tbuckley/cabot-search huggingface dataset:
Phylogenetic analysis of the Hsp70 sequences reveals the monophyly of Metazoa and specific phylogenetic relationships between animals and fungi
Authors: C. Borchiellini, N. Boury-Esnault, J. Vacelet, Y. Le Parco
Journal: Molecular Biology and Evolution (1998)

To understand the early evolution of the Metazoa, it is necessary to determine the correct phylogenetic status of diploblastic animals. Despite cladistic studies of morphological characters and recent molecular phylogenetic studies, it remains uncertain whether diploblasts are monophyletic or paraphyletic, and how the phyla of diploblasts are phylogenetically related. The heat shock protein 70 (Hsp70) sequences, because of their ubiquity and high degree of conservation, could provide a useful model for phylogenetic analysis. We have sequenced almost the entire nucleic acid sequence of cytoplasmic Hsp70 from eight diploblastic species. Our data support the monophyly of diploblastic animals. However, the phylogenetic relationships of the diploblast groups were not significantly resolved. Our phylogenetic trees also support the monophyly of Metazoa with high bootstrap values, indicating that animals form an extremely robust clade.
Excess of red cell membrane proteins in hereditary high‐phosphatidylcholine hemolytic anemia
Authors: Peter A. Lane, Frans A. Kuypers, Margaret R. Clark, Deborah A. Andrews, Gail M. Wagner, Peter Butikofer, Amy D. Shapiro, Daniel T. Y. Chiu, Bertram H. Lubin, William C. Mentzer
Journal: American Journal of Hematology (1990)

Abstract Previous descriptions of hereditary high‐phosphatidylcholine hemolytic anemia (HPCHA) have highlighted the association of increased erythrocyte membrane phosphatidylcholine with abnormal membrane cation permeability. We studied the function and composition of erythrocyte membranes from three individuals with HPCHA to characterize further the membrane abnormalities in this disorder. Despite significant macrocytosis, HPCHA red cells were dehydrated and showed an increased surface area to volume ratio compared to normal red cells. The passive efflux of K + from HPCHA erythrocytes was increased fourfold at 37°C. Total membrane phospholipid was increased 7–42%, largely due to excess phosphatidylcholine, which made up 35.8–37.2% of total phospholipid. Membrane cholesterol:phospholipid ratios were in the normal range. It appears that the excess phosphatidylcholine was not acquired during circulation, since plasma lipids were normal and all subpopulations of density‐separated HPCHA erythrocytes were similarly abnormal. The ratio of total protein to phospholipid in white ghosts was increased, indicating that membrane protein was increased to an even greater extent than membrane lipids. No abnormal membrane proteins were identified by Coomassie or periodic acid Schiff (PAS) staining. Quantitation of the major membrane proteins indicated that the total protein excess in HPCHA membranes was due to a proportional increase in all major proteins. We conclude that HPCHA erythrocytes have excess membrane proteins and hypothesize that the changes in lipid composition and cation permeability are secondary to underlying protein abnormalities, which remain to be defined.
CLINICAL AND GENETIC DETERMINANTS OF CLOPIDOGREL NON-RESPONSIVENESS IN KOREANS
Authors: Jin Joo Park, Kyung-Woo Park, Ki-Hyun Joen, Si-Hyuck Kang, Hae-Young Lee, Hyun-Jae Kang, Bon-Kwon Koo, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Journal of the American College of Cardiology (2010)
Removal of Peanut 2S Albumins, Ara h 2 and Ara h 6, from a Soluble Peanut Protein Extract Significantly Reduces Allergic Reactions in Peanut-Sensitized Mice
Authors: J. Lew, M. Kulis, L. Pons, X. Chen, H. Porterfield, A.W. Burks, S. Dreskin
Journal: Journal of Allergy and Clinical Immunology (2010)
Modulated Inflammation by Injection of High-Mobility Group Box 1 Recovers Post-Infarction Chronically Failing Heart
Authors: Kunihiko Takahashi, Satsuki Fukushima, Kenichi Yamahara, Kenta Yashiro, Yasunori Shintani, Steven R. Coppen, Husein K. Salem, Scott W. Brouilette, Magdi H. Yacoub, Ken Suzuki
Journal: Circulation (2008)

