Voltammetry of heterogeneous labile metal–macromolecular systems for any ligand-to-metal ratio: Part I. Approximate voltammetric expressions for the limiting current to obtain complexation information

We present approximate expressions and rigorous numerical simulations corresponding to the voltammetric limiting currents of a titration experiment of a heterogeneous macromolecular ligand with a metal ion under fully labile conditions. We highlight the accuracy of an approximate expression based on a polynomial expansion of the limiting current in terms of the fraction of the bound metal concentration in the bulk solution. Values of the coefficients of the polynomial expansion for macromolecular complexation are provided. The accuracy of this polynomial expression for systems exhibiting different degrees of heterogeneity together with its easy computation, suggests its application in the finding of the bulk value of the bound metal concentration from the limiting current for a given pair of total ligand and metal concentrations. Thus, straightforward calculations lead to the binding curve which can then be interpreted using the standard methods.     

Evaluation of NF2 gene deletion in sporadic schwannomas, meningiomas, and ependymomas by chromogenic in situ hybridization

Fluorescence in situ hybridization, loss of heterozygosity testing, and comparative genomic hybridization have been used to detect NF2 gene alterations in both sporadic and neurofibromatosis type 2 (NF2)-associated central nervous system tumors. In this study, we performed chromogenic in situ hybridization (CISH) and immunohistochemistry to evaluate for NF2 gene deletion in a group of sporadic meningiomas, schwannomas, and ependymomas. Twenty-two sporadic tumors, including 9 ependymomas, 10 meningiomas, and 3 schwannomas, were studied. CISH and immunohistochemistry were performed using the NF2 gene deletion probe and NF2 polyclonal antibody. Deletion of the NF2 gene was identified in 11 (50%) tumors, including 60% (6/10) of meningiomas, 33% (3/9) of ependymomas, and 67% (2/3) of schwannomas. The remaining 11 (50%) cases were diploid. Overall, immunoexpression of NF2 protein was observed in 50% (11/22) tumors, and concordance between CISH and immunohistochemistry was observed in 73% of cases. Our results support previous observations that schwannomas and meningiomas, and to a lesser degree, ependymomas, express a high incidence of NF2 gene deletion, which supports the hypothesis that NF2 gene plays an important role in their tumorigenesis. In addition, we have validated CISH as an efficient, economic, and reliable method for routinely assessing NF2 gene deletion in these tumors.     

Atrophic Congenital Melanocytic Nevus Mimicking Rapidly Involuting Congenital Hemangioma

Abstract: Congenital melanocytic nevi (CMN) are benign skin lesions present in some newborns. We describe a newborn boy with a giant CMN on the scalp. It appeared as an atrophic patch with a central nodule that was suggestive of a rapidly involuting congenital hemangioma or some other vascular tumor. Histopathology confirmed the diagnosis of CMN. Magnetic resonance imaging was normal, excluding leptomeningeal melanocytosis. We did not find any other cases of CMN with this presentation in the literature.     

Visuospatial deficits in Parkinson's disease assessed by judgment of line orientation test: error analyses and practice effects.

The Benton's Judgment of Line Orientation (JLO) is one of the tests most frequently used to assess visuospatial function. The aim of the present study was to analyze qualitative errors in Parkinson's disease (PD) following the method described by Ska, Poissant, and Joanette (1990) and to determine possible practice effects of this test. The JLO was administered to 76 idiopathic PD patients and 76 matched normal controls. The analyses of errors showed several qualitative differences between groups. Parkinson's patients made a greater proportion of complex intraquadrant errors and horizontal line errors, while they showed fewer simple intraquadrant errors than controls. The JLO test was also administered twice in an interval of 20 min in a subsample of 25 PD patients and 25 normal controls. The results did not show significant differences between the two administrations, indicating that the test is free of practice effects. In conclusion, these data provide further evidence for the existence of visuospatial deficits in PD. Moreover, the JLO has proved to be an appropriate test for the assessment of the visuospatial function in patients who require a neuropsychological follow up.     

