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At least 109 records · Page 6Linked to original sources

Mechanical response of reconstituted, freeze-dried collagen under compressive loads.

The mechanical response under uniaxial compression of collagen discs, made from freeze-dried collagen reconstituted at acid pH, was investigated at 22, 29.5 and 35 degrees C. The pH during compression was maintained at the physiological level of 7.4. The fluid transport model developed by Bert (1970) was fitted to the data. Assumptions, made in the development of the model, were tested and the range of reliability of the model is discussed. The two fitting parameters of the model were found to be stronger functions of hydration than was previously reported. The compressive response of collagen was found to be only weakly influenced by temperature. At 35 degrees C there was evidence of thermal degradation. Some creep was noted at times greater than five half-times, but no attempt was made to quantify it.

Biomechanical Phenomena↗

New insights into activation of the steroid hormone receptor superfamily.

For many years the prevailing view of how steroid hormone receptors exert their effects on gene transcription has been that these intracellular receptor proteins, upon association with their specific cognate ligands, undergo a transformation to a state where they are capable of interacting with chromatin and regulating the transcription of specific genes. It has become implicit dogma in the field of biochemical endocrinology that receptor activation is absolutely dependent upon this ligand-binding event. However, recent studies described here by Bert O'Malley and colleagues have shown that certain members of the steroid hormone receptor superfamily can be activated in a totally ligand-independent manner by a cell membrane receptor agonist, the neurotransmitter dopamine.

Animals↗

The antiprogestin-dependent GeneSwitch system for regulated gene therapy.

Antiprogestin-controlled gene regulation systems, initially developed by Bert O'Malley and colleagues, are based on the unusual properties of certain truncated progesterone receptor ligand-binding domains (PR-LBDdelta19). These modified PR-LBDs have lost the ability to respond to progestins, but have gained the ability to respond to antiprogestins as agonists, rather than as antagonists. When a modified PR-LBD is joined to specific DNA-binding and transcription activator domains, the resultant chimeric protein functions as an antiprogestin-inducible transcription factor for transgenes linked to promoters with specific DNA-binding sites. Antiprogestin-inducible gene regulation systems have been used to regulate transgene expression in cultured cells, transgenic animals, and for in vivo gene transfer studies using viral- or plasmid-based vectors. We have designed a plasmid-based, muscle-specific GeneSwitch system that is delivered to skeletal muscle by electroporation and provides regulated erythropoietin (EPO) expression in mice and rats in a manner that is dependent on orally administered mifepristone (MFP). Regulation was effective at low doses of MFP and provided regulated biological responses (hematocrit changes) for more than 6 months. This plasmid-based, antiprogestin-inducible EPO/GeneSwitch system has the potential to be a convenient, long-lasting and effective gene-based therapy for the treatment of anemia.

Anemia↗

Radiation vascular therapy: a novel approach to preventing restenosis.

In animal studies, beta and gamma radiation delivered via catheter-based systems to sites of angioplasty after arterial injury has decreased the neointimal proliferation that is a part of the restenotic process. Extending radiotherapy to the clinical setting, results of the double-blind, placebo-controlled, randomized Scripps Coronary Radiation to Inhibit Proliferation Post Stenting (SCRIPPS) study showed dramatic reductions in the rate of restenosis after coronary stenting when catheter-based gamma radiotherapy (with iridium-192) was used. In the Beta Energy Restenosis Trial (BERT), angiographic, intravascular ultrasound, and clinical outcomes were better than expected with beta brachytherapy. Strontium-90/yttrium-90 seeds were delivered via a unique catheter system in 35 patients who underwent coronary angioplasty. Future trials are being planned to confirm these promising results.

Angioplasty, Balloon, Coronary↗

A new primate model for multiple sclerosis in the common marmoset.

Experimental autoimmune encephalomyelitis (EAE) in outbred marmoset monkeys (Callithrix jacchus) is a recently developed nonhuman primate model of multiple sclerosis. Here, Bert 't Hart and colleagues compare this model to EAE in rhesus monkeys, highlighting autoimmune mechanisms in CNS inflammation and demyelination, including the role of major histocompatibility complex restriction and preclinical evaluation of innovative immunotherapies.

