Biomedical subjects

James E Johnson

Publications and source records attributed to James E Johnson.

6 recordsLinked to original sources

PubMed2003

Generation of mutated variants of the human form of the MHC class I-related receptor, FcRn, with increased affinity for mouse immunoglobulin G.

Much data support the concept that the MHC class I-related receptor FcRn serves to regulate immunoglobulin G (IgG) concentrations in serum and other diverse body sites in both rodents and humans. Previous studies have indicated that the human ortholog of FcRn is endowed with unexpectedly high stringency in binding specificity for IgGs. In contrast to mouse FcRn, which binds promiscuously to IgGs across species, human FcRn does not bind to mouse IgG1 or IgG2a, and interacts weakly with mouse IgG2b. Here, we investigate the molecular basis for this high-level specificity. We have systematically mutated human FcRn residues to the corresponding mouse FcRn residues in the regions that encompass the FcRn-IgG interaction site. Notably, mutation of the poorly conserved residue Leu137 of human FcRn to glutamic acid (L137E) generates a human FcRn mutant that binds to mouse IgG1 and mouse IgG2a with equilibrium dissociation constants of 13.2 microM and 14.4 microM, respectively. From earlier high-resolution structural analyses of the rat FcRn-rat Fc complex, residue 137 of human FcRn is predicted to contact residue 436 of IgG, which can be either His436 (mouse IgG1, mouse IgG2a) or Tyr436 (human IgG1, mouse IgG2b). The simplest interpretation of our data for the L137E mutant is therefore that replacement of the Leu137-Tyr436 (human) by the Glu137-His436 (mouse) pair generates a receptor that can bind to mouse IgG1 and mouse IgG2a. The L137E mutation reduces the affinity of human FcRn for human IgG1 by about twofold, consistent with the introduction of a less favorable Glu137-Tyr436 interaction. However, the analysis of the effects of other mutations on the binding to different IgGs indicates that the contribution to binding of the interaction of FcRn residue 137 with IgG residue 436 can vary. This suggests the existence of distinct docking topologies that are accompanied by variations in contacts between these two residues for different FcRn-IgG pairs. Our observations are of direct relevance to understanding the molecular nature of the human FcRn-IgG interaction. In turn, understanding human FcRn function has significance for the optimization of the serum half-lives of therapeutic and prophylactic antibodies.

Amino Acid Sequence↗

PubMed2003

TableView: portable genomic data visualization.

UNLABELLED: TableView is a generalized scientific visualization program for exploration of various biological data, including EST, SAGE, microarray and annotation data. Written in Java, TableView is portable, is easily used together with other software including DBMSs and is versatile enough to be applied to any tabular data AVAILABILITY: TableView is freely available at: http://ccgb.umn.edu/software/java/apps/TableView/.

Computer Graphics↗

PubMed2003

MtDB: a database for personalized data mining of the model legume Medicago truncatula transcriptome.

In order to identify the genes and gene functions that underlie key aspects of legume biology, researchers have selected the cool season legume Medicago truncatula (Mt) as a model system for legume research. A set of >170 000 Mt ESTs has been assembled based on in-depth sampling from various developmental stages and pathogen-challenged tissues. MtDB is a relational database that integrates Mt transcriptome data and provides a wide range of user-defined data mining options. The database is interrogated through a series of interfaces with 58 options grouped into two filters. In addition, the user can select and compare unigene sets generated by different assemblers: Phrap, Cap3 and Cap4. Sequence identifiers from all public Mt sites (e.g. IDs from GenBank, CCGB, TIGR, NCGR, INRA) are fully cross-referenced to facilitate comparisons between different sites, and hypertext links to the appropriate database records are provided for all queries' results. MtDB's goal is to provide researchers with the means to quickly and independently identify sequences that match specific research interests based on user-defined criteria. The underlying database and query software have been designed for ease of updates and portability to other model organisms. Public access to the database is at http://www.medicago.org/MtDB.

Chromosome Mapping↗

PubMed2002

One hundred and seventeen clades of euagarics.

This study provides a first broad systematic treatment of the euagarics as they have recently emerged in phylogenetic systematics. The sample consists of 877 homobasidiomycete taxa and includes approximately one tenth (ca. 700 species) of the known number of species of gilled mushrooms that were traditionally classified in the order Agaricales. About 1000 nucleotide sequences at the 5(') end of the nuclear large ribosomal subunit gene (nLSU) were produced for each taxon. Phylogenetic analyses of nucleotide sequence data employed unequally weighted parsimony and bootstrap methods. Clades revealed by the analyses support the recognition of eight major groups of homobasidiomycetes that cut across traditional lines of classification, in agreement with other recent phylogenetic studies. Gilled fungi comprise the majority of species in the euagarics clade. However, the recognition of a monophyletic euagarics results in the exclusion from the clade of several groups of gilled fungi that have been traditionally classified in the Agaricales and necessitates the inclusion of several clavaroid, poroid, secotioid, gasteroid, and reduced forms that were traditionally classified in other basidiomycete orders. A total of 117 monophyletic groups (clades) of euagarics can be recognized on the basis on nLSU phylogeny. Though many clades correspond to traditional taxonomic groups, many do not. Newly discovered phylogenetic affinities include for instance relationships of the true puffballs (Lycoperdales) with Agaricaceae, of Panellus and the poroid fungi Dictyopanus and Favolaschia with Mycena, and of the reduced fungus Caripia with Gymnopus. Several clades are best supported by ecological, biochemical, or trophic habits rather than by morphological similarities.

