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Biomedical subjects

M E Smith

Publications and source records attributed to M E Smith.

At least 73 records · Page 4Linked to original sources

Ancient schwannoma of the orbit.

The ancient schwannoma is a rare variant of a neurilemoma with a course typical of a slow-growing benign neoplasm. Histologically, it can be confused with a malignant mesenchymal tumor because of increased cellularity, nuclear pleomorphism, and hyperchromatism. Despite the degree of nuclear atypia, mitotic figures are absent. We describe the clinical and histopathologic features of an ancient schwannoma of the orbit.

Diagnosis, Differential↗

Herpes simplex virus mediated gene transfer to primate ocular tissues.

We evaluated the feasibility of delivering a gene into monkey eyes using a replication-competent herpes simplex virus (HSV) type 1 ribonucleotide reductase mutant (hrR3) expressing the Escherichia coli lacZ gene. To determine the efficiency of in vitro HSV-mediated gene transfer, cultured human trabecular meshwork (HTM) and human ciliary muscle (HCM) cells were infected with hrR3 and beta-galactosidase activity was measured histochemically. Six cynomolgus monkey eyes received viral injections into the anterior chamber (2 x 10(7) pfu) and/or the vitreous (5 x 10(7) pfu), and the distribution of cells expressing lacZ was evaluated. In vitro, both cultured HTM and HCM cells displayed multiplicity-dependent beta-galactosidase activity. In vivo, intracameral and/or intravitreal injection resulted in transgene expression in TM cells and in non-pigmented ciliary epithelial cells (NPE), but not in CM cells. Transgene expression was also detected in retinal pigmented epithelial (RPE) cells and sporadic retinal ganglion cells (RGC) in eyes receiving virus intracamerally and intravitreally respectively. We observed significant inflammation in the anterior chamber, TM and CM in virus-injected eyes, along with mild vitritis and retinitis. This study demonstrates successful gene transfer using hrR3 as a vector in human ocular cells and in ocular tissues in living monkeys. Further investigation of the etiology of the inflammatory response, possible cytotoxicity, and limited duration of transgene expression is necessary in order to make this technique clinically applicable.

Animals↗

Age dependence of clinical and pathological manifestations of autoimmune demyelination. Implications for multiple sclerosis.

A prominent feature of the clinical spectrum of multiple sclerosis (MS) is its high incidence of onset in the third decade of life and the relative rarity of clinical manifestations during childhood and adolescence, features suggestive of age-related restriction of clinical expression. Experimental allergic encephalomyelitis (EAE), a model of central nervous system (CNS) autoimmune demyelination with many similarities to MS, has a uniform rapid onset and a high incidence of clinical and pathological disease in adult (mature) animals. Like MS, EAE is most commonly seen and studied in female adults. In this study, age-related resistance to clinical EAE has been examined with the adoptive transfer model of EAE in SJL mice that received myelin basic protein-sensitized cells from animals 10 days (sucklings) to 12 weeks (young adults) of age. A variable delay before expression of clinical EAE was observed between the different age groups. The preclinical period was longest in the younger (<14 days of age) animals, and shortest in animals 6 to 8 weeks old at time of transfer. Young animals initially resistant to EAE eventually expressed well-developed clinical signs by 6 to 7 weeks of age. This was followed by a remitting, relapsing clinical course. For each age at time of sensitization, increased susceptibility of females compared to males was observed. Examination of the CNS of younger animal groups during the preclinical period showed lesions of acute EAE. Older age groups developed onset of signs coincident with acute CNS lesions. This age-related resistance to clinical EAE in developing mice is reminiscent of an age-related characteristic of MS previously difficult to study in vivo. The associated subclinical CNS pathology and age-related immune functions found in young animals may be relevant to the increasing clinical expression of MS with maturation, and may allow study of factors associated with the known occasional poor correlation of CNS inflammation and demyelination and clinical changes in this disease.

Age Factors↗

Observation of hydroxyl groups by 17O solid-state multiple quantum MAS NMR in sol-gel-produced silica.

