tbuckley/cabot-search huggingface dataset:
Randomized comparison of single dose of recombinant human IL-12 versus placebo for restoration of hematopoiesis and improved survival in rhesus monkeys exposed to lethal radiation
Authors: Zoya Gluzman-Poltorak, Sarita R Mendonca, Vladimir Vainstein, Hue Kha, Lena A Basile
Journal: Journal of Hematology & Oncology (2014)

The hematopoietic syndrome of the acute radiation syndrome (HSARS) is a life-threatening condition in humans exposed to total body irradiation (TBI); no drugs are approved for treating this condition. Recombinant human interleukin-12 (rHuIL-12) is being developed for HSARS mitigation under the FDA Animal Rule, where efficacy is proven in an appropriate animal model and safety is demonstrated in humans. In this blinded study, rhesus monkeys (9 animals/sex/dose group) were randomized to receive a single subcutaneous injection of placebo (group 1) or rHuIL-12 at doses of 50, 100, 250, or 500 ng/kg (groups 2–5, respectively), without antibiotics, fluids or blood transfusions, 24–25 hours after TBI (700 cGy). Survival rates at Day 60 were 11%, 33%, 39%, 39%, and 50% for groups 1–5, respectively (log rank p < 0.05 for each dose vs. control). rHuIL-12 also significantly reduced the incidences of severe neutropenia, severe thrombocytopenia, and sepsis (positive hemoculture). Additionally, bone marrow regeneration following TBI was significantly greater in monkeys treated with rHuIL-12 than in controls. Data from this study demonstrate that a single injection of rHuIL-12 delivered one day after TBI can significantly increase survival and reduce radiation-induced hematopoietic toxicity and infections. These data significantly advance development of rHuIL-12 toward approval under the Animal Rule as an effective stand-alone medical countermeasure against the lethal effects of radiation exposure.
Defucosylated Humanized Anti-CCR4 Monoclonal Antibody KW-0761 as a Novel Immunotherapeutic Agent for Adult T-cell Leukemia/Lymphoma
Authors: Toshihiko Ishii, Takashi Ishida, Atae Utsunomiya, Atsushi Inagaki, Hiroki Yano, Hirokazu Komatsu, Shinsuke Iida, Kazunori Imada, Takashi Uchiyama, Shiro Akinaga, Kenya Shitara, Ryuzo Ueda
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Adult T-cell leukemia/lymphoma (ATLL) has a very poor prognosis. We have developed the humanized defucosylated anti–CC chemokine receptor 4 (CCR4) monoclonal antibody KW-0761 as a next generation immunotherapeutic agent. The first aim of the present study was to evaluate whether the antitumor activity of KW-0761 would likely be sufficient for therapeutic clinical application against ATLL. The second aim was to fully elucidate the mechanism of antibody-dependent cellular cytotoxicity (ADCC) mediated by this defucosylated monoclonal antibody. Experimental Design: The antitumor activity of KW-0761 against ATLL cell lines was evaluated in vitro using human cells and in mice in vivo. Primary ATLL cells from 23 patients were evaluated for susceptibility to autologous ADCC with KW-0761 by two independent methods. Results: KW-0761 showed potent antitumor activity against ATLL cell lines both in vitro and in the ATLL mouse model in vivo. In addition, KW-0761 showed potent antitumor activity mediated by highly enhanced ADCC against primary ATLL cells both in vitro and ex vivo in an autologous setting. The degree of KW-0761 ADCC against primary ATLL cells in an autologous setting was mainly determined by the amount of effector natural killer cells present, but not the amount of the target molecule CCR4 on the ATLL cell surface. Conclusion: KW-0761 should be sufficiently active for therapeutic clinical application for ATLL. In addition, combination treatment strategies that augment natural killer cell activity should be promising for amplifying the effect of KW-0761. In the near future, the actual efficacy of KW-0761 will be established in pivotal clinical trials. Clin Cancer Res; 16(5); 1520–31
Airway hyperresponsiveness in asthma: not just a matter of airway inflammation
Authors: V. Brusasco, E. Crimi, R. Pellegrino
Journal: Thorax (1998)

