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PubMed2005

Opportunities for using spatial property assessment data in air pollution exposure assessments.

BACKGROUND: Many epidemiological studies examining the relationships between adverse health outcomes and exposure to air pollutants use ambient air pollution measurements as a proxy for personal exposure levels. When pollution levels vary at neighbourhood levels, using ambient pollution data from sparsely located fixed monitors may inadequately capture the spatial variation in ambient pollution. A major constraint to moving toward exposure assessments and epidemiological studies of air pollution at a neighbourhood level is the lack of readily available data at appropriate spatial resolutions. Spatial property assessment data are widely available in North America and may provide an opportunity for developing neighbourhood level air pollution exposure assessments. RESULTS: This paper provides a detailed description of spatial property assessment data available in the Pacific Northwest of Canada and the United States, and provides examples of potential applications of spatial property assessment data for improving air pollution exposure assessment at the neighbourhood scale, including: (1) creating variables for use in land use regression modelling of neighbourhood levels of ambient air pollution; (2) enhancing wood smoke exposure estimates by mapping fireplace locations; and (3) using data available on individual building characteristics to produce a regional air pollution infiltration model. CONCLUSION: Spatial property assessment data are an extremely detailed data source at a fine spatial resolution, and therefore a source of information that could improve the quality and spatial resolution of current air pollution exposure assessments.

Journal Article↗

PubMed2000

Insulin receptor substrate-1-mediated enhancement of growth hormone-induced mitogen-activated protein kinase activation.

Interaction of GH with the cell-surface GH receptor (GHR) causes activation of the GHR-associated tyrosine kinase, JAK2, and consequent triggering of signaling cascades including the STAT, Ras/Raf/MEK1/MAP kinase, and insulin receptor substrate-1(IRS-1)/PI3kinase pathways. We previously showed that IRS- and GHR-deficient 32D cells that stably express the rabbit GHR and rat IRS-1 (32D-rbGHR-IRS-1) exhibited markedly enhanced GH-induced proliferation and MAP kinase (ERK1 and ERK2) activation compared with cells expressing only the GHR (32D-rbGHR). We now examine biochemical mechanism(s) by which IRS-1 augments GH-induced MAP kinase activation. Time-course experiments revealed a similarly transient (maximal at 15 min) GH-induced ERK1 and ERK2 activation in both 32D-rbGHR and 32D-rbGHR-IRS-1 cells, but, consistent with our prior findings, substantially greater activation was seen in the IRS-1-containing cells. In both cells, GH-induced MAP kinase activation was markedly blunted by the MEK1 inhibitor, PD98059, but not by the PKC inhibitor, GF109203X. Interestingly, pretreatment with the PI3K inhibitor, wortmannin (EC50 approximately 10 nM), significantly reduced GH-induced MAP kinase activation in both 32D-rbGHR and 32D-rbGHR-IRS-1 cells. This same pattern in both cells of IRS-1-dependent augmentation and IRS-1-independent wortmannin sensitivity was also observed for GH-induced activation of Akt and MEK1 (using state-specific antibody blotting for both), despite the lack of difference in GHR, JAK2, SHP-2, p85, Akt, Ras, Raf-1, MEK1, ERK1, or ERK2 abundance between the two cells. A different PI3K inhibitor, LY294002 (50 microM), substantially inhibited (roughly 72%) GH-induced MAP kinase activation in 32D-rbGHR-IRS-1 cells, but only marginally (and statistically insignificantly) inhibited GH-induced MAP kinase activation in 32D-rbGHR cells. Because GH-induced Akt activation was completely inhibited in both cells by the same concentration of LY294002, these findings indicate that the wortmannin sensitivity of both the IRS-1-independent and -dependent GH-induced MAP kinase activation may reflect the activity of another wortmannin-sensitive target(s) in addition to PI3K in mediation of GH-induced MAP kinase activation in these cells. Notably, GH-induced STAT5 tyrosine phosphorylation, unlike Akt or MAPK activation, did not differ between the cells. Finally, while GH promoted accumulation of activated Ras in both cells, both basal and GH-induced activated Ras levels were greater in cells expressing IRS-1 than in 32D-rbGHR cells. These data indicate that while GH induces tyrosine phosphorylation of STAT5 and activation of the Ras/Raf/MEK1/MAPK and PI3K pathways, IRS-1 expression augments the latter two more than the former.

