms responsible for organ-specific tissue damage in primary biliary cirrhosis (PBC) remain an enigma, it has been suggested that the pathology is mediated by autoreactive T cells infiltrating the intrahepatic bile ducts. Previously, we have documented that there is 100-fold enrichment in the frequency of CD4+ autoreactive T cells in the liver that are specific for peptides encoded by the E2 components of the pyruvate dehydrogenase complexes (PDC-E2). We have also recently characterized the first MHC class I–restricted epitope for PDC-E2, namely amino acid 159–167, a region very similar to the epitope recognized by MHC class II–restricted CD4+ cells and by autoantibodies. The effector functions of these PDC-E2159-167–specific CD8+ cytotoxic T lymphocytes (CTLs) are not well understood. We have taken advantage of tetramer technology and report herein that there is tenfold increase in the frequency of PDC-E2159-167–specific CTLs in the liver as compared with the blood in PBC. In addition, the precursor frequency of the CTLs in blood was significantly higher in early-stage PBC. Of interest was the fact that, upon stimulation with the peptide, the response of PDC-E2159-167 tetramer-positive cells is heterogeneous with respect to IFN-γ synthesis. These data, we believe for the first time, document the enrichment of autoantigen-specific CD8+ T cells in the PBC liver, suggesting that CD8+ T cells play a significant role in the immunopathogenesis of PBC.
A NEW SCHEME OF THE ZONES AND CENTERS OF THE HUMAN CEREBRUM, WITH REMARKS ON CEREBRAL LOCALIZATION, ESPECIALLY WITH REFERENCE TO OSTEOPLASTIC OPERATIONS FOR BRAIN TUMORS.
Authors: CHAS. K. MILLS
Journal: JAMA (1902)

It is my intention in this contribution to present without extended comment or study of the literature of the subject, new diagrams of the zones and centers of the human cerebrum, and on the basis of these schemes to indicate a series of cranial areas for operation in cases of brain tumor. In 1898 I published a scheme of brain centers which is reproduced in the diagrams (Figs. 1 and 2). Then as now I believed in the separate localization in the cerebrum of the representation of sensation and of movements. My views regarding this subject have not changed in any essential particulars, and were presented in detail at the meeting of the American Neurological Association held in Boston, June, 1901.<sup>1</sup> Recently acquired clinicopathologic facts regarding cerebral localization are chiefly of interest in connection with the question of a separate center for the socalled stereognostic perception. The weight of
Live, Attenuated Measles Vaccine
Authors: Peter B. Kamin
Journal: JAMA (1963)

This article reviews the history of measles vaccine development. Such a review is considered useful for understanding the relationship of the different brands of live attenuated measles vaccine available. In 1954, the measles virus was isolated from an 11-year old boy from the US, David Edmonston, and adapted and propagated on chick embryo tissue culture (CE). The CE adapted strain, known as Edmonston A, was too virulent for vaccine purposes. The strain was attenuated by means of further passages on CE fibroblasts, resulting in a 2nd generation attenuated virus designated as Edmonston B. Again, the strain was too virulent to be applied on a large scale. Laboratories continued to pass Edmonston B on CE until a 3rd generation of more attenuated strains was developed. These strains, which are known by different names and differ from each other in the number of times the parent strain was passed on CE, provide the seeds for the vaccines now commercially available. Among the trade names for live attenuated measles vaccine derived from the Edmonston B strain are Rimevax, Attenuvax, Rouvax, Lirugen, Morbilvax, Mevilin, and Moraten. At the same time, a USSR scientist developed a different parent seed know as Leningrad 16. The measles vaccines supplied through the World Health Organization's programm e on Immunization in the Americas are prepared from seeds derived from Edmonston B.
Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes
Authors: Masayo Kagami, Yoichi Sekita, Gen Nishimura, Masahito Irie, Fumiko Kato, Michiyo Okada, Shunji Yamamori, Hiroshi Kishimoto, Masahiro Nakayama, Yukichi Tanaka, Kentarou Matsuoka, Tsutomu Takahashi, Mika Noguchi, Yoko Tanaka, Kouji Masumoto, Takeshi Utsunomiya, Hiroko Kouzan, Yumiko Komatsu, Hirofumi Ohashi, Kenji Kurosawa, Kenjirou Kosaki, Anne C Ferguson-Smith, Fumitoshi Ishino, Tsutomu Ogata
Journal: Nature Genetics (2008)
Dual function for the adaptor MIST in IFN-γ production by NK and CD4+NKT cells regulated by the Src kinase Fgr
Authors: Hiroki Sasanuma, Akiko Tatsuno, Shinya Hidano, Keiko Ohshima, Yumi Matsuzaki, Katsuhiko Hayashi, Clifford A. Lowell, Daisuke Kitamura, Ryo Goitsuka
Journal: Blood (2006)
The Role of Lipoproteins in Steroidogenesis and Cholesterol Metabolism in Steroidogenic Glands*
Authors: JOHN T. GWYNNE, JEROME F. STRAUSS
Journal: Endocrine Reviews (1982)

