tbuckley/cabot-search huggingface dataset:
Abstract 2330: NSC319726 reactivates zinc-binding p53 mis-sense mutants using a novel dual mechanism.
Authors: Xin Yu, David Lubin, Sumana Narayanan, Alexei Vazquez, Stewart Loh, Arnold J. Levine, Darren R. Carpizo
Journal: Cancer Research (2013)

Abstract TP53 is the most commonly mutated gene in human cancer for which no effective targeted anti-cancer drug exists. We identified NSC319726 (726) as a mutant p53 reactivating compound, and a lead compound for mutant p53 targeted drug development. Prior evidence indicated that the effects of 726 were allele-specific, by restoring wildtype structure and function to the third most common p53 mis-sense mutant (p53-R175H). This effect was dependent on the zinc-chelating and redox modulating properties of 726. The p53 protein binds a single zinc ion which is necessary for proper p53 structure and function. The p53-R175H mutation impairs the protein from binding zinc causing it to mis-fold and lose transcriptional function. We have investigated these properties of 726 in the mechanism of p53-R175H reactivation and provide evidence for a novel “dual” mechanism where 726 restores wild-type structure to the p53-R175H using a zinc-metallochaperone function to provide an optimal concentration of zinc to facilitate proper folding. We also demonstrate that the redox modulating properties of 726 function to transactivate the newly conformed p53-R175 and induce an apoptotic program. Lastly, we demonstrate that this zinc-metallochaperone function applies to other p53 mis-sense mutants with impaired zinc binding. This later finding extends the potential pool of patients that could be impacted by the clinical development of 726 as a mutant p53 targeted anti-cancer drug. Citation Format: Xin Yu, David Lubin, Sumana Narayanan, Alexei Vazquez, Stewart Loh, Arnold J. Levine, Darren R. Carpizo. NSC319726 reactivates zinc-binding p53 mis-sense mutants using a novel dual mechanism. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2330. doi:10.1158/1538-7445.AM2013-2330
Urinary leukotriene levels are increased during exacerbation of atopic eczema/dermatitis syndrome. Relation to clinical status
Authors: T. Adamek‐Guzik, T. J. Guzik, G. Czerniawska‐Mysik, G. Korpanty, L. Mastalerz, J. Radwan, A. Szczeklik
Journal: Allergy (2002)

Background: Leukotrienes are potent mediators of allergic inflammation and their role in the pathogenesis of allergic disorders, particularly asthma, is well established. Their importance in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS) is still unclear. We aimed to compare urinary cysteinyl leukotriene (Cys‐LT) levels during exacerbation and remission of AEDS in relation to clinical status, IgE levels, and eosinophil counts. Methods: Urinary Cys‐LTs were measured by direct enzyme immunoassay in 17 adult patients with AEDS and in 17 healthy controls in whom atopy had been excluded. Cys‐LTs were compared during exacerbation and remission of AEDS in relation to the clinical status measured by SCORAD. Total IgE levels were measured by enzyme‐linked immunoassay (ELISA). Results: Mean clinical score during the exacerbation was 64.3 ± 3.1 and during remission 22.4 ± 4 ( P &lt; 0.01). Cys‐LTs levels were significantly higher during the exacerbation of AEDS than in the control group (230.9 ± 20.8 vs 123.2 ± 9.9 pg/mg creatinine; P &lt; 0.005). During the remission, the difference between AEDS patients and the control group was not significant (96.3 ± 8.7 vs 123.2 ± 9.9 pg/mg creatinine; P = 0.8). During AEDS exacerbation Cys‐LTs levels were significantly correlated with the clinical status ( r S = 0.73, P &lt; 0.01) and with eosinophil counts ( r = 0.86; P &lt; 0.01) but not with the duration of the disease, age of patients, or IgE levels. Conclusions: Our results point to enhanced biosynthesis of Cys‐LTs during the AEDS exacerbations. Inflammatory cells, e.g. eosinophils are the most probable source of Cys‐LTs. A strong correlation between Cys‐LT levels and clinical status may in part explain preliminary clinical observations of efficacy of leukotriene antagonists in alleviating symptoms of AEDS.
913 THERAPEUTIC EFFECTS OF FXR AND TGR5 ACTIVATION IN THE MDR2 (ABCB4)−/− MOUSE MODEL OF SCLEROSING CHOLANGITIS
Authors: A. Baghdasaryan, T. Claudel, J. Gumhold, D. Silbert, S. Halsegger, R. Völkl, L. Adorini, P. Fickert, M. Trauner
Journal: Journal of Hepatology (2010)
Occult pancreatic head cancer in the setting of gallstone and common bile duct stones complicated by acute pancreatitis
Authors: Y. Bai, J. Gao, Y. Wang, F. Li, D. Zou, Z. Li
Journal: Endoscopy (2008)

