tbuckley/cabot-search huggingface dataset:
Older Subjects With Diabetes and Prediabetes Are Frequently Unaware of Having Distal Sensorimotor Polyneuropathy
Authors: Brenda W.C. Bongaerts, Wolfgang Rathmann, Margit Heier, Bernd Kowall, Christian Herder, Doris Stöckl, Christa Meisinger, Dan Ziegler
Journal: Diabetes Care (2012)

Distal sensorimotor polyneuropathy (DSPN) is a severe complication of type 2 diabetes. This study aimed to assess the prevalence of unawareness of DSPN in prediabetes and diabetes in a sample of the older population of Augsburg, Germany.Glucose tolerance status was determined in 61- to 82-year-old participants of the population-based KORA F4 Study (2006-2008) (n = 1,100). Clinical DSPN was defined as the presence of bilaterally impaired foot-vibration perception and/or bilaterally impaired foot-pressure sensation. DSPN case subjects were considered unaware of their condition when answering "no" to the question, "Has a physician ever told you that you are suffering from nerve damage, neuropathy, polyneuropathy, or diabetic foot?"Clinical DSPN was prevalent in 154 (14%) participants, 140 of whom were unaware of their disorder. At a prevalence of 23.9% (95% CI 12.6-38.8), participants with combined impaired fasting glucose and impaired glucose tolerance had the highest prevalence of DSPN. Of these, 10 of 11 (91%) were unaware of having clinical DSPN. Participants with known diabetes had an equally high prevalence of DSPN [22.0% (16.2-28.9)], with 30 of the 39 (77%) DSPN case subjects unaware of having the disorder. Among subjects with known diabetes who reported to have had their feet examined by a physician, 18 of 25 (72%) clinical DSPN case subjects emerged unaware of having DSPN.Our findings showed a high prevalence of unawareness of having clinical DSPN among the prediabetic and diabetic groups and an insufficient frequency of professional foot examinations, suggesting inadequate attention to diabetic foot prevention practice.
A randomized controlled phase II trial of a novel composition of paclitaxel embedded into neutral and cationic lipids targeting tumor endothelial cells in advanced triple-negative breast cancer (TNBC)
Authors: A. Awada, I.N. Bondarenko, J. Bonneterre, E. Nowara, J.M. Ferrero, A.V. Bakshi, C. Wilke, M. Piccart
Journal: Annals of Oncology (2014)

EndoTAG-1, composed of paclitaxel embedded in liposomal membranes targeting tumor endothelial cells, was evaluated for safety and efficacy in advanced triple-negative breast cancer (TNBC).
Evidence Against Association Between Parity and NIDDM From Five Population Groups
Authors: Veronica R Collins, Gary K Dowse, Paul Z Zimmet
Journal: Diabetes Care (1991)

Objective To determine whether a reported positive association between parity and the development of non-insulin-dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) is reproducible in other populations. Research Design and Methods We investigated the relationship in data from population-based surveys in four Pacific and Indian Ocean island nations. Women ≥ 40 yr of age at the time of the survey, excluding those in whom diabetes developed before 40 yr of age, were included in this study of Micronesians from Nauru (n = 204) and Kiribati (n = 562), Fiji Melanesians (n = 390), Fiji Indians (n = 247), and mixed-ethnic Mauritians (n = 1333). Subjects in each survey underwent a 75-g oral glucose tolerance test, and glucose tolerance status was ascertained with 1985 World Health Organization criteria. Obstetric information and family history of diabetes were determined by interview. Results Age and body mass index (BMI)-adjusted mean parity increased slightly with worsening glucose tolerance in only two groups, decreased in one group, and was inconsistent in the other two (none were statistically significant). We also found an inconsistent relationship between the number of full-term pregnancies and the prevalence of IGT and NIDDM, although in each population, there was a higher prevalence of NIDDM in the highest parity group (≥ 10 pregnancies) compared with the lowest parity group (1-3 pregnancies). In logistic regression analyses accounting for age, BMI, and family history of diabetes, odds ratio estimates for NIDDM and IGT associated with each pregnancy were not significantly greater than unity. Conclusions The results indicate that there is little if any independent association between parity and the development of abnormal glucose tolerance in these populations.
Cancer effect on periprocedural thromboembolism and bleeding in anticoagulated patients
Authors: A J Tafur, W E Wysokinski, R D McBane, E Wolny, E Sutkowska, S C Litin, P R Daniels, J P Slusser, D O Hodge, J A Heit
Journal: Annals of Oncology (2012)

