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J L Thompson

Publications and source records attributed to J L Thompson.

At least 55 records · Page 3Linked to original sources

Evidence for a non-capacitative Ca2+ entry during [Ca2+] oscillations.

Current models for the agonist-induced activation of Ca2+ entry from the extracellular medium in non-excitable cells generally emphasize a capacitative mechanism whereby Ca2+ entry is activated simply as a result of the emptying of intracellular Ca2+ stores, without any direct involvement of inositol phosphates. To date, the activation and control of Ca2+ entry have generally been studied under conditions where the agonist-sensitive stores undergo a profound and sustained depletion. However, responses under more normal physiological conditions typically involve the cyclical release and refilling of the stores associated with oscillations in [Ca2+], and the nature and control of entry under these conditions has received relatively little attention. In this study, using isolated cells from the exocrine avian nasal gland as a model system, we show that: (a) the agonist-enhanced rate of Mn2+ quench is independent of the cyclical emptying and refilling of the agonist-sensitive Ca2+ pool during oscillations; (b) the Ca2+ entry pathway is maintained in an activated state for extended periods following inhibition of oscillations under conditions in which agonist-sensitive stores can be shown to be full; (c) no Ca2+ entry could be detected in oscillating cells in experiments that followed a definitive protocol for the demonstration of capacitative entry; and (d) on initial exposure to low agonist concentrations, activation of Ca2+ entry preceded any detectable release of Ca2+ from the stores. We conclude that the essential characteristics of the control of Ca2+ entry during oscillations are incompatible with current capacitative models.

Animals↗

Ca2+ entry modulates oscillation frequency by triggering Ca2+ release.

As in many cells, the frequency of agonist-induced cytosolic Ca2+ concentration ([Ca2+]1) oscillations in exocrine avian nasal gland cells is dependent on the rate of Ca2+ entry. Experiments reveal that the initiation of each oscillatory spike is independent of the relative fullness of the stores and, furthermore, the oscillating pool is normally fully refilled by the end of each [Ca2+]1 spike. Therefore, contrary to current models, the interspike interval (which essentially sets the frequency) does not reflect the time taken to recharge the oscillating stores. Instead, the data show that it is the previously demonstrated role that Ca2+ entry plays in triggering the repetitive release of Ca2+ from the oscillating stores, rather than the recharging of those stores, that provides the basis for the observed effects of Ca2+ entry rate on oscillation frequency.

Animals↗

Effects of diet and exercise on common cardiovascular disease risk factors in moderately obese older women.

Diet and exercise studies of premenopausal women have shown reductions in obesity and other cardiovascular disease (CVD) risk factors. Forty-one healthy, moderately obese (120-140% of ideal body weight, LBW), postmenopausal women (65.6 +/- 3.3 y) participating in 24-wk diet or diet + exercise programs were studied to determine whether similar CVD risk reduction would occur. Daily energy need (DEN) was estimated from basal energy expenditure and self-reported activity. The diet + exercise group (n = 16) reduced their daily energy intake (DEI) by 2092 kJ from their DEN and expended 837 kJ/d in walking and resistance exercise. The two diet-only groups (n = 13 and n = 12) reduced their DEI by 2092 and 2929 kJ from their DEN, respectively. Body weight, waist-to-hip and subscapula-to-triceps ratios, blood lipids (total, low-density-lipoprotein, and high-density-lipoprotein cholesterol, and triacylglycerols), glucose, and insulin concentrations were measured at baseline and after 12 and 24 wk of diet and diet + exercise. Data were analyzed by using analysis of variance with repeated measures (P < or = 0.05) and Tukey's post hoc test. Loss of body weight was significant for all groups between baseline and 12 and 24 wk (baseline: 79.3 +/- 7.6 kg; 12 wk; 75.1 +/- 7.7 kg; 24 wk; 72.8 +/- 8.0 kg) but did not differ among groups. No significant time or treatment effects were observed between baseline and 24 wk for changes in mean blood lipid, glucose, and fasting insulin concentrations or measures of body fat distribution. Although 24 wk of diet or diet+exercise significantly reduced body weight in this group, this loss in body weight was not accompanied by a reduction of other commonly accepted CVD risks.

Aged↗

Effect of short-chain fatty acids on the size of enteric bacteria.

