tbuckley/cabot-search huggingface dataset:
Transient Pulmonary Infiltrations in Cystic Fibrosis due to Allergic Aspergillosis
Authors: M. Mearns, W. Young, J. Batten
Journal: Thorax (1965)

In most patients with cystic fibrosis the morbidity and mortality are largely determined by the severity of the lung lesion.Staphylococcus pyogenes is usually found in the sputum and causes a chronic suppurative bronchiolitis and bronchitis with spread of the infection to adjacent alveoli.With more effective chemotherapy other organisms, such as Pseudomonas pyocyanea, are now being cultivated from the sputum with in- creasing frequency and may predominate.Certain fungal infections such as monilia, although feared, have not apparently occurred.Recently, however, two cases of cystic fibrosis have been encountered in which Aspergillus fumigatus was found in the sputum and in which the patients developed sensitivity to the fungus with pulmonary infiltra- tion and eosinophilia.CASE REPORTS CASE 1 Born 2 June 1950.Although this boy had been suffering from progressive malnutrition and alimentary symptoms, the diagnosis of cystic fibrosis, based on absent duodenal trypsin, was not made until he was 2 years old in 1952.(This diagnosis was confirmed when the sweat was analysed in 1964 and showed a sodium concentration of 98 mEq/l.: normal
What if we had whole-genome sequence data for millions of individuals?
Authors: Peter M Visscher, Greg Gibson
Journal: Genome Medicine (2013)

The affordable whole-genome sequence is (nearly) here and already costs less than many commercial DNA tests for specific variants or genes. It seems very plausible to us that in the near future millions of people will have their genome sequenced, not just because the cost is coming down but also because individuals (in rich countries) are increasingly becoming ‘health consumers’. Here, we muse on what we could infer from having whole-genome sequence data for a million individuals.

In the absence of phenotypic data, there are six types of information that people can obtain from their own genomes. Firstly, their ancestry: how their chromosomes compare with those of typical members of diverse human populations. Secondly, things they can do something about (for example, enzyme deficiencies, BRCA1-like mutations, their pharmacogenetic responses). Thirdly, things they are unable to do anything about, most of which will be a source of anxiety [1]. Fourthly, things that explain interesting or medical phenotypes (for example, eye color or rare congenital traits). Fifthly, things they may worry about handing on to their children (and which they might want to check in their (prospective) spouse or prevent their children from being at high risk for). Finally, things they may like to pass on to their children. The first four types of information in this list relate to the person whose genome has been sequenced, the last two are about their children. Of this list, (2) and (5) lead to information that is, from a health perspective, actionable right now. At present, most knowledge on these actionable items are restricted to Mendelian traits.
Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomised phase 2/3 non-inferiority study (FIRIS study)
Authors: Kei Muro, Narikazu Boku, Yasuhiro Shimada, Akihito Tsuji, Shinichi Sameshima, Hideo Baba, Taroh Satoh, Tadamichi Denda, Kenji Ina, Tomohiro Nishina, Kensei Yamaguchi, Hiroya Takiuchi, Taito Esaki, Shinya Tokunaga, Hiroyuki Kuwano, Yoshito Komatsu, Masahiko Watanabe, Ichinosuke Hyodo, Satoshi Morita, Kenichi Sugihara
Journal: The Lancet Oncology (2010)
Mucopolysaccharidosis type IVA. N-acetylgalactosamine-6-sulfate sulfatase exonic point mutations in classical Morquio and mild cases.
Authors: S Fukuda, S Tomatsu, M Masue, K Sukegawa, H Iwata, T Ogawa, Y Nakashima, T Hori, A Yamagishi, Y Hanyu
Journal: Journal of Clinical Investigation (1992)

