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Biomedical subjects

E Tate

Publications and source records attributed to E Tate.

At least 19 recordsLinked to original sources
PubMed2006

Air trapping on computed tomography images of healthy individuals: effects of respiration and body mass index.

AIM: To evaluate the relationships of changes in the lung area during respiration and of individual body mass index (BMI) to air trapping on expiratory computed tomography (CT) in young non-smoking adults of either gender. METHODS: The volunteers were 10 women and 10 men (mean age 25.7 years) who were healthy lifelong non-smokers. We obtained both end-inspiratory and end-expiratory CT images at three levels: the upper, middle and lower lung. The ratio of cross-sectional lung area upon expiration to cross-sectional lung area upon inspiration (lung area ratio) was determined for each lung at each of the three levels. In cases showing air trapping, we calculated the percentage of area of air in relation to the total lung area in each section. BMI was calculated for each participant. RESULTS: Air trapping was present in dependent areas of the lungs of 6 women and 5 men. The mean percentage of area of air trapped was statistically greater for men (9.8+/-9.2%) than for women (4.9+/-5.2%). The mean lung area ratio was 0.52+/-0 14 among volunteers with air trapping (66 sections) and 0.69+/-0.12 among those without air trapping (54 sections) (p < 0.001). At each lung level, the mean lung area ratio was greater in individuals with air trapping than in those without. Mean BMI was also greater in these people (p = 0.009). CONCLUSION: Change in the respiratory lung area and BMI contribute to development of air trapping.

Adult↗
PubMed2005

Portal flow into the liver through veins at the site of biliary-enteric anastomosis.

The aim of this study was to establish the role played by jejunal veins in hepatopetal flow after biliary-enteric anastomosis and to evaluate the helical CT features of hepatopetal flow through the anastomosis. We retrospectively analyzed helical CT images of the liver in 31 patients with biliary-enteric anastomosis who underwent hepatic angiography with (n=13) or without (n=18) CT arterial portography within 2 weeks of the CT examination during the last 4 years. Arterial portography showed hepatopetal flow through small vessels located (communicating veins) between the elevated jejunal veins and the intrahepatic portal branches in two (9%) of 22 patients with a normal portal system. Helical CT showed focal parenchymal enhancement around the anastomosis in these two patients. All nine patients with extrahepatic portal vein occlusion (100%) had hepatopetal flow through the anastomosis, and four of the nine had decreased portal flow. CT revealed small communicating veins in two of these four patients. In five patients with normal portal perfusion despite extrahepatic portal vein occlusion, CT detected dilated communicating veins and elevated jejunal veins. The presence of communicating veins and/or focal parenchymal enhancement around the anastomosis indicates hepatopetal flow through the elevated jejunal veins.

Adult↗
PubMed2004

Segmental high intensity on T1-weighted hepatic MR images.

BACKGROUND: We investigated the diagnostic importance of segmental high-intensity (SHI) areas not corresponding to mass lesions on T1-weighted magnetic resonance (MR) images. METHODS: We conducted a retrospective investigation of hepatic MR images obtained from 634 patients during a 4-year period at our institution. Images were compared with findings reported in the patients' medical records. There were 16 patients (2.5%) with SHI areas not corresponding to a mass lesion. We compared MR images with plain computed tomographic (CT) scans (n = 16), angiograms (n = 12), and histologic findings (n = 10). RESULTS: The segments with intrahepatic bile duct dilatation showed hyperintensity on T1-weighted images. In six of 16 patients, the biliary duct was more dilated in the area of hyperintensity than in areas without hyperintensity. The SHI areas appeared as areas of low attenuation (n = 13), high attenuation (n = 1), or isoattenuation (n = 2) on plain CT scans. Histologically, these areas showed ductular proliferation and deposition of bile pigment within the hepatocytes. CONCLUSION: Segmental areas of increased signal intensity on T1-weighted images were probably due to intrahepatic cholestasis.

Adolescent↗
PubMed2001

The feasibility of retrograde catheterization of the right gastric artery via the left gastric artery.