17O NMR parameters (CQ, eta, delta(iso) and T1) are reported for both Si-O-Si and Si-OH fragments within a silica gel. The Si-OH units have a wide spread of parameters but are typically characterised by a very short T1 (approximately 0.1 ms) and CQ < 200 kHz. These observations have extremely important implications for the quantification of such units in these gels and related glassy materials by 17O NMR. In light of these observations, the 17O NMR experiments have been optimised and a distinct resonance from the OH group is observed in 1D static and magic angle spinning (MAS) NMR measurements as well in the multiple quantum (MQ) experiment.

Gels↗

Neurophysiological indices of strategy development and skill acquisition.

In order to examine neurophysiological changes associated with the development of cognitive and visuomotor strategies and skills, spectral features of the EEG were measured as participants learned to perform new tasks. In one experiment eight individuals practiced working memory tasks that required development of either spatial or verbal rehearsal and updating strategies. In a second experiment six individuals practiced a video game with a difficult visuomotor tracking component. The alpha rhythm, which is attenuated by functional cortical activation, was affected by task practice. In both experiments, a lower-frequency, centrally distributed alpha component increased between practice sessions in a task-independent fashion, reflecting an overall decrease in the extent of cortical activation after practice. A second, higher-frequency, posterior component of the alpha rhythm displayed task-specific practice effects. Practice in the verbal working memory task resulted in an increase of this signal over right posterior regions, an effect not seen after practice with the spatial working memory task or with the video game. This between-task difference presumably reflects a continued involvement of the posterior region of the right hemisphere in tasks that invoke visuospatial processes. This finding thus provides neurophysiological evidence for the formation of a task-specific neurocognitive strategy. In the second experiment a third component of the alpha rhythm, localized over somatomotor cortex, was enhanced in conjunction with acquisition of tracking skill. These alpha band results suggest that cortical regions not necessary for task performance become less active as skills develop. In both experiments the frontal midline (Fm) theta rhythm also displayed increases over the course of test sessions. This signal is associated with states of focused concentration, and its enhancement might reflect the conscious control over attention associated with maintenance of a task-appropriate mental set. Overall, the results suggest that the EEG can be used to monitor practice-related changes in the patterns of cortical activity that are associated with task processing. Additionally, these results highlight the importance of ensuring that subjects have developed stable strategies for performance before drawing inferences about the functional architecture underlying specific cognitive processes.

Adult↗

Myxoid variant of follicular dendritic cell sarcoma arising in the breast.

Follicular dendritic cell sarcoma is a malignant tumor of the follicular dendritic cell which can arise in extranodal sites. We present here a case arising as a mass in the breast of a 41-year-old woman. The tumor was composed of mildly pleomorphic spindly cells with pale ovoid nuclei and cell processes intimately admixed with mature lymphocytes. In much of the lesion the cells were dispersed in cords in a myxoid stroma, and elsewhere there were solid sheets. The neoplastic cells were immunoreactive for CD21, CD35, EMA, and S100 protein, but not for other lymphoid markers or cytokeratin. Electron microscopy showed interdigitating cytoplasmic processes with junctions but no external lamina. The differential diagnosis includes carcinoma, lymphomas, and a variety of myxoid sarcomas. The tumor recurred within a few months and displayed increased nuclear pleomorphism and lymphatic invasion but the patient appears free of disease 3 years after the further excision. This case extends the spectrum of follicular dendritic cell sarcoma in soft tissue sites.

Adult↗

Phagocytosis of myelin in demyelinative disease: a review.

In the cell-mediated demyelinating diseases such as experimental allergic encephalomyelitis and multiple sclerosis, as well as their peripheral nerve counterparts, the phagocytic cells are the agent of myelin destruction. Both resident microglia and peripheral macrophages invading the nervous system have been shown to phagocytize myelin, although microglia appear to be more active, especially at early stages of disease. Several different receptors on these cells have been implicated as myelin receptors, with the Fc- and complement receptors receiving the most attention. Other receptors, especially the macrophage scavenger receptor with its broad specificity deserves further exploration, especially in view of its affinity for phosphatidylserine, which becomes externalized with membrane disruption. Evidence is shown for cytokine regulation of phagocytic activity in both macrophages and microglia. Further investigation of the pathways of cytokine action on myelin phagocytosis through signal transduction molecules will be important for a further understanding of the events leading to myelin destruction in demyelinating diseases.