Mucopolysaccharidosis type IVA (MPS IVA) results from a genetic deficiency of N-acetylgalactosamine-6-sulfate (Gal-NAc6S) sulfatase. We have identified two different exonic mutations causing GalNAc6S sulfatase deficiency in two unrelated Japanese families, in one patient with classical Morquio disease, and in two brothers with a mild form of MPS IVA. The nucleotide sequence of the full-length cDNA derived from a patient with classical Morquio disease revealed a two-base deletion at nucleotide position 1343-1344 (1344-1345 or 1345-1346) that altered the reading frame (designated 1342delCA). This mutation, inherited from the proband's consanguineous parents, was revealed by TaqI restriction analysis of a cDNA fragment amplified by the polymerase chain reaction. In the proband with the mild form of the disease, a C to G transversion at nucleotide 667 predicted the substitution of Lys for Asn204 (N204K). Since a new AluI site was created by the N204K mutation, restriction analysis indicated that the affected brothers were homozygous for this mutation, as confirmed by the finding that both their parents had this lesion. Transient expression in GalNAc6S sulfatase deficient fibroblasts of these two mutant alleles showed completely deficient or markedly decreased enzyme activities, thereby indicating that these two mutations were responsible for the enzyme deficiency.
A subcutaneous glucose sensor with improved longevity, dynamic range, and stability of calibration.
Authors: S J Updike, M C Shults, B J Gilligan, R K Rhodes
Journal: Diabetes Care (2000)

To evaluate the lifetime, response time, linearity, glucose range, and calibration stability of two different types of continuous glucose sensor implants in a dog model.Glucose sensors based on the enzyme electrode principle that are coupled to a radio transmitter were evaluated on the bench top, sterilized, and then implanted subcutaneously in nondiabetic mongrel dogs. A multichannel radio receiver and PC data processor were used to record the sensor glucose data. Initial early reliable sensor responsivity was recognized by a vigorous hyperglycemic excursion after an intramuscular injection of glucagon. Periodically the dogs were made temporarily diabetic by blocking pancreatic insulin secretion by subcutaneous injection of a synthetic somatostatin (octreotide). By using exogenous insulin injection followed by intravenous glucose infusion, glucose levels were manipulated through the entire clinical range of interest: 2.2-38.9 mmol/l (40-700 mg/dl). Every 5-10 min, reference blood glucose samples were obtained and run in our hospital clinical laboratory. The glucose sensor data was evaluated by linear least squares optimization and by the error grid method.Beginning as early as postimplant day 7, the in vivo performances of sensors were evaluated by using glucose infusion studies performed every 1-4 weeks. Bench-top and in vivo 90% response-time sensors were in the range of 4-7 min during sensor lifetime. Best-performing sensors from both types are summarized as follows. The earlier-stage technology was less linear with a dynamic range of no more than 22 mmol/l glucose, had a best-case recalibration interval of 18 days, and had a maximum lifetime of 94 days. The improved later-stage technology sensors, which were constructed with the addition of bioprotective and angiogenic membranes, were linear over the full extended range of clinical interest (2.2-38.9 mmol/l [40-700 mg/dl glucose]), had a best-case recalibration interval of 20 days, and had a maximum lifetime of >160 days.Stable clinically useful sensor performance was demonstrated as early as 7 days after implantation and for a sensor lifetime of 3-5 months. This type of subcutaneous glucose sensor appears to be promising as a continuous and painless long-term method for monitoring blood glucose. Specifically sensors with top-layer materials that stimulate angiogenesis at the sensor/tissue interface may have better dynamic measurement range, longer lifetimes, and better calibration stability than our previously reported sensors.
A phase II open-label study of recombinant human interleukin-12 in patients with stage IA, IB, or IIA mycosis fungoides
Authors: Madeleine Duvic, Matthew L. Sherman, Gary S. Wood, Timothy M. Kuzel, Elise Olsen, Francine Foss, Robert J. Laliberté, John L. Ryan, Kristilyn Zonno, Alain H. Rook
Journal: Journal of the American Academy of Dermatology (2006)
Cirrhotics with variceal hemorrhage: The importance of the time interval between admission and the start of analysis for survival and rebleeding rates
Authors: Andrew K. Burroughs, Guerrino Mezzanotte, Andrew Phillips, Aiden P. McCormick, Neil McIntyre
Journal: Hepatology (1989)

