tbuckley/cabot-search huggingface dataset:
Concurrent occurrence of gastric adenocarcinoma and duodenal neuroendocrine cell carcinoma: a composite tumour or collision tumours ?
Authors: H Fukui, M Takada, T Chiba, R Kashiwagi, M Sakane, F Tabata, Y Kuroda, Y Ueda, H Kawamata, J Imura, T Fujimori
Journal: Gut (2001)

BACKGROUND Neuroendocrine cell (NEC) carcinoma is occasionally accompanied by adenocarcinoma but the relationship between these two morphologically distinct tumours is unclear. Two hypotheses have arisen regarding the mechanism for the association of adenocarcinoma and NEC carcinoma. One is that both are derived from a common multipotential epithelial stem cell. The second hypothesis is that adenocarcinoma and NEC carcinoma arise from a multipotential epithelial stem cell and a primitive NEC, respectively. AIMS To elucidate the relationship between the two histologically distinct tumours, adenocarcinoma of the stomach and NEC carcinoma of the duodenum. PATIENT/METHODS We present a case in which the tumour extended across the pyloric ring, the gastric portion of which revealed adenocarcinoma while the duodenal portion showed argyrophil NEC carcinoma. The two histologically distinct lesions of the tumour were examined by immunohistochemistry and genetic analysis of p53. RESULTS The gastric region was negative for chromogranin A staining but positive for carcinoembryonic antigen (CEA) staining. In contrast, the duodenal region was positive for chromogranin A but negative for CEA. All tumour regions showed a point mutation in p53 gene at exon 7 (GGC (glycine)→GTC (valine) at codon 245). The distal portion of the duodenal tumour showed an additional point mutation in p53 gene at exon 5 (GCC (alanine)→GTC (valine) at codon 129). CONCLUSIONS The two histologically distinct tumours, adenocarcinoma of the stomach and NEC carcinoma of the duodenum, appear to be derived from a common epithelial cell.
L-Histidine Decarboxylase and Tourette's Syndrome
Authors: A. Gulhan Ercan-Sencicek, Althea A. Stillman, Ananda K. Ghosh, Kaya Bilguvar, Brian J. O'Roak, Christopher E. Mason, Thomas Abbott, Abha Gupta, Robert A. King, David L. Pauls, Jay A. Tischfield, Gary A. Heiman, Harvey S. Singer, Donald L. Gilbert, Pieter J. Hoekstra, Thomas M. Morgan, Erin Loring, Katsuhito Yasuno, Thomas Fernandez, Stephan Sanders, Angeliki Louvi, Judy H. Cho, Shrikant Mane, Christopher M. Colangelo, Thomas Biederer, Richard P. Lifton, Murat Gunel, Matthew W. State
Journal: New England Journal of Medicine (2010)

Tourette's syndrome is a common developmental neuropsychiatric disorder characterized by chronic motor and vocal tics. Despite a strong genetic contribution, inheritance is complex, and risk alleles have proven difficult to identify. Here, we describe an analysis of linkage in a two-generation pedigree leading to the identification of a rare functional mutation in the HDC gene encoding L-histidine decarboxylase, the rate-limiting enzyme in histamine biosynthesis. Our findings, together with previously published data from model systems, point to a role for histaminergic neurotransmission in the mechanism and modulation of Tourette's syndrome and tics.
Src Continues Aging: Current and Future Clinical Directions
Authors: Scott Kopetz, Ami N. Shah, Gary E. Gallick
Journal: Clinical Cancer Research (2007)

