tbuckley/cabot-search huggingface dataset:
Effects of breathing supplemental oxygen before progressive exercise in patients with chronic obstructive lung disease.
Authors: J L McKeon, K Murree-Allen, N A Saunders
Journal: Thorax (1988)

A study was carried out to determine whether supplemental oxygen before exercise would improve maximum exercise performance and relieve exertional dyspnoea in 20 patients with chronic obstructive lung disease (mean FEV1 0.79 l; forced vital capacity 2.30 l). Patients performed two progressive treadmill exercise tests to a symptom limited maximum, with at least 30 minutes rest between tests. They received compressed air or supplemental oxygen from nasal prongs for 10 minutes before exercise in a double blind randomised trial with a crossover design. Heart rate and breathlessness score on a visual analogue scale were compared between tests at 75% of the maximum distance walked in the compressed air test. The mean arterial oxygen saturation (SaO2) after oxygen (93%) was significantly higher than after compressed air (91%). There was no significant change, however, in maximum distance walked or maximum heart rate, or in the breathlessness score or heart rate at 75% of maximum distance walked. The study had a power of 93% for detecting an increase of 50 metres in maximum distance walked. There was an order effect, with better performance on the second test; but the magnitude of the difference was small. It is concluded that administration of supplemental oxygen sufficient to raise SaO2 above 90% for 10 minutes before exercise is unlikely to improve maximum exercise performance or breathlessness on exertion in patients with chronic obstructive lung disease.
Distribution of Conventional and Nonconventional Introns in Tubulin (α and β) Genes of Euglenids
Authors: Rafał Milanowski, Anna Karnkowska, Takao Ishikawa, Bożena Zakryś
Journal: Molecular Biology and Evolution (2013)

The nuclear genomes of euglenids contain three types of introns: conventional spliceosomal introns, nonconventional introns for which a splicing mechanism is unknown (variable noncanonical borders, RNA secondary structure bringing together intron ends), and so-called intermediate introns, which combine features of conventional and nonconventional introns. Analysis of two genes, tubA and tubB, from 20 species of euglenids reveals contrasting distribution patterns of conventional and nonconventional introns—positions of conventional introns are conserved, whereas those of the nonconventional ones are unique to individual species or small groups of closely related taxa. Moreover, in the group of phototrophic euglenids, 11 events of conventional intron loss versus 15 events of nonconventional intron gain were identified. A comparison of all nonconventional intron sequences highlighted the most conserved elements in their sequence and secondary structure. Our results led us to put forward two hypotheses. 1) The first one posits that mutational changes in intron sequence could lead to a change in their excision mechanism—intermediate introns would then be a transitional form between the conventional and nonconventional introns. 2) The second hypothesis concerns the origin of nonconventional introns—because of the presence of inverted repeats near their ends, insertion of MITE-like transposon elements is proposed as a possible source of new introns.
Intestinal cells produce basement membrane proteins in vitro.
Authors: U Hahn, D Schuppan, E G Hahn, H J Merker, E O Riecken
Journal: Gut (1987)

The epithelial-mesenchymal interface of the intestinal mucosa obviously plays an important role in supporting the mucosal architecture. Its significance for the process of migration and differentiation of the epithelial cells remains to be resolved. It consists of a basement membrane, the anchoring zone and the subepithelial connective tissue, the origin of which is unknown. We therefore established an in vitro model to study the development of the endodermal-mesenchymal interface of the fetal human and murine intestinal mucosa. The distribution of the interstitial collagens type I, III, VI and procollagen type III as well as the basement membrane components collagen type IV and laminin was investigated immunohistochemically in these fetal explant cultures. The cultures were also adapted to serum free culture conditions. It was evident that while laminin and collagen type IV could be detected in the primary intestinal epithelium, the formation of an authentic basement membrane required the presence of both the epithelial and the mesenchymal cells. Interstitial collagens and procollagen type III were produced exclusively by the mesenchymal cells. Basement membrane formation in vitro coincided with cytodifferentiation of the endodermal cells as betrayed by electron microscopy and the activity of brush border enzymes. In conclusion, the maturation of the endoderm and the formation of the subepithelial basement membrane require the intimate proximity of viable mesenchyme in vitro.
Synovial Cyst of Ischial Tuberosity in Felty's Syndrome
Authors: Aaron M. Lefkovits
Journal: JAMA (1969)

