Genetic manipulation of the renin-angiotensin system.
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Angiotensinogen↗
Biomedical subjects
T H Le
Publications and source records attributed to T H Le.
Human hippocampal long-term sustained response during word memory processing.
Temporal behavior of activation associated with the neural substrate of human memory function was investigated during and after an auditorily instructed word memory task using multislice functional magnetic resonance imaging. The hippocampal formation, which is involved in human memory function, displayed a long-term sustained response that persisted significantly (approximately 90 s) beyond the duration of the memory task. This sustained period was approximately two-fold longer than the duration of the post-task activation observed in auditory areas and Broca's area, which are involved in the phonological loop of the verbal working memory. These observations suggest that the hippocampal memory processing involves sustained activation in the transitional function for the long-term memory over the working memory period.
Adult↗
4 T-fMRI study of nonspatial shifting of selective attention: cerebellar and parietal contributions.
Regional blood oxygenation in the cerebellum and posterior cerebral cortices was monitored with functional magnetic resonance imaging (fMRI) at four Tesla while 16 normal subjects performed three tasks with identical visual stimulation: fixation; attention focused upon either stimulus shape or color and sustained during blocks of trials (sustained attention); and rapid, serial shifts in attention between stimulus shape or color within blocks of trials (shifting attention). The stimuli were displayed centrally for 100 ms followed by a central fixation mark for 900 ms. Each stimulus was either a circle or a square displayed in either red or green. Attention shifting required switching between color and shape information after each target detection and occurred on average once every three seconds. Subjects pressed a response key upon detecting the target; reaction time and response accuracy were recorded. Two protocols for T2*-weighted echo-planar imaging were optimized, one with a surface coil for the cerebellum alone and the other with a volume coil for imaging both cerebellum and posterior brain structures (parietal, occipital, and part of temporal cortices). Because fMRI of the cerebellum is particularly susceptible to cardiac and respiratory fluctuations, novel techniques were applied to isolate brain activation signals from physiological noise. Functional activation maps were generated for contrasts of 1) sustained attention to color minus fixation; 2) sustained attention to shape minus fixation; and 3) shifting attention minus sustained attention (to color and shape; i.e., summed across blocks of trials). Consistent with the ease of these tasks, subjects performed with >80% accuracy during both sustained attention and shifting attention. Analysis of variance did not show significant differences in false alarms or true hits across either attentional condition. A subgroup of subjects whose performance data were recorded during ten minutes of continuous practice did not show significant changes over time. Both contrasts between the conditions of sustained attention to color or to shape as compared with the fixation condition showed significant bilateral activation in occipital and inferior temporal regions (Brodmann areas 18, 19, and 37). The anterior medial cerebellum was also significantly activated ipsilateral to the finger used for responding. The principal comparison of interest, the contrast between the condition of shifting attention and the condition of sustained attention produced significant and reproducible activation: lateral cerebellar hemisphere (ansiform lobule: Crus I Anterior and Crus I Posterior; left Crus I Posterior); cerebellar folium; posterior superior parietal lobule (R and L); and cuneus and precuneus (R and L).
Adult↗
Evaluation of the early response in fMRI in individual subjects using short stimulus duration.
Optical imaging studies have provided evidence of an initial increase in deoxyhemoglobin following the onset of neuronal stimulation/activation and demonstrated that this initial increase could be spatially more specific to the site of neuronal activity. These studies also raised the possibility of improving the specificity of fMRI by selective mapping of this early response. Previous MR studies reported the observation of this early response but were limited in scope and not in full agreement. This paper presents a more extensive study that (a) demonstrates the initial signal decrease in individual subjects and (b) examines its dependence on stimulus duration and subject. Binocular visual stimulation experiments were performed on 14 subjects using echo-planar imaging (EPI) with high temporal resolution. An initial signal decrease was consistently observed in regions that were more localized than those displaying the delayed positive response. In agreement with previous fMRI and optical imaging findings, the maximum signal decrease was 1-2% and occurred at approximately 2 s after the onset of the stimulus, depending on the subject. For stimulus longer then 3.0 s, the temporal dynamics and the amount of signal change of the early response was essentially independent of the stimulus duration, while the delayed response and the post-stimulus undershoot increased both in terms of magnitude and rise time as the duration of the stimulus increased; this observation is concordant with the recent optical imaging study.
Brain↗
Altered ionic calcium and cell motion in ventricular myocytes after cutaneous thermal injury.