Acute pancreatitis usually results from alcohol abuse or biliary obstruction [1], however, it can also result from pancreatic cancer [2]. The association between acute pancreatitis and pancreatic cancer has been reported [3], and the majority of these cases were initially misinterpreted as idiopathic pancreatitis. This is the first report describing a case of pancreatic cancer in the setting of biliary stones complicated by recurrent acute pancreatitis.
Obstetric anaesthetic services
Authors: P J Snow, A J M Cavenagh
Journal: BMJ (1986)

gesia has not been shown to be associated with increased perinatal mortality or morbidity, but the consequences of forceps delivery should not be dismissed too readily, as O'Driscoll and his colleagues have shown.5Safemanagementoflabour with increased availability and use of epidurals calls for a very high standard of obstetric and midwifery care, not just an increased number of consultant sessions in obstetric anaesthesia.
In vivo model of cartilage degradation--effects of a matrix metalloproteinase inhibitor.
Authors: E H Karran, T J Young, R E Markwell, G P Harper
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVES--To develop a model of cartilage degradation that (i) enables the testing of synthetic, small molecular weight matrix metalloproteinase (MMP) inhibitors as agents to prevent cartilage erosion, (ii) permits the direct assay of the principal constituents of the extracellular matrix (collagen and proteoglycan) in both the non-calcified articular cartilage and the calcified cartilage compartments, and (iii) is mediated by a chronic, granulomatous tissue that closely apposes intact articular cartilage, and in this respect resembles the pannus-cartilage junction of rheumatoid arthritis. METHODS--Femoral head cartilage was obtained from donor rats, wrapped in cotton and implanted subcutaneously into recipient animals. After a two stage papain digestion procedure, the proteoglycan and collagen contents were measured by assaying for glycosaminoglycans and hydroxyproline, respectively, in both the non-calcified cartilage that comprises the articular surface layer and the calcified cartilage compartment. The incorporation in vitro of [35S]-sulphate into glycosaminoglycans was assayed as a measure of proteoglycan biosynthesis. An osmotic minipump was cannulated to the implanted femoral head cartilage and synthetic MMP inhibitors (MI-1 and MI-2) were infused continuously over a 14 day period. RESULTS--The implanted, cotton wrapped femoral head cartilages provoked a granulomatous response that resulted in the removal of collagen and proteoglycan from the cartilage matrix. The removal of proteoglycan and collagen was exclusively from the non-calcified articular cartilage, whereas the proteoglycan and collagen content of the calcified compartment increased during the experiments. MI-1 reproducibly reduced the degradation of proteoglycan and collagen in implanted femoral head cartilage. CONCLUSIONS--We have described an in vivo model of cartilage degradation that permits the measurement of proteoglycan and collagen in both non-calcified articular cartilage and calcified cartilage compartments. The model can be used to test the effects of agents of unknown systemic bioavailability and pharmacokinetic profile by infusing them directly to the site of cartilage degradation. The removal of cartilage extracellular matrix by granulomatous tissue was inhibited by an MMP inhibitor, thus proving the involvement of this family of proteinases in cartilage catabolism in this model.
Inhalation of Medicinal Substances
Authors: J. Snow
Journal: BMJ (1851)

VARIOUS MEDICINAL SUBSTANCE&. ounce of compound mixture of iron three times daily.Soon after the change of medicine, he began to gain strength, and to improve, in every way, very rapidly.June 14tk.The quantity of urine was three pints in twenty-four hours ; of specific gravity, 1017 ; the colour was natural, the albumen much diminised.It contained a few casts, with epithelium more or less; disintegrated, and scarcely a trace of oil.At the begi'nning of July, the urine was free from albumen, and presented no trace of oil, but a very few casts with disintegrated epi- thelium; he was gai'ni'ng strength, and was much improved in appear- ance.Once after this, there was a temporary return of albumen, but it soon disappeared, and he completely regained his health and strength.He has occasionally since been under my care for trifling ailments; I have several times examined the urine, and have found it, in every respect, quite healthy.3, Woburn-square, Dec. 31, 1850.
Management of ventricular fibrillation by doctors in cardiac arrest teams
Authors: K Y Tham, R J Evans, E J Rubython, T D Kinnaird
Journal: BMJ (1994)

Successful management of a cardiac arrest in accident and emergency departments or other specialised hospital units can be expected to result in a survival rate of around 50% initially and around 20% after one year.1 The protocol for managing ventricular fibrillation and the importance of rapid defibrillation were emphasised in the European Resuscitation Council guidelines 1992 on advanced life support.2 3 We investigated knowledge of these guidelines among doctors in cardiac arrest teams with respect to the management of ventricular fibrillation.

