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R D Terry

Publications and source records attributed to R D Terry.

At least 91 records · Page 5Linked to original sources
PubMed1984

Dementia and motor neuron disease: morphometric, biochemical, and Golgi studies.

In three patients dementia without neurofibrillary tangles or Pick bodies antedated amyotrophy by several years. The motor neuron disorder in two patients was characterized by terminal bulbar symptoms; in one it was similar to classic amyotrophic lateral sclerosis. In two patients, quantitative studies of selected regions of the cortex using a computerized image analyzer disclosed, as in patients with senile dementia of Alzheimer type, a marked reduction in the number of neurons, especially those larger than 90 mu 2. The findings differed from those in Alzheimer dementia, however, in that the cells in the substantia innominata were not reduced and the levels of choline acetyltransferase and somatostatin-like immunoreactivity, determined in one patient, were within normal limits. A variable degree of sponginess of the upper layers of the cortex was attributed to attrition of pyramidal cell dendrites, observed in the one patient in whom Golgi study was successful. Because of severe degeneration of the substantia nigra in all three, the disease in these patients may represent a subset of motor neuron disease or a multisystem atrophy.

Alzheimer Disease↗
PubMed1983

Distribution of cholinergic neurons in rat brain: demonstrated by the immunocytochemical localization of choline acetyltransferase.

The neuroanatomical location and cytological features of cholinergic neurons in the rat brain were determined by the immunocytochemical localization of the biosynthetic enzyme, choline acetyltransferase (ChAT). Perikarya labeled with ChAT were detected in four major cell groups: (1) the striatum, (2) the magnocellular basal nucleus, (3) the pontine tegmentum, and (4) the cranial nerve motor nuclei. Labeled neurons in the striatum were observed scattered throughout the neostriatum (caudate, putamen) and associated areas (nucleus accumbens, olfactory tubercle). Larger ChAT-labeled neurons were seen in an extensive cell system which comprises the magnocellular basal nucleus. This more or less continuous set of neuronal clusters consists of labeled neurons in the nucleus of the diagonal band (horizontal and vertical limbs), the magnocellular preoptic nucleus, the substantia innominata, and the globus pallidus. Labeled neurons in the pontine tegmentum were seen as a group of large neurons in the caudal midbrain, dorsolateral to the most caudal part of the substantia nigra, and extended in a caudodorsal direction through the midbrain reticular formation into the area surrounding the superior cerebellar peduncle. The neurons in this latter group constitute the pedunculopontine tegmental nucleus (PPT). An additional cluster of cells was observed medially adjacent to the PPT, in the lateral part of the central gray matter at the rostral end of the fourth ventricle. This group corresponds to the laterodorsal tegmental nucleus. Large ChAT-labeled neurons were also observed in all somatic and visceral motor nerve nuclei. The correspondence of the distribution of ChAT-labeled neurons identified by our methods to earlier immunocytochemical and acetylcholinesterase histochemical studies and to connectional studies of these groups argues for the specificity of the ChAT antibody used.

Animals↗
PubMed1983

Immunocytochemical comparison of neurofibrillary tangles in senile dementia of Alzheimer type, progressive supranuclear palsy, and postencephalitic parkinsonism.

Antiserum raised against a two-cycle-purified human brain microtubule fraction that binds specifically to tangles of senile dementia of the Alzheimer type was tested on the subthalamus, basis pontis, and midbrain sections of two patients with progressive supranuclear palsy. Tangles composed of 15 nm straight fibers in these areas showed positive immunolabeling with the antiserum. The labeling tangles appeared as a fibrous meshwork in neuronal cell bodies and occasionally in short segments of axons. Corresponding sections of brains obtained from patients with idiopathic parkinsonism, striatonigral degeneration, and olivopontocerebellar atrophy treated with the same antiserum did not display peroxidase products. Only in the elderly subjects and patients with postencephalitic parkinsonism did the periaqueductal gray and median raphe show occasional cells that reacted positively with the antiserum. Tangles in the substantia nigra of patients with postencephalitic parkinsonism were also recognized by the antiserum. The results suggest that the two morphologically distinct neurofibrillary tangles share their immunological properties with components present in microtubule fractions of normal brain.

