The SPFH domain: implicated in regulating targeted protein turnover in stomatins and other membrane-associated proteins.
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Amino Acid Motifs↗
Biomedical subjects
M Driscoll
Publications and source records attributed to M Driscoll.
A nationwide survey of financing health-related services for special education students.
The Individuals with Disability Education Act (IDEA) requires state educational systems to provide school-based, health related services (RS). This survey determined the financing arrangements used by states for health-related services for school-aged children with disabilities. A survey was sent to directors of special education, Medicaid, and public health departments in each of the 50 states. Financial patterns for RS were sought at the state level for children ages 3-21 with disabilities for the 1993-1994 school year, the most recent year for which complete financial data were available. Univariate analyses probed the relationship between systems' variables and the extent of Medicaid usage by local education agencies. Respondents reported that schools tapped traditional health resources to supplement educational dollars in paying for related services in schools. Medicaid was by far the most common source with 29 states reporting established mechanisms for recouping Medicaid dollars and 10 states reporting phase-in activities. Seventeen states reported that departments of public health played some role in administration, training, and demonstrations, but only six states provided specific dollars for related services through the department. Use of private insurance was reported sporadically with only one state indicating a specific state-level program. Correlates of increased Medicaid usage were presence of interagency agreements (IAAs) (OR 11.1, p = 0.002), having specific personnel for school-based medical assistance (OR 17.7, p = 0.001), and utilizing school nursing services as a Medicaid optional service (OR 4.2, p = 0.048).
Adolescent↗
Systems change resulting from HIV/AIDS education and training. A cross-cutting evaluation of nine innovative projects.
An evaluation of nine diverse HIV/AIDS training programs assessed the degree to which the programs produced changes in the ways that health care systems deliver HIV/AIDS care. Participants were interviewed an average of 8 months following completion of training and asked for specific examples of a resulting change in their health care system. More than half of the trainees gave at least one example of a systems change. The examples included the way patient referrals are made, the manner in which agency collaborations are organized, and the way care is delivered.
Adolescent↗
The maternal and child health sites' practices regarding HIV education, counseling, and testing of women of reproductive age in Chicago: barriers to universal implementation.
OBJECTIVES: Women of reproductive age are increasingly at risk for human immunodeficiency virus (HIV) infection. Recent advances in reducing perinatal transmission have resulted in official guidelines on universal HIV education, counseling, and voluntary testing of women of reproductive age, especially pregnant women. This study assesses to what extent the maternal child health (MCH) sites are implementing these guidelines with their female patient population (including pregnant women) and examines the barriers that prevent them from implementing these guidelines. METHOD: The study uses survey data from 92 hospitals and community health centers offering MCH services in Chicago regarding their providers' practices on HIV education, counseling, and testing, implementation of zidovudine (ZDV) therapy to reduce perinatal transmission, and the barriers to implementing these services. In addition, 20 taped in-depth interviews were conducted with experts to examine the barriers to universal implementation. RESULTS: Almost half (45% of perinatal care and 50% of family planning providers) of the institutions are not consistently offering HIV testing. One-third of those institutions that offer testing are not offering pretest counseling. Thirty-nine percent of the perinatal care providers in these institutions are not providing posttest counseling to HIV-negative women. Over one-third (35%) of these institutions reported that they are not set up to implement ZDV therapy during labor and delivery. Almost half (49%) had no protocols for ZDV therapy in place. Barriers to implementation included lack of provider training, limited staff time, physician resistance, unavailability or avoidance to seek perinatal care by high-risk women, cost, absence of a statewide and hospital-specific plan, lack of reproductive choice focus in posttest counseling, lack of provider knowledge about the administration of ZDV or its availability during labor, and lack of consumer education on perinatal risk reduction. CONCLUSIONS: MCH sites and their providers need assistance to overcome many barriers they face to implement universal HIV education, counseling, and testing of women of reproductive age.
AIDS Serodiagnosis↗
Genetically targeted cell disruption in Caenorhabditis elegans.
The elimination of identified cells is a powerful tool for investigating development and system function. Here we report on genetically mediated cell disruption effected by the toxic Caenorhabditis elegans mec-4(d) allele. We found that ectopic expression of mec-4(d) in the nematode causes dysfunction of a wide range of nerve, muscle, and hypodermal cells. mec-4(d)-mediated toxicity is dependent on the activity of a second gene, mec-6, rendering cell disruption conditionally dependent on genetic background. We describe a set of mec-4(d) vectors that facilitate construction of cell-specific disruption reagents and note that genetic cell disruption can be used for functional analyses of specific neurons or neuronal classes, for confirmation of neuronal circuitry, for generation of nematode populations lacking defined classes of functional cells, and for genetic screens. We suggest that mec-4(d) and/or related genes may be effective general tools for cell inactivation that could be used toward similar purposes in higher organisms.
Animals↗
Neuropathology of degenerative cell death in Caenorhabditis elegans.
