tbuckley/cabot-search huggingface dataset:
An Unusual Symptom in Secondary Syphilis
Authors: A. A. S. Skirving
Journal: BMJ (1901)

paralysis of the muscles of both upper linbs and of the trunk, and also of the intercostal muscles, thus causing the breathing to be entirely abdominal.There was also partial paralysis of the lower limbs.No loss of sensation could be detected at any place.The temperature was 1ox0 F lpilse uIo, and respirations 3.No pam was complained of, but the'child was very restless constantly wanting to be turned from side to side.There was no-heaaiche, and the mental powers were perfect; there was no loss of control of the bladder or rectum, no priapism, and no rigidity or twitching of any of the muscles.The pupils were somewhat dilated, and seemed?inactive, but equal.There was no squint.Swallowingwas not difficult, and the speech was clear.At 7.30 P.a. of the, same day Dr. Barrs of Leeds saw the case wit;h me.when we' found that the condition of matters was very similar, except that the paralysis of the legsawas more advanced, and the muscles of degluti- tion seemed somewhat involved, and sensation seemed slightly impaired as regards delicacy of differentiation.The knee-jerks were absent.The spleen Was not felt.The respiration had at this time a most marked repemblance to that seen in a frog-that is, on inspiration a peculiar dis- .tension of the region below the chin took place.There was not, even at this time any indication of cyanosis, and the number of respirations was notjabove 30.At ihidnight the facial'muscles became involved and speech indistinct- Athe pulsd'waas failing and becoming rapid (126 per minute and inter- mittent), but the respirations were not much quickened, and there was no cyanosis At I A.X. (September xgth) the heart failed very rapidly, slight cyanosis appeared, and he died quietly ten minutes later.He was quite conscious and clear mentally up to 12.30 but after that heseemed to wander.No post-mortem examination could be obtained.
TLR-dependent cross talk between human Kupffer cells and NK cells
Authors: Zhengkun Tu, Adel Bozorgzadeh, Robert H. Pierce, Jonathan Kurtis, I. Nicholas Crispe, Mark S. Orloff
Journal: The Journal of Experimental Medicine (2008)

The liver protects the host from gut-derived pathogens yet is tolerant of antigenic challenge from food and commensal sources. Innate responses involving liver macrophages (Kupffer cells) and effector liver natural killer (NK) cells form the first line in this defense. We address the impact of Toll-like receptor (TLR) signaling on the cross talk between these two cells, and reveal how the liver displays a down-regulated inflammatory response to constitutive bacterial elements through the secretion of interleukin (IL) 10 yet retains a vigorous response to viral challenge. The data support the model that (a) human liver Kupffer cells respond to TLR ligands and indirectly activate NK cells; (b) the activation depends on cell–cell contact; (c) the Kupffer cells synthesize NK cell activating signals, among which IL-18 is critical, and NK cell inhibitory factors, including IL-10; (d) ligands that signal via myeloid differentiation factor 88 induce IL-10, giving a blunted response in the NK cells; and (e) ligands that signal via the Toll–IL-1 receptor domain–containing adaptor inducing interferon (IFN) β–IFN regulatory factor 3 pathway induce less IL-10, and also directly potentiate the stimulatory effect of IL-18 on NK cells, resulting in enhanced activation. Subversion of cellular mechanisms of innate immune response against viruses may be important for hepatotropic viruses (e.g., hepatitis B and C) to develop persistence.
Conversion of an M- group A streptococcus to M+ by transfer of a plasmid containing an M6 gene.
Authors: J R Scott, P C Guenthner, L M Malone, V A Fischetti
Journal: The Journal of Experimental Medicine (1986)

