tbuckley/cabot-search huggingface dataset:
A benchmark dose analysis of prenatal exposure to polychlorinated biphenyls.
Authors: Joseph L Jacobson, James Janisse, Mousumi Banerjee, Jennifer Jester, Sandra W Jacobson, Joel W Ager
Journal: Environmental Health Perspectives (2002)

Benchmark dose (BMD) analysis is used to determine levels of exposure to environmental contaminants associated with increased public health risk. In this study we used a benchmark approach to evaluate the risks associated with prenatal exposure to polychlorinated biphenyls (PCBs). We evaluated for intellectual impairment a cohort of children whose prenatal PCB exposure had been assessed from biologic specimens. We calculated BMDs and lower-bound confidence limits (BMDLs) for four end points using four sets of risk criteria. BMDLs were estimated using three different statistical methodologies. The BMDs and BMDLs were remarkably consistent across the four end points for each set of risk criteria, but differed substantially for the different risk criteria. The proportion of the sample considered at risk ranged from 9.8% for the least protective criteria to 74.1% for the most protective. Two methodologies, likelihood ratio and bootstrapping, generated generally similar BMDLs. BMD analysis provides a straightforward, reliable method for evaluating levels of exposure associated with increased public health risk. In the analyses performed in this study, the number of individuals considered at risk depended more on the risk criterion selected than on the outcome assessed.
Abstract 4412: S1 and gossypol induce NOXA through increased reactive oxygen species or cytoplasmic calcium and sensitize to ABT-737.
Authors: Ryan S. Soderquist, Darcy J. P. Bates, Alan Eastman
Journal: Cancer Research (2013)

Abstract The upregulation of anti-apoptotic BCL2 family members enhances the survival of cancer cells, such as in chronic lymphocytic leukemia (CLL). A class of inhibitors (termed BH3 mimetics) has been developed to inhibit BCL2 proteins and selectively kill cancer cells. These inhibitors function by occupying the groove through which BCL2 proteins interact with their binding partners. ABT-737 is a high affinity inhibitor of BCL2 and BCLXL, and navitoclax, which has a similar binding profile, has shown efficacy in clinical trials. However, resistance occurs when the cancer cells rely on additional BCL2 members, such as MCL1 or BFL1, which are not inhibited by ABT-737. Using leukemia cell lines, we compared several BH3 mimetics reported to inhibit multiple BCL2-family proteins (including MCL1 and BFL1), with the goal of enhancing the efficacy of ABT-737. We found that none of these compounds functioned as true BH3 mimetics. Instead, the compounds induced ER stress and upregulated the pro-apoptotic protein NOXA. Furthermore, two of these compounds, S1 and gossypol, sensitized leukemia cells to ABT-737 in a NOXA-dependent manner. NOXA induced by S1 or gossypol is dependent on increased reactive oxygen species or increased cytoplasmic calcium, respectively. We also tested these drug combinations in CLL cells ex vivo. S1 and gossypol combined with ABT-737 to selectively kill CLL cells but not normal lymphocytes. Interaction between CLL cells and stroma in patients promotes resistance to BCL2 inhibitors through the upregulation of MCL1 and BFL1. Co-incubation of CLL cells ex vivo with CD40 ligand-expressing stroma mimics the resistance to BCL2 inhibitors seen in patients. Importantly, this resistance was overcome when S1 or gossypol was combined with ABT-737. Our results show two novel mechanisms for upregulating NOXA and sensitizing leukemia cells to ABT-737. These combinations also kill CLL cells exposed to stroma, and may therefore target residual CLL cells in vivo, thus improving clinical outcome. Citation Format: Ryan S. Soderquist, Darcy J. P. Bates, Alan Eastman. S1 and gossypol induce NOXA through increased reactive oxygen species or cytoplasmic calcium and sensitize to ABT-737. [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 4412. doi:10.1158/1538-7445.AM2013-4412
Basophils are recruited to inflamed lungs and exacerbate memory <scp>T</scp>h2 responses in mice and humans
Authors: K. Wakahara, V. Q. Van, N. Baba, P. Bégin, M. Rubio, G. Delespesse, M. Sarfati
Journal: Allergy (2012)