Patients with active cancer are often on chronic anticoagulation and frequently require interruption of this treatment for invasive procedures. The impact of cancer on periprocedural thromboembolism (TE) and major bleeding is not known.
FOXO1-Mediated Activation of Akt Plays a Critical Role in Vascular Homeostasis
Authors: Harita Dharaneeswaran, Md. Ruhul Abid, Lei Yuan, Dylan Dupuis, David Beeler, Katherine C. Spokes, Lauren Janes, Tracey Sciuto, Peter M. Kang, Shou-Ching S. Jaminet, Ann Dvorak, Marianne A. Grant, Erzsébet Ravasz Regan, William C. Aird
Journal: Circulation Research (2014)

Rationale : Forkhead box-O transcription factors (FOXOs) transduce a wide range of extracellular signals, resulting in changes in cell survival, cell cycle progression, and several cell type-specific responses. FOXO1 is expressed in many cell types, including endothelial cells (ECs). Previous studies have shown that Foxo1 knockout in mice results in embryonic lethality at E11 because of impaired vascular development. In contrast, somatic deletion of Foxo1 is associated with hyperproliferation of ECs. Thus, the precise role of FOXO1 in the endothelium remains enigmatic. Objective : To determine the effect of endothelial-specific knockout and overexpression of FOXO1 on vascular homeostasis. Methods and Results : We show that EC-specific disruption of Foxo1 in mice phenocopies the full knockout. Although endothelial expression of FOXO1 rescued otherwise Foxo1 -null animals, overexpression of constitutively active FOXO1 resulted in increased EC size, occlusion of capillaries, elevated peripheral resistance, heart failure, and death. Knockdown of FOXO1 in ECs resulted in marked inhibition of basal and vascular endothelial growth factor–induced Akt-mammalian target of rapamycin complex 1 (mTORC1) signaling. Conclusions : Our findings suggest that in mice, endothelial expression of FOXO1 is both necessary and sufficient for embryonic development. Moreover, FOXO1-mediated feedback activation of Akt maintains growth factor responsive Akt/mTORC1 activity within a homeostatic range.
An evaluation of perfusion techniques in the study of water and electrolyte absorption in man: the problem of endogenous secretions.
Authors: K H Soergel
Journal: Gut (1969)

SECRETIONSSladen and Dawson (Gut, 9, 530-535) state that fasting intestinal contents cause negligible errors in calculated water absorption rates during intestinal perfusion studies.This conclusion is based on the finding of, generally, higher water absorption rates from glucosesaline solutions with a 2-lumen perfusion tube than with a 3-lumen tube, the latter allowing for mixing of test solution with the fasting intestinal contents before entry into the test segment.The design of the experiments which the authors undertook, to compare the performance of the two types of tube, introduced, however, additional variables (different flow rates and composition of solution in the test segment; studies performed on different days and, apparently, on different subjects), rendering their results uninterpretable as to the presence or magnitude of the effect of fasting intestinal contents on the cal- culated water absorption rate.We have observed up to 50% of the infused solution (20 ml per min) to reflux to a point 15 cm proximal to the infusion tip, resulting in an effectively perfused gut segment of unknown length when a 2-lumen tube is used.In addition, the authors elected not to reduce the variability of calculated absorption rates by accounting for the transit time of the solution through the test segment (Whalen, Harris, Geenen, and Soergel, 1966).Lastly, absorption rates should be presented in relation to the geometric mean solute concentration in the test segment, rather than to the composition of the fluid upon entry into this segment.In commenting on our estimates of fasting intestinal contents flow rates the authors quote Jacobson, Bondy, Broitman, and Fordtran (1963), as having shown that PEG 4000 adheres to the mucosal surface.On the contra- ry, Jacobson et al concluded that some water containing inert marker is trapped between the intestinal folds, making volume estimates based on marker concentration changes more accurate than the volume actually re- covered from closed intestinal loops.In view of the accumulated evidence published by others and of the inconclusive experiments of Sladen and Dawson, the use of the 2-lumen tube for the study of water and electrolyte absorption rates can, in our opinion, not be recommended.
Discovery and Biology of IL-23 and IL-27: Related but Functionally Distinct Regulators of Inflammation
Authors: Robert A. Kastelein, Christopher A. Hunter, Daniel J. Cua
Journal: Annual Review of Immunology (2006)

