tbuckley/cabot-search huggingface dataset:
Abstract 4582: CRLX522, a novel dynamic tumor-targeted cabazitaxel nanopharmaceutical
Authors: Douglas Lazarus, Sujan Kabir, Scott Eliasof
Journal: Cancer Research (2014)

Abstract Cabazitaxel is an approved treatment for castration-refractory prostate cancer. As with other taxanes, the therapeutic benefits of cabazitaxel are often compromised by immunosuppression and neurotoxicity. In order to address the obstacles to using cabazitaxel, we developed the dynamic tumor-targeted cabazitaxel nanopharmaceutical CRLX522. This nanopharmaceutical possesses significantly enhanced efficacy and improved pharmacokinetics compared to the parent drug. CRLX522 showed a superior PK profile, with a &amp;gt;400-fold increase in AUC, a significantly longer half-life and a 32-fold higher drug concentration in tumor tissue 72 hours after a single administration versus cabazitaxel alone. The improved PK and biodistribution of CRLX522 translated into superior antitumor activity in murine syngeneic and human xenograft models. In the murine B16.F10 tumor model, median survival at the MTD exceeded 58 days for CRLX522 compared to 26 days for the parent drug cabazitaxel. CRLX522 demonstrated superior efficacy over cabazitaxel with a cure rate of 100% in a xenograft model representing breast cancer tumors, compared to 50% cures for the parent drug cabazitaxel. In summary, CRLX522 represents a new and potent anticancer therapeutic that has the potential to be a best-in-class taxane. Citation Format: Douglas Lazarus, Sujan Kabir, Scott Eliasof. CRLX522, a novel dynamic tumor-targeted cabazitaxel nanopharmaceutical. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4582. doi:10.1158/1538-7445.AM2014-4582
Detection of antineutrophil cytoplasmic antibody in a patient with L-tryptophan induced eosinophilia-myalgia syndrome.
Authors: A M Cilursu, J Goeken, R R Olson
Journal: Annals of the Rheumatic Diseases (1991)

The Center for Disease Control has received numerous reports of an eosinophilia-myalgia syndrome related to products containing L-tryptophan. The case is reported of eosinophilia-myalgia syndrome and polyneuropathy associated with myeloperoxidase specific antineutrophil cytoplasmic antibody.
A new mental health strategy for England
Authors: G. Thornicroft
Journal: BMJ (2011)

<h3>BACKGROUND</h3> Small bowel transplantation remains a difficult therapeutic option endangered by a high rate of rejection and infectious complications. To improve these clinical results, it is mandatory to set up animal models to test alternative immunosuppressive regimens which may lead to immunotolerance. <h3>AIMS</h3> To determine the value of blockade of αLβ2 (LFA-1) and α4 and β7 integrins (α4β1, α4β7, and αEβ7) in the prevention of rejection of fetal small bowel grafts in mice and the effect of the association of calcineurin dependent drugs in anti-LFA-1 treated mice. <h3>METHODS</h3> Adult recipient mice engrafted with allogeneic fetal small bowel received a short course of anti-α4 and/or anti-LFA-1 monoclonal antibodies (mAb) with or without FK506 or cyclosporin A. In addition, in a set of experiment, β7−/− mice were used as recipients. Graft biopsies were performed and processed for standard histology. <h3>RESULTS</h3> Blockade of the pathways of the integrins α4 and β7 had a modest or no effect on intestinal graft survival. In contrast, transitory, short administration of anti-LFA-1 monoclonal antibody alone, when started before engraftment (day −1), allowed long term survival of intestinal grafts, even when associated with calcineurin dependent drugs. However, early withdrawal of FK506 reversed the immunosuppressive effect of anti-LFA-1 treatment. <h3>CONCLUSION</h3> These results suggest that firstly, anti-LFA-1, but not anti-α4 mAb treatment, may be useful in improving the results of intestinal transplantation, and secondly, that this treatment is not incompatible with long term administration of tacrolimus currently used in the prevention of small bowel graft rejection in humans.
Insulinotropic Action of Glucagonlike Peptide-I-(7–37) in Diabetic and Nondiabetic Subjects
Authors: David M Nathan, Eric Schreiber, Howard Fogel, Svetlana Mojsov, Joel F Habener
Journal: Diabetes Care (1992)

