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Biomedical subjects

R M Torack

Publications and source records attributed to R M Torack.

At least 19 recordsLinked to original sources
PubMed1996

Neuronal argyrophilia and phosphorylated neurofilament accumulation secondary to deafferentation.

This work tests the hypothesis that deafferentation caused by experimental brain lesions leads to the appearance of perikaryal argyrophilia and the accumulation of phosphorylated cytoskeletal proteins which are potential precursors for neurofibrillary tangle formation. Destructive lesions of the ventral tegmental area, the septum of the medial forebrain and the entorhinal cortex, when combined with systemic administration of a D-1 dopamine receptor antagonist, produced transsynaptic changes in neurons of the hippocampal formation in the midbrain. Abnormally phosphorylated neurofilament protein was demonstrated immunohistochemically in the cytoplasm of mesencephalic pyramidal neurons, particularly in the red nucleus. These same neurons also developed cytoplasmic argyrophilia in Bielschowsky histologic preparations. Although distinct neurofibrillary tangles were not produced with this paradigm, both the protein immunoreactivity and argyrophilia were arranged in cytoplasmic linear arrays. The structural changes induced in this experimental model may be an important preliminary stage for neurofibrillary tangle formation.

Animals↗
PubMed1995

Denervation induced abnormal phosphorylation in hippocampal neurons.

This study demonstrates that combined dopaminergic and cholinergic denervation of the hippocampus results in the appearance of morphologically altered, Tau reactive, apical dendrites of granule cells in the rat dentate gyrus. The denervated granule cells and their apical dendrites also display immunoreactivity to a mitogen-activated protein kinase, ERK-1, and also evidence of abnormal phosphorylation of these dendrites as revealed by SMI-31 immunoreactivity. Dopaminergic denervation alone also causes mitogen activated protein kinase reactivity without the Tau-reactive apical dendrities. These results suggest an analogy to synaptophysin loss and the appearance of dendritic threads described in Alzheimer's disease (AD), as an early stage in the formation of neurofibrillary tangles (NFT). This is the first animal model in which abnormal phosphorylation of Tau has been shown to be produced experimentally in vivo.

Alzheimer Disease↗
PubMed1994

Immunoreactive changes resulting from dopaminergic denervation of the dentate gyrus of the rat hippocampal formation.

The hypothesis that dopaminergic denervation is a factor in the development of hippocampal neurofibrillary tangles was tested in the rat with bilateral stereotaxic 6-hydroxydopamine (6-OHDA) lesions of the ventral tegmental area (VTA). This led to the postsynaptic appearance of cytoplasmic immunoreactivity to ubiquitin in neurons of the dentate gyrus. An additional postsynaptic morphologic abnormality was seen when the animals were pretreated with the D1 dopaminergic antagonist SCH 23390 and the VTA lesions were combined with septal lesions affecting cholinergic and GABAergic neurons projecting to the dentate gyrus. These changes consisted of a loss of dendritic microtubule associated protein (MAP-2) and tau immunoreactivity and a prominence of remaining dendrites in the molecular layer of the dentate gyrus. Additional investigation will be needed to determine if these transynaptic changes in dentate neurons, resulting from denervation, represent a precursor stage to neurofibrillary tangle development.

Animals↗
PubMed1992

Hippocampal pyramidal cell response to 6-hydroxydopamine lesions of the rat ventral tegmental area.

The occurrence of neurofibrillary tangles (NFT) in the perforant pathway in association with dopaminergic cell loss in the ventral tegmental area (VTA) in human mesolimbic dementia, raises the possibility that denervation is a cause of NFT formation. This was tested in the rat by lesioning dopaminergic neurons which project to the hippocampus from the ventral tegmental area by means of stereotaxic injections of 6-hydroxydopamine. This resulted in the appearance of immunoreactivity to the paired helical filament protein plus an increase of tau and MAP-2 proteins in pyramidal neurons of CA-1 and CA-2. These neuronal responses to dopaminergic denervation are consistent with a precursor stage to NFT development.

Animals↗
PubMed1992

Tyrosine hydroxylase-like (TH) immunoreactivity in Parkinson's disease and Alzheimer's disease.

We used tyrosine hydroxylase immunoreactivity (TH) to mark dopaminergic fibers in cerebral tissue from adult persons with Parkinson's disease (PD) or Alzheimer's disease (AD). In the PD cases we found a loss of dopaminergic neurons in the ventral tegmental area (VTA), severely reduced TH fibers in dopaminergic terminal fields (particularly in the hippocampal perforant pathway) and neurofibrillary tangles (NFT), that occurred only in the perforant pathway. In contrast, AD cases were characterized by a lack of significant neuron loss in the VTA and by mild loss of TH fibers. A decreased dopaminergic innervation of the perforant pathway in cases of PD appears to be associated with the occurrence of NFT in these structures.

Alzheimer Disease↗
PubMed1992

Arrested maturation of cerebral neurons, axons and myelin: a new familial syndrome of newborns.

A new lethal familial syndrome of unknown etiology is described in two male siblings who died in the newborn period. Both had corneal edema and were hypotonic, requiring assisted ventilation at birth. Neuropathological findings included an immature appearance of neocortical neurons, with cortical architecture similar to that normally seen in an infant of 5 months gestational age. Axons and myelin were absent in the cerebral and cerebellar white matter, and also in descending white matter tracts of brainstem and spinal cord. Subacute inflammation was seen in the anterior horns of the spinal cord in both cases, although there was no evidence of inflammation elsewhere in the nervous system. Electron microscopy of endothelial cells from brain, spinal cord and a number of other tissues of the second sibling showed tubuloreticular inclusions (TRIs). There are no known previous reports of similar neuropathology. Future recognition of this condition will be important for genetic counselling.

