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Biomedical subjects

J L Thompson

Publications and source records attributed to J L Thompson.

At least 37 records · Page 2Linked to original sources

Five myofibrillar lesion types in eccentrically challenged, unloaded rat adductor longus muscle--a test model.

Sarcomere disruptions are observed in the adductor longus (AL) muscles following voluntary reloading of spaceflown and hindlimb suspension unloaded (HSU) rat, which resemble lesions in eccentrically challenged muscle. We devised and tested an eccentric contraction (ECCON) test system for the 14-day HSU rat AL. Six to 7 hours following ECCON, ALs were fixed to allow immunostaining and electron microscopy (EM). Toluidine blue-stained histology semithin sections were screened for lesion density (#/mm2). Serial semithin sections from the ECCON group were characterized for myosin immunointensity of lesions. Five myofibrillar lesion types were identified in histological semithin sections: focal contractions; wide A-bands; opaque areas; missing A-bands; and hyperstretched sarcomeres. Lesion density by type was greater for ECCON than NonECCON ALs (P< or =0.05; focal contractions and opaque regions). Lesion density (#-of-all-five-types/mm2) was significantly different (ECCON: 23.91+/-10.58 vs. NonECCON: 5.48+/-1.28, P< or =0.05; ECCON vs. SHAM: 0.00+/-0.00; P< or = 0.025). PostECCON optimal tension decreased (Poi-drop, 17.84+/-4.22%) and was correlated to lesion density (R2=0.596), but prestretch tension demonstrated the highest correlation with lesion density (R2=0.994). In lesions, the darkly staining A-band lost the normally organized thick filament alignment to differing degrees across the different lesion types. Ranking the five lesion types by a measure of lesion length deformation (hypercontracted to hyperstretched) at the light microscopy level, related to the severity of thick filament registry loss across the lesion types at the electron microscopic level. This ranking suggested that the five lesion types seen in semithin sections at the light level represented a lesion progression sequence and paralleled myosin immunostaining loss as the distorted A-band filaments spread across the hyperlengthening lesion types. Lesion ultrastructure indicated damage involved calcium homeostasis loss (focal contraction lesions) and "thick-filament-centering" failure of titin (wide A-band lesions) in the early stages of lesion development.

Animals↗

Long-term inpatient audiovisual scalp EEG monitoring.

Long-term audiovisual scalp EEG monitoring is an essential diagnostic tool for the evaluation of paroxysmal disorders. The definitive classification of both nonepileptic and epileptic events is often possible only with the use of this technique. Assessment of response to treatment and the noninvasive presurgical localization of seizure foci are other important uses. The optimization of both clinical semiology and electrophysiologic data obtained from such studies is the subject of significant research efforts. Outcomes studies and advanced EEG analysis research should ultimately serve to minimize the cost of this valuable technique as well as maximizing its utility.

Adult↗

Interrater reliability of plaque morphology classification in patients with severe carotid artery stenosis.

OBJECTIVE: Ultrasonographic assessment of carotid artery plaque morphology is widely used to identify patients at high risk for stroke. However, the reliability of plaque analysis in high-grade stenosis is uncertain. We determined the interrater reliability of sonographic plaque morphology analysis in patients with severe carotid artery stenosis. MATERIALS AND METHODS: Duplex Doppler was performed on 114 patients with 80-99% stenosis of the internal carotid artery using a Siemens Quantum 2000 D with a handheld 7.5 MHz transducer. B-mode pictures with and without color coding were printed on a Sony color video printer UP-5000 W. Three raters independently evaluated plaque echolucency, heterogeneity, calcification, and surface structure. Interrater agreement was calculated by a jackknife procedure generating kappa values and two-sided 95% confidence intervals. RESULTS: Kappa values and 95% confidence intervals were 0.05 (-0.07 to 0.16) for plaque surface structure, 0.15 (0.02 to 0.28) for plaque heterogeneity, 0.18 (0.09 to 0.29) for plaque echogenicity, and 0.29 (0.19 to 0.39) for plaque calcification. The upper bounds of all of the confidence intervals were below the 0.40 level suggested for minimal reliability. CONCLUSION: The low interrater agreement indicated that unaided visual assessment of static B-mode pictures to assess plaque morphology in patients with severe carotid artery stenosis is not reliable. Other evaluation procedures and standardized criteria, as yet undeveloped, are needed to improve reliability.