The size of Escherichia coli and Salmonella enteritidis PT4 cells was measured using both transmission electron micrographs and image analysis. Incubation in the presence of formic and propionic acids resulted in larger cells, possibly as a result of DNA inhibition, with no apparent damage to the cell membranes. Bacteria incubated with propionic acid were more resistant to shrinkage after fixation, possibly as a result of altered phospholipid and fatty acid composition.

Escherichia coli↗

Effects of diet and diet-plus-exercise programs on resting metabolic rate: a meta-analysis.

Studies examining the effects of diet (D) and diet-plus-exercise (DE) programs on resting metabolic rate (RMR) report equivocal results. The purpose of this study was to use meta-analysis to determine if exercise prevents the decrease in RMR observed with dieting. Results from the 22 studies included in this analysis revealed that the majority of studies used female subjects ages 31-45 years, who were fed a relatively low-fat, high-carbohydrate diet of less than 5,023 kJ.day-1. The predominant prescribed exercise was aerobic in nature, 31-60 min in duration, performed 4-5 days per week, and of moderate intensity (51-70% of VO2max). Contrary to what is reported in narrative reviews, RMR decreased significantly with both D and DE programs, and the drop with D was significantly greater than that with DE. In conclusion, the addition of exercise to dietary restriction appears to prevent some of the decrease in RMR observed in premenopausal women.

Adult↗

In-flight and postflight changes in skeletal muscles of SLS-1 and SLS-2 spaceflown rats.

Spacelab Life Sciences-1 and -2 provided skeletal muscles from rats dissected in flight for the first time and 2 h to 14 days postflight. The muscles permitted the distinguishing of primary adaptations to microgravity from secondary reloading-induced alterations. In microgravity, rats adopted bipedal forelimb locomotion with the hindlimbs relegated to grasping activities. On landing day, body posture was abnormally low and walking was stilted at a rate one-third of normal. The adductor longus (AL) and soleus muscles exhibited decreased myofiber areas that did not recover 14 days postflight. Doubling of the nonmyofiber area indicated interstitial edema in AL muscles 2.3 h postflight. Solei did not manifest edema postflight, and neither muscle showed edema in flight. Sarcomere eccentric contraction-like lesions were detected in 2.6% of AL myofibers 4.5 h postflight; lesions were absent earlier postflight and in flight. At 9 days postflight, these lesions were repaired but regenerating AL myofibers were present, which suggests that myofiber necrosis occurred 1-2 days postflight. These studies demonstrate that muscle atrophy occurs in microgravity, whereas interstitial edema and sarcomere lesions are postflight phenomena.

Adaptation, Physiological↗

Effects of recombinant insulin-like growth factor-I and growth hormone on bone turnover in elderly women.

We evaluated the effects of recombinant insulin-like growth factor-I (IGF-I) and growth hormone (GH) on calciotropic hormones and bone turnover markers in 16 healthy elderly women 71.9 +/- 1.3 years of age (mean +/- SEM). Subjects consumed a fixed diet providing 1000 mg of calcium and 0.9 g/kg of protein for 10 days before starting baseline 24-h urine and blood collections. Specimens were collected for 6 consecutive days before initiating subcutaneous injections of GH (25 micrograms/kg/day, n = 5) and IGF-I at 60 micrograms/kg b.i.d. (high-dose, n = 5) or at 15 micrograms/kg b.i.d. (low-dose, n = 6) for 28 days. Resorption markers included urine hydroxyproline (OHP), total pyridinolines (PYD), and N-telopeptide; formation markers include osteocalcin, skeletal alkaline phosphatase (sALP), and type I procollagen carboxy-terminal extension peptide (CICP). For each subject, baseline daily turnover markers varied substantially (DV = 16-22%). With GH and high-dose IGF-I, resorption and formation markers increased progressively to maximum levels at day 21. For GH, the increase in day 21 PYD, N-telopeptide, osteocalcin, and CICP was 143, 111, 53, and 81%, respectively (p < 0.96-0.02). For high-dose IGF-I, these increases were 108, 81, 77, and 111% (p < 0.02-0.002). However, with low-dose IGF-I no change was observed in resorption markers while osteocalcin and CICP increased progressively (day 21, % increases = 88 +/- 51, 36 +/- 14). Twenty-four hour urine collections during the last days of baseline and of study drug were taken as six 4 h aliquots. When deoxyPYD was measured on these samples in the low-dose IGF-I group, a significant increase was observed only on the 0800-1200 h aliquot. Serum phosphorus concentrations increased with GH (21.2 +/- 3.3%) and high-dose IGF-I (8.8 +/- 3.6%) by day 21 but actually decreased by day 28 (-9.7 +/- 2.7, p < 0.02) with low-dose IGF-I. Urinary phosphorus excretion decreased with high-dose IGF-I only. Twenty-four hour calcium excretion increased with all treatments. These results indicate that both GH and high-dose IGF-I activate remodeling osteons. By contrast, low-dose IGF-I may directly increase osteoblastic function with only a minimal increase in bone resorption and may therefore provide a useful means to increase bone mass. The results also suggest some of the GH action on renal phosphorus handling represents a direct action of GH on the nephron which does not involve the intermediacy of IGF-I. Finally, even under controlled conditions bone turnover markers exhibit substantial daily variation so that a very large treatment effect will be required for these markers to have clinical utility.

