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Biomedical subjects

K Johnson

Publications and source records attributed to K Johnson.

At least 109 records · Page 6Linked to original sources
PubMed2000

Evidence from rheumatoid arthritis trials for approval: what does it mean? With special reference to using radiographic endpoints.

Since medicine remains largely empirical, clinical knowledge about therapy is derived primarily from experiments designed to control confounders that use inferential techniques applied to the null hypothesis model. On a public health scale, health agencies need to assess the evidentiary weight supplied for new therapies to make approval decisions. In the field of rheumatoid arthritis (RA), there are additional analytic challenges such as designation of endpoints or missing data. The intellectual architecture that underpins these exercises continues to evolve, and recently the US Food and Drug Administration released an RA Guidance Document to describe some aspects of these exercises. This article focuses on the use of measurements of radiographic endpoints in particular as an element in the evidentiary portrayal of therapeutic efficacy in RA.

Arthritis, Rheumatoid↗
PubMed2000

A method for the automated mapping of laboratory results to LOINC.

LOINC is emerging as the standard for laboratory result names, and there is great interest in mapping legacy terms from laboratory systems to it. However, the mapping task is non-trivial, requiring significant resource commitment and a good understanding of the LOINC identifying attributes for the laboratory result names. Because the number of results in a laboratory system may range from around 500 to 2000 or more, manual, one-by-one matching, even with the aid of the RELMA matching tool provided by LOINC, is time consuming and laborious. Moreover, human variation may introduce mapping inconsistencies or errors. Through our experience mapping the results from a variety of laboratory systems to LOINC, an automated mapping method has been developed and is described in this paper. This method allows for data from the laboratory information system to be provided in a manner familiar to the submitting technician, and makes use of parsing and logic rules, combined with synonyms, attribute relationships and mapping frequency data, to perform automated matching to LOINC.

Classification↗
PubMed2000

Crisis response to schools.

While community based crisis response teams offer needed resources to schools impacted by crisis, they are often not asked to help. Reports from crisis team leaders at the school shooting incidents at James W. Parker Middle School, Edinboro, Pennsylvania and Columbine High School, Littleton, Colorado are contrasted regarding utilization of community resources. Factors limiting the usefulness of community based teams include unfamiliarity with school organization, culture, and procedures. Key differences in school vs. community team precepts, decision-making, and strategic paradigms render team coordination difficult. Successful cross training presents opportunities for school-community partnership and utilization of community teams for school duty.

Adolescent↗
PubMed1999

Requirement of an E1A-sensitive coactivator for long-range transactivation by the beta-globin locus control region.

Four erythroid-specific DNase I-hypersensitive sites at the 5'-end of the beta-globin locus confer high-level transcription to the beta-globin genes. To identify coactivators that mediate long-range transactivation by this locus control region (LCR), we assessed the influence of E1A, an inhibitor of the CBP/p300 histone acetylase, on LCR function. E1A strongly inhibited transactivation of Agamma- and beta-globin promoters by the HS2, HS2-HS3, and HS1-HS4 subregions of the LCR in human K562 and mouse erythroleukemia cells. Short- and long-range transactivation mediated by the LCR were equally sensitive to E1A. The E1A sensitivity was apparent in transient and stable transfection assays, and E1A inhibited expression of the endogenous gamma-globin genes. Only sites for NF-E2 within HS2 were required for E1A sensitivity in K562 cells, and E1A abolished transactivation mediated by the activation domain of NF-E2. E1A mutants defective in CBP/p300 binding only weakly inhibited HS2-mediated transactivation, whereas a mutant defective in retinoblastoma protein binding strongly inhibited transactivation. Expression of CBP/p300 potentiated HS2-mediated transactivation. Moreover, expression of GAL4-CBP strongly increased transactivation of a reporter containing HS2 with a GAL4 site substituted for the NF-E2 sites. Thus, we propose that a CBP/p300-containing coactivator complex is the E1A-sensitive factor important for LCR function.

