Biomedical subjects

J R Carlson

Publications and source records attributed to J R Carlson.

At least 37 records · Page 2Linked to original sources

PubMed1999

An enhancer trap line identifies the Drosophila homolog of the L37a ribosomal protein.

A gene identified from an enhancer trap screen is shown to encode the Drosophila melanogaster homolog of the L37a ribosomal protein. The predicted 92 amino-acid sequence of this protein is 78% identical to mammalian L37a proteins, and contains a conserved Cys-X2 Cys-X14-Cys-X2-Cys zinc finger motif that may be involved in interactions with ribosomal RNA. The Drosophila L37a homolog is a single copy gene comprised of four exons and is ubiquitously expressed throughout the animal. Cytological localization reveals that Drosophila L37a maps to position 25C1-3, very near the previously described Minute mutation M(2)25C.

Amino Acid Sequence↗

PubMed1999

Olfactory adaptation depends on the Trp Ca2+ channel in Drosophila.

Olfactory adaptation is shown to occur in Drosophila, at both behavioral and physiological levels. In a behavioral paradigm, the extent of adaptation is shown to depend on the dose and duration of the adapting stimulus. Half-maximal adaptation occurred after 15 sec of exposure to an odor, and recovery occurred with a half-time of 1. 5 min, under a set of test conditions. Cross-adaptation was observed among all odor combinations tested, although to a lesser extent than when the same odor was used as both the adapting and the test stimulus. Mutants of the transient receptor potential (Trp) Ca2+ channel were normal in olfactory response, but defective in olfactory adaptation, when measured either behaviorally or in tests of antennal physiology. These results indicate that olfactory response and adaptation can be distinguished. Trp expression was detected in the developing antenna but, surprisingly, not in the mature antenna. These results, together with temperature-shift analysis of a temperature-sensitive trp mutant, provide evidence of a role of Trp in olfactory system development.

Adaptation, Physiological↗

PubMed1999

Odor coding in a model olfactory organ: the Drosophila maxillary palp.

Odor coding relies on the activity of different classes of receptor neurons, each with distinct response characteristics. We have examined odor coding in a model olfactory organ, the maxillary palp of Drosophila. This organ contains only 120 olfactory receptor neurons, compartmentalized in sensory hairs called sensilla, and provides an opportunity to characterize all neurons in an entire olfactory organ. Extensive extracellular recordings from single sensilla reveal that the neurons fall into six functional classes. Each of the 60 sensilla houses two neurons, which observe a pairing rule: each sensillum combines neurons of two particular classes, thereby yielding three sensillum types. The sensillum types are intermingled on the surface of the palp, but their distribution is not random. The neurons exhibit diverse response characteristics, providing the basis for an olfactory code. A particular odor can excite one neuron and inhibit another, and a particular neuron can be excited by one odor and inhibited by another. Some excitatory responses continue beyond the end of odor delivery, but responses to most odors terminate abruptly after the end of odor delivery, with some followed by a period of poststimulus quiescence. The specificity of odor response is examined in detail for the neurons of one sensillum, which were found to differ in their relative responses to a homologous series of esters. Adaptation and cross-adaptation are documented, and cross-adaptation experiments demonstrate that the two neurons within one type of sensillum can function independently. The analysis of all neuronal types in this model olfactory organ is discussed in terms of its functional organization and the mechanisms by which it encodes olfactory information.

Adaptation, Physiological↗

PubMed1999

Traumatic open anterior lumbosacral fracture dislocation. A report of two cases.

STUDY DESIGN: Case presentation. OBJECTIVES: To review the diagnosis and treatment of rare anterior lumbosacral fracture dislocations. SUMMARY OF BACKGROUND DATA: The severity of closed anterior and open and closed posterior lumbosacral dislocations has been documented; however, there have been no reports of open anterior lumbosacral dislocations in the literature. Two patients are reported who experienced acute open anterior lumbosacral fracture dislocations. METHODS: Review of the patient history and physical examination, radiologic review, operative techniques, and a review of the literature. RESULTS: Fractures healed in both patients, with no major infections. Both patients had persistent neurologic deficits at last follow-up. CONCLUSIONS: Open lumbosacral fracture dislocations are complex injuries that require diligence on the part of the surgeons involved the recognize the severity of the injury, to prevent or resolve any infectious process, to prevent further neurologic injury, and then to obtain and maintain alignment of the spine on the pelvis.

Adolescent↗

PubMed1999

A novel family of divergent seven-transmembrane proteins: candidate odorant receptors in Drosophila.

