DYNLT1 gene expression is downregulated in whole blood of patients at different Huntington's disease stages.

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG nucleotide expansion, which encodes the amino acid glutamine, in the huntingtin gene. HD is characterized by motor, cognitive, and psychiatric dysfunctions. In a previous study, we showed by qPCR that some genes altered in an HD mouse model were also altered in blood of HD patients. These alterations were mainly with respect to the dynein family. Therefore, this study aimed to investigate whether dynein light chain Tctex type 1 (DYNLT1) is altered in HD patients and if there is a correlation between DYNLT1 gene expression changes and disease progression. We assessed the DYNLT1 gene expression in the blood of 19 HD patients and 20 healthy age-matched controls. Also, in 6 of these patients, we analyzed the DYNLT1 expression at two time points, 3 years apart. The DYNLT1 gene expression in the whole blood of HD patients was significantly downregulated and this difference was widened in later stages. These data suggest that DYNLT1 could emerge as a peripheral prognostic indicator in HD and, also, might be a target for potential intervention in the future.

Molecular detection and isolation of human T-cell lymphotropic virus type I (HTLV-I) from patients with HAM/TSP in São Paulo, Brazil.

BACKGROUND: Infection with HTLV-I is etiologically linked with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However some patients with chronic progressive paraparesis resembling HAM/TSP have been shown to be infected with HTLV-II. OBJECTIVE: To clarify the role of each of these human retroviruses in the etiology of HAM/TSP in São Paulo, Brazil. STUDY DESIGN: A detailed serological and molecular analysis of HTLV-I/II infection was performed in a cohort of 19 patients with HAM/TSP attending a neurological clinic. RESULTS: Plasma samples analyzed for anti-HTLV-I/II antibodies using a Western blot assay, comprising HTLV-I (rgp46I)- and HTLV-II (rgp46II)-specific recombinant env epitopes, demonstrated reactivity to rgp46I and hence were typed as seropositive for HTLV-I. Presence of HTLV genomic sequences in peripheral blood mononuclear cells (PBMC) was sought after by PCR using consensus primers SK 110 and SK 111 for the pol region of HTLV proviral DNA followed by hybridization with type-specific probes--SK 112 (HTLV-I) and SK 188 (HTLV-II). Southern blots from all individuals hybridized with SK 112 but not with SK 188, further confirming HTLV-I infection. Cocultivation of PBMC from eight of these patients with activated lymphocytes from normal individuals resulted in active viral production, detected as presence of soluble p24gag antigen in culture supernatants. Investigation of risk factors for HTLV-I infection in these individuals revealed that five out of 19 patients studied (26.3%) had received blood transfusions previous to disease onset.

Human T cell lymphotropic virus type-1-associated myelopathy/tropical spastic paraparesis in Sao Paulo, Brazil: association with blood transfusion.

Human T cell lymphotropic virus type-1 (HTLV-1) associated myelopathy/tropical spastic paraparesis (HAM/TSP) has been epidemiologically linked to prior blood transfusion. The prevalence of transfusion as a risk factor for infection varies among endemic areas. Here we report the relative frequency of reported history of blood transfusion among 52 patients evaluated in Sao Paulo, Brazil. A patient reported history of blood transfusion prior to the onset of symptoms, found in 15 (28.8%) of the patients, was the most important risk factor identified in this group of patients when compared with a history of sexually transmitted diseases, homo/bisexuality, sexual promiscuity (three or more sexual partners a year), and intravenous drug use. The mean time between reported transfusions and the onset of symptoms was longer than previously reported. There was no trend toward a more severe evolution to motor inability among the HAM/TSP patients with a history of previous transfusion.

Human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis in São Paulo, Brazil.

We conducted a prospective clinical and epidemiologic evaluation of 45 cases of human T lymphotropic virus type I (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in São Paulo, Brazil. All enrolled patients had progressive chronic myelopathy and high titers of HTLV-I and HTLV-II antibodies, as determined by enzyme immunoassay and western blot. In 24 cases, the polymerase chain reaction (PCR) was performed so that HTLV-I could be distinguished from HLTV-II. The clinical and epidemiologic features of the patients from our study were similar to those of patients with HAM/TSP from other areas of endemicity for HTLV-I except that more patients in our study had received a blood transfusion prior to their illness. Despite the presence of HTLV-II virus in Brazil, all patients whose serum was tested by PCR were found to be infected with the HTLV-I virus.