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M R Issidorides

Publications and source records attributed to M R Issidorides.

15 recordsLinked to original sources

Lewy bodies in parkinsonism share components with intraneuronal protein bodies of normal brains.

Histochemical characteristics of the Lewy bodies, in catecholamine neurons of 10 Parkinsonian patients, were compared to those of the spherical protein bodies, the basic protein-rich markers of catecholamine neurons in man. Special methods for proteins and lipids showed that the core of the Lewy bodies, in the neurons of the locus coeruleus and the substantia nigra, contains basic proteins and lipids normally found in the protein bodies. Acid fuchsin and the lipid-soluble fluorescent dye rhodamine B stained the entire core of the Lewy body in the parkinsonian brains and the entire sphere of the protein body in the control brains. Bromsulfophthalein, another acidic dye, which selectively binds to the enzyme gluthathione-S-transferase, had affinity only for a ring-like lamina at the outer layer of the core of the Lewy body and for the outer rim of the protein body. These results demonstrate that Lewy bodies and protein bodies contain similar macromolecular components, that is lipids and two different types of proteins, which also show similar stratification in the two structures. On the other hand, the presence in several neurons of the Parkinsonian patients, of aggregates representing transitional forms between protein bodies and Lewy bodies, indicates that abnormalities of protein bodies precede, and are somehow linked to Lewy body production.

Brain Stem

Tyrosine hydroxylase-immunoreactive neurons in paraventricular and supraoptic nuclei of the human brain demonstrated by a method adapted to prolonged formalin fixation.

We studied the distribution of tyrosine hydroxylase (TH) immunoreactive (IR) neurons in the adult human hypothalamus using a modification of the peroxidase-antiperoxidase immunohistochemical method which can be applied on autopsy brain material following prolonged formalin fixation. We observed that most of the TH-IR perikarya localized within the paraventricular (PVN) and supraoptic (SON) nuclei were large and showed homogeneous staining over the entire cytoplasm and processes. These results show that in the human brain a large population of neurons within the neurosecretory nuclei are able to synthesize a catecholamine.

Adult

Similarities between neuronal Lewy bodies in parkinsonism and hepatic Mallory bodies in alcoholism.

The aim of the present study was to identify components of the Lewy body, which is a characteristic neuronal lesion in idiopathic Parkinsonism, using histochemical methods that selectively stain the Mallory body, a characteristic lesion of the hepatocyte in alcoholism. Our observation that Lewy bodies stain with phosphotungstic acid hematoxylin, the dye originally used for demonstrating alcoholic hyaline (Mallory bodies), promoted this study. The material consisted of formalin-fixed, brain stem tissue from Parkinsonian subjects, and of similarly preserved liver tissues from alcoholic individuals. The methods selected were Roque's chromotrope 2R-aniline blue, and Liisberg's rhodamine B, which stains Mallory bodies due to its affinity for sites of tissue keratinization. Hence, skin was also included in this study as control tissue. Our results showed that Lewy bodies in the brain, Mallory bodies in the liver and stratum corneum in the skin have identical staining properties with the dyes used, indicating the presence of histochemically similar components. Taking into account the reactions of these dyes with model substances, we suggest that the similar components shared by Lewy bodies and Mallory bodies are arginine-rich proteins and lipids associated with keratinization. Similar findings in both, a toxin-induced lesion of the liver, and a spontaneous lesion of the brain may offer clues for understanding the latter's mode of formation.

Alcoholism

Localization of phospholipids in human catecholamine neurons with Baker's acid haematein.