Androstadienes↗

PubMed2006

Scene estimation from speckled synthetic aperture radar imagery: Markov-random-field approach.

A novel Markov-random-field model for speckled synthetic aperture radar (SAR) imagery is derived according to the physical, spatial statistical properties of speckle noise in coherent imaging. A convex Gibbs energy function for speckled images is derived and utilized to perform speckle-compensating image estimation. The image estimation is formed by computing the conditional expectation of the noisy image at each pixel given its neighbors, which is further expressed in terms of the derived Gibbs energy function. The efficacy of the proposed technique, in terms of reducing speckle noise while preserving spatial resolution, is studied by using both real and simulated SAR imagery. Using a number of commonly used metrics, the performance of the proposed technique is shown to surpass that of existing speckle-noise-filtering methods such as the Gamma MAP, the modified Lee, and the enhanced Frost.

Journal Article↗

PubMed2001

Hypoxia stimulates osteopontin expression and proliferation of cultured vascular smooth muscle cells: potentiation by high glucose.

We examined the effect of hypoxia on proliferation and osteopontin (OPN) expression in cultured rat aortic vascular smooth muscle (VSM) cells. In addition, we determined whether hypoxia-induced increases in OPN and cell proliferation are altered under hyperglycemic conditions. Quiescent cultures of VSM cells were exposed to hypoxia (3% O(2)) or normoxia (18% O(2)) in a serum-free medium, and cell proliferation as well as the expression of OPN was assessed. Cells exposed to hypoxia for 24 h exhibited a significant increase in [(3)H]thymidine incorporation followed by a significant increase in cell number at 48 h in comparison with respective normoxic controls. Exposure to hypoxia produced significant increases in OPN protein and mRNA expression at 2 h followed by a gradual decline at 6 and 12 h, with subsequent significant increases at 24 h. Neutralizing antibodies to either OPN or its receptor beta3 integrin but not neutralizing antibodies to beta5 integrin prevented the hypoxia-induced increase in [(3)H]thymidine incorporation. Inhibitors of protein kinase C (PKC) and p38 mitogen-activated protein (MAP) kinase also reduced the hypoxia-induced stimulation of proliferation and OPN synthesis. Exposure to high-glucose (HG) (25 mmol/l) medium under normoxic conditions also resulted in significant increases in OPN protein and mRNA levels as well as the proliferation of VSM cells. Under hypoxic conditions, HG further stimulated OPN synthesis and cell proliferation in an additive fashion. In conclusion, hypoxia-induced proliferation of cultured VSM cells is mediated by the stimulation of OPN synthesis involving PKC and p38 MAP kinase. In addition, hypoxia also enhances the effect of HG conditions on both OPN and proliferation of cultured VSM cells, which may have important implications in the development of diabetic atherosclerosis associated with arterial wall hypoxia.

Animals↗

PubMedDate not supplied

Recurrent cystic radiation necrosis of the brain.

Cystic radiation necrosis is a rare complication of radiotherapy for nasopharyngeal carcinoma. The magnetic resonance imaging (MRI) characteristics have not been described. Serial MRI images were done on a patient who developed multiple cysts in the brain as a result of irradiation for his nasopharyngeal carcinoma. The characteristic MRI features included a slightly higher T1-weighted signal than cerebrospinal fluid, surrounding white matter edema as indicated by the high T2-weighted signal, and absence of gadolinium enhancement on the cyst wall. The adjacent gray matter in the anterior temporal lobes and inferior frontal lobes, which were included in the radiation field, had gadolinium enhancement. Dosimetry data and isodose contour maps revealed that his frontal lobes and anterior temporal lobes received 7920 cGy and 5040-6480 cGy of radiation respectively. Despite placement of multiple cysto-peritoneal shunts for decompression, new cysts eventually developed and previously shunted cysts enlarged in size. The management of cystic radiation necrosis of the brain remains unsatisfactory.

