tbuckley/cabot-search huggingface dataset:
Utility of Computed Tomography and Magnetic Resonance Imaging Staging Before Completion Lymphadenectomy in Sentinel Lymph Node–Positive Melanoma
Authors: Edward P. Miranda
Journal: Journal of Clinical Oncology (2006)

TO THE EDITOR: In their excellent study, Aloia et al have confirmed our results that modern computed tomography and magnetic resonance imaging do not detect distant metastases in patients with melanoma metastatic to sentinel lymph nodes. With the addition of their 314 patients to the 185 already reported, the detectable distant metastasis rate in stage III melanoma patients at the time of selective sentinel lymph node dissection (SLND) can be more accurately estimated at approximately 1.2% (range, 0.5% to 1.9%). Furthermore, because Aloia et al had several patients with distant metastases, the risk factors for detectable distant metastasis within 3 months of SLND have been further refined to include patients with very thick ( 3.5 mm) ulcerated melanomas with large tumor burdens metastatic to regional lymph node basins. Conversely, these data should not be interpreted in a way that results in tumors that are thick or ulcerated or have high regional tumor burden being classified as needing further imaging via computed tomography or magnetic resonance imaging. False-positive rates of 12% to 14% make this a potentially dangerous treatment protocol (for example, although ulceration was shown to be an independent risk factor for distant metastasis; P .018; 107 of 112; 96%; ulcerated melanomas were negative for distant metastasis). What would be particularly interesting is to know whether or not any of the five patients with distant metastases were symptomatic. In our original study, only asymptomatic patients received SLND. However, when the history of the one patient with true distant metastasis was reviewed, he had developed constitutional symptoms after initial diagnosis but before SLND. If in retrospect these patients were actually symptomatic, a valuable clue would be added to the ones already brought forth by Aloia et al, aiding the discrimination of those patients with stage III disease who do need imaging for staging from the majority who do not.
Abstract 1722: Prognostic markers in early stage non small-cell lung cancer (NSCLC)
Authors: Marjorie Romkes, Tomoko Nukui, Shama Buch, Petr Pancoska, Jose Herazo-Maya, Naftali Kaminski, Sanja Dacic, Joel L. Weissfeld, William L. Bigbee, Steven D. Shapiro, Jill M. Siegfried
Journal: Cancer Research (2012)

Abstract Conventional clinical and pathologic risk factors in stage I non small-cell lung cancer (NSCLC) provide limited prognostic information. Novel prognostic biomarkers are needed to identify patients with highest recurrence risk who will receive the greatest absolute risk reduction from adjuvant chemotherapy/radiation. Transcriptome, epigenome, and global genetic variation analyses of resected NSCLC frozen tumor samples (n=81; 29 stage 1A/52 stage 1B) were performed in order to develop an integrated prognostic signature. Only tumors that were resected within 3 months of the first biopsy-proven diagnosis were used to reduce lead time bias in timing of removal of the primary tumor. Here, the association of gene expression with disease free survival (DSF) is described. Whole genome expression data were quantile-normalized using the Illumina GenomeStudio 2011.1 software. Log-transformed data were then processed in Biometric Research Branch (BRB)-Array Tools. Prognostic models were developed with the top ranking genes using the supervised principal component survival algorithm (PCA). Risk group membership was then assigned based on this multivariate model using leave-one-out cross validation and class prediction modeling. Both models adjusted for age, gender and tumor histology. For stage 1A cases, a 113 gene signature selected by fitting a Cox proportional hazard model (Cox) was able to discriminate between poor and good DFS (α=0.001). Upon further analysis using a class prediction algorithm support vector machine (SVM), we identified an 18 gene classifier that predicted outcome SN=0.952, SP=0.571). A 10-fold cross validation ROC curve reported a value of 0.748. For stage 1B cases, the Cox model identified 141 genes (α=0.01), but the SVM prediction algorithm showed reduced SN/SP (0.75/0.25) for a 12 gene classifier, indicative of possible increased heterogeneity among the 1B cases. Nine genes overlapped between the PCA and class prediction model gene signatures. These nine are members of common lung tumorigenesis pathways, i.e. G-protein signaling regulation (KRAS/BRAF/RASSFI); tyrosine protein kinase signaling (EGFR/ERBB2); nucleotide excision repair (ERRC5 and ERCC6) and genes implicated in cell differentiation regulated by miR200B (HGD) or miR338 (TXNRD1), miRNAs independently found to be associated with prognosis in our cohort. These initial results demonstrate that a gene expression profile can distinguish stage I NCSLC tumors and predict prognoses, but require further validation. Supported in part by NIH 5P50 CA090440, P30CA047904, UPMC Institutional Funds. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1722. doi:1538-7445.AM2012-1722
Pyruvate kinase and the "high ATP syndrome".
Authors: G E Staal, G Jansen, D Roos
Journal: Journal of Clinical Investigation (1984)