Abstract Aberrant activation of members of the Src family of nonreceptor protein tyrosine kinases is common in solid tumor malignancies and may contribute to the development and/or progression of these tumors. As a result, four Src inhibitors are now in more than 50 clinical trials for at least 14 different types of solid tumors. In this review, we briefly discuss the preclinical rationale for Src inhibitors, the development strategies most likely to be successful in the clinic, and the rationale for Src inhibitors in combination with other agents as part of a more comprehensive therapeutic strategy. As the use of Src family inhibitors in clinical trials on solid tumors is in its infancy, further studies on the roles of Src family kinases in tumor progression, chemoresistance, epidermal-to-mesenchymal transition, and other properties of tumor progression will be important in designing the most effective clinical trials using these inhibitors.
CSF3R, SETBP1 and CALR mutations in chronic neutrophilic leukemia
Authors: Yajuan Cui, Bing Li, Robert Peter Gale, Qian Jiang, Zefeng Xu, Tiejun Qin, Peihong Zhang, Yue Zhang, Zhijian Xiao
Journal: Journal of Hematology & Oncology (2014)

The WHO 2008 definition of chronic neutrophilic leukemia (CNL) is based on clinical and laboratory parameters but not on molecular abnormalities. Mutations in CSF3R, SETBP1 and CALR are reported in patients with chronic neutrophilic leukemia (CNL). However, because CNL is rare, there are few large studies of this issue. We sequenced these genes in 14 patients who met the WHO-criteria of CNL. 8 subjects had CSF3R(T618I), 6 SETBP1 mutations and 1 a CALR mutation. Our data suggest mutation analysis of CSF3R, SETBP1 and CALR should be included in the diagnostic criteria for CNL. These data may also have therapy implications.
Antilipemic Activity of an Extract of Hog Gastric Mucosa
Authors: AURELIO CANTONE, VINCENZO RULLI, BALDO ROSSI
Journal: Circulation Research (1959)

In recent years numerous studies have been made on the clearing effect exerted by heparin on hyperlipemic plasma, specially in connection with the problem of atherogenesis. The present paper deals with investigations, carried out on both animals and men, concerning the hypocholesteremic, plasma-clearing, and lipotropic effects, as well as the inhibitory action on the electrocardiographic changes associated with alimentary hyperlipemia, exerted by orally active extracts of gastric juice and hog gastric mucosa.
Unaltered Dopamine Transporter Availability in Adult Attention Deficit Hyperactivity Disorder
Authors: Christopher H van Dyck, Donald M Quinlan, Lisa M Cretella, Julie K Staley, Robert T Malison, Ronald M Baldwin, John P Seibyl, Robert B Innis
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The authors examined whether patients with attention deficit hyperactivity disorder (ADHD) have altered striatal dopamine transporter levels, which may explain psychostimulant effects in this disorder. METHOD: Single photon emission computed tomography and [123I]2β-carbomethoxy-3β-(4-iodophenyl)tropane ([123I]β-CIT) were used to assess dopamine transporter availability in nine adult patients with ADHD (eight of whom were stimulant naive) and nine age- and gender-matched healthy comparison subjects. RESULTS: Striatal [123I]β-CIT binding did not differ significantly between the ADHD and comparison subjects. CONCLUSIONS: The findings suggest that a hypothesized dysregulation of dopamine function in ADHD does not entail altered dopamine transporter levels.
Impaired Atrial Receptor Responses in Dogs with Heart Failure Due to Tricuspid Insufficiency and Pulmonary Artery Stenosis
Authors: TOKOKO T. GREENBERG, WILLIAM H. RICHMOND, REGINALD A. STOCKING, PURSHOTIM D. GUPTA, JOHN P. MEEHAN, JAMES P. HENRY
Journal: Circulation Research (1973)

In a study of the effects of heart failure on the responses of cardiac receptors, ten dogs were subjected to tricuspid avulsion and pulmonary artery stenosis. One case of spontaneous heart failure was included in the series, and the electrical spike responses of atrial receptors to progressive changes in atrial stretch induced by infusion and hemorrhage were contrasted with those in normal control dogs. In the control dogs, the number of spikes per cycle increased very sharply with moderate, i.e., 5-10 cm H 2 O, venous pressure increments before reaching a maximum at 20 cm H 2 O. In the experimental dogs, the firing rate failed to increase to the same extent despite large increases in pressure. The resulting sets of curves exhibited a sharp dichotomy. This evidence for the impaired response of elements of the subendocardial receptor network is compatible with a decrease in the sensitivity of feedback mechanisms responsible for the regulation of sodium and water metabolism.
Congenital Anomalies Involving the Coronary Sinus
Authors: EMIL MANTINI, CLAUDE M. GRONDIN, C. WALTON LILLEHEI, JESSE E. EDWARDS
Journal: Circulation (1966)

