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Biomedical subjects

C Kenyon

Publications and source records attributed to C Kenyon.

At least 19 recordsLinked to original sources

Activation of a C. elegans Antennapedia homologue in migrating cells controls their direction of migration.

Anterior-posterior patterning in insects, vertebrates and nematodes involves members of conserved Antennapedia-class homeobox gene clusters (HOM-C) that are thought to give specific body regions their identities. The effects of these genes on region-specific body structures have been described extensively, particularly in Drosophila, but little is known about how HOM-C genes affect the behaviours of cells that migrate into their domains of function. In Caenorhabditis elegans, the Antennapedia-like HOM-C gene mab-5 not only specifies postembryonic fates of cells in a posterior body region, but also influences the migration of mesodermal and neural cells that move through this region. Here we show that as one neuroblast migrates into this posterior region, it switches on mab-5 gene expression; mab-5 then acts as a developmental switch to control the migratory behaviour of the neuroblast descendants. HOM-C genes can therefore not only direct region-specific patterns of cell division and differentiation, but can also act within migrating cells to programme region-specific migratory behaviour.

Animals

Non-granulated peripolar cells exist in the rat glomerulus.

The peripolar cell is a unique cell type in the mammalian glomerulus. Peripolar cells are said to be identifiable during light microscopy by their cytoplasmic granules and by their position at the vascular pole; and during scanning electron microscopy by their distinctive surface morphology. We used both techniques to count peripolar cells in 6 normal rat kidneys. Scanning microscopy revealed that 55(+/- 5)% of glomeruli contained at least one peripolar cell whereas light microscopy revealed granulated peripolar cells in only 4(+/- 2)% of glomeruli. Vascular poles which contained peripolar cells previously identified by scanning were then examined by light and by transmission electron microscopy. Serial sections through these peripolar cells demonstrated the absence of cytoplasmic granules. Our observations suggest that the majority of peripolar cells in the rat contain no granules.

Animals

Cell signals allow the expression of a pre-existent neural pattern in C. elegans.

In C. elegans, a simple pattern develops within a row of epidermal precursor cells, V1-V6. One cell, V5, gives rise to a neuroblast called the postdeirid neuroblast, while the other V cells produce epidermal cells instead. Here we describe experiments suggesting that in order for V5 to produce the postdeirid it must be in close or direct contact with neighboring V cells. Signaling between V cells is required for the formation of the neuroblast; however, which of the V cells can make a postdeirid is not determined by these signals but rather by the action of the homeotic lin-22 and pal-1 genes. These genes prevent V cells in specific body regions from responding to intercellular signals and producing postdeirids. This is a clear example of cell signals playing a permissive rather than an instructive role in neuroblast induction.

Animals

Expression of the homeotic gene mab-5 during Caenorhabditis elegans embryogenesis.

mab-5 is a member of a complex of homeobox-containing genes evolutionarily related to the Antennapedia and bithorax complexes of Drosophila melanogaster. Like the homeotic genes in Drosophila, mab-5 is required in a particular region along the anterior-posterior body axis, and acts during postembryonic development to give cells in this region their characteristic identities. We have used a mab-5-lacZ fusion integrated into the C. elegans genome to study the posterior-specific expression of mab-5 during embryogenesis. The mab-5-lacZ fusion was expressed in the posterior of the embryo by 180 minutes after the first cleavage, indicating that the mechanisms responsible for the position-specific expression of mab-5-lacZ act at a relatively early stage of embryogenesis. In embryos homozygous for mutations in the par genes, which disrupt segregation of factors during early cleavages, expression of mab-5-lacZ was no longer localized to the posterior. This suggests that posterior-specific expression of mab-5 depends on the appropriate segregation of developmental factors during early embryogenesis. After extrusion of any blastomere of the four-cell embryo, descendants of the remaining three cells could still express the mab-5-lacZ fusion. In these partial embryos, however, the fusion was often expressed in cells scattered throughout the embryo, suggesting that cell-cell interactions and/or proper positioning of early blastomeres are required for mab-5 expression to be localized to the posterior.

Animals

Regulation of cellular responsiveness to inductive signals in the developing C. elegans nervous system.

