We report a patient with Pompe disease who developed reversible nephrotic syndrome during prolonged, high-dose, experimental, enzyme replacement therapy with recombinant human acid alpha-glucosidase ...(rhGAA). Because of the development of antibodies to rhGAA and concomitant clinical decline, escalating doses of rhGAA were administered as part of an experimental immune tolerance regimen. Histologic evaluation of kidney tissue revealed glomerular deposition of immune complexes containing rhGAA itself, in a pattern of membranous nephropathy. To our knowledge, this is the first reported case of nephrotic syndrome occurring during enzyme replacement therapy. The nephrotic syndrome gradually resolved after the rhGAA dose was decreased, indicating that decreasing the antigenic load can ameliorate glomerular immune complex deposition associated with enzyme replacement in a highly sensitized patient.
Overview of MgB2 Superconductor Applications Tomsic, Michael; Rindfleisch, Matthew; Yue, Jinji ...
International journal of applied ceramic technology,
July 2007, Letnik:
4, Številka:
3
Journal Article
Recenzirano
Since 2001, when magnesium diboride (MgB2) was first reported to have a transition temperature of 39 K, conductor development has progressed to where MgB2 superconductor wire in kilometer‐long ...piece‐lengths has been demonstrated in coil form. Now that the wire is available commercially, work has started on demonstrating a MgB2 wire in superconducting devices. This article discusses the progress on MgB2 conductor and coil development, and the potential for MgB2 superconductors in a variety of commercial applications: magnetic resonance imaging, fault current limiters, transformers, motors, generators, adiabatic demagnetization refrigerators, magnetic separation, magnetic levitation, superconducting magnetic energy storage, and high‐energy physics applications.
Pacific tree frogs Hyla regilla are typically either green or brown in dorsal coloration. The frequency of green and brown individuals is known to fluctuate seasonally. Previous investigators have ...generally assumed that the green and brown body colors represent a "fixed" polymorphism and that seasonal changes in the proportion of the two body colors are a consequence of differential survival of the two color morphs. Here we report that, in addition to the "fixed" (i.e., non-color-changing) green and brown morphs of H. regilla, there are some individuals that can change hue between green and brown. The distribution of color-change ability in our study population is bimodal, suggesting that "color changers" are a distinct morph rather than one extreme of a continuous distribution of color-change ability. Our findings suggest that background brightness, not hue, triggers color change in the newly discovered morph and that this change requires days to weeks to occur. Such slow color change is not well suited for making short-term changes in color as a frog moves between differently colored substrates. Rather, seasonal changes in habitat characteristics and/or microhabitat use are likely to maintain color-change ability. Color polymorphism and color-change ability appear to represent alternative responses to divergent selection for crypsis in a heterogeneous, seasonally variable environment.
We generalise the local index formula of Connes and Moscovici to the case of spectral triples for a
*
-subalgebra
A
of a general semifinite von Neumann algebra. In this setting it gives a formula for ...spectral flow along a path joining an unbounded self-adjoint Breuer–Fredholm operator, affiliated to the von Neumann algebra, to a unitarily equivalent operator. Our proof is novel even in the setting of the original theorem and relies on the introduction of a function valued cocycle which is ‘almost’ a
(
b
,
B
)
-cocycle in the cyclic cohomology of
A
.
► This study explored the impact of maternal interaction on emotional regulation using the Still Face Paradigm. ► A longitudinal study design was used with infant–mother dyads seen at 4 and 9 months. ...► More maternal contingent responding was associated with infants who had more positive affect at both 4 and 9 months. ► More Maternal Attention Seeking play resulted in decreased positive affect at both 4 and 9 months.
This study used the Still Face Paradigm to investigate the relationship of maternal interaction on infants’ emotion regulation responses. Seventy infant–mother dyads were seen at 4 months and 25 of these same dyads were re-evaluated at 9 months. Maternal interactions were coded for attention seeking and contingent responding. Emotional regulation was described by infant stress reaction and overall positive affect. Results indicated that at both 4 and 9 months mothers who used more contingent responding interactions had infants who showed more positive affect. In contrast, mothers who used more attention seeking play had infants who showed less positive affect after the Still Face Paradigm. Patterns of stress reaction were reversed, as mothers who used more attention seeking play had infants with less negative affect. Implications for intervention and emotional regulation patterns over time are discussed.
Bios, Polis and the Autoimmune Phillips, John W.P.
