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Biomedical subjects

P Simpson

Publications and source records attributed to P Simpson.

At least 91 records · Page 5Linked to original sources

A dual role for the protein kinase shaggy in the repression of achaete-scute.

achaete and scute are expressed in a spatially restricted pattern and provide neural potential to cells. The domains of expression depend partly on extramacrochaetae whose product is itself spatially restricted and acts as a negative post-translational regulator of achaete and scute. The protein kinase shaggy also represses achaete and scute at many sites but may act via intermediate transcription factors. However shaggy and extramacrochaetae act synergistically and molecular studies suggest that they may be part of the same pathway. shaggy is functionally homologous to the mammalian glycogen synthase kinase-3 and analogy with the known physiology of this enzyme, suggests that this function of shaggy may result from the "constitutive" activity. At the site where a single neural precursor will develop, achaete and scute are initially expressed in a group of equivalent cells. The genes Notch and Delta are part of a lateral signal required to single out one precursor cell and to silence achaete and scute expression in the other cells. shaggy is required downstream of Notch for transduction of the inhibitory signal. This second role of shaggy may be due to modulation of enzymatic activity during signalling.

Animals↗

Isolation of 2,4-diacetylphloroglucinol from a fluorescent pseudomonad and investigation of physiological parameters influencing its production.

Pseudomonas sp. strain F113 was isolated from the rhizosphere of sugar beets and shown to inhibit a range of plant pathogenic fungi by producing an antibioticlike compound. An antibiotic-negative mutant strain, F113G22, was generated by transposon mutagenesis. This mutant has lost the ability to inhibit both bacterial and fungal microorganisms on high-iron medium. The antibioticlike compound was subsequently identified as 2,4-diacetylphloroglucinol (DAPG), and a high-pressure liquid chromatographic assay was developed for to detect it quantitatively in growth culture media and soil. The growth temperature had a direct bearing on DAPG production by strain F113, with maximum production at 12 degrees C. The iron concentration, pH, and oxygen had no influence on DAPG production by strain F113 under the assay conditions used. However, a low ratio of culture volume to surface area available to the microbe in the growth container was critical for optimum DAPG production. Different types of carbon sources influenced DAPG production by strain F113 to various degrees. For example, sucrose, fructose, and mannitol promoted high yields of DAPG by strain F113, whereas glucose and sorbose resulted in very poor DAPG production.

Journal Article↗

The choice of cell fate in the epidermis of Drosophila.

In Drosophila, neural precursors are formed in a spaced pattern separated by intervening epidermal cells. Segregation of neural and epidermal lineages relies on cellular interactions. Failure of this cell communication, as in the mutants Notch (N), Delta, and shaggy, results in most or all of the cells becoming neural. Cells mutant for N and shaggy, but not Delta, autonomously adopt the neural fate when adjacent to wild-type cells in mosaics. Furthermore, wild-type cells adopt the epidermal fate if adjacent cells express a lower level of N activity than themselves, but produce neural precursors if adjacent cells express a higher level of N activity. This shows that there is competition between the cells and that the N protein is required for the mechanism whereby the cells choose between alternative fates. It also suggests that N acts as a receptor for an inhibitory signal emanating from the neural precursors.

Animals↗

Sun protection in newborns. A comparison of educational methods.

We investigated the effect of education on the sun exposure of newborns. Mothers of healthy newborns (n = 275) were enrolled in the spring of 1989 and interviewed by telephone in the fall of 1989. The mothers were divided into a control group, a low-level intervention group, and a high-level intervention group. Both the low-level and high-level interventions succeeded in reducing the amount of time the newborns were allowed to spend in direct sunlight. Both types of intervention also resulted in reduced sun exposure time for the mothers. Although the number of mothers who used sunscreen was approximately the same in all three groups, when sunscreen use was controlled for, the intervention groups spent significantly less unprotected time in the sun than the control group. The mothers and newborns in both intervention groups simply spent less time outdoors.

