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Biomedical subjects

J E Johnson

Publications and source records attributed to J E Johnson.

At least 145 records · Page 8Linked to original sources

Detection of osteomyelitis in the neuropathic foot: nuclear medicine, MRI and conventional radiography.

The diagnostic efficacy of (1) combined three-phase bone scintigraphy and In-111 labeled WBC scintigraphy (Bone/WBC), (2) MRI, and (3) conventional radiography in detecting osteomyelitis of the neuropathic foot was compared. Conventional radiography was comparable to MRI for detection of osteomyelitis. MRI best depicted the presence of osteomyelitis in the forefoot. Particularly in the setting of Charcot joints, Bone/WBC was more specific than conventional radiography or MRI.

Adult↗

Rural residents' use of cardiac rehabilitation programs.

The goal of this study was to identify the factors that influence the use of cardiac rehabilitation services by rural residents. The Andersen-Newman framework, which consists of three determinants of health services utilization (predisposing, enabling, and need factors), was used to direct this research. The three data collection points were at time of discharge from the hospital, two weeks post discharge, and one week following the date that the cardiac rehabilitation program would have been completed. Packets for the three data collection points were unique and contained instruments to assess various factors influencing the use of health services. The sample (N = 254) were adults living in rural areas who had experienced a cardiac event and received treatment at one of four hospitals in two western states and who provided useable data on all three questionnaires. Findings indicated that 72 (28%) of the participants attended some portion of a rehabilitation program, and only 43 (17%) completed the full 36-week program. Four predisposing factors, one enabling factor, and two need factors were significant in explaining the number of cardiac rehabilitation sessions attended. Further research is needed to validate these factors and to identify others which may influence the use of cardiac rehabilitation by rural residents. Likewise, it is essential to examine alternate ways to meet the rehabilitative needs of rural cardiac clients.

Adult↗

Priming with secreted glycoprotein G of respiratory syncytial virus (RSV) augments interleukin-5 production and tissue eosinophilia after RSV challenge.

The respiratory syncytial virus (RSV) G glycoprotein promotes differentiation of type 2 CD4+ T lymphocytes and induces an eosinophilic response in lungs of RSV-infected mice. A unique feature of G is that a second initiation codon in the transmembrane region of the glycoprotein results in secretion of soluble protein from infected cells. Recombinant vaccinia viruses that express wild-type G (vvWT G), only secreted G (vvM48), or only membrane-anchored G (vvM48I) were used to define the influence of G priming on immunopathogenesis. Mice immunized with vvM48 had more severe illness following RSV challenge than did mice primed with vvWT G or vvM48I. Coadministration of purified G during priming with the construct expressing membrane-anchored G shifted immune responses following RSV challenge to a more Th2-like response. This was characterized by increased interleukin-5 in lung supernatants and an increase in G-specific immunoglobulin G1 antibodies. Eosinophils were present in the infiltrate of all mice primed with G-containing vectors but were greatest in mice primed with regimens including secreted G. These data suggest the form of G protein available for initial antigen processing and presentation is an important factor in promoting Th2-like immune responses, including the induction of lung eosinophilia. The ability of RSV to secrete G protein may therefore represent a viral strategy for immunomodulation and be a key determinant of disease pathogenesis.

Animals↗

Particle polymorphism caused by deletion of a peptide molecular switch in a quasiequivalent icosahedral virus.

The capsid of flock house virus is composed of 180 copies of a single type of coat protein which forms a T=3 icosahedral shell. High-resolution structural analysis has shown that the protein subunits, although chemically identical, form different contacts across the twofold axes of the virus particle. Subunits that are related by icosahedral twofold symmetry form flat contacts, whereas subunits that are related by quasi-twofold symmetry form bent contacts. The flat contacts are due to the presence of ordered genomic RNA and an ordered peptide arm which is inserted in the groove between the subunits and prevents them from forming the dihedral angle observed at the bent quasi-twofold contacts. We hypothesized that by deleting the residues that constitute the ordered peptide arm, formation of flat contacts should be impossible and therefore result in assembly of particles with only bent contacts. Such particles would have T=1 symmetry. To test this hypothesis we generated two deletion mutants in which either 50 or 31 residues were eliminated from the N terminus of the coat protein. We found that in the absence of residues 1 to 50, assembly was completely inhibited, presumably because the mutation removed a cluster of positively charged amino acids required for neutralization of encapsidated RNA. When the deletion was restricted to residues 1 to 31, assembly occurred, but the products were highly heterogeneous. Small bacilliform-like structures and irregular structures as well as wild-type-like T=3 particles were detected. The anticipated T=1 particles, on the other hand, were not observed. We conclude that residues 20 to 30 are not critical for formation of flat protein contacts and formation of T=3 particles. However, the N terminus of the coat protein appears to play an essential role in regulating assembly such that only one product, T=3 particles, is synthesized.