Basidiomycota↗

PubMed2002

Effects of training with heliox and noninvasive positive pressure ventilation on exercise ability in patients with severe COPD.

STUDY OBJECTIVES: We sought to determine whether breathing heliox or using nasal noninvasive positive pressure ventilation (NIPPV) would produce immediate improvements in exercise capability in patients with COPD, and whether training for 6 weeks with one of these modalities would result in greater exercise improvement than with training unassisted. SETTING: US military medical center. METHODS: Thirty-nine patients with severe COPD (mean FEV1 of 33.5% predicted) underwent three incremental treadmill tests to exhaustion unassisted, breathing heliox, or breathing with NIPPV. They were then randomized to undergo 6 weeks of twice-weekly rehabilitation with unassisted exercise training (UT group), training while breathing heliox (HT group), or training while breathing with NIPPV (NT group). The three exercise tests were then repeated. RESULTS: Heliox treatment did not produce any immediate benefit in exercise time or maximum workload in the 39 patients initially tested, the 32 patients who completed the protocol, or the HT group. Furthermore, no training advantage was evident in the HT group (n = 10) compared to the UT group (n = 11). NIPPV did not produce an immediate benefit in the initial tests, but produced a small increase in exercise time in the 32 patients completing the protocol in the final tests. This effect was primarily because of the NT group, who exercised significantly longer (mean +/- SD, 16.8 +/- 4.9 min vs 14.2 +/- 5.6 min, p = 0.0045) and to a higher workload (4.46 +/- 1.55 metabolic equivalents [METs] vs 4.09 +/- 1.75 METs, respectively; p = 0.038) when tested using the ventilator. Compared to the UT group, the NT group started out with a lower exercise time (7.9 +/- 3.5 min vs 12.3 +/- 5.2 min, p = 0.031) in preliminary testing, but the statistical difference was eliminated in the final tests (14.2 +/- 5.6 min vs 16.0 +/- 5.8 min, respectively; p = 0.451). The NT group actually slightly exceeded the UT group when they used the ventilator in final testing, although this was not statistically significant (16.8 +/- 4.9 min vs 16.0 +/- 5.8 min, respectively). CONCLUSION: Heliox treatment does not appear to offer an immediate or training advantage with exercise in patients with COPD. For patients who have undergone regular exercise conditioning with NIPPV, use of the ventilator produces an immediate improvement in both exercise time and maximum workload attained, and it may confer a training advantage.

Aged↗

PubMed2002

Evaluation of exertional dyspnea in the active duty patient: the diagnostic approach and the utility of clinical testing.

INTRODUCTION: Minimal information currently exists on how clinicians should approach the evaluation of the young patient with exertional dyspnea. The objective of this study was to determine the frequency of specific diseases and the most useful tests to establish the diagnosis in an active duty military population presenting with exertional dyspnea. METHODS: A total of 105 active duty military patients with complaints of exertional dyspnea and 69 active duty military asymptomatic controls were evaluated at a pulmonary disease clinic at an Army tertiary care center. All patients and controls underwent a standard evaluation that included history, physical examination, chest radiography (CXR), arterial blood gas testing, laboratory testing, full pulmonary function testing (PFT), inspiratory and expiratory pressure determinations, methacholine challenge testing, cardiopulmonary exercise testing, electrocardiography, and echocardiography. RESULTS: Obstructive lung disease was found in 52% of patients (35% with exercise-induced asthma and 12% with asthma), 10% had vocal cord dysfunction, and 14% had other diagnoses. Twenty-four percent of patients had no specific diagnosis. Methacholine challenge testing yielded a positive diagnosis in 41% of patients and spirometry in 16%. Other pulmonary tests were of limited value, with abnormal values of 11.4% for full PFT, 2.9% for arterial blood gas testing, and 0.4% for CXR. Laboratory evaluation yielded positive results in less than 5% of patients, and cardiac evaluation was normal in all patients. CONCLUSIONS: Various forms of obstructive lung disease and vocal cord dysfunction were the most common findings in this group. The routine use of spirometry and bronchoprovocation testing is warranted, but other tests, such as full PFT, CXR, and cardiac and laboratory evaluations, have limited diagnostic value in this population.

Adolescent↗