Adolescent↗

The target specificity of the extrinsic innervation of the rat small intestine.

The target specificity of the extrinsic innervation of the rat small intestine was examined by simultaneously injecting the proximal and distal small intestine with either wheat germ agglutinin-horseradish peroxidase (HRP) or fast blue. The number of single- and double-labeled cells in the nodose, dorsal root and coeliac-superior mesenteric ganglia and the dorsal motor nucleus of the vagus were counted and expressed as percentages of total labeled cells. Cells containing both HRP and Fast blue projected to both regions of the intestine. We found that the nodose and mesenteric ganglia contained significantly fewer double-labeled neurons (approximately 3 and 9% respectively) than the dorsal motor nucleus (19%) or dorsal root ganglion (20%). Presumably, a large number of double-labeled afferent or efferent neurons would limit the ability of a given component of the extrinsic innervation to control the activity of restricted regions of the small intestine (but might be important in overall regulation of intestinal function). In a separate series of experiments we examined the topography of neurons in the dorsal motor nucleus of the vagus labeled with HRP injection into either the proximal or distal small intestine. Both of these injections labeled neurons in the entire rostro-caudal extent of the nucleus, though approximately 75% of the cells were located between 720 microns caudal and 720 microns rostral to the obex. Cells in the rostral regions were found primarily in the lateral pole of the nucleus, whereas caudal regions contained labeled cells in both the medial and lateral poles.

Abdomen↗

Defibrillation efficacy using two low-profile endocardial electrodes.

The hypothesis that improved energy delivery and defibrillation efficacy can be achieved by using two widely separated endocardial electrodes and a cutaneous patch electrode was explored by positioning two 6.5 F electrodes (NuMed, Hopkinton, New York) with 5 cm platinum-iridium coils in the right ventricular apex (RVA) and the right ventricular outflow (RVO) in eight dogs. In another 12 dogs, an additional electrode was positioned in the RVA. A cutaneous patch (P) was placed at the cardiac apex. Biphasic pulses were delivered, the first pulse (6 ms) positive, the second negative (2 ms). The leading edge of the second was equal to the trailing edge of the first. RVO-/P+ and RVA-RVO-/P+ were compared with RVA-/P+ at a constant voltage setting required to achieve a 60% probability of success (P60) for RVA-/P+. At a constant voltage output, the probability of success for RVA-RVO-/P+ was significantly higher (81%) than RVO-/P+ (60%) or RVA-/P+ (67%) (p less than 0.03). The current delivered was greater for RVA-RVO-/P+ (9.9 +/- 2.3 amps) than for either RVA-RVO-/P+ (8.7 +/- 1.9 amps) or RVO-/P+ (9.0 +/- 2.0 amps) (p less than 0.0001). Similarly, the impedance was significantly lower for RVA-RVO-/P+ (66 +/- 12 omega) than for RVA-/P+ (75 +/- 12 omega) and RVO-/P+ (72 +/- 9.6 omega) (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An early embryonic product of the gene shaggy encodes a serine/threonine protein kinase related to the CDC28/cdc2+ subfamily.

The product(s) of the gene shaggy (sgg) is required for seemingly unrelated events during the development of Drosophila melanogaster. In embryos, maternal and zygotically derived sgg products are required initially to construct a normal syncytial blastoderm and later for normal segmentation. Furthermore, in mutant animals a process of intercellular communication that is required for the segregation of the neural and epidermal lineage during the formation of the central nervous system and the adult peripheral nervous system is disrupted. Here we describe a transcription unit of approximately 40 kb lying within the cloned chromosomal interval 3B1, and provide evidence that it encodes the sgg+ function. Of seven developmentally regulated transcripts that are partially generated by alternative splicing, two seem to be responsible for early sgg activity. Sequence analysis of corresponding cDNA(s) predicts a protein of 514 amino acids with a canonical catalytic domain found in serine/threonine specific protein kinases, linked to an unusual region rich in Gly, Ala and Ser. A search for homologies as well as a comparative study of the kinase catalytic domain with that of other proteins, revealed that the protein kinase domain of sgg is distantly related to the members of the CDC28/cdc2+ subfamily of protein kinases, all of which play cardinal roles in the regulation of the yeast and mammalian cell cycles. Ubiquitous expression of sgg transcripts was found during embryonic stages. A possible role of the sgg protein in a signal transduction pathway necessary for intercellular communication at different stages of development is discussed.

