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D G Munoz

Publications and source records attributed to D G Munoz.

At least 73 records · Page 4Linked to original sources
PubMed1993

Clinicopathological features of primary lateral sclerosis are different from amyotrophic lateral sclerosis.

Primary lateral sclerosis (PLS) bears close resemblance to cases of amyotrophic lateral sclerosis (ALS) presenting with spasticity, but histopathological studies have shown significant difference between the two conditions. When the lower motor neurons in cases of ALS and PLS are compared with the equivalent cells of control subjects, morphometric studies indicate significantly decreased size and increased convexity (rounding) of the cell bodies only in ALS. In both disorders there is loss or shrinkage of the largest cortical motor neurons (Betz cells) in the primary motor cortex, though this change is not conspicuous in all cases of ALS. Morphometry reveals in both diseases a general reduction in the sizes of pyramidal cells in the precentral gyrus, indicating that smaller neurons are involved. The cortical motor neurons shrink more in PLS than in ALS. It is concluded that there is clear difference between ALS and PLS. In PLS, quantitative histopathological data show that the neuronal degeneration is confined to long descending pathways, notably the corticospinal system, with no concomitant involvement of lower motor neurons. In ALS, lower motor neuron degeneration occurs in all cases, whereas involvement of the motor cortex is variable.

Aged↗
PubMed1993

Pathogenesis of mesial temporal sclerosis.

A relationship between epilepsy and damage to mesial temporal structures has long been recognized. Recent advances have clarified somewhat the issue of whether the pathological changes seen in mesial temporal sclerosis represent the cause or the effect of seizures. This paper reviews mesial temporal sclerosis from an historical perspective and summarizes recent developments in the fields of excitotoxicity, selective vulnerability, and synaptic reorganization as they pertain to the pathogenesis of mesial temporal sclerosis.

Animals↗
PubMed1993

Hirano bodies accumulate C-terminal sequences of beta-amyloid precursor protein (beta-APP) epitopes.

Hirano bodies (HB) are cytoplasmic inclusions predominantly found in the CA1 sector of the hippocampus. In Alzheimer's disease they are dislocated to the stratum pyramidale from their normal position in the stratum lacunosum. Hirano bodies are known to contain epitopes related to microfilaments (actin), neurofilaments, and microtubules (tau). In cryostat sections of the hippocampus from both Alzheimer's disease and normal patients, HB were decorated by two antisera raised against different sequences of the cytoplasmic domain of beta-amyloid precursor protein (beta-APP), and two antisera against the beta/A4 sequence of beta-APP, but not by two antisera directed against ectodomain (N-terminal) sequences of beta-APP. Thus, in contrast to dystrophic neurites in plaques, which are decorated by antibodies to either terminus of beta-APP, HB appear to be a site of preferential accumulation of C-terminal fragments of beta-APP, extending to include at least part of beta/A4.

Adult↗
PubMed1992

Quantitative dot-blot assay for proteins using enhanced chemiluminescence.

A sensitive non-radioactive method for detection of specific proteins on Western blots is commercially available. The protein is immobilized on nitrocellulose membrane and immunolabelled with HRP-conjugated secondary antibody. HRP catalyzes the oxidation of luminol, a cyclic diacylhydrazide, resulting in the emission of light which is recorded on film. Using dot blot, we have shown that the signal generated by this system is proportional to the amount of protein loaded onto the membrane. Standard curves were linear (r2 greater than 0.95) over a 10-50-fold range. Linearity was also achieved with tissue extracts probed for a specific antigen. The sensitivity of the method is such that less than 10 fmol protein can be measured. The sensitivity and range are comparable to a previously reported dot-blotting assay based on the use of 125I-protein A, but the method does not require the handling of radioactive compounds. This method was used to estimate the level of chromogranin A in a mixture of proteins extracted from human brain.

Adrenal Glands↗
PubMed1992

Delayed changes of chromogranin A immunoreactivity (CgA ir) in human striate cortex during postnatal development.