Amino Acid Sequence↗

Optimal computed tomography imaging of the midfoot: an improved technique.

A new protocol for computed tomography (CT) imaging of the midfoot is described. This imaging technique places the CT cuts parallel to and perpendicular to the talus-first metatarsal axis, as viewed on the lateral CT scout image. For imaging the midfoot, this technique is an improvement over previously described hindfoot or midfoot protocols.

Clinical Protocols↗

Total calcanectomy for the treatment of chronic calcaneal osteomyelitis.

The purpose of this study is to present the surgical and functional results of a total calcanectomy procedure as a foot salvage alternative in patients with extensive chronic osteomyelitis of the calcaneus. A retrospective review identified eight patients treated with a total calcanectomy for a chronic nonhealing plantar ulcer of the heel and osteomyelitis of the calcaneus. The primary diagnosis was insulin-dependent diabetes mellitus (six patients), pneumococcal septicemia (one patient), and an open calcaneal fracture (one patient). The average age of the patients was 52 years. Prior procedures included irrigation and debridement of the heel ulcer (seven patients), partial calcanectomy (three patients), and split thickness skin grafting (two patients). The vascular status of each limb was assessed preoperatively. Distal extremity bypass surgery was performed on two patients before calcanectomy. Osteomyelitis of the calcaneus was diagnosed by magnetic resonance imaging alone in three patients, and by technetium/indium scans and magnetic resonance imaging in five patients. The average follow-up duration was 27.3 months (range, 6-57 months). Infection at the plantar heel was controlled in all patients. In all eight cases the incisions were closed primarily. During a prolonged time of total contact casting to facilitate wound healing, one patient developed an anterior tibial ulcer that progressed to osteomyelitis and underwent below-knee amputation. Talonavicular subluxation occurred as a late complication in one patient. This was treated with a talonavicular arthrodesis and subsequent bracing for a nonunion. An assessment of functional ambulation was performed on all eight patients. Four patients maintained the same ambulation level postoperatively in a modified heel-containment orthosis. Two patients decreased one functional ambulation level, and one patient decreased two levels. One patient underwent below-knee amputation and is currently ambulatory with a prothesis. Assessment of ankle strength and range of motion of the surgical limb demonstrated decreased dorsiflexion and plantarflexion strength and a variable range of motion compared to the contralateral limb. Total calcanectomy is an alternative procedure to transtibial amputation in patients with chronic osteomyelitis of the calcaneus. Eradication of infection and preservation of the functional ambulation is achieved.

Adult↗

Older rural adults and the decision to stop driving: the influence of family and friends.

Sixty rural elders who had stopped driving as well as their friends and family members participated in a qualitative study to explore (a) the perceptions of older drivers regarding the influence of friends and family on their decision to stop driving, (b) the perceptions of friends and family regarding their influence on that decision, and (c) the impact that no longer driving had on the elder and his or her friends and family. Findings suggest that the support offered by friends and family played a significant role in the decision to stop driving. Increased loneliness and isolation impacted the older driver, although an enhanced sense of responsibility was evident among friends and family.

Adolescent↗

Nursing assessment of older rural drivers.

Fifty rural nurses and 75 rural elders participated in a study to (a) explore the perceptions of nurses regarding their role in assessing the driving abilities of rural elders and (b) to describe the nurse's influence on rural elders' decision to stop driving. Findings suggest that, although driving safety of rural elders is of concern to nurses, they do not discuss these concerns with their clients, and rural elders do not discuss driving with nurses.

Adult↗

Progenitors of dorsal commissural interneurons are defined by MATH1 expression.

MATH1 is a neural-specific basic helix-loop-helix transcription factor. Members of this family of transcription factors are involved in the development of specific subsets of neurons in the developing vertebrate nervous system. Here we examine the cells expressing MATH1 with respect to their proliferative state and co-expression of cell-type-specific differentiation markers. We localize the MATH1 protein to the nucleus of cells in the dorsal neural tube and the external germinal layer (EGL) of the developing cerebellum. Using double-label immunofluorescence, we demonstrate that MATH1-expressing cells span both the proliferating and the differentiating zones within the dorsal neural tube, but within the EGL of the cerebellum are restricted to the proliferating zone. The early differentiating MATH1-expressing cells in the dorsal neural tube co-express TAG-1, DCC-1 and LH2, markers of dorsal commissural interneurons. In addition, transgenic mice with lacZ under the transcriptional control of MATH1-flanking DNA sequences express beta-galactosidase specifically in the developing nervous system, in a manner that mimics subsets of the MATH1-expression pattern, including the dorsal spinal neural tube. Expression of the MATH1/lacZ transgene persists in differentiated dorsal commissural interneurons. Taken together, we demonstrate MATH1 expression in a differentiating population of neuronal precursors in the dorsal neural tube that appear to give rise specifically to dorsal commissural interneurons.