Brain↗

PubMed2001

[Functional properties of cooperative monoclonal antibodies against human tumor necrosis factor].

The panel of 23 newly produced monoclonal antibodies (mAbs) against human tumor necrosis factor (TNF) was examined for enhanced or cooperative TNF binding. Epitopic mapping revealed a preferential mAb generation against two epitopes designed as A1 and C1. Both A1 and C1 mAbs have neutralizing activity and display remarkable property to bind TNF synergistically comprising a pair of cooperative mAbs. C1 epitope resides within the TNF receptor-binding site (RBS) and responsible for generation of competitive neutralizing mAbs that block TNF activity by direct RBS masking. RBS-distal A1 epitope represents allosteric neutralizing mAbs that block TNF activity by conformational RBS changes. Combination of A1 and C1 mAbs resulted in synergistic TNF neutralization through complementary effect of competitive and allosteric TNF blocking mechanisms. Generation of cooperative Abs may have significance to achieve the most efficient neutralization of protein antigens with an intolerable functional activity in vivo.

Allosteric Regulation↗

PubMed2002

Neuroimaging in pediatric brain tumors: Gd-DTPA-enhanced, hemodynamic, and diffusion MR imaging compared with MR spectroscopic imaging.

BACKGROUND AND PURPOSE: Gadolinium-enhanced MR images assist in defining tumor borders; however, the relation between tumor cell extent and contrast-enhanced regions is unclear. Our aim was to improve conventional neuroimaging of pediatric brain tumors with hemodynamic, diffusion, and spectroscopic MR imaging. METHODS: We performed conventional MR and MR spectroscopic imaging in 31 children with neuroglial brain tumors. Hemodynamic MR imaging was performed in 16 patients with a first-pass intravenous bolus of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA); apparent diffusion coefficients (ADCs) were measured in 12 patients. To account for multiple measurements in a patient, we used a nested analysis of variance. RESULTS: At MR spectroscopy, choline (Cho)-containing compounds (indicating tumor) and lipid levels (indicating necrosis) did not correlate with percent Gd-DTPA enhancement on MR images. Percent enhancement was positively correlated with relative cerebral blood volumes (rCBVs) (P =.05) and negatively correlated with ADCs (P <.001). Stepwise multiple linear regression revealed that rCBV (P =.008), ADC (P =.022), and lipid (P <.001) levels were significant independent predictors of percent enhancement. Tumor spectral patterns were detected in tumor regions and outside enhancing tumor beds in patients with clinical progression; these were confirmed at neuropathologic analysis. CONCLUSION: MR spectroscopic imaging improves the assessment of pediatric brain tumors by adding biochemical information regarding tumor involvement and by depicting residual or recurrent tumor outside the Gd-DTPA-enhanced tumor bed. rCBV and ADC mapping complemented MR spectroscopic imaging. We recommend the use of MR spectroscopic imaging in addition to conventional MR imaging in assessing pediatric brain tumors.

Adolescent↗

PubMed2003

Correlation between brain reorganization, ischemic damage, and neurologic status after transient focal cerebral ischemia in rats: a functional magnetic resonance imaging study.

