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1.
Sci Adv ; 6(41)2020 Oct.
Article in English | MEDLINE | ID: mdl-33033036

ABSTRACT

The gravity field of a small body provides insight into its internal mass distribution. We used two approaches to measure the gravity field of the rubble-pile asteroid (101955) Bennu: (i) tracking and modeling the spacecraft in orbit about the asteroid and (ii) tracking and modeling pebble-sized particles naturally ejected from Bennu's surface into sustained orbits. These approaches yield statistically consistent results up to degree and order 3, with the particle-based field being statistically significant up to degree and order 9. Comparisons with a constant-density shape model show that Bennu has a heterogeneous mass distribution. These deviations can be modeled with lower densities at Bennu's equatorial bulge and center. The lower-density equator is consistent with recent migration and redistribution of material. The lower-density center is consistent with a past period of rapid rotation, either from a previous Yarkovsky-O'Keefe-Radzievskii-Paddack cycle or arising during Bennu's accretion following the disruption of its parent body.

2.
Sci Adv ; 6(41)2020 10.
Article in English | MEDLINE | ID: mdl-33033038

ABSTRACT

We investigate the shape of near-Earth asteroid (101955) Bennu by constructing a high-resolution (20 cm) global digital terrain model from laser altimeter data. By modeling the northern and southern hemispheres separately, we find that longitudinal ridges previously identified in the north extend into the south but are obscured there by surface material. In the south, more numerous large boulders effectively retain surface materials and imply a higher average strength at depth to support them. The north has fewer large boulders and more evidence of boulder dynamics (toppling and downslope movement) and surface flow. These factors result in Bennu's southern hemisphere being rounder and smoother, whereas its northern hemisphere has higher slopes and a less regular shape. We infer an originally asymmetric distribution of large boulders followed by a partial disruption, leading to wedge formation in Bennu's history.

3.
Nat Geosci ; 12(4): 247-252, 2019 Apr.
Article in English | MEDLINE | ID: mdl-31080497

ABSTRACT

The shapes of asteroids reflect interplay between their interior properties and the processes responsible for their formation and evolution as they journey through the Solar System. Prior to the OSIRIS-REx (Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer) mission, Earth-based radar imaging gave an overview of (101955) Bennu's shape. Here, we construct a high-resolution shape model from OSIRIS-REx images. We find that Bennu's top-like shape, considerable macroporosity, and prominent surface boulders suggest that it is a rubble pile. High-standing, north-south ridges that extend from pole to pole, many long grooves, and surface mass wasting indicate some low levels of internal friction and/or cohesion. Our shape model indicates that, similar to other top-shaped asteroids, Bennu formed by reaccumulation and underwent past periods of fast spin leading to its current shape. Today, Bennu might follow a different evolutionary pathway, with interior stiffness permitting surface cracking and mass wasting.

4.
Nat Astron ; 3(4): 352-361, 2019 Apr.
Article in English | MEDLINE | ID: mdl-32601603

ABSTRACT

The top-shape morphology of asteroid (101955) Bennu is commonly found among fast-spinning asteroids and binary asteroid primaries, and might have contributed significantly to binary asteroid formation. Yet a detailed geophysical analysis of this morphology for a fast-spinning asteroid has not been possible prior to the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission. Combining the measured Bennu mass and shape obtained during the Preliminary Survey phase of OSIRIS-REx, we find a significant transition in Bennu's surface slopes within its rotational Roche lobe, defined as the region where material is energetically trapped to the surface. As the intersection of the rotational Roche lobe with Bennu's surface has been most recently migrating towards its equator (given Bennu's increasing spin rate), we infer that Bennu's surface slopes have been changing across its surface within the last million years. We also find evidence for substantial density heterogeneity within this body, suggesting that its interior has a distribution of voids and boulders. The presence of such heterogeneity and Bennu's top-shape is consistent with spin-induced failure at some point in its past, although the manner of its failure cannot be determined yet. Future measurements by the OSIRIS-REx spacecraft will give additional insights and may resolve questions regarding the formation and evolution of Bennu's top-shape morphology and its link to the formation of binary asteroids.