Arteriosclerosis↗

Muscarinic receptor activation of arachidonate-mediated Ca2+ entry in HEK293 cells is independent of phospholipase C.

Receptor-enhanced entry of Ca2+ in non-excitable cells is generally ascribed to a capacitative mechanism in which the activation of the entry pathway is specifically dependent on the emptying of agonist-sensitive intracellular Ca2+ stores. Although such entry can be clearly demonstrated under conditions of maximal or near-maximal stimulation, it is uncertain whether such a mechanism can operate during the oscillatory [Ca2+]i signals that are frequently seen following stimulation with low concentrations of agonists. In this study, we report that the stimulation of human m3 muscarinic receptors stably transfected into HEK293 cells results in the appearance of a novel arachidonate-mediated Ca2+ entry pathway. We show that the generation of arachidonic acid and the activation of this pathway are specifically associated with stimulation at the low agonist concentrations that typically give rise to oscillatory [Ca2+]i signals. At such agonist concentrations, however, the generation of arachidonic acid is independent of the simultaneous activation of the phospholipase C-inositol 1,4,5-trisphosphate pathway. We further show that the arachidonate-mediated Ca2+ entry demonstrates characteristics that distinguish it from the corresponding capacitative pathway in the same cells and therefore is likely to represent an entirely distinct pathway that is specifically responsible for the receptor-enhanced entry of Ca2+ during [Ca2+]i oscillations.

Arachidonic Acid↗

Disproportionate loss of thin filaments in human soleus muscle after 17-day bed rest.

Previously we reported that, after 17-day bed rest unloading of 8 humans, soleus slow fibers atrophied and exhibited increased velocity of shortening without fast myosin expression. The present ultrastructural study examined fibers from the same muscle biopsies to determine whether decreased myofilament packing density accounted for the observed speeding. Quantitation was by computer-assisted morphometry of electron micrographs. Filament densities were normalized for sarcomere length, because density depends directly on length. Thick filament density was unchanged by bed rest. Thin filaments/microm2 decreased 16-23%. Glycogen filled the I band sites vacated by filaments. The percentage decrease in thin filaments (Y) correlated significantly (P < 0.05) with the percentage increase in velocity (X), (Y = 0.1X + 20%, R2 = 0.62). An interpretation is that fewer filaments increases thick to thin filament spacing and causes earlier cross-bridge detachment and faster cycling. Increased velocity helps maintain power (force x velocity) as atrophy lowers force. Atrophic muscles may be prone to sarcomere reloading damage because force/microm2 was near normal, and force per thin filament increased an estimated 30%.

Actin Cytoskeleton↗

A new reconstruction of the Le Moustier 1 skull and investigation of internal structures using 3-D-muCT data.

Using the non-destructive technique of 3-D micro computed tomography (3-D-microCT), we present a new, virtual reconstruction of the Le Moustier 1 Neandertal skull. This new reconstruction corrects defects found in earlier reconstruction attempts by repositioning misaligned cranial fragments, addressing the problem of asymmetry caused by pressure during the fossilization process, and placing the basioccipital in its proper anatomical position. Metric comparisons between Le Moustier 1 and juvenile and adult Neandertals demonstrate that facial height proceeded at a faster rate of growth than facial prognathism at the beginning of the adolescent period. They also confirm the anterior placement of the basioccipital. A compound painted to match the colour of the fossilized bone was used in previous reconstruction attempts and the aim of this analysis was to remove the false material to reveal to what extent the fossilized bone was preserved. The areas with the most artificial material and glue include the palate, areas around the mandibular teeth, the left frontal, and parts of the right parietal and temporal bones. The microCT data were also used to examine internal structures of the skull including the frontal sinus and the labyrinth of the inner ear. An investigation of the frontal sinus reveals morphology similar to that found in adult Neandertals, although the structure does not extend to mid-orbit. The dimension of the radius of curvature of the lateral semicircular canal falls within one standard deviation, and the anterior and posterior canals within two standard deviations, of the published Neandertal mean. As in other Neandertals, the posterior semicircular canal is in an inferior position relative to the plane of the lateral canal.