Acute Disease↗

Comparison of brachytherapy strategies based on dose-volume histograms derived from quantitative intravascular ultrasound.

PURPOSE: We present in this paper the comparison, by simulation, of different treatment strategies based either on beta- or gamma-sources, both with and without a centering device. Ionizing radiation to prevent restenosis is an emerging modality in interventional cardiology. Numerous clinical studies are presently being performed or planned, but there is variability in dose prescription, and both gamma- and beta-emitters are used, leading to a wide range of possible dose distributions over the arterial vessel wall. This paper discusses the potential merits of dose-volume histograms (DVH) based on three-dimensional (3-D) reconstruction of electrocardiogram (ECG)-gated intravascular ultrasound (IVUS) to compare brachytherapy treatment strategies. MATERIALS AND METHODS: DVH describe the cumulative distribution of dose over three specific volumes: (1) at the level of the luminal surface, a volume was defined with a thickness of 0.1 mm from the automatically detected contour of the highly echogenic blood-vessel interface; (2) at the level of the IVUS echogenic media-adventitia interface (external elastic lamina [EEL]), an adventitial volume was computed considering a 0.5-mm thickness from EEL; and (3) the volume encompassed between the luminal surface and the EEL (plaque + media). The IVUS data used were recorded in 23 of 31 patients during the Beta Energy Restenosis Trial (BERT) conducted in our institution. RESULTS: On average, the minimal dose in 90% of the adventitial volume was 37 +/- 16% of the prescribed dose; the minimal dose in 90% of the plaque + media volume was 58 +/- 24% and of the luminal surface volume was 67 +/- 31%. The minimal dose in the 10% most exposed luminal surface volume was 296 +/- 42%. Simulations of the use of a gamma-emitter and/or a radioactive source train centered in the lumen are reported, with a comparison of the homogeneity of the dose distribution. CONCLUSIONS: It is possible to derive DVH from IVUS, to evaluate the dose delivered to different parts of the coronary wall. This process should improve our understanding of the mechanisms of action of brachytherapy.

Brachytherapy↗

Measurement of the relative sweetness of stevia extract, aspartame and cyclamate/saccharin blend as compared to sucrose at different concentrations.

Special diets are used to mitigate many human diseases. When these diets require changes in carbohydrate content, then sweetness becomes an important characteristic. The range of low-calorie sweeteners available to the food industry is expanding. It is essential to have an exact knowledge of the relative sweetness of various sweeteners in relation to different sucrose concentrations. The objective of this study was to determine the variation on the relative sweetness of aspartame (APM), stevia [Stevia rebaudiana (Bert.) Bertoni] leaf extract (SrB) and the mixture cyclamate/saccharin--two parts of cyclamate and one part of saccharin--(C/S) with the increase in their concentrations, and in neutral and acid pH in equisweet concentration to 10% sucrose, using magnitude estimation. Sweetness equivalence of SrB in relation to sucrose concentrations of 20% or higher and of APM and C/S to sucrose concentrations of 40% or higher could not be determined, because a bitter taste predominated. The potency of all sweeteners decreased as the level of sweetner increased. In equi-sweet concentration of sucrose at 10%, with pH 7.0 and pH 3.0, the potency was practically the same for all sweeteners evaluated.

Aspartame↗

Leaf Ests from Stevia rebaudiana: a resource for gene discovery in diterpene synthesis.

