A massive pulmonary tumor embolism after surgical manipulation and biopsy of a pelvic mass.
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Anesthesia, Inhalation↗
Biomedical subjects
D H Jones
Publications and source records attributed to D H Jones.
The new hospice compliance plan: defining and addressing risk areas.
The Department of Health and Human Services' (HHS) Office of the Inspector General (OIG), has advised hospices and other health care providers to formulate effective controls to ensure compliance with federal and state statutes, rules, and regulations, and private-payor health care program requirements. The recently released guidelines provide a blueprint for developing such programs. This is the first of four installments that focus specifically on the 28 risk areas identified in the guidance and offer strategies for incorporating them in a hospice compliance program. The authors have organized the 28 risk areas under 9 topic domains to simplify the task of tackling the guidance. This article covers the first two areas: Admission/Certification/Recertification and Billing.
Certification↗
The new hospice compliance plan: defining and addressing risk areas. Part 2.
The Department of Health and Human Services' (HHS) Office of the Inspector General (OIG), has advised hospices and other health care providers to formulate effective controls to ensure compliance with federal and state statutes, rules, and regulations, and private-payor health care program requirements. This is the second of three installments that focus specifically on the 28 risk areas identified in the guidance and offer strategies for incorporating them in a hospice compliance program. This article covers the areas of Expensive Care, Documentation, Interdisciplinary Group, and Kickbacks.
Documentation↗
The new hospice compliance plan: defining and addressing risk areas. Part 3.
The recently released OIG guidelines to ensure compliance with federal and state statutes, rules, and regulations, and private-payor health care program requirements provide a blueprint for developing such programs. This is the last of three installments that focus specifically on the 28 risk areas identified in the guidance and offer strategies for incorporating them in a hospice compliance program. The authors have organized the 28 risk areas under 9 topic domains to simplify the task of tackling the guidance. This article covers the areas of nursing home care, marketing, and Conditions of Participation.
Guideline Adherence↗
Induction of cytotoxic T-cell responses following oral immunization with synthetic peptides encapsulated in PLG microparticles.
CTL responses play a critical role in clearing viral infections. We have investigated the potential of poly(lactide-co-glycolide) (PLG) microparticles as an oral delivery system for peptides representing CTL epitopes from measles virus nucleoprotein. Oral administration of CTL epitopes encapsulated in 50:50 PLG microparticles, resulted in vivo priming of splenic peptide-specific CTL responses. However, the observed CTL lysis was low and cofeeding of encapsulated peptide with cholera toxin as a mucosal adjuvant did not result in any significant enhancement of the observed CTL responses. The pronounced immunostimulatory effect of microparticles, combined with their excellent tissue compatibility and biodegradability makes them a valuable delivery system for synthetic peptide immunogens. However, further work is needed to improve their efficiency via the oral route.
Administration, Oral↗
ADP ribosylation factor 1 mutants identify a phospholipase D effector region and reveal that phospholipase D participates in lysosomal secretion but is not sufficient for recruitment of coatomer I.
The small GTP-binding protein, ADP-ribosylation factor 1 (ARF1) is essential for the formation of coatomer-coated vesicles from the Golgi and is also an activator of phospholipase D (PLD). Moreover, ARF1-regulated PLD is part of the signal-transduction pathway that can lead to secretion. In this study, substitution and deletion mutants of ARF1 were tested for their ability to activate PLD. These map the PLD effector region of ARF1 to the alpha2 helix, part of the beta2-strand and the N-terminal helix and its ensuing loop. ARF mutants with an increased or decreased ability to activate PLD showed similar characteristics when tested for their ability to stimulate secretion from HL60 cells. ARF1, deleted of the N-terminal 17 amino acid residues (Ndel17), did not support PLD activity or secretion, and neither did it inhibit the activity of wild-type myristoylated ARF1 (myrARF1). In contrast, Ndel17 effectively competed with wild-type myrARF1 to prevent coatomer binding to membranes. This appears to define a structural role for Ndel17, as it can bind a high-molecular mass complex in cytosol. In addition, ethanol has no effect on recruitment of coatomer to membrane. We conclude that the function of ARF-regulated PLD is in the signal-transduction pathway leading to secretion of lysosomal granules, and not as an essential component of ARF1-mediated coatomer binding.