Although insects have proven to be valuable models for exploring the function, organization, and development of the olfactory system, the receptor molecules that bind odors have not been identified in any insect. We have developed a novel search algorithm, used it to search the Drosophila genomic sequence database, and identified a large multigene family encoding seven transmembrane domain proteins that are expressed in olfactory organs. We show that expression is restricted to subsets of olfactory receptor neurons (ORNs) for a number of these genes. Different members of the family initiate expression at different times during antennal development. Some of the genes are not expressed in a mutant of the Acj6 POU-domain transcription factor, a mutant in which a subset of ORNs show abnormal odorant specificities.

Amino Acid Sequence↗

PubMed1999

The odor specificities of a subset of olfactory receptor neurons are governed by Acj6, a POU-domain transcription factor.

Little is known about how the odor specificities of olfactory neurons are generated, a process essential to olfactory coding. We have found that neuronal identity relies on the abnormal chemosensory jump 6 (acj6) gene, originally identified by a defect in olfactory behavior. Physiological analysis of individual olfactory neurons shows that in acj6 mutants, a subset of neurons acquires a different odorant response profile. Certain other neurons do not respond to any tested odors in acj6. Molecular analysis of acj6 shows that it encodes a POU-domain transcription factor expressed in olfactory neurons. Our data suggest that the odor response spectrum of an olfactory neuron, and perhaps the choice of receptor genes, is determined through a process requiring the action of Acj6.

Alleles↗

PubMed1999

Chemosensory behavior: the path from stimulus to response.

In the past year, candidates have been identified for two long-sought classes of molecules, insect odorant receptors and mammalian taste receptors. In addition, genes directing receptor gene expression and the development of specific chemosensory neurons have been described in Drosophila melanogaster and Caenorhabditis elegans. Finally, recent physiological experiments have provided new insights into the mechanisms by which chemosensory information is processed.

Animals↗

PubMed1999

Ecdysone response genes govern egg chamber development during mid-oogenesis in Drosophila.

The steroid hormone ecdysone regulates larval development and metamorphosis in Drosophila melanogaster through a complex genetic hierarchy that begins with a small set of early response genes. Here, we present data indicating that the ecdysone response hierarchy also mediates egg chamber maturation during mid-oogenesis. E75, E74 and BR-C are expressed in a stage-specific manner while EcR expression is ubiquitous throughout oogenesis. Decreasing or increasing the ovarian ecdysone titer using a temperature-sensitive mutation or exogenous ecdysone results in corresponding changes in early gene expression. The stage 10 follicle cell expression of E75 in wild-type, K10 and EGF receptor (Egfr) mutant egg chambers reveals regulation of E75 by both the Egfr and ecdysone signaling pathways. Genetic analysis indicates a germline requirement for ecdysone-responsive gene expression. Germline clones of E75 mutations arrest and degenerate during mid-oogenesis and EcR germline clones exhibit a similar phenotype, demonstrating a functional requirement for ecdysone responsiveness during the vitellogenic phase of oogenesis. Finally, the expression of Drosophila Adrenodoxin Reductase increases during mid-oogenesis and clonal analysis confirms that this steroidogenic enzyme is required in the germline for egg chamber development. Together these data suggest that the temporal expression profile of E75, E74 and BR-C may be a functional reflection of ecdysone levels and that ecdysone provides temporal signals regulating the progression of oogenesis and proper specification of dorsal follicle cell fates.

Animals↗

PubMed1999

The dare gene: steroid hormone production, olfactory behavior, and neural degeneration in Drosophila.

Steroid hormones mediate a wide variety of developmental and physiological events in insects, yet little is known about the genetics of insect steroid hormone biosynthesis. Here we describe the Drosophila dare gene, which encodes adrenodoxin reductase (AR). In mammals, AR plays a key role in the synthesis of all steroid hormones. Null mutants of dare undergo developmental arrest during the second larval instar or at the second larval molt, and dare mutants of intermediate severity are delayed in pupariation. These defects are rescued to a high degree by feeding mutant larvae the insect steroid hormone 20-hydroxyecdysone. These data, together with the abundant expression of dare in the two principal steroid biosynthetic tissues, the ring gland and the ovary, argue strongly for a role of dare in steroid hormone production. dare is the first Drosophila gene shown to encode a defined component of the steroid hormone biosynthetic cascade and therefore provides a new tool for the analysis of steroid hormone function. We have explored its role in the adult nervous system and found two striking phenotypes not previously described in mutants affected in steroid hormone signaling. First, we show that mild reductions of dare expression cause abnormal behavioral responses to olfactory stimuli, indicating a requirement for dare in sensory behavior. Then we show that dare mutations of intermediate strength result in rapid, widespread degeneration of the adult nervous system.