Retrograde catheterization of the right gastric artery was attempted in 22 patients for the purpose of proximal right gastric artery embolization. Retrograde catheterization was successfully performed in 12 of the 14 patients (86%) with smooth anastomoses. Retrograde catheterization was unsuccessful (n = 1) or time-consuming (n = 1) in two patients (14%) with smooth anastomoses. Right gastric artery embolization was successfully performed with microcoils in 13 of the patients. In all eight patients with tortuous anastomoses, catheterization was unsuccessful. Retrograde catheterization should be considered possible when preliminary angiography indicates a smooth anastomosis with the left gastric artery.

Adult↗
PubMed1999

Comparison of MR imaging with CT in depiction of tumour extension into the pterygopalatine fossa.

The computed tomography (CT) and magnetic resonance imaging (MRI) results of 30 consecutive patients with tumours in the skull base, and who had abnormalities of the pterygopalatine fossa (PPF) on CT or MRI, were retrospectively compared with respect to visualization of tumour infiltration into the PPF. CT did not depict the abnormalities in the PPF in five patients (17%), while unenhanced T1-weighted MR images depicted tumour infiltration in all patients. Obliteration of PPF fat was better visualized on CT than T2-weighted and proton density weighted MR images, as were bony abnormalities. On MRI, intracranial extension was seen in eight of 25 patients with extracranial tumour. MRI is a sensitive method of demonstrating both tumour infiltration of the PPF and perineural tumour spread.

Adolescent↗
PubMed1998

Monoaminergic effects of high-dose corticotropin in corticotropin-responsive pediatric opsoclonus-myoclonus.

Children with the opsoclonus-myoclonus syndrome (OMS) usually respond to corticotropin (adrenocorticotrophic hormone, ACTH) treatment but the mechanism of benefit is unknown. We previously showed that both cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) concentrations are low in pediatric OMS. In this study, we measured levels of CSF Dopa, catecholamines, deaminated metabolites of catecholamines, as well as HVA and 5-HIAA in eight patients before and during treatment with ACTH. All the children were ACTH-responsive with 50-70% improvement in multiple clinical features of OMS. ACTH treatment reduced the HVA concentration in every child by a mean of 21% (p < 0.001). Treatment with ACTH was associated with significant correlations between dopaminergic markers such as HVA, dihydroxyphenylacetic acid (DOPAC), and Dopa. There were no significant changes in the CSF concentrations of the noradrenergic markers norepinephrine (NE) and dihydroxyphenylglycol (DHPG), or the serotonergic marker 5-HIAA. The only child with a marked inflammatory pattern in CSF, which was reversed by ACTH, was atypical for a large increase in NE and decrease in 5-HIAA during ACTH treatment. Beneficial effects of ACTH in OMS are not associated with normalization of HVA or 5-HIAA levels. The pattern of decreased HVA and unchanged DOPAC levels could reflect decreased extraneuronal uptake of catecholamines (which steroids inhibit) or decreased 0-methylation of catecholamines in nonneuronal cells.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Cerebrospinal fluid free choline in movement disorders of paediatric onset.

We measured free choline in cerebrospinal fluid (CSF) of 78 patients with movement disorders of paediatric onset and various controls as a putative index of central phospholipid metabolism. Most of the disorders studied were myoclonic disorders, such as progressive myoclonus epilepsy, the opsoclonus-myoclonus syndrome, and essential myoclonus, but other movement disorders, interictal seizure disorders, and different neurological and nonneurological disorders were also included. There were no significant differences in CSF choline concentrations in myoclonic disorders or other movement disorders compared with controls. The CSF choline levels were lowest in children with seizure disorders including progressive myoclonus epilepsy. In progressive myoclonus epilepsy, the CSF choline values resembled other epileptic disorders rather than other myoclonic disorders. When all the data were analysed collectively, no significant relation of CSF choline was found to patient age, gender, aliquot of CSF measured, or the length of time the sample was stored at -70 degrees C. Separate analyses of data from children and adults showed a trend toward a biphasic relation between patient age and CSF choline which could be pursued in developmental studies of normal subjects. Reduced CSF choline may indicate increased choline incorporation into brain phospholipids, disturbances of choline metabolism, decreased choline release, or non-neural factors.

Acetylcholine↗
PubMed1997

A generic method for the production of cell lines expressing high levels of 7-transmembrane receptors.

