Mutations in hepatocyte nuclear factor 1beta are not a common cause of maturity-onset diabetes of the young in the U.K.
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Adult↗
Biomedical subjects
L Allen
Publications and source records attributed to L Allen.
Sentinel lymph node localization in early breast cancer.
METHODS: Thirty-two patients with clinical node-negative breast cancer underwent sentinel node localization study as part of a National Cancer Institute-sponsored multicenter trial. Anatomical and histopathologic characteristics of sentinel lymph node (SLN) and a kinetic analysis of nodal uptake were studied. Patients were injected with 1 mCi/4 ml unfiltered 99mTc-sulfur colloid in four divided doses around the palpable lesion or immediately adjacent to the excision cavity if prior biopsy was performed. SLN biopsy was performed 1.5-6 hr (mean = 3 hr) postinjection. Intraoperative localization was performed using a gamma probe. All patients underwent complete axillary dissection. RESULTS: SLN was identified in 30 of 32 (94%) patients. There were no false-negative SLN biopsies. CONCLUSION: This study supports the clinical validity of SLN biopsy in breast cancer and confirms that, unlike the blue dye technique, the learning curve with unfiltered 99mTc-sulfur colloid and the gamma detection probe is short, and SLN localization is achievable in over 90% of cases by surgeons with modest experience. The use of unfiltered 99mTc-sulfur colloid (larger particle size) with larger injected volume permits effective localization of SLNs.
Adult↗
Estrogen restores endothelial cell function in an experimental model of vascular injury.
BACKGROUND: It has been suggested that reendothelialization of damaged blood vessels protects against the vascular injury response. The goal of the present study was to determine whether estrogen restores endothelial cell function in balloon-injured rat carotid arteries. METHODS AND RESULTS: Ten-week-old male and female Sprague-Dawley rats with intact gonads underwent balloon injury to the right common carotid artery. Female rats were randomized to receive either daily subcutaneous injections of 17beta-estradiol (17betaE[2]; 20 microg x kg[-1] x d[-1]) or vehicle over the course of the study. Vessel morphology was assessed 2 weeks after injury. Significant neointima formation was observed in vehicle-treated males. This response was blunted in vehicle-treated and 17beta-E(2)-supplemented females. Intima-to-media ratios were 1.28+/-0.23 (males), 0.72+/-0.07 (vehicle-treated females), and 0.49+/-0.07 (17beta-E[2]supplemented females). To test whether reductions in neointimal lesion formation were related to the functional reendothelialization of the damaged vessel, endothelium-dependent relaxation was tested in isolated ring segments from the three experimental groups. Vessels were precontracted with phenylephrine followed by cumulative administration of acetylcholine, an endothelium-dependent vasodilator. Maximum relaxation to acetylcholine was 8.13+/-1.70% (males), 22.06+/-4.36% (vehicle-treated females), and 46.47+/-3.48% (17beta-E[2]-supplemented females). The enhanced endothelium-dependent relaxation of rings from 17betaE(2)-supplemented females correlated with reduced neointimal proliferation in this group. The concentration of nitric oxide metabolites in plasma correlated positively with plasma 17beta-E(2) concentration. CONCLUSIONS: These results suggest that estrogen protects against neointimal injury in the balloon-injured rat, at least in part, by facilitating the reendothelialization of the damaged vessel.
Acetylcholine↗
Impaired lung branching morphogenesis in the absence of functional EGF receptor.
The mammalian lung develops through branching morphogenesis which is controlled by growth factors, hormones, and extracellular matrix proteins. We have evaluated the role of EGF-receptor signaling in lung morphogenesis by analyzing the developmental phenotype of lungs in mice with an inactivated the EGF-receptor gene both in vivo and in organ culture. Neonatal EGF-receptor-deficient mice often show evidence of lung immaturity which can result in visible respiratory distress. The lungs of these mutant mice had impaired branching and deficient alveolization and septation, resulting in a 50% reduction in alveolar volume and, thus, a markedly reduced surface for gas exchange. The EGF-receptor inactivation also resulted in type II pneumocyte immaturity, which was apparent from their increased glycogen content and a reduced number of lamellar bodies. The defective branching was already evident at Day 12 of embryonic development. When explants of embryonic lungs from Day 12 embryos were cultured under defined conditions, the branching defect in EGF-receptor-deficient lungs was even more pronounced, with only half as many terminal buds as normal lungs. EGF treatment stimulated the expression of surfactant protein C and thyroid transcription factor-1 in cultured normal lungs, but not in EGF-receptor-deficient lungs, suggesting that EGF-receptor signaling regulates the expression of these marker genes during type II pneumocyte maturation. Taken together, our data indicate that signal transduction through the EGF receptor plays a major role in lung development and that its inactivation leads to a respiratory distress-like syndrome.
