tbuckley/cabot-search huggingface dataset:
Lymphatic Invasion Is Independently Prognostic of Metastasis in Primary Cutaneous Melanoma
Authors: Xiaowei Xu, Lianjun Chen, DuPont Guerry, Peter R. Dawson, Wei-ting Hwang, Patricia VanBelle, David E. Elder, Paul J. Zhang, Michael E. Ming, Lynn Schuchter, Phyllis A. Gimotty
Journal: Clinical Cancer Research (2011)

Lymphatic invasion (LI) in primary cutaneous melanomas was recently found to be common. In this study, we evaluated LI as an independent prognostic factor.This study included 251 patients with vertical growth phase (VGP) primary cutaneous melanomas who had paraffin-fixed lesional tissue and were in a prospective cohort seen between 1972 and 1991, had no clinical evidence of regional nodal disease at diagnosis, and had at least ten years of follow-up. Dual immunohistochemical staining was used to detect lymphatic endothelium (podoplanin) and melanoma cells (S-100). Multivariate logistic regression for ten-year metastasis was used to define independent prognostic factors, and a prognostic tree was developed to characterize and discriminate risk groups. Kaplan-Meier disease-free survival curves for those with and without LI within current American Joint Committee on Cancer stages were compared using the log-rank statistic.LI was observed in 43% (108 of 251) of the study melanomas. The multivariate model for ten-year metastasis identified four independent prognostic factors: tumor thickness, mitotic rate, LI, and anatomic site. The prognostic tree identified a group of patients with thin (≤1 mm thick) melanomas and poor prognosis: stage IB melanomas with LI. Survival curves for time to first metastasis showed significantly poorer prognosis for patients with LI compared with those without it for both stages IB and IIA.LI is common across the range of tumor thicknesses in primary VGP melanomas. It is an independent prognostic factor and significantly increases the risk of metastasis in patients in clinical stages IB and IIA.
THE MORPHOLOGY OF BACTERIUM SHIGAE CULTIVATED ON VARIOUS MEDIA FAVORABLE TO THE DEVELOPMENT OF FILTERABILITY AND LIFE CYCLE FORMS
Authors: Ralph W. G. Wyckoff
Journal: The Journal of Experimental Medicine (1933)

A simple micro motion picture apparatus has been developed which is so inexpensive to construct and to operate that it can be used regularly for bacteriological research. With this equipment about 6000 feet of film representing 600 hours of photography have been made of B. shigae growing upon various solid media. These pictures illustrate the principal phenomena accompanying the development of this organism on ordinary nutrient media, on media consisting exclusively of either peptones or proteins, and on media containing small amounts of LiCl. Information has thus been gained concerning the existence of a life cycle in the Shiga bacillus and concerning its filterability through Berkefeld filters. The formation and history of the various "life cycle forms" are recorded but the evidence does not point to them as phases of actual cycles. In "filterable" B. shigae cultures-such as those grown in the so-called "K" broth or in lithium chloride-containing media-many small and short rods are present. It has been found that these dwarfed organisms pass through filters impervious to the cells of rapidly growing normal cultures. This offers a simple explanation of "quick reversions." The present experiments do not provide conclusive information concerning the slower reversions which are supposed to occur only after many days of treatment and incubation.
Drug’s 5000% price rise puts spotlight on soaring US drug costs
Authors: Michael McCarthy
Journal: BMJ (2015)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Drug's 5000% price rise puts spotlight on soaring US drug costs Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
The possible occurrence of “alcoholic hepatitis” in a patient with bulimia in the absence of diagnosable alcoholism
Authors: Rafael E. Cuellar, Ralph Tarter, Amy Hays, David H. Van Thiel
Journal: Hepatology (1987)

A case of a 20-yr-old female with possible “alcoholic hepatitis” and a mixed micro/macronodular cirrhosis occurring in association with overt bulimia and a history of anorexia nervosa, but without any objective evidence of either alcoholism or alcohol abuse, is reported. The possible factors that may have contributed, either alone or in combination, to produce this unusual occurrence are discussed.
Cloning and characterization of 5E6 (Ly-49C), a receptor molecule expressed on a subset of murine natural killer cells.
Authors: E R Stoneman, M Bennett, J An, K A Chesnut, E K Wakeland, J B Scheerer
Journal: The Journal of Experimental Medicine (1996)

