tbuckley/cabot-search huggingface dataset:
Peak flow rate in Nigeria: Anthropometric determinants and usefulness in assessment of ventilatory function
Authors: E. A. Elebute, D. Femi-Pearse
Journal: Thorax (1971)

The inexpensive nature of the peak flow rate (PFR) makes it a suitable test of ventilatory function for use in some parts of Africa, where medical facilities are still poor. In order to establish standard values for PFR in Nigeria, anthropometric measurements, lung volumes, and PFR were obtained from 142 men and 88 women, all of whom were healthy Nigerians. The mean values of PFR were 482·1 1/min (±83·3) for males (average age 34·9 years) and 385·6 1/min (±65·7) for females (average age 29·4 years), both means being significantly lower than corresponding means of predicted values calculated from formulae based on previously reported studies of Caucasians. PFR was correlated with age, various physical measurements, and lung volumes. The combination of age and height gave the regression equation for predicting PFR with the lowest standard error of estimates; and virtually all lung volumes measured correlated significantly with PFR. In 16 adult Nigerian asthmatics, PFR correlated significantly with vital capacity, forced expiratory volume (1 second), and expiratory reserve volume; it was highest in those who had no symptomatic or spirometric signs of any ventilatory defect, and lowest in those who had signs of both obstructive and restrictive defects.
Genetic and phenotypic heterogeneity in familial lecithin: cholesterol acyltransferase (LCAT) deficiency. Six newly identified defective alleles further contribute to the structural heterogeneity in this disease.
Authors: H Funke, A von Eckardstein, P H Pritchard, A E Hornby, H Wiebusch, C Motti, M R Hayden, C Dachet, B Jacotot, U Gerdes
Journal: Journal of Clinical Investigation (1993)

The presence of lecithin:cholesterol acyltransferase (LCAT) deficiency in six probands from five families originating from four different countries was confirmed by the absence or near absence of LCAT activity. Also, other invariate symptoms of LCAT deficiency, a significant increase of unesterified cholesterol in plasma lipoproteins and the reduction of plasma HDL-cholesterol to levels below one-tenth of normal, were present in all probands. In the probands from two families, no mass was detectable, while in others reduced amounts of LCAT mass indicated the presence of a functionally inactive protein. Sequence analysis identified homozygous missense or nonsense mutations in four probands. Two probands from one family both were found to be compound heterozygotes for a missense mutation and for a single base insertion causing a reading frame-shift. Subsequent family analyses were carried out using mutagenic primers for carrier identification. LCAT activity and LCAT mass in 23 genotypic heterozygotes were approximately half normal and clearly distinct from those of 20 unaffected family members. In the homozygous patients no obvious relationship between residual LCAT activity and the clinical phenotype was seen. The observation that the molecular defects in LCAT deficiency are dispersed in different regions of the enzyme suggests the existence of several functionally important structural domains in this enzyme.
Characterization of estrogenicity of phytoestrogens in an endometrial-derived experimental model.
Authors: A C Hopert, A Beyer, K Frank, E Strunck, W Wünsche, G Vollmer
Journal: Environmental Health Perspectives (1998)

Severe developmental and reproductive disorders in wild animals have been linked to high exposure to persistent environmental chemicals with hormonal activity. These adverse effects of environmental estrogens have raised considerable concern and have received increasing attention. Although numerous chemicals with the capacity to interfere with the estrogen receptor (ER) have been identified, information on their molecular mechanism of action and their relative potency is rather limited. For the endometrium, the lack of information is due to the lack of a suitable experimental model. We investigated the functions of phytoestrogens in an endometrial-derived model, RUCA-I rat endometrial adenocarcinoma cells. The cells were cultured on a reconstituted basement membrane to preserve their functional differentiation and estrogen responsiveness. We assessed the relative binding affinity to the estrogen receptor of the selected phytoestrogens coumestrol, genistein, daidzein, and the putative phytoestrogen mangostin compared to estradiol by a competitive Scatchard analysis. The following affinity ranking was measured: 17beta-estradiol >>> coumestrol > genistein > daidzein >>> mangostin. In addition, we investigated the capacity of these compounds to promote the increased production of complement C3, a well-known estradiol-regulated protein of the rat endometrium. All substances tested increased the production of complement C3, although different concentrations were necessary to achieve equivalent levels of induction compared to estradiol. Mechanistically we were able to demonstrate that the increase of complement C3 production was mediated by primarily increasing its steady-state mRNA level. These findings indicate that RUCA-I cells represent a sensitive model system to elucidate relative potencies and functions of environmental estrogens in an endometrium-derived model.
Uptake and Toxicity Studies of Poly‐Acrylic Acid Functionalized Silicon Nanoparticles in Cultured Mammalian Cells
Authors: Qi Wang, Yongping Bao, Xiaohong Zhang, Paul R. Coxon, Upali A. Jayasooriya, Yimin Chao
Journal: Advanced Healthcare Materials (2012)