Cholesterol is an obligate intermediate in steroidogenesis. It may be synthesized by steroidogenic cells or taken up from circulating lipoproteins. In the adrenal, ovary, placenta, and possibly the testes of many species, including man, lipoprotein cholesterol is the major source of steroidogenic substrate. Lipoprotein cholesterol uptake is hormonally regulated in these tissues, with the exception of the placenta, and coordinated with intracellular cholesterol synthesis and mobilization of cholesteryl esters to ensure a continuous supply of free cholesterol for steroid synthesis. When the rate of cholesterol uptake exceeds the rate of steroidogenesis, intracellular cholesterol synthesis is suppressed and cholesterol in excess of cellular needs is esterified and stored for future use. During the last decade the mechanisms and regulation of lipoprotein cholesterol uptake by steroidogenic tissues have been elucidated. Two distinct lipoprotein-specific, hormonally regulated mechanisms for taking up extracellular cholesterol have been found in steroidogenic cells. Not all steroidogenic tissues possess both mechanisms. It is our purpose to review these findings.
What is the Rationale for an Extended Radical Procedure in Early Cases?
Authors: Jerome A. Urban
Journal: JAMA (1967)

Primary treatment of breast cancer succeeds when the primary tumor and its regional lymph node spread are completely extirpated or destroyed in the absence of established systemic metastases. The classical radical mastectomy has been extended to include en bloc in continuity excision of the internal mammary lymph node chain. This procedure removes the primary breast cancer in continuity with both of its primary lymph node deposits, axillary as well as internal mammary, and should result in better local control and an improved salvage rate. The patients most likely to benefit from this extended procedure are those with a high risk of internal mammary node metastases. Stage I carcinoma of the breast is defined as an early lesion confined to the breast, with no clinically suspicious axillary lymph nodes and no distant metastases suspected. Not infrequently, pathologic examination of the operative specimen will disclose metastatic axillary nodes in some clinical stage
Bronchial vascular congestion and angiogenesis
Authors: NB Charan, EM Baile, PD Pare
Journal: European Respiratory Journal (1997)

The bronchial vasculature is the systemic arterial blood supply to the lung. Although small relative to the pulmonary blood flow, the bronchial vasculature serves important functions and is modified in a variety of pulmonary and airway diseases. Congestion of the bronchial vasculature may narrow the airway lumen in inflammatory airway diseases, and formation of new bronchial vessels (angiogenesis) is implicated in the pathology of a variety of chronic inflammatory, infectious and ischaemic pulmonary diseases. The remarkable ability of the bronchial vasculature to remodel has implications for disease pathogenesis. The contributions of the bronchial vasculature to the pathogenesis of pulmonary disease are reviewed in this article.
Are intrinsic inhibitory systems activated or inhibited in pathological pain states?
Authors: K. Omote
Journal: Behavioral and Brain Sciences (1997)

Neuroplastic changes in the inhibitory systems contribute to pathological pains such as hyperalgesia. Activation or inhibition of the intrinsic inhibitory systems may depend on the pathophysiology which induces a sustained pain state. The mechanisms of hyperalgesia, opioid insensitivity following nerve injury, and opioid tolerance may be related to common neuroplastic changes. [wiesenfeld-hallin et al.]
Novel somatic mutations of theVHL gene in an erythropoietin-producing renal carcinoma associated with secondary polycythemia and elevated circulating endothelial progenitor cells
Authors: Farhad Haghighi Rad, Ayhan Ulusakarya, Sophie Gad, Mathilde Sibony, Fabrice Juin, Stéphane Richard, David Machover, Georges Uzan
Journal: American Journal of Hematology (2007)

Abstract Mutation of the VHL tumor suppressor gene is a frequent genetic event in the carcinogenesis of renal‐cell carcinoma (RCC). Circulating endothelial progenitor cells (EPCs) have important role in neoangiogenesis, and mobilization of these cells is induced by various growth factors including erythropoietin (EPO). With this regard, we analyzed a patient with EPO‐producing clear‐cell RCC and polycythemia. DNA extraction and sequencing analysis of the VHL gene were performed from the tumor and the adjacent normal renal tissue. Isolated and cultured circulating EPCs from the blood taken with phlebotomy were characterized by flow cytometry and immunofluorescence analysis. This RCC had two novel somatic mutations of the VHL gene, p.Leu128Pro and p.Asn131Lys. Culture of blood mononuclear cells revealed a strikingly high number of endothelial cell colonies derived from EPCs (nearly 10‐fold more than in controls). Elevated number of circulating EPCs seems to be related to high EPO production from RCC with novel double somatic mutation of the VHL gene in this patient. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families
Authors: P. Tonin, B. Weber, K. Offit, F. Couch, T.R. Rebbeck, S. Neuhausen, A.K. Godwin, M. Daly, J. Wagner-Costalos, D. Berman, G. Grana, E. Fox, M.F. Kane, R.D. Kolodner, M. Krainer, D.A. Haber, J.P. Struewing, E. Warner, B. Rosen, C. Lerman, B. Peshkin, L. Norton, O. Serova, W.D. Foulkes, H.T. Lynch, G.M. Lenoir, S.A. Narod, J.E. Garber
Journal: Nature Medicine (1996)
NASAL POLYPUS; ORIGIN AND TREATMENT.
Authors: CHAS. H. BAKER
Journal: JAMA (1903)