The importance of variable time of entry for analysis of survival following variceal bleeding has recently been disputed. In a study of 194 cirrhotic patients with bleeding esophageal varices in whom 2-day mortality was 3%, statistically significant differences in both survival and rebleeding rates were obtained by shifting the starting point for analysis of survival by 2 weeks following admission to hospital or by 5 days for the analysis of rebleeding. In addition, the curve of hazard function for death or for failure to control bleeding following admission clearly showed that any change in entry time in a study of variceal bleeding would introduce bias and alter survival or rebleeding rates. Thus, the starting point for analysis following variceal hemorrhage is an important confounding variable when calculating both survival and rebleeding. It should always be taken into account, particularly in clinical trials, which are often performed in centers where patients are referred from other hospitals at different times following bleeding.
Therapeutic Enhancement of ER Stress by Insulin-Like Growth Factor I Sensitizes Myeloma Cells to Proteasomal Inhibitors
Authors: Inès Tagoug, Lars Petter Jordheim, Stéphanie Herveau, Eva-Laure Matera, Anne-Laure Huber, Kamel Chettab, Serge Manié, Charles Dumontet
Journal: Clinical Cancer Research (2013)

Multiple myeloma is a clonal plasma cell disorder in which growth and proliferation are linked to a variety of growth factors, including insulin-like growth factor type I (IGF-I). Bortezomib, the first-in-class proteasome inhibitor, has displayed significant antitumor activity in multiple myeloma.We analyzed the impact of IGF-I combined with proteasome inhibitors on multiple myeloma cell lines in vivo and in vitro as well as on fresh human myeloma cells.Our study shows that IGF-I enhances the cytotoxic effect of proteasome inhibitors against myeloma cells. The effect of bortezomib on the content of proapoptotic proteins such as Bax, Bad, Bak, and BimS and antiapoptotic proteins such as Bcl-2, Bcl-XL, XIAP, Bfl-1, and survivin was enhanced by IGF-I. The addition of IGF-I to bortezomib had a minor effect on NF-κB signaling in MM.1S cells while strongly enhancing reticulum stress. This resulted in an unfolded protein response (UPR), which was required for the potentiating effect of IGF-I on bortezomib cytotoxicity as shown by siRNA-mediated inhibition of GADD153 expression.These results suggest that the high baseline level of protein synthesis in myeloma can be exploited therapeutically by combining proteasome inhibitors with IGF-I, which possesses a "priming" effect on myeloma cells for this family of compounds.
Essential roles of sphingosine-1–phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema
Authors: Carole A. Oskeritzian, Megan M. Price, Nitai C. Hait, Dmitri Kapitonov, Yves T. Falanga, Johanna K. Morales, John J. Ryan, Sheldon Milstien, Sarah Spiegel
Journal: The Journal of Experimental Medicine (2010)

Systemic exacerbation of allergic responses, in which mast cells play a critical role, results in life-threatening anaphylactic shock. Sphingosine-1–phosphate (S1P), a ligand for a family of G protein–coupled receptors, is a new addition to the repertoire of bioactive lipids secreted by activated mast cells. Yet little is known of its role in human mast cell functions and in anaphylaxis. We show that S1P2 receptors play a critical role in regulating human mast cell functions, including degranulation and cytokine and chemokine release. Immunoglobulin E–triggered anaphylactic responses, including elevation of circulating histamine and associated pulmonary edema in mice, were significantly attenuated by the S1P2 antagonist JTE-013 and in S1P2-deficient mice, in contrast to anaphylaxis induced by administration of histamine or platelet-activating factor. Hence, S1P and S1P2 on mast cells are determinants of systemic anaphylaxis and associated pulmonary edema and might be beneficial targets for anaphylaxis attenuation and prophylaxis.
Clinical and angiographic correlates and outcomes of suboptimal coronary flow inpatients with acute myocardial infarction undergoing primary percutaneous coronary intervention
Authors: Rajendra H Mehta, Kishore J Harjai, David Cox, Gregg W Stone, Bruce Brodie, Judy Boura, William O'Neill, Cindy L Grines
Journal: Journal of the American College of Cardiology (2003)
An outbreak of H1N1 influenza in a respiratory unit
Authors: D. R. Miller, G. L. Christie, P. Molyneaux, G. P. Currie
Journal: Thorax (2010)

Pandemic influenza A (H1N1) is a major global public health concern.1 We report an outbreak of H1N1 influenza involving clinical staff and patients in a teaching hospital in the North East of Scotland.

