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Biomedical subjects

D Higgins

Publications and source records attributed to D Higgins.

17 recordsLinked to original sources

Laminin selectively enhances axonal growth and accelerates the development of polarity by hippocampal neurons in culture.

We have examined the effects of laminin on the morphological development of embryonic rat hippocampal neurons maintained in tissue culture. Forty-eight hours after plating, neurons grown on a polylysine-coated substrate had become polarized, typically having one long axon and 4 or 5 minor processes. Adsorption of laminin to the substrate did not cause changes in the number of axons extended by hippocampal neurons but did cause significant increases in the length of the axonal plexus and in axonal branching. In contrast to its effects on axons, laminin did not influence the number, length, or branching of the minor processes that eventually become dendrites or the morphology of definite dendrites as assessed after 7 days in culture. In addition to selectively enhancing axonal growth, laminin greatly increased the rate of polarization of hippocampal neurons such that most became polarized within 18 h. Analysis of the time course of laminin's effects revealed that the acceleration of polarization was not associated with a change in the time of initial process formation, but rather with a selective stimulation of the growth of the longest process at all times from the 12th through the 48th h in vitro. These data suggest that even though the basic shape of hippocampal neurons may be intrinsically programmed, critical aspects of their morphological development may be modulated by extracellular matrix molecules such as laminin.

Animals

Thrombospondin promotes process outgrowth in neurons from the peripheral and central nervous systems.

Thrombospondin (TSP) is a prominent constituent of the extracellular matrix of the developing nervous system. We have examined the effects of TSP on the morphological differentiation of neurons. In short-term cultures (less than or equal to 24 hr) of embryonic rat sympathetic neurons, TSP stimulated neurite outgrowth, causing significant increase in the number of processes and their length. Similar effects were observed in cultures of rat dorsal root ganglion, hippocampal, and cerebral cortical neurons. Moreover, in cultures of central neurons, TSP was more effective than laminin in enhancing process extension. Analysis of long-term (5-7 days) cultures of sympathetic neurons indicated that processes formed in the presence of TSP had the cytochemical characteristics of axons. Thus, TSP can influence neuronal development by selectively enhancing axonal growth. The neurite-promoting region of the molecule was identified using a panel of monoclonal antibodies targeted to different regions of the protein. Process outgrowth could be totally inhibited with antibody A4.1, which recognizes the stalk region of TSP. These data suggest that the neurite-promoting activity is localized to a single region of the TSP molecule.

Animals

OBSTRUCT: a program to obtain largest cliques from a protein sequence set according to structural resolution and sequence similarity.

A program OBSTRUCT has been developed to obtain the largest possible subset according to specific constraints from a set of protein sequences whose tertiary structures have been determined crystallographically. The user can request a range in sequence similarity level and/or structural resolution. The program optionally includes sequences with known three-dimensional folds elicited from NMR data.

Protein Conformation

Effects of isoflurane anaesthesia on the median nerve somatosensory evoked potential in children.

Evoked potentials are used to determine the integrity of neural pathways during neurosurgical and orthopaedic procedures, but the extent to which they may be altered by anaesthetic agents has not been studied systematically in children. In this study we have recorded median nerve somatosensory evoked potentials (mnSSEP) in children during isoflurane anaesthesia to determine if there are changes similar to those seen in adults. We studied 10 patients using standardized anaesthetic and clinical neurophysiological techniques. Control mnSSEP were obtained with 70% nitrous oxide in oxygen and isoflurane was then administered at 0.25, 0.50 and 0.75 MAC. The latencies and amplitudes of the mnSSEP were subjected to repeated measures analysis of the variance (ANOVA) and linear regression. There were statistically significant increases in N20, P22 latencies and central conduction time (P < 0.001) and reductions in amplitude of the N20-P22 complex (P < 0.03) with increasing end-tidal isoflurane concentrations. These results are similar to the findings in adults.