To the Editor:—  A patient who had Felty's syndrome was found to have accumulation of fluid over the region of the ischial tuberosities. The rarity of this observation warrants this brief report.  Report of a Case:  A 47-year-old white man, at 25 years of age, had pain, swelling, tenderness, and heat in many of the peripheral joints. Over the years, the symptoms gradually and progressively increased in severity, and crippling deformities of rheumatoid arthritis developed in the joints of both hands and in some of the other peripheral joints. Subcutaneous nodules appeared over many bony prominences. The patient became progressively incapacitated, and since 1962, he had been unable to work. In May 1968, an infection in the right middle ear developed, complicated by mastoiditis, and the patient was admitted to the hospital. Examination revealed typical rheumatoid arthritic deformities involving almost all of the peripheral joints. Subcutaneous nodules of varying sizes
Collaborative ocular melanoma study (COMS) randomized trial of I-125 brachytherapy for medium choroidal melanoma I. visual acuity after 3 years COMS report no. 16
Authors: B M Melia, D H Abramson, D M Albert, H C Boldt, J D Earle, W F Hanson, P Montague, C S Moy, A P Schachat, E R Simpson, B R Straatsma, A K Vine, T A Weingeist
Journal: Ophthalmology (2001)
Role of Thrombophilic Gene Polymorphisms in Branch Retinal Vein Occlusion
Authors: Martin Weger, Wilfried Renner, Iris Steinbrugger, Lisa Cichocki, Werner Temmel, Olaf Stanger, Yosuf El-Shabrawi, Helga Lechner, Otto Schmut, Anton Haas
Journal: Ophthalmology (2005)
Cytotoxic effects of bortezomib in myelodysplastic syndrome/acute myeloid leukemia depend on autophagy-mediated lysosomal degradation of TRAF6 and repression of PSMA1
Authors: Jing Fang, Garrett Rhyasen, Lyndsey Bolanos, Christopher Rasch, Melinda Varney, Mark Wunderlich, Susumu Goyama, Gerrit Jansen, Jacqueline Cloos, Carmela Rigolino, Agostino Cortelezzi, James C. Mulloy, Esther N. Oliva, Maria Cuzzola, Daniel T. Starczynowski
Journal: Blood (2012)
Memory systems, frontal cortex, and the hippocampal axis
Authors: Amanda Parker
Journal: Behavioral and Brain Sciences (1999)

Three comments are made. The proposal that recollection and familiarity-based recognition take different thalamic routes does not fit recent experimental evidence, suggesting that mediodorsal thalamus acts in an integrative role with respect to prefrontal cortex. Second, the role of frontal cortex in episodic memory has been understated. Third, the role of the hippocampal axis is likely to be the computation and storage of ideothetic information.
Bortezomib and Depsipeptide Sensitize Tumors to Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand: A Novel Method to Potentiate Natural Killer Cell Tumor Cytotoxicity
Authors: Andreas Lundqvist, Scott I. Abrams, David S. Schrump, Gauri Alvarez, Dante Suffredini, Maria Berg, Richard Childs
Journal: Cancer Research (2006)

Abstract The proteasome inhibitor, bortezomib, and the histone deacetylase inhibitor, depsipeptide (FK228), up-regulate tumor death receptors. Therefore, we investigated whether pretreatment of malignant cells with these agents would potentiate natural killer (NK)–mediated tumor killing. NK cells isolated from healthy donors and patients with cancer were expanded in vitro and then tested for cytotoxicity against tumor cell lines before and after exposure to bortezomib or depsipeptide. In 11 of 13 (85%) renal cell carcinoma cell lines and in 16 of 37 (43%) other cancer cell lines, exposure to these drugs significantly increased NK cell–mediated tumor lysis compared with untreated tumor controls (P &amp;lt; 0.001). Furthermore, NK cells expanded from patients with metastatic renal cell carcinoma were significantly more cytotoxic against autologous tumor cells when pretreated with either bortezomib or depsipeptide compared with untreated tumors. Tumors sensitized to NK cell cytotoxicity showed a significant increase in surface expression of DR5 [tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)-R2; P &amp;lt; 0.05]; in contrast, surface expression of MHC class I, MIC-A/B, DR4 (TRAIL-R1), and Fas (CD95) did not change. The enhanced susceptibility to NK cell killing was completely abolished by blocking TRAIL on NK cells, and partially abolished by blocking DR5 on tumor cells. These findings show that drug-induced sensitization to TRAIL could be used as a novel strategy to potentiate the anticancer effects of adoptively infused NK cells in patients with cancer. (Cancer Res 2006; 66(14): 7317-25)
GPs should not connect to NHSnet until it is restructured
Authors: G. S-B Kelly
Journal: BMJ (1999)

EDITOR—The views of de Lusignan and Brown about NHSnet are opposite to those of representative general practitioners because NHSnet has problems that demand its restructuring. The NHS Executive, suppliers, and professions have started this task, and general practitioners should not connect to NHSnet until it is restructured.

