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Biomedical subjects

J Constantinidis

Publications and source records attributed to J Constantinidis.

At least 19 recordsLinked to original sources
PubMed1992

The adult and a new late adult forms of neuronal ceroid lipofuscinosis.

Three cases of the late adult form of neuronal ceroid lipofuscinosis (NCL) are reported. Two of these are siblings with a late clinical onset at ages 26 and 44 years. The third case, sporadic, has the oldest reported age for the onset of NCL, at 63 years and may be regarded as the first example of the "presenile" form of NCL. The clinical, morphological, histochemical, ultrastructural and genetic features of these three cases are discussed. The literature of the clinicopathological NCL cases with an onset at age of 25 and older is reviewed. The clinical and morphological differences between the late adult form and the presenile form of NCL as well as the difficulties in making the diagnosis are discussed.

Adult↗
PubMed1991

The dominant form of the pigmentary orthochromatic leukodystrophy.

The present report documents a family with three cases in two successive generations of pigmentary orthochromatic leukodystrophy (POLD). The clinical features of these cases and histochemical and ultrastructural investigations of two of the brains from successive generations are discussed. A review of the familial cases of POLD reported in the literature is also presented. Transmission of these cases was by a dominant inheritance. Onset of the clinical symptoms occurred at 42 to 54 years of age; duration of the disease was from 2-11 years, and death occurred at 45 to 57 years of age. Clinical manifestations of all three cases were severe headaches; bilateral pyramidal, pseudobulbar, cerebellar, and frontal release signs; gait disturbances; euphoria, or apathy; epileptic seizures; and dementia. The neuropathological pattern consists of slight cerebral atrophy, brownish discoloration of the cerebral white matter with demyelination and severe gliosis, sparing the sub-cortical U fibers; presence in the macrophages of lipid pigment granules that are sudanophilic, non metachromatic, and PAS and iron positive. The electron microscopic pattern of the lipid pigment in the macrophages is that of ceroid: electron-dense, membrane-bound intracytoplasmic lysosomes with curvilinear and/or fingerprint profiles.

Adult↗
PubMed1991

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↗
PubMed1991

The hypothesis of zinc deficiency in the pathogenesis of neurofibrillary tangles.

Neurofibrillary tangles (NFT) in human encephalopathies of various etiologies may result from a common pathogenetic mechanism: a functional zinc decrease leading to a deficiency of the DNA metabolizing zinc-enzymes, giving rise to abnormal neuronal DNA and synthesis of pathological proteins: NFT. In encephalopathia Saturnica, zinc decreases in the hippocampus displaced by lead; in Guam's encephalopathy, calcium deficiency permits the entry in the brain of toxic metals that may displace zinc; in Boxer's dementia and some viral encephalitides, blood-brain-barrier (BBB) is altered and abnormal metals may reach the brain; in Down's syndrome and Alzheimer's disease precapillary and capillary amyloidosis disturbs the BBB, metals (iron and aluminium) are encrusted in the amyloid and their brain level increases, whereas zinc decreases especially in the hippocampus. A deficiency of the zinc enzymes of neuronal detoxication, of glutamate catabolism and of some neurotransmitters metabolisms may also contribute in the neuronal dysfunction of these encephalopathies. A non-toxic zinc compound crossing the BBB may be useful for the treatment of these encephalopathies and especially for Alzheimer's disease.

Alzheimer Disease↗
PubMed1991

Immunohistochemical distribution of corticotropin-like intermediate lobe peptide (CLIP) immunoreactivity in the human brain.

The immunocytochemical distribution of CLIP (corticotropin-like intermediate lobe peptide) or ACTH(18-39), a small biologically active peptide, was examined in the human brain, using a monoclonal antibody against this peptide. Groups of CLIP-immunoreactive cell bodies, small to medium size and bipolar or triangular in shape, were found in the basal hypothalamus extending from the retrochiasmatic region to the premammillary nuclei area. Immunoreactive fibers with varicosities, terminals and "pipe shape" structures, were distributed within the hypothalamus, limbic structures, the brainstem and spinal cord nuclei, forming a particularly rich network in the hypothalamus, the preoptic area, the septal region, the amygdala and the upper brainstem periaqueductal gray matter. The above neuroanatomical observations confirm and extend previous findings in animals, strengthening even more the possibility that this peptide may be involved in numerous behavioral, autonomic and physiological functions such as regulation of sleep-waking cycle, pain control and respiratory and cardiovascular regulation.

Adrenocorticotropic Hormone↗
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)

Aged↗
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.

Aged↗
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.

Aged↗
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.

Aged↗
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.

Aged↗
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.

Aged↗
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↗