Aged↗
PubMed1983

Senile dementia of the Alzheimer type.

The prevalence of severe dementia in the United States is about 1.3 million cases, of which at least 50 to 60% are of the Alzheimer type. Severe dementia of the Alzheimer type is found rarely in a clearly dominant pattern, although often one or more relatives are affected. Down's syndrome in adults is often associated with Alzheimer changes. The diagnosis is a clinicopathological one; there is a considerable error rate in the clinical diagnosis early in the course of the disease, especially in regard to dementia in depression. The differential diagnosis involves a great many disorders, including multi-infarct dementia, tumors, subdural hematomas, and others. Physiological aspects of Alzheimer's disease include a diffusely slow electroencephalogram, reduced cerebral blood flow, and particular patterns noted on positron emission tomographic scanning. The latter technique has also demonstrated that oxygen extraction is normal in Alzheimer's disease, thus excluding ischemia from possible pathogenetic factors. Morphological changes, that is, the presence of plaques and tangles, are widely distributed in neocortex, paleocortex, and many deep gray areas down through the pontine tegmentum, but largely exclude the basal ganglia, thalamus, and substantia nigra. Numerous plaques without neocortical tangles are found in many demented persons older than 75 years. A severe loss of large neocortical neurons is characteristic of the disease. The chemical nature of the paired helical filaments that make up the neurofibrillary tangle has not yet been ascertained. Neurons are markedly deficient in the basal forebrain nuclei, and this deficiency may account for the severe diminution of choline acetyltransferase and acetylcholine in the neocortex and paleocortex. Muscarinic cholinergic receptors are present in normal amounts. Norepinephrine is reduced in some cases, and somatostatin in most. Substance P is low in severe cases. The etiology of the disorder is unknown and the role of aluminum is disputed. Management of patients with Alzheimer's disease is difficult, and neuroleptics are to be used with great caution because of their side effects. Substrate therapy has not been effective; physostigmine improves memory but is not suitable for general use. Trophic factors, gangliosides, and aluminum chelation are being investigated for use in pharmacological intervention.

Aged↗
PubMed1983

Monoclonal antibodies to choline acetyltransferase: production, specificity, and immunohistochemistry.

Immunohistochemical localization of choline acetyltransferase (ChAT) in cholinergic neurons has been difficult to achieve because of problems encountered in producing specific antisera. Here we describe the production and characterization of several distinct monoclonal antibodies to ChAT. Each of the monoclonal antibodies exhibits one of three general patterns of cross-species reactions; one pattern shows reactivity limited mainly to bovine ChAT, a second pattern shows reactivity only to ChAT from higher mammals including humans, and the third pattern shows reactivity to ChAT from all mammals tested. The antibodies bound specifically to two closely related bovine proteins of 68,000 and 70,000 daltons using the Western blotting technique. One of the antibodies was used to localize immunohistochemically known cholinergic structures in the rat brain, including motor neurons, basal forebrain neurons, and neostriatal neurons.

Animals↗
PubMed1982

Intrusions as a sign of Alzheimer dementia: chemical and pathological verification.

Word intrusions, a behavioral abnormality previously observed in experimental subjects receiving anticholinergic medication as well as in patients with Alzheimer dementia (Alz), were studied as a diagnostic indicator of Alz in 29 elderly nursing home residents who later came to autopsy. Those who intruded words from one portion of a mental status test to another tended to have low levels of choline acetyltransferase in the cerebral cortex (median, 104.33,p less than 0.05) and large numbers of cortical senile plaques (median, 16.0,p less than 0.01). Immediate perseverations and "guesses" on a memory test were not counted. In another group of 38 patients referred for clinical neurological examination for dementia, intrusions were associated with Alz in 84% of those who exhibited them and identified 90% of patients with this presumptive diagnosis. Word intrusion appears sufficiently characteristic of Alz to be helpful diagnostically. The association of this behavioral phenomenon with low choline acetyltransferase levels and large numbers of senile plaques suggests that these changes may be important in producing the characteristic behavioral deterioration of Alz.