The authors wrongly assume that NHSnet is secure enough to send identified patient data across it “in clear” (non-encrypted) and that NHSnet is a preferable medium for handling information to promote …
Grand Rounds - Hammersmith Hospital: New approach to superior vena caval obstruction Mechanical clearance of thrombus may help
Authors: L Robinson, J Jackson
Journal: BMJ (1994)

Superior vena caval obstruction is a well recognised complication of bronchogenic carcinoma, with distressing clinical sequelae secondary to oedema of the soft tissues, larynx, and central nervous system. Conventionally it has been treated with radiotherapy and adjuvant chemotherapy or surgery with varying degrees of success.

A 56 year old white woman presented with a 10 week history of progressive oedema of the face and upper limbs followed by a one week history of worsening dyspnoea and dry cough. She denied any other symptoms. In her history she was noted to have mild asthma controlled by inhaled bronchodilators but she was otherwise well. She had smoked 20 cigarettes a day for about 40 years and had a red florid complexion with severe oedema of the face, chest wall, and upper limbs. The jugular veins were non-pulsatile and greatly distended. She was tachypnoeic at rest with a respiratory rate of 30/min, a monophonic wheeze in the right upper zone, and bilaterial pleural effusions. Neurological examination confirmed a right Horner's syndrome. Cardiovascular and abdominal examinations showed no abnormality.

Chest radiography showed a coin lesion in the right upper lobe with associated hilar and mediastinal lymphadenopathy and small bilateral pleural effusions; this was confirmed by computed tomography of the thorax. Pleural aspiration and biopsy, bronchoscopy, and anterior mediastinotomy did not give a diagnosis but confirmed the presence of a hard thrombosed superior vena cava with dilated venous collaterals. Cytological investigation of sputum confirmed the diagnosis of squamous cell carcinoma of the bronchus.

The tumour was inoperable, so to relieve the obstruction and palliate her symptoms, she had radiotherapy at a dose of 20 Gy in five fractions over five days with concurrent oral dexamethasone. Unfortunately, her oedema seemed to get worse. Venography showed numerous opacified collateral veins around both shoulders and the chest wall …
Evaluation of Myocardial Blood Perfusion in Man with Radioactive Potassium or Rubidium and Precordial Counting
Authors: LUIGI DONATO, GIANCARLO BARTOLOMEI, ROBERTO GIORDANI
Journal: Circulation (1964)

The myocardial clearance of potassium may be obtained by precordial counting after a single intravenous injection of K 42 Cl or Rb 86 Cl. The theoretical foundations of the method and the technic developed have been presented and discussed. The distribution of the values obtained in normal subjects and in subjects with coronary insufficiency is in agreement with the clinical expectancy, and changes of the observed MCK after nitroglycerin agree with the results obtained by other investigators who measured coronary blood flow by the indirect Fick method. In agreement with the observations of other investigators in rats and dogs, the amount of K 42 or Rb 86 in the myocardium was found to change very little for an appreciable time interval after the first circulation, despite the significant recirculation and the decreasing arterial concentration. This observation and the fact that MCK values in normal subjects closely agree with the accepted values for coronary blood flow confirm Sapirstein's findings in rats and dogs, and support the view that the organ uptake of Rb 86 or K 42 immediately after single intravenous injection reflects the fractional organ blood flow. As obtained with the present technic, and similarly with the indirect Fick method, MCK reflects the flow per gram of myocardium and not the total coronary blood flow. MCK, however, has the advantage that every unit volume of myocardium, no matter how well it is perfused or through which vessels it is drained, contributes to the precordial counting rate in variable proportions determined by the efficiency of the counting method.
Mechanisms of hyperinsulinaemia in Child's disease grade B liver cirrhosis investigated in free living conditions
Authors: A V Greco
Journal: Gut (2002)

