Adenosine A2A receptor dysfunction correlates with age at onset anticipation in blood platelets of subjects with Huntington's disease.

Huntington's disease (HD) may manifest at an earlier age in affected offspring than in transmitting parents. Earlier onset in successive generations (anticipation) only partially depends on intergenerational parent-child elongation of the CAG expanded mutation. An aberrant amplification of adenosine A(2A) receptor signaling documented in peripheral blood cells of subjects with HD implies that this cellular dysfunction may be related to clinical and genetic features. Prompted by evidence of higher receptor densities in siblings of HD subjects with stronger onset anticipation, in this study we investigated a possible relationship between A(2A) receptor densities and age at onset. We measured adenosine A(2A) receptor densities in blood cell platelets from 32 patients with HD and healthy control siblings, and sought a possible linear correlation between maximum platelet A(2A) receptor binding (B(max)) values for the whole cohort of HD subjects and anticipation in years. The increased B(max) values for the 32 subjects with HD (220 in patients vs. 137 in healthy control subjects, P = 0.0001) correlated significantly with anticipation in years (r2, 0.48, P = 0.0001 by linear correlation analysis). An increased platelet A(2A) receptor B(max) may belong in a cascade of toxic events leading to earlier onset of HD: as such it could be a useful marker of onset anticipation.

Italian Huntington disease patients--data and tissue bank.

We have collected clinical and genetic data on Huntington disease (HD) patients and their families over the last 5 years at the Unit of Neurogenetics, IRCCS Neuromed of Pozzilli (IS), Italy. Data on 854 mutation carriers are included in the data bank, together with a large number of DNA samples, blood, and other tissues. In particular, lymphoblastoid cell lines from 100 patients, including subjects carrying very rare genetic conditions (CAG mutation homozygosity, juvenile and infantile onset, pre-mutations) have been established. For all these initiatives ethical approval from the bioethics committee was obtained. We wish to extend this initiative to all families, investigators, and institutions within and, possibly outside, the Italian border in an attempt to enlarge the bank and to institute a HD Research Roster.

Onset and pre-onset studies to define the Huntington's disease natural history.

Huntington's disease's (HD) clinical history has not been defined yet. However, many aspects of the most confusing clinical stages, i.e., the first and last disease phases, including the symptom progression and the disease duration, have been better approached after discovery of the responsible gene. The existence of accurate genetic tests, available for affected and pre-symptomatic subjects (i.e., mutation carriers) and the possibility to study transgenic in vivo models, are actually helping us to understand some of the aspects of HD clinical presentation. HD may present with motor symptoms other than chorea, the psychiatric manifestations may represent part of the clinical picture and cognitive deterioration may occur very early in the disease and depend on early cortical involvement. Pre-onset studies are of crucial importance in understanding the temporal sequence of the clinical events. This is also very important for future therapeutic strategies in those diseases initiating late in the life, such as HD.

[Symptomatic and surgical results after integrated CT-MR study of a central giant cell tumor of the maxilla]. / Risultati semeiologici e chirurgici conseguenti allo studio integrato TC-RM del tumore gigantocellulare centrale del massiccio facciale.

The AA. examine the possibilities of the present imaging to the diagnostic definition of the extensive and destructive forms of the Central Giant cells Tumor of the maxilla. The CT and MR studies are compared with conventional x-Ray. The analysis performed evinces, besides the well-known semeiological CT superiority for the evidence of the osseous erosions, the ability to follow by MR imaging the evolution of the tumor, in the its relationships with the fascial, muscular, adipose and fibromucous soft tissues, when it exceeds the osseous barrier of the maxillofacial skeleton, enclosed therein the palatal plane.

[Role of NMR in staging and treatment of extensive myxoma of the upper jaw]. / Ruolo della RM ai fini della stadiazione e del trattamento del mixoma esteso del mascellare superiore.

The diagnostical possibilities of the RM in the study of the odontogenic myxoma at extensive diffusion in the upper maxilla are examined. Owing to its complexity and to close connections with the surrounding soft tissues, the midfacial region makes the conventional means of imaging difficult and inadequate. Really the tumor have very high local aggressivity. Where it is much bulky, invades diffusely the cavitary components, damages their walls with laminar structure, insinuates itself among the soft tissues of the jugal, pterygo-maxillary and infraorbital regions, taking up gorges where it slips the classical clinical an also the conventional instrumental diagnostics. The AA. have verified the utility of the MR imaging to the definition of the limits of the tumor, which makes the surgery more adequate to the necessities of an oncological treatment tending both to the radicality and to conservation of structures with high morphological and functional complexity.

Beta-2-microglobulin is a reliable tumor marker in chronic lymphocytic leukemia.

Serum beta 2-microglobulin (beta 2M) was measured in 22 patients with B chronic lymphocytic leukemia (CLL) and in 15 healthy age-matched control subjects. The patients were allocated in stages in accordance with the Rai and Binet systems. The beta 2M mean value in the CLL group was significantly higher than in the control group. There was a positive correlation between beta 2M and the clinical stage in both staging systems. The mean serum levels of beta 2M in stages A, B and C of Binet's system showed statistical differences while in stage A they did not differ from those found in the control group. No correlation was demonstrated between beta 2M and the peripheral lymphocyte concentration. A slight correlation was found between beta 2M and the degree of bone marrow lymphocyte infiltration, whereas a stronger relationship was observed when the type of infiltration (non-diffuse versus diffuse) was considered. Patients with bulky disease had mean beta 2M values much higher than the others.

Serum beta 2-microglobulin in patients with monoclonal gammopathies.

Beta-2-microglobulin concentrations were determined in serum samples from 45 patients with benign and malignant monoclonal gammopathies. In the group of patients suffering from multiple myeloma or Waldenström macroglobulinemia the mean beta 2-microglobulin level was significantly higher than in the group with monoclonal gammopathy of undetermined significance. Values above 3 mg/L were highly indicative of a neoplastic process and were observed in all the Waldenström patients and in greater than 90% of myeloma patients. No significant correlation was noticed between beta 2-microglobulin and monoclonal protein levels in any of the groups examined.