Anesthesia, Inhalation

Sequential measurement of the median nerve somatosensory evoked potential during isoflurane anaesthesia in children.

We have used sequential measurements of median nerve somatosensory evoked potentials (mnSSEP) in 10 children to estimate the equilibration time of an inhalation anaesthetic agent between alveolar gas, arterial blood and brain. MnSSEP were obtained sequentially every 90-180 s. After control measurements in the absence of isoflurane, the end-tidal concentration was increased stepwise (0.25, 0.5 and 0.75 MAC). Each isoflurane concentration was maintained for 15 min. The point at which the N20 latency reached stability was determined; the mean time between reaching a stable end-tidal isoflurane concentration and this point varied between 5 min 16 s and 7 min 37 s. This technique may be useful in circumstances in which a "steady state" of anaesthesia is important, such as in the determination of MAC or during intraoperative monitoring of evoked potentials.

Anesthesia, Inhalation

Mesothelioma among employees with likely contact with in-place asbestos-containing building materials.

The occurrence of mesothelioma is a sentinel event in occupational and environmental disease. A mesothelioma surveillance system was established utilizing existing computerized Wisconsin vital statistics data maintained since 1959 and a Cancer Reporting System (CRS) established in 1978. Review of the death certificate listing of usual occupation and industry from 487 mesothelioma deaths in Wisconsin from 1959 to 1989 led to the investigation of 41 persons with likely exposure to inplace asbestos-containing building materials (ACBM): 12 school teachers, 10 school maintenance employees, 7 public building maintenance workers, 5 private building maintenance workers, and 7 commercial and factory workers performing maintenance activities. For 10 (34%) of the 29 maintenance workers the only source of asbestos exposure identified was their maintenance work. For five (17%) histories indicated some prior employment in occupations and industries with probable asbestos exposures. Opportunities for indirect occupational exposure were identified for ten who had been employed in the residential construction industry. One maintenance worker was exposed to asbestos in the household and another had neighborhood exposure. For 9 (75%) of the school teachers, the only identifiable potential source of asbestos exposure was derived from in-place ACBM in schools. One teacher had spent a season in the merchant marine aboard an iron ore-hauling ship and 2 had worked in the residential construction industry. Two of the teachers were sisters, and in two instances, two teachers had taught in the same school facility. We conclude that individuals occupationally exposed to in-place ACBM are at risk for the subsequent development of mesothelioma.

Adult

Protein synthesis is required for the initiation of dendritic growth in embryonic rat sympathetic neurons in vitro.

We have utilized an experimental paradigm which allows the manipulation of dendritic growth in sympathetic neurons in culture to examine the effects of inhibitors of protein synthesis and RNA synthesis on the development of dendrites. Embryonic rat sympathetic neurons extend only axons when they are grown in serum-free medium on a polylysine substrate. The addition of an extract of basement membrane proteins (BME) to this culture system elicits dendritic growth within 48 h. Both cycloheximide and actinomycin-D inhibited BME-induced dendritic growth in greater than 80% of the neuronal population and reduced the number of dendrites extended by greater than or equal to 97%. In contrast, cycloheximide was found to have minimal effects on axonal growth in short-term (less than or equal to 18 h) cultures as measured with respect to the percentage of the population with axons and the number of axons per neuron. However, this inhibitor did significantly reduce (84%) the length of the axonal plexus extended. These results indicate that dendritic and axonal growth in sympathetic neurons are differentially dependent on protein synthesis such that the formation of dendrites requires protein synthesis whereas the initiation, but not the elongation, of axons is relatively independent of protein synthesis.

Animals

Colorimetric end-tidal carbon dioxide monitoring during transfer of intubated children.

We report the use of a cheap, pocket-sized colorimeter to assess the end-tidal carbon dioxide concentration during transfer of intubated children. The device provided breath by breath confirmation of tracheal tube placement and identified one episode of reduced pulmonary perfusion. We would advocate the use of this detector to provide early warning of tracheal tube displacement during the transfer of children weighing more than 15 kg.