Cutaneous thermal injury resulting in burns covering approximately 45% of the total body surface area initiates metabolic alterations which contribute to subsequent myocardial dysfunction. Alterations in calcium homeostasis have been proposed as one mechanism by which burn injury alters organ function. This study used fura-2 and time-resolved single cell fluorescence microscopy to examine stress-related alterations in intracellular calcium in isolated adult rat cardiac myocytes. Ventricular myocytes were isolated from rats given a full-thickness scald burn comprising 43% of the total body surface area and fluid resuscitated with lactated Ringer's by the Parkland formula; control animals were included for comparison. Burn trauma caused a significant increase in cardiac myocyte maximal (peak systolic) and minimal (diastolic) mean cytosolic free calcium concentration ([Ca2+]i) transient ratios when compared to [Ca2+]i transient ratios measured in control rats. Isoproterenol application altered the time course of the [Ca2+]i transients of normal myocytes but this response was not observed in myocytes from the thermally injured rats. In addition, isoproterenol application to normal myocytes produced a significant increase in the amplitude of cell edge motion (+50%) compared to the cell edge motion measured in myocytes without isoproterenol stimulation; however, this cell motion response did not occur after isoproterenol application to myocytes from thermally injured rats. Caffeine application increased the maximal and minimal [Ca2+]i transient ratios of all myocytes, regardless of a burn injury, and the time course of the [Ca2+]i transients from the two groups appeared similar in the presence of caffeine as the myocytes progressed to contracture. Our data suggest that burn-mediated alterations in calcium homeostasis contribute, in part, to the cardiac contractile dysfunction which occurs after burn injury.
Animals↗
Genetically variable triplet repeats in a RING-finger ORF of Helicoverpa species baculoviruses.
Nucleotide sequence analysis of the Helicoverpa zea S-type nucleopolyhedrovirus (HzSNPV) genomic interval between the polh and iel genes has revealed an open reading frame (HOAR ORF) that contains a complex A 1-T rich triplet repeat region (RAT-repeats). HOAR ORF is predicted to encode an acidic, arginine residue rich. 712 aa protein, with a C3HC4 (RING-finger) zinc binding motif. RAT-repeats, distributed over 450 bp. consist of GAT. AAT, and GTT codons, correspond to Asp, Asn and Val residues which display an extreme codon bias not seen with nine other genes of this virus. A survey of four other (field) isolates of Helicoverpa sp. NPVs confirms a high incidence of mutation in the RAT-repeat region. A 158-bp conserved block, homologous to the pe38-ien promoter of AcMNPV, was identified upstream of HOAR ORF. The sub-region of the genome in which HOAR ORF is located is susceptible to rearrangement.
Amino Acid Sequence↗
Outpatient bowel preparation for elective colon resection.
To determine the safety and cost-effectiveness of outpatient preoperative bowel preparation with polyethylene glycol-electrolyte lavage solution, we retrospectively analyzed 726 cases of colectomy done by colon and rectal surgeons between July 1987 and July 1991. Included were 319 patients who had elective segmental or total abdominal colectomy with primary anastomosis. Patients who required protective proximal stoma were excluded. Patients requiring emergency surgery, colostomy closure, and restorative proctocolectomy were excluded. Patients were separated into two groups equally matched by age, sex, procedure done, and comorbidity: 145 had bowel preparation as outpatients and 174 as inpatients. Both groups had similar numbers of days hospitalized, days receiving nothing by mouth, and days requiring nasogastric intubation or gastrostomy tube, as well as similar postoperative complications. There was one wound infection, one anastomotic leak, and one death in each group. Cost of outpatient preparation was approximately $40. Cost of inpatient preparation, including a semiprivate room, was approximately $400. Outpatient preparation with polyethylene glycol-electrolyte lavage solution and oral antibiotics before elective colon resection can be done with equivalent safety and at a substantial cost savings.
Adult↗
Retrospective estimation and correction of physiological artifacts in fMRI by direct extraction of physiological activity from MR data.
A physiological artifact reduction method based on extracting respiratory motion and cardiac pulsation directly from functional MR data is described. In fast low angle shot (FLASH), respiratory cycles are derived utilizing the phase of the center of a navigator echo, in echo-planar imaging (EPI) from the phase of the center k-space point. Cardiac cycles are determined from projections obtained from the navigator echo (FLASH) and the center k-space line (EPI). Because direct extraction of physiological parameters eliminates the need for external monitoring, the method can be more readily implemented. Experimental results illustrate that the technique provides effective compensation for physiology-related signal fluctuations in functional MRI and performs as well as the retrospective technique using external physiological monitoring.
