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Biomedical subjects

J Kissel

Publications and source records attributed to J Kissel.

At least 19 recordsLinked to original sources
PubMed2006

Exposed water ice deposits on the surface of comet 9P/Tempel 1.

We report the direct detection of solid water ice deposits exposed on the surface of comet 9P/Tempel 1, as observed by the Deep Impact mission. Three anomalously colored areas are shown to include water ice on the basis of their near-infrared spectra, which include diagnostic water ice absorptions at wavelengths of 1.5 and 2.0 micrometers. These absorptions are well modeled as a mixture of nearby non-ice regions and 3 to 6% water ice particles 10 to 50 micrometers in diameter. These particle sizes are larger than those ejected during the impact experiment, which suggests that the surface deposits are loose aggregates. The total area of exposed water ice is substantially less than that required to support the observed ambient outgassing from the comet, which likely has additional source regions below the surface.

Ice↗
PubMed2005

Deep Impact: excavating comet Tempel 1.

Deep Impact collided with comet Tempel 1, excavating a crater controlled by gravity. The comet's outer layer is composed of 1- to 100-micrometer fine particles with negligible strength (<65 pascals). Local gravitational field and average nucleus density (600 kilograms per cubic meter) are estimated from ejecta fallback. Initial ejecta were hot (>1000 kelvins). A large increase in organic material occurred during and after the event, with smaller changes in carbon dioxide relative to water. On approach, the spacecraft observed frequent natural outbursts, a mean radius of 3.0 +/- 0.1 kilometers, smooth and rough terrain, scarps, and impact craters. A thermal map indicates a surface in equilibrium with sunlight.

Jupiter↗
PubMed2004

The Cometary and Interstellar Dust Analyzer at comet 81P/Wild 2.

The CIDA (Cometary and Interstellar Dust Analyzer) instrument on the Stardust spacecraft is a time-of-flight mass spectrometer used to analyze ions formed when fast dust particles strike the instrument's target. In the spectra of 45 presumably interstellar particles, quinone derivates were identified as constituents in the organic component. The 29 spectra obtained during the flyby of Comet 81P/Wild 2 confirm the predominance of organic matter. In moving from interstellar to cometary dust, the organic material seems to lose most of its hydrogen and oxygen as water and carbon monoxide. These are now present in the comet as gas phases, whereas the dust is rich in nitrogen-containing species. No traces of amino acids were found. We detected sulfur ions in one spectrum, which suggests that sulfur species are important in cometary organics.

Amino Acids↗
PubMed2003

Stereoselectivity of porcine beta-adrenergic receptors for ractopamine stereoisomers.

Ractopamine HCl is a beta-adrenergic receptor ((betaAR) ligand approved for use in swine to enhance carcass leanness. Ractopamine is produced commercially as a mixture of four stereoisomers (RR, RS, SR, SS). In order to determine which stereoisomers are active in the pig and whether they exhibit betaAR subtype selectivity, receptor affinity and adenylyl cyclase activation were determined using cloned porcine beta1- and beta2AR expressed in Chinese hamster ovary (CHO) cells. Dissociation constants (Kd) were determined by competitive displacement of [125I]iodocyanopindolol binding by ractopamine stereoisomers. The RR isomer had the highest affinity for both beta1- and betaAR (Kd of 29 and 26 nM, respectively). Dissociation constants for the other stereoisomers were higher (RS = 463 and 78 nM, SR = 3,230 and 831 nM, SS = 16,600 and 3,530 nM for the beta1- and beta2AR, respectively) relative to the RR stereoisomer. Isoproterenol stimulated adenylyl cyclase activity 600% relative to basal rates in CHO cells, regardless of betaAR subtype. Ractopamine stereoisomers did not significantly (P > 0.05) stimulate adenylyl cyclase through the beta1AR at moderate (near Kd) or high (10(-4) M) concentrations. In contrast, the RR isomer increased adenylyl cyclase activity 200 to 300% relative to basal rates through the beta2AR at moderate and hiconcentrations; the SR stereoisomer increased adenylyl cyclase activity nearly 100%. Neither the RS nor SS stereoisomers were effective in activating adenylyl cyclase activity through the beta2AR. A pattern of stereoselective activation similar to that for adenylyl cyclase also was exhibited for lipolysis using porcine adipocytes. The RR stereoisomer was equal to isoproterenol in stimulating lipolysis, whereas the SR isomer was 50% as effective; the RS and SR stereoisomers did not stimulate lipolysis in porcine adipocytes. The porcine betaAR exhibited stereoselectivity toward ractopamine stereoisomers with the RR isomer exhibiting the highest affinity for the (beta1- and beta2AR. In contrast, ractopamine stereoisomers seemed to be more effective at eliciting adenosine cyclic 3',5'-phosphate responses from beta2AR than beta1AR. The RR isomer ilikely the functional stereoisomer of ractopamine, but its effectiveness may be compromised by the presence of competing isomers, in particular the RS stereoisomer.

