A case of epidermolysis bullosa acquisita with bleeding tendency due to factor VIII inhibitor (acquired haemophilia).
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Autoantibodies↗
Biomedical subjects
M Nei
Publications and source records attributed to M Nei.
Linear IgA bullous dermatosis of neonatal onset: case report and review of the literature.
UNLABELLED: Several small blisters were noticed on the forehead and the trunk of a newborn boy on day 1. The blisters gradually enlarged and spread over the whole body including the oral mucosa. A skin biopsy was performed twice and subepidermal bullae with polymorphonuclear and mononuclear cell infiltration were demonstrated. Direct immunofluorescence showed linear IgA, IgG and C3 depositions along the basement membrane zone and this finding led to a diagnosis of linear IgA bullous dermatosis. So far, internationally, only one case has ever been reported on the disease at neonatal onset. The skin lesions spontaneously regressed and the mucosal lesions were controlled with diaminodiphenylsulfone. CONCLUSION: In neonates with prolonged blistering, autoimmune disease such as linear IgA bullous dermatosis should be considered within the differential diagnosis and an immunofluorescence study must be performed.
Basement Membrane↗
Genome evolution: let's stick together.
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Biological Evolution↗
Vagal nerve stimulation: adjustments to reduce painful side effects.
Vagal nerve stimulation is an approved adjunctive treatment for medically intractable epilepsy. Although it is generally well tolerated, some patients experience pain, coughing, or hoarseness during stimulation. Lowering the pulse width in these patients alleviates pain and reduces voice alteration without loss of efficacy. This allows more optimal programming of stimulation intensities.
Adult↗
Estimation of divergence times from multiprotein sequences for a few mammalian species and several distantly related organisms.
When many protein sequences are available for estimating the time of divergence between two species, it is customary to estimate the time for each protein separately and then use the average for all proteins as the final estimate. However, it can be shown that this estimate generally has an upward bias, and that an unbiased estimate is obtained by using distances based on concatenated sequences. We have shown that two concatenation-based distances, i.e., average gamma distance weighted with sequence length (d(2)) and multiprotein gamma distance (d(3)), generally give more satisfactory results than other concatenation-based distances. Using these two distance measures for 104 protein sequences, we estimated the time of divergence between mice and rats to be approximately 33 million years ago. Similarly, the time of divergence between humans and rodents was estimated to be approximately 96 million years ago. We also investigated the dependency of time estimates on statistical methods and various assumptions made by using sequence data from eubacteria, protists, plants, fungi, and animals. Our best estimates of the times of divergence between eubacteria and eukaryotes, between protists and other eukaryotes, and between plants, fungi, and animals were 3, 1.7, and 1.3 billion years ago, respectively. However, estimates of ancient divergence times are subject to a substantial amount of error caused by uncertainty of the molecular clock, horizontal gene transfer, errors in sequence alignments, etc.
Animals↗
MEGA2: molecular evolutionary genetics analysis software.
UNLABELLED: We have developed a new software package, Molecular Evolutionary Genetics Analysis version 2 (MEGA2), for exploring and analyzing aligned DNA or protein sequences from an evolutionary perspective. MEGA2 vastly extends the capabilities of MEGA version 1 by: (1) facilitating analyses of large datasets; (2) enabling creation and analyses of groups of sequences; (3) enabling specification of domains and genes; (4) expanding the repertoire of statistical methods for molecular evolutionary studies; and (5) adding new modules for visual representation of input data and output results on the Microsoft Windows platform. AVAILABILITY: http://www.megasoftware.net. CONTACT: s.kumar@asu.edu
DNA↗
ADAPTSITE: detecting natural selection at single amino acid sites.
UNLABELLED: ADAPTSITE is a program package for detecting natural selection at single amino acid sites, using a multiple alignment of protein-coding sequences for a given phylogenetic tree. The program infers ancestral codons at all interior nodes, and computes the total numbers of synonymous (c(S)) and nonsynonymous (c(N)) substitutions as well as the average numbers of synonymous (s(S)) and nonsynonymous (s(N)) sites for each codon site. The probabilities of occurrence of synonymous and nonsynonymous substitutions are approximated by s(S) / (s(S) + s(N)) and s(N) / (s(S) + s(N)), respectively. The null hypothesis of selective neutrality is tested for each codon site, assuming a binomial distribution for the probability of obtaining c(S) and c(N). AVAILABILITY: ADAPTSITE is available free of charge at the World-Wide Web sites http://mep.bio.psu.edu/adaptivevol.html and http://www.cib.nig.ac.jp/dda/yossuzuk/welcome.html. The package includes the source code written in C, binary files for UNIX operating systems, manual, and example files.