There is a variety of growths within the nasal chambers to which the name polypus has been given, and much confusion has arisen in consequence, both in regard to the origin and frequency of nasal polypus. Those who restrict the term nasal polypus to the gelatinous form find them comparatively infrequent compared to the total of nasal disorders, while others, like Zuckerkandl, who included posterior turbinate hypertrophies and fibro-adenomata, claim that they occur in every eight or nine autopsies. It is my purpose to confine this paper to the discussion of the true nasal polypus or gelatinous myxoma, although what I shall say as to their causation will apply largely to the other growths which have been classed as polypi. <h3>ORIGIN.</h3> True nasal polypus has by different pathologists been classed among the adenomata or the myxomata according to whether one or the other elements predominated in the structure.
Regional expression of sodium pump subunits isoforms and Na+-Ca++ exchanger in the human heart.
Authors: J Wang, R H Schwinger, K Frank, J Müller-Ehmsen, P Martin-Vasallo, T A Pressley, A Xiang, E Erdmann, A A McDonough
Journal: Journal of Clinical Investigation (1996)

Cardiac glycosides exert a positive inotropic effect by inhibiting sodium pump (Na,K-ATPase) activity, decreasing the driving force for Na+-Ca++ exchange, and increasing cellular content and release of Ca++ during depolarization. Since the inotropic response will be a function of the level of expression of sodium pumps, which are alpha(beta) heterodimers, and of Na+-Ca++ exchangers, this study aimed to determine the regional pattern of expression of these transporters in the heart. Immunoblot assays of homogenate from atria, ventricles, and septa of 14 nonfailing human hearts established expression of Na,K-ATPase alpha1, alpha2, alpha3, beta1, and Na+-Ca++ exchangers in all regions. Na,K-ATPase beta2 expression is negligible, indicating that the human cardiac glycoside receptors are alpha1beta1, alpha2beta1, and alpha3beta1. alpha3, beta1, sodium pump activity, and Na+-Ca++ exchanger levels were 30-50% lower in atria compared to ventricles and/or septum; differences between ventricles and septum were insignificant. Functionally, the EC50 of the sodium channel activator BDF 9148 to increase force of contraction was lower in atria than ventricle muscle strips (0.36 vs. 1.54 microM). These results define the distribution of the cardiac glycoside receptor isoforms in the human heart and they demonstrate that atria have fewer sodium pumps, fewer Na+-Ca++ exchangers, and enhanced sensitivity to inotropic stimulation compared to ventricles.
Sustained Deployments Tax Health of Military
Authors: Phil Gunby
Journal: JAMA (1996)

DOWNSIZED US FORCES are facing an upsurging mission. That's posing a major challenge for the military medical people supporting them. At least 1 US Navy battle group's officers estimate that the ships' crews could spend up to 230 days at sea this year. The US Air Force and its Reserve/ Air National Guard backup crews are being called on to fly increasing numbers of people and equipment more frequently to ever more distant and remote sites around the world, often in aircraft older than some of the pilots flying them. <h3>Some Troops to Stay</h3> Instead of beginning to pull out of Bosnia-Herzegovina in the next few months, it now appears that several thousand US Army troops will remain— in a departure from the original commitment—beyond the December 20 peace enforcement deadline. Military medical staffs, in addition to accompanying these deployments and providing telemedicine consultation, are developing fitness programs to sustain
Older shift workers should work morning shifts
Authors: C. White
Journal: BMJ (1997)