In Caenorhabditis elegans, cell-cell communication is required to form a simple pattern of sensory ray neurons and cuticular structures (alae). The C. elegans pal-1 gene initiates one developmental pathway (ray lineages) simply by blocking a cell-cell interaction that induces an alternative pathway. Here we show by mosaic analysis that pal-1+ acts by preventing specific cells from responding to inductive signals. The results indicate that although cell signals play a critical role in generating this pattern, they do not provide spatial information. Instead, signals are sent to many, if not all, of the precursor cells, and the ability to respond is spatially restricted. This patterning strategy thus differs from many well known models for pattern formation in which localized inductive signals influence a subset of cells within a field. We find that pal-1 encodes a homeodomain protein and so is likely to regulate transcription. The pal-1+ protein could block the response to cell signals either by repressing genes involved in signal transduction or by acting directly on downstream genes in a way that neutralizes the effects of the intercellular signals. Genetic experiments indicate that one candidate for such a downstream gene is the Antennapedia-like homeotic selector gene mab-5.

Amino Acid Sequence

Collateral branching innervation of rat molar teeth from trigeminal ganglion cells shown by double labelling with fluorescent retrograde tracers.

Somatotopic projections of each maxillary molar tooth were defined by injecting individual teeth with True blue and plotting the location of fluorescent cells in sections of the trigeminal ganglia. Collateral branching was investigated by injecting True blue and Diamidino yellow into pairs of maxillary molar teeth and examining the ganglia for double labelled cells. Maxillary molar teeth project to the lateral ophthalmomaxillary region of the ipsilateral ganglion with extensive overlap of the projections from individual teeth. Double labelling with both dyes demonstrated considerable collateral branching from single trigeminal ganglion cells to the molar teeth.

Animals

Selective silencing of cell communication influences anteroposterior pattern formation in C. elegans.

In C. elegans males, laterally located V cells generate a simple pattern of anterior alae (cuticular ridges) and posterior rays (mating sensilla). We have found that this pattern is generated, at least in part, by the selective interruption of cell-cell interactions. In anterior V cells, lineages leading to the production of alae are induced by cell interactions. These cell interactions are inhibited in specific posterior V cells by the activity of the gene pal-1, which allows these cells to generate rays instead of alae. The activities of cell signals and pal-1 appear to influence V cell fates by determining the state of a developmental switch that involves two homeotic genes, lin-22 and mab-5.

Alleles

Identification of genes from pattern formation, tyrosine kinase, and potassium channel families by DNA amplification.

The study of gene family members has been aided by the isolation of related genes on the basis of DNA homology. We have adapted the polymerase chain reaction to screen animal genomes very rapidly and reliably for likely gene family members. Using conserved amino acid sequences to design degenerate oligonucleotide primers, we have shown that the genome of the nematode Caenorhabditis elegans contains sequences homologous to many Drosophila genes involved in pattern formation, including the segment polarity gene wingless (vertebrate int-1), and homeobox sequences characteristic of the Antennapedia, engrailed, and paired families. In addition, we have used this method to show that C. elegans contains at least five different sequences homologous to genes in the tyrosine kinase family. Lastly, we have isolated six potassium channel sequences from humans, a result that validates the utility of the method with large genomes and suggests that human potassium channel gene diversity may be extensive.

Amino Acid Sequence

Posterior pattern formation in C. elegans involves position-specific expression of a gene containing a homeobox.

During postembryonic development in C. elegans, posterior-specific pattern formation requires the gene mab-5. Within the posterior body region, mab-5 activity controls epidermal, neuronal, and mesodermal cell differentiation, and also the direction of cell migration. Here, we show that mab-5 RNA is localized in the posterior body region, indicating that mab-5 activity is targeted to posterior cells, at least in part, by a mechanism that operates at the level of mab-5 RNA synthesis or stabilization. We also show that mab-5 contains a homeobox similar to that of the Drosophila Antennapedia gene. This suggests that mab-5 influences cell differentiation and cell migration by regulating gene expression, and clearly demonstrates that genes containing homeoboxes influence global aspects of pattern formation in organisms other than Drosophila.

Amino Acid Sequence

The nematode Caenorhabditis elegans.