The changes in chromogranin A expression in the human striate cortex from birth till 67 years were studied by immunohistochemical method in 18 autopsied patients. The first chromogranin A immunoreactivity (CgA ir) was identified at birth in layer IV (especially IVc) mainly as fine nerve terminals. By 6 months, the first perikaryal reactivity was noted in the large pyramidal neurons of layer V. The smaller neurons in layers IV, V and VI showed a progressive increase in CgA ir from 15 months to about 17 years. At approximately 9 years, immunoreactivity began to be noted in supragranular neurons in layers II and III. The final laminar distribution of CgA ir seemed to be attained at about 25 years with relatively little change thereafter. The CgA ir in the striate cortex demonstrates a prolonged period of developmental changes, lasting from birth to about 25 years.

Adolescent↗
PubMed1992

Effects of astrocytes, insulin and insulin-like growth factor I on the survival of motoneurons in vitro.

We isolated motoneurons from E15 dissociated mouse spinal cord by density centrifugation and planted them onto poly-ornithine-coated coverslips in a growth medium (DMEM/F12) supplemented with progesterone, transferrin, selenium, horse serum and muscle extract. Under these conditions only 28% of the motoneurons survived for 8 days. When living astrocytes on a separate coverslip were introduced into dishes containing motoneurons, there was a two-fold increase in neuronal survival. The addition of insulin and insulin-like growth factor I (IGF-I) to such cultures alone or together, still further increased motoneuron survival, but this did not happen in the absence of astrocytes. We conclude that (a) astrocytes exert a trophic role in the survival of spinal motoneurons, (b) the effect does not require physical contact of the cells, and (c) insulin and IGF-1 have neurotrophic activity for motoneurons, an effect possibly mediated by living astrocytes.

Animals↗
PubMed1992

Primary lateral sclerosis. Clinical features, neuropathology and diagnostic criteria.

Eight patients with a homogeneous syndrome of progressive symmetric spinobulbar spasticity were studied. Clinical features were limited to those associated with dysfunction of the descending motor tracts and included spastic quadriparesis, pseudobulbar affect, spastic dysarthria, hyper-reflexia and bilateral Babinski signs. Lower motor neuron findings were absent and higher cognitive function preserved. Median age of onset was 50.5 yrs and median disease duration was 19 yrs. Neuropathologic features (including morphometric analysis) in the single autopsied case confirmed the selective involvement of the motor cortex. There was complete absence of Betz cells from layer 5 of the precentral cortex and the remaining pyramidal cells were significantly smaller than those seen in normal controls. Magnetic resonance imaging (MRI) revealed atrophy of the precentral gyrus and positron emission tomography (PET) scans showed diminished glucose [18F]fluorodeoxyglucose uptake in the pericentral cortex. Magnetic motor cortex stimulation revealed markedly prolonged central motor conduction times. The literature is reviewed and diagnostic criteria for primary lateral sclerosis based on clinical, laboratory and imaging features are proposed.

Aged↗
PubMed1992

A non-toxic method for the demonstration of gliosis.

Neuropathology laboratories have traditionally relied upon the Holzer method for demonstration of gliosis. However, concerns about the toxicity of aniline oil have markedly reduced the application of this method in recent times. Immunostains for glial fibrillary acidic protein (GFAP) are excellent for showing gliosis in grey matter but cannot distinguish normal from abnormal astrocytes in the white matter. The traditional phosphotungstic acid hematoxylin (PTAH) method stains myelin as well as glial fibers and, thus, is not useful for recognizing areas of gliosis. Here we present a method for the routine demonstration of gliosis based on a modification of Mallory's PTAH method. The staining of myelin is eliminated by increasing the concentration of potassium permanganate to 5% (from 0.25-1% in traditional methods). The use of aminoalkylsilane adhesive ensures that the sections do not detach during the procedure. Areas of gliosis stand out against a pale background because only abnormal astrocytes and their processes are stained, both in grey and white matter. The method minimizes the use of toxic chemicals and can be completed within an eight hour work day in any routine neurohistology laboratory, using formalin fixed, paraffin-embedded tissue.

Evaluation Studies as Topic↗
PubMed1992

Tangle-associated neuritic clusters. A new lesion in Alzheimer's disease and aging suggests that aggregates of dystrophic neurites are not necessarily associated with beta/A4.

