tbuckley/cabot-search huggingface dataset:
The Activity of Taxanes in the Treatment of Sex Cord-Stromal Ovarian Tumors
Authors: Jubilee Brown, Hyun S. Shvartsman, Michael T. Deavers, Thomas W. Burke, Mark F. Munsell, David M. Gershenson
Journal: Journal of Clinical Oncology (2004)

To determine the efficacy and side effects of taxanes, with or without platinum, for the treatment of sex cord-stromal tumors of the ovary.We conducted a retrospective review of all patients seen from 1985 to 2002 at The University of Texas M.D. Anderson Cancer Center with ovarian sex cord-stromal tumors. Eligible patients underwent pathology confirmation and clinical evaluation at M.D. Anderson and received a taxane for initial or recurrent disease.Of 222 patients identified, 44 were eligible for analysis. For nine patients treated in the first-line adjuvant setting, median progression-free survival (PFS) was not reached at 51 months. Of two patients treated for measurable disease in the first-line setting, one had a complete response. Median PFS was 34.3 months; median overall survival (OS) was not reached. Median follow-up was 90.3 months (range, 39.4 to 140.5 months). Response rate for 30 patients treated with a taxane +/- platinum for recurrent, measurable disease was 42%. Median PFS was 19.6 months; median OS was not reached. Median follow-up was 100.7 months (range, 8.1 to 361.3 months). The presence of platinum correlated with response in the recurrent, measurable disease setting. The number of patients was insufficient to detect relative efficacy of paclitaxel and docetaxel. Adverse effects of paclitaxel included neutropenia (n = 6), anemia (n = 1), thrombocytopenia (n = 1), myelodysplasia (n = 1), and hypersensitivity (n = 1).Taxanes seem to be active agents in the treatment of patients with sex cord-stromal tumors of the ovary. The combination of taxanes with platinum in the treatment of this disease deserves additional investigation.
Mechanisms of Type I and Type II Pseudohypoaldosteronism
Authors: Seth B. Furgeson, Stuart Linas
Journal: Journal of the American Society of Nephrology (2010)

Pseudohypoaldosteronism (PHA) types I and II are curious genetic disorders that share hyperkalemia as a predominant finding. Together they have become windows to understanding new molecular physiology in the kidney. Autosomal recessive PHAI results from mutations in the epithelial sodium channel (ENaC), whereas autosomal dominant PHAI is characterized by mutations in the mineralocorticoid receptor. PHAII is the result of mutations in a family of serine-threonine kinases called with-no-lysine kinases (WNK)1 and WNK4. WNK4 negatively regulates the NaCl cotransporter (NCC), and PHAII mutations in WNK4 abrogate this affect. WNK4 also regulates the expression or function of renal outer medullary potassium (ROMK) channels, ENaCs, and Cl transporters. WNK1 also regulates NCC and ROMK. Aldosterone inactivates WNK1 and WNK4 activity. Whether angiotensin II can fine tune the actions of aldosterone is still unclear.
Association of DNA Repair Gene Polymorphisms With Response to Platinum-Based Doublet Chemotherapy in Patients With Non–Small-Cell Lung Cancer
Authors: Kouya Shiraishi, Takashi Kohno, Chiharu Tanai, Yasushi Goto, Aya Kuchiba, Seiichiro Yamamoto, Koji Tsuta, Hiroshi Nokihara, Noboru Yamamoto, Ikuo Sekine, Yuichiro Ohe, Tomohide Tamura, Jun Yokota, Hideo Kunitoh
Journal: Journal of Clinical Oncology (2010)

Purpose To identify polymorphisms in DNA repair genes that affect responses to platinum-based doublet chemotherapy in patients with non–small-cell lung cancer (NSCLC). Patients and Methods In total, 640 patients with NSCLC who received platinum-based doublet chemotherapy in the National Cancer Center Hospital in Japan from 2000 to 2008 and whose responses were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) participated in a study of the association between response and genotypes for 30 single nucleotide polymorphisms (SNPs) in 27 DNA repair genes. Candidate SNPs were selected in a discovery set of 201 patients, and their associations were validated in an independent set of 439 patients by prespecified P value criteria. Results Homozygotes for the minor allele TP53-72Pro of the Arg72Pro SNP in the TP53 gene showed a better response rate (54.3%) than those for the major allele TP53-72Arg (29.1%; P = 4.4 × 10 −5 ) irrespective of therapeutic regimens, and minor allele homozygotes had significantly longer progression-free and overall survivals than major allele homozygotes (hazard ratio [HR], 0.85; 95% CI, 0.74 to 0.98; P = .020; and HR, 0.86; 95% CI, 0.74 to 0.99; P = .039). Minor allele carriers for SNP Lys940Arg in the poly (ADP-ribose) polymerase 1 (PARP1) gene showed a better response rate to the paclitaxel regimen (45.8%) than to the gemcitabine regimen (10.5%; P for interaction = .019). Conclusion Polymorphisms in the TP53 and PARP1 genes are involved in inter-individual differences in the response to platinum-based doublet chemotherapy in patients with NSCLC.
Demonstration of Thy-1 antigen on pluripotent hemopoietic stem cells in the rat.
Authors: I Goldschneider, L K Gordon, R J Morris
Journal: The Journal of Experimental Medicine (1978)