Adenylyl Cyclases↗
PubMed2001

A placebo-controlled trial of gabapentin in spinal muscular atrophy.

OBJECTIVE: To evaluate the efficacy of gabapentin in increasing muscle strength of patients with spinal muscular atrophy (SMA). BACKGROUND: Preclinical data in experimental models of motor neuron disease suggest a neuroprotective effect of gabapentin. METHODS: Gabapentin (1200 mg), or placebo, was administered three times daily in a randomized, double-blind trial for 12 months. The primary outcome measure was the average percent change from baseline, based on the measurement of strength in four muscles (elbow flexion and hand grip bilaterally) for each patient. Drug efficacy was examined by comparing the percent change in strength for patients on drug vs. placebo. Secondary efficacy variables included: forced vital capacity (FVC), SMA functional rating scale (SMAFRS), and mini-Sickness Impact Profile (SIP). RESULTS: Eighty-four patients, with type II or III SMA, were enrolled at eight sites across the United States. There were no differences in baseline features. There was no difference between the placebo and drug groups in any outcome measure. CONCLUSIONS: This study demonstrates the feasibility of this trial design and provides data for the design of future clinical trials in SMA.

Acetates↗
PubMed2001

A randomized efficacy and safety trial of oxandrolone in the treatment of Duchenne dystrophy.

BACKGROUND: A pilot study suggested that oxandrolone, an anabolic steroid, improved strength in boys with Duchenne dystrophy (DD) and indicated the need for a more definitive study. METHODS: A 6-month, randomized, double-blind, placebo-controlled study of oxandrolone in boys with an established diagnosis of DD, using the change from baseline to 6 months in the average muscle strength score (MMT) as the primary efficacy measure. RESULTS: The mean change from baseline for the oxandrolone group was +0.035 and that for the placebo group was -0.140. Although the oxandrolone group did not get worse and the placebo patients showed some deterioration in strength, the difference was not significant (p = 0.13). The average of the four quantitative muscle tests (QMT) showed a significant improvement in the oxandrolone-treated boys as compared with placebo. No adverse reactions attributable to oxandrolone were recorded. CONCLUSIONS: Although oxandrolone did not produce a significant change in the average manual muscle strength score as compared with placebo, the mean change in QMT was significant. Because oxandrolone is safe, accelerates linear growth, and may have some beneficial effect in slowing the progress of weakness, it may be useful before initiating corticosteroid therapy.

Anabolic Agents↗
PubMed2001

Time-of-flight mass spectrometric analysis of ion formation in hypervelocity impact of organic polymer microspheres: comparison with secondary ion mass spectrometry, (252)Cf mass spectrometry and laser mass spectrometry.

Unisized 1.6-microm polystyrene microspheres coated with PEDOT (polyethylene-dioxythiophene) were accelerated to speeds of 6-16 km/s and shot onto a silver target. Either positive or negative ions, both instantaneously formed by the impact process, have been analyzed by time-of-flight mass spectrometry (TOF). Apparently, the processes that control the formation of ions of either polarity depend on the impact velocity. Comparing the results with those of secondary ion mass spectrometry with primary ion energy in both the elastic and the inelastic ((252)Cf-MS) energy loss regimes, some reaction mechanisms of the polymer ions for different energy densities could be elucidated. Some aspects of ion formation are also related to those found in pulsed laser ion generation from these microspheres. This investigation was performed in order to further improve the method of analyzing the organic fraction of interstellar, interplanetary, and cometary dust particles impinging on the targets of the "CIDA" time-of-flight (TOF) mass spectrometers on-board the NASA comet missions "STARDUST" and "CONTOUR".

Journal Article↗
PubMed2000

Improved estimation of dermal pesticide dose to agricultural workers upon reentry.