In October 2009, a teenage patient was admitted with an exacerbation of asthma. As there was no reason to suspect H1N1, the patient was not isolated. However, nose and throat swabs were in fact taken on the day of admission and were positive for H1N1 by PCR within 24 h. At this …
Home dampness, moulds and their influence on respiratory infections and symptoms in adults in Finland
Authors: I Pirhonen, A Nevalainen, T Husman, J Pekkanen
Journal: European Respiratory Journal (1996)

The aim of this study was to analyse the prevalence of mouldy homes and their association with respiratory symptoms and diseases in a subarctic climate. A questionnaire was mailed to a random sample of 2,000 males and females, aged 25-64 yrs, living in the county of Kuopio, Finland. A total of 1,521 (76%) responded and 1,460 were selected for the final analysis. The prevalence of homes with visible mould was 4%; with the odour of mould 5%; with damp spots, visible mould or the odour of mould 15%; and with moisture/ water damage, damp spots, visible mould or the odour of mould 23%. The number of reports of bronchitis, common cold, atopy, allergic rhinitis, rhinitis, fever and chills, hoarseness, fatigue, difficulties in concentration, lumbar backache and stomach ache were strongly associated with living in a damp home. Bronchitis, hoarseness and difficulties in concentration had the strongest associations, with adjusted odds ratios (95% confidence limits) of: 2.04 (1.49-2.78), 2.23 (1.37-3.63) and 2.17 (1.35-3.50), respectively. After controlling for a possible reporting bias by excluding those subjects reporting lumbar backache and recurrent stomach pain, eye irritation and tiredness remained significant. In conclusion, living in a home with mould problems may increase the risk of respiratory infections and symptoms in adults.
ACCULTURATION AND LATINO HEALTH IN THE UNITED STATES: A Review of the Literature and its Sociopolitical Context
Authors: Marielena Lara, Cristina Gamboa, M. Iya Kahramanian, Leo S. Morales, David E. Hayes Bautista
Journal: Annual Review of Public Health (2005)

This chapter provides an overview of the concept of acculturation and reviews existing evidence about the possible relationships between acculturation and selected health and behavioral outcomes among Latinos. The effect of acculturation on Latino health is complex and not well understood. In certain areas-substance abuse, dietary practices, and birth outcomes-there is evidence that acculturation has a negative effect and that it is associated with worse health outcomes, behaviors, or perceptions. In others-health care use and self-perceptions of health-the effect is mostly in the positive direction. Although the literature, to date, on acculturation lacks some breadth and methodological rigor, the public health significance of findings in areas in which there is enough evidence justifies public health action. We conclude with a set of general recommendations in two areas-public health practice and research-targeted to public health personnel in academia, community-based settings, and government agencies.
Marion Sulzberger, MD: 'Mr. Dermatology'
Authors: N. Y. Hoffmann
Journal: JAMA (1983)

Marion B. Sulzberger, MD, lives in Western Edge, the cusp of that posh Divisadero Street hill, with its stunted trees and great old San Francisco mansions, called Pacific Heights. Two blocks up the hill you can see the bay sparkling in the sunlight. From the pleasant old apartment building, the view catches other San Francisco rooftops, framed by distant mountains, clear as the fog rides out to sea. Two apartments on the fourth floor serve as home and office for Sulzberger and his third wife, Roberta, a professional in audiovisual education. Telephones ring constantly in the latter, where a secretary and a French assistant work at Sulzberger's Institute for Dermatologic Communication and Education. The apartment building is reminiscent of Sulzberger's childhood home in a New York City brownstone at 21 E 67th St between Madison and Fifth avenues. As the eldest of his father's third family, he lived on the
Relationship of Baseline Serum Bilirubin to Efficacy and Toxicity of Single-Agent Irinotecan in Patients With Metastatic Colorectal Cancer
Authors: Jeffrey A. Meyerhardt, Ambrose Kwok, Mark J. Ratain, J. Patrick McGovren, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2004)

