tbuckley/cabot-search huggingface dataset:
Circulating Tumor Cells: A Useful Predictor of Treatment Efficacy in Metastatic Breast Cancer
Authors: Minetta C. Liu, Peter G. Shields, Robert D. Warren, Philip Cohen, Mary Wilkinson, Yvonne L. Ottaviano, Suman B. Rao, Jennifer Eng-Wong, Francoise Seillier-Moiseiwitsch, Anne-Michelle Noone, Claudine Isaacs
Journal: Journal of Clinical Oncology (2009)

Five or more circulating tumor cells (CTCs) per 7.5 mL of blood predicts for poorer progression-free survival (PFS) in patients with metastatic breast cancer (MBC). We conducted a prospective study to demonstrate that CTC results correlate strongly with radiographic disease progression at the time of and in advance of imaging.Serial CTC levels were obtained in patients starting a new treatment regimen for progressive, radiographically measurable MBC. Peripheral blood was collected for CTC enumeration at baseline and at 3- to 4-week intervals. Clinical outcomes were based on radiographic studies performed in 9- to 12-week intervals.Sixty-eight patients were evaluable for the CTC-imaging correlations, and 74 patients were evaluable for the PFS analysis. Median follow-up was 13.3 months. A statistically significant correlation was demonstrated between CTC levels and radiographic disease progression in patients receiving chemotherapy or endocrine therapy. This correlation applied to CTC results obtained at the time of imaging (odds ratio [OR], 6.3), 3 to 5 weeks before imaging (OR, 3.1), and 7 to 9 weeks before imaging (OR, 4.9). Results from analyses stratified by type of therapy remained statistically significant. Shorter PFS was observed for patients with five or more CTCs at 3 to 5 weeks and at 7 to 9 weeks after the start of treatment.We provide, to our knowledge, the first evidence of a strong correlation between CTC results and radiographic disease progression in patients receiving chemotherapy or endocrine therapy for MBC. These findings support the role of CTC enumeration as an adjunct to standard methods of monitoring disease status in MBC.
Mortality in Offspring of Parents With Psychotic Disorders: A Critical Review and Meta-Analysis
Authors: Roger Webb, Kathryn Abel, Andrew Pickles, Louis Appleby
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Mortality risk in offspring of parents with psychotic disorders is a sensitive and important topic, but evidence on which to base plans for preventive services is limited. The authors synthesized evidence for mortality risk among offspring of parents with psychotic disorders and examined potential modifiers of risk such as offspring age and parental diagnosis. METHOD: Electronic reference and citation databases were searched. Secondary analyses were carried out to generate relative risk estimates and perform post hoc statistical power calculations. A meta-analysis of the association between maternal psychotic disorder and fetal death/stillbirth was conducted. RESULTS: Most of the relevant studies investigated the relationship between exposure to maternal schizophrenia and perinatal or infant mortality outcomes but were not truly population-based and lacked adequate power. Studies published since 1960 generally indicated higher than expected mortality risk in exposed offspring. Meta-analysis indicated an almost twofold higher risk of fetal death/stillbirth among offspring of women with psychoses. Notable gaps in the existing evidence include outcome beyond the first year of life, cause-specific mortality, and effects of exposure to specific parental conditions other than schizophrenia and of exposure to paternal versus maternal disorder. Etiological mechanisms are not fully understood. CONCLUSIONS: Large-scale population-based studies are needed to understand mortality risk in offspring of parents with psychoses. In the absence of etiological evidence, only general preventive measures can be taken. Prevention of offspring mortality at an early age is most likely to be achieved by identification and treatment of maternal disorder and greater provision of support to these vulnerable families.
Influence of anti-TNF therapy on mortality in patients with rheumatoid arthritis-associated interstitial lung disease: results from the British Society for Rheumatology Biologics Register
Authors: W G Dixon, K L Hyrich, K D Watson, M Lunt, D P M Symmons
Journal: Annals of the Rheumatic Diseases (2010)