Agricultural workers reentering fields after pesticide application to engage in hand labor activities are subject to potentially significant dermal exposures to residues on foliage and in soil. Environmental Protection Agency (EPA) guidelines for assessment of post-application exposures were originally described in the 1984 Pesticide Assessment Guidelines Subdivision K which is currently undergoing revision. A successor document will eventually appear as Series 875, Group B Postapplication Exposure Monitoring Test Guidelines. Regulatory protocols found in these documents utilize dislodgeable foliar residues, foliage-to-human-transfer coefficients, and duration of activity to estimate exposure. Dermal absorption factors are then used to estimate dose. However, the experiments from which absorption factors are derived typically involve constant or nearly constant exposures which are not consistent with assumed field exposure conditions. This can lead to inconsistent interpretation and questionable dose estimates. An AFL-CIO challenge to procedures used by EPA to estimate the dose of the fungicide captan [N-trichloromethylthio-4-cyclohexene-1,2-dicarboximide] to strawberry harvesters, which elicited a response from EPA, provides a useful opportunity for examination of the derivation and use of absorption factors. An improved, but still relatively simple, method for dermal dose estimation featuring explicit treatment of the time dependence of absorption has been developed. A benefit of the proposed method is capability for consideration of the effect of delay in post-shift washing on dose.

Agriculture↗
PubMed1999

Noninvasive determination of the arterial input function of an anticancer drug from dynamic PET scans using the population approach.

For the application of a kinetic model to PET data, it is generally necessary to obtain the arterial input function (AIF). It was the aim of the present study to introduce a method suitable for the determination of the AIF of a substance that undergoes biochemical transformation from noisy PET data: the population approach. F-18 labeled 5-fluorouracil (5-[18F]FU) was administered i.v. to eight patients suffering from liver metastases of colorectal carcinoma. Radioactivity concentrations in liver and aorta were dynamically measured with PET over 120 min. Pharmacokinetic analysis was carried out by applying a five-compartment model to individual activity-time data for the eight patients or to the mean activity-time data among the eight patients. The mean values of all parameters describing 5-FU transport and catabolism, i.e., volumes of distribution and clearances, as well as interindividual coefficients of variation (CV) were calculated according to both approaches. With our model, we were able to separate the concentration-time course of 5-FU in plasma, i.e., the AIF, from that of its major catabolite alpha-fluoro-beta-alanine (FBAL). As far as the mean parameter estimates are concerned, the differences between both approaches are not significant. For the liver data, the CV's are almost the same for both approaches. For the parameters concerning the aorta, however, there is a decrease in the CV's by using the population approach. For example, the CV of the central distribution volume of 5-FU was 30% for the individual approach and 18% for the population approach. With the population approach, it is possible to determine the AIF of drugs that undergo metabolic conversion, such as anticancer drugs, from the abdominal aorta visualized on PET images. The population approach helps to overcome noise in individual data. Since no measurements are needed in addition to the PET examination, the suggested method helps to reduce risk and pain for the patients as well as cost and thus facilitates large scale patient studies.

Adenocarcinoma↗
PubMed1997

Pharmacokinetic analysis of 5-[18F]fluorouracil tissue concentrations measured with positron emission tomography in patients with liver metastases from colorectal adenocarcinoma.

The purpose of our study was to develop a pharmacokinetic model to quantify the intracellular 5-fluorouracil (5-FU) concentration in liver metastases, which is expected to be closely correlated to therapy response. In addition, the influence of the biomodulator folinic acid on the action of 5-FU in the metastases was investigated. After i.v. application of 5-FU labeled with the positron emitter fluorine-18 (5-[18F]FU), the kinetics of the regional 5-[18F]FU/uptake was measured dynamically with positron emission tomography over 120 min in 14 patients with a total of 27 liver metastases from colorectal adenocarcinoma. Activity-time curves were evaluated in the metastases, the normal liver tissue, as well as in the aorta and analyzed by a six-compartment model. The catabolic breakdown of 5-FU to alpha-fluoro-beta-alanine (FBAL) in the normal liver tissue was modeled to separate the catabolites from the cytostatic agent 5-[18F]FU and the active 5-[18F]fluorodeoxyuridine nucleotides. With our model, all measured activity-time courses could be described adequately with only small interindividual variations in parameters connected with liver and blood. Extrahepatic clearance of 5-FU was estimated as 0.66 +/- 0.33 liters/min, whereas the hepatic clearance was 0.52 +/- 0.25 liters/min. The Michaelis-Menten parameters describing the nonlinear conversion of 5-FU to FBAL were Km = 11.3 +/- 6.4 micromol and Vmax = 147.1 +/- 130.7 micromol/min. The maximum FBAL concentration in the liver was reached between 35 and 65 min after i.v. 5-FU infusion. The most sensitive parameters for therapy monitoring were k(in) and k(out), which characterize the transport in and out of the intracellular volume of the metastases, respectively. Tumor response can only be expected if k(in) is high and k(out) is low ("trapping"). These criteria were met by 6 of the 27 metastases, which were identical to those with high values for the area under the intracellular 5-FU concentration curve (AUC[meta,IC]5-FU). The parameters k(in) and k(out) were also used to investigate the influence of the biomodulating agent folinic acid on drug effect. Five of the six metastases that showed trapping belonged to patients who received folinic acid. With the exception of one patient, however, all patients who received folinic acid had multiple metastases, of which only one was able to trap 5-FU. Because patient response can only be expected when all metastases trap 5-FU, folinic acid showed no effect on the overall clinical response. With the quantitative modeling approach used, trapping of 5-FU can be assessed noninvasively and on an individual basis. This makes it possible to adjust the dose for each individual patient to optimize the treatment schedule.