Adolescent↗

[Effect of cardiac embolism sources on origin of territorial cerebral infarcts].

BACKGROUND AND PURPOSE: To test the association of cardiac sources of embolism with territorial type brain infarcts. METHODS: From a prospective cerebral ischemia data base the 106 consecutive patients with territorial type cerebral infarcts on computerized tomography were analyzed. The 85 consecutive patients with lacunar lesions served as a comparison group. The association of cardiac sources of embolism with territorial types infarcts was assessed using univariate Chi Square tests and logistic regression models. Cardiac sources of embolism were defined as:atrial fibrillation, left cardiac thrombi, valvular vegetations, wall motion and valvular abnormalities, left atrial enlargement, open foramen ovale, septal aneurysm, mitral valve prolaps, and aortic arch atherothrombosis (all findings--except for atrial fibrillation--assessed by echocardiography). RESULTS: Atrial fibrillation was significantly associated with territorial type infarcts (odds ratio 2.2, 95% confidence interval 1.01-4.8). This effect was independent of additional cardiac diseases, other cardiac abnormalities, carotid artery stenosis, and patient age. Most likely due to the small sample size, left cardiac thrombi only showed a non-significant trend towards an association with territorial infarcts (odds ratio 3.0, 95% confidence interval 0.7-12.3). The rate of all other cardiac findings did not differ significantly between the comparison groups. CONCLUSION: Atrial fibrillation and cardiac thrombi showed an association with territorial type infarcts. Other so-called cardiac sources of embolism--except for mechanical valves and bacterial endocarditis which were not represented in our sample--revealed no clinically relevant association with embolic brain infarct pattern.

Adult↗

Energy balance in young athletes.

Very little is known about the energy needs of young athletes. Recent studies using the doubly labeled water method have shown that the recommended dietary allowances for energy may be too high for normally active children and adolescents living in affluent societies. No studies of energy balance in young athletes have been published. Self-report dietary records of young athletes indicate that energy, carbohydrate, and select micronutrient intakes of certain athletic groups and individual athletes may be marginal or inadequate. Potential consequences of inadequate energy and nutrient intakes in young athletes include poor bone health, fatigue, limited recovery from injuries, menstrual dysfunction in female athletes, and poor performance. Studies of energy balance and nutrient status in young athletes are needed to better understand the nutritional needs of this group.

Adolescent↗

Sarcomere lesion damage occurs mainly in slow fibers of reloaded rat adductor longus muscles.

Sarcomere lesions were previously observed with reloading of rat adductor longus muscles after spaceflight and hindlimb unloading (HU). Spaceflown rats displayed more lesioned fibers in the "slow-fiber" region, suggesting a damage-susceptible fiber type. Unloading induces fast myosin expression in some slow fibers, generating hybrid fibers. We examined whether lesion damage differed among slow-, hybrid-, and fast-fiber types in HU-reloaded adductor longus muscles. Temporal HU for 5, 8, 11, 14, and 17 days revealed that hybrid fiber percent, detected by antimyosin immunostaining, peaked at 29 +/- 12% by 14 days. A 14-day HU followed by 12-14 h of voluntary reloading was performed to induce lesions. chi2 analysis showed that slow fibers were preferentially damaged, accounting for 92 +/- 5% of lesioned fibers; hybrid and fast fibers accounted for 7 +/- 4 and <0.5%, respectively. Atrophy did not explain differential lesion damage across fiber types, as slow and hybrid fibers atrophied to a similar extent. Because active myofiber contractions are requisite for lesion formation, selective recruitment of slow fibers most likely explains their damage susceptibility.