Expressed sequence tags (ESTs) are providing a new approach to gene discovery in plant secondary metabolism. Stevia rebaudiana Bert. leaves produce high concentrations of diterpene steviol glycosides and should be a rich source of transcripts involved in diterpene synthesis. In order to create a resource for gene discovery and increase our understanding of steviol glycoside biosynthesis, we sequenced 5,548 ESTs from a S. rebaudiana leaf cDNA library. The EST collection was fully annotated based on database search results. ESTs involved in diterpene synthesis were identified using published sequences as electronic probes, by keyword searches of search results, and by differential representation. A significant portion of the ESTs were specific for standard leaf metabolic pathways; energy and primary metabolism represented 17.6% and 13.1% of total transcripts respectively. Diterpene metabolism in S. rebaudiana represented 1.1% of total transcripts. This study identified candidate genes for 70% of the known steps in the steviol glycoside pathway. One candidate, kaurene oxidase, was the 8th most abundant EST in the collection. Identification of many candidate genes specific to the I -deoxyxylulose 5-phosphate pathway suggests that the primary source of isopentenyl diphosphate, a precursor of geranylgeranyl diphosphate, is via the non-mevalonic acid pathway. The use of ESTs has greatly facilitated the identification of candidate genes and increased our understanding of diterpene metabolism.

DNA, Complementary↗

Forty years ago--the first paper.

In the 1950s and 1960s, chemistry was seen as a romantic and thrilling scientific discipline that promised to improve people's lives beyond measure. It was during this exciting time that The Chemical Society decided to launch a new journal aimed at disclosing the latest research results in a quick, direct, and brief way. Organic chemist, Professor Hans Wynberg of the University of Groningen in the Netherlands wrote the very first paper in Chemical Communications. What was it like to do research then? Wynberg, now 82 years of age, gave Bert Meijer some insights when he recently visited him in his lake-side home in Groningen.

Journal Article↗

Comparative effects of Stevia rebaudiana leaves and stevioside on glycaemia and hepatic gluconeogenesis.

The purpose of the present study was to compare the effect of the oral treatment (gavage) with Stevia rebaudiana (Bert.) Bertoni (SRB) and stevioside (STV) on glycaemia and gluconeogenesis of 15-h fasted rats. For this purpose, the rats received SRB (20 mg/kg x day), STV (5.5 mg/kg x day) or an equal volume of water (controls) during 15 days. To measure hepatic gluconeogenesis, liver perfusion and isolated hepatocytes were used. Glycaemia and gluconeogenesis from L-alanine (5 mM), L-glutamine (5 mM) and L-lactate (2 mM) were decreased (P < 0.05) after pre-treatment with SRB. However, the treatment with STV did not influence glycaemia and gluconeogenesis. Moreover, to get further information about the mechanism by which SRB leaves inhibit gluconeogenesis their potential role as a PPARgamma agonist was investigated. The data showed absence of activation of PPARgamma receptors. In summary, our results showed that the reduction of glycaemia promoted by the treatment with SRB leaves was mediated, at least in part, by an inhibition of hepatic gluconeogenesis. However, this effect did not involve stevioside and the activation of PPARgamma receptors.

Administration, Oral↗

On the etiology of Crohn disease.

Crohn disease (CD) is a chronic, panenteric intestinal inflammatory disease. Its etiology is unknown. Analogous to the tuberculoid and lepromatous forms of leprosy, CD may have two clinical manifestations. One is aggressive and fistulizing (perforating), and the other is contained, indolent, and obstructive (nonperforating) [Gi]-berts, E. C. A. M., Greenstein, A. J., Katsel, P., Harpaz, N. & Greenstein, R. J. (1994) Proc. Natl. Acad. Sci. USA 91, 12721-127241. The etiology, if infections, may be due to Mycobacterium paratuberculosis. We employed reverse transcription PCR using M. paratuberculosis subspecies-specific primers (IS 900) on total RNA from 12 ileal mucosal specimens (CD, n = 8; controls, n = 4, 2 with ulcerative colitis and 2 with colonic cancer). As a negative control, we used Myobacterium avium DNA, originally cultured from the drinking water of a major city in the United States. cDNA sequence analysis shows that all eight cases of Crohn's disease and both samples from the patients with ulcerative colitis contained M. paratuberculosis RNA. Additionally, the M. avium control has the DNA sequence of M. paratuberculosis. We demonstrate the DNA sequence of M. paratuberculosis from mucosal specimens from humans with CD. The potable water supply may be a reservoir of infection. Although M. paratuberculosis signal in CD has been previously reported, a cause and effect relationship has not been established. In part, this is due to conflicting data from studies with empirical antimycobacterial therapy. We conclude that clinical trials with anti-M. paratuberculosis therapy are indicated in patients with CD who have been stratified into the aggressive (perforating) and contained (nonperforating) forms.

