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Biomedical subjects

P Averback

Publications and source records attributed to P Averback.

At least 19 recordsLinked to original sources
PubMed1998

Biochemical assay for AD7C-NTP in urine as an Alzheimer's disease marker.

A reliable and specific immunoassay has been developed to detect and measure AD7C-NTP, a biochemical marker for Alzheimer's disease, in urine. The urine samples are first processed by centrifugation and ultrafiltration to fractionate and concentrate AD7C-NTP. The urinaryAD7C-NTP has the same molecular weight asAD7C-NTP in brain and cerebrospinal fluid by size exclusion chromatography. It has also retained the binding properties to the monoclonal and polyclonal antibodies developed against recombinantly produced AD7C-NTP. This assay is an enzyme linked sandwich immunoassay (ELSIA) using 96 well microtiter plates. The plate surface is coated with a monoclonal antibody (N314) which has a high affinity and specificity for AD7C-NTP, capturing it effectively from the samples. The detection was achieved using a polyclonal antibody (ADRI). The utility of the assay has been demonstrated using urine specimens from Alzheimer's disease (AD) patients and non-Alzheimer's controls. UrinaryAD7C-NTP in the AD group (2.5 ng/mL, n=66) was significantly higher than the non-AD group (0.8 ng/mL, n=134). Using 1.5 ng/mL as cut off, in this patient population, specificity and sensitivity of urinary AD7C-NTP were comparable to CSFAD7C-NTP.

Alzheimer Disease↗
PubMed1998

Spherons as a drug target in Alzheimer's disease.

Spherons are unique brain entities that are causally linked to the amyloid plaques (SPs [senile plaques]) of Alzheimer's disease (AD). SPs are the quantitatively major tissue abnormality of AD. Spherons increase in size (but not in number) gradually throughout life until they reach a size range where they burst and form SPs. Drugs targeted at attenuating the process of spheron transformation into SPs are a logical approach to AD therapy. There are 20 criteria of validity for an SP causal entity that are satisfied by spherons-and no more than a few of these 20 criteria are satisfied by any other known hypothesis. These criteria of validity are reviewed, in addition to common difficulties in understanding spheron theory and a number of common-sense considerations in AD therapeutic research. Spheron-based drug therapy in AD potentially can retard the process of spheron bursting and subsequent plaque formation by: 1) blocking the formation of SPs; 2) reducing the size of SPs; 3) delaying spheron breakdown; and 4) retarding spheron growth. Isolated spherons from human brain are intact human drug targets and can be used as human in vitro or in vivo screening targets. The paramount importance of spherons as a target for drug therapy in AD is emphasized by considering that regardless of any other type of real or potential therapy, there still already exists in every middle-aged adult a full population of spherons in the brain, filled with more than enough amyloid to bring about full-blown AD.

Journal Article↗
PubMed1997

Characterization of the AD7C-NTP cDNA expression in Alzheimer's disease and measurement of a 41-kD protein in cerebrospinal fluid.

We have isolated a novel Alu sequence-containing cDNA, designated AD7c-NTP, that is expressed in neurons, and overexpressed in brains with Alzheimer's disease (AD). The 1,442-nucleotide AD7c-NTP cDNA encodes an approximately 41-kD protein. Expression of AD7c-NTP was confirmed by nucleic acid sequencing of reverse transcriptase PCR products isolated from brain. AD7c-NTP cDNA probes hybridized with 1. 4 kB mRNA transcripts by Northern blot analysis, and monoclonal antibodies generated with the recombinant protein were immunoreactive with approximately 41-45-kD and approximately 18-21-kD molecules by Western blot analysis. In situ hybridization and immunostaining studies localized AD7c-NTP gene expression in neurons. Using a quantitative enzyme-linked sandwich immunoassay (Ghanbari, K., I. Beheshti, and H. Ghanbari, manuscript submitted for publication) constructed with antibodies to the recombinant protein, AD7c-NTP levels were measured under code in 323 clinical and postmortem cerebrospinal fluid (CSF) samples from AD, age-matched control, Parkinson's disease, and neurological disease control patients. The molecular mass of the AD7c-NTP detected in CSF was approximately 41 kD. In postmortem CSF, the mean concentration of AD7c-NTP in cases of definite AD (9.2+/-8.2 ng/ml) was higher than in the aged control group (1.6+/-0.9; P < 0.0001). In CSF samples from individuals with early possible or probable AD, the mean concentration of AD7c-NTP (4.6+/-3.4) was also elevated relative to the levels in CSF from age-matched (1.2+/-0.7) and neurological disease (1.0+/-0.9) controls, and ambulatory patients with Parkinson's disease (1.8+/-1.1) (all P < 0.001). CSF levels of AD7c-NTP were correlated with Blessed dementia scale scores (r = 0. 66; P = 0.0001) rather than age (r = -0.06; P > 0.1). In vitro studies demonstrated that overexpression of AD7c-NTP in transfected neuronal cells promotes neuritic sprouting and cell death, the two principal neuroanatomical lesions correlated with dementia in AD. The results suggest that abnormal AD7c-NTP expression is associated with AD neurodegeneration, and during the early stages of disease, CSF levels correlate with the severity of dementia.

Aged↗
PubMed1986

A new type of inclusion body in human spinal cord.