Animals↗

Cigarette smoking as a determinant of high-grade carotid artery stenosis in Hispanic, black, and white patients with stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: We sought to investigate the association of cigarette smoking with high-grade carotid artery stenosis in Hispanic, black, and white patients with cerebral ischemia in two independent samples. METHODS: Prospectively collected data from the Northern Manhattan Stroke Study (NOMASS) (n=431) and the Berlin Cerebral Ischemia Databank (BCID) (n=483) were used separately for a cross-sectional study estimating the association between cigarette smoking and high-grade carotid stenosis (defined as a luminal narrowing of > or =60%, diagnosed by duplex and/or Doppler ultrasound). In both studies, cerebral ischemia patients with normal sonographic findings or nonstenosing plaques of their carotid arteries served as a comparison group. Multivariate logistic regression models were used for statistical tests to determine the association between smoking and the dependent variable for high-grade carotid stenosis. Age, sex, hypertension, diabetes, hypercholesterolemia, and race/ethnicity were considered potential confounders. Further analyses of the NOMASS data estimated the effect of the amount of cigarette use and the impact of race/ethnicity. RESULTS: High-grade carotid stenoses were found in 14% of the NOMASS and in 21% of the Berlin patients. In Berlin the entire sample was white, whereas in New York only 19% of the cohort were white. In both samples, smoking was independently associated with severe carotid stenosis (NOMASS: odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1 to 2.0; BCID: OR, 3.9; 95% CI, 2.4 to 6.4). Patients smoking 20 pack-years or more showed a significant association (OR, 2.0; 95% CI, 1.1 to 3.9), whereas no significant effect was found for lower amounts of cigarette use. In NOMASS, white smokers displayed a significant (OR, 3.2; 95% CI, 1.1 to 8.9) association with high-grade carotid stenosis, the association for black smokers was less strong, and no association was found among Hispanics. CONCLUSIONS: Smoking is an independent determinant of severe carotid artery stenosis in patients with focal cerebral ischemia. The association differs by race/ethnicity, with the greatest effect observed among whites.

Adult↗

Effects of human growth hormone, insulin-like growth factor I, and diet and exercise on body composition of obese postmenopausal women.

To determine the effects of GH and insulin-like growth factor I (IGF-I) administration, diet, and exercise on weight loss, body composition, basal metabolic rate (BMR), muscle strength, and psychological status, 33 moderately obese postmenopausal women (67.1 +/- 5.2 yr) participated in a 12-week randomized, double blind study. Participants were placed on a diet that provided 500 Cal/day less than that needed for weight maintenance, and they walked 3 days and strength trained 2 days each week. Subjects also self-injected GH (0.025 mg/kg BW.day), IGF-I (0.015 mg/kg BW.day), a combination of these doses of GH and IGF-I, or placebo (P). Twenty-eight women completed the study, as five subjects dropped out due to intolerable side-effects (e.g. edema). Weight loss occurred in all groups, with the largest decrease occurring in the GH plus IGF-I group (5.6 +/- 1.4 kg). Fat mass significantly decreased in all groups, with the largest losses observed in GH and GH plus IGF-I groups (6.3 +/- 1.8 and 8.4 +/- 2.8 kg, respectively). Despite weight loss, BMR was maintained in all groups. Muscle strength increased with training for all groups, and depression and anxiety scores decreased in groups receiving IGF-I. These data show that obese postmenopausal women can lose weight and fat without compromising fat free mass, BMR, or gains in muscle strength, and that GH and IGF-I given together may enhance fat loss over either given alone.