According to the most recent definition, bronchial asthma is a chronic inflammatory disorder of the airways associated with reversible airway obstruction and increased airway responsiveness to a variety of stimuli.1 An intuitive inference from this definition is that a causal relationship may exist between airway inflammation and airway hyperresponsiveness. Along this line of reasoning, most of the research in the last two decades in this field was aimed at identifying inflammatory cell products possibly responsible for the pathogenesis of bronchial asthma and airway hyperresponsiveness.2 However, the common observation that the asthmatic airways are equally hyperresponsive to a variety of different stimuli does challenge the idea that a single inflammatory cell or mediator may be central to the pathogenesis of asthma and airway hyperresponsiveness and focuses on the importance of an altered mechanical response of the target organ. This view has been recently corroborated by the finding that airway responsiveness of normal individuals may become similar to that of asthmatics by simply changing the pattern of breathing during the bronchial challenge.3It is therefore legitimate to wonder how much of airway hyperresponsiveness is due to inflammation or to inherent predisposing factors.

The aims of the present review are to show that airway narrowing in asthma is the ultimate result of an interaction between complex and multiple mechanisms not necessarily and uniquely related to airway inflammation, and to revisit the evidence on which the theorem “airway inflammation equal to airway hyperresponsiveness” has been constructed.

Airway calibre in vivo is the result of a delicate balance between the force generated by the airway smooth muscle (ASM) and a number of opposing factors.4 The latter are mainly represented by autonomic mechanisms that tend to limit the ASM tone and by mechanical forces that oppose ASM shortening.

### AIRWAY SMOOTH MUSCLE (ASM)

Although it is widely …
The tetramer structure of the Nervy homology two domain, NHR2, is critical for AML1/ETO's activity
Authors: Yizhou Liu, Matthew D. Cheney, Justin J. Gaudet, Maksymilian Chruszcz, Stephen M. Lukasik, Daisuke Sugiyama, Jeff Lary, James Cole, Zbyszek Dauter, Wladek Minor, Nancy A. Speck, John H. Bushweller
Journal: Cancer Cell (2006)
New insights on the anticancer properties of dietary polyphenols
Authors: P. Fresco, F. Borges, C. Diniz, M.P.M. Marques
Journal: Medicinal Research Reviews (2006)

Cancer, one of the major causes of death across the world, has shown to be a largely preventable disease, highly susceptible to modulation by dietary factors. Phenolic compounds, abundant in vegetables and fruits ubiquitous in diet, were described to play an important role as chemopreventive agents. Since conventional therapeutic and surgical approaches have not been able to control the incidence of most cancer types, the development of chemopreventive strategies is an urgent priority in public health. The current diet phenolic intake is often insufficient to protect from mutagens (either exogenous or endogenous), which leads to the need for dietary supplementation as an alternative approach. Research efforts are placing increasing emphasis on identifying the biological mechanisms and in particular the signal transduction pathways related to the chemopreventive activities of these compounds. These effects are believed to occur by the regulation of signaling pathways such as nuclear factor-κB (NF-κB), activator protein-1 (AP-1) or mitogen-activated protein kinases (MAPK). Dietary polyphenols can exert their effects on these pathways separately or sequentially and in addition the occurrence of crosstalk between these pathways cannot be overlooked. By modulating cell signaling pathways, polyphenols activate cell death signals and induce apoptosis in precancerous or malignant cells resulting in the inhibition of cancer development or progression. However, regulation of cell signaling pathways by dietary polyphenols can also lead to cell proliferation/survival or inflammatory responses due to increased expression of several genes. The present review summarizes the most recent advances providing new insights into the molecular mechanisms underlying the promising anticarcinogenic activity of dietary polyphenols. © 2006 Wiley Periodicals, Inc. Med Res Rev
Persistent responsiveness of the neonatal ductus arteriosus in immature lambs: a possible cause for reopening of patent ductus arteriosus after indomethacin-induced closure.
Authors: R I Clyman, D Campbell, M A Heymann, F Mauray
Journal: Circulation (1985)