In December 1993 and January 1994 we conducted a telephone survey of 113 doctors in the cardiac arrest teams from 62 teaching and district hospitals in England and Wales. These hospitals were randomly selected from the 1993 directory of the British Association for Accident and Emergency Medicine. The …
Snakes in the Grass Or, The Worm Turns On
Authors: Paul M. Abrahm
Journal: JAMA (1972)

<h3>To the Editor.—</h3> This case is presented to illustrate a new avenue for parasitic infestation of patients who never have left the United States. A youngish man in January 1971 complained of watery diarrhea and flatulence for almost a month. He had some mucus but no blood in the stools. He had not been out of the country. There was abdominal tenderness, but the abdomen was soft and there was no guarding. A barium enema revealed only sigmoid spasm and coarse folds. Our villain showed up in the first stool as cysts of<i>Giardia lamblia</i>and<i>E vermicularis</i>. With quinacrine, 100 mg three times a day for one week for the<i>Giardia</i>, and pyrvinium pamoate, 50 mg seven times for the<i>E vermicularis</i>, all symptoms ceased and stool specimens were negative. The monster was considered slain. In November 1971 the same symptoms reappeared. As no source of the original infestation
A murine model of allergic rhinitis: Studies on the role of IgE in pathogenesis and analysis of the eosinophil influx elicited by allergen and eotaxin
Authors: Matthijs van de Rijn, Paul D. Mehlhop, Alex Judkins, Marc E. Rothenberg, Andrew D. Luster, Hans C. Oettgen
Journal: Journal of Allergy and Clinical Immunology (1998)

Background: Allergic rhinitis is a prevalent disease with significant morbidity. Studies of its pathophysiology in human subjects have been limited. Nasal biopsy specimens are difficult to obtain, and nasal secretions incompletely reflect the cellular and molecular events in the mucosa. IgE-mediated mast cell activation and the elaboration of factors promoting eosinophil development and chemotaxis are likely to participate in pathogenesis.Objectives: We sought to develop a murine model of allergic rhinitis, to use it to assess the role of IgE in pathogenesis, and to study the effects of IL-5 and eotaxin in the nasal mucosa.Methods: A protein extract of Aspergillus fumigatus (Af) was instilled intranasally in mice. Histologic changes were examined in wild-type and IgE-deficient (IgE–/–) animals. The effect of eotaxin administration was assessed in wild-type and IL-5 transgenic mice.Results: Af-treated mice developed a nasal mucosal eosinophil influx comparable to that described for humans. This histology was distinct from that observed in a murine model of Af-induced asthma. The pathology appeared over a time course similar to that reported for human subjects. There was no difference in the intensity of the mucosal inflammatory infiltrate of Af-treated IgE–/– mice compared with wild-type mice. Eotaxin was able to recruit eosinophils to the mucosa but only in IL-5 transgenic animals.Conclusion: We describe a murine model for allergic rhinitis with an eosinophilic infiltrate comparable to that found in human disease and have demonstrated that rhinitis can arise in the absence of IgE. We have shown that the eosinophil influx can be induced by eotaxin in the presence of IL-5. (J Allergy Clin Immunol 1998;102:65-74.)
Identifying Circulating Tumor Stem Cells That Matter: The Key to Prognostication and Therapeutic Targeting
Authors: Bishoy Faltas, Amer Zeidan, Kristi Peters, Avisnata Das, Jamal Joudeh, Arunasalam Navaraj, Nathan G. Dolloff, Harold A. Harvey, Yixing Jiang, Joshua E. Allen, David T. Dicker, Wafik S. El Deiry
Journal: Journal of Clinical Oncology (2011)

TO THEEDITOR: We read with interest the article by Iinuma et al 1 that describes their study examining the clinical significance of cancer stem cells in the peripheral blood of patients with colorectal cancer (CRC). The defining characteristics of a circulating cancer stem cell (CTSC) are its capacity for self-renewal and for initiation of distant metastases; some of these cells are also resistant to traditional chemo- therapy. 2,3 The concept that circulating tumor stem cells can be iden- tified and targeted is attractive and has major diagnostic, prognostic, and therapeutic implications for patients with metastatic cancer. However, the identification of authentic CTSCs continues to be a challenge because of the lack of a clear understanding of the biologic heterogeneity of tumor stem-cell populations and also because of the lack of characterization of surface markers that predict clinically im- portant subsets of CTSCs, such as those with aggressive malignant potential or drug resistance.
The Porphyria, Plumbism, Pottery Puzzle
Authors: Thomas D. Bird, Donald M. Wallace, Robert F. Labbe
Journal: JAMA (1982)

