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Biomedical subjects

T G Smith

Publications and source records attributed to T G Smith.

At least 19 recordsLinked to original sources

Identification and progression of a desmoid precursor lesion in patients with familial adenomatous polyposis.

BACKGROUND: Desmoid tumours occur in about 10 per cent of patients with familial adenomatous polyposis (FAP), and are an important cause of morbidity and death. The natural history of desmoids was investigated by documenting prospectively the prevalence and progression of possible precursor lesions. METHODS: A group of patients with FAP and controls were examined at laparotomy. Another group, with FAP and no clinical evidence of desmoid, and a group of controls, underwent abdominopelvic computed tomography. RESULTS: At laparotomy 13 of 42 patients with FAP had fibromatous mesenteric plaques; seven of these had not had surgery. Seven had more extensive mesenteric fibromatosis and had undergone significantly more laparotomies than the rest. Of 103 patients scanned, two had desmoid tumours and 22 (21 per cent) had mesenteric fibromatosis. On follow-up both desmoid tumours grew rapidly; mesenteric fibromatosis was unchanged in eight and resolved in four of the 12 patients rescanned. CONCLUSION: A model of desmoid tumour development is suggested, analogous to the adenoma-carcinoma sequence, in which a less benign phenotype emerges as molecular genetic abnormalities accumulate: mesenteric plaque-like desmoid precursor lesions arise in many patients with FAP before surgery as a result of abnormal fibroblast function; some, perhaps stimulated by surgery, progress to mesenteric fibromatosis; these in turn can give rise to desmoid tumours.

Adenomatous Polyposis Coli

The life history and host specificity of Hepatozoon clamatae (Apicomplexa: Adeleorina) and ITS-1 nucleotide sequence variation of Hepatozoon species of frogs and mosquitoes from Ontario.

The life cycle of an intraerythrocytic hemogregarine, Hepatozoon clamatae, was studied in green frogs (Rana clamitans melanota), bullfrogs (Rana catesbeiana), northern leopard frogs (Rana pipiens), and in the mosquito, Culex territans. Gametogenesis, fertilization, and sporogony occurred within cells of the Malpighian tubules of laboratory-reared Cx. territans that had fed on naturally infected frogs. Mature oocysts containing hundreds of sporocysts were observed in mosquitoes 30 days postfeeding. Each sporocyst enclosed 4 sporozoites. Merozoites appeared in the peripheral circulation of laboratory-reared bullfrogs, green frogs and leopard frogs that had been fed sporocysts 35-70 days previously. Attempts to infect American toads (Bufo americanus) and blue-spotted salamanders (Ambystoma laterale) were not successful. Gamonts of this parasite induced nuclear fragmentation or segmentation in host erythrocytes. The life cycle, morphological, and morphometric features of H. clamatae are compared with H. catesbianae, a similar species that also infects ranids. Nucleotide sequence analysis of the internal transcribed spacer region (ITS-1) of these sympatric species revealed that only 6 nucleotide sites of the 129 base pairs of this region were variable among 4 isolates of H. clamatae and 2 isolates of H. catesbianae. A redescription of H. clamatae is presented based on data from this study and from the original description by Stebbins in 1905.

Animals

L-arginine and superoxide dismutase prevent or reverse cerebral hypoperfusion after fluid-percussion traumatic brain injury.