Aged↗

Cyclin D1 protein expression in mantle cell lymphoma.

BACKGROUND: The t(11;14)(q13;q32) is a chromosomal abnormality usually associated with mantle cell (centrocytic) lymphomas, although it has occasionally been reported in other chronic lymphoproliferative disorders such as chronic lymphocytic leukemia, prolymphocytic leukemia, splenic lymphoma with villous lymphocytes, and multiple myeloma. This abnormality results in the translocation of the bcl-1 oncogene from chromosome 11 to the immunoglobulin heavy chain locus on chromosome 14. The bcl-1 oncogene is a member of the cyclin gene family, and high levels of cyclin D1 mRNA are consistently found in malignant B cell proliferations with t(11;14). PATIENTS AND METHODS: We examined cyclin D1 protein expression in 33 patients with low grade lymphoproliferative disorders and 2 patients with reactive hyperplasias by Western blot analysis using a polyclonal antibody. RESULTS: 8/11 mantle cell lymphomas, 0/11 chronic lymphocytic leukemias, 0/4 hairy cell leukemias, 0/2 Sezary syndrome, 0/2 monocytoid B-cell lymphomas, 0/3 follicular lymphomas, and 0/2 reactive hyperplasias had overexpression of cyclin D1. Cytogenetic analysis was performed in four cases of mantle cell lymphoma; three of these cases had the t(11;14), one of which was hypotetraploid with two copies of t(11;14). Immunophenotypically, all cases of mantle cell lymphoma and chronic lymphocytic leukemia had coexpression of CD5 and CD20. CONCLUSION: Mantle cell lymphoma may be difficult to discriminate from chronic lymphocytic leukemia, a more indolent disease, on morphologic and immunophenotypic grounds. Our findings suggest that analysis of cyclin D1 protein expression may be helpful in differentiating mantle cell lymphomas from other low grade lymphoproliferative disorders.

Antigens, Neoplasm↗

Hypertension and diabetes mellitus as determinants of multiple lacunar infarcts.

BACKGROUND AND PURPOSE: We investigated the relationship between hypertension, diabetes mellitus, and lacunes. METHODS: From 1237 cases of ischemic stroke in the Stroke Data Bank of the National Institute of Neurological and Communicative Disorders and Stroke, data from 637 patients whose initial computed tomogram showed lacunar (n = 184) or nonlacunar infarcts (n = 453) were analyzed. The group with lacunar infarcts was further divided into subgroups according to whether the patients had multiple (n = 40) or single (n = 144) lacunar infarcts. The association of hypertension and diabetes mellitus with lacunar infarcts was investigated using logistic regression models that included age, sex, and cardiac disease. Similar models were used to analyze the effects of diastolic and systolic blood pressure. RESULTS: Hypertension (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.1 to 6.0) and diabetes (OR, 2.3; 95% CI, 1.1 to 4.5) were significantly related to multiple but not to single lacunes. Cardiac disease was inversely associated with both single and multiple lacunes. Diastolic blood pressure significantly affected the probability of multiple lacunar infarcts (OR, 1.4; 95% CI, 1.04 to 1.9), whereas systolic pressure did not. CONCLUSIONS: There may be etiologically distinct lacunar infarct subgroups, with multiple lacunes being strongly related to hypertension and diabetes mellitus. Other stroke risk factors may be more important in patients with single lacunes. Diastolic rather than systolic pressure seems to be a major determinant of multiple lacunes.