Objective Whether glucagonlike peptide-I-(7–37) (GLP-I-[7–37]), a naturally occurring intestinal peptide, is insulinotropic in nondiabetic and non-insulindependent (type II) diabetic subjects. Research Design and Methods GLP-I-(7–37) or saline placebo was infused (1–5 ng · kg−1 · min−1 for 30 min) in 4 nondiabetic and 11 type II diabetic subjects in the fasting and prandial state. Glucose, insulin, and GLP-I-(7–37) levels were measured. Results GLP-I-(7–37) infusion resulted in a 3- to 10-fold increase in peak insulin levels and in insulin area under the curve in nondiabetic and diabetic subjects. In diabetic subjects, infusion concurrent with a standard meal eliminated the postprandial glucose excursion for 60 min after the meal. Insulin-releasing potency of GLP-I-(7-37) was attenuated at decreased glucose levels. Conclusions GLP-I-(7–37) has potent insulinotropic effects in nondiabetic and diabetic subjects. Whether GLP-I-(7–37) is useful as a therapeutic medication in type II diabetes requires further investigation.
Solitary squamous papilloma of the bronchus.
Authors: R J Maxwell, J R Gibbons, M D O'Hara
Journal: Thorax (1985)

A case of solitary squamous papilloma of the bronchus is described and 11 other cases from the reports published worldwide are reviewed. These tumours present in middle aged men with symptoms similar to those of bronchial carcinoma. Treatment by bronchoscopic removal or lobectomy is usually curative. Symptoms are similar to those of bronchial carcinoma, but a correct preoperative diagnosis permits more conservative surgery to be carried out. Difficulties in the histological classification of papillary tumours of the bronchus are discussed.
Vinyl Chloride: A Case Study of Data Suppression and Misrepresentation
Authors: Jennifer Beth Sass, Barry Castleman, David Wallinga
Journal: Environmental Health Perspectives (2005)

When the U.S. Environmental Protection Agency (EPA) finalized its 2000 update of the toxicological effects of vinyl chloride (VC), it was concerned with two issues: the classification of VC as a carcinogen and the numerical estimate of its potency. In this commentary we describe how the U.S. EPA review of VC toxicology, which was drafted with substantial input from the chemical industry, weakened safeguards on both points. First, the assessment down-plays risks from all cancer sites other than the liver. Second, the estimate of cancer potency was reduced 10-fold from values previously used for environmental decision making, a finding that reduces the cost and extent of pollution reduction and cleanup measures. We suggest that this assessment reflects discredited scientific practices and recommend that the U.S. EPA reverse its trend toward ever-increasing collaborations with the regulated industries when generating scientific reviews and risk assessments.
Noninvasive Approaches to Diagnose Intrathoracic Extramedullary Hematopoiesis
Authors: Anand Zade, Nilendu Purandare, Venkatesh Rangarajan, Sneha Shah, Archi Agrawal, Jha Ashish, Mukta Kulkarni
Journal: Clinical Nuclear Medicine (2012)

Extramedullary hematopoiesis refers to the presence of hematopoietic elements in locations other than the bone marrow medullary space. It occurs as a compensatory mechanism to impaired hematopoiesis resulting from a variety of pathological conditions. Because of the hazards of biopsy of a highly vascular hematopoietic mass, it is desirable to establish the diagnosis noninvasively. We report a case where 18F-fluoro-3'deoxy-L-thymidine PET/CT and 99mTc-SC scintigraphy were used as a noninvasive modality to diagnose extramedullary hematopoiesis.
On the Incidence of Intron Loss and Gain in Paralogous Gene Families
Authors: S. W. Roy, D. Penny
Journal: Molecular Biology and Evolution (2007)

Understanding gene duplication and gene structure evolution are fundamental goals of molecular evolutionary biology. A previous study by Babenko et al. (2004. Prevalence of intron gain over intron loss in the evolution of paralogous gene families. Nucleic Acids Res. 32:3724-3733) employed Dollo parsimony to infer spliceosomal intron losses and gains in paralogous gene families and concluded that there was a general excess of gains over losses. This result contrasts with patterns in orthologous genes, in which most lineages show an excess of intron losses over gains, suggesting the possibility of fundamentally different modes of intron evolution between orthologous and paralogous genes. We further studied the data and found a low level of intron position conservation with outgroups, and this led to problems with using Dollo parsimony to analyze the data. Statistical reanalysis of the data suggests, instead, that intron losses have outnumbered intron gains in paralogous gene families.
Differences In The Sensitising Potential Of The Contact Sensitisers Dinitrochlorobenzene (DNCB) And Dinitrothiocyanobenzene (DNTB) Relate To Barrier Function Of The Skin
Authors: C. Pickard, F. Louafi, K.M. Lowings, J.O. Warner, I. Kimber, P.S. Friedmann
Journal: Journal of Allergy and Clinical Immunology (2009)
Abstract P3-10-35: Using Automated Image Analysis To Validate Ki67 as a Clinical Prognostic Biomarker for Estrogen-Receptor Positive Breast Cancers
Authors: AM Magliocco, EN Kornaga, AC Klimowicz, SK Petrillo, M Konno, A. Yau
Journal: Cancer Research (2010)