The pattern and role of brain plasticity in stroke recovery has been incompletely characterized. Both ipsilesional and contralesional changes have been described, but it remains unclear how these relate to functional recovery. Our goal was to correlate brain activation patterns with tissue damage, hemodynamics, and neurologic status after temporary stroke, using functional magnetic resonance imaging (fMRI). Transverse relaxation time (T2)-weighted, diffusion-weighted, and perfusion MRI were performed at days 1 (n = 7), 3 (n = 7), and 14 (n = 7) after 2 hr unilateral middle cerebral artery occlusion in rats. Functional activation and cerebrovascular reactivity maps were generated from contrast-enhanced fMRI during forelimb stimulation and hypercapnia, respectively. Before MRI, rats were examined neurologically. We detected loss of activation responses in the ipsilesional sensorimotor cortex, which was related to T2 lesion size (r = -0.858 on day 3, r = -0.979 on day 14; p < 0.05). Significant activation responses in the contralesional hemisphere were detected at days 1 and 3. The degree of shift in balance of activation between the ipsilesional and contralesional hemispheres, characterized by the laterality index, was linked to the T2 and apparent diffusion coefficient in the ipsilesional contralesional forelimb region of the primary somatosensory cortex and primary motor cortex at day 1 (r = -0.807 and 0.782, respectively; p < 0.05) and day 14 (r = -0.898 and -0.970, respectively; p < 0.05). There was no correlation between activation parameters and perfusion status or cerebrovascular reactivity. Finally, we found that the laterality index and neurologic status changed in parallel over time after stroke, so that when all time points were grouped together, neurologic status was inversely correlated with the laterality index (r = -0.571; p = 0.016). This study suggests that the degree of shift of activation balance toward the contralesional hemisphere early after stroke increases with the extent of tissue injury and that functional recovery is associated mainly with preservation or restoration of activation in the ipsilesional hemisphere.

Animals↗

PubMed2003

[Regulatory systems of genome domains with vague boundaries].

The specific features of genome domains lacking distinct boundaries are considered. These domains cannot be mapped by testing extended genome regions for nuclease sensitivity and thereby differ from structural domains determined at the level of DNA folding in chromatin. Yet they possess the properties of typical functional domains, containing a gene or several coordinated genes along with a complex of cis-regulatory elements, which control these genes. Domains with vague boundaries may be mapped with certain structural tests, e.g., by assessing histone acetylation or the distribution of tissue-specific DNase I-hypersensitive sites through extended genome regions. The mechanisms are described in detail that regulate the function of genes in domains with vague boundaries, including overlapping domains with genes differing in tissue specificity of expression.

Animals↗

PubMed2003

A physiological correlate of the "Zoom Lens" of visual attention.

Attending a certain region in space enhances activity in visual areas retinotopically mapped to this region; stimuli presented in this region are preferentially processed. The zoom lens model of visual attention proposes that the attended region can be adjusted in size and predicts a tradeoff between its size and processing efficiency because of limited processing capacities. By means of event-related functional magnetic resonance imaging, we analyzed neural activity in multiple visual areas as a function of the size of an attended visual field region, which was defined by a spatial cue stimulus. After cueing, a target object, defined by a specific feature conjunction, had to be identified among objects within the cued region. Neural activity preceding the objects in multiple retinotopic visual areas correlated with the size of the attended region, as did subjects' performance. While the extent of activated retinotopic visual cortex increased with the size of the attended region, the level of neural activity in a given subregion decreased. These findings are consistent with the physiological predictions of the zoom lens model. Size-related modulations of neural activity were pronounced in early visual areas. We relate this finding to the small receptive field of these areas, whereby only neuronal units with receptive fields covering the attended region received a top-down bias. This preactivation of neuronal units may then have gated selective processing of the features of the object that appeared at the attended location, thus enabling feature integration and object identification.

Adult↗

PubMed1992

The retinoblastoma gene product suppresses neu oncogene-induced transformation via transcriptional repression of neu.

The retinoblastoma susceptibility gene (Rb) is a tumor suppressor gene involved in the etiology of many types of human cancers. However, the molecular mechanisms involved in tumor suppression by Rb are largely unknown. The neu gene is a dominant transforming oncogene and a member of the growth factor receptor tyrosine kinase gene family. Both inactivation of the Rb gene and overexpression of the neu gene are involved in human breast and lung cancers. Therefore, it is of interest and importance to investigate the potential interactions between Rb and neu. Here we show that Rb suppresses neu-induced transformation by focus formation assays. This transformation suppression by Rb was further shown to be due to transcriptional repression of neu using Rb expressing effector plasmid and neu promoter-chloramphenicol acetyltransferase reporter gene. The cis-acting element conferring Rb-mediated repression was mapped to a recently identified novel enhancer in the neu promoter. The data indicate that the growth factor receptor neu is a target for the Rb gene product and transcriptional repression of a dominant oncogene expression may be one of the molecular mechanisms of Rb-mediated tumor suppression.