ADP-Ribosylation Factor 1↗
Immune responses and protection obtained by oral immunization with rotavirus VP4 and VP7 DNA vaccines encapsulated in microparticles.
Protective immune responses in mice were obtained after oral immunization with rotavirus DNA vaccines encapsulated in poly(lactide-co-glycolide) (PLG) microparticles. The DNA vaccines used encoded outer capsid proteins VP4 and VP7; proteins that are the basis for rotavirus serotyping and the generation of virus neutralizing antibodies. One dose of vaccine was given to BALB/c mice by oral gavage (75 microg DNA/mouse). Rotavirus-specific serum antibodies and intestinal IgA antibodies were detectable by 6 weeks postimmunization. After challenge with homologous murine rotavirus at 12 weeks postimmunization, fecal rotavirus antigen was reduced significantly in immunized mice compared with controls. Protective immunity also was generated by oral delivery of unencapsulated VP 7 DNA vaccine but to a lesser degree. These results demonstrate that the oral route is effective for generating protective immune responses with rotavirus DNA vaccines targeting neutralization antigens.
Administration, Oral↗
Spontaneous mutation, oxidative DNA damage, and the roles of base and nucleotide excision repair in the yeast Saccharomyces cerevisiae.
The OGG1 gene of Saccharomyces cerevisiae encodes a DNA glycosylase that excises 7,8-dihydro-8-oxoguanine (8-OxoG). When compared to wild-type, ogg1 mutants show an increase in the frequency of GC to TA transversions, indicating a role for Ogg1 in the repair of 8-OxoG. Here we report an increased frequency of forward mutation to canavanine resistance in mutants defective in the nucleotide excision repair (NER) gene RAD14. This was not increased further in strains additionally defective in OGG1. However, when compared to strains solely defective in OGG1, ogg1radl4 mutants displayed an increase in spontaneous GC to TA transversions. Intriguingly, reversion of the lys1-1 ochre allele was not increased in rad14 mutants, suggesting that oxidative base damage may only represent a substrate for NER in certain regions of the genome. We also examined repair of oxidative DNA damage by transforming mutant strains with plasmid DNA treated with methylene blue plus visible light. Mutants defective in OGG1 showed no significant reduction in transformation efficiency compared with wild-type strains. In contrast, disruption of RAD14 reduced the efficiency of transformation, yet there was no further decrease in an ogg1rad14 mutant. This strongly supports a role for NER in the repair of oxidative base damage in yeast, and differs from similar experiments carried out in E. coli, where transformation efficiency is only reduced in mutants defective in both fpg and uvrA. Finally, the repair of Fpg-sensitive sites was examined at the MATalpha and HMLalpha mating type loci, and NER was found to play a role in their removal.
Canavanine↗
A strategy for improvement in care at the end of life: the VA Faculty Leaders Project.
Given the commitment of the Veterans Health Administration (VA) to excellent, compassionate end-of-life and palliative care and the VA's extensive system of academic affiliations with the nation's medical schools, there may exist an opportunity to accelerate acceptance of state-of-the-art training for improved care for dying patients. Accordingly, the VA has initiated a project to develop strategies for implementation of benchmark curricula for end-of-life and palliative care. With the support of the Robert Wood Johnson Foundation, this initiative has been implemented in 30 internal medicine residency training programs affiliated with the VA nationally.
Journal Article↗
Tibial fracture during removal of a tibial intramedullary nail.
SUMMARY: As tibial intramedullary nailing becomes the preferred treatment for tibial shaft fracture, removal of tibial nails will become more common. Removal of tibial intramedullary nails is not without complications, but a review of the literature found only one recent report of a fracture of the tibia during removal. A case report of a tibial fracture during removal of an Alta tibial nail is presented.