5.
Science ; 348(6232): 321-3, 2015 Apr 17.
Article in English | MEDLINE | ID: mdl-25883354

ABSTRACT

The inner solar system's biggest and most recent known collision was the Moon-forming giant impact between a large protoplanet and proto-Earth. Not only did it create a disk near Earth that formed the Moon, it also ejected several percent of an Earth mass out of the Earth-Moon system. Here, we argue that numerous kilometer-sized ejecta fragments from that event struck main-belt asteroids at velocities exceeding 10 kilometers per second, enough to heat and degas target rock. Such impacts produce ~1000 times more highly heated material by volume than do typical main belt collisions at ~5 kilometers per second. By modeling their temporal evolution, and fitting the results to ancient impact heating signatures in stony meteorites, we infer that the Moon formed ~4.47 billion years ago, which is in agreement with previous estimates.

6.
J Am Diet Assoc ; 108(9): 1497-502, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18755322

ABSTRACT

With the passage of the Child Nutrition and Women, Infants, and Children Reauthorization Act of 2004, schools that sponsor school meals programs are required to establish local wellness policies to address childhood obesity. Little is known about how school districts will respond to this mandate, the nature of local wellness policies, and their compliance with this mandate. The objectives of this cross-sectional descriptive study, conducted in early 2007, were to assess local wellness policies established by Pennsylvania public school districts, compare these policies to local wellness policy mandate requirements, and provide information about local wellness policy development and implementation. Local wellness policies were collected from all Pennsylvania public school districts that sponsor school meals programs (N=499). School district representatives also completed and submitted a local wellness policy checklist, providing information about local wellness policy development and implementation. Policy goal data were abstracted and entered into a Microsoft Access database along with local wellness policy data. Frequencies were calculated. All required public school districts (N=499) submitted local wellness policies. Most school district local wellness policies (85.6%-100%) met each mandate requirement (eg, included goals for nutrition education, physical activity, etc.). The most common policy goals were general and may be difficult to measure, suggesting school staff may need assistance developing action plans and measuring policy implementation. Most respondents identified the superintendent (n=377; 75.6%) and school foodservice director (n=301; 60.3%) as responsible for ensuring local wellness policy implementation. Questions remain about feasibility of these district-level personnel to ensure policy implementation at the school level. The ability of local wellness policies to impact childhood obesity will depend on efforts at both the school and district levels to implement and enforce local wellness policies.


Subject(s)
Child Nutrition Sciences/education , Child Nutritional Physiological Phenomena/physiology , Exercise/physiology , Health Policy , Nutrition Policy , Schools/organization & administration , Child , Cross-Sectional Studies , Female , Humans , Male , Obesity/epidemiology , Obesity/prevention & control , Outcome Assessment, Health Care , Pennsylvania , Public Policy
7.
Coll Antropol ; 31(1): 29-32, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17600915

ABSTRACT

Rates of childhood obesity in have reached alarming proportions in many countries. Sixteen percent of school-aged children and adolescents in the U.S. are overweight. Legislation implemented in 2004 in the U.S. requires local education agencies (LEAs) that sponsor school meal programs to establish local wellness policies to address childhood obesity. Project PA, a collaboration between a state agency and a university providing school-based interventions focuses on the school environment and policy changes. Interventions have targeted foodservice personnel, administrators, teachers, parents and students. In two recent projects schools assessed their school nutrition environments, developed nutrition policies, and implemented strategies to encourage healthier food selections. Schools identified weaknesses in the areas of marketing and communication of policies. Media attention on the childhood obesity facilitated policy changes. Time and cost were identified as barriers to policy development and there were concerns about weak enforcement of policies. These themes are discussed.


Subject(s)
Obesity/prevention & control , Schools , Child , Child Nutritional Physiological Phenomena , Diet , Exercise , Humans , Obesity/epidemiology , Overweight
8.
J Am Diet Assoc ; 106(12): 2052-6, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17126637