G-protein-coupled or 7-transmembrane receptors (7TMRs) are often studied after heterologous expression in mammalian cells such as COS-7, CHO-K1, or HEK-293s. In this paper, we describe the development of a rapid and generic method for producing stable Chinese hamster ovary cell lines expressing high levels of recombinant 7TMRs by N-terminal tagging these proteins with the hemagglutinin (HA) sequence. To illustrate the broad applicability of this technique, we have presented data from cell lines expressing a glycoprotein hormone receptor for follicle-stimulating hormone (FSHR), CXC- (CXCR-2), and CC-chemokine (CCR-1) receptors and peptide receptors from the somatostatin (SSTR1, 2, 5) and neuropeptide Y (NPY-Y2, -Y4 Rs) families. Typically, cell lines with a receptor density of 1 to 15 pmol/mg protein are produced with this method. The presence of the HA tag does not adversely affect the binding or functional activity of the receptors.

Amino Acid Sequence↗
PubMed1997

Disposition of atovaquone in humans.

Atovaquone is an antiprotozoal compound with good in vitro stability against metabolic inactivation. Previous human studies which did not involve radiolabelling had not accounted for a substantial proportion of the dose. The possible metabolism of atovaquone in men was examined in a radiolabelling study involving four healthy male volunteers. Radioactivity was eliminated almost exclusively via the feces. All radioactivity in plasma, urine, and feces was accounted for by atovaquone, with no evidence of metabolites. Radiolabelled atovaquone was administered to a patient with an indwelling biliary tube after surgery. Biliary radioactivity was approximately 10- to 40-fold higher than that in plasma and was accounted for by atovaquone. Atovaquone is not significantly metabolized in humans but is excreted into bile against a high concentration gradient.

Adult↗
PubMed1996

A controlled trial of 5-hydroxy-L-tryptophan for ataxia in progressive myoclonus epilepsy.

To study the role of serotonin in the ataxia of progressive myoclonus epilepsy, eight patients received oral 5-hydroxy-L-tryptophan (L-5-HTP) or placebo plus carbidopa for 1 month in a controlled, double-blinded, dose-ranging, cross-over, add-on study. Ataxia was evaluated using objective and subjective scales. All of the subjects had significantly slower motor performance on timed, repetitive tasks than controls and had moderately severe ataxia. L-5-HTP was not efficacious for ataxia or speed of motor performance. Serotonergic drugs that work through mechanisms different than L-5-HTP may be more effective in correcting the abnormal serotonergic neurotransmission suggested by reduction of serotonin metabolites in cerebrospinal fluid in patients with progressive myoclonus epilepsy.

5-Hydroxytryptophan↗
PubMed1996

Improved green fluorescent protein by molecular evolution using DNA shuffling.

Green fluorescent protein (GFP) has rapidly become a widely used reporter of gene regulation. However, for many organisms, particularly eukaryotes, a stronger whole cell fluorescence signal is desirable. We constructed a synthetic GFP gene with improved codon usage and performed recursive cycles of DNA shuffling followed by screening for the brightest E. coli colonies. A visual screen using UV light, rather than FACS selection, was used to avoid red-shifting the excitation maximum. After 3 cycles of DNA shuffling, a mutant was obtained with a whole cell fluorescence signal that was 45-fold greater than a standard, the commercially available Clontech plasmid pGFP. The expression level in E. coli was unaltered at about 75% of total protein. The emission and excitation maxima were also unchanged. Whereas in E. coli most of the wildtype GFP ends up in inclusion bodies, unable to activate its chromophore, most of the mutant protein is soluble and active. Three amino acid mutations appear to guide the mutant protein into the native folding pathway rather than toward aggregation. Expressed in Chinese Hamster Ovary (CHO) cells, this shuffled GFP mutant showed a 42-fold improvement over wildtype GFP sequence, and is easily detected with UV light in a wide range of assays. The results demonstrate how molecular evolution can solve a complex practical problem without needing to first identify which process is limiting. DNA shuffling can be combined with screening of a moderate number of mutants. We envision that the combination of DNA shuffling and high throughput screening will be a powerful tool for the optimization of many commercially important enzymes for which selections do not exist.

Animals↗
PubMed1996

In vitro selection of peptides acting at a new site of NMDA glutamate receptors.