Long-term resistance to many infections depends on the innate ability of the immune system to coordinate the development of antigen-specific adaptive responses. Deficiencies in these events can result in increased susceptibility to pathogens, whereas an inability to regulate an appropriate response can lead to devastating pathological conditions. For over a decade, interleukin (IL)-12 has been recognized as the canonical cytokine that links innate and adaptive immunity, and with the discovery of IL-23 and IL-27 as cytokines related to IL-12, there has been a concerted effort to understand the relationship between these factors. The results emerging from these studies have provided fundamental new insights into the developmental pathways that promote the differentiation and function of CD4 + T helper cells and offer a dramatically altered perspective on the cause and prevention of autoimmune disease. In this review, we aim to highlight the discoveries that have led to our current understanding of the biology of IL-23 and IL-27 in the context of their role in resistance to infection, immune-mediated inflammation, and cancer.
Lysis of colonic epithelial cells by allogeneic mononuclear and lymphokine activated killer cells derived from peripheral blood and intestinal mucosa: evidence against a pathogenic role in inflammatory bowel disease.
Authors: P R Gibson, E van de Pol, W Pullman, W F Doe
Journal: Gut (1988)

A sensitive 4 h 51Cr-release cytotoxicity assay has been developed using as targets colonic epithelial cells obtained by Dispase-collagenase digestion of resected mucosa or colonoscopic biopsies. Peripheral blood mononuclear cells (MNC) from most healthy donors showed low, but significant levels of cytotoxicity for normal epithelial cell target cells of 8.7 (4.4) % (mean (SD] and similar levels were found in 14 ulcerative colitis (6.5 (4.4) %) and 16 Crohn9s disease (6.2 (5.2) %) patients. Neither drug therapy nor disease activity influenced the results. The sensitivity of colonic epithelial cells isolated from inflamed and histologically normal mucosa to lysis by peripheral blood MNC from a single donor was not affected by the underlying disease. Anti-epithelial cell activity did not correlate with anti-K562 activity and the cytotoxic cell was plastic non-adherent and Leu-11b-. None of 15 MNC populations isolated from mucosa of normal, tumour bearing, or chronically inflamed intestine exhibited significant lysis of colonic epithelial cells despite killing of K562 target cells in 10. Lymphokine activated killer (LAK) cells, generated by interleukin-2 stimulation in vitro of nine intestinal and seven peripheral blood MNC populations, exhibited high levels of lysis of K562 cells but, on every occasion, failed to lyse colonic epithelial cells. These data indicate that spontaneously cytotoxic or LAK cells are unlikely to play a role in the generation of colonic epithelial cell injury by direct cytotoxicity in inflammatory bowel disease.
Two Types of Ventricular Fibrillation in Isolated Rabbit Hearts
Authors: Tsu-Juey Wu, Shien-Fong Lin, James N. Weiss, Chih-Tai Ting, Peng-Sheng Chen
Journal: Circulation (2002)

The combined effects of excitability and action potential duration (APD) restitution on wavefront dynamics remain unclear.We used optical mapping techniques to study Langendorff-perfused rabbit hearts. In protocol IA (n=10), D600 at increasing concentrations was infused during ventricular fibrillation (VF). With concentration increased to 0.5 mg/L, fast VF (dominant frequency, 19.1+/-1.8 Hz) was consistently converted to ventricular tachycardia (VT). However, increasing D600 further to 2.5 or 5.0 mg/L converted VT to slow VF (11.9+/-2.3 Hz, P=0.0011). In an additional 4 hearts (protocol IB), tetrodotoxin converted a preexisting VT to slow VF (11.0+/-1.4 Hz). Optical maps show wandering wavelets in fast VF, organized reentry in VT, and spatiotemporal periodicity in slow VF. In protocol II, we determined APD and conduction time(-1) (CT(-1)) restitutions during D600 infusion. CT(-1) was used as an estimate of excitability. At 0.1 mg/L, APD and CT(-1) restitutions were steep and flat, respectively. APD restitution became flattened when D600 increased to 0.5 mg/L, converting fast VF to VT. Further increasing D600 to 2.5 or 5.0 mg/L steepened CT(-1) restitution and widened the range of S(1) pacing cycle lengths over which CT(-1) decreased, converting VT to slow VF.Two types of VF exist in isolated rabbit hearts. Fast (type I) VF is associated with a steep APD restitution, a flat CT(-1) restitution, and wandering wavelets. Slow (type II) VF is associated with a flat APD restitution, a steep CT(-1) restitution, and spatiotemporal periodicity. Both excitability and APD restitution are important in VF maintenance.
Treatment of obstruction of the superior vena cava by combination chemotherapy with and without irradiation in small-cell carcinoma of the bronchus.
Authors: S G Spiro, S Shah, P G Harper, J S Tobias, D M Geddes, R L Souhami
Journal: Thorax (1983)