Classical Friedreich's ataxia and its genotype.

Fourteen patients with classical features of Friedreich's ataxia (FRDA) were examined. The clinical diagnosis of FRDA was afterwards confirmed in all patients by the appropriate DNA investigation which showed markedly increased amounts of GAA repeats on both alleles of the frataxin gene. None of our patients presented with atypical features such as late-onset FRDA, FRDA with retained deep tendon reflexes or with a very slow course. Five of them are not yet confined to a wheelchair. But for 1 patient who died at age 36 years and had the largest number of GAA repeats on both alleles, there was no significant correlation between number of repeats in the shortest allele, age at onset, age at wheelchair dependence, duration of the disease and main clinical signs. All patients but 3 had between 500 and 1,050 GAA repeats. The 3 patients with, respectively, 400, 450 and 500 repeats on the shortest allele had a clinical course comparable to the other patients. Even in the case of variations in the number of repeats in the same sibship, there were only modest differences between the siblings concerning age at onset of the disease, symptoms and signs and age at wheelchair dependence. There were no qualitative differences in the main clinical features and laboratory investigations in the full-blown phase of the disorder. Molecular biology has become a major element in the diagnosis of FRDA. DNA testing for FRDA should be applied to every case of idiopathic autosomal recessive or sporadic ataxia. However, the clinical features of FRDA remain fully characteristic in many patients and keep their diagnostic value.     

Clinical features and genetic analysis of a Spanish family with spinocerebellar ataxia 6

Objective - To present the clinical features and DNA analysis of a Spanish SCA6 family. Material and methods - Four symptomatic members of the family (mean age at onset: 53.75 ± 5.21) were examined. SCA6 CAG trinucleotide repeat was analysed in the proband by the polymerase chain reaction (PCR). Results - Early dysphagia, ophthalmoparesis and neck dystonia in the oldest patient, without the loss of vibratory and proprioceptive sensation supporting the theory of phenotypic variability within families with SCA6 . Our results are in accordance with the theory that the size of the repeat pattern correlates with the age at onset of the symptoms. Analysis of the SCA6 CAG trinucleotide repeat at the CACNA1A gene in the patient's DNA demonstrated an expanded allele of 22 CAG repeat units. Conclusions - This study identifies phenotypic differences in the surviving kindred. The diagnosis of SCA6 in family members or single affected patients can be made by direct molecular analysis. This makes predictive testing possible.     

Anti‐GM2 ganglioside antibodies are a biomarker for acute canine polyradiculoneuritis

Acute canine polyradiculoneuritis (ACP) is considered to be the canine equivalent of the human peripheral nerve disorder Guillain‐Barré syndrome (GBS); an aetiological relationship, however, remains to be demonstrated. In GBS, anti‐glycolipid antibodies (Abs) are considered as important disease mediators. To address the possibility of common Ab biomarkers, the sera of 25 ACP dogs, 19 non‐neurological, and 15 epileptic control dogs were screened for IgG Abs to 10 glycolipids and their 1 : 1 heteromeric complexes using combinatorial glycoarrays. Anti‐GM2 ganglioside Abs were detected in 14/25 ACP dogs, and anti‐GA1 Abs in one further dog. All controls except for one were negative for anti‐glycolipid Abs. In this cohort of cases and controls, the glycoarray screen reached a diagnostic sensitivity of 60% and a specificity of 97%; a lower sensitivity (32%) was reported using a conventional glycolipid ELISA. To address the possible pathogenic role for anti‐GM2 Abs in ACP, we identified GM2 in canine sciatic nerve by both mass spectrometry and thin layer chromatography overlay. In immunohistological studies, GM2 was localized predominantly to the abaxonal Schwann cell membrane. The presence of anti‐GM2 Abs in ACP suggests that it may share a similar pathophysiology with GBS, for which it could thus be considered a naturally occurring animal model.