Use of short tandem repeats loci to study the genetic structure of several populations from Zulia State, Venezuela.

Genetic relationships between populations can be studied by comparing genotypic and allelic similarities. This investigation aims to demonstrate that selected autosomal microsatellite markers could be used to study the genetic structures of different populations living in northwest Venezuela, in Zulia State. Seven autosomal systems (CSF1PO, TPOX, TH01, vWA, D7S820, D13S317, and D5S818) were tested by PCR in a multiplex format on 688 different chromosomes from unrelated individuals living in Maracaibo, "Isla de Toas," and "San José de Heras," and from two Amerindian populations from the "Sierra de Perijá," Barí' and Yukpa. Allele frequencies, Hardy-Weinberg equilibria, genetic distances, phylogenetic trees, and ethnic admixtures were estimated. The study shows the existence of a clear genetic difference among these populations in accordance with their historic evolution. The populations of Maracaibo and "Isla de Toas" showed a triracial origin, with a large European contribution, followed by an Amerindian component and a small African component. The indigenous groups, Barí' and Yukpa, showed exclusively an Amerindian component, and "San José de Heras" showed only an African component. These results indicate that microsatellite markers are useful for molecular anthropology in a regional and worldwide context and provide important genetic information about contemporary populations of Venezuela.     

Ovarian transplantation between monozygotic twins discordant for premature ovarian failure

Monozygotic 24-year-old twins presented with discordant ovarian function. One had had premature ovarian failure at the age of 14 years, whereas her sister had normal ovaries and three naturally conceived children. After unsuccessful egg-donation therapy, the sterile twin received a transplant of ovarian cortical tissue from her sister by means of a minilaparotomy. Within three months after transplantation, the recipient's cycles resumed and serum gonadotropin levels fell to the normal range. During the second cycle, she conceived, and her pregnancy progressed uneventfully. At 38 weeks' gestation, she delivered a healthy-appearing female infant.     

EEG evidence for mirror neuron dysfunction in autism spectrum disorders

Autism spectrum disorders (ASD) are largely characterized by deficits in imitation, pragmatic language, theory of mind, and empathy. Previous research has suggested that a dysfunctional mirror neuron system may explain the pathology observed in ASD. Because EEG oscillations in the mu frequency (8-13 Hz) over sensorimotor cortex are thought to reflect mirror neuron activity, one method for testing the integrity of this system is to measure mu responsiveness to actual and observed movement. It has been established that mu power is reduced (mu suppression) in typically developing individuals both when they perform actions and when they observe others performing actions, reflecting an observation/execution system which may play a critical role in the ability to understand and imitate others' behaviors. This study investigated whether individuals with ASD show a dysfunction in this system, given their behavioral impairments in understanding and responding appropriately to others' behaviors. Mu wave suppression was measured in ten high-functioning individuals with ASD and ten age- and gender-matched control subjects while watching videos of (1) a moving hand, (2) a bouncing ball, and (3) visual noise, or (4) moving their own hand. Control subjects showed significant mu suppression to both self and observed hand movement. The ASD group showed significant mu suppression to self-performed hand movements but not to observed hand movements. These results support the hypothesis of a dysfunctional mirror neuron system in high-functioning individuals with ASD.     

Interstitial quinacrine activates a distinctive immune response effective for tumor immunotherapy

BACKGROUND: Interstitial immunotherapy consists of the local injection of immune cells or molecules with cytotoxic properties to destroy neoplastic cells. Intratumor injection of quinacrine induces intense recruitment of activated immune cells that leads to necrosis and elimination of experimental malignant neoplasms; this effect seems to be mediated by immune molecules. METHODS: We measured the tissue content of activated immune cells and various cytokines at different times during the first 8 days after a single interstitial injection of 150 mg quinacrine in rats. RESULTS: A large cell infiltrate by macrophages, CD4(+), CD8(+), and natural killer cells was evident a few hours after quinacrine injection. In comparison with controls, tissue contents of 4 cytokines had a marked increase: macrophage chemoattractant protein-1 increased 115-fold; interleukin-6, 9-fold; RANTES (regulated on activation, normal T cell expressed and secreted), 13-fold; and macrophage inflammatory protein-2, 10-fold. Other cytokines, like interleukins 1beta, 2, 4, 10, interferon-gamma, tumor necrosis factor-alpha, complement 3, and C reactive protein did not increase significantly, indicating that the endogenous local response to quinacrine follows a singular pathway of immune activation. CONCLUSIONS: Interstitial quinacrine is a strong activator of innate immunity and is not mediated by the usual mechanisms of immune recognition. It constitutes an original approach for regional immunotherapy of neoplasms that is not mediated solely by induction of local, cytotoxic chemical necrosis.     

Cerebrospinal fluid concentrations of idebenone in Friedreich ataxia patients

We studied plasma and cerebrospinal fluid (CSF) concentrations of idebenone in five Friedreich ataxia patients on treatment with this antioxidant, and plasma and CSF ubiquinone-10 (Q (10)) concentrations in 15 controls. CSF idebenone concentrations were below the detection limit in 3 Friedreich ataxia patients and no association could be demonstrated between plasma and CSF idebenone values. Q (10) CSF concentrations (median: 2.25 nmol/L) were approximately 300 times lower than those of plasma (median: 0.77 micro mol/L). No correlation was observed between plasma and CSF Q (10) concentrations. A significantly positive correlation was observed between CSF total protein values (range 8.1 - 107.5 mg/dL; median: 29.5) and CSF Q (10) concentrations (Spearman test: r = 0.664; p = 0.01). Our findings suggest that less idebenone is distributed to the brain than to other tissues, although CSF does not appear to be an appropriate material for treatment monitoring of idebenone and other quinoid compounds.