In a randomised prospective trial of chemotherapy with and without radiotherapy in small-cell carcinoma of the bronchus, 37 of 366 patients presented with obstruction of the superior vena cava at the time of diagnosis. In the study all patients received four cycles of combination chemotherapy over a period of 12 weeks and, provided there was not progressive disease, then received either radiotherapy to the mediastinum and primary tumour followed by eight further courses of chemotherapy or eight cycles of chemotherapy alone. Of the 37 patients presenting with superior vena caval obstruction, nine had relapsed and treatment was stopped during or after the initial four cycles of chemotherapy. Of the remainder, 15 patients received radiotherapy plus chemotherapy and 13 chemotherapy alone. After four cycles of chemotherapy (12 weeks) 21 of the 37 patients had initial complete relief of symptoms secondary to superior vena caval obstruction, 10 had substantial but partial relief, and six had no relief. Twelve patients developed recurrence of superior vena caval obstruction, of whom six had received radiotherapy and four chemotherapy alone; two relapsed in the initial 12 weeks of the study. The median survival of the patients with superior vena caval obstruction allocated at diagnosis to either treatment arm was identical. The survival of patients with obstruction was similar to that of other patients in the main study. Chemotherapy is an effective treatment for superior vena caval obstruction and there appears to be no additional advantage in giving radiotherapy after 12 weeks of cyclical chemotherapy.
Individualized Patient Dosing in Phase I Clinical Trials: The Role of Escalation With Overdose Control in PNU-214936
Authors: Jonathan D. Cheng, James S. Babb, Corey Langer, Steinar Aamdal, Francisco Robert, Lars Rupert Engelhardt, Olov Fernberg, Joan Schiller, Goran Forsberg, R. Katherine Alpaugh, Louis M. Weiner, André Rogatko
Journal: Journal of Clinical Oncology (2004)

A patient-specific dose-escalation scheme using a Bayesian model of Escalation with Overdose Control (EWOC) was conducted to establish the maximum tolerated dose (MTD) of PNU-214936 in advanced non-small-cell lung cancer (NSCLC). PNU-214936 is a murine Fab fragment of the monoclonal antibody 5T4 fused to a mutated superantigen staphylococcal enterotoxin A (SEA).Seventy-eight patients with NSCLC were treated with an individualized dose of PNU-214936 calculated using EWOC, based on their anti-SEA antibody level, and given as a 3-hour infusion on 4 consecutive days.Fever (82%; grade 3 to 4, 2.6%) and hypotension (57%; grade 3 to 4, 9%) were the most common toxicities. Eight dose-limiting toxicities occurred, as defined as any grade 4 toxicity occurring within the first 5 days. The MTD was defined as a function of pretreatment anti-SEA antibody level. MTD ranged from 103 ng/kg for patients with anti-SEA concentrations < or = 10 pmol/mL, to 601 ng/kg for patients with anti-SEA concentrations of 91 to 150 pmol/mL. A minor tumor response was demonstrated in five of 66 assessable patients.EWOC determined phase I doses of PNU-214936 that were adjusted for patient anti-SEA antibody level, while safeguarding against overdose. Furthermore, the method permitted the construction of a dosing algorithm that would allow patients in subsequent clinical investigations to be treated with a dose of PNU-214936 that is tailored to their specific tolerance for the agent, as reflected by their pretreatment anti-SEA.
INDUCED UNRESPONSIVENESS TO SIMPLE ALLERGENIC CHEMICALS
Authors: Jack R. Battisto, Merrill W. Chase
Journal: The Journal of Experimental Medicine (1965)