Abnormal (dystrophic) neurites are widespread in the brains of patients with Alzheimer's disease (AD). Subsets of these neurites cluster in intimate association with amyloid deposits, constituting classic senile plaques. Two major markers expressed by many plaque-associated neurites are the microtubule associated protein tau and chromogranin A, a soluble protein of large dense core synaptic vesicles. The authors show a new type of lesion, tangle-associated neuritic clusters (TANCs), in which abnormal neurites form dense aggregates, each centered by an extracellular (ghost) neurofibrillary tangle, rather than an amyloid deposit. Neurites in TANCs are similar to plaque neurites in shape and expression of tau and chromogranin A, and different from a second, nonaggregating subset of dystrophic neurites in AD, neuropil threads. TANCs are abundant in the hippocampus of all patients with AD; a few are found in some aged nondemented people, and in the nucleus basalis of Meynert and occasionally the neocortex of AD patients. Ultrastructurally, the core of a TANC is made up of extracellular bundles of straight filaments. This core is not recognized by antibodies to native or synthetic beta A4 peptide, the major protein of plaque amyloid, thus showing that not all neuritic clusters in AD are associated with this peptide.

Adolescent↗
PubMed1991

Motoneuron survival in vitro: effects of pyruvate, alpha-ketoglutarate, gangliosides and potassium.

When grown in a serum and muscle extract containing medium, about 20% of chick motoneurons survived for one week. The presence of pyruvate during the first hour of culture doubles the number of motoneurons that survive. The subsequent addition of 5 mM alpha-ketoglutarate, 10-20 mM potassium, or 100 microM GM1 ganglioside results in a further increase in motoneurons surviving. These effects of alpha-ketoglutarate, potassium and GM1 ganglioside are not additive. Using such compounds in the culture medium, one can have a three-fold increase in the survival of motoneurons.

Animals↗
PubMed1991

SMI-32 immunoreactivity in human striate cortex during postnatal development.

SMI-32, an antibody which recognizes the non-phosphorylated epitopes on the neurofilament proteins was used to study the morphological changes in the human striate cortex during postnatal development. Striate cortices from 12 autopsied patients with ages ranging from 1 day to 70 years were obtained. Using the avidin-biotin-peroxidase method, the first SMI-32 immunoreactive neurons were identified at sublayers Vb/VIa on the first postnatal day. At 5 months, the next group of neurons to develop immunoreactivity were in IVb. By 15 months, SMI-32 immunoreactive neurons were observed at III, IVa, IVb, V and VI. The changes in SMI-32 immunoreactivity (ir) were stabilized from 3 years and after. The SMI-32 ir in the striate cortex could be a useful morphological correlate for studying developmental diseases affecting the neocortex.

Adult↗
PubMed1991

A new syndrome of mental retardation and epilepsy characterized by dense microsphere accumulation.

Dense microspheres (DMS) are enigmatic structures found within dendrites in the normal human cortex; their composition and function are unknown. We describe a case of a 29-year-old male with a history of mental retardation and epilepsy in whom the unique neuropathological finding was a marked excess of DMS, most notably in the neocortex. This is a previously undescribed neuropathological syndrome, and represents the first unequivocal association of DMS with a neurological disorder.

Adult↗
PubMed1991

The pathological basis of multi-infarct dementia.

Analysis of the pathology of multi-infarct dementia is best carried out using a two-axis approach. The first axis describes the tissue damage, classified as macroinfarcts, cortical microinfarcts, basal ganglionic lacunes, white matter lacunes, dilated perivascular spaces, diffuse white matter rarefaction, and perivascular edema. The second axis describes the vascular abnormalities, classified as atherosclerosis involving the extracranial or intracranial arteries, arteriolosclerosis, congophilic angiopathy, emboli, and no structural abnormality. Multiple infarcts and white matter rarefaction are commonly seen as a component of Alzheimer disease, in keeping with the development of congophilic angiopathy and possibly other vascular changes in the latter disease. Evidence is presented to support the concept that the white matter rarefaction of Alzheimer disease and aging is associated with perivascular edema, rather than partial infarction.

Age Factors↗
PubMed1991

Muscle derived motoneuron trophic factors promote the survival of motoneurons in vitro only when serum is present in the growth medium.