The erythrocytes of a patient with the so-called "high ATP syndrome" were characterized by a high ATP content and low 2,3-diphosphoglycerate level. The pyruvate kinase activity was specifically increased (about twice the normal level). After separation of the erythrocytes according to age by discontinuous Percoll density centrifugation, the pyruvate kinase activity was found to be increased in all Percoll fractions. Pyruvate kinase of the patient's cells was characterized by a decreased K0.5 for the substrate phosphoenolpyruvate and no inhibition by ATP. The Michaelis constant (Km) value for ADP, the nucleotide specificity, the thermostability, pH optimum, and immunological specific activity were normal. It is concluded that the high pyruvate kinase activity is due to a shift in the R(elaxed) in equilibrium T(ight) equilibrium to the R(elaxed) form.
A CLINICAL STUDY OF MULTIPLE NEURITIS IN YOUNG CHILDREN.
Authors: ANNE STURGIS DANIEL
Journal: JAMA (1898)

The following brief clinical studies of multiple neuritis embrace only those cases in which were found motor and sensory paralysis of symmetric development, but do not include that form of neuritis which affects only the muscles of the palate or of the nose, as shown by regurgitations of fluids, with nasal voice or those cases affecting only the ocular muscles. Diphtheria is undoubtedly by far the greatest cause of multiple neuritis. Comparatively few cases are caused by the other infectious diseases. Smallpox is not infrequently a cause of the disease, but I have seen no mention made of chicken-pox giving rise to the disease. I, unfortunately, have one case to report of the production of the disease by arsenic given during the course of treatment of chorea. I have twelve cases to report, the causes of which were: arsenic administered for chorea, 1 child; diphtheria, 9 cases; varicella, 1 case,
Maintenance of Hydration in “Post-Coronary” Marathon Runners
Authors: T. Kavanagh, R. J. Shephard
Journal: British Journal of Sports Medicine (1975)

Three post-coronary patients participated in the Hawaiian Marathon race in December 1973, covering the 26¼ miles in 250-259 minutes at an average speed of 6.1-6.3 mph. Preloading with 850 ml. of a proprietary electrolyte/glucose solution “Erg”, and further 300 ml. drinks of the same fluid every 30 min. were sufficient to maintain a state of hyperhydration, as evidenced both by calculations of water balance and objective measures of red cell count and haematocrit; it is argued that substantial dehydration need not be incurred even in younger runners with much higher sweat rates. The “Erg” preparation provided good stabilisation of plasma sodium ion concentrations, but potassium ions rose by the end of the race. Substantial increments of L.D.H. and S.G.O.T. persisted three hours after a race, making a careful exercise history important to the diagnosis of myocardial infarction. Glucose levels had reached the lower limit of normal by the end of the race, and rises of blood urea suggested some protein catabolism; however, cholesterol levels remained substantially unchanged. A small increase of blood bilirubin was noted during and after the race.
A Biographical History of Medicine: Excerpts and Essays on the Men and Their Work
Authors: Ilza Veith
Journal: JAMA (1971)

This book is a composite of all the medicohistorical essays included by Dr. Talbott in the individual issues of<i>JAMA</i>during the 11 years of his editorship. The historical essays, like the reproductions of works of art on the covers of<i>JAMA</i>that replaced the "institutional" cover design, are hallmarks of Dr. Talbott's imaginative editorship. Each of the short essays, dealing with the life and achievements of one outstanding physician, gives an impressive, though somewhat cursory introduction to medical greatness in chronological arrangement. There is no indication why certain personalities have been selected for inclusion while others have been omitted—except that Dr. Talbott has expressed a preference for dealing with figures of the past, and in fact, only one person currently alive is included. Through these individual vignettes we are enabled to experience the unfolding of medical knowledge, presented chronologically and by specialties, from the time of Hammurabi (2250 BC)
Abstract OT3-1-08: The PROCEED trial KCSG BR11-01: Phase III multicenter randomized open label study of irinotecan plus capecitabine versus capecitabine in patients previously treated with anthracycline and taxane for HER2 negative metastatic breast cancer
Authors: IH Park, KS Lee, S-A Im, KH Jung, KH Park, Y-H Im, S Lee, YJ Kim, H-J Kim, S Lee, MH Lee, T-Y Kim, K-H Lee, S-B Kim, J-H Ahn, B-H Nam, J Ro
Journal: Cancer Research (2013)