Adult↗
Massage and ultrasound as therapeutic modalities in exercise-induced muscle damage.
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Exercise↗
Epidermal growth factor receptor transmembrane domain: 2H NMR implications for orientation and motion in a bilayer environment.
As part of a study of receptor tyrosine kinase behavior in membranes, we have collected extensive NMR data from three well-defined probe locations within the transmembrane region of the human EGF receptor. Spectra were obtained for selectively deuterated alanine residues in a series of peptides corresponding to the putative transmembrane domain (with short extramembranous extensions). Peptides were incorporated into fluid unsonicated liposomes of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and POPC containing 33 mol % cholesterol to mimic common lipid composition of cell plasma membranes. The peptide concentration was in the range of 1-6 mol % relative to that of phospholipid. Data acquired at 35 degreesC have been analyzed quantitatively to determine their implications to receptor spatial orientation and dynamics. If it is presumed that the single transmembrane portion approximates an alpha-helix of 3.6 residues per turn, this helix was found to be tilted away from the membrane perpendicular, about which there was rapid axial diffusion. However, rotation about the peptide long axis was static on the NMR time scale of 10(-)4 s, and the peptide appeared to have a preferred direction(s) of lean. The results for this peptide, whose hydrophobic length is greater than the membrane hydrophobic thickness, were very similar between membranes of POPC and membranes of POPC containing 33 mol % cholesterol, despite considerable host matrix differences in thickness and order. Allowed values of peptide tilt occupied a narrow range: between 10 and 14 degrees in POPC and between 10 and 12 degrees in POPC/cholesterol. Although the existence of some preferred direction(s) of lean was demanded by the results, the direction of lean was not uniquely determined. We have interpreted these results, which were essentially unchanged at 65 degreesC, as reflecting the behavior of peptide monomers undergoing rapidly reversible peptide-peptide interactions. For transmembrane monomers, interference with rotation about the peptide long axis might be understood to arise from an energy benefit (in a tilted peptide) to prevention of particular amino acid side chains near the membrane surfaces from moving in and out of hydrophobic or hydrophilic environments. It will be desirable to test the conclusion of preferential lean of a monomeric receptor since such behavior could provide a mechanism for modulating monomer association with other species (i.e., signal transduction).
Alanine↗
Sequence-related behaviour of transmembrane domains from class I receptor tyrosine kinases.
2H NMR spectroscopy and freeze-fracture electron microscopy were used to compare the transmembrane domains of two Class I protein receptor tyrosine kinases (the EGF receptor and Neu/erbB-2) regarding overall behaviour in fluid lipid bilayer membranes. The 34-residue peptide, EGFRtm, was synthesised to contain the 23 amino acid hydrophobic stretch (Ile622 to Met644) thought to span the membrane of the human EGF receptor, plus the first 10 amino acids (Arg645 to Thr654) of the cytoplasmic domain. Deuterium probes replaced selected 1H nuclei at sites corresponding to Ala623, Met644, and Val650. The 38-residue peptide, Neutm, was synthesised having the 21 residue hydrophobic stretch (Ile660 to Ile680) calculated to span the membrane in rat Neu/erbB-2, plus residues Lys681 to Thr691 of the contiguous cytoplasmic domain. Deuterium probes replaced selected 1H nuclei at Ala661, Leu667, and Val676. A third peptide, Neutm*, was also prepared, corresponding to the transmembrane domain of a constitutively-activating Neu/erbB-2 transformant in which Val664 is replaced by Glu: it was deuterated in a manner identical to Neutm. Peptides were studied by 2H NMR spectroscopy at 1 mol% and 6 mol% in unsonicated fluid bilayers of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and in POPC containing 33 mol% cholesterol, over the range 12 degrees to 65 degreesC. Overall motion was found to be different for each of the three peptides under a given set of conditions. EGFRtm spectra were characteristic of axially symmetric motion in membranes of POPC alone, and in POPC/cholesterol at 35 degreesC and above. In contrast, spectra of the transmembrane peptides, Neutm and Neutm*, were characteristic of significantly axially asymmetric motion under all conditions studied (and regardless of sample preparation method). Addition of 33% cholesterol to membranes was accompanied by spectral changes consistent with increased formation of peptide dimers/oligomers in all cases. The transformant peptide, Neutm*, showed greater spectral evidence of immobilisation than did the wild type - probably reflecting a greater tendency to form large oligomers. Sequence-related details within the transmembrane domains of Class I receptor tyrosine kinases appear to exert important control over their associations within membranes. Freeze-fracture electron microscopy of the NMR samples demonstrated their liposomal nature. Peptide-related intramembranous particles (IMPs) were present which likely represent oligomers of the transmembrane peptide. IMP size and distribution were similar under a given set of conditions for all three peptides, suggesting that the differences seen by NMR spectroscopy reflect structures smaller than the 2 nm resolution limit of freeze-fracture EM and peptide relationships within its 20 nm accuracy of identifying lateral position.