In Caenorhabditis elegans necrosis-like neuronal death is induced by gain-of-function (gf) mutations in two genes, mec-4 and deg-1, that encode proteins similar to subunits of the vertebrate amiloride-sensitive epithelial Na+ channel. We have determined the progress of cellular pathology in dying neurons via light and electron microscopy. The first detectable abnormality is an infolding of the plasma membrane and the production of small electron-dense whorls. Later, cytoplasmic vacuoles and larger membranous whorls form, and the cell swells. More slowly, chromatin aggregates and the nucleus invaginates. Mitochondria and Golgi are not dramatically affected until the final stages of cell death when organelles, and sometimes the cells themselves, lyse. Certain cells, including some muscle cells in deg-1 animals, express the abnormal gene products and display a few membrane abnormalities but do not die. These cells either express the mutant genes at lower levels, lack other proteins needed to form inappropriately functioning channels, or are better able to compensate for the toxic effects of the channels. Overall, the ultrastructural changes in these deaths suggest that enhanced membrane cycling precedes vacuolation and cell swelling. The pathology of mec-4(gf) and deg-1(gf) cells shares features with that of genetic disorders with alterations in channel subunits, such as hypokalemic periodic paralysis in humans and the weaver mouse, and with degenerative conditions, e.g., acute excitotoxic death. The initial pathology in all of these conditions may reflect attempts by affected cells to compensate for abnormal membrane proteins or functions.
Animals↗
unc-8, a DEG/ENaC family member, encodes a subunit of a candidate mechanically gated channel that modulates C. elegans locomotion.
Mechanically gated ion channels are important modulators of coordinated movement, yet little is known of their molecular properties. We report that C. elegans unc-8, originally identified by gain-of-function mutations that induce neuronal swelling and severe uncoordination, encodes a DEG/ENaC family member homologous to subunits of a candidate mechanically gated ion channel. unc-8 is expressed in several sensory neurons, interneurons, and motor neurons. unc-8 null mutants exhibit previously unrecognized but striking defects in the amplitude and wavelength of sinusoidal tracks inscribed as they move through an E. coli lawn. We hypothesize that UNC-8 channels could modulate coordinated movement in response to body stretch. del-1, a second DEG/ENaC family member coexpressed with unc-8 in a subset of motor neurons, might also participate in a channel that contributes to nematode proprioception.
Amino Acid Sequence↗
Molecular modeling of mechanotransduction in the nematode Caenorhabditis elegans.
Genetic and molecular studies of touch avoidance in the nematode Caenorhabditis elegans have resulted in a molecular model for a mechanotransducing complex. mec-4 and mec-10 encode proteins hypothesized to be subunits of a mechanically gated ion channel that are related to subunits of the vertebrate amiloride-sensitive epithelial Na+ channel. Products of mec-5, a novel collagen, and mec-9, a protein that includes multiple Kunitz-type protease inhibitor repeats and EGF repeats, may interact with the channel in the extracellular matrix. Inside the cell, specialized 15-protofilament microtubules composed of mec-12 alpha-tubulin and mec-7 beta-tubulin may be linked to the mechanosensitive channel by stomatin-homologous MEC-2. MEC-4 and MEC-10 are members of a large family of C. elegans proteins, the degenerins. Two other degenerins, UNC-8 and DEL-1, are candidate components of a stretch-sensitive channel in motor neurons. Implications for advancing understanding of mechanotransduction in other systems are discussed.
Animals↗
Molecules that mediate touch transduction in the nematode Caenorhabditis elegans.
Despite the widespread importance of mechanotransduction in biology, remarkably little is known about the nature of the molecules that mediate mechanical signaling. Mechanosensation in the nematode Caenorhabditis elegans is mediated by six mechanosensory neurons called touch receptor cells. Genetic analysis has resulted in the identification of over 400 mutations that disrupt the function of the touch receptors. Molecular characterization of the genes revealed has identified subunits of a candidate mechanosensory ion channel, tubulins expressed specifically in the touch receptors, and extracellular matrix proteins needed for mechanotransduction. mec-4 and mec-10 encode members of a C. elegans gene family related to the vertebrate epithelial Na+ channel that are hypothesized to encode subunits of a mechanosensory channel. mec-6 may encode another channel subunit. Inside the cell, alpha-tubulin MEC-12, beta-tubulin MEC-7 and a candidate linker protein MEC-2 may interact with the mechanotransducing channel to deliver gating tension. In the extracelluar matrix, collagen MEC-5 and MEC-9 and MEC-1 may interact with extracellular channel domains. A molecular model for mechanotransduction is discussed.
Animals↗
Inserting and maintaining peripherally inserted central catheters.
Peripherally inserted central catheters are a type of vascular access device that has many advantages for patients with longer-term and special infusion needs. Increasingly common in home and hospital settings, nurses should know how to insert, maintain, and educate patients and families about these devices. One hospital's experiences implementing a model program is described.
Bandages↗
Sequence and transmembrane topology of MEC-4, an ion channel subunit required for mechanotransduction in Caenorhabditis elegans.