Abstract Background: Most patients with metastatic breast cancer (MBC) experience disease progression after being treated with an anthracycline or taxane. Irinotecan, a semisynthetic agent derived from the natural alkaloid camptothecin is metabolized to the active metabolite SN-38 which targets topoisomerase I leading to single and double strand DNA breaks. Irinotecan as a single agent demonstrated tumor activity with an objective response rate ranging from 5 to 23% in patients with MBC refractory to taxane and anthracycline. Irinotecan increased the activity of 5-FU, the active metabolite of capecitabine, and overcomes the negative effect of thymidylate synthase overexpression, which is the main target of an active metabolite of 5-FU. A phase II study that evaluated the efficacy and safety of irinotecan and capecitabin combination (IX) showed that the median progression free survival (PFS) was 7.6 months (95% CI, 5.0-10.2months), and the median OS was 22.6 months (95% CI, 15.4 – 29.8 months) with good tolerability in anthracycline and taxane pretreated MBC patients. Based on these results, we planned to conduct a multicenter, randomized phase III study which assesses the efficacy of irinotecan and capecitabine combination therapy compared with capecitabine alone in patients with anthracycline and taxane resistant MBC. Methods: In this trial, patients with HER2 normal tumor who previously received anthracycline and taxane based chemotherapies are enrolled. Eligible patients are randomly assigned in a 1:1 ratio to receive irinotecan plus capecitabine or capecitabine alone. The primary end point of this trial is PFS and a total number of accrual patients will be 222. Randomization is done using a random block size permutation method and stratified by hormone receptor status (negative vs. positive), first line vs. ≥second lines, visceral metastasis (negative vs. positive). Patients receive irinotecan at 80 mg/m2 on day 1 and 8 every 3 weeks and capecitabine 1000mg/m2 bid from day 1 to day 14 every 3 weeks. In control arm, patients receive capecitabine 1250mg/m2 bid from day 1 to day 14 every 3 weeks. Response will be assessed using RECIST1.1 criteria and toxicity will be graded according to NCI-CTCAE 4.0 criteria. Study Status: A total of 107 patients consented for the study since June 2011, and accrual is ongoing. Clinical trial information: NCT01501669. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-1-08.
A new variant of punctate acrokeratoderma associated with a pigmentary disorder
Authors: T. SATOH, H. YOKOZEKI, I. KATAYAMA, K. NISHIOKA
Journal: British Journal of Dermatology (1993)

We report a Japanese patient with skin‐coloured keratotic papules on the hands and feet, and pronounced hyperkeratosis of the palms and soles. There was no evidence of fragmentation of dermal elastic tissue on histology. Freckle‐like pigmentation was also present on the dorsa of the hands and feet, and this appeared to be closely related to the keratotic disorder. The mode of inheritance was autosomal dominant. We consider our case to be a new variant of familial punctate acrokeratoderma. associated with a pigmentary disorder.
PTU-015 Expanded CD14hi/CD16+ monocytes in acute liver injury (ALI): angels or demons?
Authors: R D Abeles, C G Antoniades, G K Manakkat Vijay, N Vergis, J R Maggs, W Bernal, D L Shawcross, J A Wendon, D Vergani
Journal: Gut (2012)