Human liver cirrhosis is commonly associated with increased fasting and glucose induced insulin concentrations. However, whether the hyperinsulinaemia is a consequence of increased pancreatic insulin secretion, decreased hepatic insulin removal, or impaired feedback regulation of insulin secretion is still doubtful. To investigate these issues, insulin secretion-during 24 hours of standardised living conditions-insulin sensitivity, and hepatic insulin extraction were assessed in cirrhotic patients compared with matched healthy subjects.Nine Child's disease grade B cirrhotic patients and seven healthy volunteers, participated in the study. The subjects were studied on two separate days, one for the assessment of insulin secretion during a standardised 24 hour life period (calorimetric chamber), and one for the determination of insulin sensitivity.Insulin secretion rates were reconstructed from plasma C peptide concentrations by deconvolution, and indices of beta cell function were derived using a mathematical model describing the functional dependence of insulin secretion on plasma glucose concentrations. Insulin sensitivity was determined using the euglycaemic hyperinsulinaemic clamp technique.Cirrhotic patients showed a marked hypersecretory response, both in absolute terms (mean (SEM) 295 (53) versus 138 (11) nmol/m(2), p<0.02), and in relation to glucose (175 (26) versus 57 (5) pmol/min/m(2), p<0.02). In particular, the beta cell dose-response function was shifted upward compared with controls. The sensitivity of insulin secretion to the rate of glucose change was also increased. Insulin sensitivity, markedly reduced in cirrhosis (157 (10) versus 296 (30) ml/min/m(2), p<0.002), was strongly inversely correlated (r=0.89, p<0.002) in these patients with insulin secretion at 5 mM glucose. Insulin clearance and hepatic insulin extraction were not reduced. A frank hypermetabolism with increased lipid oxidation was found in this series.This study suggests that hyperinsulinaemia, at least in Child's disease grade B cirrhotic patients, is the consequence of increased beta cell sensitivity to glucose, while hepatic insulin extraction does not seem to play a significant part.
Expansion Dating: Calibrating Molecular Clocks in Marine Species from Expansions onto the Sunda Shelf Following the Last Glacial Maximum
Authors: E. D. Crandall, E. J. Sbrocco, T. S. DeBoer, P. H. Barber, K. E. Carpenter
Journal: Molecular Biology and Evolution (2011)

The rate of change in DNA is an important parameter for understanding molecular evolution and hence for inferences drawn from studies of phylogeography and phylogenetics. Most rate calibrations for mitochondrial coding regions in marine species have been made from divergence dating for fossils and vicariant events older than 1–2 My and are typically 0.5–2% per lineage per million years. Recently, calibrations made with ancient DNA (aDNA) from younger dates have yielded faster rates, suggesting that estimates of the molecular rate of change depend on the time of calibration, decaying from the instantaneous mutation rate to the phylogenetic substitution rate. aDNA methods for recent calibrations are not available for most marine taxa so instead we use radiometric dates for sea-level rise onto the Sunda Shelf following the Last Glacial Maximum (starting ∼18,000 years ago), which led to massive population expansions for marine species. Instead of divergence dating, we use a two-epoch coalescent model of logistic population growth preceded by a constant population size to infer a time in mutational units for the beginning of these expansion events. This model compares favorably to simpler coalescent models of constant population size, and exponential or logistic growth, and is far more precise than estimates from the mismatch distribution. Mean rates estimated with this method for mitochondrial coding genes in three invertebrate species are elevated in comparison to older calibration points (2.3–6.6% per lineage per million years), lending additional support to the hypothesis of calibration time dependency for molecular rates.
Reconciling computer models and stem cell models of human cardiac repolarization: reply
Authors: L. Han, Y. Li, J. Tchao, A. D. Kaplan, B. Lin, Y. Li, J. Mich-Basso, A. Lis, N. Hassan, B. London, G. C. L. Bett, K. Tobita, R. L. Rasmusson, L. Yang
Journal: Cardiovascular Research (2015)

We appreciate the interest in our recent study of the familial hypertrophic cardiomyopathy in induced pluripotent stem cells.1 Questions were raised about our experimental system, based on unpublished findings using simulations from a computer model of human ventricular myocytes. Christ et al. conclude that discrepancies between the iPSC-derived cardiomyocytes and the computer model indicate either a peculiarity in the specific human we studied or a problem with iPSC-derived cardiomyocytes in general. We readily agree that some properties in our HCM cells may be patient specific: this is part of the promise of personalized medicine. However, we propose an alternative interpretation for the discrepancy between iPSC-derived cardiomyocytes and model simulations: the model is not an accurate representation of the cardiomyocytes under study. Nevertheless, computer models can, and should, be used in conjunction with these …
THE SERUM LIPIDS IN MEN RECEIVING HIGH CHOLESTEROL AND CHOLESTEROL-FREE DIETS*
Authors: William E. Connor, Robert E. Hodges, Roberta E. Bleiler
Journal: Journal of Clinical Investigation (1961)