Abnormalities, Multiple↗
PubMed1992

Analysis of the prion protein gene in thalamic dementia.

Thalamic degenerations or dementias are poorly understood conditions. The familial forms are (1) selective thalamic degenerations and (2) thalamic degenerations associated with multiple system atrophy. Selective thalamic degenerations share clinical and pathologic features with fatal familial insomnia, an autosomal dominant disease linked to a mutation at codon 178 of the prion protein (PrP) gene that causes the substitution of asparagine for aspartic acid (178Asn mutation). We amplified the carboxyl terminal coding region of the PrP gene from subjects with selective thalamic dementia or thalamic dementia associated with multiple system atrophy. Three of the four kindreds with selective thalamic dementia and none of the three kindreds with thalamic dementia associated with multiple system atrophy had the PrP 178Asn mutation. Thus, analysis of the PrP gene may be useful in diagnosing the subtypes of thalamic dementia. Moreover, since selective thalamic dementia with the PrP 178Asn mutation and fatal familial insomnia share clinical and histopathologic features, we propose that they are the same disease.

Base Sequence↗
PubMed1990

Tyrosine hydroxylase-like (TH) immunoreactivity in human mesolimbic system.

A practical methodology has been described for the use of human postmortem brain tissue in both tyrosine hydroxylase and dopamine beta-hydroxylase immunohistochemistry in which in situ perfusion with paraformaldehyde is followed by immersion fixation in Bouin's fixative. These studies indicate that TH-like immunoreactive fibers and terminals are not uniformly distributed in the human hippocampal complex. A distinctive lesser innervation is noted for the structures that compose the perforant pathway and may be important for the predilection of these areas for pathological change particularly as occurs in Alzheimer's disease.

Adult↗
PubMed1989

Vascular glycosaminoglycans in periventricular leukoencephalopathy.

Three cases of adult dementia with periventricular leukoencephalopathy demonstrated staining with alcian blue dye (alcianophilia) in thickened cerebral arteries and arterioles of the abnormal white matter. The property of alcianophilia identifies glycosaminoglycans (GAGs); retention of alcian blue staining at high MgCl2 concentrations (0.7 M) in these cases indicates that the GAGs are highly sulfated and are likely to represent heparan sulfate. Arteriosclerotic risk factors (including hypertension) were absent in all cases, suggesting that GAG deposition occurred as part of a separate cerebral vasculopathic process. These findings suggest that cerebral white matter changes associated with dementia do not always represent Binswanger's disease.

Adult↗
PubMed1988

The association of ventral tegmental area histopathology with adult dementia.

Six cases of adult dementia with mesolimbic pathology are reported. The core clinical syndrome consists of parkinsonism, progressive dementia, and behavioral disturbances (generally depression). The histopathologic findings uniformly include a loss of pigmented neurons in the ventral tegmental area plus neurofibrillary tangles and/or cell loss in the entorhinal cortex and pyramidal cell layer of the hippocampus (perforant pathway). Neuronal depletion in the ventral tegmental area frequently is associated with similar cell loss in the adjacent substantia nigra and in the locus ceruleus. The development of neurofibrillary tangles in the perforant pathway occurs in the absence of senile plaques and is possibly related to diminished dopaminergic input.

Aged↗
PubMed1988

Validation of clinical diagnostic criteria for Alzheimer's disease.

Clinical investigations of Alzheimer's disease (AD) have been limited by diagnostic inaccuracy. We employed explicit clinical inclusion and exclusion criteria to identify subjects with senile dementia of the Alzheimer type (SDAT). In a consecutive series of 26 postmortem examinations from this sample, AD was histologically verified in all subjects and was the primary dementing illness. Seventeen of the 26 SDAT subjects had been diagnosed when only mildly demented. Two control subjects were examined neuropathologically; AD was absent in both. We conclude that research clinical diagnostic criteria for SDAT, even in its mild stage, are valid.

Aged↗
PubMed1986

T-lymphocyte function in Alzheimer's disease.

T-lymphocyte function in Alzheimer's disease (AS) was evaluated by means of delayed type hypersensitivity (DTH) and mitogen responsiveness using concanavalin A (Con A) and BCG vaccine as stimulators. DTH and the response to Con A was significantly lower in AD than in normal aging. The Con A response included one group in which the thymidine uptake was lower than the minimum normal response while another group was within the normal range. This subset could account for the inconsistency in previous reports of T-cell function in AD.

Alzheimer Disease↗
PubMed1983

The pathogenetic significance of congophilic angiopathy.

Congophilic angiopathy has been separated into two forms. A primary vasculopathy is described in which amyloid deposition is the initial morphological brain change and is of pathogenetic importance in the development of dementia or brain hemorrhage. Another form occurs in Alzheimer's disease and is incidental to the brain damage resulting from senile plaques.

Amyloidosis↗
PubMed1982

Historical aspects of normal and abnormal brain fluids. II. Hydrocephalus.

A history of internal hydrocephalus from Vesalius to the present has been presented. Several intriguing aspects of hydrocephalus have been explored, including the existence of this disorder before tha 16th century and the possibility of medical management. The exciting promise and discouraging failure of experimentally devised choroid plexectomy has been recounted. Finally, the remaining enigma of spontaneous arrest has been discussed.

Body Fluids↗