Artifacts↗
Artifact reduction in EPI with phase-encoded reference scan.
Echo-planar imaging is becoming widely used for various applications. However, because of inherent limitations, images obtained with EPI are often degraded by artifacts arising from the inconsistency between the odd and even echoes in the acquired data. Several correction techniques, including those based on reference measurement, have been previously reported. In this paper, a correction method based on phase-encoded reference measurement is described. This technique is demonstrated with experimental data obtained at 4 Tesla and compared with techniques that use nonphase-encoded reference scan. Results from experimental studies indicate that the present approach reduces the ghost intensity by a factor of 2-3.
Algorithms↗
Demonstration of efficacy of combining corticosteroids and colchicine in two patients with idiopathic sclerosing mesenteritis.
Sclerosing mesenteritis is an uncommon condition of unknown etiology. It is likely to be the fibrous evolution of mesenteric panniculitis. It often has an indolent course but may be complicated by progressive bowel obstruction. The treatment of the symptomatic forms is not well established. The observations of two women (20 and 65 years old) with a relentless downhill course of biopsy-proved sclerosing mesenteritis are described. A treatment regimen with corticosteroid therapy (initially 1 mg/kg/day) and colchicine (1 mg/day) led, in both cases, to a rapid improvement. Abdominal computer tomography showed reduction in the tumor size. The combination of corticosteroids and colchicine is helpful in the management of symptomatic sclerosing mesenteritis. Follow-up with abdominal computed tomography is useful in evaluating the therapeutic impact.
Adult↗
Effects of different oxidative insults on intermediary metabolism in isolated perfused rat hearts.
13C and 31P NMR were used to evaluate exogenous substrate utilization and endogenous phosphate metabolites in perfused rat hearts exposed to tert-butylhydroperoxide (tert-BOOH) and hydrogen peroxide (H2O2). Both reagents caused a reduction in developed pressure compared to controls and, in agreement with previous 31P NMR data, had different effects on intracellular high-energy phosphates and glycolysis. 13C Isotopomer analysis of tissue extracts showed that H2O2 and tert-BOOH also had significantly different effects on substrate utilization by the citric acid cycle. The contribution of exogenous lactate and glucose to acetyl-CoA was 43% in controls and increased to over 80% in the presence of either oxidant. With tert-BOOH, exogenous glucose and lactate were both significant contributors to acetyl-CoA (44 +/- 2 and 41 +/- 3%). However, with H2O2, exogenous lactate supplied a much higher fraction of acetyl-CoA (72 +/- 2%) than glucose (9 +/- 1%). Also, when [2-(13)C] glucose was supplied, accumulation of [2-(13)C] and [5-(13)C] fructose 1,6-bisphosphate was observed in the presence of H2O2, indicating inhibition of glyceraldehyde-3-phosphate dehydrogenase. These results indicate that despite this glycolytic inhibition, H2O2 increased the utilization of pyruvate precursors when lactate was present as an alternative carbohydrate substrate.
Animals↗
Structural and functional properties of mutant Arg203Pro from yeast phosphoglycerate kinase, as a model of phosphoglycerate kinase-Uppsala.
A pathological variant of human phosphoglycerate kinase, phosphoglycerate kinase-Uppsala, associated with chronic nonspherocytic hemolytic anemia has been found to differ from the normal enzyme by substitution of an arginine at position 206 (corresponding to position 203 in yeast) by a proline. In order to understand the structural and functional consequences of this mutation, the corresponding mutant in yeast phosphoglycerate kinase was constructed. The three-dimensional structure of this mutant was resolved at 2.9 A. Although the overall structure is not modified, small local changes were observed. The kinetic parameters of the mutant were not found to be greatly affected, the catalytic constant being lowered by only 10-20%. The most significant difference when compared with the wild-type enzyme is a decrease in stability by about 3 kcal/mol. The physiological implications of this instability are discussed.
Circular Dichroism↗
Retrospective estimation and correction of physiological fluctuation in functional MRI.