To determine whether treatment with L-arginine or superoxide dismutase (SOD) would prove effective in reducing cerebral hypoperfusion after traumatic brain injury (TBI), we measured cerebral blood flow (CBF) using laser Doppler flowmetry (LDF) in rats treated before or after moderate (2.2 atm) fluid-percussion (FP) TBI. Rats were anesthetized with isoflurane and prepared for midline FP TBI and then for LDF by thinning the calvaria using an air-cooled drill. Rats were then randomly assigned to receive sham injury, sham injury plus L-arginine (100 mg/kg, 5 min after sham TBI), TBI plus 0.9% NaCl, TBI plus L-arginine (100 mg/kg, 5 min post-TBI), TBI plus SOD (24,000 U/kg pre-TBI + 1600 units/kg/min for 15 min after TBI), or TBI plus SOD and L-arginine. A second group of rats received TBI plus saline, L-, or D-arginine (100 mg/kg, 5 min after-TBI). After treatment and TBI or sham injury, CBF was measured continuously using LDF for 2 h and CBF was expressed as a percent of the preinjury baseline for 2 h after TBI. Rats treated with saline or D-arginine exhibited significant reductions in CBF that persisted throughout the monitoring period. Rats treated with L-arginine alone or in combination with SOD exhibited no decreases in CBF after TBI. CBF in the SOD-treated group decreased significantly within 15 min after TBI but returned to baseline levels by 45 min after TBI. These studies indicate that L-arginine but not D-arginine administered after TBI prevents posttraumatic hypoperfusion and that pretreatment with SOD will restore CBF after a brief period of hypoperfusion.

Animals

Fractal methods and results in cellular morphology--dimensions, lacunarity and multifractals.

This paper discusses the concepts of fractal geometry in a cellular biological context. It defines the concept of the fractal dimension. D, as a measure of complexity and illustrates the two different general ways of quantitatively measuring D by length-related and mass-related methods. Then, these several Ds are compared and contrasted. A goal of the paper is to find methods other than length-related measures that can distinguish between two objects that have the same D but are structurally different. The mass-related D is shown potentially to be such a measure. The concept of lacunarity, L, is defined and methods of measuring L are illustrated. L is also shown to be a potentially distinguishing measure. Finally, the notion of multifracticality is defined and illustrated to exist in certain individual nerve and glial cells.

Cell Size

The genus Hepatozoon (Apicomplexa: Adeleina).

Hemogregarines of the genus Hepatozoon are intraerythrocytic apicomplexan parasites that have been described from all groups of tetrapod vertebrates. Gametogenesis, fertilization, and sporogonic development, which culminates in the formation of polysporocystic oocysts, occur in the gut or hemocoel of a hematophagous arthropod definitive host. Merogonic development occurs in the internal organs of vertebrate hosts after they ingest these infected arthropods. The presence of cystic stages, observed for many Hepatozoon species, increases life cycle complexity and exploits the feeding behavior of vertebrate hosts. The inconsistency of morphological characteristics of these parasites, especially those associated with gamont structure, coupled with low host specificity of the parasites for their invertebrate and vertebrate hosts, have rendered species differentiation difficult. A systematic review of the hemogregarine complex has resulted in the expansion of the genus Hepatozoon to include all members of the genus Haemogregarina that infect amphibians, snakes, lizards, crocodilians, birds, and mammals.

Animals

beta-Cyclodextrin: 52-week toxicity studies in the rat and dog.

A 52-wk toxicity study by dietary administration was performed in Sprague-Dawley rats and in pure-bred beagle dogs with beta-cyclodextrin, a starch derivative that acts as a molecular inclusion agent. Doses of 0 (control), 12,500, 25,000 and 50,000 ppm were selected for the rat study, and 0 (control), 6200, 12,500 and 50,000 ppm were selected for the dog study. The liver and kidney were identified at the histopathological examination as target organs for toxicity in the rat at doses of 50,000 and 25,000 ppm, with the hepatic changes associated with increased plasma liver enzyme and reduced plasma triglyceride concentrations. In the dog study, there was no pathological evidence of systemic toxicity, although there were minor changes in urinalysis and biochemical parameters and a slightly higher incidence of liquid faeces. These changes were considered to be of no toxicological importance. The results in these studies, therefore, indicate that the non-toxic effect level was 12,500 ppm in the rat (equivalent to 654 or 864 mg/kg/day for males or females, respectively) and 50,000 ppm in the dog (equivalent to 1831 or 1967 mg/kg/day for males or females, respectively).

Analysis of Variance

Surface complexity of human neocortical astrocytic cells: changes with development, aging, and dementia.