Abstract Poly‐acrylic acid (PAAc) terminated silicon nanoparticles (SiNPs) have been synthesized and employed as a synchronous fluorescent signal indicator in a series of cultured mammalian cells: HHL5, HepG2 and 3T3‐L1. Their biological effects on cell growth and proliferation in both human and mouse cell lines have been studied. There was no evidence of in vitro cytotoxity in the cells exposed to PAAc terminated SiNPS when assessed by cell morphology, cell proliferation and viability, and DNA damage assays. The uptake of the nanocrystals by both HepG2 and 3T3‐L1 cells was investigated by confocal microscopy and flow cytometry, which showed a clear time‐dependence at higher concentrations. Reconstructed 3‐D confocal microscope images exhibited that the PAAc‐SiNPs were evenly distributed throughout the cytosol rather than attached to outer membrane. This study provides fundamental evidence for the safe application and further modification of silicon nanoparticles, which could broaden their application as cell markers in living systems and in micelle encapsulated drug delivery systems.
Response of the Main Pulmonary Artery of Dogs to Neuronally Released Versus Blood-Borne Norepinephrine
Authors: ROLAND H. INGRAM, JAN P. SZIDON, ALFRED P. FISHMAN
Journal: Circulation Research (1970)

The effects of sympathetic nerve stimulation and of norepinephrine infusions on the dynamic elastic properties of the main pulmonary artery were studied in 20 anesthetized, open-chest dogs. Pulmonary arterial pressure and diameter were linearly related between 5 to 45 mm Hg and at heart rates of 40 to 200 beats/min. Sympathetic nerve stimulation changed the stiffness (pressure-diameter slope) of the pulmonary artery by +35%; infusion of norepinephrine (0.25 µg/kg/min) by only +14%. Diameter intercepts, determined by extrapolation of the linear pressure-diameter line, were unchanged during stimulation, but decreased significantly during the infusion of norepinephrine. Local application of norepinephrine to the wall duplicated the changes produced by sympathetic nerve stimulation. Histologically, the arrangement of smooth muscle in the outer layers of the media of the artery suggested linkage of smooth muscle with continuous elastic fibers, whereas smooth-muscle cells of the deeper layers of the media appeared to connect with each other, and elastic fibers were discontinuous. The topical application of elastase to the outer wall effected a loss of elastic fibers in the outer layers of the media. After elastase, neither stimulation nor norepinephrine infusions increased stiffness; diameter intercepts decreased with both. The observations are consistent with the idea that stiffening of this artery during nerve stimulation is produced by contraction of smooth muscle attached to elastic fibers and that the anatomical arrangement for stiffening is located in the outer layer of the media, where the sympathetic nerve endings are located. In contrast, blood-borne norepinephrine stimulates predominantly the inner layers.
Albumin metabolism: effect of the nutritional state and the dietary protein intake
Authors: W. P. T. James, A. M. Hay
Journal: Journal of Clinical Investigation (1968)

Nine malnourished and nine children who had recovered from malnutrition were given a single injection of albumin-(131)I and were studied during consecutive periods in which the dietary protein was changed.Malnourished children had significantly lower catabolic rates of albumin than had recovered children on the same protein intake. Both nutritional groups, however, showed a progressive fall in catabolic rate after 3-5 days on a low protein diet (0.7-1.0 g/kg per day), and the maximum effect was seen in the 2nd wk of low protein feeding. The catabolic rate could return to normal within 3 wk in a malnourished child fed 4 g of protein/kg per day. The albumin synthetic rate was measured by a computer technique suitable for nonsteady-state conditions. The synthetic rate in the malnourished groups (101 mg/kg per day) fed on a low protein diet was significantly lower than the rate in the recovered groups (148 mg/kg per day). The synthetic rate responded rapidly to a change in diet; when the rate fell, the intravascular albumin mass was maintained by two compensating mechanisms: (1) a net transfer of extravascular albumin into the intravascular pool; and (2) by a delayed fall in the catabolic rate. The net transfer of albumin into the intravascular compartment diminished as the catabolic rate fell. ADAPTATION TO A LOW PROTEIN DIET WAS ASSOCIATED WITH: (a) low synthetic and catabolic rates of albumin; (b) a reduced extravascular albumin mass; and (c) a capacity for a rapid return to normal in the synthetic rate when the dietary protein was increased.
Studies in the Arctic with the Flicker-Fusion Nitroglycerin Test
Authors: R. W. Hopkins
Journal: New England Journal of Medicine (1952)