Three approaches were used to demonstrate the presence of Thy-1 antigen on the surface of pluripotent hemopoietic stem cells in the rat. In the first, stem cells from fetal liver, neonatal spleen, and adult bone marrow were prevented from forming hemopoietic colonies in the spleens of irradiated recipients spleen (colony-forming unit assay) by incubation with antibodies to Thy-1 antigen. Highly specific rabbit heteroantiserum to purified rat brain Thy-1 antigen and mouse alloantisera to Thy-1.1-positive thymocytes were equally effective. This inhibition was neutralized by purified Thy-1 antigen. In a second series of experiments, Thy-1-positive and Thy-1-negative populations of nucleated bone marrow cells were separated by the FACS. All of the hemopoietic stem cell activity was recovered in the Thy-1-positive population. The stem cells were among the most strongly positive for Thy-1 antigen, being in the upper 25th percentile for relative fluorescence intensity. The relationships of Thy-1 antigen to the rat bone marrow lymphocyte antigen (BMLA) was shown in a third series of experiments. Rabbit anti-BMLA serum, which is raised against a null population of lymphocyte-like bone marrow cells, has been shown to have anti-stem cell activity. Here we demonstrate by double immunofluorescence, cocapping, and differential absorption studies that Thy-1 and BMLA are parts of the same molecule.
Effects of the CETP Inhibitor Evacetrapib Administered as Monotherapy or in Combination With Statins on HDL and LDL Cholesterol
Authors: Stephen J. Nicholls, H. Bryan Brewer, John J. P. Kastelein, Kathryn A. Krueger, Ming-Dauh Wang, Mingyuan Shao, Bo Hu, Ellen McErlean, Steven E. Nissen
Journal: JAMA (2011)

STATINS2][3][4][5][6] Nonetheless, cardiovascular disease remains the number one cause of death. 7Accordingly, considerable efforts have focused on development of novel therapeutic agents designed to address residual cardiovascular risk.Because individuals from the general population with elevations of high-density lipoprotein cholesterol (HDL-C) have a reduced incidence of coronary heart disease, 8 it has been assumed that finding an appropriate therapy to increase HDL-C levels would yield substantial clinical benefit.However, development of drugs that increase HDL-C levels has been challenging and fraught with failures, including the premature termination of
Hematopoietic and Lymphatic Cancers in Relatives of Patients With Infectious Mononucleosis
Authors: Henrik Hjalgrim, Klaus Rostgaard, Johan Askling, Mette Madsen, Hans H Storm, Charles S Rabkin, Mads Melbye
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Young adults with a history of Epstein-Barr virus (EBV)-related infectious mononucleosis have an increased risk for Hodgkin's lymphoma. EBV is detected in Hodgkin's lymphoma Reed–Sternberg cells from some patients, but in young adult patients, it is detected at a relatively low frequency in these cells. Hodgkin's lymphoma and infectious mononucleosis are both associated with high social class, and unknown confounding factors that are also associated with socioeconomic status might explain or contribute to the apparent association between these diseases. To indirectly assess the importance of socioeconomic status on the association between these diseases, we determined the risk for hematopoietic and lymphatic cancers in first-degree relatives of patients with confirmed EBV-related infectious mononucleosis. Methods: We identified parents, siblings, and offspring of 17 045 persons with serologically confirmed EBV-related infectious mononucleosis. Subjects in these cohorts were linked with the population-based Danish Cancer Register to identify those developing hematopoietic/lymphatic cancers after the index patient was diagnosed with infectious mononucleosis. The relative risk for cancer in the infectious mononucleosis family members was expressed as standardized incidence ratios (SIRs; i.e., the ratio between the number of cancers observed and the number of cancers expected, obtained from age-specific, sex-specific, and period-specific incidence rates). Results: We identified 8052 parents, 5264 siblings, and 28 605 offspring of patients with EBV-related infectious mononucleosis who were followed for a total of 892 213 person-years at risk. The risk for Hodgkin's lymphoma was unaltered in the combined group of first-degree relatives of these patients (SIR = 0.99; 95% confidence interval [95% CI] = 0.62 to 1.59; number of cases [n] = 17), in the group of parents (SIR = 0.83; 95% CI = 0.31 to 2.22; n = 4), in the group of siblings (SIR = 0.96; 95% CI = 0.31 to 2.97; n = 3), and in the group of offspring (SIR = 1.08; 95% CI = 0.58 to 2.02; n = 10). Conclusion: The unremarkable risk for Hodgkin's lymphoma in family members of patients with EBV-related infectious mononucleosis indicates that socioeconomic confounding is an unlikely explanation for the association between EBV-related infectious mononucleosis and Hodgkin's lymphoma.
Perforation of gastric squamous carcinoma metachronous to laryngeal carcinoma: metastatic in origin?
Authors: G F Whalen, W K Huizinga, A Marszalek
Journal: Gut (1988)