Amino Acid Sequence↗

The genetics of a small autosomal region of Drosophila melanogaster containing the structural gene for alcohol dehydrogenase. VII. Characterization of the region around the snail and cactus loci.

The genetic interval 35C to 36A on chromosome arm 2L of Drosophila melanogaster has been saturated for mutations with visible or lethal phenotypes. 38 loci have been characterized, including several maternal-effect lethals (vasa, Bic-C, chiffon, cactus and cornichon) and several early embryonic lethals, including snail and fizzy. About 130 deletions have been used to order these loci. Complex interactions between mutant alleles have been uncovered in the immediate genetic environs of the snail gene, as has further evidence for an interaction between this region and that including the nearby genes no-ocelli and elbow.

Alcohol Dehydrogenase↗

Clinical application of the metabolic cart to the delivery of total parenteral nutrition.

In critically ill patients, the inaccuracy of predictive formulas for nutritional assessment often leads to inappropriate and potentially detrimental feeding regimens. This study evaluates the clinical utility of the metabolic cart in an urban university hospital setting. Twenty-six studies were performed on each of 26 patients (18 surgical, 8 medical) using an MMC Horizon metabolic cart. Although 58% of patients were overweight, 42% were still shown to have a kwashiorkorlike pattern of malnutrition. Three patients demonstrated a marasmic-like pattern. Fifteen percent of studies showed patients to be hypometabolic and 62% hypermetabolic. Harris-Benedict resting energy expenditure, based on actual or ideal body weight, underestimated needs; however, addition of a metabolic activity factor overestimated needs. Only 32% of patients were fed appropriately; 41% were underfed, and 27% were overfed. Urine area nitrogen correlated poorly with energy expenditure. Measured RQ appropriately reflected substrate utilization in 77% of studies; multiple factors may have caused differences between measured and predicted RQ in 23%. Use of the metabolic cart determines precisely the metabolic state, identifies problems with substrate utilization, and enables the physician to design the most efficacious nutritional regimen.

Adolescent↗

Lateral inhibition and the development of the sensory bristles of the adult peripheral nervous system of Drosophila.

Cells in the neurectoderm of Drosophila face a choice between neural and epidermal fates. On the notum of the adult fly, neural cells differentiate sensory bristles in a precise pattern. Evidence has accumulated that the bristle pattern arises from the spatial distribution of small groups of cells, proneural clusters, from each of which a single bristle will result. One class of genes, which includes the genes of the achaete-scute complex, is responsible for the correct positioning of the proneural clusters. The cells of a proneural cluster constitute an equivalence group, each of them having the potential to become a neural cell. Only one cell, however, will adopt the primary, dominant, neural fate. This cell is selected by means of cellular interactions between the members of the group, since if the dominant cell is removed, one of the remaining, epidermal, cells will switch fates and become neural. The dominant cell therefore prevents the other cells of the group from becoming neural by a phenomenon known as lateral inhibiton. They, then, adopt the secondary, epidermal, fate. A second class of genes, including the gene shaggy and the neurogenic genes mediate this process. There is some evidence that a proneural cluster is composed of a small number of cells, suggesting a contact-based mechanism of communication. The molecular nature of the protein products of the neurogenic genes is consistent with this idea.

Animals↗

Proneural clusters: equivalence groups in the epithelium of Drosophila.