Reopening of the ductus arteriosus after successful indomethacin-induced closure has become a major problem with indomethacin treatment. In full-term human newborns and lambs, the ductus behaves like ischemic tissue after its initial constriction. Its ability to continue to relax or contract depends on the amount of left-to-right shunt through the ductus lumen. To see if ductus constriction in preterm lambs would produce the same loss of ductus responsiveness, we delivered 42 lambs by cesarean section and ventilated them for 6.6 +/- 0.5 (+/- SE) hr. We measured ductus arteriosus resistance and left-to-right shunt with the use of radionuclide-labeled microspheres. After the hemodynamic measurements were obtained, the ductus was studied in vitro. Immature lambs were more likely to have reactive ductus (after their initial ductus constriction) than were more mature lambs. This was due to a diminished degree of ductus constriction as well as persistence of ductus responsiveness in immature lambs when compared with more mature lambs. This persistence of ductus responsiveness in immature lambs after ductus constriction may account for the high reopening rate in preterm infants after successful indomethacin-induced closure.
The impending demise of the icon: A critique of the concept of iconic storage in visual information processing
Authors: Ralph Norman Haber
Journal: Behavioral and Brain Sciences (1983)

Abstract Without disputing the experimental evidence that subjects have available most of the content of brief displays for a fraction of a second, or that visual stimuli Persist after their physical termination for a similar time, I argue that this evidence is irrelevant to perception. Specifically, the notion of an icon as a brief storage of information persisting after stimulus termination cannot possibly be useful in any typical visual information-processing task except reading in a lightning storm. Since the visual world that provides the stimuli for perception is continuous and not chopped up by tachistoscopes, and since our eyes and heads are rarely motionless, no realistic circumstances exist in which having a frozen iconic storage of information could be helpful. Rather, the presence of such an icon interferes with perception. This paper examines instances of normal perception, and then reviews experimental evidence on temporal integration, saccadic suppression, masking, and the photoreceptor basis of visual persistence, to further demonstrate that a storage of excitation cannot be a useful device for storing information. Finally, I note that little would have to be changed in our theories of visual perception or information processing if we simply forgot all about the icon and iconic memory as an early stage of processing.
Obstructive sleep apnea syndrome in a patient with medulloblastoma
Authors: G. Greenough, M. Sateia, C. E. Fadul
Journal: Neuro-Oncology (1999)

We present one adult patient with medulloblastoma who developed polysomnographically documented obstructive sleep apnea after posterior fossa surgery. The sleep apnea worsened in conjunction with clinical and imaging-con-firmed neoplastic progression and clinically improved after craniospinal radiation therapy. Medulloblastoma or its surgical treatment has never before been implicated in a sleep-related breathing disorder. We discuss possible mechanisms for its occurrence and management implications.
Expression and regulation of the atrial natriuretic factor encoding gene during development and disease
Authors: A HOUWELING, M VANBORREN, A MOORMAN, V CHRISTOFFELS
Journal: Cardiovascular Research (2005)

The endocrine function of the heart was shown by the identification of a potent inhibitor of renal tubular NaCl reabsorbtion, atrial natriuretic peptide/factor (ANP), in atrial extracts. Since then, Nppa, the gene encoding ANP, has become an important tool for molecular and developmental biologists. Expression of Nppa is an early and specific marker for the differentiating working myocardium of the atria and ventricles of the developing heart. Around the time of birth, ventricular Nppa expression is down-regulated, to be reactivated in response to a variety of cardiovascular disorders. Many aspects of the regulatory pathways that control Nppa gene expression during cardiac development or disease have been revealed. However, several fundamental issues remain to be resolved. Particularly, the regulatory mechanisms underlying the ventricular Nppa expression in the embryonic heart and the reactivation in the failing ventricle remain unclear. Here we review current knowledge on the transcriptional regulation of the Nppa gene.
Comparison of narrow band imaging with high resolution white light endoscopy for the assessment of non-steroidal anti-inflammatory drug induced gastroduodenal injury
Authors: V. Subramanian, E. Telakis, J. Mannath, V. Ramappa, M. Desai, M. Wireko, K. Ragunath, C. J. Hawkey
Journal: Gut (2011)