Abstract Background Although the contribution of basophils as inducers or amplifiers of T h2 responses is still debated, prolonged basophil/ CD 4 T cell interactions were observed in lungs but not lymph nodes ( LN s) of parasite‐infected mice. However, the impact of basophils on the function of tissue CD 4 effector T cells remains unknown. Methods Basophils were purified from the lungs of ovalbumin ( OVA )‐sensitized and OVA ‐challenged ( OVA ‐immunized) mice or human peripheral blood for in vivo and in vitro functional studies. Pulmonary basophils were adoptively transferred to OVA ‐sensitized hosts to assess airway inflammation in bronchoalveolar lavage fluid ( BALF ) and T h2 responses in lung explants and draining LN s. Basophils were co‐cultured with effector T cells or A g‐specific naïve T cells alone or in combination with dendritic cells ( DC s); IL ‐4 production was determined by flow cytometry and ELISA . Results Basophils accumulated in lungs of OVA ‐immunized mice. Adoptive transfer of basophils to OVA ‐sensitized hosts enhanced lung IL ‐4 and IL ‐13 release while co‐administration of OVA further aggravated airway inflammation and T h2 responses in LN s. Mechanistic in vitro studies revealed that pulmonary basophils interacted with lung CD 4 effectors, in the absence of DC s, to increase T cell survival and T h2 cytokine expression at the single cell level but amplified OVA ‐loaded DC ‐driven T h2 differentiation. Finally, human basophils augmented in vitro IL ‐4 expression in effector memory CD 4 T cells that include CRTH 2 + cells through IL ‐4 and TCR ‐independent pathways. Conclusions Basophils may worsen T h2 inflammatory disorders through direct interactions with pathogenic CD 4 T cells as well as by enhancing DC ‐induced T h2 cell development.
Polygraphic Studies and Sleep Disorders-Reply
Authors: Joyce D. Kales
Journal: JAMA (1979)

In Reply.—  Our position consistently has been that the primary care physician is able to diagnose and care for the vast majority of patients with sleep disorders without referring them for specialized, all-night sleep studies. That Dr Regestein has found it necessary to evaluate only 10% of the patients in his sleep disorders clinic with all-night sleep recordings lends strong support to our position.  It is probable that most of the patients seen in his clinic have been screened by their physician before referral. Since only 10% of Dr Regestein's patients require polygraphic sleep recordings, one would expect in general practice for the overall percentage to be much smaller of those patients with sleep disorders who would require all-night monitoring.  Both our experience and that of Dr Regestein indicate that by taking a thorough medical history, the physician can screen for specific etiologic and contributing factors for a given sleep
Forty Years of the International Association for Study of Lung Cancer Pathology Committee
Authors: Ming-Sound Tsao, William D. Travis, Elisabeth Brambilla, Andrew G. Nicholson, Masayuki Noguchi, Fred R. Hirsch
Journal: Journal of Thoracic Oncology (2014)

Lung cancer classification during the last four decades has undergone major changes and evolution, mostly lead by pathologists who were actively involved in the International Association for the Study of Lung Cancer (IASLC) Pathology Committee. The Committee members have led the development and writing of the second (1981), third (1999 and 2004), and fourth (2015) editions of the World Health Organization classifications on lung tumors. Committee members were responsible for defining and refining the classifications of small-cell carcinoma and adenocarcinoma subtypes that are relevant to their clinical behavior. Particularly notable was development of the 2011 IASLC/American Thoracic Society/European Respiratory Society international, multidisciplinary lung adenocarcinoma classification. The multidisciplinary approach that represents the IASLC culture in research, education, and practice in clinical management of lung cancer patients have paved the way for integrating pathology practice into the new era of personalized cancer care.
Mentoring the Mentors: The Yoda Factor in Promoting Scientific Integrity
Authors: Madeline M. Motta
Journal: The American Journal of Bioethics (2002)