Adult↗
PubMed1982

The importance of video editing in automated image analysis in studies of the cerebral cortex.

Editing of the video image in computerized image analysis is readily accomplished with the appropriate apparatus, but slows the assay very significantly. In dealing with the cerebral cortex, however video editing is of considerable importance in that cells are very often contiguous to one another or are partially superimposed, and this gives an erroneous measurement unless those cells are artificially separated. Also important is elimination of vascular cells from consideration by the automated counting apparatus. A third available mode of editing allows the filling-in of the cytoplasm of cell bodies which are not fully stained with sufficient intensity to be wholly detected. This study, which utilizes 23 samples, demonstrates that, in a given area of a histologic section of cerebral cortex, the number of small cells is greater and the number of large neurons is smaller with editing than without. In that not all cases follow this general pattern, inadequate editing may lead to significant errors on individual specimens as well as to the calculated mean. Video editing is therefore an essential part of the morphometric study of cerebral cortex by means of automated image analysis.

Aged↗
PubMed1981

Some morphometric aspects of the brain in senile dementia of the Alzheimer type.

Image analysis apparatus was used to count and measure glial and neuronal perikarya in ten size classes in the midfrontal region and superior temporal gyrus of 18 patients with senile dementia of the Alzheimer type for comparison with 12 age-matched normal specimens. Brain weight was about 8% less in the dementia group. The major differences had to do with larger neurons, which in dementia were reduced by about 40% in the frontal cortex and 46% in the temporal region. The concentration of neuritic plaques did not correlate significantly with brain weight, cortical thickness, or cell counts.

Aged↗
PubMed1981

Cortical somatostatin-like immunoreactivity in cases of Alzheimer's disease and senile dementia of the Alzheimer type.

The activity of choline acetyltransferase (ChAT) and the concentration of somatostatin-like immunoreactive material (SLI) have been measured in 8 brain regions from 12 normal individuals and 12 cases of presenile and senile dementia of the Alzheimer type. ChAT activity was significantly lower in all 8 brain regions of demented patients and the SLI concentration was significantly reduced in 7 of the the 8. There were correlations between the extent of the reductions of ChAT activity and SLI concentration in four brain regions, and a greater reduction of parietal cortex SLI in younger patients than in the more elderly.

Aged↗
PubMed1981

Fibrous Astrocytes in senile dementia of the Alzheimer type.

Fibrous astrocytes were stained by the Sternberger (peroxidase-antiperoxidase) method, using paraffin sections of mid-frontal cerebral cortex of patients with senile dementia and of normals of similar age. The populations of fibrous astrocytes were similar in the molecular layer, but were widely divergent in layers II through VI. Here the mean count of fibrous astrocytes in senile dementia of the Alzheimer type was more than four times that of the normal aged cortex.

Aged↗
PubMed1981

Immunocytochemical studies of neurofibrillary tangles.