The segregation of neural precursors from epidermal cells during development of the nervous system of Drosophila relies on interactions between cells that are thought to be initially equivalent. During development of the adult peripheral nervous system, failure of the cellular interactions leads to the differentiation of a tuft of sensory bristles at the site where usually only one develops. It is thus thought that a group of cells at that site (a proneural cluster) has the potential to make a bristle but that in normal development only one cell will do so. The question addressed here is do these cells constitute an equivalence group (Kimble, J., Sulston, J. and White, J. (1979). In Cell Lineage, Stem Cells and Cell Determination (ed. N. Le Douarin). Inserm Symposium No. 10 pp. 59-68, Elsevier, Amsterdam)? Within clusters mutant for shaggy, where several cells of a cluster follow the neural fate and differentiate bristles, it is shown that these display identical neuronal specificity: stimulation of the bristles evoke the same leg cleaning response and backfilling of single neurons reveal similar axonal projections in the central nervous system. This provides direct experimental evidence that the cells of a proneural cluster are developmentally equivalent.

Animals↗

Mutant Drosophila embryos in which all cells adopt a neural fate.

In the Drosophila embryo, early developmental decisions lead to all cells adopting one of several initial fates, such as those characteristic of the germ layers. The central nervous system is formed subsequently from the neurogenic region of the ectoderm, in which progenitor cells of the neuroblasts and ventral epidermis are intermingled. Two classes of genes govern the segregation of neuroblasts and peripheral sensory organs. The pro-neural class of genes, for example, the achaete-scute complex, participates in the initial decision to make each uniquely positioned neuroblast or sensory organ, but are initially expressed in groups of cells. The segregation of a neuroblast or sensory organ from an equivalent group of equipotential cells involves a mechanism of lateral inhibition whereby the future epidermal cells are prevented from engaging in the primary dominant neural fate. In the absence of this inhibitory signal, all cells of the group will become neural by default. The neurogenic class of genes is thought to mediate these cell interactions. Here we report that cells in embryos mutant for shaggy which are unable to adopt any of the early initial fates, instead develop neural characteristics.

Animals↗

Effects of temazepam premedication on cognitive recovery following alfentanil-propofol anaesthesia.

The effects of temazepam 20 mg and placebo were compared for premedication in patients anaesthetized with propofol and alfentanil and undergoing day surgery. Temazepam 20 mg significantly reduced preoperative anxiety and increased recovery time. A series of computerized cognitive tasks revealed significant deficits in attention and memory following anaesthesia, which were increased in range and magnitude by temazepam, which were apparent 30 min after surgery and had largely, but not completely, recovered at 4 h. This study has demonstrated that computerized cognitive testing can identify a wider profile of impairments produced by temazepam than has been found in previous work using non-computerized techniques.

Adolescent↗

A study of shaggy reveals spatial domains of expression of achaete-scute alleles on the thorax of Drosophila.

A study of shaggy mutant clones on the notum reveals that a greater number of cells are diverted into the bristle pathway of differentiation and fewer cells remain to produce the epidermis, shaggy clones differentiate supernumerary microchaetae and macrochaetae but these are found in the correct spatial locations, e.g. clusters of macrochaetae are formed round the position of the extant macrochaetae. The shaggy mutant phenotype requires the functioning of the genes of the achaete-scute (AS-C) complex but a dosage study shows that it is unlikely that the AS-C is overexpressed in shaggy cells. Data are presented that argue, also, for a correct spatial expression of the AS-C in shaggy mutants. A study of clones doubly mutant for shaggy and different achaete and scute alleles is consistent with the hypothesis that the clusters of macrochaetae formed by shaggy represent the restricted spatial domains of expression of the AS-C. The results can be reconciled with the known role for the AS-C, in determining which bristle types differentiate where, and a role for shaggy in the cell interactions, within domains of the AS-C expression, leading to the definition of only one bristle mother cell.

Alleles↗