5E6 is a cell surface molecule expressed on a subpopulation of murine natural killer (NK) cells that are involved in the specific rejection of H-2d or H-2f (hemopoietic histocompatibility determinant 2) bone marrow cell grafts. Here, we isolated and cloned the gene encoding 5E6 and determined the nucleotide sequence of the cDNA. 5E6 is nearly identical to Ly-49C; the deduced amino acid sequence reveals a polypeptide of 266 amino acids with a molecular weight of 31,284 that contains multiple cysteine residues to explain its disulfide-linked homodimer structure and five potential N-linked glycosylation sites. 5E6 is a type II integral membrane protein with an extracellular carbohydrate recognition domain characteristic of C-type (Ca(2+)-dependent) animal lectins. Chromosomal mapping indicates that 5E6 is located within the NK gene complex on chromosome 6. The sequence of 5E6 mRNA and the degree of glycosylation of 5E6 protein are under genetic control. Immunoprecipitation before removal of N-linked sugars reveals different size molecules. There are several nucleotide differences among BALB/c, B6, and NZB mRNAs; however, none of them would be expected to affect N-glycosylation. Of particular interest are two findings: (a) BALB/c, B6, and (BALB/c x B6)F1 5E6 reduced molecules are approximately 65, 54, and 54 kD, and (b) the cDNA sequence of (BALB/c x B6)F1 is identical to B6. Thus, there appears to be allelic exclusion of 5E6 expression that may be related to the ability of F1 hybrid mice to reject parental H-2d bone marrow cell grafts.
Early Outcomes of Tricuspid Valve Replacement in Young Children
Authors: Heather L. Bartlett, Dianne L. Atkins, Trudy L. Burns, Kelly J. Engelkes, Sarah J. Powell, Christine B. Hills, James H. Moller
Journal: Circulation (2007)

Background— Early outcomes after tricuspid valve replacement in young children are ill defined. The experience of the Pediatric Cardiac Care Consortium (45 centers, 1984 to 2002) was reviewed to evaluate the results of tricuspid valve replacement in children &lt;6 years of age. Methods and Results— Ninety-seven patients who underwent initial tricuspid valve replacement are included in the present analysis. The most frequent cardiac diagnoses were Ebstein’s anomaly (40%), pulmonary atresia (11%), and tetralogy of Fallot (8%). Age at tricuspid valve replacement was 2.9±1.7 years (mean±SD). Mean patient weight was 12.7±6.1 kg. The major outcome was survival to discharge. Associations among age, diagnosis, valve type/size, and outcome were evaluated through the use of χ 2 analysis and logistic regression model fitting approaches. Hospital mortality was 26% and was very high (64%) in patients &lt;1 year of age. A large size-to-weight ratio was the strongest predictor of mortality based on multivariable analysis ( P &lt;0.001). Mortality was 54% for patients with a size-to-weight ratio &gt;2.5. Other complications included heart block requiring a pacemaker (13%) and thrombosis (5%). Pacemaker implantation was associated with the use of a mechanical valve (23% versus 6% bioprosthetic valve; P =0.01) Conclusions— Tricuspid valve replacement in young children is associated with high mortality, especially in infants &lt;1 year of age. Surgical options other than tricuspid valve replacement such as transplantation may need to be considered in infants.
Susceptibility loci for murine HIV-associated nephropathy encode trans-regulators of podocyte gene expression
Authors: Natalia Papeta, Ka-Tak Chan, Sindhuri Prakash, Jeremiah Martino, Krzysztof Kiryluk, David Ballard, Leslie A. Bruggeman, Rachelle Frankel, Zongyu Zheng, Paul E. Klotman, Hongyu Zhao, Vivette D. D’Agati, Richard P. Lifton, Ali G. Gharavi
Journal: Journal of Clinical Investigation (2009)

Multiple studies have linked podocyte gene variants to diverse sporadic nephropathies, including HIV-1-associated nephropathy (HIVAN). We previously used linkage analysis to identify a major HIVAN susceptibility locus in mouse, HIVAN1. We performed expression quantitative trait locus (eQTL) analysis of podocyte genes in HIV-1 transgenic mice to gain further insight into genetic susceptibility to HIVAN. In 2 independent crosses, we found that transcript levels of the podocyte gene nephrosis 2 homolog (Nphs2), were heritable and controlled by an ancestral cis-eQTL that conferred a 3-fold variation in expression and produced reactive changes in other podocyte genes. In addition, Nphs2 expression was controlled by 2 trans-eQTLs that localized to the nephropathy susceptibility intervals HIVAN1 and HIVAN2. Transregulation of podocyte genes was observed in the absence of HIV-1 or glomerulosclerosis, indicating that nephropathy susceptibility alleles induce latent perturbations in the podocyte expression network. Presence of the HIV-1 transgene interfered with transregulation, demonstrating effects of gene-environment interactions on disease. These data demonstrate that transcript levels of Nphs2 and related podocyte-expressed genes are networked and suggest that the genetic lesions introduced by HIVAN susceptibility alleles perturb this regulatory pathway and transcriptional responses to HIV-1, increasing susceptibility to nephropathy.
The Effect of Pranlukast on Allergen-induced Bone Marrow Eosinophilopoiesis in Subjects with Asthma
Authors: Krishnan Parameswaran, Richard Watson, Gail M. Gauvreau, Roma Sehmi, Paul M. O'Byrne
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