�� The vision to transform scientiac research into a profession that promotes ethical research practices must begin with an educational strategy aimed at strengthening the very life force of the academic research enterprise, namely, the research mentor and mentee relationship. The foremost reason that mentor leadership training should precede teaching research ethics is that ethical value transformation can only be sustained if it occurs at the sociocultural level of the medical research community. Because research mentor relationships make up the infrastructure of the medical research enterprise, they are the key players in the realization of a comprehensive organizational strategy for scientiac integrity in academic research. More than any other factor in the learning process, the partnership of the teacher and the student determines the value of an education. In the nurture of that partnership lies the mentor’s art (Daloz 1999). Implementing a mentor-centered curriculum for teaching research ethics requires genuine institutional commitment to accountability for research integrity at the highest level of academia. The principal way that university commitment is manifested is through the establishment of an Oface for Research Integrity that sponsors innovative educational initiatives and that encompass the substantive issues and the implicit ethical concerns intrin
Carotid Artery Occlusion-Reply
Authors: William S. Fields
Journal: JAMA (1976)

I certainly have no disagreement with Drs Oller and Deaner regarding early operation following an acute occlusion. This is rarely done except under the most unusual of circumstances. For example, if a patient in the hospital has a carotid bruit on admission and suddenly a contralateral hemiplegia develops with disappearance of the bruit, I would have such a patient taken directly to the operating room without an arteriogram on the assumption that a stenotic artery had abruptly become occluded by thrombus. I have had this experience only on two occasions out of many, and the result in each instance was prompt and virtually complete recovery. I am familiar with the recent paper from Dr Oller and his colleagues regarding a noninvasive modality for the accurate diagnosis of carotid occlusion. There are many other satisfactory techniques for accomplishing this purpose. I still feel very strongly that there is little
The Potential Use of 1-123 IMP Scintigraphy for Pelvic Bone Metastases in Hepatocellular Carcinoma A Comparison With Ga-67 Scintigraphy
Authors: Yuji Suto, NOBORU TANIGAWA, TAKASHI IWAMIYA, MASANOBU SHABANA, YOSHIO OHTA
Journal: Clinical Nuclear Medicine (1994)

Conventional bone scintigraphy is often inconclusive in detecting bone metastases of hepatocellular carcinoma, suggesting the necessity of alternative scintigraphic agents. In this study, the diagnostic value of I-123 IMP scintigraphy was evaluated in 8 patients with 12 pelvic bone metastases from hepatocellular carcinoma, then compared with Ga-67 scintigraphy. Eleven of 12 lesions (91.7%) were detected by I-123 IMP scintigraphy; Ga-67 scintigraphy visualized 8 lesions (66.7%) in the same patient population. I-123 IMP scintigraphy is useful for detecting pelvic bone metastases of hepatocellular carcinoma with less physiologic accumulation in the intestine as compared with Ga-67 scintigraphy.
Connell Suture Not Cause of Death.
Authors: F. Gregory Connell
Journal: JAMA (1903)

<h3>To the Editor:</h3> —On page 91 of the December issue of the<i>American Journal of Surgery and Gynecology</i>I notice an item entitled "Death from the Connell Suture." A perusal of this item reminds one of the definition that appeared some time ago in a small school dictionary, where the word "crab" was defined as "a red fish that crawls backward." Now, to the superficial observer, this definition was eminently satisfactory; but to the inquiring mind—one that was after the facts in the case—it was found to be all right, too, except that a crab is not red, nor is it a fish, nor does it crawl backward. So, too, with the item referred to, the superficial observer is satisfied. It is enough for him to read that death and the fatal hemorrhage were caused by the "Connell suture," and that had a "Czerny-Lembert suture been employed, this fatal termination might have
Authors' reply to Davies and colleagues, Donnelly, and Pilling and Anderson
Authors: G. Lewis
Journal: BMJ (2012)

Our study compared a physical activity intervention plus usual care with usual care alone.1 The intervention did not improve depressive symptoms compared with usual care. As many correspondents have stated, we did not evaluate “exercise” or even “physical activity” but the effect of our intervention on depression. The headline that “exercise is no help for depression” clearly goes beyond our findings and …
Abstract 3538: The HIF-1α hypoxia response in mouse tumor-infiltrating T lymphocytes induces functional CD137 (4-1BB) for immunotherapy
Authors: Asis Palazon, Ivan Martinez-forero, Alvaro Teijeira, Aizea Morales-Kastresana, Carlos Alfaro, Miguel Fernandez de Sanmamed, Sandra Hervas-Stubbs, Maria Jure-Kunkel, Julian Aragones, Ignacio Melero
Journal: Cancer Research (2012)