<h3>Introduction</h3> The diagnosis of NSAID induced gastroduodenal injury is often associated with difficulties in determination of the degree of injury. The Lanza score and its many modifications are commonly used in clinical trials, but are considered subjective and susceptible to errors in interpretation. The aim of this study was to determine the inter-observer variability in assessing NSAID induced gastroduodenal injury among endoscopists with and without experience in narrow band imaging (NBI) using both high resolution white light endoscopy (HR-WLE) and NBI. <h3>Methods</h3> Corresponding NBI and HR-WLE images were taken during endoscopy from healthy volunteers taking different NSAID preparations. Six blinded endoscopists (three experts in NBI imaging) counted the number of ulcers, erosions and haemorrhagic lesions to derive a five point modified Lanza scale and evaluated image quality on a 10 point visual analogue score (VAS). Overall agreement and κ value with bias corrected 95% CIs using bootstrapping techniques were calculated to assess interobserver reliability. <h3>Results</h3> The inter-observer agreement (κ) with HR-WLE among all six endoscopists was 0.62 (95% CI 0.52 to 0.72), which improved significantly with NBI to 0.76 (95% CI 0.69 to 0.84, p=0.02). The inter-observer agreement among expert endoscopists with HR-WLE was ‘substantial’ (κ=0.75, 95% CI 0.63 to 0.87) and improved with NBI to ‘almost perfect agreement (κ=0.87, 95% CI 0.78 to 0.95, p=0.06) which almost reached statistical significance. The inter-observer agreement among non-expert endoscopists with HR-WLE was ‘moderate’ (κ=0.54, 95% CI 0.42 to 0.67) and significantly improved with NBI to ‘substantial’ (κ=0.72, 95% CI 0.60 to 0.82, p=0.02). Non-expert endoscopists found significantly higher number of mucosal haemorrhages on NBI images (p=0.03). VAS scores for NBI images were higher than HR-WLE for experts while the opposite was true for non-experts. VAS scores for NBI images were however consistently higher than HR-WLE when the paired images were presented side by side. <h3>Conclusion</h3> Inter-observer reliability between both expert and non-expert endoscopists for assessment of NSAID induced injury is better with NBI than HR-WLE images. NBI imaging improves the visualisation of mucosal haemorrhages especially in non-expert endoscopists.
Factors Associated With Medical Students' Career Choices Regarding Internal Medicine
Authors: Karen E. Hauer
Journal: JAMA (2008)

Shortfalls in the US physician workforce are anticipated as the population ages and medical students' interest in careers in internal medicine (IM) has declined (particularly general IM, the primary specialty serving older adults). The factors influencing current students' career choices regarding IM are unclear.To describe medical students' career decision making regarding IM and to identify modifiable factors related to this decision making.Web-based cross-sectional survey of 1177 fourth-year medical students (82% response rate) at 11 US medical schools in spring 2007.Demographics, debt, educational experiences, and number who chose or considered IM careers were measured. Factor analysis was performed to assess influences on career chosen. Logistic regression analysis was conducted to assess independent association of variables with IM career choice.Of 1177 respondents, 274 (23.2%) planned careers in IM, including 24 (2.0%) in general IM. Only 228 (19.4%) responded that their core IM clerkship made a career in general IM seem more attractive, whereas 574 (48.8%) responded that it made a career in subspecialty IM more attractive. Three factors influenced career choice regarding IM: educational experiences in IM, the nature of patient care in IM, and lifestyle. Students were more likely to pursue careers in IM if they were male (odds ratio [OR] 1.75; 95% confidence interval [CI], 1.20-2.56), were attending a private school (OR, 1.88; 95% CI, 1.26-2.83), were favorably impressed with their educational experience in IM (OR, 4.57; 95% CI, 3.01-6.93), reported favorable feelings about caring for IM patients (OR, 8.72; 95% CI, 6.03-12.62), or reported a favorable impression of internists' lifestyle (OR, 2.00; 95% CI, 1.39-2.87).Medical students valued the teaching during IM clerkships but expressed serious reservations about IM as a career. Students who reported more favorable impressions of the patients cared for by internists, the IM practice environment, and internists' lifestyle were more likely to pursue a career in IM.
Bacterial entry and intracellular processing of Neisseria gonorrhoeae in epithelial cells: immunomorphological evidence for alterations in the major outer membrane protein P.IB.
Authors: J F Weel, C T Hopman, J P van Putten
Journal: The Journal of Experimental Medicine (1991)