Image-to-image fluctuation due to physiological motion is a major limitation to the accurate detection of neuronal activity with functional MRI. In this paper, a new and general technique for the estimation and compensation of the physiological effects is presented. By simultaneously monitoring the respiration and heart beat during the acquisition of imaging data, and retrospectively synchronizing the imaging data with physiological activity, physiological effects are estimated and removed. This technique does not rely on the periodicity of the respiration or the heart beat, does not affect the signal changes arising from neuronal activation, and is beneficial to images acquired with any speed. Experimental studies performed with FLASH and EPI sequences have demonstrated that the new technique is effective in reducing physiological fluctuation and improving the sensitivity of functional MRI and is generally applicable.
Algorithms↗
Extrahepatic biliary obstruction resulting from a pancreatic pseudoaneurysm.
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Acute Disease↗
Effects of oxidant exposure on substrate utilization and high-energy phosphates in isolated rat hearts.
The effects of a xanthine oxidase-mediated free radical-generating system containing purine and iron-loaded transferrin or solutions containing hydrogen peroxide and iron-loaded transferrin on substrate utilization and high-energy phosphates were evaluated by nuclear magnetic resonance (NMR) spectroscopy in isolated perfused rat hearts. Hearts were supplied with lactate, acetate, and glucose, and the contribution of each substrate to acetyl coenzyme A was measured in control hearts and in the presence of a free radical-generating system. Perfused hearts were monitored by 31P NMR, and tissue extracts were analyzed by 13C NMR. Free radicals decreased the phosphocreatine and beta-ATP peak areas and reduced contractile function. Under control conditions, lactate, acetate, and endogenous sources were the major contributors of acetyl coenzyme A units, with only 5% originating from glucose. In the presence of a xanthine oxidase-mediated free radical-generating system, the glucose contribution increased to 54%, while contributions from acetate and endogenous sources were significantly reduced. Both 13C and 31P NMR analyses showed no significant accumulation of glycolytic sugar phosphates, suggesting little inhibition of glyceraldehyde-3-phosphate dehydrogenase. The increased contribution of glucose to the tricarboxylic acid cycle relative to acetate and endogenous sources is consistent with activation of pyruvate dehydrogenase. In contrast, hearts exposed to a hydrogen peroxide-based free radical-generating system showed an increase in lactate utilization, a decrease in acetate utilization, and no change in glucose utilization compared with control hearts. Glycolytic sugar phosphates were found to accumulate, suggesting possible inhibition of glyceraldehyde-3-phosphate. Thus, different radicals or their metabolites may have varying effects on myocardial metabolism.
Acetates↗
Long-term evaluation of immune status in leprosy patients undergoing multiple drug therapy.
A long-term survey of leprosy patients of all clinical types, starting at the time of diagnosis, was carried out to monitor clinical, bacteriological and immunological parameters at regular intervals during multiple drug therapy (MDT). The patients were assigned to two groups for treatment following WHO guidelines: paucibacillary (PB) and multibacillary (MB). Immunoglobulin levels, specific antibodies, skin-test responses to different soluble mycobacterial antigens (new tuberculins), and in vitro proliferative responses to mitogens and to antigens were measured during treatment, as were clinical changes, the bacterial index, and clinical improvement. No exact relations between disease activity and IgM antibody levels, both IgM immunoglobulin and specific IgM antibody to a species-specific antigen (ND-O-BSA), could be seen for MB patients. Changes in in vitro cell-mediated immunity and skin-test response seemed to be more directly related to the bacterial load and could reflect the improvement of bacteriological and clinical parameters during MDT.
Agglutination Tests↗
Reconstitution of intestinal continuity after extended left colectomy.
We wish to reintroduce an infrequently employed technique to re-establish intestinal continuity after extended resection of the left colon, transverse colon, and distal ascending colon. It involves bringing the proximal ascending colonic stump through the distal ileal mesenteric defect to reach the distal rectal stump in a tensionless fashion.
Anastomosis, Surgical↗
Disseminated histoplasmosis with glomerulonephritis mimicking Wegener's granulomatosis.
Renal complications of disseminated histoplasmosis include chronic recurrent abcesses of the interstitium and urogenital tract. To our knowledge, glomerulonephritis has never been reported in histoplasmosis. We describe a case of proven histoplasmosis presenting with oral granulomatous ulceration and segmental glomerulonephritis that mimicked Wegener's granulomatosis (WG). All symptoms and renal parameters remitted under itraconazole treatment alone. In conclusion, glomerulonephritis may complicate the course of chronic disseminated histoplasmosis. Since it can masquerade as WG, systematic tissue staining for intracellular microorganisms should be done when WG is suspected.
Diagnosis, Differential↗