Animals↗

Deblurring.

In most instances, traditional EEG methodology provides insufficient spatial detail to identify relationships between brain electrical events and structures and functions visualized by magnetic resonance imaging or positron emission tomography. This article describes a method called Deblurring for increasing the spatial detail of the EEG and for fusing neurophysiologic and neuroanatomic data. Deblurring estimates potentials near the outer convexity of the cortex using a realistic finite element model of the structure of a subject's head determined from their magnetic resonance images. Deblurring is not a source localization technique and thus makes no assumptions about the number or type of generator sources. The validity of Deblurring has been initially tested by comparing deblurred data with potentials measured with subdural grid recordings. Results suggest that deblurred topographic maps, registered with a subject's magnetic resonance imaging and rendered in three dimensions, provide better spatial detail than has heretofore been obtained with scalp EEG recordings. Example results are presented from research studies of somatosensory stimulation, movement, language, attention and working memory. Deblurred ictal EEG data are also presented, indicating that this technique may have future clinical application as an aid to seizure localization and surgical planning.

Brain↗

Mental effort-related EEG modulation during video-game play: comparison between juvenile subjects with epilepsy and normal control subjects.

PURPOSE: This study investigated the effects of mental effort exerted during video-game play on features of the EEG in juvenile subjects diagnosed with seizure disorders and in age-matched clinically healthy subjects. METHODS: EEG was recorded from 14 children (9-15 years old) as they played a video game, watched another person playing a video-game, and sat quietly with their eyes open. Seven of the subjects had been clinically diagnosed with seizure disorders, three of whom had also exhibited photosensitivity. RESULTS: Three spectral components of the EEG showed cognitive load-related modulation. The amplitude of a frontal midline theta (6-7 Hz) signal increased with video-game play relative to the watching and eyes open resting conditions. A posterior alpha band (9-12 Hz) signal was attenuated during the playing and the watching conditions relative to the resting condition. A central mu (10-13 Hz) rhythm was attenuated during the game-playing condition. No significant differences were found between the patient and control groups for any of these features. Incidence of epileptiform events did not discriminate test conditions in the children with epilepsy. CONCLUSIONS: The results from this small sample suggest that video-game play tends to produce similar responses from children with epilepsy and in healthy control subjects. These responses in the juvenile population are similar to responses elicited by increased mental load in normal adult populations.

Adolescent↗

Plasma cell mucositis: a review and case report.

The simultaneous involvement of the mucous membranes of the oral cavity and upper aerodigestive tract by lesions characterised clinically by an intensely erythematous, lobulated surface and histologically by a dense connective tissue infiltrate composed of non-neoplastic plasma cells may be called plasma cell mucositis. We present a review of the literature, consisting of 14 cases, outlining the multifocal site distribution, chronicity and systemic background that distinguish this entity and report a single case with confirmation of the polyclonal nature of the plasma cell infiltrate using gene rearrangement studies.

Diagnosis, Differential↗

Analysis of genomic regions involved in regulation of the rabbit surfactant protein A gene in transgenic mice.

The gene encoding surfactant protein (SP) A, a developmentally regulated pulmonary surfactant-associated protein, is expressed in a lung-specific manner, primarily in pulmonary type II cells. SP-A gene transcription in the rabbit fetal lung is increased by cAMP. To delineate the genomic regions involved in regulation of SP-A gene expression, lines of transgenic mice carrying fusion genes composed of various amounts of 5'-flanking DNA from the rabbit SP-A gene linked to the human growth hormone structural gene as a reporter were established. We found that as little as 378 bp of 5'-flanking DNA was sufficient to direct appropriate lung cell-selective and developmental regulation of transgene expression. The same region was also sufficient to mediate cAMP induction of transgene expression. Mutagenesis or deletion of either of two DNA elements, proximal binding element and a cAMP response element-like sequence, previously found to be crucial for cAMP induction of SP-A promoter activity in transfected type II cells, did not affect lung-selective or temporal regulation of expression of the transgene; however, overall levels of fusion gene expression were reduced compared with those of wild-type transgenes.