3T3 Cells↗

PubMed2004

[Thyrotoxic encephalopathy showing reversible diffusion-weighted imaging abnormalities].

A 31-year-old man was transferred to our emergency room (ER) with acute onset of high-grade fever and consciousness disturbance. His consciousness at ER was severely disturbed with restlessness. No apparent focal neurological signs were seen. MRI with diffusion-weighted images (DWI) showed high signal intensities at the corpus callosum, left cerebellar hemisphere, left deep white matter and right middle cerebellar peduncle. These lesions were low signals in apparent diffusion coefficient(ADC) map, indicating cytotoxic edema. EEG showed enhanced fast waves seen in predominantly frontal regions. CSF examination was normal except elevated initial pressure of 210 mmH2O. He was treated with high dose dexamethasone and acyclovir. His consciousness and high-grade fever with systemic inflammatory responses were dramatically improved after these treatments. Subsequent data showed hyperthyroidism with anti-thyroid stimulating hormone receptor antibodies. This case was thought to be a thyrotoxic encephalopathy with beneficial response to corticosteroid therapy. Abnormalities seen in DWI and EEG were normalized ten days later.

Acyclovir↗

PubMed2004

Models for the neuroethical debate in the community.

Citing a line from ancient Sanskrit wisdom, "there is nothing in the world so purifying as knowledge," John Timpane urges the adoption of a roots-up process by which citizens, in organized forums, deliberate critical neuroethical issues. The author suggests several ways such a deliberative process might play out with some top neuroethics issues--enhancement, stem-cell research, and the use of "brainprints"--to show how the citizen groups might form consensus recommendations. "We have time before the wave of the new neuroscience crests," he writes. "Best to discuss it now before the wave is upon us."

Aging↗

PubMed2005

Optimisation of statistical methodologies for a better diagnosis of neurological and psychiatric disorders by means of SPECT.

In the last years there has been a wide consensus on the importance of brain imaging in assessing neurodegenerative and psychiatric disorders. Different techniques for functional and anatomical examination are currently clinically implemented in neurology and psychiatry to improve sensitivity, specificity and accuracy of the diagnosis of various diseases. In addition, the increasing life expectancy in the Western world raises the social importance and the economical impact of age-related neurodegenerative disorders since the incidence of Alzheimer disease and Parkinson disease is higher in the elderly. An early diagnosis of neuro-psychiatric diseases and the assessment of "natural" changes of regional cerebral blood flow (rCBF) distribution during normal aging are hence of utmost importance. In the recent past brain disorders have extensively been investigated by means of optimised nuclear medicine techniques, instruments and algorithms. Diagnosis can be better achieved by identifying those structures in which CBF or metabolism deviate from normality resulting in significant changes as compared to a reference database. In the present paper we present some studies investigating, by means of recently implemented diagnostic tools, patients bearer of various neuro-psychiatric disorders. The improved nuclear medicine techniques and instrumentation, the state-of-the-art software for brain imaging standardisation and the use of sophisticated multivariate data analysis are extensively reviewed.

Algorithms↗

PubMed2006

[Study on safety of apnea test in clinical determination of brain death].