The process by which mechanical stimuli are converted into cellular responses is poorly understood, in part because key molecules in this mode of signal transduction, the mechanically gated ion channels, have eluded cloning efforts. The Caenorhabditis elegans mec-4 gene encodes a subunit of a candidate mechanosensitive ion channel that plays a critical role in touch reception. Comparative sequence analysis of C. elegans and Caenorhabditis briggsae mec-4 genes was used to initiate molecular studies that establish MEC-4 as a 768-amino acid protein that includes two hydrophobic domains theoretically capable of spanning a lipid bilayer. Immunoprecipitation of in vitro translated mec-4 protein with domain-specific anti-MEC-4 antibodies and in vivo characterization of a series of mec-4lacZ fusion proteins both support the hypothesis that MEC-4 crosses the membrane twice. The MEC-4 amino- and carboxy-terminal domains are situated in the cytoplasm and a large domain, which includes three Cys-rich regions, is extracellular. Definition of transmembrane topology defines regions that might interact with the extracellular matrix or cytoskeleton to mediate mechanical signaling.
Amino Acid Sequence↗
A model for the delivery of care for HIV-positive clients.
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Adolescent↗
Cell death in C. elegans: molecular insights into mechanisms conserved between nematodes and mammals.
As is the case for most metazoans, C. elegans cells have the potential to undergo developmental cell death (programmed cell death) or a necrotic-like death in response to cell injury. Analysis of mutations that disrupt the reproducible pattern of cell death that occurs during C. elegans development has defined a genetic pathway for programmed cell death. This program involves the activities of certain genes, such as ces-1 and the ces-2 bZIP transcription factor, which regulate the life/death decision in specific subsets of cells. ced-9, a Bcl-2 family member, acts globally to negatively regulate the activities of ced-4S (which promotes cell death) and ced-4L, which promotes cell life. ced-3 encodes a member of the ICE cysteine protease family that is essential for execution of all programmed cell deaths. Once cells die, corpses are phagocytized and consumed in what appear to be at least two parallel pathways that require the activities of ced-1, ced-6, ced-7 and ced-2, ced-5, ced-10. Degradation of corpse DNA requires the product of the nuc-1 gene. Degenerative cell death, characterized by cell swelling, can be induced by different cell injuries including that conferred by mutant degenerin ion channels (encoded by deg-1, mec-4, mec-10 and unc-8) and by expression of human beta-amyloid peptide. Remarkable parallels between nematode and mammalian death programs have advanced understanding of human cell death mechanisms.
Animals↗
Mechanosensory signalling in C. elegans mediated by the GLR-1 glutamate receptor.
NEURONAL signalling across synapses involves activation of many neurotransmitter receptors on postsynaptic cells. glr-1 encodes a potential glutamate receptor in the nematode Caenorhabditis elegans which is most similar to vertebrae AMPA-type ionotropic glutamate receptors. glr-1 is expressed in motor neurons and interneurons, including interneurons implicated in the control of locomotion. Here we investigate the contribution of glr-1 to the normal signalling of these neurons, by generating a deletion mutation in glr-1. We find that mutant worms are deficient in their ability to withdraw backwards when mechanically stimulated, but they withdraw normally in response to chemical repellents. The ASH sensory neurons mediate withdrawal responses both to mechanical stimuli and to repellents, and ASH makes chemical synapses with glr-1-expressing interneurons. Our results suggest that postsynaptic interneurons use different neurotransmitter receptors to process two sensory stimuli detected by one sensory neuron.
Amino Acid Sequence↗
Methods for the study of cell death in the nematode Caenorhabditis elegans.
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Animals↗
A transmembrane domain of the putative channel subunit MEC-4 influences mechanotransduction and neurodegeneration in C. elegans.
Aberrant ion channel activity plays a causative role in several human disorders. Inappropriately regulated channel activity also appears to be the basis for neurodegeneration induced by dominant mutations of Caenorhabditis elegans mec-4 (mec-4(d)), a member of the degenerin gene family postulated to encode a subunit of a mechanosensory channel. The degenerin gene family has been defined by two C. elegans genes, mec-4 and deg-1, which can mutate to gain-of-function alleles that induce degeneration of specific groups of neurons. A related mammalian gene, rat alpha-rENaC, induces an amiloride-sensitive Na+ current when introduced to Xenopus oocytes, strongly suggesting that degenerin genes encode ion channel proteins. Deduced amino-acid sequences of the degenerins include two predicted membrane-spanning domains. Here we show that conserved amino acids within the second membrane-spanning domain (MSDII) are critical for MEC-4 activity and that specific substitutions within MSDII, whether encoded in cis or in trans to a mec-4(d) mutation, block or delay the onset of degeneration. Remarkably, MSDII from two other family members, C. elegans deg-1 and rat alpha-rENaC, can functionally substitute for MEC-4 MSDII in chimaeric proteins. Our results support a structural model for a mechanosensory channels in which multiple MEC-4 subunits are oriented such that MSDII lines the channel pore, and a neurodegeneration model in which aberrant ion flow through this channel is a key event.
Alleles↗
Shifting the focus to primary and preventive care. New Jersey launches healthcare reform.
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Diagnosis-Related Groups↗