Motoneuron cultures were established from E6 chick spinal cord. Motoneurons survived for less than 2 days in chemically defined medium. The addition of muscle extract to the medium supported the survival of only a small portion (approximately 2%) of motoneurons for 8 days in vitro. A similar low survival rate was observed when the growth medium was supplemented with serum. The addition of muscle extract to serum containing medium resulted in the survival of about 20% of the motoneurons for 8 days. No differences were seen in the ability of tissue extracts prepared from E8 hindlimb, or muscle obtained from E11, E15, E18 and P3 chicks to support motoneuron survival in the presence of serum. It is apparent that although there are trophic factors present in muscle that support motoneuron survival in vitro, the actions of such trophic factors are dependent upon the presence of yet other factors found in serum.

Animals↗
PubMed1991

Chromogranin A-like immunoreactive neurites are major constituents of senile plaques.

The distribution of chromogranin A (CgA), a soluble protein in dense-core synaptic vesicles expressed by a variety of neuronal cell types, was studied immunocytochemically in Alzheimer's disease and normal aging. In addition to its presence in neuronal perikarya and process, CgA-like immunoreactivity (CgA-li) was demonstrated in multiple dystrophic neurites forming the crown of senile plaques. Two different monoclonal antibodies, LK2H10 and PHE5, gave identical results. In the two regions of the brain studied--the calcarine cortex and the molecular layer of the dentate gyrus--the areal density of plaques associated with CgA-like immunoreactive neurites was greater than the density of Congo red-stainable amyloid cores, but smaller than the density of beta amyloid peptide deposits identified by the Campbell silver stain. By comparison, other synaptically released peptides--somatostatin 28, somatostatin 14, substance P, cholecystokinin, neurotensin, vasoactive intestinal peptide, and leu-enkephalin--were immunocytochemically detected in less than 30% of plaques. Thus CgA appears unique among known synaptically released substances in being present in dystrophic neurites in virtually all classic (i.e., Congo red stainable) plaques and additionally in a subpopulation of preamyloid plaques.

Aged↗
PubMed1990

The distribution of chromogranin A-like immunoreactivity in the human hippocampus coincides with the pattern of resistance to epilepsy-induced neuronal damage.

The distribution of chromogranin A-like immunoreactivity in the hippocampus of adult humans who were free of neurological disease was examined by immunohistochemical methods. Immunoreactivity was restricted to the cytoplasm of certain neuronal populations, most notably the mossy fibers of denate granule cells (and a subset of their perikarya), and the perikarya of pyramidal cells of the cornu Ammonis 2 (CA2) sector. Additionally, staining was observed in neurons in the stratum oriens, a population of neurons at the periphery of the CA4 sector, scattered, probably short-axon perikarya in the CA1 sector, and fibers in the perforant path and the molecular layer of the dentate gyrus. Pyramidal neurons in the CA1 and CA3 sectors were not immunoreactive. The two prominently immunoreactive neuronal populations, CA2 pyramids and dentate granule cells, are those spared in human and experimental epileptic brain damage, whereas CA1 and CA3 pyramids, lacking chromogranin, are characteristically destroyed in this condition. The known activities of chromogranin in the periphery as a calcium-binding protein and as a precursor of active peptides (autocrine inhibitory modulators) suggest that its distribution in the hippocampus may help to explain the observed pattern of resistance to epileptic brain damage.

Adult↗
PubMed1990

Calcitonin gene-related peptide identifies spinal motoneurons in vitro.

Cell dissociation of E6 chick spinal cord followed by isolation of larger low-density cells by using a discontinuous density metrizamide gradient resulted in the obtention of a motoneuron-enriched fraction of cells. These cells were cultured in the presence of horse serum and muscle extract for a period of 8 days and examined for the presence of calcitonin gene-related peptide. More than 90% of such cells were positive for calcitonin gene-related peptide. When E14 spinal cord was examined, calcitonin gene-related peptide was present only in the axons of primary sensory neurons and in the somas of motoneurons in the ventral horns. It is concluded that more than 90% of the neurons in our cultures are motoneurons.

Animals↗