Astrocytes from area 11 of the human neocortex were Golgi-impregnated. The material was taken from four human subjects, (1) a neonate without obvious CNS damage, (2) a middle-aged adult serving as control, (3) an aged individual without apparent mental disturbances, and (4) an aged patient with dementia. Camera-lucida drawings of 7 to 26 astrocytic cells from each donor were digitized into a personal computer, and analyzed for their fractal dimension D which is an objective and quantitative measure of the complexity of the cell's borders. Both radial and multipolar astrocytes from neonatal cortex showed a comparatively low fractal dimension (D approximately 1.39), that is, low surface complexity. Adult ("control") astrocytes were characterized by a high fractal dimension (D = 1.57), corresponding to their large surface complexity. Astrocytes from the aged subject showed a somewhat smaller fractal dimension (D = 1.51) and, thus, surface complexity; this difference was however not highly significant. In contrast, astrocytes from the subject with dementia showed a significant reduction in surface complexity (D = 1.47). Parallel changes were observed in the brain volume compartment occupied by the process of individual astrocytes. These data suggest that formation and maintenance of astrocytic processes and/or side branches correlate positively with the degree of information processing within their neuronal environment.

Adult

Comparative fractal analysis of cultured glia derived from optic nerve and brain demonstrate different rates of morphological differentiation.

O-2A progenitor cells derived from neonatal rat cerebral hemispheres or optic nerves, were induced to differentiate in culture into either oligodendrocytes or type 2 astrocytes. The fractal dimensions, a measure of morphological complexity, of the differentiating glial cells were measured over time. Analysis of the changes in fractal dimension (D) with respect to time revealed specific rates of growth for each glial phenotype and a specific final D. The time course of these changes is well fit by a simple mathematical model. While brain-derived oligodendrocytes matured faster than the astrocytes, they ultimately attained comparable levels of complexity, with similar maximum fractal dimensions. Oligodendrocytes from nerve also matured faster than nerve derived astrocytes, in contrast, however, they attained a greater morphological complexity than nerve astrocytes. While the brain-derived oligodendrocytes showed a faster rate of maturation than their optic nerve counterparts, astrocytes from both regions had similar rates of morphological differentiation. Self-similarity, a defining property of fractal objects was investigated, by determining the fractal dimension of cells over a range of magnifications. The calculated fractal dimension remained constant over a 10-fold range in optical magnification, illustrating that cultured glial cells exhibit this important characteristic of fractal objects. In addition, we analyzed the branching patterns of glial processes by the Sholl method and found that the results were not as interpretable or meaningful as those of fractal analysis.

Animals

The development of Hepatozoon sipedon sp. nov. (Apicomplexa: Adeleina: Hepatozoidae) in its natural host, the Northern water snake (Nerodia sipedon sipedon), in the culicine vectors Culex pipiens and C. territans, and in an intermediate host, the Northern leopard frog (Rana pipiens).

The life cycle of Hepatozoon sipedon sp. nov. was studied in two snake species, the Northern water snake and the Eastern garter snake, in its mosquito hosts Culex pipiens and C. territans, and in the Northern leopard frog. Gametogenesis, fertilization and sporogony occurred within fat body cells in the haemocoel of mosquitoes that had fed on infected water snakes. Mature oocysts averaging 263 microns in diameter and containing more than 500 sporocysts were observed in mosquitoes 28 days post-feeding. Each sporocyst enclosed eight sporozoites. Dizoic cysts were found in the liver of frogs that had been fed infected mosquitoes seven days previously. Two rounds of merogony in various internal organs and intraerythrocytic gamonts were observed in snakes that had been fed frogs which had been orally inoculated with infected mosquitoes. Developmental stages were not seen in snakes that were fed infected mosquitoes directly. A comparison of this life cycle with those described for other Hepatozoon species infecting snakes is presented with reference to the different modes of transmission featured by these parasites.

Animals

Morphology, ultrastructure and taxonomic status of Toddia sp. in northern water snakes (Nerodia sipedon sipedon) from Ontario, Canada.