The molecular nature of neurofibrillary tangles of senile dementia of the Alzheimer type (SDAT) was studied by immunoperoxidase and immunofluorescence techniques. Five antiserums, including anti-humanbrain-2-cycle-purified-microtubule-fractions (2 x MT), anti-calf-brain-2 x MT, anti-sea-urchin-egg-tubulin, antibeef-brain-tubulin, and anti-human-brain-neurofilament(NF)-210-kilodalton(kd)-protein were tested for their binding to neurofibrillary tangles. The antihuman-2 x MT serum stained structures resembling neurofibrillary tangles, neurites of neuritic plaques, and microglialike cells in SDAT brains, but no such staining pattern was detected in normal brain sections. In neurons isolated from SDAT brains, about 40% of the tangles were labeled by the anti-human-2xMT serum with an identical pattern. Other antiserums tested did not preferentially bind tanglelike structures in tissue sections and bound to less than 5% of the tangles in isolated neurons. These results suggest that the antigenic sites of tubulin and NF proteins are not shared by neurofibrillary tangles. Different from the calf preparation, the human-2 x MT fractions contained a prominent protein band that was identical to ferritin in molecular weight and cross-reacted with anti-human-2 x MT and anti-human-ferritin serums. However, antiserums to this ferritinlike protein, or anti-ferritin, did not stain neurofibrillary tangles. Although neither the calf 2 x MT nor two other human MT fractions failed to elicit an antiserum that stained tangles, these fractions were able to remove the antihuman-2 x MT serum activity that binds to tangles. The data suggest that the protein (or proteins) that makes up neurofibrillary tangles of SDAT is present in various quantities in microtubule fractions of normal brain.

Alzheimer Disease↗
PubMed1980

Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer disease and Alzheimer senile dementa.

Both Alzheimer's disease and senile dementia of the Alzheimer type (AD/SDAT) are progressive dementias characterized neuropathologically by the presence in the cerebral cortex of numerous neurofibrillary tangles and neuritic plaques. We use the abbreviation AD/SDAT to denote all such cases, irrespective of age of onset. Studies of neurotransmitter-related parameters in autopsied brain tissues from patients with AD/SDAT have, to date, been confined to five putative transmitter systems. Acetycholine-releasing neurones seem to be most markedly and consistently affected, as judged by the extensive reductions in choline acetyltransferase (ChAT) and acetylcholinesterase activities that have been reported. Despite numerous studies, there is no consistent evidence for the involvement of neurones releasing dopamine, noradrenaline, serotonin, or gamma-aminobutyric acid in AD/SDAT, nor for loss of muscarinic cholinergic receptors. Thus, the involvement of cholinergic neurones in AD/SDAT seems to be specific. However, the possible involvement of neurones using other chemicals as transmitters has yet to be explored. The recent recognition of the existence of so-called 'peptidergic neurones' in the mammalian brain (for review see ref. 8) and the availability of radioimmunoassay (RIA) techniques for studying these peptides, have led us to begin a systematic investigation of neuropeptides in autopsied brain tissue from cases of AD/SDAT, and from neurologically normal individuals. We report here results obtained with a RIA for somatostatin, showing that somatostatin-like immunoreactivity in the cerebral cortex is reduced in tissue from AD/SDAT patients.

Aged↗
PubMed1980

Pathological verification of ischemic score in differentiation of dementias.

Fourteen case histories of persons who had a histological diagnosis of either senile dementia of the Alzheimer type, multiinfarct dementia, or a mixed dementia composed of these two types and who showed evidence of a moderate to severe dementia on psychological testing were rated for the presence of thirteen clinical features comprising Hachinski's Ischemic Score. These features are frequently considered primarily characteristic of vascular dementia. Persons with senile dementia of the Alzheimer type were clearly differentiable from persons with multiinfarct dementia and mixed dementia, while the latter two groups were indistinguishable from one another. In our sample, eight features were found to characterize those persons with vascular dementia. These data verify the usefulness of the Ischemic Score in differentiating between senile dementia of the Alzheimer type and vascular dementia.

Aged↗
PubMed1979

Evidence that Alzheimer neurofibrillary tangles originate from neurotubules.

Antiserum against normal human neurotubules purified by in-vitro assembly precipitated both neurotubules and a polypeptide isolated from Alzheimer neurofibrillary tangles in Ouchterlony double-diffusion tests. The antiserum specifically labelled neurofibrillary tangles, in isolated neurons by immunofluorescence and in tissue sections by the peroxidase-antiperoxidase technique. These results indicate that neurofibrillary tangles in Alzheimer's disease probably originate from neurotubules.

Adult↗