A classification is presented of anomalies involving the coronary sinus. These anomalies are classified into four anatomic groups on the basis of (1) enlargement of the coronary sinus, (2) absence of the coronary sinus, (3) atresia of the right atrial coronary sinus ostium, and (4) hypoplasia of the coronary sinus. Anomalies involving the coronary sinus often are associated with other venous anomalies, either of the systemic or the pulmonary circulation. In some there is no basic disturbance of the circulation. Those conditions involving the coronary sinus which are of major functional significance participate in shunts, either left-to-right or right-to-left in nature. Enlargement of the coronary sinus in the absence of a shunt usually indicates that a systemic venous channel joins the coronary sinus anomalously.
A case of lymphomatoid granulomatosis masquerading as a lung abscess
Authors: M McCloskey
Journal: Thorax (2004)

Lymphomatoid granulomatosis (LG) is a rare T cell rich, B cell non-Hodgkin’s lymphoma which is difficult to diagnose. We present a patient with LG who demonstrated many of the difficulties in diagnosis and highlighted the importance of reviewing the diagnosis if treatment does not have the anticipated effect.
Toward a Comprehensive Set of Asthma Susceptibility Genes
Authors: Yohan Bossé, Thomas J. Hudson
Journal: Annual Review of Medicine (2006)

Epidemiological and twin studies have demonstrated that asthma is under genetic and environmental influences. Numerous candidate gene association studies as well as genome-wide linkage scans have followed, aiming to elucidate the genetic architecture underlying this complex disease. Several promising asthma susceptibility genes were identified, and a comprehensive catalogue of these genes seems a realistic goal within 5 to 10 years. However, a key challenge is to understand the combination of genes and environmental factors that gives rise to the disease in a specific individual. Currently, most of the reports of asthma susceptibility genes are either preliminary or controversial, with little knowledge about the genetic mechanisms leading to abnormal function of the gene that promotes the development of asthma. Replications of published associations are relatively few. Many factors, including the inherent complexity of asthma as well as methodological issues, can explain these inconsistencies. Promising genetic tools are emerging with the completion of the International HapMap Project that will increase the scope of gene-discovery investigations. It is hoped that these tools, combined with validation studies in additional populations, will enable the creation of a comprehensive catalogue of susceptibility genes for asthma. Notwithstanding the difficulties in making sense of the vast amount of new genetic data, we already see the emergence of new biological pathways of atopy, airway remodeling, and asthma that may lead to novel therapeutic approaches.
Framework for optimisation of the clinical use of colistin and polymyxin B: the Prato polymyxin consensus
Authors: Roger L Nation, Jian Li, Otto Cars, William Couet, Michael N Dudley, Keith S Kaye, Johan W Mouton, David L Paterson, Vincent H Tam, Ursula Theuretzbacher, Brian T Tsuji, John D Turnidge
Journal: The Lancet Infectious Diseases (2014)
S100 Family Members and Trypsinogens Are Predictors of Distant Metastasis and Survival in Early-Stage Non-Small Cell Lung Cancer
Authors: Sven Diederichs, Etmar Bulk, Björn Steffen, Ping Ji, Lara Tickenbrock, Kerstin Lang, Kurt S. Zänker, Ralf Metzger, Paul M. Schneider, Volker Gerke, Michael Thomas, Wolfgang E. Berdel, Hubert Serve, Carsten Müller-Tidow
Journal: Cancer Research (2004)