Aged↗

Antibacterial activity of formic and propionic acids in the diet of hens on Salmonellas in the crop.

1. The inclusion of formic and propionic acids in the form of Bio-Add to the food of hens made no difference to the pH of the intestinal tract, but resulted in higher concentrations of these acids in the contents of the crop and gizzard. 2. Organic acids in the crop contents were bactericidal for Salmonella serotype Enteritidis PT4 in vitro, and also caused sub-lethal damage because fewer cells were recovered on selective salmonella media (brilliant green phenol red agar) than on non-selective media (nutrient agar). 3. Inclusion of Bio-Add in the food at 12g/kg may reduce the number of lactic acid-producing bacteria in the crop, and hence the amount of naturally produced organic acids.

Animal Feed↗

Effects of diet and exercise on energy expenditure in postmenopausal women.

The purpose of this study was to determine the effect of a 24-wk diet + exercise (DE) or diet-only program on basal metabolic rate (BMR), bone mineral density (BMD), energy expended during daily activities, muscle strength, and maximal oxygen consumption (VO2max) in 40 postmenopausal women. Daily energy need was determined by measuring BMR and assessing physical activity with 8-d self-reported activity records. The DE group consumed 2092 kJ/d less than the daily energy need and walked and performed strength-training exercises during which they expended an additional 837 kJ/d. The two diet-only groups consumed either 2092 kJ/d (D-2092) or 2929 kJ/d (D-2929) less than the daily energy need. BMD, BMR, muscle strength, VO2max, and energy expended during lying, sitting, standing, and walking were measured at baseline and after 12 and 24 wk of treatment. A significant decrease in BMR and energy expended during sitting and walking occurred in all groups, with no significant differences observed among groups. Although the declines in BMR were significant, they were small and may not have been physiologically relevant. No changes in BMD or VO2max occurred, whereas strength increased significantly in the DE group. The results showed that postmenopausal women significantly improved their body composition over a period of 6 mo without experiencing a large decline in BMR, BMD, or select components of energy expenditure.

Aged↗

Laryngopharyngeal sensory testing with modified barium swallow as predictors of aspiration pneumonia after stroke.

Improved diagnostic tests that can accurately identify subjects at high risk for aspiration pneumonia (AP) are needed. One measure of this accuracy is the false-negative rate (FNR), which determines the failure of a test to identify a group at high risk. This study compares FNRs for AP among dysphagic stroke patients for two prognostic techniques: modified barium swallow (MBS) alone and MBS combined with laryngopharyngeal sensory discrimination testing (MBS + LPSDT). MBS and LPSDT were performed within 4 weeks of stroke in 20 subjects who were prospectively followed for at least 2 years to identify the frequency of AP. MBS identified 10 patients as not at risk based on the finding of no aspiration on initial MBS; four of these patients developed AP (FNR = 40%). MBS + LPSDT identified five patients as not at risk based on the findings of neither aspiration nor bilateral sensory deficits; none of these patients developed AP (FNR = 0%). The combination of MBS criterion (aspiration) with the LPSDT criterion (bilateral sensory deficits) improves prognostication of outcome in dysphagic stroke patients by identifying a subgroup at high risk for developing AP (nonaspirators with bilateral deficits).

Adult↗

Effect of 17 days of bed rest on peak isometric force and unloaded shortening velocity of human soleus fibers.