Normal guinea pigs fed chemical haptens develop a specific state of unresponsiveness, inhibiting subsequent development of dermal sensitization with the same hapten and modifying profoundly the synthesis of anaphylactic antibody in response to hapten conjugated to guinea pig proteins. The degree of unresponsiveness has been tested by exposing hapten-fed animals to intense haptenic stimulation. Animals of groups that were demonstrably unresponsive to picryl chloride could be made to form hapten-specific antibody by injecting picrylated bovine gamma globulin. Specific anaphylactic-type antibodies, presumably 7S gamma(1), were synthesized, and in animals given PBGG adsorbed to alumina there arose a measurable concentration of precipitating antibody, presumably 7S gamma(2), perhaps slightly earlier than in similarly treated control animals. Attempts to impose contact-type reactivity on such unresponsive animals met with limited success. Injection of picrylated guinea pig erythrocyte stromata in a complete Freund's adjuvant, with subsequent applications of picryl chloride to the dermis, led to definite contact sensitivity to 0.3 per cent picryl chloride, whereas parallel treatment of normal control animals induced sensitivity to 0.006 or 0.002 per cent. By this double method of stimulation, hapten-fed animals did not advance in sensitivity by reason of the secondary dermal applications of the simple chemical, whereas control animals developed increasingly higher sensitivity by these contacts in what appeared to be a stepwise manner. Picryl chloride-fed guinea pigs injected intradermally with picryl chloride either after or before forming picryl-specific circulating antibody still remained unable to develop picryl-specific contact hypersensitivity. Control animals synthesizing picryl-specific antibody subsequently responded to intradermal injection of picryl chloride with contact-type sensitivity. Interpretations of these results are discussed and the view is presented that delayed-type hypersensitivity and circulating antibodies of the varieties measured here are formed independently of each other.
A single course of rituximab does not abrogate anti-infliximab antibodies in patients with rheumatoid arthritis
Authors: B J F van den Bemt, K Vos, A A d. Broeder, M Blom, R M Thurlings, G M Bartelds, S O Stapel, P Barrera, P P Tak, M T Nurmohamed, G-J Wolbink
Journal: Annals of the Rheumatic Diseases (2009)

The development of anti-infliximab antibodies in 8% to 43% of infliximab-treated patients is associated with decreased efficiency and increased risk of adverse effects.1–3 An intervention that can diminish anti-infliximab antibody formation is therefore warranted. Rituximab, a chimeric monoclonal antibody that selectively depletes CD20-positive B lymphocytes, could potentially inhibit the human antibody response against infliximab. Therefore, we assessed the proportion of patients with rheumatoid arthritis (RA) in which treatment with rituximab resulted in the depletion of anti-infliximab antibodies.

Consecutive patients with RA with detectable anti-infliximab antibodies, who were initiated on treatment with either rituximab or adalimumab, were included in this prospective controlled cohort study. …
Cytopathic effects in cultures inoculated with material from Crohn's disease.
Authors: C O Morain, H Prestage, P Harrison, A J Levi, D A Tyrrell
Journal: Gut (1981)

Rectal biopsy homogenates, faecal samples, and leucocyte rich plasma obtained from 39 patients were inoculated into tissue cultures. A non-transmissible cytopathic effect was observed in cultures inoculated with material from patients with Crohn9s disease. In a blind study this cytopathic effect was observed in three specimens from three patients with Crohn9s disease, in six specimens from four patients with ulcerative colitis, and six specimens from five patients with upper gastrointestinal disease. The cytopathic effect is unlikely to be associated with the bowel diseases tested. These results are also consistent with the failure of others to isolate a virus by the techniques used. With the limited range of techniques used no evidence was obtained to implicate conventional viruses in the pathogenesis of Crohn9s disease.
Cyclins, Cdks, E2f, Skp2, and More at the First International RB Tumor Suppressor Meeting
Authors: Rod Bremner, Eldad Zacksenhaus
Journal: Cancer Research (2010)

The RB1 gene was cloned because its inactivation causes the childhood ocular tumor, retinoblastoma. It is widely expressed, inactivated in most human malignancies, and present in diverse organisms from mammals to plants. Initially, retinoblastoma protein (pRB) was linked to cell cycle regulation, but it also regulates senescence, apoptosis, autophagy, differentiation, genome stability, immunity, telomere function, stem cell biology, and embryonic development. In the 23 years since the gene was cloned, a formal international symposium focused on the RB pathway has not been held. The "First International RB Tumor Suppressor Meeting" (Toronto, Canada, November 19-21, 2009) established a biennial event to bring experts in the field together to discuss how the RB family ("pocket proteins"), as well as its regulators and effectors, influence biology and human disease. We summarize major new breakthroughs and emerging trends presented at the meeting.
Early growth and adult respiratory function in men and women followed from the fetal period to adulthood
Authors: D. Canoy, J. Pekkanen, P. Elliott, A. Pouta, J. Laitinen, A.-L. Hartikainen, P. Zitting, S. Patel, M. P Little, M.-R. Jarvelin
Journal: Thorax (2006)

While some studies suggest that poor fetal growth rate, as indicated by lower birth weight, is associated with poor respiratory function in childhood, findings among adults remain inconsistent. A study was undertaken to determine the association between early growth and adult respiratory function.