Background— Inflammation plays an important role in the progress of adverse ventricular remodeling after myocardial infarction. High-mobility group box 1 (HMGB1) is a nuclear protein, which has recently been uncovered to also act as a modifier of inflammation when released. We hypothesized that HMGB1 injection could preferentially modulate local myocardial inflammation, attenuate ventricular remodeling, and subsequently improve cardiac performance of postinfarction chronic heart failure. Methods and Results— Three weeks after left coronary artery ligation, HMGB1 (2.5 μg) or PBS was intramyocardially injected into rat hearts. At 28 days after injection, left ventricular ejection fraction was significantly improved after HMGB1 injection compared to PBS (39.3±1.4 versus 33.3±1.8%; P &lt;0.01). Accumulation of CD45 + inflammatory cells, two thirds of which were OX62 + dendritic cells, in the peri-infarct area was significantly attenuated by HMGB1 injection. Dramatic changes in the expression of major proinflammatory cytokines were not detected by microarray or RT-PCR. Adverse ventricular remodeling including cardiomyocyte hypertrophy (cardiomyocyte cross-sectional area; 439±7 versus 458±6 μm 2 ; P &lt;0.05) and extracellular collagen deposition (collagen volume fraction; 11.9±0.4 versus 15.2±0.6%; P &lt;0.01) was attenuated by HMGB1 injection. Analyses of signal transduction pathways revealed that HMGB1 injection activated ERK1/2, but not p38, Akt, and Smad3. Cardiac regeneration and neovascularization were not observed. Conclusion— HMGB1 injection modulated the local inflammation in the postinfarction chronically failing myocardium, particularly via reducing the accumulation of dendritic cells. This modulated inflammation resulted in attenuated fibrosis and cardiomyocyte hypertrophy, which thereby improved global cardiac function. These data suggest that HMGB1 may be valuable for the chronic heart failure treatment.
Management of scientific services and the changing face of the laboratory
Authors: J K Fawcett
Journal: BMJ (1981)

prevalence figures, from well populations and hospital clinics, which in turn are the result of self-selection, referral patterns, and the age composition of the screened population.The data emphasise that, with a trend towards less selection of women for screening, the pre- dictive power of a positive diaphanoscopic test would be lower and that for a negative test higher than in their series.One case appears to be missing from their results but it does not materially influence the outcome.
Frequency of swallowing in duodenal ulceration and hiatus hernia.
Authors: S P Calloway, P Fonagy, R F Pounder
Journal: BMJ (1982)

inflamed mucosa with no parasites.Sections from the mucosa of ileum and caecum and the rectal biopsy specimen, trypsinised and stained with antisera to immunoglobulins, kappa and lambda chains, and IgA secretor piece, using the immunoperoxidase method, showed similar numbers and distribu- tions of positive lymphocytes to those in normal controls.Peripheral lympho- cyte subpopulations showed normal T-and B-cell proportions with a normal distribution of surface immunoglobulin classes on B cells.T-cell trans- formation was normal after stimulation by phytohaemagglutinin.Serum M~~~C aecal epithelial microvillar surface showing cryptosporidium schizont containing merozoites.X 18 000 (original magnification).IgG concentrations and complement components C3 and C4 were normal, serum IgA was low (400 mg/l; normal 860-3700 mg/l), IgM low (510 mg/l; normal, 700-3700 mg/l), and IgE raised (205 U/ml using paper radio- immunosorbent test; normal adult mean 122 U/ml).
Parachute approach to evidence based medicine: As obvious as ABC
Authors: Barnaby C Reeves
Journal: BMJ (2006)

EDITOR—I strongly oppose the proposition of Potts et al.1 For all the difficulties of doing high quality randomised controlled trials of some research questions, or in challenging settings, making arbitrary decisions about the “obviousness” of the effectiveness of interventions based on observational evidence cannot be the way forward. This point is well made by the readers with expert knowledge who have already responded about the specific examples described by Potts et al.2

Other readers have criticised the naivete of the argument but seem to accept the underlying sentiment that the world should not always wait for evidence from randomised controlled trials. This point of …
A Field Test for the Assay of Human Whole-blood Cholinesterase
Authors: D. R. Davies, J. D. Nicholls
Journal: BMJ (1955)