Background Anti-tumour necrosis factor (anti-TNF) therapy has been associated with reports of rapid severe progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, reports also exist of favourable responses to anti-TNF therapy in patients with ILD. The aim of this study was to examine the influence of anti-TNF therapy on mortality in patients with pre-existing RA-ILD. Methods Using data from the British Society for Rheumatology Biologics Register, a national prospective observational study, 367 patients with pre-existing RA-ILD were identified (299 treated with anti-TNF therapy and 68 treated with traditional disease-modifying antirheumatic drugs (DMARDs)). Results 70/299 patients (23%) in the anti-TNF cohort died after a median follow-up of 3.8 years compared with 14/68 (21%) in the DMARD cohort after a median follow-up of 2.1 years. The mortality was 68 deaths/1000 person years (pyrs) (95% CI 53 to 86) in the anti-TNF cohort and 92/1000 pyrs (95% CI 50 to 155) in the DMARD cohort, generating an age- and sex-adjusted mortality rate ratio (aMRR) of 1.26 (95% CI 0.69 to 2.31). After further adjustment for potential confounders, the aMRR fell to 0.81 (95% CI 0.38 to 1.73) for the anti-TNF cohort compared with the DMARD cohort. RA-ILD was the underlying cause of death in 15/70 (21%) and 1/14 (7%) patients in the anti-TNF and DMARD cohorts, respectively. Conclusion The mortality in patients with RA-ILD is not increased following treatment with anti-TNF therapy compared with traditional DMARDs. The proportion of deaths attributable to RA-ILD is higher in patients treated with anti-TNF therapy, although reporting bias may exist.
Neurochemical and Psychopharmacologic Aspects of Aggressive Behavior
Authors: B S Eichelman
Journal: Annual Review of Medicine (1990)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Stromal Depletion Goes on Trial in Pancreatic Cancer
Authors: K. Garber
Journal: JNCI Journal of the National Cancer Institute (2010)

For decades, surgeons and pathologists have likened pancreatic tumors to rocks. That’s because a dense, fibrotic mass called the stroma surrounds the cancer cells in the tumor. Such stroma, consisting of connective tissue, fibroblasts, leukocytes, and blood vessels, accompanies most solid tumors, but its extent and compactness are exceptional in pancreatic cancer. And since pancreatic cancer is exceptional also in its deadliness, researchers have wondered whether the stroma is at least partly responsible. Some recent studies now make that case. They argue for the idea that the stroma is blocking drug penetration and contributing to tumor survival, and that drugs that punch holes in the stromal barrier can be effective. “It’s hard to get drug into a rock,” said Robert Wolff, M.D., an oncologist at the University of Texas M. D. Anderson Cancer Center in Houston. “If you can soften up the rock, you may be able to get a better therapeutic index.” Skeptics remain, but several combination therapies are now in clinical trials to test this “stromal depletion hypothesis.” And some oncologists, including Wolff, are already giving certain patients a stromatargeted drug in an off-label indication, outside clinical trials.
Prevention of Rheumatic Fever and Diagnosis and Treatment of Acute Streptococcal Pharyngitis
Authors: Michael A. Gerber, Robert S. Baltimore, Charles B. Eaton, Michael Gewitz, Anne H. Rowley, Stanford T. Shulman, Kathryn A. Taubert
Journal: Circulation (2009)

