Biomedical subjects

Jonathan Nissanov

Publications and source records attributed to Jonathan Nissanov.

13 recordsLinked to original sources

PubMed2006

Altered cellular distribution and subcellular sorting of gamma-tubulin in diffuse astrocytic gliomas and human glioblastoma cell lines.

Centrosome amplification is a pivotal mechanism underlying tumorigenesis but its role in gliomas is underinvestigated. The present study specifically examines the expression and distribution of the centrosome-associated cytoskeletal protein gamma-tubulin in 56 primary diffuse astrocytic gliomas (grades II-IV) and in 4 human glioblastoma cell lines (U87MG, U118MG, U138MG, and T98G). Monoclonal anti-peptide antibodies recognizing epitopes in C-terminal or N-terminal domains of the gamma-tubulin molecule were used in immunohistochemical, immunofluorescence, and immunoblotting studies. In tumors in adults (n = 46), varying degrees of localization were detected in all tumor grades, but immunoreactivity was significantly increased in high-grade anaplastic astrocytomas and glioblastomas multiforme as compared to low-grade diffuse astrocytomas (p = 0.0001). A similar trend was noted in diffuse gliomas in children but the sample of cases was too small as to be statistically meaningful. Two overlapping patterns of ectopic cellular localization were identified in both primary tumors and glioblastoma cell lines: A punctate pattern, in which gamma-tubulin was partially co-distributed with pericentrin in the pericentriolar region, and a diffuse pattern, independent of pericentrin staining, denoting a soluble pool of gamma-tubulin. Cellular gamma-tubulin was detected in both soluble and insoluble (nocodazole-resistant) fractions of glioblastoma cells. Divergent localizations of gamma-tubulin and pericentrin suggest a differential distribution of these 2 centrosome-associated proteins in glioblastoma cell lines. Our results indicate that overexpression and ectopic cellular distribution of gamma-tubulin in astrocytic gliomas may be significant in the context of centrosome protein amplification and may be linked to tumor progression and anaplastic potential.

Antigens↗

PubMed2005

MRI diffusion coefficients in spinal cord correlate with axon morphometry.

Following spinal cord injury, diffusion MRI (DWI) has been shown to detect injury and functionally significant neuroprotection following treatment that otherwise would go undetected with conventional MRI. The underlying histologic correlates to directional apparent diffusion coefficients (ADC) obtained with DWI have not been determined, however, and we address this issue by directly correlating ADC values with corresponding axon morphometry in the normal rat cervical spinal cord. ADC values transverse (perpendicular) and longitudinal (parallel) to axons both correlate with axon counts, however each directional ADC reflects distinct histologic parameters. DWI may therefore be capable of providing specific histologic data regarding the integrity of white matter.

Animals↗

PubMed2004

Assessment of axonal fiber tract architecture in excised rat spinal cord by localized NMR q-space imaging: simulations and experimental studies.

NMR q-space imaging is a method designed to obtain information from porous materials where diffusion-diffraction phenomena were observed from which pore size was derived. Recently, the technique has been applied to the study of biological structures as well. Although diffusive diffraction has so far not been observed in multicellular systems, displacement profiles have been used with some success as a means to estimate structure size. However, there have been no quantitative correlations of the retrieved structure sizes with histology. Clearly, the complexity of tissue architecture poses significant challenges to the interpretation of q-space data. In this work, simulations were first performed on a two-compartment model to demonstrate the effects of interference of the diffraction patterns arising from intra and extra-axonal compartments and finite boundary permeability on q-space data. Second, q-space echo attenuation was simulated on the basis of histologic images of various rat spinal cord fiber tracts and the information obtained from the displacement profiles were compared with structural parameters computed from the histologic images. The results show that calculated mean displacements and kurtosis parallel mean axon size and axonal density. Finally, spatially localized q-space measurements were carried out at the locations where simulations had previously been performed, resulting in displacement data that support those obtained by simulation. The data suggest the NMR q-space approach has potential for nondestructive analysis of the axonal architecture in the mammalian spinal cord.

Animals↗

PubMed2004

Design and implementation of software for assembly and browsing of 3D brain atlases.

Visualization software for three dimensional digital brain atlases present many challenges in design and implementation. These challenges include the design of an effective human interface, management of large data sets, display speed when slicing the data set for viewing/browsing, and the display of delineated volumes of interest (VOI). We present a software design, implementation and storage architecture that addresses these issues, allowing the user to navigate through a reconstructed volume quickly and smoothly, with an easy-to-use human interface. The software (macostat, for use with Macintosh OS) allows the user to rapidly display slices of the digital atlas at any arbitrary slicing angle, complete with delineated VOIs. The VOIs can be assigned colors of the user's choosing. The entire atlas, or selected portions, may be resliced with slices stored as individual image files, complete with delineations. These delineations may be transferred to corresponding sections of experimental materials using our analysis program (brain). The software may be obtained from the laboratory's web site: http://www.neuroterrain.org

Brain↗

PubMed2004

Surface alignment of an elastic body using a multiresolution wavelet representation.