Abstract Background: Ki67, an indicator of proliferation, has been shown to be a useful prognostic and predictive marker for breast cancer. Ki67 can be used to identify two distinct estrogen-receptor positive subtypes: luminal A and luminal B. Luminal A breast cancers have been identified as having a lower proliferation and better outcome compared to luminal B. Furthermore, early clinical trials suggest that Ki67 may be useful in identifying a subset of patients that are sensitive to adjuvant docetaxel treatment. Currently, only estrogen-receptor (ER), progesterone-receptor (PR), and human epidermal growth-factor (HER2) are routinely performed. We have optimized and validated an immunohistochemical (IHC) Ki67 assay and automated computerized image analysis platform for routine clinical testing. Materials and Methods: Immunohistochemical staining was quantitatively assessed using the ACIS® III platform on a cohort (N=761) of tamoxifen treated patients who were diagnosed with breast cancer in Calgary between 1990 and 2001. Tissue microarrays were constructed using three 0.6 mm cores. Ki67 results were available for 510 patients, 461 of which are ER/PR positive and HER2 negative. Staining was performed using the DAKO FLEX ready-to-use system. The percent nuclear area positive was calculated using ACIS III and the maximum value was used in statistical analysis Results: X-tile statistical software was used to identify an optimal Ki67 cut point to distinguish differential overall survival in node negative ER positive cancers of 18.75%. This cut point was then used to categorize the 461 ER/PR positive and HER2 negative breast cancers into luminal A (407; 88.3%) or luminal B (54; 11.7%) subtypes. The 8-year breast cancer specific survival was 85.2% (95% CI = 81.3% - 89.1%) for luminal A and 53.6% (95% CI = 39.3% - 67.9%) for luminal B (P&amp;lt;0.0001). Cox regression showed a hazard ratio of 1.63 (95% CI = 0.99 — 2.67, p=0.055), adjusting for age, tumor size, grade and lymph node status. Discussion: Quantification of Ki67 expression using automated image analysis can be used clinically to distinguish luminal A from luminal B in ER/PR positive and HER2 negative breast cancers. The purpose of this project was to develop a reliable Ki67 assay that can be easily adopted by other testing centers. Using a ready-to-use IHC system — such as DAKO FLEX — allows for consistent results between other clinical laboratories. Additionally, using an automated, quantitative imaging system — such as the ACIS® III — reduces inter-observer variation that can occur by human visual assessment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-35.
PROLONGED MYOCARDIAL RETENTION OF 15-PHENYL-5- TELLURAPENTADECANOIC ACID: A NEW AGENT FOR POTENTIAL LABELING WITH 1-123
Authors: M M Goodman, F F Knapp, H W Strauss, D R Elmaleh, S Y Kopiwoda, A P Callahan, L A Ferren
Journal: Clinical Nuclear Medicine (1981)

Goodman, M M; Knapp, F F Jr.; Strauss, H W; Elmaleh, D R; Kopiwoda, S Y; Callahan, A P; Ferren, L A Author Information
Treatment of Stasis Ulcers
Authors: Robert R. Linton
Journal: JAMA (1963)

<h3>To the Editor:</h3> —(1) In regard to the use of local antibiotics, I perhaps should have been a little more specific. I use only bacitracin and occasionally neomycin. Neither of these agents can be used parenterally, so there is no danger of sensitivity to a parenterally administered antibiotic which may be needed in the future. I would not quarrel too much with the use of ordinary vaseline. I have done this for years, but I have found that the two antibiotics mentioned above add a little in management. (2) There is an occasional patient who must be put to bed and who requires elevation of the leg above the level of the heart, as has been suggested. In my office practice, it is necessary to put a patient at bed rest in only one in 20 times or less. I find that if the bandage is applied properly, with plenty
Accuracy and Outcomes of Screening Mammography in Women With a Personal History of Early-Stage Breast Cancer
Authors: Nehmat Houssami, Linn A. Abraham, Diana L. Miglioretti, Edward A. Sickles, Karla Kerlikowske, Diana S.M. Buist, Berta M. Geller, Hyman Bernard Muss, Les Irwig
Journal: JAMA (2011)