Acetyltransferases↗
PubMed1999

bloated tubules (blot) encodes a Drosophila member of the neurotransmitter transporter family required for organisation of the apical cytocortex.

We have identified a novel member of the vertebrate sodium- and chloride-dependent neurotransmitter symporter family from Drosophila melanogaster. This gene, named bloated tubules (blot), shows significant sequence similarity to a subgroup of vertebrate orphan transporters. blot transcripts are maternally supplied and during embryogenesis exhibit a complex and dynamic pattern in a subset of ectodermally derived epithelia, notably in the Malpighian tubules, and in the nervous system. Animals mutant for this gene are larval lethals, in which the Malpighian tubule cells are distended with an enlarged and disorganised apical surface. Embryos lacking the maternal component of blot expression die during early stages of development. They show an inability to form actin filaments in the apical cortex, resulting in impaired syncytial nuclear divisions, severe defects in the organisation of the cortical cytoskeleton, and a failure to cellularise. For the first time, a neurotransmitter transporter-like protein has been implicated in a function outside the nervous system. The isolation of blot thus provides the basis for an analysis of the relationship between the function of this putative transporter and epithelial morphogenesis.

Amino Acid Sequence↗
PubMed1999

Role of C3 cleavage in monocyte activation during extracorporeal circulation.

BACKGROUND: We previously demonstrated that inhibiting formation of terminal complement components (C5a and C5b-9) prevents platelet and neutrophil (PMN) but not monocyte activation during simulated extracorporeal circulation (SECC). This study examined whether earlier complement inhibition during SECC, blocking C3a formation, would additionally prevent monocyte activation. METHODS AND RESULTS: SECC was established by recirculating heparinized whole blood from human volunteers on a membrane oxygenator. CAB-2, a chimeric protein constructed from genes encoding the complement regulatory proteins CD46 and CD55, inactivates the C3/C5 convertases and blocks in vitro generation of C3a, C5a, and C5b-9. CAB-2 was used in 4 experiments at a final concentration of 300 micrograms/mL and 4 experiments at 30 micrograms/mL; 4 control runs used vehicle alone. Samples were assayed for C3a and C5b-9, monocyte activation (CD11b upregulation), PMN activation (CD11b upregulation and elastase release), and platelet activation (P-selectin expression and monocyte-platelet conjugate formation). CAB-2 at both doses significantly inhibited formation of C3a and C5b-9 during SECC. High-dose CAB-2 significantly blocked monocyte and PMN CD11b upregulation and PMN elastase release. CAB-2 also inhibited formation of platelet activation-dependent monocyte-platelet conjugates. CONCLUSIONS: Blockade of complement activation early in the common pathway inhibited monocyte CD11b upregulation during SECC, suggesting that early complement components contribute most to monocyte activation during SECC. As expected, PMN and platelet activation were blocked by terminal complement inhibition. This investigation further elucidates the relation between complement and blood cell activation during simulated cardiopulmonary bypass.

Blood Platelets↗
PubMed1999

Interaction of Smad complexes with tripartite DNA-binding sites.

The Smad family of transcription factors function as effectors of transforming growth factor-beta signaling pathways. Smads form heteromultimers capable of contacting DNA through the amino-terminal MH1 domain. The MH1 domains of Smad3 and Smad4 have been shown to bind to the sequence 5'-GTCT-3'. Here we show that Smad3 and Smad4 complexes can contact three abutting GTCT sequences and that arrays of such sites elevate reporter expression relative to arrays of binding sites containing only two GTCTs. Smad3/4 complexes bound synergistically to probes containing two of the four possible arrangements of three GTCT sequences and showed a correlated ability to synergistically activate transcription through these sites. Purified Smad3 and Smad4 were both able to contact three abutting GTCT sequences and reporter experiments indicated that either protein could mediate contact with all three GTCTs. In contrast, the Smad4 MH1 domain was essential for reporter activation in combination with Smad1. Together, these results show that Smad complexes are flexible in their ability to interact with abutting GTCT triplets. In contrast, Smads have high affinity for only one orientation of abutting GTCT pairs. Functional Smad-binding sites within several native response elements contain degenerate GTCT triplets, suggesting that trimeric Smad-DNA interaction may be relevant in vivo.