ABSTRACT

The objective of this study was to describe the extent and locations of soft drink advertisements on high school campuses in Pennsylvania and identify factors related to extent of these advertisements. Surveys were distributed to 271 school foodservice directors in a random sample of high schools in Pennsylvania. These high schools were selected to be representative of the entire population of high schools in Pennsylvania based on chosen demographic characteristics. A three-phase survey strategy was used, involving distribution of a postcard reminder 1 to 2 weeks after the initial survey distribution, and mailing of a second survey to nonrespondents 1 to 2 weeks after mailing of the postcard. Two hundred twenty-eight school foodservice directors (84%) returned surveys. Linear multiple regression analyses were done using SPSS (version 11.5.1, 2002, SPSS Inc, Chicago, IL). Approximately two thirds (66.5%) of respondents indicated soft drink advertisements exist in at least one location in their school, with the most prevalent locations being on vending machines (62%) and school grounds, such as playing fields (27%). Slightly more than 10% of respondents indicated soft drink advertisements displayed in the cafeteria. Extent of soft drink advertisement locations was positively related to existence of a pouring-rights contract, subscription to Channel One, and receipt of incentives from soft drink bottlers based on sales, but negatively related to average daily participation in school lunch. These findings suggest that commercialization and sales incentives might interact to contribute to school environments that are not "nutrition-friendly." Schools' efforts to establish wellness policies as mandated by the Child Nutrition and WIC Reauthorization Act of 2004 provide ideal opportunities to examine school environments for advertising that might conflict with the healthful environments they are aiming to establish, and perhaps to develop policies to address these practices.


Subject(s)
Advertising/statistics & numerical data , Carbonated Beverages , Food Dispensers, Automatic/statistics & numerical data , Food Services , Schools , Adolescent , Adolescent Nutritional Physiological Phenomena , Female , Health Promotion/organization & administration , Humans , Linear Models , Male , Obesity/epidemiology , Obesity/prevention & control , Pennsylvania , Predictive Value of Tests
9.
J Am Diet Assoc ; 106(2): 242-7, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16442872

ABSTRACT

OBJECTIVE: The objective of this study was to identify factors that predict offering and sale of competitive foods, as well as factors that predict average daily participation in school lunch. DESIGN: Surveys were distributed to 271 school foodservice directors in a random sample of high schools in Pennsylvania that were selected to be representative of the entire population of high schools in Pennsylvania based on chosen demographic characteristics. SUBJECTS: Two hundred twenty-eight school foodservice directors (84%) returned surveys. STATISTICAL ANALYSES: Descriptive and multiple regression analyses were done using SPSS version 11.5 (2002, SPSS Inc, Chicago, IL). RESULTS: Percentage of students eligible for free or reduced-price meals and timing of lunch were significant predictors of a la carte sales. Enrollment was negatively associated with number of vending machines per student. The number of less nutritious food items offered in vending machines and existence of soft drink machines owned by soft drink companies, for which the school receives a percent of sales, both predicted number of vending machines per student. Enrollment was inversely related to average daily participation in school lunch. The percentage of students eligible for free/reduced-price meals and enforcement of a policy prohibiting parents or students from bringing food into the cafeteria from local fast-food establishments positively predicted average daily participation in school lunch. CONCLUSIONS: These findings may be useful to school wellness councils in developing wellness policies as mandated by the Child Nutrition and WIC Reauthorization Act of 2004, as well as in structuring school environments to promote more healthful food choices by students.


Subject(s)
Food Dispensers, Automatic/statistics & numerical data , Food Services/statistics & numerical data , Food/statistics & numerical data , Schools , Adolescent , Adolescent Nutritional Physiological Phenomena , Beverages/statistics & numerical data , Female , Food/economics , Food Dispensers, Automatic/economics , Food Preferences , Food Services/economics , Health Promotion , Humans , Male , Nutritive Value , Pennsylvania , Predictive Value of Tests , Regression Analysis , Restaurants
10.
J Am Diet Assoc ; 106(2): 271-6, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16442877

ABSTRACT

The objectives of this study were to describe the extent, nature, and enforcement of school competitive food policies in Pennsylvania public high schools and to determine if there are differences between school foodservice directors' and principals' perceptions of the existence and enforcement of these policies. A survey was distributed to 271 school foodservice directors and 100 principals in a representative, random sample of high schools. Two hundred twenty-eight school foodservice directors (84%) and 79 principals (79%) returned surveys. Descriptive statistics, chi2 analyses, and a proportions test were done using SPSS statistical software (SPSS base 11.5 for Windows, 2002, SPSS Inc, Chicago, IL). Few nutrition policies were reported related to setting nutritional standards for competitive foods (0.5% to 15.0%). Respondents' reporting of existence of policies not always enforced ranged from 0% to 12.8%. School foodservice directors reported uncertainty about existence of several policies outside their direct domain, but with potential effect on school meals participation. Differences were found between school foodservice directors' and principals' reporting of policies, with principals more often reporting policy existence and enforcement. These findings suggest the need for communication, both about existence of policies and chain of command in enforcement of policies. Given the local wellness policy provision of the Child Nutrition and WIC Reauthorization Act of 2004, opportunities exist for nutrition professionals to contribute to development of policies that influence the nutritional quality of school foods.