Autoradiography↗

The scientific observatories on Mont Blanc.

Since the first ascent of Mont Blanc by Jacques Balmat and Dr. Michel-Gabriel Paccard in 1786, numerous scientific events have taken place on the highest peak of Europe. Horace Benédict de Saussure, since his first ascent in 1787, made numerous observations on barometric pressure, temperature, geology, and mountain sickness on Mont Blanc. Over the next 100 years, scientists and physicians climbed Mont Blanc and made many interesting although anecdotal reports. Science on Mont Blanc exploded at the end of the 19th century. A major player at that time was Joseph Vallot (1854-1925), who constructed an observatory in 1890 at 4,358 m on the Rochers des Bosses and then moved it in 1898 to a better location at 4,350 m. There Vallot and invited scientists made observations over more than 30 years: studies in geology, glaciology, astronomy, cartography, meteorology, botany, physiology and medicine were performed and published in the seven volumes of the Annales de l'Observatoire du Mont Blanc, between 1893 and 1917, and in the Comptes Rendus de l'Académie des Sciences. While Jules Janssen and Xaver Imfeld were preparing the construction of the new observatory on the top of Mont Blanc, Dr. Jacottet died in 1891 at the Observatoire Vallot from a disease that was clearly attributed by Dr. Egli-Sinclair to the effect of high altitude. This was probably the first case of high altitude pulmonary edema documented by an autopsy and suspected to be directly due to high altitude. Extensive studies on ventilation were made from 1886 to 1900. Increase in ventilation with altitude was documented, with the phenomenon of "ventilatory acclimatization." Paul Bert's theories on the role of oxygen in acute mountain sickness were confirmed in 1903 and 1904 by studying the effects of oxygen inhalation. In 1913, Vallot documented for the first time the decrease in physical performance at the top of Mont Blanc using squirrels. After that pioneering era, few studies were done until 1984, when a team of the Association pour la Recherche en Physiologie de l'Environnement (ARPE) renovated the observatory and started to organize annual scientific expeditions.

Altitude Sickness↗

Harnessing deep learning for proteome-scale detection of amyloid signaling motifs.

MOTIVATION: Amyloid signaling sequences adopt the cross-&#x3b2; fold that is capable of self-replication in the templating process. Propagation of the amyloid fold from the receptor to the effector protein is used for signal transduction in the immune response pathways in animals, fungi, and bacteria. So far, a dozen of families of amyloid signaling motifs (ASMs) have been classified. Unfortunately, due to the wide variety of ASMs it is difficult to identify them in large protein databases available, which limits the possibility of conducting experimental studies. To date, various deep learning (DL) models have been applied across a range of protein-related tasks, including domain family classification and the prediction of protein structure and protein-protein interactions. RESULTS: In this study, we develop tailor-made bidirectional LSTM and BERT-based architectures to model ASM, and compare their performance against a state-of-the-art machine learning grammatical model. Our research is focused on developing a discriminative model of generalized ASMs, capable of detecting ASMs in large datasets. The DL-based models are trained on a diverse set of motif families and a global negative set, and used to identify ASMs from remotely related families. We analyze how both models represent the data and demonstrate that the DL-based approaches effectively detect ASMs, including novel motifs, even at the genome scale. AVAILABILITY AND IMPLEMENTATION: The models are provided as a Python package, asmscan-bilstm, and a Docker image at https://github.com/chrispysz/asmscan-proteinbert-run. The source code can be accessed at https://github.com/jakub-galazka/asmscan-bilstm and https://github.com/chrispysz/asmscan-proteinbert. Data and results are at https://github.com/wdyrka-pwr/ASMscan.

Deep Learning↗

On the histroy of the free skin graft.

Skin graft procedures had already been performed prior to Reverdin's great discovery. Skin grafting apparently originated with the Hindus 3,000 years ago, but until the beginning of the nineteenth century only a few trials were reported. In the first half of the nineteenth century, skin graft procedures were done by Baronio, Cooper, Bünger, and Dieffenbach. Bert's experimental work in 1963 opened the way for the pioneers Reverdin, Ollier, Wolfe, and Thiersch, who contributed the free skin graft.