An M28-derived group A streptococcal strain deleted for the gene encoding M protein was converted to M+ by introduction of a plasmid carrying emm6, the structural gene for type 6 M protein from strain D471. The reconstituted M+ strain, JRS2, resists phagocytosis in human blood and is opsonized by anti-M6 hyperimmune serum, but not by anti-M28 serum. Immunofluorescent microscopy and ELISA demonstrate the presence of M protein on its surface. In addition, JRS2 removes opsonic antibodies from hyperimmune rabbit sera generated by immunization with purified ColiM6 protein and with a synthetic amino-terminal peptide derived from M6. Immunization of rabbits with JRS2 generates opsonic anti-M6 antibodies. These results indicate that the cloned emm6 gene contains the information necessary to convert a phagocytosis-sensitive streptococcus to phagocytosis resistance. Furthermore, it also contains the determinants for M type specificity and those required to elicit opsonic antibodies. It thus appears to determine all the traits associated with M protein.
Phase II Trial of ZD1839 in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Authors: Ezra E. W. Cohen, Fred Rosen, Walter M. Stadler, Wendy Recant, Kerstin Stenson, Dezheng Huo, Everett E. Vokes
Journal: Journal of Clinical Oncology (2003)

Purpose: The epidermal growth factor receptor (EGFR) is a mediator of squamous cell carcinoma of the head and neck (SCCHN) development. ZD1839 is an orally active, selective EGFR tyrosine kinase inhibitor. This phase II study sought to explore the activity, toxicity, and pharmacodynamics of ZD1839 in SCCHN. Patients and Methods: Patients with recurrent or metastatic SCCHN were enrolled through the University of Chicago Phase II Consortium. Patients were allowed no more than one prior therapy for recurrent or metastatic disease and were treated with single-agent ZD1839 500 mg/d. Patient tumor biopsies were obtained and stained immunohistochemically for EGFR, extracellular signal-regulated kinase 1 (ERK1), and phosphorylated ERK1 (p-ERK). Study end points included response rate, time to progression, median survival, and inhibition of p-ERK. Results: Fifty-two patients were enrolled (40 male and 12 female) with a median age of 59 years (range, 34 to 84 years). Fourteen patients received ZD1839 through a feeding tube. Half the cohort received ZD1839 as second-line therapy. Forty-seven patients were assessable for response, with an observed response rate of 10.6% and a disease control rate of 53%. Median time to progression and survival were 3.4 and 8.1 months, respectively. The only grade 3 toxicity encountered was diarrhea in three patients. Performance status and development of skin toxicity were found to be strong predictors of response, progression, and survival. Ten biopsy samples were assessable and revealed no significant change in EGFR or p-ERK expression with ZD1839 therapy. Conclusion: ZD1839 has single-agent activity and is well tolerated in refractory SCCHN. In contrast to other reports, development of skin toxicity was a statistically significant predictor of response and improved outcome.
Will Identifying or Targeting Altered Marker Expression in Response to Cytotoxic Therapy Be of Prognostic or Therapeutic Value?
Authors: Christopher H. Crane, Howard D. Thames, Stanley R. Hamilton
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.04.156 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12885831 Will Identifying or Targeting Altered Marker Expression in Response to Cytotoxic Therapy Be of Prognostic or Therapeutic Value? Christopher H. CranexChristopher H. CraneSearch for articles by this author , Howard D. ThamesxHoward D. ThamesSearch for articles by this author , Stanley R. HamiltonxStanley R. HamiltonSearch for articles by this author Show More 1Department of Radiation Oncology2Department of Biomathematics3Department of Pathology, University of Texas M.D. Anderson Cancer, Center Houston, TX https://doi.org/10.1200/JCO.2003.04.156 Full Text PDF Figures and Tables "Will Identifying or Targeting Altered Marker Expression in Response to Cytotoxic Therapy Be of Prognostic or Therapeutic Value?." Journal of Clinical Oncology, 21(18), pp. 3381–3382© 2003 by American Society of Clinical Oncology
The Significance of Vasoactive Intestinal Peptide in Immunomodulation
Authors: Mario Delgado, David Pozo, Doina Ganea
Journal: Pharmacological Reviews (2004)

