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Biomedical subjects

D G Munoz

Publications and source records attributed to D G Munoz.

At least 55 records · Page 3Linked to original sources
PubMed1996

Diffuse vacuolization (spongiosis) and arteriolosclerosis in the frontal white matter occurs in vascular dementia.

OBJECTIVE: To examine quantitatively white-matter changes at different sites in patients with definite vascular dementia and Alzheimer's disease. DESIGN: Prospective clinical and neuropathological series. SETTING: University Hospital clinics (Helsinki, Finland and London, Ontario). SUBJECTS: Twenty-two patients with a clinical and neuropathological diagnosis of vascular dementia and 20 patients with Alzheimer's disease. MEASURES: The frequencies of focal white-matter lesions, arteriolosclerosis, and cerebral amyloid angiopathy were assessed. Validated ratings and cell counts were done in the subcortical U-fiber, centrum semiovale, and periventricular areas of the frontal white matter. Degrees of abnormality (none, mild, moderate, severe) were rated for spongiosis (vacuolization of white matter), état criblé (widening of perivascular spaces), myelin loss, oligodendrocyte density, axonal loss, and overall. Densities of oligodendrocytes and astrocytes (cells per square millimeter) were determined. RESULTS: Patients with vascular dementia showed focal white-matter lesions and arteriolosclerosis more often than patients with Alzheimer's disease. The patients with vascular dementia also had significantly greater spongiosis (P<.001), état criblé (P=.004), myelin loss (P<.005) and overall white-matter abnormality (P<.001). Arteriolosclerosis was found in association with spongiosis but not with état criblé. Cerebral amyloid angiopathy did not appear to be related to any of the white-matter changes in patients with either vascular dementia or Alzheimer's disease. The U-fiber area showed fewer changes, and the periventricular area tended to be most affected. CONCLUSION: In addition to focal infarcts, patients with vascular dementia showed widespread diffuse changes, including spongiosis and arteriolosclerosis, along with état criblé and myelin loss. White-matter changes in patients with Alzheimer's disease could not be related to infarction. Pathologic changes in small blood vessels are associated with diffuse white-matter changes and may have a distinct role in the genesis of vascular dementia.

Aged↗
PubMed1996

Temporal pattern of cognitive decline and incontinence is different in Alzheimer's disease and diffuse Lewy body disease.

Incontinence is a hallmark of dementia, but little is known about its inception in different types of dementing disease. We recorded the dates of onset of dementia and of urinary incontinence in 73 demented patients followed for 5.6 +/- 2.5 years. The pathologic diagnosis was Alzheimer's disease (AD) in 29 cases, diffuse Lewy body disease (DLBD) in 11 cases, AD with Lewy bodies (AD+LB) in 13 cases, and AD with vascular lesions (AD+VL) in 20 cases. The onset of urinary incontinence was significantly earlier in DLBD cases (3.2 +/- 1.4 years after dementia onset) than in AD (5.9 +/- 2.5), AD+LB (5.8 +/- 2.4), and AD+VL (6.5 +/- 2.3) (p < 0.01). At the onset of bladder incontinence, the mean score in the Extended Dementia Scale was significantly higher (i.e., cognition was better) in DLBD cases (109.3 +/- 70.8) than in AD (21.3 +/- 40.4), AD+LB (45.6 +/- 45.1), and AD+VL (39.2 +/- 54.9) cases (p < 0.01). Urinary incontinence is associated with severe cognitive decline in pure AD but usually precedes severe mental failure in DLBD cases. This temporal pattern of cognitive decline and incontinence could be useful in differentiating these two dementing illnesses.

Aged↗
PubMed1995

Human cerebrovascular nerve fibers immunoreactive for synaptophysin, chromogranin A and tyrosine hydroxylase.