Distant metastasis is the predominant cause of death in early-stage non-small cell lung cancer (NSCLC). Currently, it is impossible to predict the occurrence of metastasis at early stages and thereby separate patients who could be cured by surgical resection alone from patients who would benefit from additional chemotherapy. In this study, we applied a comparative microarray approach to identify gene expression differences between early-stage NSCLC patients whose cancer ultimately did or did not metastasize during the course of their disease. Transcriptional profiling of 82 microarrays from two patient groups revealed differential expression of several gene families including known predictors of metastasis (e.g., matrix metalloproteinases). In addition, we found S100P, S100A2, trypsinogen C (TRY6), and trypsinogen IVb (PRSS3) to be overexpressed in tumors that metastasized during the course of the disease. In a third group of 42 patients, we confirmed the induction of S100 proteins and trypsinogens in metastasizing tumors and its significant correlation with survival by real-time quantitative reverse transcription-PCR. Overexpression of S100A2, S100P, or PRSS3 in NSCLC cell cultures led to increased transendothelial migration, corroborating the role of S100A2, S100P, and PRSS3 in the metastatic process. Taken together, we provide evidence that expression of S100 proteins and trypsinogens is associated with metastasis and predicts survival in early stages of NSCLC. For the first time, this implicates a role of S100 proteins and trypsinogens in the metastatic process of early-stage NSCLC.
Hsp90 and p130cas: novel regulatory factors of MMP-13 expression in human osteoarthritic chondrocytes
Authors: Z Fan, G Tardif, D Hum, N Duval, J-P Pelletier, J Martel-Pelletier
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Background:</h3> Human osteoarthritic (OA) chondrocytes were previously classified into L (low)- and H (high)-OA according to matrix metalloproteinase-13 (MMP-13) basal levels and interleukin 1β (IL1β) inducibility. In H-OA chondrocytes, the regulatory proteins p130<sup>cas</sup> and nuclear matrix protein 4 (NMP4) acting on the MMP-13 promoter were identified. <h3>Objective:</h3> To identify regulators of MMP-13 expression/production in human L-OA chondrocytes, to determine their effect on the expression of other MMPs and the effect of IL1β on these molecules. <h3>Methods:</h3> The identification of the L-OA chondrocyte proteins interacting specifically with the AGRE site of the MMP-13 promoter was performed by mass spectrometry. Heat shock protein 90β (Hsp90β), p130<sup>cas</sup> and NMP4 small interfering RNAs (siRNAs) were transfected into L-OA chondrocytes and incubated with or without IL1β. Gene expression was determined by real-time PCR, MMP-1 and MMP-13 production by ELISA, and signalling pathway activation by western blotting and ELISA. <h3>Results:</h3> Hsp90β was identified as a protein of the L-OA/AGRE-specific complex. Silencing p130<sup>cas</sup> and Hsp90β significantly increased MMP-13 expression (about four- and twofold, respectively) and production. sip130<sup>cas</sup> affected to a lesser extent MMP-1 expression (twofold) and production. siNMP4 showed no effect. Expression of MMP-2, -3, -9 and -14 was unaffected. Silencing both Hsp90β and p130<sup>cas</sup> had a significant additive effect on MMP-13, but not on MMP-1 expression, the level of which was similar to that with sip130<sup>cas</sup> alone. IL1β decreased p130<sup>cas</sup> and Hsp90β expression/production, indicating another pathway by which this cytokine upregulates MMP expression. The IL1β-triggered signalling pathways responsible for MMP upregulation were unaffected in the silenced cells. <h3>Conclusion:</h3> This study illustrates the complex regulation of MMP-13 by showing the inhibitory effect of the two cytoplasmic molecules, p130<sup>cas</sup> and Hsp90β, in L-OA chondrocytes.
Tackling the Diversity of Triple-Negative Breast Cancer
Authors: Nicholas C. Turner, Jorge S. Reis-Filho
Journal: Clinical Cancer Research (2013)