Animals↗

A putative phosphatidylserine binding motif is not involved in the lipid regulation of protein kinase C.

Protein kinase C is specifically regulated by diacylglycerol and the amino phospholipid, phosphatidylserine. The molecular basis for the phosphatidylserine specificity was recently proposed to arise from the presence of a putative phosphatidylserine binding motif, FXFXLKXXXKXR, localized in the C2 domain of protein kinase C (Igarashi, K., Kaneda, M., Yamaji, A., Saido, T. C., Kikkawa, U., Ono, U., Inoue, K., and Umeda, M. (1995) J. Biol. Chem. 270, 29075-29078). To determine whether this motif mediates the interaction of protein kinase C with phosphatidylserine, the carboxyl-terminal basic residues were mutated to Ala in protein kinase C betaII (K236A and R238A), and the phosphatidylserine regulation of the mutant enzyme was examined. Membrane binding and activity measurements revealed that the phosphatidylserine regulation for the mutant protein was indistinguishable from that of wild-type protein kinase C. Specifically, neither the apparent membrane affinity for phosphatidylserine-containing membranes in the presence or absence of diacylglycerol nor the phosphatidylserine-dependence for activation was affected by removal of the conserved basic residues at the carboxyl terminus of the consensus sequence. In addition, a synthetic peptide corresponding to the amino terminus of the consensus sequence (FTFNVK) had no effect on the concentration of phosphatidylserine resulting in half-maximal activation of protein kinase C. These results reveal that the carboxyl-terminal basic residues in the consensus motif FXFXLKXXXKXR are not responsible for the phosphatidylserine selectivity of protein kinase C and that, furthermore, the region of the C2 domain containing this motif is not involved in the membrane binding of protein kinase C.

Amino Acid Sequence↗

Resolution of space-group ambiguity and structure determination of nodamura virus to 3.3 A resolution from pseudo-R32 (monoclinic) crystals.

Monoclinic crystals of nodamura virus (NOV) have two virus molecules per asymmetric unit. Packing analysis reveals a pseudo-rhombohedral (pseudo-C2 monoclinic) arrangement of particles in the actual P2(1) space group (a = 562.1, b = 354.1, c = 612.8 A, beta = 110.9 degrees ). The R32 symmetry is broken rotationally and translationally. The pseudo-symmetry of the unit cell results in three possible monoclinic origins and also restrains the four particles in the unit cell to similar orientations. NOV particles deviate by less than 3 degrees from the ideal orientations, causing overlap of peaks in the rotation function and the generation of peaks that were not interpretable as particle symmetry elements. The space-group ambiguity was resolved by analysing the relationship between the particle orientations determined by high-resolution rotation functions and the attenuation of peak heights in native Patterson maps. Particles were centered less than 1 A from the R32 special positions. Three different approaches were required to identify the correct particle center. Following the solutions of the rotation and translation problems, phases were computed using the coordinates of flock house virus (FHV), another member of this virus family. The phases were improved by real-space molecular averaging with a 120-fold non-crystallographic symmetry and by solvent flattening with a spherical mask. The final model for the NOV structure was built using the 3.3 A averaged map. While the overall subunit structure was very similar to that of other nodaviruses, FHV and black beetle virus, NOV showed distinct structural features near particle threefold and quasi-threefold axes and at the protein-RNA interfaces that are consistent with phenotype differences among the related viruses.

Journal Article↗

Wnt signalling required for expansion of neural crest and CNS progenitors.

Interactions between cells help to elaborate pattern within the vertebrate central nervous system (CNS). The genes Wnt-1 and Wnt-3a, which encode members of the Wnt family of cysteine-rich secreted signals, are coexpressed at the dorsal midline of the developing neural tube, coincident with dorsal patterning. Each signal is essential for embryonic development, Wnt-1 for midbrain patterning, and Wnt-3a for formation of the paraxial mesoderm, but the absence of a dorsal neural-tube phenotype in each mutant suggests that Wnt signalling may be redundant. Here we demonstrate that in the absence of both Wnt- and Wnt-3a there is a marked deficiency in neural crest derivatives, which originate from the dorsal neural tube, and a pronounced reduction in dorsolateral neural precursors within the neural tube itself. These phenotypes do not seem to result from a disruption in the mechanisms responsible for establishing normal dorsoventral polarity. Rather, our results are consistent with a model in which local Wnt signalling regulates the expansion of dorsal neural precursors. Given the widespread expression of different Wnt genes in discrete areas of the mammalian neural tube, this may represent a general model for the action of Wnt signalling in the developing CNS.

Animals↗