Protein bodies in catecholamine neurons of the normal human brain contain arginine-rich proteins similar to those present in the core of Lewy bodies in Parkinsonian brains. Lewy bodies are known also to contain phospholipids in their core, demonstrable with Baker's acid haematein. We used Baker's procedure on catecholamine neurons of normal brains to test whether the protein bodies also contain phospholipids. Postmortem tissues of three control individuals were used in this study. Locus coeruleus and substantia nigra were dissected out from the fresh brains and two sets of blocks were made from each area. One set was fixed in formol-calcium for the preservation of lipids, the second was fixed in Bouin's solution and treated with hot pyridine for the extraction of lipids. Finally, both sets were subjected to the same chroming and staining procedure according to Baker. In catecholamine neurons the protein bodies were stained with acid haematein, indicating the presence of phospholipids. Since this staining resisted pyridine extraction we conclude that these phospholipids are firmly bound to the basic proteins. Thus, protein bodies in healthy catecholamine neurons give the same positive reaction for phospholipids as that reported for the core of Lewy bodies in damaged neurons in Parkinsonism.

Aged

Fine structure of neuronal spherical arginine-rich bodies of substantia nigra and locus coeruleus in the human brain.

Neuronal spherical bodies, rich in arginine, of catecholamine neurons in man display staining reactions of mitotic chromosomes and myelin basic protein. They show a unique fine structure and density in the EM after phosphotungstic acid hematoxylin block-staining. With an electron-lucent core, a dense rim and a limiting double membrane they stand out and are differentiated from all other neuronal inclusions, especially melanin. Protein bodies were found inside mitochondria, where they apparently originate as small globules in the matrix. They later enlarge into spheres by obliterating the cristae, but retaining the outer membranes of the parent mitochondrion. The arginine-rich basic protein of the spherical bodies, it is argued, may be involved in the modulation of excitability of the catecholamine neurons in man.

Adult

Short and long-term effects of neuroleptics in relation to their cellular mechanism of action.

1. Some mechanisms of action of neuroleptics at cellular level are reviewed, mainly the effects on synaptic transmission and the effects on chromatin. 2. As regard to the effects at synaptic level, a brief review is presented on the available evidence in support of the currently prevailing dopamine hypothesis. 3. Studies carried out on the mechanisms and sites of action of neuroleptics on chromatin show that: a. Behavioral changes caused by psychotropic drugs in experimental animals are associated with chromatin alterations and induced macromolecular syntheses. b. Parkinsonian and possibly drug-induced extrapyramidal symptoms are associated with aberrations in protein synthesis. c. Destabilization under "stress" of the heterochromatin in schizophrenics seems to be due to histone modifications and is partly prevented by neuroleptic treatment.

Antipsychotic Agents

Protein-rich cytoplasmic bodies of substantia nigra and locus ceruleus. A comparative study in parkinsonian and normal brain.

A histochemical study of substantia nigra and locus ceruleus from postmortem brains showed the presence of small spherical cytoplasmic bodies stained selectively by the anionic phosphotungstic acid-hematoxylin (PTAH) stain at a pH of 2.5. The metachromatic reaction to PTAH indicates that these protein bodies contain a protein rich in free basic amino groups. The protein bodies are localized within the neuronal perikaryon as well as in their dendritic processes. These bodies abundantly present in the substantia nigra and locus ceruleus of normal brains were noticeably reduced or absent in parkinsonian brains. Lewy bodies when present show that their core gives the same metachromatic reaction to PTAH as do the protein bodies. These findings suggest that an abnormality of protein synthesis in the substantia nigra and locus ceruleus of parkinsonian brains may be related to the absence of protein bodies and the formation of Lewy bodies and play a role in pathogenesis of the parkinsonian state.

Aged

Histochemical changes in the blood cells of schizophrenic patients under pimozide treatment.

Chromatin structure and nucleohistone pattern were investigated histochemically in the neutrophils of 11 schizophrenics and 16 healthy controls. Compared to controls, all schizophrenic parents prior to medication showed a distinctly different histochemical pattern consisting of increased concentration and abnormal distribution of nucleohistones. This pattern has been attributed to an increase of arginine-rich histones in schizophrenics. Pimozide administration exerted a normalizing effect on the nucleohistone distribution pattern. These findings further support our view that genomic expression abnormalities may be related to schizophrenic illness.

Adolescent