Subject(s)
Administrative Personnel/psychology , Food Services/standards , Food/standards , Nutrition Policy , Schools , Adolescent , Adolescent Nutritional Physiological Phenomena , Attitude to Health , Data Collection , Dietetics , Female , Humans , Male , Nutritive Value , Pennsylvania , Pilot Projects
11.
J Am Diet Assoc ; 105(8): 1243-9, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16182640

ABSTRACT

OBJECTIVE: This study examined the types and extent of competitive foods available in public high schools in Pennsylvania. DESIGN: We developed, pilot tested, and distributed surveys to school foodservice directors in a random sample of 271 high schools in Pennsylvania. SUBJECTS: Two hundred twenty-eight surveys were returned, for a response rate of 84%. Statistical analyses were performed: Descriptive statistics were used to examine the extent of competitive food sales in Pennsylvania public high schools. The survey data were analyzed using SPSS software version 11.5.1 (2002, SPSS base 11.0 for Windows, SPSS Inc, Chicago, IL). RESULTS: A la carte sales provide almost dollar 700/day to school foodservice programs, almost 85% of which receive no financial support from their school districts. The top-selling a la carte items are "hamburgers, pizza, and sandwiches." Ninety-four percent of respondents indicated that vending machines are accessible to students. The item most commonly offered in vending machines is bottled water (71.5%). While food items are less often available through school stores and club fund-raisers, candy is the item most commonly offered through these sources. CONCLUSIONS: Competitive foods are widely available in high schools. Although many of the items available are low in nutritional value, we found several of the top-selling a la carte options to be nutritious and bottled water the item most often identified as available through vending machines.


Subject(s)
Food Dispensers, Automatic/statistics & numerical data , Food Preferences , Food Services/statistics & numerical data , Food/statistics & numerical data , Schools , Adolescent , Adolescent Nutritional Physiological Phenomena , Beverages/statistics & numerical data , Female , Food Dispensers, Automatic/economics , Food Dispensers, Automatic/standards , Food Services/economics , Food Services/standards , Humans , Male , Nutritive Value , Pennsylvania , Pilot Projects , Surveys and Questionnaires , United States
12.
J Bacteriol ; 183(18): 5223-9, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11514503

ABSTRACT

In the respirofermentative yeast Kluyveromyces lactis, only a single genetic locus encodes glucose transporters that can support fermentative growth. This locus is polymorphic in wild-type isolates carrying either KHT1 and KHT2, two tandemly arranged HXT-like genes, or RAG1, a low-affinity transporter gene that arose by recombination between KHT1 and KHT2. Here we show that KHT1 is a glucose-induced gene encoding a low-affinity transporter very similar to Rag1p. Kht2p has a lower K(m) (3.7 mM) and a more complex regulation. Transcription is high in the absence of glucose, further induced by low glucose concentrations, and repressed at higher glucose concentrations. The response of KHT1 and KHT2 gene regulation to high but not to low concentrations of glucose depends on glucose transport. The function of either Kht1p or Kht2p is sufficient to mediate the characteristic response to high glucose, which is impaired in a kht1 kht2 deletion mutant. Thus, the KHT genes are subject to mutual feedback regulation. Moreover, glucose repression of the endogenous beta-galactosidase (LAC4) promoter and glucose induction of pyruvate decarboxylase were abolished in the kht1 kht2 mutant. These phenotypes could be partially restored by HXT gene family members from Saccharomyces cerevisiae. The results indicate that the specific responses to high but not to low glucose concentrations require a high rate of glucose uptake.


Subject(s)
Fungal Proteins , Gene Expression Regulation, Bacterial , Glucose/metabolism , Kluyveromyces/metabolism , Monosaccharide Transport Proteins/genetics , Transcription, Genetic , Culture Media , Kinetics , Kluyveromyces/genetics , Kluyveromyces/growth & development , Monosaccharide Transport Proteins/metabolism , Mutation
13.
Cell Calcium ; 29(5): 359-67, 2001 May.
Article in English | MEDLINE | ID: mdl-11292392