Algorithms↗
Reliabilities of parsimony-based and likelihood-based methods for detecting positive selection at single amino acid sites.
The reliabilities of parsimony-based and likelihood-based methods for inferring positive selection at single amino acid sites were studied using the nucleotide sequences of human leukocyte antigen (HLA) genes, in which positive selection is known to be operating at the antigen recognition site. The results indicate that the inference by parsimony-based methods is robust to the use of different evolutionary models and generally more reliable than that by likelihood-based methods. In contrast, the results obtained by likelihood-based methods depend on the models and on the initial parameter values used. It is sometimes difficult to obtain the maximum likelihood estimates of parameters for a given model, and the results obtained may be false negatives or false positives depending on the initial parameter values. It is therefore preferable to use parsimony-based methods as long as the number of sequences is relatively large and the branch lengths of the phylogenetic tree are relatively small.
Amino Acid Substitution↗
Evolutionary dynamics of the T-cell receptor VB gene family as inferred from the human and mouse genomic sequences.
The diversity of T-cell receptors is generated primarily by the variable-region gene families, each of which is composed of a large number of member genes. The entire genomic sequence of the variable region (VB) of the T- cell receptor beta chain from humans and mice has become available. To understand the evolutionary dynamics of the VB gene family, we conducted a phylogenetic analysis of all VB genes from humans and mice, as well as a detailed analysis of internal DNA duplications in the human genomic VB region. The phylogenetic tree obtained shows that human and mouse VB genes intermingle extensively rather than forming two separate clusters and that many gene duplications occurred both before and after the divergence between primates and rodents. Analyzing the genomic maps of transposable elements (e.g., LINEs and SINEs) and relic VB genes in the VB gene region, we present evidence that a 20-kb VB region duplicated tandemly four times in the human lineage during the last 32 Myr, and 6 out of the 15 VB genes in this region have become nonfunctional during this period. Our results show that the VB gene family is subject to evolution by a birth-and-death process rather than to concerted evolution.
Amino Acid Sequence↗
Purifying selection and birth-and-death evolution in the ubiquitin gene family.
Ubiquitin is a highly conserved protein that is encoded by a multigene family. It is generally believed that this gene family is subject to concerted evolution, which homogenizes the member genes of the family. However, protein homogeneity can be attained also by strong purifying selection. We therefore studied the proportion (p(S)) of synonymous nucleotide differences between members of the ubiquitin gene family from 28 species of fungi, plants, and animals. The results have shown that p(S) is generally very high and is often close to the saturation level, although the protein sequence is virtually identical for all ubiquitins from fungi, plants, and animals. A small proportion of species showed a low level of p(S) values, but these values appeared to be caused by recent gene duplication. It was also found that the number of repeat copies of the gene family varies considerably with species, and some species harbor pseudogenes. These observations suggest that the members of this gene family evolve almost independently by silent nucleotide substitution and are subjected to birth-and-death evolution at the DNA level.
Animals↗
Evolution of vertebrate immunoglobulin variable gene segments.
Evolution of Ig V gene segments are generally characterized by (a) evolution by "the birth and death process" and (b) diversifying selection. However, the detailed evolutionary pattern of V gene segments varies among species due to the fact that the humoral immune system itself has changed during vertebrate evolution. The change in somatic diversification system coupled with the change in lymphocyte development has imposed a significant impact on the evolution of Ig genes. In order to understand the evolution of immunological genes it is important to view it in the context of the evolution of the entire immune system itself.
Animals↗
An unusual form of purifying selection in a sperm protein.