Animals↗
PubMed1999

Differential mechanisms of inorganic pyrophosphate production by plasma cell membrane glycoprotein-1 and B10 in chondrocytes.

OBJECTIVE: Increased nucleoside triphosphate pyrophosphohydrolase (NTPPPH) activity in chondrocytes is associated with cartilage matrix inorganic pyrophosphate (PPi) supersaturation in chondrocalcinosis. This study compared the roles of the transforming growth factor beta (TGFbeta)-inducible plasma cell membrane glycoprotein-1 (PC-1) and the closely related B10 NTPPPH activities in chondrocyte PPi metabolism. METHODS: NTPPPH expression was studied using reverse transcriptase-polymerase chain reaction and Western blotting. Transmembrane PC-1 (tmPC-1), water-soluble secretory PC-1 (secPC-1), and transmembrane B10 were expressed by adenoviral gene transfer or plasmid transfection, and expression of PPi was assessed in cultured articular chondrocytes and immortalized NTPPPH-deficient costal chondrocytes (TC28 cells). RESULTS: PC-1 and B10 messenger RNA were demonstrated in articular cartilages in situ, in untreated cultured normal articular chondrocytes, and in TC28 cells. Expression of tmPC-1 and secPC-1, but not B10, rendered the NTPPPH-deficient TC28 cells able to increase expression of extracellular PPi, with or without addition of TGFbeta (10 ng/ml) to the media. More plasma membrane NTPPPH activity was detected in cells transfected with tmPC-1 than in cells transfected with B10. Furthermore, confocal microscopy with immunofluorescent staining of articular chondrocytes confirmed preferential plasma membrane localization of PC-1, relative to B10. Finally, both PC-1 and B10 increased the levels of intracellular PPi, but PC-1 and B10 appeared to act principally in different intracellular compartments (Golgi and post-Golgi versus pre-Golgi, respectively). CONCLUSION: PC-1 and B10 NTPPPH activities were not redundant in chondrocytes. Although increased PC-1 and B10 expression caused elevations in intracellular PPi, the major effects of PC-1 and B10 were exerted in distinct subcellular compartments. Moreover, PC-1 (transmembrane and secreted), but not B10, increased the levels of extracellular PPi. Differential expression of PC-1 and B10 could modulate cartilage mineralization in degenerative joint diseases.

Brefeldin A↗
PubMed1999

Parosteal osteosarcoma of a metatarsal with intramedullary invasion.

A 70-year-old man presented with increasing swelling of 2 years' duration, on the dorsal aspect of the forefoot. Imaging studies revealed a heavily calcified surface lesion of bone with early invasion of the underlying second metatarsal. Both imaging findings and the subsequent resection histology were consistent with a parosteal osteosarcoma, which is particularly rare at this site and at this age. The differential diagnosis of a mineralizing surface lesion of bone arising in the foot is discussed.

Aged↗
PubMed1999

Correction.

Explore the source record for details and available documents.

Journal Article↗
PubMed1999

A novel surfactant nanoemulsion with broad-spectrum sporicidal activity against Bacillus species.

Two nontoxic, antimicrobial nanoemulsions, BCTP and BCTP 401, have been developed. These emulsions are composed of detergents and oils in 80% water. BCTP diluted up to 1:1000 inactivated>90% of Bacillus anthracis spores in 4 h and was also sporicidal against three other Bacillus species. This sporicidal activity is due to disruption of the spore coat after initiation of germination without complete outgrowth. BCTP 401 diluted 1:1000 had greater activity than BCTP against Bacillus spores and had an onset of action of <30 min. Mixing BCTP or BCTP 401 with Bacillus cereus prior to subcutaneous injection in mice reduced the resulting skin lesion by 99%. Wound irrigation with BCTP 1 h after spore inoculation yielded a 98% reduction in skin lesion size, and mortality was reduced 3-fold. These nanoemulsion formulas are stable, easily dispersed, nonirritant, and nontoxic compared with other available sporicidal agents.