Amino Acid Sequence↗

PubMed1998

Olfactory coding in a compound nose. Coexpression of odorant-binding proteins in Drosophila.

Odorant-binding proteins (OBPs) are small, soluble proteins present in the aqueous medium surrounding olfactory receptor neurons. Their function in olfaction is unknown: they have been proposed to facilitate the transit of hydrophobic molecules to olfactory receptors, to deactivate the odorant stimulus, and/or to play a role in chemosensory coding. We have examined the genomic organization and expression patterns of two olfactory-specific genes (OS-E and OS-F) of Drosophila melanogaster, the products of which are members of a protein family in Drosophila sharing sequence similarity with moth OBPs. We found that the OS-E and OS-F transcription units are located < 1 kb apart. They are oriented in the same direction and display a similar intron-exon organization. Expression of both OS-E and OS-F proteins is spatially restricted to the ventrolateral region of the Drosophila antenna. Within this region, both OS-E and OS-F proteins are expressed within two different types of sensory hairs: in most, if not all, sensilla trichodea and in approximately 40% of the interspersed small sensilla basiconica. We consistently observe that OS-E and OS-F are coexpressed, indicating that an individual sensillum can contain more than one odorant-binding protein. This finding has potential implications for the roles of odorant-binding proteins in olfactory coding.

Animals↗

PubMed1998

Autoinducer of virulence as a target for vaccine and therapy against Staphylococcus aureus.

Staphylococcus aureus causes pathologies ranging from minor skin infections to life-threatening diseases. Pathogenic effects are largely due to production of bacterial toxin, which is regulated by an RNA molecule, RNAIII. The S. aureus protein called RAP (RNAIII activating protein) activates RNAIII, and a peptide called RIP (RNAIII inhibiting peptide), produced by a nonpathogenic bacteria, inhibits RNAIII. Mice vaccinated with RAP or treated with purified or synthetic RIP were protected from S. aureus pathology. Thus, these two molecules may provide useful approaches for the prevention and treatment of diseases caused by S. aureus.

Amino Acid Sequence↗

PubMed1998

A comparison of biodegradable microparticles and MF59 as systemic adjuvants for recombinant gD from HSV-2.

A recombinant form of glycoprotein D from herpes simplex virus type-2 (gD2) was encapsulated into polylactide-co-glycolide (PLG) microparticles using a previously established solvent evaporation technique. The mean size of the microparticles was about 1 micron and high encapsulation efficiency of the antigen was achieved (70-80%). The microparticles were administered intramuscularly to Balb/C mice and the immune responses were compared with those obtained with the oil in water adjuvant MF59. The serum IgG response to gD2 induced by the microparticles was comparable with that induced by MF59. The serum neutralization titres were also comparable for microparticles and the emulsion. However, the microparticles induced a higher IgG2a isotype response and a more potent serum IFN-gamma response than MF59, suggesting a more Th1 type of response. The MF59 induced higher levels of serum IL-4 and IL-5 cytokines, suggesting a more Th2 type of response.

Adjuvants, Immunologic↗

PubMed1998

Wrist arthrodesis after failed wrist implant arthroplasty.

Wrist arthroplasty has not achieved large success to date, and there are patients with failures in their procedures who will need arthrodesis. We review our experience in revising a wrist implant arthroplasty to an arthrodesis with a block graft of fresh-frozen allograft femoral head or iliac crest bone graft. Fixation was achieved with an intramedullary Steinmann pin. Ten patients with 12 failed wrist implants required wrist arthrodesis; 7 had wrist arthrodesis with a bulk allograft femoral head, 4 with an iliac crest bone autograft, and 1 without a bone graft. After an average follow-up period of 5 years, all patients were pain free and fusion had been achieved. Complications included 1 patient with acute carpal tunnel syndrome, 2 patients with nonunions requiring secondary bone grafting procedures, and 2 patients requiring revisions of their intramedullar pins. In both nonunions, iliac crest bone graft was used for the initial arthrodesis. All the patients were satisfied. Arthrodesis after failed wrist implant arthroplasty is a satisfactory procedure, and a fresh-frozen allograft can be used effectively in wrist fusion.

Adult↗

PubMed1998

Elder abuse: two Native American views.