First identified by Said and Mutt some 30 years ago, the vasoactive intestinal peptide (VIP) was originally isolated as a vasodilator peptide. Subsequently, its biochemistry was elucidated, and within the 1st decade, their signature features as a neuropeptide became consolidated. It did not take long for these insights to permeate the field of immunology, out of which surprising new attributes for VIP were found in the last years. VIP is rapidly transforming into something more than a mere hormone. In evolving scientifically from a hormone to a novel agent for modifying immune function and possibly a cytokine-like molecule, VIP research has engaged many physiologists, molecular biologists, biochemists, endocrinologists, and pharmacologists and it is a paradigm to explore mutual interactions between neural and neuroendocrine links in health and disease. The aim of this review is firstly to update our knowledge of the cellular and molecular events relevant to VIP function on the immune system and secondly to gather together recent data that support its role as a type 2 cytokine. Recognition of the central functions VIP plays in cellular processes is focusing our attention on this "very important peptide" as exciting new candidates for therapeutic intervention and drug development.
Occupational irritants and asthma: an Estonian cross-sectional study of 34 000 adults
Authors: Orianne Dumas, Emeline Laurent, Jean Bousquet, Andres Metspalu, Lili Milani, Francine Kauffmann, Nicole Le Moual
Journal: European Respiratory Journal (2014)

Occupational exposures make important contributions to asthma morbidity. The role of low/moderate level irritant exposures remains unclear. We aimed to determine which occupational exposures are associated with asthma in an eastern European country with low asthma prevalence. The Estonian Genome Center of University of Tartu collected data from 50 077 adults in 2002–2011. Asthma was assessed through a questionnaire regarding diagnosed diseases, current health status and medication. Exposures to 22 agents during the current and longest held jobs were estimated using an asthma-specific job–exposure matrix. Analyses included 34 015 subjects (aged 18–65 years, 67.0% females), of which 1209 (3.6%) reported asthma (608 with physician-confirmed diagnosis). After adjusting for age, sex and smoking habits, lifetime occupational exposure to known asthmagens (20.4%) was significantly associated with physician-diagnosed asthma (OR 1.28, 95% CI 1.03–1.59), especially high molecular weight agents (flour: OR 2.36, 95% CI 1.31–4.27; animals: OR 1.62, 95% CI 1.00–2.60). Exposure to low/moderate levels of irritants (17.4%) was associated with physician-diagnosed asthma (OR 1.88, 95% CI 1.48–2.37). More pronounced associations were observed in subjects reporting current treated asthma. Beyond confirming the effect of known asthmagens (which are well-known, mostly from observations in western countries), the results provide evidence for a role of low/moderate exposure to irritants. This finding, observed in a country with a low prevalence of asthma and atopy, provides new insight into the understanding of asthma heterogeneity.
Successful treatment of thrombotic thrombocytopenic purpura with high‐dose corticosteroid
Authors: Michihiro Toyoshige, Yuzuru Zaitsu, Koichiro Okafuji, Yasushi Inoue, Yukio Hiroshige, Noboru Matsumoto, Kohei Kaku, Toshio Kaneko
Journal: American Journal of Hematology (1992)
Assessment of surgeons in the workplace
Authors: K. Walsh
Journal: Journal of the Royal Society of Medicine (2004)

I welcome many of the ideas set out by Professor Rowley in his editorial (August 2004 JRSM1). Clearly, assessment in the workplace is the way forward. But where does the patient come in all this? Will patients be told that a junior surgeon will be performing their operation and that a more senior one will be assessing them as they do it? Surely these assessments should not be done until the patient has given explicit and informed consent. In one study only 38% of teaching hospitals in the United States informed patients that students would be involved in their care.2 Do we do any better when junior surgeons are involved?

Some people may argue that society as a whole will benefit as a result of better assessment of surgical skills. But it should be up to the patient as an individual to decide whether or not to contribute to society in this way. How would we feel if it was a member of our own family? A study by Diekema et al.3 showed that children of doctors were less likely to see trainees than other children attending an emergency department.
Improved Diagnostic Evaluation of Suspected Tuberculosis
Authors: Davinder P.S. Dosanjh, Timothy S.C. Hinks, John A. Innes, Jonathan J. Deeks, Geoffrey Pasvol, Sarah Hackforth, Hansa Varia, Kerry A. Millington, Rubamalar Gunatheesan, Valerie Guyot-Revol, Ajit Lalvani
Journal: Annals of Internal Medicine (2008)