The innervation of human cerebral blood vessels has been examined using synaptophysin, a marker of synaptic vesicles, and chromogranin A, a marker of large dense-core vesicles. The catecholaminergic marker tyrosine hydroxylase was used for comparison. Synaptophysin and tyrosine hydroxylase demonstrated a similar distribution of nerve fibers whereas chromogranin A terminals were only sparsely evident. Our results suggest that there is not a subset of nerve fibers in existence which has a distribution different than that of catecholaminergic fibers. Furthermore, in view of its unexpected sparse distribution, chromogranin A in the nervi vasorum is not likely to be a significant contributor to cerebral blood flow regulation.

Adult↗
PubMed1995

Qualitative and quantitative differences in senile plaque dystrophic neurites of Alzheimer's disease and normal aged brain.

We have investigated the relationship of plaque dystrophic neurites expressing beta-amyloid precursor protein (beta APP) to those bearing markers of neurofibrillary degeneration (tau), or accumulating the synaptic protein chromogranin A (CgA). In cortical and hippocampal plaques in Alzheimer's disease (AD) beta APP colocalized with CgA in a neuritic population largely distinct from the subset of neurites labeled by tau. Putaminal plaques generally incorporated only CgA/beta APP, but not tau neurites, and with a rare exception cerebellar plaques were not associated with neurites. Neocortical and hippocampal plaques, the only common type in a group of elderly non-demented subjects (non-AD), incorporated CgA/beta APP, but not tau neurites. In addition to this qualitative difference between the two groups, neocortical plaques with CgA/beta APP neurites were one order of magnitude more common in AD than in non-AD. We propose a hierarchical model of plaque formation in which A beta deposits do not incorporate tau neurites unless neurites bearing synaptic proteins and beta APP are also present. Finally, the minimal association of tau neurites with putaminal plaques, in the presence of tau-immunoreactive neuropil threads and neurofibrillary tangles in the neighborhood, suggests that plaque-independent mechanisms of development of tau neurites operate in AD.

Aged↗
PubMed1994

Effect of chromogranin A on central autonomic control of blood pressure.

We investigated the effect of exogenous chromogranin A (CgA) on central autonomic structures involved in the control of blood pressure. Actions of CgA were assessed on neurons in the rostral ventrolateral medulla, the most important brain area for cardiovascular control and for generation of sympathetic activity. Changes in renal sympathetic nerve activity, arterial pressure, heart rate, and somato-sympathetic reflexes were measured after microinjections of chromogranin A into the rostral ventrolateral medulla of anesthetized rats. The sites of microinjection of chromogranin A were determined from well known sympathetic and cardiovascular responses to microinjection of the inhibitory amino acid glycine. Significant decreases in renal nerve activity and arterial blood pressure began 10 min after microinjection of chromogranin A into the rostral ventrolateral medulla, and the maximum effect was observed at 20 min. Moreover, the bulbar component of somato-sympathetic reflexes was depressed 20 min after microinjections of chromogranin A. Our results indicate that chromogranin A can modify the activity of neurons within rostral ventrolateral medulla involved in regulation of cardiovascular autonomic control.

Animals↗
PubMed1994

Chromogranin A applied to the nucleus accumbens decreases locomotor activity induced by activation of the mesolimbic dopaminergic system in the rat.

The aim of the study was to obtain supporting evidence, using a behavioral paradigm, of the hypothesis that chromogranin A attenuates transmitter release in the CNS. We studied the effects of chromogranin A injected into the nucleus accumbens on locomotor activity triggered by application of picrotoxin into the ventral tegmental area of rats. Injection of picrotoxin into the ventral tegmental area, which is known to disinhibit dopaminergic mesolimbic neurons, caused a significant increase in horizontal activity. Distance covered during locomotion and movement time increased more than twofold, whereas stereotypy time and number, indices of nonlocomotor behavior, were not significantly affected by picrotoxin. Pressure injection of chromogranin A into the nucleus accumbens prior to injection of picrotoxin into the ventral tegmental area prevented these locomotor effects and had little or no effect on nonlocomotor behavior. Similarly, the picrotoxin-induced activity was prevented by injecting cobalt chloride into the nucleus accumbens. The results show that chromogranin A has an attenuating effect, either directly or indirectly, on dopaminergic neurotransmission in the nucleus accumbens that can be exemplified by inhibiting picrotoxin-induced locomotor activity. Further studies are needed to determine the mechanism of chromogranin A action in the nucleus accumbens.