Primary prevention of acute rheumatic fever is accomplished by proper identification and adequate antibiotic treatment of group A beta-hemolytic streptococcal (GAS) tonsillopharyngitis. Diagnosis of GAS pharyngitis is best accomplished by combining clinical judgment with diagnostic test results, the criterion standard of which is the throat culture. Penicillin (either oral penicillin V or injectable benzathine penicillin) is the treatment of choice, because it is cost-effective, has a narrow spectrum of activity, and has long-standing proven efficacy, and GAS resistant to penicillin have not been documented. For penicillin-allergic individuals, acceptable alternatives include a narrow-spectrum oral cephalosporin, oral clindamycin, or various oral macrolides or azalides. The individual who has had an attack of rheumatic fever is at very high risk of developing recurrences after subsequent GAS pharyngitis and needs continuous antimicrobial prophylaxis to prevent such recurrences (secondary prevention). The recommended duration of prophylaxis depends on the number of previous attacks, the time elapsed since the last attack, the risk of exposure to GAS infections, the age of the patient, and the presence or absence of cardiac involvement. Penicillin is again the agent of choice for secondary prophylaxis, but sulfadiazine or a macrolide or azalide are acceptable alternatives in penicillin-allergic individuals. This report updates the 1995 statement by the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee. It includes new recommendations for the diagnosis and treatment of GAS pharyngitis, as well as for the secondary prevention of rheumatic fever, and classifies the strength of the recommendations and level of evidence supporting them.
Streptococcal pyrogenic exotoxin B antibodies in a mouse model of glomerulonephritis
Authors: Y.-H. Luo, C.-F. Kuo, K.-J. Huang, J.-J. Wu, H.-Y. Lei, M.T. Lin, W.-J. Chuang, C.-C. Liu, C.-F. Lin, Y.-S. Lin
Journal: Kidney International (2007)
Coordinate Secretion of Acid Hydrolases in Rat Bile
Authors: Nicholas F. Larusso, Stanley Fowler
Journal: Journal of Clinical Investigation (1979)

Three lysosomal glycosidases, β-glucuronidase (EC 3.2.1.31), β-galactosidase (EC 3.2.1.23), and N-acetyl-β-glucosaminidase (EC 3.2.1.30) have been investigated in bile that was freshly collected from rats through a complete bile fistula. Assay conditions have been established on the basis of appropriate kinetic studies. The biliary excretion patterns for these enzymes were found to vary considerably from rat to rat during the 24-h collection period. In a given animal, however, the three hydrolases were excreted in parallel and showed a gradual increase in activity with time, most marked after 10- 12 h of collection. 24-h biliary outputs of the three hydrolases averaged ≅3% of their respective contents in total liver, and bile diversion had no effect on hepatic glycosidase activity or total protein content. Other enzymes known to be associated primarily with mitochondria, endoplasmic reticulum, and cell sap were also detected in bile, generally in smaller amounts. The biliary excretion of the plasma membrane markers, alkaline phosphodiesterase I and 5′-nucleotidase, however, was comparable to that of the lysosomal hydrolases. Biliary excretion of total protein was relatively constant and corresponded to 3.0% of the total hepatic protein content per day, whereas biliary bile acid secretion decreased during the first 12 h and then remained constant. Exocytic bulk discharge of hepatocyte lysosomes is proposed as the most likely mechanism for the biliary excretion of lysosomal enzymes. These results call attention to the possible pathophysiologic significance of biliary excretion of hepatic lysosomal contents as a means of residue disposal.
Acute hypertension selectively potentiates constrictor responses of large coronary arteries to serotonin by altering endothelial function in vivo.
Authors: K G Lamping, W P Dole
Journal: Circulation Research (1987)