The level of cholinesterase (ChE) in the blood is a valuable index of the amount of anticholinesterase which has been absorbed into the system, and it has in fact been used for this purpose (Metcalf, 1951 Davies, 1952a; Marchand, 1952).Since anticholin- esterases are being used extensively in agriculture and for insect vector control-very often far removed from laboratory facilities-the determination of such an index under field conditions would be useful.The essential requirement of a field test is simplicity.The procedure and equipment required should be simple, few reagents be necessary, and the time taken for the performance of the test be reduced to a minimum.Finally, the test should be sufficiently uncomplicated to be carried out by non-specialist personnel.Aldridge and Davies (1952) have discussed the possi- bility of applying the generally used techniques for ChE assay to field conditions, and-came to the con- clusion that, for reasons given, these were unsuitable.They did, however, suggest that the electrometric method of Michel (1949) was satisfactory under certain circumstances.They based their suggestion on the fact that this technique lent itself to the rapid and easy estimation of considerable numbers of samples.While subsequent experience has shown this to be true, there are two major disadvantages.The pH meter is not reliable enough to use in the field; and the glass elec- trode is most certainly too fragile for this purpose.Fleisher and Pope (1954) have applied the Hestrin (1949) colorimetric method to the estimation of whole- blood ChE.Their method possesses the advantage that it is a colorimetric technique and that single estimations can be completed, including the collection of the blood sample, in twenty-five minutes.Its disadvantages as a field test are (1) relatively few tests can be performed in a given time, and (2) at least six reagents and an equally large number of manipulative processes are involved.Furthermore, the technique requires the use of a spectrophotometer.Limperos and Ranta (1953) have described a test which they have used under field conditions and which approximates to the requirements.The principle is the same as that of the electrometric method.The differ- ences are (1) that changes in pH are followed by changes in a bromthymol blue (B.T.B.) solution incorporated in the reaction mixture, and (2i the test is carried out in an unbuffered medium.The levels of enzyme activity are assessed by the colour of the solution after a given interval of twenty minutes, and these colours are green, olive green, olive brown, and orange.In practice the distinction between the first two and the second two is difficult.This is a serious disadvantage, since (as is shown below) this is the important range.A second major disadvantage is that under certain conditions of illumination the combination of blood and B.T.B.
Mycophenolate mofetil monotherapy for pemphigus vulgaris
Authors: R-O. Bredlich, M. Grundmann-Kollmann, S. Behrens, M. Kerscher, R.U. Peter
Journal: British Journal of Dermatology (1999)

S ir, Treatment of autoimmune blistering diseases remains difficult due to the potential side‐effects of conventional immunosuppressive drugs and new therapeutic options with an improved benefit/risk ratio are desirable. In dermatology, successful treatment of pemphigus vulgaris and pemphigoid has been reported with mycophenolate mofetil in combination with high‐dose prednisone. 1–3 We report a 78‐year‐old male Caucasian patient with severe pemphigus vulgaris and diabetes mellitus who was treated with mycophenolate mofetil monotherapy. A 78‐year‐old man had suffered from pemphigus vulgaris since 1995. Autoantibodies against 130 kDa pemphigus antigen were confirmed by Western immunoblotting of serum. The patient had received high‐dose prednisone monotherapy (1 mg/kg body weight) and a combination of azathioprine (1·5 mg/kg body weight) and prednisone (0·5 mg/kg body weight). While having high‐dose prednisone therapy he developed severe diabetes, requiring reduction of the prednisone dose. During combination therapy of azathioprine and a reduced dose of prednisone he developed thrombocytopenia. Owing to diabetic nephrosclerosis with hypertension, cyclosporin A was contraindicated. We therefore decided to start mycophenolate mofetil (MMF) monotherapy, at a dose of 1 g twice daily. No new blisters and erosions occurred after 2 weeks and the patient cleared completely after 6 weeks. Mycophenolate mofetil was tolerated without any side‐effects for the complete follow‐up period. The patient is still free of symptoms. As MMF inhibits the de novo pathway of purine synthesis that is used by lymphocytes it seems to be more specific for B and T lymphocytes than azathioprine. Therefore, it might have a higher immunosuppressive activity than azathioprine with fewer unwanted effects. The most common reported side‐effect of mycophenolate mofetil is gastrointestinal disturbance followed by reversible, dose‐related haematological effects. Very few cases of lymphoproliferative disorders have been reported. The drug does not produce clinically significant nephrotoxicity or liver damage, therefore it may be of value for patients who cannot take cyclosporin A or methotrexate 4 because of diabetic nephrosclerosis with hypertension or thrombocytopenia.
White Blood Cell Count Predicts Reduction in Coronary Heart Disease Mortality With Pravastatin
Authors: Ralph A.H. Stewart, Harvey D. White, Adrienne C. Kirby, Stephane R. Heritier, R. John Simes, Paul J. Nestel, Malcolm J. West, David M. Colquhoun, Andrew M. Tonkin
Journal: Circulation (2005)