Animals↗

Guidance of intracoronary radiation therapy based on dose-volume histograms derived from quantitative intravascular ultrasound.

Application of ionizing radiation to prevent restenosis in atherosclerotic vessels treated by balloon angioplasty is a new treatment under investigation in interventional cardiology and radiology. There is variability in dose prescription, and both gamma- and beta-emitters are used, leading to a wide range of dose distribution over the arterial vessel wall. We present a new modality of dosimetry based on a method that three-dimensional (3-D) image reconstruction of electrocardiogram (ECG)-gated intravascular ultrasound (IVUS) images. Dose volume histograms (DVH) are used to describe the cumulative distribution of dose over two specific volumes: i) at the level of the luminal surface, defined with a thickness of 0.1 mm from the automatically detected contour of the highly echogenic blood-vessel interface, and ii) the adventitia volume is computed considering a 0.5-mm thickness from the echogenic media-adventitia interface. DVH provide a tool for reporting the actual delivered dose at the site believed to be the target: the adventitia, and to detect excessive radiation which could lead to vascular complications. Simulation of a gamma-emitter or of a radioactive source train in the center of the lumen are possible. The data obtained from the first ten patients included in the beta-irradiation trial (BERT 1.5) conducted in our institution are presented, supporting the use of DVH based on quantitative IVUS measurements for optimal dose prescription in vascular interventional radiation therapy.

Brachytherapy↗

Gene flow versus local adaptation in the northern acorn barnacle, Semibalanus balanoides: insights from mitochondrial DNA variation.

In reciprocal transplant experiments, Bertness and Gaines (1993) found that Semibalanus balanoides juveniles that had settled in an upper Narragansett Bay estuary survived better in that estuary that did juveniles from coastal localities. The observed pattern of survivorship led to the claim that local adaptation may result from a combination of limited gene flow between and strong selection within these habitats. Here we test the hypothesis that limited gene flow has led to habitat-specific population differentiation using sequence and restriction fragment length polymorphism analyses of the mitochondrial DNA D-loop region of S. balanoides. Samples were analyzed from replicated coastal and estuary localities in both Narragansett Bay, Rhode Island, and Damariscotta River, Maine. The patterns of F(ST) indicate that gene flow between coast and estuary is extensive (Nm > 100) and is not lower in the estuary with lower flushing rates (Narragansett Bay). Given the high estimate of genetic exchange, adaptations for unpredictable environments seem more likely than local adaptation in this species because loci that respond to selection in one generation are essentially homogenized by the next seasons' settlement. Nevertheless, these estimates of neutral gene flow can help identify the strength of selection necessary for local adaptation to accumulate in Semibalanus.

Animals↗

Physiological implications of altitude training for endurance performance at sea level: a review.