Abstract The response to hypoxia modulates the expression of multiple genes. The tumor microenvironment of transplanted and spontaneous mouse tumors is profoundly deprived of oxygenation as confirmed by PET imaging. CD8 and CD4 tumor-infiltrating T lymphocytes (TILs) of transplanted colon carcinomas, melanomas and spontaneous breast adenocarcinomas are CD137 (4-1BB) positive, as opposed to their counterparts in tumor draining lymph nodes and spleen. Expression of CD137 on activated T lymphocytes is markedly enhanced by hypoxia and the prolyl-hydroxilase inhibitor DMOG. Importantly, hypoxia does not up-regulate CD137 in inducible HIF-1α knock-out T cells, and such HIF-1α-deficient T cells remain CD137-negative even when becoming TILs, in clear contrast to co-infiltrating HIF-1α-sufficient T cells. The fact that CD137 is selectively expressed on TILs was exploited to confine the effects of immunotherapy with agonist anti-CD137 monoclonal antibodies (mAb) to the tumor tissue, thereby avoiding liver inflammation, while still permitting synergistic therapeutic effects with PD-L1/B7-H1 blockade. 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 3538. doi:1538-7445.AM2012-3538
False Electrocardiographic Diagnosis of Atrial Flutter
Authors: Richard L. Golden
Journal: JAMA (1973)

To the Editor.—  The simulation of atrial  by electrocardiographic artefacts may be of varied origin, including a broken wire in an extremity electrode, 1 myoclonic contractions of the pectoralis major muscle secondary to cold, 2 and the muscle tremor of Parkinson disease. 3-5 While the electrical artefact produced by the tremor of Parkinson disease is usually easily recognized, a well-defined flutter  may occasionally be produced. This simulated  may appear only in the standard leads with bilateral tremor, or may be confined to certain of the standard leads when unilateral. 3 However, the spurious pattern may also be seen in the chest leads in some cases, increasing the difficulty of diagnosis. 4 Various methods have been proposed to eliminate these false  patterns such as warming the patient in the case of cold-induced tremor, 2 and holding the affected extremity in parkinsonism. 3 Saint-Pierre 5 has suggested placing
Impact of introducing near patient testing for standard investigations in general practice.
Authors: E Rink, S Hilton, A Szczepura, J Fletcher, B Sibbald, C Davies, P Freeling, J Stilwell
Journal: BMJ (1993)

The debate surrounding the use of new drugs for age related macular degeneration has sparked worldwide controversy. <b>Robert Campbell and colleagues</b> highlight how differing funding systems have affected use of these drugs in different countries and suggest how to deal with similar challenges in future
48. Adeno-Associated Viral (AAV) Vector- Mediated Systemic Delivery of mda-7/IL24 Inhibits Tumor Growth by Antitumor Bystander Effect
Authors: Ichiro Tahara, Koichi Miyake, Toshiyuki Kurai, Yukihiko Hirai, Eiji Uchida, Takashi Tajiri, Takashi Shimada
Journal: Molecular Therapy (2006)