In order to gain a greater understanding of what "elder abuse" means to the American public, a random sample of adults from seven culturally diverse counties in North Carolina was interviewed. Two of the six Native American groups residing in North Carolina were represented in the sample. The two Native American groups' responses were compared with each other and with the views of a panel of elder mistreatment experts. There were areas of agreement and disagreement. The relevance of the findings is discussed in relation to research, practice, education, and policy.

Adult↗

PubMed1998

small wing encodes a phospholipase C-(gamma) that acts as a negative regulator of R7 development in Drosophila.

Phospholipase C-(gamma) (PLC-(gamma)) is activated in many cell types following growth factor stimulation. Our understanding of the role of PLC-(gamma) in cell growth and differentiation has been severely limited by the dearth of mutations in any organism. In this study, we show that the Drosophila gene small wing (sl), identified by Bridges in 1915, encodes a PLC-(gamma). Mutations of sl result in extra R7 photoreceptors in the compound eye, consistent with overactivation of the receptor tyrosine kinase pathways that control R7 development. The data presented here provide the first genetic evidence that PLC-(gamma) is involved in Ras-mediated signaling and indicate that PLC-(gamma) acts as a negative regulator in such pathways in Drosophila.

Alleles↗

PubMed1997

Coexpression of two odorant-binding protein homologs in Drosophila: implications for olfactory coding.

Odorant-binding proteins (OBPs) are small soluble proteins present in the aqueous medium surrounding olfactory receptor neurons. Their function in olfaction is still unknown: they have been proposed to facilitate the transit of hydrophobic molecules to olfactory receptors, to deactivate the odorant stimulus, and/or to play a role in chemosensory coding. In this study we examine the genomic organization and expression patterns of two olfactory-specific genes (OS-E and OS-F) of Drosophila melanogaster, the products of which are members of a protein family in Drosophila sharing sequence similarity with moth OBPs. We show that the OS-E and OS-F transcription units are located <1 kb apart. They are oriented in the same direction and display a similar intron-exon organization. Expression of both OS-E and OS-F proteins is restricted spatially to the ventrolateral region of the Drosophila antenna. Within this region both OS-E and OS-F proteins are expressed within two different types of sensory hairs: in most, if not all, sensilla trichodea and in approximately 40% of the interspersed small sensilla basiconica. We consistently observe that OS-E and OS-F are coexpressed, indicating that an individual sensillum can contain more than one odorant-binding protein. The functional significance of the observed expression pattern and its implications for olfactory coding are discussed.

Animals↗

PubMed1997

The maxillary palp of Drosophila: ultrastructure and physiology depends on the lozenge gene.

The ultrastructure and physiology of the maxillary palp of Drosophila melanogaster have been studied in wild-type and lozenge mutants. Olfactory physiology in the maxillary palp is shown to depend upon the lozenge(lz) gene. Reduced response amplitudes were recorded for all odorants tested, and the physiological defect was shown to map to the lz locus. The structure of the maxillary palp sensilla is described by scanning electron microscopy (SEM) at high magnification, initially in the wild-type. A linear arrangement of pores, connected by furrows, was found in one class of sensilla, the basiconic sensilla. In the lz3 mutant, morphological alterations in the basiconic sensilla and duplications of sensilla are documented by SEM. The correlation of structural abnormalities in the lz sensilla and physiological abnormalities in odorant response are consistent with an olfactory role for the basiconic sensilla of the maxillary palp.

Animals↗

PubMed1997

The Drosophila antenna: ultrastructural and physiological studies in wild-type and lozenge mutants.

The physiology and ultrastructure of the antenna in Drosophila melanogaster have been examined in wild-type and lozenge mutants. Scanning electron microscopy (SEM) of sensilla on the antennal surface has revealed that in the wild-type the basiconic sensilla contain linear arrays of pores connected by longitudinal furrows and transected by shorter furrows. Sensilla trichodea also are shown to have pores, as revealed by examining transverse sections by transmission electron microscopy (TEM); these data directly address a longstanding controversy. Coeloconic sensilla, previously described as "pit sensilla" and as "grooved" sensilla, are shown to rise directly from the antennal surface, as opposed to lying below the antennal surface in pits; the previously observed grooves correspond to the junctions between bundled, finger-like projections. This description of coeloconic sensilla is supported by analysis of lz mutants, in which the projections of coeloconic sensilla splay apart. Coeloconic sensilla are also shown to undergo duplication on the lz3 antenna. Physiological recordings from the antenna show that responses to all odorants tested are severely decreased in lz mutants. Measurements made from different parts of the antenna show similar defects. Evidence is provided that both the physiological and ultrastructural defects map to the lz locus.

Animals↗