Background— Elevated serum inflammatory marker levels are associated with a greater long-term risk of cardiovascular events. Because 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) may have an antiinflammatory action, it has been suggested that patients with elevated inflammatory marker levels may have a greater reduction in cardiovascular risk with statin treatment. Methods and Results— We evaluated the association between the white blood cell count (WBC) and coronary heart disease mortality during a mean follow-up of 6.0 years in the Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Study, a clinical trial comparing pravastatin (40 mg/d) with a placebo in 9014 stable patients with previous myocardial infarction or unstable angina. An increase in baseline WBC was associated with greater coronary heart disease mortality in patients randomized to placebo (hazard ratio for 1×10 9 /L increase in WBC, 1.18; 95% CI, 1.12 to 1.25; P &lt;0.001) but not pravastatin (hazard ratio, 1.02; 95% CI, 0.96 to 1.09; P =0.56; P for interaction=0.004). The numbers of coronary heart disease deaths prevented per 1000 patients treated with pravastatin were 0, 9, 30, and 38 for baseline WBC quartiles of &lt;5.9, 6.0 to 6.9, 7.0 to 8.1, and &gt;8.2×10 9 /L, respectively. WBC was a stronger predictor of this treatment benefit than the ratio of total to high-density lipoprotein cholesterol and a global measure of cardiac risk. There was also a greater reduction ( P =0.052) in the combined incidence of cardiovascular mortality, nonfatal myocardial infarction, and stroke with pravastatin as baseline WBC increased (by quartile: 3, 41, 61, and 60 events prevented per 1000 patients treated, respectively). Conclusions— These data support the hypothesis that individuals with evidence of inflammation may obtain a greater benefit from statin therapy.
ELECTRON MICROSCOPIC STUDY OF THE EFFECT OF VITAMIN A ON THE DIFFERENTIATION OF RECONSTRUCTED EMBRYONIC CHICK SKIN
Authors: SEICHIRO SAGAMI, YUKIO KITANO
Journal: British Journal of Dermatology (1970)

In reconstructed embryonic chick skin, the mass of epidermal cells was separated from the mesenchymal portion by a continuous basallamina. The findings on the cytoplasmic organelles, e.g. filamentous structures, desmosomes, keratohyalin, and membrane coating granules of the peripheral and central epidermal cells, corresponded to those of the epidermis when the centre of the cell-mass was presumed to he the surface of the epidermis. The addition of 5 i.u./ml. vitamin A in the culture medium inhibited the process of keratinization. Filamentous structures and desmosomes were sparse even in the centre of the epidermal cell-mass. There were wide intercellular spaces and the basal lamina was obscure and discontinuous. The endoplasmic reticulum was dilated and the Golgi zones were distinct. Thus the vitamin A-treated cell resembles the secretory cell and shows less tendency to differentiate towards a keratinocyte. The development of lysosomes in the vitamin A-treated cells confirmed that vitamin A releases protease.
Killing of gram-negative bacteria by lactoferrin and lysozyme.
Authors: R T Ellison, T J Giehl
Journal: Journal of Clinical Investigation (1991)

Although lactoferrin has antimicrobial activity, its mechanism of action is not full defined. Recently we have shown that the protein alters the Gram-negative outer membrane. As this membrane protects Gram-negative cells from lysozyme, we have studied whether lactoferrin's membrane effect could enhance the antibacterial activity of lysozyme. We have found that while each protein alone is bacteriostatic, together they can be bactericidal for strains of V. cholerae, S. typhimurium, and E. coli. The bactericidal effect is dose dependent, blocked by iron saturation of lactoferrin, and inhibited by high calcium levels, although lactoferrin does not chelate calcium. Using differing media, the effect of lactoferrin and lysozyme can be partially or completely inhibited; the degree of inhibition correlating with media osmolarity. Transmission electron microscopy shows that E. coli cells exposed to lactoferrin and lysozyme at 40 mOsm become enlarged and hypodense, suggesting killing through osmotic damage. Dialysis chamber studies indicate that bacterial killing requires direct contact with lactoferrin, and work with purified LPS suggests that this relates to direct LPS-binding by the protein. As lactoferrin and lysozyme are present together in high levels in mucosal secretions and neutrophil granules, it is probable that their interaction contributes to host defense.
Fibre Optics in Medicine and Surgery
Authors: P. J. Brand, L. T. Cotton
Journal: BMJ (1973)