Abstract Triple-negative breast cancer (TNBC) comprises a highly diverse collection of cancers. Here, we review this diversity both in terms of gene expression subtypes and the repertoire of genetic events. Transcriptomic analyses of TNBC have revealed at least six subtypes, with the luminal androgen receptor (luminal AR) or molecular apocrine cancers forming a distinct group within triple-negative disease. Distinct from the gene expression subtypes, a diverse set of genetic events have been described in TNBC, with a number of potentially targetable genetic events found although all at relatively low frequency. Clinical trials to define the clinical utility of therapies targeting these low-frequency events will require substantial screening efforts to identify sufficient patients. Set against the diversity of TNBC, clinical studies of patients with triple-negative disease will need to be either focused on molecularly defined subsets with upfront molecular stratification, or powered for a secondary endpoint analysis of a molecularly defined subset. Such approaches will be crucial to realize the potential of precision medicine for patients with TNBCs. Clin Cancer Res; 19(23); 6380–8. ©2013 AACR.
Heterogeneity of bovine snout epidermal prekeratin
Authors: F. WISSLER, C. CARRUTHERS
Journal: British Journal of Dermatology (1975)

The prekeratin of the snout of cows was extracted with 0-1 mol/l citric acid-sodium citrate buffer, pH 2-6. The results of equilibrium ultracentrifugation analyses of this prekeratin strongly suggest that this protein is not homogeneous. This conclusion is in accordance with the observations of two other investigators whose data infer that there is no major homogeneous keratin precursor in cow's lip or snout epidermis.
Effect of metoclopramide in guinea-pig ileum longitudinal muscle: evidence against dopamine-mediation.
Authors: M A Zar, O Ebong, D N Bateman
Journal: Gut (1982)

The investigation examines the hypothesis that metoclopramide-induced potentiation of gastrointestinal motility is mediated through dopamine receptors. In vitro studies on the longitudinal muscle of the guinea-pig ileum were performed. Metoclopramide, in concentrations comparable with those seen in plasma after therapeutic doses in man, selectively potentiated the cholinergic response Dopamine (1-100 microM) inhibited cholinergic transmission by inhibiting neuronal acetylcholine release. The inhibitory action of dopamine was antagonised by phentolamine, and alpha-adrenoceptor antagonist, but not by the dopamine receptor antagonists metoclopramide or primozide. Bromocriptine inhibited cholinergic responses by a postsynaptic mechanism which was not antagonised by metoclopramide, primozide, or phentolamine. The results are consistent with the view that metoclopramide-induced potentiation of gastrointestinal motility does not involve local dopamine receptors.
Predictive factors for the tolerance of non-invasive ventilation in amyotrophic lateral sclerosis patients
Authors: Daniel Gonzalez, Jesús Sancho, Emilio Servera, Pilar Bañuls, Julio Marín
Journal: European Respiratory Journal (2011)

Noninvasive ventilation (NIV) increases the survival of amyotrophic lateral sclerosis (ALS) patients. NIV tolerance factors vary according to different studies.

Aim: To assess the predictive factors which have an impact on NIV tolerance in ALS patients.

Material and methods: Prospective study which included ALS for whom NIV was indicated between January 2004 to January 2010. Demographic, neurological function, respiratory function and night-time monitoring data (before and after the adjustment of NIV with a volume ventilator) were collected. Tolerance of NIV was defined as use > 4 hours a day.

Results: 71 patients who accepted NIV were included, of whom: 34 (47.9%) men, 62.34±8.79 years old, MIC 26.08±3.81 kg/m2, 35.2% with bulbar onset, time from onset of disease to NIV 40.78±41.78 months, ALSFRS-R 30.25±7.15, Norris bulbar 28.08±9.70, FVC 1.60±0.96 L, FVC% 52.57±24.57%, PCF 3.75±1.98 L/s, MIC 2.11±1.05 L, PImax -48.04±24.33 cmH2O, PEmax 73.38±44.33 cmH2O, Tc90 34.27±30.92%, PaO2 74.88±12.94 mmHg, PaCO2 50.33±9.10 mmHg, 74.6% of patients with symptoms of hypoventilation, Tc90 with NIV 1.98±4.05%, PaO2 with NIV 83.54±10.19 mmHg, PaCO2 with NIV 42.16±4.65 mmHg, 18.3% with symptoms of hypoventilation with NIV, hours of use 9.28±4.89 h. In 7 patients (9.9%) NIV tolerance was poor (<4h). NIV tolerance factors were: Tc90 with NIV (OR 0.87, p 0.02, IC95% 0.73-0.97) and persistent symptoms of hypoventilation with NIV (OR 8.14, p 0.013, IC95% 1.55-42.62).

