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S M Gentleman

Publications and source records attributed to S M Gentleman.

49 records · Page 3Linked to original sources
PubMed1992

Quantification of plaque types in sulci and gyri of the medial frontal lobe in patients with Alzheimer's disease.

beta-Amyloid protein (beta A4) deposition was characterised in the sulci and gyri of frontal cortex in 14 cases of Alzheimer's disease. A quantitative study was made of two distinct plaque sub-types (diffuse and classic) using immunocytochemistry and image analysis using a discriminant function design. As reported previously more beta A4 was observed in sulci than gyri. Diffuse plaques were more numerous than classic plaques in sulci and gyri (P less than 0.01). Classic plaques were more abundant in the sulci (P less than 0.01). Increased beta A4 deposition in the sulci is accounted for by increased numbers of classic plaques. No correlation was observed between the numbers of diffuse and classic plaques in either region. Our data suggest that the two plaque types form discrete populations and that their evolution is governed by distinct pathophysiological parameters.

Alzheimer Disease↗
PubMed1992

Quantification of beta A4 protein deposition in the medial temporal lobe: a comparison of Alzheimer's disease and senile dementia of the Lewy body type.

The distribution of beta-amyloid protein (beta A4) was examined in the medial temporal lobes from cases of Alzheimer's disease (AD) (n = 13), senile dementia of Lewy body type (SDLT) (n = 12) and age matched controls (n = 9). Using a previously described image analysis technique the extent of beta A4 pathology was determined in ten distinct anatomical sites within the medial temporal lobe. AD and SDLT cases contained very similar amounts of beta A4 in the areas sampled and both contained significantly more beta A4 than the age matched controls, particularly in the dentate and parahippocampal gyri. The similarity of the beta A4 load in the two conditions is in contrast to reported differences in the number of neurofibrillary tangles which can be observed. It is suggested that AD and SDLT represent a spectrum of pathology which centres around the aberrant processing of the beta A4 precursor protein.

Aged↗
PubMed1992

Quantitative differences in the deposition of beta A4 protein in the sulci and gyri of frontal and temporal isocortex in Alzheimer's disease.

The distribution of beta-amyloid protein (beta A4) in the frontal and temporal isocortex of 14 Alzheimer's disease brains was examined using a combination of immunohistochemistry and computer image analysis. The area of cortex covered by beta A4 deposits was determined and expressed as a percentage of the total cortical grey matter area in each field of interest. Significantly more beta A4 was found in the grey matter of the sulci as compared to that of the gyral crests in both the frontal and the temporal lobes (P less than 0.05). Furthermore, in each case, greater quantities of beta A4 were observed in the frontal rather than the temporal lobes. This apparent differential vulnerability is likely to reflect underlying anatomical connections or perhaps differences in cell packing density and appears to strengthen the case for an anatomical basis for the spread of the disease pathology.

Alzheimer Disease↗
PubMed1992

Quantifying the pattern of beta/A4 amyloid protein distribution in Alzheimer's disease by image analysis.

We have undertaken a study of the distribution of the beta/A4 amyloid deposited in the cerebral cortex in Alzheimer's disease. Previous studies which have examined the differential distribution of amyloid in the cortex in order to determine the laminar pattern of cortical pathology have not proved to be conclusive. We have developed an alternative method for the solution of this problem. It involves the immunostaining of sections followed by computer-enhanced image analysis. A mathematical model is then used to describe both the amount and the pattern of amyloid across the cortex. This method is both accurate and reliable and also removes many of the problems concerning inter and intra-rater variability in measurement. This method will provide the basis for further quantitative studies on the differential distribution of amyloid in Alzheimer's disease and other cases of dementia where cerebral amyloidosis occurs.

Alzheimer Disease↗
PubMed1991

beta A4 amyloid protein deposition in brain after head trauma.

Previous reports have suggested that both repetitive head trauma and a single injury can be associated with the presence of diffuse beta A4 amyloid protein plaques in long-term survivors. We have studied sixteen patients (aged 10-63 years) who sustained head injury and survived for only 6-18 days. Immunostaining with an antibody to beta A4 amyloid showed extensive deposits of the protein in the cortex in six of the sixteen patients (38%). Thus, severe head injury can trigger beta A4 deposition in the brain within days.

Adult↗
PubMed1989

Distribution of galanin-like immunoreactivity in the human brain.

The distribution of galanin-like immunoreactivity has been studied in complete coronal sections taken from 9 normal human brains (4 male, 5 female mean age 54, range 42-72 years). Galanin-immunoreactive cells were restricted largely to the basal nucleus of Meynert and to the supraoptic, ventromedial and posterior areas of the hypothalamus. Fibre staining was more widespread, seen throughout the hypothalamus and in the diagonal band, septum, amygdala, hippocampus and scattered throughout the cortex. This distribution may indicate a role for galanin in the modulation of hypothalamic and basal forebrain function in man.

Adult↗
PubMed1989

Novel peptide pancreastatin: its occurrence and codistribution with chromogranin A in the central nervous system of the pig.