Animals↗
PubMed1994

Amygdalar sclerosis: preoperative indicators and outcome after temporal lobectomy.

Isolated amygdalar sclerosis (AS) in the presence of an intact hippocampus has been described in a subset of patients who have undergone a temporal lobectomy for the relief of seizures. Clinical observation suggested that these patients might be distinguishable, before and after operation, from those with typical mesial temporal sclerosis, which implies combined amygdalar and hippocampal sclerosis (AHS). From a three year series, all 11 patients classified as having AS were included in this study. These patients were compared with a group of 20 randomly chosen patients with AHS. The groups were found to be well matched in duration of ongoing seizures, full scale IQ, and duration of follow up (mean 19 months). Compared with patients with AHS, patients in the AS group were less likely to have had a seizure in early childhood, a variety of auras, EEG abnormalities localised to one temporal lobe, or an abnormal MRI before operation. They also performed better on preoperative memory tests. At follow up, patients in the AS group were less likely to be seizure free and more likely to have a deterioration in memory after undergoing anterior temporal lobectomy, including part of the hippocampus. The results show that there are preoperative indicators of mesial temporal pathology that are also of prognostic importance given the differences in outcome between the two pathological groups.

Adolescent↗
PubMed1994

The pathology and nosology of primary progressive aphasia.

We present three cases of primary progressive aphasia (PPA) with Pick-variant pathology to support a hypothesis of an underlying nosologic relatedness. Neuropathologic examination demonstrated focal brain atrophy with corresponding neuronal loss and gliosis, accompanied by superficial spongiosis. Specific histologic findings were ballooned neurons (Pick cells) in the atrophic areas, and in two of the cases, Pick bodies. They were immunoreactive for tau. In contrast to classic Pick's disease, there were no Pick bodies in the hippocampus. The intense neurofilament immunoreactivity of the perikarya of the ballooned neurons greatly facilitated their recognition. Based on our cases and a critical review of the literature, we hypothesize that the common underlying pathology of PPA is a variant of Pick's disease. Furthermore, we propose the concept of "Pick complex" to include other neurodegenerative diseases characterized by focal cortical degeneration, such as PPA, frontal lobe dementia, ALS with PPA, and corticonigral and corticobasal ganglionic degenerations.

Aged↗
PubMed1994

Chondromyxoid fibroma of the occipital bone.

Chondromyxoid fibroma is an uncommon bone tumour, found predominantly in the metaphyses of the long bones of the lower limbs. The authors describe a patient in whom the tumour arose from the occipital bone. To the authors' knowledge, this is only the second report of chondromyxoid fibroma occurring in this location.

Adult↗
PubMed1993

Chromogranin A inhibits retinal dopamine release.

Chromogranin A (CGA), a peripherally active prohormone, is a soluble component in the secretory granules of many endocrine tissues and is cosecreted with their peptide or amine hormones. Using an antibody prepared against purified rat adrenal CGA, immunostaining was localized to the inner and outer plexiform layers of the rat retina and to selected ganglion cells. Exogenous CGA (purified from human adrenals) when applied to perfused rat retina potently inhibited the potassium-induced release of endogenous dopamine (DA). This action was dose-dependent, with an IC50 of 3 nM; at 100 nM CGA retinal DA release was completely abolished.

Animals↗
PubMed1993

Chromogranin A, a soluble synaptic vesicle protein, is found in cortical neurons other than previously defined peptidergic neurons in the human neocortex.