Decision-making often involves motivational conflict because of the competing demands of approach and avoidance for a common resource: behavior. This conflict must be resolved as a necessary precursor for adaptive behavior. Here we show a role for the paraventricular thalamus (PVT) in behavioral control during motivational conflict. We used Pavlovian counterconditioning in male rats to establish a conditioned stimulus (CS) as a signal for reward (or danger) and then transformed the same CS into a signal for danger (or reward). After such training, the CS controls conflicting appetitive and aversive behaviors. To assess PVT involvement in conflict, we injected an adeno-associated virus (AAV) expressing the genetically encoded Ca<sup>2+</sup> indicator GCaMP and used fiber photometry to record population PVT Ca<sup>2+</sup> signals. We show distinct profiles of responsivity across the anterior–posterior axis of PVT during conflict, including an ordinal relationship between posterior PVT CS responses and behavior strength. To study the causal role of PVT in behavioral control during conflict, we injected AAV expressing the inhibitory hM4Di DREADD and determined the effects of chemogenetic PVT inhibition on behavior. We show that chemogenetic inhibition across the anterior–posterior axis of the PVT, but not anterior or posterior PVT alone, disrupts arbitration between appetitive and aversive behaviors when they are in conflict but has no effect when these behaviors are assessed in isolation. Together, our findings identify PVT as central to behavioral control during motivational conflict. <b>SIGNIFICANCE STATEMENT</b> Animals, including humans, approach attractive stimuli and avoid aversive ones. However, they frequently face conflict when the demands of approach and avoidance are incompatible. Resolution of this conflict is fundamental to adaptive behavior. Here we show a role for the paraventricular thalamus, a nucleus of the dorsal midline thalamus, in the arbitration of appetitive and aversive behavior during motivational conflict.
The Cost-effectiveness of Misoprostol-Reply
Authors: Anna N. A. Tosteson
Journal: JAMA (1991)

In Reply.—  We appreciate the thoughtful comments of Drs Hillman and Bloom, Dr Roth, and Mr Jacobs. We agree with Dr Roth and Drs Hillman and Bloom that measures of cost-effectiveness other than cost per YOLS are useful; we provided two such measures in our study 1 as cost per any bleeding and cost per fatal bleeding event. However, cost per YOLS is the standard measure in the field, allowing policymakers to make meaningful comparisons by using the same metric across disparate therapies competing for the same scarce resources. Thus, we believe it is appropriately the central measure of our cost-effectiveness analysis. Effectiveness measures were matched with costs. In our analysis, YOLSs were derived from the remaining life expectancy associated with only those deaths prevented in the 1-year time period of misoprostol therapy.  We share Dr Roth's and Drs Hillman and Bloom's concern that patients with nonbleeding ulcers be included
Prediction of fluid responsiveness in severe preeclamptic patients with oliguria
Authors: Clément Brun, Laurent Zieleskiewicz, Julien Textoris, Laurent Muller, Jean-Pierre Bellefleur, François Antonini, Maxime Tourret, Denis Ortega, Armand Vellin, Jean-Yves Lefrant, Léon Boubli, Florence Bretelle, Claude Martin, Marc Leone
Journal: Intensive Care Medicine (2012)
SDX-308, a nonsteroidal anti-inflammatory agent, inhibits NF-κB activity, resulting in strong inhibition of osteoclast formation/activity and multiple myeloma cell growth
Authors: Rentian Feng, Gülsüm Anderson, Guozhi Xiao, Gary Elliott, Lorenzo Leoni, Markus Y. Mapara, G. David Roodman, Suzanne Lentzsch
Journal: Blood (2006)

Abstract Multiple myeloma is characterized by increased osteoclast activity that results in bone destruction and lytic lesions. With the prolonged overall patient survival achieved by new treatment modalities, additional drugs are required to inhibit bone destruction. We focused on a novel and more potent structural analog of the nonsteroidal anti-inflammatory drug etodolac, known as SDX-308, and its effects on osteoclastogenesis and multiple myeloma cells. SDX-101 is another structural analog of etodolac that is already used in clinical trials for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). Compared with SDX-101, a 10-fold lower concentration of SDX-308 induced potent (60%-80%) inhibition of osteoclast formation, and a 10- to 100-fold lower concentration inhibited multiple myeloma cell proliferation. Bone resorption was completely inhibited by SDX-308, as determined in dentin-based bone resorption assays. SDX-308 decreased constitutive and RANKL-stimulated NF-κB activation and osteoclast formation in an osteoclast cellular model, RAW 264.7. SDX-308 effectively suppressed TNF-α–induced IKK-γ and IκB-α phosphorylation and degradation and subsequent NF-κB activation in human multiple myeloma cells. These results indicate that SDX-308 effectively inhibits multiple myeloma cell proliferation and osteoclast activity, potentially by controlling NF-κB activation signaling. We propose that SDX-308 is a promising therapeutic candidate to inhibit multiple myeloma growth and osteoclast activity and that it should receive attention for further study.
Acquired copy number alterations of miRNA genes in acute myeloid leukemia are uncommon
Authors: Giridharan Ramsingh, Meagan A. Jacoby, Jin Shao, Rigoberto E. De Jesus Pizzaro, Dong Shen, Maria Trissal, Angela H. Getz, Timothy J. Ley, Matthew J. Walter, Daniel C. Link
Journal: Blood (2013)