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J Constantinidis

Publications and source records attributed to J Constantinidis.

At least 73 records · Page 4Linked to original sources
PubMed1991

Hypothesis regarding amyloid and zinc in the pathogenesis of Alzheimer disease: potential for preventive intervention.

In Alzheimer disease (AD) the "primum movens" is amyloid (AM) production within the cerebral cortex. Cerebral AM alone may be asymptomatic. Clinical symptoms (amnesia, instrumental disorders) appear when AM induces neighboring neuritic alterations: paired hellical filaments (PHF), and distant neuronal body lesions; neurofibrillary tangles (NFT), i.e. pathologic synthesis of abnormal proteins. The timing for these inductions should be equal to the survival after the onset of amnesia: a mean of 14 months for the induction of the peri-AM neuritic alterations and a mean of 52 months for the induction of the distant to AM NFT in the hippocampic neuronal bodies. We postulate that the AM induces this neuronal pathology by producing functional zinc deficiency. The hippocampal zinc decreases in AD. The mechanism of the AM-induced zinc deficiency may be the following: the AM is formed within the walls of capillaries (senile plaques), disturbs the blood-brain barrier (BBB) and toxic metals (i.e., iron, aluminum, mercury) may enter in the cerebral cortex, where they displace the zinc in some enzymes. NFT and neuronal dysfunction may be produced by deficiency of the following zinc enzymes: (a) those of DNA metabolism, inducing abnormal DNA in the neurons and therefore abnormal protein synthesis, PHF-NFT; (b) those of glutamate (GLU) dehydrogenase (which catabolizes GLU), resulting in an excitotoxic increase of GLU; (c) those of neuronal detoxification, superoxydedismutase, carbonic anhydrase, and lactate dehydrogenase leading to neuronal toxicity. During the window between AM formation and PHF-NFT production (14-52 months), a zinc complex crossing the BBB may be useful to prevent AM of producing PHF-NFT, and also to normalize neuronal detoxification.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1990

Vascular dementia. A clinicopathological study.

We have reviewed the clinical and pathological records of 40 aged patients who showed only vascular lesions on histological examination. They were followed up for 3.5 +/- 6.3 years before death, and in 28 cases the diagnosis of dementia was done during life. Demographic data, vascular and systemic illnesses, psychiatric neurological and neuropsychological disturbances, and pathological findings were compared between demented and non-demented patients. The number of strokes, several neurological and almost all neuropsychological disturbances, the volume of macroscopic cerebral infarct, especially in frontal, occipital and basal regions, the lacunar state and the white matter lesions, were significantly greater in demented patients. However most of them had less than 100 ml3 of brain infarct. The relative influence of each type of cerebral vascular lesion upon the dementia syndrome was determined by means of multivariate analysis. The volume of macroscopic cerebral infarct, the white matter lesion and the lacunar state showed quite similar contributions to mental deterioration.

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PubMed1990

Selective disconnection of specific visual association pathways in cases of Alzheimer's disease presenting with Balint's syndrome.

During a recent clinical and neuropathological evaluation of a large autopsy population of brains our attention was drawn to a subset of patients with Alzheimer's disease (AD) presenting with a major impairment of visuospatial skills referred to as Balint's syndrome. In this subset a shift in the distribution of certain pathological profiles had occurred in that the visual areas of the occipital and posterior parietal regions had an increased number of lesions, whereas the prefrontal cortex had fewer lesions than usually observed in AD. Previous quantitative analyses have shown that generally in AD, primary sensory cortical areas are less damaged than association areas of the frontal and temporal lobes, as demonstrated by the laminar and regional distribution of two neuropathological features of the disease, neurofibrillary tangles and neuritic (senile) plaques. The distribution of pathological lesions in the AD cases with Balint's syndrome revealed that specific visual association pathways were disrupted, which are normally spared in AD. These data suggest that in some cases of AD, the particular psychological and neurological symptomatology may be caused by the selective loss of specific corticocortical systems, as reflected in the differential distribution of the neuropathological markers of the disease.