We tested the hypothesis that acute coronary artery hypertension may damage vascular endothelium and alter vasomotor responses to humoral agents. We examined effects of intracoronary infusion of the endothelium-dependent agent serotonin and two endothelium-independent agents, angiotensin II and methoxamine, on large coronary artery diameter in the blood perfused dog heart. Responses were examined before and 30 minutes after brief periods of coronary hypertension (200 mm Hg for 10 seconds to 15 minutes). In open-chest anesthetized dogs, the left anterior descending coronary artery was perfused at constant pressure. Coronary diameter (D) was measured with piezoelectric crystals. At a control perfusion pressure of 80 mm Hg, serotonin produced dose-dependent constriction of the large coronary artery (mean +/- SEM; delta D = -22 +/- 10 microns at 5 micrograms/min; -108 +/- 50 microns at 50 micrograms/min). Increasing perfusion pressure to 200 mm Hg increased flow 515 +/- 79% and coronary diameter 509 +/- 9 microns. After 15 minutes of hypertension, when coronary diameter had returned to baseline values, the constriction of the large artery to serotonin was potentiated (delta D = -89 +/- 33 microns at 5 micrograms/min; -207 +/- 45 microns at 50 micrograms/min; p less than 0.05). Hypertension for 1-5 minutes potentiated constrictor responses of large coronary arteries for at least 2 1/2 hours. Removal of endothelium prevented effects of hypertension on constrictor responses of large arteries to serotonin. Hypertension did not alter constrictor responses to angiotension II (1 and 2.5 micrograms/min) or methoxamine (50 and 100 micrograms/min) or the dilator response to acetylcholine (40 micrograms/min). Acute hypertension altered endothelial morphology. There were small endothelial craters following 10 seconds of hypertension, and disruption of endothelial junctions with leukocyte adherence following 1-15 minutes of hypertension. We conclude that acute hypertension alters constrictor responses of large coronary arteries to serotonin by impairing endothelial function and not by directly affecting vascular smooth muscle. These effects of acute hypertension on vascular reactivity are selective in that they do not involve non-endothelium-dependent agents or the endothelium-dependent agent, acetylcholine. The effect of hypertension also persists long after pressure is restored to normotensive levels.
Pathologic Complete Response Rates in Young Women With <i>BRCA1</i>-Positive Breast Cancers After Neoadjuvant Chemotherapy
Authors: Tomasz Byrski, Jacek Gronwald, Tomasz Huzarski, Ewa Grzybowska, Magdalena Budryk, Malgorzata Stawicka, Tomasz Mierzwa, Marek Szwiec, Rafal Wiśniowski, Monika Siolek, Rebecca Dent, Jan Lubinski, Steven Narod
Journal: Journal of Clinical Oncology (2009)

To estimate the rate of pathologic complete response (pCR) to neoadjuvant chemotherapy in BRCA1 mutation carriers according to chemotherapy regimen.From a registry of 6,903 patients, we identified 102 women who carried a BRCA1 founder mutation and who had been treated for breast cancer with neoadjuvant chemotherapy. Pathologic complete response was evaluated using standard criteria.Twenty-four (24%) of the 102 BRCA1 mutation carriers experienced a pCR. The response rate varied widely with treatment: a pCR was observed in one (7%) of 14 women treated with cyclophosphamide, methotrexate, and fluorouracil (CMF); in two (8%) of 25 women treated with doxorubicin and docetaxel (AT); in 11 (22%) of 51 women treated with doxorubicin and cyclophosphamide (AC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC), and in 10 (83%) of 12 women treated with cisplatin.A low rate of pCR was observed in women with breast cancer and a BRCA1 mutation who were treated with AT or CMF. A high rate of pCR was seen after treatment with cisplatin. An intermediate rate of PCR was associated with AC or FAC. The relative benefits of AC and platinum therapy need to be confirmed through follow-up of this and other cohorts.
Epigenetic mechanisms in health and disease
Authors: S M van der Maarel
Journal: Annals of the Rheumatic Diseases (2008)

Epigenetic modifications of our genome involve DNA methylation, covalent modifications of the histone tails, nucleosome occupancy and turnover and higher-order chromatin folding. These mitotically heritable epigenetic modifications can affect transcription regulation and are increasingly recognised to be causally involved in a broad spectrum of human conditions, ranging from monogenic to multifactorial disorders. While our understanding of these epigenetic disease mechanisms steadily increases, the challenge will be to develop new drugs that specifically deal with the epigenetic lesion.
Open access and beyond
Authors: Shawn Mathur, Christian Schmidt, Chhaya Das, Philip W Tucker
Journal: Molecular Cancer (2006)

Abstract Uncensored exchange of scientific results hastens progress. Open Access does not stop at the removal of price and permission barriers; still, censorship and reading disabilities, to name a few, hamper access to information. Here, we invite the scientific community and the public to discuss new methods to distribute, store and manage literature in order to achieve unfettered access to literature.
Target-Specific Expression of Presynaptic NMDA Receptors in Neocortical Microcircuits
Authors: Katherine A. Buchanan, Arne V. Blackman, Alexandre W. Moreau, Dale Elgar, Rui P. Costa, Txomin Lalanne, Adam A. Tudor Jones, Julia Oyrer, P. Jesper Sjöström
Journal: Neuron (2012)