Protamines are small, highly basic DNA-binding proteins found in the sperm of animals. Interestingly, the proportion of arginine residues in one type of protamine, protamine P1, is about 50% in mammals. Upon closer examination, it was found that both the total number of amino acids and the positions of arginine residues have changed considerably during the course of mammalian evolution. This evolutionary pattern suggests that protamine P1 is under an unusual form of purifying selection, in which the high proportion of arginine residues is maintained but the positions may vary. In this case, we would expect that the rate of nonsynonymous substitution is not particularly low compared with that of synonymous substitution, despite purifying selection. We would also expect that the selection for a high arginine content results in a high frequency of the nucleotide G in the coding region of this gene, because all six arginine codons contain at least one G. These expectations were confirmed in our study of mammalian protamine genes. Analysis of nonmammalian vertebrate genes also showed essentially the same patterns of evolutionary changes, suggesting that this unusual form of purifying selection has been active since the origin of bony vertebrates. The protamine gene of an insect species shows similar patterns, although its purifying selection is less intense. These observations suggest that arginine-rich selection is a general feature of protamine evolution. The driving force for arginine-rich selection appears to be the DNA-binding function of protamine P1 and an interaction with a protein kinase in the fertilized egg.
Amino Acid Sequence↗
Efficiencies of fast algorithms of phylogenetic inference under the criteria of maximum parsimony, minimum evolution, and maximum likelihood when a large number of sequences are used.
In phylogenetic inference by maximum-parsimony (MP), minimum-evolution (ME), and maximum-likelihood (ML) methods, it is customary to conduct extensive heuristic searches of MP, ME, and ML trees, examining a large number of different topologies. However, these extensive searches tend to give incorrect tree topologies. Here we show by extensive computer simulation that when the number of nucleotide sequences (m) is large and the number of nucleotides used (n) is relatively small, the simple MP or ML tree search algorithms such as the stepwise addition (SA) plus nearest neighbor interchange (NNI) search and the SA plus subtree pruning regrafting (SPR) search are as efficient as the extensive search algorithms such as the SA plus tree bisection-reconnection (TBR) search in inferring the true tree. In the case of ME methods, the simple neighbor-joining (NJ) algorithm is as efficient as or more efficient than the extensive NJ+TBR search. We show that when ME methods are used, the simple p distance generally gives better results in phylogenetic inference than more complicated distance measures such as the Hasegawa-Kishino-Yano (HKY) distance, even when nucleotide substitution follows the HKY model. When ML methods are used, the simple Jukes-Cantor (JC) model of phylogenetic inference generally shows a better performance than the HKY model even if the likelihood value for the HKY model is much higher than that for the JC model. This indicates that at least in the present case, selecting of a substitution model by using the likelihood ratio test or the AIC index is not appropriate. When n is small relative to m and the extent of sequence divergence is high, the NJ method with p distance often shows a better performance than ML methods with the JC model. However, when the level of sequence divergence is low, this is not the case.
Algorithms↗
Positive selection in the evolution of mammalian interleukin-2 genes.
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Amino Acid Sequence↗
EKG abnormalities during partial seizures in refractory epilepsy.
PURPOSE: This study assessed the frequency and character of ictal cardiac rhythm and conduction abnormalities in intractable epilepsy. Sudden unexpected death in epilepsy (SUDEP) is a major cause of excess mortality in people with refractory epilepsy, and cardiac arrhythmias during seizures may be responsible. The frequency of cardiac abnormalities during seizures in patients with refractory epilepsy must be determined. METHODS: Fifty-one seizures in 43 patients with intractable partial epilepsy were analyzed prospectively from CCTV-EEG monitoring with one ECG channel. Arrhythmias, repolarization abnormalities, and PR and QTc intervals were determined for preictal (3 min), ictal, and postictal (3 min) periods for one or more seizures per patient. Parametric statistics were used for continuous variables, and nonparametric statistics were used for categoric variables. RESULTS: Of the patients, 39% had one or more abnormalities of rhythm and/or repolarization during or immediately after seizures. Abnormalities included asystole (one), atrial fibrillation (one), marked or moderate sinus arrhythmia (six), supraventricular tachycardia (one), atrial premature depolarizations (APDs; eight), ventricular premature depolarizations (VPDs; two), and bundle-branch block (three). Mean seizure duration was longer in patients with abnormalities than in those without (204 vs. 71 s; p < 0.001). Generalized tonic-clonic seizures were also associated with increased occurrence of ictal ECG abnormalities (p = 0.006) as compared with complex partial seizures. There were no clinically significant differences in mean preictal and ictal/postictal PR and QTc intervals. CONCLUSIONS: Cardiac rhythm and conduction abnormalities are common during seizures, particularly if they are prolonged or generalized, in intractable epilepsy. These abnormalities may contribute to SUDEP.