Animals↗
Qualitative magnetic resonance imaging findings in geriatric depression. Possible link between later-onset depression and Alzheimer's disease?
BACKGROUND: Several clinical and neuroimaging investigations support the notion that underlying brain changes may relate to depression in older patients, especially those with a later-age initial episode. However uncertainty still exists about diagnostic and pathogenic significance of structural brain abnormalities in aged depressives, in part because many studies lack all-elderly and age-similar normal comparison populations. METHODS: Brain morphology of elderly depressives (N = 30) and normal controls (N = 36) was compared by assessing magnetic resonance imaging (MRI) brain scans with qualitative criteria-based scales. Ratings included lateral and third ventricle enlargement, and cortical, medial temporal, and caudate atrophy. RESULTS: Significant differences between depressed and control groups were not demonstrated. Later-onset depressives had significantly more left medial temporal and left caudate atrophy than early-onset counterparts of similar age. Medial temporal atrophy significantly correlated with cognitive impairment and was not related to physical illness. Depressives with medial temporal atrophy (N = 7) were older and had later age at onset of depression than those without such changes. Cerebrovascular disease risk factors did not predict MRI abnormalities. CONCLUSIONS: Results indicate non-specificity and lack of homogeneity of qualitatively measured structural brain changes in geriatric depression, but suggest that pathology of specific, lateralized brain regions may be implicated in some later-onset patients. The relationship between medial temporal atrophy and late-onset depression raises the possibility that such patients may suffer from as-yet undeclared Alzheimer's disease. Lack of association between cerebrovascular disease risk factors and brain changes suggests other pathophysiological contributions.
Aged↗
Colonic transit time assessed by 67 Ga-citrate in a case-series of patients with recto-sigmoid adenomas.
One plausible mechanism by which dietary factors may influence colorectal carcinogenesis is through their effect on intestinal transit time. This study examined colonic transit by means of oral 67Ga-citrate in a case-series of patients who had developed recto-sigmoid adenoma. Adenoma patients had a significantly shorter transit time than constipated patients (P = 0.01) and our results also suggest (but do not show conclusively) that colonic transit in adenoma patients is similar to that of normal controls. Although these findings require confirmation from a larger study, they raise the hypothesis that colonic transit times are not delayed in patients who harbour recto-sigmoid adenomas.
Adenoma↗
Effects of mechanical factors on growth and maturation of the lung in fetal sheep.
Previous fetal studies indicated that endocrine factors control surfactant maturation, whereas mechanical forces affect lung growth, but not surfactant. We altered mechanical forces in fetal sheep lungs at 100-108 days gestation by tracheal ligation (TL, n = 15, 7 successful studies) to accelerate lung growth, transection of cervical spinal cord (TCSC, n = 17, 6 successful studies) to produce lung hypoplasia, or sham operation (n = 11, 6 successful studies). The reasons for the high mortality rates are not known. At delivery (130-142 days), groups were similar in gestational age, weight, and cortisol. Effects on lung growth were similar to, but effects on surfactant differed from, previous reports. TL increased lung growth but decreased saturated phosphatidylcholine (SatPC) and surfactant protein (SP)A and apparently decreased SP-B and relative numbers of alveolar type II cells (based on immunohistochemical studies of 1 animal in each group); TCSC had opposite effects. In contrast to a previous study (J. A. Kitterman, G. C. Liggins, G. A. Campos, J. A. Clements, C. S. Forster, C. H. Lee, and R. K. Creasy, J. Appl. Physiol, 51: 384-390, 1981), SatPC did not correlate with cortisol. We conclude that altering mechanical forces in fetal lung affects not only lung growth but also surfactant maturation and possibly alveolar epithelial differentiation and disturbs the normal correlation between cortisol and surfactant. Associated changes in insulin-like growth factor I (IGF-I; increased by TL, P = 0.003) suggest a possible role for IGF-I in these effects.
Animals↗
Maintenance of the differentiated type II cell phenotype by culture with an apical air surface.
The study of differentiated functions of alveolar type II cells has been hampered because of the lack of good in vitro systems. We report that culture of type II cells on collagen gels with an apical surface exposed to air promotes expression of differentiated type II cell characteristics. Cells cultured in this manner are cuboidal, contain lamellar bodies, and produce tubular myelin; in addition, they secrete phosphatidylcholine in response to exogenous ATP. Cultures contain mRNA for surfactant proteins A, B, and C and surfactant proteins A, B, and D. In contrast, when type II cells are cultured with an apical surface exposed to liquid rather than to air, the cells are squamous, do not express surfactant proteins or their respective mRNA, and do not contain lamellar bodies or produce tubular myelin. Type II cells cultured on plastic for 7 days, which no longer express mRNA for surfactant proteins, can be induced to express these mRNA by changing culture conditions to that of an air surface. The culture system described in this paper should be useful for studies of surfactant metabolism, regulation of alveolar epithelial phenotypic expression, and the processing of transiently expressed transgenes.