Acclimatisation to environmental hypoxia initiates a series of metabolic and musculocardio-respiratory adaptations that influence oxygen transport and utilisation, or better still, being born and raised at altitude, is necessary to achieve optimal physical performance at altitude, scientific evidence to support the potentiating effects after return to sea level is at present equivocal. Despite this, elite athletes continue to spend considerable time and resources training at altitude, misled by subjective coaching opinion and the inconclusive findings of a large number of uncontrolled studies. Scientific investigation has focused on the optimisation of the theoretically beneficial aspects of altitude acclimatisation, which include increases in blood haemoglobin concentration, elevated buffering capacity, and improvements in the structural and biochemical properties of skeletal muscle. However, not all aspects of altitude acclimatisation are beneficial; cardiac output and blood flow to skeletal muscles decrease, and preliminary evidence has shown that hypoxia in itself is responsible for a depression of immune function and increased tissue damage mediated by oxidative stress. Future research needs to focus on these less beneficial aspects of altitude training, the implications of which pose a threat to both the fitness and the health of the elite competitor. Paul Bert was the first investigator to show that acclimatisation to a chronically reduced inspiratory partial pressure of oxygen (P1O2) invoked a series of central and peripheral adaptations that served to maintain adequate tissue oxygenation in healthy skeletal muscle, physiological adaptations that have been subsequently implicated in the improvement in exercise performance during altitude acclimatisation. However, it was not until half a century later that scientists suggested that the additive stimulus of environmental hypoxia could potentially compound the normal physiological adaptations to endurance training and accelerate performance improvements after return to sea level. This has stimulated an exponential increase in scientific research, and, since 1984, 22 major reviews have summarised the physiological implications of altitude training for both aerobic and anaerobic performance at altitude and after return to sea level. Of these reviews, only eight have specifically focused on physical performance changes after return to sea level, the most comprehensive of which was recently written by Wolski et al. Few reviews have considered the potentially less favourable physiological responses to moderate altitude exposure, which include decreases in absolute training intensity, decreased plasma volume, depression of haemopoiesis and increased haemolysis, increases in sympathetically mediated glycogen depletion at altitude, and increased respiratory muscle work after return to sea level. In addition, there is a risk of developing more serious medical complications at altitude, which include acute mountain sickness, pulmonary oedema, cardiac arrhythmias, and cerebral hypoxia. The possible implications of changes in immune function at altitude have also been largely ignored, despite accumulating evidence of hypoxia mediated immunosuppression. In general, altitude training has been shown to improve performance at altitude, whereas no unequivocal evidence exists to support the claim that performance at sea level is improved. Table 1 summarises the theoretical advantages and disadvantages of altitude training for sea level performance. This review summarises the physiological rationale for altitude training as a means of enhancing endurance performance after return to sea level. Factors that have been shown to affect the acclimatisation process and the subsequent implications for exercise performance at sea level will also be discussed. Studies were located using five major database searches, which included Medline, Embase, Science Citation Index, Sports Discus, and Sport, in

Acclimatization↗

Outcome from balloon induced coronary artery dissection after intracoronary beta radiation.

OBJECTIVE: To evaluate the healing of balloon induced coronary artery dissection in individuals who have received beta radiation treatment and to propose a new intravascular ultrasound (IVUS) dissection score to facilitate the comparison of dissection through time. DESIGN: Retrospective study. SETTING: Tertiary referral centre. PATIENTS: 31 patients with stable angina pectoris, enrolled in the beta energy restenosis trial (BERT-1.5), were included. After excluding those who underwent stent implantation, the evaluable population was 22 patients. INTERVENTIONS: Balloon angioplasty and intracoronary radiation followed by quantitative coronary angiography (QCA) and IVUS. Repeat QCA and IVUS were performed at six month follow up. MAIN OUTCOME MEASURES: QCA and IVUS evidence of healing of dissection. Dissection classification for angiography was by the National Heart Lung Blood Institute scale. IVUS proven dissection was defined as partial or complete. The following IVUS defined characteristics of dissection were described in the affected coronary segments: length, depth, arc circumference, presence of flap, and dissection score. Dissection was defined as healed when all features of dissection had resolved. The calculated dose of radiation received by the dissected area in those with healed versus non-healed dissection was also compared. RESULTS: Angiography (type A = 5, B = 7, C = 4) and IVUS proven (partial = 12, complete = 4) dissections were seen in 16 patients following intervention. At six month follow up, six and eight unhealed dissections were seen by angiography (A = 2, B = 4) and IVUS (partial = 7, complete = 1), respectively. The mean IVUS dissection score was 5.2 (range 3-8) following the procedure, and 4.6 (range 3-7) at follow up. No correlation was found between the dose prescribed in the treated area and the presence of unhealed dissection. No change in anginal status was seen despite the presence of unhealed dissection. CONCLUSION: beta radiation appears to alter the normal healing process, resulting in unhealed dissection in certain individuals. In view of the delayed and abnormal healing observed, long term follow up is indicated given the possible late adverse effects of radiation. Although in this cohort no increase in cardiac events following coronary dissections was seen, larger populations are needed to confirm this phenomenon. Stenting of all coronary dissections may be warranted in patients scheduled for brachytherapy after balloon angioplasty.

Angina Pectoris↗