The local and regional spread of squamous cancer of the head and neck is well described. We report a possible unusual pattern of spread from a primary laryngeal carcinoma, which presented as gastric perforation.
Prospective Randomised Controlled Trial Comparing Trigone-Sparing versus Trigone-Including Intradetrusor Injection of AbobotulinumtoxinA for Refractory Idiopathic Detrusor Overactivity
Authors: Rustom P. Manecksha, Ivor M. Cullen, Sarfraz Ahmad, Graeme McNeill, Robert Flynn, Thomas E.D. McDermott, Ronald Grainger, John A. Thornhill
Journal: European Urology (2011)
Cancer detection and biopsy classification using concurrent histopathological and metabolomic analysis of core biopsies
Authors: Meredith V Brown, Jonathan E McDunn, Phillip R Gunst, Elizabeth M Smith, Michael V Milburn, Dean A Troyer, Kay A Lawton
Journal: Genome Medicine (2012)

Metabolomics, the non-targeted interrogation of small molecules in a biological sample, is an ideal technology for identifying diagnostic biomarkers. Current tissue extraction protocols involve sample destruction, precluding additional uses of the tissue. This is particularly problematic for high value samples with limited availability, such as clinical tumor biopsies that require structural preservation to histologically diagnose and gauge cancer aggressiveness. To overcome this limitation and increase the amount of information obtained from patient biopsies, we developed and characterized a workflow to perform metabolomic analysis and histological evaluation on the same biopsy sample. Biopsies of ten human tissues (muscle, adrenal gland, colon, lung, pancreas, small intestine, spleen, stomach, prostate, kidney) were placed directly in a methanol solution to recover metabolites, precipitate proteins, and fix tissue. Following incubation, biopsies were removed from the solution and processed for histology. Kidney and prostate cancer tumor and benign biopsies were stained with hemotoxylin and eosin and prostate biopsies were subjected to PIN-4 immunohistochemistry. The methanolic extracts were analyzed for metabolites on GC/MS and LC/MS platforms. Raw mass spectrometry data files were automatically extracted using an informatics system that includes peak identification and metabolite identification software. Metabolites across all major biochemical classes (amino acids, peptides, carbohydrates, lipids, nucleotides, cofactors, xenobiotics) were measured. The number (ranging from 260 in prostate to 340 in colon) and identity of metabolites were comparable to results obtained with the current method requiring 30 mg ground tissue. Comparing relative levels of metabolites, cancer tumor from benign kidney and prostate biopsies could be distinguished. Successful histopathological analysis of biopsies by chemical staining (hematoxylin, eosin) and antibody binding (PIN-4, in prostate) showed cellular architecture and immunoreactivity were retained. Concurrent metabolite extraction and histological analysis of intact biopsies is amenable to the clinical workflow. Methanol fixation effectively preserves a wide range of tissues and is compatible with chemical staining and immunohistochemistry. The method offers an opportunity to augment histopathological diagnosis and tumor classification with quantitative measures of biochemicals in the same tissue sample. Since certain biochemicals have been shown to correlate with disease aggressiveness, this method should prove valuable as an adjunct to differentiate cancer aggressiveness.
Aging and Atherosclerosis
Authors: Julie C. Wang, Martin Bennett
Journal: Circulation Research (2012)