<h3>Introduction</h3> CD14hi/CD16+ monocytes resemble tissue macrophages and normally constitute ∼5% of circulating monocytes. Expansion of CD14hi/CD16+ monocytes has been implicated in the perpetuation of liver injury and hepatic fibrosis in chronic liver disease. We therefore wanted to explore whether CD14hi/CD16+ monocytes are implicated in ALI; show features of activated endothelial adhesion (CD11b) and chemotaxis (CCR5); and phenotypically resemble classically activated “M1” or alternatively activated “M2” macrophages. “M1” macrophages secrete pro-inflammatory cytokines, express high levels of HLA-DR and CD86 and are implicated in tissue damage. “M2” macrophages, are immunoregulatory, express scavenger receptors such as CD163 and are involved in tissue repair. <h3>Methods</h3> Blood was sampled from patients within 24–48 h of admission consisting of 33 hyper-Acute Liver Failure (hyperALF: jaundice to encephalopathy &lt;7 days), 8 Subacute/Acute Liver Failure (S/ALF: jaundice to encephalopathy &gt;7 days), and 18 healthy controls (HC). Flow cytometery was performed to investigate monocyte phenotype (CD14, CD16, HLA-DR, CD86, CD163, CD11b and CCR5). <h3>Results</h3> Compared to HC, total monocyte count was elevated in S/ALF, but reduced in hyperALF (p&lt;0.001), while CD14hi/CD16+ monocytes were expanded in percentage of total monocytes and absolute numbers in S/ALF (17.4%; 0.14) compared to HC (4%; 0.014) (p&lt;0.001). Although the percentage of CD14hi/CD16+ monocytes in hyperALF was higher (5.6%, p&lt;0.01), the absolute number (0.013) was similar to HC. Though all CD14hi/CD16+ monocytes expressed HLA-DR, the Mean Fluorescence Intensity (MFI) was reduced compared to HC (&lt;0.001). HyperALF CD14hi/CD16+ monocytes had lower HLA-DR MFI compared to S/ALF (p&lt;0.001). A similar pattern was seen for CD86 expression (p&lt;0.01). CD14hi/CD16+ monocytes showed increased expression of CD163 in hyperALF but not in S/ALF compared to HC (&lt;0.01). Compared to HC, CD11b and CCR5 were up-regulated in all ALF groups (p&lt;0.001). <h3>Conclusion</h3> We have demonstrated an expansion of CD14hi/CD16+ monocytes in ALI with an activated phenotype for adhesion and migration. CD14hi/CD16+ monocytes phenotypically resemble M1 macrophages in S\ALF, possibly reflecting a pathogenic role in the perpetuation of liver injury, while they resemble M2 in hyperALF and may be instrumental to the resolution of liver injury. This distinction requires further investigation should therapeutic strategies to target monocyte migration be attempted. <h3>Competing interests</h3> None declared.
Abstract 2714: High HIV-1 DNA copy number defines a unique subset of AIDS-related lymphoma
Authors: Leanne C. Huysentruyt, Paige M. Bracci, Michael S. McGrath
Journal: Cancer Research (2011)

Abstract Despite highly active antiretroviral therapy (HAART), the risk of developing non-Hodgkin lymphoma is ∼100X greater in the HIV-infected population compared to non-infected individuals and AIDS-related lymphoma (ARL) prevalence is expected to rise in the future. Preliminary reports have suggested that some ARLs contain HIV-infected macrophages that may contribute to ARL pathogenesis. A recent study evaluating HIV sequence evolution in the contest of metastatic ARL found lymphoma specific HIV compartmentalized within sites of lymphoma that was distinct from HIV present in non-lymphoma sites (Salemi et al, PLOSone Dec 3, 2009). These data suggested the existence of a lymphoma specific form of HIV evolving within individuals who develop ARL. The goal of this research was to determine the prevalence and quantity of HIV-1 DNA in 119 ARL biopsies from the entire span of the HIV epidemic (1982-2007) by utilizing whole genomic amplified (WGA) ARL DNA, provided by the AIDS and Cancer Specimen Resource (ACSR). The presence of HIV-1 DNA was determined by quantitative amplification of the HIV gag gene using single copy genes to define HIV copy numbers per genomic equivalent. Of the 119 ARL cases, 45% contained detectable levels of HIV-1 DNA (&amp;gt; 1 copy per 30,000 cells). The relationship between HIV DNA presence and tumor immunophenotype was determined using ARL data from the ACSR on the cases studied. The level of HIV per genomic equivalent in the 45% HIV DNA positive cases was as high as one/cell equivalent. There was a significant (p&amp;lt;0.01) decrease in the prevalence of HIV-1 DNA-positive ARL cases post-HAART (after 1996; 39%) as compared to pre-HAART (before 1996; 54%). Additionally, our data suggest that the overall amount of HIV-1 DNA present in ARLs was less in the post-HAART era when compared to the pre-HAART era. The HIV DNA positive cases fell into a positive outcome category (MUM1 negative and CD10 positive) based on lymphoma immunophenotype literature (p&amp;lt; 0.02). Thus, a subset of ARLs containing high levels of HIV DNA, falls into a better outcome category based on immunophenotype data and may represent a different lymphoma pathogenic process. The existence of lymphoma specific variants of HIV is currently under investigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2714. doi:10.1158/1538-7445.AM2011-2714
Parents' awareness of overweight in themselves and their children: cross sectional study within a cohort (EarlyBird 21)
Authors: A N Jeffery, L D Voss, B S Metcalf, S Alba, T J Wilkin
Journal: BMJ (2004)