Context Women with a personal history of breast cancer (PHBC) are at risk of developing another breast cancer and are recommended for screening mammography.Few high-quality data exist on screening performance in PHBC women.Objective To examine the accuracy and outcomes of mammography screening in PHBC women relative to screening of similar women without PHBC. Design and SettingCohort of PHBC women, mammogram matched to non-PHBC women, screened through facilities (1996-2007) affiliated with the Breast Cancer Surveillance Consortium.Participants There were 58 870 screening mammograms in 19 078 women with a history of early-stage (in situ or stage I-II invasive) breast cancer and 58 870 matched (breast density, age group, mammography year, and registry) screening mammograms in 55 315 non-PHBC women. Main Outcome MeasuresMammography accuracy based on final assessment, cancer detection rate, interval cancer rate, and stage at diagnosis. ResultsWithin 1 year after screening, 655 cancers were observed in PHBC women (499 invasive, 156 in situ) and 342 cancers (285 invasive, 57 in situ) in non-PHBC women.Screening accuracy and outcomes in PHBC relative to non-PHBC women were cancer rates of 10.5 per 1000 screens (95% CI, 9.7-11.3)vs 5.8 per 1000 screens (95% CI, 5.2-6.4),cancer detection rate of 6.8 per 1000 screens (95% CI, 6.2-7.5)vs 4.4 per 1000 screens (95% CI, 3.9-5.0),interval cancer rate of 3.6 per 1000 screens (95% CI, 3.2-4.1)vs 1.4 per 1000 screens (95% CI, 1.1-1.7),sensitivity 65.4% (95% CI, 61.5%-69.0%)vs 76.5% (95% CI, 71.7%-80.7%),specificity 98.3% (95% CI, 98.2%-98.4%)vs 99.0% (95% CI, 98.9%-99.1%),abnormal mammogram results in 2.3% (95% CI, 2.2%-2.5%)vs 1.4% (95% CI, 1.3%-1.5%)(all comparisons PϽ.001).Screening sensitivity in PHBC women was higher for detection of in situ cancer (78.7%; 95% CI, 71.4%-84.5%)than invasive cancer (61.1%; 95% CI, 56.6%-65.4%),PϽ.001; lower in the initial 5 years (60.2%;95% CI, 54.7%-65.5%)than after 5 years from first cancer (70.8%; 95% CI, 65.4%-75.6%),P=.006; and was similar for detection of ipsilateral cancer (66.3%; 95% CI, 60.3%-71.8%)and contralateral cancer (66.1%; 95% CI, 60.9%-70.9%),P=.96.Screen-detected and interval cancers in women with and without PHBC were predominantly early stage. ConclusionMammography screening in PHBC women detects early-stage second breast cancers but has lower sensitivity and higher interval cancer rate, despite more evaluation and higher underlying cancer rate, relative to that in non-PHBC women.
Diagnosis and clinical management of alcohol related physical complications: summary of NICE guidance
Authors: S. Swain, T. Krause, P. Laramee, S. Stewart
Journal: BMJ (2010)

Continued hazardous and harmful drinking can result in dependence and tolerance, with risk of alcohol withdrawal syndrome on abrupt reduction or cessation; it may also result in damage to almost any organ or system in the body. Hazardous and harmful drinkers are commonly encountered among hospital patients, with 863 300 alcohol related admissions to hospital in 2007-8, an increase of 69% since 2002-3.1 The cost to the NHS of treating acute and chronic drinking is estimated to be as much as £2.7bn a year.2 This article summarises recommendations made in the recent guidance from the National Institute for Health and Clinical Excellence (NICE) for the diagnosis and clinical management of alcohol related physical complications in adults and children (aged over 10 years).3 That guideline should be read in conjunction with the NICE public health guidance on the prevention and early identification of alcohol use disorders in adults and young people4 and the forthcoming NICE clinical guideline on the management of alcohol dependence and harmful alcohol use.5 NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Acute alcohol withdrawal #### Admission to hospital
Heterogeneity of clonal development in chronic myeloproliferative disorders
Authors: Anna Maria Ferraris, Rosa Mangerini, Omar Racchi, Davide Rapezzi, Michela Rolfo, Salvatore Casciaro, Gian Franco Gaetani
Journal: American Journal of Hematology (1999)