We investigated the mechanisms by which leukotriene receptor antagonists decrease airway eosinophil number. In a randomized, double-blind crossover study, we examined the effects of 2 weeks of treatment with pranlukast 300 mg twice a day or placebo on allergen-induced changes in airway eosinophil number and bone marrow eosinophil progenitors in 15 subjects with mild asthma. Pranlukast treatment for 2 weeks decreased mean sputum eosinophil count from 0.15 x 10(6)/g (5.3% of cells) before treatment to 0.02 x 10(6)/g (0.7% of cells) after treatment (p < 0.05), whereas placebo did not. Pranlukast also decreased the eosinophil count (5.6% at 7 hours and 7.5% at 24 hours) (p < 0.05) after allergen inhalation compared with placebo (13.8% at 7 hours and 15.3% at 24 hours). There was a similar trend for sputum cells immunostaining for EG2, eotaxin, interleukin-5, and regulated upon activation, normal T cell expressed and secreted. Pranlukast also significantly attenuated the allergen-induced increase in the number of bone marrow eosinophil/basophil cfu (mean 0.3) at 24 hours compared with placebo (mean 6.2). The proportion of CD34(+) cells expressing the eotaxin receptor CC chemokine receptor 3, 24 hours after allergen inhalation, was also reduced by pranlukast. We conclude that, the cysteinyl leukotriene receptor antagonist, pranlukast, attenuates allergen-induced increase in airway eosinophils by decreasing bone marrow eosinophilopoiesis and airway chemotactic and eosinophilopoietic cytokines.
Comparative Study of Protoporphyrins in Erythropoietic Protoporphyria and Griseofulvin-Induced Murine Protoporphyria
Authors: Maureen B. Poh-Fitzpatrick, Angelo A. Lamola, Gregory L. Zalar, Mark Weinstein, Frank Doleiden, Maria Freeman
Journal: Journal of Clinical Investigation (1977)

Excess erythrocyte protoporphyrins of human congenital erythropoietic protoporphyria and of griseofulvin-induced murine hepatic protoporphyria were found to be associated with hemoglobin and stroma fractions in similar relationships. More than 99.5% of total erythrocyte protoporphyrin was bound to hemoglobin in each case. However, profound differences were found when protoporphyrin concentration was measured in erythrocytes that had been segregated into populations of progressive age on discontinuous density gradients. In erythropoietic protoporphyria, porphyrin content diminished rapidly with age; in murine protoporphyria, the aging erythrocyte populations became progressively more porphyrin rich. In vitro diffusion of protoporphyrin from plasma across the intact erythrocyte membrane was demonstrated. The equimolar binding affinity of protoporphyrin to hemoglobin was shown to be 40 times that of protoporphyrin to serum albumin. This strong affinity provides the driving force for the observed transmembrane diffusion, and explains the high erythrocyte/plasma porphyrin ratio in murine hepatic protoporphyria. The opposite rapid efflux of intra-erythrocytic protoporphyrin into plasma previously shown in uncomplicated erythropoietic protoporphyria occurs despite this strong hemoglobin affinity, implying continuous efficient clearance of protoporphyrin from plasma by the liver. Furthermore, these and other data suggest that a hepatic synthetic source for any significant fraction of the blood protoporphyrin in erythropoietic protoporphyria is highly improbable.
Effectiveness of Lifestyle Interventions for Individuals With Severe Obesity and Type 2 Diabetes
Authors: Jessica L. Unick, Daniel Beavers, John M. Jakicic, Abbas E. Kitabchi, William C. Knowler, Thomas A. Wadden, Rena R. Wing
Journal: Diabetes Care (2011)