ABSTRACT

Store-operated Ca(2+) entry, stimulated by depletion of intracellular Ca(2+) pools, has not been fully elucidated in vascular smooth muscle cells of pig coronary arteries. Therefore, [Ca(2+)](i) was measured in cultured cells derived from extramural pig coronary arteries using the Fura-2/AM fluorometry. Divalent cation entry was visualized with the Fura-2 Mn(2+)-quenching technique. Ca(2+) stores were depleted either by repetitive stimulation of P2Y purinoceptors with ATP (10 micromol/L), or by the sarcoendoplasmic Ca(2+)-ATPase inhibitor 2,5-Di-(tert-butyl)-1,4-benzohydroquinone (BHQ; 1 micromol/L) in Ca(2+)-free medium (EGTA 1 mmol/L). Addition of Ca(2+)(1 mmol/L) induced refilling of ATP-sensitive Ca(2+) stores and an increase in [Ca(2+)](i) in the presence of BHQ. Both could be significantly diminished by Ni(2+)(5 and 1mmol/L), La(3+)(10 micromol/L), Gd(3+)(10 micromol/L), and Mg(2+)(5.1 mmol/L). In contrast to the BHQ-mediated rise in [Ca(2+)](i), refilling of ATP-depleted stores was affected by neither flufenamate (0.1 mmol/L), nor by nitrendipine, nifedipine, and nisoldipine (each 1 micromol/L). The data suggest that after store depletion in pig coronary smooth muscle cells ATP and BHQ may converge on a common, Ni(2+)-, La(3+)-, Gd(3+)-, and Mg(2+)- sensitive Ca(2+) entry pathway, i.e. on a store-operated Ca(2+) entry. An additional contribution of the Na(+)/Ca(2+) exchanger cannot be excluded. Flufenamate-sensitive non-selective cation channels and dihydropyridine-sensitive L-type Ca(2+) channels are not involved in refilling of Ca(2+) stores after previous depletion by repetitive P2Y purinoceptor stimulation. The store-operated Ca(2+) entry in-between repetitive purinoceptor stimulation, i.e. in the absence of the agonist, may be responsible for the maintenance of agonist-induced rhythmic Ca(2+) responses.


Subject(s)
Calcium/metabolism , Muscle, Smooth, Vascular/metabolism , Receptors, Purinergic P2/metabolism , Adenosine Triphosphate/metabolism , Animals , Calcium Channel Blockers/pharmacology , Calcium-Transporting ATPases/antagonists & inhibitors , Cations, Divalent , Cells, Cultured , Coronary Vessels/cytology , Dihydropyridines/pharmacology , Fura-2 , Hydroquinones/pharmacology , Intracellular Fluid/metabolism , Magnesium , Manganese , Muscle, Smooth, Vascular/cytology , Sarcolemma/metabolism , Swine
14.
Environ Res ; 84(2): 100-7, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11068923

ABSTRACT

Cross-sectional studies were conducted in three riverside communities in the state of Pará in the Amazon Region of Brazil. Two of these communities, Brasília Legal and São Luís do Tapajós, are located in a watershed exposed to mercury pollution from artisanal gold mining, and the third, Santana do Ituqui, is outside this area. The studies were based upon a community census and included all persons volunteering for participation in each community. All participants were surveyed by questionnaire for health history, occupation, residence, and diet. Clinical evaluations were also done on each subject, along with collection of blood, urine, feces, and hair. Fish samples were collected to represent the most frequently consumed species. Mercury was measured in hair and fish. Although no signs or symptoms of overt mercury intoxication were observed, persons in Brasília Legal and São Luís do Tapajós had higher levels of mercury in hair than residents of Santana de Ituqui, located out of the risk area. Levels of mercury in fish were below Brazilian health guidance limits, but the high rates of fish consumption among these populations raise concerns for the possible effects of chronic exposure, especially among young children and women of childbearing age.


Subject(s)
Environmental Exposure/statistics & numerical data , Mercury Compounds/adverse effects , Water Pollution, Chemical/adverse effects , Water Pollution, Chemical/statistics & numerical data , Adolescent , Adult , Age Distribution , Aged , Animals , Brazil/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Female , Fishes , Food Contamination , Hair/chemistry , Humans , Infant , Male , Mercury Compounds/analysis , Middle Aged , Seafood/analysis , Surveys and Questionnaires , Water Supply
15.
Z Kardiol ; 89 Suppl 3: 62-7, 2000.
Article in German | MEDLINE | ID: mdl-10810787

