Prevalence of Anderson-Fabry disease in male patients with late onset hypertrophic cardiomyopathy

Background-Although studies have suggested that "late-onset" hypertrophic cardiomyopathy (HCM) may be caused by sarcomeric protein gene mutations, the cause of HCM in the majority of patients is unknown. This study determined the prevalence of a potentially treatable cause of hypertrophy, Anderson-Fabry disease, in a HCM referral population.Methods and Results-Plasma alpha-galactosidase A (alpha-Gal) was measured in 79 men with HCM who were diagnosed at greater than or equal to40 years of age (52.9 +/- 7.7 years; range, 40-71 years) and in 74 men who were diagnosed at <40 years (25.9 +/- 9.2 years; range, 8-39 years). Five patients (6.3%) with late-onset disease and 1 patient (1.4%) diagnosed at <40 years had low alpha-Gal activity. Of these 6 patients, 3 had angina, 4 were in New York Heart Association class 2, 5 had palpitations, and 2 had a history of syncope. Hypertrophy was concentric in 5 patients and asymmetric in 1 patient. One patient had left ventricular outflow tract obstruction. All patients with low alpha-Gal activity had alpha-Gal gene mutations.Conclusion-Anderson-Fabry disease should be considered in all cases of unexplained hypertrophy. Its recognition is important given the advent of specific replacement enzyme therapy

Lentivector Transduction Improves Outcomes Over Transplantation of Human HSCs Alone in NOD/SCID/Fabry Mice

Fabry disease is a lysosomal storage disorder caused by a deficiency of a-galactosidase A (a-gal A) activity that results in progressive globotriaosylceramide (Gb(3)) deposition. We created a fully congenic nonobese diabetic (NOD)/severe combined immunodeficiency (SCID)/Fabry murine line to facilitate the in vivo assessment of human cell-directed therapies for Fabry disease. This pure line was generated after 11 generations of backcrosses and was found, as expected, to have a reduced immune compartment and background a-gal A activity. Next, we transplanted normal human CD34(+) cells transduced with a control (lentiviral vector-enhanced green fluorescent protein (LV-eGFP)) or a therapeutic bicistronic LV (LV-a-gal A/internal ribosome entry site (IRES)/hCD25). While both experimental groups showed similar engraftment levels, only the therapeutic group displayed a significant increase in plasma a-gal A activity. Gb(3) quantification at 12 weeks revealed metabolic correction in the spleen, lung, and liver for both groups. Importantly, only in the therapeutically-transduced cohort was a significant Gb(3) reduction found in the heart and kidney, key target organs for the amelioration of Fabry disease in humans.Fil: Pacienza, Natalia Alejandra. University Health Network; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Yoshimitsu, Makoto. Kagoshima University; Japón. University Health Network; CanadáFil: Mizue, Nobuo. University Health Network; CanadáFil: Au, Bryan C. Y.. University Health Network; CanadáFil: Wang, James C. M.. University Health Network; CanadáFil: Fan, Xin. University Health Network; CanadáFil: Takenaka, Toshihiro. Kagoshima University; JapónFil: Medin, Jeffrey A. University Health Network; Canadá. University of Toronto; Canad

Full-gap superconductivity robust against disorder in heavy-fermion CeCu2Si2

A key aspect of unconventional pairing by the antiferromagnetic spin-fluctuation mechanism is that the superconducting energy gap must have opposite sign on different parts of the Fermi surface. Recent observations of non-nodal gap structure in the heavy-fermion superconductor CeCu$_2$Si$_2$ were then very surprising, given that this material has long been considered a prototypical example of a superconductor where the Cooper pairing is magnetically mediated. Here we present a study of the effect of controlled point defects, introduced by electron irradiation, on the temperature-dependent magnetic penetration depth $\lambda(T)$ in CeCu$_2$Si$_2$. We find that the fully-gapped state is robust against disorder, demonstrating that low-energy bound states, expected for sign-changing gap structures, are not induced by nonmagnetic impurities. This provides bulk evidence for $s_{++}$-wave superconductivity without sign reversal.Comment: 5 pages, 4 figures + Supplemental Material (1 page, 1 figure). Will appear in Phys. Rev. Let

Triplanar Model for the Gap and Penetration Depth in YBCO

YBaCuO_7 is a trilayer material with a unit cell consisting of a CuO_2 bilayer with a CuO plane of chains in between. Starting with a model of isolated planes coupled through a transverse matrix element, we consider the possibility of intra as well as interplane pairing within a nearly antiferromagnetic Fermi liquid model. Solutions of a set of three coupled BCS equations for the gap exhibit orthorhombic symmetry with s- as well as d-wave contributions. The temperature dependence and a-b in plane anisotropy of the resulting penetration depth is discussed and compared with experiment.Comment: To appear in Physical Review B1 01Mar97; 12 pages with 10 figures; RevTeX+eps