STUDIES on the ability of the human being to distinguish a rapidly flickering light have been used in ophthalmologic research for well over a century.1 , 2 During the past ten years its use has extended beyond the laboratory of the ophthalmologist; it was recently proposed as a test for evaluating cardiovascular status in clinical patients.3 This report is presented to call attention to its potentialities and to report a series of observations made in the Arctic.The rapidity with which a nerve can respond to a rapid succession of stimuli has long been used as an index of its functional capacity. . . .
Anaphylactic release of a prekallikrein activator from human lung in vitro.
Authors: H L Meier, A P Kaplan, L M Lichtenstein, S Revak, C G Cochrane, H H Newball
Journal: Journal of Clinical Investigation (1983)

We have demonstrated the in vitro IgE-mediated release of a prekallikrein activator from human lung. The lung prekallikrein activator was partially purified by sequential chromatography on sulfopropyl-Sephadex, DEAE-Sephacel, and Sepharose 6B. Purified human prekallikrein was converted to its active form (kallikrein) by the lung protease. The generated kallikrein was shown to be biologically active; that is, it generates bradykinin from purified human high-molecular weight kininogen and also cleaves benzoyl-propyl-phenyl-arginyl-p-nitroanilide, a known synthetic substrate of kallikrein. The lung prekallikrein activator differs from the known physiologic activators of prekallikrein (the activated forms of Hageman factor) with respect to: (a) size (it has a mol wt of approximately 175,000); (b) synthetic substrate specificity (D-propyl/phenyl/arginyl-p-nitroanilide is a substrate for the activated forms of Hageman factor, but not the lung protease); (c) antigenic specificity (an anti-Hageman factor immunoadsorbent column did not remove significant amounts of the lung protease, while it removed most of the activity of activated Hageman factor fragments); and (d) inhibition profile (the lung proteases was not inhibited by corn trypsin inhibitor). This prekallikrein activator provides a physiologic mechanism by which prekallikrein can be directly activated during IgE-mediated reactions of the lung. While the role of this lung prekallikrein activator in immediate hypersensitivity reactions and in other inflammatory processes is not clear, it does represent a first and important interface between IgE-mediated reactions and the Hageman factor-dependent pathways of the inflammatory response.
Characterization of organic anion transporter regulation, glutathione metabolism and bile formation in the obese Zucker rat
Authors: Andreas Geier, Christoph G. Dietrich, Tobias Grote, Ulrich Beuers, Thomas Prüfer, Peter Fraunberger, Siegfried Matern, Carsten Gartung, Alexander L. Gerbes, Manfred Bilzer
Journal: Journal of Hepatology (2005)
417. Combination Brain and Systemic Injections of AAV Results in Whole Body Therapy and Extension of Lifespan in the Niemann-Pick Mouse
Authors: Marco A. Passini, Jie Bu, Jonathan A. Fidler, Joseph W. Foley, James C. Dodge, Robin J. Ziegler, Wendy W. Yang, Jennifer Clarke, Tatyana V. Taksir, Denise A. Griffiths, Michael A. Zhao, Catherine R. O'Riordan, Lamya S. Shihabuddin, Edward H. Schuchman, Seng H. Cheng
Journal: Molecular Therapy (2006)

The majority of lysosomal storage diseases contain both CNS and visceral pathology. Many experimental designs use either intracranial injection of viral vectors to treat the neurodegenerative phenotype of the disease, or systemic delivery to treat the viscera. In this study, we tested whether a combination of brain and systemic injections of adeno-associated virus (AAV) vectors could increase lifespan, provide whole body reversal of pathology, and improve motor and cognitive function in the acid sphingomyelinase knock out (ASMKO) mouse model of Niemann-Pick disease. ASMKO mice at 4 weeks of age were injected systemically with AAV8- hASM, and subsequently, the same animals were injected into the brain with AAV2-hASM. All the mice treated by combination injections survived to 54 weeks of age. This was a significant improvement over untreated ASMKO mice, animals that had been treated by systemic injection only or by brain injection only, which had median life spans of 34 weeks, 45 weeks, and 43 weeks, respectively. Thus the brain alone injections did not protect animals from dying. Animals treated by the combination therapy also displayed normal weight gain, and significant functional recovery on the rotarod (motor task) and the Barnes maze (cognitive task) throughout the time course of the study. These data support the contention that combination therapy can improve the quality of life before and within the time frame of extended survival.
Implication of Plasma Free Hemoglobin in Massive Clostridial Hemolysis
Authors: Howard R. Terebelo
Journal: JAMA (1982)