Animals↗
PubMed1999

Reamed intramedullary nailing of the femur: 551 cases.

BACKGROUND: The care of the patient with the fractured femur entails a multiple surgical team approach. Healing of the fracture and expediency in the operating room are both important. We sought to determine the results of the treatment of fractures of the femoral shaft with interlocking femoral nails inserted with closed techniques, and to compare the outcomes of fractures nailed by using a fracture table with those stabilized with the leg draped free on a radiolucent table. METHODS: Eight hundred eighty-two consecutive patients with fractures of the femoral shaft treated with a first-generation intramedullary nail at the authors' institution during the years 1986 to 1996 were identified. Five hundred fifty-one fractures in 515 patients met the inclusion criteria. RESULTS: Treatment with an intramedullary nail led to a union rate of 98.9%. There were six infections, all occurring in closed fractures. Thirty-eight percent of the fractures had hardware removed, most commonly because of pain. One nail and 13 locking bolts broke. Four hundred eighteen fractures had adequate radiographs available to assess fracture alignment. No fracture healed with more than 10 degrees of angulation in either plane. Forty-four fractures healed with more than 5 degrees of angulation. A distal third fracture was found to be associated with an increased incidence of malalignment. There were no differences in outcomes between fractures stabilized with or without a fracture table. CONCLUSION: Reamed intramedullary nailing of femoral shaft fractures results in a low rate of nonunion, malunion, infection, and hardware failure. There is no difference in the outcomes of fractures treated with and without the use of a fracture table. This is particularly useful in the patient with multiple injuries for whom transfer to a fracture table may not be time effective.

Adolescent↗
PubMed1999

Rifapentine pharmacokinetics in adolescents.

OBJECTIVE: Determination of rifapentine pharmacokinetics in healthy adolescent children. DESIGN: Prospective Phase II clinical trial. SETTING: Clinical research center within a university children's hospital. PATIENTS: Twelve subjects ranging in age from 12 to 15 years, male and female. INTERVENTIONS: A single oral dose of rifapentine was administered to healthy adolescent volunteers, 450 mg if <45 kg or 600 mg if > or =45 kg. Blood was collected at serial intervals (0, 2, 3, 4, 5, 6, 8, 12, 18, 24, 48 and 72 h postdose). Subjects were observed for adverse effects during the period of study. MEASUREMENTS: High pressure liquid chromatography was used to measure the plasma concentration of rifapentine and 25-desacetyl rifapentine in each blood sample. For each subject a plot of mean plasma concentration vs. time data for rifapentine and its metabolite (i.e. 25-desacetyl rifapentine) were created. Subsequently model-independent methods were used to determine the pharmacokinetic profiles for each subject. RESULTS: All subjects tolerated rifapentine without adverse effects. The 2-h postdose plasma concentrations of rifapentine (6.59 to 9.05 microg/ml) and 25-desacetyl rifapentine (0.57 to 2.64 microg/ml) far exceeded the MIC of Mycobacterium tuberculosis to rifapentine (approximately 0.12 microg/ml). The combination of a high Cmax (rifapentine, 9.95 to 18.63 microg/ml; 25-desacetyl rifapentine, 3.73 to 7.46 microg/ml) and lengthy terminal elimination phase t1/2 (rifapentine, 10 to 23 h; 25-desacetyl rifapentine, 14 to 35 h) resulted in potentially effective plasma concentrations of both compounds that persisted for at least 48 h in most subjects. CONCLUSIONS: A well-tolerated oral rifapentine dose produced rapid and sustained plasma drug concentrations in adolescents that should effectively treat infections caused by M. tuberculosis. Rifapentine pharmacokinetics appears to be similar in adolescent and adult populations.

Adolescent↗