Purpose To examine the predictive value of baseline serum bilirubin measurement for chemotherapy-related toxicity or efficacy among patients receiving irinotecan for metastatic colorectal cancer. Methods We performed a secondary analysis of a cohort of 287 patients treated in a multicenter, phase III study with single-agent irinotecan administered either weekly or once every 3 weeks. Patients were grouped into three categories of baseline bilirubin measurements (0 to 0.4, 0.5 to 0.9, and 1.0 to 1.5 mg/dL). We performed analyses of overall survival, time to progression, and treatment-related toxicity based on bilirubin category, as well as using bilirubin as a continuous variable. Results With a median follow-up of 15.8 months, baseline serum bilirubin was not predictive of 1-year survival (42.4%, bilirubin 0 to 0.4; 42.3%, bilirubin 0.5 to 0.9; 48.1%, bilirubin 1.0 to 1.5 mg/dL), median overall survival (10.1, 9.7, and 15.6 months, respectively; P = .5), or median time to progression (2.8, 3.0, and 4.1 months, respectively; P = .5). Patients with elevated bilirubin had a significantly greater risk grade 3 to 4 neutropenia; however, this was limited to patients treated on a weekly schedule (P trend = .03) and not once every 3 weeks (P trend = .8). Other toxicities were not significantly different by initial bilirubin measurement. Conclusion Although modest elevations of bilirubin (1.0 to 1.5 mg/dL) are associated with increased grade 3 to 4 neutropenia in patients treated with weekly irinotecan, baseline serum bilirubin does not reliably predict overall irinotecan-related toxicity or efficacy. Additional methods, including potential application of pharmacogenetic information, are needed to optimize irinotecan dosing and tailor therapy to individual patients.
Molecular Heterogeneity and Receptor Coamplification Drive Resistance to Targeted Therapy in<i>MET</i>-Amplified Esophagogastric Cancer
Authors: Eunice L. Kwak, Leanne G. Ahronian, Giulia Siravegna, Benedetta Mussolin, Darrell R. Borger, Jason T. Godfrey, Nicholas A. Jessop, Jeffrey W. Clark, Lawrence S. Blaszkowsky, David P. Ryan, Jochen K. Lennerz, A. John Iafrate, Alberto Bardelli, Theodore S. Hong, Ryan B. Corcoran
Journal: Cancer Discovery (2015)

MET inhibition is effective in some patients with MET-amplified esophagogastric cancer (EGC), but understanding acquired and de novo resistance mechanisms will be critical to improving therapy. We identified KRAS mutation as a novel cause of acquired resistance in a patient after a 2-year response to a MET inhibitor. We also observed that 40% to 50% of patients with MET-amplified EGC harbor coamplification of HER2 and/or EGFR concurrently in the same tumor cells, which can drive de novo resistance. One patient with concurrent MET and HER2 amplification was refractory to HER2 blockade, but responded to combined MET/HER2 inhibition. We also found striking heterogeneity in MET amplification between distinct metastatic lesions and primary tumors in individual patients with EGC. In these patients, MET inhibition led to mixed responses and disease progression through outgrowth of non-MET-amplified clones, which could be monitored in circulating tumor DNA. Thus, receptor coamplification and molecular heterogeneity may be key drivers of clinical resistance in MET-amplified EGC.
PARP Inhibitors: Will the New Class of Drugs Match the Hype?
Authors: Rabiya S. Tuma
Journal: JNCI Journal of the National Cancer Institute (2009)

BRCA proteins play a role in DNA repair. Healthy cells have several different DNA repair pathways at their disposal; PARP is required for the base excision repair pathway, which mends single-strand nicks, whereas the BRCA proteins are critical for the homologous recombination pathway, which fi xes double-strand breaks. Cells can survive when one repair system breaks down, but they start to die when two of the DNA repair mechanisms stop functioning. Therefore, the combination of a PARP inhibitor and loss of a functional BRCA protein leads to cell death. Preclinical data suggested that the hypothesis was correct; tumor cells that lacked functional BRCA1 or -2 died in the presence of PARP inhibition in vitro. Researchers found that cells that had one normal BRCA allele and one mutant BRCA allele — which is typical of most cells in an individual who carries a BRCA1 or -2 mutation — tolerate PARP inhibition without a problem. In the tumor cells, however, which have lost their remaining functional BRCA gene, PARP inhibition is toxic.