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PubMed1990

Lowe syndrome: clinical and neuropathological studies of an adult case.

A 23-year-old male with clinically diagnosed Lowe syndrome had bilateral cataracts, glaucoma, pendulous nystagmus, severe mental and growth retardation, hypotonia, areflexia, joints hyperextensibility, proteinuria, aminoaciduria, and metabolic acidosis. There was also severe epileptic activity (Lennox-Gastaut syndrome). The neuropathological examination revealed a marked cerebellar atrophy and central chromatolysis in the cerebral cortex. These observations do not confirm the hypothesis of dysmyelination as formulated in previous studies. The reported case rather suggests the existence of a dynamic process starting as a still-undefined metabolic abnormality that, in turn, causes various and inconsistent lesions at the microscopic level.

Adult↗
PubMed1990

Substance P immunoreactivity in Alzheimer disease: a study in cases presenting symmetric or asymmetric cortical atrophy.

Substance P-like immunoreactivity was visualized by immunohistochemical methods in 20 postmortem brains: 6 senile, 4 presenile Alzheimer dementia (AD), 3 AD with interhemispheric asymmetric cortical atrophy, and 7 control cases. For all pathological cases, the SP-like immunoreactivity was significantly reduced in the neocortical areas and in the hippocampus. This contrasted with an enhanced SP-like immunoreactivity in the pallidum and the substantia nigra in AD brains and a more pronounced SP-like immunoreactivity in the more atrophic side in the asymmetrically atrophied brains.

Aged↗
PubMed1990

[Alzheimer's dementia and zinc].

In Alzheimer's dementia (AD) the Primum Movens is Amyloid (AM) production on precapillaries: Dyshoric Angiopathy, and capillaries: Senile Plaques (SP) producing Blood-Brain-Barrier (BBB) disturbances, entry in the brain of toxic metals which displace the zinc. Cerebral AM alone may be asymptomatic. Clinical symptoms (Amnesia, Instrumental Disorders) appear when AM induces Neighbouring neuritic alterations: Paired Hellical Filaments (PHF) and Distant neuronal body lesions: Neurofibrillary Tangles (NFT). The AM is coded by a locus on the chromosome 21 and a duplication of this locus should be the etiology of cerebral AM in AD. In AD cerebral zinc decreases particularly in the hippocampus. The zinc-enzyme Superoxyde-Dismutase (SOD) is coded by a locus also on the chromosome 21 near AM and the plasma level of SOD is high in AD. Zinc deposits observed in capillary AM-SP, result probably from the excess of plasmatic SOD. Other metals: Iron, aluminium are also observed in the AM-SP and their excess in the brain may be related to the decrease of zinc by metal to metal displacement. The decrease of functional zinc in the brain may interfere in the pathogenesis of PHF-NFT by metalotoxicity, neighbouring and distant to AM. Without AM, NFT are produced also by metalotoxicity and therefore brain zinc displacement. a) by lead: Encephalopathia saturnica b) by many metals: Guam Encephalopathy c) by aluminium d) by BBB disturbances leading probably to an abnormal entry of metals in the brain (Dementia Pugilistica, viral encephalitides). NFT may be produced by the deficiency of the following zinc enzymes: 1. Those of DNA metabolism, indicating abnormal DNA and therefore abnormal protein synthesis: PHF-NFT. 2. Those of neuronal detoxication: SOD, Carbonic Anhydrase, Lactate Dehydrogenase leading to neuronal toxicity particularly in the hippocampus normally rich in SOD. 3. Of Glutamate (GLU) Dehydrogenase (GDH) resulting in an excitotoxic increase of GLU. 4. Those of the metabolism of neurotransmitters (NT): neuropeptides, Histamine, GABA, Acetylcholine. Therapeutic proposition: a zinc complex crossing the BBB should be useful a) to prevent that the AM produces PHF-NFT by Neighbouring and Distant metalotoxicity and DNA changes; b) to regularise zinc-enzymes of neuronal detoxification and of neurotransmitters metabolisms. Preliminary trials by zinc Aspartate give yet promising results.