An algorithm for nonlinear registration of an elastic body is developed. Surfaces (outlines) of known anatomic structures are used to align all other (internal) points. The deformation field is represented with a multiresolution wavelet expansion and is modeled by the partial differential equations of linear elasticity. A hierarchical approach that reduces algorithm complexity is adopted. The performance of the algorithm is evaluated by two-dimensional alignment of sections from mouse brains located in the olfactory bulbs. The registration algorithm was guided by manually delineated contours of a subset of brain structures and validated based on another subset of brain structures. The wavelet alignment algorithm produced a twofold to fivefold improvement in accuracy over an affine (linear) alignment algorithm.

Algorithms↗

PubMed2003

Subicular dendritic arborization in Alzheimer's disease correlates with neurofibrillary tangle density.

Intracellular accumulation of PHFtau in Alzheimer's disease (AD) disrupts the neuronal cytoskeleton and other neuronal machinery and contributes to axonal and dendritic degeneration, and neuronal death. Furthermore, amyloid-beta (Abeta) has been reported to be toxic to neurons and neurites. While loss of presynaptic elements is an established feature of AD, the nature and extent of dendritic degeneration has been infrequently studied. We investigated MAP2-immunoreactive dendrites using a novel method of high-throughput quantification and also measured cortical thickness and the densities of NeuN-immunoreactive neurons, PHFtau neurofibrillary tangles (NFTs), and Abeta plaque burden in the subiculum in AD and elderly controls. Corrected for atrophy, the "dendritic arborization index" was significantly reduced by up to 66% in all three layers of the subiculum. Laminar thickness was reduced by an average 33% and there was a marked reduction in neuron density of approximately 50%. As expected, NFTs and Abeta plaques were significantly increased in AD. Dendritic arborization indices negatively correlated with NFT densities while no significant correlations were found with Abeta plaque densities. The pattern of dendritic loss in the subiculum and the correlations with NFT densities respectively suggest that deafferentation and intrinsic neurofibrillary degeneration both may contribute to dendritic loss in AD.

Aged↗

PubMed2003

Elastic 3-D alignment of rat brain histological images.

A three-dimensional wavelet-based algorithm for nonlinear registration of an elastic body model of the brain is developed. Surfaces of external and internal anatomic brain structures are used to guide alignment. The deformation field is represented with a multiresolution wavelet expansion and is modeled by the partial differential equations of linear elasticity. A progressive estimation of the registration parameters and the usage of an adaptive distance map reduce algorithm complexity, thereby providing computational flexibility that allows mapping of large, high resolution datasets. The performance of the algorithm was evaluated on rat brains. The wavelet-based registration method yielded a twofold improvement over affine registration.

Anatomy, Cross-Sectional↗

PubMed2003

Distribution of microtubule-associated protein MAP2-immunoreactive interstitial neurons in the parahippocampal white matter in subjects with schizophrenia.

OBJECTIVE: Evidence suggests that schizophrenia is a neurodevelopmental disorder that may involve abnormal connectivity between various cortical and subcortical brain areas. The parahippocampal gyrus is an area important for higher cognition in which a variety of cytoarchitectural, neuronal morphometric, and innervation abnormalities in schizophrenia have been reported. Previous studies have reported abnormal distributions of interstitial white matter neurons in prefrontal, parietal, and temporal neocortices, which suggests that schizophrenia may be related to prenatal disturbances in the cortical subplate, a transitory structure involved in the formation of connections in the developing cortex from which the interstitial white matter neurons derive. Abnormalities in the distribution of interstitial white matter neurons in the parahippocampal gyrus in schizophrenia may indicate an alteration in the migration of subplate neurons or in the pattern of programmed cell death that could lead to defective cortical circuitry and impaired cognition. METHOD: The authors used a monoclonal antibody against the microtubule-associated protein MAP2 to label interstitial white matter neurons in the anterior region of the parahippocampal gyrus from 41 individuals with schizophrenia and 15 comparison subjects. The distribution of MAP2-labeled neurons in relation to the gray matter/white matter boundary was determined by computer-assisted microscopy. RESULTS: The number of interstitial white matter neurons decreased with increasing white matter depth in both groups, but significantly more slowly in the schizophrenia group, with interstitial white matter neurons located deeper in white matter in schizophrenia subjects. CONCLUSIONS: These findings indicate there is an abnormality in the residua of the cortical subplate in the anterior region of the adult parahippocampal gyrus in schizophrenia subjects.

Adult↗

PubMed2003

Informatics center for mouse genomics: the dissection of complex traits of the nervous system.

In recent years, there has been an explosion in the number of tools and techniques available to researchers interested in exploring the genetic basis of all aspects of central nervous system (CNS) development and function. Here, we exploit a powerful new reductionist approach to explore the genetic basis of the very significant structural and molecular differences between the brains of different strains of mice, called either complex trait or quantitative trait loci (QTL) analysis. Our specific focus has been to provide universal access over the web to tools for the genetic dissection of complex traits of the CNS--tools that allow researchers to map genes that modulate phenotypes at a variety of levels ranging from the molecular all the way to the anatomy of the entire brain. Our website, The Mouse Brain Library (MBL; http://mbl.org) is comprised of four interrelated components that are designed to support this goal: The Brain Library, iScope, Neurocartographer, and WebQTL. The centerpiece of the MBL is an image database of histologically prepared museum-quality slides representing nearly 2000 mice from over 120 strains--a library suitable for stereologic analysis of regional volume. The iScope provides fast access to the entire slide collection using streaming video technology, enabling neuroscientists to acquire high-magnification images of any CNS region for any of the mice in the MBL. Neurocartographer provides automatic segmentation of images from the MBL by warping precisely delineated boundaries from a 3D atlas of the mouse brain. Finally, WebQTL provides statistical and graphical analysis of linkage between phenotypes and genotypes.