Adult↗
PubMed1997

A pilot trial of prednisone in facioscapulohumeral muscular dystrophy. FSH-DY Group.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant, 4q35-linked, slowly progressive muscular dystrophy with no known effective treatment. Since prednisone improves strength in Duchenne dystrophy, we performed a pilot, open-label trial of prednisone in eight subjects fulfilling strict diagnostic criteria for FSHD. Prednisone (1.5 mg/kg/day; maximum 80 mg/day) was administered for 12 weeks. Manual muscle testing, maximum voluntary isometric contraction testing, and muscle mass estimations by dual energy x-ray absorptiometry and urinary creatinine excretion were performed at baseline and at 12 weeks. There were no significant changes in strength or muscle mass. We conclude that prednisone given for 12 weeks does not produce major improvement in strength or increase muscle mass in FSHD. The study did not have sufficient power or length of follow-up to address the possibility that prednisone might arrest or slow disease progression.

Adolescent↗
PubMed1996

Evidence for anticipation and association of deletion size with severity in facioscapulohumeral muscular dystrophy. The FSH-DY Group.

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by marked inter- and intrafamilial heterogeneity in its clinical expression. The contribution of genetic factors to this variability is not well characterized. We examined the relationship of phenotype to genotype in a clinically and genetically well-defined FSHD population. Quantitative isometric myometry (QMT) scores, normalized for age, gender, and height, were used to quantify disease severity. We found a significant (r = 0.92, p < 0.004) correlation between disease severity and the size of the 4q35-associated deletion. In addition, when relative disease severity of parent-offspring pairs was compared, the offspring were found to be significantly more severely affected (p = 0.011). This generational effect suggests the presence of anticipation in FSHD and raises the possibility of an underlying dynamic mutation.

Adolescent↗
PubMed1995

Mass-spectrometric in situ studies of cometary organics for p/Halley and options for the future.

When the VEGA and GIOTTO spacecrafts flew by comet p/Halley in 1986 the mass-spectrometers Puma and PIA measured the composition of cometary dust particles impacting at speeds of well above 65 km/s. Ion formation upon impact lead to mostly atomic ions. However, a small fraction of the ions measured could be related to molecules. A sophisticated analysis allowed for the first time to point to the chemical nature of cometary organics based on actual mass spectra. With the instrument CoMA for the NASA-BMFT mission CRAF much higher mass-resolution and molecule masses become accessible for in situ measurement, and will yield complementary information to the gas chromatograph CIDEX also onboard CRAF.

Astronomical Phenomena↗
PubMed1994

Facioscapulohumeral muscular dystrophy (FSHD): design of natural history study and results of baseline testing. FSH-DY Group.

Faciscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder with a characteristic distribution of weakness and variable severity. Prospective, longitudinal data on FSHD are essential for the design of therapeutic trials and in assessment of genetic heterogeneity. We enrolled 32 well-defined FSHD patients and 32 normal subjects in a natural history study of FSHD. All subjects underwent baseline quantitative muscle testing (QMT), manual muscle testing (MMT), and functional testing. QMT demonstrated substantial weakness in muscles usually spared in FSHD. Major right/left side-to-side differences in strength were documented but, unexpectedly, were not related to handedness. Using the QMT data on normal subjects, we developed regression models relating strength to age, gender, and height and used these models to standardize QMT measurements in FSHD patients, expressing them as the number of SDs from average normal performance. This model-based strategy should facilitate the construction of composite scores to describe the natural history of FSHD and could be useful for constructing sensitive measures of progression in other neuromuscular diseases.

Adult↗
PubMed1992

Ulysses dust measurements near Jupiter.