Oligomeric N-methyl D-aspartate receptor (NMDAR) in brain is a ligand-gated ion channel that becomes selectively permeable to ions upon binding to ligands. For NMDAR channel, the binding of glutamate and glycine results in opening of the calcium permeable channel. Because the calcium influx mediated by NMDAR is important for synaptic plasticity and excitotoxicity, the function of NMDA receptors has been implicated in both health and disease. Native NMDA receptors are thought to be heteromeric pentamers with a central ion conduction pathway. There are five genes (NR1, 2A, 2B, 2C, and 2D) encoding various subunits that have been cloned, and NR1 is thought to be the essential subunit since it forms a functional channel by itself. To study NMDAR structure and function, we have searched for peptide modulators of NR1 using random peptide bacteriophage libraries. The peptides were identified based on their specific association with a purified receptor fusion protein that contains the putative ligand binding domain. We report the identification of one group of cyclic peptides (Mag-1) with a consensus sequence of CDGLRHMWFC. Using biochemical binding analysis and patch clamp electrophysiological recording, we show that the synthetic Mag-1 peptides cause noncompetitive inhibition of the receptor channel activity.

Amino Acid Sequence↗
PubMed1995

Cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic acid in the pediatric opsoclonus-myoclonus syndrome.

To study the purported role of central monoamine disturbances in the pathophysiology of the opsoclonus-myoclonus syndrome, the serotonin metabolite 5-hydroxyindoleacetic acid and the dopamine metabolite homovanillic acid were measured in cerebrospinal fluid samples from 27 affected children and 47 age- and gender-matched control subjects by high-pressure liquid chromatography with electrochemical detection. 5-Hydroxyindoleacetic acid and homovanillic acid concentrations in the cerebrospinal fluid were approximately 30 to 40% lower in opsoclonus-myoclonus patients compared to control subjects, and the normal inverse correlation between age and monoamine metabolite concentrations in the cerebrospinal fluid of control subjects was not found in opsoclonus-myoclonus patients. Patients with the lowest values were less than 4 years old, and a subgroup had extremely low levels, but differences in older children were not significant. Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid and homovanillic acid were more positively correlated in control subjects than in opsoclonus-myoclonus patients. None of the patients exhibited high levels of monoamine metabolites. Homovanillic acid levels were slightly lower in the cerebrospinal fluid of patients receiving corticotropin or steroids at the time of lumbar puncture. Clinical variables that could be excluded were paraneoplastic etiology, anesthetic for lumbar puncture, syndrome duration, age at onset, gender, response to steroids, length of time until initiation of corticotropin or steroids, presence of seizures, opsoclonus, and functional impairment. These data suggest a disturbance and possible altered ontogeny of serotonin or dopamine neurotransmission in a subpopulation of children with opsoclonus-myoclonus with low cerebrospinal fluid levels of 5-hydroxyindoleacetic acid and homovanillic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1995

A generic method for expression and use of "tagged" soluble versions of cell surface receptors.

A general method for expression, purification, immobilization, detection and radiolabeling of extracellular domains (ECD) of type I membrane proteins. The type I interleukin-1 receptor (IL-1RtI), the alpha-subunit of interleukin-2 receptor (IL-2R alpha) and E-selectin are used as illustrative examples of cell surface receptors. DNA encoding the ECD of the proteins are fused at their 3' end to a chimeric DNA which serves to generically "tag" the recombinant ECD. The resulting fusion protein contains a substrate sequence for protein kinase-A (PKA) adjacent to the signal sequence from human placental alkaline phosphatase (HPAP), The HPAP signal sequence directs the formation of the phosphatidylinositol-glycan (PI-G) anchorage of the protein at the cell surface. When these chimeric genes are expressed in CHO cells, the ECDs are detected on the cell surface and can be released by treatment with phosphatidylinositol-specific phospholipase-C (PI-PLC). Based on protein processing known to occur for native HPAP, twenty amino acids from the HPAP signal sequence remain at the C-terminus of the ECD. A high affinity monoclonal antibody was generated against this common epitope. This antibody can be used to detect, purify and immobilize the ECDs. In addition, the ECDs can be radiolabeled with 32P by treatment with PKA and maintain the ability to bind their natural ligands. This "tagging" method has been successfully applied to many other type I proteins which serve as cell surface receptors.