New pericapillary inclusion bodies were found in 17 cases of sporadic amyotrophic lateral sclerosis (ALS). The inclusion bodies consisted of paracrystalline arrays with 5-7 nm electron-dense subunits, were discernible with the light microscope and had the staining properties of protein. They were surrounded by capillary-wall basement membrane and were often associated with peripheral fibrils. Astrocytic fibrillary bodies, without paracrystalline material, were also found. The ultrastructure and staining of the fibrils suggests that the paracrystalline material is within pericapillary astrocytes. The nature and significance of the inclusion bodies are unknown, but their presence suggests that there may be pericapillary abnormalities in the spinal cord in ALS and possibly other disorders.

Amyotrophic Lateral Sclerosis↗
PubMed1983

Dense microspheres in normal human brain.

The normal postinfancy human brain contains microscopical structure referred to as the dense microsphere (DMS). The function and significance of the DMS are presently unknown. The light microscopical, topographical, histochemical and ultrastructural aspects of the DMS are described, based on the study of 106 normal and 50 diseased brains. The frequency of DMS in random samples of temporal neocortex was compared in 96 normals, 10 cases of Alzheimer's disease, 10 cases of Parkinson's disease, 10 cases of schizophrenia, and 20 cases of other nervous diseases. No significant differences were found between diagnostic categories but there was statistically significant reduction in frequency with ageing. These findings are discussed in relation to the possible significance of the DMS.

Adolescent↗
PubMed1982

Reovirus and the pathogenesis of some forms of chronic mental illness.

Focal microdegenerative changes in the nuclei of the ansa peduncularis and the septum pellucidum are present in most cases of presenile and senile dementia, Parkinson's disease and schizophrenia (7,8). These nuclei interconnect and have extensive synaptic connections with the areas of the brain recently shown to contain non-cytopathic reovirus antigen and reovirus-like particles in the normal adult (9,10). The reovirus-involved regions closely approximate the overall pattern of the topography of brain atrophy in Alzheimer's dementia and Parkinson's disease. Mechanisms are suggested whereby mutant defective reovirus present in all adult human brains is responsible or related to the major forms of chronic mental illness including the common types of dementia and schizophrenia.

Brain↗
PubMed1982

Immunofluorescent staining of dense microspheres in human brain.

The dense microsphere (DMS) is a newly delineated, nonautofluorescent gray-matter structure of constant morphology and unknown significance, which is found principally in cerebral cortex, hypothalamus, amygdala, and hippocampus in the normal and diseased adult human brain. It resembles a nonperikaryal cytoplasmic inclusion body, and is acquired after birth. Is density (frequency) is constant in persons younger than 70 years, and significantly decreases in the brains of senile persons. Indirect immunohistochemical studies using guinea pig, goose, and rabbit antireovirus antisera demonstrated positive fluorescence of the DMS, which indicates the presence of an DMS, which indicates the presence of an anti-DMS antibody that may be an antireovirus antibody.

Adult↗
PubMed1981

Lesions of the nucleus ansae peduncularis in neuropsychiatric disease.

The nucleus of the ansa peduncularis in the substantia innominata frequently contains degenerating neurons in patients with Huntington's disease, Alzheimer's disease, schizophrenia, and possibly other neurological and neuropsychiatric conditions. A large number of the degenerating cells are found only exceptionally in neurologically normal patients who are without mental symptoms, and the significance of the lesion may be related to quantitative factors, analogous to granulovacuolar degeneration of the hippocampus. The cells show massive distention with solvent-extractable lipid-pigment vacuolar droplet material that imparts a distinctive light and electron microscopic appearance.

Adolescent↗
PubMed1981

Structural lesions of the brain in young schizophrenics.

Swollen, degenerate and fragmented neurons of the septal nuclei and the nucleus ansae peduncularis are commonly found in chronic neurological diseases such as Alzheimer's or Huntington's disease, and rarely found in neurologically normal control patients without mental symptoms. These pathological lipid and pigment laden neurons appear to be a common feature of schizophrenia and have been consistently found in a series of unselected young (mean age 38) schizophrenics.

Adult↗
PubMed1981

Parasynaptic corpora amylacea in the striatum.

Typical corpora amylacea (CA) were found within synaptic processes in the striatum from subjects with Huntington's and Alzheimer's diseases. The CA compressed and distorted the synaptic vesicles. It is possible that this unusual synaptic "lesion" is more common than is realized and that a significant number of CA are synapse-related before synaptic elements are destroyed.

Adult↗
PubMed1981

Unusual particles in motor neuron disease.

Regions of neurofilamentous degeneration adjacent to and contiguous with filamentous enlargements in areas of neuronal degeneration in the spinal cord were found in six cases of sporadic motor neuron disease (MND). Unusual particles, 28 nm in diameter, were found within the lesions. The lesion might possibly be significant in relation to neuronal degeneration in MND.

Aged↗
PubMed1980

A study of the rate of cell depletion in solid tissue.

The rate of disappearance of microneurons from the granular layer of the cerebellum of the rat during post-mortem autolysis was measured by image analysis of serial sections of perfusion preparations at various intervals during the first 24 hr after death. The cell population shows a logarithmic decrease during this period. The possible relation to cell death in disease and practical applications of this finding as a gauge of post-mortem interval are discussed.

Animals↗