Atherosclerosis is classed as a disease of aging, such that increasing age is an independent risk factor for the development of atherosclerosis. Atherosclerosis is also associated with premature biological aging, as atherosclerotic plaques show evidence of cellular senescence characterized by reduced cell proliferation, irreversible growth arrest and apoptosis, elevated DNA damage, epigenetic modifications, and telomere shortening and dysfunction. Not only is cellular senescence associated with atherosclerosis, there is growing evidence that cellular senescence promotes atherosclerosis. This review examines the pathology of normal vascular aging, the evidence for cellular senescence in atherosclerosis, the mechanisms underlying cellular senescence including reactive oxygen species, replication exhaustion and DNA damage, the functional consequences of vascular cell senescence, and the possibility that preventing accelerated cellular senescence is a therapeutic target in atherosclerosis.
Alveolar and serum antiphospholipid antibodies in acute respiratory distress syndrome associated with catastrophic antiphospholipid syndrome
Authors: F J Wiedermann
Journal: Annals of the Rheumatic Diseases (2006)

Bucciarelli and colleagues analysed the clinical and laboratory characteristics of patients with catastrophic antiphospholipid syndrome (APS) and acute respiratory distress syndrome (ARDS).1 They found that ARDS is the dominant pulmonary manifestation of catastrophic APS.

In their discussion the authors report on the paper by Maneta-Peyret et al ,2 who detected antilipid autoantibodies of the IgG class exclusively in the bronchoalveolar fluid (BALF) of patients with ARDS. These antibodies were directed against anionic phospholipids and reacted principally with phosphatidic acid. The antibodies showed significant binding on negatively charged phosphatidylserine and at a lower level on phosphatidylinositol in an enzyme linked immunosorbent assay (ELISA). These phospholipids occur in the pulmonary surfactant. Detection of antiphospholipid antibodies (aPL) in the BALF of patients with ARDS suggests involvement of …
Myeloperoxidase modulates the phagocytic activity of polymorphonuclear neutrophil leukocytes. Studies with cells from a myeloperoxidase-deficient patient.
Authors: O Stendahl, B I Coble, C Dahlgren, J Hed, L Molin
Journal: Journal of Clinical Investigation (1984)

Patients lacking the primary granulae enzyme, myeloperoxidase (MPO), do not usually show any increased susceptibility to infection or altered inflammatory response, in contrast to several other biochemical defects in polymorphonuclear neutrophils. We have now evaluated the role of MPO on phagocyte function in a patient with complete MPO deficiency suffering from generalized pustular psoriasis. We found that the MPO-deficient neutrophils showed enhanced phagocytosis (greater than 200% of normal) of IgG- and C3b-opsonized yeast particles and prolonged N-formylmethionyl-leucyl-phenylaline-mediated stimulation of superoxide production. When purified human MPO was added to normal neutrophils during cell adhesion, their Fc- and C3b-mediated phagocytosis was reduced without affecting cell viability. 1 microgram/ml of MPO reduced the Fc and C3b phagocytosis to 47 and 65%, respectively, whereas 10 micrograms/ml reduced the activity to 20 and 54%. Both attachment and ingestion were reduced to a similar extent, indicating that MPO affected the receptor function per se. When MPO was added to the hyperactive MPO-deficient cells, phagocytosis was reduced more rapidly. Catalase, azide, and methionine eliminated the inhibitory effect, and catalase and methionine, in fact, enhanced the phagocytic activity of adherent neutrophils. These data indicate that, apart from being a potent antimicrobial system, the oxidizing activity of the MPO-H2O2-halide system may modulate the inflammatory response by impairing certain receptor-mediated recognition mechanisms of phagocytic cells, which otherwise could elicit inflammatory reactions and tissue injury.
Autonomic dysregulation: a mechanism of asthma death
Authors: Jaymin B. Morjaria, Tim Rowland, Puneet Tailor, Shaan Hyder, Caroline E. Wright, Simon P. Hart, Alyn H. Morice
Journal: European Respiratory Journal (2014)

To the Editor: 

Therapeutic advances in the management of asthma have led to a gradual but sustained reduction in mortality [1, 2]. However, the death of otherwise healthy young individuals remains a tragic and all too frequent occurrence. The unheralded demise of two of our patients with previously minimally troublesome asthma led us to reconsider the mode of death in such patients. Numerous studies and retrospective reports have attributed such mortality to preventable factors such as inadequate severity assessment, discontinuity of medical care, poor concordance to prescribed therapies and poor management of acute asthma exacerbations [3, 4]; others have attributed fatalities to significant behavioural, socioeconomic or psychosocial factors including smoking, denial, depression and alcohol abuse [1, 5, 6].

