Cultured fibroblasts established from skin biopsies from patients with the Lesch-Nyhan syndrome are deficient in hypoxanthine-guanine phosphoribosyl-transferase (EC 2.4.2.8) activity. This deficiency makes possible the use of chemicals that select either for or against deficient variants in cultured fibroblasts. Two-way selection has been achieved by the use of 6-thioguanine, which selects for ...

BACKGROUND Lesch-Nyhan disease is a rare X-linked neurodevelopemental metabolic disorder caused by a wide variety of mutations in the HPRT1 gene leading to a deficiency of the purine recycling enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt). The residual HGprt activity correlates with the various phenotypes of Lesch-Nyhan (LN) patients and in particular with the different degree o...

Defining neurogenetic phenotypes (or how to compare needles in haystacks) Accurate diagnosis is the foundation of clinical neurology, providing both the physician and the patient with a guide to the future, hopefully leading to a treatment, and sometimes pointing towards a cure. Unlike many other clinical disciplines, the day-today practice of neurology involves a pantheon of symptoms and long ...

substrates and products have no effect. Fractionation of normal erythrocytes by hypotonic lysis reveals a decline in the specific activity of A-PRT as the red cells age. In patients with the Lesch-Nyhan syndrome, the decline in A-PRT activity with ageing of cells is much less marked. Furthermore, the concentrations of free PRPP are as much as 10-fold elevated in the erythrocytes of these childr...

We construct a canonical invertible double for general first order elliptic differential operators over smooth compact manifolds with boundary and derive a natural formula for the Calderón projector which yields a generalization of the famous Cobordism Theorem. Assuming symmetric principal symbol of the tangential operator and unique continuation property (UCP) from the boundary, we obtain the ...

BACKGROUND The aim of this study was to examine the association between the MAOA-uVNTR gene polymorphism in a homogeneous subgroups of patients with alcohol dependence categorized according to Lesch's typology. METHODS DNA was provided from alcohol dependent (AD) patients (n=370) and healthy control subjects (n=168) all of Polish descent. The history of alcoholism was obtained using the Polis...

DISCOVERY AND CHARACTERIZATION OF A NOVEL INHIBITOR OF MATRIX METALLOPROTEASE-13 (MMP13) THAT REDUCES CARTILAGE DAMAGE IN VIVO WITHOUT JOINT FIBROPLASIA SIDE EFFECTS Adam R. Johnson, # Alexander G. Pavlovsky, Daniel F. Ortwine, Faith Prior, Chiu-Fai Man, Dirk A. Bornemeier, Craig A. Banotai, W. Thomas Mueller, Patrick McConnell, Chunhong Yan, Vijay Baragi, Charles Lesch, W. Howard Roark, Michae...

We have studied three patients with the Lesch-Nyhan syndrome to assess the effect of dietary purines on erythrocyte hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity. During dietary purine restriction HGPRT activity rose in all three patients; resumption of normal dietary purine intake or the addition of adenine (10 mg/kg per day) to a purinefree diet resulted in a fall in HGPRT a...

A 3-year-old boy referred for persistent tongue bleeding was diagnosed with a rare self-mutilating disease that had also affected his lip and fingers. He underwent multiple odontectomy and partial glossectomy and continues to undergo behavior therapy and on-demand splints and restraints. He has stopped self-biting and has gained appetite and weight. Lesch-Nyhan Syndrome can cause significant mo...

Abstract. Given two unitary involutions σ1 and σ2 satisfying Gσi = −σiG on kerB on a compact manifold with cylindrical end, M. Lesch, K. Wojciechowski ([LW]) and W. Müller ([M]) established the formula describing the difference of two eta-invariants with the APS boundary conditions associated with σ1 and σ2. In this paper we establish the analogous formula for the zeta-determinants of Dirac Lap...