THE FOLLOWING article describes the solution to a fascinating porphyria, plumbism, pottery puzzle. <h3>Report of a Case</h3> In July 1978, while in California, a 41-year-old woman noted the gradual onset of pain in both knees, spreading to her feet and lower back over a period of weeks. In November, episodic vomiting, decreased appetite, and abdominal cramps developed. These symptoms led to hospitalization in December 1978. Family history was positive for chronic constipation in her father. There was moderate abdominal distention and tenderness without rebound tenderness. Bowel sounds were present, vibratory sensation was decreased in both feet, and ankle reflexes were absent. X-ray films of the abdomen revealed dilated bowel. Upper and lower gastrointestinal tract series revealed normal findings. Spinal fluid protein and glucose levels and cell counts were normal. The patient's hematocrit reading was 31%; hemoglobin level, 10 g/dL; corrected reticulocyte count, 3.7%; mean corpuscular volume, 94 cu μm; mean
HLA-B alleles and complotypes in Mexican patients with seronegative spondyloarthropathies.
Authors: G Vargas-Alarcon, A Garcia, S Bahena, H Melin-Aldana, F Andrade, G Ibanez-de-Kasep, J Alcocer-Varela, D Alarcon-Segovia, J Granados
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--To analyse major histocompatibility complex (MHC) haplotypes in Mexican mestizo patients with seronegative spondyloarthropathies (SSpA) and normal controls, to discover if there are other antigens, besides B27, in the HLA region that might show association with the disease. METHODS--The study included 100 Mexican mestizo patients with SSpA and 200 of their first degree relatives. These groups were compared with 85 ethnically matched controls. The class I and class III MHC antigens were obtained by standard methods. The significance of differences between patients and controls was tested by chi 2 analysis; linkage disequilibrium among the different alleles in each haplotype was estimated by computing delta values. RESULTS--We found a significantly increased frequency of the HLA-B27 antigen (pcorr. = 1 x 10(-5), odds ratio (OR) = 33.4, 95% confidence interval (CI) = 9.3-142.0). In the group of 45 SSpA patients negative for the B27 antigen, independent increased frequencies of HLA-B49 antigen (pcorr. = 0.03, OR = 6.5, 95% CI = 1.5-32.8)) and the FC31 complotype (pcorr. = 0.04, OR = 3.7, 95% CI = 1.2-11.1) were found. Significant delta values were obtained for the [B27;SC30] haplotype (p = 0.0005) but not for haplotypes marked by the FC31 complotype. HLA-B antigens on the homologous chromosome in B27 positive patients were mainly HLA-B51 (18%) and HLA-B60 (16%); however, the observed genotypes B27/B51 and B27/B60 were not significantly different than expected from the allele frequencies alone. CONCLUSIONS--These data suggest that in Mexicans additional genes within the MHC region besides the HLA-B27 antigen, might be related to the genetic susceptibility for developing SSpA. Relevant antigens included the HLA-B49 and the FC31 complotype.
Haloperidol: Did It Cause the Respiratory Arrest?
Authors: Lewis Glickman
Journal: JAMA (1992)

To the Editor.  —I wish to take issue with Bedell and colleagues' characterization as   of 2 mg of intramuscular haloperidol given  agitation to an 80-year-old, 34-kg woman with a respiratory illness who subsequently had a respiratory arrest. 1 If 2 mg was  overdose responsible for the patient's respiratory arrest, haloperidol would either have to depress the medullary respiratory center or, simply by putting the patient to sleep, would have to decrease the respiratory rate enough to cause respiratory failure.  Haloperidol, unlike the benzodiazepines, does not depress the medullary respiratory center. Unlike the other drugs reported by the authors to have caused iatrogenic cardiac arrests,
Systemic Use of Local Anesthetics
Authors: John Adriani
Journal: JAMA (1966)

<h3>To the Editor:—</h3> I cannot agree with Dr. Ruben that the statement which I made concerning the intravenous use of local anesthetics is incorrect. While it is true that they are used by certain clinicians for a variety of purposes, these drugs have little to offer therapeutically by the intravenous route when one considers their lethal potential. The same thing may be accomplished by using other drugs which are safer. Their clinical usefulness, systemically, is limited and once again I say, there is little or no justification for using them for their systemic effects.
Stimulation of granulation tissue formation by platelet-derived growth factor in normal and diabetic rats.
Authors: G R Grotendorst, G R Martin, D Pencev, J Sodek, A K Harvey
Journal: Journal of Clinical Investigation (1985)