Analysis of Variance↗

PubMed2003

A guide to building image-centric databases.

There is a paucity of image-centric neuroinformatics infrastructure within the individual investigator's laboratory despite the obvious need for automation and integration of experimental results. Yet, solutions can often be readily built using off-the-shelf databases and associated tools. Doing so simplifies day-to-day research operation and increases throughput. Proper construction of in-house solutions may also expedite community-wide integration of private and public data repositories. Here we describe neuroinformatics approaches at different levels of functionality, required expertise, and size of image datasets. The simplest approach offers ease of image browsing and rudimentary searching. More sophisticated systems provide powerful search capabilities, a means of tracking analysis, and even automated serial processing pipelines. In this practicum, we provide guidance in selecting among the different options.

Animals↗

PubMed2002

Parahippocampal tau pathology in healthy aging, mild cognitive impairment, and early Alzheimer's disease.

Abnormally phosphorylated tau accumulates as neurofibrillary tangles and neuropil threads in older persons with and without Alzheimer's disease. The relationship between neurofibrillary tangles and neuropil threads and how they relate to cognitive function is unknown. This study investigated the relationship between phosphorylated tau lesions and cognitive function in 31 persons participating in the Religious Orders Study, a prospective, longitudinal clinicopathological study of aging and Alzheimer's disease. All subjects underwent detailed neuropsychological performance testing within a year of death and evidenced a spectrum of cognitive performance ranging from normal abilities to mild dementia. Measures of neurofibrillary tangle density and phosphorylated tau immunoreactive structures (predominantly neuropil threads) in the entorhinal and perirhinal cortices by quantitative image analysis were significantly correlated (r = 0.5). In multiple linear regression analyses controlling for age, sex, and education, parahippocampal neurofibrillary tangles and neuropil threads were significantly lower in persons without cognitive impairment compared to those with mild cognitive impairment and/or Alzheimer's disease. Further, neurofibrillary tangles were significantly correlated to measures of episodic memory but not other cognitive abilities; neuropil tangles were not significantly related to memory or other cognitive functions. These data indicate that phosphorylated tau pathology in the ventromedial temporal lobe develop prior to the onset of clinical dementia and their presence is associated with cognitive impairment, particularly impairment of episodic memory.

Aged↗

PubMed2002

Differential effects of prenatal cocaine exposure on selected subunit mRNAs of the GABA(A) receptor in rabbit anterior cingulate cortex.

We have previously shown that in the dopamine-rich anterior cingulate cortex (ACC), significant changes in gamma-aminobutyric acid (GABA) immunoreactivity occur in the offspring of rabbits given intravenous injections of cocaine (3 mg/kg) twice daily during pregnancy. In the present study, the effects of prenatal cocaine exposure on the developmental expression of specific GABA(A) receptor subunit mRNAs were investigated. We compared the distribution of the alpha1, beta2, and gamma2 subunit mRNAs in cocaine- and saline-treated offspring aged postnatal days 20 and 60 (P20, P60). At P20, prenatal cocaine exposure resulted in a significant increase in alpha1 subunit mRNA in ACC lamina III and a significant reduction in the amounts of the beta2 subunit mRNA in ACC lamina II. No differences between cocaine- and saline-treated controls were detected for gamma2 subunit mRNA levels in ACC. Although the pattern of labeling was altered in cocaine-exposed animals, Nissl sections revealed no differences in lamination, indicating that the changes in GABA(A) subunit mRNAs could not be attributed to abnormal cytoarchitectonics. In P60 brains, no significant differences were observed between cocaine- and saline-treated material, indicating that the observed differences were transient. Collectively, our data show that prenatal cocaine exposure elicits differential, lamina-specific changes in mRNA levels encoding selected subunits of the GABA(A) receptor. Since these changes occur during a critical period when fine tuning of synaptic organization is achieved by processes of selective elimination or stabilization of synapses, we suggest that specific subunit mRNAs of the GABA(A) receptor play a role in cortical development.

Amino Acid Sequence↗

PubMed2000

Three-dimensional imaging of the craniofacial complex.

Orthodontic treatment requires the rearrangement of craniofacial complex elements in three planes of space, but oddly the diagnosis is done with two-dimensional images. Here we report on a three-dimensional (3D) imaging system that employs the stereoimaging method of structured light to capture the facial image. The images can be subsequently integrated with 3D cephalometric tracings derived from lateral and PA films (www.clinorthodres.com/cor-c-070). The accuracy of the reconstruction obtained with this inexpensive system is about 400 µ.

Journal Article↗