The mineral composition of five insects as sold for human consumption in Southern Africa

Edible insects have been proposed as an alternative protein source that is economically and  environmentally preferable to livestock, and certain species may be high in nutrients that benefit human health. We present data describing the mineral content of five edible insects as sold in South Africa and Zimbabwe. We report high variation between and within species, and note that these insects contain significant quantities of potentially beneficial, and potentially harmful, micronutrients. Two caterpillars were notably high in Fe and Zn, which are important nutrients for combating iron deficiency anemia. Na content varied both between and within species, suggesting that some sellers add quantities of salt that could be harmful to health. Mn levels were high in edible termites. We concluded that caterpillars can be promoted as nutrient rich foods in southern Africa; that added salt should be limited in commercial products; and that further research is required to determine whether common serving sizes of termites may put consumers in danger of manganese poisoning. Key words: Edible insects, nutrition, mineral composition, micronutrients, Lepidoptera.Abbreviation: DALYs, Disability-adjusted life years; Na, sodium; K, potassium; Ca, calcium; Mg, magnesium; Al, aluminium; P, phosphorus; S, sulphur; Cu, copper; Fe, iron; Mn, manganese; Zn, zinc; DRI, daily recommended intake

Coherence, incoherence and scaling along the c axis of YBa_2Cu_3O_{6+x}

The optical properties of single crystals of YBa_2Cu_3O_{6+x} have been examined along the c axis above and below the critical temperature (T_c) for a wide range of oxygen dopings. The temperature dependence of the optically-determined value of the dc conductivity (\sigma_{dc}) in the normal state suggests a crossover from incoherent (hopping-type) transport at lower oxygen dopings (x \lesssim 0.9) to more coherent anisotropic three-dimensional behavior in the overdoped (x \approx 0.99) material at temperatures close to T_c. The assumption that superconductivity occurs along the c axis through the Josephson effect yields a scaling relation between the strength of the superconducting condensate (\rho_{s,c}, a measure of the number of superconducting carriers), the critical temperature, and the normal-state c-axis value for \sigma_{dc} just above T_c; \rho_{s,c} \propto \sigma_{dc} T_c. This scaling relation is observed along the c axis for all oxygen dopings, as well as several other cuprate materials. However, the agreement with the Josephson coupling model does not necessarily imply incoherent transport, suggesting that these materials may indeed be tending towards coherent behavior at the higher oxygen dopings.Comment: Six pages with four figures and one tabl

Microwave properties of Nd_0.5Sr_0.5MnO_3: a key role of the (x^2-y^2)-orbital effects

Transmittance of the colossal magnetoresistive compound Nd_0.5Sr_0.5MnO_3 showing metal-insulator phase transition has been studied by means of the submm- and mm-wavelength band spectroscopy. An unusually high transparency of the material provided direct evidence for the significant suppression of the coherent Drude weight in the ferromagnetic metallic state. Melting of the A-type antiferromagnetic states has been found to be responsible for a considerable increase in the microwave transmission, which was observed at the transition from the insulating to the metallic phase induced by magnetic field or temperature. This investigation confirmed a dominant role of the (x^2-y^2)-orbital degree of freedom in the low-energy optical properties of Nd_0.5Sr_0.5MnO_3 and other doped manganites with planar (x^2-y^2)-orbital order, as predicted theoretically. The results are discussed in terms of the orbital-liquid concept.Comment: 8 pages, 3 figure

Magnetoresistance in Heavily Underdoped YBa_2Cu_3O_{6+x}: Antiferromagnetic Correlations and Normal-State Transport

We report on a contrasting behavior of the in-plane and out-of-plane magnetoresistance (MR) in heavily underdoped antiferromagnetic (AF) YBa_2Cu_3O_{6+x} (x<0.37). The out-of-plane MR (I//c) is positive over most of the temperature range and shows a sharp increase, by about two orders of magnitude, upon cooling through the Neel temperature T_N. A contribution associated with the AF correlations is found to dominate the out-of-plane MR behavior for H//c from far above T_N, pointing to the key role of spin fluctuations in the out-of-plane transport. In contrast, the transverse in-plane MR (I//a(b);H//c) appears to be small and smooth through T_N, implying that the development of the AF order has little effect on the in-plane resistivity.Comment: 4 pages, 5 figures, accepted for publication in Phys.Rev.Let