Obesity is a serious public health concern.More than half of British adults are overweight, and obesity among preschool children has increased by an alarming 70% in the past generation. 1 2We aimed to explore parents' awareness of overweight and obesity in themselves and their children, and their degree of concern about weight.
Rai1 duplication causes physical and behavioral phenotypes in a mouse model of dup(17)(p11.2p11.2)
Authors: Katherina Walz, Richard Paylor, Jiong Yan, Weimin Bi, James R. Lupski
Journal: Journal of Clinical Investigation (2006)

Genomic disorders are conditions that result from DNA rearrangements, such as deletions or duplications. The identification of the dosage-sensitive gene(s) within the rearranged genomic interval is important for the elucidation of genes responsible for complex neurobehavioral phenotypes. Smith-Magenis syndrome is associated with a 3.7-Mb deletion in 17p11.2, and its clinical presentation is caused by retinoic acid inducible 1 (RAI1) haploinsufficiency. The reciprocal microduplication syndrome, dup(17)(p11.2p11.2), manifests several neurobehavioral abnormalities, but the responsible dosage-sensitive gene(s) remain undefined. We previously generated a mouse model for dup(17)(p11.2p11.2), Dp(11)17/+, that recapitulated most of the phenotypes observed in human patients. We have now analyzed compound heterozygous mice carrying a duplication [Dp(11)17] in one chromosome 11 along with a null allele of Rai1 in the other chromosome 11 homologue [Dp(11)17/Rai1(-) mice] in order to study the relationship between Rai1 gene copy number and the Dp(11)17/+ phenotypes. Normal disomic Rai1 gene dosage was sufficient to rescue the complex physical and behavioral phenotypes observed in Dp(11)17/+ mice, despite altered trisomic copy number of the other 18 genes present in the rearranged genomic interval. These data provide a model for variation in copy number of single genes that could influence common traits such as obesity and behavior.
Cloning and expression of Trypanosoma cruzi ribosomal protein P0 and epitope analysis of anti-P0 autoantibodies in Chagas' disease patients.
Authors: Y A Skeiky, D R Benson, M Parsons, K B Elkon, S G Reed
Journal: The Journal of Experimental Medicine (1992)

Chagas' disease, caused by the intracellular protozoan parasite Trypanosoma cruzi, is a major cause of heart failure in endemic areas. Antigenic mimicry by T. cruzi antigens sharing epitopes with host macromolecules has been implicated in the pathogenesis which is thought to have a significant autoimmune component. We report herein on the cloning and characterization of a full-length cDNA from a T. cruzi expression library encoding a protein, TcP0, that is homologous to the human 38-kD ribosomal phosphoprotein HuP0. The T. cruzi P0 protein shows a clustering of residues that are evolutionarily conserved in higher eukaryotes. This includes an alanine- and glycine-rich region adjacent to a highly charged COOH terminus. This "hallmark" domain is the basis of the crossreactivity of the highly immunogenic eukaryotic P protein family. We found that T. cruzi-infected individuals have antibodies reacting with host (self) P proteins, as well as with recombinant TcP0. Deletion of the six carboxy-terminal amino acids abolished the reactivity of the T. cruzi infection sera with TcP0. This is similar to the specificity of anti-P autoantibodies described for a subset of patients with systemic lupus erythematosus (SLE) (Elkon, K., E. Bonfa, R. Llovet, W. Danho, H. Weissbach, and N. Brot. 1988. Proc. Natl. Acad. Sci. USA. 85:5186). These results suggest that T. cruzi P proteins may contribute to the development of autoreactive antibodies in Chagas' disease, and that the underlying mechanisms of anti-P autoantibody may be similar in Chagas' and SLE patients. This study represents the first definitive report of the cloning of a full-length T. cruzi antigen that mimics a characterized host homologue in structure, function, and shared antigenicity.
Dissociation of Hepatic Steatosis and Insulin Resistance in Mice Overexpressing DGAT in the Liver
Authors: Mara Monetti, Malin C. Levin, Matthew J. Watt, Mini P. Sajan, Stephen Marmor, Brian K. Hubbard, Robert D. Stevens, James R. Bain, Christopher B. Newgard, Robert V. Farese, Andrea L. Hevener, Robert V. Farese
Journal: Cell Metabolism (2007)
The favorable impact of CEBPA mutations in patients with acute myeloid leukemia is only observed in the absence of associated cytogenetic abnormalities and FLT3 internal duplication
Authors: Aline Renneville, Nicolas Boissel, Nathalie Gachard, Dina Naguib, Christian Bastard, Stéphane de Botton, Olivier Nibourel, Cécile Pautas, Oumedaly Reman, Xavier Thomas, Claude Gardin, Christine Terré, Sylvie Castaigne, Claude Preudhomme, Hervé Dombret
Journal: Blood (2009)