Body Weight

Dear Dr. Eger:.

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Adult

Hypothalamic Na+ and Ca++ ions and temperature set-point: new mechanisms of action of a central or peripheral thermal challenge and intrahypothalamic 5-HT, NE, PGEi and pyrogen.

The effects of changes in ambient and central temperature, amines, PGEu and pyrogen were investigated with respect to the mechanism of Na+-Ca++ ratio in the posterior hypothalamus of the unrestrained cat. Guide tubes were implanted bilaterally above the posterior hypothalamic area of 23 cats so as to accommodate push-pull cannulae. After a Na+ or Ca++ sensitive site was identified by perfusion at 50 mul/min of an artificial CSF containing 10.4 mM excess Ca++ ions or 13.6 mM excess Na+ ions, several types of experiments were undertaken with the results summarized as follows: if the cat was exposed to a cold or warm environmental temperature as the posterior hypothalamus was perfused with excess cation, the typical hypothermia was produced by Ca++ and hyperthermia by Na+ ions. However, if the cat was exposed to peripheral cooling or warming 30 min prior to the perfusion, the fall or rise produced by Ca++ or Na+ was attenuated or prevented. In other experiments, 1.0 muCi 45Ca++ was injected in the ion sensitive site in the posterior hypothalamus to label stores of the cation. Raising of ambient temperature caused a retention of 45Ca++ in this hypothalmic area, whereas a cold environmental temperature enhanced the efflux of 45Ca++ at the same perfusion site. The magnitude of change in 45Ca++ efflux depended upon the intensity of the thermal challenge. Similarly, warming of the anterior hypothalmic, preoptic area by means of implanted thermodes caused an immediate diminution in 45Ca++ efflux in the posterior hypothalamus, whereas cooling of this anterior region augmented the extrusion of 45Ca++ ions from the posterior area. When substances which produce a temperature change were applied to the same thermosensitive zone, the direction of shift in 45Ca++ flux in the posterior area corresponded to the signal for heat production or heat loss. That is, the microinjection of 5-HT, PGE1 or Salmonella typhosa into the anterior hypothalamus enhanced the efflux of 45Ca++ in the posterior hypothalamus as hyperthermia developed, whereas a similar microinjection of norepinephrine reduced the 45Ca++ output from the same sites. Finally, locally anesthetizing the cells of the anterior hypothalamus by the nerve blocker, procaine, prevented the cold and heat-induced 45Ca++ eflux and retention, respectively. These results suggest that if the Na+-Ca++ ratio in the posterior hypothalamus establishes and maintains the set-point for body temperature of 37 degrees -38 degrees C, the mechanism of lability of Ca++ through changes in binding characteristics, transport, or metabolism of the cation serves two purposes: (1) the active defense of the set-point temperature through gradations in ion shifts; and (2) the upward or downward change in set-point value, pathological or normal, triggered by virtue of impulses relayed from the anterior hypothalamus.

Animals

Anxiety and endocrine responses to surgery: paradoxical effects of preoperative relaxation training.

It has been argued that surgery is a form of psychological stress, and that the response to it should therefore be modifiable by psychological means. To test this hypothesis, we assessed the effect of preoperative relaxation instructions on endocrine, cardiovascular, and subjective responses in 21 patients undergoing minor abdominal surgery. Controls (N = 19) received general procedural information. In the relaxation group only, there was a significant increase in cortisol and adrenaline concentration from immediately before induction of anesthesia to immediately after surgery. Noradrenaline values were unaffected by relaxation. In contrast, relaxation reduced state-anxiety on the preoperative day and the two postoperative days; maximal peroperative systolic and diastolic blood pressures were also reduced. The results are consistent with previous evidence that adrenaline and cortisol responses to surgery are greater in less anxious patients.

Adaptation, Psychological