Recent reports have suggested a previously unexpected variability in the expression of the dominant neoplastic clone in myeloproliferative disorders (MPD). We evaluated 49 female patients with MPD and informative at the X-linked androgen receptor (AR) locus to establish the X chromosome inactivation pattern of hemopoietic cells. Whereas in chronic myelogenous leukemia (CML) the granulocytes (PMN) were uniformly of monoclonal origin, a striking heterogeneity of clonal development was found in PMN from patients with other MPD, with up to 50% of them expressing a polyclonal pattern of X inactivation. Am. J. Hematol. 60:158–160, 1999. © 1999 Wiley-Liss, Inc.
Early Electrophysiological Abnormalities and Clinical Neuropathy
Authors: Lars Hyllienmark, Nils Alstrand, Björn Jonsson, Johnny Ludvigsson, Gerald Cooray, Jeanette Wahlberg-Topp
Journal: Diabetes Care (2013)

The aim of this study was to elucidate whether subclinical nerve dysfunction as reflected by neurophysiological testing predicts the development of clinical neuropathy in patients with type 1 diabetes.Fifty-nine patients were studied twice with neurophysiological measurements at baseline and at follow-up. At baseline, patients were 15.5±3.22 years (range 7-22 years) of age, and duration of diabetes was 6.8±3.3 years. At follow-up, patients were 20-35 years of age, and disease duration was 20±5.3 years (range 10-31 years).At baseline, patients showed modestly reduced nerve conduction velocities and amplitudes compared with healthy subjects, but all were free of clinical neuropathy. At follow-up, clinical neuropathy was present in nine (15%) patients. These patients had a more pronounced reduction in peroneal motor nerve conduction velocity (MCV), median MCV, and sural sensory nerve action potential at baseline (P<0.010-0.003). In simple logistic regression analyses, the predictor with the strongest association with clinical neuropathy was baseline HbA1c (R2=48%, odds ratio 7.9, P<0.002) followed by peroneal MCV at baseline (R2=38%, odds ratio 0.6, P<0.006). With the use of a stepwise forward analysis that included all predictors, first baseline HbA1c and then only peroneal MCV at baseline entered significantly (R2=61%). Neuropathy impairment assessment showed a stronger correlation with baseline HbA1c (ρ=0.40, P<0.002) than with follow-up HbA1c (ρ=0.034, P<0.007).Early defects in nerve conduction velocity predict the development of diabetic neuropathy. However, the strongest predictor was HbA1c during the first years of the disease.
Role of the Neural Niche in Brain Metastatic Cancer
Authors: John Termini, Josh Neman, Rahul Jandial
Journal: Cancer Research (2014)

Metastasis is the relentless pursuit of cancer to escape its primary site and colonize distant organs. This malignant evolutionary process is biologically heterogeneous, yet one unifying element is the critical role of the microenvironment for arriving metastatic cells. Historically, brain metastases were rarely investigated because patients with advanced cancer were considered terminal. Fortunately, advances in molecular therapies have led to patients living longer with metastatic cancer. However, one site remains recalcitrant to our treatment efforts, the brain. The central nervous system is the most complex biologic system, which poses unique obstacles but also harbors opportunities for discovery. Much of what we know about the brain microenvironment comes from neuroscience. We suggest that the interrelated cellular responses in traumatic brain injury may guide us toward new perspectives in understanding brain metastases. In this view, brain metastases may be conceptualized as progressive oncologic injury to the nervous system. This review discusses our evolving understanding of bidirectional interactions between the brain milieu and metastatic cancer.
Trends of intrathoracic blood volume (ITBV) and cardiac output (CO) in a group of critically ill patients
Authors: R. Piccione, E. Bernardi, S. Campagna, A. Caribotti, M. Fae, S. Spedicato, M. J. Volpini, C. Uguccioni, M. Nastasi
Journal: Intensive Care Medicine (1996)
Elastase, a marker for neutrophils in skin infiltrates
Authors: A. M. LAMMERS, P. C. M. KERKHOF, J. SCHALWIJK, P. D. MIER
Journal: British Journal of Dermatology (1986)

The enzyme elastase (EC 3.4.21.37) has proved to be a convenient and extremely sensitive marker for the quantification of neutrophils in cutaneous infiltrates. Fluorometric assay using the synthetic substrate MeOSuc‐Ala‐Ala‐Pro‐Val‐N‐methylcoumarin permitted the measurement of this enzyme in as few as five cells and was linear up to about 1000 cells per sample. The mean activity of lysates of human blood‐derived neutrophils was 0.57 ± 0.08 pmol of 7‐amino‐4‐methyl‐coumarin released per hour per neutrophil. Extracts of normal human skin contained no measurable elastase activity but resulted in a slight inhibition of the neutrophil enzyme (mean 12%). Application to the in vivo situation has been demonstrated by the use of leukotriene B4 as chemotactic agent. A reproducible neutrophil infiltrate was found at a dose of 2 ng, well below the threshold for the appearance of microabscesses.