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PubMed1989

Balint's syndrome in Alzheimer's disease: specific disruption of the occipito-parietal visual pathway.

Previous quantitative neuropathologic analyses have shown that the association cortices of the temporal and frontal lobes are more damaged than the visual regions of the occipital lobe in Alzheimer's disease. In the present paper, we report on a subpopulation of Alzheimer's disease patients presenting a visual defect referred to as Balint's syndrome, and displaying a global caudal shift in pathology. Balint's syndrome is a defect in visuospatial skills, and the distribution of pathology suggests that the connections underlying this functional component of the visual system are devastated, whereas they are normally spared in Alzheimer's disease. These results suggest that multiple subtypes of Alzheimer's disease exist with differential distribution of pathology and corresponding neurologic symptomatology, and that neuritic plaque and neurofibrillary tangle formation involve the loss of specific corticocortical projections associated with specific functional deficits and identifiable neurologic syndromes.

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PubMed1989

An improved immunohistostaining procedure for peptides in human brain.

Floating sections from human brains immersed for more than forty years in formalin, or from brains freshly fixed for a short time are treated by KMnO4-Pal's modified solutions to suppress the endogenous peroxidase activity before using the peroxidase-antiperoxidase method (PAP), or to remove the autofluorescence of lipofuscin, which is very intense in brains from old patients, before using the immunofluorescence method. Following this, immersion of sections in NaOH and H2O2 allows for the demasking of antigenic sites. These treatments enhance the immunolabelling considerably, with results comparable to those obtained with freshly fixed tissues, and facilitate the discrimination between specifically and unspecifically stained structures.

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PubMed1989

Immunohistochemical colocalization of delta sleep-inducing peptide and luteinizing hormone-releasing hormone in rabbit brain neurons.

The anatomical distributions of luteinizing hormone-releasing hormone and delta sleep-inducing peptide immunoreactivity in the rabbit brain were studied by indirect immunofluorescence technique. The comparison of adjacent serial sections, one being immunolabeled with an antiserum to luteinizing hormone-releasing hormone, the other with an antiserum to delta sleep-inducing peptide, showed that the respective distribution patterns of immunoreactivity exhibited a remarkable overlap through the basal forebrain and hypothalamic regions. A sequential double-immunolabelling (elution-restaining method) clearly indicated that all the luteinizing hormone-releasing hormone-immunoreactive cell bodies displayed delta sleep-inducing peptide immunoreactivity. These cell bodies were sparse and mainly located throughout the septal-preoptico-suprachiasmatic region and the ventrolateral hypothalamus. The colocalization of luteinizing hormone-releasing hormone and delta sleep-inducing peptide immunoreactivity was also observed in many fibres supplying all these brain regions and terminal areas such as the organum vasculosum of the lamina terminalis, the subfornical organ, the median eminence and the pituitary stalk. These neuroanatomical findings are suggestive of interaction between delta sleep-inducing peptide and luteinizing hormone-releasing hormone in various brain areas including some circumventricular organs.

Brain↗
PubMed1989

Immunohistochemical distribution of delta sleep inducing peptide in the rabbit brain and hypophysis.

The distribution of delta sleep inducing peptide (DSIP) in the rabbit brain has been studied with immunohistochemical techniques. DSIP-like immunoreactivity was predominantly detected in the basal forebrain, hypothalamus and hypophysis. Even in colchicine-pretreated animals, immunolabeled cell bodies were relatively few. They were mostly scattered through the ventrolateral septum, the diagonal band of Broca and preoptic areas. Clusters of positive cell bodies were also found in the arcuate nucleus and adjacent lateral hypothalamic areas. Large populations of varicose fibers and terminal-like structures were observed in the juxtaventricular zone of the ventrolateral septum, in the preoptic areas and lamina terminalis especially around the preoptic recess of the third ventricle and more caudally, in the ventromedial nucleus of the hypothalamus. Dense networks of immunolabeled fibers were visualized in the median eminence and pituitary stalk where many fibers could be seen in close apposition to the capillaries. Many DSIP-immunoreactive fibers were observed in the subfornical organ. Other extra-hypothalamic regions displaying a low-to-moderate density of immunoreactive fibers were the indusium griseum, the hippocampus, the fimbria of the fornix, the subcommissural organ, the medial habenula and, occasionally, the medial periaqueductal gray. Most cells of the pars intermedia and a few cells of the pars distalis of the anterior pituitary were DSIP-immunoreactive. Taken together these results in the rabbit brain emphasize the predominant localization of DSIP-like immunoreactivity in areas related to the hypothalamic neurosecretory systems.