The fate of the major outer membrane protein of the gonococcus, P.IB, during the adherence, entry, and intracellular processing of the bacteria in infected epithelial cells was investigated using post-embedding immunoelectron microscopy. Various domains of the P.IB molecule were probed at different stages in the infection. These studies revealed that P.IB epitope exposure remained unaltered during the initial attachment of the bacteria to the host cells. In contrast, upon secondary attachment of the bacteria to the eukaryotic cells, apparent zones of adhesion were formed between the gonococci and the host cell membrane, which were characterized by loss of a defined P.IB epitope. These zones of adhesion with the altered P.IB immunoreactivity continued to exist and increased in number during cellular penetration, suggesting that they were essential to bacterial invasion into the eukaryotic cells. After bacterial entry, two classes of gonococci could be recognized; morphologically intact, P.IB-positive bacteria and disintegrated organisms that showed a change in, and, in a later stage, a complete loss of P.IB immunoreactivity. The intracellular alterations in the P.IB antigen could be prevented by treatment of the host cells with the lysosomotropic agent chloroquine. These observations point to a mechanism by which a subpopulation of intracellular gonococci can escape the epithelial cell defense by preventing or resisting exposure to host cell proteolytic activity.
U.S. Centers for Disease Control and Prevention Guidelines for the Treatment of Sexually Transmitted Diseases: An Opportunity To Unify Clinical and Public Health Practice
Authors: Kimberly A. Workowski, William C. Levine, Judith N. Wasserheit
Journal: Annals of Internal Medicine (2002)

Sexually transmitted diseases (STDs) constitute an epidemic of tremendous magnitude, with an estimated 15 million persons in the United States acquiring a new STD each year. Effective clinical management of STDs is a strategic common element in efforts to prevent HIV infection and to improve reproductive and sexual health. Sexually transmitted diseases may result in severe, long-term, costly complications, including facilitation of HIV infection, tubal infertility, adverse outcomes of pregnancy, and cervical and other types of anogenital cancer. The publication of national guidelines for the management of STDs, by the U.S. Centers for Disease Control and Prevention (CDC), has been a key component of federal initiatives to improve the health of the U.S. population by preventing and controlling STDs and their sequelae. This paper presents new recommendations from the 2002 CDC Guidelines for the Treatment of Sexually Transmitted Diseases in the context of current disease trends and public health.
Black Cohosh Increases Metastatic Mammary Cancer in Transgenic Mice Expressing c-<i>erb</i>B2
Authors: Vicki L. Davis, Manuel J. Jayo, Arline Ho, Mary P. Kotlarczyk, Mary L. Hardy, Warren G. Foster, Claude L. Hughes
Journal: Cancer Research (2008)

Abstract Black cohosh is an herbal extract that is often used as an alternative to estrogen-based replacement therapies to treat hot flushes that frequently accompany the transition to menopause. Although cancer-free women as well as breast cancer patients and survivors use black cohosh to relieve vasomotor symptoms, there is limited information on its potential to influence breast cancer development or progression. Therefore, in this study, the effects of black cohosh on mammary tumorigenesis were investigated in the MMTV-neu mouse model due to its similarities to HER2+ breast cancer, including stochastic development of mammary tumors, which frequently progress to metastatic disease. Using an adjusted dose for the mice to correlate to the recommended dose in women (40 mg/d), no differences were detected in the incidence or onset of mammary tumors in black cohosh–treated versus control females. The lack of effect on mammary tumor development suggests that black cohosh would not influence breast cancer risk if given to women before tumor formation. In contrast, black cohosh significantly increased the incidence of lung metastases in tumor-bearing animals compared with mice fed the isoflavone-free control diet. Additional studies will be needed to correlate these findings to women taking different black cohosh products at various times during breast cancer development; however, these results suggest caution for women using black cohosh, especially for extended periods of time. As metastatic progression is linked to patient survival, these data stress the importance of investigating how women's therapies influence all stages of mammary tumorigenesis, particularly for assessing their safety. [Cancer Res 2008;68(20):8377–83]
Erratum. Cardiometabolic Risk in a Rural Ugandan Population. Diabetes Care 2013;36;e143
Authors: Georgina A.V. Murphy, Gershim Asiki, Elizabeth H. Young, Janet Seeley, Rebecca N. Nsubuga, Manjinder S. Sandhu, Anatoli Kamali
Journal: Diabetes Care (2017)

In the article cited above, a minor error was made in the calculation of the Framingham Risk Score (FRS). The sentences “The mean value of FRS was 3.30 (SD 6.5), with 3.5% …