Search PubMed⌕ Search

Biomedical subjects

M A Pappolla

Publications and source records attributed to M A Pappolla.

51 records · Page 3Linked to original sources
PubMed1989

The "normal" brain. "Abnormal" ubiquitinilated deposits highlight an age-related protein change.

Known morphologic changes that characterize "normal" brain senescence are insufficient to explain the widespread, age-related decline of psychomotor functions. We report that the heavily ubiquitinilated deposits can be consistently detected by immunohistochemistry in the normal senescent brain. Immunostaining of hippocampal sections from aged brains with an anti-ubiquitin antibody was unrelated to neurofibrillary degeneration or senile plaque formation. In contrast, ubiquitin deposits were not detectable in brain sections from neurologically and neuropathologically normal young individuals who had died of nonneurological causes. This finding shows an unrecognized protein change in the normal aged brain.

Adult↗
PubMed1989

Image analysis microspectroscopy of senile plaque capillary amyloid in Alzheimer's disease. A preliminary study.

The relationship between cerebral amyloid and the microvasculature in senile plaques was studied with image analysis microspectroscopy. This imaging technique permitted topographic quantification of amyloid concentration within microscopic subregions of single senile plaques. The highest concentration of amyloid was measured at the walls of intraplaque capillaries. Spectroscopic images revealed a decreasing gradient of amyloid concentration with increasing distance from intraplaque capillaries. The concentration of amyloid in nonplaque capillaries was lower than that measured in capillaries within well-developed amyloid plaques. These findings support the premise that plaque amyloid deposition starts at the level of the capillary.

Alzheimer Disease↗
PubMed1988

Colloid (hyaline) inclusion bodies in the central nervous system: their presence in the substantia nigra is diagnostic of Parkinson's disease.

Intracytoplasmic "colloid" inclusions have been described within neurons of several discrete central nervous system nuclei in a variety of entities. Although they lack specificity for any particular disease, they are believed to represent one of the morphologic changes of neuronal aging. Because premature aging of the substantia nigra has been one of the claimed mechanisms occurring in Parkinson's disease, the prevalence of colloid inclusions was studied within the substantia nigra in 15 patients with Parkinson's disease, 15 age-matched controls, 50 "normal" individuals, 10 patients with dementia of Alzheimer's type, and two patients with amyotrophic lateral sclerosis. Colloid bodies were found in the substantia nigra of all patients with Parkinson's disease and were virtually absent in the other populations. Histochemical and ultrastructural analyses showed that colloid bodies differ from early and mature Lewy bodies. They may represent the "pale" inclusions rarely mentioned in the literature and often mistaken for early Lewy bodies. "Colloid" bodies in the substantia nigra are diagnostic of Parkinson's disease. These findings support the theory of "premature" aging of the substantia nigra in this disease.

Adult↗
PubMed1988

Computerized image-analysis microspectroscopy of tissue sections.

A simple technique using monochromatic light was applied to computer-assisted image analysis of tissue sections. The method consists of the determination of the spectral characteristics of different elements of interest and selective monochromatic illumination of a microscopic field followed by image analysis. Results show a dramatic increase in resolution and contrast. By means of an image subtraction technique at two wavelengths, it was possible to achieve specific optical isolation and quantification of image components.

Animals↗
PubMed1987

Serum protein leakage in aged human brain and inhibition of ligand binding at alpha 2-adrenergic and cholinergic binding sites.

Serum proteins are known to extravasate into the brain parenchyma in senile and presenile dementia (Glenner: Hum. Pathol. 16:433-435, 1986; Wisniewski and Kozlowski: Ann. NY Acad. Sci. 396:119-129, 1982). We have recently demonstrated that human serum Cohn fraction IV (alpha-globulin enriched) inhibits ligand binding at putative dopamine and serotonin2 receptors labeled by [3H]spiroperidol in human brain (Andorn, Pappolla, Fox, Klemens, and Martello: Proc. Natl. Acad. Sci. USA 83:4572-4575, 1986). We now demonstrate that serum proteins can be identified in the neuropil and in neuronal cell bodies in normal aged brain, that alpha-globulin-enriched fractions inhibit ligand binding at alpha 2-adrenergic and muscarinic binding sites in human brain as well, and that serum proteins can be identified within neuronal cytoplasm and axons.