OBJECTIVE: To determine the occurrence of severe complications such as hypotension, pulmonary artery hypertension as well as hypercapnia during apnea test in the affirmation of brain death and to investigate the possible effective prophylactic interventions. METHODS: Conventional apnea test was performed in 15 clinically suspected brain death patients. Stable circulation was achieved by adjusting preload only (n=4) or combined with titrating norepinephrine (NE, n=11). Blood gas was respectively analyzed before apnea test, 10 minutes after 100% fraction of oxygen (FiO(2)) ventilation, at each 2-minute interval after disconnecting ventilator and 5 minutes after reventilation. Hemodynamic parameters and dosage of NE were recorded at the same time points. Plasma concentration of lactate was measured before and at the end of apnea test. RESULTS: Spontaneous breath occurred in 1 case among 15 suspected brain death patients. Partial pressure of carbon dioxide (PaCO(2)) reached higher than 60 mm Hg (1 mm Hg=0.133 kPa) within 8 minutes in positive apnea test patients (P<0.01). pH significantly decreased (P<0.05), but partial pressure of oxygen (PaO(2)) maintained higher than 100 mm Hg during the test. Heart rate (HR) and mean artery pressure (MAP) slightly lowered (P>0.05), but pulmonary artery pressure (PAP) markedly elevated (P<0.05) at the end of the test in comparison with their base lines. On the other hand, HR and MAP increased in the negative apnea test case after ventilator disconnection. Severe arrhythmia events did not occur in all the cases. There was no change in the dosage of NE infusion, the range of which was 0.10-0.60 microg.kg(-1).min(-1) with the mean level of (0.23+/-0.17) microg.kg(-1).min(-1). The trend of HR, MAP, PAP and pulmonary arterial wedge pressure (PAWP) alterations was the same in patients no matter whether or not NE was used. HR, MAP and PAWP lowered, while PAP enhanced. Plasma lactate level was not significantly altered at the end of the test compared with the base line (from (1.41+/-0.05) mmol/L to (1.47+/-0.07) mmol/L). CONCLUSION: Adequate oxygenation could be maintained during conventional apnea test. The risk of inducing severe hypotension is low in non brain death patients. Based on adequate preload, low dose of NE infusion could prevent patients with high risk circulation instability from severe hypotension.

Adult↗

PubMed1991

MRI and stereotaxis. Choice of an approach route on an independent console.

The authors report their experience of cerebral stereotaxis for biopsy purposes. Since January 1990, they have been using MRI which provides vascular images and makes it possible to simulate surgical procedures beforehand. The authors have developed a specific program on an independent console. MRI sections are acquired with a 1.5 Tesla Sigma (G.E.) apparatus in 3DFT volume and T1-weighted SPRG sequence, after gadolinium injection. The sections are memorized and reconstructed by a SUN computer. After automatic recognition of the referential of a Leksell G plane, the target and the puncture vector are chosen by a radiologist and a neurosurgeon. The X, Y, Z co-ordinates of the point of puncture and the angles of penetration into the cerebral volume are delivered automatically. Provided the entire measurement chain is constantly tested and corrected if necessary, the precision of the system is of the order of one millimetre.

Brain Mapping↗

PubMed1990

Primary malignant hepatic tumors in children--a clinicoradiological profile.

A retrospective analysis of clinicoradiological records of 14 patients with primary malignant tumors of liver (12 hepatoblastomas, 2 embryonal sarcomas) was done. High levels of alpha feto protein were found in four out of six patients and plain X-ray calcification was seen in 33% of patients with hepatoblastoma. Hepatoblastoma was predominantly (80%) a right lobar, illdefined, heterogenous solid mass, which was mixed attenuating on CT scan with areas of patchy enhancement. Angiography was useful in vascular mapping for surgery. A rare association of congenital dysplastic kidney with hepatoblastoma was noted. The imaging protocol for a malignant hepatic tumor and possible differentiating features from the rare entity of embryonal sarcoma are discussed.

Carcinoma, Hepatocellular↗

PubMed1993

I-compounds--endogenous DNA markers of nutritional status, ageing, tumour promotion and carcinogenesis.

Certain bulky DNA modifications increase with age in laboratory animals without known exposure to carcinogens and are known as indigenous or I-compounds. Most of the spots detected on TLC maps by the nuclease P1-enhanced bisphosphate version or the monophosphate version of the 32P-postlabelling assay fit this definition of I-compounds. Chromatographic profiles and levels of these nucleotides greatly depend on animal species, strain, tissue and gender, but are also influenced by the diet and by chemical exposures. Thus, both genetic and environmental factors contribute to the formation of I-compounds. It appears that they are derived from endogenous DNA-reactive compounds generated during normal nutrient metabolism and that regulatory mechanisms exist which control their levels in tissue DNA.

Aging↗