The purpose of this study was to examine the effect of prolonged bed rest (BR) on the peak isometric force (P0) and unloaded shortening velocity (V0) of single Ca(2+)-activated muscle fibers. Soleus muscle biopsies were obtained from eight adult males before and after 17 days of 6 degrees head-down BR. Chemically permeabilized single fiber segments were mounted between a force transducer and position motor, activated with saturating levels of Ca2+, and subjected to slack length steps. V0 was determined by plotting the time for force redevelopment vs. the slack step distance. Gel electrophoresis revealed that 96% of the pre- and 87% of the post-BR fibers studied expressed only the slow type I myosin heavy chain isoform. Fibers with diameter > 100 microns made up only 14% of this post-BR type I population compared with 33% of the pre-BR type I population. Consequently, the post-BR type I fibers (n = 147) were, on average, 5% smaller in diameter than the pre-BR type I fibers (n = 218) and produced 13% less absolute P0. BR had no overall effect on P0 per fiber cross-sectional area (P0/CSA), even though half of the subjects displayed a decline of 9-12% in P0/CSA after BR. Type I fiber V0 increased by an average of 34% with BR. Although the ratio of myosin light chain 3 to myosin light chain 2 also rose with BR, there was no correlation between this ratio and V0 for either the pre- or post-BR fibers. In separate fibers obtained from the original biopsies, quantitative electron microscopy revealed a 20-24% decrease in thin filament density, with no change in thick filament density. These results raise the possibility that alterations in the geometric relationships between thin and thick filaments may be at least partially responsible for the elevated V0 of the post-BR type I fibers.

Actin Cytoskeleton↗

Microemboli in patients with vertebrobasilar ischemia: association with vertebrobasilar and cardiac lesions.

BACKGROUND AND PURPOSE: Microembolic high-intensity transient signals (HITS) on transcranial Doppler ultrasound (TCD) are associated with carotid stenosis, artificial heart valves, and other cardiac conditions. Only one case report describes stroke-related HITS in the posterior cerebral circulation. This study was designed to assess prospectively the prevalence of asymptomatic microemboli in vertebrobasilar ischemia and to determine whether potential cardioembolic sources, vertebral or basilar occlusive disease, and infarct subtypes predict the detection of HITS. METHODS: We investigated 52 consecutive patients with acute or recent vertebrobasilar ischemia within 48 hours after admission. TCD monitoring was performed according to established criteria for 20 minutes on each posterior cerebral artery. Fetal origin of the posterior cerebral artery was an exclusion criterion and ruled out by carotid compression. RESULTS: Microembolic signals were detected in 10 patients (19.2%). In a multivariate logistic regression analysis that included all independent variables, potential cardiac sources were significantly associated with HITS (odds ratio [OR], 14.3; 95% confidence interval [CI], 1.6 to 128.4), in particular when more than one cardiac abnormality (OR, 32.7; CI, 4.1 to 259.3) or a high-risk source (OR, 14.0; 95% CI, 2.3 to 84.9) was found. Vertebrobasilar vessel lesions and infarct subtype were not related to the detection of microemboli. CONCLUSIONS: Cardiac sources of embolism are a determinant of HITS in posterior cerebral circulation ischemia, suggesting that cardioembolic infarcts in that territory might be more common than suspected. Vertebrobasilar vessel abnormalities are less likely to lodge microemboli, which may indicate histopathological changes different from carotid artery disease.

Aged↗

Products of partial digestion with Hae III. Part 1. Characterization, casework experience and confirmation of the theory of three-, four- and five-banded RFLP pattern origins using partial digestion.

The sizes of Hae III partial digestion products at D1S7, D2S44, D4S139, D5S110, D10S28, and D17S26 were evaluated in experimentally generated partial digestions of liquid blood DNA. The partial digestion products were highly predictable, suggesting a very high level of sequence conservation in regions flanking variable number tandem repeat (VNTR) blocks. Partial digestion bands associated with three-or-more-banded patterns were also characterized. Partial digestion of three-banded patterns can be used to determine whether the extra bands arise due to internal Hae III sites in the VNTR block and to identify hidden three-banded patterns. Partial digestion products from forensic casework also conformed to size expectations. Presumed partial digestion bands from 27 forensic samples were compared to the experimentally generated data. The causes of partial digestion are examined and recommendations for interpreting forensic DNA evidence exhibiting partial digestion products are given.

Blood Stains↗