In Caenorhabditis elegans patterns of cell division, differentiation, and morphogenesis can be observed with single-cell resolution in intact, living animals. Mechanisms that determine behaviors of individual cells during development are being dissected by means of genetic, cell biological, and molecular approaches.

Animals

A gene involved in the development of the posterior body region of C. elegans.

Many regional differences in Caenorhabditis elegans body pattern are generated after hatching. Here I describe a gene, mab-5, that is required for the postembryonic development of nearly all ectodermal and mesodermal features that normally characterize a posterior body region. In addition, this gene is necessary for most cell migrations toward the posterior, but not for cell migrations toward the anterior. mab-5+ activity is cell-autonomous. In animals carrying a mutation in the gene lin-22, increases or decreases in mab-5+ gene dosage produce corresponding increases or decreases in the size of the region in which cells adopt posterior-specific fates. The model that best explains the data is that during postembryonic development, posterior-specific patterns of cell differentiation and cell migration are initiated by graded positional information, and that a common step in the different cellular responses to this information is mediated by mab-5 activity.

Animals

Midazolam in conservative dentistry. A cross-over trial.

In a double-blind trial, 50 patients were randomly allocated to receive up to 0.29 mg/kg diazepam (Valium 5 mg/ml) or 0.14 mg/kg of midazolam (midazolam hydrochloride 5 mg/ml) intravenously at a first session of conservative dentistry, the alternative being administered at the second session. Good operating conditions were reported under each sedative and no important physiological differences were observed. Most patients failed to return to 'street fitness' 30 minutes after either session of treatment. Previous reports of reduced incidence of venous thrombophlebitis with midazolam were not convincingly confirmed in this trial, but data quality was poor. For about half the patients, the amnesic effect was stronger following midazolam.

Adolescent

I.v. flunitrazepam and i.v. diazepam in conservative dentistry. A cross-over trial.

In a randomized cross-over trial in 82 outpatients aged 15-45 yr undergoing conservative dentistry, a solution of flunitrazepam 0.25 mg ml-1 i.v. (average dose 0.014 mg kg-1) was compared with a solution of diazepam 5 mg ml-1 i.v. (0.29 mg kg-1). Cardiovascular changes, operating conditions and side-effects were similar. Forty minutes after the start of injection, about 85% of all patients could not remember the local anaesthetic injection. Thirty minutes after the end of treatment, only 25% of all patients had recovered. One week later, most patients receiving each drug had only vague memories of their treatment; they had felt more relaxed immediately after the i.v. injection than before. Drowsiness was equally common after flunitrazepam and diazepam. Ataxia was more prolonged with flunitrazepam but arm pain and venous thrombophlebitis were less frequent.

Adolescent

Subanaesthetic dosage of Althesin as a sedative for conservative dentistry. A controlled trial.

A randomized partial cross-over clinical trial of two intravenous techniques for outpatient conservative dentistry was performed in 61 patients. Subanaesthetic incremental doses of Althesin were used at 52 sessions and a single sedative dose of diazepam at 45 sessions. Each technique produced similar cardiovascular and respiratory changes. With Althesin, recovery after operation was more rapid and there was some evidence of a stronger anxiolytic effect and of less frequent and less severe thrombophlebitis. In contrast, Althesin was sometimes associated with jaw tremor or shivering and was less frequently mentioned by those patients who expressed a strong preference for one of the two techniques.

Adult

From von Graefe's clinic to the Ecole des Beaux-Arts. The meteoric career of Richard Liebreich.

Richard Liebreich was a student of Helmholtz and took one of the first ophthalmoscopes to von Graefe's clinic. While von Graefe's assistant in Berlin, he created the first atlas of ophthalmoscopy. Liebreich moved to Paris, where he achieved great success, due in part to successful surgery on Emperor Napoleon III's mother-in-law. After the fall of Napoleon in 1870, Liebreich moved to London, where he became the head of ophthalmology at St. Thomas hospital and medical school. Following several personal attacks in the medical literature, Liebreich returned to Paris, where he gradually retired from practice, yet continued a creative life as a sculptor, painter, and researcher in artistic technique.

England