OBJECTIVE Rates of severe obesity (BMI ≥40 kg/m2) are on the rise, and effective treatment options are needed. We examined the effect of an intensive lifestyle intervention (ILI) on weight loss, cardiovascular disease (CVD) risk, and program adherence in participants with type 2 diabetes who were severely obese compared with overweight (BMI 25 to &amp;lt;30 kg/m2), class I (BMI 30 to &amp;lt;35 kg/m2), and class II (BMI 35 to &amp;lt;40 kg/m2) obese participants. RESEARCH DESIGN AND METHODS Participants in the Action for Health in Diabetes (Look AHEAD) trial were randomly assigned to ILI or diabetes support and education (DSE). DSE participants received a less intense educational intervention, whereas ILI participants received an intensive behavioral treatment to increase physical activity (PA) and reduce caloric intake. This article focuses on the 2,503 ILI participants (age 58.6 ± 6.8 years). RESULTS At 1 year, severely obese participants in the ILI group lost −9.04 ± 7.6% of initial body weight, which was significantly greater (P &amp;lt; 0.05) than ILI participants who were overweight (−7.43 ± 5.6%) and comparable to class I (−8.72 ± 6.4%) and class II obese (−8.64 ± 7.4%) participants. All BMI groups had comparable improvements in fitness, PA, LDL cholesterol, triglycerides, blood pressure, fasting glucose, and HbA1c at 1 year. ILI treatment session attendance was excellent and did not differ among weight categories (severe obese 80% vs. others 83%; P = 0.43). CONCLUSIONS Severely obese participants in the ILI group had similar adherence, percentage of weight loss, and improvement in CVD risk compared with less obese participants. Behavioral weight loss programs should be considered an effective option for this population.
A Prostate-Specific Membrane Antigen-Targeted Monoclonal Antibody–Chemotherapeutic Conjugate Designed for the Treatment of Prostate Cancer
Authors: Michael D. Henry, Shenghua Wen, Matthew D. Silva, Sudeep Chandra, Mark Milton, Peter J. Worland
Journal: Cancer Research (2004)

Abstract MLN2704 is an antibody-chemotherapeutic conjugate designed to target prostate-specific membrane antigen (PSMA). PSMA is a transmembrane receptor whose expression is largely restricted to prostatic epithelium and prostate cancer cells with its expression level increasing during the progression of malignancy. MLN2704 consists of a de-immunized, monoclonal antibody that is specific for PSMA conjugated to drug maytansinoid 1 (DM1), a microtubule-depolymerizing compound. After antibody binding to PSMA and the subsequent cellular internalization of this complex, DM1 is released leading to cell death. MLN2704 has an approximate half-life of 39 hours in scid mice bearing CWR22 tumor tissue, and the antibody effectively penetrates xenograft tumor tissue. Optimization of dosage and schedule of MLN2704 administration defined interdependency between these conditions that maximized efficacy with no apparent toxicity. Tumor growth delays of ∼100 days could be achieved on the optimized schedule of one dose of 60 mg/kg MLN2704 every 14 days for five doses (q14d×5). The unconjugated antibody (MLN591) demonstrated essentially no antitumor activity and DM1 alone or a non-PSMA targeted antibody–DM1 conjugate was only weakly active. Furthermore, we show that MLN2704 is active in a novel model of osteoblastic prostate cancer metastasis.
Respiratory infections associated with nontuberculous mycobacteria in non-HIV patients
Authors: M. Dailloux, M. L. Abalain, C. Laurain, L. Lebrun, C. Loos-Ayav, A. Lozniewski, J. Maugein
Journal: European Respiratory Journal (2006)

The incidence of nontuberculous mycobacteria (NTM) pulmonary diseases in HIV-negative patients was studied prospectively from January 1, 2001 to December 31, 2003 by 32 sentinel sites distributed throughout France. In total, 262 patients who yielded NTM isolates from respiratory clinical specimens, met the bacteriological, radiological and clinical criteria established by the American Thoracic Society for NTM respiratory disease. Among the 262 NTM isolates, 234 were slow-growing mycobacteria (125 Mycobacterium avium-intracellulare complex (MAC), 66 M. xenopi , 34 M. kansasii ) and 28 were rapidly growing mycobacteria (25 M. abscessus complex). In the Paris area, M. xenopi was the most frequently isolated species, followed by MAC. Most patients (&gt;50%), except those with M. kansasii , had underlying predisposing factors such as pre-existing pulmonary disease or immune deficiency. Asthenia, weight loss, chronic cough and dyspnoea were the most common clinical symptoms. The classical radiological appearance of NTM infections was indistinguishable from that observed in patients with pulmonary tuberculosis. In summary, the incidence of nontuberculous mycobacteria pulmonary infections in HIV-negative patients was estimated at 0.74, 0.73 and 0.72 cases per 100,000 inhabitants in 2001, 2002 and 2003, respectively.
Small nucleolar RNA signatures as biomarkers for non-small-cell lung cancer
Authors: Jipei Liao, Lei Yu, Yuping Mei, Maria Guarnera, Jun Shen, Ruiyun Li, Zhenqiu Liu, Feng Jiang
Journal: Molecular Cancer (2010)