Top of pageAbstract
Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) possesses cancer cell specific apoptosis inducing properties without harming normal cells. Intriguingly, mda-7/IL-24 not only induces apoptosis but also has immune modulatory and antiangiogenic properties as well as potent antitumor bystander effects, making it an ideal candidate for new gene therapy for divergent cancers. Adenovirus-mediated direct injection of the mda-7/IL24 gene into tumor cells has been shown to be effective to induce cancer cell specific apoptosis in a wide spectrum of cancer models. In this study, we examined a feasibility of adeno-associated vector (AAV) mediated systemic gene therapy using mda-7/IL24 which may eradicate not only primary tumors but also metastatic tumors by its multifaceted anticancer properties. We generated AAV vector expressing secretable mda-7/IL24 (AAV2/1-mda7). In vitro studies showed that conditioned medium collected from C2C12 cells trasduced with AAV2/1-mda7 is able to induce both tumor cell specific apoptosis and inhibition of angiogenesis in a HUVEC tube formation assay. To analyze in vivo effect of AAV mediated systemic delivery of mda-7/IL24, we generated a model of subcutaneous tumor by injection of Ehrlich ascites cells into the dorsum of DDY mice. A single injection of the AAV2/1-mda7 (2.0 |[times]| 1011 particles) was given into the tail vain of the tumor model mice 7 days after tumor cell innoculation. ELISA assay showed that the concentration of mda-7/ IL24 in plasma was gradually increased to reach the plateau (200 ng/ ml) two weeks after vector injection. Distribution study of injected AAV vector by PCR analysis showed that main organ to release mda-7/IL24 was liver. Tumor growth was significantly inhibited in mice injected with AAV2/1-mda-7, but not control AAV2/1-EGFP. TUNEL and immunohistochemical analyses demonstrated significant induction of tumor cell specific apoptosis and reduction of vascular formation in tumor tissues. The survival effect was also observed in treated mice. These results clearly demonstrated that systemic continuous delivery of mda-7/IL24 is very effective for cancer treatment. Intravenous injection of AAV vector is non-invasive and applicable to treat all types of cancer including metastatic tumors and hematological malignancies. AAV vector mediated systemic delivery of mda-7/IL24 represents an important approach for cancer gene therapy.
DC-SIGN, C1q, and gC1qR form a trimolecular receptor complex on the surface of monocyte-derived immature dendritic cells
Authors: Kinga K. Hosszu, Alisa Valentino, Uma Vinayagasundaram, Rama Vinayagasundaram, M. Gordon Joyce, Yan Ji, Ellinor I. B. Peerschke, Berhane Ghebrehiwet
Journal: Blood (2012)
Strategies are needed to deal with migration resulting from climate change
Authors: B. Roehr
Journal: BMJ (2010)

Good international laws and policies will become necessary for dealing with the migration of populations of low lying island nations that may disappear as oceans rise, environmentalists have warned.

Susan Martin, an expert in migration policy at Georgetown University, Washington, DC, told a forum at the think tank the Center for American Progress on 1 March: “You are likely to see increased [external] migration as the variability of the environment increases as a result of climate change,” be it drought or …
Numerical representations: Abstract or supramodal? Some may be spatial
Authors: Giuseppe Vallar, Luisa Girelli
Journal: Behavioral and Brain Sciences (2009)

Abstract The target article undermines the existence of a shared unitary numerical format, illustrating a variety of representations. The “abstract”/“not-abstract” dichotomy does not capture their specific features. These representations are “supramodal” with respect to the sensory modality of the stimulus, and independent of its specific notation, with a main role of spatial codes, both related and unrelated to the mental number line.
CERTIFIED MILK AND THE GENERAL MILK SUPPLY OF LOUISVILLE.
Authors: HENRY ENOS TULEY
Journal: JAMA (1907)

Milk is the most universally used commodity in every community, and the problems which confront the sanitarian in providing a city with a clean milk supply are many, varied and complex. The enormous mortality among infants during their first year of life is sufficient evidence of the importance of this subject. Harrington<sup>1</sup>gives some very convincing statistical data, and Straus, of New York, gives the percentage of deaths during the first year as 32 per cent. of the whole number of births. Hence we believe that the consideration of this question by the members of this section will be productive of great good to all. Louisville has just passed through a wave of milk reform which has resulted in a great improvement in its supply, and we do not believe that the results can be surpassed by any city in the country. To emphasize the necessity for reform it
Granulocytic sarcoma presenting as bilateral adrenal masses
Authors: Binod K. Singh, Sajive Aleyas, Youjun Hu, Kenneth W. Zamkoff, Douglas E. Gladstone
Journal: American Journal of Hematology (2005)

Granulocytic sarcoma (GS) is a collection of immature myeloid cells contained outside the bone marrow often seen in association with acute myeloid leukemia or as a sign of leukemic transformation in myeloproliferative disorders. Rarely, GS is an isolated finding unaccompanied by another hematological disorder. GS can occur at a variety of sites, most commonly involving the bone, soft tissue, lymph nodes, or skin. We report GS presenting as bilateral adrenal masses in a patient without an antecedent hematologic illness. Am. J. Hematol. 79:73–75, 2005. © 2005 Wiley-Liss, Inc.
Axonal loss and neuroinflammation caused by peroxisome-deficient oligodendrocytes
Authors: Celia M Kassmann, Corinna Lappe-Siefke, Myriam Baes, Britta Brügger, Alexander Mildner, Hauke B Werner, Oliver Natt, Thomas Michaelis, Marco Prinz, Jens Frahm, Klaus-Armin Nave
Journal: Nature Genetics (2007)