Adult↗
PubMed1986

Neuronal aging.

Explore the source record for details and available documents.

Aging↗
PubMed1986

Human serum Cohn fraction IV (alpha-globulin [correction of globin] enriched) inhibits ligand binding at neurotransmitter receptors in human brain.

Human serum proteins are found in significant density in the neuropil in brains of demented individuals. The functional significance of these abnormally distributed proteins has been unknown. We now report that alpha-globulin-enriched fractions of human serum decrease the specific binding of [3H]spiroperidol at its binding sites in postmortem human frontal cortex and caudate. The substances in this serum fraction apparently exert their effect by a direct action on the binding site. Since [3H]spiroperidol labels serotoninergic and dopaminergic among other neurotransmitter receptors, these results suggest that components of human serum inhibit the binding of ligands at neurotransmitter receptors.

Animals↗
PubMed1986

Lewy bodies of Parkinson's disease. Immune electron microscopic demonstration of neurofilament antigens in constituent filaments.

Recently it has been shown by light microscopic immunochemistry that Lewy bodies (LBs) react with antibodies raised against neurofilament proteins (NFPs). Because of the ubiquity of the NFPs within neurons, the heterogeneous makeup of the inclusions, and the varying patterns of immunolabeling, we undertook to determine whether the labeled elements are indeed constituent filaments. Employing a preembedding technique, we investigated sections of the same LBs by light and electron immunochemistry. Decoration of the filaments was obtained with a monoclonal anti-NFP antibody. Whereas cores of mature LBs were unreactive by light microscopy, these same cores yielded a positive reaction at the ultrastructural level. Early LBs were intensely labeled in both the core and periphery. These results demonstrate that the filamentous profiles that form the LBs are antigenically identical to neurofilaments and suggest a posttranslational modification of the filaments as they "age" within the inclusion.

Antigens↗
PubMed1984

PAS reaction stains phagocytosed atypical mycobacteria in paraffin sections.

In 4% formaldehyde-fixed, paraffin-embedded tissues, PAS negativity for mycobacteria in the literature has been axiomatic. However, recent observations of disseminated human mycobacteriosis have shown that intracellular (phagocytosed) organisms stained strongly positive with the routine PAS technique. This staining was abolished by a sequential hydrolytic procedure, which suggests that the carbohydrate residues of the mycobacterial peptidoglycolipids are responsible for the reaction. This staining characteristic in tissue sections is of diagnostic importance, since few bacteria of medical relevance are concomitantly acid-fast and PAS positive. The nature of this affinity is for the aqueous form of basic fuchsin.

Histocytochemistry↗
PubMedDate not supplied

The heat shock/oxidative stress connection. Relevance to Alzheimer disease.

Involvement of free-radical oxidations in the aging process has been a topic of interest since Harman's original contribution. Because of the close association between aging and Alzheimer disease (AD) and the qualitative similarity in the neuropathology of both conditions, it has been proposed by many investigators that oxidative stress may be important in Ad. If such modality of injury was indeed involved, one should expect to find markers of oxidation and heat shock (since free radicals are key mediators of heat-shock induction) in brains of patients with AD. In fact, several studies documented abnormal expression of antioxidant enzymes and heat-shock proteins (HSP) along with other markers of oxidation in AD brains. We showed that abnormally expressed antioxidant enzymes are topographically associated with senile plaques and neurofibrillary tangles, and that the activity of these enzymes is (contrary to what one would expect) markedly reduced. These findings have recently been confirmed by other investigators. Despite a large amount of evidence that suggests an association between oxidative stress and the pathogenesis of AD, it is not yet known whether oxidative stress is a cause or consequence of the disorder. Future research efforts regarding the oxidative stress hypothesis of AD should include attempts at generating AD pathology by oxidative means in laboratory animals, determining the role and integrity of the heat-shock response in AD, as well as that of various antioxidant systems, growth factors, and hormones with antioxidant and neuroprotective properties.

Alzheimer Disease↗