71 ± 4-51 51-44 ± 4-61 52-04 4-64 rates in the lateral popliteal and posterior tibial nerves (P < 0001).The results of our investigation do not support the finding previously reported that lrypertensive patients suffer from a sub- clinical peripheral neuropathy.Even in those -patients with markedly elevated diastolic pressures ( < 150 mm Hg) no significant slowing of conduction was dis- covered.We are very grateful to Mr. Basil Hellman for his assistance with the statistics and to Dr. D.
Blood Lead Concentrations in Children and Method of Water Fluoridation in the United States, 1988–1994
Authors: Mark D. Macek, Thomas D. Matte, Thomas Sinks, Dolores M. Malvitz
Journal: Environmental Health Perspectives (2005)

Some have hypothesized that community water containing sodium silicofluoride and hydrofluosilicic acid may increase blood lead (PbB) concentrations in children by leaching of lead from water conduits and by increasing absorption of lead from water. Our analysis aimed to evaluate the relation between water fluoridation method and PbB concentrations in children. We used PbB concentration data (n=9,477) from the Third National Health and Nutrition Examination Survey (1988-1994) for children 1-16 years of age, merged with water fluoridation data from the 1992 Fluoridation Census. The main outcome measure was geometric mean PbB concentration, and covariates included age, sex, race/ethnicity, poverty status, urbanicity, and length of time living in residence. Geometric mean PbB concentrations for each water fluoridation method were 2.40 microg/dL (sodium silicofluoride), 2.34 microg/dL (hydrofluosilicic acid), 1.78 microg/dL (sodium fluoride), 2.24 microg/dL (natural fluoride and no fluoride), and 2.14 microg/dL (unknown/mixed status). In multiple linear and logistic regression, there was a statistical interaction between water fluoridation method and year in which dwelling was built. Controlling for covariates, water fluoridation method was significant only in the models that included dwellings built before 1946 and dwellings of unknown age. Across stratum-specific models for dwellings of known age, neither hydrofluosilicic acid nor sodium silicofluoride were associated with higher geometric mean PbB concentrations or prevalence values. Given these findings, our analyses, though not definitive, do not support concerns that silicofluorides in community water systems cause higher PbB concentrations in children. Current evidence does not provide a basis for changing water fluoridation practices, which have a clear public health benefit.
Biliopleural Fistula as a Late Complication of Percutaneous Transhepatic Cholangioscopy
Authors: X. De Meester, D. Vanbeckevoort, R. Aerts, W. Van Steenbergen
Journal: Endoscopy (2005)

Biliothoracic fistulas, including biliopleural and biliobronchial fistulas, are rare complications of biliary tract diseases. Biliopleural fistulas have been reported after percutaneous transhepatic procedures such as percutaneous transhepatic drainage (PTD) [1] [2] and liver biopsy [3]. Prolonged external biliary drainage with formation of a fistulous tract, and catheter dysfunction by either blockage or by dislocation, should predispose to a biliopleural communication. Percutaneous transhepatic cholangioscopy (PTC) is most frequently carried out in patients with biliary lithiasis [4]. It requires the creation of a transhepatic tract by progressive dilation and maturation for a period of about 2 weeks. Although both conditions for the development of a biliopleural fistula are present, i. e. biliary obstruction and a prolonged biliary drainage period, the development of pleurobilia has not previously been reported.
A nonhuman primate model of chikungunya disease
Authors: Stephen Higgs, Sarah A. Ziegler
Journal: Journal of Clinical Investigation (2010)

Chikungunya disease is a severely debilitating, mosquito-borne, viral illness that has reached epidemic proportions in Africa, Asia, and the islands of the Indian Ocean. A mutation enhancing the ability of the chikungunya virus (CHIKV) to infect and be transmitted by Aedes albopictus has increased the geographical range at risk for infection due to the continuing global spread of this mosquito. Research into disease pathogenesis, vaccine development, and therapeutic design has been hindered by the lack of appropriate animal models of this disease. The meticulous study reported in this issue of the JCI by Labadie et al. is one of the first reports describing CHIKV infection of adult immunocompetent nonhuman primates. Using traditional and modern molecular and immunological approaches, the authors demonstrate that macaques infected with CHIKV are a good model of human CHIKV infection and also show that persistent arthralgia in humans may be caused by persistent CHIKV infection of macrophages.