Inclusions characteristic of an infection caused by Toddia sp. were found in the erythrocytes and erythroblasts of 15 of 26 northern water snakes (Nerodia sipedon sipedon) collected near Kingston, Ontario, Canada. Erythrocytes contained translucent inclusions, small acidophilic bodies, and square-shaped crystalloid structures. Erythrocytes infected with Toddia sp. were more rounded than uninfected erythrocytes and had pycnotic nuclei. We observed icosahedral virus particles measuring 195 to 210 nm formed from a membrane-bounded viral assembly site in the cytoplasm of the host erythrocyte. As a result of the viral identity of this parasite, we recommend that the etiologic agent of Toddia sp. infections from this and other species of North American snakes be renamed Snake Erythrocytic Virus.

Animals

Quantitative phylogenetic constancy of cerebellar Purkinje cell morphological complexity.

Golgi-stained material of cerebellar cortices from 17 species was examined by measuring the fractal dimensions of the borders of Purkinje cells, which is a quantitative, objective measure of morphological complexity. Nine species (from birds to man) were chosen for a comparison with ANOVA and no statistically significant differences were found in their fractal dimensions. In contrast, a wide range of differences was found in the membrane areas across species lines. The Sholl coefficient, a measure of branch formation and termination away from the soma, showed no consistent pattern for each cell. We interpret our results as indicating a constancy in morphological cellular complexity of Purkinje cells during late evolutionary time.

Analysis of Variance

Early dendrite development in spinal cord cell cultures: a quantitative study.

Neurons in dissociated cell culture provide a favorable system for the quantitative analysis of structural changes and the examination of structure-function relationships during development. Fragment C of tetanus toxin was used to label neurons in murine spinal cord cell cultures and dendrite outgrowth was monitored by a number of measures. The dissociated neurons increased in morphologic complexity from approximate spheres to highly branched structures during the first week in culture. Much of the structural complexity of the dendrite arbor, as quantified by fractal dimension, was established within 48 hr after plating, i.e., prior to the development of interneuronal contacts. During the first few days in culture, dendrite branching complexity increased more rapidly than dendrite size, whereas after 4 days, fractal dimension remained relatively constant while dendrites continued to grow. Fractal analysis has provided data which suggest that the early development of dendrite branching complexity is determined intrinsically. Fractal dimension, as an effective index of morphologic complexity, should be a useful tool for the further study of extrinsic signals which might modify the generation or stabilization of dendrite form.

Animals

Technical aspects of acoustic myography (AMG) of human skeletal muscle: contact pressure and force/AMG relationships.

The effect of contact pressure on acoustic myographic (AMG) recordings was examined during voluntary isometric contractions of the human quadriceps muscle in 20 normal males. A piezoelectric disk for recording muscle sounds was placed over rectus femoris at approximately mid-thigh and secured with a rubber electromyography (EMG) strap. Contact pressure was monitored by a load cell placed between the AMG device and the strap. With the subject seated, force at different percentage levels of maximum voluntary contraction (MVC) were held for 5 s each. Both AMG and EMG recordings were full-wave rectified and integrated (IAMG and IEMG) and expressed as a percentage of activity at MVC. Two contraction series were performed with 2 different contact pressures. Pressure 1 (P1), of 180 Pa was applied in all subjects. A higher pressure of either 790 Pa (P2; in 5 subjects) or 1200 Pa (P3; in 15 subjects) was also applied. No significant changes in IAMG activity (P > 0.1) occurred between P1 and P2 but P3 produced increases in IAMG at all force levels (P < 0.05 at 10, 50 and 75% MVC). Both linear and non-linear relationships between force and IAMG were observed in different subjects but the relationship also varied with the 2 contact pressures within some subjects. The force/IEMG relationship was linear in all cases. These results provide quantitative evidence that contact pressure can influence the degree of IAMG activity if the pressure is high enough. The change in the force/IAMG relationship with pressure in some subjects suggests that the different relationships observed are not determined by physiological differences between subjects but rather by technical factors.

Acoustics

Prospective survey of the use of the laryngeal mask airway in 2359 patients.