Air↗
Biochemical detection of type I cell damage after nitrogen dioxide-induced lung injury in rats.
We have previously shown that injury to lung epithelial type I cells can be detected biochemically by measuring the airway fluid content of a type I cell-specific protein, rTI40, in a model of severe acute lung injury [M. C. McElroy, J.-F. Pittet, S. Hashimoto, L. Allen, J. P. Wiener-Kronish, and L. G. Dobbs. Am. J. Physiol. 268 (Lung Cell. Mol. Physiol. 12): L181-L186, 1995]. The first objective of the present study was to evaluate the utility of rTI40 in the assessment of alveolar injury in a model of milder acute lung injury. Rats were exposed to 18 parts/ million NO2 for 12 h; control rats received filtered air for 12 h. In NO2-exposed rats, the total amount of rTI40 in bronchoalveolar fluid was elevated 2-fold compared with control values (P < 0.001); protein concentration was 8.5-fold of control values (P < 0.001). The increase in rTI40 was associated with morphological evidence of injury to type I cells limited to the proximal alveolar regions of the lung. The second objective was to correlate the severity of alveolar type I cell injury with functional measurements of lung epithelial barrier integrity. NO2 inhalation stimulated distal air space fluid clearance despite a significant increase in lung endothelial and epithelial permeability to protein. These data demonstrate that rTI40 is a useful biochemical marker for mild focal injury and that exposure to NO2 alters lung barrier function. Taken together with our earlier studies, these results suggest that the quantity of recoverable rTI40 can be used as an index of the severity of damage to the alveolar epithelium.
Animals↗
A parametric study of face recognition when image degradations are combined.
This article expands and quantifies one of the classic reports of modern visual perception research--Harmon and Julesz' (1973) demonstration of an enhancement in recognition performance when area averaging (blocking) and spatial frequency filtering are sequentially applied. Our goals were twofold: first, to determine if the existence of the phenomena could be confirmed and replicated in a parametric study; second, to determine if the new results supported the critical band masking theory originally proposed by Harmon and Julesz. We confirmed the presence of the phenomenon for stimuli subtending approximately six deg of visual angle vertically, but observed a surprisingly different pattern of results for smaller stimuli subtending approximately one deg. These and other recent findings from other laboratories raise questions about their masking theory as a complete explanation of the phenomena.
Attention↗
Two-year treatment of growth hormone (GH) receptor deficiency with recombinant insulin-like growth factor I in 22 children: comparison of two dosage levels and to GH-treated GH deficiency.
We have reported 1-yr results of a double blind, placebo-controlled trial of recombinant human insulin-like growth factor I (rhIGF-I) replacement in 16 children from the Ecuadorian GH receptor-deficient (GHRD) population. This report extends observations of rhIGF-I efficacy at two dosage levels [120 micrograms/kg BW twice daily (n = 15) and 80 micrograms/kg twice daily (n = 7)] over 2 yr, compares biochemical responses [serum IGF-I and IGF-binding protein-3 (IGFBP-3)] and their relationship to growth effects, and compares treatment effects of rhIGF-I in GHRD to rhGH in idiopathic GH deficiency (GHD). There were no baseline differences between the low and high dose groups for growth velocity (GV), bone age (BA), SD score for height, or percent mean body weight for height (MBWH). Over 2 yr of rhIGF-I treatment, there were no differences in GV or in changes in height SD score, height age (HA), or BA between the two groups; a subgroup of six subjects at the higher dose followed for a third year continued at the second year GV. The higher dose resulted in a greater change in percent MBWH. GV in yr 1 and 2 for the entire group and in yr 3 for a subgroup were greater for GH-treated GHD (n = 11). The GHD group showed a greater change in SD score for height and HA, but did not differ from the rhIGF-I-treated GHRD group in the change in BA (delta BA) or delta HA/delta BA over 2 yr. There was a greater change in percent MBWH in GHRD. There were no differences between dosage groups for serum IGF-I levels at baseline or the near-normal trough levels 12 h after rhIGF-I injection; these individual levels correlated with HA gain in yr 1 and 2. IGFBP-3 levels were markedly low, with no changes of significance with treatment. Comparable growth responses to the two dosage levels and the biochemical changes indicate a plateau effect at or below 80 micrograms/kg BW twice daily. The growth response and favorable trough levels of IGF-I despite the overall lack of increase in circulating IGFBP-3 levels suggest an alternative mechanism for sustaining IGF-I levels and avoiding rapid clearance of rhIGF-I. The greater increase in MBWH with treatment of GHRD than with treatment of GHD may reflect comparable effects on lean body mass without the lipolytic effects of GH in the GHRD subjects. The difference in growth response between rhIGF-I-treated GHRD and rhGH-treated GHD groups is consistent with the hypothesis that 20% or more of GH-influenced growth is due to the direct effects of GH on bone. Nonetheless, the comparable delta HA/delta BA suggests similar long term effects of replacement therapy in the two conditions.