Adult↗

Transcranial Doppler ultrasonography in cerebral arteriovenous malformations. Diagnostic sensitivity and association of flow velocity with spontaneous hemorrhage and focal neurological deficit.

BACKGROUND AND PURPOSE: We sought to investigate (1) the sensitivity of transcranial Doppler ultrasonography (TCD) for diagnosis of cerebral arteriovenous malformations (AVMs) and (2) the association of feeding artery flow velocity profiles with spontaneous hemorrhage and focal neurological deficit in AVM patients. METHODS: We examined 114 consecutive AVM patients prospectively by TCD; 22 non-AVM patients with acute cerebral hemorrhage and 52 normal subjects served as controls. To estimate the association of blood flow velocity patterns in feeding arteries with spontaneous hemorrhage and focal neurological deficit, the total group of AVM subjects was divided into patients with and without a history of bleeding and also into those with and without clinical signs of "steal" (focal deficit unrelated to hemorrhage). RESULTS: Sensitivity for large and medium-sized AVMs was high (> 80%), whereas 62% of small AVMs were missed. TCD was also highly sensitive (80%) in a group of five AVM patients with acute hemorrhage. Flow velocity profiles were not related to spontaneous hemorrhage (mean velocity, 111 cm/s in patients with hemorrhage versus 114 cm/s in patients without hemorrhage; P = .65) or clinical signs of steal (mean velocity, 111 cm/s versus 113 cm/s in patients with and without steal, respectively; P = .89). CONCLUSIONS: We concluded that (1) TCD is highly sensitive for large and medium-sized AVMs; (2) in acute cerebral hemorrhage TCD may help to differentiate AVM from non-AVM bleeds; (3) the predictive value of TCD findings for clinical sequelae of AVMs remains undetermined; and (4) the concept of hemodynamic steal in AVMs is not supported by TCD data.

Adult↗

The effects of recombinant human insulin-like growth factor-I and growth hormone on body composition in elderly women.

The purpose of this study was to determine the effects of recombinant human GH (rhGH; 0.025 mg/kg.day) and one of two doses of recombinant human insulin-like growth factor-I (rhIGF-I; 0.015 and 0.060 mg/kg, twice daily) on body composition in elderly women. Sixteen healthy elderly women (mean age +/- SEM, 71.9 +/- 1.3 yr) were randomly assigned to receive either rhGH (GH; n = 5), low dose rhIGF-I (n = 6), or high dose rhIGF-I (n = 5). A 2-week predrug baseline period was followed by 4 weeks of hormone treatment, with a standardized diet fed throughout. All groups experienced a significant increase in serum IGF-I and IGFBP-3 levels over the treatment period, accompanied by significant decreases in IGF-II (P < 0.05). Fat mass decreased in all groups, with significant increases in lean body mass and nitrogen retention occurring in the high dose IGF and GH groups. Total body water did not change, whereas increases observed in intracellular fluid approached significance (P = 0.06). These anabolic changes were accompanied by numerous negative side-effects in the GH and high dose IGF groups, including headaches, lethargy, joint swelling/pain, and bloatedness. The low IGF dose was well tolerated. These results demonstrate that the administration of rhGH and rhIGF-I for 4 weeks results in anabolic changes in body composition in elderly women.

Aged↗

Review of spaceflight and hindlimb suspension unloading induced sarcomere damage and repair.