Patients undergoing anaesthesia in which the laryngeal mask airway was used were prospectively audited over a 6-month period. A simple record sheet was completed at the time of anaesthetic administration and 2359 completed forms were analysed to assess problems encountered with its use. It was used successfully in 2350 patients (99.61%); of these, 1399 patients (59%) breathed spontaneously through the airway and 960 patients (41%) underwent intermittent positive pressure ventilation of the lungs. Two patients (0.08%) were reported to have regurgitated during the use of the laryngeal mask airway, but no serious sequelae associated with its use were encountered.

Adolescent

A comparative fractal analysis of various mammalian astroglial cell types.

Camera-lucida drawings of Golgi-impregnated astroglial cells and their processes are described by the fractal dimension of their borders, which is an objective, quantitative measure of morphological complexity. Protoplasmic astrocytes from human neocortex have fractal dimensions (D) that are larger than those of fibrous astrocytes from the cat optic nerve. Marginal astrocytes from monkey cerebropontile angle have two kinds of processes: (1) short, thick processes with endfeet abutting the pial surface, with relatively high D's, and (2) very long, thin processes extending into the neuronal tissue, with very low D's. These data indicate that short astrocytic processes may have a complex surface (and have a high D), whereas long processes are rather smooth (and have a low D). A comparison between transmission electron microscopy morphometry and measures of D at the light microscopic level, performed on different parts of rabbit retinal Müller glial cells, suggests that D is strongly correlated to the surface-to-volume ratio which, in part, determines the length constant of a cable for core-conductance of currents. We provide data supporting the hypothesis that astroglial cell geometry is adjusted to allow for sufficient spatial buffering K+ currents, even through very long processes.

Animals

Amitriptyline prevents N-methyl-D-aspartate (NMDA)-induced toxicity, does not prevent NMDA-induced elevations of extracellular glutamate, but augments kainate-induced elevations of glutamate.

The effect of amitriptyline on kainate- and N-methyl-D-aspartate (NMDA)-induced toxicity and release of amino acids from cerebellar granule neurons was studied. The ED50 for amitriptyline, imipramine, and nortriptyline protection against NMDA-induced toxicity was 6.9, 6.5, and 1.3 microM, respectively. None of these compounds protected against kainate-induced toxicity. Even though amitriptyline was protective against NMDA-induced toxicity, it had no effect on the NMDA-induced increase in extracellular levels of glutamate or aspartate from these cells, indicating a dissociation between NMDA receptor activation (as indicated by glutamate content elevations) and NMDA-induced toxicity. However, kainate and quisqualate treatment resulted in elevations of glutamate and taurine levels that were further augmented in the presence of 25 microM amitriptyline. These findings confirm the reports of others that tricyclic antidepressants have neuroprotective effects related to the NMDA receptor and expand on these reports by showing that even though there is protection against toxicity, the NMDA receptor is nevertheless activated, suggesting an involvement of these compounds at sites removed from the receptor. Furthermore, this is the first report showing an interaction of tricyclic antidepressants with the function of non-NMDA receptors.

Amitriptyline

A fractal analysis of pyramidal neurons in mammalian motor cortex.

Pyramidal neurons in the mammalian cerebral cortex can be described by a fractal dimension (Mandelbrot, 1982), which is an objective, quantitative measure of the complexity of their soma/dendritic borders. In the cat, the fractal dimensions of lamina V cells, which include pyramidal tract neurons (PTN), indicate that these cells are more complex than other pyramidal neurons (PN) in the same region of motor cortex. The lamina V cells of the cat are also more complex than those in motor cortex of the monkey. Moreover, lamina III neurons in the monkey are more complex than monkey lamina V neurons. The fractal dimension of the intracortical axon collateral arborizations of the same pyramidal neurons indicated, in all cases, that the branching of these terminals is less complex than the branching of the dendrites of the same cells. In line with the observation that the fractal dimensions of some homologous cellular populations are different in different species, it is suggested that the fractal dimension and the degree of morphological complexity may relate to the requirement for the number of separable functions to be accommodated within one neuron. For example, as the size of the cortex and the number of neurons in a region increase, the opportunity exists within a given cortical zone, for individual functions to be segregated and for functional specialization to be accommodated with less morphological complexity of the individual neurons performing each of these functions.

Animals