In a previous study we found that dietary cho- lesterol provided in the form of egg yolk had a great effect upon the serum cholesterol and phos- pholipid levels in healthy human subjects (2).This effect was obtained with the use of high cholesterol and cholesterol-free diets which were bal- anced closely in the amounts of fat and in fatty acid composition.The range of cholesterol intake so tested was from 1,700 to 4,800 mg per day, amounts clearly above the usual daily American consumption of 500 to 1,000 mg.The present investigation was designed to examine the serum lipid responses of six men given dietary cholesterol as egg yolk in amounts compatible with usual dietary intakes.The effects of egg yolk cho- lesterol and crystalline cholesterol were also compared. METHODSSubjects.Six men, aged 41 to 52 years, were selected from prison volunteers and hospitalized on a metabolic ward for 13 weeks.After a complete medical examination they were found to be in good health; none was obese.Their urinalyses, blood counts, erythrocyte sedimenta- tion rates and chest X-rays were normal.Dietary plan.Initially, the men received a general diet for 1 week (3,000 calories, 70 g protein, 120 g fat, and 425 mg cholesterol).They then were given various experimental formulas as the sole source of nourishment for the next 12 weeks.Each man received the formula in three separate meals administered through an intra- gastric tube in order to insure precise quantities of each nutrient.Aside from differences in their content of egg yolk and crystalline cholesterol, the formulas of all subjects were identical for each period (Table I).The caloric con- tent was 3,000; the protein was 70 g derived from casein,
Bronchial asthma improved after removal of a phaeochromocytoma
Authors: JA Janssen, HL Tjiong
Journal: European Respiratory Journal (1991)

It is uncommon for bronchial asthma to be a symptom of phaeochromocytoma. We describe a patient with a phaeochromocytoma who presented with worsening of her asthma and persistent dyspnoea between attacks. She had markedly elevated levels of catecholamines. After surgical resection of the phaeochromocytoma there was a lasting improvement of the bronchial asthma. We hypothesize that worsening of bronchial asthma in phaeochromocytoma patients may be due to catecholamine-induced deterioration of asthma.
Intermittent Hypoxia Induces Hyperlipidemia in Lean Mice
Authors: Jianguo Li, Laura N. Thorne, Naresh M. Punjabi, Cheuk-Kwan Sun, Alan R. Schwartz, Philip L. Smith, Rafael L. Marino, Annabelle Rodriguez, Walter C. Hubbard, Christopher P. O’Donnell, Vsevolod Y. Polotsky
Journal: Circulation Research (2005)

Obstructive sleep apnea, a syndrome leading to recurrent intermittent hypoxia (IH), has been associated previously with hypercholesterolemia, independent of underlying obesity. We examined the effects of experimentally induced IH on serum lipid levels and pathways of lipid metabolism in the absence and presence of obesity. Lean C57BL/6J mice and leptin-deficient obese C57BL/6J- Lep ob mice were exposed to IH for five days to determine changes in serum lipid profile, liver lipid content, and expression of key hepatic genes of lipid metabolism. In lean mice, exposure to IH increased fasting serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, phospholipids (PLs), and triglycerides (TGs), as well as liver TG content. These changes were not observed in obese mice, which had hyperlipidemia and fatty liver at baseline. In lean mice, IH increased sterol regulatory element binding protein 1 (SREBP-1) levels in the liver, increased mRNA and protein levels of stearoyl–coenzyme A desaturase 1 (SCD-1), an important gene of TG and PL biosynthesis controlled by SREBP-1, and increased monounsaturated fatty acid content in serum, which indicated augmented SCD-1 activity. In addition, in lean mice, IH decreased protein levels of scavenger receptor B1, regulating uptake of cholesterol esters and HDL by the liver. We conclude that exposure to IH for five days increases serum cholesterol and PL levels, upregulates pathways of TG and PL biosynthesis, and inhibits pathways of cholesterol uptake in the liver in the lean state but does not exacerbate the pre-existing hyperlipidemia and metabolic disturbances in leptin-deficient obesity.