Amino Acid Sequence↗
t(11;22)(q23;q11.2) In acute myeloid leukemia of infant twins fuses MLL with hCDCrel, a cell division cycle gene in the genomic region of deletion in DiGeorge and velocardiofacial syndromes.
We examined the MLL genomic translocation breakpoint in acute myeloid leukemia of infant twins. Southern blot analysis in both cases showed two identical MLL gene rearrangements indicating chromosomal translocation. The rearrangements were detectable in the second twin before signs of clinical disease and the intensity relative to the normal fragment indicated that the translocation was not constitutional. Fluorescence in situ hybridization with an MLL-specific probe and karyotype analyses suggested t(11;22)(q23;q11. 2) disrupting MLL. Known 5' sequence from MLL but unknown 3' sequence from chromosome band 22q11.2 formed the breakpoint junction on the der(11) chromosome. We used panhandle variant PCR to clone the translocation breakpoint. By ligating a single-stranded oligonucleotide that was homologous to known 5' MLL genomic sequence to the 5' ends of BamHI-digested DNA through a bridging oligonucleotide, we formed the stem-loop template for panhandle variant PCR which yielded products of 3.9 kb. The MLL genomic breakpoint was in intron 7. The sequence of the partner DNA from band 22q11.2 was identical to the hCDCrel (human cell division cycle related) gene that maps to the region commonly deleted in DiGeorge and velocardiofacial syndromes. Both MLL and hCDCrel contained homologous CT, TTTGTG, and GAA sequences within a few base pairs of their respective breakpoints, which may have been important in uniting these two genes by translocation. Reverse transcriptase-PCR amplified an in-frame fusion of MLL exon 7 to hCDCrel exon 3, indicating that an MLL-hCDCrel chimeric mRNA had been transcribed. Panhandle variant PCR is a powerful strategy for cloning translocation breakpoints where the partner gene is undetermined. This application of the method identified a region of chromosome band 22q11.2 involved in both leukemia and a constitutional disorder.
Abnormalities, Multiple↗
The EGF receptor transmembrane domain: 2H NMR study of peptide phosphorylation effects in a bilayer environment.
Phosphorylation events are considered to be key control points in receptor tyrosine kinase function. We have used wide-line 2H NMR spectroscopy to look for physical effects of phosphorylating a threonine residue within the cytoplasmic domain of the human EGF receptor, as sensed at a distant site in the transmembrane portion. Modifications were made to Thr654 (a cytoplasmic residue suggested to be involved in regulation of EGF binding and of cytoplasmic domain function), and effects were sought at Ala623 (near the extracellular membrane surface but within the membrane-spanning region). The study was carried out on synthetic peptides corresponding to the EGF receptor transmembrane domain plus 10 or 11 residues of the cytoplasmic domain, assembled into lipid bilayer membranes. Three peptides were compared that differed only at Thr654. This residue was alternately: nonphosphorylated but left as a (-)-charged C-terminus (-Thr654COO-), nonphosphorylated and with a neighboring amidated glycine residue as the C-terminus (-Thr654GlyCONH2), or phosphorylated and with a neighboring amidated glycine residue as the C-terminus (-Thr654PO4-GlyCONH2). Bilayer membranes were composed of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) or 2:1 POPC/cholesterol, containing 6 mol % peptide relative to phospholipid. The deuterated site, Ala623, was intrinsically conformationally sensitive; yet spatial orientation and motional order of the probe location were found not to be obviously influenced by phosphorylation.