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death. Early detection of NSCLC will improve its outcome. The current techniques for NSCLC early detection are either invasive or have low accuracy. Molecular analyses of clinical specimens present promising diagnostic approaches. Non-coding RNAs (ncRNAs) play an important role in tumorigenesis and could be developed as biomarkers for cancer. Here we aimed to develop small nucleolar RNAs (snoRNAs), a common class of ncRNAs, as biomarkers for NSCLC early detection. The study comprised three phases: (1) profiling snoRNA signatures in 22 NSCLC tissues and matched noncancerous lung tissues by GeneChip Array, (2) validating expressions of the signatures by RT-qPCR in the tissues, and (3) evaluating plasma expressions of the snoRNAs in 37 NSCLC patients, 26 patients with chronic obstructive pulmonary disease (COPD), and 22 healthy subjects.In the surgical tissues, six snoRNAs were identified, which were overexpressed in all tumour tissues compared with their normal counterparts. The overexpressions of the genes in tumors were confirmed by RT-qPCR. The snoRNAs were stably present and reliably detectable in plasma. Of the six genes, three (SNORD33, SNORD66 and SNORD76) displayed higher plasma expressions in NSCLC patients compared with the cancer-free individuals (All < 0.01). The use of the three genes produced 81.1% sensitivity and 95.8% specificity in distinguishing NSCLC patients from both normal and COPD subjects. The plasma snoRNA expressions were not associated with stages and histological types of NSCLC (All > 0.05).The identified snoRNAs provide potential markers for NSCLC early detection.
Hepatic RIG-I Predicts Survival and Interferon-α Therapeutic Response in Hepatocellular Carcinoma
Authors: Jin Hou, Ye Zhou, Yuanyuan Zheng, Jia Fan, Weiping Zhou, Irene O.L. Ng, Huichuan Sun, Lunxiu Qin, Shuangjian Qiu, Joyce M.F. Lee, Chung-Mau Lo, Kwan Man, Yuan Yang, Yun Yang, Yingyun Yang, Qian Zhang, Xuhui Zhu, Nan Li, Zhengxin Wang, Guoshan Ding, Shi-Mei Zhuang, Limin Zheng, Xiaoling Luo, Yuan Xie, Anmin Liang, Zhugang Wang, Ming Zhang, Qiang Xia, Tingbo Liang, Yizhi Yu, Xuetao Cao
Journal: Cancer Cell (2013)
HER2 Activating Mutations Are Targets for Colorectal Cancer Treatment
Authors: Shyam M. Kavuri, Naveen Jain, Francesco Galimi, Francesca Cottino, Simonetta M. Leto, Giorgia Migliardi, Adam C. Searleman, Wei Shen, John Monsey, Livio Trusolino, Samuel A. Jacobs, Andrea Bertotti, Ron Bose
Journal: Cancer Discovery (2015)

Abstract The Cancer Genome Atlas project identified HER2 somatic mutations and gene amplification in 7% of patients with colorectal cancer. Introduction of the HER2 mutations S310F, L755S, V777L, V842I, and L866M into colon epithelial cells increased signaling pathways and anchorage-independent cell growth, indicating that they are activating mutations. Introduction of these HER2 activating mutations into colorectal cancer cell lines produced resistance to cetuximab and panitumumab by sustaining MAPK phosphorylation. HER2 mutants are potently inhibited by low nanomolar doses of the irreversible tyrosine kinase inhibitors neratinib and afatinib. HER2 gene sequencing of 48 cetuximab-resistant, quadruple (KRAS, NRAS, BRAF, and PIK3CA) wild-type (WT) colorectal cancer patient-derived xenografts (PDX) identified 4 PDXs with HER2 mutations. HER2-targeted therapies were tested on two PDXs. Treatment with a single HER2-targeted drug (trastuzumab, neratinib, or lapatinib) delayed tumor growth, but dual HER2-targeted therapy with trastuzumab plus tyrosine kinase inhibitors produced regression of these HER2-mutated PDXs. Significance: HER2 activating mutations cause EGFR antibody resistance in colorectal cell lines, and PDXs with HER2 mutations show durable tumor regression when treated with dual HER2-targeted therapy. These data provide a strong preclinical rationale for clinical trials targeting HER2 activating mutations in metastatic colorectal cancer. Cancer Discov; 5(8); 832–41. ©2015 AACR. See related commentary by Pectasides and Bass, p. 799. This article is highlighted in the In This Issue feature, p. 783