The distribution of pancreastatin immunoreactivity was investigated in porcine brain, spinal cord, dorsal root ganglia, and pituitary. In the brain, immunoreactive cell bodies were present in many areas including the cortex, basal ganglia, hippocampus, thalamus, hypothalamus, mesencephalic reticular formation, cerebellum, and medulla oblongata. Immunoreactive fibres were most abundant in the globus pallidus, stria terminalis, entopeduncular nucleus, hippocampus, and in the substantia nigra. In the spinal cord, immunoreactive cells were found in laminae IV-IX. Immunoreactive fibres were concentrated in the dorsal horn. Pancreastatin immunoreactivity was localised to fibres and small cells (5-10% of the total) in the dorsal root ganglia. In the posterior pituitary, many immunoreactive fibres were present and in the anterior lobe subsets of gonadotrophs and thyrotrophs were pancreastatin-immunoreactive. The localisation of pancreastatin showed a parallel distribution with chromogranin A. Coexistence of pancreastatin with calcitonin gene-related peptide (CGRP) immunoreactivity in cell bodies in the spinal cord, including motoneurones, and with CGRP or galanin immunoreactivities in dorsal root ganglion cells was also noted. The differential pattern of pancreastatin immunostaining was reflected in the extractable levels of peptide with highest concentrations in the cortex (55.8 +/- 6.0 pmol/g wet weight, mean +/- S.E.M.), thalamus (60.0 +/- 5.0 pmol/g), hypothalamus (54.4 +/- 6.5 pmol/g), and anterior pituitary (2,714 +/- 380 pmol/g). Characterisation of pancreastatin immunoreactivity in the hypothalamus and pituitary by gel permeation and high-pressure liquid chromatography revealed multiple molecular forms, one of which was indistinguishable from natural porcine pancreastatin. The widespread distribution of pancreastatin immunoreactivity suggests this peptide may play a part in several neuroendocrine, autonomic, somatic, and sensory functions, and its colocalisation with chromogranin A is consistent with a precursor-product relationship.

Animals↗
PubMed1989

A demonstration of the advantages of immunostaining in the quantification of amyloid plaque deposits.

Extracellular amyloid deposits are a feature of both Alzheimer type dementia and the 'normal' aging process. Quantification of amyloid plaque deposits may well be useful in distinguishing between the senescent changes associated with 'normal' aging and the pathological processes underlying dementia. To determine the most reliable and reproducible method for visualisation of the amyloid we have compared conventional silver staining techniques with beta-amyloid immunocytochemistry on a large sample of post-mortem brain tissue from both demented (n = 15, age range 60-87) and non-demented (n = 65, age range 14-99) patients. The degree of amyloid deposition was rated on a four point scale and ratings for the two techniques were significantly correlated (P less than 0.01). However, the immunocytochemical approach has a number of distinct advantages for quantification. The antibody to beta-amyloid is highly specific and does not stain neurofibrillary tangles or background features, it is considerably more sensitive than silver staining in highlighting diffuse amyloid deposits and, perhaps most importantly, it produces high contrast staining which allows easier image digitisation and subsequent computer image analysis.

Adolescent↗
PubMed1988

The hypothermic response of mice to delta-9-tetrahydrocannabinol is enhanced by chlorpromazine, thioxanthenes, alpha-adrenoceptor antagonists and pentolinium but not by SCH 23390 or sulpiride.

Chlorpromazine, given either subcutaneously (0.375 mg/kg) or unilaterally into the preoptic/anterior hypothalamic area through a chronically implanted cannula (20 micrograms), was found to enhance the hypothermic response to delta-9-tetrahydrocannabinol (THC; 5 mg/kg i.p.) in unrestrained adult male MF1 mice, kept at 22 degrees C. In mg/kg terms, chlorpromazine was no more potent when injected into the preoptic/anterior hypothalamic area than when given subcutaneously. Phentolamine (54 micrograms) had no significant effect on hypothermia induced by THC when injected into the hypothalamus although it did enhance this response when given subcutaneously (15 mg/kg). Hypothermia induced by THC was also enhanced by flupentixol (0.375 mg/kg s.c.), piflutixol (23.4 micrograms/kg s.c.), pentolinium (5 mg/kg s.c.), prazosin (0.1875 mg/kg s.c.) and indoramin (6 mg/kg s.c.) but not by SCH 23390 (6 mg/kg s.c.) or sulpiride (40 mg/kg s.c.). When taken together with the results from a previous study, these data support the hypothesis that chlorpromazine enhances hypothermia induced in mice by THC by antagonizing alpha-adrenoceptors so as to decrease the capacity of the animals to minimise peripheral blood flow by vasoconstriction. The present data also support the hypothesis that flupentixol and piflutixol interacted with THC not by antagonizing dopamine at D1 or D2 receptors but rather by blocking alpha-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Life-long overexpression of S100beta in Down's syndrome: implications for Alzheimer pathogenesis.

Chronic overexpression of the neurite growth-promoting factor S100beta has been implicated in the pathogenesis of neuritic plaques in Alzheimer's disease. Such plaques are virtually universal in middle-aged Down's syndrome, making Down's a natural model of Alzheimer's disease. We determined numbers of astrocytes overexpressing S100beta, and of neurons overexpressing beta-amyloid precursor protein (beta-APP), and assayed for neurofibrillary tangles in neocortex of 20 Down's syndrome patients (17 weeks gestation to 68 years). Compared to controls, there were twice as many S100beta-immunoreactive (S100beta+) astrocytes in Down's patients at all ages: fetal, young, and adult (p = 0.01, or better, in each age group). These were activated (i.e., enlarged), and intensely immunoreactive, even in the fetal group. There were no neurofibrillary changes in fetal or young Down's patients. The numbers of S100beta+ astrocytes in young and adult Down's patients correlated with the numbers of neurons overexpressing beta-APP (p < 0.05). Our findings are consistent with the idea that conditions--including Down's syndrome--that promote chronic overexpression of S100beta may confer increased risk for later development of Alzheimer's disease.

Adult↗