Hindlimb suspension unloading (HSU) and spaceflight microgravity induce atrophy of the slow adductor longus muscle fibers which, following reloading, exhibit eccentric contraction (EC)-like lesions (abnormal widening of sarcomeres with A band disruption and excessively wavy, extracted Z lines). These lesions are similar morphologically to those produced in normal muscles after strenuous eccentric exercise. It appears that atrophic muscles exhibit increased susceptibility to eccentric damage because lesions are produced during nonstressful voluntary movements upon return to weightbearing. The EC-like lesions are absent in the unweighted conditions, but appear in HSU rats 15-60 minutes after reloading and in space-flown rates about 4 hrs after landing. By 12 hours, many EC-like lesioned sarcomeres are fully covered by longitudinal patches of Z line-like material which increases in density by 48 hours, producing the so-called "Z line streaming" morphology. In this case, Z line streaming is indicative of rapid repair of damaged sarcomeres rather than the onset of sarcomere breakdown. Immunoelectron microscopy is necessary to determine the composition of this dense material. By 9 days of reloading at 1 gravity, sarcomeres have regained normal structure, except for very rare persistence of faint Z patches. The morphological data indicate that Z patches serve at least two functions: 1) to permit contractile force to be transmitted across the damaged sarcomeres and 2) to provide a scaffold upon which sarcomeres are reconstructed in an active functional muscle.

Animals↗

Daily energy expenditure in male endurance athletes with differing energy intakes.

The 24-h energy expenditure (24-h EE), resting EE (REE), sleeping EE (SEE), and spontaneous physical activity (SPA) were compared between six male endurance athletes whose reported energy intake was low (LOW) and did not match that theoretically required for weight maintenance and four whose reported energy intake appeared adequate (ADQ) and matched their estimated EE. Groups did not differ in age, body weight, fat-free mass, and daily EE estimated from activity records. The LOW athletes reported an energy intake 6338 +/- 2164 kJ.d-1 less than estimated EE. The 24-h EE, REE, SEE, and SPA of the LOW athletes were significantly lower than the ADQ athletes (862, 523, 770 kJ.d-1, and 43 min.d-1, respectively). Using all subjects, there was a significant positive correlation between REE and free thyroxine (FT4) (r = 0.82) and SEE and FT4 (r = 0.66). Thus, part of the LOW athlete's ability to maintain body weight on a seemingly low energy intake appears due to a lower daily sedentary EE.

Activities of Daily Living↗

Cardiac sources of embolism in patients with pial artery infarcts and lacunar lesions.

BACKGROUND AND PURPOSE: On the assumption that the majority of lacunes are caused by small-vessel diseases and that pial artery infarcts arise from cardio-embolic or large-vessel diseases, 194 patients from the Berlin Cerebral Ischemia Data Bank with either lacunar or pial artery infarcts were analyzed for the frequency of cardiac sources of embolism. The primary hypothesis was that the frequency of cardiac sources of embolism is higher among pial artery infarct subjects. METHODS: The presence of cardiac sources of embolism was estimated by electrocardiographic and transthoracic and transesophageal echocardiographic studies. Cranial computed tomography scans were evaluated by two masked observers. RESULTS: The overall rate of cardiac sources of embolism did not differ significantly between the lacunar and the pial artery infarct group (66% versus 71%; odds ratio, 0.80; confidence interval, 0.43 to 1.50). Echocardiographic evidence of cardiac thrombi was positively associated with pial artery infarcts (odds ratio, 0.18; confidence interval, 0.04 to 0.80); atrial fibrillation and all other cardiac sources were not. CONCLUSIONS: Left cardiac thrombi are significantly associated with pial artery infarcts. Other presumed cardiac sources of embolism, including atrial fibrillation, may often represent coincidental findings or have a less strong tendency to result in pial artery infarcts.

Adolescent↗

Effects of kindling on subsequent learning, memory, behavior, and seizure susceptibility.

To determine the long-term effects of seizures on the developing brain we kindled 20-, 40-, and 60-day-old rats to stage 5 seizures and then elicited an additional 15 seizures using the same kindling stimulation. At age 80 days, all animals that reached stage 5 kindling, and their respective age-matched controls, underwent behavioral testing using the Morris water maze, open field test, and handling test. Prior to euthanasia the animals had seizure threshold tested using flurothyl inhalation. No differences were noted in time to platform in the water maze or activity level in the open field test between the kindled rats and controls in any of the three age groups. Rats kindled at age 20 and 40 were more emotional than the controls in the handling test. In the flurothyl inhalation test, rats kindled at 40 and 60 days of age had a shorter latency to all seizures stages than the controls. These results demonstrate that while kindling results in no alteration of learning, memory, or activity level, it does result in altered emotionality and activity level in immature animals, as well as reduced seizure threshold in pubescent and mature rats. The animal model used appears to be an important variable in determining the long-term effects of seizures.