Submicrometer- to micrometer-sized particles were recorded by the Ulysses dust detector within 40 days of the Jupiter flyby. Nine impacts were recorded within 50 Jupiter radii with most of them recorded after closest approach. Three of these impacts are consistent with particles on prograde orbits around Jupiter and the rest are believed to have resulted from gravitationally focused interplanetary dust. From the ratio of the impact rate before the Jupiter flyby to the impact rate after the Jupiter flyby it is concluded that interplanetary dust particles at the distance of Jupiter move on mostly retrograde orbits. On 10 March 1992, Ulysses passed through an intense dust stream. The dust detector recorded 126 impacts within 26 hours. The stream particles were moving on highly inclined and apparently hyperbolic orbits with perihelion distances of >5 astronomical units. Interplanetary dust is lost rather quickly from the solar system through collisions and other mechanisms and must be almost continuously replenished to maintain observed abundances. Dust flux measurements, therefore, give evidence of the recent rates of production from sources such as comets, asteroids, and moons, as well as the possible presence of interstellar grains.

Dust↗
PubMed1987

The dust distribution within the inner coma of comet P/Halley 1982i: encounter by Giotto's impact detectors.

Analysis of the data from Giotto's Dust Impact Detection System experiment (DIDSY) is presented. These data represent measurement of the size of dust grains incident on the Giotto dust shield along its trajectory through the coma of comet P/Halley on 1986 March 13/14. First detection occurred at some 287000 km distance from the nucleus on the inbound leg; the majority of the DIDSY subsystems remained operational after closest approach (604 km) yielding the last detection at about 202000 km from the nucleus. In order to improve the data coverage (and especially for the smallest grains, to approximately 10(-19) kg particle mass), data from the PIA instrument has been combined with DIDSY data. Flux profiles are presented for the various mass channels showing, to a first approximation, a 1/R2 flux dependence, where R is the distance of the detection point from the cometary nucleus, although significant differences are noted. Deviations from this dependence are observed, particularly close to the nucleus. From the flux profiles, mass and geometrical area distributions for the dust grains are derived for the trajectory through the coma. Groundbased CCD imaging of the dust continuum in the inner coma at the time of encounter is also used to derive the area of grains intercepted by Giotto. The results are consistent with the area functions derived by Giotto data and the low albedo of the grains deduced from infrared emission. For the close encounter period (-5 min to +5 min), the cumulative mass distribution function has been investigated, initially in 20 second periods; there is strong evidence from the data for a steepening of the index of the mass distribution for masses greater than 10(-13) kg during passage through dust jets which is not within the error limits of statistical uncertainty. The fluences for dust grains along the entire trajectory is calculated; it is found that extrapolation of the spectrum determined at intermediate masses (cumulative mass index alpha = 0.85) is not able to account for the spacecraft deceleration as observed by the Giotto Radio Science Experiment and by ESOC tracking operations. Data at large masses (>10(-8) kg) recently analysed from the DIDSY data set show clear evidence of a decrease in the mass distribution index at these masses within the coma, and it is shown that such a value of the mass index can provide sufficient mass for consistency with the observed deceleration. The total particulate mass output from the nucleus of comet P/Halley at the time of encounter would be dependent on the maximum mass emitted if this change in slope observed in the coma were also applicable to the emission from the nucleus; this matter is discussed in the text. The flux time profiles have been converted through a simple approach to modeling of the particle trajectories to yield an indication of nucleus surface activity. There is indication of an enhancement in flux at t approximately -29 s corresponding to crossing of the dawn terminator, but the flux detected prior to crossing of the dawn terminator is shown to be higher than predicted by simple modelling. Further enhancements corresponding to jet activity are detected around +190 s and +270 s.

Astronomical Phenomena↗
PubMed1979

Effect of flavoxate on hyperactive detrusor muscle.

The effect of Flavoxate on hyperactive detrusor contraction was studied in 37 patients, including 11 patients in whom the drug was administered intravenously during the urodynamic study. Beside the evaluation of frequency, nocturia and enuresis, the amplitude and the onset of uninhibited detrusor contraction (in correlation to bladder volume) was registered. The results showed subjective improvement in 61.3%. The complaints mentioned above improved in approximately 50%. The urodynamic data showed diminishing of the mean pressure during uninhibited detrusor contraction by almost 50% and the delay of the onset by 80% of bladder capacity. However, average bladder capacity increase was only 19%. It finally became obvious that the effect of Flavoxate was markedly worse in the neurogenic bladder group in comparison to the motoric urge patients.

Adolescent↗