Adolescent↗
Fifty-million-year-old polymorphism at an immunoglobulin variable region gene locus in the rabbit evolutionary lineage.
The Ig heavy chain variable region (V(H)) genes encode the antigen-binding regions of antibodies. The rabbit genome contains more than 100 V(H) genes, but only one (V(H)1) is preferentially used in the VDJ gene rearrangement. Three highly divergent alleles occur at this V(H)1 locus in most rabbit populations. These three V(H) alleles are also present in snowshoe hare populations, indicating that the polymorphism of the V(H)1 alleles is trans-specific. Here we report the results of a phylogenetic analysis of rabbit Ig germ-line V(H) genes (alleles) together with V(H) genes from humans and mice. We have found that all rabbit V(H) genes belong to one mammalian V(H) group (group C), which also includes various human and mouse V(H) genes. Using the rate of nucleotide substitution obtained from human and mouse V(H) sequences, we have estimated that the V(H)1 polymorphism in the rabbit lineage has been maintained for about 50 million years. This extremely long persistence of V(H)1 polymorphism is apparently caused by overdominant selection, though the real mechanism is unclear.
Animals↗
Diversity and evolution of T-cell receptor variable region genes in mammals and birds.
The receptor of a T lymphocyte (TCR) recognizes nonself antigens in the company of major histocompatibility complex (MHC) molecules presented to it by the antigen-presenting cell. The variable region of TCR is encoded by either a concatenation of variable region (TCR-V), diversity region (TCR-D), and joining region (TCR-J) genes, or a concatenation of TCR-V and TCR-J genes. The TCR-V genes exist as a multigene family in vertebrate species. Here we study the evolutionary relationships of TCR-V genes from humans, sheep, cattle, rabbits, mice, and chicken. These six species can be classified into two groups according to the frequency of gamma(delta) T-cells in their peripheral T-cell populations. The "gamma(delta) low" group of species includes humans and mice, in which gamma(delta)T-cells constitute very limited portion of the T-cell population. The "gamma(delta) high" group includes sheep, cattle, rabbits, and chicken, in which gamma(delta) T-cells comprise up to 60% of the T-cell population. Here, we compiled TCR-V sequences from the six species and conducted a phylogenetic analysis. We identified various TCR-V gene subgroups based on the analysis. We found that humans and mice have representatives from nearly all of the subgroups identified, while other species have lost subgroups to different extent. Therefore, the gamma(delta) low species have a high degree of diversity of TCR-V genes, while gamma(delta) high species all have limited diversity of TCR-V genes. This pattern is similar to that found for immunoglobulin variable region (IGV) genes.
Animals↗
Locus specificity of polymorphic alleles and evolution by a birth-and-death process in mammalian MHC genes.
We have conducted an extensive phylogenetic analysis of polymorphic alleles from human and mouse major histocompatibility complex (MHC) class I and class II genes. The phylogenetic tree obtained for 212 complete human class I allele sequences (HLA-A, -B, and -C) has shown that all alleles from the same locus form a single cluster, which is highly supported by bootstrap values, except for one HLA-B allele (HLA-B*7301). Mouse MHC class I loci did not show locus-specific clusters of polymorphic alleles. This was considered to be because of either interlocus genetic exchange or the confusing designation of loci in different haplotypes at the present time. The locus specificity of polymorphic alleles was also observed in human and mouse MHC class II loci. It was therefore concluded that interlocus recombination or gene conversion is not very important for generating MHC diversity, with a possible exception of mouse class I loci. According to the phylogenetic trees of complete coding sequences, we classified human MHC class I (HLA-A, -B, and -C) and class II (DRB1) alleles into three to five major allelic lineages (groups), which were monophyletic with high bootstrap values. Most of these allelic groups remained unchanged even in phylogenetic trees based on individual exons, though this does not exclude the possibility of intralocus recombination involving short DNA segments. These results, together with the previous observation that MHC loci are subject to frequent duplication and deletion, as well as to balancing selection, indicate that MHC evolution in mammals is in agreement with the birth-and-death model of evolution, rather than with the model of concerted evolution.
Alleles↗