Administration, Inhalation↗

MK801 pretreatment reduces kainic acid-induced spontaneous seizures in prepubescent rats.

MK801 is a noncompetitive blocker of N-methyl-D-aspartate receptors which has antiepileptic properties. To evaluate whether MK801 pretreatment in immature rats affects the future spontaneous recurrent seizure (SRS) rate or seizure susceptibility in a model of limbic epilepsy, MK801 (0.2 or 1.0 mg/kg, i.p.) or saline was administered to prepubescent rats 30 min prior to kainic acid (KA; 10 mg/kg, i.p.). With or without MK801 pretreatment, KA caused prolonged status epilepticus. SRS rate over the next 4 weeks, as assessed by intermittent video monitoring, was significantly lower in MK801 treated rats than in those which received KA alone. In addition, fewer MK801 treated rats (43%) developed SRS than those which got KA alone (88%). Susceptibility to generalized seizures was then tested using the volatile convulsant flurothyl; at both doses of MK801, flurothyl seizure latency was significantly greater in pretreated animals. These results show that MK801 pretreatment prior to KA induced status epilepticus reduces subsequent SRS frequency and flurothyl seizure susceptibility, while not substantially altering the acute epileptogenic effects of KA.

Animals↗

Acute pancreatitis of unknown etiology in the elderly.

OBJECTIVE: The incidence of acute pancreatitis in the elderly patient is increasing, and a significant number of such patients have no clearly defined etiology of their pancreatitis. To delineate the role of early organ failure versus progressive pancreatic disease in the morbidity and mortality, the authors' experience with patients older than 60 years with acute pancreatitis was reviewed. SUMMARY BACKGROUND DATA: As many as 30%-40% of elderly patients with acute pancreatitis have an unclear etiology and such patients have high rates of early organ failure and death. While some authorities have shown that pre-existing disease in these elderly patients did not contribute to subsequent morbidity, others have demonstrated that poor outcome was related to co-existing medical illness. METHODS: Their review of acute pancreatitis in the elderly was grouped into known and unknown etiology patients. Various parameters such as morbidity, mortality and length of stay were then compared between the two groups. Severity of organ failure and acute pancreatitis on admission were both graded and attempts made to correlate this severity with subsequent outcome. RESULTS: Unknown etiology patients had a greater number of Ranson's criteria (3.5 +/- .44 vs. 2.4 +/- .18) (p < 0.02), higher morbidity (48% vs. 22%) (p < 0.05), higher mortality (24% vs. 8.3%), and more SICU days (4.4 +/- 1.3 vs. 1.6 +/- .44) (p < 0.05) when compared with the known etiology group. Duration of symptoms, admission hypotension, and Ranson's criteria were unsuccessful in predicting mortality. Functional status of the various organ systems on admission did predict subsequent mortality. CONCLUSIONS: Elderly patients with acute pancreatitis of unknown etiology present with a more severe disease, have higher morbidity and longer SICU stays, and appear to have greater compromise of organ function. Organ function compromise correlates with mortality and appears more significant than severity of pancreatic disease. Aggressive support of such organ systems may be beneficial in the management of these patients.

Acute Disease↗

Estimated condom failure and frequency of condom use among gay men.

OBJECTIVES: Condoms are designed to bar transmission of the human immunodeficiency virus (HIV), but they sometimes fail. This paper explores the effect of experience with condoms on condom failure among gay men. METHODS: Risk of condom failure (breakage or slippage) on a single occasion is estimated for four sexual acts reported over 12 months by a sample of gay New York City men (n = 741). The estimation procedure assumes that each episode in which a condom is used is an independent event. Evidence is offered to support this assumption. RESULTS: Risk of condom failure in a single episode was fairly high, particularly in anal intercourse, for men who had engaged in each act only a few times in the previous year. It declined rapidly with experience (e.g., to below 1% for receptive anal intercourse after about 10 episodes in the previous year). Condoms failed less often in oral than anal sex, but estimated risk of failure also decreased with experience. CONCLUSIONS: Gay men should be especially cautious the first few times they use a condom; after moderate experience, however, they may expect a low risk of condom failure.

Adolescent↗