Alkaline Phosphatase↗
PubMed1995

Ligand binding kinetics of IL-2 and IL-15 to heteromers formed by extracellular domains of the three IL-2 receptor subunits.

Studies on the binding of IL-2 to its receptor (IL-2R) have generally been limited to receptors expressed on cell surfaces. This has hampered detailed kinetic and mechanistic studies at the molecular level. We have prepared the soluble extracellular domains of all three receptor subunits (called alpha, beta and gamma) by recombinant techniques and have used these to perform detailed kinetic studies of their binding properties using the technique of surface plasmon resonance. We describe a novel approach whereby the receptors are assembled on an antibody surface, being held by an epitope engineered into the C-terminus of each of these domains. Thus the receptors are oriented naturally leading to homogeneous ligand binding kinetics. We have characterized the interactions of the heteromeric complexes of these subunits with mouse and human IL-2 and their analogs, as well as the recently discovered cytokine, IL-15. We have also studied the extracellular domains of the mouse receptor subunits for the first time and have used these as well as mouse-human hybrid receptors to probe the mechanism of assembly of these complexes. We show that no additional proteins are required to reproduce the properties of these complexes in vitro. In addition, kinetic studies with site-specific analogs of IL-2 and the mouse-human receptor hybrids clearly indicate that the extracellular domains of alpha and beta can together readily bind ligand with kinetic properties distinct from those of the constituent subunits. In contrast, a complex containing ligand and the extracellular domains of beta and gamma was comparatively difficult to assemble and required prolonged exposure to IL-2. Our method enabled us to calculate the stoichiometry of these complexes and to determine that anchoring these subunits is necessary to efficiently drive complex formation. The kinetic and equilibrium differences between the mouse and human receptor complexes, and between IL-2 and IL-15 binding to these receptors clarify the roles of the alpha and gamma subunits in the differential response of cells to different cytokines that may be present simultaneously in the environment.

Amino Acid Sequence↗
PubMed1995

A sensitive and semi-quantitative pediatric myoclonus evaluation scale.

One of the difficulties in evaluating myoclonus in childhood is the lack of a standardized scale which addresses the constraints of pediatric scoring. The scale needs to be simple and rapid as well as sensitive and semi-quantitative and applicable across different ages. We videotaped children and young adults with myoclonus of various etiologies, such as progressive myoclonus epilepsy, opsoclonus-myoclonus and other acquired etiologies, and scored the videotapes using a new scale. Each clinical type of myoclonus (spontaneous, action and sensory-evoked myoclonus) was graded separately on a five-point scale for severity, intensity and distribution. Data were evaluated as separate scores and also combined for a total score. Validity and reliability were tested using a judge panel of three blinded, trained observers. Action myoclonus was the predominant form of myoclonus in our patients, and was significantly greater than spontaneous and sensory-evoked myoclonus in frequency, intensity and distribution. Separate statistical analysis performed for progressive myoclonus epilepsy and for opsoclonus-myoclonus showed the same pattern. Total scores between etiologies of myoclonus for frequency and distribution categories were significantly different. Subscores and total scores were highly correlated. We found the new scale to be flexible and adaptable for children and there were few missing values due to non-applicability of a scale item. It was useful for all pediatric age groups. The scale and videotape instructions provide a reliable tool for use in pediatric myoclonic disorders.

Adolescent↗
PubMed1995

Neurobehavioral and psychosocial functioning of children with opsoclonus-myoclonus syndrome.

Childhood opsoclonus-myoclonus syndrome (OMS) is a movement disorder which typically strikes children in the early preschool years, seriously affecting intellectual, social-emotional and general adaptive development. This series of 13 cases with well-documented neurological histories, aged 1.7 to 16.3 years, provides an initial systematic evaluation of these children's neuropsychological, psychosocial and adaptive status. As expected, children with OMS had significantly reduced intelligence and severe speech and motor output problems; however, most of them also demonstrated a range of preserved neurocognitive abilities and impressive goal-directedness and communicative effort. Psychosocial problems included mild behavioral impairment on the Achenbach Child Behavior Checklist, and severe adaptive limitations on the Vineland Adaptive Behavior Scales despite relatively strong social skills. Developmental factors and likelihood of subcortical localization are discussed, and practical guidelines are provided for behavioral and educational management of these children.

Adolescent↗