Conclusions: NIV tolerance in ALS patients is high. The persistence of SpO2 <90% episodes and hypoventilation despite NIV are determinant factors in poor NIV tolerance.
Diabetes Treatment and Cardiovascular Safety
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2011)

This is the third of a series of articles based on presentations at the American Diabetes Association (ADA) 70th Scientific Sessions, held 25–29 June 2010 in Orlando, Florida, pertaining to the need for large-scale cardiovascular (CV) safety requirements for the treatment of diabetes. The term “contrarian” is defined in various ways as “a person who takes an opposing view,” as “one who rejects the majority opinion” (1), or as “an investor who goes against current market trends” (2). What might be characterized as a “contrarian” debate on diabetes discussed the new requirement for large-scale CV safety studies on all new glucose-lowering medications. There was also a discussion of an increasingly recognized issue, potential inaccuracies of capillary glucose test meters, and of point-of-care A1C testing technologies.

At the symposium, Steven Nissen (Cleveland Clinic, Cleveland, OH) addressed the question of whether diabetes drugs should have a higher bar for CV safety than other drugs. He began with an acknowledgment of relationships with multiple pharmaceutical companies, although stating that all income from such went to “charity.” He then complained about the “ridiculous title for a debate,” to suggest that the outcome (presumably his) would be a foregone conclusion. He stated that “all drugs must be required to show a health outcomes benefit,” and that “diabetes drugs are being held to [a] standard that is neither greater nor less than other fields.” He acknowledged microvascular benefits of reduction in glycemia but stated that “some of the drugs that lower blood sugar actually increase the risk of macrovascular complications” and suggested this to override microvascular disease, as “CVD is the cause of death in most diabetic patients.” Furthermore, he questioned the use of biomarkers as “surrogate for real outcomes data” and termed the blood glucose concentration as simply a “biomarker.” “Blood glucose measurements,” he suggested, …
Human Effector and Memory CD8+ T Cell Responses to Smallpox and Yellow Fever Vaccines
Authors: Joseph D. Miller, Robbert G. van der Most, Rama S. Akondy, John T. Glidewell, Sophia Albott, David Masopust, Kaja Murali-Krishna, Patryce L. Mahar, Srilatha Edupuganti, Susan Lalor, Stephanie Germon, Carlos Del Rio, Mark J. Mulligan, Silvija I. Staprans, John D. Altman, Mark B. Feinberg, Rafi Ahmed
Journal: Immunity (2008)
Essentials of Radiology
Authors: S. C. Shanks
Journal: BMJ (1950)

<h3>Abstract</h3> Since the emergence of SARS-CoV-2, five different variants of concern (VOCs) have been identified: Alpha, Beta, Gamma, Delta, and Omicron. Due to confounding factors in the human population, such as pre-existing immunity, comparing severity of disease caused by different VOCs is challenging. Here, we investigate disease progression in the rhesus macaque model upon inoculation with the Delta, Omicron BA.1, and Omicron BA.2 VOCs. Disease severity in rhesus macaques inoculated with Omicron BA.1 or BA.2 was lower than those inoculated with Delta and resulted in significantly lower viral loads in nasal swabs, bronchial cytology brush samples, and lung tissue in rhesus macaques. Cytokines and chemokines were upregulated in nasosorption samples of Delta animals compared to Omicron BA.1 and BA.2 animals. Overall, these data suggests that in rhesus macaques, Omicron replicates to lower levels than the Delta VOC, resulting in reduced clinical disease.