Background: The role of new T-cell–based blood tests for tuberculosis in the diagnosis of active tuberculosis is unclear. Objective: To compare the performance of 2 interferon-γ assays and tuberculin skin testing in adults with suspected tuberculosis. Design: Prospective study conducted in routine practice. Setting: 2 urban hospitals in the United Kingdom. Patients: 389 adults, predominantly of South Asian and black ethnicity, with moderate to high clinical suspicion of active tuberculosis. Intervention: Tuberculin skin testing, the enzyme-linked immunospot assay (ELISpot) incorporating early secretory antigenic target-6 and culture filtrate protein-10 (standard ELISpot), and ELISpot incorporating a novel antigen, Rv3879c (ELISpotPLUS) were performed during diagnostic assessment by independent persons who were blinded to results of the other test. Measurements: Sensitivity, specificity, predictive values, and likelihood ratios. Results: 194 patients had a final diagnosis of active tuberculosis, of which 79% were culture-confirmed. Sensitivity for culture confirmed and highly probable tuberculosis was 89% (95% CI, 84% to 93%) with ELISpotPLUS, 85% (CI, 79% to 90%) with standard ELISpot, 79% (CI, 72% to 85%) with 15-mm threshold tuberculin skin testing, and 83% (CI, 77% to 89%) with stratified thresholds of 15 and 10 mm in vaccinated and unvaccinated patients, respectively. The ELISpotPLUS assay was more sensitive than tuberculin skin testing with 15-mm cutoff points (P = 0.01) but not with stratified cutoff points (P = 0.10). The ELISpotPLUS assay had 4% higher diagnostic sensitivity than standard ELISpot (P = 0.02). Combined sensitivity of ELISpotPLUS and tuberculin skin testing was 99% (CI, 95% to 100%), conferring a negative likelihood ratio of 0.02 (CI, 0 to 0.06) when both test results were negative. Limitations: Local standards for tuberculin skin testing differed from others used internationally. The study sample included few immunosuppressed patients. Conclusion: The ELISpotPLUS assay is more sensitive than standard ELISpot and, when used in combination with tuberculin skin testing, enables rapid exclusion of active infection in patients with moderate to high pretest probability of tuberculosis.
Phase I and Pharmacodynamic Trial of the DNA Methyltransferase Inhibitor Decitabine and Carboplatin in Solid Tumors
Authors: Kim Appleton, Helen J. Mackay, Ian Judson, Jane A. Plumb, Carol McCormick, Gordon Strathdee, Chooi Lee, Sophie Barrett, Sarah Reade, Dalal Jadayel, Adrian Tang, Katharine Bellenger, Lynsay Mackay, Albert Setanoians, Andreas Schätzlein, Chris Twelves, Stanley B. Kaye, Robert Brown
Journal: Journal of Clinical Oncology (2007)

The DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (decitabine) induces DNA demethylation and re-expression of epigenetically silenced genes, and increases carboplatin sensitivity of tumor xenograft models. We designed a clinical study to determine the feasibility of delivering a dose of decitabine, combined with carboplatin, that would be capable of producing equivalent biologic effects in patients with solid tumors.In a two-stage design, 33 patients received escalating doses of decitabine administered as a 6-hour infusion on day 1 followed by carboplatin, area under the concentration-time curve (AUC) 5 (cohort 1) and AUC 6 (cohort 2), on day 8 of a 28-day cycle. Pharmacodynamic analyses included 5-methyl-2'-deoxycytidine levels, MAGE1A CpG island methylation, and fetal hemoglobin (HbF) expression.The major toxicity was myelosuppression. Dose limiting toxicities, prolonged grade 4 neutropenia (one patient), and sepsis and grade 3 anorexia/fatigue (one patient), were seen in two of four patients treated with decitabine 135 mg/m2 and carboplatin AUC 5. Dose limiting toxicity comprising neutropenic sepsis (one patient) and grade 3 fatigue (one patient) was seen in two of 10 patients treated at decitabine 90 mg/m2 and carboplatin AUC 6. Decitabine induced dose-dependent, reversible demethylation in peripheral-blood cells (PBCs) maximally at day 10. Furthermore, decitabine 90 mg/m2 induced demethylation of the MAGE1A CpG island in PBCs, buccal cells, and tumor biopsies, as well as elevation of HbF expression.Decitabine can be combined safely with carboplatin at a dose and schedule that causes epigenetic changes equivalent to or greater than that observed in mice with carboplatin-sensitized xenografts. The recommended dose/schedule for phase II trials is decitabine 90 mg/m2 (day 1) followed by carboplatin AUC 6 (day 8) every 28 days.
Autoregulation of Inducible Nitric Oxide Synthase Expression by RNA Interference Provides Neuroprotection in Neonatal Rats
Authors: Zhi Wang, Chenzhuo Feng, Huijuan Zhao, Xiaoyan Ren, Shuling Peng, Zhiyi Zuo
Journal: Theranostics (2015)