Amino Acid Sequence↗
Contributions of Na+/H+ exchanger isoforms to preimplantation development of the mouse.
Previous work provided evidence of Na+/H+ exchanger activity in the apical domain of mouse trophectodermal plasma membranes that provides a route for entry of extracellular Na+ (Manejwala et al., 1989). This activity was hypothesized to contribute to the trans-trophectodermal Na+ flux that is required for blastocoel expansion. In the present work, we have used reverse transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemistry to identify members of the Na+/H+ exchanger (NHE) family that are likely to participate in this process. When cDNA preparations from ovulated oocytes and several stages of preimplantation development were tested with PCR primers specific for the NHE-1, -2, -3, and -4 isoforms of the exchanger, only amplicons representing the NHE-1 and NHE-3 isoforms were detected. The identity of these amplicons was confirmed by direct sequencing. NHE-1 mRNA is present in oocytes and in all preimplantation stages, increasing threefold on a per embryo basis between the 4-cell and blastocyst stages. NHE-3 mRNA, on the other hand, was only detected in oocytes. Immunocytochemical analysis of blastocysts revealed that NHE-1 is localized in the basolateral domain of the trophectoderm, whereas NHE-3 is localized in the apical domain, a situation like that in epithelia of adult organs. We conclude that NHE-3, an oogenetic product that persists into the blastocyst stage, is the Na+/H+ exchanger isoform most likely to be involved in blastocoel expansion.
Animals↗
Comparison of the immunological and protective responses elicited by microencapsulated formulations of the F1 antigen from Yersinia pestis.
Purified native F1 antigen from Yersinia pestis was used to assess controlled-release vaccine delivery systems in poly(lactide-co-glycolide) (PLG) microparticles and liposomes. Antigen encapsulated in PLG microparticles induced high serum titres when injected i.p. in mice: mucosal IgA was also detected. Mice immunized with F1 in Alhydrogel or PLGs were protected against subcutaneous challenge with Y. pestis. F1 antigen surface-labelled onto liposome vesicles stimulated high serum titres in Balb/c mice and also induced a mucosal response: F1-labelled liposomes protected mice against challenge with up to 1 x 10(5) organisms. These findings indicate that a significant immune response is induced by immunizing with F1 formulated in PLGs and liposomes and that protection was achieved after only one dose.
Administration, Oral↗
Panhandle PCR: a technical advance to amplify MLL genomic translocation breakpoints.
Translocations involving a breakpoint cluster region of the MLL gene at chromosome band 11q23 are the most common molecular abnormalities in acute leukemias of infants and acute leukemias related to chemotherapy with DNA topoisomerase II inhibitors. Molecular cloning of MLL genomic breakpoints by PCR has previously been difficult because MLL has many translocation partners and several breakpoints involve unknown partner genes. We review a new approach to MLL genomic breakpoint cloning called panhandle PCR. By adding an oligonucleotide sequence to the unknown 3' partner gene that is complementary to a known 5' MLL sequence, we have been able to generate a genomic template with an intrastrand loop for PCR schematically shaped like a pan with a handle. The intrastrand loop contains the translocation breakpoint and unknown partner DNA, while the handle contains the known 5' sequence from MLL and a complement to that sequence. Primers both derived from MLL are used to amplify the breakpoint by panhandle PCR. Panhandle PCR offers the advantage of having specificity for the strand of interest at both primer annealing sites without requiring specific primers for the many partner genes of MLL. Panhandle PCR is a straightforward method that represents a technical advance in MLL genomic breakpoint cloning.
Chromosome Deletion↗