Animals↗
PubMed1988

Distribution and colocalization of delta sleep inducing peptide (DSIP) with corticotropin-like intermediate lobe peptide (CLIP) in the human hypophysis.

DSIP and CLIP [ACTH(18-39)] immunoreactive (IR) neurons and fibers were examined in the human hypophysis and pituitary stalk using immunmohistofluorescence and peroxidase-antiperoxidase methods. Double-stained and adjacent stained sections demonstrate that DSIP is colocalized in about 75% of CLIP-IR-like cells in the anterior pituitary and in residual intermediate lobe cells. Only few CLIP-IR-like fibers are observed in the posterior lobe. On the contrary, a high density of DSIP-IR fibers is visualized in the stalk. It is suggested that DSIP acts as a sleep promoting factor (one of many other actions) and that CLIP increases the paradoxical sleep, so that these two peptides could play a role in the regulating system of the sleep-waking cycle.

Adrenocorticotropic Hormone↗
PubMed1988

[Distribution of the delta sleep-inducing peptide in the brain of rabbits: study by immunofluorescence].

Using the indirect immunofluorescence method, the distribution of the Delta Sleep Inducing Peptide (DSIP)-containing neurons was studied in the rabbit brain. DSIP antisera were raised in rat by multiple injections of synthetic DSIP conjugated to thyroglobulin. Some DSIP immunoreactive cell bodies were detected in the diagonal band of Broca and anterior part of the hypothalamus. Large populations of immunofluorescent fibers and terminals were visualized mainly through the organum vasculosum of the lamina terminalis, the preoptic areas, the subfornical organ, the thalamus, the ventromedial hypothalamus and infundibulum. Further, most of the cells of the intermediate lobe of the hypophysis displayed DSIP-immunoreactivity. The predominant localization of DSIP-immunoreactive fibers and terminals in certain circumventricular organs suggests that DSIP could play a specific role in the neurohumoral regulation.

Animals↗
PubMed1987

An immunohistochemical study of pro-somatostatin-derived peptides in the human brain.

The distribution of pro-somatostatin-derived-peptide-positive profiles was examined by indirect immunohistofluorescence in nine post-mortem human brains (age 58-73 years). Three specific antisera were used for this study which recognize, respectively, somatostatin-28, somatostatin-28 (1-12) and somatostatin (1-14). Pro-somatostatin-derived-peptide-positive immunoreactive profiles were observed throughout the neuraxis. Cell bodies were found within archeo-, paleo- and neocortical areas, the subcortical white matter, in the nucleus accumbens, caudate nucleus and putamen, as well as in the hypothalamus, the reticular thalamic nucleus and the reticular formation of the brainstem. Fibers and terminals were seen in the same areas as well as in various thalamic nuclei, in the brainstem and spinal cord. Pro-somatostatin-derived-peptide-positive fibre tracts include the bed nucleus of the stria terminalis, the diagonal band of Broca, the stria medullaris, the inter-thalamic adhesion, the posterior commissure and the spinothalamic tract. Furthermore, differences between human and animal brains were noted and some somatostatin systems reported which may be implicated in certain human neuropathological states.

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PubMed1986

Substance P neuronal cell bodies in the human brain: complete mapping by immunohistofluorescence.