Subcutaneous implantation of Hunt-Schilling wound chambers in rats induces a wound repair response causing the chamber first to fill with fluid and subsequently with connective tissue. The presence of a type I collagen gel encouraged a more rapid dispersion of cells throughout the chamber but had no effect on the rate of new collagen deposition. Addition of platelet-derived growth factor (PDGF; 50 ng/chamber) to the collagen-filled chambers caused an earlier influx of connective tissue cells, a marked increase in DNA synthesis, and a greater collagen deposition in the chamber during the first 2 wk after implantation. After 3 wk, however, the levels of collagen were similar in PDGF-supplemented and control chambers. Diabetic animals exhibited a decreased rate of repair which was restored to normal by addition of PDGF to the wound chamber. Combinations of PDGF and insulin caused an even more rapid increase in collagen deposition. These results suggest that the levels of various growth factors, particularly PDGF, may be limiting at wound sites and that supplementation of wounds with these factors can accelerate the rate of new tissue formation.
Transfusion History and Cancer Risk in Older Women
Authors: James R. Cerhan, Robert B. Wallace, Aaron R. Folsom, John D. Potter, Ronald G. Munger, Ronald J. Prineas
Journal: Annals of Internal Medicine (1993)

Objective: To test the hypothesis that history of blood transfusion is associated with an increased incidence of cancer in older women. Design: Prospective cohort study. Setting: General community in the state of Iowa. Participants: Random sample of 37 337 cancer-free Iowa women ages 55 to 69 years. Measurements: Transfusion history was assessed with a mailed questionnaire completed in January 1986. Cancer incidence in 5 years was ascertained by a population-based cancer registry. Results: Women who had ever received a blood transfusion were at an increased risk for non-Hodgkin lymphoma (relative risk [RR] = 2.20; 95% CI, 1.35 to 3.58) and kidney cancer (RR = 2.53; CI, 1.34 to 4.78). The relative risks for these cancers were greater with decreasing time from first transfusion. No increased risk occurred for cancers of the breast, lung, uterine corpus, ovary, pancreas, colon, rectum, skin (melanoma), or for all cancers considered together. Conclusion: These findings suggest that previous blood transfusion may be a risk factor for non-Hodgkin lymphoma and kidney cancer but is not associated with the most common neoplasms.
Recommendations for Management of Diabetes During Ramadan
Authors: Monira Al-Arouj, Samir Assaad-Khalil, John Buse, Ibtihal Fahdil, Mohamed Fahmy, Sherif Hafez, Mohamed Hassanein, Mahmoud Ashraf Ibrahim, David Kendall, Suhail Kishawi, Abdulrazzaq Al-Madani, Abdullah Ben Nakhi, Khaled Tayeb, Abraham Thomas
Journal: Diabetes Care (2010)

Since our last publication about diabetes and fasting during Ramadan (1), we have received many inquires and comments concerning important issues that were not discussed in the previous document, including the voluntary 1- to 2-day fasts per week that many Muslims practice throughout the year, as well as the effect of prolonged fasting (more than 18 h a day) in regions far from the equator during Ramadan when it occurs in summer—a phenomenon expected to affect millions worldwide for the next 10–15 years. Since 2005, there have been substantial additions to the literature, including two studies examining the effect of structured education and support for safe fasting, both of which had promising results (2,3). In addition, new medications, such as the incretin-based therapies, have been introduced with less risk for hypoglycemia.

According to a 2009 demographic study, Islam has 1.57 billion adherents, making up 23% of the world population of 6.8 billion, and is growing by ∼3% per year (4). Fasting during Ramadan, a holy month of Islam, is a duty for all healthy adult Muslims. The high global prevalence of type 2 diabetes—6.6% among adults age 20–79 years (5)—coupled with the results of the population-based Epidemiology of Diabetes and Ramadan 1422/2001 (EPIDIAR) study, which demonstrated among 12,243 people with diabetes from 13 Islamic countries that ∼43% of patients with type 1 diabetes and ∼79% of patients with type 2 diabetes fast during Ramadan (6), lead to the estimate that worldwide more than 50 million people with diabetes fast during Ramadan.

Ramadan is a lunar-based month, and its duration varies between 29 and 30 days. Muslims who fast during Ramadan must abstain from eating, drinking, use of oral medications, and smoking from predawn to after sunset; however, there are no restrictions on food or fluid intake between sunset …