Prolonged tissue oxygenation and maintenance of intravascular oncotic pressure are severely impaired with the absence of an effective RBC mass. We recently encountered a patient with a nondetectable hematocrit value (0%) attributed to Clostridium perfringens hemolysis. The patient maintained normal BP, tissue oxygenation, and mentation and survived longer than four hours, despite ineffective transfusion therapy. Plasma free hemoglobin was responsible for the preservation of tissue oxygenation, intravascular oncotic pressure, and pH. Existing studies in animals support stroma-free hemoglobin as an effective blood product in humans.
Pulmonary aspiration: high dose steroids should be abandoned.
Authors: D W Ryan
Journal: BMJ (1984)

become more important-thus explaining the common finding of young patients with acute myocardial infarction without any measurable risk factors.With the failure of multiple risk factor intervention in those at moderate risk,3 there is little immediate alternative but to focus particularly on those found to be at high risk.The yield is now partly identifiable and the motivation of physicians and in- dividuals is high.5 6 M F
TCT-22 Residual Intrastent Thrombus Calculated With FD-OCT In STEMI Patients Treated With Primary PCI, Is Related To Discharge Left Ventricular Ejection Fraction
Authors: fabrizio imola, Laura Gatto, Enrico Romagnoli, vito ramazzotti, maria teresa mallus, alessandro manzoli, Tomasz Pawlowski, Francesco Prati
Journal: Journal of the American College of Cardiology (2014)
Effects of chromium on DNA replication in vitro.
Authors: E T Snow
Journal: Environmental Health Perspectives (1994)

Chromium is an environmentally significant human carcinogen with complicated metabolism and an unknown mechanism of mutagenesis. Chromium(VI) is taken up by cells as the chromate anion and is reduced intracellularly via reactive intermediates to stable Cr(III) species. Chromium(III) forms tight complexes with biological ligands, such as DNA and proteins, which are slow to exchange. In vitro, CrCl3.6H2O primarily interacts with DNA to form outer shell charge complexes with the DNA phosphates. However, at micromolar concentrations, the Cr(III) binds to a low number of saturable tight binding sites on single-stranded M13 DNA. Additional chromium interacts in a nonspecific manner with the DNA and can form intermolecular DNA cross-links. Although high concentrations of Cr(III) inhibit DNA replication, micromolar concentrations of Cr(III) can substitute for Mg2+, weakly activate the Klenow fragment of E. coli DNA polymerase I (Pol I-KF), and act as an enhancer of nucleotide incorporation. Alterations in enzyme kinetics induced by Cr(III) increase DNA polymerase processivity and the rate of polymerase bypass of DNA lesions. This results in an increased rate of spontaneous mutagenesis during DNA replication both in vitro and in vivo. Our results indicate that chromium(III) may contribute to chromate-induced mutagenesis and may be a factor in the initiation of chromium carcinogenesis.
Contributions of Upper Airway Mechanics and Control Mechanisms to Severity of Obstructive Apnea
Authors: Magdy Younes
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The contributions of pharyngeal mechanical abnormalities, flow demand, and compensatory effectiveness to obstructive sleep apnea severity were determined in 82 patients. Flow demand was estimated from mean inspiratory flow on continuous positive airway pressure. Mechanical load on upper airway muscles was estimated from minimal effective continuous positive airway pressure, flow demand, and minimum flow observed during brief pressure dial downs. Compensatory effectiveness was estimated by relating polysomnographic severity and mechanical load. Mechanical load was more severe in men, in supine position, and in older and heavier patients. Higher flow demand contributed significantly to mechanical load in men and in those who are obese. At the same mechanical load, severity was independent of age, sex, or body mass index but was greater in the supine position and in REM sleep. Mechanical load accounted for only 34% of variability in severity. Eighty-two percent of patients experienced periods of stable breathing despite mechanical loads that would produce continuous cycling without compensation. I conclude that most patients can adequately compensate for the abnormal mechanics, at least part of the time. Higher flow demand contributes to severity in men and in obesity. Severity is largely due to factors other than mechanical load. Compensatory effectiveness is impaired in the supine position and in REM sleep, but not by age, sex, or body mass index.
Pressure-diameter relations during early diastole in dogs. Incompatibility with the concept of passive left ventricular filling.
Authors: H N Sabbah, P D Stein
Journal: Circulation Research (1981)