ABSTRACT

Antiarrhythmic drugs can be divided into four Vaughan Williams classes (I-IV) according to defined electrophysiological effects on the myocardium. Thus, the Vaughan Williams classification also coincides with the main myocardial targets of the antiarrhythmics, i.e., myocardial sodium-, potassium-, and calcium-channels or beta-adrenergic receptors. A more detailed characterization which is also based on the myocardial targets of a drug is given by the "Sicilian Gambit" approach of classification. Nevertheless, the appropriate drug for the management of a given clinical arrhythmia has to be chosen according to the electrophysiological effects of the respective drug. A main determinant of the antiarrhythmic or proarrhythmic properties of a drug is the frequency dependence of its electrophysiological effects. The sodium-channel blockade induced by class-I substances is enhanced with increasing heart rates. Thus, class-I antiarrhythmics can be subclassified as substances showing a more exponential, an approximately linear, or rather saturated block-frequency relation. Class-III antiarrhythmics (potassium-channel blockade) can be further differentiated according to the component of the delayed rectifier potassium current (IK) which is inhibited by a drug. Class-III drugs inhibiting selectively the rapidly activating and deactivating IKr component exhibit a marked reverse rate dependence, i.e., the drug induced prolongation of the cardiac action potential is minimized at high rates. On the other hand, during bradycardia the pronounced action potential prolongation may cause early afterdepolarizations and triggered activity leading to torsades de pointes arrhythmias (acquired QT syndrome). Class-III substances inhibiting the slowly activating IKs component are currently under investigation and are expected to show a direct rate dependence. Experimental data available so far point to an action potential prolonging effect at least independent of rate. However, it is uncertain whether proarrhythmic effects can be thus avoided, especially in light of the fact that one form of congenital QT syndrome (LQT1) seems to be linked to dysfunction of the IKs-channel.


Subject(s)
Anti-Arrhythmia Agents/classification , Adrenergic beta-Antagonists/pharmacology , Adrenergic beta-Antagonists/therapeutic use , Anti-Arrhythmia Agents/pharmacology , Anti-Arrhythmia Agents/therapeutic use , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/physiopathology , Bradycardia/drug therapy , Bradycardia/physiopathology , Calcium Channel Blockers/pharmacology , Calcium Channel Blockers/therapeutic use , Heart Rate/drug effects , Heart Rate/physiology , Humans , Ion Channels/antagonists & inhibitors , Long QT Syndrome/congenital , Long QT Syndrome/drug therapy , Long QT Syndrome/physiopathology , Potassium Channel Blockers , Sodium Channel Blockers
16.
Basic Res Cardiol ; 93 Suppl 1: 125-32, 1998.
Article in English | MEDLINE | ID: mdl-9833140

ABSTRACT

Rate or frequency-dependence is a characteristic property of antiarrhythmic drugs belonging to the Vaughan William classes I and III. The rate-dependence of class I drugs (i.e., increasing blockade of fast Na(+)-channels with faster rates) results from periodical drug binding to Na(+)-channel sites which are preferably available in the activated and/or inactivated channel states (use-dependence). With respect to their binding and unbinding kinetics, class I drugs can be subdivided into three groups (group 1-group 3) which differ in their block-frequency relations as well as in their onset kinetics of channel blockade. These properties can serve as predictors of the anti- and proarrhythmic potential of class I drugs. Class III drugs (blockers of potassium channels) are mostly characterized by reverse rate-dependence (loss of class III action at faster rates). However, this property cannot be attributed to reverse use-dependence, i.e., binding to channels in the rested state. It is more likely due to different rate-dependent contributions of the two components of the delayed rectifier potassium current to repolarization, when the rapidly activating, the rectifying component IKr is specifically blocked by class III drugs, while the slowly activating component IKs remains unchanged. In spite of their reverse rate-dependence, class III drugs exert an antifibrillatory effect when fibrillation is induced by frequent stimulation. This can be attributed to the slow time course of the decline (offset kinetics) of the class III effect accompanying a sudden increase in frequency. Proarrhythmic effects of class III drugs result from the delay in repolarization that may favor the development of early afterdepolarizations. The proarrhythmic potential of class III drugs is species dependent and is favored if the contribution of IKr to the repolarization phase of the action potential is comparatively large.