Neuropeptides in the cerebral cortex have previously been identified in non-pyramidal neurons only. By comparing the location of chromogranin A (CgA), a soluble protein of large dense-core synaptic vesicles, with that of SMI-32, neuropeptide Y (NPY), parvalbumin (PV) and calbindin (CaBP) using double label immunohistochemistry, we demonstrate that CgA is present in pyramidal neurons as well as in several subtypes of non-pyramidal neurons.

Adult↗
PubMed1993

Pathologic correlates of increased signals of the centrum ovale on magnetic resonance imaging.

The pathologic correlates of increased signal in the white matter of the centrum ovale in postmortem magnetic resonance imaging were investigated in an unselected series of 15 autopsies. Two types of magnetic resonance imaging hyperintensities could be separated on the basis of size (10-mm cutoff): extensive and punctate. The pathologic basis of extensive hyperintensities was large areas of pallor with ill-defined margins, located in the central white matter and sparing the subcortical U fibers on both myelin and axonal stains. Microscopically, these areas showed diffuse vacuolation and significant reduction in the areal densities of glial cells. This change was never seen in areas that did not show extensive white matter hyperdensities on magnetic resonance imaging. The correlates of punctate magnetic resonance imaging hyperintensities were less well defined; dilated Virchow-Robin spaces probably represent a common cause of this phenomenon.

Aged↗
PubMed1993

Amygdaloid sclerosis in temporal lobe epilepsy.

Hippocampal sclerosis is the sole abnormality found in approximately 65% of all temporal lobe specimens resected for intractable temporal lobe epilepsy. Up to 27% of en bloc temporal lobectomy specimens, however, show no definitive pathological changes. The lateral amygdaloid nucleus from 8 consecutive patients who underwent temporal lobectomy in whom no definitive hippocampal pathology was present and corresponding tissue from 8 consecutive patients with hippocampal sclerosis were subjected to quantitative estimation of neuronal density and astrogliosis. As compared to amygdaloid tissue from autopsy control subjects with no history of neurological disease, both the patient group with and that without hippocampal sclerosis consistently exhibited severe neuronal loss and gliosis with no quantitative differences between the two groups. Blinded clinical review of both groups of patients revealed that the development of hippocampal sclerosis was associated with a history of early brain insult; this history was absent in patients with isolated amygdaloid sclerosis. Neuropsychological testing prior to surgery demonstrated that patients with hippocampal sclerosis displayed a greater degree of memory impairment than did those without hippocampal sclerosis. We conclude that amygdaloid sclerosis occurs in the absence of hippocampal sclerosis, and that these patients form a distinct group with no history of early brain insult and milder memory impairment than that seen in patients afflicted with hippocampal sclerosis.

Adult↗
PubMed1993

Differential incorporation of processes derived from different classes of neurons into senile plaques in Alzheimer's disease.

The incorporation of neurites into amyloid deposits is an important step in the formation of senile plaques in Alzheimer's disease. It is unknown whether all neuronal types contribute neurites equally to plaques, or whether the processes of certain types are preferentially incorporated. We addressed this question by comparing the incorporation into neocortical plaques of neurites containing the widely distributed neuronal markers chromogranin A (CgA), parvalbumin (PV) and calbindin D-28K (CaBP) in relation to the number of neuronal perikarya expressing each of these substances in the neocortex. We found a consistent, statistically significant ranking, so that CgA-immunoreactive (ir) neurites were preferentially incorporated into plaques in comparison with PV-ir, and PV-ir were favoured over CaBP-ir neurites.

Aged↗
PubMed1993

Dense microspheres in the human hippocampus.

Dense microspheres (DMS) are structures found within neuronal processes of the adult human brain. Although best known as a feature of the neocortex, they are also found in the hippocampal formation. We describe a characteristic pattern of DMS distribution in the human hippocampus. The functional significance of this pattern is unknown, but it casts doubt on the proposed relationship of DMS to senile plaques. We also present evidence that DMS are composed of protein, but without a significant component of carbohydrate or neutral glycoprotein.

Adult↗