Derivative chromosome 11 in a child resulting from a complex rearrangement involving chromosomes 3, 6 and 11 in father: Significance of parental karyotyping

The presence of derivative chromosome in a child with phenotypic features necessitates the need of parental karyotyping to ascertain the exact amount of loss or gain of the genetic material. The aim of this study was to emphasize the importance of parental karyotyping. Cytogenetic evaluation of the proband and his father were carried out at Laboratory. Cytogenetic analysis was performed on phytohemagglutinin stimulated cultures. The derivative chromosome 11 in proband was ascertained to have additional material from chromosome 6p arising from complex chromosomal rearrangement in the father. Karyotyping is the basic, cost-effective preliminary investigation in a child with mental subnormality or congenital anomalies.     

Somatic alterations in mitochondrial DNA produce changes in cell growth and metabolism supporting a tumorigenic phenotype

There have been many reports of mitochondrial DNA (mtDNA) mutations associated with human malignancies. We have observed allelic instability in UV-induced cutaneous tumors at the mt-Tr locus encoding the mitochondrial tRNA for arginine. We examined the effects of somatic alterations at this locus by modeling the change in a uniform nuclear background by generating cybrids harboring allelic variation at mt-Tr. We utilized the naturally occurring mtDNA variation at mt-Tr within the BALB/cJ (BALB) and C57BL/6J (B6) strains of Mus musculus to transfer their mitochondria into a mouse ρ⁰ cell line that lacked its own mtDNA. The BALB haplotype containing the mt-Tr 9821insA allele produced significant changes in cellular respiration (resulting in lowered ATP production), but increased rates of cellular proliferation in cybrid cells. Furthermore, the mtDNA genotype associated with UV-induced tumors endowed the cybrid cells with a phenotype of resistance to UV-induced apoptosis and enhanced migration and invasion capabilities. These studies support a role for mtDNA changes in cancer.     

Induction of cytochrome P450 1A1 expression in captive river otters fed Prudhoe Bay crude oil: evaluation by immunohistochemistry and quantitative RT-PCR

Numerous studies have explored the relationships between exposure to a variety of environmental contaminants, such as polycyclic aromatic hydrocarbons, and induction of cytochrome P450 1A (CYP1A) in different vertebrates. Few controlled studies, however, simulated chronic long-term exposure with repeated non-lethal sampling of the same individuals, which should better represent repeated exposure incidents in animals inhabiting polluted areas. In this study, we investigated the effects of chronic exposure to crude oil on levels of CYP1A1 in endothelial cells of skin biopsies and peripheral mononuclear blood cells in captive river otters (Lontracanadensis) using repeated sampling of the same individuals. We hypothesized that ingestion of oil would result in an increase in levels of CYP1A1 in both targets, and predicted that the relationship between prolonged exposure and expression of CYP1A1 would reach a plateau indicative of continuous detoxification of hydrocarbons. Fifteen wild-caught male otters were acclimated to captivity, and then fed diets containing no oil (control) or diets containing weathered crude oil at 5 mg day^-1 kg^-1 body weight (low-dose) and 50 mg day^-1 kg^-1 body weight (high-dose), at the Alaska Sealife Center in Seward, Alaska, USA. Expression of CYP1A1 was assessed with immunohistochemical analysis of CYP1A1 protein in skin biopsies and by quantitative RT-PCR analysis of CYP1A1 mRNA in mononuclear blood cells. Both assays revealed a decrease between capture and the transfer to captivity, indicating that the enclosure at the Alaska Sealife Center, and the food we offered to the otters were free of potential inducers of CYP1A1. During the exposure period, increases in CYP1A1 expression were registered by both techniques, followed by a decline in CYP1A1 after oil administration ended. Levels of endothelial CYP1A1 in the high-dose group were comparable to those recorded for wild river otters in PWS in 1996 and 1997. Levels of CPY1A1 mRNA in mononuclear blood cells, however, were well below levels recorded for river otters in Prince William Sound, and no correlation was detected between values obtained from the two methods. Thus, our results from this longitudinal study with repeated sampling of the same individuals provide support for the use of cytochrome P450 1A1 as a biomarker for hydrocarbon exposure. Nonetheless, our results also suggest that the induction process of CYP1A1 may be complicated and interacting with other processes in vivo. Such interactions may obscure our ability to describe specific, quantitative, predictable, dose-response relationships between exposure to hydrocarbons and induction of CYP1A1, which are required of reliable biomarkers. Evaluations of such interactions based on theoretical physiological models in live-animals merit further investigation.     

Computation of spiking activity for a stochastic spatial neuron model: effects of spatial distribution of input on bimodality and CV of the ISI distribution

We obtain computational results for a new extended spatial neuron model in which the neuronal electrical depolarization from resting level satisfies a cable partial differential equation and the synaptic input current is also a function of space and time, obeying a first order linear partial differential equation driven by a two-parameter random process. The model is first described explicitly with the inclusion of all biophysical parameters. Simplified equations are obtained with dimensionless space and time variables. A standard parameter set is described, based mainly on values appropriate for cortical pyramidal cells. When the noise is small and the mean voltage crosses threshold, a formula is derived for the expected time to spike. A simulation algorithm, involving one-dimensional random processes is given and used to obtain moments and distributions of the interspike interval (ISI). The parameters used are those for a near balanced state and there is great sensitivity of the firing rate around the balance point. This sensitivity may be related to genetically induced pathological brain properties (Rett's syndrome). The simulation procedure is employed to find the ISI distribution for some simple patterns of synaptic input with various relative strengths for excitation and inhibition. With excitation only, the ISI distribution is unimodal of exponential type and with a large coefficient of variation. As inhibition near the soma grows, two striking effects emerge. The ISI distribution shifts first to bimodal and then to unimodal with an approximately Gaussian shape with a concentration at large intervals. At the same time the coefficient of variation of the ISI drops dramatically to less than 1/5 of its value without inhibition.     

Dandy-Walker malformations in a case of partial trisomy 9p (p12.1→pter) due to maternal translocation t(9;12)(p12.1;p13.3)

We describe a five-year-old proband presented with Dandy-Walker malformations, right microopthalmia, hamstring contractures, undescended testis with absence of testis in right scrotum in addition to typical trisomy 9p clinical features. Routine cytogenetic studies with GTG - banding showed 46,XY,der(12)t(9;12) (p12;q13.3),mat karyotype (trisomy 9p). Chromosomal analysis of the father was normal and phenotypically normal mother had 46,XX,t(9;12)(p12;q13) karyotype. Fluorescence in situ hybridization analysis with single copy probes bA5OIA2 (9p11.2), bA562M8 (12p12.1) and centromere probes (9) showed break point at 9p12.1 region. The gene dosage effect of Chromosome 9p along with environmental factors might be associated with Dandy- Walker malformations in the patient.