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Nervous system Lyme borreliosis--revisited [corrected; erratum to be published].
A great deal of confusion surrounds the diagnosis, clinical phenomenology, and treatment of Lyme borreliosis. Most diagnostic methods currently in use are indirect and do not differentiate between prior exposure and current infection. A critical review of the literature permits the characterization of a distinct set of neurologic disorders that are almost certainly caused by this infection and their differentiation from the plethora of syndromes that have been anecdotally linked to infection, but in which causality has never been established. This article describes the range of clinical disorders associated with Lyme borreliosis, provides an overview of current approaches to diagnosis, and reviews current treatment protocols.
Inhibitors of HIV-1 replication [corrected; erratum to be published] that inhibit HIV integrase.
HIV-1 replication depends on the viral enzyme integrase that mediates integration of a DNA copy of the virus into the host cell genome. This enzyme represents a novel target to which antiviral agents might be directed. Three compounds, 3,5-dicaffeoylquinic acid, 1-methoxyoxalyl-3,5-dicaffeoylquinic acid, and L-chicoric acid, inhibit HIV-1 integrase in biochemical assays at concentrations ranging from 0.06-0.66 microgram/ml; furthermore, these compounds inhibit HIV-1 replication in tissue culture at 1-4 microgram/ml. The toxic concentrations of these compounds are fully 100-fold greater than their antiviral concentrations. These compounds represent a potentially important new class of antiviral agents that may contribute to our understanding of the molecular mechanisms of viral integration. Thus, the dicaffeoylquinic acids are promising leads to new anti-HIV therapeutics and offer a significant advance in the search for new HIV enzyme targets as they are both specific for HIV-1 integrase and active against HIV-1 in tissue culture.
alpha1-antitrypsin gene mutation hot spot associated with the formation of a retained and degraded null variant [corrected; erratum to be published].
Null alpha1-antitrypsin (alpha1AT) alleles represent the end of a continuum of variants associated with profound alpha1AT deficiency and an increased risk of emphysema. This study characterizes the molecular basis of QOclayton, a new example of an alpha1AT null allele arising from a mutational hot spot in the alpha1AT gene. The QOclayton allele is identical to the normal M1(V213) alpha1AT allele except for an insertion of a cytosine. This insertion occurs in the alpha1AT sequence which normally has seven cytosines corresponding to amino acid residues 360 to 362. The QOclayton mutation is located in the same reiterated DNA sequence as the alpha1AT QObolton deletion mutation and the insertion mutation allele QOsaarbruecken. The QOclayton cytosine insertion causes a 3' frameshift and results in the formation of a termination codon at residue 376, the same consequence as the alpha1AT QOmattawa mutation (L353 T-insertion with a 3' frameshift). To determine the molecular mechanisms responsible for the absence of alpha1AT associated with the QOclayton gene, an in vitro model of QOclayton was established using Chinese hamster ovary cells (CHO) transfected with the QOclayton gene. These cells were evaluated for alpha1AT mRNA expression, protein synthesis and secretion. Although the QOclayton gene expresses a similar amount of alpha1AT mRNA as compared with the normal alpha1AT gene, no QOclayton protein is secreted. Protein trafficking and double-label immunofluorescence demonstrate that the QOclayton protein is retained in the rough endoplasmic reticulum or pre-Golgi compartment and is degraded (t1/2 = 6.5 h). Since QOmattawa, QObolton, and QOsaarbruecken have similar termination sites in the alpha1AT mRNA, they may share a similar intracellular fate.
The arcuate wedge osteotomy, and the composite nature of bone [erratum to be published].
The limitations of the "pie-shaped" wedge osteotomy were reviewed and the preliminary means of making an arcuate wedge osteotomy were discussed. New instrumentation was introduced that will facilitate performance of arcuate cuts in bone. Figure 8 demonstrates practical application of the technique.
Neuronally restricted RNA splicing regulates the expression of a novel GABAA receptor subunit conferring atypical functional properties [corrected; erratum to be published].
We report the isolation and characterization of a cDNA encoding a novel member of the GABA receptor gene family, epsilon. This polypeptide is 506 amino acids in length and exhibits its greatest amino acid sequence identity with the GABAA receptor gamma3 subunit (47%), although this degree of homology is not sufficient for it to be classified as a fourth gamma subunit. The epsilon subunit coassembles with GABAA receptor alpha and beta subunits in Xenopus laevis oocytes and transfected mammalian cells to form functional GABA-gated channels. alpha1beta1epsilon GABAA receptors, like alpha1beta1gamma2s receptors, are modulated by pentobarbital and the steroid 5alpha-pregnan-3alpha-ol-20-one but, unlike alpha1beta1gamma2s receptors, are insensitive to flunitrazepam. Additionally, alpha1beta1epsilon receptors exhibit rapid desensitization kinetics, as compared with alpha1beta1 or alpha1beta1gamma2s. Northern analysis demonstrates widespread expression of a large epsilon subunit transcript in a variety of non-neuronal tissues and expression of a smaller transcript in brain and spinal cord. Sequence analysis demonstrated that the large transcript contained an unspliced intron, whereas the small transcript represents the mature mRNA, suggesting regulation of expression of the epsilon subunit via neuronally restricted RNA splicing. In situ hybridization and immunocytochemistry reveal a pattern of expression in the brain restricted primarily to the hypothalamus, suggesting a role in neuroendocrine regulation, and also to subfields of the hippocampus, suggesting a role in the modulation of long term potentiation and memory.
Congenital hypothyroidism caused by a mutation in the Na+/l-symporter.
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Rejoinder to Eigenmann PA, Haengelli CA, Food colourings and preservatives--allergy and hyperactivity (Lancet 2004; 364:823-4) and an erratum.
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Deep brain stimulation for Parkinson's disease: Potential risk of tissue damage associated with external stimulation--erratum.
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Wide spectral range third-order autocorrelator based on ultrafast nonresonant nonlinear refraction: erratum.
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Treatment of traumatic spondylolisthesis of the axis with nonrigid immobilization: erratum.
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Erratum: Complete chloroplast genomes and phylogenetic analysis of 7 Murraya species in China: Erratum.
[This corrects the article DOI: 10.1097/st9.0000000000000091.].
Erratum: a quantification of the lung surface area in emphysema using computed tomography.
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Erratum: career risk of hepatitis C virus infection among U.S. emergency medical and public safety workers.
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Erratum for Durovka et al., "Complete genome sequence of Cronobacter muytjensii bacteriophage vB_Cmu_VP5".
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