Subject(s)
Anti-Arrhythmia Agents/therapeutic use , Heart Rate/drug effects , Action Potentials/drug effects , Animals , Anti-Arrhythmia Agents/classification , Anti-Arrhythmia Agents/pharmacokinetics , Humans , Ligands , Sodium Channel Blockers
18.
Eur J Biochem ; 249(1): 248-57, 1997 Oct 01.
Article in English | MEDLINE | ID: mdl-9363776

ABSTRACT

The variability of Kluyveromyces lactis strains in sensitivity to glucose is correlated with genetic differences in Kluyveromyces hexose transporter (KHT) genes. The glucose sensitive strain JA6 was shown to contain an additional gene, KHT2, not found in strains that are less sensitive. KHT2 is tandemly arranged with KHT1 which is identical to the low-affinity transporter gene RAG1, except for the C-terminus. Sequence analysis indicated that most of KHT2 had been lost by a recombination event between KHT1 and KHT2 generating the chimeric gene RAG1. Recombination between KHT1 and KHT2 was also found in mutants of JA6 selected as 2-deoxyglucose resistant colonies. These mutants, like kht1 kht2 double mutants were unable to grow on glucose when respiration was blocked (Rag- phenotype) and glucose repression was strongly reduced. kht1 or kht2 single mutants of JA6 were Rag+ but still an influence of the kht mutations on glucose repression was detectable. Repression was not affected in a Rag- mutant deleted for the phosphoglucose isomerase gene suggesting that the influence of transporter genes on repression is not caused by a reduction of the glycolytic flux. The data rather suggest that sensitivity to glucose repression is dependent on the rate of glucose uptake.


Subject(s)
Genes, Fungal , Glucose/metabolism , Kluyveromyces/genetics , Kluyveromyces/metabolism , Monosaccharide Transport Proteins/genetics , Monosaccharide Transport Proteins/metabolism , Mutation , Amino Acid Sequence , Base Sequence , Biological Transport, Active , DNA, Fungal/genetics , Glycolysis , Kluyveromyces/growth & development , Molecular Sequence Data , Phenotype , Recombination, Genetic , beta-Galactosidase/metabolism
20.
Circulation ; 92(5): 1169-78, 1995 Sep 01.
Article in English | MEDLINE | ID: mdl-7648662

ABSTRACT

BACKGROUND: The present study was performed to test the hypothesis that the altered force-frequency relation in human failing dilated cardiomyopathy may be attributed to alterations in intracellular calcium handling. METHODS AND RESULTS: The force-frequency relation was investigated in isometrically contracting ventricular muscle strip preparations from 5 nonfailing human hearts and 7 hearts with end-stage failing dilated cardiomyopathy. Intracellular calcium cycling was measured simultaneously by use of the bioluminescent photoprotein aequorin. Stimulation frequency was increased stepwise from 15 to 180 beats per minute (37 degrees C). In nonfailing myocardium, twitch tension and aequorin light emission rose with increasing rates of stimulation. Maximum average twitch tension was reached at 150 min-1 and was increased to 212 +/- 34% (P < .05) of the value at 15 min-1. Aequorin light emission was lowest at 15 min-1 and was maximally increased at 180 min-1 to 218 +/- 39% (P < .01). In the failing myocardium, average isometric tension was maximum at 60 min-1 (106 +/- 7% of the basal value at 15 min-1, P = NS) and then decreased continuously to 62 +/- 9% of the basal value at 180 min-1 (P < .002). In the failing myocardium, aequorin light emission was highest at 15 min-1. At 180 min-1, it was decreased to 71 +/- 7% of the basal value (P < .01). Including both failing and nonfailing myocardium, there was a close correlation between the frequencies at which aequorin light emission and isometric tension were maximum (r = .92; n = 19; P < .001). Action potential duration decreased similarly with increasing stimulation frequencies in nonfailing and end-stage failing myocardium. Sarcoplasmic reticulum 45Ca2+ uptake, measured in homogenates from the same hearts, was significantly reduced in failing myocardium (3.60 +/- 0.51 versus 1.94 +/- 0.18 (nmol/L).min-1.mg protein-1, P < .005). CONCLUSIONS: These data indicate that the altered force-frequency relation of the failing human myocardium results from disturbed excitation-contraction coupling with decreased calcium cycling at higher rates of stimulation.


Subject(s)
Calcium/metabolism , Cardiomyopathy, Dilated/metabolism , Myocardial Contraction/physiology , Myocardium/metabolism , Action Potentials , Adult , Aequorin , Cardiomyopathy, Dilated/physiopathology , Electric Stimulation , Female , Humans , In Vitro Techniques , Male , Sarcoplasmic Reticulum/metabolism
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