We have shown that autoregulation of gene expression by RNA interference is achievable in cell cultures.To determine whether this novel concept could be used to produce neuroprotection under in vivo condition, postnatal day (PND) 3 rats received intracerebroventricular injection of lentivirus that carried or did not carry code for short hairpin RNA (shRNA) of inducible nitric oxide synthase (iNOS).The expression of this shRNA was controlled by an iNOS promoter (piNOS-shRNA) or cytomegalovirus promoter (pCMV-shRNA).The rats were subjected to brain hypoxia-ischemia at PND7.Ischemic brain tissues had increased iNOS expression.This increase was attenuated by virus carrying piNOS-shRNA.Virus carrying pCMV-shRNA reduced iNOS to a level that was lower than control.Brain tissue loss and functional impairment after the hypoxia-ischemia were attenuated by the virus carrying piNOS-shRNA but not by pCMV-shRNA.Our results provide proof-of-concept evidence that autoregulation of iNOS expression by RNA interference induces neuroprotection in vivo and that appropriate regulation of gene expression is important.
RalA Function in Dermal Fibroblasts Is Required for the Progression of Squamous Cell Carcinoma of the Skin
Authors: Adam G. Sowalsky, Addy Alt-Holland, Yulia Shamis, Jonathan A. Garlick, Larry A. Feig
Journal: Cancer Research (2010)

A large body of evidence has shown that stromal cells play a significant role in determining the fate of neighboring tumor cells through the secretion of various cytokines. How cytokine secretion by stromal cells is regulated in this context is poorly understood. In this study, we used a bioengineered human tissue model of skin squamous cell carcinoma progression to reveal that RalA function in dermal fibroblasts is required for tumor progression of neighboring neoplastic keratinocytes. This conclusion is based on the observations that suppression of RalA expression in dermal fibroblasts blocked tumorigenic keratinocytes from invading into the dermal compartment of engineered tissues and suppressed more advanced tumor progression after these tissues were transplanted onto the dorsum of mice. RalA executes this tumor-promoting function of dermal fibroblasts, at least in part, by mediating hepatocyte growth factor (HGF) secretion through its effector proteins, the Sec5 and Exo84 subunits of the exocyst complex. These findings reveal a new level of HGF regulation and highlight the RalA signaling cascade in dermal fibroblasts as a potential anticancer target.
HBxAg in the liver from carrier patients with chronic hepatitis and cirrhosis
Authors: Wenliang Wang, Thomas W. London, Laura Lega, Mark A. Feitelson
Journal: Hepatology (1991)

Formalin-fixed, paraffin-embedded specimens from 110 cases of chronic hepatitis and 108 cases of cirrhosis were stained for HBxAg by the avidin-biotin complex technique using specific antisera made against full-length HBxAg polypeptide or derived synthetic peptides. These tissues were also stained for the HBsAg and HBcAg by the peroxidase—anti-peroxidase method. Among patients with chronic hepatitis, 86% were HBsAg positive in liver cells, 60% were surface antigen positive and 32% were core antigen positive. Among patients with cirrhosis, 97% were HBsAg positive in liver cells, 72% were surface antigen positive and 17% were positive for core antigen. Staining specificity was demonstrated, in part, by using preimmune sera in the place of primary antibody, by blocking of the primary antibody with the appropriate antigen before assay and by testing uninfected liver controls. The persistence and high frequency of HBxAg in liver cells from patients with chronic liver disease suggest that it may play one or more important roles in the pathogenesis of chronic infection. It is possible that detection of HBxAg in the liver could be an additional new diagnostic marker for hepatitis B virus infection. However, the function(s) of HBxAg in the pathogenesis of the chronic liver disease, if any, remains to be explained. (HEPATOLOGY 1991;14:29-37.)