Whilst these associations are undeniably important they do not adequately explain the observed clinical picture of precipitous deterioration, loss of consciousness, and death. Robin et al . [7] reported two patients with an abrupt demise, one during a telephone conversation and with no prior asthma-related symptoms. Grubb et al . [8] followed a teenage boy with a history of long-standing asthma after repeated near fatal asthma episodes requiring resuscitation. Our similar experience of two unexpected fatalities caused us to question bronchoconstriction as the primary mode of death. Others have suggested that vasovagally-induced bradycardia results in a potentially lethal syncope in predisposed individuals. We have sought to test this hypothesis in subjects from our asthma clinic who have a history of unconsciousness precipitated by exacerbations using the simulated diving reflex of facial immersion to replicate such events [9].

Participants were recruited through the Academic and Outpatient Respiratory department at Castle Hill Hospital (Cottingham, UK) over a 12-month period. Subjects were excluded if they had significant cardiovascular …
An Immunohistochemical Study of Morules in Endometrioid Lesions of the Female Genital Tract: CD10 Is a Characteristic Marker of Morular Metaplasia
Authors: Silvia Chiarelli, Catalina Buriticá, Piero Litta, Susana Ciani, Rosa Guarch, Francisco F. Nogales
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To analyze immunohistochemically morules in endometrioid lesions to show that CD10 is a sensitive marker for morular metaplasia. Experimental Design: Immunohistochemical analysis of 53 instances of morular metaplasia comprising 1 cyclic endometrium and 52 endometrioid lesions associated with focal glandular complexity corresponding to 9 polyps, 4 atypical polypoid adenomyomas, 24 complex endometrial hyperplasias (18 with and 6 without atypia), 12 grade 1 endometrioid adenocarcinomas in early clinical stages of both uterus and ovary, and three ovarian adenofibromas. Immunohistochemistry in paraffin sections was done for CD10, β-catenin, estrogen and progesterone receptors, and cytokeratins 5-6, 7, 8, 13, 18, 19, 20, and 34β-E12. Results: Morules were negative for estrogen and progesterone receptors and had β-catenin–positive nuclei. Cytokeratins 8, 18, 19 were positive; cytokeratins 7 and 20 were negative; and cytokeratins 5-6, 13, and 34β-E12 were weakly positive. All cases revealed strongly positive membranous CD10 staining in morules, which was absent in glands. CD10 positivity allowed easy identification of morules at low power in various types of surgical specimens and in curettings. CD10 also highlighted early morular metaplasia in glandular epithelium. In cases associated with squamous, keratinizing metaplasia, CD10 discriminated between both types of metaplasia. Conclusions: CD10 staining represents a useful marker of morules in endometrioid neoplasms of the female genital tract, permitting identification of lesions usually associated with an attenuated malignancy. Considering the immunohistochemical and genetic similarities of morules in tumors of different organs, it is likely that this marker may be also useful to diagnose morular metaplasia in similar neoplasms of extragenital locations.
NORCCAP (Norwegian colorectal cancer prevention): a randomised trial to assess the safety and efficacy of carbon dioxide versus air insufflation in colonoscopy
Authors: M Bretthauer
Journal: Gut (2002)

Background: To eliminate the risk of combustion during electrosurgical procedures and to reduce patient discomfort, carbon dioxide (CO<sub>2</sub>) insufflation has been recommended during colonoscopy. However, air insufflation is still the standard method, perhaps due to the lack of suitable equipment and shortage of randomised studies. Aims: This randomised controlled trial was conducted to assess patient tolerance and safety when using CO<sub>2</sub> insufflation during colonoscopy. Patients: Over an eight month period a successive series of patients referred for a baseline colonoscopy due to findings in a flexible sigmoidoscopy screening trial were randomly assigned to the use of either air or CO<sub>2</sub> insufflation during colonoscopy. Methods: End tidal CO<sub>2</sub> (ETCO<sub>2</sub>), a non-invasive parameter of arterial pCO<sub>2</sub>, was registered before and repeatedly during and after the examination. The patient9s experience of pain during and after the examination was registered using a visual analogue scale (VAS). Sedation was not used routinely. Results: CO<sub>2</sub> insufflation was used in 121 patients (51%) and air in 119 patients (49%). The groups were similar in age, sex, and caecal intubation rate. No rise in ETCO<sub>2</sub> was registered. There were statistically significant differences in VAS scores between the groups with less pain reported when using CO<sub>2</sub>. Conclusions: This randomised study of unsedated patients shows that CO<sub>2</sub> insufflation is safe during colonoscopy with no rise in ETCO<sub>2</sub> level. CO<sub>2</sub> was found to be superior to air in terms of pain experienced after the examination.