Traditionally, NMDA receptors are located postsynaptically; yet, putatively presynaptic NMDA receptors (preNMDARs) have been reported. Although implicated in controlling synaptic plasticity, their function is not well understood and their expression patterns are debated. We demonstrate that, in layer 5 of developing mouse visual cortex, preNMDARs specifically control synaptic transmission at pyramidal cell inputs to other pyramidal cells and to Martinotti cells, while leaving those to basket cells unaffected. We also reveal a type of interneuron that mediates ascending inhibition. In agreement with synapse-specific expression, we find preNMDAR-mediated calcium signals in a subset of pyramidal cell terminals. A tuned network model predicts that preNMDARs specifically reroute information flow in local circuits during high-frequency firing, in particular by impacting frequency-dependent disynaptic inhibition mediated by Martinotti cells, a finding that we experimentally verify. We conclude that postsynaptic cell type determines presynaptic terminal molecular identity and that preNMDARs govern information processing in neocortical columns.
Epidemiologic study of vinyl chloride workers: mortality through December 31, 1972.
Authors: W C Cooper
Journal: Environmental Health Perspectives (1981)

A population of 10,173 men, employed in 37 plants, was identified as having worked for at least one year in jobs involving probable exposure to vinyl chloride monomer (VCM) prior to January 1, 1973. Of the 9677 men whose vital status was determined, 707 were known to have died. For 699, death certificates were obtained. The standardized mortality ratio (SMR) for all causes was 89, that for all malignancies was 104. The only type of malignancy found in significant excess was in the category of malignant neoplasms of the brain and other parts of the nervous system; 12 deaths occurred where 5.9 were expected, for an adjusted SMR of 203. There were slight but inconclusive upward trends in all malignancies, and for malignancies of the respiratory tract, digestive tract, and central nervous system associated with reported levels of maximum exposure to VCM. When groups in whom less than 20 years had elapsed from the first exposure were compared with those with 20 or more elapsed years, and 25 or more elapsed years, no significantly different SMR's were detected for major primary sites of malignancy. Plans for an updated study of mortality, to include deaths in the period 1973-1979 are briefly discussed.
Fabry's disease: biochemical and histochemical studies on hair roots for carrier detection
Authors: A. J. M. VERMORKEN, P. J. J. M. WETERINGS, G. Th. SPIERENBURG, C. A. BENNEKOM, P. WIRTZ, C. H. M. M. BRUYN, T. L. OEI
Journal: British Journal of Dermatology (1978)

A method to assay α‐galactosidase and acid phosphatase activities in single hair roots is described. Enzyme histochemical studies show that the distribution of acid phosphatase in the human hair root matches that of α‐galactosidase. Histochemically, the main activity is located in the upper part of the sheath near the orifice of the duct of the sebaceous gland. This is confirmed by enzyme assays on different parts of the hair root after dissection. The variation in the values found in individual hair roots is improved by relating α‐galactosidase to acid phosphatase activities. Storage experiments indicate a remarkable stability of both α‐galactosidase and acid phosphatase in human hair roots.
Diabetic Neuropathies: Update on Definitions, Diagnostic Criteria, Estimation of Severity, and Treatments
Authors: Solomon Tesfaye, Andrew J.M. Boulton, Peter J. Dyck, Roy Freeman, Michael Horowitz, Peter Kempler, Giuseppe Lauria, Rayaz A. Malik, Vincenza Spallone, Aaron Vinik, Luciano Bernardi, Paul Valensi
Journal: Diabetes Care (2010)

Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13-18 October 2009, expert panels were convened to provide updates on classification, definitions, diagnostic criteria, and treatments of diabetic peripheral neuropathies (DPNs), autonomic neuropathy, painful DPNs, and structural alterations in DPNs.
Endobronchial Ultrasound–guided Transbronchial Needle Aspiration for Non–Small Cell Lung Cancer Staging
Authors: C. Matthew Kinsey, Douglas A. Arenberg
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

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