Adolescent↗
The Hemopump as a left ventricular assist device in pediatric applications: initial Canadian applications.
Three children aged 11 months, and eight and nine years were supported with a Hemopump as a potentially life saving measure for circulatory failure. Left ventricular assist time ranged from 10 to 32 h. None of the three patients could be successfully weaned from the device because of complications of bleeding, arrhythmia or neurological insult. Despite poor outcomes, each patient demonstrated important hemodynamic stabilization with the device. The Hemopump is suggested as a potentially life saving treatment modality for selected pediatric patients who have critical left ventricular failure.
Canada↗
The impact of the transition to high school on the self-system and perceived social context of poor urban youth.
Examined the effects of the normative school transition to senior high school (n = 330) on the self-system and perceived school and peer social contexts of poor, black (n = 83), European American (n = 115), Latino (n = 105), and Asian American (n = 27) youth in the public school systems of three Eastern urban cities. The only negative effect of the school transition on the self-system was a decline in grade point average (GPA). Concurrently, the school transition was perceived to be associated with changes in the school and peer contexts. Across the transition, students reported increased disengagement from school (i.e., increased social support and extracurricular involvement) and increased engagement with peers (i.e., decreased daily hassles and increased involvement). These changes in the school and peer microsystems, like the changes in the self-system, were also common across race/ethnicity and gender. In addition, transition-associated school changes, and in particular changes in daily academic demands/hassles and involvement in school activities, were associated with changes in the academic dimensions of the self-system (i.e., academic efficacy expectations and GPA). Results and implications for preventive intervention are discussed within a developmental mismatch framework.
Achievement↗
Hypercoagulability following multiple trauma.
We sought evidence of hypercoagulability in 59 seriously injured trauma patients. An extended coagulation profile (consisting of tissue plasminogen activator antigen concentration, plasminogen activator inhibitor, serum antithrombin III, protein C antigen, functional protein C, protein S antigen, D-dimer, and prothrombin fragment 1.2) was compared to control values. Laboratory evidence of hypercoagulability was seen in 85% (n = 50) of the patients. Patients with an Injury Severity Score (ISS) > or = 16 (n = 36) had significantly elevated levels of D-dimer and decreased levels of functional protein C compared to patients with an ISS < or = 15 (n = 23). Functional protein C had a negative correlation (r = -0.44; p < 0.001) with the ISS. A hypercoagulable state exists immediately following severe trauma. Greater injury severity may increase this hypercoagulable state. Decreased levels of functional protein C best correlated with increased injury severity.
Adult↗
A comprehensive appraisal of 241Am in soils around Rocky Flats, Colorado.
Soils east of Rocky Flats Plant (RFETS) near Golden, Colorado, were contaminated with actinides because of accidental release of oils laden with plutonium isotopes. Consequently, these soils were contaminated by 241Am due to radioactive decay of 241Pu (t1/2 = 14.4 y). A spatial analysis of 241Am activity in soils east of RFETS was conducted to elucidate the magnitude and the mode of 241Am dispersion in the soil environment. 241Am activity of 178 soil samples ranged from 0.037 Bq kg-1 to 10,004 Bq kg-1 with a mean of 214 Bq kg-1, median of 7.28 Bq kg-1, standard deviation of 942 Bq kg-1, and a coefficient of variation of 4.3. Spatial analysis of 241Am in soils around RFETS was conducted using indicator kriging, which is a nonparametric technique especially suitable to model a conditional cumulative distribution function (ccdf) of highly skewed environmental data such as 241Am. The ccdf was used to generate an E-type (mean of the conditional cdf) surface. The resulted surfaces were consistent with the hypothesis that the westerly winds were the dominant mechanism of americium dispersal. The spatial distribution and dispersal mechanisms of 241Am were similar to those of 239+240Pu. The ccdf was also used to construct probability of exceedence maps of 241Am in soils. For the purpose of this report two threshold values for the probability maps were selected: (1) the mean measured background activity of 241Am (0.4 Bq kg-1), and (2) the programmatic preliminary remediation goal for residential occupancy scenario (87.7 Bq kg-1). The probability-of-exceedance maps provide estimates of spatial uncertainty associated with each threshold. The E-type maps in conjunction with the probability-of-exceedance maps provide a robust framework for future cleanup options and land use decisions.
Americium↗
Spin-orbit coupling in free-space Laguerre-Gaussian light beams.
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Journal Article↗
Atom dynamics in multiple Laguerre-Gaussian beams.
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Journal Article↗
Second-harmonic generation and the orbital angular momentum of light.
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Journal Article↗