The localization of substance P-immunoreactive (SP-IR) cells was studied in 5 postmortem brains from aged human subjects using technical improvements combined with the indirect immunofluorescence method. The presence of various forms of SP-IR cells was observed in paleocortical and neocortical areas as well as in the basal ganglia, the brainstem and the spinal cord. The distribution of these SP-IR cell bodies was transposed onto our previous mapping of SP-IR fibers and terminals. The morphological differences between SP-containing cell bodies or areas of human and rat central nervous systems and the SP-changes in various states of human pathology are shortly discussed.

Aged↗
PubMed1986

Neuropeptides in Alzheimer's disease: a review and morphological results.

The anatomic distribution of classical neurotransmitters, i.e. NA, DA, 5HT, ACH and GABA in the post-mortem autopsied brain of Alzheimer's disease (AD) has been reviewed. In addition, the results and reviews reported in this paper give evidence for the change of a large number of neuropeptides in AD on the basis of immunohistochemical criteria. Among numerous peptidergic systems, abnormalities in SP, SS, NT and VIP have been observed. Therefore, no changes in the concentrations of CCK and TRH were reported. In this study, using immunohistochemical methods for SS changes in post-mortem brain material of three cases of AD and two controls, the following changes were observed: An important reduction of the SS-positive cell bodies and fibres in the cortex, the hippocampus, parahippocampic cortex, and neocortex, particularly in the parietal and frontal areas, as well as a reduction of SS cell bodies and fibres in the sub-cortical white matter. An amorphous SS-positive material in or close to the corona of a number of senile plaques. An important decrease of SS fibres and cell bodies in the lateral septi nuclei. An increase of the number and immunoreactive intensity of SS-positive fibres in the substantia innominata. In animal studies, an interaction between SS- and ACH turnover in the substantia innominata is reported. The GABA decrease as well as the SS deficit in the cortex area and sub-cortical white matter may lead to the interaction between SS and other neurotransmitters in AD.

Aged↗
PubMed1986

Differential effects of acute and chronic administration of haloperidol on substance P and enkephalins in diverse rat brain areas.

Rats received 10 mg/kg/day of haloperidol during up to 9.5 weeks. Substance P, Leu- and Met-enkephalins, were studied in brain using immunohistochemical methods. Haloperidol modified the peptides immunoreactivity in most brain areas. The time necessary to observe the effects of haloperidol on the peptides varied individually, depending on the peptide and the brain area. Moreover, inversions of these effects were often observed, generally occurring between in 5th and 7th day of drug administration. Substance P was increased after haloperidol in the hypophysis, a finding hereto not described. This descriptive study identified none of these three peptides as a single and specific target for dopaminergic receptor blockade. Methodological issues in evaluating the effects of neuroleptics on brain peptides are discussed.

Amygdala↗
PubMed1986

Heredity and dementia.

This is a study on the heredity of dementia in the ageing of the Alzheimer, vascular and Pick types. The incidence of the same type of dementia among parents, siblings and offspring of the probands is higher than that in the general population. Alzheimer dementia (AD): Presenile familial AD follows a dominant mode of inheritance: many pedigrees with numerous cases in successive generations, and higher incidence of AD among the parents than among the siblings. Senile familial AD seems to follow a recessive mode: pedigree with 2 or more cases usually in only one generation, and higher incidence of AD among the siblings than among the parents. Yet presenile and senile AD cases are sometimes found in the same family. The heredity factors involved in AD may be partially common for the presenile and senile forms. Vascular dementia (VD): In families of VD probands, the incidence of VD and brain strokes is higher in parents than in siblings, and familial vascular cases are more numerous in two generations than in one. A familial diathesis seems to exist for VD, following a dominant mode of inheritance. Pick dementia (PD): The form of brain lobar atrophy of PD with gliosis, argyrophilic inclusions (AI) and/or ballooned neurons (BN), when it is familial, follows a dominant mode of inheritance: many pedigrees with numerous cases in successive generations. The form of PD without AI or BN, but with only gliosis, when it is familial, seems to follow a recessive mode: some pedigrees with 2 or more cases in only one generation.

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