Science, technology & society (New Delhi, India),
03/2012, Letnik:
17, Številka:
1
Journal Article
Recenzirano
Discourses about immunological structure have been historically productive in both the biological sciences and in political theory. In this article I argue that a deeper historical structure ...underlies both kinds of discourse and I attempt to draw some implications from this in relation to the current state of biomedical research in Singapore. Taking the establishment of Singapore’s dedicated biomedical research institution, Biopolis, as a starting point, the article raises several questions: the first concerns the role of biomedical research in Singapore in relation to its larger political economy; the second concerns the relationship between Asian bioscience in relation to international trends; the third concerns the deeper historical structures that, as I will argue, underlie the contemporary situation. After discussing the role of Biopolis in Singapore I outline some theoretical considerations towards an understanding of the kinds of immunological structure that characterize the relations discussed in the first part. I argue that the structure of relations might be understood as auto-immunological (or self-immunizing) and in making the case I draw selectively on disparate fields: mathematics, biology and philosophy.
Porphyria is a group of metabolic disorders due to altered enzyme activities within the heme biosynthetic pathway. It is a systemic disease with multiple potential contributions to mitochondrial ...dysfunction and oxidative stress. Recently, it has become possible to measure mitochondrial function from cells isolated from peripheral blood (cellular bioenergetics) using the XF96 analyzer (Seahorse Bioscience). Mitochondrial respiration in these cells is measured with the addition of activators and inhibitors of respiration. The output is measured as the O2 consumption rate (OCR) at basal conditions, ATP linked, proton leak, maximal, reserve capacity, non-mitochondrial, and oxidative burst. We performed cellular bioenergetics on 22 porphyria (12 porphyria cutanea tarda (PCT), seven acute hepatic porphyria (AHP), and three erythropoietic protoporphyria (EPP)) patients and 18 age and gender matched healthy controls. Of porphyria cases, eight were active (2 PCT, 1 EPP, and 5 AHP) and 14 in biochemical remission. The OCR were decreased in patients compared to healthy controls. The bioenergetic profile was significantly lower when measuring proton leak and the non-mitochondrial associated OCR in the eight active porphyria patients when compared to 18 healthy controls. In conclusion, we demonstrate that the bioenergetic profile and mitochondrial activities assessed in porphyria patients and is different than in healthy control individuals. Further, our novel preliminary findings suggest the existence of a mitochondrial dysfunction in porphyria and this may be used as potential non-invasive biomarker for disease activity. This needs to be assessed with a systematic examination in a larger patient cohort. Studies are also suggested to examine mitochondrial metabolism as basis to understand mechanisms of these findings and deriving mitochondrial based therapies for porphyria.
High-altitude pulmonary hypertension (HAPH) is a consequence of chronic alveolar hypoxia, leading to hypoxic vasoconstriction and remodeling of the pulmonary circulation. Brisket disease in cattle is ...a naturally occurring animal model of hypoxic pulmonary hypertension. Genetically susceptible cattle develop severe pulmonary hypertension and right heart failure at altitudes >7,000 ft. No information currently exists regarding the identity of the pathways and gene(s) responsible for HAPH or influencing severity. We hypothesized that initial insights into the pathogenesis of the disease could be discovered by a strategy of (1) sequencing of functional candidates revealed by single nucleotide polymorphism (SNP) analysis and (2) gene expression profiling of affected cattle compared with altitude-matched normal controls, with gene set enrichment analysis (GSEA) and Ingenuity pathway analysis (IPA). We isolated blood from a single herd of Black Angus cattle of both genders, aged 12–18 months, by jugular vein puncture. Mean pulmonary arterial pressures were 85.6±13 mmHg STD in the 10 affected and 35.3±1.2 mmHg STD in the 10 resistant cattle, P<0.001. From peripheral blood mononuclear cells, DNA was hybridized to an Affymetrix 10K Gene Chip SNP, and RNA was used to probe an Affymetrix Bovine genome array. SNP loci were remapped using the Btau 4.0 bovine genome assembly. mRNA data was analyzed by the Partek software package to identify sets of genes with an expression that was statistically different between the two groups. GSEA and IPA were conducted on the refined expression data to identify key cellular pathways and to generate networks and conduct functional analyses of the pathways and networks. Ten SNPs were identified by allelelic association and four candidate genes were sequenced in the cohort. Neither endothelial nitric oxide synthetase, NADH dehydrogenase, TG-interacting factor-2 nor BMPR2 were different among affected and resistant cattle. A 60-gene mRNA signature was identified that differentiated affected from unaffected cattle. Forty-six genes were overexpressed in the affected and 14 genes were downregulated in the affected cattle by at least 20%. GSEA and Ingenuity analysis identified respiratory diseases, inflammatory diseases and pathways as the top diseases and disorders (P<5.14×10–14), cell development and cell signaling as the top cellular functions (P<1.20×10–08), and IL6, TREM, PPAR, NFkB cell signaling (P<8.69×10–09) as the top canonical pathways associated with this gene signature. This study provides insights into differences in RNA expression in HAPH at a molecular level, and eliminates four functional gene candidates. Further studies are needed to validate and refine these preliminary findings and to determine the role of transcribed genes in the development of HAPH.
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