Animals↗

Discharge characteristics of laryngeal single motor units during phonation in young and older adults and in persons with parkinson disease.

Discharge characteristics of laryngeal single motor units during phonation in young and older adults, and in persons with Parkinson disease. The rate and variability of the firing of single motor units in the laryngeal muscles of young and older nondisordered humans and people with idiopathic Parkinson disease (IPD) were determined during steady phonation and other laryngeal behaviors. Typical firing rates during phonation were approximately 24 s/s. The highest rate observed, during a cough, was 50 s/s. Decreases in the rate and increases in the variability of motor unit firing were observed in the thyroarytenoid muscle of older and IPD male subjects but not female subjects. These gender-specific age-related changes may relate to differential effects of aging on the male and female voice characteristics. The range and typical firing rates of laryngeal motor units were similar to those reported for other human skeletal muscles, so we conclude that human laryngeal muscles are probably no faster, in terms of their contraction speed, than other human skeletal muscles. Interspike interval (ISI) variability during steady phonation was quite low, however, with average CV of approximately 10%, with a range of 5 to 30%. These values appear to be lower than typical values of the CV of firing reported in three studies of limb muscles of humans. We suggest therefore that low ISI variability is a special although not unique property of laryngeal muscles compared with other muscles of the body. This conceivably could be the result of less synaptic "noise" in the laryngeal motoneurons, perhaps as a result of suppression of local reflex inputs to these motoneurons during phonation.

Action Potentials↗

Differential effects of intraventricular injections of tachykinin NK1 and NK3 receptor agonists on normal and sham drinking of NaCl by sodium-deficient rats.

The effects of lateral ventricular injections of succinyl-[Asp6, N-Me-Phe8]-substance P (SENK; 25, 100, 200 ng), a tachykinin NK3 receptor agonist, and [Sar9, Met(O2)11]-substance P (Sar Met; 100, 200 ng), an NK1 receptor agonist, on normal (gastric fistula closed) and sham drinking (gastric fistula open) of hypertonic NaCl by sodium-deficient rats were compared. Intraventricular injections of Sar Met had no effect on NaCl intake in either condition. Injections of 100 ng and 200 ng SENK caused an equal suppression of NaCl intake in the 2 fistula conditions. The latency to drink was not affected, but the initial lick rate was significantly lower and decayed more rapidly after 100 ng SENK than after saline or 25 ng SENK. The results show that (a) the tachykinin subtypes are not equally involved in the control of need-induced salt intake; (b) negative feedback from the stomach and distal gastrointestinal tract is not required for intraventricular injections of SENK to suppress sodium appetite; (c) the activation of NK3 receptors decreases the oral excitatory influence of hypertonic NaCl in sodium-deficient rats.

Animals↗

Detecting transient cognitive impairment with EEG pattern recognition methods.

This paper describes an initial evaluation of a new method for assessing transient states of cognitive impairment associated with intoxication or fatigue: neural network pattern recognition applied to features of the electroencephalogram (EEG) recorded from subjects performing a standardized task. Nine subjects performed a working memory task during an extended testing session occurring over the course of one night, and encompassing an alert baseline period, a state of mild acute intoxication, and a state of fatigue compounded by "hangover" or intoxication after-effects. Relative to the alert baseline, task performance was less accurate in the other test conditions, providing evidence of transient cognitive impairment. These states of impairment were associated with changes in spectral characteristics of the EEG. Neural network-based EEG pattern recognition techniques were used to develop and test detectors of these changes. Brief testing data samples originating from the alert baseline condition could be discriminated from those recorded during the state of acute intoxication with 98% accuracy (p < 0.0001), and from those recorded during the state of fatigue/hangover with 92% accuracy (p < 0.001). Furthermore, networks trained on data from a group of subjects were found to accurately classify data from test subjects who were not part of the training group. These results demonstrate the feasibility of using neurophysiological monitoring methods for detecting transient cognitive impairment.

Acute Disease↗