We studied left ventricular (LV) pressure-diameter relations in 13 open-chest mongrel dogs to explore whether ventricular filling is passive, active, or a combination of both. Left ventricular internal diameter along the minor axis and thickness of the LV free wall were measured with ultrasonic dimension gauges. Pressures in the LV, left atrium (LA), and aorta were measured with catheter-tip micromanometers. Pressure in the LV during the rapid filling phase of diastole decreased from 13 +/- 1 mm Hg to 3 +/- 0.4 mm Hg (mean +/- SE). During this period, LV internal diameter increased from 32.6 +/- 1.5 to 36.7 +/- 1.5 mm, and this represented 49% of the total change of LV diameter that occurred during diastole. The pressure-diameter relation that we observed during the rapid phase of filling suggests that active enlargement rather than passive distension of the left ventricle occurred. Reduction of pressure within the left ventricle during rapid filling, while the ventricular diameter increased, appears to be due to forces within the LV wall that act to restore the LV to its diastolic dimensions. This allows the LV to draw blood from the atrium by creating a pressure in the LV that is lower than in the LA. On the other hand, during the latter part of diastole, following atrial contraction, the pressure-diameter relation suggests that the left ventricle undergoes passive distention.
OP0066 Targeting the Lowest Efficacious Dose for Rheumatoid Arthritis Patients in Remission: Clinical and Structural Impact of a Step-Down Strategy Trial Based on Progressive Spacing of TNF-Blocker Injections (Strass Trial)
Authors: B. Fautrel, F. Gandjbakhch, V. Foltz, T. Pham, J. Morel, T. Alfaiate, E. Dernis, P. Gaudin, X. Mariette, F. Tubach
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Biologic tapering has been associated to relapse or structural damage progression in rheumatoid arthritis (RA). <h3>Objectives</h3> To compare the impact of a DAS28-driven step-down strategy based on TNF-blocker injection spacing (S arm) to a maintenance strategy (M arm) in an equivalence RCT conducted in established RA patients in DAS28 remission with etanercept (ETA) or adalimumab (ADA). <h3>Methods</h3> Inclusion criteria were: ETA or ADA &gt; 1 year, DAS28 remission &gt; 6 months, stable damage on X-rays. Patients were randomized and followed 3-monthly for 18 months. In the S arm, the inter-injection interval was increased every 3 months up to full stop at 4th step. If DAS28 remission was lost, tapering was reversed to the previous step. Hand and foot X-rays at baseline and 18 months. Study endpoints were disease activity (DAS28), relapse (ΔDAS28&gt;0.6 + DAS28&gt;2.6), and X-ray damage assessed by vdH-SHS (2 independent readers, blinded of patient characteristics and treatment arm). Progression was defined as ΔvdH-SHS&gt;1. <h3>Results</h3> 137 patients were included, 64 and 73 in the S and M arm (mean/%: age 55 yrs, female 78%, RA duration 9.5 yrs, RF+ 68%, ACPA+ 78%, erosive 88%, DAS28 1.8, DAS44 1.0, ETA 54 %, ADA 46 %). At 18 months, 47 (73.4%) patients of the S-arm tapered TNF-blockers, of whom 24 (37.5%) stopped. Mean DAS28 and mean HAQ were not significantly different between arms. Relapse occurred at least once more frequently in the S than in the M arm (81% vs. 56%, p=0.0009) (Figure). Structural damage progression was not significantly different between arms (p=0.3) (Figure). Only 4 (6.7%) and 3 (4.5%) patients progressed in the S and M arms. <h3>Image/graph</h3> <h3>Conclusions</h3> Although relapses were more frequent, the Spacing strategy results in non-significant increase of disease activity and functional impairment, with no significant structural progression. Target the lowest efficacious dose in RA in remission may be considered as the new paradigm for such patients (ClinicalTrials.gov n°: NCT00780793). <h3>Disclosure of Interest</h3> None Declared